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Background: This study evaluated the level of burden in pediatric and adolescent atopic dermatitis (AD) patients in Japan, the associated burden on caregivers/families, and whether this burden varied with age. Methods: Data were drawn from the Adelphi Pediatric AD Disease Specific Programme (DSP)™, a cross‐sectional survey of physicians and their patients conducted in Japan between July and December 2022. Physicians reported patient demographics, clinical characteristics, disease burden, and current/previous therapies. Patients and/or caregivers reported perceived disease severity and impact of AD, including the Children's Dermatology Life Quality Index (CDLQI) and Dermatitis Family Impact questionnaire (DFI). Results: Overall, 55 physicians provided data for 537 AD patients aged ≤17. Mean (SD) overall scores for CDLQI, POEM, and DFI were 9.3 (6.3), 8.3 (6.8), and 11.7 (7.2), respectively. Age was associated with higher patient and/or caregiver‐reported CDLQI scores, which increased by 0.543 points per year of age (P = 0.01). Patients with severe disease reported a more significant impact on quality of life factors compared with mild patients (P < 0.001). Age was associated with higher caregiver‐reported burden, with DFI scores increasing by 0.325 per year (P = 0.01). Physician‐reported impact on caregivers showed that age was significantly associated with increased burden on sleep, daily activities, work, and mood (P < 0.05), with disease severity associated with impact across all factors (P < 0.01). Conclusions: Both increasing age and disease severity were associated with the increased impact of AD on patients and their caregivers. Disease control/modification through appropriate therapeutic intervention at a younger age may relieve the burden of pediatric AD on patients and their families. [ABSTRACT FROM AUTHOR]

Objective Stable and swift placement of a guiding catheter in endovascular therapies for acute vertebrobasilar artery occlusion is often difficult because of the tortuous bends of the vertebral or subclavian artery especially in older people. The use of a delivery assist guiding catheter (DAGC) shortens the time with stable support to deliver a therapeutic treatment catheter to the target lesions. Herein, we reported the clinical and radiographic outcomes in endovascular therapies utilizing the DAGC for acute vertebrobasilar artery occlusions in actual clinical settings. Materials and Methods Between January 2018 and December 2021, 33 consecutive patients (males, 20[60.6%]; median age, 78 years) using a DAGC for acute vertebrobasilar artery occlusion were analyzed retrospectively. Reperfusion was graded using postinterventional angiograms based on the "thrombolysis in cerebral infarction" (TICI) classification. Furthermore, the time from puncture to recanalization and the rate of effective recanalization achievement were investigated. Results Effective recanalization with TICI 2b or 3 was achieved in 28 (84.8%) patients, and the median time from puncture to recanalization was only 44 minutes, despite the high rate of older patients in our cohort. In contrast, asymptomatic intracranial hemorrhage as a complication was observed in only 3 (9.1%) patients. Conclusion The DAGC contributes to the shortening of recanalization time and improves the outcomes of endovascular therapies for acute vertebrobasilar artery occlusion. [ABSTRACT FROM AUTHOR]

Background Buerger disease, also known as Winiwarter–Buerger disease or thromboangiitis obliterans (TAO), is a non-specific inflammation of small- and medium-sized arteries with thrombus obliteration and without atherosclerotic changes. Patients with TAO can develop chronic limb-threatening ischaemia (CLTI) and are at risk of limb amputation despite smoking cessation and exercise therapy recommendations. Case summary A 72-year-old Japanese man presented with painful discolouration of toes and renal impairment. He was diagnosed with Rutherford classification Stage 6 CLTI with immunoglobulin A nephropathy. He refused limb amputation. Clinical symptoms reduced after treatment with low-intensity pulsed ultrasound (LIPUS). LIPUS is a non-invasive option to alleviate peripheral arterial disease symptoms. Despite the initiation of conventional therapy measures, there was a worsening of the limb condition. The non-invasive investigational treatment option of LIPUS was initiated after the poor clinical outcomes of the conventional therapy measures. The patient's symptoms in the bilateral lower limbs, ulcers, and the blue-coloured toes gradually lessened. After 1 year of treatment with LIPUS, he had achieved better walking independence with improved quality of life. Discussion Low-intensity pulsed ultrasound is a non-invasive option for therapeutic angiogenesis with the potential to improve ischaemic limb conditions in patients with peripheral arterial disease and to avoid major amputation procedures. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a significant clinical, economic, and human burden. The JAK1 Atopic Dermatitis Efficacy and Safety (JADE) program's Phase 3 trials demonstrated that as a treatment for moderate‐to‐severe AD in adults with previous exposure to immunotherapy, abrocitinib showed superior efficacy and safety compared with standard of care (SoC), consisting of topical corticosteroids. This study assessed the cost‐effectiveness of abrocitinib with SoC versus SoC alone for this patient population in Japan from a societal perspective. A hybrid decision tree and Markov model were used to capture the initial treatment and long‐term maintenance phases. Clinical inputs at 16 weeks were obtained through a Bayesian network meta‐analysis of four pivotal trials from the JADE program. Clinical inputs at 52 weeks were derived from the JADE EXTEND trial. Response‐specific utility inputs were obtained from published literature. Resource use, costs, and productivity inputs were gathered from Japanese claims analysis, literature, public documents, and expert opinion. Costs and quality‐adjusted life years (QALYs) were discounted at 2.0% per year and incremental cost‐effectiveness ratios (ICERs) were calculated. Sensitivity and scenario analyses were performed to validate the base case results and explore a payer perspective. Over a lifetime horizon and with the base‐case societal perspective, abrocitinib produced a mean gain of 0.75 QALYs, incremental costs of JPY (¥) 2 270 386 (USD [$] 17 265.6), and a resulting ICER of ¥3 034 514 ($23 076.5) per QALY compared with SoC. From a payer perspective, the incremental costs increased to ¥4 476 777 ($34 044.4), with an ICER of ¥5 983 495 ($45 502.6) per QALY. The results were most sensitive to treatment‐specific, response‐based utility weights, drug costs, and productivity‐related inputs. From a Japanese societal perspective, abrocitinib demonstrated superior QALYs and with a willingness‐to‐pay threshold of ¥5 000 000 ($38 023.4) per QALY, can be considered cost‐effective compared with SoC as a treatment for moderate‐to‐severe AD in adult patients with previous immunosuppressant exposure. [ABSTRACT FROM AUTHOR]

Water plays a significant role in the deterioration of reinforced concrete buildings; therefore, it is essential to evaluate the water content of the cover concrete. This study explores a novel non-destructive method for assessing the water content using sub-terahertz (sub-THz) waves. Among the four frequencies selected to evaluate the water content, an increase in reflectance was observed as the unit volume water content increased, and smaller data scatter was confirmed as the frequency increased. The derived empirical equation can classify the corrosion risk of the rebar environment based on the water content obtained using reflectance measurements. In other words, it can contribute to the diagnosis of the building integrity associated with rebar corrosion. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to clarify how patient‐perceived aggravating factors change during the course of AD. Methods: This study involved a questionnaire‐based survey administered to 115 patients with AD at our hospital. The changes in patient‐perceived aggravating factors were examined as treatment progressed by readministering the questionnaire to 36 patients 6 months later. Results: The most frequent aggravating factors at the first visit were sweating, emotional stress, and house dust. The number of patients who identified food, dust mites, house dust, pollen, and pets as aggravating factors decreased during the course of the disease. However, the number of patients who identified sweating, environmental factors, emotional stress, and lack of sleep as aggravating factors did not differ from those at the first visit; this included those who newly identified these as aggravating factors. Conclusion: Many patients with AD are concerned about the aggravating factors, and it may be possible to reduce aggravating factor‐related anxiety by informing patients that certain aggravating factors may change during treatment. Hence, it is necessary to ask patients about the aggravating factors at the first visit and fixed intervals and resolve them immediately. [ABSTRACT FROM AUTHOR]

Objectives: The cytokine oncostatin M (OSM) elicits pathogenic effects involving disruption of the epithelial barrier function as a part of immunological response networks. It is unclear how these integrated cytokine signals influence inflammation and other physiological processes in the pathology of chronic rhinosinusitis (CRS). We investigated the expression and distribution of OSM and OSM receptor (OSMR) in CRS patients' sinonasal specimens, and we compared the results with a panel of inflammatory cytokine levels and clinical features. Patients and Methods: We classified CRS patients as eosinophilic (ECRS, n = 36) or non-eosinophilic (non-ECRS, n = 35) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis phenotypic criteria and compared their cases with those of 20 control subjects. We also examined OSM's stimulatory effects on cytokine receptor expression levels using the human bronchial epithelium cell line BEAS-2B. Results: RT-PCR showed that the OSM mRNA levels were significantly increased in the CRS patients' ethmoid sinus mucosa. The OSM mRNA levels were positively correlated with those of TNF-α, IL-1β, IL-13, and OSMR-β. In BEAS-2B cells, OSM treatment induced significant increases in the OSMRβ, IL-1R1, and IL-13Ra mRNA levels. Conclusions: OSM is involved in the pathogenesis of CRS in both type 1 and type 2 inflammation, suggesting the OSM signaling pathway as a potential therapeutic target for modulating epithelial stromal interactions. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) is characterized by daily recurring wheal and flare with itch for more than 6 weeks. The extrinsic coagulation system has been shown to be activated in correlation with CSU severity. We have reported that tissue factor (TF), a trigger of the extrinsic coagulation cascade, is synergistically expressed on vascular endothelial cells by simultaneous stimulation with TF inducers (TFI), followed by activation of the extrinsic coagulation cascade and hyper permeability in vitro. However, vascular endothelial cells are not likely to be simultaneously stimulated by multiple TFIs under physiological conditions. Therefore, in order to know whether sequential, rather than simultaneous, stimuli with interval may induce synergistic activation of TF, we investigated the time course of the priming effects of each TFI for synergistic TF expression in vascular endothelial cells (HUVECs). We stimulated HUVECs with a TFI (first stimulation) and then stimulated cells with another TFI at indicated time points (second stimulation) and detected TF expression and activity. The TF expression induced by simultaneous stimulation diminished in a few hours. However, both synergistic enhancement of TF expression and activation level of the coagulation cascade were detected even when the second stimulation was added 18 or 22 h after the first stimulation. Thus, the priming effect of TFI for synergistic TF expression may persist for a half day or longer. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch and pruritus anywhere on the body for more than 6 weeks. Although basophil- and mast cell-released inflammatory mediators, such as histamine, play important roles in the pathogenesis of CSU, the detailed underlying mechanism is not clear. Since several auto-antibodies, IgGs which recognize IgE or the high-affinity IgE receptor (FcεRI) and IgEs against other self-antigens, are detected in CSU patients, they are considered to activate both mast cells in the skin and basophils circulating in the blood. In addition, we and other groups demonstrated that the coagulation and complement system also contribute to the development of urticaria. Here, we summarized the behaviors, markers and targets of basophils in relation to the coagulation–complement system, and for the treatment of CSU. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is attributable to both a genetic predisposition and environmental factors. Among numerous cytokines involved in the pathogenesis of AD, interleukin‐33 (IL‐33), reportedly escaping exocytotically in response to a scratch, is abundantly expressed in the skin tissues of patients with AD and is postulated to induce inflammatory and autoimmune responses. In this study, we first demonstrated that peptidylprolyl cis/trans isomerase, NIMA‐interacting 1 (Pin1), a unique enzyme which isomerizes the proline residues of target proteins, is abundantly expressed in keratinocytes, and that the areas where it is present in the skin tissues of AD patients became expanded due to hyperkeratosis. Thus, we investigated the effects of Pin1 on the regulation of IL‐33 expression using the human keratinocyte cell line HaCaT. Interestingly, silencing of the Pin1 gene or treatment with Pin1 inhibitors dramatically reduced IL‐33 expressions in HaCaT cells, although Pin1 overexpression did not elevate it. Subsequently, we showed that Pin1 binds to STAT1 and the nuclear factor‐kappaB (NF‐κB) subunit p65. Silencing the Pin1 gene with small interfering RNAs significantly reduced the phosphorylation of p65, while no marked effects of Pin1 on the STAT1 pathway were detected. Thus, it is likely that Pin1 contributes to increased expression of IL‐33 via the NF‐κB subunit p65 in HaCaT cells, at least modestly. Nevertheless, further study is necessary to demonstrate the pathogenic roles of Pin1 and IL‐33 in AD development. [ABSTRACT FROM AUTHOR]

Spindle cell variant of ameloblastic carcinoma (SpCAC) is a rare subtype of ameloblastic carcinoma. Herein, we describe an additional case of SpCAC of the mandible of a 76-year-old Japanese male. We discuss diagnostic problems we encountered in this case, focusing on unusual expression of myogenic/myoepithelial markers, such as smooth muscle actin and calponin. [ABSTRACT FROM AUTHOR]

Skin diseases are common in children. However, the prevalence of childhood skin diseases in Japan has not been reported extensively. In this study, dermatologists conducted face‐to‐face examinations of primary school children over a 10‐year period to determine the prevalence of each skin disease. Atopic dermatitis (AD, 12.3%) was the most common disease among first graders, followed by eczema other than AD (9.7%), molluscum contagiosum (1.9%), and verruca vulgaris (1.1%). Among sixth graders, acne vulgaris was most common (9.6%), followed by AD (8.9%), eczema other than AD (6.7%), and verruca vulgaris (3.1%). The prevalence of AD remained stable among first graders after 2010, at approximately 10%–15%, but it increased slightly among sixth graders. Of the 87 children who had AD in first grade, 51 (58.6%) were in remission in sixth grade. On the other hand, AD was diagnosed in 30 (4.5%) sixth graders who had been among the 665 children who did not have it in first grade. The more severe the symptoms were in first grade, the more likely a child was to still have AD in sixth grade, and the more severe the later symptoms tended to be. This study investigated recent trends in skin diseases in Japanese primary school children and found that the prevalence of some skin diseases differed between first and sixth graders. It was also found that children with moderate AD in first grade were more likely to be moderate in sixth grade than those with mild AD. [ABSTRACT FROM AUTHOR]

The prevalence of urticaria has been reported mostly in Europe and North America. However, precise information regarding its subtypes and clinical characteristics in primary care practice, especially in Asian countries, are scant. Patients with urticaria and/or angioedema who visited nine primary clinics of accredited dermatologists and allergologists in Japan were recruited from October to November 2020. The information of age, sex, disease duration, urticaria control test (UCT), and concomitant urticaria subtypes were collected. A total of 1061 patients participated. The number of patients was high in the 20 to 50 age groups with a peak in the 40s. The most frequent urticaria subtype was chronic spontaneous urticaria (CSU) followed by dermographism, acute spontaneous urticaria (ASU), angioedema, and cholinergic urticaria (CholU) (66.8%, 22.7%, 18.9%, 14.1% and 5.7% in all patients with urticaria). CSU development increased with age from the 20s to 50s, especially in females. Dermographism had a peak in the 40s. ASU had bimodal peaks in childhood and in the 30s. CholU was common in males in the 10–20s. Most angioedema patients were female with an increase in their 30s. Angioedema was solely present in 14 of 1061 participants (1.3%), while 136 (12.8%) had angioedema concomitant with urticaria. UCT showed poorly controlled urticaria with lower scores in patients with concomitant CSU and other subtypes than in those with CSU alone. Urticaria tends to develop in young to middle‐aged females. The most common urticaria subtype is CSU, while the number of patients with CholU is high and that of angioedema is low in Japan. [ABSTRACT FROM AUTHOR]

In the design and production of electrical and electronic devices and circuits, it is desirable to have a calculation formula for obtaining exact inductance values, which are generally fundamental for coils. In this paper, a formula that can be applied to the exact calculations of the self‐inductance of arbitrary‐shaped single‐layer coils is presented, and its application to the several types of coils that are technologically valuable is reported. Specifically, the formula employs a new coefficient corresponding to the Nagaoka coefficient and the shape function determined by the coil. Moreover, it realizes a versatile and convenient inductance calculation method. In addition, as the formula is derived via an analytical method, it has the advantage that it can be calculated with a short‐time numerical integration. As examples of the application of the formula, rhombic, race‐track, elliptic, and regular polygonal coils were discussed, and the process and result of deriving the shape function and new coefficient for each coil were presented. Furthermore, regarding the calculation formula for regular polygonal coils, we made a regular pentagonal coil and conducted an experiment, and the validity of the calculation formula was confirmed. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is frequently detected in the skin of patients with atopic dermatitis (AD). AD skin‐derived strains of S. aureus (AD strain) are selectively internalized into keratinocytes (HaCaT cells) compared to standard strains. However, the mechanism of AD strain internalization by keratinocytes and effect of the skin environment on internalization remain unclear. HaCaT cells were exposed to heat‐killed AD or standard strains of fluorescently labeled S. aureus, with or without interferon (IFN)‐γ, interleukin (IL)‐4, and IL‐13 cytokines, for 24 h. Filaggrin and fibronectin expression in HaCaT cells was knocked down using small interfering RNA. The amount of internalized S. aureus was evaluated using a cell imaging system. The effects of INF‐γ, IL‐4, and S. aureus exposure on mRNA expression in HaCaT cells were analyzed using single‐cell RNA sequencing. AD strains adhered to HaCaT cells in approximately 15 min and were increasingly internalized for up to 3 h (2361 ± 467 spots/100 cells, mean ± SD), whereas the standard strain was not (991 ± 71 spots/100 cells). In the presence of IFN‐γ, both the number of internalized strains and fibronectin expression significantly decreased compared to in the control, whereas Th2 cytokines had no significant effects. The number of internalized AD strains was significantly higher in filaggrin knockdown and lower in fibronectin knockdown HaCaT cells compared to in the control. RNA sequencing revealed that IFN‐γ decreased both fibronectin and filaggrin expression. Keratinocyte internalization of the AD strain may be predominantly mediated by the INF‐γ‐fibronectin pathway and partially regulated by filaggrin expression. [ABSTRACT FROM AUTHOR]

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence‐based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity‐related patient outcomes with respect to several important points requiring decision‐making in clinical practice. [ABSTRACT FROM AUTHOR]

The prevalence of atopic dermatitis (AD) has been steadily increasing in recent decades, reaching a steady plateau at the end of the 20th century. However, most of them were surveys of children, and the current prevalence and severity of AD in adults are unknown. A longitudinal survey including 40 649 freshmen attending Hiroshima University between 2002 and 2019 was conducted, with the aim to determine changes in AD prevalence in young adults over the age of 18 years. All data were longitudinally collected at a fixed time of the year. The AD diagnosis and severity assessment were made by dermatologists based on the diagnostic criteria in the Japanese Guidelines for AD. History or comorbidities of asthma and allergic rhinitis/conjunctivitis, current AD management, and use of topical corticosteroids (TCS) were also surveyed using a questionnaire. The prevalence of AD in university freshmen is slightly increasing from 9.1% in 2002 to 12.0% in 2010, remaining steady at around 10–11% until 2019, with poorly controlled AD present in nearly 10%. History or comorbidities of asthma and allergic rhinitis/conjunctivitis slightly increased from 2006 to 2019 in both the students with and without AD. Facial eczema was common among those with severe and most severe AD, whereas approximately 50% of the students with moderate AD and approximately 20% of those with mild AD exhibited facial eczema. The percentage of students treating AD at medical institutions and those self‐managing was almost the same. This survey also revealed the presence of substantial anxiety regarding TCS use for AD and the necessity of promoting more effective explanation and education on AD by medical professionals. [ABSTRACT FROM AUTHOR]

Previous studies have shown the efficacy of delgocitinib (DEL) ointment, a topical Janus kinase inhibitor, against atopic dermatitis (AD). However, there is no available information regarding the efficacy of DEL ointment in maintaining remission. Data of patients with AD who received remission maintenance therapy twice weekly with DEL or topical corticosteroid (TCS) on the affected skin of each upper limb were extracted from the medical records. Efficacy was assessed based on changes in pruritus numerical rating scale (NRS) score, stratum corneum hydration (SCH), erythema index (EI). Of 25 patients, four patients (16%) had eczema flare‐ups on the TCS side and eight patients (32%) on the DEL side. The extent of change in each parameter between TCS‐ and DEL‐treated areas of the skin did not differ significantly. The mean changes in the NRS and EI showed a slight improvement on the side treated with TCS and were slightly worse on the side treated with DEL. However, the SCH of the DEL group was maintained, while that of the TCS group worsened. TCS is more likely to be effective than DEL in terms of remission maintenance therapy. However, topical DEL is as effective as topical steroid in the maintenance therapy of AD in dry skin patients. [ABSTRACT FROM AUTHOR]

Background: Sweat aggravates atopic dermatitis (AD). In patients with AD, type-I hypersensitivity to sweat may be shown by histamine release from patients' basophils in response to the semi-purified sweat antigen (QR), and the presence of specific immunoglobulin E (IgE) binding to MGL_1304, the component of QR. However, there has been no information on the immunological changes of type-I hypersensitivity to the sweat antigen in patients with well-controlled AD using topical corticosteroids (TCSs) and/or biologics as treatments. Method: Histamine-releasing tests using patients' basophils and QR and the detection of serum IgE against MGL_1304 and mite allergen Der f 1 were performed in patients with AD who were well controlled by topical TCS with/without dupilumab for 53–96 weeks. Results: In total, 14 patients were enrolled. Seven patients received TCS therapy alone (TCS group), and seven patients received TCS with dupilumab therapy (dupilumab group). In all participants, the level of specific IgE against MGL_1304 decreased after treatments, but histamine release from basophils in response to QR did not show a statistically significant reduction; rather, it increased. In the dupilumab group, all changes in histamine release induced by QR (increase), the IgE level against MGL_1304 (decrease), and that against Der f 1 (decrease) were statistically significant, whereas the TCS group showed no significant change in any of them. Conclusion: The well-controlled condition for 53–96 weeks resulted in no reduction of the hyperreactivity of basophils against in patients with AD, even with the treatment with dupilumab. This study suggests persistent basophil hyperreactivity to sweat antigen over a year or longer. [ABSTRACT FROM AUTHOR]

Cholinergic urticaria (CholU)‐like rash and dermal pain on sweating occur in patients with acquired idiopathic generalized anhidrosis (AIGA). However, it is unclear whether these are symptoms specific to AIGA among the various types of acquired generalized anhidrosis/hypohidrosis (AGAH). Moreover, the pathogenesis underlying CholU‐like rash and dermal pain observed with anhidrosis remains to be clarified. A 20‐year‐old Japanese man with Sjögren's syndrome (SS) presented with anhidrosis. Transient stinging pain on the skin and pinpoint wheals were observed when his body temperature increased. Thermoregulatory sweat testing revealed anhidrotic areas covering 69% of the body surface area with a symmetrical distribution. A high concentration of histamine was detected (506 ng/mL) in the sweat. A skin biopsy specimen from the anhidrotic area showed the inflamed secretory portion of eccrine glands. This suggested inflammation‐mediated damage to sweat glands, consistent with AGAH related to SS. Furthermore, immunohistochemical analysis revealed an ectopic distribution of dermcidin, a sweat‐specific peptide, in the dermal tissue surrounding the secretory portion of eccrine glands. The expression of claudin‐3, a tight junction (TJ) component of sweat glands, decreased or distributed in a mottled manner in the secretory portion. No decreased expression of muscarinic cholinergic receptor M3 was detected. These results suggested that sweat had leaked into the dermis in association with impaired TJ in the secretory portion, along with the damage to inflamed sweat glands related to SS. Collectively, CholU‐like rash and dermal pain on sweating were observed in an AGAH patient with SS. The sweat leakage into the dermis may contribute to the development of the rash and pain. [ABSTRACT FROM AUTHOR]

Background: The difference in the clinical impact of alcohol consumption on kidney function based on sex remains to be elucidated. This study aimed to assess the association between the dose of alcohol consumption and the incidence of proteinuria and chronic kidney disease stratified by sex.Methods: This retrospective cohort study included 26,788 workers (19,702 men and 7086 women) with normal renal function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) at annual health examinations between January 2010 and March 2015 in Japan. The main exposure was alcohol consumption. The primary outcomes were the incidence of proteinuria (dipstick urinary protein ≥ 1) and incidence of low estimated glomerular filtration rate (eGFR; rate < 60 mL/min per 1.73 m2; decreased from the baseline eGFR by 25%).Results: During a median observational period of 4 years (interquartile range: 2-6), 1993 (10.1%) men and 462 (6.5%) women developed proteinuria, whereas 667 (3.4%) men and 255 (3.6%) women developed low eGFR. After adjustment for clinically relevant factors using a Cox proportional hazards model, alcohol consumption of ≥ 46 g/day in females was significantly associated with the incidence of proteinuria (hazard ratio, 1.57; 95% confidence interval, 1.10-2.26) and low eGFR (hazard ratio, 1.62; 95% confidence interval, 1.04-2.53). However, no significant association between alcohol consumption and primary outcomes was observed in men.Conclusions: In conclusion, daily higher alcohol consumption was significantly associated with a higher incidence of proteinuria and low eGFR among women. Women might be prone to high alcohol consumption with kidney dysfunction. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) mostly develops in early childhood and tends to resolve with age. However, its time course in severity before and after adolescence varies widely among patients. To investigate the course of disease severity from birth to 19 years old of adult patients with AD, we conducted a nationwide Web‐based survey of 3090 Japanese adult subjects diagnosed with AD, using a questionnaire to choose a pattern that most resembled their own out of 10 courses of AD severity. Patients in the 20s and 30s age groups tended to choose the option "gradually improved" or "improved by the age of 12", but patients in the 40s or older age group tended to choose the option "aggravation between the age of 12 and 19". Those who chose "AD development at age 20 or older" increased as the generation was older. This survey revealed that the time course of AD severity from birth to 19 years old varies depending on the generation targeted in this study. It is presumed that the acquired factors affecting the natural history of AD have changed over the past 50 years in Japan. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) negatively affects patients' daily lives. Poor medication adherence is a major barrier to treatment success. However, factors causing patients' poor adherence are unclear. This study aimed to identify factors associated with improvement of medication adherence in Japanese patients with AD and to evaluate illness burden and unmet medical needs for AD. We retrospectively analyzed Web‐based questionnaire surveys conducted in 2018 in patients with AD aged 15 years and above who had been in‐ or outpatients within the past year from the survey. Quality of life using the EuroQol 5‐Dimension (EQ‐5D), and work productivity and activity impairment using Work Productivity and Activity Impairment Questionnaire (WPAI) were compared between patients and matched controls who had not visited a hospital for any disease within the past year. Subpopulation analysis was performed to explore factors affecting medication adherence. Unmet medical needs in AD treatment were identified by the percentage of patients who rated issues on the questionnaire as important but who were unsatisfied with them. In this study, we identified 1739 patients with AD. The scores of EQ‐5D and WPAI showed that patients had statistically lower quality of life and higher impairment of work and activities than controls. High medication adherence scores were seen in patients with high health literacy levels and those who were well satisfied with communication with health‐care providers, information received from them, or explanations of AD. Current unmet medical needs for AD were medical treatment costs, ease of hospital visits and explanations about disease prognosis. Patients tended to put a higher priority on communication with physicians than on that with nurses and pharmacists. In conclusion, we have identified patients' higher health literacy levels and satisfaction with the communication with their health‐care provider as potential factors to improve medication adherence. [ABSTRACT FROM AUTHOR]

The velocity of a linearly moving cylindrical conductor can be measured using two methods: the laser-Doppler method and the eddy current method. In this article, we focused on an eddy current linear velocity sensor (LVS) with excellent environmental resistance while analyzing its theory to clarify its characteristics. Consequently, we were able to obtain an exact analytical solution by solving Maxwell’s equation using the Fourier transform. In addition, we built an experimental apparatus that enables cylindrical conductors to move linearly and then used it to conduct an inspection experiment. As a result, a good agreement between the theory and the experiment was obtained for the speed characteristics. Therefore, we could confirm the validity of the theoretical analysis, and thus it has become possible to predict various characteristics related to LVSs. The analysis results of the theory are expected to greatly contribute to the optimization of LVSs. [ABSTRACT FROM AUTHOR]

Omalizumab (OMA) is highly effective for refractory chronic spontaneous urticaria (CSU), but its high cost exerts a great economic burden on patients and society. Current knowledge is lacking regarding the economic impact of long‐term administration of OMA on patients with CSU in the real‐world setting. We retrospectively investigated drug costs relevant to CSU treatment during the period before through to 12 months after starting OMA in actual clinical practice. This study involved 32 patients who received at least two injections of OMA (300 mg/4 weeks) and achieved good responses of urticaria control test score of 12 or more and/or weekly urticaria activity score of 6 or less within 12 weeks. Median drug costs of the overall patient cohort increased from ¥14 496/month to ¥104 522 after starting OMA, but reduced to ¥48 810 in 12 months along with reduced amount of OMA administration and concomitant medication use. In patients pretreated with antihistamine alone or plus alternative medicines such as H2 blocker and antileukotriene prior to OMA, the increased drug costs by adding OMA decreased to approximately 30% in 12 months mainly due to the OMA dose reduction and interval extension of OMA. The drug cost reduction was also observed in patients pretreated with intensive multi‐agents, due to discontinuation of expensive immunosuppressants. In conclusion, the introduction of OMA significantly increased the total drug costs relevant to CSU management, but the costs decreased to half in 12 months, along with dose‐reduced and interval‐extended OMA and discontinued concomitant drugs in patients with CSU who responded well to OMA. [ABSTRACT FROM AUTHOR]

The pathogenesis of chronic spontaneous urticaria (CSU), also called chronic idiopathic urticaria, has been considered to be associated with the activation of the extrinsic blood coagulation cascade. However, the trigger for the extrinsic coagulation cascade in patients with CSU remains unclear. We previously reported that histamine and lipopolysaccharide (LPS) synergistically induced the expression of tissue factor (TF), a trigger for the extrinsic coagulation cascade, in human umbilical vein endothelial cells (HUVEC). Because the elevation of tumor necrosis factor (TNF)‐α, interleukin (IL)‐33, IL‐1β and vascular endothelial growth factor (VEGF) in serum has also been observed in patients with CSU, we examined the effects of LPS, TNF‐α, IL‐33, IL‐1β, VEGF and histamine on TF expression in HUVEC by reverse transcription polymerase chain reaction and flow cytometry, as well as examining the activity that triggers the extrinsic coagulation cascade and induces intercellular gap formation of HUVEC in the presence of plasma by Actochrome® TF activity assay and impedance sensor, respectively. The expression of TF mRNA and surface protein of TF on HUVEC in response to histamine or VEGF were synergistically enhanced by the treatment with LPS, TNF‐α, IL‐33 or IL‐1β. Moreover, the activation of the extrinsic coagulation pathway and intercellular gap formation of HUVEC in response to histamine or VEGF were also synergistically increased in the presence of TNF‐α and LPS. Thus, TF expression on vascular endothelial cells was strongly enhanced by co‐stimulation with CSU‐related molecules in blood. Blocking a common pathway of LPS, TNF‐α, IL‐33 and IL‐1β, and/or that of VEGF and histamine may be an effective therapeutic measure for patients with severe and refractory CSU. [ABSTRACT FROM AUTHOR]

Meshed skin grafting is a common technique in operations to minimize surgery on the donor site area. However, the donor site area is empirically determined by surgeons due to the lack of a reliable formula to calculate the donor area required to cover a skin defect. To determine the minimal size for donor skin, the expansion rates of 1.5:1, 3:1, and 6:1 meshed skin graft and the area actually covered by them were investigated in real‐world operations. About 51 patients who received 57 operations with meshed skin grafts were enrolled in this study. The average clinical coverage rates of area in cases in which 1.5:1, 3:1, or 6:1 meshed skin grafting was performed were 1.02, 1.29, or 2.18, respectively. Those rates were notably low when recipient sites were concave. The average expansion rates of 1.5:1, 3:1, and 6:1 meshed skin grafts were about 1.16, 1.61, and 2.32, respectively. These results indicate that the size of donor skin should be about 85%, 60%, and 45% size of the recipient site to achieve the target 1.5:1, 3:1, and 6:1 meshed skin graft, respectively. In addition, the donor area should be adjusted in consideration of the shape of the recipient sites. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI) have been administrated as a standard medication in many cases of malignant melanoma (MM). They may be effective even for MM in advanced stages. However, it is still challenging to reduce the burden of MM, which were or became refractory to ICI, especially those without BRAF gene mutation. Re‐administration of ICI after other modalities of treatment may be an option of treatment, but the efficacy and safety of retreatment with ICI have not been well established. We experienced four patients with advanced MM retreated with programmed cell death 1 (PD‐1) inhibitor. All cases were refractory to the first PD‐1 inhibitor, nivolumab, and then treated with dacarbazine (DTIC), followed by pembrolizumab. Two of the four cases achieved a partial response by switching to pembrolizumab as the second PD‐1 inhibitor, and the other two cases resulted in progressive disease. In all cases, no new severe adverse events developed upon PD‐1 inhibitor retreatment. Even if the first PD‐1 inhibitor proves to be ineffective, it is worth re‐administrating PD‐1 inhibitor following a bridging therapy with DTIC. [ABSTRACT FROM AUTHOR]

Skin care against aggravating factors is important to prevent skin lesions from flare‐up in the treatment of atopic dermatitis (AD). Tannic acid (TA), a natural polyphenolic and protein‐denaturing agent, has activity to denature antigens relevant to the AD flare. To assess the efficacy of a bath additive containing TA (TA‐bath additive) on pruritus of AD, we carried out a randomized double‐blind trial, in which 21 patients with AD completed the blinded sequential treatments with the TA‐bath additive and a bath additive without TA (placebo‐bath additive) in a cross‐over manner. A significant improvement of pruritus was observed in the afternoon and night by using the TA‐bath additive and in the afternoon by the placebo‐bath additive in patients with AD. No superiority of the TA‐bath additive to the placebo was revealed in the overall patient cohort. However, the added TA in the bath additive exerted its efficacy especially on itch at night in patients with mild‐to‐moderate disease. Bathing by using the series of the bath additive with TA and that without TA improved AD skin lesions throughout this study. No adverse effects related to the use of the TA‐ and placebo‐bath additives were observed. In conclusion, the bath additive containing TA may help skin care of patients with itch and skin lesions of the mild AD. [ABSTRACT FROM AUTHOR]

To the Editor, The involvement of the coagulation cascade has been demonstrated in the pathogenesis of chronic spontaneous urticaria (CSU) by a number of observations, including successful treatment of CSU with anticoagulants.[[1]] We previously reported that blood coagulation potential is elevated in CSU and that histamine and agonists for toll-like receptors (TLRs) may synergistically induce tissue factor (TF) expression on vascular endothelial cells.[[3]] Immunohistochemical staining revealed TF expression by eosinophils in the lesion of CSU.[5] However, monocytes are considered to be the main source of TF in the blood, causing clot formation.[6] We here investigated the level of TF expression on monocytes in the blood of patients with CSU, and the potential of TF on monocytes to trigger the extrinsic coagulation cascade and consequential inter-cellular gap formation of vascular endothelial cells. To test whether the LPS-induced TF of monocytes has a procoagulant activity, monocytes isolated from normal donors were stimulated with LPS and measured for their TF activity. Since the activation of TLRs transduces various cascades of the cells, other stimuli that share intracellular signal transductions with TLRs that induce monocyte TF expression may also contribute to the histamine-resistant or partially resistant CSU. [Extracted from the article]

Although SADBE is applied in daily practice for skin diseases such as alopecia areata, it may lead to CLH formation at the sensitization site. Previous reports of CLH related to SADBE also showed the development of CLH at the sensitization site, rather than at the lesion for the treatments with SADBE2,3 Local, intense sensitization with a high concentration of SADBE might play a role in a preparatory step of CLH, and SADBE repeatedly used for the treatment in areas in distance might trigger and/or promote the lesion formation in the area of sensitization. Keywords: case report; cutaneous lymphoid hyperplasia; external sensitization; squaric acid dibutyl ester EN case report cutaneous lymphoid hyperplasia external sensitization squaric acid dibutyl ester 88 90 3 06/17/21 20210701 NES 210701 Cutaneous lymphoid hyperplasia (CLH) is a lymphoproliferative reaction which histologically and/or clinically mimics malignant lymphoma.1 While no trigger may be found in many cases of CLH, infections, systemic medications, and foreign agents can be associated with CLH. [Extracted from the article]

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. The current strategies to treat AD in Japan from the perspective of evidence‐based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity‐related patient outcomes with respect to several important points requiring decision‐making in clinical practice. [ABSTRACT FROM AUTHOR]

The mutual inductance between coils is one of the important parameters of a system of coils. However, because the theoretical analysis of mutual inductances is difficult, a precise analysis of racetrack‐shaped coils has not yet been conducted. Although a method that involves the use of the finite element method for obtaining an approximation is available, this study aims to obtain the analytical solution which enables the computation of values with very high accuracy. The authors propose a novel magnetic field analysis method for deriving the analytical solution for the magnetic field and for the self‐inductance of the arbitrary‐shaped coils. In this study, the analytical solution is derived for the mutual inductance using a novel analysis method and numerous experiments using coils of different shapes are carried out. The experimental results were almost identical to the theoretical results, confirming the validity of the proposed analysis method. Furthermore, the authors show that even when the specifications and arrangements of the coils are changed, computational analysis can be performed in a short time. [ABSTRACT FROM AUTHOR]

The article presents a study on the mechanism of human and mouse skin mast cell activation by neuropeptide, neuromedin U (NMU). It discusses the characterization of NMU, an analysis of receptor proteins for NMU, the release of NMU from human keratinocytes, and the activation of connective tissue-type mast cells and human skin-derived mast cells by NMU.

Background: Use of contrast-enhanced cross-sectional imaging is considered standard practice for investigating mucoepidermoid carcinoma (MEC) in the salivary glands. The purpose of this study was to present the common features of MEC on computed tomography (CT) and magnetic resonance imaging (MRI) without contrast enhancements, and to investigate the possibility of discriminating between MEC and pleomorphic adenoma based on the features observed on both modalities. Methods: Twenty cases of biopsy-confirmed MEC originating in the salivary glands were reviewed and characterized by two oral and maxillofacial radiologists with regard to the following aspects: detectability, margin, border, encapsulation, content, contrast between lesion and masticator muscle, and bone changes. Results: Ninety percent of bone changes caused by MEC were detected by CT and sixty-nine percent of tumor existences were detected by MRI. The lesion border could provide a clue to distinguish MEC from pleomorphic adenoma. Conclusions: Observation of MEC features was possible by both CT and MRI. Among the features, the lesion border could be a clue to distinguish MEC from pleomorphic adenoma. [ABSTRACT FROM AUTHOR]

Epithelial mesenchymal transition (EMT), the transition of epithelial cells into motile mesenchymal cells, plays an important role in embryogenesis, cancer invasion, and metastasis. Ameloblastomas are common epithelial odontogenic tumors, occurring exclusively in the mandible with locally invasive growth. Thirty-seven ameloblastoma cases were evaluated for the involvement of EMT by immunohistochemical staining and western blotting using antibodies against Slug, Snail, Twist, TGF-β, and E-cadherin. Double immunostaining was also performed. Slug and TGF-β were expressed in the nuclei of peripheral and stellate reticulum cells of ameloblastoma nests. Twenty cases of Snail, 36 of Slug, 8 of Twist, and 19 of TGF-β showed strong expression in tumor cells in follicular and plexiform patterns. Expression of Slug and TGF-β increased in regions where the expression of E-cadherin was reduced. EMT was found to be associated with the local invasive growth of ameloblastoma. These data suggest that reduced expression of E-cadherin and over-expression of Slug, Snail, and TGF-β induce EMT. Given that ameloblastomas are characterized by local invasiveness, EMT might be related to their development. Thus, strong expression of Slug and TGF-β and reduced expression of E-cadherin might be related to the local invasiveness of ameloblastoma. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease. Certain populations of patients are resistant to standard therapies with topical steroids and/or calcineurin inhibitors, and require systemic medication, such as immunosuppressants. Recently, several reports have shed light on the anti-allergic effects of carotenoids. Therefore, we investigated the effect of p.o. administration of β-carotene or lycopene on AD-like symptoms of HR-1 hairless mice fed with a low zinc/magnesium diet. Mice were divided into four groups: (i) fed with a standard diet (Co group); (ii) low zinc/magnesium diet ( HR group); (iii) low zinc/magnesium and β-carotene diet ( HR-C group); and (iv) low zinc/magnesium and lycopene diet ( HR-L group). They were then fed these diets for 8 weeks. Severities of dermatitis were assessed by their appearance, and histopathological and hematological observations. Mice in the HR group developed AD-like dermatitis both clinically and histologically. HR-C and HR-L group mice also developed xerosis and wrinkle-like skin changes, but they were milder than those of HR group mice. Histological analysis revealed that epidermis thickening and inflammatory cell infiltration in the skin of the HR-C and HR-L groups were both statistically less than those of the HR group. The concentration of thymus and activation regulated chemokine in the skin of the HR-L group and the concentration of CCL27 in the skin of the HR-C group were significantly lower than those of the HR group, respectively. In conclusion, p.o. administration of β-carotene or lycopene prevents AD-like symptoms in association with a suppression of T-helper 2 chemokines in a murine model. Ingestion of carotenoids may be beneficial for patients with AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis ( AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. Most patients have an atopic predisposition. The definitive diagnosis of AD requires the presence of all three features: (i) pruritus; (ii) typical morphology and distribution of the eczema; and (iii) chronic and chronically relapsing course. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a major risk factor for periodontal disease and affects various cellular functions. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration; however, the effect of hyperglycemia on PDLSCs is unclear. The aim of this study is to investigate whether hyperglycemia affects periodontal tissue regeneration, using human PDLSCs and high-glucose medium as a model of DM.Methods: PDLSCs were obtained from healthy adult human mandibular third molars. Cell proliferation, osteoblastic differentiation, and proinflammatory cytokine expression were investigated by culturing PDLSCs in media supplemented with four different glucose concentrations representative of control patients (5.5 mM), patients with postprandial or controlled DM (8.0 mM), and patients with uncontrolled DM (12.0 and 24.0 mM). The molecular effects of hyperglycemia on PDLSC physiology were examined with a focus on the nuclear factor (NF)-(κB signaling pathway. The involvement of NF-κB was investigated with a specific NF-κB inhibitor in PDLSCs under hyperglycemic conditions.Results: High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF-κB activation and subsequent interleukin (IL)-6 and IL-8 expression. Treatment with an NF-κB inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL-6 expression caused by the high-glucose environment.Conclusion: The results of this study demonstrate that hyperglycemia inhibits human PDLSC proliferation and osteoblastic differentiation. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4 (IgG4)-related disease comprises a recently recognized systemic syndrome characterized by mass-forming lesions that are found mainly in exocrine tissue and consist of lymphoplasmacytic infiltrates and sclerosis. There are numerous IgG4-positive plasma cells in the affected tissues, and the serum IgG4 level is increased in patients. The subject was a 77-year-old man with pathologically provable IgG4-related disease involving the unilateral trigeminal nerve in the left cheek region. A tumor-like lesion measuring 40 × 15 × 15 mm in the soft tissues of the left cheek was observed on computed tomography and magnetic resonance imaging, and extended along the infraorbital nerves to the anterior region of the maxilla. The mass was hypointense on T2-weighted images and showed mild contrast enhancement. Positron emission tomography showed accumulation in the left cheek (SUVmax: 3.9). Lymphoid follicles of various sizes surrounded by fibrosis were seen in the resected tumor. Immunostaining for IgG and IgG4 showed diffuse distribution of IgG- and IgG4-positive plasma cells in the interfollicular area, and the ratio of IgG4-positive plasma cells to IgG-positive plasma cells was 59 %. IgG4-related disease of the head and neck may be suggested by the combination of clinical signs and symptoms and radiologic findings of an infiltrative mass lesion. Although a definitive diagnosis cannot presently be obtained using IgG4-related disease comprehensive diagnostic criteria, we concluded that the present case was IgG4-related disease based on the good clinical course. [ABSTRACT FROM AUTHOR]