Notes

Endothelial GABBR2 Regulates Post-ischemic Angiogenesis through Curbing the particular Glycolysis Pathway.
To describe the detailed retinal phenotype ofKCNV2-associatedretinopathy.

Multicenter international retrospective case series.

Review of retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), including qualitative and quantitative analyses.

Three distinct macular FAF features were identified i) centrally increased signal (n=35, 41.7%), ii) DAF (n=27, 31.1%), and iii) ring of increased signal (n=37, 44.0%). Five distinct FAF groups were identified based on combinations of those characteristics, with 23.5% of patients changing FAF group over a mean (range) follow-up of 5.9 years (1.9-13.1 years). Qualitative assessment was performed by grading OCT into five grades (i) continuous EZ (20.5%), (ii) EZ disruption (26.1%), (iii) EZ absence, without optical gap and with preserved retinal pigment epithelium (RPE) complex (21.6%); iv) loss of EZ and an hyporeflective zone at the foveola (6.8%); and (v) outer retina and RPE complex loss (25.0%). Eighty-six patients had scrs of age.
To examine systemic associations of sarcoid uveitis and association with uveitis clinical phenotype and ethnicity.

Retrospective cross-sectional study.

A total of 362 subjects with definite or presumed sarcoid uveitis from Moorfields Eye Hospital, Royal Victorian Eye and Ear, and Auckland District Health Board.

Data were collected from the review of clinical notes, imaging, and investigations. Sarcoidosis was diagnosed in accordance with the International Workshop on Ocular Sarcoidosis guidelines.

Diagnosis of associated systemic disease secondary to sarcoidosis.

A total of 362 subjects with sarcoid uveitis were identified. Median age was 46 years, and 226 (62.4%) were female. Granulomatous anterior uveitis (47.8%), intermediate uveitis with snowballs (46.4%), and multifocal choroiditis (43.1%) were the most frequent clinical presentations, and disease was bilateral in 313 (86.5%). Periphlebitis was observed in 21.0%, and solitary optic nerve or choroidal granuloma in 11.3%. Lung parenchymal disean ethnicities require further investigation.
To study the impact of an oxygen management strategy incorporating oxygen saturation (SpO
) targeting and fraction of inspired oxygen monitoring on the incidence of retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and mortality.

This retrospective cohort study analyzed the incidence of any ROP, severe ROP, ROP requiring treatment (surgery and/or bevacizumab), BPD, and mortality among 23-28weeks of gestational age infants admitted to the neonatal intensive care unit in 3 epochs Epoch 1 (2007-2010) before implementation of SpO
histograms; Epoch 2 (2012-2014), with development of a software tool capable of generating automatic bedside SpO
histograms; and Epoch 3 (2016-2019), with further software enhancements, incorporating simultaneous SpO
and fraction of inspired oxygen measurements.

During Epochs 1, 2, and 3, there were 601, 381, and 550 eligible infants, respectively, for a total of 1532 eligible infants. Mortality, any ROP, severe ROP, ROP needing treatment, and BPD all showed significant downward trends across the 3 epochs. The aOR of mortality was significantly lower in Epoch 3 compared with Epoch 1 (aOR 0.48). The aORs of any ROP and of BPD were significantly lower in Epochs 2 and 3 compared with Epoch 1 (respectively, ROP aORs 0.53 and 0.38; BPD aOR 0.43 and 0.43). The aOR of ROP needing treatment was significantly lower in Epoch 3 compared with Epoch 1 (aOR 0.43).

We have demonstrated improvement in rates of mortality, any ROP, ROP requiring treatment, and BPD after implementation of a novel oxygen management strategy.
We have demonstrated improvement in rates of mortality, any ROP, ROP requiring treatment, and BPD after implementation of a novel oxygen management strategy.Dual orexinergic antagonists (DORAs) have been recently developed as a pharmacotherapy alternative to established hypnotics. Hypnotics are largely evaluated in preclinical rodent models in the dark/active period yet should be ideally evaluated in the light/inactive period, analogous to when sleep disruption occurs in humans. We describe here the hypnotic efficacy of DORA-22 in rodent models of sleep disturbance produced by cage changes in the light/inactive period. Rats were administered DORA-22 or the GABA receptor-targeting hypnotic eszopiclone early in the light period, then exposed to six hourly clean cage changes with measurements of NREM sleep onset latency. Both compounds initially promoted sleep (hours 1 and 2), with DORA-22 exhibiting a more rapid hypnotic onset; and exhibited extended efficacy, evident six hours after administration in a sleep latencies test. A common complaint concerning hypnotic use is lingering hypersomnolence, and this is a concern in pharmacotherapy of the elderly. A second study was designed to determine a minimal dose of DORA-22 which would initially promote sleep but exhibit minimal extended hypnotic effect.Animals were administered DORA-22, then exposed for six hours to a single cage previously dirtied by a conspecific, followed by return to home cage. EEG measures indicated that all DORA-22 doses largely promoted sleep in the first hour. The lowest dose (1 mg/kg) did not decrease sleep onset latency at the six-hour timepoint, suggesting no residual hypersomnolence. We described here DORA-22 hypnotic efficacy during the normal sleep period of nocturnal rats, and demonstrate that well-chosen (low) hypnotic doses of DORA-22 may be hypnotically effective yet have minimal lingering effects.When simultaneously performing asymmetrical movements with both hands, there is a tendency for the action of one limb to interfere with control of the other. Little is known about how sensory feedback influences interference. We conducted two experiments to determine how manipulating force feedback and visual feedback alter bimanual coordination during center-out reaching. In the adaptive experiment, asymmetrical reaching was induced by a visual feedback rotation for the right hand while the left hand operated under kinesthetic control (i.e., without visual feedback); in the non-adaptive experiment, asymmetrical reaching was induced by having participants move their right hand to rotated targets under veridical visual feedback, again with the left hand operating under kinesthetic control. In both experiments, we applied a spring resistive force to each hand, with different groups of participants experiencing 0 N/m, 30 N/m, or 60 N/m of resistance. In the adaptive experiment, interference increased with an increase in the force demands for movement in a dose-response fashion (i.e., the higher the resistive force, the larger the interference), but this result did not hold generally for the non-adaptive experiment. Our results indicate that adapting to a visuomotor perturbation may increase sensitivity to feedback gains, including to sensory information not present in the perturbation. Additionally, interference may reflect the application of an explicit strategy used for one limb to control the other, and the addition of an implicit adapting process may bolster this communication of motor information across motor cortices.The biological function and evolutionary history of protein-coding genes are not only written in their nucleotide sequences. The comparison of genomic contexts throughout different lineages may highlight genomic mechanisms in the generation of new protein families, while the conservation of gene clusters may unravel, for instance, metabolic pathways. Various tools and databases exist that allow for the analysis and comparison of genomic contexts, but each has its own limitations. Online databases allow for quick comparisons, but only for those genomes for which data were pre-calculated. More advanced tools may allow for the comparison of any genome, but are often limited to a given phylogenetic kingdom or provide only a snapshot of the genomic contexts without further information about the genes involved. Here, we introduce GCsnap, a flexible Python-based tool that allows for the interactive comparison of the genomic contexts of protein-coding genes from any genome at any taxonomic level, integrating them with functional and structural information. By connecting the output to different protein databases, users can navigate through the different genomic contexts from a simple interactive platform, facilitating the further analysis of the contexts found. GCsnap is not limited to a single input format, can perform batch jobs and accepts protein classification maps. Results are stored in detailed, human and machine-readable files, and customizable, publication-ready figures. GCsnap is freely available from https//github.com/JoanaMPereira/GCsnap and can be set up easily on any computer.Patients who undergo radical cystectomy (RC) are at elevated risk of venous thromboembolism and associated morbidity and mortality. Guidelines recommend extended thromboprophylaxis (ETP), typically with heparins, but adherence is low. Outside urology, low-dose apixaban has been used for postoperative ETP with success. learn more We describe our first experiences with low-dose apixaban for ETP after RC for bladder cancer. In our sample of 72 patients who underwent RC for cancer and subsequently received apixaban 2.5 mg twice daily for ETP, there were no symptomatic thromboembolic events and no major bleeding events. Other complication rates were in line with historical reports. Our experience with apixaban 2.5 mg twice daily for ETP after RC demonstrates safety and potential efficacy. A transition from injectable to oral thromboprophylaxis has the potential to improve adherence and patient satisfaction, while allowing the possibility of further extending prophylaxis beyond 28 d, which may be beneficial in selected patients. Further evaluation of apixaban for thromboprophylaxis in urologic cancer surgery is warranted. PATIENT SUMMARY Home injectable heparin is used for 4 weeks after bladder removal surgery to prevent blood clots. We evaluated our use of the oral medication apixaban for prevention of blood clots after bladder removal surgery and found that none of our patients had major bleeding events or symptomatic blood clots. We conclude that there should be further evaluation of the use of oral instead of injectable medication to prevent blood clots after urology surgery.
Pathological stage and grade of renal pelvis urothelial carcinoma (RPUC) are difficult to estimate before radical nephroureterectomy (RNU).

To examine tumor size as an independent predictor of muscle-invasive and/or non-organ-confined rates of RPUC at RNU.

Within the Surveillance, Epidemiology and End Results (SEER) database (2004-2016), we identified nonmetastatic RPUC at RNU.

First, we examined stage and grade distributions. Second, two separate univariable and subsequent multivariable logistic regression models (LRMs) were fitted to test the association between tumor size and the rate of (1) muscle-invasive or higher (pT2-4N0-2) and (2) non-organ-confined (pT3-4N0-2) RPUC at RNU.

Of 4657 patients, 3052 (65.5%) had pT2-4N0-2 and 2382 (51.2%) pT3-4N0-2 RPUC at RNU. The median tumor size was 3.7 cm (interquartile range 2.5-5.0). The high-grade RPUC rate ranged from 71.1% to 87.2% (p < 0.001) among SEER registries. Conversely, no differences were recorded for stage (p > 0.05) or tumor size (p = 0.
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