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Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). The first national epidemiological survey of SJS/TEN was carried out in 2008. We conducted a new survey to identify changes from the previous survey. Objective The present survey aimed to estimate the number of SJS/TEN patients in Japan between 2016 and 2018 (primary survey) and to clarify clinical epidemiological profiles (secondary survey). Methods A primary survey asking for numbers of SJS/TEN patients during the study period was sent to 1205 institutions nationwide. A secondary survey was sent to institutions reporting SJS/TEN patients, seeking detailed information. Results Yearly prevalence per million was 2.5 for SJS and 1 for TEN. The secondary survey allowed analysis of 315 SJS cases and 174 TEN cases from 160 institutions. Mean age was 53.9 years in SJS, and 61.8 years in TEN. Mortality rate was 4.1 % for SJS and 29.9 % for TEN. In TEN, mean age and mortality rates had increased from the previous survey. The ratio of expected to observed mortality calculated by SCORTEN score was lowest with high-dose steroid therapy (0.40), followed by steroid pulse therapy (0.52). Conclusion The present findings suggest that the mortality rate of TEN has increased because of increases in mean ages of patients and patients with malignant neoplasm as underlying disease. When comparing the ratio of expected mortality to actual mortality, high-dose steroid therapy achieved the greatest reduction in mortality.

Numerical methods to simulate flight and impact of windborne debris are described. The problems are treated as fluid–structure interaction problems based on the ALE finite element flow analysis in order to deal with arbitrary shape of flying objects as well as dynamical change of aerodynamic forces. For the flight simulation, the computational domain travels with the flying object because usually the fight distance is much longer than the size of the debris. For the numerical impact process, the magnitude of the impact force is determined by iteration so that the velocity of the sphere after impact converges to zero. Furthermore, in order to suppress unphysical step-by-step pressure oscillation, the time step at the impact is subdivided into a set of multiple short time steps with a smooth impact force function. Several numerical examples of a rigid sphere show satisfactory features of these methods.

The programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is known to inhibit the activation of effector CD8Our aim was to elucidate the mechanisms by which the PD-1/PD-L1 pathway exerts its regulatory roles in CD8PD-L1-deficient (Pdl1Compared with wild-type mice, Pdl1PD-L1 on MCs negatively regulates CD8

International audience; The reduction of particulate emissions is one of the most important challenges facing the development of future gasoline engines. Several studies have demonstrated the impact of fuel chemical composition on the emissions of particulate matter, more particularly, the detrimental effect of high boiling point components such as heavy aromatics. Fuel contamination is likely to become a critical issue as new regulations such as Real Driving Emissions RDE involves the use of market fuel. The objective of this study is to investigate several experimental approaches to detect the presence of Diesel contamination in Gasoline which is likely to alter pollutant emissions. To achieve this, a fuel matrix composed of 12 fuels was built presenting diesel fuel in varying concentrations from 0.1 to 2% v/v. The fuel matrix was characterized using several original techniques developed in this study. These are Near Infrared spectroscopy (NIR) associated to Principal Component Analysis (PCA) and Partial Least Square (PLS) modelling, filtration. Their capacity to identify diesel fuel was compared to standard methods, such as, distillation, washed and unwashed gums, high boiling components by gas chromatography (EN16270 and VDA265). Furthermore, vehicle tests were conducted to evaluate the impact of Diesel contamination on tailpipe particle emissions on Worldwide harmonised Light vehicle Test Procedure WLTP. Vehicle test results suggest a significant impact of Diesel contamination on Particle emissions. A good detection of Diesel fuel (down to 0.5% v/v) is accomplished using filtration, NIR and high boiling components. Filtration and NIR have the added benefit of availability, ease of use and small test duration. This work highlights the critical impact of Diesel fuel contamination on pollutant emissions from future Gasoline engines. It proposes a novel practical approach of measuring Diesel contamination in market gasoline fuels.

Purpose: Cervical cancer is one of the leading causes of cancer-related deaths among women worldwide. The purpose of this study is to assess the therapeutic effect of the newly developed cyclin-dependent kinase 9 (CDK9) inhibitor FIT-039 on cervical neoplasia induced by human papillomavirus (HPV) infection. Experimental Design: We examined FIT-039 for its effect on HPV gene expression in HPV+ cervical cancer cells. Primary keratinocytes monolayer and organotypic raft culture models were used to evaluate HPV viral replication and cervical intraepithelial neoplasia (CIN) phenotypes. Preclinical pharmacokinetics and toxicity tests for FIT-039 were also conducted. Finally, the anti-HPV effect of FIT-039 was further examined in vivo, using HPV+ cervical cancer xenografts. Results: FIT-039 inhibits HPV replication and expression of E6 and E7 viral oncogenes, restoring tumor suppressors p53 and pRb in HPV+ cervical cancer cells. The therapeutic effect of FIT-039 was demonstrated in CIN model of an organotypic raft culture, where FIT-039 suppressed HPV18-induced dysplasia/hyperproliferation with reduction in viral load. FIT-039 also repressed growth of HPV16+, but not HPV− cervical cancer xenografts without any significant adverse effects. Safety and pharmacokinetics of FIT-039 were confirmed for systemic and topical routes. Conclusions: The CDK9 inhibitor FIT-039 showed potent anti-HPV activity without significant toxicity in preclinical studies. Thus, FIT-039 is expected to be a novel therapeutic for CIN to prevent cervical cancer. Clin Cancer Res; 24(18); 4518–28. ©2018 AACR.

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, Highlights • Patients with Parkinson's disease (PD) and REM sleep behavior disorder (RBD) had severe olfactory deficits. • Olfactory function is associated with RBD in patients with PD. • Olfactory dysfunction might be important in the development of PD.

Atopic dermatitis (AD) is a heterogeneous disease with unique clinical manifestations across age groups and race/ethnicities. Characteristic molecular mechanisms, known as endotypes, including IgE level, status of epidermal barrier genes, and differential cytokine axes activation in the background of TH2 upregulation, are also implicated. In adults, the TH22, TH17, and TH1 pathways are involved, and a weakened epidermal barrier is characteristic. In contrast, pediatric patients exhibit less TH1 activation, and defects in epidermal lipid metabolism contribute to their barrier defect. European American patients are characterized by higher differential TH2/TH22 activation, lower expression of the TH1/TH17 axes, and suppression of filaggrin (FLG) and loricrin gene expressions. Asian patients have accentuated polarity of the TH22/TH17 pathways, and also exhibit epidermal barrier defects despite relative maintenance of FLG and loricrin expression. African American patients do not exhibit FLG mutations and have distinct attenuation of TH17/TH1 axes activation. Dissecting the molecular basis of AD endotypes has provided an important framework upon which targeted therapeutics are being developed. An increased understanding of these subtypes and the alteration of biomarkers that correlate with disease can ultimately push AD treatment in an era of personalized medicine.

The signalling lymphocytic activation molecule family member 8 (SLAMF8)/CD353 is a member of the CD2 family of proteins. Its ligand has not been identified. SLAMF8 is expressed by macrophages and suppresses cellular functions. No study has yet explored SLAMF8 expression or function in human mastocytosis, which features oncogenic KIT-mediated proliferation of human mast cells. SLAMF8 protein was expressed in human mastocytosis cells, immunohistochemically. SLAMF8 expression was also evident in the human mast cell lines, HMC1.2 (expressing oncogenic KIT) and LAD2 (expressing wild-type KIT) cells. SLAMF8 knock-down significantly reduced the KIT-mediated growth of HMC1.2 cells but not that of LAD2 cells. SLAMF8 knock-down HMC1.2 cells exhibited significant attenuation of SHP-2 activation and oncogenic KIT-mediated RAS-RAF-ERK signalling. An interaction between SLAMF8 and SHP-2 was confirmed in HMC1.2 cells and all pathological mastocytosis specimens examined (19 of 19 cases, 100%). Thus, SLAMF8 is involved in oncogenic KIT-mediated RAS-RAF-ERK signalling and the subsequent growth of human neoplastic mast cells mediated by SHP-2. SLAMF8 is a possible therapeutic target in human mastocytosis patients.

Atopic dermatitis (AD) is a common T-cell-mediated inflammatory disease of the skin. Signatures of AD are characterized by an impaired skin barrier, aberrant Th2-type cytokine production and intensive pruritus. Transcriptomic analysis, however, has revealed a heterogeneous pathogenesis and the co-existence of multiple cytokine axes of Th17, Th22 and Th1 types, especially in intrinsic (a subtype of AD without skin barrier impairment), pediatric and Asian types of AD. Furthermore, the therapeutic effect of anti-IL-4 receptor α against AD was not as high as that of IL-17 blockage against psoriasis, which implies a modification of the disease spectrum by non-Th2-type cytokine axes in AD. These lines of evidence indicate a need for personalized or precision medicine appropriate for each subtype of AD.

A numerical method is developed to simulate the process that a falling rigid sphere hits rigid ground and bounces back in air. The problem is treated as fluid-structure interaction problem based on...

Type 2 immunity and inflammation underlie allergic skin disorders, such as atopic dermatitis (AD). In type 2 inflammation, IL-4, IL-13, and IL-5, which are signature type 2 cytokines, are mainly produced by type 2 helper T (Th2) cells and form the characteristic features of AD. Epithelial cell-derived cytokines such as IL-25, IL-33, and TSLP initiate type 2 inflammation by modulating various cells, including group 2 innate lymphoid cells. Moreover, IL-31, a newly identified type 2 cytokine produced mainly by Th2 cells, induces pruritus by acting on sensory neurons in the skin. Based on both basic and clinical findings, several biologics targeting Th2 cytokines have been developed and exhibited significant efficacy as therapeutic reagents for AD. We have summarized the roles of each cytokine (IL-4, 5, 13, 25, 31, and 33, and TSLP) in the development of type 2 inflammation, especially AD, from the view of basic studies in mice and clinical trials/observation in humans.

Background The programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is known to inhibit the activation of effector CD8+ T cells. However, just how this regulatory pathway is involved in the pathophysiology of CD8+ T-cell–mediated inflammatory skin diseases remains unclear. Objective Our aim was to elucidate the mechanisms by which the PD-1/PD-L1 pathway exerts its regulatory roles in CD8+ T-cell–mediated cutaneous immune responses. Methods PD-L1–deficient (Pdl1–/–) mice were used for the murine contact hypersensitivity model. Inflammatory responses such as IFN-γ production from CD8+ T cells in the skin was evaluated by flow cytometry. Results Compared with wild-type mice, Pdl1–/– mice exhibited exacerbated ear swelling and increased numbers of IFN-γ+ CD8+ T cells in the skin. Adoptive T-cell transfer experiments revealed the involvement of the PD-1/PD-L1 pathway in the elicitation phase of contact hypersensitivity. Bone marrow chimera experiments showed that PD-L1 on radioresistant cells was responsible for this regulatory pathway. Flow cytometric analysis revealed that among the radioresistant cells in the skin, PD-L1 was most highly expressed on mast cells (MCs) before and after elicitation. Administration of anti–PD-L1 blocking antibody during the elicitation phase significantly enhanced ear swelling responses and increased the number of IFN-γ+CD8+ T cells in the skin of wild-type mice, whereas no significant effects were observed in MC-deficient (WBB6F1/J-KitW/KitW-v/J and C57BL/6-KitW-sh/W-sh) mice. The high level of expression of PD-L1 on human skin MCs was confirmed by database analysis and immunohistochemical analysis. Conclusion PD-L1 on MCs negatively regulates CD8+ T-cell activation in the skin.

A nanosecond pump–probe device for time-resolved serial femtosecond crystallography has been developed at SACLA., X-ray free-electron lasers (XFELs) have opened new opportunities for time-resolved X-ray crystallography. Here a nanosecond optical-pump XFEL-probe device developed for time-resolved serial femtosecond crystallography (TR-SFX) studies of photo-induced reactions in proteins at the SPring-8 Angstrom Compact free-electron LAser (SACLA) is reported. The optical-fiber-based system is a good choice for a quick setup in a limited beam time and allows pump illumination from two directions to achieve high excitation efficiency of protein microcrystals. Two types of injectors are used: one for extruding highly viscous samples such as lipidic cubic phase (LCP) and the other for pulsed liquid droplets. Under standard sample flow conditions from the viscous-sample injector, delay times from nanoseconds to tens of milliseconds are accessible, typical time scales required to study large protein conformational changes. A first demonstration of a TR-SFX experiment on bacteriorhodopsin in bicelle using a setup with a droplet-type injector is also presented.

Aromatic solvents are known to stabilize levoglucosan (1,6-anhydro-β- d -glucopyranose), the major pyrolysis intermediate of cellulose, against thermal degradation including char formation. In this article, pyrolysis of cellulose, a crystalline component of biomass, was investigated in the aromatic solvents 1,3-diphenoxybenzene, diphenyl sulfide, and benzophenone under nitrogen at 280 °C. Thermal degradation of cellulose (Whatman filter paper) was markedly delayed in the aromatic solvents and gave thin film-like char after the removal of unreacted cellulose through hydrolysis. The yields of levoglucosan and 5-hydroxymethylfurfural were greatly enhanced in the aromatic solvents. These observations are discussed at the molecular level in terms of the interactions of cellulose crystallites and the pyrolysis products with the aromatic solvents. A possible char formation mechanism via 5-hydroxymethylfurfural involving the ultrastructure of the cell wall is also discussed. This study provides insight into the molecular-based cellulose pyrolysis mechanisms and efficient and selective thermochemical production of bio-based materials and chemicals.

Surgeons are increasingly being faced with the challenge of treating elderly patients with colon cancer. The present study therefore aimed to compare the short-term outcomes of single-port laparoscopic surgery (SILS) for elderly patients with colon cancer (≥70 years) with those in younger patients (41–69 years; control group). Among 100 patients with colorectal cancer who had been treated with single-port laparoscopic surgery between January 2011 and December 2014, 56 (56.0%) were ≥70 years of age. The results of treatment and short-term outcomes in the elderly group (n=56) were retrospectively compared with the younger patients in the control group (n=44). The sex distribution, body mass index, history of prior surgery and the American Society of Anesthesiologists physical status classification were similar between the groups. Onodera's prognostic nutritional index demonstrated significant differences between the elderly and control groups (38.3 vs. 49.8; P

Photosystem II (PSII) is a huge membrane-protein complex consisting of 20 different subunits with a total molecular mass of 350 kDa for a monomer. It catalyses light-driven water oxidation at its catalytic centre, the oxygen-evolving complex (OEC). The structure of PSII has been analysed at 1.9 Å resolution by synchrotron radiation X-rays, which revealed that the OEC is a Mn4CaO5 cluster organized in an asymmetric, 'distorted-chair' form. This structure was further analysed with femtosecond X-ray free electron lasers (XFEL), providing the 'radiation damage-free' structure. The mechanism of O=O bond formation, however, remains obscure owing to the lack of intermediate-state structures. Here we describe the structural changes in PSII induced by two-flash illumination at room temperature at a resolution of 2.35 Å using time-resolved serial femtosecond crystallography with an XFEL provided by the SPring-8 ångström compact free-electron laser. An isomorphous difference Fourier map between the two-flash and dark-adapted states revealed two areas of apparent changes: around the QB/non-haem iron and the Mn4CaO5 cluster. The changes around the QB/non-haem iron region reflected the electron and proton transfers induced by the two-flash illumination. In the region around the OEC, a water molecule located 3.5 Å from the Mn4CaO5 cluster disappeared from the map upon two-flash illumination. This reduced the distance between another water molecule and the oxygen atom O4, suggesting that proton transfer also occurred. Importantly, the two-flash-minus-dark isomorphous difference Fourier map showed an apparent positive peak around O5, a unique μ4-oxo-bridge located in the quasi-centre of Mn1 and Mn4 (refs 4,5). This suggests the insertion of a new oxygen atom (O6) close to O5, providing an O=O distance of 1.5 Å between these two oxygen atoms. This provides a mechanism for the O=O bond formation consistent with that proposed previously

Urinary tract resection is the only procedure that can cure colorectal cancer that directly invades the ureter. In these cases, open surgery is commonly used. Here, we describe our experience of a case of sigmoidectomy following Boari flap construction with single-incision laparoscopic surgery (SILS) for advanced colon cancer with ureteric invasion. A 68-year-old woman was referred to our hospital with left flank pain. Left hydroureteronephrosis was detected on ultrasonography. Computed tomography revealed a solid mass in the sigmoid colon and hydroureteronephrosis due to swelling of a mesenteric lymph node. Computed tomography detected no signs of distant metastasis. Colonoscopy revealed an ulcerated, bleeding, and stricturing lesion in the sigmoid colon, which was identified as an adenocarcinoma with a moderate degree of differentiation at histological examination. Under general anesthesia, the patient was placed in the Trendelenburg semi-right lateral position. An umbilical incision was made for the insertion of a single multichannel port for SILS. Sigmoidectomy and Boari flap reconstruction were performed. There were no perioperative complications. The total operating time was 572 minutes (including Boari flap procedure of 174 minutes), and estimated blood loss was 200 mL. Single-incision laparoscopic sigmoidectomy with Boari flap construction is technically feasible with sigmoid cancer and ureteral invasion.

This review aims to highlight recently published articles on atopic dermatitis (AD). Updated are the insights into epidemiology, pathology, diagnostics, and therapy. Epidemiologic studies have revealed a positive correlation between AD and systemic conditions, such as rheumatoid arthritis, inflammatory bowel disease, and neonatal adiposity. Pathologic findings highlight the involvement of novel barrier factors (desmoplakin and claudin), novel immune cell subsets (pathogenic effector TH2 cells and group 2 innate lymphoid cells), and differential skewing of helper T cells (eg, TH17 dominance in Asians with AD). As diagnostics, noninvasive examinations of the transepidermal water loss of neonates, the density of epidermal Staphylococcus species, and the gut flora might prognosticate the onset of AD. As for therapy, various methods are proposed, including conventional (petrolatum and UV) and molecule-oriented regimens targeting Janus kinase, signal transducer and activator of transcription 3, extracellular signal-regulated kinase, sirtuin 1, or aryl hydrocarbon receptor.

In multiple stages forging, an appropriate pre-form has reduced production cost, loss of material, and forging load, and it has also improved die life. However, it is difficult for beginner to make the process design of the pre-form because they have poor technical information. For example, experts have experimental knowledge how to form an oval cylinder by upsetting of a right cylinder with a mild-wedged die. This oval upsetting needs no container with oval hole. This paper investigates the oval upsetting with the relationship between the nose angle of the mild-wedged die and the shape of the product for assistance of the process design in forging. As the results, when the mild-wedged die having an appropriate angle and nose radius was applied to the upsetting, the oval cross-sectional ratio of the major axis to the minor axis achieved 1.45.

Cowden syndrome is a rare autosomal dominant disorder characterized by multiple hamartomas of the ectoderm and brain. A 36-year-old Japanese man presented with right facial seizure during sleep and was admitted to our hospital. He showed cobblestoning over the tongue and palmar pitting but no neurological abnormalities while he was not having a seizure. Brain magnetic resonance imaging showed focal cortical dysplasia in the left frontal lobe. Electroencephalography showed sharp waves over the left frontal lesion. A genetic analysis revealed a novel mutation of PTEN. The administration of carbamazepine ended the seizures. This is the first Japanese case of Cowden syndrome with a novel PTEN gene mutation and cortical dysplasia.

The pathway of homeostatic IgG extravasation is not fully understood, in spite of its importance for the maintenance of host immunity, the management of autoantibody-mediated disorders, and the use of antibody-based biologics. Here we show in a murine model of pemphigus, a prototypic cutaneous autoantibody-mediated disorder, that blood-circulating IgG extravasates into the skin in a time- and dose-dependent manner under homeostatic conditions. This IgG extravasation is unaffected by depletion of Fcγ receptors, but is largely attenuated by specific ablation of dynamin-dependent endocytic vesicle formation in blood endothelial cells (BECs). Among dynamin-dependent endocytic vesicles, IgG co-localizes well with caveolae in cultured BECs. An Abl family tyrosine kinase inhibitor imatinib, which reduces caveolae-mediated endocytosis, impairs IgG extravasation in the skin and attenuates the murine pemphigus manifestations. Our study highlights the kinetics of IgG extravasation in vivo, which might be a clue to understand the pathological mechanism of autoantibody-mediated autoimmune disorders., Ablファミリーチロシンキナーゼが抗体の血管外輸送を制御することを解明 --生体内での抗体輸送メカニズム--. 京都大学プレスリリース. 2019-10-21.

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. Electronic supplementary material The online version of this article (10.1186/s13063-019-3570-6) contains supplementary material, which is available to authorized users.

BACKGROUND Postoperative adjuvant chemotherapy is not indicated for T1N1M0/T2N0M0/T3N0M0 gastric cancer. However, approximately 10% to 30% of these patients experience recurrence and metastasis. METHODS Among 658 patients with gastric cancer who received gastrectomy with curative intent, 130 T1N1M0/T2N0M0 and 73 T3N0M0 patients were enrolled. Overall survival (OS) and relapse-free survival (RFS) were analyzed based on TP53 codon 72 polymorphisms Arg/Arg, Arg/Pro, and Pro/Pro. The hazard ratio (HR) for each subgroup was compared by TP53 codon 72 polymorphisms. RESULTS Of the 189 patients for whom polymorphism analysis results were available, the 5- and 10-year OS was 84.9% and 65.1%, respectively. The 5- and 10-year RFS was 81.8% and 65.4%, respectively. When the study cohort was divided into two groups according to polymorphism status (ie, "Arg/Arg and Arg/Pro" vs Pro/Pro), both the OS (HR, 2.799; 95% confidence interval [CI], 1.071-7.315; P = .036) and RFS (HR, 2.639; 95% CI, 1.025-6.794; P = .044) of the Pro/Pro group were significantly lower than those for the Arg/Arg and Arg/Pro groups across the entire observation period. CONCLUSIONS The TP53 codon 72 Pro/Pro polymorphism may isolate a relatively high-risk patient group in T1N1M0/T2N0M0/T3N0M0 gastric cancer.

Background Percutaneous sensitization is associated with various allergic diseases, including asthma and food allergies. However, the immunologic mechanisms underlying how the skin regulates percutaneous sensitization are still unclear. Objective We aimed to investigate whether and how CD4+Foxp3+ regulatory T (Treg) cells residing in the skin regulate percutaneous sensitization in the skin. Methods Selective reduction of numbers of cutaneous Treg cells was achieved by means of intradermal injection of diphtheria toxin into the ear skin of Foxp3DTR mice, in which Treg cells specifically express the diphtheria toxin receptor fused with green fluorescent protein. Results Thirty percent to 40% of cutaneous Treg cells were capable of IL-10 production in both mice and human subjects. Selective reduction of cutaneous Treg cells at the sensitization site promoted migration of antigen-bearing dendritic cells (DCs) to the draining lymph nodes (dLNs). Accordingly, sensitization through the skin with reduced numbers of Treg cells led to enhanced antigen-specific immune responses in the dLNs, including both effector T-cell differentiation and T cell–dependent B-cell responses, such as the development of germinal center B cells expressing IgG1 and IgE. Furthermore, antigen-bearing cutaneous DC migration was enhanced in mice with IL-10 deficiency restricted to the cutaneous Treg cell compartment, suggesting an important role of cutaneous IL-10+ Treg cells in limiting percutaneous sensitization. Treg cells with a skin-homing phenotype in skin dLNs expressed high levels of IL-10, suggesting that they contribute to renewal and maintenance of the cutaneous IL-10+ Treg cell population. Conclusion Skin-resident Treg cells limit percutaneous sensitization by suppressing antigen-bearing DC migration through in situ IL-10 production.

A 67-year-old man was diagnosed with esophageal cancer. Computed tomography(CT)revealed multiple sites of bilateral mediastinal lymph node swelling. Serum levels of soluble interleukin-2 receptor(sIL-2R)were elevated; however, serum levels of angiotensin-converting enzyme(ACE)were normal. Thus, we could not confirm a diagnosis of sarcoidosis. Esophagectomy with neck lymph node dissection was performed. The resected specimen, comprising the mediastinal lymph nodes, showed noncaseating epithelioid cell granuloma; this supported the diagnosis of sarcoidosis. Cases of sarcoidosis associated with esophageal cancer are rare. It is difficult to distinguish between metastasis and sarcoid-like reactions from swollen lymph nodes using preoperative CT or positron emission tomography(PET). It is possible to differentiate lymph node metastasis from its sarcoid reaction it the patient received.

Atopic dermatitis (AD) is characterized by severe pruritus and recurrent eczema with a chronic disease course. Impaired skin barrier function, hyperactivated TH2 cell–type inflammation, and pruritus-induced scratching contribute to the disease pathogenesis of AD. Skin microbial alterations complicate the pathogenesis of AD further. Mouse models are a powerful tool to analyze such intricate pathophysiology of AD, with a caution that anatomy and immunology of the skin differ between human subjects and mice. Here we review recent understanding of AD etiology obtained using mouse models, which address the epidermal barrier, skin microbiome, TH2 immune response, and pruritus.

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.

Eosinophilic pustular folliculitis (EPF) is a sterile inflammatory dermatosis of unknown etiology. In addition to classic EPF, which affects otherwise healthy individuals, an immunocompromised state can cause immunosuppression-associated EPF (IS-EPF), which may be referred to dermatologists in inpatient services for assessments. Infancy-associated EPF (I-EPF) is the least characterized subtype, being observed mainly in non-Japanese infants. Diagnosis of EPF is challenging because its lesions mimic those of other common diseases, such as acne and dermatomycosis. Furthermore, there is no consensus regarding the treatment for each subtype of EPF. Here, we created procedure algorithms that facilitate the diagnosis and selection of therapeutic options on the basis of published work available in the public domain. Our diagnostic algorithm comprised a simple flowchart to direct physicians toward proper diagnosis. Recommended regimens were summarized in an easy-to-comprehend therapeutic algorithm for each subtype of EPF. These algorithms would facilitate the diagnostic and therapeutic procedure of EPF.