Trisomy 5 mosaicism in amniotic fluid with normal outcome

A case of prenatally diagnosed true mosaicism for trisomy 5 with a clinically normal outcome is presented. Trisomy 5 was detected in 23% of cells obtained by amniocentesis, but it was not detected from cells obtained by fetal blood sampling. While in this case the finding at amniocentesis did not reflect the status of the fetus, care must be exercised in reaching this conclusion in all cases.     

Paediatric surveillance: performance review and the primary care team

Primary care teams should state the aims of a preventive service and, through performance review, assess whether these aims have been achieved. The paediatric surveillance scheme in one practice is described, and the results of certain intermediate outcome measures are given.     

The intercorrelations between blood levels of ferritin,sCD163, and IL-18 in COVID-19 patients and their association to prognosis

Immunologic Research - Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation, severe respiratory failure, and multiple organ dysfunction caused by a cytokine storm involving...     

Secondary fusion proteins as a mechanism of BCR::ABL1 kinase-independent resistance in chronic myeloid leukaemia

Drug resistance in chronic myeloid leukaemia (CML) may occur via mutations in the causative BCR::ABL1 fusion or BCR::ABL1-independent mechanisms. We analysed 48 patients with BCR::ABL1-independent resistance for the presence of secondary fusion genes by RNA sequencing. We identified 10 of the most frequently detected secondary fusions in 21 patients. Validation studies, cell line models, gene expression analysis and drug screening revealed differences with respect to proliferation rate, differentiation and drug sensitivity. Notably, expression of RUNX1::MECOM led to resistance to ABL1 tyrosine kinase inhibitors in vitro. These results suggest secondary fusions contribute to BCR::ABL1-independent resistance and may be amenable to combined therapies.     

Crystal structure of the TSH receptor (TSHR) bound to a blocking-type TSHR autoantibody

A complex of the TSH receptor extracellular domain (amino acids 22-260; TSHR260) bound to a blocking-type human monoclonal autoantibody (K1-70) was purified, crystallised and the structure solved at 1.9?? resolution. K1-70 Fab binds to the concave surface of the TSHR leucine-rich domain (LRD) forming a large interface (2565??(2)) with an extensive network of ionic, polar and hydrophobic interactions. Mutation of TSHR or K1-70 residues showing strong interactions in the solved structure influenced the activity of K1-70, indicating that the binding detail observed in the complex reflects interactions of K1-70 with intact, functionally active TSHR. Unbound K1-70 Fab was prepared and crystallised to 2.22?? resolution. Virtually no movement was observed in the atoms of K1-70 residues on the binding interface compared with unbound K1-70, consistent with 'lock and key' binding. The binding arrangements in the TSHR260-K1-70 Fab complex are similar to previously observed for the TSHR260-M22 Fab complex; however, K1-70 clasps the concave surface of the TSHR LRD in approximately the opposite orientation (rotated 155°) to M22. The blocking autoantibody K1-70 binds more N-terminally on the TSHR concave surface than either the stimulating autoantibody M22 or the hormone TSH, and this may reflect its different functional activity. The structure of TSHR260 in the TSHR260-K1-70 and TSHR260-M22 complexes show a root mean square deviation on all C(α) atoms of only 0.51??. These high-resolution crystal structures provide a foundation for developing new strategies to understand and control TSHR activation and the autoimmune response to the TSHR.     

Stand up for your health: Is it time to rethink the physical activity paradigm?

The area of physical activity and health research has been energised by the creation of a new paradigm: sedentary behaviour. Sedentary behaviour and physical activity are increasingly viewed as different constructs with independent effects on the disease process. The creation of the new sedentary behaviour paradigm is likely to have a significant impact on research and interventions aimed at the prevention and management of diabetes in the future. This article highlights the key concepts and implications of this new paradigm.