Transnational Capacity Building Efforts in Global Neurosurgery: A Review and Analysis of Their Impact and Determinants of Success.

BACKGROUND: Neurosurgical capacity building efforts attempt to address the shortage of neurosurgeons and lack of neurosurgical capacity in low- and middle-income countries. This review sought to characterize neurosurgical capacity building efforts in low- and middle-income countries and the challenges they face, and identify factors that predict higher engagement, better training, and performance of high-impact activities. METHODS: A scoping review using PubMed and Embase databases was performed and relevant articles were identified. Programs were classified into 6 categories and the activities they performed were classified as having a high-, medium-, or mild impact on capacity. Programs were also classified using the Olivieri engagement and training criteria. RESULTS: Fifty-seven articles representing 42 unique efforts were included. The most important determinant of impact was a program's design and intent. Furthermore, 91% of training and twinning programs received high (class 2 or 3) engagement classifications compared to 17% of mission trips and training camps (P < 0.001); 91% of training and twinning programs received high training classifications compared to 64% of mission trips and training camps (P = 0.015); and 91% of training and twinning programs reported performing high-impact activities compared to 29% of mission trips and training camps (P < 0.001). CONCLUSIONS: Training and twinning programs are more engaged, offer better training, and are more likely to perform high-impact activities compared to mission trips and training camps, suggesting that these types of programs offer the greatest chance of producing substantial and sustainable improvements to neurosurgical capacity.

Fabrication and characterization of citral-loaded oil-in-water Pickering emulsions stabilized by chitosan-tripolyphosphate particles.

Citral-loaded oil-in-water Pickering emulsions were fabricated with chitosan-tripolyphosphate particles (CS-TPP Ps) as stabilizers using a high-shear rotor homogenizer. The influence of the contents of CS-TPP Ps on the physical and chemical properties of the Pickering emulsions was investigated at 40 °C for 14 days. The morphology and chemical stability of the citral-loaded Pickering emulsions were determined by laser diffraction, optical microscopy, confocal laser scanning microscopy and solid-phase microextraction-gas chromatography (SPME-GC). Results showed that the droplet size of the Pickering emulsions decreased from 14.4 to 11 µm as the concentration of CS-TPP Ps increased. The droplet size of the Pickering emulsion with 0.6% w/v CS-TPP Ps remained unchanged during storage. GC illustrated that the Pickering emulsion with 0.6% w/v CS-TPP Ps showed the best chemical stability, with 52.33% citral remaining after 14 days of monitoring. Overall, the encapsulation of citral in CS-TPP Ps Pickering emulsions enhanced its chemical stability in acidic surroundings.

Preparation and characterization of citral-loaded solid lipid nanoparticles.

Citral-loaded solid lipid nanoparticles (citral-SLNs) were prepared via a high-pressure homogenization method, using glyceryl monostearate (GMS) as the solid lipid and a mixture of Tween 80 (T-80) and Span 80 (S-80) at a weight ratio of 1:1 as the surfactant. The microstructure and properties of the citral-SLNs were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermal gravimetric analysis (TGA). The chemical stability of citral in the citral-SLNs was analyzed by solid-phase microextraction gas chromatography (SPME-GC). The GC results showed that 67.0% of the citral remained in the citral-SLN suspensions after 12 days, while only 8.22% remained in the control. Therefore, the encapsulation of citral in the solid lipid can enhance its stability in acidic surroundings.

Prefrontal Cortex-Mediated Impairments in a Genetic Model of NMDA Receptor Hypofunction Are Reversed by the Novel M1 PAM VU6004256.

Abnormalities in the signaling of the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) within cortical and limbic brain regions are thought to underlie many of the complex cognitive and affective symptoms observed in individuals with schizophrenia. The M1 muscarinic acetylcholine receptor (mAChR) subtype is a closely coupled signaling partner of the NMDAR. Accumulating evidence suggests that development of selective positive allosteric modulators (PAMs) of the M1 receptor represent an important treatment strategy for the potential normalization of disruptions in NMDAR signaling in patients with schizophrenia. In the present studies, we evaluated the effects of the novel and highly potent M1 PAM, VU6004256, in ameliorating selective prefrontal cortical (PFC)-mediated physiologic and cognitive abnormalities in a genetic mouse model of global reduction in the NR1 subunit of the NMDAR (NR1 knockdown [KD]). Using slice-based extracellular field potential recordings, deficits in muscarinic agonist-induced long-term depression (LTD) in layer V of the PFC in the NR1 KD mice were normalized with bath application of VU6004256. Systemic administration of VU6004256 also reduced excessive pyramidal neuron firing in layer V PFC neurons in awake, freely moving NR1 KD mice. Moreover, selective potentiation of M1 by VU6004256 reversed the performance impairments of NR1 KD mice observed in two preclinical models of PFC-mediated learning, specifically the novel object recognition and cue-mediated fear conditioning tasks. VU6004256 also produced a robust, dose-dependent reduction in the hyperlocomotor activity of NR1 KD mice. Taken together, the current findings provide further support for M1 PAMs as a novel therapeutic approach for the PFC-mediated impairments in schizophrenia.