Effects of weather variability and air pollutants on emergency admissions for cardiovascular and cerebrovascular diseases.

This is an Author's Original Manuscript of an Article submitted for consideration in the International journal of environmental health research copyright (c) 2012 Taylor & Francis; International journal of environmental health research is available online at http://www.tandfonline.com/10.1080/09603123.2011.650155信州大学博士（医学）・学位論文・平成23年3月31日授与（甲第901号）・掘綾We examined the effect of ambient temperature, air pressure and air pollutants on daily emergency admissions by identifying the cause of admission for each type of stroke and cardiovascular disease using generalized linear Poisson regressionmodels allowing for overdispersion, and controlling for seasonal and inter-annual variations, days of the week and public holidays, levels of influenza and respiratory syncytial viruses. Every 1 degrees C decrease in mean temperature was associated with an increase in the daily number of emergency admissions by 7.83% (95% CI 2.06-13.25) for acute coronary syndrome (ACS) and heart failure, by 35.57% (95% CI 15.59-59.02) for intracerebral haemorrhage (ICH) and by 11.71% (95% CI 4.1-19.89) for cerebral infarction. An increase of emergency admissions due to ICH (3.25% (95% CI 0.94-5.51)), heart failure (3.56% (95% CI 1.09-5.96)) was observed at every 1 hPa decrease in air pressure from the previous days. We found stronger detrimental effect of cold on stroke than cardiovascular disease.Articlejournal articl

Reduction of lipid accumulation rescues Bietti’s crystalline dystrophy phenotypes

眼の難病クリスタリン網膜症の発症メカニズムを解明 --治療薬の有力候補発見により創薬研究の進展に期待--. 京都大学プレスリリース. 2018-03-27.Bietti’s crystalline dystrophy (BCD) is an intractable and progressive chorioretinal degenerative disease caused by mutations in the CYP4V2 gene, resulting in blindness in most patients. Although we and others have shown that retinal pigment epithelium (RPE) cells are primarily impaired in patients with BCD, the underlying mechanisms of RPE cell damage are still unclear because we lack access to appropriate disease models and to lesion-affected cells from patients with BCD. Here, we generated human RPE cells from induced pluripotent stem cells (iPSCs) derived from patients with BCD carrying a CYP4V2 mutation and successfully established an in vitro model of BCD, i.e., BCD patient-specific iPSC-RPE cells. In this model, RPE cells showed degenerative changes of vacuolated cytoplasm similar to those in postmortem specimens from patients with BCD. BCD iPSC-RPE cells exhibited lysosomal dysfunction and impairment of autophagy flux, followed by cell death. Lipidomic analyses revealed the accumulation of glucosylceramide and free cholesterol in BCD-affected cells. Notably, we found that reducing free cholesterol by cyclodextrins or δ-tocopherol in RPE cells rescued BCD phenotypes, whereas glucosylceramide reduction did not affect the BCD phenotype. Our data provide evidence that reducing intracellular free cholesterol may have therapeutic efficacy in patients with BCD

The effect of isoflavone-daidzein oral medication on cutaneous wound healing in female ovariectomized mice

This study investigated the influence of oral administration of isoflavone-daidzein on the cutaneous wound healing process in female ovariectomized mice. Eight-week-old female mice were divided into groups of ovariectomized mice and mice administered daidzein after an ovariectomy. Two full-thickness wounds on the dorsum were made in mice in both groups. There was no significant difference between wound areas of the two groups from wounding to healing during 15 days. The area in the group administered daidzein tended to be smaller than that in the ovariectomized group during the inflammatory phase 4 and 5 days after wounding . The rate of re-epithelialization in the group administered daidzein tended to be higher than that in the ovariectomized group in the inflammatory phase on day 3 (40.7 ± 17.6% and 21.0 ± 16.8%, respectively). Therefore, the administration of daidzein under lack of estrogen is expected to reduce the inflammation period and promote re-epithelialization. この研究は、卵巣摘出した雌マウスに皮膚創傷を作製し、経口投与したイソフラボン の一種であるダイゼインが、創傷治癒にどのような影響を与えるかを観察したもので ある。8 週令の雌マウスを卵巣摘出群と卵巣摘出し創作製した後にダイゼインを与え た2 群に分けた。両群共、卵巣摘出後、ダイゼインを含まない精製飼料で２週間飼育 後に、左右の背部に直径4mm の皮膚全層欠損層を作製した。創作製後、ダイゼインを 含まない飼料とダイゼインを含む飼料で2 週間飼育した。ダイゼインは、飼料1g に 0.01mg 含むように作製した。両群の創面積は、2 週間の間の毎日において、有意差は 見られなかった。しかし、炎症期である創作製後4 と5 日では、ダイゼイン食で飼育 した群が無ダイゼイン食で飼育した群が、やや創面積が小さい傾向がみられた（それ ぞれ、p 値が0.061、0.083 であった）。創作製後の3 日での、再上皮化の割合は、ダイゼイン群で40.7 ± 17.6%、無ダイゼイン群で21.0 ± 16.8%となり、ダイゼイ ン群はより上皮化が進んでいる傾向が見られた (p = 0.07)。これらの結果は、エス トロゲン欠乏状態で、ダイゼインの経口投与が、創傷治癒において、炎症を抑制し上 皮化を促進することを示唆している

Effects of weather variability and air pollutants on emergency admissions for cardiovascular and cerebrovascular diseases

This is an Author's Original Manuscript of an Article submitted for consideration in the International journal of environmental health research copyright (c) 2012 Taylor & Francis; International journal of environmental health research is available online at http://www.tandfonline.com/10.1080/09603123.2011.650155信州大学博士（医学）・学位論文・平成23年3月31日授与（甲第901号）・掘綾We examined the effect of ambient temperature, air pressure and air pollutants on daily emergency admissions by identifying the cause of admission for each type of stroke and cardiovascular disease using generalized linear Poisson regressionmodels allowing for overdispersion, and controlling for seasonal and inter-annual variations, days of the week and public holidays, levels of influenza and respiratory syncytial viruses. Every 1 degrees C decrease in mean temperature was associated with an increase in the daily number of emergency admissions by 7.83% (95% CI 2.06-13.25) for acute coronary syndrome (ACS) and heart failure, by 35.57% (95% CI 15.59-59.02) for intracerebral haemorrhage (ICH) and by 11.71% (95% CI 4.1-19.89) for cerebral infarction. An increase of emergency admissions due to ICH (3.25% (95% CI 0.94-5.51)), heart failure (3.56% (95% CI 1.09-5.96)) was observed at every 1 hPa decrease in air pressure from the previous days. We found stronger detrimental effect of cold on stroke than cardiovascular disease.Articlejournal articl

Galactic Core-Collapse Supernovae at IceCube: “Fire Drill” Data Challenges and follow-up

The next Galactic core-collapse supernova (CCSN) presents a once-in-a-lifetime opportunity to make astrophysical measurements using neutrinos, gravitational waves, and electromagnetic radiation. CCSNe local to the Milky Way are extremely rare, so it is paramount that detectors are prepared to observe the signal when it arrives. The IceCube Neutrino Observatory, a gigaton water Cherenkov detector below the South Pole, is sensitive to the burst of neutrinos released by a Galactic CCSN at a level >10σ. This burst of neutrinos precedes optical emission by hours to days, enabling neutrinos to serve as an early warning for follow-up observation. IceCube\u27s detection capabilities make it a cornerstone of the global network of neutrino detectors monitoring for Galactic CCSNe, the SuperNova Early Warning System (SNEWS 2.0). In this contribution, we describe IceCube\u27s sensitivity to Galactic CCSNe and strategies for operational readiness, including "fire drill" data challenges. We also discuss coordination with SNEWS 2.0

All-Energy Search for Solar Atmospheric Neutrinos with IceCube

The interaction of cosmic rays with the solar atmosphere generates a secondary flux of mesons that decay into photons and neutrinos – the so-called solar atmospheric flux. Although the gamma-ray component of this flux has been observed in Fermi-LAT and HAWC Observatory data, the neutrino component remains undetected. The energy distribution of those neutrinos follows a soft spectrum that extends from the GeV to the multi-TeV range, making large Cherenkov neutrino telescopes a suitable for probing this flux. In this contribution, we will discuss current progress of a search for the solar neutrino flux by the IceCube Neutrino Observatory using all available data since 2011. Compared to the previous analysis which considered only high-energy muon neutrino tracks, we will additionally consider events produced by all flavors of neutrinos down to GeV-scale energies. These new events should improve our analysis sensitivity since the flux falls quickly with energy. Determining the magnitude of the neutrino flux is essential, since it is an irreducible background to indirect solar dark matter searches

TXS 0506+056 with Updated IceCube Data

Past results from the IceCube Collaboration have suggested that the blazar TXS 0506+056 is a potential source of astrophysical neutrinos. However, in the years since there have been numerous updates to event processing and reconstruction, as well as improvements to the statistical methods used to search for astrophysical neutrino sources. These improvements in combination with additional years of data have resulted in the identification of NGC 1068 as a second neutrino source candidate. This talk will re-examine time-dependent neutrino emission from TXS 0506+056 using the most recent northern-sky data sample that was used in the analysis of NGC 1068. The results of using this updated data sample to obtain a significance and flux fit for the 2014 TXS 0506+056 "untriggered" neutrino flare are reported

Recent neutrino oscillation results with the IceCube experiment

The IceCube South Pole Neutrino Observatory is a Cherenkov detector instrumented in a cubic kilometer of ice at the South Pole. IceCube’s primary scientific goal is the detection of TeV neutrino emissions from astrophysical sources. At the lower center of the IceCube array, there is a subdetector called DeepCore, which has a denser configuration that makes it possible to lower the energy threshold of IceCube and observe GeV-scale neutrinos, opening the window to atmospheric neutrino oscillations studies. Advances in physics sensitivity have recently been achieved by employing Convolutional Neural Networks to reconstruct neutrino interactions in the DeepCore detector. In this contribution, the recent IceCube result from the atmospheric muon neutrino disappearance analysis using the CNN-reconstructed neutrino sample are presented and compared to the existing worldwide measurements