Examination of the effect of acute levodopa administration on the loudness dependence of auditory evoked potentials (LDAEP) in humans

Rationale: The loudness dependence of the auditory evoked potential (LDAEP) is considered a noninvasive in vivo marker of central serotonergic functioning in humans. Nevertheless, results of genetic association studies point towards a modulation of this biomarker by dopaminergic neurotransmission. Objective: We examined the effect of dopaminergic modulation on the LDAEP using L-3,4-dihydroxyphenylalanine (levodopa)/benserazide (Madopar®) as a challenge agent in healthy volunteers. Methods: A double-blind placebo-controlled challenge design was chosen. Forty-two healthy participants (21 females and 21 males) underwent two LDAEP measurements, following a baseline LDAEP measurement either placebo or levodopa (levodopa 200mg/benserazide 50mg) were given orally. Changes in the amplitude and dipole source activity of the N1/P2 intensities (60, 70, 80, 90, and 100dB) were analyzed. Results: The participants of neither the levodopa nor the placebo group showed any significant LDAEP alterations compared to the baseline measurement. The test-retest reliability (Cronbachs Alpha) between baseline and intervention was 0.966 in the verum group and 0.759 in the placebo group, respectively. Conclusions: The administration of levodopa showed no effect on the LDAEP. These findings are in line with other trials using dopamine receptor agonist

Textile sensors for stab and cut detection

Manufacturers are aiming for more flexible and lightweight protective clothing to increase wearing comfort. A cardigan with a knitted stab-resistant inlay and an alarm system is presented. The stab-resistant inlay is based on a multilayer ultra-high molecular weight poly ethylene (UHMW-PE) fabric. Stab resistance was evaluated according to the standard of the Association of Test Laboratories for Bullet, Stab or Pike Resistant Materials and Construction Standard (VPAM 2011). Furthermore sensors for the detection of cuts and pressure were integrated. Both sensors can trigger alarms if the wearer is attacked. Normal pressure occurring through leaning on a wall or sitting is filtered out and does not trigger an alarm

Making Muscle Elastic: The Structural Basis of Myomesin Stretching

The muscle M-band protein myomesin comprises a 36-nm long filament made of repetitive immunoglobulin–helix modules that can stretch to 2.5-fold this length, demonstrating substantial molecular elasticity

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinico-pathological analysis

BACKGROUND: Minichromosome maintenance (MCM) proteins are essential for the initiation of DNA replication and have been found to be relevant markers for prognosis in a variety of tumours. The aim of this study was to assess the proliferative activity of diffuse large B-cell lymphoma (DLBCL) in tissue microarray (TMA) using one of the minichromosome maintenance proteins (Mcm2) and to explore its potential value to predict prognosis. METHODS: Immunohistochemistry for Mcm2 was performed on TMAs constructed from 302 cases of DLBCL. A monoclonal mouse antibody was used after heat induced antigen retrieval. Mcm2 expression was scored quantitatively. Positivity for Mcm2 was defined as presence of nuclear expression of Mcm2 in greater than or equal to 40 % of tumour cells. A statistical analysis was carried out of the association of Mcm2 and the clinico-pathological characteristics. RESULTS: Mcm2 expression was clearly evident in the nuclei of proliferating non-neoplastic cells and tumour cells. Positivity for Mcm2 was found in 46% (98/211) of analysable cases. A significant correlation existed between Mcm2 expression and presence of bulky disease (p = 0.003). Poor disease specific survival was observed in patients with DLBCL positive for Mcm2 expression in the univariate analysis (p = 0.0424). CONCLUSION: Mcm2 expression can be used to assess tumour proliferation and may be useful as an additional prognostic marker to refine the prediction of outcome in DLBCL

Can we import quality tools? a feasibility study of European practice assessment in a country with less organised general practice

<p>Abstract</p> <p>Background</p> <p>Quality is on the agenda of European general practice (GP). European researchers have, in collaboration, developed tools to assess quality of GPs. In this feasibility study, we tested the European Practice Assessment (EPA) in a one-off project in Belgium, where general practice has a low level of GP organisation.</p> <p>Methods</p> <p>A framework for feasibility analysis included describing the recruiting of participants, a brief telephone study survey among non-responders, organisational and logistic problems. Using field notes and focus groups, we studied the participants' opinions.</p> <p>Results</p> <p>In this study, only 36 of 1000 invited practices agreed to participate. Co-ordination, administrative work, practice visits and organisational problems required several days per practice. The researchers further encountered technical problems, for instance when entering the data and uploading to the web-based server. In subsequent qualitative analysis using two focus groups, most participant GPs expressed a positive feeling after the EPA procedure. In the short period of follow-up, only a few GPs reported improvements after the visit. The participant GPs suggested that follow-up and coaching would probably facilitate the implementation of changes.</p> <p>Conclusion</p> <p>This feasibility study shows that prior interest in EPA is low in the GP community. We encountered a number of logistic and organisational problems. It proved attractive to participants, but it can be augmented by coaching of participants in more than a one-off project to identify and achieve targets for quality improvement. In the absence of commitment of the government, a network of universities and one scientific organisation will offer EPA as a service to training practices.</p

Prevalence of primary headaches in Germany: results of the German Headache Consortium Study

We investigated the prevalence of migraine (MIG), tension-type headache (TTH), and chronic headache in a population-based sample in Germany. A total of 18,000 subjects aged between 18 and 65 years were screened from 2003 until 2005 using a validated questionnaire. Overall 9,944 participants (55.2%) responded (mean age 43 ± 13.1 years, 52.7% women). Headache frequency <15 days/month was reported by 5,350 (55.5%) subjects of whom 1,601 (16.6%, [95% confidence interval (95% CI): 15.9–17.4]) reported episodic MIG, 1,202 (12.5%, 95% CI 11.8–13.1) episodic TTH, and 1,150 (11.9%, [11.3–12.6]) episodic MIG + episodic TTH, 1,396 (14.5%, [13.8–15.2]) unclassifiable headache. In women, episodic MIG peaked between 36 and 40 years, episodic MIG + TTH between 18 and 35 years and episodic TTH between 56 and 66 years. In men, episodic MIG was predominant between 36 and 45 years, episodic MIG + TTH between 26 and 35 years and episodic TTH showed comparable frequency between 36 and 66 years. Headache ≥15 days/month was reported by 2.6% (n = 255, [95% CI 2.3–3]). Chronic MIG was reported by 1.1% (n = 108, [0.91–1.33]), chronic TTH (n = 50, [95% CI 0.4–0.7]), chronic MIG + TTH 0.8% (n = 74, 95% CI 0.6–0.9) and unclassifiable headache 0.2% (n = 23, [95% CI 0.1–0.3]). Chronic headache was more frequent in women compared to men with the highest prevalence between 46 and 65 years. It is of note that the number of subjects with chronic headache is small in all age groups. The results of our large, population-based study provide reliable, age- and sex-specific estimates of the prevalence of primary headache disorders in Germany. The prevalence with respect to episodic and chronic primary headache disorders in Germany is comparable to other European countries and the USA