Construction of a 5G-based, three-dimensional, and efficiently connected emergency medical management system.

Background: Shenzhen is unique in its need for ad hoc responses to emergencies. The need for emergency medicine also demonstrates a trend of sustained growth. Objective: A three-dimensional and efficiently connected emergency medical management model using fifth generation mobile communication technology (5G) was established to improve the efficiency and level of management in emergency medicine. Method: A mixed-frequency band private network collaborative emergency treatment mode was built under daily emergency scenarios using 5G. The efficiency of a three-dimensional telemedicine treatment mode was tested using prehospital emergency medicine. Also, the feasibility of quickly establishing a temporary network information system using unmanned aerial vehicle (UAV) and/or high-throughput communication satellites under disaster-caused power outages and network interruptions was examined. A monitoring system was constructed for suspected cases using 5G amid public health emergencies, which raised the Emergency Department's efficiency and security in responding to the pandemic. Results: The three-dimensional rescue system supported by 5G showed that the radius of the emergency medical rescue services expanded from 5 to 60 km, and the cross-district emergency reaction time reduced from 1 h to <20 min. Thus, it was feasible to construct a communication network expeditiously with devices carried by UAV under disastrous scenarios. The system developed based on 5G could be used in managing suspected cases of public emergencies. Among the 134 suspected cases in the early stage of the pandemic, no nosocomial infection was detected. Conclusion: A three-dimensional, efficiently connected emergency medical management system based on 5G was constructed, following which the emergency rescue radius quickly expanded and the emergency response time reduced. Thus, with the aid of new technology, an emergency information network system was built expeditiously under specific scenarios, such as a natural disaster, and the level of management under public health emergencies advances. The confidentiality of patient information is a critical issue regarding the application of new technology.

Effects of sustained GABA releasing implants on pancreatic islets in mice.

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that is strongly and selectively synthesized in and secreted from pancreatic beta cells. Exogenously delivered GABA has been proposed to induce beta cell regeneration in type 1 diabetes, but these results have been difficult to replicate and may depend on the specifics of the animal model and drug delivery method used. Here, we developed a GABA-releasing ethylene-vinyl acetate polymer implant for sustained GABA delivery to the intraperitoneal space as an alternative to injected or oral GABA. We explored the effect of the GABA-releasing polymer implants compared to implanted osmotic pumps loaded with GABA on islet size in non-diabetic, outbred mice. We also attempted to monitor in vivo GABA release using HPLC on blood samples, but these measurements were confounded by high variability within treatment groups and unexpectedly high serum GABA levels in mice receiving GABA-negative implants. The ethylene-vinyl acetate polymer implants became heavily fibrosed with abdominal adhesion tissue, while the osmotic pumps had no macroscopic fibrosis. Histological analysis showed no significant effect of the sustained GABA delivery polymer or osmotic pumps on islet size, alpha cell to beta cell ratio, or the number of Ki67-positive islet cells. The GABA treatment time course was limited to two weeks due to the drug-release window of the polymer, while others reported islet-trophic effects of GABA after 10 to 12 weeks of treatment. In summary, our study is consistent with the concept that exogenous GABA administration does not significantly alter islet cell mass in non-diabetic CD-1 mice in the short-term. However, more data are needed including higher GABA doses and more prolonged treatment regimens for a better comparison with contrasting reports.

Protein Nanoparticle Charge and Hydrophobicity Govern Protein Corona and Macrophage Uptake.

Protein nanoparticles are biomaterials composed entirely of proteins, with the protein sequence and structure determining the nanoparticle physicochemical properties. Upon exposure to physiological or environmental fluids, it is likely that protein nanoparticles, like synthetic nanoparticles, will adsorb proteins and this protein corona will be dependent on the surface properties of the protein nanoparticles. As there is little understanding of this phenomenon for engineered protein nanoparticles, the purpose of this work was to create protein nanoparticles with variable surface hydrophobicity and surface charge and establish the effect of these properties on the mass and composition of the adsorbed corona, using the fetal bovine serum as a model physiological solution. Albumin, cationic albumin, and ovalbumin cross-linked nanoparticles were developed for this investigation and their adsorbed protein coronas were isolated and characterized by gel electrophoresis and nanoliquid chromatography mass spectrometry. Distinct trends in corona mass and composition were identified for protein nanoparticles based on surface charge and surface hydrophobicity. Proteomic analyses revealed unique protein corona patterns and identified distinct proteins that are known to affect nanoparticle clearance in vivo. Further, the protein corona influenced nanoparticle internalization in vitro in a macrophage cell line. Altogether, these results demonstrate the strong effect protein identity and properties have on the corona formed on nanoparticles made from that protein. This work builds the foundation for future study of protein coronas on the wide array of protein nanoparticles used in nanomedicine and environmental applications.

Alginate/chitosan microparticles for gastric passage and intestinal release of therapeutic protein nanoparticles.

Enzymes with intracellular activity have significant potential to treat diseases. Protein nanoparticles (NPs) considerably enhance intracellular delivery of enzymes. We have previously shown that a Salmonella effector enzyme, AvrA, delivered by NPs is capable of modulating inflammatory signals in a murine dextran sulfate sodium (DSS) colitis model. The NPs were instilled intrarectally, limiting delivery to the distal colon. Localized intestinal delivery of protein therapeutics via the oral route is a highly attractive alternative approach. However, the harsh conditions in the gastrointestinal tract can severely reduce protein function. The approach described here is to deliver therapeutic protein NPs encapsulated within gastro-protective microparticles (MPs) made from alginate and chitosan that subsequently release NPs in the small intestine and colon. A flow focusing microfluidic device was used to form alginate droplets encapsulating protein NPs. Droplets were then simultaneously crosslinked with calcium and coated with chitosan. Protein NPs encapsulated within crosslinked alginate/chitosan MPs were protected and retained their activity after incubation in simulated gastric fluid (SGF). Subsequent incubation in simulated intestinal fluid (SIF) induced release of bioactive protein NPs. Oral administration of AvrA NPs encapsulated in alginate/chitosan MPs delivered protein to intestinal epithelia and reduced clinical and histological scores of inflammation in a murine DSS-induced colitis model. Altogether, NPs in alginate/chitosan MPs are a potential oral delivery vehicle for protein therapeutics.

Bioengineering Bacterially Derived Immunomodulants: A Therapeutic Approach to Inflammatory Bowel Disease.

Bacterial enteric pathogens have evolved efficient mechanisms to suppress mammalian inflammatory and immunoregulatory pathways. By exploiting the evolutionary relationship between the gut and pathogenic bacteria, we have developed a potential mucosal therapeutic. Our findings suggest that engineered preparations of the Salmonella acetyltransferase, AvrA, suppress acute inflammatory responses such as those observed in inflammatory bowel disease (IBD). We created 125 nm diameter cross-linked protein nanoparticles directly from AvrA and carrier protein to deliver AvrA in the absence of Salmonella. AvrA nanoparticles are internalized in vitro and in vivo into barrier epithelial and lamina propria monocytic cells. AvrA nanoparticles inhibit inflammatory signaling and confer cytoprotection in vitro, and in murine colitis models, we observe decreased clinical and histological indices of inflammation. Thus, we have combined naturally evolved immunomodulatory proteins with modern bioengineering to produce AvrA nanoparticles, a potential treatment for IBD.

Gender-specific total knee arthroplasty in Singaporean women.

PURPOSE: To compare the outcome of 145 women who underwent conventional total knee arthroplasty (TKA) with 77 women who underwent gender-specific TKA. METHODS: Records of 222 women who underwent primary TKA using a conventional (n=145) or gender-specific (n=77) size E or F prosthesis for end-stage osteoarthritis were reviewed. The gender-specific prosthesis has a narrower mediolateral dimension. Patients were assessed for flexion, Oxford Knee Score, Knee Society function and knee scores, and Short Form-36 Health Survey preoperatively and postoperatively (at 6 months and 2 years). RESULTS: The 2 groups were comparable in terms of age (67.8 vs. 68.1 years, p=0.789), body mass index (28.6 vs. 27.8 kg/m(2), p=0.189), and preoperative scores. 12 women with conventional TKA and 4 women with gender-specific TKA were lost to followup. Compared with women with conventional TKA, women with gender-specific TKA had better flexion at 6 months (116° vs. 121.9°, p=0.007) and 2 years (118.7° vs. 124.6°, p=0.006), better bodily pain score at 2 years (65.1 vs. 72.4, p=0.049), and greater improvement in bodily pain score from baseline to 2 years (30 vs. 38.5, p=0.034). CONCLUSION: Gender-specific TKA enables better knee flexion and less bodily pain in women who have a high propensity to develop mediolateral overhang of the femoral component.