Exploring the short linear motif-mediated protein-protein interactions of CrkL through ProP-PD.

Adaptor proteins play a pivotal role in cellular signaling mediating a multitude of protein-protein interaction critical for cellular homeostasis. Dysregulation of these interactions has been linked to the onset of various cancer pathologies and exploited by viral pathogens during host cell takeover. CrkL is an adaptor protein composed of an N-terminal SH2 domain followed by two SH3 domains that mediate interactions with diverse partners through the recognition of specific binding motifs. In this study, we employed proteomic peptide-phage display (ProP-PD) to comprehensively explore the short linear motif (SLiM)-based interactions of CrkL. Furthermore, we scrutinized how the binding affinity for selected peptides was influenced in the context of the full-length CrkL versus the isolated N-SH3 domain. Importantly, our results provided insights into SLiM-binding sites within previously reported interactors, as well as revealing novel human and viral ligands, expanding our understanding of the interactions mediated by CrkL and highlighting the significance of SLiM-based interactions in mediating adaptor protein function, with implications for cancer and viral pathologies.

Retrospective single-center historical comparative study between proGAV and proGAV2.0 for surgical revision and implant duration.

OBJECTIVE: Cerebrospinal fluid (CSF) diversion shunt systems remain to be the most common treatment for pediatric hydrocephalus. Different valve systems are used to regulate CSF diversion. Preventing complications such as occlusions, ruptures, malpositioning, and over- or underdrainage are the focus for further developments. The proGAV and proGAV2.0 valve system are compared in this retrospective study for revision-free survival and isolated valve revision paradigms. METHODS: In the first part of the study, the shunt and valve revision-free survival rates were investigated in a retrospective historical comparison design for a period of 2 years in which each valve was used as standard valve (proGAV: July 2012-June 2014; proGAV2.0: January 2015-December 2016) with subsequent 30-month follow-up period, respectively. In the second part of the study, the implant duration was calculated by detecting isolated valve (valve-only) revisions together with another valve explantation during the entire period of the first study and its follow-up period. RESULTS: Two hundred sixty-two patients (145 male and 117 female, mean age 6.2 ± 6.1 years) were included in the cohort of revision-free survival. During the 30-month follow-up period, 41 shunt revisions, including 27 valve revisions (shunt survival rate: 72.1%, valve survival rate: 81.6%) were performed in the proGAV cohort and 37 shunt revisions, including 21 valve revisions (shunt survival rate: 74.8% and valve survival rate: 85.0%) were performed in the proGAV2.0 cohort without showing statistically significant differences. In the second part of the study, 38 cases (mean age 4.0 ± 3.9 years) met the inclusion criteria of receiving a valve-only-revision. In those patients, a total of 44 proGAV and 42 proGAV2.0 were implanted and explanted during the entire study time. In those, a significantly longer implant duration was observed for proGAV (mean valve duration 961.9 ± 650.8 days) compared to proGAV2.0 (mean length of implantation period 601.4 ± 487.8 days; p = 0.004). CONCLUSION: The shunt and valve revision-free survival rates were found to be similar among the groups during 30 month follow-up. In patients who received "valve only" revisions and a subsequent explanation, the implant duration was significantly longer in the proGAV. Although the amount of patients with valve-only-revisions are small compared to the entire cohort certain patients seem to be at higher risk for repeated valve revisions.

Biparietal meander expansion technique for sagittal suture synostosis in patients older than 1 year of age-technical note.

OBJECTIVE: Sagittal suture synostosis (SSS) is the most common form of craniosynostosis. For older patients, the strategy for surgical correction needs to consider diminished growth dynamics of the skull and an active reconstruction cranioplasty aims to sustain stability for the active child. We describe our technique of biparietal meander expansion (BME) technique for SSS for patients older than 1 year and retrospectively reviewed the perioperative course as well as the subjective experience of patients and caregivers during follow-up. METHODS: The BME technique incorporates bilateral serpentine craniotomies and fixation of the consecutively expanded bone tongues with crossing sutures for patients with SSS older than 12 months of age at surgery. We reviewed patients undergoing this surgical technique for correction of SSS and collected data about the clinical course and performed a patients reported outcome measure (PROM) for patients or caregivers to evaluate subjective experience and outcome after surgical treatment. RESULTS: BME was performed in 31 patients (8 females; median age: 43 months; range 13-388). The mean length of operation was 172.7±43 minutes (range 115-294). Patients experienced no immediate complications or neurological morbidity after surgery. Considering a total of 21 completed PROM questionnaires, the head shape after surgery was evaluated as either "better" (57%) or "much better" (43%) compared to preoperatively. Eighty-one percent of patients or caregivers answered that the patient experiences no limitation in daily activities. Although 42.8% perceived the hospital as strenuous, 90.5% would choose to undergo this treatment again. CONCLUSION: BME is a feasible technique for older SSS patients resulting in immediate stability of the remodelled calvarium with a more normal head shape. The survey among caregivers or patients revealed a favourable subjectively experienced outcome after this type of surgical treatment of SSS in the more complex context of an older patient cohort.