Suchergebnisse

IntroductionHealth care systems have faced unprecedented challenges due to the COVID-19 pandemic. Access to timely population-based data has been vital to informing public health policy and practice.
MethodsWe describe how ICES, an independent not-for-profit research and analytic institute in Ontario, Canada, pivoted existing research infrastructure and engaged health system stakeholders to provide near real-time population-based data and analytics to support Ontario's COVID-19 pandemic response.
ResultsSince April 2020, ICES provided the Ontario COVID-19 Provincial Command Table and public health partners with regular and ad hoc reports on SARS-CoV-2 testing and COVID-19 vaccine coverage. These reports: 1) helped identify congregate care/shared living settings that needed testing and prevention efforts early in the pandemic; 2) provided early indications of inequities in testing and infection in marginalized neighbourhoods, including areas with higher proportions of immigrants and visible minorities; 3) identified areas with high test positivity, which helped Public Health Units target and evaluate prevention efforts; and 4) contributed to altering the province's COVID-19 vaccine roll-out strategy to target high-risk neighbourhoods and helping Public Health Units and community organizations plan local vaccination programs. In addition, ICES is a key component of the Ontario Health Data Platform, which provides scientists with data access to conduct COVID-19 research and analyses.
Discussion and ConclusionICES was well-positioned to provide rapid analyses for decision-makers to respond to the evolving public health emergency, and continues to contribute to Ontario's pandemic response by providing timely, relevant reports to health system stakeholders and facilitating data access for externally-funded COVID-19 research.

© 2019 by the authors. ; [Background]: Intra-vesical instillation of Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is an effective therapy for high-grade non-muscle invasive bladder cancer (NMIBC), which provokes a local immune response resulting in 70% of patients free of relapse after three years. Because non-responder patients usually have a bad prognosis, the early identification of treatment failure is crucial. We hypothesized that, if an effective immune response was taking place in the bladder, soluble factors would be released to the urine many days after BCG instillations. ; [Methods]: An extensive panel of cytokines and chemokines released into the urine seven days after every BCG instillation was screened in a cohort of NMIBC patients over three years. ; [Results]: The determinations of the urinary concentrations of cytokines, chemokines, and creatinine showed that increasing concentrations of C-X-C motif chemokine 10 (CXCL10) also known as interferon-inducible protein 10 (IP10) could be detected during the six-week induction cycle of BCG-treated patients released into the urine by CD14+ cells. In vitro, CXCL10 facilitated the recruitment of effector immune cells after the BCG-mediated upregulation of CXCR3 in both T- and natural killer (NK)-cells. Conclusions: The high concentrations of chemokine detected one week after the encounter with mycobacteria suggest that the CXCL10 axis might be related to the intensity of the immune anti-tumor response. ; This research was funded by the Madrid Regional Government (S2010/BMD-2326 IMMUNOTHERCAN-CM (B2017/BMD-3733)/FEDER), and the Spanish Ministries of Economy and Health (SAF2015-69169-R, RTC-2017-6379-1, RTI2018-093569-B-I00 (MINECO/FEDER)); E.M.G.C. and S.L.C. were the recipients of fellowships from the La Caixa and Spanish Ministry of Education (FPU), respectively; C.S. was an Erasmus-visiting student from Sorbonne University. The APC was partially funded by CSIC. ; Peer reviewed

The fermentation of Korean red ginseng (RG) increases the bioavailability and efficacy of RG, which has a protective role in various diseases. However, the ginsenoside-specific molecular mechanism of the fermented RG with Cordyceps militaris (CRG) has not been elucidated in non-alcoholic fatty liver disease (NAFLD). A mouse model of NAFLD was induced by a fast-food diet (FFD) and treated with CRG (100 or 300 mg/kg) for the last 8 weeks. CRG-mediated signaling was assessed in the liver cells isolated from mice. CRG administration significantly reduced the FFD-induced steatosis, liver injury, and inflammation, indicating that CRG confers protective effects against NAFLD. Of note, an extract of CRG contains a significantly increased amount of ginsenosides (Rd and Rg3) after bioconversion compared with that of conventional RG. Moreover, in vitro treatment with Rd or Rg3 produced anti-steatotic effects in primary hepatocytes. Mechanistically, CRG protected palmitate-induced activation of mTORC1 and subsequent inhibition of mitophagy and PPARα signaling. Similar to that noted in hepatocytes, CRG exerted anti-inflammatory activity through mTORC1 inhibition-mediated M2 polarization. In conclusion, CRG inhibits lipid-mediated pathologic activation of mTORC1 in hepatocytes and macrophages, which in turn prevents NAFLD development. Thus, the administration of CRG may be an alternative for the prevention of NAFLD.

AbstractIntroductionAt its basic level, HIV infection requires a replication‐competent virus and a susceptible target cell. Elevated levels of vaginal inflammation has been associated with the increased risk of HIV infection as it brings highly activated HIV target cells (CCR5+CD4+ T cells; CCR5+CD4+CD161+ Th17 T cells) to the female genital tract (FGT) where they interact with HIV. Decreased HIV risk has been associated with a phenotype of decreased immune activation, called immune quiescence, described among Kenyan female sex workers who were intensely exposed to HIV yet remain uninfected. Current prevention approaches focus on limiting viral access. We took the novel HIV prevention approach of trying to limit the number of HIV target cells in the genital tract by reducing inflammation using safe, affordable and globally accessible anti‐inflammatory drugs.MethodsWe hypothesized that the daily administration of low doses of acetylsalicylic acid (ASA 81 mg) or hydroxychloroquine (HCQ 200 mg) would reduce inflammation thereby decreasing HIV target cells at the FGT. Low‐risk HIV seronegative women from Nairobi, Kenya were randomized for six weeks therapy of ASA (n = 37) or HCQ (n = 39) and tested to determine the impact on their systemic and mucosal immune environment.ResultsThe results showed that HCQ use was associated with a significant reduction in the proportion of systemic T cells that were CCR5+CD4+ (p = 0.01) and Th17 (p = 0.01). In the ASA arm, there was a 35% and 28% decrease in the proportion of genital T cells that were CD4+CCR5+ (p = 0.017) and Th17 (p = 0.04) respectively. Proteomic analyses of the cervical lavage showed ASA use was associated with significantly reduced amount of proteins involved in the inflammatory response and cell recruitment at the mucosa, although none of the individual proteins passed multiple comparison correction. These changes were more apparent in women with Lactobacillus dominant microbiomes.ConclusionTogether, these data indicate that taking low‐dose ASA daily was associated with significant reduction in HIV target cells at the FGT. This study provides proof‐of‐concept for a novel HIV‐prevention approach that reducing inflammation using safe, affordable and globally accessible non‐steroidal anti‐inflammatory agents is associated with significant reduction in the proportion of HIV‐target cells at the FGT.

Hepatic veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life‐threatening complication of haematopoietic stem cell transplant (HSCT) conditioning and chemotherapy. Defibrotide is approved for treatment of hepatic VOD/SOS with pulmonary or renal dysfunction [i.e., multi‐organ dysfunction (MOD)] after HSCT in the United States and severe VOD/SOS after HSCT in patients aged older than 1 month in the European Union. Defibrotide was available as an investigational drug by an expanded‐access treatment programme (T‐IND; NCT00628498). In the completed T‐IND, the Kaplan–Meier estimated Day +100 survival for 1000 patients with documented defibrotide treatment after HSCT was 58·9% [95% confidence interval (CI), 55·7–61·9%]. Day +100 survival was also analysed by age and MOD status, and post hoc analyses were performed to determine Day +100 survival by transplant type, timing of VOD/SOS onset (≤21 or >21 days) and timing of defibrotide treatment initiation after VOD/SOS diagnosis. Day +100 survival in paediatric patients was 67·9% (95% CI, 63·8–71·6%) and 47·1% (95% CI, 42·3–51·8%) in adults. All patient subgroups without MOD had higher Day +100 survival than those with MOD; earlier defibrotide initiation was also associated with higher Day +100 survival. The safety profile of defibrotide in the completed T‐IND study was similar to previous reports.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017 ; Support NIH R01EY021834, R01EY014225 and P30EY14801, the Australian Federal Government CRC Scheme through the Vision Cooperative Research Centre, Florida Lions Eye Bank, Research to Prevent Blindness, Drs KR Olsen and ME Hildebrandt, Drs Raksha Urs and Aaron Furtado, Henri and Flore Lesieur Foundation (JMP), Hyderabad Eye Research Foundation, European Research Council ERC-AdG 294099 and CSIC iCoop Program ; Peer reviewed

Measurements of S and other volatiles during pre-eruptive crystallization suggest high gas flux during the 946 CE Paektu eruption.

TonEBP is a key transcriptional activator of M1 phenotype in macrophage, and its high expression is associated with many inflammatory diseases. During the progression of the inflammatory responses, the M1 to M2 phenotypic switch enables the dual role of macrophages in controlling the initiation and resolution of inflammation. Here we report that in human and mouse M1 macrophages TonEBP suppresses IL-10 expression and M2 phenotype. TonEBP knockdown promoted the transcription of the IL-10 gene by enhancing chromatin accessibility and Sp1 recruitment to its promoter. The enhanced expression of M2 genes by TonEBP knockdown was abrogated by antagonism of IL-10 by either neutralizing antibodies or siRNA-mediated silencing. In addition, pharmacological suppression of TonEBP leads to similar upregulation of IL-10 and M2 genes. Thus, TonEBP suppresses M2 phenotype via downregulation of the IL-10 in M1 macrophages. ; National Research Foundation of Korea (NRF) grant - Korea government (MEST) NRF-2011-0020163 NRF-2012R1A1A2043693 NRF-2011-0029697 Research Fund of Ulsan National Institute of Science and Technology 1.110015.01 Global PhD Fellowship of Korea NRF-2014H1A2A1019656

Ha Youn Lee,1,2 Sun Mi Choi,1,2 Jinwoo Lee,1,2 Young Sik Park,1,2 Chang-Hoon Lee,1,2 Deog Kyeom Kim,2,3 Sang-Min Lee,1,2 Ho Il Yoon,2,4 Jae-Joon Yim,1,2 Young Whan Kim,1,2 Sung Koo Han,1,2 Chul-Gyu Yoo1,2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 4Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: Tiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1) decline in chronic obstructive pulmonary disease (COPD) patients with <70% predicted FEV1. However, the rate of FEV1 decline is known to be faster at early stages, which suggests that the effects of tiotropium may be more prominent in early-stage of COPD patients. The aim of this study was to test the hypothesis that tiotropium modifies the rate of FEV1 decline in COPD patients with an FEV1≥70%.Methods: We retrospectively reviewed the records of COPD patients diagnosed between January 1, 2004, and July 31, 2012, at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. The inclusion criteria were as follows: age ≥40 years, postbronchodilator (BD) FEV1≥70% of predicted and FEV1/FVC (forced vital capacity) <0.70, and spirometry more than two times at certain times of the year. Conversely, the exclusion criteria were as follows: asthma, lung cancer, pulmonary tuberculosis, pulmonary resection, or long-term use of a short-acting muscarinic antagonist. The annual lung function decline in patients using tiotropium was compared with that in patients not using the drug.Results: Of the 587 patients enrolled in the study, 257 took tiotropium. Following propensity score matching, 404 patients were included in the analysis. The mean annual rate of post-BD FEV1 decline was 23.9 (tiotropium) and 22.5 (control) mL/yr (P=0.86); corresponding pre-BD values were 30.4 and 21.9 mL/yr (P=0.31), respectively. Mean annual rate of post-BD FVC decline was 55.1 (tiotropium) and 43.5 (control) mL/yr (P=0.33); corresponding pre-BD values were 37.1 and 33.3 mL/yr (P=0.13).Conclusion: Therefore, tiotropium does not reduce the rate of lung function decline in COPD patients with FEV1≥70%. Keywords: tiotropium, chronic obstructive pulmonary disease, lung function decline

Purpose: The purpose of this study was to demonstrate a negative association between intraocular pressure(IOP) and age in 2 Asian populations. In addition, we evaluated genetic and nongenetic factors associated withIOP.Design: Family-based cohort study.Participants: Study subjects 10 years of age from one Korean (The Healthy Twin; n 1431) and 2Mongolian populations (The GENDISCAN; n 859 and 806) with IOP values.Methods: The IOP values were measured with a noncontact tonometer. Each participant received astandard health examination and received questionnaires, which include candidate risk factors on IOP. Mixedmodels were used to identify risk factors for IOP. Variance-component methods were applied to estimate theheritability of IOP.Main Outcome Measures: The negative trend of IOP with aging and evaluation of impact of genetic andnongenetic components on IOP.Results: The mean ages were 43.6, 34.1, and 36.3 years for the Korean, Orhontuul, and Dashbalbarpopulations, respectively. The mean IOPs were 14.4 mmHg (95% confidence interval [CI], 14.3.14.6) in theKoreans and 14.1 mmHg (95% CI, 13.9.14.3) and 12.6 mmHg (95% CI, 12.4.12.9) in the Orhontuul andDashbalbar populations, respectively. In the 3 populations, the IOP decreased as age increased. We replicatedan association of systolic blood pressure (SBP) with IOP. In addition, components of the metabolic syndrome(MS), such as plasma glucose, lipid level, and body mass index, showed positive associations with IOP, afteradjusting for age and SBP. The IOP also had strong genetic contributions in all populations (heritability,0.47.0.51).Conclusions: Negative associations between age and IOP were observed in all 3 populations, which cannotbe explained by the increasing prevalence of myopia in the younger generation. The different age trend in IOPmay in part be responsible for differences in the prevalence of glaucoma subtypes. Our findings suggest thatassociations between IOP and MS components were independent of established risk factors such as SBP or age.In addition, the importance of inherited risks requires further genetic dissection of IOP determinants for biologicalunderstandings of underlying pathophysiology.Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussedin this article. Ophthalmology 2011;xx:xxx ⓒ 2011 by the American Academy of Ophthalmology. ; Supported by National Research Foundation of Korea Grant funded by the Korean Government Ministry of Education, Science and Technology (NRF-2011-355-E00060). This study was also supported by National Research Foundation of Korea (grant no. 2010-0025814; grant no. 2010- 0029113; grant no. M10305030000), the Samsung Biomedical Research Institute (grant no. SBRIC-A9-218-1) and the second stage of the Brain Korea 21 Project. ; OAIID:oai:osos.snu.ac.kr:snu2012-01/102/0000040632/1 ; SEQ:1 ; PERF_CD:SNU2012-01 ; EVAL_ITEM_CD:102 ; USER_ID:0000040632 ; ADJUST_YN:N ; EMP_ID:A077602 ; DEPT_CD:902 ; CITE_RATE:4.223 ; FILENAME:1.Epidemiologic Characteristics of Intraocular Pressure in the Korean and Mongolian Populations.pdf ; DEPT_NM:보건학과 ; EMAIL:jsung@snu.ac.kr ; SCOPUS_YN:Y ; CONFIRM:Y