Association Between SLFN11 and Antitumor Activity of Trabectedin

Background/Aim: Trabectedin is a DNA-damaging agent and has been approved for the treatment of patients with advanced soft tissue sarcoma. Schlafen 11 (SLFN11) was identified as a dominant determinant of the response to DNA-damaging agents. The aim of the study was to clarify the association between SLFN11 expression and the antitumor activity of trabectedin. Materials and Methods: The antitumor activity of trabectedin was evaluated under different expression levels of SLFN11 regulated by RNA interference and CRISPR-Cas9 systems, and the combined antitumor activity of ataxia telangiectasia and Rad3-related protein kinase (ATR) inhibitor and trabectedin in sarcoma cell lines using in vitro a cell viability assay and in vivo xenograft models. Results: SLFN11-knockdown cell lines had a lower sensitivity to trabectedin, compared to parental cells. ATR inhibitor enhanced the antitumor activity of trabectedin in SLFN11-knockdown cells and in a SLFN11-knockout xenograft model. Conclusion: SLFN11 expression might be a key factor in the antitumor activity of trabectedin

Estivation grounds of the sand lance Ammodytes japonicus (Ammoditidae) in the Mihara Strait, mid-western Seto Inland Sea, Japan

瀬戸内海西部水域は過去に大規模な海砂利採取が為され，潜砂習性を持ち砂中で夏眠するイカナゴ資源の減少が明白な状況にあることから，イカナゴの生息底質の環境悪化が懸念されている。そこで，イカナゴの主要生息地の1つであった安芸灘三原瀬戸において，2014年と2015年の夏期にドレッジ調査を実施し，イカナゴの生息状況と底質性状を分析した。夏眠イカナゴは竹原沖から大三島南部の三原瀬戸西部エリア（3地点）と三原湾細島周辺の三原瀬戸東部エリア（2地点）で確認された。これら5 地点はいずれもイカナゴが好むとされる粒径0.25mm–4.0mmの砂粒子をおよそ80％の重量割合で含む砂底質であった。一方，イカナゴの出現が確認できなかった地点 の砂粒子成分の含有率は有意に低かった。三原瀬戸におけるイカナゴの夏眠生息に適した砂底質の分布は地理的に限られた状態にあり，イカナゴ資源回復を制約する要因になっている可能性が示唆された。The sand lance Ammodytes japonicus in the Seto Inland Sea is known to estivate in fine sandy grounds when water temperatures reach above 19ºC, usually from late June to early December. Catches of the sand lance have decreased drastically since the mid-1980s, coinciding with large-scale quarrying for bottom sands, which strongly suggests that sand lance populations have been seriously impacted as a result of deterioration and disturbances to sandy-bottom habitats. Mihara Strait was once a major fishing ground for sand lance and has also suffered from quarrying. To evaluate the present condition of the sandy areas of Mihara Strait as potential estivation grounds of the sand lance, we sampled sediments at 11 survey points, using a square-shaped dredge towed by the training vessel Toyoshio-maru of Hiroshima University, in 2014 and 2015. We then analyzed the physical characteristics of the sediment samples. Sand lance individuals were observed in the sediments collected from five survey points: three on the western side and two on the eastern side of the strait. Sediments at these five survey points comprised sandy elements of 0.25–4.0 mm diameter, which constituted over 80% of the weight ratio of the sediment samples. Sediments from the other survey points included pebble elements and had significantly lower weight ratios of sandy elements, suggesting the unsuitability of the substrate at those points for burrowing by the sand lance. Thus, it is suggested that sandy grounds for estivation of the sand lance are geographically limited in Mihara Strait at present, a situation that may restrict population recovery of this species in these waters.本研究は，環境省環境研究総合推進費S-13「持続可能な沿岸海域実現を目指した沿岸海域管理手法の開発（2014-2018年度；代表 柳 哲雄）」の助成を受け，サブテーマ「閉鎖性海域・瀬戸内海における栄養塩濃度管理法の開発（テーマリーダー 西嶋 渉）」のプロジェクト事業の一環として実施したものである

Systemic and Ocular Determinants of Choroidal Structures on Optical Coherence Tomography of Eyes with Diabetes and Diabetic Retinopathy

Knowledgeof the choroidal structures in eyes with diabetes and diabetic retinopathy (DR) should provide information on the pathogenesis of DR. A prospective study was performed to determine the systemic and ocular factors that affect the choroidal structures in eyes with diabetes. Two-hundred consecutive diabetic subjects consisted of 160 treatment-naïve patients with different stages of DR and 40 patients with proliferative DR with prior panretinal photocoagulation (PRP). All underwent blood and urine tests and enhanced depth imaging optical coherence tomography (EDI-OCT). The cross-sectional EDI-OCT images of the subfoveal choroid were binarized to measure the total choroidal area (TCA), luminal area, and stromal area. Multivariate regression analyses were performed to determine the systemic and ocular factors that were significantly correlated with the choroidal structures. The subfoveal choroidal thickness, TCA, luminal area, and stromal area were larger at more advanced stage of DR, and smaller in eyes with PRP than those without (P < 0.001). The TCA and stromal area were significantly and positively correlated with the degree of albuminuria (P = 0.034, P = 0.025, respectively). The choroidal lumen and stroma may increase as the stages of DR progress and decrease after PRP. Albuminuria may be associated with the choroidal stromal edema

Impact of hemodialysis on local vessel healing and thrombus formation after drug-eluting stent implantation

AbstractBackgroundAlthough hemodialysis (HD) is a suggested risk factor for stent thrombosis, its contribution to local vessel healing after drug-eluting stent (DES) implantation is unclear.MethodsA total of 121 patients (152 lesions treated with DES) who underwent 8-month follow-up coronary angiography with optical coherence tomography (OCT) were enrolled, and the findings were compared between patients with and without HD. To match baseline differences, mid-term OCT findings of 42 propensity score-matched lesions (21 non-HD vs. 21 HD) were compared. Effects of HD on the efficacy of antiplatelet therapy were also evaluated by VerifyNow assay (Accumetrics, San Diego, CA, USA).ResultsPatients with HD had a significantly higher rate of thrombus formation than those without (64% vs. 33%, p=0.007), although the baseline parameters and lesion characteristics differed between the groups. Multivariate logistic regression analysis revealed that HD was associated with an increased risk of thrombus formation (odds ratio 5.991, 95% confidence interval: 1.972–18.199, p=0.002). Even after propensity-matching for patient background and balancing of angiographic and OCT variables, the risk of thrombus formation remained significantly higher in HD patients. The P2Y12-reaction unit was significantly increased after HD (Pre HD: 211±75 vs. Post HD: 262±59, p=0.01), but patients without HD showed no increase during the same elapsed time (221±88 vs. 212±96, p=0.19).ConclusionsHD is a potential risk factor for subclinical thrombus attachment after DES therapy. Systemic problems, such as residual platelet reactivity, associated with HD as well as local vessel features in HD patients might contribute to the increased incidence of thrombus attachment and subsequent onset of thrombotic event after DES implantation

Efficacy of proton pump inhibitor in combination with rikkunshito in patients complaining of globus pharyngeus

Objective : Globus pharyngeus (GP) is a common symptom of laryngopharyngeal reflux disease (LPRD), and proton pump inhibitor (PPI) and rikkunshito, a traditional Japanese medicine having prokinetic effect improve LPRD symptoms. In the present study, we examined the efficacy of high-dose PPI in combination with rikkunshito in patients complaining of GP. Methods : 106 patients complaining of GP without any organic endoscopic findings were enrolled. Results : Patients were first administrated with high-dose PPI alone for 4 to 8 weeks and the symptom was improved in 65 patients. Among 41 patients with PPI-refractory GP, 22 patients were administrated with high-dose PPI in combination with rikkunshito, and the symptom was improved in 14 of 22 patients 4 weeks later. The average value of a modified reflux symptom index of the responders was similar to that of non-responders. Only a few patients had positive values in reflux finding scores in both groups. Conclusion : The present findings suggest the existence of a high prevalence of LPRD in patients complaining of GP. The data also suggest that gastroesophageal dysmotility is involved in GP, in addition to excessive acid reflux. The pretherapeutic laryngopharyngeal symptoms and endoscopic findings could not predict the efficacy of the treatment for GP

Association between Household Exposure to Secondhand Smoke and Dental Caries among Japanese Young Adults: A Cross-Sectional Study

The long-term effects of secondhand smoke (SHS) on dental caries among Japanese young adults remain unclear. The purpose of this cross-sectional study was to evaluate whether household exposure to SHS is associated with dental caries in permanent dentition among Japanese young adults. The study sample included 1905 first-year university students (age range: 18-19 years) who answered a questionnaire and participated in oral examinations. The degree of household exposure to SHS was categorized into four levels according to the SHS duration: no experience (-), past, current SHS = 10 years. Dental caries are expressed as the total number of decayed, missing, and filled teeth (DMFT) score. The relationships between SHS and dental caries were determined by logistic regression analysis. DMFT scores (median (25th percentile, 75th percentile)) were significantly higher in the current SHS >= 10 years (median: 1.0 (0.0, 3.0)) than in the SHS-(median: 0.0 (0.0, 2.0)); p = 0.001). DMFT >= 1 was significantly associated with SHS >= 10 years (adjusted odds ratio: 1.50, 95% confidence interval: 1.20-1.87, p = 10 years) was associated with dental caries in permanent dentition among Japanese young adults

Exercise on the Structure and Circulation of Choroid

Aims To determine the effects of dynamic exercise on the circulation and the luminal and stromal areas of the choroid in normal eyes. Methods This was a prospective interventional study of 38 eyes of 38 normal subjects enrolled by invitation. The systolic and diastolic blood pressures, heart rate, intraocularpressure, mean ocular perfusion pressure (MOPP), choroidal blood velocity, and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded before, and immediately after mild dynamic exercise. The same measurements were recorded after 10 min of rest. The choroidal blood velocity was measured bylaser speckle flowgraphy, and the mean blur rate was used for the evaluations. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross sectional choroidal area, luminal areas, stromal areas, and the ratio of luminal area to total choroidal area (L/C ratio) were determined from these images. Results The systolic and diastolic blood pressures, heart rate, MOPP, and the mean blur rate were significantly increased immediately after the exercise and significantly decreased 10 minutes after the exercise. There wereno significant changes in the mean CCT, the mean total choroidal area, the mean luminal and stromal areas, and the mean L/C ratio after the exercise. Conclusions Our results suggest that a rest period is needed before measurements of blood flow velocity but not necessary for the EDI-OCT imaging to determine the choroidal thickness and area

Influenza A (H3N2) infection followed by anti-signal recognition particle antibody-positive necrotizing myopathy: A case report

A 60-year-old Japanese woman presented with subacute progressive muscle pain and weakness in her proximal extremities. She was diagnosed with influenza A (H3N2) infection a week before the onset of muscle pain. At the time of admission, she exhibited weakness in the proximal muscles of the upper and lower limbs, elevated serum liver enzymes and creatinine kinase, and myoglobinuria. She did not manifest renal failure and cardiac abnormalities, indicating myocarditis.Electromyography revealed myogenic changes, and magnetic resonance imaging of the upper limb showed abnormal signal intensities in the muscles, suggestive of myopathy. Muscle biopsy of the biceps revealed numerous necrotic regeneration fibers and mild inflammatory cell infiltration, suggesting immune-mediated necrotizing myopathy (IMNM). Necrotized muscle cells were positive for human influenza A (H3N2). Autoantibody analysis showed the presence of antibodies against the signal recognition particle (SRP), and the patient was diagnosed with anti-SRP-associated IMNM. She was resistant to intravenous methylprednisolone pulse therapy but recovered after administration of oral systemic corticosteroids and immunoglobulins. We speculate that the influenza A (H3N2)infection might have triggered her IMNM. Thus, IMNM should be considered as a differential diagnosis in patients with proximal muscle weakness that persists after viral infections

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements