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001) or a better state of consciousness at admission (p=0.001) were associated with a higher probability of decannulation. Conclusions Fibrobronoscopy assessment of patency of airways and accurate evaluation of the state of consciousness using the CRS-R are relevant in this setting of care to better identify patients who are more likely to have the tracheostomy tube removed. These results may help clinicians choose the appropriate timing and intensity of rehabilitation interventions and plan for discharge.Many drug delivery systems rely on degradation or dissolution of the carrier material to regulate release. In cases where mechanical support is required during regeneration, this necessitates composite systems in which the mechanics of the implant are decoupled from the drug release profile. To address this need, we developed a system in which microspheres (MS) were sequestered in a defined location between two nanofibrous layers. This bilayer delivery system (BiLDS) enables simultaneous structural support and decoupled release profiles. To test this new system, PLGA (poly-lactide-co-glycolic acid) microspheres were prepared using a water-in-oil-in-water (w/o/w) emulsion technique and incorporated Alexa Fluor-tagged bovine serum albumin (BSA) and basic fibroblast growth factor (bFGF). These MS were secured in a defined pocket between two polycaprolactone (PCL) nanofibrous scaffolds, where the layered scaffolds provide a template for new tissue formation while enabling independent and local release from the co-delivered MS. Scanning electron microscopy (SEM) images showed that the assembled BiLDS could localize and retain MS in the central pocket that was surrounded by a continuous seal formed along the margin. Cell viability and proliferation assays showed enhanced cell activity when exposed to BiLDS containing Alexa Fluor-BSA/bFGF-loaded MS, both in vitro and in vivo. MS delivered via the BiLDS system persisted in a localized area after subcutaneous implantation for at least 4 weeks, and bFGF release increased colonization of the implant. BI3802 These data establish the BiLDS technology as a sustained in vivo drug delivery platform that can localize protein and other growth factor release to a surgical site while providing a structural template for new tissue formation.Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative brain disorders, primarily affecting the frontal and/or temporal lobes. Three main subtypes are recognised, each with distinct clinical and cognitive profiles behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). Subtype-specific cerebellar grey matter atrophy has been associated with cognitive dysfunction in FTD; however, the extent and severity of structural abnormalities in the cerebro-cerebellar circuits in these disorders has not been investigated. This study aimed to identify patterns of cerebellar white matter changes and their relations to cognitive deficits in the main FTD subtypes. Results revealed bilateral cerebellar white matter changes in all FTD subtypes compared with controls, with greater cerebellar white matter changes in bvFTD than SD and PNFA. Both afferent and efferent cerebellar pathways were associated with cognition. The profiles of the involvement of cerebellar pathways in cognition varied across FTD syndromes. In bvFTD, the output pathway of the cerebellum was only associated with measures of episodic memory. The input pathway was associated with measures of attention, working memory, visuospatial, episodic memory, executive function, and emotion. In SD, both the output and input pathways were associated with measures of working memory, language, and emotion. Finally, in PNFA, both the output and input pathway of the cerebellum were associated with attention, language, and executive function. Additionally, the input pathway was associated with working memory, visuospatial, and emotion. This study is the first to identify patterns of cerebellar white matter changes across FTD syndromes, which in turn relate to cognitive deficits. These findings extend our understanding of the cerebro-cerebellar networks and provide new insight into the role of cerebellar white matter in cognition.Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumour with an extremely poor prognosis due to its insidious initiation and a lack of therapeutic strategies. Resveratrol suppresses pancreatic cancer progression and attenuates pancreatitis by modulating multiple targets, including nuclear factor kappa B (NFκB) signalling pathways. However, the effect of resveratrol on pancreatic cancer initiation and its mechanisms remain unclear. In this study, we utilised the LSL-KrasG12D/+; Pdx1-Cre (KC) spontaneous pancreatic precancerous lesion mouse model to explore the anti-tumourigenesis mechanisms of resveratrol in vivo. In vitro acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasias (PanINs) formation assays were performed by pancreatic acinar cell 3-dimensional (3D) culture. Histopathological analysis was used to examine the pathological morphology of pancreatic tissues. Resveratrol prevented the progression of pancreatic precancerous lesions and inhibited the activation of NFκB signalling pathway-related molecules in KC mouse pancreatic tissues. In addition, resveratrol reduced the severity of cerulein-induced pancreatitis and the formation of ADM/PanINs in vivo and in vitro, which may be related to its effect on NFκB inactivation. Furthermore, pancreatic acinar 3D culture demonstrated that activation of the NFκB signalling pathway promoted the formation of ADM/PanINs in vitro, and this initiating effect of NFκB was blocked by resveratrol. Resveratrol slowed the tumourigenesis of pancreatic cancer by inhibiting NFκB activation.Background Medical decision-making is complex and involves a variety of decision criteria, many of which are universally recognised. However, decision-making analyses have demonstrated that certain decision criteria are not used uniformly among clinicians. Aim We describe decision criteria, which for various contexts are only used by a minority of decision makers. For these, we introduce and define the term "insular criteria". Methods 19 studies analysing clinical decision-making based on decision trees were included in our study. All studies were screened for decision-making criteria that were mentioned by less than three local decision makers in studies involving 8-26 participants. Results 14 out of the 19 included studies reported insular criteria. We identified 42 individual insular criteria. They could be intuitively allocated to seven major groups, these were comorbidities, treatment, patients' characteristics/preferences, caretaker, scores, laboratory and tumour properties/staging. Conclusion Insular criteria are commonly used in clinical decision-making, yet, the individual decision makers may not be aware of them.