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Polyphenols are common constituents of the diet, and research on their health benefits has developed quickly over the past few years. Our purpose is to review recent findings highlighting daily dietary polyphenol intake and the diverse function of polyphenols and their possible relationships to cardiovascular disease (CVD). Several cohort studies have reported an inverse relationship between the daily consumption of polyphenols and CVD risk. Many studies showed that beverages could be a large source of polyphenols. Our previous findings provide that Japanese people intake polyphenols mainly from beverages, especially coffee and green tea (in descending order of polyphenol content). Many kinds of polyphenols act as an antioxidant against low-density lipoprotein oxidation, which is known to promote atherosclerosis. Recent accumulating evidence suggests that dietary polyphenols could exert their cardioprotective actions through their potential to improve metabolic disorder and vascular inflammation. These findings raise the possibility that polyphenols have a wide variety of roles in the intestine, liver and vascular tissue. In addition to identifying mechanisms of polyphenol bioactivity by basic research, much more epidemiological and clinical evidence linking reduced cardiovascular risk with dietary polyphenols intake are needed.

Greenland runoff, from ice mass loss and increasing rainfall, is increasing. That runoff, as discharge, impacts the physical, chemical, and biological properties of the adjacent fjords. However, where and when the discharge occurs is not readily available in an open database. Here we provide data sets of high-resolution Greenland hydrologic outlets, basins, and streams, as well as a daily 1958 through 2019 time series of Greenland liquid water discharge for each outlet. The data include 24 507 ice marginal outlets and upstream basins and 29 635 land coast outlets and upstream basins, derived from the 100 m ArcticDEM and 150 m BedMachine. At each outlet there are daily discharge data for 22 645 d – ice sheet runoff routed subglacially to ice margin outlets and land runoff routed to coast outlets – from two regional climate models (RCMs; MAR and RACMO). Our sensitivity study of how outlet location changes for every inland cell based on subglacial routing assumptions shows that most inland cells where runoff occurs are not highly sensitive to those routing assumptions, and outflow location does not move far. We compare RCM results with 10 gauges from streams with discharge rates spanning 4 orders of magnitude. Results show that for daily discharge at the individual basin scale the 5 % to 95 % prediction interval between modeled discharge and observations generally falls within plus or minus a factor of 5 (half an order of magnitude, or +500 %/-80 %). Results from this study are available at https://doi.org/10.22008/promice/freshwater (Mankoff, 2020a) and code is available at http://github.com/mankoff/freshwater (last access: 6 November 2020) (Mankoff, 2020b).

Natural disasters are often associated with forced residential relocation, thereby affected people experience a change of food environment that results in the increased body mass index. However, there are a few studies that examined whether a change in food environment caused risk of obesity after a natural disaster. To address this question, we leveraged a natural experiment of residential relocation in the aftermath of the 2011 Japan Earthquake and Tsunami. Our baseline data came from a nationwide cohort study of older community-dwelling adults conducted 7 months prior to the disaster. By chance, one of the field sites (Iwanuma City, Miyagi Prefecture) was directly in the line of the tsunami. Approximately 2.5 years after the disaster, we ascertained the residential addresses and health status of 3,594 survivors aged 65 years or older (82.1% follow-up rate). Fixed effects multinomial logistic regression showed that shortened distances to food outlets/bars increased the risks of transitioning from BMI in the normal range (18.5–22.9) to obesity (≥25.0) (Odds ratios: 1.46 for supermarkets; 1.43 for bars; 1.44 times for fast food outlets). Radically changed food access after a natural disaster may raise the risk of obesity among older survivors.

Ibrutinib, a covalent inhibitor of Bruton Tyrosine Kinase (BTK), is approved for treatment of patients with relapsed/refractory or treatment-naïve chronic lymphocytic leukemia (CLL). Besides directly inhibiting BTK, ibrutinib possesses immunomodulatory properties through targeting multiple signaling pathways. Understanding how this ancillary property of ibrutinib modifies the CLL microenvironment is crucial for further exploration of immune responses in this disease and devising future combination therapies. Here, we investigated the mechanisms underlying the immunomodulatory properties of ibrutinib. In peripheral blood samples collected prospectively from CLL patients treated with ibrutinib monotherapy, we observed selective and durable downregulation of PD-L1 on CLL cells by 3 months post-treatment. Further analysis showed that this effect was mediated through inhibition of the constitutively active signal transducer and activator of transcription 3 (STAT3) in CLL cells. Similar downregulation of PD-1 was observed in CD4+ and CD8+ T cells. We also demonstrated reduced interleukin (IL)-10 production by CLL cells in patients receiving ibrutinib, which was also linked to suppression of STAT3 phosphorylation. Taken together, these findings provide a mechanistic basis for immunomodulation by ibrutinib through inhibition of the STAT3 pathway, critical in inducing and sustaining tumor immune tolerance. The data also merit testing of combination treatments combining ibrutinib with agents capable of augmenting its immunomodulatory effects.

Research suggests that cardiometabolic disease risks are elevated among survivors of natural disasters, possibly mediated by changes in diet. Using the Brief Dietary History Questionnaire, we examined (1) dietary patterns among older survivors of the 2011 Great East Japan Earthquake and Tsunami, and (2) the contribution of posttraumatic stress symptoms (PTSS)/depressive symptoms, as well as relocation to temporary housing on dietary patterns and (3) gender differences in the associations. Data came from a prospective cohort study of 1,375 survivors aged 65–89 years (44.6% male). PTSS/depression onset was evaluated in 2013, 2.5 years after the disaster. Dietary data was collected with a self-administered brief-type diet history questionnaire in 2020. A principal component analysis identified three posterior dietary patterns. Diet 1 consisted of high intake of vegetables, soy products, and fruits; Diet 2 consisted of carbohydrate-rich foods and snacks/sweets; Diet 3 consisted of high intake of alcoholic beverages, meat, and seafood. Least-squares linear regression revealed that individuals with PTSS/depression were less likely to exhibit Diet 1, while individuals with PTSS were more likely to exhibit Diet 2&3. Especially, males who had depression showed an unhealthy dietary pattern. Those who have lived in a trailer-style temporary housing reported less consumption of Diet 3. Survivors of disaster with symptoms of mental illness tended to exhibit less healthy dietary patterns after 9 years. Diet varied by type of post-disaster mental illness, gender, and current social circumstances. We lacked pre-disaster BDHQ data, which is a limitation.

Using one of the world most powerful laser facility, we demonstrate for the first time that high-contrast multi-picosecond pulses are advantageous for proton acceleration. By extending the pulse duration from 1.5 to 6 ps with fixed laser intensity of 10 18  W cm −2 , the maximum proton energy is improved more than twice (from 13 to 33 MeV). At the same time, laser-energy conversion efficiency into the MeV protons is enhanced with an order of magnitude, achieving 5% for protons above 6 MeV with the 6 ps pulse duration. The proton energies observed are discussed using a plasma expansion model newly developed that takes the electron temperature evolution beyond the ponderomotive energy in the over picoseconds interaction into account. The present results are quite encouraging for realizing ion-driven fast ignition and novel ion beamlines.

A large number of particle detectors employ liquid argon as their target material owing to its high scintillation yield and its ability to drift ionization charge over large distances. Scintillation light from argon is peaked at 128 nm and a wavelength shifter is required for its efficient detection. In this work, we directly compare the light yield achieved in two identical liquid argon chambers, one of which is equipped with polyethylene naphthalate (PEN) and the other with tetraphenyl butadiene (TPB) wavelength shifter. Both chambers are lined with enhanced specular reflectors and instrumented with SiPMs with a coverage fraction of approximately 1%, which represents a geometry comparable to the future large scale detectors. We measured the light yield of the PEN chamber to be 39.4±0.4(stat)±1.9(syst)% of the yield of the TPB chamber. Using a Monte Carlo simulation this result is used to extract the wavelength shifting efficiency of PEN relative to TPB equal to 47.2±5.7%. This result paves the way for the use of easily available PEN foils as a wavelength shifter, which can substantially simplify the construction of future liquid argon detectors.

Background The role of adjuvant hepatic intra-arterial infusion chemotherapy (HAI) is considered to be a promising option. Methods We examined treatment effects of adjuvant HAI using cisplatin in 37 hepatocellular carcinoma (HCC) patients with portal vein infiltration (PVI) who underwent hepatectomy in comparison with those in 85 patients who did not. Results PVI in 89 patients. Increased levels of aspartate transaminase, tumor markers, size and microvessel tumor infiltration (MVI) or cirrhosis, poorly differentiation, non-adjuvant HAI was associated with lower overall survival ( p  = 0.09). Poor differentiation, MVI and HAI were independently risk factors associated with tumor-free and overall survivals by the multivariate analysis ( p  < 0.05). Adjuvant HAI tended to show longer survivals in comparison with no-HAI ( p  = 0.08) and the multivariate analysis revealed significant efficacy of HAI for better prognosis. Conclusion Adjuvant HAI showed effectiveness on prolonging tumor-free and patient survival in HCC with PVI and is a promising option in the daily clinical practice.

We examined correlating clinical biomarkers for the physical aspect of frailty among community-dwelling older adults in Japan, using Japanese Gerontological Evaluation Study (JAGES). We used information from the JAGES participants (N = 3,128) who also participated in the community health screening in 2010. We grouped participants’ response to the Study of Osteoporotic Fracture (SOF) Frailty Index into robust (=0), intermediate frail (=1), and frail (=2+) ones to indicate physical aspect of frailty. Independent of sex and age, results from multinomial logistic regression showed above normal albumin and below normal HDL and haemoglobin levels were positively associated with intermediate frail (RRR = 1.99, 95% CI = 1.22–3.23; RRR = 1.36, 95% CI = 1.33–1.39; RRR = 1.36, 95% CI = 1.23–1.51, resp.) and frail cases (RRR = 2.27, 95% CI = 1.91–2.70; RRR = 1.59, 95% CI = 1.51–1.68; RRR = 1.40, 95% CI = 1.28–1.52, resp.). Limited to women, above normal Hb1Ac level was similarly associated with intermediate frail and frail cases (RRR = 1.18, 95% CI = 1.02, 1.38; RRR = 2.56, 95% CI = 2.23–2.95, resp.). Use of relevant clinical biomarkers can help in assessment of older adults’ physical aspect of frailty.

Background:A prospective observational study was conducted to test the hypothesis that relative deprivation was associated with incident physical or cognitive disability, independent of absolute income.Methods:Study subjects consist of 9463 non-disabled people aged 65+ years in the Aichi Gerontological Evaluation Study (AGES), Aichi prefecture, Japan. Baseline mail-in survey in 2003 gathered information on income, educational attainment, lifestyle factors (smoking, alcohol consumption and health check-up) and healthcare utilisation. Three-year incidence of disability was assessed through public long-term care insurance databases and resident registry.Results:A total of 7673 subjects (81%) with complete information were analysed. Our measure of relative deprivation was the Yitzhaki index across eight reference groups, which calculates the deprivation suffered by each individual as a function of the aggregate income shortfall for each person relative to everyone else with higher incomes in that person’s reference group. Cox regression demonstrated that, after controlling for sociodemographic factors (including absolute income), the hazard ratio (and 95% confidence intervals) of incident physical/cognitive disability per one standard deviation increase in relative deprivation ranged from 1.13 (0.99 to 1.29) to 1.15 (1.01 to 1.31) in men and from 1.11 (0.94 to 1.31) to 1.18 (1.00 to 1.39) in women, depending on the definition of the reference group. Additional adjustment for lifestyle factors attenuated the hazard ratios to statistical non-significance.Conclusion:Relative deprivation may be a mechanism underlying the link between income inequality and disability in older age, at least among men. Lifestyle factors in part explain the association between relative deprivation and incident disability.