Barrypayne5806

Lithium has been used to treat major depressive disorder, yet the neural circuit mechanisms underlying this therapeutic effect remain unknown. Here, we demonstrated that the ventral tegmental area (VTA) dopamine (DA) neurons that project to the medial prefrontal cortex (mPFC), but not to nucleus accumbens (NAc), contributed to the antidepressive-like effects of lithium. Projection-specific electrophysiological recordings revealed that high concentrations of lithium increased firing rates in mPFC-, but not NAc-, projecting VTA DA neurons in mice treated with chronic unpredictable mild stress (CMS). In parallel, chronic administration of high-dose lithium in CMS mice restored the firing properties of mPFC-projecting DA neurons, and also rescued CMS-induced depressive-like behaviors. Nevertheless, chronic lithium treatment was insufficient to change the basal firing rates in NAc-projecting VTA DA neurons. Furthermore, chemogenetic activation of mPFC-, but not NAc-, projecting VTA DA neurons mimicked the antidepressive-like effects of lithium in CMS mice. Chemogenetic downregulation of VTA-mPFC DA neurons' firing activity abolished the antidepressive-like effects of lithium in CMS mice. Finally, we found that the antidepressant-like effects induced by high-dose lithium were mediated by BNDF signaling in the mesocortical DA circuit. Together, these results demonstrated the role of mesocortical DA projection in antidepressive-like effects of lithium and established a circuit foundation for lithium-based antidepressive treatment.Introduction Ceiling fans are a widespread energy-efficient appliance required for managing the sweltering weather extremes encountered in northern Australian states including Queensland. Ceiling fans are also a rare cause of serious head injury in children requiring neurosurgical intervention. There is limited available evidence on the presentation, mechanism, and management of these injuries. Methods A retrospective analysis of children who suffered ceiling fan injuries admitted to the Queensland Children's Hospital, a level-1 paediatric trauma hospital in Brisbane, Queensland, under the neurosurgery unit from November 2014 to July 2018 was performed. Results Seventeen children (64.7% male) with a mean age of 4.24 years (range 0.66-7.25) sustained ceiling fan injuries requiring neurosurgical management during this period. Children were injured following being accidentally lifted or thrown into the ceiling fan path; jumping, playing, climbing, or being pushed from a bunk bed; or climbing on other furniture. All patients suffered skull fractures (88.2% depressed), and 65% suffered extra-axial or intracerebral haemorrhage. Operative management was required in 76.5% of the patients. No patients suffered adverse outcomes, and no complications, including infections, were recorded. Conclusions Despite their rarity, paediatric ceiling fan injuries requiring neurosurgical management are a cause of significant morbidity. Surgical management targeted elevation of depressed fractures and washout of open fractures rather than evacuation of intracranial collections. Almost all included patients required transfer with associated social and economic implications. Such injuries are largely preventable with improved supervision and safety awareness. Hazard modification may be extended to regulatory changes or improved ceiling fan design.Background Smoking cessation programs for patients with cancer suggest 6-mo quit rates between 22% and 40%, and 1-y rates of 33%. selleck chemicals We sought to investigate the long-term outcomes of an intensive, preoperative smoking cessation program in patients undergoing lung resection. Material and methods A retrospective analysis of an IRB-approved, prospective database was performed. Elective lung resections between January 1, 2015 and June 30, 2017 were identified. Demographics, smoking status, pack years, occurrence of smoking cessation counseling, complications, and quit date were obtained. Smoking cessation included face-to-face motivational interviewing, choice of nicotine replacement therapy, discussion that surgery may be canceled or delayed without cessation, and follow-up as needed. Results A total of 340 patients underwent lung resection. Of these, 82 patients were classified as current smokers. All were advised to quit and encouraged to meet with a certified tobacco treatment specialist. Sixty-three patients met with a tobacco treatment specialist and 19 did not. Overall, 60 patients (73%) were able to quit before surgery. At 2 y postoperatively, 15 (18%) were lost to follow-up and 9 (11%) had died. Excluding deaths and censoring those lost to follow-up, cessation rates at 6, 12, and 24 mo postoperatively were 55.3%, 55.6%, and 51.7%, respectively. Conclusions Implementation of an intensive smoking cessation program in the preoperative period demonstrated high initial, mid-term, and long-term success rates. The preoperative period, particularly one centered around lung cancer, is an effective time for smoking cessation intervention and can lead to a high rate of cessation up to 2 y after surgery.Hydrogels are used in a wide range of biomedical applications, including three-dimensional (3D) cell culture, cell therapy and bioprinting. To enable processing using advanced additive fabrication techniques and to mimic the dynamic nature of the extracellular matrix (ECM), the properties of the hydrogels must be possible to tailor and change over time with high precision. The design of hydrogels that are both structurally and functionally dynamic, while providing necessary mechanical support is challenging using conventional synthesis techniques. Here, we show a modular and 3D printable hydrogel system that combines a robust but tunable covalent bioorthogonal cross-linking strategy with specific peptide-folding mediated interactions for dynamic modulation of cross-linking and functionalization. The hyaluronan-based hydrogels are covalently cross-linked using strain-promoted alkyne-azide cycloaddition using multi-arm poly(ethylene glycol). In addition, a de novo designed helix-loop-helix peptide was conjugated to the hyaluronan backbone to enable specific peptide-folding modulation of cross-linking density, cross-linking kinetics and functionality.