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奥贝胆酸改善原发性胆汁性胆管炎患者的胆汁酸排泄

作者： C.·索伦森(C.T. sorensen)

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临床肝胆病杂志 2021年第3期37卷 724-724页

作者： kJARGAARD k FRISCH k sorensen M 徐晓桐金晶兰不详吉林大学第一医院感染病中心肝病科

来自丹麦的kj rgaard等针对奥贝胆酸是核胆汁酸法尼醇X受体的激动剂,可调节胆汁酸代谢,对熊去氧胆酸治疗应答不佳的原发性胆汁性胆管炎患者,验证奥贝胆酸治疗是否会影响结合胆汁酸的肝脏转运。

关键词：胆汁酸代谢法尼醇X受体原发性胆汁性胆管炎结合胆汁酸应答不佳奥贝胆酸激动剂熊去氧胆酸治疗

新型冠状病毒肺炎流行期抗生素在呼吸道感染中的合理使用

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英国医学杂志中文版 2021年第6期24卷 350-354页

作者： Jerome A Leis karen B Born Guylene Theriault Olivia Ostrow Allan Grill k Brian Johnston 唐晓(译) Division of Infectious Diseases and General Internal Medicine Sunnybrook Health Sciences CentreTorontoOntarioCanada Department of Medicine University of TorontoTorontoOntarioCanada Institute of Health Policy Management&EvaluationDalla Lana School of Public HealthFaculty of MedicineUniversity of TorontoTorontoOntarioCanada Department of Family Medicine McGill UniversityMontrealQuebecCanada Division of Pediatric Emergency Medicine The Hospital for Sick ChildrenTorontoOntarioCanada Department of Pediatrics University of TorontoTorontoOntarioCanada Centre for Quality Improvement and Patient Safety University of TorontoTorontoOntarioCanada Department of Family Medicine Markham Stouffville HospitalMarkhamOntarioCanada Department of Family&Community Medicine University of TorontoTorontoOntarioCanada Quality of Care NL/Choosing Wisely NL Memorial University of NewfoundlandSt.John′sNewfoundlandCanada 首都医科大学附属北京朝阳医院呼吸与危重症医学科

一名68岁的老年女性,既往有慢性高血压、2型糖尿病病史,因"咳痰、发热3天"致电家庭医生。她起初预约了一次虚拟就诊,医生认为她没有严重的不适或气短,考虑她可能存在病毒性支气管炎。

关键词：呼吸道感染流行期家庭医生老年女性肺炎抗生素 2型糖尿病

Automated Cell Detection and Morphometry on Growth Plate Images of Mouse Bone

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Applied Mathematics 2014年第18期5卷 2866-2880页

作者： Maria-Grazia Ascenzi Xia Du James I. Harding Emily N. Beylerian Brian M. de Silva Ben J. Gross Hannah k. kastein Weiguang Wang karen M. Lyons Hayden Schaeffer Department of Orthopaedic Surgery University of California Los Angeles California USA Department of Mathematics University of California Los Angeles California USA Department of Mathematics University of California Irvine California USA

Microscopy imaging of mouse growth plates is extensively used in biology to understand the effect of specific molecules on various stages of normal bone development and on bone disease. Until now, such image analysis has been conducted by manual detection. In fact, when existing automated detection techniques were applied, morphological variations across the growth plate and heterogeneity of image background color, including the faint presence of cells (chondrocytes) located deeper in tissue away from the image’s plane of focus, and lack of cell-specific features, interfered with identification of cells. We propose the first method of automated detection and morphometry applicable to images of cells in the growth plate of long bone. Through ad hoc sequential application of the Retinex method, anisotropic diffusion and thresholding, our new cell detection algorithm (CDA) addresses these challenges on bright-field microscopy images of mouse growth plates. Five parameters, chosen by the user in respect of image characteristics, regulate our CDA. Our results demonstrate effectiveness of the proposed numerical method relative to manual methods. Our CDA confirms previously established results regarding chondrocytes’ number, area, orientation, height and shape of normal growth plates. Our CDA also confirms differences previously found between the genetic mutated mouse Smad1/5CkO and its control mouse on fluorescence images. The CDA aims to aid biomedical research by increasing efficiency and consistency of data collection regarding arrangement and characteristics of chondrocytes. Our results suggest that automated extraction of data from microscopy imaging of growth plates can assist in unlocking information on normal and pathological development, key to the underlying biological mechanisms of bone growth.

关键词： Anisotropic Diffusion Cell Detection Growth Plate Mouse Retinex

UniPron is A Fully Effective Non-hormonal Reversible Contraceptive in Baboon Model (Papio Anubis)

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Journal of Reproduction and Contraception 2008年第2期19卷 107-118页

作者： Jael A.Obiero Maureen N.Mburu Benson M.Ndung'u kenneth k.Waititu Isaac Mulei Idle O.Farah Peter G.Mwethera Department of Reproductive Health and Reproductive Biology Institute of Primate ResearchKarenNairobiKenya

Objective To determine the safety and efficacy of UniPron as a reversible contraceptive.Methods Vaginal swabs were obtained before and after UniPron administration, cultured onto appropriate culture media and bacteria identification was done based on type of media used, Gram stain reactions, colony morphology and biochemical tests. Vaginal biopsy tissues were processed using paraffin wax method, stained with hematoxylin and eosin and examined under light microscopy to determine the effect of the product on vaginal tissues. The effect of UniPron on sperm was examined by mixing the product with electroejaculated spermatozoa in vitro at different concentrations. For efficacy studies, male baboons of proven fertility were mated with UniPron treated or untreated females of proven fertility during the fertile stages. Results All the five females （100%） that were treated with UniPron did not conceive and they regained total fertility when the treatment was stopped while all the controls conceived. At a concentration of 40%, UniPron completely immobilized spermatozoa in an in-vitro system. UniPron mechanism of action was by lowering the vaginal pH and on application in baboon, the pH was lowered for at least 3 h after which it went back to normal.Conclusions As we plan for a study to test UniPron as a microbicide to prevent STIs including HIV, our current study has established that this novel product is effective in contraception and harmless to vaginal tissues and vaginal microbial flora in a baboon model （Papio anubis）.

关键词： Papio anubis UniPron vagina epithelium pH microflora microbicidal contraceptive

Nationwide retrospective study of hepatitis B virological response and liver stiffness improvement in 465 patients on nucleos(t)ide analogue

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World Journal of Gastroenterology 2022年第31期28卷 4390-4398页

作者： Alnoor Ramji karen Doucette Curtis Cooper Gerald Yosel Minuk Mang Ma Alexander Wong David Wong Edward Tam Brian Conway David Truong Philip Wong Lisa Barrett Hin Hin ko Sarah Haylock-Jacobs Nishi Patel Gilaad G kaplan Scott Fung Carla S Coffin Department of Medicine University of British ColumbiaVancouver v6t 1z3Canada Department of Medicine University of AlbertaEdmonton t6g 2r7Canada Department of Medicine The Ottawa Hospital Research InstituteUniversity of OttawaOttawa ON K1H 8L6Canada Department of Medicine University of ManitobaWinnipeg r3e 3j7Canada Department of Medicine University of SaskatchewanSaskatoon s7n 5e5Canada Department of Medicine University Health NetworkToronto m5g 2c4Canada Pacific Gastroenterology Associates Vancouver v6z 2k5Canada Vancouver Infectious Disease Centre Vancouver v6z 2c7Canada Department of Medicine McGill UniversityMontreal h3a 0g4Canada Department of Microbiology and Immunology Dalhousie UniversityHalifax b3h 4r2Canada Cumming School of Medicine University of CalgaryCalgary t2n 1n4Canada

BACkGROUND Hepatitis B virus(HBV)nucleos(t)ide analog(NA)therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen(HBsAg)*** is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine(LAM)to tenofovir disoproxil fumarate(TDF).AIM To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement(LSM)(i.e.,FibroScan®).METHODS Retrospective,observational cohort study from the Canadian HBV *** collected included demographics,NA,HBV DNA,alanine aminotransferase(ALT),and *** were HBV monoinfected patients,treatment naïve,and received 1 NA with minimum 1 year *** In 465(median 49 years,37%female,35%hepatitis B e antigen+at baseline,84%Asian,6%White,and 9%Black).Percentage of 64(n=299)received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years,*** mean baseline LSM was 11.2 kPa(TDF)vs 8.3 kPa(LAM)(P=0.003).At 5-year follow-up,the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM(P=0.83).There was a significant difference in fibrosis regression between groups(i.e.,mean-4.2 kPa change in TDF and-1.6 kPa in LAM,P<0.05).The last available data on treatment showed that all had normal ALT,but more TDF patients were virologically suppressed(<10 IU/mL)(n=170/190,89%)vs LAM-treated(n=35/58,60%)(P<0.05).None cleared *** In this real-world North American study,approximately 5 years of NA achieves liver fibrosis regression rarely leads to HBsAg loss.

关键词： Nucleos(t)ide analog therapy Functional cure Hepatitis B virus surface antigen loss Fibrosis regression Liver stiffness measurement Transient elastography

理解和使用《新一代科学教育标准》(NGSS)之旅

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中国科技教育 2016年第4期 6-7页

作者： karen Mesmer 周建中 Mesmer科学教育咨询机构江苏汉博教育培训中心

我走进威斯康星大学奥斯哥斯校区的教室,准备参加一个由美国科学教师协会（NSTA）资助的《新一代科学教育标准》初始版本的审阅工作,这个版本是提交公众审阅之前的版本。我已经阅读了《k—12科学教育框架》的大部分内容,并且对于将框架... 详细信息

我走进威斯康星大学奥斯哥斯校区的教室,准备参加一个由美国科学教师协会（NSTA）资助的《新一代科学教育标准》初始版本的审阅工作,这个版本是提交公众审阅之前的版本。我已经阅读了《k—12科学教育框架》的大部分内容,并且对于将框架如何转换成标准用于指导课堂教学很好奇。

关键词：科学教育标准威斯康星大学教师协会教育框架课堂教学版本审阅教室

Metabolic regulation by p53

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世界最新医学信息文摘 2015年第5期 6-6页

作者： Oliver D.k.Maddocks karen H.Vousden

We are increasingly aware that cellular metabolism plays a vital role in diseases such as cancer, and that p53 is an important regulator of metabolic pathways. By transcriptional activation and other means, p53 is able to contribute to the regulation of glycolysis, oxidative phosphorylation, glutaminolysis, insulin sensitivity, nucleotide biosynthesis, mitochondrial integrity, fatty acid oxidation, antioxidant response, autophagy and m TOR signalling. The ability to positively and negatively regulate many of these pathways, combined with feedback signalling from these pathways to p53, demonstrates the reciprocal and flexible nature of the regulation, facilitating a diverse range of responses to metabolic stress. Intriguingly, metabolic stress triggers primarily an adaptive( rather than pro-apoptotic) p53 response, and p53 is emerging as an important regulator of metabolic homeostasis. A better understanding of how p53 coordinates metabolic adaptation will facilitate the identification of novel therapeutic targets and will also illuminate the wider role of p53 in human biology.

关键词： p53 Homeostasis Metabolism Glycolysis Oxidative phosphorylation Autophagy

Genome-Wide Linkage and Positional Association Analyses Identify Associations of Novel AFF3 and NTM Genes with Triglycerides:The GenSalt Study

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Journal of Genetics and Genomics 2015年第3期42卷 107-117页

作者： Changwei Li Lydia A.L.Bazzano Dabeeru C.Rao James E.Hixson Jiang He Dongfeng Gu Charles C.Gu Lawrence C.Shimmin Cashell E.Jaquish karen Schwander De-Pei Liu Jianfeng Huang Fanghong Lu Jie Cao Shen Chong Xiangfeng Lu Tanika N.kelly Department of Epidemiology Tulane University School of Public Health and Tropical Medicine Department of Medicine Tulane University School of Medicine Division of Biostatistics Washington University School of Medicine Department of Epidemiology Human Genetics and Environmental SciencesUniversity of Texas School of Public Health State key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center of Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical College Division of Prevention and Population Sciences National HeartLungBlood Institute National Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine Shandong Academy of Medical Sciences Department of Epidemiology and Biostatistics Nanjing Medical University School of Public Health

We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity （GenSalt） study. The GenSalt study was conducted among 1906 participants from 633 Han Chinese families. Lipids were measured from overnight fasting blood samples using standard methods. Multipoint quantitative trait genome-wide linkage scans were performed on the high-density lipoprotein, low-density lipoprotein, and log- transformed triglyceride phenotypes. Using dense panels of single nucleotide polymorphisms （SNPs）, single-marker and gene-based association analyses were conducted to follow-up on promising linkage signals. Additive associations between each SNP and lipid phenotypes were tested using mixed linear regression models. Gene-based analyses were performed by combining P-values from single- marker analyses within each gene using the truncated product method （TPM）. Significant associations were assessed for replication among 777 Asian participants of the Multi-ethnic Study of Atherosclerosis （MESA）. Bonferroni correction was used to adjust for multiple testing. In the GenSalt study, suggestive linkage signals were identified at 2p11.2-2q12.1 [maximum multipoint LOD score （MML） = 2.18 at 2q11.2] and t lq24.3-11q25 （MML = 2.29 at 11q25） for the log-transformed triglyceride phenotype. Follow-up analyses of these two regions revealed gene-based associations of charged multivesicular body protein 3 （CHMP3）, ring finger protein 103 （RNF103）, AF4/FMR2 family, member 3 （AFF3）, and neurotrirnin （NTM） with triglycerides （P = 4 ×10^-4, 1.00 × 10^-5, 2.00 × 10^-5, and 1.00 × 10^-7, respectively）. Both the AFF3 and NTM triglyceride associations were replicated among MESA study participants（P = 1.00 × 10^-7 and 8.00× 10^-5, respectively）. Furthermore, NTM explained the linkage signal on chromosome 11, In conclusion, we identified novel genes associated with lipid

关键词： Lipids Linkage analysis Positional association analysis Gene-based analysis