Decreased ADP-Ribosyl Cyclase Activity in Peripheral Blood Mononuclear Cells from Diabetic Patients with Nephropathy

Aims/hypothesis. ADP-ribosyl-cyclase activity (ADPRCA) of CD38 and other ectoenzymes mainly generate cyclic adenosine 5’diphosphate-(ADP-) ribose (cADPR) as a second messenger in various mammalian cells, including pancreatic beta cells and peripheral blood mononuclear cells (PBMCs). Since PBMCs contribute to the pathogenesis of diabetic nephropathy, ADPRCA of PBMCs could serve as a clinical prognostic marker for diabetic nephropathy. This study aimed to investigate the connection between ADPRCA in PBMCs and diabetic complications. Methods. PBMCs from 60 diabetic patients (10 for type 1 and 50 for type 2) and 15 nondiabetic controls were fluorometrically measured for ADPRCA based on the conversion of nicotinamide guanine dinucleotide (NGD+) into cyclic GDP-ribose. Results. ADPRCA negatively correlated with the level of HbA1c (P = .040, R2 = .073), although ADPRCA showed no significant correlation with gender, age, BMI, blood pressure, level of fasting plasma glucose and lipid levels, as well as type, duration, or medication of diabetes. Interestingly, patients with nephropathy, but not other complications, presented significantly lower ADPRCA than those without nephropathy (P = .0198) and diabetes (P = .0332). ANCOVA analysis adjusted for HbA1c showed no significant correlation between ADPRCA and nephropathy. However, logistic regression analyses revealed that determinants for nephropathy were systolic blood pressure and ADPRCA, not HbA1c. Conclusion/interpretation. Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy

Preventive effects of betamethasone valerate ointment for radiation-induced severe oral mucositis in patients with oral or oropharyngeal cancer: protocol for a multicentre, phase II, randomised controlled trial (Bet-ROM study)

Introduction: This is a randomised, multi-centre, open-label, phase II study to evaluate the efficacy of betamethasone valerate ointment on radiation-induced oral mucositis in patients with head and neck cancer undergoing concomitant radiotherapy with cisplatin or cetuximab.Methods and analysis: The trial will take place at seven hospitals in Japan. Patients will be randomised (1:1) into betamethasone and control groups after the occurrence of grade 1 oral mucositis. In the betamethasone group, patients will use betamethasone valerate ointment five times a day, in addition to usual oral hygiene guidance. The primary endpoint is the incidence and onset time of grade 3 oral mucositis. The secondary endpoints are the incidence and onset time of grade 2 oral mucositis, incidence and onset time of oral candidiasis, completion of radiation therapy and adverse events. Target accrual is 102 patients with a two-sided type I error rate of 5% and 80% power to detect an 80% risk reduction in the incidence of grade 3 oral mucositis.Ethics and dissemination: This study was approved by the Clinical Research Review Board of Nagasaki University (No. CRB20-009). All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publication. The datasets generated during the study will be available from the corresponding author on reasonable request.Trial registration number: jRCTs071200013

A Role of Staphyococcus aureus, Interleukin-18, Nerve Growth Factor and Semaphorin 3A, an Axon Guidance Molecule, in Pathogenesis and Treatment of Atopic Dermatitis

Staphylococcus aureus (SA) is usually present not only in the skin lesions of atopic dermatitis (AD) but also in the atopic dry skin. SA discharges various toxins and enzymes that injure the skin, results in activation of epidermal keratinocytes, which produce and release IL-18. IL-18 that induces the super Th1 cells secreting IFN-γ and IL-13 is supposed to be involved in development of AD and its pathogenesis. Indeed, the number of SA colonies on the skin surface and the serum IL-18 levels in patients with AD significantly correlated with the skin scores of AD lesions. Also, there is strong positive correlation between the skin scores and serum IL-18 levels in DS-Nh mice (P<0.0001, r=0.64), which develop considerable AD-like legions when they are housed under conventional conditions, but develop skin legions with less severity and less frequency under specific pathogens free (SPF) conditions. Therefore, they are well-known as model mice of AD, in which SA is presumed to be critical factor for the development of AD lesions. Also, theses DS-Nh mice pretreated with Cy developed more remarkable AD-like lesions in comparison with non-treated ones. The levels of INF-r and IL-13 in the supernatants of the lymph node cell cultures stimulated with staphylococcal enterotoxin B (SEB) or ConA were increased in the Cy-treated mice, although the serum levels of total IgE were not. In this experiment, we revealed that Cy-treated mice, to which CD25 +CD4 + reguratory T cells taken from non-treated ones had been transferred, developed the AD-like legions with less severity and less number of SA colonies on the skin surface. Therefore, it is presumed that CD25 +CD4 + reguratory T cells might be involved in the suppression of super Th1 cells which are induced by IL-18 and are involved in the development of AD-like lesions rather than IgE production. The efficient induction of CD25 +CD4 + reguratory T cells is expected for the new type of treatment of AD. We also found that farnesol (F) and xylitol (X) synergistically inhibited biofilm formation by SA, and indeed the ratio of SA in total bacteria at sites to which the FX cream containing F and X had been applied was significantly decreased 1 week later, accompanied with improvement of AD, when compared with that before application and at placebo sites. Therefore, the FX cream is a useful skin-care agent for atopic dry skin colonized by SA. The nerve growth factor (NGF) in the horny layer (the horn NGF) of skin lesions on the cubital fossa was collected by tape stripping and measured using ELISA in AD patients before and after 2 and 4 weeks treatments. Simultaneously, the itch and eruptions on the whole body and on the lesions, in which the horn NGF was measured, were recorded, and also the peripheral blood eosinophil count, serum LDH level and serum total IgE level were examined. The level of NGF was significantly higher in AD patients than in healthy controls, correlated with the severity of itch, erythema, scale/xerosis, the eosinophil count and LDH level, and also significantly decreased after treatments with olopatadine and/or steroid ointment for 2 and 4 weeks. Therefore, the measurement of the NGF by this harmless method seems to be useful to assess the severity of AD and the therapeutic effects on AD. In AD patients, C-fiber in the epidermis increase and sprout, inducing hypersensitivity, which is considered to aggravate the disease. Semaphorin 3A (Sema3A), an axon guidance molecule, is a potent inhibitor of neurite outgrowth of sensory neurons. We administered recombinant Sema3A intracutaneously into the skin lesions of NC/Nga mice, an animal model of AD, and investigated the effect of Sema3A on the skin lesions and their itch. Sema3A dose-dependently improved skin lesions and attenuated the scratching behavior in NC/Nga mice. Histological examinations revealed a decrease in the epidermal thickness, the density of invasive nerve fibers in the epidermis, inflammatory infiltrate including mast cells and CD4 +T cells, and the production of IL-4 in the Sema3A-treated lesions. Because the interruption of the itch-scratch cycle likely contributes to the improvement of the AD-like lesions, Sema3A is expected to become a promising treatment of patients with refractory AD

言語聴覚療法におけるリスクマネジメントと養成校での教育

研究報告Original Paper医療現場におけるリスクマネジメントの重要性が認識され、多くの病院で医療事故防止のためのアプローチが試みられているが、言語聴覚士は資格制定からの日が浅く、養成校では言語聴覚療法そのものに関する教育のみに主眼が置かれ、医療安全に関する教育は十分とは言えない状況である。日本言語聴覚士協会の調査によれば、事故、ヒヤリハット、苦情、不満等を体験した回答者は83%に上り、事例の具体的記載内容では身体的危害に関するものが70%、患者との人間関係に関するものが27%であった。言語聴覚士にとってのリスクは、基本的な業務遂行上の問題、情報伝達・人間関係・守秘義務に関する問題、専門的臨床能力に関する問題、全般的な安全に関する問題に分類された。養成校におけるリスクマネジメント教育は、個々の専門科目のシラバスの改訂、臨床実習手引書の改訂と実習前教育、当該科目の新設によって改善が図られるべきである。As the importance of risk management in medical field has been emphasized these days, various kinds of approaches have been taken to help prevent medical incidents and accidents in many hospitals. It is only several years since the national law of the certification system of speech-language-hearing therapists was established, so education for those therapists at institutes tended to be focused on professional skill, not on medical safety. A survey organized by Japanese association of speech-language-hearing therapists showed that 83% of respondents had experienced accidents, incidents and complaints by their patients. 70% of specific instances of what they had experienced were concerned with physical damages and 27% of them were concerned with human relationships. The risk in speech-language-hearing therapy was assorted into four types of problems, 1) basic performance, 2) communication, human relationship and confidentiality, 3) professional ability and 4) general safety, which were then examined. We concluded that risk management education had to be improved by revising each syllabus of professional subjects, by amending each guidebook for clinical practice, by guiding students just before carrying out that practice and by setting up new subjects

Latin American immigrants have limited access to health insurance in Japan: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Japan provides universal health insurance to all legal residents. Prior research has suggested that immigrants to Japan disproportionately lack health insurance coverage, but no prior study has used rigorous methodology to examine this issue among Latin American immigrants in Japan. The aim of our study, therefore, was to assess the pattern of health insurance coverage and predictors of uninsurance among documented Latin American immigrants in Japan.</p> <p>Methods</p> <p>We used a cross sectional, mixed method approach using a probability proportional to estimated size sampling procedure. Of 1052 eligible Latin American residents mapped through extensive fieldwork in selected clusters, 400 immigrant residents living in Nagahama City, Japan were randomly selected for our study. Data were collected through face-to-face interviews using a structured questionnaire developed from qualitative interviews.</p> <p>Results</p> <p>Our response rate was 70.5% (n = 282). Respondents were mainly from Brazil (69.9%), under 40 years of age (64.5%) and had lived in Japan for 9.45 years (SE 0.44; median, 8.00). We found a high prevalence of uninsurance (19.8%) among our sample compared with the estimated national average of 1.3% in the general population. Among the insured full time workers (n = 209), 55.5% were not covered by the Employee's Health Insurance. Many immigrants cited financial trade-offs as the main reasons for uninsurance. Lacking of knowledge that health insurance is mandatory in Japan, not having a chronic disease, and having one or no children were strong predictors of uninsurance.</p> <p>Conclusions</p> <p>Lack of health insurance for immigrants in Japan is a serious concern for this population as well as for the Japanese health care system. Appropriate measures should be taken to facilitate access to health insurance for this vulnerable population.</p

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

Effects of Neuropeptides In The Development Of The Atopic Dermatitis Of Mouse Models

Background: Neuropeptides are considered to be factors that trigger, exacerbate or modulate allergic diseases and inflammatory skin reactions. In addition, it has been indicated that allergic diseases are highly correlated with stress. Methods: 2,4,6-Trinitrochlorbenzene (TNCB) and crowding stress were applied to mouse atopic dermatitis (AD) models for the purpose of provoking chronic dermatitis. In addition, TNCB-sensitized mice were given olopatadine hydrochloride (10 or 3 mg/kg), an anti-allergic agent, orally. The neuropeptide content in the skin tissues and serum IgE levels were measured in these mice. Results: Repeated local application of TNCB solution induced itching skin lesions, together with an increase in levels of substance P, a decrease in calcitonin generelated peptide levels and early augmentation of IgE production. Treatment with crowding stress brought about a transient increase in substance P. Furthermore, we observed significant decreases in substance P and serum IgE levels when the administration of olopatadine hydrochloride was started before the elicitation of chronic dermatitis caused by repeated application of TNCB solution. These changes were more definite in the group administered a higher dose of the drug (10 mg/kg). Conclusions: It is suggested that repeated contact allergic dermatitis or mental stress may promote the development and exacerbation of AD and that substance P has a role in this response. In addition, it seems that an anti-allergic drug, such as olopatadine hydrochloride, possibly downregulates substance P, thereby suppressing the development of AD. In the future, the development and clinical application of a drug that strongly influences the release of neuropeptides, such as substance P, and the expression of neuropeptide receptors would be expected for the treatment of AD