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The coronavirus disease 2019 (COVID-19) pandemic has caused significant changes. This study aimed to investigate the impact of COVID-19 on patients with chronic pain.Patients with chronic pain from 23 university hospitals in South Korea participated in this study. The anonymous survey questionnaire consisted of 25 questions regarding the following: demographic data, diagnosis, hospital visit frequency, exercise duration, time outside, sleep duration, weight change, nervousness and anxiety, depression, interest or pleasure, fatigue, daily life difficulties, and self-harm thoughts. Depression severity was evaluated using the Patient Health Questionnaire-9 (PHQ-9). Logistic regression analysis was used to investigate the relationship between increased pain and patient factors.A total of 914 patients completed the survey, 35.9% of whom had decreased their number of visits to the hospital, mostly due to COVID-19. The pain level of 200 patients has worsened since the COVID-19 outbreak, which was more prominent in complex regional pain syndrome (CRPS). Noticeable post-COVID-19 changes such as exercise duration, time spent outside, sleep patterns, mood, and weight affected patients with chronic pain. Depression severity was more significant in patients with CRPS. The total PHQ-9 average score of patients with CRPS was 15.5, corresponding to major depressive orders. The patients' decreased exercise duration, decreased sleep duration, and increased depression were significantly associated with increased pain.COVID-19 has caused several changes in patients with chronic pain. During the pandemic, decreased exercise and sleep duration and increased depression were associated with patients' increasing pain.

The consumption of processed and refined food lacking in fiber has led to global prevalence of obesity and cardiometabolic diseases. Fiber-fortification into these foods can yield potential health improvements to reduce disease risk. This meta-analyses aimed to evaluate how fiber-fortified food consumption changes body composition, blood pressure, blood lipid-lipoprotein panel, and glycemic-related markers. Searches were performed from 5 databases, with 31 randomized controlled trial eventually analyzed. Hedges��� g values (95% confidence interval [CI]) attained from outcome change values were calculated using random-effects model. Fiber-fortified food significantly reduced body weight (���0.31 [���0.59, ���0.03]), fat mass (���0.49 [���0.72, ���0.26]), total cholesterol (���0.54 [���0.71, ���0.36]), low-density lipoprotein cholesterol (���0.49 [���0.65, ���0.33]), triglycerides (���0.24 [���0.36, ���0.12]), fasting glucose (���0.30 [���0.49, ���0.12]), and HbA1c (���0.44 [���0.74, ���0.13]). Subgroup analysis differentiated soluble fiber as significantly reducing triglycerides and insulin while insoluble fiber significantly reduced body weight, BMI, and HbA1c. Greater outcome improvements were observed with solid/semi-solid food state than liquid state. Additionally, fiber fortification of p-value = 0.036). Findings from this study suggest that consuming food fortified with dietary fiber can improve anthropometric and cardiometabolic outcomes.

Context Xanthophyll intake is known to improve eye health; however, its benefits on visual outcomes have not been systematically studied, particularly in a population with eye diseases. Objective A systematic review, meta-analysis, and meta-regression were conducted to investigate the effect of xanthophyll intake on visual outcomes, and further subgroup analysis was performed on the basis of eye disease status. Data Sources The PubMed, Scopus, Embase, CINAHL, Cochrane, and Web of Science databases were searched, and relevant randomized controlled trials were identified. Data Extraction For systematic review, meta-analysis, and meta-regression, 43, 25, and 21 articles were selected, respectively. Data Analysis Xanthophyll intake enhanced macular pigment optical density (MPOD) for both heterochromatic flicker photometry (weighted mean difference [WMD], 0.05; 95% confidence interval [CI], 0.03–0.07) and autofluorescence imaging (WMD, 0.08; 95%CI, 0.05–0.11) measurements and decreased photostress recovery time (WMD, –2.35; 95%CI, –4.49 to –0.20). While enhancement in visual acuity logarithm of the minimum angle of resolution was observed in response to the xanthophyll-rich food and supplement intake only for patients with eye disease (WMD, –0.04; 95%CI, –0.07 to –0.01). Meta-regression showed a positive correlation between change in MPOD (heterochromatic flicker photometry) and the corresponding change in serum lutein levels (regression coefficient = 0.068; P = 0.00). Conclusion Intake of xanthophyll-rich food or supplements can improve eye health. Additional improvement in visual acuity was observed in patients with eye disease. A positive association between MPOD and serum lutein level, while absent with dietary xanthophyll intake, suggests the importance of bioavailability when examining the effect of xanthophyll on eye health. Systematic Review Registration PROSPERO registration no. CRD42021295337.

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The paper is to study the reasons why the global competitiveness of the Japanese industry has weakened significantly in the automobile industry. Four leading causes will be analyzed to weaken Japanese global competitiveness regarding technical, market, policy, and corporate factors. Above all, the human element, which is consisted of the dynamics of entrepreneurs, workers, experts, politicians, and administrative bureaucrats, is the most critical in analyzing the technical, market, policy, and corporate factors of global competitiveness in each industry. In Japan, workers and experts were responsible for technology transfer within the industry. Japan was far ahead of Korea regarding technological equipment, but there were frequent cases of human leaking. Japanese automakers’ entrepreneurs failed to the quality management of the overseas workforce while promoting a growth-centered corporate strategy, resulting in a massive recall in 2009. As for the Japanese automobile industry, global competitiveness has been weakened due to the inability of the technicians to supply an overseas workforce to cope with the boom period of the worldwide market. In addition, politicians and bureaucrats, via the government's industrial support or policy, played an inevitable role in enhancing the competitiveness of Japan in early development. As an industry incumbent, Japan formed an industrial ecosystem while pursuing industrial development through government-led industrial policy. Thus, when the economy came into a recession, especially macroeconomic stagnation, there should have been timely action or policy support at the government level. With the technological development of products, the market of the industry was booming or depressed at that time, along with the government's policy and strategic support to develop each sector and to maintain its global competitiveness. The Japanese government failed to take advantage of the market due to the wrong choice of investment period and, thus, caused to lessen the gap with Korea. The investment reduction or cost reduction decided by entrepreneurs as one of the main factors, explained in detail by the corporate factor as the internal cause, is noteworthy among the four factors of weakening global competitiveness. The biggest reason Toyota lost global competitiveness, mainly due to its massive recall in the automobile industry, is that it made small investments during critical periods, delayed investments, or impractical cost reduction strategies in significant investment periods. The technology, market, and policy factors are the leading causes because of the necessary-to-sufficient relationship with the investment or cost reduction. With the decision-making process for investment or cost reduction by entrepreneurs, Toyota Motors would have avoided the massive recall in the global arena.

Several studies have reported the pathogenic role of Malassezia in atopic dermatitis (AD); the significance of Malassezia’s influence on AD needs to be further investigated. Dupilumab, a monoclonal antibody to anti-Interleukin (IL) 4Rα, and ruxolitinib, a Janus kinase (JAK)1/2 inhibitor, are the first approved biologics and inhibitors widely used for AD treatment. In this study, we aimed to investigate how Malassezia Restricta (M. restricta) affects the skin barrier and inflammation in AD and interacts with the AD therapeutic agents ruxolitinib and anti-IL4Rα. To induce an in vitro AD model, a reconstructed human epidermis (RHE) was treated with IL-4 and IL-13. M. restricta was inoculated on the surface of RHE, and anti-IL4Rα or ruxolitinib was supplemented to model treated AD lesions. Histological and molecular analyses were performed. Skin barrier and ceramide-related molecules were downregulated by M. restricta and reverted by anti-IL4Rα and ruxolitinib. Antimicrobial peptides, VEGF, Th2-related, and JAK/STAT pathway molecules were upregulated by M. restricta and suppressed by anti-IL4Rα and ruxolitinib. These findings show that M. restricta aggravated skin barrier function and Th2 inflammation and decreased the efficacy of anti-IL4Rα and ruxolitinib.

Understanding how ecological communities assemble is an urgent research priority. In this study, we used a phylogenetic community ecology approach to examine how ecological and evolutionary processes shape biodiversity patterns of plant pathogenic fungi, Fusarium graminearumand F. asiaticum. High-throughput screening revealed that the isolates had a wide range of phenotypic variation in stress tolerance traits. The low phylogenetic signals in stress tolerance traits suggested that Fusarium species rapidly and divergently evolve these traits among related taxa. Our results indicate that co-occurring strains were more likely to be similar in stress tolerance than expected by chance. Competition assays of the pooled strains were conducted to investigate the cause of clustering. During stress conditions and wheat colonization, only a few strains dominated the fungal communities, resulting in reduced diversity. Overall, our findings support the modern coexistence theory that abiotic stress and competition lead to phenotypic and phylogenetic similarities among coexisting organisms by excluding large, low-competitive clades. We suggest that agricultural environments and competition for host infection lead to locally clustered communities of plant pathogenic fungi in the field.

Botulinum toxin type A is widely used to treat primary axillary hyperhidrosis and has proven to be an effective and safe approach. Onabotulinumtoxin A was approved by the FDA as a treatment for primary axillary hyperhidrosis. This study aimed to evaluate the efficacy and safety of Neu-BoNT/A in subjects diagnosed with primary axillary hyperhidrosis.The Hyperhidrosis Disease Severity Scale, gravimetric measurement of sweat, and Global Assessment Scale were analyzed at weeks 4, 8, 12, and 16 to determine the effect of treatment. Adverse events, physical examination, and vital signs were monitored.Subjects treated with Neu-BoNT/A showed statistically significant improvement by all 3 methods at weeks 4, 8, 12, and 16 (P value = 0.00). There were no severe adverse events or significant changes in vital signs, physical examination, or laboratory tests.Neu-BoNT/A can be effectively and safely used for primary axillary hyperhidrosis.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background: Several dermoscopic findings that could be helpful in diagnosing onychomycosis have been reported in many cases, but they have not been sufficiently utilized in clinical practice. Objective: To evaluate and identify the dermoscopic findings that may assist in the accurate diagnose of onychomycosis. Methods: The study included 42 patients with clinical features suggestive of onychomycosis based on the clinical history, physical examination, dermoscopic findings, and mycological investigation. Clinical photographs and nail dermoscopy images were obtained, which were retrospectively reviewed and analyzed according to the onychomycosis classification. Results: In total, 42 representative nails were reviewed. Common dermoscopic patterns such as yellow/brown discoloration and subungual hyperkeratosis were found in our onychomycosis patients. Key findings observed in specific subtypes were distolateral subungual onychomycosis with "jagged edges with spikes", proximal subungual onychomycosis or white superficial onychomycosis with irregularly bordered homogeneous leukonychia with postinflammatory hyperpigmentation on the proximal nail fold, and fungal melanonychia with nail plate roughness and nail fold hyperkeratosis. Conclusion: Our study, along with previous studies, demonstrated dermoscopy as a quick and effective tool for diagnosing onychomycosis. In addition, periungual dermoscopic findings can be an important clue in onychomycosis diagnosis, especially in cases of fungal melanonychia and leukonychia.

Background: Treatment of herpes zoster not only includes antiviral therapy but also treatment of herpes zoster-associated pain. Severe herpes zoster-associated pain often limits a patient’s activities of daily living and may significantly lower functional status and quality of life. It also functions as an important predictor of postherpetic neuralgia. Thus, effective treatment of zoster pain is highly necessary. The effectiveness of a drug may depend on the method of administration, with each route having merits and limitations. Accurate epidural drug delivery directly into an affected spinal segment can maximize the effects of the drug, while minimizing systemic adverse drug effects. Here, we present three cases of successful control of zoster pain using an electrical stimulating catheter with a steering guidewire. Case Presentation: We treated three patients suffering from herpes zoster with continuous segmental block using an electrical stimulating catheter. The first case involved a 54-year old man with severe right-sided low back and thigh pain, the second patient was a 72-year-old woman suffering from multiple painful grouped vesicles on the left flank, the third patient was a 72-year-old man with multiple vesicles on the right arm. The three patients were treated with continuous segmental block via an electrical stimulating catheter, which was able to localize stimulation to the affected spinal segment. There were no procedure-related complications, and the pain levels of the patients decreased significantly. Conclusions: Continuous segmental block through electrical stimulation using an electrical stimulating catheter with a steering guidewire can be precisely positioned, providing targeted drug delivery and effective management of herpes zoster.

Context Dietary fats are one of the well-known stimulators of carotenoid absorption, but the effects of the quantity and the type of dietary fats on carotenoid absorption have not yet been studied systematically. Objective This review aimed to analyze data from both in vitro studies and randomized controlled trials (RCTs) to examine the effects of dietary fats on the bioaccessibility and bioavailability of carotenoids. Data Sources A systematic search of 5 databases (Scopus, PubMed, Embase, CINAHL and the Cochrane Library) was conducted. Study Selection In vitro studies and RCTs were selected according to the PICOS criteria and were reviewed independently by 2 investigators. Date Extraction Key study characteristics from the eligible in vitro studies and RCTs were extracted independently by 2 investigators using a standardized table. Results A total of 27 in vitro studies and 12 RCTs were included. The meta-regression of in vitro studies showed that the bioaccessibility of carotenoids, except for lycopene, was positively associated with the concentration of dietary fats. The meta-analysis of RCTs showed that the bioavailability of carotenoids was enhanced when a higher quantity of dietary fats was co-consumed. Moreover, fats rich in unsaturated fatty acids resulted in greater improvement in carotenoid bioavailability (SMD 0.90; 95%CI, 0.69–1.11) as compared with fats rich in saturated fatty acids (SMD 0.27; 95%CI, 0.08–0.47). Conclusions Co-consuming dietary fats, particularly those rich in unsaturated fatty acids, with carotenoid-rich foods can improve the absorption of carotenoids. Systematic Review Registration PROSPERO registration number CRD42020188539.

Background In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD). Objective We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience. Methods We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations. Results We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate. Conclusion We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.

Biologics, such as tumor necrosis factor-α and interleukin inhibitors, are commonly used for treating immunological skin diseases, including psoriasis, psoriatic arthritis, and atopic dermatitis. The cluster of differentiation inhibitors and immune checkpoint inhibitors has also been used for treating bullous disorders and melanoma, respectively. Other small-molecule inhibitors, such as JAK inhibitors, have been introduced for treating atopic dermatitis and alopecia areata. Hence, given the importance of cytokines and small molecules in antifungal immunity, using these new treatments are proposed to increase the risk of fungal infections. Thus, this review presents an overview of the reported incidences and possible mechanisms of fungal infections related to the use of biologics, including small-molecule inhibitors used for dermatological treatments.

Alopecia areata (AA) is an autoimmune condition related to the collapse of the immune privilege of hair follicles. Certain AA populations present severe clinical manifestations, such as total scalp hair or body hair loss and a treatment refractory property. The aim of this study was to assess the effects of allogenic human mesenchymal stem cells (hMSCs) from healthy donors on the peripheral blood mononuclear cells (PBMCs) of severe AA patients, with a focus on the change in the cell fraction of Th1, Th17, and Treg cells and immunomodulatory functions. PBMCs of 10 AA patients and eight healthy controls were collected. Levels of Th17, Th1, and Treg subsets were determined via flow cytometry at baseline, activation status, and after co-culturing with hMSCs. All participants were severe AA patients with SALT > 50 and with a long disease duration. While the baseline Th1 and Treg levels of AA patients were comparable to those of healthy controls, their Th17 levels were significantly lower than those of the controls. When stimulated, the levels of CD4+IFN-γ+ T cells of the AA patients rose sharply compared to the baseline, which was not the case in those of healthy controls. The cell fraction of CD4+Foxp3+ regulatory T cells also abruptly increased in AA patients only. Co-culturing with allogenic hMSCs in activated AA PBMCs slightly suppressed the activation levels of CD4+INF-γ+ T cells, whereas it significantly induced the differentiation of CD4+Foxp3+ regulatory T cells. However, these changes were not prominent in the PBMCs of health controls. To examine the pathomechanisms, PBMCs of healthy donors were treated with IFN-γ to induce AA-like environment and then treated with allogenic grants and compared with ruxolitinib as a positive treatment control. hMSC treatment was shown to significantly inhibit the mRNA levels of proinflammatory cytokines, such as IFN-γ, TNF-α, IL-1α, IL-2R, IL-15, and IL-18, and chemokines, such as CCR7 and CCR10, in IFN-treated PBMCs. Interestingly, hMSCs suppressed the activation of JAK/STAT signaling by IFN in PBMCs with an effect that was comparable to that of ruxolitinib. Furthermore, the hMSC treatment showed stronger efficacy in inducing Foxp3, IL-10, and TGF-β mRNA transcription than ruxolitinib in IFN-treated PBMCs. This study suggests that allogenic hMSC treatments have therapeutic potential to induce immune tolerance and anti-inflammatory effects in severe AA patients.

In this study, the levels of plasma estradiol-17β (E

Deciding whether to continue or discontinue aspirin prior to interventional procedures is a major concern for pain physicians. Many guidelines have been published on the discontinuation of aspirin before invasive procedures; however, the recommendations are inconsistent and do not consider individual platelet function. Furthermore, many studies have shown a high prevalence of aspirin resistance in patients taking this medication.To determine the necessity of discontinuing aspirin prior to interventional pain procedures in relation to individual platelet function.Multicenter, cross-sectional study.University-affiliated hospitals.We examined platelet function among patients scheduled for an interventional pain procedure by measuring their closure time using collagen/epinephrine cartridges in a commercial platelet-function analyzer. The patients were categorized into either an aspirin-taking or nonaspirin-taking group (Group A or Group N, respectively). The proportion of patients who showed normal/abnormal platelet function was calculated and compared between the groups.A total of 1,111 patients were included in this study. In Group A, 56.4% (102/181) showed normal platelet function, whereas 43.6% (79/181) showed abnormal platelet function. In Group N, 85.8% (798/930) and 14.2% (132/930) showed normal and abnormal platelet function, respectively.The proportion of laboratory, not clinical aspirin resistance was evaluated. Factors affecting platelet function were not investigated exhaustively.The high prevalence of normal platelet function in patients taking aspirin suggests no necessity of discontinuation before procedures in such patients. Abnormal platelet function can occur even in patients who are not taking aspirin. Therefore, platelet function should be measured and considered on a case-by-case basis prior to interventional procedures, and discontinuation of aspirin should be decided based on these factors.