Threshold of Surface Initiator Concentration for Polymer Brush Growth by Surface-Initiated Atom Transfer Radical Polymerization.

The surface modification of various materials by grafting functional molecules has attracted much attention from fundamental research to practical applications because of its ability to impart various physical and chemical properties to the surfaces. One promising approach is the use of polymer brushes synthesized by atom transfer radical polymerization (ATRP) from surface-tethered initiators (SIs). In this study, for the purpose of controlling the grafting amounts/densities of polymer brushes, we developed a facile method to precisely regulate SI concentrations of SI layers (SILs) by serial dilution based on a sol-gel method. By simply mixing organosilanes terminated with and without an initiator group ((p-chloromethyl) phenyltrimethoxysilane (CMPTMS) and phenyltrimethoxysilane (PTMS), respectively) with tetraethoxysilane (TEOS), SI concentrations of SILs could be arbitrarily tuned precisely by varying dilution factors of (CMPTMS + PTMS)/CMPTMS (DFs, 1-107). The resulting SILs prepared at different DFs were highly smooth and transparent. X-ray photoelectron spectroscopy (XPS) also confirmed that the SIs were homogeneously distributed at the topmost surface of the SILs and their concentrations were proven to be accurately and precisely controlled from high to extremely low, comparable to theoretical values. Subsequent SI-ATRP in air ("paint-on" SI-ATRP) of two different types of monomers (hydrophobic/nonionic (2,3,4,5,6-pentafluorostyrene) and hydrophilic/ionic (sodium 4-styrenesulfonate)) demonstrated that polymer brushes with different grafting amounts/densities were successfully grafted only from SILs with DFs of 1-104 (theoretical SI concentrations: 3.9 × 10-4 ∼ 3.5 units/nm2), while at DFs of 105 and above (theoretical SI concentrations: <3.9 × 10-5 units/nm2), no sign of polymer brush growth was confirmed by thickness, XPS, and water contact angle data. Therefore, we are the first to gather evidence that the approximate threshold of SI concentration required for "paint-on" SI-ATRP might be on the order of 10-4 ∼ 10-5 units/nm2.

Evaluation of an immunochromatography-based rapid antigen test, Inspecter Kowa® SARS-CoV-2, using saliva specimens for the detection of SARS-CoV-2.

BACKGROUND: In the context of the coronavirus disease 2019 (COVID-19) pandemic, a rapid and reliable point-of-care test is an essential tool for controlling the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In particular, an immunochromatography test (ICT) that uses saliva specimens for rapid antigen detection not only reduces the risk of secondary infections but also reduces the burden on medical personnel. METHODS: The newly developed salivary antigen test kit "Inspecter Kowa® SARS-CoV-2" is an ICT to which saliva specimens can be directly applied. We evaluated its usefulness in comparison with reverse transcription quantitative PCR (RT-qPCR) and the Espline® SARS-CoV-2 Kit for the detection of SARS-CoV-2 using nasopharyngeal swab specimens. In this study, 140 patients with suspected symptomatic COVID-19 who visited our hospital were enrolled, and nasopharyngeal swab and saliva specimens were collected after they consented to participate in the study. RESULTS: Inspector Kowa SARS-CoV-2 was positive in 45 of 61 (73.8%) saliva that were positive by RT-qPCR and the Espline® SARS-CoV-2 Kit was also positive in 56 of 60 (93.3%) Np swabs that were positive by RT-qPCR. Good antigen detection was achieved by ICT with saliva and nasopharyngeal swab specimens when viral load was ≥105 copies/mL, whereas detection sensitivity was low when viral load was <105 copies/mL, especially in saliva specimens. CONCLUSION: This ICT for the detection of SARS-CoV-2 salivary antigen is an attractive tool that does not require specialized equipment and allows patients to perform the entire process from sample collection to self-diagnose and to reduce the burden on medical care during a pandemic.

Glycogen synthase kinase 3ß/CCR6-positive bone marrow cells correlate with disease activity in multicentric Castleman disease-TAFRO.

Multicentric Castleman disease-thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal dysfunction and organomegaly (MCD-TAFRO)-is an emergent phenotype characterized by lymphoproliferation, fluid collection, hemocytopenia and multiple organopathy. Although studies have demonstrated an aberrant blood cytokine/chemokine profile referred to as "chemokine storm", the pathogenesis remains unclear. We aimed to identify pathogenic key molecules, potential diagnostic targets and therapeutic markers in MCD-TAFRO using serum cytokine/chemokine profiles. We performed the targeted cytokine/chemokine multiplex analysis in six cases of MCD-TAFRO with remission or non-remission status. We observed significant changes in serum concentrations of CCL2, CCL5, and Chitinase-3-like-1 in the MCD-TAFRO patients with active state compared to inactive state. Ingenuity pathway analysis revealed that glycogen synthase kinase 3 (GSK3) and CCR6, which is expressed in megakaryocytes, were detected as upstream positive regulators for activating MCD-TAFRO status. More GSK3ß+ CCR6+ cells like megakaryocytes were detected in the bone marrow of patients with MCD-TAFRO than in those with systemic lupus erythematosus, MCD-not otherwise specified or autoimmune haemophagocytic lymphohistiocytosis. The cellularity of GSK3ß+ CCR6+ cells was correlated with disease activity, including thrombocytopenia and anaemia. In conclusion, GSK3ß and CCR6 of bone marrow cells were potentially involved in the pathogenesis of MCD-TAFRO and may act as diagnostic targets and therapeutic markers.

Transparent Composite Films Showing Durable Antifogging and Repeatable Self-Healing Properties Based on an Integral Blend Method.

Antifogging coatings for infrastructures and transparent objects have attracted much attention lately from the perspective of safety and visibility. We have developed a one-pot process to fabricate transparent composite films showing long-lasting antifogging and fast repeatable self-healing properties based on an integral blend (IB) method. This method does not require any specific pretreatments of inorganic fillers/particles. Thus, the precursor solutions could be prepared in a single step by simply mixing raw materials, e.g., poly(vinylpyrrolidone) (PVP) having different molecular weights (MWs: 55, 360, and 1300 k), nano-clay particles (NCPs), and amino-terminated organosilane (AOS). In this study, to control the degree of cross-linking between the PVP matrices and NCPs, addition of AOS as a cross-linker to the PVP matrices (weight percentage of AOS to the PVP matrices, α = 0.01-300%) was carefully controlled. Transparency and self-healing abilities/kinetics of the resulting samples were found to be strongly influenced by both the MWs of PVP and α values. Samples spin-coated with the lowest MW of PVP (55 k) and α values of 0.01-1% gave highly transparent and durable antifogging performance. For example, no fogging was observed for 7 days under >80% relative humidity, and scratches about 30 µm in width could be completely self-healed within a few hours. However, samples with α > 10% gave opaque/grayish films that did not show any self-healing abilities because of an increase in cross-linking of the matrices. The optimized precursor solution was also deposited directly onto the glass slides covered with a transparent porous silica nano-framework (SNF) by a spray-coating method. Due to the formation of the hard and superhydrophilic/hygroscopic SNF with a large surface area, durability of antifogging and self-healing properties of the composite films were moderately improved, compared to those on the flat glass slides.

Prognostic value of admission serum magnesium in acute myocardial infarction complicated by malignant ventricular arrhythmias.

OBJECTIVES: Although electrolyte abnormalities are related to worse clinical outcomes in patients with acute myocardial infarction (AMI), little is known about the association between admission serum magnesium level and adverse events in AMI patients complicated by out-of-hospital cardiac arrest presenting with malignant ventricular arrhythmias (OHCA-MVA). We investigated the prognostic value of serum magnesium level on admission in these patients. METHODS: We retrospectively analyzed the data of 165 consecutive reperfused AMI patients complicated with OHCA-MVA between April 2007 and February 2020 in our university hospital. Serum magnesium concentration was measured on admission. The primary outcome was in-hospital death. RESULTS: Fifty-four patients (33%) died during hospitalization. Higher serum magnesium level was significantly related to in-hospital death (Fine & Gray's test; p < 0.001). In multivariable logistic regression analyses, serum magnesium level on admission was independently associated with in-hospital death (hazard ratio 2.68, 95% confidence interval 1.24-5.80) even after adjustment for covariates. Furthermore, the incidences of cardiogenic shock necessitating an intra-aortic balloon pump (p = 0.005) or extracorporeal membrane oxygenation (p < 0.001), tracheal intubation (p < 0.001) and persistent vegetative state (p = 0.002) were significantly higher in patients with higher serum magnesium level than in those with lower serum magnesium level. CONCLUSIONS: In reperfused AMI patients complicated by OHCA-MVA, admission serum magnesium level might be a potential surrogate marker for predicting in-hospital death.

Large-Scale Formation of Fluorosurfactant-Doped Transparent Nanocomposite Films Showing Durable Antifogging, Oil-Repellent, and Self-healing Properties.

Transparent nanocomposite films with multiple functionalities, such as durable antifogging, dynamic oleophobic, self-healing properties, were successfully prepared by a simple spin- or spray-coating method using aqueous solutions of poly(vinylpyrrolidone) (PVP) and aminopropyl-functionalized nanoclay (AMP-clay) platelets. In this study, anionic/waterborne perfluorooctanesulfonic acid potassium salt (PFOS) was premixed with the aqueous PVP solution to achieve a homogeneous dispersion of PFOS. Due to the addition of PFOS, the resulting nanocomposite film surfaces displayed statically hydrophobic (static water contact angle over 90°) and dynamically oleophobic (5 µL of oil droplets could slide off of the surface at low sliding/substrate tilt angles of less than 10°) behaviors. In spite of our nanocomposite film surface exhibiting a statically hydrophobic nature, the antifogging properties remained unchanged even after being left under high-humidity conditions (over 80% relative humidity) for 3 days. Thanks to both exceptional water-absorbing properties of PVP/AMP-clay matrices and good mobility of PFOS driven by moisture, our oil-repellent nanocomposite films could be repeatedly self-healed even after both severe physical (cutting, scratching, or falling sand abrasion) and chemical (vacuum UV oxidation) damages. Large-scale fabrication of this multifunctional nanocomposite film (30 cm × 30 cm) could also be successfully demonstrated by a spray-coating method based on in situ gel formation.

Loss of the adhesion G-protein coupled receptor ADGRF5 in mice induces airway inflammation and the expression of CCL2 in lung endothelial cells.

BACKGROUND: Adhesion G-protein coupled receptor F5 (ADGRF5) was recently identified as an essential regulator of pulmonary surfactant homeostasis in alveolar type II cells. We previously showed that in addition to abnormal surfactant accumulation, Adgrf5-deficient (Adgrf5-/-) mice exhibit emphysema-like signs, suggesting a possible role for ADGRF5 in immune regulation. Here, we extended the phenotypic analysis of Adgrf5-/- mice to help understand its biological role in the lung, and especially in immune regulation. METHODS: Histological features of lungs were evaluated by Alcian blue and Masson's trichrome staining. Quantitative real-time PCR (qPCR) and western blot analyses were performed to analyze the differential expression of genes/proteins related to airway inflammation in lungs between wildtype and Adgrf5-/- mice. Acid-base status was assessed by performing blood gas tests and urine pH measurements. Inflammatory cell counting was performed using Giemsa-stained bronchoalveolar lavage cells. Serum IgE concentrations were determined by enzyme-linked immunosorbent assay. The expression of Ccl2, S100a8, S100a9, and Saa3 in primary lung endothelial cells (ECs) was determined by qPCR and/or western blotting. Finally, the effect of administrating RS504393 to 2-week-old Adgrf5-/- mice on gene expression in the lungs was analyzed by qPCR. RESULTS: Adgrf5-/- mice exhibited several features of chronic airway inflammation (mucous cell metaplasia, mucus hyperproduction, subepithelial fibrosis, respiratory acidosis, high serum IgE, mast cell accumulation, and neutrophilia) in parallel with elevated expression of genes involved in mucous cell metaplasia (Muc5ac, Muc5b, Slc26a4, and Clca1), fibrosis (Tgfb1, Col1a1, Fn1, and Tnc), and type 2 immune response (Il4, Il5, Il13, IL-25, and IL-33) at 12 and/or 30 weeks of age. In contrast, mRNA expression of Ccl2, S100a8, and S100a9 was upregulated in embryonic or neonatal Adgrf5-/- lungs as well as in lung ECs of Adgrf5-/- mice at 1 week of age. RS504393 treatment suppressed the upregulation of S100a8, S100a9, Slc26a4, and Il5 in Adgrf5-/- lungs. CONCLUSIONS: Targeted disruption of ADGRF5 results in the development of airway inflammation, which is likely mediated by the type 2 immune response and possibly CCL2-mediated inflammation. ADGRF5 also has a potential role in the regulation of genes encoding CCL2 in lung ECs, thereby maintaining immune homeostasis.

Smooth and Transparent Films Showing Paradoxical Surface Properties: The Lower the Static Contact Angle, the Better the Water Sliding Performance.

Smooth and transparent hydrophilic films showing excellent water sliding properties were prepared by using a sol-gel solution of 2-[methoxy (ethyleneoxy)10 propyl]trimethoxysilane and tetraethoxysilane. The resulting hybrid films were statically hydrophilic (static water contact angles (CAs) were in the range of 30-45°), but water droplets (50 µL) could move smoothly on an inclined surface (minimum sliding angle was 6°) without pinning or tailing because of low CA hysteresis (5 ± 1°). Thanks to this hybrid film formation on aluminum (Al) substrate, drainage performance during condensation and frosting/defrosting markedly improved compared to that on hydrophilic, bare Al, or hydrophobic monolayer-covered Al substrates.

Hydrosurgical debridement as an approach to wound healing: an animal thermal burn model.

OBJECTIVE: This study investigates the advantages of hydrosurgical debridement compared with surgical debridement. METHOD: Thermal skin burns were created on the backs of male Wistar rats. Surgical debridement was used to treat one wound and hydrosurgical debridement (Versajet Hydrosurgery System, Smith&Nephew, UK) used to treat the second wound. Debridement time, blood loss volume, time-to-heal and histologic changes in the wound areas were compared. RESULTS: A total of 23 rats were used in the study. Debridement time and time-to-heal were significantly shorter with hydrosurgical debridement than with surgical debridement (p<0.01 and p<0.05, respectively). Blood loss volume was significantly less with hydrosurgical debridement (p<0.01), and the wound surface area was significantly smaller on days two (p<0.01), four (p<0.05) and seven (p<0.05). Dense inflammatory cell infiltration into dermal muscle was deeper after surgical debridement (p=0.017). Reactive fibrotic tissue at the wound surface was significantly thinner (p<0.001) and the vascular endothelial cell count was significantly higher (p<0.001) after hydrosurgical debridement. CONCLUSION: The hydrosurgical system used appears to provide for minimally invasive debridement that can be performed in a relatively short period of time. Use of the device appears to minimise injury to healthy tissue and ameliorate inflammation, which in turn promotes early wound healing and reduces scar contracture. Hydrosurgical debridement appears to cause less damage to normal tissues. Furthermore, it is easier and requires less time.

Omniphobic Metal Surfaces with Low Contact Angle Hysteresis and Tilt Angles.

Various metal (Al, Ti, Fe, Ni, and Cu) surfaces with native oxide layers were rendered "omniphobic" by a simple thermal treatment of neat liquid trimethylsiloxy-terminated polymethylhydrosiloxanes (PMHSs) with a range of different molecular weights (MWs). Because of this treatment, the PMHS chains were covalently attached to the oxidized metal surfaces, giving 2-10 nm thick PMHS layers. The resulting surfaces were fairly smooth, liquid-like, and showed excellent dynamic omniphobicity with both low contact angle hysteresis (≲5°) and substrate tilt angles (≲8°) toward small-volume liquid drops (5 µL) with surface tensions ranging from 20.5 to 72.8 mN/m. Droplet mobility was improved overall as a result of heating the substrates to 70 °C. The reaction kinetics and final dynamic dewetting properties were found to be not dependent of the types of metals employed or MWs of PMHS, but mainly dominated by both reaction temperatures and reaction times.

Factors impairing cell proliferation in the granulation tissue of pressure ulcers: Impact of bacterial burden.

The authors aimed to assess the factors that impair cell proliferation in the granulation tissue of pressure ulcers using immunohistochemistry for the cell proliferation marker Ki-67. This was a single center, cross-sectional study. The study included 86 patients with stage III or IV pressure ulcers. Two granulation tissue biopsy specimens were obtained from 86 patients. The specimens were used for histological examination, Ki-67 immunohistochemistry, and bacterial count assessment. The % of Ki-67-stained cells was considered as the Ki-67 index. Pearson's product-moment correlation coefficient (r) was used to assess the relationship between the Ki-67 index and other quantitative variables, including age, body mass index, bacterial count (Log10 CFU/g), serum albumin level, hemoglobin level, white blood cell count, and C-reactive protein level. The Mann-Whitney U test was used to compare the mean Ki-67 index according to gender, diabetes, smoking status, and wound culture. Univariate and multivariate linear regression analyses were used to assess the association between the Ki-67 index and other parameters. The Mann-Whitney U test revealed that the bacteria-positive group had a lower Ki-67 index (p = 0.045). Bacterial count demonstrated a significant negative correlation with the Ki-67 index (r = -0.325, p = 0.002). Multivariate linear regression analysis showed that bacterial count was a significant predictor of the Ki-67 index. The adjusted ß-coefficient was -1.34 (95% confidence interval, -2.01 to -0.66, p < 0.001). Among the isolated bacteria, Corynebacterium spp. and Staphylococcus aureus were significantly associated with a low Ki-67 index, but Pseudomonas aeruginosa was not. These results suggest a negative relationship between bacterial count and cell proliferation in pressure ulcer granulation tissue, as indicated by the Ki-67 index. Granulation tissue formation in pressure ulcers may be accelerated if high bacterial load is treated appropriately.

Polyurethane-Based Ionogels Exhibiting Durable Thermoresponsive Optical Behavior Under High-Temperature Conditions.

Polyurethane (PU)-based transparent and flexible ionogels, showing unusual thermo-responsive optical properties, were successfully prepared by mixing PU-precursor and a hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (EMIM-TFSI). Although the initial ionogels were transparent at room temperature, significant increases in opacity were observed with increasing temperature up to 120°C, because of macroscopic phase separation of the PU-matrix and hydrophobic EMIM-TFSI. In addition, the optical transition temperature could be arbitrarily controlled simply by varying the mixing ratio of EMIM-TFSI within the PU-matrix. As confirmed by UV-Vis spectra acquired at different temperatures, this thermo-responsive optical behavior was found to be reversible, repeatable and durable even after 30 cycles of a thermal-stress testing between 30 and 100°C.

Self-Healing Superhydrophobic Materials Showing Quick Damage Recovery and Long-Term Durability.

Superhydrophobic coatings/materials are important for a wide variety of applications, but the majority of these man-made coatings/materials still suffer from poor durability because of their lack of self-healing ability. Here, we report novel superhydrophobic materials which can quickly self-heal from various severe types of damage. In this study, we used poly(dimethylsiloxane) (PDMS) infused with two liquids: trichloropropylsilane, which reacts with ambient moisture to self-assemble into grass-like microfibers (named silicone micro/nanograss) on the surfaces and low-viscosity silicone oil (SO), which remains within the PDMS matrices and acts as a self-healing agent. Because of the silicone micro/nanograss structures on the PDMS surfaces and the effective preserve/protection system of a large quantity of SO within the PDMS matrices, our superhydrophobic materials showed quick superhydrophobic recovery under ambient conditions (within 1-2 h) even after exposure to plasma (24 h), boiling water, chemicals, and outside environments. Such an ability is superior to the best self-healing superhydrophobic coatings/materials reported so far.

Zoledronic acid increases the circulating soluble RANKL level in mice, with a further increase in lymphocyte-derived soluble RANKL in zoledronic acid- and glucocorticoid-treated mice stimulated with bacterial lipopolysaccharide.

The nitrogen-containing bisphosphonate (BP) zoledronic acid (ZA) is a potent antiresorptive drug used in conjunction with standard cancer therapy to treat osteolysis or hypercalcemia due to malignancy. However, it is unclear how ZA influences the circulating levels of bone remodeling factors. The aim of this study was to evaluate the effects of ZA on the serum levels of soluble receptor activator of NF-kB ligand (sRANKL) and osteoprotegerin (OPG). The following four groups of C57BL/6 mice were used (five mice per group): (1) the placebo+phosphate-buffered saline (PBS) group, in which placebo-treated mice were injected once weekly with PBS for 4weeks; (2) the placebo+ZA group, in which placebo-treated mice were injected once weekly with ZA for 4weeks; (3) the prednisolone (PSL)+PBS group, in which PSL-treated mice were injected once weekly with PBS for 4weeks; and (4) the PSL+ZA group, in which PSL-treated mice were injected once weekly with ZA for 4weeks. At the 3-week time point, all mice were subjected to oral inflammatory stimulation with bacterial lipopolysaccharide (LPS). The sera of these mice were obtained every week and the levels of sRANKL and OPG were measured using enzyme-linked immunosorbent assay. At the time of sacrifice, femurs were prepared for micro-computed tomography (micro-CT), histological, and histomorphometric analyses. Our data indicated that ZA administration remarkably reduced bone turnover and significantly increased the basal level of sRANKL. Interestingly, the PSL+ZA group showed a dramatically elevated sRANKL level after LPS stimulation. In contrast, the PSL+ZA group in nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice), which are characterized by the absence of functional T- and B-lymphocytes, showed no increase in the sRANKL level. Our data suggest that, particularly with combination treatment of ZA and glucocorticoids, surviving lymphocytes might be the source of inflammation-induced sRANKL. Thus, circulating sRANKL levels might be modulated by ZA.

Ostectomy and Medial Plantar Artery Flap Reconstruction for Charcot Foot Ulceration Involving the Midfoot.

Charcot foot is a serious complication of diabetes, characterized by deformity and overlying ulceration. The condition most commonly affects the midfoot. However, little information is available on the use of a medial plantar artery flap to treat diabetic midfoot ulceration. The purpose of the present study was to evaluate the versatility of ostectomy and medial plantar flap reconstruction for midfoot plantar ulceration associated with rocker-bottom deformity secondary to Charcot foot. Four patients underwent ostectomy and medial plantar flap reconstruction. Before flap reconstruction, the devitalized soft tissues and bone were radically resected. After the infection had been controlled, the ulcerated portion was minimally excised, and the bony prominence underlying the ulcer was removed. A medial plantar artery flap was applied to the ulcer. The donor site was covered with a split-thickness skin graft or artificial dermis. In all patients, the ulcers healed and independent ambulation was achieved. However, 1 patient experienced ulcer recurrence, and subsequent infection necessitated a major amputation. Limb salvage is challenging in the setting of deformity and intractable plantar ulceration. The advantages of medial plantar artery flap reconstruction are that tissues with a rich blood supply are used to cover the exposed bone, and the flap can withstand the pressure and shear stress of the patient's body weight. However, a dominant artery in the foot is sacrificed. Therefore, the patency of the dorsalis pedis artery must be confirmed in every patient. The results of the present study have demonstrated that a medial plantar artery can be an effective alternative for diabetic patients with a plantar ulcer secondary to Charcot foot.