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Background: Cochlear implants and hearing aids may facilitate the development of listening and spoken language (LSL) in deaf/hard of hearing young children, but they require aural rehabilitation therapy-often unavailable outside urban areas-for optimal outcomes. This trial assessed the relative effectiveness of LSL therapy delivered either in person or by interactive video. The hypothesis was that telehealth service delivery would be noninferior to in-person therapy. Methods: Most parents refused randomization of their children to telehealth or in-person conditions; therefore, randomization was impossible. In consultation with the funder (NIDCD), the study design was modified. Parents were allowed to select their preferred study condition, and the study team was blinded to group membership. Forty-two families were in the in-person group and 35 in telehealth (40 and 30, respectively, after attrition). Primary endpoints were total score, auditory comprehension, and expressive communication on the Preschool Language Scale, 5th edition. There were several secondary speech, hearing, and language outcome measures. Assessments occurred at baseline and at follow-up after 6 months of LSL therapy. Results: Propensity scores were used to create two matched groups. At baseline, groups did not differ on PLS-5 scores. Change from baseline to F/U on age-equivalents for all three scores was nearly identical for both groups, although the telehealth group was younger, on average, than the in-person group. Discussion: Telehealth was noninferior to in-person services for all primary endpoints. For secondary outcomes, neither group demonstrated a significant advantage. Magnitudes of estimated group differences were small, suggesting nonsignificant differences not predominantly because of sample size. The telehealth group showed greater improvement on 15/24 of secondary language outcome measures. The findings provide evidence that telehealth is equivalent to in-person care for providing LSL therapy to young children with cochlear implants and hearing aids.

In colloidal quantum dot light-emitting diodes (QD-LEDs), replacing organic hole transport layers (HTLs) with their inorganic counterparts is expected to yield distinct advantages due to their inherent material robustness. However, despite the promising characteristics of all-inorganic QD-LEDs, some challenges persist in achieving stable operation; for example, the electron overflow toward the inorganic HTL and charge accumulation within working devices return a temporal inconsistency in device characteristics. To address these challenges, we propose an operational approach that employs an alternating-current (AC) in all-inorganic QD-LEDs. We carry out comprehensive studies on the optoelectrical characteristics of all-inorganic QD-LEDs under direct-current (DC) or AC operation and demonstrate that AC operation can facilitate efficient charge carrier recombination within the QD emissive layer, leading to improved device efficiency and temporally invariant optoelectronic characteristics. Leveraging the intrinsic material robustness of inorganic charge transport layers (CTLs), our current study suggests a promising pathway toward enhancing the performance and stability of QD-LEDs, particularly for futuristic display applications.

Importance: Disparities persist across the trajectory of serious illness, including at the end of life. Patient navigation has been shown to reduce disparities and improve outcomes for underserved populations., Objective: To determine the effectiveness of a lay patient navigator intervention, Apoyo con Cariño, in improving palliative care outcomes among Hispanic patients., Design, Setting, and Participants: This was a multicenter randomized clinical trial that took place across academic, nonprofit, safety-net, and community health care systems in urban, rural, and mountain/frontier regions of Colorado from January 2017 to January 2021. Self-identifying Hispanic adults with serious noncancer medical illness and limited prognosis were recruited. Data were collected and analyzed from July 2022 to July 2023., Interventions: Participants randomized to the intervention group received 5 home visits from a bilingual, bicultural lay patient navigator; participants randomized to control received care as usual. Both groups received culturally tailored educational materials. Investigators/outcome accessors remained blinded to participant assignment., Main Outcomes and Measures: Change in score from baseline to 3 months on the Functional Assessment of Chronic Illness Therapy (FACIT) General quality of life (QOL) scale (primary outcome), Advance Care Planning (ACP) Engagement Survey, Brief Pain Inventory, Edmonton Symptom Assessment Scale, and FACIT Spiritual Well-Being subscale; at 6 months, advance directive (AD) documentation; and at 46 months or death, hospice utilization and length of stay, as well as aggressiveness of care at end of life., Results: Of 209 patients enrolled (mean [SD] age, 63.6 [14.3] years; 108 [51.7%] male), 105 patients were randomized to control and 104 patients to the intervention. There were no statistically significant differences in the change in mean (SD) QOL score between the intervention and control groups (5.0 [16.5] vs 4.3 [15.5]; P = .75). Participants in the intervention group, compared with the control group, had statistically significant greater increases in mean (SD) ACP engagement (0.8 [1.3] vs 0.1 [1.4]; P < .001) and were more likely to have a documented AD (62 of 104 [59.6%] vs 28 of 105 [26.9%]; P < .001). There were no statistically significant differences in mean (SD) change in pain intensity score (0-10) between patients in the intervention group compared with control (-0.4 [2.6] vs -0.5 [2.8]; P = .79), nor pain interference (-0.2 [3.7] vs -0.4 [3.7]; P = .71). Patients receiving the intervention were more likely to be referred to hospice compared with patients receiving control (19 of 43 patients [44.2%] vs 7 of 33 patients [21.2%]; P = .04) and less likely to receive aggressive care at end of life (27 of 42 patients [64.3%] vs 28 of 33 patients [84.8%]; P = .046)., Conclusion and Relevance: In this randomized clinical trial, a culturally tailored patient navigator intervention did not improve QOL for patients. However, the intervention did increase ACP engagement, AD documentation, and hospice utilization in Hispanic persons with serious medical illness., Trial Registration: ClinicalTrials.gov Identifier: NCT03181750.

Bone damage is a complex orthopedic problem primarily caused by trauma, cancer, or bacterial infection of bone tissue. Clinical care management for bone damage remains a significant clinical challenge and there is a growing need for more advanced bone therapy options. Nanotechnology has been widely explored in the field of orthopedic therapy for the treatment of a severe bone disease. Among nanomaterials, gold nanoparticles (GNPs) along with other biomaterials are emerging as a new paradigm for treatment with excellent potential for bone tissue engineering and regenerative medicine applications. In recent years, a great deal of research has focused on demonstrating the potential for GNPs to provide for enhancement of osteogenesis, reduction of osteoclastogenesis/osteomyelitis, and treatment of bone cancer. This review details the latest understandings in regards to GNPs based therapeutic systems, mechanisms, and the applications of GNPs against various bone disorders. The present review aims to summarize i) the mechanisms of GNPs in bone tissue remodeling, ii) preparation methods of GNPs, and iii) functionalization of GNPs and its decoration on biomaterials as a delivery vehicle in a specific bone tissue engineering for future clinical application., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This study evaluated the ameliorative effects of Korean-red-ginseng-derived polysaccharide (KRG-P) on antibiotic-associated diarrhea (AAD) induced by administering lincomycin in mice. Changes of intestinal barrier proteins, the intestinal microbiome and short-chain fatty acid (SCFA) contents were investigated. Lincomycin was orally administered for 9 days to induce diarrhea; subsequently, 100 mg/kg and 300 mg/kg of KRG-P were administered orally for 12 days. The diarrhea was observed in the AAD group; further KRG-P administration improved the diarrhea. Analysis of changes in the intestinal microbial flora of the mice revealed that the harmful bacterial flora (such as Proteobacteria) were increased in the AAD group, whereas beneficial bacterial flora (such as Firmicutes) were decreased. However, KRG-P administration resulted in decreased Proteobacteria and increased Firmicutes, supporting the improvement of the microbial flora imbalance caused by AAD. Moreover, an analysis of the SCFAs (acetic acid, propionic acid, and butylic acid) in the caecum revealed that SCFAs' contents in the AAD group were substantially reduced but tended to increase upon KRG-P administration. Based on these results, KRG-P, which is primarily composed of carbohydrates can improve lincomycin-induced diarrhea, likely owing to the recovery of SCFA content by improving the intestinal microbial imbalance and intestinal barrier proteins.

The synthesis of carbamoyl fluorides via visible-light induced DDQ catalysis of secondary amines is described. This protocol employs sodium trifluorosulfinate and molecular oxygen for the in situ generation of carbonyl difluoride, which is reacted with amines to afford the corresponding carbamoyl fluorides efficiently. Moreover, carbamoyl fluorides are easily transformed to synthetically useful carbonyl compounds under mild reaction conditions.

In this article, the development of fluorescent imaging probes for the detection of Alzheimer's disease (AD)-associated protein aggregates is described. Indane derivatives with a donor-π-acceptor (D-π-A) structure were designed and synthesized. The probes were evaluated for their ability to bind to β-amyloid (Aβ) protein aggregates, which are a key pathological hallmark of AD. The results showed that several probes exhibited significant changes in fluorescence intensity at wavelengths greater than 600 nm when they were bound to Aβ aggregates compared to the Aβ monomeric form. Among the tested probes, four D-π-A type indane derivatives showed promising binding selectivity to Aβ aggregates over non-specific proteins such as bovine serum albumin (BSA). The molecular docking study showed that our compounds were appropriately located along the Aβ fibril axis through the hydrophobic tunnel structure. Further analysis revealed that the most active compound having dimethylaminopyridyl group as an election donor and dicyano group as an electron acceptor could effectively stain Aβ plaques in brain tissue samples from AD transgenic mice. These findings suggest that our indane-based compounds have the potential to serve as fluorescent probes for the detection and monitoring of Aβ aggregation in AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Melanoma, a highly malignant and aggressive form of skin cancer, poses a significant global health threat, with limited treatment options and potential side effects. In this study, we developed a temperature-responsive hydrogel for skin regeneration with a controllable drug release. The hydrogel was fabricated using an interpenetrating polymer network (IPN) of N -isopropylacrylamide (NIPAAm) and poly(vinyl alcohol) (PVA). PVA was chosen for its adhesive properties, biocompatibility, and ability to address hydrophobicity issues associated with NIPAAm. The hydrogel was loaded with doxorubicin (DOX), an anticancer drug, for the treatment of melanoma. The NIPAAm-PVA (N-P) hydrogel demonstrated temperature-responsive behavior with a lower critical solution temperature (LCST) around 34 °C. The addition of PVA led to increased porosity and faster drug release. In vitro biocompatibility tests showed nontoxicity and supported cell proliferation. The N-P hydrogel exhibited effective anticancer effects on melanoma cells due to its rapid drug release behavior. This N-P hydrogel system shows great promise for controlled drug delivery and potential applications in skin regeneration and cancer treatment. Further research, including in vivo studies, will be essential to advance this hydrogel system toward clinical translation and impactful advancements in regenerative medicine and cancer therapeutics., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Half-bridge silicon strain gauges are widely used in the fabrication of diaphragm-type high-pressure sensors, but in some applications, they suffer from low output sensitivity because of mounting position constraints. Through a special design and fabrication approach, a new half-bridge silicon strain gauge comprising one arc gauge responding to tangential strain and another linear gauge measuring radial strain was developed using Silicon-on-Glass (SiOG) substrate technology. The tangential gauge consists of grid patterns, such as the reciprocating arc of silicon piezoresistors on a thin glass substrate. When two half-bridges are connected to form a full bridge with arc-shaped gauges that respond to tangential strain, they have the advantage of providing much higher output sensitivity than a conventional half-bridge. Pressure sensors tested under pressure ranging from 0 to 50 bar at five different temperatures indicate a linear output with a typical sensitivity of approximately 16 mV/V/bar, a maximum zero shift of 0.05% FS, and a span shift of 0.03% FS. The higher output level of pressure sensing gauges will provide greater signal strength, thus maintaining a better signal-to-noise ratio than conventional pressure sensors. The offset and span shift curves are quite linear across the operating temperature range, giving the end user the advantage of using very simple algorithms for temperature compensation of offset and span shift.

Ten traditional herbal extracts effective against diarrhea, infectious diseases, and bacterial activity were selected and analyzed for Peyer's patch cell-mediated intestinal immunomodulatory activity in vitro and in vivo . Among the 10 herbal extracts, Zingiber officinale Rosc. (ZO) extract induced the highest secretion of immunoglobulin A (IgA) and granulocyte macrophage colony-stimulating factor (GM-CSF) in the cells of Peyer's patches. Furthermore, animal experiments showed that IA production was enhanced with the oral administration of ZO extract (100 mg/kg and 300 mg/kg) for 10 days. In addition, 6-, 8-, 10-gingerol, and 6-, 8-, 10-shogaol, the six major index compounds of ZO extract, were analyzed using HPLC. Our study findings confirm the intestinal immunomodulatory activity of ZO extract and lay a strong foundation for future analytical studies aimed at determining the active components of ZO extracts.

TREK-1 (TWIK-related potassium channel-1) is a subunit of the two-pore domain potassium (K2p) channel and is widely expressed in the brain. TREK-1 knockout mice were shown to have antidepressant-like effects, providing evidence for the channel's potential as a therapeutic target. However, currently there is no good pharmacological inhibitor specifically targeting TREK-1 containing K2p channels that also displays similar antidepressant-like effects. Here, we sought to find selective and potent inhibitors for TREK-1 related dimers both in vitro and in vivo. We synthesized and evaluated 2-hydroxy-3-phenoxypropyl piperidine derivatives yielding a library from which many TREK-1 targeting candidates emerged. Among these, hydroxyl-phenyl- (2a), piperidino- (2g), and pyrrolidino- (2h) piperidinyl substituted compounds showed high potencies to TREK-1 homodimers with significant antidepressant-like effects in forced swim test and tail suspension test. Interestingly, these compounds were found to have high potencies to TWIK-1/TREK-1 heterodimers. Contrastingly, difluoropiperidinyl-4-fluorophenoxy (3e) and 4-hydroxyphenyl-piperidinyl-4-fluorophenoxy (3j) compounds had high potencies to TREK-1 homodimer but lower potency to TWIK-1/TREK-1 heterodimers without significant antidepressant-like effects. We observed positive correlation between inhibition potency to TWIK-1/TREK-1 and immobility time, and no correlation between inhibition potency to TREK-1 homodimer and immobility time. This was consistent with molecular docking simulations of selected compounds to TREK-1 homodimeric and TWIK-1/TREK-1 heterodimeric models. Existing antidepressant fluoxetine was also found to potently inhibit TWIK-1/TREK-1 heterodimers. Our study reveals novel potent TWIK-1/TREK-1 inhibitors 2a, 2g, and 2h as potential antidepressants and suggest that the TWIK-1/TREK-1 heterodimer could be a potential novel molecular therapeutic target for antidepressants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Organic liquid scintillation detectors are widely used to measure the presence of radiation. With these devices, there are advantages in that they are easy to manufacture, large in size, and have a short fluorescence decay time. However, they are not suitable for gamma spectroscopy because they are composed of a low-atomic-number material. In this regard, alternative materials for the secondary solute used in basic organic liquid scintillators have been investigated, and the applicability of alternative materials, the detection characteristics, and neutron/gamma identification tests were all assessed. 7-Diethylamino-4-methylcoumarin (DMC), selected as an alternative material, is a benzopyrone derivative in the form of colorless crystals with high fluorescence, a high quantum yield in the visible region, and excellent light stability. In addition, it has a large Stokes shift, and solubility in a solvent is good. Through an analysis in this study, it was found that the absorption wavelength range of DMC coincides with the emission wavelength range of PPO, which is the primary solute used with DMC. Finally, it was confirmed that the optimal concentration of DMC was 0.08 wt%. As a result of performing gamma and neutron measurement tests using a DMC-based liquid scintillator, it was found to perform well (FOM = 1.42) compared to a commercial liquid scintillator, BC-501A., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fused deposition modeling (FDM) is a three-dimensional (3D) printing technology typically used in tissue engineering. However, 3D-printed row scaffolds manufactured using material extrusion techniques have low cell affinity on the surface and an insufficient biocompatible environment for desirable tissue regeneration. Thus, in this study, plasma treatment was used to render surface modification for enhancing the biocompatibility of 3D-printed scaffolds. We designed a plasma-based 3D printing system with dual heads comprising a plasma device and a regular 3D FDM printer head for a layer-by-layer nitrogen plasma treatment. Accordingly, the wettability, roughness, and protein adsorption capability of the 3D-printed scaffold significantly increased with the plasma treatment time. Hence, the layer-by-layer plasma-treated (LBLT) scaffold exhibited significantly enhanced cell adhesion and proliferation in an in vitro assay. Furthermore, the LBLT scaffold demonstrated a higher tissue infiltration and lower collagen encapsulation than those demonstrated by a non-plasma-treated scaffold in an in vivo assay. Our approach has great potential for various tissue-engineering applications via the adjustment of gas or precursor levels. In particular, this system can fabricate scaffolds capable of holding a biocompatible surface on an entire 3D-printed strut. Thus, our one-step 3D printing approach is a promising platform to overcome the limitations of current biocompatible 3D scaffold engineering., (© 2023 IOP Publishing Ltd.)

Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. Epetraborole, a benzoxaborole, is a clinical candidate developed for Gram-negative infections and has been confirmed to exhibit favorable activity against a well known pulmonary pathogen, Mycobacterium abscessus. However, according to ClinicalTrials.gov, in 2017, a clinical phase II study on the use of epetraborole to treat complicated urinary tract and intra-abdominal infections was terminated due to the rapid emergence of drug resistance during treatment. Nevertheless, epetraborole is in clinical development for nontuberculous mycobacteria (NTM) disease especially for Mycobacterium avium complex-related pulmonary disease (MAC-PD). DS86760016, an epetraborole analog, was further demonstrated to have an improved pharmacokinetic profile, lower plasma clearance, longer plasma half-life, and higher renal excretion than epetraborole in animal models. In this study, DS86760016 was found to be similarly active against M. abscessus in vitro , intracellularly, and in zebrafish infection models with a low mutation frequency. These results expand the diversity of druggable compounds as new benzoxaborole-based candidates for treating M. abscessus diseases., Competing Interests: The authors declare no conflict of interest.

This study aimed to synthesize 23 coumarin derivatives and analyze their anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. A cytotoxicity test performed on LPS-induced RAW264.7 macrophages revealed that none of the 23 coumarin derivatives were cytotoxic. Among the 23 coumarin derivatives, coumarin derivative 2 showed the highest anti-inflammatory activity by significantly reducing nitric oxide production in a concentration-dependent manner. Coumarin derivative 2 inhibited the production of proinflammatory cytokines, including tumor necrosis factor alpha and interleukin-6, and decreased the expression level of each mRNA. In addition, it inhibited the phosphorylation of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, nuclear factor kappa-B p65 (NF-κB p65), and inducible nitric oxide synthase. These results indicated that coumarin derivative 2 inhibited LPS-induced mitogen-activated protein kinase and NF-κB p65 signal transduction pathways in RAW264.7 cells, as well as proinflammatory cytokines and enzymes related to inflammatory responses, to exert anti-inflammatory effects. Coumarin derivative 2 showed potential for further development as an anti-inflammatory drug for the treatment of acute and chronic inflammatory diseases.

Plant-derived extracellular nanovesicles contain RNA and proteins with unique and diverse pharmacological mechanisms. The extracellular nanovesicles encapsulating plant extracts resemble exosomes as they have a round, lipid bilayer morphology. Ginseng is anti-inflammatory, anti-cancer, immunostimulant, and osteogenic/anti-osteoporotic. Here, we confirmed that ginseng-derived extracellular nanovesicles (GDNs) inhibit osteoclast differentiation and elucidated the associated molecular mechanisms. We isolated GDNs by centrifugation with a sucrose gradient. We measured their dynamic light scattering and zeta potentials and examined their morphology by transmission electron microscopy. We used bone marrow-derived macrophages (BMMs) to determine the potential cytotoxicity of GDNs and establish their ability to inhibit osteoclast differentiation. The GDNs treatment maintained high BMM viability and proliferation whilst impeding osteoclastogenesis. Tartrate-resistant acid phosphatase and F-actin staining revealed that GDNs at concentrations >1 μg mL -1 strongly hindered osteoclast differentiation. Moreover, they substantially suppressed the RANKL-induced IκBα, c-JUN n-terminal kinase, and extracellular signal-regulated kinase signaling pathways and the genes regulating osteoclast maturation. The GDNs contained elevated proportions of Rb1 and Rg1 ginsenosides and were more effective than either of them alone or in combination at inhibiting osteoclast differentiation. In vivo bone analysis via microcomputerized tomography, bone volume/total volume ratios, and bone mineral density and bone cavity measurements demonstrated the inhibitory effect of GDNs against osteoclast differentiation in lipopolysaccharide-induced bone resorption mouse models. The results of this work suggest that GDNs are anti-osteoporotic by inhibiting osteoclast differentiation and are, therefore, promising for use in the clinical prevention and treatment of bone loss diseases.

Currently, silicon-strain-gauge-based diaphragm pressure sensors use four single-gauge chips for high-output sensitivity. However, the four-single-gauge configuration increases the number of glass frit bonds and the number of aluminum wire bonds, reducing the long-term stability, reliability, and yield of the diaphragm pressure sensor. In this study, a new design of general-purpose silicon strain gauges was developed to improve the sensor output voltage while reducing the number of bonds. The new gauges consist grid patterns with a reciprocating arc of silicon piezoresistors on a thin glass backing. The gauges make handling easier in the bonding process due to the use of thin glass for the gauge backing. The pressure sensors were tested under pressure ranging from 0 to 50 bar at five different temperatures, with a linear output with a typical sensitivity of approximately 16 mV/V/bar and an offset shift of -6 mV to 2 mV. The new approach also opens the possibility to extend arc strain gauges to half-bridge and full-bridge configurations to further reduce the number of glass frit and Al wire bonds in the diaphragm pressure sensor.

29 Si silica nanoparticles (SiO 2 NPs) are promising magnetic resonance imaging (MRI) probes that possess advantageous properties for in vivo applications, including suitable biocompatibility, tailorable properties, and high water dispersibility. Dynamic nuclear polarization (DNP) is used to enhance 29 Si MR signals via enhanced nuclear spin alignment; to date, there has been limited success employing DNP for SiO 2 NPs due to the lack of endogenous electronic defects that are required for the process. To create opportunities for SiO 2 -based 29 Si MRI probes, we synthesized variously featured SiO 2 NPs with selective 29 Si isotope enrichment on homogeneous and core@shell structures (shell thickness: 10 nm, core size: 40 nm), and identified the critical factors for optimal DNP signal enhancement as well as the effective hyperpolarization depth when using an exogenous radical. Based on the synthetic design, this critical factor is the proportion of 29 Si in the shell layer regardless of core enrichment. Furthermore, the effective depth of hyperpolarization is less than 10 nm between the surface and core, which demonstrates an approximately 40% elongated diffusion length for the shell-enriched NPs compared to the natural abundance NPs. This improved regulation of surface properties facilitates the development of isotopically enriched SiO 2 NPs as hyperpolarized contrast agents for in vivo MRI.

Background: Asthma exacerbations with respiratory failure (AERF) are associated with hospital mortality of 7% to 15%. Extracorporeal membrane oxygenation (ECMO) has been used as a salvage therapy for refractory AERF, but controlled studies showing its association with mortality have not been performed., Research Question: Is treatment with ECMO associated with lower mortality in refractory AERF compared with standard care?, Study Design and Methods: This is a retrospective, epidemiologic, observational cohort study using a national, administrative data set from 2010 to 2020 that includes 25% of US hospitalizations. People were included if they were admitted to an ECMO-capable hospital with an asthma exacerbation, and were treated with short-acting bronchodilators, systemic corticosteroids, and invasive ventilation. People were excluded for age < 18 years, no ICU stay, nonasthma chronic lung disease, COVID-19, or multiple admissions. The main exposure was ECMO vs No ECMO. The primary outcome was hospital mortality. Key secondary outcomes were ICU length of stay (LOS), hospital LOS, time receiving invasive ventilation, and total hospital costs., Results: The study analyzed 13,714 patients with AERF, including 127 with ECMO and 13,587 with No ECMO. ECMO was associated with reduced mortality in the covariate-adjusted (OR, 0.33; 95% CI, 0.17-0.64; P = .001), propensity score-adjusted (OR, 0.36; 95% CI, 0.16-0.81; P = .01), and propensity score-matched models (OR, 0.48; 95% CI, 0.24-0.98; P = .04) vs No ECMO. Sensitivity analyses showed that mortality reduction related to ECMO ranged from OR 0.34 to 0.61. ECMO was also associated with increased hospital costs in all three models (P < .0001 for all) vs No ECMO, but not with decreased ICU LOS, hospital LOS, or time receiving invasive ventilation., Interpretation: ECMO was associated with lower mortality and higher hospital costs, suggesting that it may be an important salvage therapy for refractory AERF following confirmatory clinical trials., (Copyright © 2022. Published by Elsevier Inc.)

We report the stereocontrolled synthesis of 1,6-diazecanes via a tandem aza-Prins type reaction of N -acyliminium ions with allylsilanes. It involves an aza-Prins type dimerization and cyclization in a single-step operation. This reaction represents the first example of 10-membered N-heterocycle synthesis using an aza-Prins reaction. Also, the interesting formation of an unusual tetracyclic compound through further cyclization of 1,6-diazecane and bicyclic compounds by the intramolecular cyclization of linear allylsilane are described. This tandem aza-Prins protocol provides a new synthetic strategy for the direct synthesis of medium-sized nitrogen heterocycles.

The embedding of radicals at different locations within core@shell silica nanoparticles contributes to enhanced polarization capability and can be self-polarized without adding external radicals. With grafting the radical source homogenously inside of the nanoparticles, a significant 29 Si hyperpolarization signal enhancement of 49.4 was obtained.

Objective: Older hospitalized adults with an existing diagnosis of cancer rarely receive cancer treatment after discharge to a skilled nursing facility (SNF). It is unclear to what degree these outcomes may be driven by cumulative effects of previous cancer treatment and their complications vs an absolute functional threshold from which it is not possible to return. We sought to understand post-acute care outcomes of adults newly diagnosed with cancer and explore functional improvement during their SNF stay., Design: Retrospective cohort study, 2011-2013., Setting and Participants: Surveillance, Epidemiology, and End Results - Medicare database of patients with new stage II-IV colorectal, pancreatic, bladder, or lung cancer discharged to SNF., Methods: Primary outcome was time to death after hospital discharge. Covariates include cancer treatment receipt and hospice use. A Minimum Data Set (MDS)-Activities of Daily Living (ADL) score was calculated to measure changes in ADLs during SNF stay. Patient groups of interest were compared descriptively using means and standard deviations for continuous variables and frequencies and percentages for categorical variables. Logistic regression was used to compare patient groups., Results: A total of 6791 cases were identified. Forty-six percent of patients did not receive treatment or hospice, 25.0% received no treatment but received hospice, 20.8% received treatment but no hospice, and 8.5% received both treatment and hospice. Only 43% of decedents received hospice. Patients who received treatment but not hospice had the best survival. There were limited improvements in MDS-ADL scores in the subset of patients for whom we have complete data. Those with greater functional improvement had improved survival., Conclusions and Implications: The majority of patients did not receive future cancer treatment or hospice care prior to death. There was limited improvement in MDS-ADL scores raising concern this population might not benefit from the rehabilitative intent of SNFs., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Although it is possible to acquire high-resolution and low-resolution paired datasets, their use in directly supervised learning is impractical in real-world applications. In the present work, we focus on a practical methodology for image acquisition in real-world conditions. The main method of noise reduction involves averaging multiple noisy input images into a single image with reduced noise; we also consider unpaired datasets that contain misalignments between the high-resolution and low-resolution images. The results show that when more images are used for average denoising, better performance is achieved in the super-resolution task. Quantitatively, for a fixed noise level with a variance of 60, the proposed method of using 16 images for average denoising shows better performance than using 4 images for average denoising; it shows 0.68 and 0.0279 higher performance for the peak signal-to-noise ratio and structural similarity index map metrics, as well as 0.0071 and 1.5553 better performance for the learned perceptual image patch similarity and natural image quality evaluator metrics, respectively.

Solar-thermal materials absorb sunlight and convert it into heat, which is released into the surrounding medium. Utilization of solar energy for solvent heating can be a potential method of eco-friendly organic reactions. However, to date, significant heating of the entire volume of a solvent by 1 sun illumination has not been reported. In the present work, a network structure of solar-thermal materials has been proposed for zero energy heating of a solvent under 1 sun illumination. A network-structured solar-thermal material with an additional catalytic function was fabricated by sputtering palladium into a melamine sponge. The nanocrystalline palladium-decorated melamine sponge (Pd-sponge) has excellent sunlight absorption properties in the entire wavelength range that enable efficient solar-thermal conversion. The Pd-sponge can reduce heat loss to the surroundings by effectively blocking thermal radiation from the heated solvent. The temperature of the reaction solution with the ethanol-water mixture filled in the Pd-sponge increased from 23 to 59 °C under 1 sun illumination. The elevated temperature of the reaction solutions by solar-thermal conversion successfully accelerated the heterogeneous Pd-catalyzed Suzuki coupling reactions with high conversions. Easy and low-energy-consuming multicycle use of the solar-thermal and catalytic properties of the Pd-sponge has also been demonstrated.

Background: Twenty-five percent to 45% of COPD is caused by exposures other than active smoking. Secondhand tobacco smoke (SHS) has been suggested as an independent cause of COPD, based on its association with increased respiratory symptoms and a small decrease in lung function, but its impact on respiratory health and lung function after exposure cessation has not been explored., Research Question: What are the consequences of airline SHS exposure on respiratory health and lung function decades after cessation?, Study Design and Methods: We performed a cohort study involving flight attendants because of their exposure to SHS that stopped > 20 years ago. We included subjects ≥ 50 years of age with > 1 year vs ≤ 1 year of airline SHS exposure (ie, exposed vs unexposed). Respiratory quality of life, as determined by the St. George's Respiratory Questionnaire (SGRQ), was the primary outcome for respiratory health. Key secondary outcomes included general quality of life (the Rand Corporation modification of the 36-item Short Form Health Survey Questionnaire; RAND-36), respiratory symptoms (COPD Assessment Test; CAT), and spirometry., Results: The study enrolled 183 SHS-exposed and 59 unexposed subjects. Exposed subjects were 66.7 years of age, and 90.7% were female. They were hired at 23.8 years of age, were exposed to airline SHS for 16.1 years, and stopped exposure 27.5 years before enrollment. Prior SHS exposure was associated with worsened SGRQ (6.7 units; 95% CI, 2.7-10.7; P = .001), RAND-36 physical and social function, and CAT vs unexposed subjects. SHS exposure did not affect prebronchodilator spirometry or obstruction, but was associated with lower postbronchodilator FEV 1 and FEV 1 /FVC, total lung capacity, and diffusing capacity of the lungs for carbon monoxide in a subset of subjects. Former smoking and SHS exposure synergistically worsened SGRQ (β = 8.4; 95% CI, 0.4-16.4; P = .04). SHS exposure in people who never smoked replicated primary results and was associated with worsened SGRQ vs unexposed people (4.7 units; 95% CI, 0.7-7.0; P = .006)., Interpretation: Almost three decades after exposure ended, airline SHS exposure is strongly and dose-dependently associated with worsened respiratory health, but less robustly associated with airflow abnormalities used to diagnose COPD., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Stereoselective synthesis of C 4 -substituted benzo[ a ]quinolizidines via redox-controlled catalytic C-C-bond-forming reactions was carried out. Aerobic DDQ-catalyzed allylation of N -Cbz tetrahydroisoquinolines efficiently provided α-allylated products 5 , which were transformed to enones 6 via cross-metathesis reactions using the second-generation Hoveyda-Grubbs catalyst. Palladium-catalyzed hydrogenation of 6 prompted alkene reduction, protecting group removal, and intramolecular reductive amination in one step to afford the desired benzo[ a ]quinolizidines 7 as single diastereomers., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Aims: To develop a decision tree model using US features to differentiate testicular torsion and other conditions of acute scrotum and to investigate predictive parameters of unsalvageable testis in testicular torsion., Materials and Methods: Scrotal US was reviewed in patients aged <30 years who presented with acute scrotum from 2014 to 2020. US findings of whirlpool sign, testicular volume ratio, heterogeneous echotexture, testicular vascularity, epididymis enlargement and/or hyperemia, and avascular nodule were evaluated and compared. A decision tree model was created using the conditional inference tree analysis and the accuracy was calculated. Univariate logistic regression analysis was performed to find out the predictive US features of unsalvageable testes., Results: Total of 381 patients (13.2±7.2 years old; range, 1 day-30 years) were included. Thirty-four patients were diagnosed with testicular torsion, and the others with orchitis or epididymo-orchitis (n=59), epididymitis (n=264), and appendage torsion (n=24). In the conditional inference tree analysis, whirlpool sign, avascular nodule, and increased testicular vascularity were the most significant discriminators (p<0.001), and the whirlpool sign was the first discriminator. The overall accuracy of the conditional inference tree was 91.1% (95% confidence interval [CI], 87.8-93.7%). Heterogeneous echotexture (odds ratio [OR], 74.99; 95% CI, 2.75-2046.26; p=0.01) and symptom-to-operation time >24 h (OR, 49.28; 95% CI, 1.92-1262.03; p=0.02) were significant predictors of unsalvageable testis., Conclusions: Conditional inference tree analysis showed that the whirlpool sign of the spermatic cord, avascular nodule, and altered testicular vascularity were significant discriminators. Heterogeneous echotexture and symptom-to-operation delay were important prognostic factors for unsalvageable testis.

Covalent surface modification of silica nanoparticles (SNPs) offers great potential for the development of multimodal nanomaterials for biomedical applications. Herein, we report the synthesis of covalently conjugated bifunctional SNPs and their application to in vivo multimodal imaging. Bis(methallyl)silane 15 with cyclopropene and maleimide, designed as a stable bifunctional linker, was efficiently synthesized by traceless Staudiger ligation, and subsequently introduced onto the surface of monodispersed SNPs via Sc(OTf) 3 -catalyzed siloxane formation. The bifunctional linker-grafted SNP 20 underwent both thiol-conjugated addition and tetrazine cycloaddition in one pot . Finally, positron emission tomography/computed tomography and fluorescence imaging study of dual functional SNP [125I]28 labeled with NIR dye and 125 I isotope showed a prolonged circulation in mice, which is conducive to the systemic delivery of therapeutics.

The serine protease inhibitor Rv3364c of Mycobacterium tuberculosis (MTB) is highly expressed in cells during MTB exposure. In this study, we showed that the 12 WLVSKF 17 motif of Rv3364c interacts with the BAR domain of SNX9 and inhibits endosome trafficking to interact with p47phox, thereby suppressing TLR4 inflammatory signaling in macrophages. Derived from the structure of this Rv3364c peptide motif, 2,4-diamino-6-(4- tert -butylphenyl)-1,3,5-trazine, DATPT as a 12 WLVSKF 17 peptide-mimetic small molecule has been identified. DATPT can block the SNX9-p47phox interaction in the endosome and suppress reactive oxygen species and inflammatory cytokine production; it demonstrated significant therapeutic effects in a mouse model of cecal ligation and puncture-induced sepsis. DATPT has considerably improved potency, with an IC 50 500-fold ( in vitro ) or 2000-fold ( in vivo ) lower than that of the 12 WLVSKF 17 peptide. Furthermore, DATPT shows potent antibacterial activities by reduction in ATP production and leakage of intracellular ATP out of bacteria. These results provide evidence for peptide-derived small molecule DATPT with anti-inflammatory and antibacterial functions for the treatment of sepsis.

Silicon particles have garnered attention as promising biomedical probes for hyperpolarized 29 Si magnetic resonance imaging and spectroscopy. However, due to the limited levels of hyperpolarization for nanosized silicon particles, microscale silicon particles have primarily been the focus of dynamic nuclear polarization (DNP) applications, including in vivo magnetic resonance imaging (MRI). To address these current challenges, we developed a facile synthetic method for partially 29 Si-enriched porous silicon nanoparticles (NPs) (160 nm) and examined their usability in hyperpolarized 29 Si MRI agents with enhanced signals in spectroscopy and imaging. Hyperpolarization characteristics, such as the build-up constant, the depolarization time ( T 1 ), and the overall enhancement of the 29 Si-enriched silicon NPs (10 and 15%), were thoroughly investigated and compared with those of a naturally abundant NP (4.7%). During optimal DNP conditions, the 15% enriched silicon NPs showed more than 16-fold higher enhancements─far beyond the enrichment ratio─than the naturally abundant sample, further improving the signal-to-noise ratio in in vivo 29 Si MRI. The 29 Si-enriched porous silicon NPs used in this work are potentially capable to serve as drug-delivery vehicles in addition to hyperpolarized 29 Si in vivo , further enabling their potential future applicability as a theragnostic platform.

The run/cysteine-rich-domain-containing Beclin1-interacting autophagy protein (Rubicon) is essential for the regulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by interacting with p22phox to trigger the production of reactive oxygen species (ROS) in immune cells. In a previous study, we demonstrated that the interaction of Rubicon with p22phox increases cellular ROS levels. The correlation between Rubicon and mitochondrial ROS (mtROS) is poorly understood. Here, we report that Rubicon interacts with p22phox in the outer mitochondrial membrane in macrophages and patients with human ulcerative colitis. Upon lipopolysaccharide (LPS) activation, the binding of Rubicon to p22phox was elevated, and increased not only cellular ROS levels but also mtROS, with an impairment of mitochondrial complex III and mitochondrial biogenesis in macrophages. Furthermore, increased Rubicon decreases mitochondrial metabolic flux in macrophages. Mito-TIPTP, which is a p22phox inhibitor containing a mitochondrial translocation signal, enhances mitochondrial function by inhibiting the association between Rubicon and p22phox in LPS-primed bone-marrow-derived macrophages (BMDMs) treated with adenosine triphosphate (ATP) or dextran sulfate sodium (DSS). Remarkably, Mito-TIPTP exhibited a therapeutic effect by decreasing mtROS in DSS-induced acute or chronic colitis mouse models. Thus, our findings suggest that Mito-TIPTP is a potential therapeutic agent for colitis by inhibiting the interaction between Rubicon and p22phox to recover mitochondrial function.

The present study describes evaluation of epigenetic regulation by a small molecule as the therapeutic potential for treatment of Huntington's disease (HD). We identified 5-allyloxy-2-(pyrrolidin-1-yl)quinoline (APQ) as a novel SETDB1/ESET inhibitor using a combined in silico and in vitro cell based screening system. APQ reduced SETDB1 activity and H3K9me3 levels in a HD cell line model. In particular, not only APQ reduced H3K9me3 levels in the striatum but it also improved motor function and neuropathological symptoms such as neuronal size and activity in HD transgenic (YAC128) mice with minimal toxicity. Using H3K9me3-ChIP and genome-wide sequencing, we also confirmed that APQ modulates H3K9me3-landscaped epigenomes in YAC128 mice. These data provide that APQ, a novel small molecule SETDB1 inhibitor, coordinates H3K9me-dependent heterochromatin remodelling and can be an epigenetic drug for treating HD, leading with hope in clinical trials of HD.

Three-dimensional (3D) printing shows potential for use as an advanced technology for forming biomimetic tissue and other complex structures. However, there are limits and restrictions on selection of conventional bioinks. Here we report the first 3D-printable platelet lysate (PLMA)-based hydrogel, which consists of platelet lysate from whole blood of humans that can simulate the 3D structure of tissues and can be formed into a crosslinked hydrogel layer-by-layer to build cell-laden hydrogel constructs through methacrylated photo-polymerization. Furthermore, it can be customized for use with various tissues by controlling the physical properties according to irradiation time and concentration. In particular, different cells can be mixed and printed, and the integrity of the 3D printed structure can maintain its shape after crosslinking. The bio-ink exhibits excellent cell diffusion and proliferation at low concentrations, which improves moldability and biocompatibility. The 3D-printable PLMA bioinks may constitute a new strategy to create customized microenvironments for the repair of various tissues in vivo using materials derived from the human body., (© 2021 IOP Publishing Ltd.)

Rationale: Rural chronic obstructive pulmonary disease (COPD) patients have worse outcomes and higher mortality compared with urban patients. Reasons for these disparities likely include challenges to delivery of care that have not been explored., Objective: To determine challenges faced by rural primary care providers when caring for COPD patients., Methods: Rural primary care providers in 7 primarily western states were asked about barriers they experienced when caring for COPD patients., Results: A total of 71 rural primary care medical providers completed the survey, of which 51% were physicians and 49% were advanced practice providers (APPs). A total of 61% used Global Initiative for Chronic Obstructive Lung Disease or American Thoracic Society/European Respiratory Society guidelines as an assessment and treatment resource. The presence of multiple chronic conditions and patient failure to recognize and report symptoms were the greatest barriers to diagnose COPD. A total of 89% of providers used spirometry to diagnose COPD, but only 62% were satisfied with access to spirometry. Despite recommendations, 41% of providers never test for alpha-1 antitrypsin deficiency. A total of 87% were comfortable with their ability to assess symptoms, but only 11% used a guideline-recommended assessment tool. Although most providers were satisfied with their ability to treat symptoms and exacerbations, only 66% were content with their ability to prevent exacerbations. Fewer providers were happy with their access to pulmonologists (55%) or pulmonary rehabilitation (37%). Subgroup analyses revealed differences based on provider type (APP versus physician) and location (Colorado and Kansas versus other states), but not on population or practice size., Conclusions: Rural providers face significant challenges when caring for COPD patients that should be targeted in future interventions to improve COPD outcomes., (JCOPDF © 2021.)

Introduction: Stamm's S-point is gaining importance as a bleeding focus in severe epistaxis. However, prevalence and features of S-point bleeding compared to non S-point bleeding have not been studied., Objective: To investigate the characteristics of patients with S-point bleeding among those with severe epistaxis and to compare the factors involved in the treatment of epistaxis., Methods: We retrospectively analyzed medical records of 268 patients admitted to the otorhinolaryngology department of Konkuk University Hospital and Chung-Ang University Hospital with epistaxis of which the bleeding focus clarified. Patients with anterior nasal bleeding (n=129) were excluded. The study was conducted at the department of otorhinolaryngology from January 2008 to August 2019. Collected data included patients' demographic information, bleeding focus, body mass index underlying medical and sinonasal diseases, laboratory test results (initial hemoglobin, platelet count, and triglyceride level), use of anticoagulants, direction of epistaxis, initial and final treatments, and need for blood transfusion., Results: The prevalence of S-point bleeding was 28.8% of non-anterior bleeding cases. Mean body mass index score was lower in the S-point group (23.41±3.71) compared to the non S-point group (24.93±3.97) (p=0.039). Underweight patients tended to show a greater incidence of S-point bleeding (15.0%) than non S-point bleeding (2.0%) (p=0.010). Incidence of anemia was higher in the S-point group (67.5%) than in the non S-point group (36.4%). Anemia (Odds ratio [OR]: 3.635; 95% confidence interval [CI]: 1.669-7.914, p=0.001) and underweight (body mass index<18.5, OR: 8.559, CI: 1.648-44.445, p=0.011) were significantly associated with S-point bleeding., Conclusion: Prevalence of S-point bleeding was significant, underlining the importance of examining the S-point in patients with severe epistaxis. Patients with S-point bleeding had lower body mass index scores and a higher incidence of anemia than those with non S-point bleeding., (Copyright © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Background: To investigate the protective effects of exogenous spermine on renal ischemia-reperfusion injury in rats., Methods: (I) Different doses of spermine were injected into rats to determine the safe dose on the kidneys. Kidney toxicity was assessed by hematoxylin and eosin (HE) staining of kidney tissue and enzyme-linked immunosorbent assay (ELISA) detection of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in the venous blood. (II) A rat model of renal ischemia-reperfusion injury was established. Different doses of spermine were injected into the rats through the tail vein 30 minutes before and 3 days after the establishment of the model. Blood samples and kidney tissues were collected and renal injury was assessed via HE staining of the renal tissue, detection of apoptosis using the TUNEL assay, and detection of NGAL and KIM-1 in blood samples using ELISA. (III) Human HK-2 renal tubular epithelial cells were cultured under hypoxia/reoxygenation conditions. To evaluate the protective effects of spermine, apoptosis was assessed by flow cytometry and TUNEL assay. The mechanisms underlying the effects of spermine were studied using Western blot analyses., Results: At spermine concentrations below 200 µM (2 mL/kg body weight), no significant damage to the kidney was observed by HE staining, and there was no significant difference in NGAL and KIM-1 levels between rats treated with spermine and control rats (P<0.05). At spermine doses below 200 µM, HE staining showed that the degree of renal ischemia-reperfusion injury was gradually alleviated with increasing doses of spermine. TUNEL assays demonstrated that spermine reduced the apoptosis of renal tissue, and increasing doses of spermine gradually decreased the levels of NGAL and KIM-1 in the blood compared with the control group (P<0.05). Western blot analysis revealed that spermine increased the expression of pro-caspase9, phosphorylated protein kinase B (p-Akt), hypoxia-inducible factor 1 alpha (HIF-1α), B cell lymphoma 2 (Bcl-2), and Bcl2 interacting protein 3 (BNIP3), and decreased the expression of cleaved caspase-3, Bax and cytochrome C compared to control cells., Conclusions: Exogenous spermine exerted a protective effect on renal ischemia-reperfusion injury in rats by inhibiting the apoptosis of renal tubular epithelial cells., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-21-280). The authors have no conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

We present a comparison between the thermal sensing behaviors of 4H-SiC Schottky barrier diodes, junction barrier Schottky diodes, and PiN diodes in a temperature range from 293 K to 573 K. The thermal sensitivity of the devices was calculated from the slope of the forward voltage versus temperature plot. At a forward current of 10 μA, the PiN diode presented the highest sensitivity peak (4.11 mV K -1 ), compared to the peaks of the junction barrier Schottky diode and the Schottky barrier diode (2.1 mV K -1 and 1.9 mV K -1 , respectively). The minimum temperature errors of the PiN and junction barrier Schottky diodes were 0.365 K and 0.565 K, respectively, for a forward current of 80 μA±10 μA. The corresponding value for the Schottky barrier diode was 0.985 K for a forward current of 150 μA±10 μA. In contrast to Schottky diodes, the PiN diode presents a lower increase in saturation current with temperature. Therefore, the nonlinear contribution of the saturation current with respect to the forward current is negligible; this contributes to the higher sensitivity of the PiN diode, allowing for the design and fabrication of highly linear sensors that can operate in a wider temperature range than the other two diode types.

Background/aims: The efficacy and safety of mepolizumab in patients with severe eosinophilic asthma has been evaluated in a global clinical trial programme. This post hoc analysis assesses the efficacy and safety of mepolizumab in Korean patients., Methods: Data from Korean patients in the Phase III, placebo-controlled, randomised DREAM (MEA112997/NCT01000506) and MENSA (MEA115588/ NCT01691521) studies were included. Patients ≥ 12 years old with severe eosinophilic asthma received mepolizumab (DREAM: 75, 250 or 750 mg intravenously [IV]; MENSA: 75 mg IV or 100 mg subcutaneously [SC]), or placebo every 4 weeks for 52 weeks (DREAM) or 32 weeks (MENSA). The primary outcome was the rate of clinically significant asthma exacerbations. Secondary outcomes included forced expiratory volume in 1 second (FEV1), Asthma Control Questionnaire (ACQ) and St George's Respiratory Questionnaire (SGRQ) scores (MENSA only). Blood eosinophil counts (BEC) and safety were assessed throughout., Results: Reductions in the rate of clinically significant asthma exacerbations were observed with the approved (100 mg SC) and bioequivalent (75 mg IV) doses of mepolizumab in Korean patients who participated in DREAM and MENSA. In MENSA, trends for improvements from baseline at week 32 in pre-bronchodilator FEV1 (75 mg IV group), ACQ-5 and SGRQ scores (in both treatment groups) were seen versus placebo in Korean patients. Incidence of on-treatment adverse events was similar in Korean patients versus non-Korean patients as were observed reductions from baseline in BEC., Conclusion: Mepolizumab treatment provided clinical benefits for Korean patients with severe eosinophilic asthma; the safety profile is consistent with the overall population.

Objective: Epistaxis is a commonly encountered condition; however, factors that have been associated with epistaxis are controversial. Although several previous studies have evaluated the relationship between meteorological factors and epistaxis, studies conducted in Korea has been nearly reported. We attempted to evaluate the meteorological factors associated with the frequency of patients presenting with epistaxis in a tertiary hospital., Methods: We retrospectively reviewed the medical records of patients presenting with spontaneous epistaxis in an urban tertiary medical center, during one year. Patients with a clear etiology for epistaxis (such as trauma, previous surgery) were regarded as cases of secondary epistaxis and were excluded from this study. Daily climatic data were collected from the website of Korea Meteorological Administration. Meteorological factors affecting the frequency of patients presenting with epistaxis were statistically analyzed., Results: Among 350 enrolled subjects, 219 were males and 131 were females, and the mean age was 44.94 ± 26.02 years. Univariate and multivariate regression analyses revealed that minimal temperature and mean wind speed were significant factors that affected the presence of patients presenting with epistaxis to the hospital. Furthermore, ordinal logistic regression analysis showed that decreases in minimal temperature and mean relative humidity were associated with a increase in the number of patients presenting with epistaxis., Conclusion: Minimal temperature and mean wind speed were significantly different between days with epistaxis and days without epistaxis patients presenting with epistaxis, and minimal temperature and mean relative humidity were associated with number of patients presenting with epistaxis. Our findings suggested that these meteorological factors might affect the spontaneous epistaxis in Seoul, Korea., Competing Interests: Declaration of Competing Interest Not applicable., (Copyright © 2020. Published by Elsevier B.V.)

The endoplasmic reticulum (ER) apparatus is a part of the secretory pathway that transports proteins to the plasma membrane through vesicle trafficking, enabling post-translational modification of the newly synthesized proteins. Several diseases such as inflammation, neurodegenerative disorder, and bipolar disorder are closely associated with dysfunction of the ER stress response. Herein, we present an ER-targeting, intracellular delivery approach that utilized cell-penetrating peptide (CPP)-conjugated lipid/polymer hybrid nanovehicles (LPNVs). For this, we patched Penetratin, a type of CPP, onto the LPNVs with vesicular membranes formulated with poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). We found that the Penetratin-conjugated LPNV (LPNVPnt) was readily taken up by cells and showed specific ER-targeting ability, which was comparable to that of LPNVs conjugated with other types of CPPs. Moreover, we observed that remarkable lysosomal escape of the LPNVs occurred due to effective pH buffering with the aid of PEO-b-PCL-b-PEO. These results highlighted that our LPNVPnt system could pave the way for the development of an elaborate drug delivery technology for ER-targeting at the intracellular level.

Background: Up to 50% of chronic obstructive pulmonary disease (COPD) patients do not receive recommended care for COPD. To address this issue, we developed Proactive Integrated Care (Proactive iCare), a health care delivery model that couples integrated care with remote monitoring., Methods: We conducted a prospective, quasi-randomized clinical trial in 511 patients with advanced COPD or a recent COPD exacerbation, to test whether Proactive iCare impacts patient-centered outcomes and health care utilization. Patients were allocated to Proactive iCare (n=352) or Usual Care ( =159) and were examined for changes in quality of life using the St George's Respiratory Questionnaire (SGRQ), symptoms, guideline-based care, and health care utilization., Findings: Proactive iCare improved total SGRQ by 7-9 units ( p < 0.0001), symptom SGRQ by 9 units ( p <0.0001), activity SGRQ by 6-7 units (p <0.001) and impact SGRQ by 7-11 units ( p <0.0001) at 3, 6 and 9 months compared with Usual Care. Proactive iCare increased the 6-minute walk distance by 40 m ( p <0.001), reduced annual COPD-related urgent office visits by 76 visits per 100 participants (p <0.0001), identified unreported exacerbations, and decreased smoking ( p =0.01). Proactive iCare also improved symptoms, the b ody mass index-airway o bstruction- d yspnea- e xercise tolerance (BODE) index and oxygen titration ( p <0.05). Mortality in the Proactive iCare group (1.1%) was not significantly different than mortality in the Usual Care group (3.8%; p =0.08)., Interpretation: Linking integrated care with remote monitoring improves the lives of people with advanced COPD, findings that may have been made more relevant by the coronavirus 2019 (COVID-19) pandemic., Competing Interests: RWV, PBK, SJM, DLPD, TJF, SSJ, NFV, DJL, AB, TJS, DPR, CMK, SC, RLK and JMW received funding from the Colorado Cancer, Cardiovascular Disease and Chronic Pulmonary Disease Prevention, Early Detection and Treatment Program (CCPD). RWV and MG received funding from the National Institutes of Health. PBK worked for Robert Bosch Healthcare from 2010 to 2015 and for Philips Healthcare from 2015 to 2017, after the study was completed. RKA, FDV, JKZ and TMB had no conflicts of interest., (JCOPDF © 2021.)

In-situ chemical oxidation (ISCO) requires an injection of oxidants into a contaminated site. However, the oxidants decompose and react with contaminants during transport to the contaminated region, which causes oxidant over-consumption. In-situ oxidant generation can solve this problem, and electrochemical methods can be applied to achieve this. Electrochemical oxidation is highly dependent on electrode material type. In this study, we evaluated graphite and carbon fiber as candidates for electrochemical oxidant generation and phenol as the model compound. The carbon fiber anode oxidized the phenol more effectively than graphite, with removal proportional to the applied current. Carbonate electrolytes were more effective at oxidizing phenols than sulfate electrolytes. The faster carbon fiber anode phenol oxidation is due to its large surface area. Carbonate radicals in the carbonate electrolyte contribute to phenol oxidation as well as further intermediate oxidation. The carbon fiber cathode was not an effective phenol oxidizer even though it generated more hydrogen peroxide. This is because there was no catalyst to transform the hydrogen peroxide into hydroxyl radicals. Results indicate that electrochemical oxidation using carbon fiber is an effective method for treating phenol found in groundwater with high concentrations of (bi)carbonate., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Benign paroxysmal positional vertigo (BPPV) is one of the most common vestibular disorders. An investigation into the factors related to BPPV could contribute to its prevention and appropriate management. We investigated the association between climatic factors and incidence of BPPV in this study. A total of 365 patients who were diagnosed with idiopathic BPPV in the emergency room of our hospital in 2015 were included. The number of patients diagnosed with BPPV per week was calculated (every week). Climatic factors, including daily average humidity, temperature, atmospheric pressure, cloud amount, sunshine amount, and daylight time, were documented daily. The weekly mean climatic value in each week was calculated. Simple correlation analysis and multivariate regression analyses were performed to identify climatic factors associated with the number of patients diagnosed with BPPV. Simple correlation analysis revealed a significant association between the humidity (r = 0.276, p = 0.048), temperature (r = 0.275, p = 0.049), and cloud amount (r = 0.293, p = 0.035) and the number of BPPV patients diagnosed per week. Multivariate regression analysis revealed that only the cloud amount was a statistically significant factor associated with the number of BPPV patients diagnosed every week. A significant positive association was discovered between the cloud amount and BPPV incidence. Cloud amount can therefore have an association with the incidence of BPPV.