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Geisler Buur posted an update 6 months ago
Subgroup analysis in studies targeting the hemoglobin gene revealed a significant reduction in the persistence of gene-edited cells whether homology-directed repair or nonhomologous end-joining were used. No adverse side effects were reported. Significant heterogeneity in study design and outcome reporting was observed and the potential for bias was identified in all studies. CRISPR-Cas9 gene edited cells engraft similarly to unedited hematopoietic cells. Persistence of gene edited cells, however, remains a challenge and improved methods of targeting hematopoietic stem cells are needed. Reducing heterogeneity and potential risk of bias will hasten the development of informative clinical trials.Transmission of malaria-causing parasites to and by the mosquito relies on active parasite migration and constitutes bottlenecks in the Plasmodium life cycle. Parasite adaption to the biochemically and physically different environments must hence be a key evolutionary driver for transmission efficiency. To probe how subtle but physiologically relevant changes in environmental elasticity impact parasite migration, we introduce 2D and 3D polyacrylamide gels to study ookinetes, the parasite forms emigrating from the mosquito blood meal and sporozoites, the forms transmitted to the vertebrate host. We show that ookinetes adapt their migratory path but not their speed to environmental elasticity and are motile for over 24 h on soft substrates. In contrast, sporozoites evolved more short-lived rapid gliding motility for rapidly crossing the skin. Strikingly, sporozoites are highly sensitive to substrate elasticity possibly to avoid adhesion to soft endothelial cells on their long way to the liver. Hence, the two migratory stages of Plasmodium evolved different strategies to overcome the physical challenges posed by the respective environments and barriers they encounter.
Therapeutics exist to treat fibrotic lung disease in adults, but these have not been investigated in children. Defining biomarkers for pediatric fibrotic lung disease in children is crucial for clinical trials. Children with surfactant protein C (SFTPC) dysfunction mutations develop fibrotic lung disease over time. We evaluated chest computed tomography (CT) changes over time in children with SFTPC dysfunction mutations.
We performed an institutional review board-approved retrospective review of children with SFTPC dysfunction mutations. We collected demographic and clinical information. Chest CT scans were evaluated using visual and computerized scores. Chest CT scores and pulmonary function tests were reviewed.
Eleven children were included. All children presented in infancy and four children suffered from respiratory failure requiring mechanical ventilation. Those who performed pulmonary function tests had stable forced vital capacities over time by percent predicted, but increased forced vital capaclung growth. Ground glass opacities are the primary early imaging findings while fibrotic features dominate later. CT findings suggest the development of and increases in fibrotic features that may serve as potential biomarkers for antifibrotic therapeutic trials.
To validate an MR-compatible version of the ScandiDos Delta
Phantom+on a 0.35T MR guided linear accelerator (MR-Linac) system and to determine the effect of plan complexity on the measurement results.
36 clinical treatment plans originally delivered on a 0.35T MR linac system were re-planned on the Delta
Phantom+MR geometry following our clinical quality assurance (QA) protocol. The QA plans were then measured using the Delta
Phantom+MR and the global gamma pass rates were compared to previous results measured using a Sun Nuclear ArcCHECK-MR. Both 3%/3mm and 2%/2mm global gamma pass rates with a 20% dose threshold were recorded and compared. Plan complexity was quantified for each clinical plan investigated using 24 different plan metrics and each metric’s correlation with the overall 2%/2mm global gamma pass rate was investigated using Pearson correlation coefficients.
Both systems demonstrated comparable levels of gamma pass rates at both the 3%/3mm and 2%/2mm level for all plan complexity metriR has been validated for clinical use on a 0.35T MR-Linac with results being comparable to an ArcCHECK-MR system in use clinically for almost five years. Most plan complexity metrics did not correlate with lower 2%/2mm gamma pass rates using the ArcCHECK-MR but several metrics were found to be moderately correlated with lower 2%/2mm global gamma pass rates for the Delta4 Phantom+ MR.
Neurocognitive dysfunction has been associated with post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). However, although PTSD is often comorbid with MDD, there is little neurocognitive work to date on individuals who suffer from both PTSD and MDD. Here, we compared neurocognitive domains in individuals with PTSD, MDD, and comorbid PTSD and MDD with those of healthy controls.
Participants comprised of mothers enrolled in the Drakenstein Child Health Study, a study exploring child health determinants in the Drakenstein district, Western Cape. N=175 mothers (between 18 and 50years) were recruited and divided into 4 groups PTSD, MDD, PTSD with MDD, and healthy controls. Participants were assessed using the computerized NIH Toolbox, and paper and pencil neurocognitive tests. Domains assessed included executive function, memory, attention, learning, and processing speed.
Distinct patterns of neurocognitive dysfunction were observed in this sample. PTSD was associated with more intrusion errors and MDD was associated with delayed recall impairment, relative to healthy controls. PTSD with comorbid MDD was associated with processing speed impairments, relative to healthy controls, and monodiagnostic groups. No group differences were observed on measures of attention and executive function.
Distinct patterns of neurocognitive dysfunction were associated with diagnoses of MDD and PTSD. Greater anticipated dysfunction and impairment in comorbid PTSD and MDD was not observed, however. Lurbinectedin DNA modulator Further work is needed to replicate and extend these findings.
Distinct patterns of neurocognitive dysfunction were associated with diagnoses of MDD and PTSD. Greater anticipated dysfunction and impairment in comorbid PTSD and MDD was not observed, however. Further work is needed to replicate and extend these findings.
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