Health and productivity management initiatives to promote worker health and improve the workplace environment at the Fukushima Daiichi nuclear power plant.

BACKGROUND: Since the Fukushima Daiichi nuclear power plant (FDNPP) accident in 2011, measures have been taken to address occupational health risks, such as heat illness and infectious diseases, and ensure fitness for duty with the Tokyo Electric Power Company and its contractors. However, with the decommissioning operations set to span several decades and an aging workforce, there arose a need for proactive occupational health strategies that not only addressed these risks but also promoted employee health and created a comfortable work environment. With the Japanese government's promotion of health and productivity management (HPM) for corporations, an HPM-based initiative was launched at the FDNPP in 2019. CASE: We designed an HPM questionnaire tailored to the unique conditions at the FDNPP for contractors in 2019. Subsequently, we adjusted the questionnaire annually in light of evolving societal contexts and insights derived from contractors' feedback. This initiative also involved the annual recognition of outstanding contractors. These efforts have led to a steady increase in the number of contractors participating in the HPM survey, with respondents' scores continually improving. We also emphasized dissemination of HPM practices from contractors to their subcontractors due to the complex subcontracting structure at FDNPP, and our results showed that more contractors have been extending these efforts to their subcontractors. CONCLUSIONS: Our findings suggest that individual contractors are steadily enhancing their HPM efforts. We are committed to continually offering support to advance HPM throughout the FDNPP.

New flavan trimer from Daemonorops draco as osteoclastogenesis inhibitor.

Dragon's blood is a red resin obtained from different plants and is considered highly efficacious and used in medicine owing its wound healing function. Two new compounds (7 and 8) were isolated from the dragon's blood of Daemonorops draco fruits, along with eight known compounds (1-6, 9, and 10). Their structures, including their absolute configurations, were elucidated by nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and electronic circular dichroism (ECD) analysis. According to the spectroscopic data, 8 was determined to be a quinone methide derivative of flavan and 7 was deduced to be a flavan trimer. All compounds were evaluated for their anti-osteoclastogenesis activity, compound 1 and 7 exhibited anti-osteoclastogenesis activity with IC50 values of 31.3 and 36.8 µM, respectively.

The differences of the economic losses due to presenteeism and treatment costs between high-stress workers and non-high-stress workers using the stress check survey in Japan.

OBJECTIVES: This study sought to examine differences in the economic losses due to presenteeism and costs of medical and dental treatment between high-stress workers and non-high-stress workers using the stress check survey. METHODS: We conducted a cross-sectional study from April 1, 2018 to March 31, 2019 in a pharmaceutical company. High-stress workers were classified with the Brief Job Stress Questionnaire using two methods: the sum method and the score converted method. The incidence of presenteeism and its costs were determined using a questionnaire. The costs of medical and dental treatment were calculated according to claims. We compared the costs between high-stress and non-high-stress workers using Wilcoxon's rank-sum test. RESULTS: Of 3910 workers, 6.3% were classified as high-stress using the sum method and 6.6% were classified as high-stress using the score converted method. The costs associated with presenteeism and medical treatment among high-stress workers were higher than the costs among non-high-stress workers, whereas the costs associated with dental treatment were not. CONCLUSIONS: To motivate employers to improve stressful work environments, it is recommended that presenteeism measurement items be added to the stress check survey, and that the methods used in this study be used to calculate the loss associated with high-stress workers in Japanese companies. However, we must be careful in interpreting absolute presenteeism loss amounts because they are poorly reliable and valid.

Anticipated health effects and proposed countermeasures following the immediate introduction of telework in response to the spread of COVID-19: The findings of a rapid health impact assessment in Japan.

OBJECTIVES: The health effects of telework, which was introduced extensively in the immediate context of the COVID-19 pandemic crisis in Japan, on teleworkers, their families, and non-teleworkers, are unknown. Accordingly, we developed a rapid health impact assessment (HIA) to evaluate positive and negative health effects of telework on these groups and recommended easily implementable countermeasures. METHODS: Immediately after an emergency was declared in Japan, we implemented a rapid, five-step HIA. We screened and categorized health effects of telework for the three above-mentioned groups, extracting their content, directionality, and likelihood. Following a scoping exercise to determine the HIA's overall implementation, five experienced occupational health physicians appraised and prioritized the screened items and added new items. We outlined specific countermeasures and disseminated the results on our website. A short-term evaluation was conducted by three external occupational health physicians and three nurses. RESULTS: Following screening and appraisal, 59, 29, and 27 items were listed for teleworkers, non-teleworkers, and family members of teleworkers, respectively, covering work, lifestyle, disease and medical care, and home and community. Targeted countermeasures focused on the work environment, business management, communications, and lifestyles for teleworkers; safety and medical guidelines, work prioritization, and regular communication for non-teleworkers; and shared responsibilities within families and communication outside families for family members of teleworkers. CONCLUSION: The HIA's validity and the countermeasures' practical applicability were confirmed by the external evaluators. They can be easily applied and adapted across diverse industries to mitigate the wider negative effects of telework and enhance its positive effects.

Follow-Up of Occupational Health Issues and Measures Taken in Fukushima Daiichi Nuclear Power Plant Where Decommissioning Work Has Continued Over 6 Years Since 2014.

OBJECTIVES: To follow up arising occupational health (OH) issues, measures taken, and their performances in the Fukushima Daiichi Nuclear Power Plant since 2014, and thus share experiences and extend the contribution of OH to long-term decommissioning work and preparation for future disasters. METHODS: Necessary information from official reports and through the OH-related activities involved was collected and analyzed. RESULTS: The issues were categorized into establishment of the OH management system, three individual issues, and others. During the 6 years until end 2019, the OH management system has been strengthened and OH measures have been enriched gradually by visualizing the broader picture, even though some resistance and problems have been encountered. CONCLUSIONS: Improvement in the autonomy of contractors and their ability to respond to environmental changes is necessary.

[System and human resources for occupational health in the republic of the Philippines: Management of occupational health activities at overseas workplaces for Japanese enterprises].

OBJECTIVES: This study aimed to consider the appropriate occupational health system for Japanese enterprises in the Philippines based on information on the regulations and development of specialists. METHODS: We collected information using an information-gathering checklist. Along with literature and internet surveys, we conducted interviews by visiting local business sites, central government agencies in charge of medical and health issues, and educational institutions with specialized occupational physician training curricula. RESULTS: Occupational health administration in the Philippines is managed by the Department of Labor and Employment, which issues the Occupational Safety and Health Standards that specify the legal requirements for occupational health. A new law(Republic Act 11058),enacted in 2018 to strengthen the Occupational Safety and Health Standards, has newly established a penalty provision in case of violations. Professional personnel responsible for occupational health are grouped as safety officers and occupational health personnel, including occupational physicians and occupational nurses; training is conducted at the Occupational Safety and Health Center of the Department of Labor and Employment and educational institutions. The basic medical insurance system and the workers' compensation system are operated by the Philippine Health Insurance Corporation and Social Security Committee, respectively, both of which are government agencies. CONCLUSIONS: We confirmed that occupational health activities in the Philippines are based on government regulations, namely, the Occupational Safety and Health Standards. In addition, the enactment of a new law calls for strict compliance with corporate occupational health activities. To manage proper occupational health activities at overseas workplaces, Japanese corporations should clarify corporate-wide policies and support local employers in complying with regulations and utilizing highly specialized personnel.

[Safety and Efficacy of TAS-102 with Bevacizumab for the Treatment of Unresectable Metastatic Colorectal Cancer - A Case Report].

Chemotherapywith TAS-102 with bevacizumab(Bmab)is a new treatment for metastatic colorectal cancer. A 67-year-old male patient with synchronous multiple liver metastases was treated with TAS-102 with Bmab as a fifth-line chemotherapy. It was demonstrated that liver metastases decreased in size by1 3%bycomputed tomography(CT)after 3 months of TAS-102 with Bmab therapy. The Grade 3 or worst adverse event that was experienced was neutropenia. The patient was able to continue treatment with TAS-102 with Bmab for 6 months. TAS-102 with Bmab treatment was safetyand efficacious as a late-line chemotherapytreatment for metastatic colorectal cancer.

A nonhuman primate model of human radiation-induced venocclusive liver disease and hepatocyte injury.

BACKGROUND: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. METHODS AND MATERIALS: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. RESULTS: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. CONCLUSIONS: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

The microenvironment in hepatocyte regeneration and function in rats with advanced cirrhosis.

UNLABELLED: In advanced cirrhosis, impaired function is caused by intrinsic damage to the native liver cells and from the abnormal microenvironment in which the cells reside. The extent to which each plays a role in liver failure and regeneration is unknown. To examine this issue, hepatocytes from cirrhotic and age-matched control rats were isolated, characterized, and transplanted into the livers of noncirrhotic hosts whose livers permit extensive repopulation with donor cells. Primary hepatocytes derived from livers with advanced cirrhosis and compensated function maintained metabolic activity and the ability to secrete liver-specific proteins, whereas hepatocytes derived from cirrhotic livers with decompensated function failed to maintain metabolic or secretory activity. Telomere studies and transcriptomic analysis of hepatocytes recovered from progressively worsening cirrhotic livers suggest that hepatocytes from irreversibly failing livers show signs of replicative senescence and express genes that simultaneously drive both proliferation and apoptosis, with a later effect on metabolism, all under the control of a central cluster of regulatory genes, including nuclear factor κB and hepatocyte nuclear factor 4α. Cells from cirrhotic and control livers engrafted equally well, but those from animals with cirrhosis and failing livers showed little initial evidence of proliferative capacity or function. Both, however, recovered more than 2 months after transplantation, indicating that either mature hepatocytes or a subpopulation of adult stem cells are capable of full recovery in severe cirrhosis. CONCLUSION: Transplantation studies indicate that the state of the host microenvironment is critical to the regenerative potential of hepatocytes, and that a change in the extracellular matrix can lead to regeneration and restoration of function by cells derived from livers with end-stage organ failure.

Differentiation and transplantation of human embryonic stem cell-derived hepatocytes.

BACKGROUND & AIMS: The ability to obtain unlimited numbers of human hepatocytes would improve the development of cell-based therapies for liver diseases, facilitate the study of liver biology, and improve the early stages of drug discovery. Embryonic stem cells are pluripotent, potentially can differentiate into any cell type, and therefore could be developed as a source of human hepatocytes. METHODS: To generate human hepatocytes, human embryonic stem cells were differentiated by sequential culture in fibroblast growth factor 2 and human activin-A, hepatocyte growth factor, and dexamethasone. Functional hepatocytes were isolated by sorting for surface asialoglycoprotein-receptor expression. Characterization was performed by real-time polymerase chain reaction, immunohistochemistry, immunoblot, functional assays, and transplantation. RESULTS: Embryonic stem cell-derived hepatocytes expressed liver-specific genes, but not genes representing other lineages, secreted functional human liver-specific proteins similar to those of primary human hepatocytes, and showed human hepatocyte cytochrome P450 metabolic activity. Serum from rodents given injections of embryonic stem cell-derived hepatocytes contained significant amounts of human albumin and alpha1-antitrypsin. Colonies of cytokeratin-18 and human albumin-expressing cells were present in the livers of recipient animals. CONCLUSIONS: Human embryonic stem cells can be differentiated into cells with many characteristics of primary human hepatocytes. Hepatocyte-like cells can be enriched and recovered based on asialoglycoprotein-receptor expression and potentially could be used in drug discovery research and developed as therapeutics.