Mask-induced dermatoses during the COVID-19 pandemic: a questionnaire-based study in 12 Korean hospitals.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, various adverse skin reactions to long-term mask wearing have been reported. AIM: To assess the clinical features of mask-induced dermatoses and to recommend prevention and treatment options. METHODS: From April to August 2020, questionnaires including topics such as demographic information, pre-existing skin disorders, reported mask-related symptoms, daily mask-wearing duration and frequency, types of masks used and whether the participant was a healthcare worker, were distributed to patients in 12 hospitals. Dermatologists assessed skin lesions, confirmed diagnosis and recorded treatments. RESULTS: Itchiness was the most frequent symptom, mostly affecting the cheeks. The most common skin disease was new-onset contact dermatitis (33.94%), followed by new-onset acne (16.97%) and worsening of pre-existing acne (16.97%). Daily wearing of masks was significantly (P = 0.02) associated with new-onset contact dermatitis. More than half of patients with pre-existing skin problems experienced disease worsening while wearing masks. Longer duration of wearing (> 6 h/day, P = 0.04) and use of cotton masks (P < 0.001) significantly increased acne flare-up. Healthcare workers had a higher incidence of skin disease. Skin lesions were generally mild and well tolerated with topical treatment. The study had some limitations: the effect of seasonal characteristics and other risk factors were not assessed, and the patients were visiting dermatological clinics and had interest in their skin status, thus, there may have been selection bias. CONCLUSION: Mask-induced/-triggered dermatoses contribute to increase the dermatological burden during the pandemic.

Investigation of photodarkening in tandem-pumped Yb-doped fibers.

Investigation of photodarkening (PD) in Yb-doped fibers tandem-pumped at 1018 nm is reported. For a homemade Yb-doped aluminosilicate double-clad fiber (YADF), the transmitted power of a 633 nm probe beam is reduced by 2.4% over 2 hours for the tandem pumping configuration at 1018 nm, which is significantly smaller than 33.3% for a laser diode (LD) pumping at 976 nm. A tandem-pumped Yb fiber amplifier also shows a much smaller decrease in the amplified output power over time than a LD-pumped Yb fiber amplifier. Based on fluorescence spectra of the YADF, we can not only associate PD of the YADF to intrinsic oxygen deficiency centers or Tm3+ impurities but also confirm the impact of the excited Yb3+ ion density on PD. The benefits of the tandem pumping in a high-power Yb fiber laser system will be discussed.

Therapeutic effects of kefir grain Lactobacillus-derived extracellular vesicles in mice with 2,4,6-trinitrobenzene sulfonic acid-induced inflammatory bowel disease.

Kefir is a fermented product from yeast and lactic acid bacteria, and has been associated with various health benefits including relieving inflammatory bowel disease. Recently, it has been shown that gram-positive bacteria produce extracellular vesicles (EV). The EV could be appearing as potentially important mediators of cell to cell interaction. In this study, we explored the role of kefir grain Lactobacillus-derived EV in modulating inflammation responses via alleviating the production of inflammatory cytokines in tumor necrosis factor-α (TNF-α)-induced inflammation in Caco-2 cells and the 2,4,6-trinitrobenzene sulfonic acid-induced inflammatory bowel disease mouse model. Kefir-derived Lactobacillus EV were isolated by ultracentrifugation of the culture medium of 3 different kefir-derived strains (i.e., Lactobacillus kefir, Lactobacillus kefiranofaciens, and Lactobacillus kefirgranum). Nanoparticle tracking analysis showed that the size of isolated kefir-derived Lactobacillus EV was within 80 to 400 nm, and kefir-derived Lactobacillus EV uptake into recipient Caco-2 cells was confirmed by fluorescence labeling. Treatment of each kefir-derived Lactobacillus EV onto TNF-α-stimulated Caco-2 cells significantly reduced the level of both mRNA expression and secretion of IL-8, and Western blot analysis revealed that such an effect was related to inhibition of TNF-α signaling mediated by reducing the phosphorylation of p65, a subunit of NF-kB. Subsequent administration of kefir-derived Lactobacillus EV into inflammatory bowel disease-induced mice significantly alleviated the body weight loss and rectal bleeding, and enhanced stool consistency. Histological examination showed that kefir-derived Lactobacillus EV substantially reduced the infiltration of transmural leukocytes and loss of goblet cells within the colon, and the serum level of myeloperoxidase was significantly lower in the EV-treated group than control group. Our study demonstrates that kefir-derived Lactobacillus EV can be potentially used for developing innovative strategies for alleviating inflammatory bowel disease.

Postharvest processing decreases the richness of bacterial taxa in the phyllosphere of broccoli.

AIMS: Diverse bacterial communities residing on the surfaces of fresh vegetables are important for food quality and safety; however, knowledge of the phyllosphere microbiota on fresh vegetables and of how it changes during postharvest stage is poorly understood. METHODS AND RESULTS: We used culturing to quantify bacterial abundance and 16S rRNA 454 pyrosequencing to analyse the bacterial community composition on broccoli florets collected from farms (preharvest) and retail stores (postharvest). The bacterial community compositions of the preharvest and postharvest broccoli were significantly different. The number of non-Escherichia coli coliform bacteria (Hafnia sp. and Rahnella sp.) was higher in the postharvest broccoli than in the preharvest broccoli. Minor bacterial taxa at the phylum and genus levels had markedly disappeared in the postharvest broccoli, resulting in low bacterial species richness in the postharvest broccoli. CONCLUSIONS: The dominant bacterial taxa persist and prevail in the phyllosphere of broccoli during the postharvest stage. SIGNIFICANCE AND IMPACT OF THE STUDY: A popular crop of leafy vegetables, broccoli, is of great agricultural and nutritional importance. This study provides a detailed description of changes in the bacterial community of broccoli in harvest and storage. This study presents novel data on the impact of postharvest conditions on the bacterial populations on broccoli florets.

Development of immune and microbial environments is independently regulated in the mammary gland.

Breastfeeding is important for mammals, providing immunological and microbiological advantages to neonates, together with the nutritional supply from the mother. However, the mechanisms of this functional diversity in the mammary gland remain poorly characterized. Here, we show that, similar to the gastrointestinal tract, the mammary gland develops immune and microbial environments consisting of immunoglobulin A (IgA) and the microflora, respectively, both of which are important for protecting neonates and the mother from infectious diseases. The IgA production and microflora development are coordinated in the gastrointestinal tract but seem to be independently regulated in the mammary gland. In particular, the chemokine (C-C motif) ligand 28 and poly-Ig receptor, crucial molecules for the IgA production in milk, were expressed normally in germ-free lactating mice but were almost undetectable in postweaning mothers, regardless of the microflora presence. Our findings offer insights into potentially improving the quality of breastfeeding, using both immunological and microbiological approaches.

Retinoblastoma protein (Rb) links hypoxia to altered mechanical properties in cancer cells as measured by an optical tweezer.

Hypoxia modulates actin organization via multiple pathways. Analyzing the effect of hypoxia on the biophysical properties of cancer cells is beneficial for studying modulatory signalling pathways by quantifying cytoskeleton rearrangements. We have characterized the biophysical properties of human LNCaP prostate cancer cells that occur in response to loss of the retinoblastoma protein (Rb) under hypoxic stress using an oscillating optical tweezer. Hypoxia and Rb-loss increased cell stiffness in a fashion that was dependent on activation of the extracellular signal-regulated kinase (ERK) and the protein kinase B (AKT)- mammalian target of rapamycin (MTOR) pathways. Pharmacological inhibition of MEK1/2, AKT or MTOR impeded hypoxia-inducible changes in the actin cytoskeleton and inhibited cell migration in Rb-deficient cells conditioned with hypoxia. These results suggest that loss of Rb in transformed hypoxic cancer cells affects MEK1/2-ERK/AKT-MTOR signalling and promotes motility. Thus, the mechanical characterization of cancer cells using an optical tweezer provides an additional technique for cancer diagnosis/prognosis and evaluating therapeutic performance.

Critical role of TSLP-responsive mucosal dendritic cells in the induction of nasal antigen-specific IgA response.

Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine involved in T helper 2 type immune responses. The primary target of TSLP is myeloid dendritic cells (DCs), however, little is known about the mechanism by which TSLP elicits respiratory IgA immune responses upon mucosal immunization. Here, we found that the levels of TSLP and TSLPR were upregulated in the mucosal DCs of mice nasally immunized with pneumococcal surface protein A (PspA) plus cholera toxin (CT) compared with those immunized with PspA alone. PspA-specific IgA responses, but not IgG Ab responses were significantly reduced in both serum and mucosal secretions of TSLPR knockout mice compared with wild-type mice after nasal immunization with PspA plus CT. Furthermore, CD11c+ mucosal DCs isolated from TSLPR knockout mice nasally immunized with PspA plus CT were less activated and exhibited markedly reduced expression of IgA-enhancing cytokines (e.g., APRIL, BAFF, and IL-6) compared with those from equivalently immunized wild-type mice. Finally, exogenous TSLP promoted production of IgAs in an in vitro DC-B cell co-culture system as exhibited by enhanced IL-6 production. These results suggest that TSLP-TSLPR signaling is pivotal in the induction of nasal respiratory immunity against pathogenic pneumococcal infection.

A Large National Cohort Study of the Association between Bisphosphonates and Osteonecrosis of the Jaw in Patients with Osteoporosis: A Nested Case-control Study.

The purpose of this study was to examine the association between bisphosphonate exposure and osteonecrosis of the jaw (ONJ) in Korean patients with osteoporosis. A nested case-control study was performed using the claims database during 2002 to 2010 provided by the National Health Insurance Service. We identified a cohort of individuals with diagnosis of osteoporosis during 2002 to 2010. Cases and controls were identified during 2004 to 2010, and the date of potential cases of ONJ was defined as the index date. Bisphosphonate exposure was evaluated during 2 y prior to the index date. The association between bisphosphonate exposure and ONJ was tested by performing a conditional logistic regression analysis for matched data, and odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Subjects were classified as nonuser, recent user, past user, or continuous user, depending on the prescription of bisphosphonates in 2 periods (1 to 2 y and 0 to 1 y prior to the index date). Continuous users were defined as patients who were exposed to bisphosphonate in both periods. We also examined the impact of bisphosphonate medication compliance by measuring the cumulative duration of exposure (CDE) on the risk of ONJ. A total of 212 cases with ONJ and 2,120 controls matched by sex, age, income level, and insurance type were identified among 109,787 patients with osteoporosis out of 1,025,340 enrollees in the sample cohort. The odds of having ONJ after adjusting for patient comorbidities significantly increased in continuous users of bisphosphonates (OR, 3.9; 95% CI, 2.4 to 6.2) compared to nonusers. Increased odds of ONJ were observed as CDE increased. The adjusted OR in patients with 1.5 y < CDE ≤ 2 y prior to the index date was 7.8 (95% CI, 4.0 to 15.5) versus nonusers. Our study results support significantly increased occurrences of potential ONJ in patients with osteoporosis who were exposed to bisphosphonates compared to those without exposure.

Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques.

We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans.

ATM-mediated phosphorylation of the chromatin remodeling enzyme BRG1 modulates DNA double-strand break repair.

ATP-dependent chromatin remodeling complexes such as SWI/SNF (SWItch/Sucrose NonFermentable) have been implicated in DNA double-strand break (DSB) repair and damage responses. However, the regulatory mechanisms that control the function of chromatin remodelers in DNA damage response are largely unknown. Here, we show that ataxia telangiectasia mutated (ATM) mediates the phosphorylation of BRG1, the catalytic ATPase of the SWI/SNF complex that contributes to DSB repair by binding γ-H2AX-containing nucleosomes via interaction with acetylated histone H3 and stimulating γ-H2AX formation, at Ser-721 in response to DNA damage. ATM-mediated phosphorylation of BRG1 occurs rapidly and transiently after DNA damage. Phosphorylated BRG1 binds γ-H2AX-containing nucleosomes to form the repair foci. The Ser-721 phosphorylation of BRG1 is critical for binding γ-H2AX-containing nucleosomes and stimulating γ-H2AX formation and DSB repair. BRG1 binds to acetylated H3 peptides much better after phosphorylation at Ser-721 by DNA damage. However, the phosphorylation of Ser-721 does not significantly affect the ATPase and transcriptional activities of BRG1. These results, establishing BRG1 as a novel and functional ATM substrate, suggest that the ATM-mediated phosphorylation of BRG1 facilitates DSB repair by stimulating the association of this remodeler with γ-H2AX nucleosomes via enhancing the affinity to acetylated H3. Our work also suggests that the mechanism of BRG1 stimulation of DNA repair is independent of the remodeler's enzymatic or transcriptional activities.

Relative adrenal insufficiency in chronic liver disease: its prevalence and effects on long-term mortality.

BACKGROUND: The relationship between relative adrenal insufficiency (RAI) and chronic liver disease is unclear. AIM: To determine the frequency with which RAI is observed in noncritically ill patients at various stages of chronic liver disease, and the correlation between RAI and disease severity and long-term mortality. METHODS: In total, 71 non-critically ill patients with liver cirrhosis (n = 54) and chronic hepatitis (n = 17) were evaluated prospectively. A short stimulation test (SST) with 250 µg of corticotrophin was performed to detect RAI. RAI was defined as an increase in serum cortisol of <9 µg/dL in patients with a basal total cortisol of <35 µg/dL. RESULTS: RAI was observed in only 13 (24.1%) of 54 patients with cirrhosis. Compared to those without RAI, cirrhotic patients with RAI had significantly higher Child-Turcotte-Pugh score (10.3 ± 1.7 vs. 7.1 ± 1.8, mean ± s.d., P < 0.001) and Model for End-Stage Liver Disease score (14.5 ± 6.6 vs. 9.4 ± 3.7, P = 0.017). The cortisol response to corticotropin was negatively correlated with the severity of cirrhosis (P < 0.05). In addition, the mortality rate was higher in cirrhotic patients with RAI (69.2%) than in those without RAI (4.9%; P < 0.001) during the follow-up period of 20.1 ± 13.5 months (range, 5.8-51.1 months). The cumulative 1-year survival rates in cirrhotic patients with and without RAI were 69.2% and 95.0%, respectively (P = 0.05), while the corresponding cumulative 3-year survival rates were 0% and 95.0% (P < 0.001). CONCLUSIONS: Relative adrenal insufficiency is more commonly observed in those with severe cirrhosis, and is clearly associated with more advanced liver disease and a shortened long-term survival. This suggests that relative adrenal insufficiency is an independent prognostic factor in non-critically ill patients with cirrhosis.

ß-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells.

ß-Lapachone activates multiple cell death mechanisms including apoptosis, autophagy and necrotic cell death in cancer cells. In this study, we investigated ß-lapachone-induced cell death and the underlying mechanisms in human hepatocellular carcinoma SK-Hep1 cells. ß-Lapachone markedly induced cell death without caspase activation. ß-Lapachone increased PI uptake and HMGB-1 release to extracellular space, which are markers of necrotic cell death. Necrostatin-1 (a RIP1 kinase inhibitor) markedly inhibited ß-lapachone-induced cell death and HMGB-1 release. In addition, ß-lapachone activated poly (ADP-ribosyl) polymerase-1(PARP-1) and promoted AIF release, and DPQ (a PARP-1 specific inhibitor) or AIF siRNA blocked ß-lapachone-induced cell death. Furthermore, necrostatin-1 blocked PARP-1 activation and cytosolic AIF translocation. We also found that ß-lapachone-induced reactive oxygen species (ROS) production has an important role in the activation of the RIP1-PARP1-AIF pathway. Finally, ß-lapachone-induced cell death was inhibited by dicoumarol (a NQO-1 inhibitor), and NQO1 expression was correlated with sensitivity to ß-lapachone. Taken together, our results demonstrate that ß-lapachone induces programmed necrosis through the NQO1-dependent ROS-mediated RIP1-PARP1-AIF pathway.

Oral immunization with whole yeast producing viral capsid antigen provokes a stronger humoral immune response than purified viral capsid antigen.

UNLABELLED: Weak antibody responses to protein antigens after oral immunization remain a serious problem. Yeasts have a rigid cell wall and are inherently resistant to harsh conditions, suggesting that recombinant antigens made in yeast could have a greater chance of making contact with the immune cells of the gastrointestinal (GI) tract in intact form. We compared antibody responses to oral immunization with purified recombinant antigen, used in the conventional manner, and responses to whole recombinant yeast producing the antigen intracellularly. Recombinant capsid protein (CP) of red-spotted grouper necrosis virus (RGNNV) was used as model antigen and Saccharomyces cerevisiae as host. The purified CP was obtained from the S. cerevisiae producing the RGNNV CP. Whole recombinant yeast producing RGNNV CP provoked 9-27 times higher anti-RGNNV CP IgG titres than purified RGNNV CP. Moreover, sera from mice immunized with the recombinant yeast had neutralizing activity against RGNNV, while those from mice immunized with purified CP did not. These results show that whole recombinant yeast is a promising platform for antigen delivery by oral immunization. SIGNIFICANCE AND IMPACT OF THE STUDY: Provoking sufficient antibody responses by oral immunization has been an enormous challenge because of the harsh conditions of the gastrointestinal (GI) tract. Immunization strategies using purified antigen to make oral vaccines are incapable of commercialization because excessive amount of antigen is required to provoke antibody responses. Therefore, resolving the problems concerning the cost and effectiveness of oral vaccines is a high priority. Our results suggest that recombinant yeast has great potential for inducing antigen-specific immune responses by oral immunization. We believe that oral immunization using recombinant yeast can be a breakthrough technology.

A cascaded two-step Kalman filter for estimation of human body segment orientation using MEMS-IMU.

Orientation of human body segments is an important quantity in many biomechanical analyses. To get robust and drift-free 3-D orientation, raw data from miniature body worn MEMS-based inertial measurement units (IMU) should be blended in a Kalman filter. Aiming at less computational cost, this work presents a novel cascaded two-step Kalman filter orientation estimation algorithm. Tilt angles are estimated in the first step of the proposed cascaded Kalman filter. The estimated tilt angles are passed to the second step of the filter for yaw angle calculation. The orientation results are benchmarked against the ones from a highly accurate tactical grade IMU. Experimental results reveal that the proposed algorithm provides robust orientation estimation in both kinematically and magnetically disturbed conditions.

Association between urine cotinine levels, continuous performance test variables, and attention deficit hyperactivity disorder and learning disability symptoms in school-aged children.

BACKGROUND: We examined the cross-sectional relationship between environmental tobacco smoke exposure, continuous performance test (CPT) measures, and attention deficit hyperactivity disorder (ADHD) or learning disability symptoms in school-aged children. METHOD: In total, 989 children (526 boys, mean age 9.1 ± 0.7 years), recruited from five South Korean cities participated in this study. We used urine cotinine as a biomarker for environmental tobacco smoke exposure, and obtained the children's scores on a CPT. Parents completed the Korean versions of the ADHD rating scale-IV (ADHD-RS) and learning disability evaluation scale (LDES). Using generalized linear mixed model (GLMM), we assessed the associations between urine cotinine concentrations, neuropsychological variables, and symptoms of ADHD and learning disabilities. Additionally, we conducted structural equation models to explore the effects' pathways. RESULTS: After adjusting for a range of relevant covariates, GLMM showed urinary cotinine levels were significantly and positively associated with CPT scores on omission errors, commission errors, response time, and response time variability, and with parent- and teacher-rated ADHD-RS scores. In addition, urine cotinine levels were negatively associated with LDES scores on spelling and mathematical calculations. The structural equation model revealed that CPT variables mediated the association between urine cotinine levels and parental reports of symptoms of ADHD and learning disabilities. CONCLUSIONS: Our data indicate that environmental exposure to tobacco smoke is associated with ADHD and learning disabilities in children, and that impairments in attention and inhibitory control probably mediate the effect.

Comparison of cell proliferation and epigenetic modification of gene expression patterns in canine foetal fibroblasts and adipose tissue-derived mesenchymal stem cells.

OBJECTIVES: This study compared rate of cell proliferation, viability, cell size, expression patterns of genes related to pluripotency and epigenetic modification between canine foetal fibroblasts (cFF) and canine adipose tissue-derived mesenchymal stem cells (cAd-MSC). MATERIALS AND METHODS: Proliferation pattern, cell viability as well as cell size at each passage of cFF and cAd-MSC were measured when cultures reached confluence. In addition, real-time PCR was performed to investigate expression of Dnmt1, HDAC1, OCT4, SOX2, BAX, BCL2 genes with reference to ß-actin gene expression as an endogenous control in both cell lines. RESULTS: cFF and cAd-MSC differed in number of generations, but not in doubling times, at all passages. Mean cell size of cAd-MSC was significantly smaller than that of cFF. Cell viability was significantly lower in cFFs and apoptotic level was significantly lower in cAd-MSC compared to passage-matched cFF. In the expression of genes related to pluripotency and epigenetic modification, level of HDAC1 in cAd-MSC was significantly higher than in cFF, but expression of Dnmt1 did not differ between the two groups. OCT4 and SOX2 were significantly more highly expressed in cAd-MSC compared to cFF. CONCLUSIONS: cAd-MSC have higher stem-cell potential than cFF in terms of proliferation patterns, epigenetic modification and pluripotency, thus cAd-MSC could be more appropriate than cFF as donors of nuclei in somatic cell nuclear transfer for transgenesis.

Lessons learned from cloning dogs.

The aim of this article is to review dog cloning research and to suggest its applications based on a discussion about the normality of cloned dogs. Somatic cell nuclear transfer was successfully used for production of viable cloned puppies despite limited understanding of in vitro dog embryo production. Cloned dogs have similar growth characteristics to those born from natural fertilization, with no evidence of serious adverse effects. The offspring of cloned dogs also have similar growth performance and health to those of naturally bred puppies. Therefore, cloning in domestic dogs can be applied as an assisted reproductive technique to conserve endangered species, to treat sterile canids or aged dogs, to improve reproductive performance of valuable individuals and to generate disease model animals.