Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system characterized by relapses and autoimmunity caused by antibodies against the astrocyte water ...channel protein aquaporin-4. Over the past decade, there have been significant advances in the biologic knowledge of NMOSD, which resulted in the IDENTIFICATION of variable disease phenotypes, biomarkers, and complex inflammatory cascades involved in disease pathogenesis. Ongoing clinical trials are looking at new treatments targeting NMOSD relapses. This review aims to provide an update on recent studies regarding issues related to NMOSD, including the pathophysiology of the disease, the potential use of serum and cerebrospinal fluid cytokines as disease biomarkers, the clinical utilization of ocular coherence tomography, and the comparison of different animal models of NMOSD.
The major problems for photocatalysts are the poor visible light-driven activity, separation process for the recycling of photocatalysts, and fast recombination of photoexcited carriers. We tried to ...solve these problems by the growth of Bi2WO6 flower nanostructures on the conductive wire mesh substrates, and the deposition of Ag nanoparticles on Bi2WO6 using a double-potentiostatic electrodeposition method to make the visible-light driven metal wire mesh/Ag-Bi2WO6 as an immobilized photocatalyst. Close contact among Bi2WO6 with Ag nanoparticle and metal wire mesh facilitated effective separation of photoexcited charges, leading to improved photocatalytic activities. The results of diffuse reflection spectra, electrochemical impedance spectra, and photocurrent response confirmed the enhanced charge separation and increased optical absorption by the decoration of Ag nanoparticles. The optimized wire mesh/Ag-Bi2WO6 photocatalyst exhibited a high visible-light driven activity. Rhodamine B was completely degraded within 60 min of irradiation. Three-dimensional flower-like Bi2WO6 nanostructure and wire-mesh structure of the substrate maximize the contact area between photocatalyst and the dye molecules. Decorated Ag nanoparticle extended the range of absorption wavelength from UV light to visible light region. The immobilized photocatalyst can be easily recycled and reused without centrifugation and filtration process.
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•‧3D metal wire mesh/Ag-Bi2WO6 was prepared as an immobilized photocatalyst.•‧Wire mesh/Ag-flower-like Bi2WO6 shows enhanced photocatalytic activity.•‧Introducing Ag nanoparticle and metal wire mesh facilitated separation of photoexcited charges.•‧The major active species generated in the photocatalyst are .•O2− and h+.•‧Immobilized photocatalysts can be easily reused without centrifugation or filtration.
Recently, multidrug resistance (MDR) has become a major clinical chemotherapeutic burden that robustly diminishes the intracellular drug levels through various mechanisms. To overcome the doxorubicin ...(Dox) resistance in tumor cells, we designed a hierarchical nanohybrid system possessing copper-substituted mesoporous silica nanoparticles (Cu-MSNs). Further, Dox was conjugated to copper metal in the Cu-MSNs framework through a pH-sensitive coordination link, which is acutely sensitive to the tumor acidic environment (pH 5.0–6.0). In the end, the nanocarrier was coated with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), a P-gp inhibitor-entrenched compact liposome net for obstructing the drug efflux pump. Copper ions in the framework synergize the antitumor activity of Dox by enhancing the intracellular reactive oxygen species (ROS) levels through a Fenton-like reaction-mediated conversion of hydrogen peroxide. Furthermore, intracellularly generated ROS triggered the apoptosis by reducing the cellular as well as mitochondrial membrane integrity in MDR cells, which was confirmed by the mitochondrial membrane potential (MMP) measurement. The advancement of the design and critical improvement of cytotoxic properties through free radical attack demonstrate that the proposed hierarchical design can devastate the MDR for efficient cancer treatment.
Robotic thoracoscopic surgery was first done in mainland China in 2009 and has gained popularity in the past few years. Here, we present the largest Chinese series of robotic lobectomy for ...early-stage non-small cell lung cancer (NSCLC) to date. We aimed to compare the perioperative outcomes of our three-arm robotic-assisted lobectomy (RAL3) and video-assisted lobectomy (VAL) for p-stage I NSCLC and report the approach of the robotic anatomic lobar resections of our center.
We retrospectively collected and analyzed the data of 1075 stage I NSCLC patients who underwent minimally invasive lobectomies (237 RAL3 cases and 838 VAL cases) by the same surgical team from May 2013 to April 2016. Propensity score matching (PSM) was used to minimize the bias between the two groups. Perioperative outcomes were analyzed.
Compared to the VALs, the RAL3s had more retrieved lymph nodes (LNs) (9.70
. 8.45, P=0.000), less POD1 drain (230.91
. 279.79 mL, P=0.001), shorter chest tube duration (3.84
. 4.33 d, P=0.003) and shorter postoperative length of stay (4.97
. 5.45 d, P=0.004), but a higher cost (¥93,244.84
. ¥67,055.82, P=0.000). No significant difference was observed between the RAL3 and VAL groups concerning the average skin-to-skin time (90.84
. 92.25 min, P=0.624), conversion rate (1.3%
. 0.87%, P=1.000) and prolonged postoperative hospital stay (PPHS) rate (3.0%
. 4.3%, P=0.694).
This study confirms that RAL3 is a safer and more effective technique than VAL for the treatment of early-stage NSCLC.
Acute lung injury (ALI) is characterised by severe pulmonary inflammation, alveolar-capillary barrier disruption, and pulmonary oedema. Therefore, establishing effective therapeutic targets for ALI ...prevention is crucial. The present study reports a novel function of RNF128 in regulating LPS-induced ALI. Severe lung damage and increased immune cell infiltration were detected in RNF128-deficient mice. In vitro experiments revealed that RNF128 inhibits neutrophil activation by binding to myeloperoxidase (MPO) and reducing its levels and activity. Moreover, RNF128 regulates alveolar macrophage activation and neutrophil infiltration by interacting with TLR4, targeting it for degradation, and inhibiting NF-κB activation, hence decreasing pro-inflammatory cytokines. Our results demonstrate for the first time that RNF128 is a negative regulator of MPO and TLR4 in neutrophils and alveolar macrophages, respectively. However, AAV9-mediated RNF128 overexpression alleviated lung tissue damage and reduced inflammatory cell infiltration. Thus, RNF128 is a promising therapeutic candidate for pharmacological interventions in ALI.
There are many COVID-19 vaccines currently available, however, Low- and middle-income countries (LMIC) still have large proportions of their populations unvaccinated. Decision-makers must decide how ...to effectively allocate available vaccines (e.g. boosters or primary series vaccination, which age groups to target) but LMIC often lack the resources to undergo quantitative analyses of vaccine allocation, resulting in ad-hoc policies. We developed Covid19Vaxplorer (https://covid19vaxplorer.fredhutch.org/), a free, user-friendly online tool that simulates region-specific COVID-19 epidemics in conjunction with vaccination with the purpose of providing public health officials worldwide with a tool for vaccine allocation planning and comparison. We developed an age-structured mathematical model of SARS-CoV-2 transmission and COVID-19 vaccination. The model considers vaccination with up to three different vaccine products, primary series and boosters. We simulated partial immunity derived from waning of natural infection and vaccination. The model is embedded in an online tool, Covid19Vaxplorer that was optimized for its ease of use. By prompting users to fill information through several windows to input local parameters (e.g. cumulative and current prevalence), epidemiological parameters (e.g basic reproduction number, current social distancing interventions), vaccine parameters (e.g. vaccine efficacy, duration of immunity) and vaccine allocation (both by age groups and by vaccination status). Covid19Vaxplorer connects the user to the mathematical model and simulates, in real time, region-specific epidemics. The tool then produces key outcomes including expected numbers of deaths, hospitalizations and cases, with the possibility of simulating several scenarios of vaccine allocation at once for a side-by-side comparison. We provide two usage examples of Covid19Vaxplorer for vaccine allocation in Haiti and Afghanistan, which had as of Spring 2023, 2% and 33% of their populations vaccinated, and show that for these particular examples, using available vaccine as primary series vaccinations prevents more deaths than using them as boosters.
Chronic health conditions are becoming increasingly prevalent. As part of chronic care, sharing patient-generated health data (PGHD) is likely to play a prominent role. Sharing PGHD is increasingly ...recognized as potentially useful for not only monitoring health conditions but for informing and supporting collaboration with caregivers and healthcare providers. In this paper, we describe a new design for the fine-grained control over sharing one's PGHD to support collaborative self-care, one that centers on giving people with health conditions control over their own data. The system, Data Checkers (DC), uses a grid-based interface and a preview feature to provide users with the ability to control data access and dissemination. DC is of particular use in the case of severe chronic conditions, such as spinal cord injuries and disorders (SCI/D), that require not just intermittent involvement of healthcare providers but daily support and assistance from caregivers. In this paper, after providing relevant background information, we articulate our steps for developing this innovative system for sharing PGHD including (a) use of a co-design process; (b) identification of design requirements; and (c) creation of the DC System. We then present a qualitative evaluation of DC to show how DC satisfied these design requirements in a way that provided advantages for care. Our work extends existing research in the areas of Human-Computer Interaction (HCI), Computer-Supported Cooperative Work (CSCW), Ubiquitous Computing (Ubicomp), and Health Informatics about sharing data and PGHD.
Previously, a web-based, patient-facing decision aid for lung cancer screening, shouldiscreen.com, was developed and evaluated. An initial evaluation was completed before the Medicare coverage ...decision and recruited a nondiverse sample of mostly former smokers, limiting the understanding of the potential effectiveness of the tool among diverse populations. This study evaluates shouldiscreen.com among African Americans in Metro Detroit.
Using insights obtained from participatory workshops in this population, content changes to shouldiscreen.com were implemented, and this modified version was evaluated with a before-after study. Measures included knowledge of lung cancer screening, decisional conflict, and concordance between individual preference and screening eligibility. Surveys occurred between April and July 2018. Participants were contacted 6 months after the survey to assess subsequent screening behaviors. Analysis took place in 2019.
Data were collected from 74 participants aged 45-77 years, who were current/former smokers with no history of lung cancer. The average knowledge score increased by 25% from 5.7 (SD=1.94) before to 7.1 (SD=2.30) after (out of 13 points). Decisional conflict was halved between before and after. Concordance between individual preference and eligibility for screening increased from 22% (SD=41) to 35% (SD=47). Half of the participants felt uncomfortable answering surveys electronically and requested paper versions.
The use of the tool led to small improvements in lung cancer screening knowledge and increased concordance with current recommendations. Additional design modifications and modes of information delivery of these decision aids should be considered to increase their efficacy in helping populations with lower educational attainment and computer literacy.
One of the hallmarks of cancer is increased cell proliferation. Measurements of cell proliferation by estimation of DNA synthesis with several radiolabeled nucleosides have been tested to assess ...tumor growth. Deoxycytidine can be phosphorylated by deoxycytidine kinase (dCK) and is incorporated into DNA. This study evaluated a radiofluorinated deoxycytidine analog, 5-18Ffluoro-2′-deoxycytidine (18FFdCyd), as a proliferation probe and compared it with 5-18Ffluoro-2′-deoxyuridine (18FFdUrd), 3′-deoxy-3'-18Ffluorothymidine (18FFLT), and 18Ffluorodeoxyglucose (18FFDG) in a tumor-bearing mouse model. 18FFdCyd was synthesized from two precursors by direct electrophilic substitution. The serum stability and partition coefficient of 18FFdCyd were evaluated in vitro. Positron emission topography (PET) imaging of Lewis lung carcinoma (LLC)-bearing mice with 18FFdCyd, 18FFdUrd, 18FFLT, and 18FFDG were evaluated. 18FFdCyd was stable in mouse serum and normal saline for up to 4 h. With all radiotracers except 18FFLT, PET can clearly delineate the tumor lesion. 18FFdCyd and 18FFdUrd showed high accumulation in the liver and kidney. The SUV and tumor-to-muscle (T/M) ratios derived from PET imaging of the radiotracers were 18FFDG > 18FFdCyd > 18FFdUrd > 18FFLT. Selective retention in tumors with a favorable tumor/muscle ratio makes 18FFdCyd a protential candidate for further investigation as a proliferation imaging agent.
•18FFdCyd was synthesized from two precursors by direct electrophilic substitution with high radiochemical purity.•PET imaging of tumor-bearing mice with 18FFdCyd, 18FFdUrd, 18FFLT, and 18FFDG were evaluated.•18FFdCyd was stable in mouse serum or normal saline for up to 4 h.•The SUV and tumor-to-muscle (T/M) ratios of the radiotracers were 18FFDG > 18FFdCyd > 18FFdUrd > 18FFLT.•Further investigation for tumor proliferation of 18FFdCyd was warranted.
The D3Q19 multi relaxation time (MRT) lattice Boltzmann model is adopted to simulate the instability phenomenon within a three-dimensional cavity at various depth–width aspect ratios ranging from 1 ...to 3. The computations are conducted on a single node multi graphic processing unit (GPU) system, consisting of three nVIDIA M2070 devices using OpenMP. Results show that transition takes place between 1750<Recr<1950, for cubic cavity and 1100<Recr<1450, for deep cavity flows with aspect ratio 2 and 3. This indicates that an increase of the depth–width aspect ratio would induce the transition at lower Reynolds number and is consistent with the previous results for two-dimensional cavities, though the critical Reynolds number is approximately 75% lower for three dimensional cavity.