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Sarcopenia is a syndrome characterised by progressive and systemic loss of skeletal muscle mass and strength. In order to prevent sarcopenia and lead a healthy life, it is necessary to maintain muscle mass and prevent loss of muscle mass. Insect faeces have long been consumed as tea in China, both as a medicine and as a functional food. In the present work, we investigated the efficacy of cherry caterpillar faeces tea (PT) for treating sarcopenia, particularly concerning muscle building and atrophy suppression using C2C12 cells. PT treatment (0.2 mg/mL) increased myotube widths by approximately 40%, and increased the expression levels of Myod, Myog, and MYHC. Additionally, PGC1α, TFAM, SDHA, BCAT, and BCKDH were upregulated in a PT concentration-dependent manner. For PGC1α, which is the transcription coactivator, the protein expression level also increased in a concentration-dependent manner. The findings demonstrated that PT could stimulate PGC1α and activate mitochondria via branched-chain amino acid metabolism and the electron transport chain in C2C12 myoblasts. Furthermore, PT suppressed LPS-induce expression of IL6 and TNFα, and reduced the protein expression levels of the ubiquitin ligases Atrogin-1 and MuRF, which are major cause of muscle atrophy. These results indicated that PT could be effective for muscle building and suppression of atrophy.

Objective:Typhoon Hagibis struck Japan on October 12, 2019. This study documents and characterizes deaths caused by Hagibis and helps identify strategies to reduce mortality in future disasters.Methods:Japanese residents, who were killed by Typhoon Hagibis, as reported by Japan’s Fire and Disaster Management Agency, were considered for the study. Details were collected from mainstream Japanese media, and flooding data from hazard maps published by local municipalities.Results:Out of the 99 total fatalities, 65 (73.0%) were aged 65 years or above. Among those who drowned indoors (20), 18 (90.0%) lived in high-risk areas of flooding, and their bodies were found on the first floor of their residences. A total of 10 (55.6%) out of the 18 fatalities lived in homes with 2 or more floors, indicating that they could have moved upstairs to avoid the floodwater. However, 6 (33.3%) could not do so due to existing health issues.Conclusions:Relatively elderly people, particularly those in areas at high risk of flooding, were most affected. Seeking higher ground is a standard safety measure in times of flooding, but this may not be possible for everyone depending on their health status, structure of their residence, and the depth of floodwaters.

Izumi Yoshida,1,2 Hikari Taniguchi,1 Masashi Sakamoto,1 Takatoshi Maeno1 1Sakura Medical Center, Toho University, Chiba, Japan; 2Toho-Kamagaya Hospital, Kamagaya-shi, Chiba, 273-0132, JapanCorrespondence: Izumi YoshidaSakura Medical Center, Toho University, Sakura-shi, Chiba, 285-8741, JapanTel +81-43-462-8811Fax +81-43-462-8835Email izumi.yoshida@med.toho-u.ac.jpPurpose: To investigate the association between the inclusion of components identified on images in target spots of photodynamic therapy (PDT) and exudate relapse in eyes with age-related macular degeneration (AMD).Methods: Forty-one eyes (39 patients) with polypoidal choroidal vasculopathy (PCV) and 32 eyes (31 patients) with typical AMD (tAMD) who underwent PDT were retrospectively investigated. Each component identified on fluorescein (FA) or indocyanine angiography (IA), optical coherence tomography (OCT), or color photography was graded as not depicted, covered with a margin ≥ 500 μm or < 500 μm, and protruding. Associations between these grades and the dry rate (proportion of subjects with continuous absence of exudate over following 12-month period) and the relapse index (2 × number of injections administered + accumulation of exudate for 12 months post-PDT) were investigated.Results: In PCV, the association between worse coverage and decreasing dry rates for feeder vessels and polyps approached statistical significance. With coverage margins ≥ 500 μm, dry rate tended to be greater than with coverage margins < 500 μm for feeder vessels, classic lesions, and occult lesions on FA. In the tAMD group, coverage with margins ≥ 500 μm tended to yield a higher dry rate than coverage with margins < 500 μm for CNV on IA. Coverage with margins ≥ 500 μm for occult and classic lesions on FA yielded no dry subjects, and all subjects with classic lesions or staining had recurrence (P = 0.009 and 0.050). Worse coverage and worse dry rate in PCV and worse relapse index in tAMD were related to pigment epithelial detachment on OCT (P = 0.040 and 0.006).Conclusion: Polyps in PCV and pigment epithelial detachment (PED) in tAMD were verified as appropriate targets, corresponding to the existing guidelines, and feeder vessels, classic lesion, occult lesion, and PED in PCV and CNV on IA in tAMD were suggested as further targets. OCT was superior to FA for evaluating PED.Keywords: photodynamic therapy, age-related macular degeneration, spot size, angiography

We investigated the association between the duration of intraretinal fluid (IRF) or subretinal fluid (SRF) and the response to antivascular endothelial growth factor injection in patients with undertreated age-related macular degeneration (ARMD). The Ethics Committee of Toho University Sakura Medical Center approved this study (no. S18030). Eighty eyes of ARMD patients with VA ≤20/100 were retrospectively assessed. Each injection’s efficacy was classified, and the fluid accumulation prior to each injection was evaluated. The effect changes following to accumulated IRF, SRF, the longest persistent IRF period (≥10 months), and their determining factors were evaluated. Throughout observation, acquired refractoriness was rarely associated with increased accumulation of IRF or SRF. The injection span had a tendency to be short, and the polypoidal choroidal vasculopathy and occult choroidal neovasculopathy (CNV) proportions had a tendency to be higher among patients with diminished effects than among those with maintained effects. VA differed significantly with continuous IRF duration, but not with accumulated fluid. The diminishing effect of injections during long-standing IRF was rarely associated with undertreatment. The mechanism underlying acquired refractoriness remains unknown; the effect change demonstrated various patterns, including diminished and improved responses. The longest continuous IRF duration was associated with VA decline. Shortening the duration of continuous IRF may be necessary.

Bone loss and bone-related disease are associated with the deregulation of osteoclast function, and therefore agents that affect osteoclastogenesis have attracted attention. The purpose of the present study was to discover modified kavalactone analogs as potential anti-osteoclastogenic agents. We assessed the effect of 26 analogs on osteoclast differentiation in vitro. The most potent compound, (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one (22), suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of RAW264 cells with IC50 values of 4.3 µM. A partial structure-activity relationship study revealed the importance of fluorine and its position within the 5,6-dehydrokawain skeleton. The results of a pit formation assay suggested that compound 22 prevents osteoclastic bone resorption by inhibiting osteoclastogenesis. Moreover, compound 22 downregulated mRNA expression levels of RANKL-induced nuclear factor of activated T cells c1 (NFATc1) and osteoclastogenesis-related genes. These results suggest that (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one scaffold could lead to the identification of new anti-resorptive agents.

Objective: This study aimed to evaluate a risk of flooding and landslides among home-care patients, to reveal an extent to which patients require support for evacuation, and to determine whether risk was accurately perceived among the patients. Methods: This is a cross-sectional study targeting the patients who were actively treated at the home-care clinic in Fukui Prefecture, Japan. We collected data on the patients’ sociodemographic and clinical characteristics. Additionally, we collected data on their risk of flooding and landslides through hazard maps and distributed a questionnaire to these patients regarding their risk awareness of flooding and landslides. Results: Of the 199 eligible home-care patients, 84.9% (169 of 199) were at risk of flooding and/or landslides, and 58.6% (99 of 169) of them needs support during evacuation. Furthermore, of those who were at risk of flooding and/or landslides, 46.0% (45 of 99) had accurate risk assessments. Factors that resulted in inadequate risk awareness of flooding and landslides included: not placing importance on evacuation, not using medical equipment, and living on the first floor. Conclusions: There was limited risk awareness of flooding and/or landslides among the home-care patients. The information of the risk factors regarding inadequate risk awareness of flooding and landslides should be used to sophisticate flooding and landslides evacuation strategy.

Emergency evacuation during disasters may have significant health impacts on vulnerable populations. The Japanese Government issued evacuation orders for surrounding residents of the Fukushima Daiichi nuclear power plant (FDNPP) immediately after the March 11, 2011, nuclear accident. Little is known of difficulties associated with the disaster-specific evacuation from health care facilities located in this area. Among the 338 patients hospitalized at Futaba Hospital, located 4.6 km west of FDNPP, at the time of the accident, 39 patients (11.5%), predominantly critically ill patients who were bedridden or disabled, died before the evacuation was completed. The shortage of hospital staff and disruption of infrastructure resulted in a lack of adequate care provision, such as infusion therapy or sputum suctioning, leading to premature death of some hospitalized patients during the emergency hospital evacuation. As hospital evacuation is sometimes unavoidable during disasters, potential health impacts of hospital evacuation should be recognized and reflected in disaster preparedness plans.

Introduction Left atrial (LA) roof ablation using the cryoballoon technique, combined with pulmonary vein isolation (PVI), has been reported to be beneficial for ablation therapy in patients with persistent atrial fibrillation (AF). Left posterior wall ablation also results in improved patient outcomes. However, the contribution of these techniques to the success of cryoballoon ablation (CBA) treatment of AF is not known. The present study examined the influence of the roofline block and isolation area on outcomes after CBA. Methods and results We enrolled 78 patients with persistent AF. LA roof ablation was performed using a 28-mm cryoballoon with a single freezing of 3 minutes at each region (median number of freezes: 4) after PVI. After CBA, bipolar voltage amplitude mapping was performed during sinus rhythm using the NavX mapping system. Patients were divided into two subgroups according to the voltage and activation map: the roof-conduction (n = 46) and roofline-block groups (n = 32). Atrial tachyarrhythmia recurred in 20 patients of the conduction group and 4 patients of the roofline-block group. The rate of 12-month freedom from tachyarrhythmia after a single ablation procedure was 78% (95% confidence interval [CI], 60%-89%) in the roofline-block group and 45% (95% CI, 30%-60%) in the conduction group (P = .048). Cox proportional hazard analysis revealed that the isolated area was not a significant predictor of recurrence (hazard ratio, 0.94; 95% CI, 0.86-1.02; P = .15). Conclusion Creating a complete roofline block is the major factor predicting the maintenance of sinus rhythm in patients with persistent AF.

Obesity is a risk factor for many diseases, including type 2 diabetes and cardiovascular disease, and is related to the rising morbidity and mortality. Discovery of agents targeting adipogenesis, especially from natural sources, is important for the treatment of obesity. Here, we aimed to identify anti-adipogenic substances in methanol extracts of Physalis peruviana and to investigate their effect, along with underlying mechanisms. Activity-guided fractionation of the extract revealed 4β-hydroxywithanolide E (HWE) and withanolide E (WE) as the adipogenesis inhibitors. Both compounds suppressed mRNA expression of central adipogenic transcription factors, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer-binding protein α in the early stage of adipocyte differentiation. The inhibitory action of these two withanolides on adipogenesis was largely limited to this stage. The proliferation of preadipocytes was markedly suppressed by treatment with HWE and WE for 24 and 48 h in the differentiation medium, and cell-cycle arrest in the G0/G1 phase was observed. Therefore, our results suggested that withanolides from P. peruviana to be novel anti-adipogenic compounds that modulate mitotic clonal expansion.

As a Japanese folk medicine, Tithonia diversifolia is used for cardiovascular disease prevention and health maintenance. We isolated T. diversifolia-derived orizabin based on the nitric oxide production inhibitory effect. This study aimed to consider orizabin as a novel functional compound with anti-atherosclerotic activity. Orizabin significantly inhibited the adhesion of THP-1 cells to human umbilical vein endothelial cells (HUVECs) and suppressed the mRNA expression of adhesion molecules in HUVECs. In Phorbol 12-myristate 13-acetate stimulated THP-1 cells, orizabin suppressed macrophage differentiation, CD36 expression (1% at 10 μM), and NFκB transcriptional activity. Furthermore, orizabin suppressed oxidized low-density lipoprotein (oxLDL) uptake in macrophages and the Akt phosphorylation. On the contrary, we revealed that phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN) mRNA and protein expression were promoted significantly by orizabin (mRNA, 270-fold at 10 μM). Our study presented the possibility that T. diversifolia-derived orizabin is novel anti-atherosclerotic compound via the suppression of Akt phosphorylation, and T. diversifolia may be effective as a new crop for vascular health maintenance. PRACTICAL APPLICATIONS: In this study, the differentiation of monocytes was suppressed without any toxicity, it was obvious in the image, and the oxLDL uptake in monocytes was clearly suppressed by orizabin. Our findings presented that T. diversifolia-derived compound orizabin specifically contributes to the promotion of PTEN expression and suppression of Akt signal in cells, and acts to suppress inflammation by suppression of NFκB transcriptional activity. As a component derived from food, it has a strong function and can be used to maintain the health for blood vessels. It is also a finding that deserves to expand production currently being carried out on a small scale. Furthermore, the promoting effect of PTEN known as a cancer suppressor in orizabin may result in further use for pharmaceuticals research. Orizabin can be safely used as a food-derived compound for maintaining human health.

Circadian rhythms are endogenous oscillations of approximately 24-h periods and regulate diel changes in physiological biochemical processes. We examined the effects of black ginger (Kaempferia parviflora) on the expression of circadian clock genes and the disruption of circadian rhythms using in vitro and in vivo assays. K. parviflora extract increased the amplitude of circadian rhythms, extended the circadian period, and caused phase delays in NIH3T3 cells. We identified chemical components involved in the circadian clock gene expression using high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance. 3,5,7,3′,4′-Pentamethoxyflavone, 5,7,4′-trimethoxyflavone, and 5,7-dimethoxyflavone were identified as components that regulated the circadian clock gene expression. In addition, we examined the effects of K. parviflora on behavioral entrainment in mice subjected to experimental jet lag (6-h phase advance), finding that K. parviflora enhanced adaptation to jet lag. These results suggested that polymethoxyflavones in K. parviflora could regulate the circadian clock and reduce circadian disruption.

The inhibitory activities of the antimycin-class antibiotics UK-2A, antimycin A, and splenocin B against the production of anti-inflammatory cytokine IL-4, which is related to IgE-mediated allergic responses in rat basophilic leukemia (RBL-2H3) cells, were evaluated. Although antimycin A and splenocin B showed cytotoxicity at concentrations at which IL-4 release from the cells was restricted, UK-2A was found to restrict IL-4 release without cytotoxicity. Three UK-2A analogues (4–6) were then synthesized and assessed. Compound 5 restricted IL-4 release dose-dependently without cytotoxicity, and its effect was more potent than that of UK-2A.

Masashi Sakamoto, Ryuya Hashimoto, Izumi Yoshida, Makoto Ubuka, Takatoshi Maeno Department of Ophthalmology, Toho University Sakura Medical Center, Shimoshizu, Sakura, Japan Purpose: To investigate the potential risk factors for neovascular glaucoma (NVG) after vitrectomy in eyes with proliferative diabetic retinopathy.Subjects and methods: In this retrospective, observational, comparative study, patients with proliferative diabetic retinopathy who underwent vitrectomy at Toho University Sakura Medical Center between December 2011 and November 2016 and who were followed for ≥12 months after surgery were included. Subject parameters examined included age, glycated hemoglobin (HbA1c), fasting blood glucose, administration of insulin, and estimated glomerular filtration rate. Ocular parameters examined included preoperative best-corrected visual acuity, preoperative IOP, operative history (specifically panretinal photocoagulation), lens status, ocular pathology (eg, iris/angle neovascularization, tractional retinal detachment, diabetic macular edema, vitreous hemorrhage, combined tractional retinal detachment), intraoperative retinal tamponade use, vitrectomy gauge, combined lens extraction/vitrectomy procedure, subsequent surgical procedures, and pre- and postoperative intravitreal bevacizumab. Correlations between variables and postoperative NVG development were examined using logistic regression analyses (backward elimination method).Results: A total of 254 eyes of 196 consecutive subjects (146 men [74.5%], 54.0±10.8 years old) were included. Sixty of 254 eyes (23.6%) developed NVG. Several preoperative factors increased the risk of developing NVG, including iris/angle neovascularization (P=0.042), preoperative high IOP (P=0.005), low HbA1c (P=0.004), and administration of insulin (P=0.045). Intraoperative retinal tamponade also increased NVG risk (P=0.021, backward elimination method).Conclusion: Preoperative parameters such as elevated IOP, iris/angle neovascularization, fasting blood sugar and HbA1c discrepancies, administration of insulin, as well as use of retinal tamponade during retinal surgery were identified as the risk factors for developing NVG. Keywords: neovascular glaucoma, proliferative diabetic retinopathy, vitrectomy&nbsp

Izumi Yoshida,1 Tomoaki Shiba,2 Yuichi Hori,1 Takatoshi Maeno2 1Department of Ophthalmology, Toho University Sakura Medical Center, Chiba, Sakura, Japan; 2Department of Ophthalmology, Toho University Omori Medical Center, Tokyo, Japan Purpose: Detecting primary breaks and confirming detachment preoperatively are important. Lincoff stated that retinal detachments progress according to gravity; his law has become popular. We evaluated Lincoff’s law with a slight modification to determine whether it remains suitable for present cases independent of refractive error and previous cataract surgery.Patients and methods: Group 1 included superior region detachments not exceeding the 12 o’clock midline; the original break was within 1 1/2 clock hours of the highest detachment border. Group 2 included shallow inferior detachment; the original break corresponded to the more spread side of the 6 o’clock midline. Group 3 detachments were beyond 12 o’clock; the original break was within a triangle with a 12 o’clock apex (A) or within 1 1/2 hours of 12 o’clock (B); (A) and (B) were stated in the original report. Another five classifications were applied for small numbers of detachments. Consecutive initial rhegmatogenous retinal detachment surgery patients were included; medical records and detachment charts were examined. Eyes were classified into categories and rates were calculated. Eyes that had never undergone previous cataract surgery besides those in which the macula remained attached were divided into groups at a –6D cutoff (Groups 1, 2, and 3[B]); we compared groups in each category. We compared phakic eyes, pseudophakic eyes, and eyes ruptured at the posterior capsule (Groups1, 2, and 3[B]).Results: Finally, 747 eyes were categorized. In Groups 1, 2, 3(A), and 3(B), corresponding rates were 92, 86, 70, and 89%, respectively. Between the above and below -6D groups, there was no significant difference in rate in any category. There were no significant differences between phakic, pseudophakic, and ruptured eyes.Conclusion: Lincoff’s law was suitable for the present cases and independent of refractive error and previous cataract surgery. Keywords: rhegmatogenous retinal detachment, retinal break locations, shapes of detachments, refractive error, previous cataract surgery&nbsp

Masashi Sakamoto, Izumi Yoshida, Ryuya Hashimoto, Hidetaka Masahara, Takatoshi Maeno Department of Ophthalmology, Toho University Sakura Medical Center, Sakura, Japan Purpose: To identify risk factors for retinal breaks during macular hole (MH) surgery.Patients and methods: This retrospective, observational, comparative study included the medical records of 364 consecutive patients (382 eyes) who underwent vitrectomy for MH at Toho University Sakura Medical Center between January 2012 and May 2017. The patients comprised 135 men and 229 women with mean age 67.6±8.0 years. Six eyes with a pre-existing retinal tear treated by laser photocoagulation before MH surgery were excluded. Data on sex, age, presence or absence of lattice degeneration, axial length (measured using an IOL Master®), preoperative refraction, whether or not combined lens extraction/vitrectomy had been performed, whether or not the lens was pseudophakic before vitrectomy, and whether or not a posterior vitreous detachment had been created intraoperatively were collected. The lattice degeneration status was classified as none (0), treated using laser photocoagulation (1), or untreated (2).Results: The only item identified in logistic regression analysis with the backward elimination method to be a significant risk factor for retinal breaks during MH surgery was the presence of lattice degeneration (P

INTRODUCTION Pulmonary vein isolation (PVI) with wide antral ablation leads to better outcomes in atrial fibrillation ablation therapy, but the ablation area is relatively small during cryoballoon ablation (CBA). The present study tested the hypothesis that wide ablation can lead to better outcomes in CBA. METHODS AND RESULTS Ninety-six patients with atrial fibrillation were enrolled (paroxysmal 76%, 64.1 ± 11.7 years). All patients underwent preprocedural computed tomography and the PV diameter at left atrial PV junction was measured. PV isolation was performed using a 28-mm CB for 3 minutes with single freezing. Sinus rhythm bipolar voltage amplitude maps with the NavX mapping system were generated after ablation. According to the voltage map, patients were divided into 3 subgroups (68 in the extensive isolation group, 17 in the individual isolation group, and 10 in the incomplete isolation group). Atrial tachyarrhythmias recurred in 9 patients of the extensive isolation group and 6 in the individual isolation group. The rate of 12-month freedom from tachyarrhythmia after a single ablation procedure was 84% (95% confidence interval [C.I.], 72%-91%) in the extensive group and 57% (95% C.I., 28%-78%) in the individual group (P = 0.048). Multiple logistic regression analyses revealed that maximal PV diameter was the only predictor to achieve extensive PVI (odds ratio, 1.57; 95% C.I. 1.08-2.29 P = 0.018). CONCLUSION Extensive isolation is superior to individual isolation for achieving freedom from atrial arrhythmia in long term follow-up by CBA. Evaluating PV diameter at the left atrial PV junction is essential for applying CBA.

Masashi Sakamoto, Ryuya Hashimoto, Izumi Yoshida, Takatoshi Maeno Department of Ophthalmology, Sakura Medical Center of Toho University, Shimoshizu, Sakura, Japan Purpose: We retrospectively reviewed patients with postoperative neovascular glaucoma (NVG) after vitrectomy for proliferative diabetic retinopathy to investigate how variables assessed before, during, and after vitrectomy are associated with the requirement for filtration surgery. Patients and methods: The subjects in this retrospective, observational, comparative study were 55 consecutive patients (61 eyes) who underwent vitrectomy for proliferative diabetic retinopathy at Toho University Sakura Medical Center between December 2011 and November 2016, were followed up for at least 6 months after surgery, and developed NVG within 2 years after surgery. They comprised 44 men and 11 women of mean age 52.4±9.1 years, who were followed up for a mean 7.1±6.1 months. We collected data on the following 16 variables: sex, age, history of panretinal photocoagulation completed within 3 months before vitrectomy, presence/absence of a lens, obvious iris/angle neovascularization, tractional retinal detachment, diabetic macular edema, vitreous hemorrhage, visual acuity and intraocular pressure before vitrectomy and at the onset of NVG, glycated hemoglobin, fasting blood glucose, estimated glomerular filtration rate, and use of intraoperative gas tamponade. Results: Logistic regression analysis with the backward elimination method identified preoperative fasting hyperglycemia (P=0.08), high intraocular pressure at the onset of NVG (P=0.04), and use of gas tamponade during vitrectomy (P=0.008) to be significant risk factors for requirement of filtration surgery. Conclusion: Preoperative fasting hyperglycemia, high intraocular pressure at the onset of NVG, and use of gas tamponade during vitrectomy predispose patients to require filtration surgery in the event of postoperative NVG. Keywords: neovascular glaucoma, proliferative diabetic retinopathy, vitrectomy, gas tamponade

Some β-glucans have attracted attention due to their functionality as an immunostimulant and have been used in processed foods. However, accurately measuring the β-glucan content of processed foods using existing methods is difficult. We demonstrate a new method, the Sodium hypochlorite Extracting and Enzymatic Digesting (SEED) assay, in which β-glucan is extracted using sodium hypochlorite, dimethyl sulfoxide, and 5 mol/L sodium hydroxide and then digested into β-glucan fragments using Westase which is an enzyme having β-1,6- and β-1,3 glucanase activity. The β-glucan fragments are further digested into glucose using exo-1,3-β-d-glucanase and β-glucosidase. We measured β-glucan comprising β-1,3-, -1,6-, and -1,(3),4- bonds in various polysaccharide reagents and processed foods using our novel method. The SEED assay was able to quantify β-glucan with good reproducibility, and the recovery rate was90% for food containing β-glucan. Therefore, the SEED assay is capable of accurately measuring the β-glucan content of processed foods.

Anti-inflammatory activity of aculeatin and toddaculin, which are coumarins with a similar structure isolated from Toddalia asiatica (L.) LAM., was evaluated using lipopolysaccharide (LPS)-stimulated RAW264 mouse macrophage cells. Both aculeatin and toddaculin significantly inhibited mRNA expression of inflammatory mediators and nitric oxide production. Furthermore, Toddaculin suppressed LPS-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 and inhibited LPS-induced activation of nuclear factor-kappaB (NF-κB). However, aculeatin did not exhibit such effects, suggesting that aculeatin and toddaculin suppress LPS-induced inflammation of RAW264 cells via different mechanisms. The cellular uptake of these compounds was also evaluated. Toddaculin was detected in RAW264 cells after 4 and 24 h. However, aculeatin levels were not observed in RAW264 cells at all incubation intervals. These results indicate that de-epoxidation of a prenyl group can increase hydrophobicity of molecule and is thought to accelerate cellular uptake and/or interactions with the phospholipid bilayers of cell membranes.

After the Fukushima Daiichi nuclear power plant accident, the air dose gradually decreases every year due to the physical decay of radioactive materials and environmental changes, as well as countermeasures. However, there is little information on personal behavioural patterns and individual dose from external exposure among the inhabitants around the nuclear power plant. To evaluate the dose from external exposure in Minamisoma city, and compare the differences with outside Fukushima Prefecture, we started the external dose assessment project in cooperation with city officials in Minamisoma and three other cities in Japan where the natural terrestrial background radiation level is relatively high. In these four cities, external dose was measured every hour for two weeks using an individual electronic dosimeter D-shuttle. The places of activity of participants were recorded every hour to compare and evaluate the dose from external exposure, and to clarify whether there is a difference in the exposure dose by behaviour. The annual effective doses from external exposure for 100 participants from four municipalities ranged from 0.566 to 1.295 with a mean value of 0.784 mSv, which was below the level where it is necessary to initiate further remedial actions. Mean external dose in Minamisoma city (0.820 mSv/year) was comparable to those in municipalities with a relatively high natural radiation background in Japan (0.793, 0.806, and 0.718 mSv/year in Fukuyama, Nanto, and Tajimi, respectively). The time spent at home and in the workplace accounted for most of the time of the participants, and this also contributed to the majority of the total dose from external exposure. The amount of exposure at times other than while at home or in the workplace was very small regardless of the indoor or outdoor location in the city. For future dose reduction and radiation protection, continuous dosimetry and countermeasures at home and in the workplace are important for individuals who present high values.

Under the coronavirus disease 2019 (COVID-19) pandemic, the deaths of healthcare professionals have been increasingly reported worldwide. We performed a cross-sectional, observational study using news reports on the websites among selected countries as of April 2020. We found 120 dead medical doctors due to COVID-19 in Western Europe and Asia-Pacific countries; 67 in Italy (47 in the Northern part), 34 in China (22 in Hubei), 6 in France, 4 in the UK, the USA and Spain and 1 in South Korea, respectively. Among them, 90% were men, and specialties were reported as general practitioners for 30% and as physicians for 11.6%. The overall proportions of dead medical doctors amounted to 1.9 per 10 000 confirmed cases and 30.2 per 10 000 dead cases, respectively. Proactive measures are warranted to protect doctors especially who often encounters with COVID-19 patients.

Backgrounds: To investigate the association between intraretinal fluid (IRF) or subretinal fluid (SRF) persistence and response to anti-vascular endothelial growth factor injection in age-related macular degeneration (ARMD). Methods: Eighty-nine eyes of ARMD patients with VA ≤ 20/100 or persistent subretinal hyper-reflective material were retrospectively assessed. Each injection’s efficacy was classified, and fluid accumulation prior to each injection was evaluated. Effect changes within the longest persistent IRF period (≥ 10 months) and their association with previous treatment and accumulated IRF and SRF were determined. Results: Injection span was shorter and the polypoidal choroidal vasculopathy and occult choroidal neovasculopathy (CNV) proportions were higher among patients with diminished than among those with maintained effects. Throughout observation, acquired refractoriness appeared rarely associated with increased IRF or SRF. VA differed significantly with IRF duration, but not accumulated fluid. Conclusions: Diminishing effect of injections during long- standing IRF was associated with highly active CNV rather than with undertreatment. The mechanism underlying acquired refractoriness remains unknown; the effect change demonstrated various patterns, including diminished and improved responses. Persistent IRF duration was associated with VA decline. To shorten the duration of persistent IRF, it may be necessary to ensure strict control in refractory patients with high CNV activity.

Introduction. The aim of this study was to investigate the postoperative prediction error measured by optical biometry and acoustic biometry in eyes after phacovitrectomy for rhegmatogenous retinal detachment (RRD) with no macular involvement. Methods. Forty-nine eyes of 49 patients (32 male, 17 female; mean age 62.6 ± 7.5 years) with RRD without macular involvement who underwent phacovitrectomy (RRD group) and 49 eyes of 33 patients (21 male, 12 female; mean age 74.1 ± 7.1 years) without macular disease who underwent cataract surgery (control group) were included in this retrospective comparative study. The difference between the preoperative predictive value and the postoperative refractive value was measured both by optical and acoustic biometry and compared in each group. Results. The postoperative refractive error calculated by acoustic biometry was −0.81 ± 0.75D and that calculated by optic biometry was −0.44 ± 0.77D in the RRD group. The postoperative refractive error calculated by acoustic biometry was −0.21 ± 0.64D and that calculated by optic biometry was 0.27 ± 0.71D in the control group. Significant myopic shifts were observed in the RRD group using both acoustic biometry and optic biometry but not in the control group. Conclusion. Phacovitrectomy for RRD with no macular involvement resulted in a significant myopic shift when compared with cataract surgery alone in patients without macular disease when calculated by both acoustic biometry and optic biometry.

Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent.

Intradialytic exercise-induced blood volume (BV) reduction may cause intradialytic hypotension in hemodialysis (HD) patients. However, BV recovery time after intradialytic exercise remains unknown. Hemodialysis patients were recruited, and their relative BV change (%ΔBV) were measured with intradialytic exercise (n = 12). After confirming the linearity of %ΔBV for 30 min, patients exercised using a stationary cycle in the supine position. The target exercise intensity was a 10% increase in heart rate (HR), corresponding to relatively low-intensity exercise. Baseline %ΔBV (assumed baseline) were calculated for the 30 min before exercise using linear regression analysis. The mean intradialytic exercise start and end times after HD initiation were 93.0 ± 8.4 and 116.4 ± 8.3 min, respectively, a mean exercise duration of 23.5 ± 2.6 min. Percentage change in blood volume declined rapidly upon exercise initiation and gradually increased above the assumed baseline throughout HD. At the end of HD, %ΔBV in the exercise group was significantly higher than the assumed baseline (measured - assumed baseline %ΔBV: 2.17 ± 0.62%; p = 0.02). Intradialytic exercise with low intensity in the supine position attenuated ultrafiltration-induced BV reduction at the end of HD. Therefore, intradialytic exercise may prevent intradialytic hypotension during later HD, although its intensity was relatively low level.

The following conventional calcium correction formula (Payne) is broadly applied for serum calcium estimation: corrected total calcium (TCa) (mg/dL) = TCa (mg/dL) + (4 - albumin (g/dL)); however, it is inapplicable to chronic kidney disease (CKD) patients. A total of 2503 venous samples were collected from 942 all-stage CKD patients, and levels of TCa (mg/dL), ionized calcium ([iCa(2+) ] mmol/L), phosphate (mg/dL), albumin (g/dL), and pH, and other clinical parameters were measured. We assumed corrected TCa (the gold standard) to be equal to eight times the iCa(2+) value (measured corrected TCa). Then, we performed stepwise multiple linear regression analysis by using the clinical parameters and derived a simple formula for corrected TCa approximation. The following formula was devised from multiple linear regression analysis: Approximated corrected TCa (mg/dL) = TCa + 0.25 × (4 - albumin) + 4 × (7.4 - p H) + 0.1 × (6 - phosphate) + 0.3. Receiver operating characteristic curves analysis illustrated that area under the curve of approximated corrected TCa for detection of measured corrected TCa ≥ 8.4 mg/dL and ≤ 10.4 mg/dL were 0.994 and 0.919, respectively. The intraclass correlation coefficient demonstrated superior agreement using this new formula compared to other formulas (new formula: 0.826, Payne: 0.537, Jain: 0.312, Portale: 0.582, Ferrari: 0.362). In CKD patients, TCa correction should include not only albumin but also pH and phosphate. The approximated corrected TCa from this formula demonstrates superior agreement with the measured corrected TCa in comparison to other formulas.

Purpose: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). Methods: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. Results: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with Δserum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for ΔCAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for Δmean IMT. Conclusion: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.