Abstract Background Children with an obstetric brachial plexus injury (OBPI) can experience problems in the performance of meaningful activities such as writing, bimanual activities, and ...participation in sports and leisure activities. Aims To quantify the everyday functioning and participation of 7–8 year-old children with an OBPI, with special emphasis on writing, and to investigate associated characteristics. Methods Parents of children with an OBPI were sent a self-report questionnaire regarding the school performance, writing abilities, bimanual hand use, and participation in sports and leisure activities of their child, assessed with the Vineland Adaptive Behavior Scales (VABS sub-scale writing), the ABILHAND-kids, and the Children’s Assessment of Participation and Enjoyment (CAPE). Furthermore, questions were asked about socio-demographic variables, medical history, pain, and the use of assistive devices. Results Fifty three questionnaires were filled in (response 61%). According to the parents, 66% of their children were almost completely recovered, and 58% had a near normal arm function. Most of the children preferred to use their non-involved hand. More than 45% of the children complained about pain, and 39.6% had difficulties with writing, which resulted in a mean developmental delay of 8 months on the VABS sub-scale. Children with writing problems significantly more often had neurosurgery, were living with a single parent, more often received assistance at school, and had a significantly lower ABILHAND-kids score, compared to children with no writing problems. Conclusions Large percentages of 7–8 year-old children with an OBPI experience difficulties with writing and have musculoskeletal pain. Restrictions in participation were less pronounced.
The aggressive B-cell non-Hodgkin lymphomas diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are characterised by a high proliferation rate. The anaphase-promoting ...complex/cyclosome (APC/C) and its co-activators Cdc20 and Cdh1 represent an important checkpoint in mitosis. Here, the role of the APC/C and its co-activators is examined in DLBCL and MCL.
The expression and prognostic value of Cdc20 and Cdh1 was investigated using GEP data and immunohistochemistry. Moreover, the therapeutic potential of APC/C targeting was evaluated using the small-molecule inhibitor proTAME and the underlying mechanisms of action were investigated by western blot.
We demonstrated that Cdc20 is highly expressed in DLBCL and aggressive MCL, correlating with a poor prognosis in DLBCL. ProTAME induced a prolonged metaphase, resulting in accumulation of the APC/C-Cdc20 substrate cyclin B1, inactivation/degradation of Bcl-2 and Bcl-xL and caspase-dependent apoptosis. In addition, proTAME strongly enhanced the anti-lymphoma effect of the clinically relevant agents doxorubicin and venetoclax.
We identified for the first time APC/C as a new, promising target in DLBCL and MCL. Moreover, we provide evidence that Cdc20 might be a novel, independent prognostic factor in DLBCL and MCL.
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