Artificial urethral sphincter in male dogs with urethral sphincter mechanism incompetence: 19 cases (2010-2017).

OBJECTIVE: To assess the outcome and safety of surgically placed artificial urethral sphincters in male dogs with urethral sphincter mechanism incompetence. MATERIALS AND METHODS: We included dogs with urethral sphincter mechanism incompetence treated by placing an artificial urethral sphincter from January 1, 2010 to December 31, 2017. The continence score (scale 1 to 5, with 5 indicating complete continence) was evaluated before and after implantation. Follow-up information was obtained from the institution's medical records (short-term up to 12 months) and questionnaires were completed by telephone (long-term ≥12 months) for evaluation. RESULTS: Medical therapy was unsuccessful in 18 dogs and unknown in one dog before the artificial urethral sphincter placement. Short-term continence improved in 16 of the 19 (84%) dogs. Four patients were lost to follow-up. Nine of 15 (60%) dogs showed long-term continence improvement, eight of 15 (53%) remained completely continent. The median follow-up was 1785 (range 2 to 3234) days. The complication rate was 56% (9/16). Minor complications, including haematoma, stranguria/temporary dyssynergia and mild inflammation at the port, were reported in four of 16 (25%) dogs. Five of 16 (31%) experienced major complications, including stranguria/mechanical urethral obstruction, persistent dyssynergia, fistula at the port and port rotation. CLINICAL SIGNIFICANCE: Artificial urethral sphincter placement is a valid option for treating incontinent male dogs that show an insufficient response or become refractory to medical or other prior surgical management. A high-complication rate is associated with this procedure.

Potential emerging chemical risks in the food chain associated with substances registered under REACH.

A screening procedure for the identification of potential emerging chemical risks in the food and feed chain developed in a previous EFSA-sponsored pilot study was applied to 15021 substances registered under the REACH Regulation at the time of evaluation. Eligible substances were selected from this dataset by excluding (a) intermediates handled under strictly controlled conditions, (b) substances lacking crucial input data and (c) compounds considered to be outside the applicability domain of the models used. Selection of eligible substances resulted in a considerable reduction to 2336 substances. These substances were assessed and scored for environmental release (tonnage and use information from REACH registration dossiers), biodegradation (predictions from BIOWIN models 3, 5 and 6 evaluated in a battery approach), bioaccumulation in food/feed (ACC-HUMANsteady modelling) and chronic human health hazards (classification according to the CLP Regulation for carcinogenicity, mutagenicity, reproductive toxicity and repeated dose toxicity as well as IARC classification for carcinogenicity). Prioritisation based on the scores assigned and additional data curation steps identified 212 substances that are considered potential emerging risks in the food chain. Overall, 53% of these substances were prioritised due to chronic hazards identified in REACH registrations dossiers only (i.e. hazards not identified in classifications from other sources). Bioaccumulation in food and feed predicted on the basis of ACC-HUMANsteady modelling identified many substances that are not considered bioaccumulative in aquatic or terrestrial organisms based on screening criteria of the relevant ECHA guidance documents. Furthermore, 52% of the priority substances have not yet been assessed for their presence in food/feed by EU regulatory agencies. This finding and illustrative examples suggest that the screening procedure identified substances that have the potential to be emerging chemical risks in the food chain. Future research should investigate whether they actually represent emerging chemical risks as defined in EFSA's mandate.

Real-Time Dynamics of the Formation of Hydrated Electrons upon Irradiation of Water Clusters with Extreme Ultraviolet Light.

Free electrons in a polar liquid can form a bound state via interaction with the molecular environment. This so-called hydrated electron state in water is of fundamental importance, e.g., in cellular biology or radiation chemistry. Hydrated electrons are highly reactive radicals that can either directly interact with DNA or enzymes, or form highly excited hydrogen (H^{*}) after being captured by protons. Here, we investigate the formation of the hydrated electron in real-time employing extreme ultraviolet femtosecond pulses from a free electron laser, in this way observing the initial steps of the hydration process. Using time-resolved photoelectron spectroscopy we find formation timescales in the low picosecond range and resolve the prominent dynamics of forming excited hydrogen states.

Tumor volume as a predictive parameter in the sequential therapy (induction chemotherapy) of head and neck squamous cell carcinomas.

PURPOSE: Tumor volume in locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated by induction chemotherapy (ICT) and followed by radiochemotherapy (RCT) was measured. The presence of potential correlation of initial tumor volume and volume reduction after ICT and RCT with remission status, overall survival (OS) and disease-free survival (DFS) were investigated. Furthermore, reliability of approximation of the tumor volume relying on its diameter to manual three-dimensional measurement was assessed. METHODS: Data of patients with LAHNSCC treated by ICT consisting of docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by definite RCT were retrospectively analyzed. The tumor volume was calculated slice-by-slice in contrast-enhanced CT or MRI before and after ICT as well as after complete treatment. The volume was compared to radiologic remission status, correlated with OS and DFS, and to volume estimation using tumor diameter. RESULT: 65 patients were included. Primary tumor volume did not correlate with complete remission rate (CR) after ICT and RCT, OS or DFS. The change in tumor volume between baseline imaging and post-RCT had a significant impact on OS (p = 0.026) and DFS (p = 0.028). The agreement between tumor volume and radiologic remission was 72.14%. CONCLUSION: The initial tumor volume had no influence on CR, OS or DFS. A severe response to ICT did not predict a powerful RCT outcome. The change in tumor volume post-RCT had an impact on OS and DFS. Tumor volume estimation using its diameter seems to be a reliable method.

Development of a novel scoring system for identifying emerging chemical risks in the food chain.

The European Food Safety Authority (EFSA) is responsible for risk assessment of all aspects of food safety, including the establishment of procedures aimed at the identification of emerging risks to food safety. Here, a scoring system was developed for identifying chemicals registered under the European REACH Regulation that could be of potential concern in the food chain using the following parameters: (i) environmental release based on maximum aggregated tonnages and environmental release categories; (ii) biodegradation in the environment; (iii) bioaccumulation and in vivo and in vitro toxicity. The screening approach was tested on 100 data-rich chemicals registered under the REACH Regulation at aggregated volumes of at least 1000 tonnes per annum. The results show that substance-specific data generated under the REACH Regulation can be used to identify potential emerging risks in the food chain. After application of the screening procedure, priority chemicals can be identified as potentially emerging risk chemicals through the integration of exposure, environmental fate and toxicity. The default approach is to generate a single total score for each substance using a predefined weighting scenario. However, it is also possible to use a pivot table approach to combine the individual scores in different ways that reflect user-defined priorities, which enables a very flexible, iterative definition of screening criteria. Possible applications of the approaches are discussed using illustrative examples. Either approach can then be followed by in-depth evaluation of priority substances to ensure the identification of substances that present a real emerging chemical risk in the food chain.

Hippocampal commissure defects in crosses of four inbred mouse strains with absent corpus callosum.

It is known that four common inbred mouse strains show defects of the forebrain commissures. The BALB/cJ strain has a low frequency of abnormally small corpus callosum, whereas the 129 strains have many animals with deficient corpus callosum. The I/LnJ and BTBR T+ tf/J strains never have a corpus callosum, whereas half of I/LnJ and almost all BTBR show severely reduced size of the hippocampal commissure. Certain F1 hybrid crosses among these strains are known to be less severely abnormal than the inbred parents, suggesting that the parent strains have different genetic causes of commissure defects. In this study, all hybrid crosses among the four strains were investigated. The BTBR × I/Ln hybrid expressed almost no defects of the hippocampal commissure, unlike its inbred parent strains. Numerous three-way crosses among the four strains yielded many mice with no corpus callosum and severely reduced hippocampal commissure, which shows that the phenotypic defect can result from several different combinations of genetic alleles. The F2 and F3 hybrid crosses of BTBR and I/LnJ had almost 100% absence of the corpus callosum but about 50% frequency of deficient hippocampal commissure. The four-way hybrid cross among all four abnormal strains involved highly fertile parents and yielded a very wide phenotypic range of defects from almost no hippocampal commissure to totally normal forebrain commissures. The F2 and F3 crosses as well as the four-way cross provide excellent material for studies of genetic linkage and behavioral consequences of commissure defects.