Asthma families show transmission disequilibrium of gene variants in the vitamin D metabolism and signalling pathway

The vitamin D prophylaxis of rickets in pregnant women and newborns may play a role in early allergic sensitization. We now asked if an already diseased population may have inherited genetic variants in the vitamin D turnover or signalling pathway. Serum levels of calcidiol (25-OH-D(3)) and calcitriol (1,25-(OH)(2)-D(3)) were retrospectively assessed in 872 partipants of the German Asthma Family Study. 96 DNA single base variants in 13 different genes were genotyped with MALDI-TOF and a bead array system. At least one positive SNP with a TDT of p < 0.05 for asthma or total IgE and calcidiol or calcitriol was seen in IL10, GC, IL12B, CYP2R1, IL4R, and CYP24A1. Consistent strong genotypic association could not be observed. Haplotype association were found only for CYP24A1, the main calcidiol degrading enzyme, where a frequent 5-point-haplotype was associated with asthma (p = 0,00063), total IgE (p = 0,0014), calcidiol (p = 0,0043) and calcitriol (p = 0,0046). Genetic analysis of biological pathways seem to be a promising approach where this may be a first entry point into effects of a polygenic inherited vitamin D sensitivity that may affect also other metabolic, immunological and cancerous diseases

Transient reduction of tinnitus intensity is marked by concomitant reductions of delta band power

<p>Abstract</p> <p>Background</p> <p>Tinnitus is an auditory phantom phenomenon characterized by the sensation of sounds without objectively identifiable sound sources. To date, its causes are not well understood. Previous research found altered patterns of spontaneous brain activity in chronic tinnitus sufferers compared to healthy controls, yet it is unknown whether these abnormal oscillatory patterns are causally related to the tinnitus sensation. Partial support for this notion comes from a neurofeedback approach developed by our group, in which significant reductions in tinnitus loudness could be achieved in patients who successfully normalized their patterns of spontaneous brain activity. The current work attempts to complement these studies by scrutinizing how modulations of tinnitus intensity alter ongoing oscillatory activity.</p> <p>Results</p> <p>In the present study the relation between tinnitus sensation and spontaneous brain activity was investigated using residual inhibition (RI) to reduce tinnitus intensity and source-space projected magnetencephalographic (MEG) data to index brain activity. RI is the sustained reduction (criteria: 50% for at least 30 s) in tinnitus loudness after cessation of a tonal tinnitus masker. A pilot study (n = 38) identified 10 patients who showed RI. A significant reduction of power in the delta (1.3–4.0 Hz) frequency band was observed in temporal regions during RI (p ≤ 0.001).</p> <p>Conclusion</p> <p>The current results suggest that changes of tinnitus intensity induced by RI are mediated by alterations in the pathological patterns of spontaneous brain activity, specifically a reduction of delta activity. Delta activity is a characteristic oscillatory activity generated by deafferented/deprived neuronal networks. This implies that RI effects might reflect the transient reestablishment of balance between excitatory and inhibitory neuronal assemblies, via reafferentation, that have been perturbed (in most tinnitus individuals) by hearing damage. As enhancements have been reported in the delta frequency band for tinnitus at rest, this result conforms to our assumption that a normalization of oscillatory properties of cortical networks is a prerequisite for attenuating the tinnitus sensation. For RI to have therapeutic significance however, this normalization would have to be stabilized.</p

Applicability of T1-weighted MRI in the assessment of forensic age based on the epiphyseal closure of the humeral head

This work investigates the value of magnetic resonance imaging analysis of proximal epiphyseal fusion in research examining the growth and development of the humerus and its potential utility in establishing forensic age estimation. In this study, 428 proximal humeral epiphyses (patient age, 12-30years) were evaluated with T1-weighted turbo spin echo (T1 TSE) sequences in coronal oblique orientation on shoulder MRI images. A scoring system was created following a combination of the Schmeling and Kellinghaus methods. Spearman's rank correlation analysis revealed a significant positive relationship between age and ossification stage of the proximal humeral epiphysis (all subjects: rho=0.664, p<0.001; males: 0.631, p<0.001; females: rho=0.651, p<0.001). The intra- and inter-observer reliability assessed using Cohen's kappa statistic was =0.898 and =0.828, respectively. The earliest age of epiphysis closure was 17years for females and 18years for males. MRI of the proximal humeral epiphysis can be considered advantageous for forensic age estimation of living individuals in a variety of situations, ranging from monitoring public health to estimating the age of illegal immigrants/asylum seekers, minors engaged in criminal activities, and illegal participants in competitive sports, without the danger of radiation exposure

p16 Mutation Spectrum in the Premalignant Condition Barrett's Esophagus

Background: Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions. Methods and Findings: We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett’s esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma. Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation. The percentage of patients with p16 mutations increased with increasing histologic grade. In addition, samples from 3 out of 19 patients (15.8%) who underwent esophagectomy were found to have mutations. Conclusions: The results of this study suggest the environment of the esophagus in BE patients can both generate an

Altered oscillatory brain dynamics after repeated traumatic stress

Kolassa I-T, Wienbruch C, Neuner F, et al. Altered oscillatory brain dynamics after repeated traumatic stress. BMC Psychiatry. 2007;7(1): 56.BACKGROUND: Repeated traumatic experiences, e.g. torture and war, lead to functional and structural cerebral changes, which should be detectable in cortical dynamics. Abnormal slow waves produced within circumscribed brain regions during a resting state have been associated with lesioned neural circuitry in neurological disorders and more recently also in mental illness. METHODS: Using magnetoencephalographic (MEG-based) source imaging, we mapped abnormal distributions of generators of slow waves in 97 survivors of torture and war with posttraumatic stress disorder (PTSD) in comparison to 97 controls. RESULTS: PTSD patients showed elevated production of focally generated slow waves (1-4 Hz), particularly in left temporal brain regions, with peak activities in the region of the insula. Furthermore, differential slow wave activity in right frontal areas was found in PTSD patients compared to controls. CONCLUSION: The insula, as a site of multimodal convergence, could play a key role in understanding the pathophysiology of PTSD, possibly accounting for what has been called posttraumatic alexithymia, i.e., reduced ability to identify, express and regulate emotional responses to reminders of traumatic events. Differences in activity in right frontal areas may indicate a dysfunctional PFC, which may lead to diminished extinction of conditioned fear and reduced inhibition of the amygdala

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with &gt;80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Isolation, identification, and characterization of novel arenaviruses, the etiological agents of boid inclusion body disease

Boid inclusion body disease (BIBD) is a progressive, usually fatal disease of constrictor snakes, characterized by cytoplasmic inclusion bodies (IB) in a wide range of cell types. To identify the causative agent of the disease, we established cell cultures from BIBD-positive and -negative boa constrictors. The IB phenotype was maintained in cultured cells of affected animals, and supernatants from these cultures caused the phenotype in cultures originating from BIBD-negative snakes. Viruses were purified from the supernatants by ultracentrifugation and subsequently identified as arenaviruses. Purified virus also induced the IB phenotype in naive cells, which fulfilled Koch's postulates in vitro. One isolate, tentatively designated University of Helsinki virus (UHV), was studied in depth. Sequencing confirmed that UHV is a novel arenavirus species that is distinct from other known arenaviruses including those recently identified in snakes with BIBD. The morphology of UHV was established by cryoelectron tomography and subtomographic averaging, revealing the trimeric arenavirus spike structure at 3.2-nm resolution. Immunofluorescence, immunohistochemistry, and immunoblotting with a polyclonal rabbit antiserum against UHV and reverse transcription-PCR (RT-PCR) revealed the presence of genetically diverse arenaviruses in a large cohort of snakes with BIBD, confirming the causative role of arenaviruses. Some snakes were also found to carry arenavirus antibodies. Furthermore, mammalian cells (Vero E6) were productively infected with UHV, demonstrating the potential of arenaviruses to cross species barriers. In conclusion, we propose the newly identified lineage of arenaviruses associated with BIBD as a novel taxonomic entity, boid inclusion body disease-associated arenaviruses (BIBDAV), in the family Arenaviridae