We aimed to examine whether the number of types of hazardous operations at work experienced through a lifetime is associated with cancer incidence, and additionally examined the combined effects with ...lifestyle‐related factors. Using a nationwide, multicenter, hospital inpatient dataset (2005‐2015), we conducted a matched case‐control study with 1 149 296 study subjects. We classified the participants into those with none, 1, or 2 or more types of hazardous operation experience, based on information of special medical examinations taken, mandatory in Japan for workers engaged in hazardous operations. Using those with no experience as the reference group, we estimated the odds ratios for cancer incidence (all sites, lung, stomach, colon and rectum, liver, pancreas, bile duct, and bladder) by conditional logistic regression with multiple imputations. We also examined the effects of the combination with hazardous operations and lifestyle‐related factors. We observed increased risks for cancer of all sites, and lung, pancreas, and bladder cancer associated with the experience of hazardous operations. Multivariable‐adjusted ORs (95% CIs) of cancer incidence of all sites were 1 (reference), 1.16 (1.12, 1.21), and 1.17 (1.08, 1.27) for none, 1, and 2 or more types of hazardous operation experience, respectively (P for trend <.001). Potential combined associations of hazardous operations with smoking were observed for lung, pancreas, and bladder cancer, and with diabetes for pancreas cancer. Engaging in hazardous operations at work and in combination with lifestyle‐related factors may increase the risk of cancer. We highlight the potential for those engaged in hazardous work to avoid preventable cancers.
Compared with those with no experience of occupational hazardous operation, the incidence of total, lung, pancreas, and bladder cancer was clearly increased as the number of types of hazardous operation work experience increased. Potential combined associations of hazardous operations with smoking were also observed for lung, pancreas, and bladder cancer, and with diabetes for pancreas cancer.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cancer cells utilise the glycolytic pathway to support their rapid growth and proliferation. Since cells in most solid tumours are subjected to severe microenvironmental stresses including low ...nutrient and oxygen availability, such cancer cells must develop mechanisms to overcome these unfavourable growth conditions by metabolic adaptation. Although the liver kinase B1 (LKB1)-adenosine monophosphate-activated kinase (AMPK) signalling pathway plays a pivotal role in maintaining energy homeostasis under conditions of metabolic stress, the role of LKB1-AMPK signalling in aiding cancer cell survival and in malignant tumours has not yet been fully elucidated. We show that glucose starvation promotes cancer cell invasiveness and migration through LKB1-AMPK-regulated MMP-9 expression. Most intriguingly, triggering the LKB1-AMPK signalling pathway by glucose starvation-induced oxidative stress facilitates selective autophagy, which in turn enhances Keap1 degradation and the subsequent activation of Nrf2. Following this, Nrf2 regulates the transactivation of MMP-9 via Nrf2 binding sites in the promoter region of the MMP-9 gene. These mechanisms also contribute to the suppression of excessive oxidative stress under glucose starvation, and protect against cell death. Our data clearly shows that LKB1-AMPK signalling not only maintains energy and oxidative stress homeostasis, but could also promote cancer progression during metabolic stress conditions by MMP-9 induction.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To evaluate seasonal fluctuations in intraocular pressure (IOP) in primary open-angle glaucoma (POAG) and its associated factors.
POAG patients treated only with glaucoma eye drops were enroled. ...Winter and summer IOPs were evaluated. The Seasonal fluctuation rate of IOP was defined as follows: (mean winter IOP-mean summer IOP)/mean IOP in all seasons. Multiple linear regression analysis was used to explore factors associated with the seasonal IOP fluctuation rate including: age, gender, family history of glaucoma, type of glaucoma, number of eye drops, type of eye drops, mean deviation (MD) value, MD slope, disc haemorrhage, central corneal thickness and spherical equivalent.
Winter IOP was higher than summer IOP in 204 POAG eyes of 204 patients, including 162 eyes with normal tension glaucoma (NTG) (13.2 ± 2.7 vs. 12.0 ± 2.3 mmHg, P < 0.001). The mean age and follow-up duration were 63.3 ± 11.4 years and 140.0 ± 66.9 months. Initial MD and MD slope were -2.1 ± 3.4 dB and -0.07 ± 0.50 dB/year, respectively. POAG was positively associated with the rate of seasonal IOP fluctuations compared to NTG (β = 5.29, P = 0.013). Family history, and timolol and carteolol use were also factors associated with the IOP fluctuation rate (β = -6.27, P = 0.007; β = 4.94, P = 0.030; and β = 4.51, P = 0.042, respectively).
We confirmed seasonal IOP fluctuations in POAG. Type of glaucoma, family history of glaucoma, and β-blocker use might influence IOP fluctuations.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Epithelial cells require attachment to a support, such as the extracellular matrix, for survival. During cancer progression and metastasis, cancerous epithelial cells must overcome their dependence ...on adhesion signals. Dependence on glucose metabolism is a hallmark of cancer cells, but the nutrient requirements of cancer cells under anchorage-deficient conditions remain uncharacterized. Here, we report that cancer cells prioritize glutamine-derived tricarboxylic acid cycle energy metabolism over glycolysis to sustain anchorage-independent survival. Moreover, glutamine-dependent metabolic reprogramming is required not only to maintain ATP levels but also to suppress excessive oxidative stress through interaction with cystine. Mechanistically, AMPK, a central regulator of cellular responses to metabolic stress, participates in the induction of the expression of ASCT2, a glutamine transporter, and enhances glutamine consumption. Most interestingly, AMPK activation induces Nrf2 and its target proteins, allowing cancer cells to maintain energy homeostasis and redox status through glutaminolysis. Treatment with an integrin inhibitor was used to mimic the alterations in cell morphology and metabolic reprogramming caused by detachment. Under these conditions, cells were vulnerable to glutamine starvation or glutamine metabolism inhibitors. The observed preference for glutamine over glucose was more pronounced in aggressive cancer cell lines, and treatment with the glutaminase inhibitor, CB839, and cystine transporter inhibitor, sulfasalazine, caused strong cytotoxicity. Our data clearly show that anchorage-independent survival of cancer cells is supported mainly by glutaminolysis via the AMPK-Nrf2 signal axis. The discovery of new vulnerabilities along this route could help slow or prevent cancer progression.
Display omitted
•AMPK-Nrf2 signaling is crucial in metabolic reprogramming during cancer progression.•Cancer metabolism does not preeminently depend on glycolysis.•Glutaminolysis mainly supports anchorage-independent cancer cell survival.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We aimed to investigate the risks of cardiovascular diseases associated with specific occupations, using a nation-wide, multicentre, hospital-based registry data from the Inpatient ...Clinico-Occupational Survey. The analysis included 539,110 controls (non-circulatory disease) and 23,792 cases (cerebral infarction, intracerebral/subarachnoid hemorrhage, acute myocardial infarction) aged ≥ 20 years who were initially hospitalized during 2005-2015. The participants' occupational and clinical histories were collected by interviewers and medical doctors. Occupations were coded into 81 categories according to the Japanese standard occupation classification. Multivariable logistic regression analysis adjusted for age, admission year and hospital, smoking, alcohol consumption, hypertension, and shift-work was conducted by sex using general clerical workers as the reference. Increased risks of cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, and acute myocardial infarction, were observed in 15, 20, 25, and 1 occupation(s) in men, and 9, 2, 2, and 10 occupations in women. Motor vehicle drivers, food and drink preparatory workers, fishery workers, cargo workers, civil engineer workers, and other manual workers in men and other manual workers in women faced increased risks of all three stroke subtypes. Our findings demonstrate associations between specific occupations and the risk of cardiovascular disease incidence and suggest that the risk may vary by occupation.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The utility of chest x-ray examination (CXR) in mandatory annual health examinations for occupational health is debatable in Japan. This study aimed to provide basic data to consider future policies ...for mandatory annual health examinations in the workplace. A nationwide descriptive survey was performed to determine the rate of detection of tuberculosis, lung cancer, and other diseases through CXR in organizations associated with National Federation of Industrial Health Association. The rate of finding on CXR conducted during annual health examinations in FY2016 was evaluated. Data regarding diagnosis based on follow-up examination findings were obtained and compared with the national statistics. In addition, CXR findings were compared with the results of low-dose lung computed tomography performed at the Hitachi Health Care Center. From 121 surveyed institutions, 88 institutions with 8,669,403 workers were included. For all ages, 1.0% of examinees required follow-up examination. Among 4,764,985 workers with diagnosis data, the tuberculosis detection rate was 1.8-5.3 per 100,000 persons. For Lung cancer, 3,688,396 workers were surveyed, and 334 positive cases were detected. The lung cancer detection rate using CXR was 9.1-24.4 per 100,000 persons. From 164 cases with information regarding the clinical stage, 72 (43.9%) had Stage I lung cancer. From 40,045 workers who underwent low-dose computed tomography multiple times, 31 lung cancer cases, all with Stage I disease, were detected (detection rate: 77.4 per 100,000 persons). Our findings suggest that CXR plays a little role in the detection of active tuberculosis. With regard to LC screening, the detection rate of LC by CXR was lower, approximately 50%, than the expected rate (41.0 per 100,000 persons) of LC morbidity based on the age-sex distribution of this study population. However, the role of CXR for LC screening cannot be mentioned based on this result, because assessment of mortality reduction is essential to evaluate the role.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Inpatient Clinico-Occupational Survey collected data from 3.76 million patients, showing that the average length of stay declined by 16.1 d in FY2008 and by 14.1 d in FY2015. In this study, we ...assessed the length of hospital stay and readmission, stratified by ICD-10 and employment status. A cross-sectional study was conducted on data from FY2008, including those from 65,806 first hospitalizations and 16,653 readmissions in FY2008, where 62,260 first admissions and 29,242 readmissions in FY 2015. The length of hospital stay was longest in those admitted due to external influences (24.8 d), followed by musculoskeletal disorders (22.5 d). This remained unchanged in FY2015, however, lengths of stay of those were reduced by 20.1 and 20.0 d, respectively. The length of hospital stay for most diseases was longer upon readmission than on first admission, and longer for those who were unemployed. It is necessary to give attention to patients who need to be discharged early due to work, or plan for frequent hospitalization in order to reduce the length of each hospital stay because of the expected increase in the number of elderly workers brought on by a declining birth rate and an aging population.
Abstract
This cross-sectional study aimed to investigate the promoting and inhibitory factors of diabetic retinopathy (DR) according to diabetes mellitus (DM) stage using standardized evaluation of ...fundus images by artificial intelligence (AI). A total of 30,167 participants underwent blood and fundus examinations at a health screening facility in Japan (2015–2016). Fundus photographs were screened by the AI software, RetCAD and DR scores (DRSs) were quantified. The presence of DR was determined by setting two cut-off values prioritizing sensitivity or specificity. DM was defined as four stages (no DM: DM0; advanced DM: DM3) based on treatment history and hemoglobin A1c (HbA1c) levels. Associated factors of DR were identified using logistic regression analysis. For cutoff values, multivariate analysis revealed age, sex, systolic blood pressure (SBP), smoking, urinary protein, and HbA1c level as positively associated with the risk of DR among all DM stages. In addition to glycemic control, SBP and Fibrosis-4 index might act as promoting factors for DR at all or an earlier DM stage. T-Bil, cholinesterase, and T-cho level might be protective factors at an advanced DM stage.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To fully understand the mechanisms governing learning and memory, animal models with minor interindividual variability and higher cognitive function are required. THA rats established by crossing ...those with high learning capacity exhibit excellent learning and memory abilities, but the factors underlying their phenotype are completely unknown. In the current study, we compare the hippocampi of parental strain Wistar rats to those of THA rats via metabolomic analysis in order to identify molecules specific to the THA rat hippocampus. Higher branched-chain amino acid (BCAA) levels and enhanced activation of BCAA metabolism-associated enzymes were observed in THA rats, suggesting that acetyl-CoA and acetylcholine are synthesized through BCAA catabolism. THA rats maintained high blood BCAA levels via uptake of BCAAs in the small intestine and suppression of BCAA catabolism in the liver. Feeding THA rats with a BCAA-reduced diet decreased acetylcholine levels and learning ability, thus, maintaining high BCAA levels while their proper metabolism in the hippocampus is the mechanisms underlying the high learning ability in THA rats. Identifying appropriate BCAA nutritional supplements and activation methods may thus hold potential for the prevention and amelioration of higher brain dysfunction, including learning disabilities and dementia.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In Japan, there is no publicly funded screening for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections (using HBs antigen and HCV antibody, respectively) among workers, and workplace ...health programmes play a crucial role in reducing viral hepatitis-related deaths. The national number of hepatitis screening tests conducted in the workplace is unknown. To provide baseline data for policy formulation, we conducted a nationwide survey to estimate these parameters using data from approximately 10.5 million workers (6.8 million men and 3.8 million women) who underwent mandatory health examinations in their workplaces between April 2016 and March 2017. Among these workers, 494,303 (5.23%, 95% confidence interval CI 5.22%-5.24%) and 313, 193 (3.82%, 95% CI 3.81%-3.84%) were screened for HBV and HCV, respectively. Among those who were screened, 0.28% (95% CI 0.27-0.30%) and 0.35% (95% CI 0.33-0.37%) tested positive for HBs antigen and HCV antibody, respectively. According to the age-specific prevalence from the survey an estimated 0.30 and 0.14 million workers in Japan require treatment for HBV and HCV, respectively. To reduce viral hepatitis-related deaths by efficiently identifying workers who need treatment and promoting access to treatment, one-time hepatitis screening of all workers should be considered.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
