Increased sleep fragmentation in experimental autoimmune encephalomyelitis

Sleep disturbance in patients with multiple sclerosis is prevalent and has multifactorial causes. In mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, we determined the dynamic changes of sleep architecture and the interactions between sleep changes and EAE symptoms. The changes of sleep patterns were mainly reflected by altered sleep stage distribution and increased sleep fragmentation. Increased waking and decreased non-rapid eye movement sleep occurred after EAE onset and persisted through the symptomatic phase. There also was increased sleep state transition, indicating a reduction of sleep cohesiveness. Furthermore, the extent of sleep fragmentation correlated with the severity of disease. This is the first study of sleep characteristics in EAE mice demarcating specific changes related to the autoimmune disorder without confounding factors such as psychosocial impact and treatment effects. The reduction of sleep efficiency and cohesiveness supports the notion that enhancing sleep might facilitate the recovery of mice from EAE, pertinent to the multimodality treatment of multiple sclerosis.     

Amelioration of Endotoxin-Induced Uveitis in Rabbit by Topical Administration of Tacrolimus Proglycosome Nano-Vesicles

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 h. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.     

Mathematical modeling of the impact of recirculation on exchange kinetics in tandem extracorporeal membrane oxygenation and therapeutic plasma exchange

Vascular access connection configurations during tandem extracorporeal membrane oxygenation (ECMO) and therapeutic plasma exchange (TPE) may impact exchange kinetics. In these tandem procedures, typically the TPE inlet line is proximal to the TPE return line with respect to blood flow in the ECMO device, maximizing the opportunity for replacement fluid homogenization within the ECMO circuit. However, if TPE inlet and return line connections are switched, recirculation—a phenomenon in which replacement fluid leaving the TPE return line is prematurely drawn into the TPE inlet line prior to satisfactory homogenization within the ECMO circuit—will occur. Such recirculation could diminish TPE efficacy in patients on ECMO and mitigate therapeutic benefits. Using a mathematical model of recirculation in tandem ECMO and TPE, we demonstrate that the predicted impact of recirculation is negligible and vascular access connection positioning does not appear to be a point of clinical concern with regard to TPE kinetics.     

Simulated Transfer of Liquids and Powders from Hands and Clothing to the Mouth

A series of laboratory experiments was carried out to assess transfer of liquids (vinegar) and powders (calcium acetate and magnesium carbonate) from hands, arms, gloves, respirators, clothing, and pens to the oral cavity or the perioral area (the area surrounding the mouth). Experiments were carried out with four volunteers. The donor area (the hands, arms, gloves, and so on) was loaded with a known mass of the test substance and was then brought into contact the receiver area (the oral cavity or the perioral area). The percentage of the substance on the donor that transferred to the receiver (the transfer efficiency or TE) was assessed using saliva samples and gauze wipes of the perioral area. Magnesium carbonate was measured on gauze and in saliva using inductively coupled plasma/atomic emission spectrometry. Calcium acetate and vinegar were measured using ion chromatography/electrochemical detection. Average transfer efficiencies were calculated for each substance and transfer scenario; these were compared using ANOVA and Kruskal-Wallis tests. Overall, direct transfer from the hands to the oral cavity was significantly higher (mean TE = 51.6) than indirect transfer from the hands to the oral cavity via the perioral area by licking the lips (mean TE = 11.5). The results suggested higher TEs for liquids than for solids and that hand-to-mouth TEs may increase with water solubility. Transfer from bare arms to the perioral area was higher than from arms covered by cotton sleeves for both liquids and powders. Although TE data are often required by models estimating exposure by inadvertent ingestion, relatively few published data are available. This study has provided evidence of some factors that may influence transfer of chemicals from hands or objects to the mouth (physical form, use of clothing, and so on) and has provided data that are essential for the development of predictive exposure models of inadvertent ingestion exposure.     

Cell attenuated porcine epidemic diarrhea virus strain Zhejiang08 provides effective immune protection attributed to dendritic cell stimulation

Since 2010, the porcine epidemic diarrhea coronavirus (PEDV) has caused significant damage to the global pork industry. However, classical PEDV vaccine strains only provide limited protection against emerging strains. In this study, we successfully isolated and attenuated the PEDV epidemic strain Zhejiang08, which was characterized by good cell adaptation and high-titer production 48 h post infection in Vero E6 cells. The attenuated virus induced a high level of virus-specific neutralizing antibodies until 120 days after immunization in piglets and provided complete protection when challenged with an emerging virus strain on day 14 post immunization. Moreover, the capability to activate dendritic cells (DCs) of this isolate was identified. Higher expression levels of IL-12 and IFN-γ were recorded in DCs after treatment with Zhejiang08 for 24 h. Furthermore, genome sequencing and phylogenetic analysis revealed high homology between the main antigen epitopes of Zhejiang08 and PEDV pandemic isolates following 2011. Combining the glycosylation site prediction results and their distribution within the spatial structure of the S protein, led to the conclusion that the observed more effective host immune response of Zhejiang08 compared to CV777 was possibly associated with a lack of the potential glycosylation site in the 296 amino acids of the S protein. In summary, we illustrated that the attenuated virus represents a promising vaccine candidate.     

Short‐term changes in chewing efficiency and subjective evaluation in normal dentate subjects after insertion of oral appliances with an occlusal flat table

Oral appliances with an occlusal flat table are used as treatment dentures. However, the short‐term effect of insertion of such oral appliances on chewing has not been reported. This study aimed to determine whether experimental and continuous insertion of oral appliances with an occlusal flat table has an effect on chewing efficiency and Oral Health Impact Profile (OHIP) in healthy participants. Ten participants each in the oral‐appliance and control (no oral‐appliance insertion) groups attended six data collection sessions for 5 consecutive days. Participants answered the OHIP questionnaire and underwent the chewing efficiency test. For each parameter, intergroup differences were investigated in terms of change from baseline to immediately after oral‐appliance insertion (0 hour; P < .05) and from 0 hour to 24, 48, 72 and 96 hours after oral‐appliance insertion (P < .05). There were significant differences between groups in the degree of change in chewing efficiency and OHIP scores for functional limitation, physical pain, physical disability and handicap from baseline to 0 hour (all, P < .001); among these, only OHIP scores for functional limitation and physical pain demonstrated significant differences in degree of change between the two groups at 96 hours after appliance insertion (P = .477 and .275, respectively). Differences between the two groups in the degree of change in other parameters were not significant. Insertion of oral appliances caused a decrease in chewing efficiency and an increase in OHIP scores. Continuous insertion improved functional limitation and physical pain within 96 hours.