The Flavor and Extract Manufacturers Association (FEMA) Expert Panel relies on the weight of evidence from all available data in the safety evaluation of flavoring substances. This process includes data from genotoxicity studies designed to assess the potential of a chemical agent to react with DNA or otherwise cause changes to DNA, either in vitro or in vivo. The Panel has reviewed a large number of in vitro and in vivo genotoxicity studies during the course of its ongoing safety evaluations of flavorings. The adherence of genotoxicity studies to standardized protocols and guidelines, the biological relevance of the results from those studies, and the human relevance of these studies are all important considerations in assessing whether the results raise specific concerns for genotoxic potential. The Panel evaluates genotoxicity studies not only for evidence of genotoxicity hazard, but also for the probability of risk to the consumer in the context of exposure from their use as flavoring substances. The majority of flavoring substances have given no indication of genotoxic potential in studies evaluated by the FEMA Expert Panel. Examples illustrating the assessment of genotoxicity data for flavoring substances and the consideration of the factors noted above are provided. The weight of evidence approach adopted by the FEMA Expert Panel leads to a rational assessment of risk associated with consumer intake of flavoring substances under the conditions of use.Purpose The aim of the present retrospective single-center study is to evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the evaluation of renal oncocytoma.Method Thirteen patients with histopathologically confirmed renal oncocytoma and 26 patients with histopathologically confirmed renal cell carcinoma were included in this retrospective single-center study on whom CEUS was performed between 2005 and 2015. The applied contrast agent was a second-generation blood pool agent. CEUS examinations were performed and interpreted by a single radiologist with more than 15 years of experience (EFSUMB Level 3).Results CEUS examinations were successfully performed in all included patients without any adverse effects. Renal oncocytomas showed varying echogenicity (46% hypoechoic, 23% hyperechoic, 8% iso-/hyperechoic, 8% isoechoic). In two cases renal oncocytoma only demarcated upon i.v. application of contrast medium. In bilateral oncocytosis, lesions presented as hyperechoic. Only 23% of renal oncocytomas showed slight vascularization using Color Doppler. No oncocytoma-specific pattern of microperfusion could be elucidated 85% of the oncocytomas presented hyperenhancing, of whom 50% also showed delayed venous wash-out; 8% of renal oncocytomas showed venous wash-out without early arterial hyperenhancement.Conclusions Within the frame of the present study and in line with the recent state of knowledge, no specific sonomorphological feature – including CEUS – could be detected allowing for adequate discrimination between oncocytoma and renal cell carcinoma.Anti-Müllerian hormone (AMH) and inhibin B are considered possible biomarkers of central precocious puberty (CPP). The aim of this study was to evaluate serum levels of AMH and inhibin B, to investigate their regulatory patterns, and to study their clinical significance in girls with CPP. In total, 48 girls with CPP and 35 age-matched prepubertal control girls were enrolled in the study. AMH and inhibin B levels were determined in the CPP and control groups. In the patient group, AMH and inhibin B levels were evaluated during 1 year of gonadotropin releasing hormone analog (GnRHa) treatment. The mean inhibin B level in the CPP group was significantly higher than that in the control. AMH levels were not different between the two groups. After GnRHa treatment. AMH and inhibin B levels decreased significantly. selleck inhibitor Based on the ROC analysis, the cutoff value for inhibin B to determine CPP was 19.59 pg/mL, with 83.3% sensitivity and 82.9% specificity, and the area under the curve was 0. 852. Inhibin B was useful for determining CPP and the therapeutic effects of GnRHa treatment in girls with CPP. AMH interacted, in part, with the hypothalamo-pituitary gonadal axis, but its clinical implications in CPP should be further investigated.OBJECTIVES Correct inhaler technique is essential to optimal clinical outcomes in asthma patients. The study aim was to use real-life data from the iHARP database to determine patient factors associated with the performance of inhaler technique errors associated with poor asthma outcomes (as identified in the Critikal study) in patients with asthma prescribed the Turbuhaler (TH), Metered Dose Inhaler (MDI), and Accuhaler (AH) device. METHODS This was a retrospective cross-sectional study using the iHARP database, a multinational initiative including questionnaires and technique review. Identification of inhaler technique errors specifically associated with poor asthma outcomes was performed by reference to the Critikal study. Multivariable logistic regression was used to identify demographic and clinical factors associated with ≥1 of these errors. RESULTS Factors significantly associated with ≥1 inhaler technique error and worsening asthma outcomes for the TH cohort include female gender, very poor to average self-assessment of inhaler technique; for the MDI cohort, female gender, secondary education, and current smoking status; and, in the AH cohort, lack of inhaler technique review by a trained healthcare professional in the previous twelve months and very poor to average self-assessment of inhaler technique. CONCLUSIONS Numerous specific patient demographic and clinical factors associated with the performance of these errors have been identified, differing according to device. Inhaler technique error associated with poor asthma outcomes is further widespread across devices. Knowledge of these factors and the frequency of their occurence may assist in optimising device selection and training.Introduction Transcatheter aortic valve replacement (TAVR) has been demonstrated to be a good alternative to surgery for treating severe aortic stenosis (AS) across the whole range of surgical risk patients. Whereas most periprocedural TAVR complications have significantly decreased over time, conduction disturbances remain high. Approaches to decrease this shortcoming are under continuous investigation.Areas covered Overview of the actual evidence regarding conduction disturbances in the TAVR setting, focusing on modifiable factors. PubMed and Embase databases were used for literature search.Expert opinion Several factors have been associated with an increased risk of conduction disturbances post-TAVR, and some of them may be modifiable. While some transcatheter valve systems have been associated with higher rates of conduction disturbances, additional randomized data are needed to draw definite conclusions about newer generation transcatheter valve systems. Nowadays, good hemodynamic valve function can be obtained without excessive valve oversizing, which has been associated with an increased risk of conduction disturbances in some studies.