Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive ...cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5'-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation.
For magnetically isotropic high-spin molecular nanomagnets containing 17 Fe3+ ions per molecule linked via oxide and hydroxide ions, packed in a crystallographic cubic symmetry, magnetothermal ...experiments suggest their potential use as sub-Kelvin magnetic refrigerants.
We study the magnetothermal properties of magnetically isotropic high-spin molecular nanomagnets containing 17 Fe3+ ions per molecule linked via oxide and hydroxide ions, packed in a crystallographic cubic symmetry. Low-temperature magnetization and heat capacity experiments reveal that each molecular unit carries a net spin ground state as large as S=35/2 and a magnetic anisotropy as small as D=−0.023K, while no magnetic order, purely driven by dipolar interactions, is to be expected down to very-low temperatures. These characteristics suggest that the Fe17 molecular nanomagnet can potentially be employed as a sub-Kelvin magnetic refrigerant.
PURPOSE: To report long-term anatomical and functional results after pars plana vitrectomy with peeling of the internal limiting membrane (ILM) for idiopathic macular hole.
DESIGN: Prospective, ...nonrandomized, consecutive series.
METHODS: Ninety-nine patients with a follow-up of at least 12 months were included. The surgical technique consisted of a standard pars plana vitrectomy, removal of the ILM, and an intraocular gas tamponade (15% hexafluoroethane C
2F
6 gas mixture) followed by head-down positioning for at least 5 days. Follow-up examinations included a clinical examination, Goldmann perimetry, optical coherence tomography, and static microperimetry using a Rodenstock scanning laser ophthalmoscope (SLO-105). Stimulus size was 0.2 degrees (Goldmann II), intensities employed were 0 and 12 dB. Twenty-degree fields were used for all tests.
RESULTS: Mean period of review was 32 months (median 34). Anatomic closure was achieved in 86 (87%) of 99 patients by one surgical procedure. Nine patients underwent a successful second operation with an improvement of visual acuity in 7 patients. The closure rate after two surgical interventions was 96%. Best-corrected visual acuity improved from a median of 20/100 preoperatively to a median of 20/40 postoperatively (
P < .001). An improvement of visual acuity was achieved in 94% of patients. In 13 of 99 patients (13%) a combined vitrectomy and cataract surgery with intraocular lens implant was performed; 72 patients (73%) underwent cataract surgery later. Ninety of 99 patients (91%) were pseudophakic on last presentation. Paracentral scotomata did not change in size, density, or shape over time. Its incidence was not correlated with the stage of the macular hole. No postoperative epiretinal membrane formation or late reopening of the macular hole was observed. One patient presented with a peripheral visual field defect after vitrectomy.
CONCLUSIONS: Macular hole surgery with peeling of the ILM without the use of adjuvants or ILM staining leads to good functional long-term results. Paracentral scotomata remained subclinical in most cases and may be due to a mechanical trauma of the nerve fiber layer.
With expanding potential clinical applications of functional magnetic resonance imaging (fMRI) it is important to test how reliable different measures of fMRI activation are between subjects and ...sessions and between centres. This study compared variability across 17 patients with multiple sclerosis (MS) and 22 age-matched healthy controls (HC) in 5 European centres performing an fMRI block design with hand tapping. We recruited subjects from sites using 1.5 T scanners from different manufacturers. 5 healthy volunteers also were studied at each of 4 of the centres. We found that reproducibility between runs and sessions for single individuals was consistently much greater than between individuals. There was greater run-to-run variability for MS patients than for HC. Measurements of maximum signal change (MSC) appeared to provide higher reproducibility within individuals and greater sensitivity to differences between individuals than region of interest (ROI) suprathreshold voxel counts. The variability in measurements between centres was not as great as that between individuals. Consistent with these observations, we estimated that power should not be reduced substantially with use of multi-, as opposed to single-, centre study designs with similar numbers of subjects. Multi-centre interventional studies in which fMRI is used as an outcome measure thus appear practical even when implemented in conventional clinical environments.
Objective:
This study investigated the percentage of patients who achieved hemostasis with 4-factor prothrombin complex concentrate (4-factor PCC) 35 U/kg. The primary end point was to determine the ...effect of 4-factor PCC 35 U/kg on bleeding progression, assessed using computed tomography.
Methods:
This was a retrospective, observational, single-center study conducted in patients with a major bleed admitted to a level 1 trauma center from May 1, 2013, to June 15, 2015, who received 4-factor PCC 35 U/kg for reversal of a direct factor Xa inhibitor taken prior to admission.
Results:
Thirty-three patients were included in the study, with 31 patients in the final analysis. The mean (standard deviation) age was 73 (14.8) years; 54.5% of patients were female. Of the 33 patients, 13 presented with a traumatic brain injury, 9 with an aneurysmal subarachnoid hemorrhage, 8 with an intracerebral hemorrhage, 1 with a gastrointestinal bleed, 1 with a hematoma with active extravasation, and 1 with an intra-abdominal bleed. The most frequently used direct factor Xa inhibitor was rivaroxaban (81.8%). Overall, 83.8% of patients achieved hemostasis with 4-factor PCC 35 U/kg. Progression of hemorrhage was observed in 4 patients on repeat computed tomography scan and 1 patient had continued surgical bleeding. No thromboembolic events were reported.
Conclusions:
Low-dose, 4-factor PCC 35 U/kg appeared to produce hemostasis in a majority of the patients. This may be an effective dosing regimen for anticoagulant reversal of factor Xa inhibitors in clinically bleeding patients.
Objective: Evaluation of long‐term functional outcome after macular hole surgery and its correlation with postoperative optical coherence tomography (OCT).
Methods: Before and after surgery a ...complete clinical examination and OCT were performed in 38 patients. Best corrected postoperative visual acuity (VA) was correlated to the following OCT parameters: preoperative base and minimum diameter of the hole, hole height, hole form factor, retinal thickness and nerve‐fibre layer measurements postoperatively, postoperative foveal contour, appearance of retinal pigment epithelium layer and photoreceptor layer.
Results: Over a mean follow up of 67 months, VA improved significantly (P = 0.01). Retinal thickness and retinal thickness and nerve‐fibre layer measurements of the operated eye did not differ from fellow eye. A negative correlation was seen between final VA and preoperative base diameter of the hole (r = −0.41, P = 0.02) and hole height (r = −0.45, P = 0.01). The correlation between hole form factor values and final VA (r = 0.36, P = 0.04) was weak. Appearance of the photoreceptor band was the only OCT parameter significantly correlating with final VA (r = −0.42, P = 0.01) and explaining the observed increase (r = −0.32, P = 0.05) in VA.
Conclusion: Appearance of the photoreceptor layer on postoperative OCT correlates to functional outcome and may help to explain cases of unsatisfactory postoperative VA despite successful hole closure.
To describe the impact of indocyanine green (ICG) staining of the internal limiting membrane (ILM) on the functional outcome of anatomically successful macular hole surgery by comparing consecutive ...patient series with and without ILM staining.
Eighteen consecutive patients who had undergone ICG-assisted vitrectomy (0.05%) for idiopathic macular hole were retrospectively analysed (visual acuity, gain in lines, Goldmann perimetry) and compared with two consecutive series of patients who had undergone macular hole surgery without the use of ICG immediately before (n=22) and after (n=17) the introduction of ICG in our institution. The osmolarity of the ICG solution applied was 275 mosmol, pH was 7.5.
Although there was no statistically significant difference in duration of preoperative symptoms (P>0.3) and preoperative visual acuity (P>0.5), the functional outcome in patients after ICG-assisted vitrectomy was significantly lower (P<0.001 for visual acuity). The incidence of visual field defects was 50% (9/18) in patients after ICG application.
Our findings suggest potential damage to the neurosensory retina in association with the intraoperative administration of the ICG solution. Whether this is caused by toxic effects of the dye itself, mechanical trauma to the retina or other mechanisms remains unknown.
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