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UnlabelledIncident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.IntroductionVertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.MethodsVF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.ResultsSixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017).ConclusionsThe incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

Background: Spinal cord injury without radiographic abnormality (SCIWORA) represents a traumatic myelopathy, either transient or permanent, that is not associated with visible vertebral fractures or ligamentous abnormalities on plain radiographs or CT. MRI has become essential in the diagnosis and evaluation of trauma patients and in predicting the long-term neurological outcome. Methods: The medical charts of 578 children with vertebral trauma at the Children's Hospital of Eastern Ontario and the Hospital for Sick Children were retrospectively reviewed. Results: Forty-five patients were identified as having traumatic myelopathy. Three of these patients had SCIWORA. Two sustained thoracic spinal cord injuries as a result of motor vehicle accidents and permanent neurological deficits. The third was involved in a sports-related injury and sustained a cervical spine injury that improved in 48 h. Conclusions: SCIWORA is uncommon. The serious neurological sequelae that can result from a missed diagnosis merit more attention in identifying a spinal lesion in children with traumatic myelopathy. MRI has played a valuable role in this respect and may be even more predictive of outcome than the presenting neurological findings. The SCIWORA acronym can be modified to SCIWONA (spinal cord injury without neuroimaging abnormality) in order to highlight the importance of MRI in the prognosis. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Comprehensive proteomic analysis is essential to elucidate molecular pathways and protein functions. Despite tremendous progress in proteomics, current studies still suffer from limited proteomic coverage and dynamic range. Here, we utilize micropillar array columns (µPACs) together with wide-window acquisition and the AI-based CHIMERYS search engine to achieve excellent proteomic comprehensiveness for bulk proteomics, affinity purification mass spectrometry and single cell proteomics. Our data show that µPACs identify ≤50% more peptides and ≤24% more proteins, while offering improved throughput, which is critical for large (clinical) proteomics studies. Combining wide precursor isolation widths of m/z 4-12 with the CHIMERYS search engine identified +51-74% and +59-150% more proteins and peptides, respectively, for single cell, co-immunoprecipitation, and multi-species samples over a conventional workflow at well-controlled false discovery rates. The workflow further offers excellent precision, with CVs <7% for low input bulk samples, and accuracy, with deviations <10% from expected fold changes for regular abundance two-proteome mixes. Compared to a conventional workflow, our entire optimized platform discovered 92% more potential interactors in a protein-protein interaction study on the chromatin remodeler Smarca5/Snf2h. These include previously described Smarca5 binding partners and undescribed ones including Arid1a, another chromatin remodeler with key roles in neurodevelopmental and malignant disorders., (© 2024. The Author(s).)

This work demonstrates the utility of high-throughput nanoLC-MS and label-free quantification (LFQ) for sample-limited bottom-up proteomics analysis, including single-cell proteomics (SCP). Conditions were optimized on a 50 μm internal diameter (I.D.) column operated at 100 nL/min in the direct injection workflow to balance method sensitivity and sample throughput from 24 to 72 samples/day. Multiple data acquisition strategies were also evaluated for proteome coverage, including data-dependent acquisition (DDA), wide-window acquisition (WWA), and wide-window data-independent acquisition (WW-DIA). Analyzing 250 pg HeLa digest with a 10-min LC gradient (72 samples/day) provided >900, >1,800, and >3,000 protein group identifications for DDA, WWA, and WW-DIA, respectively. Total method cycle time was further reduced from 20 to 14.4 min (100 samples/day) by employing a trap-and-elute workflow, enabling 70% mass spectrometer utilization. The method was applied to library-free DIA analysis of single-cell samples, yielding >1,700 protein groups identified. In conclusion, this study provides a high-sensitivity, high-throughput nanoLC-MS configuration for sample-limited proteomics.

Cross-linking mass spectrometry has become a powerful tool for the identification of protein-protein interactions and for gaining insight into the structures of proteins. We previously published MS Annika, a cross-linking search engine which can accurately identify cross-linked peptides in MS2 spectra from a variety of different MS-cleavable cross-linkers. In this publication, we present MS Annika 2.0, an updated version implementing a new search algorithm that, in addition to MS2 level, only supports the processing of data from MS2-MS3-based approaches for the identification of peptides from MS3 spectra, and introduces a novel scoring function for peptides identified across multiple MS stages. Detected cross-links are validated by estimating the false discovery rate (FDR) using a target-decoy approach. We evaluated the MS3-search-capabilities of MS Annika 2.0 on five different datasets covering a variety of experimental approaches and compared it to XlinkX and MaXLinker, two other cross-linking search engines. We show that MS Annika detects up to 4 times more true unique cross-links while simultaneously yielding less false positive hits and therefore a more accurate FDR estimation than the other two search engines. All mass spectrometry proteomics data along with result files have been deposited to the ProteomeXchange consortium via the PRIDE partner repository with the dataset identifier PXD041955.

Digital subtraction angiography provides excellent spatial and temporal resolution; however, it lacks the capability to depict the nonvascular anatomy of the brain and spinal cord.A review of the institutional database identified five patients in whom a new integrated fusion workflow of cross-sectional imaging and 3D rotational angiography (3DRA) provided important diagnostic information and assisted in treatment planning. These included two acutely ruptured brain arteriovenous malformations (AVM), a small superficial brainstem AVM after radiosurgery, a thalamic microaneurysm, and a spine AVM, and fusion was crucial for diagnosis and influenced further treatment.Fusion of 3DRA and cross-sectional imaging may help to gain a deeper understanding of neurovascular diseases. This is advantageous for planning and providing treatment and, most importantly, may harbor the potential to minimize complication rates. Integrating image fusion in the work-up of cerebrovascular diseases is likely to have a major impact on the neurovascular field in the future., (© 2023. The Author(s).)