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Abstract Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses, and clinically characterised by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous‐violaceous edges. Underlying diseases include rheumatoid arthritis, inflammatory bowel disease, haematopoietic malignancy, and aortitis syndrome. However, there was a limited number of cases of concomitant pyoderma gangrenosum and IgA vasculitis. Herein, we report a case presenting persistent large skin wounds as a diagnosis of pyoderma gangrenosum in the setting of IgA cutaneous vasculitis, which was successfully treated by a TNF‐α inhibitor. A 67‐year‐old obese female presented palpable purpura on her lower extremities. A skin biopsy taken from the purpuric eruption showed leukocytoclastic vasculitis with IgA and C3 depositions in the vessel walls of the upper dermis, leading to the diagnosis of IgA vasculitis. Small skin ulcers rapidly expanded in several days, eventually developing perforating skin ulcers with irregular erythematous and violaceous edges on both lower extremities following the tapered oral prednisolone at a dose of 25 mg per day. Based on the clinical manifestation and histological analysis, we diagnosed her skin wound as pyoderma gangrenosum. After the adalimumab administration, the spreading ulceration was dampened, leading to the acceleration of wound epithelialisation.

Abstract Chloroplasts are thought to have co-evolved through endosymbiosis, after a cyanobacterial-like prokaryote was engulfed by a eukaryotic cell; however, it is impossible to observe the process toward chloroplasts. In this study, we constructed an experimental symbiosis model to observe the initial stage in the process from independent organisms to a chloroplast-like organelle. Our system of synthetic symbiosis is capable of long-term coculture of two model organisms: a cyanobacterium (Synechocystis sp. PCC6803) as a symbiont and a ciliate (Tetrahymena thermophila) as a host with endocytic ability. The experimental system was clearly defined, because we used a synthetic medium and the cultures were shaken to avoid spatial complexity. We determined the experimental conditions for sustainable coculture, by analyzing population dynamics using a mathematical model. We experimentally demonstrated that the coculture was sustainable for at least 100 generations, through serial transfers. Moreover, we found that cells isolated after the serial transfer improved the probability of coexistence of both species without extinction in re-coculture. The constructed system will be useful for understanding the initial stage of primary endosymbiosis from cyanobacteria to chloroplasts, i.e., the origin of algae and plants.

Abstract The coronavirus disease 2019 (COVID‐19) vaccine is positively changing the health crises of this pandemic and is currently essential to overcome the COVID‐19 pandemic. The vaccine shows high efficacy against the infection and impairs the severity of symptoms. However, this vaccination is associated with concerns, such as vaccine‐associated adverse reactions, which are currently highlighted issues for clinicians. We experienced two cases of mild cutaneous adverse reaction following COVID‐19 vaccine administration, which was successfully controlled by prior administration of the antihistamine agent fexofenadine 3 days before COVID‐19 vaccination for 7 days.

Resistant maltodextrin (RMD) attenuates the blood glucose response in healthy adults, as supported by meta-analysis. One of the potential mechanisms is disaccharidase inhibition. We hypothesized that the conventional method determining released glucose might lead to misestimation of the inhibitory effects because RMD is partly digested and the glucose amount released from RMD could change in the presence or absence of substrates. We examined digestibility change of RMD and compared the inhibitory effects by determination of released glucose (Glu method), fructose (Fru method), and p-nitrophenol from p-nitrophenyl- α -D-glucopyranoside (pNPG method). The Glu method overestimated the inhibition rate (18.9 to 60.2% for maltase). The Fru method showed inhibition for sucrase by 6.46 to 10.9% and isomaltase by 14.4 to 28.6%. The pNPG method showed α-glucosidase inhibition of 11.0 to 28.1%. These results indicate that the Glu method is not suitable for inhibition assay of partially digestible dextrin and that RMD has disaccharidase inhibition.

Abstract Mycosis fungoides is recognized as an indolent cutaneous malignant T-cell lymphoma. In contrast, there are few therapeutic options for advanced forms of mycosis fungoides. Since immunotherapy is desirable as an alternative therapeutic option, identifying candidate molecules is an important goal for clinicians. Although tumor-derived negative immunomodulatory molecules, such as PD-1/PD-L1, have been identified in various malignancies, the useful positive immunological drivers of mycosis fungoides are largely unknown. We found that the stimulator of interferon (IFN) genes (STING) was highly upregulated in early-stage mycosis fungoides. Immunohistochemical examination revealed different STING staining patterns in patients with mycosis fungoides. Although there were no significant differences in clinical factors’ characteristics, STING expression was associated with the survival of patients with mycosis fungoides. The survival rate was significantly poor in patients with low STING-expressing mycosis fungoides. Univariate and multivariate analyses revealed that low STING expression was associated with an increased hazard ratio. Our results indicate that STING expression independently influences the prognosis of mycosis fungoides.

Abstract Roof‐dependent atrial flutter (AFL) is a major tachyarrhythmia rotating in the left atrium (LA). Here, we describe a case of roof‐dependent AFL during atrial fibrillation ablation. LA posterior wall (LAPW) debulking ablation was performed before the induction. Atrial tachycardia (AT) was induced by burst pacing, and the 3D mappings showed a focal pattern from the LA inferior area. The post‐pacing interval from the roof and bottom line corresponded to the AT cycle length. The LAPW debulking ablation masked roof‐dependent AFL due to the lack of endocardium potentials in the LAPW. We report that roof‐dependent AFL connected by epicardium fibers.

Abstract Psoriasis is a chronic inflammatory skin disease that involves various systemic organs and tissues and is characterized by scaly erythematous skin. Among the different types of psoriasis, psoriatic arthritis (PsA) is frequently reported, and occasionally develops into severe arthritis leading to joint dysfunction. There are various tools, especially questionnaires, to identify the presence of PsA in European and American populations; however, little is known about the utility of these tools in the Asian population. In this study, we investigated the utility of a representative tool, the psoriasis epidemiology screening tool (PEST) questionnaire, to identify PsA among Japanese patients with psoriasis. A total of 143 patients with psoriasis were enrolled in this study. Among them, 29 patients were diagnosed with PsA. The frequency of PsA was significantly increased in patients with PEST scores > 3, with a sensitivity of 93.1% and a specificity of 78.9%. Among the questions in the PEST questionnaire, “Have you ever had a swollen joint?” showed the highest frequency to answer “Yes” among patients with PsA. Univariate and multivariate analyses revealed that high PEST scores (> 3) was an independent variable in PsA patients. Taken together, our study suggests that the PEST questionnaire is a useful tool to identify PsA among Japanese patients with psoriasis.

Atypical lipomatous tumor (ALT) has been defined as a well-differentiated liposarcoma exhibiting a higher frequency of a local recurrence after surgical resection. ALT is mainly classified into deep type and superficial type. Compared with deep type ALT, superficial type ALT is rarely observed. One of the most important issues is that little has been known about superficial type ALT and it is not easy to predict the presence of superficial type ALT before surgical resection. To clarify the clinical manifestations of superficial type ALT, we examined 15 cases with superficial type ALT and 118 cases with benign lipoma, and analyzed their differences in clinical characteristics and the findings of MRI test. In clinical characteristics, the tumor size of superficial type ALT was significantly greater than that of benign lipoma, and superficial type ALT showed a significantly higher frequency of the tumor size of more than 4 cm. Superficial type ALT exhibited poor tumor mobility and hardness with elastic soft. In addition, a significantly higher frequency of tumor location of superficial type ALT was observed in extremities. Among tumor sites at the trunk, buttocks, and shoulder were high frequent location in superficial type ALT. In an MRI examination, superficial type ALT exhibited a significantly higher frequency of the septal structures compared with benign lipoma. The combinations of clinical characteristics, including physical examinations, MRI, and histological examinations, are helpful for the diagnosis of superficial type ALT.

Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great importance to identify a potential biomarker to estimate tumor advancement in extramammary Paget’s disease. Dermcidin is an antimicrobial peptide derived from the eccrine gland and is identified as a biomarker in various malignancies. To investigate the potential of dermcidin in extramammary Paget’s disease, we investigated dermcidin expression in tumors using the immunostaining technique. Although previous studies have reported that extramammary Paget’s disease has no positive staining against dermcidin, 14 out of 60 patients showed positive staining of dermcidin in our study. To clarify the characteristics of positive dermcidin in extramammary Paget’s disease, we investigated the clinical characteristics of positive dermcidin extramammary Paget’s disease patients. Positive dermcidin patients showed a significantly high frequency of lymph node metastasis. We next investigated the impact of positive dermcidin on overall survival. Univariate analysis identified that positive dermcidin showed a significantly increased hazard ratio in overall survival, suggesting that dermcidin might be a prognostic factor for extramammary Paget’s disease.

End stage renal disease (ESRD) patients may display the deficiency in vegetable-derived micronutrient, such as vitamins and minerals, due to the potassium-restricted diet. VCRESC, a drink type micronutrient supplement containing enough amounts of daily-required vitamins, is prescribed for patients with micronutrient deficiency in Japan. 58 years old woman under the chronic hemodialysis with non-diabetic ESRD. Before the initiation of VCRESC, her blood vitamins and Hcy levels were measured. She was introduced 125 ml/day of VCRESC oral intake over 12 months period. After first two weeks of VCRESC initiation, she was temporary advised to stop VCRESC for two weeks. Subsequently she was re-initiated VCRESC supplement until the end of the study. Her blood micronutrient levels were monitored at 2 and 4 weeks, 3 and 12 months after the initiation of study. Results: Some of her baseline blood vitamins (B6, B12, C) level exhibited lower when compared to Japanese standard value. After 2 weeks initiation of VCRESC, her vitamins (A, B1 B2, B6, B12, C and folate) levels elevated remarkably. After temporal termination of the VCRESC for 2 weeks, her vitamin B1, B2, C, E levels were suppressed, though vitamin A and B6 levels were not altered when compared to the levels observed at 2 weeks after the initiation of the study. At either 3 or 12 months after the initiation of study, vitamin B groups, E, C and folate was higher when compared to standard value; vitamin A levels remained in high standard range. Her Hcy level was higher than normal value in the beginning of study and reduced for 29% at the end of the study. Conclusion: Hcy level in dialysis patients has been shown to be an independent risk factor for vascular complications. VCRESC could be the potential nutritional intervention in the ESRD patient under chronic hemodialysis for the prevention of vascular complications.

Purpose. In this study, we developed various ternary complexes of encapsulated polyplexes and lipoplexes using chondroitin sulfate (CS) and investigated their universal usefulness for gene delivery. Methods. To prepare the cationic complexes, pDNA was mixed with some cationic vectors such as poly-L-arginine, poly-L-lysine, N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA)-cholesterol liposomes, and DOTMA- dioleylphosphatidylethanolamine (DOPE) liposomes. CS was added to the cationic complexes for constructions of ternary complexes. We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of the ternary complexes. Result. The cationic polymers and cationic liposomes bound to pDNA and formed stable cationic polyplexes and lipoplexes, respectively. Those cationic complexes showed high transgene efficiency in B16-F10 cells; however, they also had high cytotoxicity and strong agglutination with erythrocytes. CS could encapsulate the polyplexes and lipoplexes and form stable anionic particles without disrupting their structures. The ternary complexes encapsulated by CS showed high transgene efficiency in B16-F10 cells with low cytotoxicity and agglutination. As the result of animal experiments, the polyplexes had little transgene efficiency after intravenous administration in mice, whereas polyplexes encapsulated by CS showed specifically high transgene efficiency in the spleen. The capsulation of CS, however, reduced the high transgene efficiency of the lipoplexes. Conclusion. These results indicate that CS can contribute to polyplex-mediated gene delivery systems for effective and safe gene therapy.