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Background: The exponential growth of image-based diagnostic and minimally invasive interventions requires a detailed three-dimensional anatomical knowledge and increases the demand towards the undergraduate anatomical curriculum. This randomized controlled trial investigates whether musculoskeletal ultrasound (MSUS) or arthroscopic methods can increase the anatomical knowledge uptake.
Methods: Second-year medical students were randomly allocated to three groups. In addition to the compulsory dissection course, the ultrasound group (MSUS) was taught by eight, didactically and professionally trained, experienced student-teachers and the arthroscopy group (ASK) was taught by eight experienced physicians. The control group (CON) acquired the anatomical knowledge only via the dissection course. Exposure (MSUS and ASK) took place in two separate lessons (75 minutes each, shoulder and knee joint) and introduced standard scan planes using a 10-MHz ultrasound system as well as arthroscopy tutorials at a simulator combined with video tutorials. The theoretical anatomic learning outcomes were tested using a multiple-choice questionnaire (MCQ), and after cross-over an objective structured clinical examination (OSCE). Differences in student's perceptions were evaluated using Likert scale-based items.
Results: The ASK-group (n = 70, age 23.4 (20--36) yrs.) performed moderately better in the anatomical MC exam in comparison to the MSUS-group (n = 84, age 24.2 (20--53) yrs.) and the CON-group (n = 88, 22.8 (20--33) yrs.; p = 0.019). After an additional arthroscopy teaching 1 % of students failed the MC exam, in contrast to 10 % in the MSUS- or CON-group, respectively. The benefit of the ASK module was limited to the shoulder area (p < 0.001). The final examination (OSCE) showed no significant differences between any of the groups with good overall performances. In the evaluation, the students certified the arthroscopic tutorial a greater advantage concerning anatomical skills with higher spatial imagination in comparison to the ultrasound tutorial (p = 0.002; p < 0.001).
Conclusions: The additional implementation of arthroscopy tutorials to the dissection course during the undergraduate anatomy training is profitable and attractive to students with respect to complex joint anatomy. Simultaneous teaching of basic-skills in musculoskeletal ultrasound should be performed by medical experts, but seems to be inferior to the arthroscopic 2D-3D-transformation, and is regarded by students as more difficult to learn. Although arthroscopy and ultrasound teaching do not have a major effect on learning joint anatomy, they have the potency to raise the interest in surgery.
Mit den Krankheiten häuft sich im Alter auch die Zahl der einzunehmenden Medikamente. Das bringt viele Probleme mit sich. Das Institut für Allgemeinmedizin der Goethe-Universität untersucht in enger Kooperation mit der Universität Maastricht die Folgen der Multimedikation und entwickelt gemeinsam mit Hausärzten Strategien, um unerwünschte Wirkungen zu vermeiden.
The caption of Figure 1 in the paper at doi:10.1155/2012/182767 has to be corrected as shown here. Also, should be corrected as follows: J. Tillein, S. Heid, E. Lang, R. Hartmann, and A. kral, “Development of brainstem-evoked responses in congenital auditory deprivation,” Neural Plasticity, vol. 2012, Article ID 182767, 11 Pages, 2012. s.a. urn:nbn:de:hebis:30:3-267673
Neural oscillations subserve many human perceptual and cognitive operations. Accordingly, brain functional connectivity is not static in time, but fluctuates dynamically following the synchronization and desynchronization of neural populations. This dynamic functional connectivity has recently been demonstrated in spontaneous fluctuations of the Blood Oxygen Level-Dependent (BOLD) signal, measured with functional Magnetic Resonance Imaging (fMRI). We analyzed temporal fluctuations in BOLD connectivity and their electrophysiological correlates, by means of long (≈50 min) joint electroencephalographic (EEG) and fMRI recordings obtained from two populations: 15 awake subjects and 13 subjects undergoing vigilance transitions. We identified positive and negative correlations between EEG spectral power (extracted from electrodes covering different scalp regions) and fMRI BOLD connectivity in a network of 90 cortical and subcortical regions (with millimeter spatial resolution). In particular, increased alpha (8-12 Hz) and beta (15-30 Hz) power were related to decreased functional connectivity, whereas gamma (30-60 Hz) power correlated positively with BOLD connectivity between specific brain regions. These patterns were altered for subjects undergoing vigilance changes, with slower oscillations being correlated with functional connectivity increases. Dynamic BOLD functional connectivity was reflected in the fluctuations of graph theoretical indices of network structure, with changes in frontal and central alpha power correlating with average path length. Our results strongly suggest that fluctuations of BOLD functional connectivity have a neurophysiological origin. Positive correlations with gamma can be interpreted as facilitating increased BOLD connectivity needed to integrate brain regions for cognitive performance. Negative correlations with alpha suggest a temporary functional weakening of local and long-range connectivity, associated with an idling state.
Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers.
Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment.
Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects.
BACKGROUND: Mutations in the chromodomain helicase DNA binding protein 7 gene (CHD7) lead to CHARGE syndrome, an autosomal dominant multiple malformation disorder. Proteins involved in chromatin remodeling typically act in multiprotein complexes. We previously demonstrated that a part of human CHD7 interacts with a part of human CHD8, another chromodomain helicase DNA binding protein presumably being involved in the pathogenesis of neurodevelopmental (NDD) and autism spectrum disorders (ASD). Because identification of novel CHD7 and CHD8 interacting partners will provide further insights into the pathogenesis of CHARGE syndrome and ASD/NDD, we searched for additional associated polypeptides using the method of stable isotope labeling by amino acids in cell culture (SILAC) in combination with mass spectrometry.
PRINCIPLE FINDINGS: The hitherto uncharacterized FAM124B (Family with sequence similarity 124B) was identified as a potential interaction partner of both CHD7 and CHD8. We confirmed the result by co-immunoprecipitation studies and showed a direct binding to the CHD8 part by direct yeast two hybrid experiments. Furthermore, we characterized FAM124B as a mainly nuclear localized protein with a widespread expression in embryonic and adult mouse tissues.
CONCLUSION: Our results demonstrate that FAM124B is a potential interacting partner of a CHD7 and CHD8 containing complex. From the overlapping expression pattern between Chd7 and Fam124B at murine embryonic day E12.5 and the high expression of Fam124B in the developing mouse brain, we conclude that Fam124B is a novel protein possibly involved in the pathogenesis of CHARGE syndrome and neurodevelopmental disorders.
INTRODUCTION: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML.
TRIAL DESIGN: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size.
PATIENTS AND METHODS: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of <20,000/µl at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint.
RESULTS: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days.
CONCLUSIONS: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm.
Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.
We searched for a drug capable of sensitization of sarcoma cells to doxorubicin (DOX). We report that the dual PI3K/mTOR inhibitor PI103 enhances the efficacy of DOX in several sarcoma cell lines and interacts with DOX in the induction of apoptosis. PI103 decreased the expression of MDR1 and MRP1, which resulted in DOX accumulation. However, the enhancement of DOX-induced apoptosis was unrelated to DOX accumulation. Neither did it involve inhibition of mTOR. Instead, the combination treatment of DOX plus PI103 activated Bax, the mitochondrial apoptosis pathway, and caspase 3. Caspase 3 activation was also observed in xenografts of sarcoma cells in nude mice upon combination of DOX with the specific PI3K inhibitor GDC-0941. Although the increase in apoptosis did not further impact on tumor growth when compared to the efficient growth inhibition by GDC-0941 alone, these findings suggest that inhibition of PI3K may improve DOX-induced proapoptotic effects in sarcoma. Taken together with similar recent studies of neuroblastoma- and glioblastoma-derived cells, PI3K inhibition seems to be a more general option to sensitize tumor cells to anthracyclines.