Ca2+ release and buffering effects of synthetic hydroxyapatite following bacterial acid challenge

Background Synthetic particulate hydroxyapatite (HAP; Ca-5(PO4)(3)(OH)) is used as ingredient in oral care products but its effects on cariogenic biofilms are not clear yet. The primary mode of action of HAP may be acting as a calcium phosphate reservoir when deposited in oral biofilms and release Ca2+ and (hydrogen) phosphate ions upon bacterial acid challenge. The aim of this in vitro study was to test this hypothesis by investigating release of Ca2+ ions and potential buffering effects from HAP upon bacterial acid challenge in planktonic cultures and biofilms of Streptococcus mutans. Methods Planktonic cultures of S. mutans were grown in BHI broth with 1% sucrose or with additional 5% HAP or 5% silica for up to 48 h. Separately, biofilms of S. mutans were grown in BHI for 72 h in total. After 24 h of this biofilm culture, either BHI alone or BHI with additional 0.5% HAP or 0.5% silica was added. After 48 h, BHI with 1% sucrose was added to allow bacterial acid formation. Ca2+ release was determined colorimetrically and pH measurements were performed using a pH electrode. For statistical analysis, non-parametrical procedures were applied (n >= 10; Mann-Whitney U test; alpha = 0.05). Results Relevant release of Ca2+ was only evident in planktonic cultures or biofilms with HAP but not in both other groups (p <= 0.001). In suspended biofilms with HAP, median pH was 4.77 after 72 h and about 0.5 pH units higher as compared to both other groups (4.28 or 4.32, respectively; p <= 0.001). Conclusions Under the tested conditions, synthetic HAP releases Ca2+ ions upon bacterial acid challenge and may also show some buffering capacity but further studies are needed to investigate whether the concentrations tested here can also be reached clinically in dental biofilms

Objective hearing tests in pediatric audiology: AGERA recommendations for follow-up diagnosis in infants that fail newborn hearing screening tests

This paper presents the recommendations compiled by the German Electric Response Audiometry Working Group (Arbeitsgruppe Elektrische Reaktions-Audiometrie, AGERA) and the Association of German Audiologists and Neuro-otologists (Arbeitsgemeinschaft Deutschsprachiger Audiologen und Neurootologen, ADANO) for infants that fail newborn hearing screening (NHS) tests. Outlined are procedures for follow-up diagnosis using objective hearing tests to rule out or confirm a therapeutically relevant auditory defect and assessment of the severity thereof

Effects of rifampin, itraconazole and esomeprazole on the pharmacokinetics of alisertib, an investigational aurora a kinase inhibitor in patients with advanced malignancies

Aim Two studies investigated the effect of gastric acid reducing agents and strong inducers/inhibitors of CYP3A4 on the pharmacokinetics of alisertib, an investigational Aurora A kinase inhibitor, in patients with advanced malignancies. Methods In Study 1, patients received single doses of alisertib (50 mg) in the presence and absence of either esomeprazole (40 mg once daily [QD]) or rifampin (600 mg QD). In Study 2, patients received single doses of alisertib (30 mg) in the presence and absence of itraconazole (200 mg QD). Blood samples for alisertib and 2 major metabolites were collected up to 72 h (Study 1) and 96 h (Study 2) postdose. Area under the curve from time zero extrapolated to infinity (AUC ) and maximum concentrations (C ) were calculated and compared using analysis of variance to estimate least squares (LS) mean ratios and 90% confidence intervals (CIs). Results The LS mean ratios (90% CIs) for alisertib AUC and C in the presence compared to the absence of esomeprazole were 1.28 (1.07, 1.53) and 1.14 (0.97, 1.35), respectively. The LS mean ratios (90% CIs) for alisertib AUC and C in the presence compared to the absence of rifampin were 0.53 (0.41, 0.70) and 1.03 (0.84, 1.26), respectively. The LS mean ratios (90% CIs) for alisertib AUC and C in the presence compared to the absence of itraconazole were 1.39 (0.99, 1.95) and 0.98 (0.82, 1.19), respectively. Conclusions The use of gastric acid reducing agents, strong CYP3A inhibitors or strong metabolic enzyme inducers should be avoided in patients receiving alisertib

Effects of training on employee suggestions and promotions: Evidence from personnel records

We evaluate the effects of employer-provided formal training on employee suggestions for productivity improvements and on promotions among male blue-collar workers. Using more than 20 years of personnel data of four entry cohorts in a German company, we address issues such as unobserved heterogeneity and the length of potential training effects. Our main finding is that workers are more likely to make suggestions and to be promoted after they have received formal training. However, the effect on suggestions is only short term. Promotion probabilities are greatest directly after training, but also seem to be affected in the long term