Association of GABRG3, GABRB3, HTR2A gene variants with autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental and neurobehavioral disorder characterized by impaired social communication, repetitive and restricted patterns of behavior, activity, or interest, and altered emotional processing. Reported prevalence is 4 times higher in men and it has increased in recent years. Immunological, environmental, epigenetic, and genetic factors play a role in the pathophysiology of autism. Many neurochemical pathways and neuroanatomical events are effective in determining the disease. It is still unclear how the main symptoms of autism occur because of this complex and heterogeneous situation. In this study, we focused on gamma amino butyric acid (GABA) and serotonin, which are thought to contribute to the etiology of autism; it is aimed to elucidate the mechanism of the disease by investigating variant changes in the GABA receptor subunit genes GABRB3, GABRG3 and the HTR2A gene, which encodes one of the serotonin receptors. 200 patients with ASD between the ages of 3-9 and 100 healthy volunteers were included in the study. Genomic DNA isolation was performed from peripheral blood samples taken from volunteers. Genotyping was performed using the RFLP method with PCR specific for specific variants. Data were analyzed with SPSS v25.0 program. According to the data obtained in our study; In terms of HTR2A (rs6313 T102C) genotypes, the homozygous C genotype carrying frequency in the patient group and the homozygous T genotype carrying frequency in the GABRG3 (rs140679 C/T) genotypes were found to be significantly higher in the patient group compared to the control group (*p: 0.0001, p: 0.0001). It was determined that the frequency of individuals with homozygous genotype was significantly higher in the patient group compared to the control group and having homozygous genotypes increased the disease risk approximately 1.8 times. In terms of GABRB3 (rs2081648 T/C) genotypes, it was determined that there was no statistically significant difference in the frequency of carrying homozygous C genotype in the patient group compared to the control group (p: 0.36). According to the results of our study, we think that the HTR2A (rs6313 T102C) polymorphism is effective in modulating the empathic and autistic characteristics of individuals, and that the HTR2A (rs6313 T102C) polymorphism is more distributed in the post-synaptic membranes in individuals with a higher number of C alleles. We believe that this situation can be attributed to the spontaneous stimulatory distribution of the HTR2A gene in the postsynaptic membranes because of T102C transformation. In genetically based autism cases, carrying the point mutation in the rs6313 variant of the HTR2A gene and the C allele and the point mutation in the rs140679 variant of the GABRG3 gene and accordingly carrying the T allele provide a predisposition to the disease.

MR image reconstruction using densely connected residual convolutional networks.

MR image reconstruction techniques based on deep learning have shown their capacity for reducing MRI acquisition time and performance improvement compared to analytical methods. Despite the many challenges in training these rather large networks, novel methodologies have enhanced the capability for having clinical-grade MR image reconstruction in real-time. In recent literature, novel developments have facilitated the utilization of deep networks in various image processing inverse problems. In particular, it has been reported multiple times that the performance of deep networks can be improved by using short connections between layers. In this study, we introduce a novel MRI reconstruction method that utilizes such short connections. The dense connections are used inside densely connected residual blocks. Inside these blocks, the feature maps are concatenated to the subsequent layers. In this way, the extracted information is propagated until the last stage of the block. We have evaluated this densely connected residual block's efficiency in MRI reconstruction settings, by augmenting different types of effective deep network models with these blocks in novel structures. The quantitative and qualitative results indicate that this original introduction of the densely connected blocks to the MR image reconstruction problem improves the reconstruction performance significantly.

Projection-Based cascaded U-Net model for MR image reconstruction.

BACKGROUND AND OBJECTIVE: Background and Objective: Recent studies in deep learning reveal that the U-Net stands out among the diverse set of deep models as an effective network structure, especially for imaging inverse problems. Initially, the U-Net model was developed to solve segmentation problems for biomedical images while using an annotated dataset. In this paper, we will study a novel application of the U-Net structure for the important inverse problem of MRI reconstruction. Deep networks are particularly efficient for the speed-up of the MR image reconstruction process by decreasing the data acquisition time, and they can significantly reduce the aliasing artifacts caused by the undersampling in the k-space. Our aim is to develop a novel and efficient cascaded U-Net framework for reconstructing MR images from undersampled k-space data. The new framework should have improved reconstruction performance when compared to competing methodologies. METHODS: In this paper, a novel cascaded framework utilizing the U-Net as a sub-block is being proposed. The introduced U-Net cascade structure is applied to the magnetic resonance image reconstruction problem. The connection between the cascaded U-Nets is realized in the form of a recently developed projection-based updated data consistency layer. The novel structure is implemented in the PyTorch environment, which is one of the standards for deep learning implementations. The recently created fastMRI dataset which forms an important benchmark for MRI reconstruction is used for training and testing purposes. RESULTS: We present simulation results comparing the novel method with a variety of competitive deep networks. The new cascaded U-Net structures PSNR performance stands on average 1.28 dB higher than the baseline U-Net. The improvement, when compared to the standard CNN, is on average 3.32 dB. CONCLUSIONS: The proposed cascaded U-Net configuration results in an improved reconstruction performance when compared to the CNN, the cascaded CNN, and also the singular U-Net structures, where the singular U-Net forms the baseline reconstruction method from the fastMRI package. The use of the projection-based updated data consistency layer also leads to improved quantitative (including SSIM, PSNR, and NMSE results) and qualitative results when compared to the use of the conventional data consistency layer.

MRI reconstruction with joint global regularization and transform learning.

Sparsity based regularization has been a popular approach to remedy the measurement scarcity in image reconstruction. Recently, sparsifying transforms learned from image patches have been utilized as an effective regularizer for the Magnetic Resonance Imaging (MRI) reconstruction. Here, we infuse additional global regularization terms to the patch-based transform learning. We develop an algorithm to solve the resulting novel cost function, which includes both patchwise and global regularization terms. Extensive simulation results indicate that the introduced mixed approach has improved MRI reconstruction performance, when compared to the algorithms which use either of the patchwise transform learning or global regularization terms alone.

Osseofix® system for percutaneous stabilization of osteoporotic and tumorous vertebral compression fractures - clinical and radiological results after 12 months.

PURPOSE: Determining whether implantation of an expandable titanium mesh cage (Osseofix® system) is a successful and safe minimally invasive therapy for osteoporotic and tumorous vertebral compression fractures (VCFs). MATERIALS AND METHODS: 32 patients (25 women, 7 men, mean age 71) with 46 osteoporotic or tumorous VCFs (T6 to L4) from June 2010 to January 2012 were included. All of them were stabilized with the Osseofix® system. Preinterventionally we performed X-ray, MRI, and bone density measurements (DXA). The clinical and radiological results were evaluated preop, postop and 12 months postop based on the visual analog scale (VAS) and the Oswestry Disability Index (ODI), X-ray (Beck Index, Cobb angle) and CT. RESULTS: There was a significant improvement in pain intensity (VAS) (7.8 to 1.6) as well as a significant reduction in the mean ODI (71.36 % to 30.4 %) after 12 months. The mean kyphotic angle according to Cobb showed significant improvements (12.3° to 10.8°) after 12 months. Postinterventional imaging showed one case of loss of height in a stabilized lumbar vertebral body (2.2 %) in osteoporosis and one case with adjacent fracture (2.2 %) in osteoporosis. We saw no changes in the posterior vertebral wall. Except for one pronounced postoperative hematoma, we saw no surgical complications including no cement leakage. CONCLUSION: The clinical mid-term results are good at a low complication rate. The stabilization of symptomatic osteoporotic and tumorous VCFs with the Osseofix® system is a safe and effective procedure, even in fractures with posterior wall involvement. The Osseofix® system is an interesting alternative to the established procedures of cement augmentation. KEY POINTS: • The Osseofix® system is well suited for stabilizing osteoporotic and tumorous VCFs.• It is a safe and effective procedure without cement leakage and with a low complication rate.• The procedure is an interesting alternative to established cement augmentation procedures.

Protease-activated receptor-1 cleaved at R46 mediates cytoprotective effects.

BACKGROUND: Activated protein C (aPC) mediates powerful cytoprotective effects through the protease-activated receptor-1 (PAR1) that translate into reduced harm in mouse injury models. However, it remains elusive how aPC-activated PAR1 can mediate cytoprotective effects whereas thrombin activation does the opposite. OBJECTIVES: We hypothesized that aPC and thrombin might induce distinct active conformations in PAR1 causing opposing effects. METHODS: We analyzed antibody binding to, and cleavage and signalling of PAR1 in either endogenously expressing endothelial or overexpressing 293T cells. RESULTS: In thrombin-cleaved PAR1 neither the tethered ligand nor the hirudin-like domain were available for anti-PAR1 ATAP2 and WEDE15 binding unless the tethered ligand was quenched. In contrast, aPC irreversibly prevented ATAP2 binding while not affecting WEDE15 binding. Reporter constructs with selective glutamine substitutions confirmed R41 as the only thrombin cleavage site in PAR1, whereas aPC preferentially cleaved at R46. Similarly, we report distinct cleavage sites on PAR3, K38 for thrombin and R41 for aPC. A soluble peptide corresponding to R46-cleaved PAR1 enhanced the endothelial barrier function and reduced staurosporine toxicity in endothelial as well as in 293T cells if PAR1 was expressed. Overexpression of PAR1 variants demonstrated that cleavage at R46 but not R41 is required for cytoprotective aPC signaling. CONCLUSIONS: We provide a novel concept on how aPC and thrombin mediate distinct effects. We propose that the enzyme-specific cleavage sites induce specific conformations which mediate divergent downstream effects. This unexpected model of PAR1 signaling might lead to novel therapeutic options for the treatment of inflammatory diseases.

Transcriptional profiling of XdrA, a new regulator of spa transcription in Staphylococcus aureus.

Transcription of spa, encoding the virulence factor protein A in Staphylococcus aureus, is tightly controlled by a complex regulatory network, ensuring its temporal expression over growth and at appropriate stages of the infection process. Transcriptomic profiling of XdrA, a DNA-binding protein that is conserved in all S. aureus genomes and shares similarity with the XRE family of helix-turn-helix, antitoxin-like proteins, revealed it to be a previously unidentified activator of spa transcription. To assess how XdrA fits into the complex web of spa regulation, a series of regulatory mutants were constructed; consisting of single, double, triple, and quadruple mutants lacking XdrA and/or the three key regulators previously shown to influence spa transcription directly (SarS, SarA, and RNAIII). A series of lacZ reporter gene fusions containing nested deletions of the spa promoter identified regions influenced by XdrA and the other three regulators. XdrA had almost as strong an activating effect on spa as SarS and acted on the same spa operator regions as SarS, or closely overlapping regions. All data from microarrays, Northern and Western blot analyses, and reporter gene fusion experiments indicated that XdrA is a major activator of spa expression that appears to act directly on the spa promoter and not through previously characterized regulators.

[Amputation of the leg with impaired circulation. The orthopaedic surgeon's view]. / Die Amputation der durchblutungsgestörten Extremität aus der Sicht des Orthopäden.

Despite therapeutic improvements in the treatment of arterial circulatory problems of the leg, several tens of thousands of amputations are performed every year. The amputation is not the end of the treatment but is the beginning of the rehabilitation. Decisive criteria for a successful rehabilitation are the quality of the leg-stump, the immediate and early care, and an adequate artificial leg.

Variability of SCCmec in the Zurich area.

A periodic survey of methicillin-resistant Staphylococcus aureus (MRSA) in Zurich in 2004 and 2006 revealed a consistently low prevalence of MRSA. SCCmec and ccr typing showed fluctuations in the proportions of SCCmec types and in the carriage of mobile virulence determinants. Together with the presence of variant SCCmecs these findings suggest a high clonal diversity and level of SCCmec recombination. The prevalence of a local "drug clone", associated with low-level methicillin resistance and rapid growth, significantly decreased. This clone had spread among intraveneous drug users, steadily increasing from 1994 to 2001 and was dominant in 2001. Apparently, changes in the management of the Zurich drug scene have restricted the spread of this clone.

Mosaic staphylococcal cassette chromosome mec containing two recombinase loci and a new mec complex, B2.

A novel staphylococcal cassette chromosome (SCC) mec from a clinical methicillin-resistant Staphylococcus aureus isolate (ST100/CC5) had a mosaic structure, composed of SCC DNA from several different backgrounds. It harbored two complete ccr loci and a new variant of mec complex B, with DeltamecR1 interrupted by the aminoglycoside resistance transposon Tn4001.

Working with the bereaved: U.S. Army experiences with nontraditional families.

This paper uses a postmodern family perspective to examine the interaction between Army Casualty Assistance Officers (CAOs) and the families of deceased soldiers. The data we examine are open-ended survey responses of CAOs (N = 188) who assisted bereaved families of soldiers killed in three unrelated air disasters. Five themes emerged from our analysis of the qualitative responses: postmodern family structures, contested definitions of "significant other," language, diversity, and emotion. These themes appear to be related to the difficult demands associated with bereavement work. We argue that the experiences of the CAO are comparable to the experiences of others who may work with the bereaved (e.g., police officers, medical workers, and disaster workers) when working in similar familial contexts.

[Experience with the management of fresh cruciate ligament rupture in athletes]. / Erfahrungen mit der Versorgung der frischen Kreuzbandruptur bei Sportlern.

Since 1984 we have done over the top repair of the acutely torn anterior cruciate ligament combined with augmentation by McIntosh lateral-substitution over the top procedure with iliotibial band in view of frequent instabilities following simple reconstruction. After treatment by continuous passive motion and early weight bearing is possible. The results at review were good. This method is recommended to avoid the risk of rerupture.