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Asbestos, especially chrysotile, continues to be exposed to humans globally. Hence, it should be disposed properly to prevent asbestos-related diseases, including mesothelioma and lung cancer. This study aimed to verify whether forsterite, a heating product of chrysotile, can cause carcinogenicity, particularly mesothelioma. Forsterite (FO-1000) and enstatite (EN-1500) produced by heating chrysotile at 1,000°C and 1,500°C, respectively, were subjected. We injected 10 mg of chrysotile, FO-1000, or EN-1500 in rats intraperitoneally and observed the development of peritoneal mesothelioma until 24 months. The incidence of peritoneal mesothelioma in the chrysotile group was 91.2%, whereas in the FO-1000 and EN-1500 groups, peritoneal mesothelioma did not develop. Urinary 8-hydroxy-2'-deoxyguanosine and serum N-ERC/mesothelin concentrations significantly increased in the chrysotile group that developed peritoneal mesothelioma, while they only temporarily changed in the FO-1000 or EN-1500 groups during early treatment. Furthermore, there was a significant homozygous deletion of the CDKN2A/p16 gene in the chrysotile group compared to the control group, in contrast to no significant difference in the FO-1000 and EN-1500 groups. Therefore, this study provides clear evidence that forsterite is a nonmesothelioma carcinogen and suggests that forsterite and enstatite are sufficient substances for chrysotile detoxification.

Objective: The Concurrent Approach for Respiratory Epidemiological Surveillance and Symptom Screening (CARES) combines symptom screening to prevent external respiratory infections by managing staff and visitor health and surveillance to monitor the infection rates within the facility and take timely decisions on activity programs based on outbreak prevalence. This study examines the efficacy of the CARES strategy in preventing respiratory infection outbreaks in long-term care facilities., Design: Prospective cohort study utilizing historical controls including an intervention and control group., Setting: This study was conducted in two long-term care facility wards (total: 110 beds) in Japan., Patients: We enrolled patients aged 1-72 years from the target ward with severe intellectual and physical disabilities from October 1, 2018, to March 31, 2019, and from October 1, 2017, to March 31, 2018, for the intervention (n = 104) and control (n = 98) groups, respectively. The study included all admitted patients and excluded those hospitalized or discharged during the study period., Intervention: The total number of days that activity programs, new admissions, and visitations were cancelled in the two groups was compared before and after the introduction of CARES., Results: CARES reduced the duration of new admission cancellations and visitation cancellations by 16 and 23 days, respectively ( α = 0.1, P value < 0.001). Additionally, the maximum duration of activity program cancellations was reduced by 2 days. Furthermore, five cases of presenteeism were prevented., Conclusions: CARES improves patients' quality of life by continuation of activity programs, new patient admission, and ongoing visitations.

Background: In the United States and the United Kingdom, the roles of nurses in antimicrobial stewardship (AS) have been described in guidelines. However, in Japan, no previous studies have clarified nurses' recognition of the role of AS. Moreover, how the AS roles were implemented among nurses in Japan has not been fully clarified. The objectives of this study were to determine the perceptions of infection control nurses (ICNs) in Japan regarding the AS role of nurses and the extent of nurses' practice., Methods: A questionnaire survey of ICNs was conducted., Results: Four hundred responses (response rate, 30.8%) were analyzed. Some of the items that have already gained consensus as the AS role of nurses were not recognized as the AS role of nurses by ICNs or had low implementation rates in Japan. Meanwhile, both recognition and implementation rates were high for the 5 types of care proposed., Discussion: The reason the ICNs agreed that these 5 types of care are AS roles for nurses is that they know that such care can prevent infection and thereby obviate the need for antimicrobial administration. However, whether nurses themselves understand that these are roles for nurses in AS is unclear. To promote AS in Japan, communicating the fact that nurses already contribute to AS, strengthening nurse education, and improving staffing are desirable., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to identify how doctors and nurses experienced sharps injuries in operating rooms and the risks for these injuries by analyzing data from 78 Japanese hospitals participating in the nationwide EPINet surveillance system. The years of professional experience of the cases were classified into tertiles separately for doctors and nurses. Suture needles accounted for 54.9% of injuries in doctors and 48.3% of injuries in nurses. Among doctors, injuries occurred most frequently during the use of an item (range: 58.1-64.3%), while among nurses, injuries occurred most frequently (range: 24.7-29.0%) between steps of a multi-step procedure. The frequency of injury by a suture needle held by someone else was 41.1-47.3% (range) among doctors, and 27.0-48.1% (range) among nurses. In conclusion, sharps injuries in the operating room need to address the circumstances of injury and holder of devices based on the specific risk for doctors and nurses to decrease the number of injuries.

Objective: Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). This study aims to assess factors associated with SSI after colorectal surgery in Japan, using a Japanese national database for HAIs., Design: A retrospective nationwide surveillance-based study., Setting: Japanese healthcare facilities., Methods: Data on colon and rectal surgeries performed from 2008 through 2010 were extracted from a national monitoring system for healthcare-associated infections, the Japan Nosocomial Infections Surveillance (JANIS). Factors associated with SSI after colon and rectal surgery were assessed using multivariate logistic regression., Results: The cumulative incidence of SSI for colon and rectal surgery was 15.0% (6,691 of 44,751) and 17.8% (3,230 of 18,187), respectively. Traditional risk factors included in the National Nosocomial Infections Surveillance (NNIS) modified risk index were significant in predicting SSI in the final model for both colon and rectal surgery. Among the additional variables routinely collected in JANIS were factors independently associated with the development of SSI, such as male sex (adjusted odds ratio [aOR], 1.20 [95% confidence interval (CI), 1.14-1.27]), ileostomy or colostomy placement (aOR, 1.13 [95% CI, 1.04-1.21]), emergency operation (aOR, 1.40 [95% CI, 1.29-1.52]), and multiple procedures (aOR, 1.22 [95% CI, 1.13-1.33]) for colon surgery as well as male sex (aOR, 1.43 [95% CI, 1.31-1.55]), ileostomy or colostomy placement (aOR, 1,63 [95% CI, 1.51-1.79]), and emergency operation (aOR, 1.43 [95% CI, 1.20-1.72]) for rectal surgery., Conclusions: For colorectal operations, inclusion of additional variables routinely collected in JANIS can more accurately predict SSI risk than can the NNIS risk index alone.

Background: Determining incidence rates of needlestick and sharps injuries (NSIs) using data from multiple hospitals may help hospitals to compare their in-house data with national averages and thereby institute relevant measures to minimize NSIs. We aimed to determine the incidence rate of NSIs using the nationwide EPINet surveillance system., Methodology/principal Findings: Data were analyzed from 5,463 cases collected between April 2009 and March 2011 from 67 Japanese HIV/AIDS referral hospitals that participated in EPINet-Japan. The NSI incidence rate was calculated as the annual number of cases with NSIs per 100 occupied beds, according to the demographic characteristics of the injured person, place, timing, device, and the patients' infectious status. The NSI incidence rates according to hospital size were analyzed by a non-parametric test of trend. The mean number of cases with NSIs per 100 occupied beds per year was 4.8 (95% confidence interval, 4.1-5.6) for 25 hospitals with 399 or fewer beds, 6.7 (5.9-7.4) for 24 hospitals with 400-799 beds, and 7.6 (6.7-8.5) for 18 hospitals with 800 or more beds (p-trend<0.01). NSIs frequently occurred in health care workers in their 20 s; the NSI incidence rate for this age group was 2.1 (1.6-2.5) for hospitals having 399 or fewer beds, 3.5 (3.0-4.1) for hospitals with 400-799 beds, and 4.5 (3.9-5.0) for hospitals with 800 or more beds (p-trend<0.01)., Conclusions/significance: The incidence rate of NSIs tended to be higher for larger hospitals and in workers aged less than 40 years; injury occurrence was more likely to occur in places such as patient rooms and operating rooms. Application of the NSI incidence rates by hospital size, as a benchmark, could allow individual hospitals to compare their NSI incidence rates with those of other institutions, which could facilitate the development of adequate control strategies.

Vancomycin-intermediate Staphylococcus aureus (VISA) and its precursor, heterogeneous VISA (hVISA), are increasingly the cause of vancomycin treatment failure. Prolonged glycopeptide treatment causes the emergence of these pathogens. However, we recently reported that hVISA can be generated by methicillin-resistant S. aureus (MRSA) exposure to imipenem (Katayama et al., Antimicrob Agents Chemother. 53:3190-6). We report here a retrospective prevalence study of VISA and hVISA on 750 MRSA clinical strains isolated from 31 Japanese national university hospitals in 1990, the year before the introduction of injectable vancomycin into clinical use in Japan in 1991. No VISA strain was identified, but population analysis identified 38 hVISA strains (5.1%) from 19 hospitals. We also determined the nucleotide sequences of vraSR, walRK, clpP, and rpoB genes whose mutations are known to be associated with vancomycin resistance. When compared with vancomycin-susceptible MRSA strain N315, six of the 38 hVISA strains possessed nonsynonymous mutations in vraSR, seven in walRK, and two in rpoB genes, Thirteen of 38 (34.2%) hVISA strains possessed at least one of these mutations. Results were consistent with our hypothesis that hVISA was present in Japanese hospitals before the clinical introduction of vancomycin.

Chrysotile (CH), the most common form of asbestos, is rendered less toxic by heating it at 1000°C and converting it to forsterite (FO-1000). However, further safety tests are needed to evaluate human health risk of these materials. It has been reported that serum concentrations of megakaryocyte potentiating factor N-ERC/mesothelin become elevated in patients with mesotheliomas caused by asbestos exposure. In this study, a single 2mg dose of CH or FO-1000 was intratracheally administered to rats. Within 180days after the administrations, serum N-ERC/mesothelin concentrations, levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in lung tissues and pathological changes in respiratory organs were determined. In the CH group, a significant increase in serum N-ERC/mesothelin concentrations was observed immediately after intratracheal administration, and the elevation lasted for 30days. In lung tissues, positive staining for 8-OHdG in bronchioles, alveolar epithelium, inflammatory cells, and granulomas was evidence of a marked DNA oxidative damage. Furthermore, measurements of 8-OHdG in lung tissues based on the HPLC-ECD method suggested that serum N-ERC/mesothelin concentrations tended to increase when there are significant DNA damages in lung tissues. In contrast, in the FO-1000 group, a marked rise in serum N-ERC/mesothelin concentrations occurred only in the early phase (1-7days) after intratracheal administration. Similarly, FO-1000 induced elevation of 8-OHdG in lung tissues was transient and modest compared with those of the CH-treated animals. In both the CH and FO-1000 groups, we observed significant correlations between serum N-ERC/mesothelin concentrations and lung 8-OHdG concentrations (r=0.559, p=0.001 for the CH group; r=0.516, p=0.01 for the FO-1000 group). In summary, we demonstrated the possibility of using serum N-ERC/mesothelin concentrations as a useful biomarker for early phase exposure to either CH or FO-1000., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Active oxygen causes various problems including male infertility through the oxidation of DNA, proteins, and lipids. In the present study, we examined the immunohistochemical localization of molecules involved in oxidative stress including 8-hydroxy-2-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), and protein disulfide isomerase (PDI) in mature and developing rat testes. In mature rat testes, 8-OHdG was detected in leptotene, zygotene, and early pachytene spermatocytes, while its expression was weak in late pachytene stage spermatocytes. On the other hand, SOD was detected in late pachytene spermatocytes but not in early pachytene and former spermatocytes, suggesting the efficient removal of active oxygen by SOD in late pachytene spermatocytes. In developing rat testes, 8-OHdG expression peaked at 4 weeks when spermatocytes started to differentiate to the late pachytene stage, while SOD started to be expressed at 4 weeks after birth. These findings suggest that the defense system against oxidative stress by SOD is developed in late pachytene stage spermatocytes at 4 weeks after birth. The present findings aid our understanding of the defensive mechanism against oxidative stress in developing and mature testes.

Chrysotile (CH) is a pathogenic waste building material that can potentially be rendered innocuous via conversion to forsterite (FO) by heating at high temperatures. We compared the ability of FO and CH to cause oxidative DNA damage and lung injury. A single 1-mg intratracheal dose of CH or FO was administered to rats. Significant changes were observed 3 to 7 days after CH injection in alveolar macrophages, neutrophils, eosinophils, lymphocytes, total protein, and lactate dehydrogenase. High concentrations of 8-hydroxy-29-deoxyguanosine (8-OHdG) were also observed in the macrophages, other infiltrating inflammatory cells, granulomas, and in bronchiolar and alveolar epithelial cells. The overexpression of 8-OHdG was limited to airway epithelial and inflammatory cells surrounding the fibrotic foci 540 days after injection, indicating that the inflammatory effects of CH were persistent yet decreased with time. Compared to the CH group, acute lung inflammation observed in the FO group was less apparent and exhibited no progressive fibrosing lesions. The expression of 8-OHdG was transient and weak in the bronchiolar epithelial cells as well as in the inflammatory cells, consistent with low concentrations of 8-OHdG observed in the lungs. These findings confirm that FO causes significantly less inflammation and oxidative DNA damage in the lungs than CH.

Unlabelled: We sought to establish a causal relationship between oxidative stress and porphyria in patients and carriers. We reported changes in urinary porphyrin concentrations related to 8-hydroxy-2'-deoxyguanosine., Methods: We measured urinary 8-hydroxy-2'-deoxyguanosine concentration in porphyria patients and carriers with multifactorial inheritance as a possible marker of attack. The porphyria types included 10 patients with porphyria cutanea tarda, 5 with variegate porphyria, 8 with hereditary coproporphyria, 7 with congenital erythropoietic porphyria, 5 with erythropoietic protoporphyria, 5 with acute intermittent porphyria, 7 erythropoietic protoporphyria carriers, and 7 acute intermittent porphyria carriers., Results: Urinary porphyrin concentrations in these patients were significantly higher than those in healthy subjects (p<0.001). Urinary 8-hydroxy-2'-deoxyguanosine concentrations were significantly high in dermatopathy porphyria types namely porphyria cutanea tarda (p<0.001), variegate porphyria (p<0.05), hereditary coproporphyria (p<0.05), congenital erythropoietic phyria (p<0.05), and erythropoietic protoporphyria (p<0.001)., Conclusion: These results reveal that urinary 8-hydroxy-2'-deoxyguanosine concentration in cutis porphyria types is a good predictor of attack and abatement.

Urinary and cerebrospinal fluid (CSF) levels of 8-hydroxydeoxyguanosine (8-OHdG) were examined to estimate the relevance of oxidative stress in children with brain damage. Urinary 8-OHdG levels were measured in 51 children with various forms of central nervous system (CNS) disorders (status epilepticus [SE], hypoxic-ischemic encephalopathy [HIE], CNS infections and chronic epilepsy) and these levels were compared with those in 51 healthy children. CSF 8-OHdG levels were measured in 25 children with brain damage and in 19 control subjects. In addition, urinary and CSF levels of 8-OHdG were compared between the children with brain damage and healthy children. Finally, the relationship between urinary and CSF levels of 8-OHdG was determined in 12 children that provided both urinary and CSF samples. Our results showed that urinary 8-OHdG levels in children with HIE and CNS infections were higher than those of controls (Steel test; p < 0.05 and p < 0.05, respectively) and that CSF 8-OHdG levels were higher in children with SE, HIE, and CNS infections than in control subjects (Steel test; p < 0.01, 0.05 and 0.05, respectively). In addition, a positive correlation between the levels of urinary and CSF 8-OHdG was noted in the 12 children that provided both CSF and urinary samples (Spearman's rank correlation; rho = 0.82, p < 0.01). Further, we observed changes in the urinary 8-OHdG in a patient with HHV-6 encephalopathy, and found that the changes correlated well with the patient's clinical condition. These results suggest that oxidative stress is strongly related to acute brain damage in children, and that 8-OHdG is a useful marker of brain damage. Therefore, repeated measurements of urinary 8-OHdG may be helpful in estimating the extent of brain damage.

Beryllium chloride and/or zinc chloride were intraperitoneally injected into mice. The amount of beryllium (Be) injected corresponded to 1/10th of the LD50 dose intravenously administered. The amount of zinc (Zn) injected was the same as Be. The changes in porphyrin metabolism of the mice were studied. Delta-aminolevulinic acid dehydratase (ALA-D) activities in the blood were found to increase significantly in Zn and BeZn groups when compared to the control level. The blood porphobilinogen deaminase (PBG-D) activity in the Zn group was slightly less than that in the controls. The ALA-D and PBG-D activities in liver were higher in the Be and BeZn groups than in the controls. The splenic ALA-D activities were significantly higher in the Zn and BeZn groups than in the control and Be groups. The splenic PBG-D activities were markedly higher in the Be and/or Zn groups than in the controls. An increase in ALA-D activities in the blood and spleen was observed in the BeZn group, together with an increase in ALA-D activities caused by Zn administration. Furthermore, the increase in PBG-D activities in liver and spleen was observed in the Be and/or Zn groups. The results suggested that chemical similarity between Be and Zn brought about these phenomena.

The effect of beryllium (Be) compounds on porphyrins was investigated in pregnant mice. The blood protoporphyrin (Proto) and zinc protoporphyrin (Zn Proto) concentrations were increased in pregnancy. Regardless of pregnancy or nonpregnancy, the Proto concentration was decreased after Be injection. Delta-aminolevulinic acid dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D) activities in blood were significantly elevated in the pregnant untreated (Con-pregnant) group, compared to the nonpregnant mice untreated (Con-nonpregnant) and nonpregnant mice treated with Be (Be-nonpregnant) groups. The blood ALA-D activity of the pregnant mice treated with Be (Be-pregnant group) tended to decrease, compared to Con-pregnant group. The blood PBG-D activity in the Be-pregnant group was significantly lower compared with that of the Con-pregnant group. The ALA-D and PBG-D activities in the spleen were also significantly elevated in the Con-pregnant group, compared to nonpregnant groups. However, it was noted that these values in the Be-pregnant group were almost the same as that of the Con-nonpregnant group and were significantly lower than that in the Con-pregnant group. The elevation of ALA-D and PBG-D activities in the blood and spleen, which play a role in the hematopoietic function of mice, was observed in the Con-pregnant mice compared to the nonpregnant mice. However, the phenomenon was not observed in the Be-pregnant mice, it suggesting that Be suppressed the pregnancy-induced increase in hematopoietic function.