Correction to: The protean world of non-coding RNAs in glioblastoma

Journal of Molecular Medicine -     

Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

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The association of early postoperative desaturation in the operating theatre with hospital discharge to a skilled nursing or long-term care facility

It is unclear which criteria should be used to define readiness for tracheal extubation in the operating theatre. We studied the effects of desaturation in the operating theatre immediately after tracheal extubation on long-term outcomes. Performing a pre-specified, retrospective analysis of 71,025 cases involving previously independent adults undergoing non-cardiac surgery, we evaluated the association between desaturation events (oxygen saturation < 90%) within 10 min of tracheal extubation and adverse discharge (to a skilled nursing facility or long-term care facility). A total of 404 (12.3%) cases with, and 5035 (7.4%) cases without, early postoperative desaturation had an adverse discharge. Early postoperative desaturation was associated with higher odds of being discharged to a nursing facility (adjusted odds ratio 1.36 (95%CI 1.20–1.54); p < 0.001). Increased duration of desaturation augmented the effect (p for trend < 0.001). Desaturation was associated with a higher risk of respiratory, renal and cardiovascular complications as well as increased duration of hospital stay, postoperative intensive care unit admission frequency and cost. Several modifiable factors were associated with desaturation including: high intra-operative long-acting opioid administration; high neostigmine dose; high intra-operative inspired oxygen concentration; and low oxygen delivery immediately before tracheal extubation. There was substantial provider variability between anaesthetists in the incidence of postoperative desaturation unexplained by patient- and procedure-related factors. Early postoperative desaturation is a potentially preventable complication associated with a higher risk of adverse discharge disposition. Anaesthetists may consider developing guidelines to define tracheal extubation readiness that contain postoperative desaturation as an adverse outcome after tracheal extubation.     

Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice

Exendin-4 is now considered as a promising drug for the treatment of cerebral ischemia. To determine the neuroprotective effects of intranasal exendin-4, C57BL/6J mice were intranasally administered with exendin-4 daily for 7 days before middle cerebral artery occlusion (MCAO) surgery. Intranasally administered exendin-4 produced higher brain concentrations and lower plasma concentrations when compared to identical doses administered interperitoneally. Neurological deficits and volume of infarcted lesions were analyzed 24 h after ischemia. Intranasal administration of exendin-4 exhibited significant neuroprotection in C57BL/6 mice subjected to MCAO by reducing neurological deficit scores and infarct volume. The neuroprotective effects of exendin-4 were blocked by the knockdown of GLP-1R with shRNA. However, exendin-4 has no impact on glucose and insulin levels which indicated that the neuroprotective effect was mediated by the activation of GLP-1R in the brain. Exendin-4 intranasal administration restored the balance between pro- and anti-apoptotic proteins and decreased the expression of Caspase-3. The anti-apoptotic effect was mediated by the cAMP/PKA and PI3K/Akt pathway. These findings provided evidence that exendin-4 intranasal administration exerted a neuroprotective effect mediated by an anti-apoptotic mechanism in MCAO mice and protected neurons against ischemic injury through the GLP-1R pathway in the brain. Intranasal delivery of exendin-4 might be a promising strategy for the treatment of ischemic stroke.     

Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement

This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB) in converting poor learning mice to good learning ones. NaB, but not sodium formate, was found to upregulate plasticity-related molecules, stimulate NMDA- and AMPA-sensitive calcium influx and increase of spine density in cultured hippocampal neurons. NaB induced the activation of CREB in hippocampal neurons via protein kinase A (PKA), which was responsible for the upregulation of plasticity-related molecules. Finally, spatial memory consolidation-induced activation of CREB and expression of different plasticity-related molecules were less in the hippocampus of poor learning mice as compared to good learning ones. However, oral treatment of cinnamon and NaB increased spatial memory consolidation-induced activation of CREB and expression of plasticity-related molecules in the hippocampus of poor-learning mice and converted poor learners into good learners. These results describe a novel property of cinnamon in switching poor learners to good learners via stimulating hippocampal plasticity.     

Efficacy and safety of topical difluprednate in persistent diabetic macular edema

To evaluate the efficacy and safety of treatment of diabetic macular edema (persistent type) with difluprednate ophthalmic emulsion 0.05 % (off label use). 20 patients with persistent diabetic macular edema were enrolled. In all subjects, more than 4 months had passed since prior treatment. All patients were treated with difluprednate ophthalmic emulsion 0.05 % three times daily for 3 months. At the end of 3 months the visual acuity had increased by two lines to a mean value of 0.61 ± 0.18 on logMAR from a baseline value of 0.885 ± 0.20 and the central retinal thickness had decreased from 423 ± 72.04 microns to 345 ± 68.7 microns. Hence, there was a total of 18.4 % decrease in retinal thickness on difluprednate. Major side effects included raised intraocular pressure in 20 %. Difluprednate is a potent and strong steroid which causes a rapid decrease in persistent diabetic macular edema. However, the potential side effect of raised intraocular pressure limits its use as an adjuvant therapy in non-steroid responders.