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Abstract Background Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering diseases targeting desmoglein 3 (Dsg3) or desmoglein 1 (Dsg1). The current scoring system, pemphigus disease area index (PDAI), has limitations including inter‐ and intra‐evaluator variability, as well as a time‐consuming evaluation process. Objectives To identify objective and quantitative surrogate markers for assessing disease severity in PV and PF. Methods Eleven PV and PF patients were included. PDAI scores and candidate biomarkers [anti‐Dsg3 antibody, anti‐Dsg1 antibody, thymus and activation‐regulated chemokine (TARC)/CCL17, immunoglobulin E (IgE) levels and eosinophil counts] were measured before oral corticosteroid treatment. Pearson's correlation coefficient was used for correlations between PDAI and candidate biomarkers. Results Serum TARC/CCL17 levels significantly correlated with PDAI scores in PV and PF (R = 0.72, p = 0.02), while anti‐Dsg3 antibody levels correlated with PDAI scores for PV (R = 0.86, p = 0.012). No significant correlations were observed for anti‐Dsg1 antibody, eosinophil counts or IgE levels. Conclusions Serum TARC/CCL17 may be a quantitative and unbiased disease biomarker in pemphigus patients, although further studies involving larger patient cohorts are needed.

Abstract Background Pembrolizumab (PEM), an immune checkpoint inhibitor (ICI), is often used for triple-negative breast cancer, but can also be used to treat solid tumors that exhibit high microsatellite instability (MSI-High). However, patients with breast cancer rarely have MSI-High, the use of PEM in such cases in clinical practice is uncertain due to lack of sufficient supporting data. Here, we report the case of a premenopausal woman in who received PEM for MSI-High luminal-type breast cancer. Case presentation A 40-year-old premenopausal Asian woman was diagnosed with stage IIA (T2N0M0) breast cancer and had an Oncotype DX recurrence score of 38. After surgery, she received 4 courses of chemotherapy with docetaxel and cyclophosphamide. After 3 months of tamoxifen therapy, the patient complained of abdominal pain due to right iliac metastasis, and biopsy of the metastatic lesion showed of luminal type; she was sequentially treated with fulvestrant, a CDK4/6 inhibitor, and an anticancer drug (TS1), but over the next year, metastasis to the bone and para-aortic lymph nodes increased. Tumor was MSI-High; PEM was started, and after three courses, bone metastases were reduced, para-aortic lymph node metastases resolved, opioids were discontinued, and the patient returned to society; PEM was administered for 1 year with no worsening of bone metastases on imaging. Asymptomatic brain metastasis less than 1 cm was detected and gamma knife was performed. Six months after completion of PEM, the patient is working with no new lesions. Conclusion We report a case of luminal-type breast cancer with bone metastases and MSI-High, which was treated with PEM and showed a rapid therapeutic response.

The catalytic reforming of bioethanol can produce green hydrogen (H2) and acetic acid (AcOH). In the present study, the conversion of aqueous ethanol (EtOH) over 4 wt%Ru-4 wt%Sn/TiO2 in a flow reactor was investigated at different temperatures at 0.1 MPa or at various pressures at 260 °C. The ethanol conversion was rather slow in liquid water, while the reactivity increased significantly when water was evaporated. Under gas-phase conditions at 0.1 MPa, the conversion rate increased with increasing reaction temperature, but the AcOH yield and H2 purity decreased due to by-production of CH4, CO, and CO2. The CH4 and CO generated by fragmentation of acetaldehyde (AA), an intermediate, were suppressed by increasing reaction pressure, although the formation of CH4 and CO2 generated from AcOH was pressure independent. Thus, the highest-pressure conditions in steam at a given reaction temperature are preferred for the production of pure H2. The initial step, EtOH → AA, was the rate-determining reaction, and the model experiments using AA as a substrate showed that the Cannizzaro reaction of two AA molecules to form EtOH and AcOH occurred preferentially. This oxidation system was confirmed to be effective at EtOH concentrations of up to 500 g/L in water.

Background: Schnitzler syndrome is a rare disorder with chronic urticaria, and there is no report summarizing the current status in Japan. Methods: A nationwide survey of major dermatology departments in Japan was conducted in 2019. We further performed a systematic search of PubMed and Ichushi-Web, using the keywords “Schnitzler syndrome” and “Japan” then contacted the corresponding authors or physicians for further information. Results: Excluding duplicates, a total of 36 clinically diagnosed cases were identified from 1994 through the spring of 2022, with a male to female ratio of 1:1. The median age of onset was 56.5 years. It took 3.3 years from the first symptom, mostly urticaria, to reach the final diagnosis. The current status of 30 cases was ascertained; two patients developed B-cell lymphoma. SchS treatment was generally effective with high doses of corticosteroids, but symptoms sometimes recurred after tapering. Colchicine was administered in 17 cases and was effective in 8, but showed no effect in the others. Tocilizumab, used in six cases, improved laboratory abnormalities and symptoms, but lost its efficacy after several years. Rituximab, used in five cases, was effective in reducing serum IgM levels or lymphoma mass, but not in inflammatory symptoms. Four cases were treated with IL-1 targeting therapy, either anakinra or canakinumab, and achieved complete remission, except one case with diffuse large B-cell lymphoma. Conclusions: Since Schnitzler syndrome is a rare disease, the continuous collection and long-term follow-up of clinical information is essential for its appropriate treatment and further understanding of its pathophysiology.

This review presents several aspects of the innovative concept of sebaceous immunobiology, which summarizes the numerous activities of the sebaceous gland including its classical physiological and pathophysiological tasks, namely sebum production and the development of seborrhea and acne. Sebaceous lipids, which represent 90% of the skin surface lipids in adolescents and adults, are markedly involved in the skin barrier function and perifollicular and dermal innate immune processes, leading to inflammatory skin diseases. Innovative experimental techniques using stem cell and sebocyte models have clarified the roles of distinct stem cells in sebaceous gland physiology and sebocyte function control mechanisms. The sebaceous gland represents an integral part of the pilosebaceous unit and its status is connected to hair follicle morphogenesis. Interestingly, professional inflammatory cells contribute to sebocyte differentiation and homeostasis, whereas the regulation of sebaceous gland function by immune cells is antigen-independent. Inflammation is involved in the very earliest differentiation changes of the pilosebaceous unit in acne. Sebocytes behave as potent immune regulators, integrating into the innate immune responses of the skin. Expressing inflammatory mediators, sebocytes also contribute to the polarization of cutaneous T cells towards the Th17 phenotype. In addition, the immune response of the perifollicular infiltrate depends on factors produced by the sebaceous glands, mostly sebaceous lipids. Human sebocytes in vitro express functional pattern recognition receptors, which are likely to interact with bacteria in acne pathogenesis. Sex steroids, peroxisome proliferator-activated receptor ligands, neuropeptides, endocannabinoids and a selective apoptotic process contribute to a complex regulation of sebocyte-induced immunological reaction in numerous acquired and congenital skin diseases, including hair diseases and atopic dermatitis.

Innate lymphoid cells (ILCs) harbor tissue-resident properties in border zones, such as the mucosal membranes and the skin. ILCs exert a wide range of biological functions, including inflammatory response, maintenance of tissue homeostasis, and metabolism. Since its discovery, tremendous effort has been made to clarify the nature of ILCs, and scientific progress revealed that progenitor cells of ILC can produce ILC subsets that are functionally reminiscent of T-cell subsets such as Th1, Th2, and Th17. Thus, now it comes to the notion that ILC progenitors are considered an innate version of naïve T cells. Another important discovery was that ILC progenitors in the different tissues undergo different modes of differentiation pathways. Furthermore, during the embryonic phase, progenitor cells in different developmental chronologies give rise to the unique spectra of immune cells and cause a wave to replenish the immune cells in tissues. This observation leads to the concept of layered immunity, which explains the ontology of some cell populations, such as B-1a cells, γδ T cells, and tissue-resident macrophages. Thus, recent reports in ILC biology posed a possibility that the concept of layered immunity might disentangle the complexity of ILC heterogeneity. In this review, we compare ILC ontogeny in the bone marrow with those of embryonic tissues, such as the fetal liver and embryonic thymus, to disentangle ILC heterogeneity in light of layered immunity.

To investigate the mechanism of autoimmunity and peripheral tolerance in the skin, several transgenic mouse strains expressing membrane-bound ovalbumin (mOVA) as an epidermal self-antigen under the control of keratinocyte-specific promotors, such as keratin 5 and keratin 14, were employed in combination with adoptive transfer of CD8+ T cells from OT-I mice (OT-I T cells) that recognize an ovalbumin-derived peptide. However, these strains showed bodyweight loss and required additional inflammatory stimuli, such as γ-irradiation and tape-stripping, to induce skin inflammation. In this study, we generated a mouse strain expressing mOVA under the control of human involucrin promoter (involucrin-mOVA mice). In contrast to previous strains, involucrin-mOVA mice spontaneously developed skin inflammation after the transfer of OT-I T cells in the absence of external stimuli without significant bodyweight loss. We focused on the skin infiltration process of OT-I T cells and found that transferred OT-I T cells accumulated around the hair follicles in the early phase of skin inflammation, and in the later phase, the skin inflammation spontaneously resolved despite the remaining OT-I T cells in the skin. Our involucrin-mOVA mice will provide a promising tool to investigate the pathogenesis and the tolerance mechanisms of cytotoxic skin autoimmunity.

Abstract Hydrogen bond donor solvents such as aromatic solvents inhibit the secondary degradation of cellulose‐derived primary pyrolysis products. In a previous study, we found that the formation of solid carbonized products was completely inhibited during cellulose pyrolysis in aromatic solvents, with 5‐hydroxymethylfurfural (5‐HMF) recovered in certain yields instead. This indicated that 5‐HMF is an intermediate in cellulose carbonization. To confirm this hypothesis, the thermal reactivity of 5‐HMF was investigated. At 280 °C, pure 5‐HMF polymerized into a hard glassy substance through OH group elimination, but further conversion was slow. When pyrolyzed in the presence of glycerol, a model of coexisting primary pyrolysis products from cellulose, a coupling reaction proceeded. Reactions characteristic of cellulose carbonization then occurred, including the formation of acidic groups and benzene‐type structures in the solid products. These results confirmed the above hypothesis. The molecular mechanism of cellulose carbonization is discussed, focusing on the crystalline nature.

Photosystem II (PSII) catalyzes light-induced water oxidation through an Si-state cycle, leading to the generation of di-oxygen, protons and electrons. Pump–probe time-resolved serial femtosecond crystallography (TR-SFX) has been used to capture structural dynamics of light-sensitive proteins. In this approach, it is crucial to avoid light contamination in the samples when analyzing a particular reaction intermediate. Here, a method for determining a condition that avoids light contamination of the PSII microcrystals while minimizing sample consumption in TR-SFX is described. By swapping the pump and probe pulses with a very short delay between them, the structural changes that occur during the S1-to-S2 transition were examined and a boundary of the excitation region was accurately determined. With the sample flow rate and concomitant illumination conditions determined, the S2-state structure of PSII could be analyzed at room temperature, revealing the structural changes that occur during the S1-to-S2 transition at ambient temperature. Though the structure of the manganese cluster was similar to previous studies, the behaviors of the water molecules in the two channels (O1 and O4 channels) were found to be different. By comparing with the previous studies performed at low temperature or with a different delay time, the possible channels for water inlet and structural changes important for the water-splitting reaction were revealed.

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometre to micrometre scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges that are not encountered in traditional macromolecular crystallography experiments. Here, XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A are described. The results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample-preparation and delivery methods required for each type of experiment affect the crystal structure of the enzyme.

Trial design: Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. Methods: Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. Results: A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. Conclusions: No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study.

How antibody reaches tissues from circulation is critical for understanding antibody-mediated immunity. Here the authors show that IgG extravasation in the skin is mediated by endothelial caveolin transport independently of FcR, and is targetable by imatinib, which reduces IgG-dependent pathology in a mouse model of pemphigus.

Abstract Background Human papilloma viruses (HPVs) infect squamous epithelial cells and form verrucous lesions, or warts. Besides the psychosocial problems caused by the disfiguring warts, a subset of HPVs can be the primary etiologic agent for malignancies such as cervical cancer. However, there is no curative antiviral therapy for HPV infection. We recently found that the viral RNA transcription of DNA viruses requires cyclin dependent kinase 9 (CDK9) in the host cells, and that FIT039, a specific inhibitor of CDK9, suppressed the proliferation of DNA viruses such as herpes simplex virus 1 (HSV-1), HSV-2, human adenovirus, human cytomegalovirus, hepatitis virus B, and HPVs. Here, we describe a protocol to evaluate the safety and antiviral effect of FIT039 on common warts in human skin. Methods and design A multi-institutional, single-blind, placebo-controlled randomized phase I/II clinical trial was designed to evaluate the safety and efficacy of FIT039 on common warts on the extremities. A total of 44 adults with a primary diagnosis of verruca vulgaris on the extremities without serious comorbidities will be randomized into either the intervention group with an FIT039-releasing transdermal patch or a control group for a duration of 14 days. Outcomes will be assessed at baseline and postintervention. Participants will be further assessed at 2 months follow-up. The primary endpoint for efficacy is the resolution of the warts. The safety endpoint is the incidence of adverse events and adverse drug reactions. The secondary endpoints are changes in the dimensions of the wart, the cross-sectional area of the wart, and the number of clots within the area of the wart. Discussion This study is the first to assess the efficacy of FIT039 and will contribute to the development of antiviral agents that can cure refractory common warts in immunocompromised patients. Trial registration UMIN Clinical Trials, UMIN000029695. Registered on 1 November 2017.

Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore.

Introduction: It is not concluded whether the association between olfactory dysfunction and REM sleep behavior disorder (RBD) were worsen cognitive function in patients with Parkinson's disease (PD). We sought to evaluate the impact of these symptoms in PD. Methods: We examined 62 patients with PD using an olfactory test (Odor Stick Identification Test for Japanese: OSIT-J) and polysomnography (PSG). We divided the patients into 3 groups: PD with clinical RBD (n = 32), PD with subclinical RBD (n = 11), and PD with normal REM sleep (n = 19). We compared their clinical backgrounds, results of OSIT-J, autonomic functions, and cognitive functions such as Montreal cognitive assessment Japanese version (MoCA-J). Some factors associated with RBD were analyzed by multiple regression. Results: There were significant differences in the results of OSIT-J, and autonomic and cognitive functions between the 3 groups. There were significant differences in the total OSIT-J score between the 3 groups (PD with clinical RBD: 3.3 ± 2.2, PD with subclinical RBD: 4.0 ± 2.6, PD with normal REM sleep: 6.7 ± 3.0, p

Abstract Background Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. Methods A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. Results The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p

Using photosensitive caged-compound for femtosecond crystallography at X-ray free electron lasers would allow the structure determination of reaction intermediates. Here the authors demonstrate the feasibility of this approach with a caged NO-compound and present the initial NO-bound intermediate structure of cytochrome P450 nitric oxide reductase.

Due to each country’s energy policy, various types of gasoline such as ethanol blended gasoline, high/low aromatic content gasoline, etc. are sold in the market. As the production of engines and their part supply chains become more globalized, it is important to develop engines that can be compatible with various types of gasoline. To maintain engine durability, it is necessary to clarify the effects of these gasoline components on engine durability. To understand the friction of metal to metal contact, which are directly connected to engine durability, we examined synthetically the relationship between gasoline components and lubricity.

Cancer immunotherapy has highlighted the clinical relevance of enhancing anti-tumor response of CD8+ T cells in several cancer types. Little is known, however, about the involvement of the immune system in extramammary Paget's disease (EMPD). We examined the cytotoxicity and the effector functions of CD8+ T cells using paired samples of peripheral blood and tumors by flow cytometry. Expression levels of perforin, granzyme B, IFN-g, TNF-a, and IL-2 in CD8+ tumor-infiltrating lymphocytes (TILs) were significantly lower than those in CD8+ T cells of peripheral blood. Significantly higher expression of PD-1 was found in CD8+TILs than in CD8+ T cells of peripheral blood. A high number of CD8+ cells was significantly associated with poor overall survival (OS) adjusted with age, sex, and clinical stage (hazard ratio [HR] = 5.03, P = 0.045, 95% confidence interval [CI] 1.03-24.4). On the other hand, the number of PD-1+ cells was not associated with OS or disease-free survival (DFS). Moreover, we found that tumor cells produced immunosuppressive molecule indoleamine 2,3-dyoxygenae (IDO). In conclusion, CD8+ TILs displayed an exhausted phenotype in EMPD. IDO expression seemed more relevant in inducing CD8 exhaustion than PD-1 upregulation or PD-L1 expression by immune cells. Restoring the effector functions of CD8+ TILs could be an effective treatment strategy for advanced EMPD.

The fast pyrolysis of cellulose produces levoglucosan (LG), but secondary pyrolysis reactions tend to reduce the yield. The present study assessed the fast pyrolysis of cellulose by infrared (IR) heating under nitrogen flow. Because the nitrogen was not efficiently heated, gaseous LG was immediately cooled, resulting in a maximum yield of 52.7% under optimized conditions. Slow nitrogen flow and a high IR power level provided a greater gas yield by raising the temperature of the cellulose, and the formation of CO could be used as an indicator of the gasification of LG. Glycolaldehyde (GA) was the major byproduct, and the GA yield remained relatively constant under all conditions. Accordingly, GA was not a secondary product from the LG but was likely produced from the reducing ends of cellulose and other intermediate carbohydrates. The pyrolysis of cellulose proceeded within a narrow region of carbonized material that absorbed IR radiation more efficiently. The bulk of each cellulose sample could be decomposed in spite of this heterogeneous process by maintaining fast pyrolysis conditions for a sufficient length of time. This technique is a superior approach to LG production compared with other fast pyrolysis methods based on heat conduction.

Torrefaction used in combination with pelletization is a promising technology to upgrade solid biofuels and has been demonstrated worldwide. In comparison with normal biomass pellets, which disintegrate under wet conditions, one of the advantages of torrefied biomass pellets is better water resistance. An understanding of the differences in water proof properties for torrefied biomass pellets by different production schemes can promote their further application. In the communication, various torrefied pellets were exposed to indoor and outdoor conditions, and changes in moisture content and diameter were examined. Two production schemes for the torrefied pellets were used for comparison: the torrefaction of wood chips followed by pelletization (pre-torrefaction) and the pelletization of wood chips followed by torrefaction (post-torrefaction). It was found that the post-torrefied pellets had much lower moisture levels than the pre-torrefied pellets in both indoor and outdoor tests. In the outdoor test with no-roof condition, the rate of increase in moisture content for the pre-torrefied pellets was more than double that for the post-torrefied pellets, and the post-torrefied pellets exhibited almost no diameter change. The results on the superior water resistance of post-torrefied pellets were nearly consistent with those reported in previous literature. Torrefied pellets have been considered for industrial use, such as in co-combustion and gasification on a large scale. Taking advantage of the different water resistances, torrefied pellets could also be used by personal and community consumers on a small scale for long-term indoor and outdoor storages as advanced solid biofuels with high waterproof performance, energy density, and lower biodegradation.

Single-crystal infrared (IR) spectroscopy is a promising method for protein structure analysis, where a protein crystal sample is fixed in a micro flow cell. Single-crystal calcium fluoride (CaF2) is expected as the flow cell substrate material for its excellent optical property. However, CaF2 is a highly brittle material having strong anisotropy, thus is extremely difficult to machine. Up to date, there is no available literature on fabrication of CaF2 flow cells. In this study, micro flow cells of single-crystal CaF2 were fabricated by ultraprecision cutting technology. Fly cutting was conducted using a single-crystal diamond tool having straight edges to generate a depth-varying rectangle cross section for the flow cell. The effects of cutting direction, workpiece orientation, undeformed chip thickness and tool rake angle on cutting behavior were investigated. Based on experiments and analysis, optimal conditions for ductile machining of micro grooves in CaF2 were identified. As a result, a 10 μm deep CaF2 micro flow cell with surface roughness of 2.4 nmRa was successfully fabricated. Using the fabricated flow cell, IR spectroscopic analysis of a protein single crystal at room temperature was succeeded. This study demonstrated the effectiveness of ultraprecision cutting technology in CaF2 micro flow cell fabrication, which contributes to the IR analysis of protein, and in turn, the advance of life science.

Introduction: The REM sleep behavior disorder (RBD) screening questionnaire (RBDSQ) has been used as a screening tool for RBD. We investigated the clinical characteristics of probable RBD (pRBD) using the RBDSQ in patients with Parkinson's disease (PD). Methods: Seventy patients with PD (age: 69.2 ± 8.9 years old, 31 males and 49 females, length of PD morbidity: 7.4 ± 6.4 years, Hoehn and Yahr: 2.7 ± 0.8) underwent examination including the RBDSQ and Mini-Mental State Examination (MMSE) in both 2011 and 2013. We assessed the changes and characteristics of pRBD associated with PD during the two year interval. Results: Nineteen patients (27.1%) in 2011 and 27 patients (38.6%) in 2013 were diagnosed as having pRBD because they scored 6 or higher on the RBDSQ. During the 2 year interval, twelve patients showed persistent pRBD, 15 developed pRBD, and 7 showed improved pRBD. In 2013, PD patients with pRBD took higher amounts of levodopa equivalents and scored lower on the MMSE than those without pRBD. Also, more PD patients with pRBD had dementia than those without pRBD. Similarly, more patients with persistent and developed pRBD had dementia than those without. Conclusion: We found that RBD symptoms might fluctuate during the clinical course of PD, and RBD symptoms might temporarily affect cognitive impairment.

Keratosis lichenoides chronica (KLC) is a rare keratotic disorder of unknown origin. Effective treatment has not been established yet. Here, we present adult-onset KLC, which was treated by narrow-band ultraviolet B (NB-UVB) monotherapy. Although NB-UVB was reported to be effective for pediatric-onset KLC, it has not been clear if this regimen is also useful for adult-onset type because pediatric-onset KLC is suggested to be different in nature. We assume that KLC is treatable by NB-UVB regardless of the age of the patient.

In multi-stage closed die forging, an optimum shape of a preform is required to economically manufacture more complicate and precise products. This preform promotes to distribute an appropriate volume, and it helps to reduce material loss and forging load at the final stage for the final products. However, it is difficult for beginners to design the preforms, especially, in processes of locally-lateral upsetting. The preform is needed to make automobile parts such as a connecting rod, a crank shaft, and a knuckle arm. In this paper, locally-lateral upsetting of a rod billet for the typical preform is tried by using different punches and configuration to promote the asymmetric flow of the work material. The punch has each cylindrical nose with a different radius. Furthermore, the punch is set at a different rotating angle from the axial direction of the rod to promote the asymmetric material flow. As the results, the largest asymmetric material flow is appeared when the cylindrical punch with the large radius and rotating 45° is used.

Primary palmoplantar hyperhidrosis (PPH) is a disorder that involves excessive sweating on the palms and soles. Although the pathophysiology of PPH remains unknown, some treatments, including topical aluminum chloride (AC) and tap water iontophoresis (TWI), are effective at suppressing the perspiration. Herein, we report the kinetics of the skin pH of two cases of PPH treated with AC and TWI. We found that the skin pH decreased in accordance with the reduction in sweating. This finding indicates that the reduction in sweating may be attributed to the reduction of skin pH in AC and TWI. Whether or not the pH-regulated function of aquaporin can explain this finding remains unknown.

Aquaporin-5 (AQP-5) is a water-transporting protein expressed in mammal sweat glands. It has been reported that the expression of AQP-5 is involved in sweating of mice, rats, and horses. However, the physiological function of human AQP-5 is still uncertain. In this report, we examined the expression pattern of AQP-5 in the skin lesions of palmoplantar hyperhidrosis in patients with Nagashima-type palmoplantar hyperkeratosis (PPK). We found that there was no significant difference in AQP-5 expression in the palmoplantar skin of healthy subjects and patients with palmoplantar hyperhidrosis. Our findings suggest that a mechanism other than AQP-5 may be involved in the pathogenesis of hyperhidrosis in PPK.

Prostaglandin E2 (PGE2) is produced in the skin and is suggested to play a role in the regulation of cutaneous immune homeostasis and responses. However, the multifaceted functions of PGE2 continue to elude our understanding, especially because of the multiplicity of PGE2 receptors--EP1, EP2, EP3, and EP4. While cAMP-elevating EP4 is known to activate the functions of cutaneous dendritic cells (DCs), including Langerhans cells (LCs) and dermal DCs, the role of cAMP-suppressing EP3 in this process remains unknown. Here we demonstrated that an EP3 receptor selective agonist, ONO-AE-248, inhibited chemotaxis and co-stimulatory molecule expressions of DCs in vitro. A suboptimal dose of antigen was sufficient to induce contact hypersensitivity in EP3-deficient mice. Intriguingly, EP3 deficiency did not impair skin inflammation at all when the antigen dose was sufficiently high. EP3 limited the functions of cutaneous DCs only when the antigen dose was low. In contrast to EP4, the observed unappreciated function of EP3 may stabilize the cutaneous DCs to halt the impetuous response to a suboptimal dose of antigen. Taken together, PGE2-EP3 signaling is essential for fine-tuning excessive skin inflammation by restricting DC functions.

Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic vascular disorder characterized by multifocal venous malformations (VMs). Little is known about the perinatal management of pregnant women with BRBNS owing to the limited number of reported cases. We present the case of a 36-year-old primigravida with BRBNS who underwent an uneventful cesarean section under spinal anesthesia for breech presentation. A thorough systemic examination revealed VMs in various organs, including the skin, conjunctiva, larynx, gastrointestinal tract, lungs, and vulva. Prior to spinal anesthesia, careful examination using imaging modalities was conducted to assess the spinal and epidural involvement of the VMs to avoid complications, including accidental puncture of the VMs, associated bleeding, and epidural hematoma. In pregnant women with BBNS, it is imperative to scrutinize the localization and distribution of VMs throughout the body to anticipate potential complications and select the appropriate delivery mode and anesthetic management. [ABSTRACT FROM AUTHOR]