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We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory., Psychology, Accepted Manuscript

Purpose: Although p53 is rarely mutated in ccRCC, its overexpression has been linked to poor prognosis. The current study sought to elucidate the unique role of p53 in ccRCC with genomic, proteomic, and functional analyses., Materials and Methods: Data from the Cancer Genome Atlas (TCGA) were evaluated for genomic and proteomic characteristics of p53; a tissue micro array (TMA) study was carried out to evaluate the association of p53 and phosphorylated p53 (pp53) with clinical outcome. Mechanistic in vitro experiments were performed to confirm a pro-apoptotic loss of p53 in ccRCC and p53 isoforms as well as posttranslational modifications of p53 where assessed to provide possible reasons for a functional inhibition of p53 in ccRCC., Results: A low somatic mutation rate of p53 could be confirmed. Although mRNA levels were correlated with poor prognosis and clinicopathological features, there was no monotonous association of mRNA levels with survival outcome. Higher p53 protein levels could be confirmed as poor prognostic features. In vitro, irradiation of ccRCC cell lines markedly induced levels of p53 and of activated (phosphorylated) p53. However, irradiated ccRCC cells demonstrated similar proliferation, migration, and p53 transcriptional activity like non-irradiated controls indicating a functional inhibition of p53. p53 isoforms and could not be correlated with clinical outcome of ccRCC patients., Conclusions: p53 is rarely mutated but the wildtype p53 is functionally inhibited in ccRCC. To investigate mechanisms that underlie functional inhibition of p53 may provide attractive therapeutic targets in ccRCC., (© 2021. The Author(s).)

In a prospective, randomized, open study, the therapeutic efficacy of a long-term prophylaxis with standard heparin (SH) was compared with that of low-molecular-weight heparin (LMWH) Dalteparin in 166 patients who had spinal fractures with spinal cord injury. 86 patients were treated with SH 2 x 7500 U s.c. and 80 patients were treated with LMWH 1 x 5000 anti-Xa U s.c. once daily. The screening was implemented by daily bedside-examination. In case of clinical thromboembolism-symptoms patients had confirmatory venography or lung scans. In the SH-group 12 (14.0%) patients had deep vein thrombosis and in the LMWH-group 6 (7.5%). Pulmonary embolism was detected two times in the SH-group (2.33%) and only one time in the LMWH-group (1.25%). A significant difference could not be shown, but is descriptive evident.

During 1988 to 1992 18 patients with spondylodiscitis and neurological deficits were treated in our clinic. Tuberculous spondylodiscitis was diagnosed in 4 patients and 14 suffered from non specific spondylodiscitis. The mean age was 59 years (range 25-77). 16 (89%) of the patients had risk factors like diabetes mellitus, genitourinary tract infection, respiratory tract infection, rheumatism, intervertebral disc operation and old spine fracture. MR-tomography revealed the most valuable diagnostic method. 14 patients with progressive spinal cord compression, and root lesions because of gross vertebral damage and epidural abscess underwent operative removal of the focus with intercorporal spondylodesis. Postoperative neurological examination revealed improvement in 7 and no changes in the other 7 patients. In 4 patients with non specific spondylodicitis and radicular deficits conservative treatment was performed and spontaneous interbody fusion without persisting neurological complaints occurred.