Lifestyle and work predictors of fatigue in Japanese manufacturing workers

BACKGROUND: Fatigue is one of the most common symptoms encountered in medical practice. However, little is known about the causal relationship between change in lifestyle and fatigue. AIM: To help prevent fatigue-related disorders, we investigated the association between changes in lifestyle and fatigue among employees. METHODS: We studied data sets from the High-risk and Population Strategy for Occupational Health Promotion study for employees at 10 workplaces in Japan. The baseline survey was done in 1999 and the follow-up survey in 2003 via a questionnaire which examined lifestyle and fatigue variables using the vitality domain scale of the SF-36 Health Survey. The lifestyle factors focused on were diet, smoking and alcohol habits and working conditions. Four-year changes in lifestyle that predicted the vitality domain score in the follow-up survey were examined by analysis of covariance RESULTS: Of the 6284 participants in the baseline survey, 4507 replied to the follow-up survey, of whom 3498, with a mean age of 37 (SD 18) years, returned valid responses. A low vitality score at follow-up was predicted by a change in lifestyle factors such as an increase in overtime work, change to non-sedentary work and increased frequency of eating between meals (P < 0.01, P < 0.01 and P = 0.02, respectively). CONCLUSION: Fatigue in salaried workers as measured by the vitality domain of the SF-36 is predicted by an increase in overtime work, change to non-sedentary work and an increase in the frequency of eating between meals.     

Life expectancy among Japanese of different smoking status in Japan: NIPPON DATA80

BACKGROUND: The life expectancy is an important measure for describing health status among population. Several studies from the United States and Europe showed the harm of smoking by describing the life expectancies with different smoking status. No such study is examined in Japan, the country with the world's highest life expectancy irrespective of high smoking rate among men. METHODS: The abridged life table method was applied to calculate the life expectancies of men and women among different smoking status from age 40 until age 85. Age-specific mortality rates stratified by different smoking status were obtained from follow-up data from random sample in Japanese population (NIPPON DATA80). RESULTS: Proportion of current smokers was 62.9% in men and 8.8% in women at the baseline survey in 1980. The life expectancies of 40-year-old never smokers, ex-smokers and current smokers were 42.1, 40.4, and 38.6 years in men and 45.6, 45.9, and 43.4 years in women. The life expectancy of 40-year-old men who smoked less than one pack per day was 39.0 and was longer than that of those who smoked one or two packs (38.8) and more than two packs (38.1). CONCLUSION: Life expectancy decreased gradually as the grade of smoking increased in the Japanese population.     

Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma

BackgroundHigh-grade meningiomas are aggressive tumors with high morbidity and mortality rates that frequently recur even after surgery and adjuvant radiotherapy. However, limited information is currently available on the biology of these tumors, and no alternative adjuvant treatment options exist. Although we previously demonstrated that high-grade meningioma cells were highly sensitive to gemcitabine in vitro and in vivo, the underlying molecular mechanisms remain unknown.MethodsWe examined the roles of hENT1 (human equilibrative nucleoside transporter 1) and dCK (deoxycytidine kinase) in the gemcitabine sensitivity and growth of meningioma cells in vitro. Tissue samples from meningiomas (26 WHO grade I and 21 WHO grade II/III meningiomas) were immunohistochemically analyzed for hENT1 and dCK as well as for Ki-67 as a marker of proliferative activity.ResultshENT1 and dCK, which play critical roles in the intracellular transport and activation of gemcitabine, respectively, were responsible for the high gemcitabine sensitivity of high-grade meningioma cells and were strongly expressed in high-grade meningiomas. hENT1 expression was required for the proliferation and survival of high-grade meningioma cells and dCK expression. Furthermore, high hENT1 and dCK expression levels correlated with stronger tumor cell proliferative activity and shorter survival in meningioma patients.ConclusionsThe present results suggest that hENT1 is a key molecular factor influencing the growth capacity and gemcitabine sensitivity of meningioma cells and also that hENT1, together with dCK, may be a viable prognostic marker for meningioma patients as well as a predictive marker of their responses to gemcitabine.     

Coronary artery calcification in Japanese men in Japan and Hawaii

Explanations for the low prevalence of atherosclerosis in Japan versus the United States are often confounded with genetic variation. To help remove such confounding, the authors compared coronary artery calcification (CAC), a marker of subclinical atherosclerosis, between Japanese men in Japan and Japanese men in Hawaii. Findings were based on risk factors and CAC measured from 2001 to 2005 in 311 men in Japan and 300 men in Hawaii. Men were aged 40-50 years and without cardiovascular disease. After age adjustment, there was a threefold excess in the odds of prevalent CAC scores of > or = 10 in Hawaii versus Japan (relative odds = 3.2, 95% confidence interval: 2.1, 4.9). Whereas men in Hawaii had a generally poorer risk factor profile, men in Japan were four times more likely to smoke cigarettes (49.5% vs. 12.7%, p < 0.001). In spite of marked risk factor differences between the samples, none of the risk factors explained the low amounts of CAC in Japan. After risk factor adjustment, the relative odds of CAC scores of > or = 10 in Hawaii versus Japan was 4.0 (95% confidence interval: 2.2, 7.4). Further studies are needed to identify factors that protect against atherosclerosis in Japanese men in Japan.     

Prediction of pathological complete response after neoadjuvant chemotherapy in breast cancer: comparison of diagnostic performances of dedicated breast PET,whole-body PET,and dynamic contrast-enhanced MRI

Purpose

To compare the diagnostic performance of ring-type dedicated breast PET (dbPET), whole-body PET (WBPET), and DCE-MRI for predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NAC).

Methods

This prospective study included 29 women with histologically proven breast cancer on needle biopsy between July 2016 and July 2019 (age: mean 55 years; range 35–78). Patients underwent WBPET followed by ring-type dbPET and DCE-MRI pre- and post-NAC for preoperative evaluation. pCR was defined as an invasive tumor that disappeared in the breast. Standardized uptake values corrected for lean body mass (SULpeak) were calculated for dbPET and WBPET scans. Maximum tumor length was measured in DCE-MRI images.

Reduction rates were calculated for quantitative evaluation. Two radiologists independently evaluated the qualitative findings. Reduction rates and qualitative findings were compared between the pCR (n?=?7) and non-pCR (n?=?22) groups for each modality. Differences in quantitative and qualitative data between the two groups were analyzed statistically.

Results

Significant differences were observed in the reduction rates of dbPET and DCE-MRI (P?=?0.01 and 0.03, respectively) between the two groups. Univariate and multiple logistic regression analyses revealed that SULpeak reduction rates in WBPET and dbPET (P?=?0.02 and P?=?0.01, respectively) and in dbPET (odds ratio, 16.00; 95% CI 1.57–162.10; P?=?0.01) were significant indicators associated with pCR, respectively. No between-group differences were observed in qualitative findings in the three modalities.

Conclusion

SULpeak reduction rate of dbPET?>?82% was an independent indicator associated with pCR after NAC in breast cancer.

     

Inhibition of vascular adhesion protein-1 enhances the anti-tumor effects of immune checkpoint inhibitors

Modulation of the immunosuppressive tumor microenvironment (TME) is essential for enhancing the anti-tumor effects of immune checkpoint inhibitors (ICIs). Adhesion molecules and enzymes such as vascular adhesion protein-1 (VAP-1), which are expressed in some cancers and tumor vascular endothelial cells, may be involved in the generation of an immunosuppressive TME. In this study, the role of VAP-1 in TME was investigated in 2 murine colon cancer models and human cancer cells. Intraperitoneal administration of the VAP-1-specific inhibitor U-V296 inhibited murine tumor growth by enhancing IFN-γ-producing tumor antigen-specific CD8⁺ T cells. U-V296 exhibited significant synergistic anti-tumor effects with ICIs. In the TME of mice treated with U-V296, the expression of genes associated with M2-like macrophages, Th2 cells (Il4, Retnla, and Irf4), angiogenesis (Pecam1), and fibrosis (Acta2, Loxl2) were significantly decreased, and the Th1/Th2 balance was increased. H₂O₂, an enzymatic product of VAP-1, which promoted the production of IL-4 by mouse Th2 and inhibited IFN-γ by mouse Th1 and human tumor-infiltrating lymphocytes, was decreased in tumors and CD31⁺ tumor vascular endothelial cells in the TMEs of mice treated with VAP-1 inhibitor. TCGA database analysis showed that VAP-1 expression was a negative prognostic factor in human cancers, exhibiting a significant positive correlation with IL-4, IL4R, and IL-13 expression and a negative correlation with IFN-γ expression. These results indicated that VAP-1 is involved in the immunosuppressive TMEs through H₂O₂-associated Th2/M2 conditions and may be an attractive target for the development of combination cancer immunotherapy with ICIs.     

Diagnosis, countermeasure and classification of acidosis]

Acidosis is the result of the net addition of hydrogen ion to the extracellular space or loss of bicarbonate from that space. Hydrogen ion may be added by the increased production of strong acids, an increase in CO2 concentration, or the addition of exogenous acids. The common approach to the differential diagnosis of metabolic acidosis is to divide the patients into two categories based on whether the anion gap in plasma is increased or not. Metabolic acidosis with normal anion gap (hyperchloremic) suggests that bicarbonate has been effectively replaced by chloride. In contrast, metabolic acidosis with an increased anion gap suggests addition to the body fluids of an acid other than hydrochloric acids or its equivalent.     

Development of beta-lactam resistance and increased quinolone MICs during therapy of experimental Pseudomonas aeruginosa endocarditis.

The in vivo efficacies of pefloxacin, a new fluoroquinolone, and amikacin-ceftazidime were compared in 50 rabbits with experimental aortic endocarditis caused by Pseudomonas aeruginosa. Animals were randomly chosen to receive 4 or 10 days of no therapy (controls), pefloxacin (40 mg/kg [body weight] per day, intramuscularly [i.m.]), or amikacin (30 or 80 mg/kg per day, i.m.)-ceftazidime (150 mg/kg per day, i.m.). Pefloxacin and both amikacin regimens significantly reduced vegetation bacterial densities compared with controls at days 4 and 10 of treatment (P less than 0.0005). By day 10 of therapy, between 33 and 40% of vegetations from amikacin-ceftazidime recipients contained ceftazidime-resistant bacteria (MICs, greater than 25 micrograms/ml); nitrocefin agar overlay confirmed that these ceftazidime-resistant variants were constitutive overproducers of beta-lactamase. At therapy days 4 and 10, approximately 30% of vegetations sampled from pefloxacin recipients contained bacteria for which pefloxacin MICs were four- to eightfold higher than the MIC for the parental strain used to initially induce endocarditis (MIC, 0.19 microgram/ml). These variants also exhibited increases in ciprofloxacin and ticarcillin MICs, as well as pleotropic resistance to chloramphenicol (but not to amikacin, ceftazidime, or tetracycline). Amikacin-ceftazidime, as well as pefloxacin, was effective in this model of aortic pseudomonal endocarditis. However, in vivo development of ceftazidime resistance and step-ups in pefloxacin MICs among intravegetation isolates were associated with inability to completely eradicate P. aeruginosa from aortic vegetations.     

Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure

OBJECTIVE: The aged population is at a higher risk of mortality as a result of complications of injury or infection, such as acute lung injury. The objective of this study was to analyze pulmonary inflammatory responses in young and aged mice after administration of lipopolysaccharide. DESIGN: Prospective, controlled laboratory study. SETTING: Animal resource facilities and research laboratory. SUBJECTS: Young (2-3 months old) and aged (18-20 months old) female BALB/c mice. INTERVENTIONS: Animals received intraperitoneal injection of lipopolysaccharide derived from Pseudomonas aeruginosa. Control mice received saline alone. After 24 hrs, mice were killed. Pulmonary neutrophil infiltration was assessed histologically and by myeloperoxidase activity. Pulmonary levels of the CXC chemokines, monocyte inflammatory protein-2 and KC, and cytokines, tumor necrosis factor-alpha and interleukin-1beta, were assessed by enzyme-linked immunosorbent assay. MEASUREMENTS AND MAIN RESULTS: Lungs of aged mice given lipopolysaccharide showed a six-fold higher neutrophil infiltration and three-fold higher level of myeloperoxidase activity than lungs of young mice given lipopolysaccharide. Pulmonary levels of monocyte inflammatory protein-2 and KC were significantly higher in the lungs of aged mice given lipopolysaccharide, compared with younger mice. Levels of tumor necrosis factor-alpha and interleukin-1beta in the lung were analyzed as well. After lipopolysaccharide treatment, there was no difference in the level of tumor necrosis factor-alpha in lungs of young and aged animals, but interleukin-1beta was two-fold higher in the lungs of the aged group. These data suggest that at this time point, interleukin-1beta may contribute to the higher production of CXC chemokines observed in lungs of aged mice vs. young mice receiving lipopolysaccharide. CONCLUSIONS: The hyperreactive systemic inflammatory response seen in aged individuals after lipopolysaccharide administration is accompanied by an exacerbated pulmonary inflammatory response, which may contribute to the higher mortality seen in the aged given an inflammatory insult.