Maternal body weight and first trimester screening for chromosomal anomalies

Prenatal risk ratios for Down syndrome adjust for maternal weight because maternal serum 2 biomarker levels decrease with increasing maternal weight. This is accomplished by converting 3 serum biomarker values into a multiple of the expected median (MOM) for women of the same 4 gestational age. Weight is frequently not recorded and the impact of using MOMs not adjusted for 5 weight for calculating risk ratios is unknown. The aim of this study is to examine the effect of 6 missing weight on first trimester Down syndrome risk ratios by comparing risk ratios calculated 7 using weight-unadjusted-and –adjusted MOMs. Findings at the population level indicate that the 8 impact of not adjusting for maternal weight on first trimester screening results for chromosomal 9 anomalies would lead to under-identification of 84 per 10,000 pregnancies.NHMR

Methods of classification for women undergoing induction of labour: a systematic review and novel classification system

Background: The lack of reproducible methods for classifying women having an induction of labour (IOL) has led to controversies regarding the association of IOL and health outcomes for mother and baby. Objectives: To identify research papers that describe a methodology for classifying women having an IOL, and to evaluate the utility of these methods of classification for clinical, research and surveillance purposes. Search strategy: We conducted electronic searches in CINAHL, EMBASE and WEB of KNOWLEDGE from database inception until Oct 2013 and searched reference lists. Selection criteria: Two reviewers independently assessed eligibility. Studies had to describe a method for classifying women with an IOL using a minimum of two categories, regardless of whether or not this was the main purpose of the study. Data collection: Data were extracted on study characteristics, quality and results. Pre-specified criteria were used to evaluate the utility of these methods of classification for IOL. Main results: Seven studies met the inclusion criteria. All studies categorised women according to the presence or absence of a medical indication for IOL. Uncertainties and/or deficiencies were identified across all methods of classification related to the criteria of total inclusivity, reproducibility, clinical utility, implementability and data availability limiting their usefulness. Conclusion: Current methods of classifying women with an IOL are inadequate for clinical, research and surveillance purposes. Limitations with classification systems based on medical indications suggest that an alternative method of classification is required for women having IOL

Effects of vitamin D deficiency on neurobehavioural outcomes in children: a systematic review

Introduction: Vitamin D plays an important role in brain development in experimental studies; however, the effect of vitamin D deficiency on child development remains inadequately characterized. We aimed to estimate the effects of vitamin D deficiency on neurobehavioural outcomes in children up to 18 years of age. Methods: We searched PubMed, EMBASE, PsycINFO, Scopus, Cochrane Library, Web of Science and Open Grey for published studies up to 10th January 2020. We included all studies that assessed the effects of maternal or child vitamin D status or vitamin D supplementation on neurobehavioural outcomes in children. Study findings were synthesized qualitatively as the high level of heterogeneity in study populations and methodologies precluded a quantitative meta-analysis. Results: Our search identified 5,633 studies, of which 31 studies with 31,375 participants from 18 countries were included in the systematic review. Of the studies identified, one was a randomised controlled trial (RCT) of vitamin D supplementation in children, while 30 were observational. The RCT (n=55) reported a beneficial effect of supplementation with lower doses compared to higher doses of vitamin D on motor development. Twelve mother-child studies (n=17,136) and five studies in children (n=1,091) reported an association between low maternal or child 25-hydroxyvitamin D levels and impaired neurobehavioural outcomes in children, while 15 mother-child studies (n=20,778) and eight studies in children (n=7,496) reported no association. Conclusions: Although animal studies point to an effect of vitamin D deficiency on brain development, there are few studies on the effects of vitamin D deficiency on neurobehavioural outcomes in children and their findings are inconsistent. There is a need for well-conducted, adequately powered studies to further determine these effects in children

Iron deficiency in early pregnancy using serum ferritin and soluble transferrin receptor concentrations are associated with pregnancy and birth outcomes.

Background: There are several biomarkers for measuring iron deficiency (ID) in pregnancy, but evidence of their prevalence in association with inflammation and adverse pregnancy outcomes is inconclusive. Objectives: To describe the prevalence and determinants of ID in women in the first trimester of pregnancy and associations with pregnancy and birth outcomes. Design: A record-linkage cohort study of archived serum samples of women attending first trimester screening and birth and hospital data to ascertain maternal characteristics and pregnancy outcomes. Sera were analysed for iron stores (ferritin; μg/L), tissue iron (soluble transferrin receptor, sTfR; nmol/L) and inflammatory (C-reactive protein, CRP; mg/L) biomarkers. Total body iron (TBI) was calculated from serum ferritin and sTfR concentrations. Multivariate logistic regression analyzed risk factors and pregnancy outcomes associated with ID using the definitions: serum ferritin <12 μg/L, TfR ≥21.0 nmol/L and TBI<0 mg/kg. Results: Of 4,420 women, the prevalence of ID based on ferritin, sTfR and TBI was 19.6%, 15.3% and 15.7%, respectively. Risk factors of ID varied depending on which iron parameter was used and included maternal age <25 years, multiparity, socioeconomic disadvantage, high maternal body weight and inflammation. ID was associated with reduced risk of gestational diabetes (GDM) defined using serum ferritin and TBI, but not sTfR and increased risk of large for gestation age (LGA) infants defined using TBI only. Conclusions: Nearly 1 in 5 Australian women begin pregnancy with ID. Evidence suggests excess maternal weight and inflammation play a role in the relationships between ID and GDM and LGA infants.NHMR

Halo Star Streams in the Solar Neighborhood

We have assembled a sample of halo stars in the solar neighborhood to look for halo substructure in velocity and angular momentum space. Our sample includes red giants, RR Lyrae, and red horizontal branch stars within 2.5 kpc of the Sun with [Fe/H] less than -1.0. It was chosen to include stars with accurate distances, space velocities, and metallicities as well as well-quantified errors. We confirm the existence of the streams found by Helmi and coworkers, which we refer to as the H99 streams. These streams have a double-peaked velocity distribution in the z direction. We use the results of modeling of the H99 streams by Helmi and collaborators to test how one might use v_z velocity information and radial velocity information to detect kinematic substructure in the halo. We find that detecting the H99 streams with radial velocities alone would require a large sample. We use the velocity distribution of the H99 streams to estimate their age. From our model of the progenitor of the H99 streams, we determine that it was accreted between 6 and 9 Gyr ago. The H99 streams have [alpha/Fe] abundances similar to other halo stars in the solar neighborhood, suggesting that the gas that formed these stars were enriched mostly by Type II SNe. We have also discovered in angular momentum space two other possible substructures, which we refer to as the retrograde and prograde outliers. The retrograde outliers are likely to be halo substructure, but the prograde outliers are most likely part of the smooth halo. The retrograde outliers have significant structure in the v_phi direction and show a range of [alpha/Fe]. The methods presented in this paper can be used to exploit the kinematic information present in future large databases like RAVE, SDSSII/SEGUE, and Gaia.Comment: 46 pages, 13 figures, and 9 tables. Minor changes to text to match proofed version of the paper. Low resolution figures. High resolution version at http://www.astro.wisc.edu/~kepley/solar_streams.p

Does the Method of Biopsy Affect the Incidence of Sentinel Lymph Node Metastases?

More detailed examination of the sentinel lymph node (SLN) in breast cancer has raised concerns about the clinical significance of micrometastases, specifically isolated tumor cells detected only through immunohistochemical (IHC) staining. It has been suggested that these cells do not carry the same biologic implications as true metastatic foci and may represent artifact. A retrospective institutional review board-approved review was conducted on clinically node-negative breast cancer patients who underwent SLN biopsy (SLNB) between 1997 and 2003. Retrospective analysis of tumor characteristics and the method of the initial diagnostic biopsy were correlated with the presence and nature of metastatic disease in the SLN. Of 537 SLNBs, 123 (23%) were hematoxylin-eosin (H&E) positive. SLN positivity strongly correlated with tumor size (p < 0.001) and tumor grade (p = 0.025), but not with the method of biopsy (needle versus excisional biopsy). Prior to July 2002, we routinely evaluated H&E-negative SLNs with IHC ( n  = 381). Of the 291 H&E-negative patients, 26 had IHC-only detected micrometastases (9%). The likelihood of detecting IHC-only metastases did not correlate with tumor size or grade, but was significantly higher in patients undergoing excisional biopsy than core needle biopsy. While the method of biopsy has no demonstrable effect on the likelihood of finding metastases in the SLN by routine serial sectioning and H&E staining, it may significantly impact the likelihood of finding micrometastases by IHC. IHC should not be used routinely in the evaluation of the SLN and caution should be used when basing treatment decisions (completion axillary lymph node dissection or adjuvant therapy) on IHC-only detected micrometastases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72849/1/j.1075-122X.2006.00179.x.pd

Multiple effects of silymarin on the hepatitis C virus lifecycle

Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production. Silymarin did not block HCVcc binding to cells but inhibited the entry of several viral pseudoparticles (pp), and fusion of HCVpp with liposomes. Silymarin but not silibinin inhibited genotype 2a NS5B RNA-dependent RNA polymerase (RdRp) activity at concentrations 5 to 10 times higher than required for anti-HCVcc effects. Furthermore, silymarin had inefficient activity on the genotype 1b BK and four 1b RDRPs derived from HCV-infected patients. Moreover, silymarin did not inhibit HCV replication in five independent genotype 1a, 1b, and 2a replicon cell lines that did not produce infectious virus. Silymarin inhibited microsomal triglyceride transfer protein activity, apolipoprotein B secretion, and infectious virion production into culture supernatants. Silymarin also blocked cell-to-cell spread of virus. CONCLUSION: Although inhibition of in vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's antiviral action appear to include blocking of virus entry and transmission, possibly by targeting the host cell

High maternal iron status, dietary iron intake and iron supplement use in pregnancy and risk of gestational diabetes mellitus: In-house study and systematic review

Background: High iron measured using dietary and serum biomarkers have been associated with type 2 diabetes; however it is uncertain whether a similar association exists for gestational diabetes mellitus (GDM). Objectives: To conduct a cohort study examining first trimester body iron stores and subsequent risk of GDM and to include these findings in a systematic review of all studies examining the association between maternal iron status, iron intake (dietary and supplemental) and the risk of GDM. Methods: Serum samples for women with first trimester screening were linked to birth and hospital records for data on maternal characteristics and GDM diagnosis. Blood was analysed for ferritin, soluble transferrin receptor (sTfR) and C-reactive protein (CRP). Associations between iron biomarkers and GDM were assessed using multivariate logistic regression. A systematic review and meta-analysis, registered with PROSPERO (CRD42014013663) included all studies published in English from Jan 1995 to March 2014 that examined the association between iron and GDM and included an appropriate comparison group. Results: Of 3, 776 women, 3.4% subsequently developed GDM. Adjusted analyses found increased odds of GDM for ferritin (OR 1.41; 95% CI: 1.11, 1.78) but not for sTfR (OR 1.00, 95% CI: 0.97, 1.03) levels. Two trials of iron supplementation in early pregnancy found no association with GDM. Increased risk of GDM was associated with higher levels of maternal ferritin and serum iron and dietary heme iron intakes. Conclusions: Increased risk of GDM among women with high serum ferritin and iron levels and dietary heme iron intakes warrants further investigation.NHMR

A randomized control trial of phototherapy and 20% albumin versus phototherapy and saline in Kilifi, Kenya

Objective: The study evaluated the efficacy of phototherapy and 20% albumin infusion to reduce total serum bilirubin (TSB) in neonates with severe hyperbilirubinemia. The primary outcome was a reduction of TSB at the end of treatment. The secondary outcomes were the need for exchange transfusion, inpatient mortality, neurological outcomes at discharge, and development outcomes at 12-months follow-up. Results: One hundred and eighteen neonates were randomly assigned to phototherapy and 20% albumin (n = 59) and phototherapy and saline (n = 69). The median age at admission was 5 (interquartile range (IQR) 3–6) days, and the median gestation was 36 (IQR 36–38) weeks. No significant differences were found in the change in TSB (Mann–Whitney U =609, p = 0.98) and rate of change in TSB per hour after treatment (Mann–Whitney U = 540, p = 0.39) between the two groups. There were no significant differences between the two groups in the proportion of participants who required exchange transfusion (χ2 (2) = 0.36, p = 0.546); repeat phototherapy (χ2 (2) = 2.37, p = 0.123); and those who died (χ2 (2) = 0.92, p = 0.337). Trial registration The trial was registered in the International Standardized Randomized Controlled Trial Number (ISRCTN); trial registration number ISRCTN89732754

Ecodialysis: first strategies to limit damages and reduce costs

In the medical field, the attention to the environmental impact of industrial processes and products is still limited. In recent years there has been an increased sensitivity towards the environment; meanwhile, the economic burden of hazardous waste disposal is becoming evident. Dialysis is a "big producer" of waste and it has been estimated that disposal costs can be up to 10-40% of the cost of disposables. So there are several reasons of interest on "ecodialysis": the high amount of waste defined as "potentially hazardous", which requires a very expensive management and the recyclability potential of the non-contaminated waste, that has not yet been fully explored in dialysis. This primary study has been performed in collaboration with the Politecnico di Torino. Its aim has been to define a schedule of activities by a few brainstorming sessions. This schedule is to be readily performed or it should be developed in detail to optimize, by reducing and recycling, the waste production during the dialysis session. The discussion identified seven basic points for the eco-sustainability of haemodialysis to: [1] reduce packaging; [2] facilitate separation of materials, and [3] their discharge; [4] differentiate materials; [5] clearly highlight the potentially hazardous materials; [6] improve the recyclability of plastic products; [7] propose a path of recovery and reuse. Although a full optimization requires a close cooperation with the manufacturers and is achievable only in the long term, the reduction of one pound of potentially contaminated materials could presently lead, on a national scale, to a saving of several million euros, which can be better employed in investments to improve our treatments