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| 1 | Evolving concepts in bone infection: redefining “biofilm”,“acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”显示文摘Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure. | Elysia A. Masters Ryan P. Trombetta Karen L. de Mesy Bentley Brendan F Boyce Ann Lindley Gill Steven R. Gill Kohei Nishitani Masahiro Ishikawa Yugo Morita Hiromu Ito Sheila N. Bello-Irizarry Mark Ninomiya James D. Brodell Jr. Charles C. Lee Stephanie P. Hao Irvin Oh Chao Xie Hani A. Awad John L. Daiss John R. Owen Stephen L. Kates Edward M. Schwarz Gowrishankar Muthukrishnan | 2019 | Bone Research2019，7，3： | 19 |
| 2 | Dietary and metabolomic determinants of relapse in ulcerative colitis patients: A pilot prospective cohort study显示文摘AIM To identify demographic, clinical, metabolomic, and lifestyle related predictors of relapse in adult ulcerative colitis(UC) patients.METHODS In this prospective pilot study, UC patients in clinical remission were recruited and followed-up at 12 mo to assess a clinical relapse, or not. At baseline information on demographic and clinical parameters was collected. Serum and urine samples were collected for analysis of metabolomic assays using a combined direct infusion/liquid chromatography tandem mass spectrometry and nuclear magnetic resolution spectroscopy. Stool samples were also collected to measure fecal calprotectin(FCP). Dietary assessment was performed using a validated self-administered food frequency questionnaire. RESULTS Twenty patients were included(mean age: 42.7 ± 14.8 years, females: 55%). Seven patients(35%) experienced a clinical relapse during the follow-up period. While 6 patients(66.7%) with normal body weight developed a clinical relapse, 1 UC patient(9.1%) who was overweight/obese relapsed during the follow-up(P = 0.02). At baseline, poultry intake was significantly higher in patients who were still in remission during follow-up(0.9 oz vs 0.2 oz, P = 0.002). Five patients(71.4%) with FCP > 150 μg/g and 2 patients(15.4%) with normal FCP(≤ 150 μg/g) at baseline relapsed during the follow-up(P = 0.02). Interestingly, baseline urinary and serum metabolomic profiling of UC patients with or without clinical relapse within 12 mo showed a significant difference. The most important metabolites that were responsible for this discrimination were trans-aconitate, cystine and acetamide in urine, and 3-hydroxybutyrate, acetoacetate and acetone in serum. CONCLUSION A combination of baseline dietary intake, fecal calprotectin, and metabolomic factors are associated with risk of UC clinical relapse within 12 mo. | Ammar Hassanzadeh Keshtel iFloris F van den Brand Karen L Madsen Rupasri Mandal Rosica ValchevaKaren I Kroeker Beomsoo Han Rhonda C Bell Janis Cole Thomas Hoevers David S Wishart Richard N Fedorak Levinus A Dieleman | 2017 | World Journal of Gastroenterology2017，23，21： | 9 |
| 3 | p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory RhoC to LIMK2 signaling pathway promotes cell survival显示文摘响应 DNA 损坏的房间命运的中央仲裁人是 p53,它调整涉及房间周期拘捕,幸存和 apoptosis 的基因的表示。尽管 DNA 损坏开始的许多回答被描绘了,肌动朊细胞骨架管理者的角色大部分是未知的。我们现在显示出那 RhoC 和秘鲁利玛机场之代号 kinase (LIMK2 ) 2 是 genotoxic 代理人导致的直接 p53 目标基因。尽管 RhoC 和 LIMK2 在肌动朊细胞骨架规定有生长得很好的角色,我们的结果显示 LIMK2 的激活也有支持幸存的功能追随者 DNA 损坏。由调停 siRNA 的击倒或选择的药理学封锁的 LIMK 抑制敏化房间到无线电 -- 或化疗,以便当与 LIMK 抑制结合了时,当单身地管理了时,是尚不致命的治疗导致了房间死亡。我们的调查结果建议把 LIMK 禁止者与 genotoxic 治疗相结合能比单个代理人的管理更有效,并且加亮在肌动朊细胞骨架管理者和 DNA 之间的一个新奇连接导致损坏的房间幸存机制。 | Daniel R Croft Diane Crighton Michael S Samuel Filipe C Lourenco June Munro Jenifer Wood Karim Bensaad Karen H Vousden Owen J Sansom Kevin M Ryan Michael F Olson | 2011 | Cell Research2011，21，4： | 3 |
| 4 | Stratification of outcomes for mucinous appendiceal adenocarcinoma with peritoneal metastasis by histological grade显示文摘AIM To investigate the importance of a three-tiered histologic grade on outcomes for patients with mucinous appendiceal adenocarcinoma(MAA).METHODS Two hundred and sixty-five patients with MAA undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were identified from a prospective database from 2004 through 2014. All pathology was reviewed by our gastrointestinal subspecialty pathologists and histological grade was classified as well-differentiated, moderately differentiated, and poorly differentiated. Survival analysis was performed using Cox proportional hazards regression.RESULTS There were 201(75.8%) well-, 45(16.9%) moderatelyand 19(7.2%) poorly-differentiated tumors. Histological grade significantly stratified the 5-year overall survival(OS), 94%, 71% and 30% respectively(P < 0.001) as well as the 5-year disease-free survival(DFS) 66%, 21% and 0%, respectively(P < 0.001). Independent predictors of DFS included tumor grade(HR = 1.78, 95%CI: 1.21-2.63, P = 0.008), lymph node involvement(HR = 0.33, 95%CI: 0.11-0.98, P < 0.02), previous surgical score(HR = 1.31, 95%CI: 1.1-1.65, P = 0.03) and peritoneal carcinomatosis index(PCI)(HR = 1.05, 95%CI: 1.02-1.08, P = 0.002). Independent predictors of OS include tumor grade(HR = 2.79, 95%CI: 1.26-6.21, P = 0.01), PCI(HR = 1.10, 95%CI: 1.03-1.16, P = 0.002), and complete cytoreduction(HR = 0.32, 95%CI: 0.11-0.92, P = 0.03). Tumor grade and PCI were the only independent predictors of both DFS and OS. Furthermore, histological grade and lymphovascular invasion stratified the risk of lymph node metastasis into a low(6%) and high(40%) risk groups. CONCLUSION Our data demonstrates that moderately differentiated MAA have a clinical behavior and outcome that is distinct from well-and poorly-differentiated MAA. The threetier grade classification provides improved prognostic stratification and should be incorporated into patient selection and treatment algorithms. | Travis Edward Grotz Richard E Royal Paul F Mansfield Michael James Overman Gary N Mann Kristen Ashlee Robinson Karen A Beaty Safiea Rafeeq Auerlio Matamoros Michelle W Taggart Keith Francis Fournier | 2017 | World Journal of Gastrointestinal Oncology2017，9，9： | 2 |
| 5 | Biomaterial developments for bone tissue engineering显示文摘 | Karen J.L Burg Scott Porter James F Kellam | 2000 | Biomaterials2000，，23： | 2 |
| 6 | What is driving China' s decline in energy intensity? 显示文摘 | Karen F | 2004 | Resource and Energy Economics2004，26，1： | 1 |
| 7 | Peroxisome proliferator activated receptor up-regulates the bcl-2 anti- apoptosis protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis 显示文摘 | Karen F Rodrigo Q Patricio R | 2007 | J Biolcham2007，282，37： | 1 |
| 8 | Role of endothelin-1 in lung disease显示文摘 | Karen A Ivan F McMurtry | 2001 | Respir Res2001，2，2： | 1 |
| 9 | Radical Scavengers from the Entomogenous Deuteromycete Beauveria amorpha显示文摘 | Hu F L Karen S Stefka S | 2002 | Planta Medica2002，68，： | 1 |
| 10 | Facial asymmetry quantification for expression-invariant human identification 显示文摘 | Liu Yanxi Schmidt Karen L Cohn Jeffrey F | 2003 | Computer Vision and Image Understanding2003，91，12： | 1 |
| 11 | Nutritional therapies for mental health disorders 显示文摘 | Shaheen E L Karen F V | 2008 | Nutrition Journal2008，7，2： | 1 |
| 12 | 查看详情显示文摘 | Elaine M T Donald J L J John H.L Debbie A M Peter B F Karen B | | 0，，： | 1 |
| 13 | Radical scavengers from the entomogenous deuteromycete Beauveria amorpha 显示文摘 | HU F L Karen S Stefka S | 2002 | Plant Medica2002，68，： | 1 |
| 14 | Navy shipboard time synchronization service options and analysis 显示文摘 | GLASS Mark E O'DONOGHUE Karen F | 2008 | IEEE Computer and Information Science2008，46，： | 1 |
| 15 | Bevondblue-Targeting depression in young people显示文摘 | Jane B Karen F | 2002 | Youth Stud Austr2002，21，： | 1 |
| 16 | Image understanding for iris biometrics:a survey 显示文摘 | Kevin W B Karen H Patrick J F | 2008 | Computer Vision and Image Understanding2008，110，2： | 1 |
| 17 | Foam Production During Steam Displacement of Aqueous Surfactants显示文摘 | Michaels Karen F Udell | | 0，，03： | 1 |
| 18 | Hyperuricemia and cardiovascular events in successfully treated hypertensive patients显示文摘 | Michael H Karen K Steinberg Donna F Stroup | 1999 | Hypertension1999，34，： | 1 |
| 19 | The quality of urban environments: Mapping variation in access to community resources 显示文摘 | Karen W Daniel E Adrian F | 2003 | Urban Studies2003，40，1： | 1 |
| 20 | Effects of hemoconcentration and sympathetic activation on serum lipid response to brief mental stress显示文摘 | ELIZABETH A B MATTEW F M KAREN A MATTHE WS | 2002 | Psycho-somatic Medicine2002，64，： | 1 |
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