C. Elegans Meets Data Sonification: Can We Hear Its Elegant Movement?

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Hypotensive Effect of Latanoprost/Timolol Versus Travoprost/Timolol Fixed Combinations in NTG Patients: A Randomized, Multicenter, Crossover Clinical Trial

Citation: Shoji T, Sato H, Mizukawa A, et al. Hypotensive effect of latanoprost/timolol versus travoprost/timolol fixed combinations in NTG patients: a randomized, multicenter, cross-over clinical trial. Invest Ophthalmol Vis Sci. 2013;54:6242-6247. DOI:10.1167/iovs.13-11942 PURPOSE. To compare the ocular hypotensive effect of travoprost plus timolol (TTFC) and latanoprost plus timolol fixed combinations (LTFC) in patients with normal-tension glaucoma (NTG). METHODS. A two-sequence 12-week, multicenter, prospective, randomized, single-blinded, crossover clinical trial examined 59 NTG patients. If both eyes were eligible, only one eye (chosen at random) was used for analytical purposes. After a 12-week run-in period with dorzolamide plus timolol fixed combination (DTFC), patients were randomized into one of the two crossover sequences of treatment for 12 weeks with TTFC or LTFC and were subsequently crossed over to the alternative treatment for a further 12 weeks. The primary endpoint was reduction in IOP after 12 weeks of each treatment sequence. The effect of treatment on IOP was assessed using a linear mixed model. RESULTS. The mean baseline IOP was 14.8 6 3.3 mm Hg (95% confidence interval [CI], 14.1-15.3 mm Hg) for treatment with DTFC. The TTFC treatment period showed consistently lower mean IOP compared with LTFC treatment period at all measurement time points. Mean reduction in IOP at 12 weeks was significantly greater in the TTFC group than in the LTFC group (À2.4 6 2.3 mm Hg vs. À1.1 6 2.3 mm Hg; P ¼ 0.021). No interaction between the drug and treatment sequence was detected. The effects of intraocular lens implantation and measurement time were also not significant. The tolerability profiles of both treatments were similar. CONCLUSIONS. The additional reduction in IOP was greater with TTFC than with LTFC, and their tolerability profiles were similar. (http://www.umin.ac.jp/ctr/ number, UMIN 000005974.) Keywords: fixed combination, normal-tension glaucoma, randomized study G laucoma is one of the main causes of blindness and irreversible deterioration of vision worldwide. 1 It affects approximately 70 million people and is the leading cause of irreversible blindness in approximately 10% of those affected. Approximately half of all patients with glaucoma live in East Asia. 5 Normal-tension glaucoma is often used to describe patients with open-angle glaucoma when their untreated IOP is maintained within a statistically normal range. Multicenter clinical trials have confirmed the importance of reducing IOP in patients with POAG and NTG, 8 When two drugs are required to control IOP, there are a number of potential advantages to using a fixed combination, including no risk of drug washout, 9 reduced exposure to preservatives, and ultimately better patient compliance and quality of life. 10 To our knowledge, few studies are available 11 that compare these fixed combinations in Asian patients, particularly those with NTG. Travoprost plus timolol (TTFC) and latanoprost plus timolol fixed combinations (LTFC) are prostaglandin/timolol fixed combinations medication currently available in Japan. Thus, the purpose of the present study was to compare the ocular hypotensive effect of LTFC and TTFC in glaucoma patients not fully controlled with monotherapy

Long-Term Effects of Polychlorinated Biphenyls and Dioxins on Pregnancy Outcomes in Women Affected by the Yusho Incident

Background: Maternal exposure to polychlorinated biphenyls (PCBs) is associated with increased proportions of spontaneous abortion and stillbirth in animal studies. In Japan in 1968, accidental human exposure to rice oil contaminated with PCBs and other dioxin-related compounds, such as polychlorinated dibenzofurans (PCDFs), led to the development of what was later referred to as Yusho oil disease. Objective: The aim of this study was to investigated the association of maternal PCB and dioxin exposure with adverse pregnancy outcomes in Yusho women. Methods: In 2004, we interviewed 214 Yusho women (512 pregnancies) about their pregnancy outcomes over the past 36 years. Pregnancy outcomes included induced abortion, spontaneous abortion, preterm delivery, and pregnancy loss. Results: In pregnancy years 1968-1977 (within the first 10 years after exposure), the proportions of induced abortion [adds ration adjusted for age at delivery (ORadj) = 5.93; 95% confidence interval (CI), 2.21-15.91; two-tailed p < 0.001) and preterm delivery (ORadj = 5.70; 95% CI, 1.17-27.79; p = 0.03) were significantly increased compared with the proportions in pregnancy years 1958-1967 (10 years before the incident). Spontaneous abortion (ORadj = 2.09; 95% CI, 0.84-5.18), and pregnancy loss (ORadj = 2.11; 95% CI, 0.92-4.87) were more frequent (OR = 2.18; 95% CI, 1.02-4.66), but these were not significant (p = 0.11 and p = 0.08, respectively) in pregnancy years 1968-1977. We found no significant increases in the proportions of these adverse pregnancy outcomes in pregnancies occurring during 1978-1987 or 1988-2003 compared with those in pregnancies before 1968. Conclusion: High levels of PCB/PCDF exposure had some adverse effects on pregnancy outcome in Yusho women

Tumor size and proliferative marker geminin levels associated with SUVmax levels on PET for breast cancers

It has been well established that maximum standardized uptake value (SUVmax) for 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers ≤2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67- high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53

Suppression of mitochondrial oxygen metabolism mediated by the transcription factor HIF-1 alleviates propofol-induced cell toxicity

A line of studies strongly suggest that the intravenous anesthetic, propofol, suppresses mitochondrial oxygen metabolism. It is also indicated that propofol induces the cell death in a reactive oxygen species (ROS)-dependent manner. Because hypoxia-inducible factor 1 (HIF-1) is a transcription factor which is involved in cellular metabolic reprogramming by modulating gene expressions of enzymes including glycolysis pathway and oxygen utilization of mitochondria, we examined the functional role of HIF-1 activity in propofol-induced cell death. The role of HIF-1 activity on oxygen and energy metabolisms and propofol-induced cell death and caspase activity was examined in renal cell-derived RCC4 cells: RCC4-EV cells which lack von Hippel-Lindau protein (VHL) protein expression and RCC4-VHL cells, which express exogenous VHL, and in neuronal SH-SY5Y cells. It was demonstrated that HIF-1 is involved in suppressing oxygen consumption and facilitating glycolysis in cells and that the resistance to propofol-induced cell death was established in a HIF-1 activation-dependent manner. It was also demonstrated that HIF-1 activation by treatment with HIFα-hydroxylase inhibitors such as n-propyl gallate and dimethyloxaloylglycine, alleviated the toxic effects of propofol. Thus, the resistance to propofol toxicity was conferred by HIF-1 activation by not only genetic deletion of VHL but also exposure to HIFα-hydroxylase inhibitors

Bioactive Sesterterpenes and Triterpenes from Marine Sponges: Occurrence and Pharmacological Significance

Marine ecosystems (>70% of the planet’s surface) comprise a continuous resource of immeasurable biological activities and immense chemical entities. This diversity has provided a unique source of chemical compounds with potential bioactivities that could lead to potential new drug candidates. Many marine-living organisms are soft bodied and/or sessile. Consequently, they have developed toxic secondary metabolites or obtained them from microorganisms to defend themselves against predators [1]. For the last 30–40 years, marine invertebrates have been an attractive research topic for scientists all over the world. A relatively small number of marine plants, animals and microbes have yielded more than 15,000 natural products including numerous compounds with potential pharmaceutical potential. Some of these have already been launched on the pharmaceutical market such as Prialt® (ziconotide; potent analgesic) and Yondelis® (trabectedin or ET-743; antitumor) while others have entered clinical trials, e.g., alpidin and kahalalide F. Amongst the vast array of marine natural products, the terpenoids are one of the more commonly reported and discovered to date. Sesterterpenoids (C25) and triterpenoids (C30) are of frequent occurrence, particularly in marine sponges, and they show prominent bioactivities. In this review, we survey sesterterpenoids and triterpenoids obtained from marine sponges and highlight their bioactivities

子育て支援に向けての保育者養成校と保育園の連携 一「きずなDAY」の事例より一

　2011年4月に設立された神女中山手保育園と保育士養成校である神戸女子短期大学幼児教育学科は，同保育園設立時より保育園の理念と養成校教育の改善に向けて連携を深めてきた。その一つに両組織が共同で行う「きずなDAY」という行事がある。この行事は，保育園設立の翌年(2012)より4年間に亘って毎年12月に行われた結果，保育現場と保育士養成の課題を連携しながら考えるための前提となるラポールの基盤が形成されてきた。本報告は，この基盤をもとに，より質の高い保育と子育て支援および保育士養成教育を展開するため，これまでの「きずなDAY」の内容やねらいを事例の資料とまとめ，この実践過程で見えてきた保育施設と保育士養成校の課題について述べたものである。なお今回の事例には，第4回目(2015年12月)については日程の関係で資料には含めていない

Activin signaling as an emerging target for therapeutic interventions

After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic stem cells, and even higher brain functions. Activins signal through a combination of type I and II transmembrane serine/threonine kinase receptors. Activin receptors are shared by multiple transforming growth factor-β (TGF-β) ligands such as myostatin, growth and differentiation factor-11 and nodal. Thus, although the activity of each ligand is distinct, they are also redundant, both physiologically and pathologically in vivo. Activin receptors activated by ligands phosphorylate the receptor-regulated Smads for TGF-β, Smad2 and 3. The Smad proteins then undergo multimerization with the co-mediator Smad4, and translocate into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. Signaling through receptors and Smads is controlled by multiple mechanisms including phosphorylation and other posttranslational modifications such as sumoylation, which affect potein localization, stability and transcriptional activity. Non-Smad signaling also plays an important role in activin signaling. Extracellularly, follistatin and related proteins bind to activins and related TGF-β ligands, and control the signaling and availability of ligands