Neutral Per- and Polyfluoroalkyl Substances, Butyl Carbitol, and Organic Corrosion Inhibitors in Aqueous Film-Forming Foams: Implications for Vapor Intrusion and the Environment.

Per- and polyfluoroalkyl substances (PFAS), butyl carbitol, and corrosion inhibitors are components of aqueous film-forming foams (AFFFs). Volatile (neutral) fluorotelomerization (FT)- and electrochemical fluorination (ECF)-based PFAS, butyl carbitol, and organic corrosion inhibitors were quantified in 39 military specification (MilSpec), non-MilSpec, and alcohol resistant-AFFF concentrates (undiluted) from 1974 to 2010. Fluorotelomer alcohols were found only in FT-based AFFFs and N-methyl- and N-ethyl-perfluoroalkyl sulfonamides, and sulfonamido ethanols were found only in ECF-based AFFFs. Neutral PFAS and benzotriazole, 4-methylbenzotriazole, and 5-methybenzotriazole occurred at mg/L levels in the AFFFs, while butyl carbitol occurred at g/L levels. Neutral PFAS concentrations in indoor air due to vapor intrusion of a nearby undiluted AFFF release are estimated to be anywhere from 2 to >10 orders of magnitude higher than documented background indoor air concentrations. Estimated butyl carbitol and organic corrosion inhibitor concentrations were lower than and comparable to indoor concentrations recently measured, respectively. The wide range of neutral PFAS concentrations and Henry's law constants indicate that field, soil-gas measurements are needed to validate the estimations. Co-discharged butyl carbitol likely contributes to oxygen depletion in AFFF-impacted aquifers and may hinder the natural PFAS aerobic biotransformation. Organic corrosion inhibitors in AFFFs indicate that these are another source of corrosion inhibitors in the environment.

Design and Control of an Upper Limb Bionic Exoskeleton Rehabilitation Device Based on Tensegrity Structure.

Upper limb exoskeleton rehabilitation devices can improve the quality of rehabilitation and relieve the pressure of rehabilitation medical treatment, which is a research hotspot in the field of medical robots. Aiming at the problems such as large volume, high cost, low comfort, and difficulty in promotion of traditional exoskeleton rehabilitation devices, and considering the lightweight, discontinuous, high flexibility, and high biomimetic characteristics of tensegrity structure, we designed an upper limb bionic exoskeleton rehabilitation device based on tensegrity structure. First, this article uses mapping methods to establish a mapping model for upper limb exoskeletons based on the tensegrity structure and designs the overall structure of upper limb exoskeletons based on the mapping model. Second, a bionic elbow joint device based on gear and rack was designed, and the stability of the bionic elbow joint was proved using the positive definite matrix method. This device can simulate the micro displacement between bones of the human elbow joint, improve the axial matching ability between the upper limbs and the rehabilitation device, and enhance the comfort of rehabilitation. Third, an impedance control scheme based on back propagation (BP) neural network was designed to address the low control accuracy of flexible structures and patient spasms. Finally, we designed the impedance control scheme of the PSO-BP neural network based on a fuzzy rehabilitation state evaluator. The experimental results show that the exoskeleton rehabilitation device has good flexion motion stability and assist ability and has significant advantages in volume and mobility. The control strategy proposed in this paper has high control precision and adaptive ability and has potential application value in the field of medical rehabilitation.

TME-Responsive Nanoplatform with Glutathione Depletion for Enhanced Tumor-Specific Mild Photothermal/Gene/Ferroptosis Synergistic Therapy.

Background: Triple negative breast cancer (TNBC) is one of the worst prognosis types of breast cancer that urgently needs effective therapy methods. However, cancer is a complicated disease that usually requires multiple treatment modalities. Methods: A tumor microenvironment (TME)-responsive PFC/TRIM37@Fe-TA@HA (abbreviated as PTFTH) nanoplatform was constructed by coating Fe3+ and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA) to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro. Once internalized into tumor cells through CD44 receptor-mediated active targeting, the HA shell of PTFTH would be preliminarily disassembled by hyaluronidase (HAase) to expose the Fe-TA metal-phenolic networks (MPNs), which would further degrade in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Fe3+ and PFC/TRIM37. Results: PTFTH showed good biocompatibility in vitro. On the one hand, the released Fe3+ could deplete the overexpressed glutathione (GSH) through redox reactions and produce Fe2+, which in turn converts endogenous H2O2 into highly cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). On the other hand, the local hyperthermia generated by PTFTH under 808 nm laser irradiation could not only improve CDT efficacy through accelerating the Fe2+-mediated Fenton reaction, but also enhance TRIM37-siRNA delivery for gene therapy (GT). The consumption of GSH and accumulation of •OH synergistically augmented intracellular oxidative stress, resulting in substantial tumor cell ferroptosis. Moreover, PTFTH possessed outstanding contrast enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) ability. Conclusion: This PTFTH based multiple-mode therapeutic strategy has successfully achieved a synergistic anticancer effect in vitro and has the potential to be translated into clinical application for tumor therapy in future.

The changes of IgE levels in type 2 inflammatory diseases after treatment of dupilumab: a systematic review and meta-analysis.

BACKGROUND: Dupilumab is approved for multiple type 2 inflammatory diseases. In the treatment procedure, the changes of IgE levels need further analysis. We evaluated the changes of IgE levels through meta-analysis, aiming to provide a more comprehensive result. RESEARCH DESIGN AND METHODS: Databases were searched to select eligible publications. After being included, study quality was assessed. The standardized mean difference (SMD) was used as an evaluation. RESULTS: Seven studies were included. At week 4, the level of IgE did not decrease significantly, with SMD = -0.12 (95%CI: -0.31, 0.07) (P > 0.05). At week 8, 12, 16, 24, and 52, the level of IgE decreased significantly, which was SMD = -0.26 (95%CI: -0.48, -0.03); -0.25 (95%CI: -0.32, -0.18); -0.49 (95%CI: -0.65, -0.33); -0.30 (95%CI: -0.38, -0.22); -0.40 (95%CI: -0.48, -0.32) (P < 0.05). In AD studies, with the increase of IgE levels, due to the decrease in the total dose of dupilumab, the efficacy index showed a decreasing trend. CONCLUSIONS: Levels of IgE can be significantly decreased in patients with dupilumab treatment. In AD patients, the efficacy was related to total dose; for patients with high IgE levels, efficacy may be better with the dose increased.

Medical Care at California Wildfire Incident Base Camps.

OBJECTIVE: The California Emergency Medical Services Authority manages and deploys California Medical Assistance Teams (CAL-MAT) to disaster medical incidents in the state. This analysis reviews diagnoses for ambulatory medical visits at multiple wildland fire incident base camp field sites in California during the 2020 fire season. METHODS: Clinical data without personal health information were extracted retrospectively from patient care records from all patients seen by a provider. Results were entered into Excel spreadsheets with calculation of summary statistics. RESULTS: During the 2020 fire season, CAL-MAT teams deployed 21 times for a total of 327 days to base camps supporting large fire incidents and cared for 1756 patients. Impacts of heat and environmental smoke are a constant factor near wildfires; however, our most common medical problem was rhus dermatitis (54.5%) due to poison oak. All 2020 medical missions were further complicated by prevention and management of coronavirus disease (COVID-19). CONCLUSIONS: There is very little literature regarding the acute medical needs facing responders fighting wildland fires. Ninety-five percent of clinical conditions presenting to a field medical team at the wildfire incident base camp during a severe fire season in California can be managed by small teams operating in field tents.

Remodeling of the tumor microenvironment using an engineered oncolytic vaccinia virus improves PD-L1 inhibition outcomes.

Immune checkpoint inhibitor (ICI) immunotherapies have vastly improved therapeutic outcomes for patients with certain cancer types, but these responses only manifest in a small percentage of all cancer patients. The goal of the present study was to improve checkpoint therapy efficacy by utilizing an engineered vaccinia virus to improve the trafficking of lymphocytes to the tumor, given that such lymphocyte trafficking is positively correlated with patient checkpoint inhibitor response rates. We developed an oncolytic vaccinia virus (OVV) platform expressing manganese superoxide dismutase (MnSOD) for use as both a monotherapy and together with anti-PD-L1. Intratumoral OVV-MnSOD injection in immunocompetent mice resulted in inflammation within poorly immunogenic tumors, thereby facilitating marked tumor regression. OVV-MnSOD administration together with anti-PD-L1 further improved antitumor therapy outcomes in models in which these monotherapy approaches were ineffective. Overall, our results emphasize the value of further studying these therapeutic approaches in patients with minimally or non-inflammatory tumors.

Procyanidin B2 protects against d-galactose-induced mimetic aging in mice: Metabolites and microbiome analysis.

To elucidate the possible mechanisms for the preventive effect of procyanidin B2 on aging, a combined analysis of metabolic profile and gut microbiome was carried out in the present study. The mimetic aged mice induced by d-galactose injection (500 mg/kg, sc daily), and the preventive group was fed with the diet plus 0.2% procyanidin B2. After 7 weeks of treatment, the spatial memory was assayed using the Morris water maze test. Procyanidin B2 significantly ameliorated the impaired memory and antioxidant abilities induced by d-galactose. Furthermore, metabolomics analysis of plasma based on LC/Q-TOF-MS demonstrated that phosphatidyl cholines, oleic acid, linoleic acid, carnitine, pantothenic acid, and taurocholic acid were significantly increased in the mice treated with procyanidin B2, and pyruvic acid, hydroxybutyric acid, hippuric acid, and cholic acid were decreased significantly. Together, gut microbiome analysis using Illumina sequencing showed that there were significant differences in the Firmicutes/Bacteroidetes ratio and abundance of Roseburia, Lachnospiraceae, and Bifidobacterium between the aging and supplemental procyanidin B2 groups. In summary, procyanidin B2 possessed potential prevention of the cognitive and oxidative impairment via the metabolic pathway regulation related to citrate cycle, fatty acid, and bile acid in the aged mice, accompanied by remodeling the gut flora.