Up-regulation of gonadotropin mRNA-expression at the onset of gametogenesis in the roach (Rutilus rutilus): Evidence for an important role of brain-type aromatase (cyp19a1b) in the pituitary

The present study characterized changes in key parameters of reproduction in adult roach (Rutilus rutilus) from Lake Grosser Mueggelsee (Berlin, Germany) during natural gametogenesis. Fish of both sexes were sampled in monthly intervals between April and August in order to cover the onset of gametogenesis. Investigated parameters included gonad histology, plasma levels of 17β-oestradiol (E2), testosterone (T), 11-ketotestosterone (11-KT), and 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) as well as the expression of gonadotropin subunits in the pituitary. Furthermore, the mRNA-expression of brain-type aromatase (cyp19a1b), androgen receptor (ar), and estrogen receptor isoforms was studied at the pituitary level. The onset of gametogenesis - as indicated by follicles with cortical alveoli in females and first spermatogonia B in males - was observed in July, accompanied by a significant up-regulation of follicle-stimulating hormone β (fshβ) mRNA in the pituitary in both sexes. On the other hand, luteinizing hormone β (lhβ) mRNA increased later on in August. In males, the increase of fshβ mRNA in July coincided with a rise in plasma 11-KT concentrations. In females, E2 in plasma increased later, not until August, shortly before true vitellogenesis (late cortical alveoli stage). Expression of sex steroid receptors in the pituitary revealed only minor seasonal fluctuations. Most pronounced, ar mRNA displayed the highest level pre-spawning in both sexes. Interestingly, cyp19a1b mRNA-expression in the pituitary increased in parallel with fshβ already before any changes in plasma E2 or T occurred. These data suggest an important role of pituitary FSH and aromatase at the onset of gametogenesis in the roach.     

Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation

Hodgkin lymphoma (HL) relapsing after allogeneic stem cell transplantation (alloSCT) presents a major clinical challenge. In the present investigation, we evaluated brentuximab vedotin, a CD30-directed Ab-drug conjugate, in 25 HL patients (median age, 32 years; range, 20-56) with recurrent disease after alloSCT (11 unrelated donors). Patients were > 100 days after alloSCT, had no active GVHD, and received a median of 9 (range, 5-19) prior regimens. Nineteen (76%) had refractory disease immediately before enrollment. Patients received 1.2 or 1.8 mg/kg of brentuximab vedotin IV every 3 weeks (median, 8 cycles; range, 1-16). Overall and complete response rates were 50% and 38%, respectively, among 24 evaluable patients. Median time to response was 8.1 weeks, median progression-free survival was 7.8 months, and the median overall survival was not reached. Cough, fatigue, and pyrexia (52% each), nausea and peripheral sensory neuropathy (48% each), and dyspnea (40%) were the most frequent adverse events. The most common adverse events ≥ grade 3 were neutropenia (24%), anemia (20%), thrombocytopenia (16%), and hyperglycemia (12%). Cytomegalovirus was detected in 5 patients (potentially clinically significant in 1). These results support the potential utility of brentuximab vedotin for selected patients with HL relapsing after alloSCT.     

Direction of SMR and Beta Change with Attention in Adults

Introduction. The aim of this study was to clarify the interpretation of sensory-motor rhythm (SMR; 13–15 Hz) and beta (16–20 Hz) changes with respect to attention states.

Method. For this purpose, EEG was recorded from 11 participants during (a) a multiple object tracking task (MOT), which required externally directed attention; (b) the retention phase of a visuo-spatial memory task (VSM), which required internally directed attention and avoidance of sensory distraction; and (c) the waiting intervals between trials, which constituted a no-task-imposed control condition. The 2 active tasks were consecutively presented at 2 difficulty levels (i.e., easy and hard). Two analyses of variance were conducted on EEG log spectral amplitudes in the alpha (8–12 Hz), SMR, and beta bands from F3, F4, C3, C4 and P3, P4.

Results. The first 15 analysis compared the MOT to the VSM by difficulty levels and revealed a significant task effect (p < .0005) but no effect of difficulty. The results showed that externally directed attention (MOT) resulted in lower values than internally directed attention (VSM) in all three bands. The second analysis averaged the difficulty levels together and added the no-task-imposed reference condition. The results again showed a significant task effect that did not interact with site, hemisphere, or, more important, band. Post hoc tests revealed that both MOT and VSM produced significantly smaller means than the no-task-imposed condition. This pattern of log-amplitude means and the lack of task interaction with any other factor indicate that task-induced attention reduces EEG power in the same proportion across the 3 bands and the 6 channels studied.

Conclusions. These results contradict a frequent interpretation concerning the relationship between the brain's aptitude to increase low beta in neurofeedback programs and improved sustain attention capacities.     

Stimulus Intensity for Hand Held and Robotic Transcranial Magnetic Stimulation

BackgroundTranscranial Magnetic Stimulation (TMS) is based on a changing magnetic field inducing an electric field in the brain. Conventionally, the TMS coil is mounted to a static holder and the subject is asked to avoid head motion. Additionally, head resting frames have been used. In contrast, our robotized TMS system employs active motion compensation (MC) to maintain the correct coil position.Objective/hypothesisWe study the effect of patient motion on TMS. In particular, we compare different coil positioning techniques with respect to the induced electric field.MethodsWe recorded head motion for six subjects in three scenarios: (a) avoiding head motion, (b) using a head rest, and (c) moving the head freely. Subsequently, the motion traces were replayed using a second robot to move a sensor to measure the electric field in the target region. These head movements were combined with 2 types of coil positioning: (1) using a coil holder and (2) using robotized TMS with MC.ResultsAfter 30 min the induced electric field was reduced by 32.0% and 19.7% for scenarios (1a) and (1b), respectively. For scenarios (2a)–(2c) it was reduced by only 4.9%, 1.4% and 2.0%, respectively, which is a significant improvement (P < 0.05). Furthermore, the orientation of the induced field changed by 5.5°, 7.6°, 0.4°, 0.2°, 0.2° for scenarios (1a)–(2c).ConclusionWhile none of the scenarios required rigid head fixation, using a simple holder to position a coil during TMS can lead to substantial deviations in the induced electric field. In contrast, robotic motion compensation results in clinically acceptable positioning throughout treatment.     

A retrospective analysis of the therapeutic effects of 0.01% atropine on axial length growth in children in a real-life clinical setting

Graefe's Archive for Clinical and Experimental Ophthalmology - Several randomized controlled studies have demonstrated the beneficial effects of 0.01% atropine eye drops on myopia progression...     

Insulin is essential for in vitro chondrogenesis of mesenchymal progenitor cells and influences chondrogenesis in a dose-dependent manner

Purpose

Insulin is a commonly used additive in chondrogenic media for differentiating mesenchymal stem cells (MSCs). The indispensability of other bioactive factors like TGF-β or dexamethasone in these medium formulations has been shown, but the role of insulin is unclear. The purpose of this study was to investigate whether insulin is essential for MSC chondrogenesis and if there is a dose-dependent effect of insulin on MSC chondrogenesis.

Methods

We cultivated human MSCs in pellet culture in serum-free chondrogenic medium with insulin concentrations between 0 and 50 μg/ml and assessed the grade of chondrogenic differentiation by histological evaluation and determination of glycosaminoglycan (GAG), total collagen and DNA content. We further tested whether insulin can be delivered in an amount sufficient for MSC chondrogenesis via a drug delivery system in insulin-free medium.

Results

Chondrogenesis was not induced by standard chondrogenic medium without insulin and the expression of cartilage differentiation markers was dose-dependent at insulin concentrations between 0 and 10 μg/ml. An insulin concentration of 50 μg/ml had no additional effect compared with 10 μg/ml. Insulin was delivered by a release system into the cell culture under insulin-free conditions in an amount sufficient to induce chondrogenesis.

Conclusions

Insulin is essential for MSC chondrogenesis in this system and chondrogenic differentiation is influenced by insulin in a dose-dependent manner. Insulin can be provided in a sufficient amount by a drug delivery system. Therefore, insulin is a suitable and inexpensive indicator substance for testing drug release systems in vitro.     

13th St. Gallen International Breast Cancer Conference 2013: Primary Therapy of Early Breast Cancer Evidence,Controversies, Consensus – Opinion of a German Team of Experts (Zurich 2013)

Zusammenfassung

Alle zwei Jahre findet in St. Gallen (Schweiz) die internationale Konsensuskonferenz zur Behandlung des primären Mammakarzinoms statt. Da sich das internationale Panel in St. Gallen aus Experten unterschiedlicher Länder zusammensetzt, spiegelt der Konsensus ein internationales Meinungsbild wider. Vor diesem Hintergrund erscheint es aus deutscher Sicht sinnvoll, die Abstimmungsergebnisse für den Therapiealltag in Deutschland zu konkretisieren. Eine deutsche Arbeitsgruppe mit acht Brustkrebsexperten, von denen zwei Mitglieder des internationalen St. Gallen-Panels sind, hat daher die Abstimmungsergebnisse der St. Gallen-Konsensuskonferenz (2013) für den Klinikalltag in Deutschland kommentiert. Inhaltliche Schwerpunkte der diesjährigen St. Gallen-Konferenz waren operative Fragestellungen der Brust und der Axilla, strahlentherapeutische und systemische Therapieoptionen sowie die klinische Relevanz der Tumorbiologie. Intensiv diskutiert wurde der klinische Einsatz von Multigen-Assays, inkl. ihrer Bedeutung für die individuelle Therapieentscheidung.