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Frankfurt am Main, Germany

Neumann K.,University of Frankfurt am Main | Stephens D.,University of Cardiff
Folia Phoniatrica et Logopaedica | Year: 2011

Objective: To develop a clear and meaningful set of definitions of types of hearing impairment. Method: A critical analysis was made of previous definitions together with a consideration of current knowledge of functions and dysfunctions of the auditory system. Results and Conclusions: A coherent set of definitions compatible with the contemporary understanding of auditory disorders and their perceptual effects is proposed. Copyright © 2010 S. Karger AG, Basel. Source


Diener S.J.,University of Heidelberg | Wessa M.,University of Heidelberg | Ridder S.,University of Heidelberg | Lang S.,University of Heidelberg | And 3 more authors.
Journal of Affective Disorders | Year: 2012

Background: Uncontrollable stress is frequently accompanied by a primarily opioid-mediated stress analgesia. In posttraumatic stress disorder (PTSD) exaggerated stress-induced analgesia to trauma reminders was proposed. The present study investigated whether enhanced analgesia occurs in response to a trauma-unrelated cognitive stressor in PTSD. Methods: Functional magnetic resonance imaging data were obtained from fourteen outpatients with PTSD and 14 trauma-exposed subjects without PTSD (NPTSD) during mechanical painful stimulation before and after stress. Blood oxygenation level-dependent (BOLD) responses were assessed during painful stimulation. Pain ratings, pain thresholds and pain tolerance were assessed pre- and post-stress. Heart rate and blood pressure were recorded before, during and after stress. Results: In comparison to NPTSD, PTSD-patients showed significantly more analgesia in terms of an increase of pain threshold and tolerance and a decrease in pain ratings after the stressor. Post-stress, PTSD-patients compared to NPTSD displayed more activation of the rostral anterior cingulate cortex and decreased neural activity in brain areas associated with pain perception. However heart rate increase during stress and blood pressure decrease post-stress was lower in PTSD pointing to a dysregulation of the cardiovascular system in response to stress. Limitations: The small sample size represents a limiting factor in interpreting the results and might have led to low levels of significance for the group differences in BOLD response changes. Conclusions: These findings show enhanced stress reactivity and accompanying reduced pain perception in PTSD-patients in contrast to traumatized participants without PTSD. The results suggest that the previously reported enhanced analgesic response after trauma-related stress in PTSD transfers to trauma-unrelated stressors. © 2011 Elsevier B.V. All rights reserved. Source


Jonsson T.,University of Iceland | Stefansson H.,University of Iceland | Steinberg S.,University of Iceland | Jonsdottir I.,University of Iceland | And 24 more authors.
New England Journal of Medicine | Year: 2013

Background: Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer's disease. Few rare variants affecting the risk of late-onset Alzheimer's disease have been found. Methods: We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer's disease and control participants and then tested for an association with Alzheimer's disease. We performed replication tests using case-control series from the United States, Norway, the Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons. Results: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P = 3.42×10-10). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P = 2.1×10-12 in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers (P = 0.003). Conclusions: Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.) Copyright © 2012 Massachusetts Medical Society. Source


Haeussinger F.B.,University of Tubingen | Heinzel S.,University of Tubingen | Heinzel S.,University of Wurzburg | Heinzel S.,German Center for Neurodegenerative Diseases | And 5 more authors.
PLoS ONE | Year: 2011

Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: (25.0 ± 2.8) years), we characterized the individual distribution of tissue-specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes (V gray) traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of (23.6 ± 0.7)mm considering the deepest 5% of light. Of the detected photon packages scalp and bone absorbed (96.4 ± 9.7)% and V gray absorbed (3.1 ± 1.8)% of the energy. The mean V gray volume (1.1 ± 0.4)cm 3 was negatively correlated (r= -.76) with the SCD and frontal sinus volume (r= -.57) and was reduced by 41.5% in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD (r=.46) and the traversed frontal sinus volume (r=.43). Sulcal morphology had no significant impact on V gray. Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance. © 2011 Haeussinger et al. Source


Rodel F.,University of Frankfurt am Main | Sprenger T.,University of Gottingen | Kaina B.,University Medical Center Mainz | Liersch T.,University of Frankfurt am Main | And 3 more authors.
Current Medicinal Chemistry | Year: 2012

Evasion from apoptotic cell death is reported to be a pivotal mechanism by which tumor cells acquire resistance to therapeutic treatment. Targeting the apoptotic pathways may constitute a promising strategy to counteract therapy resistance and to re-sensitize cancer cells. Expression of survivin, the smallest and structurally unique member of the inhibitor of apoptosis protein (IAP) family, has been shown to be associated with poor clinical outcome, more aggressive clinicopathologic features and resistance to both, conventional chemo and radiation therapy. Moreover, survivin detection in cancer tissue, in circulating tumor cells and in patient's serum has prognostic and predictive relevance and may display a prerequisite for marker based molecular therapies. Indeed, due to its universal over expression in malignant tissue, and its prominent role at disparate networks of cellular division, intracellular signaling, apoptosis and adaption to unfavorable surroundings, survivin has been shown to be a suitable target for a targeted therapy. The applicability of survivindriven strategies in clinical practice is currently under investigation as the first survivin antagonists (small molecule inhibitors, antisense oligonucleotides and immunotherapy) successfully entered phase I/II trials. Taken together, these data provide a rationale for the implementation of both, survivin as a molecular diagnostic tool and survivin targeted therapies, within future clinical practice. © 2012 Bentham Science Publishers. Source

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