Association Between Workplace Social Support and Use of Health-Promoting Wearable Devices: A Prospective Cohort Study of Japanese Employees.

We examined the relationship between workplace environmental factors, including support from supervisors and colleagues, and the continued use of a wearable device meant to promote occupational health. One hundred employees at a Japanese manufacturing company participated in a 3-month study, and information related to their physical health status was recorded by a wearable device. We analyzed the results using the χ2 test and logistic regression analysis. We found that men aged 40-49 years and employees reporting low support from supervisors and colleagues were significantly more likely to be continuing device users. Participants with low workplace support had adjusted odds ratios approximately two to three times higher than those with high levels of support, which was significant. Employees with low workplace support were able to communicate at work, access appropriate support, and enthusiastically participate in occupational health promotion with little psychological difficulty in using the device. Occupational health promotion using wearable devices can complement traditional face-to-face occupational health promotion.

The effects of switching EGFR-TKI treatments for non-small cell lung cancer because of adverse events.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used to treat patients with non-small cell lung cancer (NSCLC) and EGFR driver mutations. Although some patients discontinued these treatments because of adverse events, it is unclear whether switching EGFR-TKI because of adverse events provides a benefit. METHODS: This retrospective study evaluated data from 22 patients with EGFR mutation-positive NSCLC who received at least two EGFR-TKIs that were switched because of adverse events (March 2011 to September 2017). Progression-free survival 2 (PFS2) was defined as the time from starting of the first EGFR-TKI treatment to disease progression during the second EGFR-TKI treatment. RESULTS: Seventeen patients received gefitinib as the first EGFR-TKI treatment, while four patients received afatinib and one patient received erlotinib. The median time to failure of the first EGFR-TKI treatment was 1.6 months. The EGFR-TKIs were switched because of hepatotoxicity (n = 16), interstitial lung disease (n = 3), and other reasons (n = 3). The median washout period was 1.1 months. Seventeen patients received erlotinib as the second EGFR-TKI treatment, while three patients received gefitinib and two patients received afatinib. The median PFS for the second EGFR-TKI treatment was 15.2 months. The median PFS2 was 17.7 months and the median overall survival was 32.8 months. CONCLUSIONS: Switching EGFR-TKIs because of adverse events provided a clinical benefit for patients with EGFR mutation-positive NSCLC. Appropriate judgment regarding switching from one EGFR-TKI to another may improve the performance status and prognosis of patients with EGFR mutation-positive NSCLC.

Comparisons between tumor burden and other prognostic factors that influence survival of patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: The use of baseline tumor burden (TB) as a prognostic factor for non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) and associations between TB and other prognostic biomarkers remain unclear. In this study, we investigated the association between TB and survival in NSCLC patients treated with ICIs in comparison with other biomarkers. METHODS: We retrospectively evaluated 83 NSCLC patients with ICIs administered between February 2016 and December 2018. TB was measured as the sum of the unidimensional diameters of up to five target lesions. RESULTS: The median observation period was 14.2 months. A total of 42 patients died during the follow-up. Univariate Cox regression analysis showed that baseline TB was associated with OS. Cox regression analysis adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) alone or with addition of programmed cell death ligand 1 expression and treatment line showed that TB was a prognostic factor for OS. Using time-dependent receiver operating characteristic curve analysis, the optimal TB cutoff for predicting OS was 12 cm, and patients were divided into a high TB group (n = 21) and a low TB group (n = 62). The low TB group achieved significantly longer OS than the high TB group (median OS: 18.5 months, [95% CI = 11.7-not reached] vs. 2.3 months [95% CI = 1.3-2.9], P < 0.001). CONCLUSION: TB is a useful, clinically measurable prognostic factor of survival in NSCLC patients treated with ICIs.

The association between tumor burden and severe immune-related adverse events in non-small cell lung cancer patients responding to immune-checkpoint inhibitor treatment.

OBJECTIVES: The use of immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) has demonstrated survival benefits, although some treatment responders (defined as patients with non-progressive disease) are forced to discontinue treatment because of severe immune-related adverse events (irAEs). An association between treatment efficacy and irAEs has been reported. However, it is unclear which treatment responders are likely to develop severe irAEs. We aimed to examine risk factors for ICI-related severe irAEs in patients with NSCLC. MATERIALS AND METHODS: Between February 2016 and October 2018, we retrospectively evaluated 42 patients with NSCLC at our institution who responded to ICI treatment. Tumor burden was measured as the sum of the unidimensional diameters of up to five target lesions, according to the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: ICIs were discontinued in 15 of 42 treatment responders because of severe irAEs. Tumor burden was a significant independent predictor of severe irAEs (p = 0.03). The odds ratio of severe irAEs and tumor burden over 90 mm was 8.62 (95% confidence interval = 1.96-37.9, p = 0.004). CONCLUSION: A high tumor burden was a risk factor for severe irAEs in patients with NSCLC who responded to ICI treatment.

Acquired resistance to decitabine and cross-resistance to gemcitabine during the long-term treatment of human HCT116 colorectal cancer cells with decitabine.

The aim of the present study was to determine the effects of long-term exposure of decitabine (DAC) to HCT116 colorectal cancer (CRC) cells on the acquisition of resistance to DAC as well as cross-resistance to anticancer drugs used for CRC or other epigenetic modifiers. In the present study, DAC-resistant HCT116 CRC cells were established through long-term treatment with increasing concentrations of DAC (10 to 540 nM); and the cross-resistance to other drugs was subsequently examined. DAC-resistant HCT116 cells were obtained following a 104-day treatment with DAC, including DAC-free intervals. The results demonstrated that the IC50 value of DAC was increased ~100-fold in DAC-resistant HCT116 cells. Messenger (m)RNA expression of secreted frizzed-related protein 1 (SFRP1), which is regulated by DNA methylation, was not detected in DAC-resistant cells; however, SFRP1 mRNA was present in HCT116 cells treated with DAC for 52 days. DNA methyltransferase 1 (DNMT1) protein levels were slightly decreased until day 81 and then returned to control levels in DAC-resistant cells. Further experiments using DAC-resistant HCT116 cells revealed that these cells exhibited cross-resistance to gemcitabine (Gem); however, cross-resistance was not observed for other DNMT inhibitors (azacitidine and zebularine), histone deacetylase inhibitors (trichostatin A, vorinostat and valproic acid) or anticancer drugs for CRC (5-fluorouracil, irinotecan and oxaliplatin). Furthermore, the protein expression levels of cytidine deaminase (CDA) were increased, while those of deoxycytidine kinase (dCK) were decreased in DAC-resistant HCT116 cells; by contrast, the mRNA expression levels for these proteins were not significantly altered. In conclusion, the results of the present study indicated that the long-term treatment of HCT116 cells with DAC led to the acquisition of resistance to both DAC and Gem. In addition, these results may be partly attributed to changes in CDA and/or dCK, which are involved in metabolic pathways common to these two drugs.

Imido transfer of sulfonylimino-lambda3-bromane makes possible the synthesis of sulfonylimino-lambda3-iodanes.

Sulfonylimino-lambda(3)-bromane functions as a reactive nitrenoid, because of the hyperleaving group ability of aryl-lambda(3)-bromanyl groups, and undergoes transimidations to iodobenzenes at room temperature under metal-free conditions probably via an S(N)2-type nitrenoid transition state, yielding sulfonylimino-lambda(3)-iodanes.

Apoptosis-induced decrease of intrathyroidal CD4(+)CD25(+) regulatory T cells in autoimmune thyroid diseases.

BACKGROUND: We previously showed that the proportion of CD4(+) T cells was lower and both the proportion and intensity of Fas expression on intrathyroidal CD4(+) T cells were higher in the thyroid than in the peripheral blood of patients with autoimmune thyroid disease (AITD). OBJECTIVE: To clarify whether the intrathyroidal CD4(+)CD25(+) regulatory T (Treg) cells are decreased by Fas-mediated apoptosis in patients with AITD. DESIGN: We examined intrathyroidal and peripheral lymphocytes in 20 patients with AITD (15 patients with Gravesâ disease and five patients with Hashimotoâs disease) and peripheral lymphocytes in 10 healthy volunteers by three-color flow cytometry. MAIN OUTCOME: The proportion of CD4(+)CD25(+) cells was lower in the thyroid of patients with AITD than in the peripheral blood of the same patients or the peripheral blood of the healthy subjects. The proportions of CD4(+)CD25(+)CD69() cells and Forkhead box P3 (Foxp3)(+)CD4(+)CD25(+) cells, which constitute more specific Treg subsets than CD4(+)CD25(+) cells, were also lower in the thyroid than in the peripheral blood of patients with AITD. The proportion of apoptotic cells was higher among intrathyroidal CD4(+) cells than among peripheral CD4(+) cells and higher among intrathyroidal CD4(+)CD25(+) cells than among intrathyroidal CD4(+)CD25() cells. CONCLUSION: These results indicate that intrathyroidal Treg cells are decreased in response to apoptosis in patients with AITD. This decrease in Treg cells may contribute to the incomplete regulation of autoreactive T cells in AITD.

Windmill-Like Porphyrin Arrays as Potent Light-Harvesting Antenna Complexes.

Up to 14 porphyrin rings are present in the title compounds 1, which are readily available with high regioselectivity from linear nickel-zinc porphyrins. Upon irradiation with light a rapid energy transfer from the peripheral porphyrin rings to the diporphyrin core takes place.