Mapping translocation breakpoints by next-generation sequencing

Balanced chromosome rearrangements (BCRs) can cause genetic diseases by disrupting or inactivating specific genes, and the characterization of breakpoints in disease-associated BCRs has been instrumental in the molecular elucidation of a wide variety of genetic disorders. However, mapping chromosome breakpoints using traditional methods, such as in situ hybridization with fluorescent dye-labeled bacterial artificial chromosome clones (BAC-FISH), is rather laborious and time-consuming. In addition, the resolution of BAC-FISH is often insufficient to unequivocally identify the disrupted gene. To overcome these limitations, we have performed shotgun sequencing of flow-sorted derivative chromosomes using "next-generation" (Illumina/Solexa) multiplex sequencing-by-synthesis technology. As shown here for three different disease-associated BCRs, the coverage attained by this platform is sufficient to bridge the breakpoints by PCR amplification, and this procedure allows the determination of their exact nucleotide positions within a few weeks. Its implementation will greatly facilitate large-scale breakpoint mapping and gene finding in patients with disease-associated balanced translocations.     

Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia

Copy number variations (CNVs) account for a substantial proportion of human genomic variation, and have been shown to cause neurodevelopmental disorders. We sought to determine the relevance of CNVs to the aetiology of schizophrenia (SZ). Whole-genome, high-resolution, tiling path BAC array comparative genomic hybridization (array CGH) was employed to test DNA from 93 individuals with DSM-IV SZ. Common DNA copy number changes that are unlikely to be directly pathogenic in SZ were filtered out by comparison to a reference dataset of 372 control individuals analyzed in our laboratory, and a screen against the Database of Genomic Variants. The remaining aberrations were validated with Affymetrix 250K SNP arrays or 244K Agilent oligo-arrays and tested for inheritance from the parents. A total of 13 aberrations satisfied our criteria. Two of them are very likely to be pathogenic. The first one is a deletion at 2p16.3 that was present in an affected sibling and disrupts NRXN1. The second one is a de novo duplication at 15q13.1 spanning APBA2. The proteins of these two genes interact directly and play a role in synaptic development and function. Both genes have been affected by CNVs in patients with autism and mental retardation, but neither has been previously implicated in SZ.     

Sleep disorders in Behçet's disease, and their relationship with fatigue and quality of life

Behçet’s disease, a systemic vasculitis, can cause varying degrees of activity limitation, fatigue and quality of life impairment. To date, there have been no studies regarding sleep disturbance and its relationship with fatigue and life quality in Behçet’s disease. We aimed to evaluate sleep disorders and polysomnographic parameters, and to determine their relationship with fatigue and quality of life in Behçet’s disease. Fifty‐one patients with Behçet’s disease without any neurological involvement were interviewed regarding sleep disorders. Twenty‐one subjects with no sleep complaints were included as the control group. Sleep‐related complaints were evaluated in a face‐to‐face interview. Sleep quality, excessive daytime sleepiness, fatigue, depression, anxiety, disease activity/severity, and quality of life questionnaires and an overnight polysomnography were performed. Prevalences of restless legs syndrome (35.3%) and obstructive sleep apnea syndrome with/without other sleep disorders (32.5%) were higher than in the control group and the general population. Fatigue was higher in patients with restless legs syndrome and obstructive sleep apnea syndrome, and in those with lower minimum oxygen saturation; hence, only patients with restless legs syndrome had quality of life impairment. Sleep efficiency index and sleep continuity index were lower, and wake after sleep onset, respiratory disturbance index and apnea–hypopnea index were higher than in controls (P < 0.01). Neither sleep disorders nor polysomnographic parameters were related to disease activity and severity. In conclusion, it is important to question sleep disorder followed by a polysomnography, if necessary, in order to improve quality of life and fatigue in Behçet’s disease.     

An effective method for videorecording the nasal–dorsal part of a rhinoplasty – a multiple case study

Rhinoplasty is a difficult procedure to record for several reasons which include the narrow, dark and deep surgical field cluttered with many instruments, and the heads and hands of the surgical team often blocking the view. This study discusses 13 rhinoplasty cases that were recorded using the authors’ technique. A three-minute, unedited segment was extracted from the mid-portion of each surgical case, and that footage was evaluated by three specialist examiners. Results indicate that the authors’ technique can offer a effective solution in the video recording of the nasal–dorsal part of a rhinoplasty.     

Modification of Surface and Subsurface Properties of AA1050 Alloy by Shot Peening

AA1050 Al alloy samples were shot-peened using stainless-steel shots at shot peening (SP) pressures of 0.1 and 0.5 MPa and surface cover rates of 100% and 1000% using a custom-designed SP system. The hardness of shot-peened samples was around twice that of unpeened samples. Hardness increased with peening pressure, whereas the higher cover rate did not lead to hardness improvement. Micro-crack formation and embedment of shots occurred by SP, while average surface roughness increased up to 9 µm at the higher peening pressure and cover rate, indicating surface deterioration. The areal coverage of the embedded shots ranged from 1% to 5% depending on the peening parameters, and the number and the mean size of the embedded shots increased at the higher SP pressure and cover rate. As evidenced and discussed through the surface and cross-sectional SEM images, the main deformation mechanisms during SP were schematically described as crater formation, folding, micro-crack formation, and material removal. Overall, shot-peened samples demonstrated improved mechanical properties, whereas sample surface integrity only deteriorated notably during SP at the higher pressure, suggesting that selecting optimal peening parameters is key to the safe use of SP. The implemented methodology can be used to modify similar soft alloys within confined compromises in surface features.     

The seasonal and monthly distribution of body limbs affected by burns in paediatric patients in southeast Turkey

Studies on the frequency of burned limbs according to season and months are limited. The burning of some body limbs, especially in some months, shows that the causes of burns are different, and knowing the reasons is important for providing preventive measures. The aims of this study were to determine the distribution rate of child burns by months and seasons and to contribute to preventive measures by determining the distribution of the burning of body limbs by months. We retrospectively evaluated 419 paediatric patients (0‐17 years of age) who were hospitalised in the burn unit between 1 May 2017 and 1 November 2018. The demographic characteristics of the patients were recorded according to age, gender, months, and seasons of the patients admitted; cause of burns; degree of burns; total body surface area; and burning regions. The distribution of burns by months was established as being mainly in May to October. As for the distribution of the patients according to the seasons, it was found that it was most common in summer, 122 (29.1%), and in the autumn season as well, it was 122 (29.1%). While body burns increased in the summer‐autumn seasons (P < .023), genital area burns were the lowest in winter and were the highest in summer and autumn seasons. Genital site burns increased statistically in September, October, and November (P < .010). Burn traumas are observed to be more frequent in some seasons and months. The environments where individuals live, forms of life, forms of warming, areas of interest, and sociocultural and economic levels are the causes of this variability.     

Arginine vasopressin (AVP) and treatment with arginine vasopressin receptor antagonists (vaptans) in congestive heart failure,liver cirrhosis and syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Arginine vasopressin (AVP) is the major physiological regulator of renal water excretion and blood volume. The AVP pathways of V_1aR-mediated vasoconstriction and V₂R-induced water retention represent a potentially attractive target of therapy for edematous diseases. Experimental and clinical evidence suggests beneficial effects of AVP receptor antagonists by increasing free water excretion and serum sodium levels. This review provides an update on the therapeutic implication of newly developed AVP receptor antagonists in respective disorders, such as chronic heart failure, liver cirrhosis and syndrome of inappropriate antidiuretic hormone secretion.