Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development,hepatic mRNA expression,thyroid hormone levels,and circulating bile acid concentrations in chicken embryos

The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highest doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism.     

Comparative study of dissolved and nanoparticulate Ag effects on the life cycle of an estuarine meiobenthic copepod,Amphiascus tenuiremis

Many nanotoxicological studies have assessed the acute toxicity of nanoparticles (NPs) at high exposure concentrations. There is a gap in understanding NP chronic environmental effects at lower exposure concentrations. This study reports life-cycle chronic toxicity of sublethal exposures of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) relative to dissolved silver nitrate (AgNO₃) for the estuarine meiobenthic copepod, Amphiascus tenuiremis, over a range of environmentally relevant concentrations, i.e., 20, 30, 45, and 75?µg-Ag?L^?1. A concentration-dependent increase in mortality of larval nauplii and juvenile copepodites was observed. In both treatment types, significantly higher mortality was observed at 45 and 75?µg-Ag?L^?1 than in controls. In AgNO₃ exposures, fecundity declined sharply (1.8–7 fold) from 30 to 75?µg Ag?L^?1. In contrast, fecundity was not affected by PVP-AgNPs exposures. A Leslie matrix population-growth model predicted sharply 60–86% of decline in overall population sizes and individual life-stage numbers from 30–75?µg-Ag L^?1 as dissolved AgNO₃. In contrast, no population growth suppressions were predicted for any PVP-AgNPs exposures. Slower release of dissolved Ag from PVP-AgNPs and/or reduced Ag uptake in the nanoform may explain these sharp contrasts in copepod response.     

Aided auditory steady-state responses in infants

Infants with hearing loss routinely receive hearing aids several months before reliable behavioral responses to amplified sound can be observed. This necessitates objective measures to validate hearing-aid fittings. A single report has demonstrated the use of ASSRs to determine aided thresholds in children but data in young infants is still lacking. The current study explored aided ASSR compared to unaided ASSR thresholds and subsequent behavioral thresholds in a group of six young infants with hearing loss who received hearing aids between three and six months of age. Aided ASSR thresholds were obtained in 83% of frequencies where aided behavioral thresholds were obtained, with a mean threshold difference of 13±13 dB. The aided ASSR-based threshold estimates were within 15 dB of behavioral thresholds in 63% of cases, indicating a moderate correlation (r = 0.55). Comparing aided and unaided ASSR measurements revealed an average functional gain of 36±15 dB. These results indicate that ASSRs can provide the first evidence of robust hearing aid benefit in young infants several months before behavioral responses are observed.     

Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer: A Retrospective Matched Case-Control Study

Background

Somatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.

The impact of type 1 and type 2 diabetes mellitus on the oocyte and the preimplantation embryo

Whereas the importance of close monitoring and tight glycemic control in diabetic pregnancies cannot be ignored, the growing body of knowledge surrounding the different effects of diabetes mellitus on the earliest stages of reproduction underscores the need for aggressive screening among reproductive-aged women at risk for diabetes and the importance of preconceptual counseling among women with known diabetes. This article reviews the salient pathophysiology of type 1 diabetes and type 2 diabetes in reproduction, specifically within the context of the preovulatory oocyte and the preimplantation embryo. In doing so, this review illustrates the need for novel and safe therapies and interventions tailored to address the specific characteristics of these diseases in the periconceptual period.     

Spheciosterol sulfates, PKCzeta inhibitors from a philippine sponge Spheciospongia sp

Three new sterol sulfates, spheciosterol sulfates A-C (1-3), and the known sterol sulfate topsentiasterol sulfate E (4) have been isolated from the sponge Spheciospongia sp., collected in the Philippines. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1-4 inhibited PKCzeta with IC50 values of 1.59, 0.53, 0.11, and 1.21 microM, respectively. In a cell-based assay, 1-4 also inhibited NF-kappaB activation with EC50 values of 12-64 microM.