Together, our results demonstrate that stimulus-related activity, including its variability, is a blend of two factors 1) the effects of the external stimulus itself, and 2) the effects of the ongoing dynamics spilling over from the prestimulus period - the state at stimulus onset - with the second dwarfing the influence of the first.We present a novel method to map the functional organization of the human auditory cortex noninvasively using magnetoencephalography (MEG). More specifically, this method estimates via reverse correlation the spectrotemporal receptive fields (STRF) in response to a temporally dense pure tone stimulus, from which important spectrotemporal characteristics of neuronal processing can be extracted and mapped back onto the cortex surface. We show that several neuronal populations can be found examining the spectrotemporal characteristics of their STRFs, and demonstrate how these can be used to generate tonotopic gradient maps.  https://www.selleckchem.com/products/icfsp1.html  In doing so, we show that the spatial resolution of MEG is sufficient to reliably extract important information about the spatial organization of the auditory cortex, while enabling the analysis of complex temporal dynamics of auditory processing such as best temporal modulation rate and response latency given its excellent temporal resolution. Furthermore, because spectrotemporally dense auditory stimuli can be used with MEG, the time required to acquire the necessary data to generate tonotopic maps is significantly less for MEG than for other neuroimaging tools that acquire BOLD-like signals.
  Hypothalamus-pituitary-gonadal (HPG)-axis disturbances are a common phenomenon in patients with classic congenital adrenal hyperplasia (CAH). 11-oxygenated androgens have been suggested to play a role in this context.
 
  Cross-sectional single center study including 89 patients (N = 42 men, N = 55 women) with classic CAH.
 
  Differences in steroid markers in men with hypogonadism and women with secondary amenorrhea with a special focus on 11-ketotestosterone (11KT) and 11β-hydroxyandrostenedione (11OHA4).
 
  Hypogonadotropic hypogonadism was present in 23 % of men and 61 % of those women currently not on contraceptives suffered from irregular menstrual cycles or amenorrhea. Testicular adrenal rest tumor (TART) was documented in 28 % of men. 11KT (3.5x) and 11OHA4 (5.7x) among other adrenal steroids were significantly elevated in men with hypogonadism and in women with amenorrhea in comparison to those with a regular cycle (11KT 5.2x; 11OHA4 3.7x). 11-oxygenated androgens were not higher in men with TART than in those without. There was a negative association of 11KT and 11OHA4 with FSH but not with LH in men. As expected, all steroids were strongly correlated with each other and cases of disproportionally elevated 11-oxygenated androgens that could explain for HPG-disturbances or TART in otherwise controlled patients were rare and also found in eugonadal individuals.
 
  In CAH, 11-oxygenated androgens are elevated in women with menstrual disturbances and in men with hypogonadotropic hypogonadism. Due to the close correlation of 11-oxygenated androgens with other adrenal steroids it remains to be shown if their measurement is superior to conventional markers of androgen control.
 In CAH, 11-oxygenated androgens are elevated in women with menstrual disturbances and in men with hypogonadotropic hypogonadism. Due to the close correlation of 11-oxygenated androgens with other adrenal steroids it remains to be shown if their measurement is superior to conventional markers of androgen control.Pharmaceutical formulations utilizing protein drugs as powders can be used as drug delivery systems in various ways. Besides powders for inhalation, another promising approach is their use as suspensions in non-aqueous liquids for subcutaneous administration providing high protein stability and good injectability. In this study protein powder suspensions were prepared using a swing-mill. Milling of lyophilizates containing a model monoclonal antibody in presence of the suspension vehicle was compared to cryogenic dry milling. Wet media milling led to injectable suspensions, but resulted in monomer loss and increase in protein aggregation. When the lyophilizates were cryogenic dry ball milled less aggregation and monomer loss were detected. Differences related to protein integrity were found for different process parameters, which were successfully optimized. If not cooled with liquid nitrogen, dry milling resulted in increased damage to the mAb. The type of polyol stabilizer, as well as the protein to stabilizer ratio, did not affect the preservation of protein integrity. As finding the right milling duration is time and resource intensive, a correlation between lyophilizate cake hardness and milling duration was established. Based on this approach high concentration lyophilizates were successfully micronized. Suspensions of cryogenic milled powders lead to clogging of 25G needles, which could be prevented by an additional sieving step. Depending on the suspension vehicle, low viscosity formulations ( less then 10 mPa·s) even at high concentrations (≥100 mg/ml protein concentration) were obtained featuring good injectability.The emergence of pan-resistant strains in nosocomial settings underscores the urgent need of novel therapies targeting vital bacterial functions. Bacterial iron metabolism is a fascinating target for new antimicrobials. Iron mimetic metal Ga(III) has been repurposed as an antimicrobial drug, in pre-clinical studies and recent clinical studies have raised the possibility of using Ga(III) for the treatment of P. aeruginosa pulmonary infection. Ga(III) has been approved by FDA for the treatment of cancer, autoimmune and bone resorption disorders. However, some critical issues affect the therapeutic schedule of Ga(III), principally the intra-venous (i.v.) administration, and the nephrotoxicity caused by prolonged administration. Ga(III) aerosolization could represent a viable alternative for treatment of lung infections, since delivery of antimicrobial agents to the airways maximizes drug concentration at the site of infection, improves the therapeutic efficacy, and alleviates systemic toxic effects. We demonstrate the advantage of inhaled vs i.