International Water Quality Guidelines for Polycyclic Aromatic Hydrocarbons: Advances to Improve Jurisdictional Uptake of Guidelines Derived Using The Target Lipid Model.

A large number of different of polycyclic aromatic hydrocarbons (PAHs) have been found in environmental media, yet water quality guidelines (WQGs) are only available for a small subset of PAHs, limiting our ability to adequately assess environmental risks from these compounds. The target lipid model (TLM) was published over 20 years ago and has been extensively validated in the literature, but it has still not been widely adopted by jurisdictions to derive WQGs for PAHs. The goal of our study was to better align the methods for deriving TLM-based WQGs with international derivation protocols.

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.

Recent Developments in Species Sensitivity Distribution Modeling.

The species sensitivity distribution (SSD) is a statistical approach that is used to estimate either the concentration of a chemical that is hazardous to no more than x% of all species (the HCx) or the proportion of species potentially affected by a given concentration of a chemical. Despite a significant body of published research and critical reviews over the past 20 yr aimed at improving the methodology, the fundamentals remain unchanged. Although there have been some recent suggestions for improvements to SSD methods in the literature, in general, few of these suggestions have been formally adopted.

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset.

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase () is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers.

Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the European PanCareLIFE cohort study.

Background: Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline.

Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study.

Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs.

Receptor tyrosine kinase gene expression profiles of Ewing sarcomas reveal ROR1 as a potential therapeutic target in metastatic disease.

Receptor tyrosine kinases (RTKs) have provided molecular targets for the development of novel, prognosis-improving agents in many cancers; however, resistances to these therapies occur. On the cellular level, one resistance mechanism is attributed to functional RTK redundancies and compensatory cross-signaling, leading to perception of RTKs as signaling and target networks. To provide a basis for better exploitation of this network in Ewing sarcoma, we generated comprehensive qPCR gene expression profiles of RTKs in Ewing sarcoma cell lines and 21 untreated primary tumors.

Sampling and analysis of microcystins: Implications for the development of standardized methods.

Microcystins (MC), a group of cyanotoxins, have been found in lakes and rivers worldwide. One goal of MC research is to develop models which predict MC concentrations, but these efforts have been hampered by a lack of standardized methods necessary for comparing data across studies. Here, we investigate the effect of chemical analysis (HPLC-PDA and ELISA), sample collection (whole water, plankton tow and surface scum), and choice of normalizing parameter (volume, dry weight, and chlorophyll a) on reported MC concentrations.

Pressurized liquid extraction of toxins from cyanobacterial cells.

The suitability of pressurized liquid extraction (PLE) of cyanotoxins from cells was investigated. The stability of cyanotoxins (MCYST-RR, MCYST-LR, and anatoxin-a) was evaluated at nine combinations of pressure and temperature (7, 10, and 14 MPa and 60 degrees C, 80 degrees C and 100 degrees C) using 75% (v/v) methanol in water (MeOH) as solvent. Additional experiments investigated the stability of cyanotoxins when water was used as solvent (at a pressure of 14 MPa and a temperature of 40 degrees C, 50 degrees C, 60 degrees C, 80 degrees C, or 100 degrees C).