Natural killer (NK) cell tolerance to self is partly ensured by major histocompatibility complex (MHC) class I-specific inhibitory receptors on NK cells, which dampen their reactivity when engaged. However, NK cells that do not detect self MHC class I are not autoreactive. We used dynamic fluorescence correlation spectroscopy to show that MHC class I-independent NK cell tolerance in mice was associated with the presence of hyporesponsive NK cells in which both activating and inhibitory receptors were confined in an actin meshwork at the plasma membrane. In contrast, the recognition of self MHC class I by inhibitory receptors "educated" NK cells to become fully reactive, and activating NK cell receptors became dynamically compartmentalized in membrane nanodomains. We propose that the confinement of activating receptors at the plasma membrane is pivotal to ensuring the self-tolerance of NK cells.
The purpose of this study was to determine the most appropriate surgical treatment from three procedures used for fractures of the distal radius. In a retrospective comparative study, 166 out of 237 patients who underwent surgery for AO/ASIF A3 or C2 distal radius fractures were evaluated. Surgical procedures were external fixation or open reduction and internal fixation with either palmar or dorsal plates. Radiological outcomes were palmar tilt, radial angle, radial length and ulnar variance. Functional outcomes were range of motion and grip strength. In addition, outcomes according to Gartland and Werley and the Disabilities of the Arm, Shoulder and Hand questionnaire were compared. Further outcome criteria were the treatment time and the number of complications. Data were analysed using an analysis of variance statistical procedure respective of the chi2-test. Open reduction and internal fixation, in particular palmar plate fixation, demonstrated the best radiological and functional results. Subjective assessment of ORIF proved better than that of external fixation as treatment time was shorter and complications were more rarely seen. However, most of the differences between groups were not significant. Although there were no significant differences between groups, our data indicates that most dorsally displaced distal radius fractures can be treated successfully by open reduction and internal fixation. Palmar plate fixation seems to have slight advantages compared to both the external fixation and dorsal plate fixation surgical procedure.
Patients face significant limitations regarding general health after calcaneal fractures. The usual foot-scores measure only 2 dimensions of outcome: function and pain. To measure all dimensions of outcome, SF-36 is a better alternative.
We recently described a new neurodevelopmental syndrome (TAF1/MRXS33 intellectual disability [ID] syndrome) (MIM# 300966) caused by pathogenic variants involving the X-linked gene TATA-box binding protein associated factor 1 (TAF1), which participates in RNA polymerase II transcription. The initial study reported 11 families, and the syndrome was defined as presenting early in life with hypotonia, facial dysmorphia, and developmental delay that evolved into ID and/or autism spectrum disorder. We have now identified an additional 27 families through a genotype-first approach. Familial segregation analysis, clinical phenotyping, and bioinformatics were capitalized on to assess potential variant pathogenicity, and 450 |
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