Citations

Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates similar to TDP-43 and FUS, followed by bioinformatics to predict prion-like domains in a subset of them. We sequenced one of these genes, TAF15 , in patients with ALS and identified missense variants, which were absent in a large number of healthy controls. These disease-associated variants of TAF15 caused formation of cytoplasmic foci when expressed in primary cultures of spinal cord neurons. Very similar to TDP-43 and FUS, TAF15 aggregated in vitro and conferred neurodegeneration in Drosophila , with the ALS-linked variants having a more severe effect than wild type. Immunohistochemistry of postmortem spinal cord tissue revealed mislocalization of TAF15 in motor neurons of patients with ALS. We propose that aggregation-prone RNA-binding proteins might contribute very broadly to ALS pathogenesis and the genes identified in our yeast functional screen, coupled with prion-like domain prediction analysis, now provide a powerful resource to facilitate ALS disease gene discovery.

Interaction between the electrical system of implanted cardiovascular devices and electrical stimulation of acupuncture points (electro-acupuncture) can be life-threatening. As a result, there is reluctance to use this modality in patients who have been implanted with any cardiac device. A patient with a total artificial heart was successfully treated with electro-acupuncture for inflammatory arthritis without any adverse events. This case illustrates the safety of electro-acupuncture in patients with a total artificial heart.

Our objective was to examine the rate of revision and its predictive factors in patients undergoing total shoulder arthroplasty (TSA). We used prospectively collected data from the Mayo Clinic Total Joint Registry to examine five-, ten- and 20-year revision-free survival following TSA and the predictive factors. We examined patient characteristics (age, gender, body mass index, comorbidity), implant fixation (cemented versus uncemented), American Society of Anesthesiologists class and underlying diagnosis. Univariate and multivariable adjusted hazard rates were calculated using Cox regression analysis. A total of 2207 patients underwent 2588 TSAs. Their mean age was 65.0 years (19 to 91) and 1163 (53%) were women; osteoarthritis was the underlying diagnosis in 1640 shoulders (63%). In all, 212 TSAs (8.2%) were revised during the follow-up period. At five, ten and 20 years, survival rates were 94.2% (95% confidence interval (CI) 93.2 to 95.3), 90.2% (95% CI 88.7 to 91.7) and 81.4% (95% CI 78.4 to 84.5), respectively. In multivariable analyses men had a higher hazard ratio of revision of 1.72 (95% CI 1.28 to 2.31) (p < 0.01) compared with women, and those with rotator cuff disease had a hazard ratio of 4.71 (95% CI 2.09 to 10.59) (p < 0.001) compared with patients with rheumatoid arthritis. We concluded that male gender and rotator cuff disease are independent risk factors for revision after TSA. Future studies are needed to understand the biological rationale for these differences.