Reelin-immunoreactivity in the hippocampal formation of 9-month-old wildtype mouse: effects of APP/PS1 genotype and ovariectomy

Reelin, an extracellular matrix protein has an important role in the migration, correct positioning and maturation of neurons during development. Though it is generally down-regulated in the postnatal period, expression of this large glycoprotein continues in the adult brain in some cell populations. In the present study, we examined the distribution of reelin-immunoreactivity (-ir) in the hippocampal formation of 9-month-old wildtype mice (WT). Then, reelin-ir in normal mice was compared to that of transgenic mice (APP/PS1) carrying mutated human APP and PS1 genes, which are linked to the familial form of Alzheimer's disease (AD). The APP/PS1 mice were additionally burdened with a second risk factor for AD, namely depletion of circulating gonadal hormones by ovariectomy (APP/PS1 + OVX). The analyses revealed that in adult WT reelin-ir is expressed by Cajal-Retzius cells and a subgroup of interneurons throughout the hippocampal formation. In addition, layer II projection neurons in the lateral entorhinal subfields are reelin-ir. Interestingly, ovariectomy decreases the number of reelin-ir cells in the hilus in WT mice, whereas AD-related genotype alone induces only a non-significant reduction. Unexpectedly, additional stress, e.g., depletion of gonadal hormones, does not aggravate the slight reduction in the reelin cell number in the APP/PS1 mice. We propose that the changes in normal reelin-ir are linked to disturbances in repair mechanisms in which APP/PS1 and gonadal hormones are involved and which are perturbed in neurodegenerative conditions, namely AD.     

Attitudes among parents of persons with autism spectrum disorder towards information about genetic risk and future health

Clinical relevance of genetic testing is increasing in autism spectrum disorder (ASD). Information about genetic risk may contribute to improved diagnostics, treatment and family planning, but may also be perceived as a burden. Knowledge about the families’ preferences with regard to genetic risk information is important for both health care professionals and policy makers. We investigated attitudes towards sharing information about genetic risk of ASD and knowledge about future health among parent members of the Norwegian Autism Association (N = 1455) using a questionnaire, and the relationships with parent and child characteristics, such as age, gender and ASD severity. Most preferred autonomy in deciding whom to inform about genetic risk of ASD (74.4%) and a minority supported extensive intra-familial disclosure of the genetic risk (41.1%). The majority agreed that it is an obligation to know as much as possible relevant for future health (58.0%) and only 51.7% agreed to a principle of a ‘right not to know’. In regression models, the attitudes were associated with opinions about benefits and harms of genetic testing (e.g., treatment, family planning, understanding of ASD pathology, insurance discrimination and family conflict). In sum, the findings show that most parents want to know as much as possible relevant for their children’s future health and keep their autonomy and intra-familial confidentiality about genetic risk information. Nearly half of the parents were not concerned with a “right not to know”. These attitudes can inform development of guidelines and bioethics in the age of genomic precision medicine.Subject terms: Genetic counselling, Ethics, Medical ethics     

Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action,Efficacy and Safety

Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.     

Evaluation of antigens from various Leishmania species in a Western blot for diagnosis of American tegumentary leishmaniasis

A Western blot method that uses antigens from culture promastigote forms of Leishmania (Viannia) braziliensis, L. (Leishmania) amazonensis, L. (Leishmania) tropica, and a trypanosomatid (strain 268T) isolated from naturally infected tomatoes was evaluated for laboratory diagnosis of American tegumentary leishmaniasis (ATL). Serum samples were obtained from 108 patients with ATL (group I), 23 chagasic patients (group II), 32 patients with other diseases (group III), and 78 healthy individuals (group IV). The overall analysis showed a sensitivity of 76.90%, 90.40%, 78.50%, and 87.90%, a specificity of 100%, 93.80%, 87.80%, and 77.10%, a positive predictive value of 100%, 94.00%, 89.50%, and 72.50%, a negative predictive value of 75.70%, 90.00%, 75.40%, and 90.20%, and a concordance coefficient kappa of 0.7358, 0.8400, 0.6491, and 0.6287 for L. (V.) braziliensis, L. (L.) amazonensis, L. (L.) tropica, and strain 268T antigens, respectively. The antigenic profile recognized by serum samples from patients with ATL and with Chagas' disease permits serologic distinction between these infections.     

Characterization Methods along the Process Chain of Electrical Steel Sheet—From Best Practices to Advanced Characterization

Non-oriented (NO) electrical steel sheets find their application in rotating electrical machines, ranging from generators for wind turbines to motors for the transportation sector and small motors for kitchen appliances. With the current trend of moving away from fossil fuel-based energy conversion towards an electricity-based one, these machines become more and more important and, as a consequence, the leverage effect in saving energy by improving efficiency is huge. It is already well established that different applications of an electrical machine have individual requirements for the properties of the NO electrical steel sheets, which in turn result from the microstructures and textures thereof. However, designing and producing tailor-made NO electrical steel sheet is still challenging, because the complex interdependence between processing steps, the different phenomena taking place and the resulting material properties are still not sufficiently understood. This work shows how established, as well as advanced and newly developed characterization methods, can be used to unfold these intricate connections. In this context, the respective characterization methods are explained and applied to NO electrical steel as well as to the typical processing steps. In addition, several experimental results are reviewed to show the strengths of the different methods, as well as their (dis)advantages, typical applications and obtainable data.     

Über die Verminderung der Harnchloride bei der Akuten FibrinÖsen LungenentzÜndung

Ohne Zusammenfassung