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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 | Imaging target mRNA and siRNA-mediated gene silencing in vivo with ribozyme-based re- porters显示文摘 | So MK Gowrishankar G I-Iasegawa S | 2008 | Chembiochem2008，9，16： | 1 |
| 3 | Mechanisms for the intracellular manipulation of organelles by conventional electroporation显示文摘 | Esser A T Smith K C Gowrishankar T R | 2010 | Biophysical Journal2010，98，11： | 1 |
| 4 | Towards solid tumor treatment by irreversible electroporation: intrinsic redistribution of fields and currents in tissue显示文摘 | Esser A T Smith K C Gowrishankar T R | 2007 | Technology in Cancer Research and Treatment2007，6，4： | 1 |
| 5 | Profound natriuresis,extracellular fluid volume contraction,and hypernatremia with hypertonic losses following trauma显示文摘 | Gowrishankar M Sapir D Pace K et a1 | 1997 | Geriatr Nephrol Urol1997，7，2： | 1 |
| 6 | Production and applications of esterases显示文摘 | PANDA T GOWRISHANKAR B S | 2005 | Applied Microbiology and Biotechnology2005，67，2： | 1 |
| 7 | Prolonged Network Li- fetime and Data Wholeness by Clusters Using B-Ct Algorithm 显示文摘 | Thiyagarajan P Gowrishankar O K Sudhakar K | 2013 | In- ternational Journal of Computer Science and Mobile Computing2013，3，2： | 1 |
| 8 | Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome显示文摘 | Loeffler K Gowrishankar M Yiu V | 2004 | Pediatr Nephrol2004，19，3： | 1 |
| 9 | Characterization of the host immune response in human ganglia after herpes zoster显示文摘 | Gowrishankar K Steain M Cunninqham AL | 2010 | J Virol2010，84，17： | 1 |
| 10 | Fiberoptic bronchoscopy in unresolved atelectasis in infants 显示文摘 | Vijayasekaran D Gowrishankar NC Nedunehelian K | 2010 | Indian Pediatr2010，47，7： | 1 |
| 11 | Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome 显示文摘 | Loeffler K Gowrishankar M Yiu V | 2004 | Pediatr Nephrol2004，19，3： | 1 |
| 12 | Electrical behavior and pore accumu- lation in a multicellular model for conventional and supra- electroporation显示文摘 | Gowrishankar T R Weaver J C | 2006 | Biochemical and Biophysical Research Communi- cation2006，349，2： | 1 |
| 13 | Non diabetie renal disease in type 2 diabetes mellitus显示文摘 | Soni SS Gowrishankar S Kishan AG | 2006 | Nephrology2006，11，6： | 1 |
| 14 | Ix>-- Wer airway anomalies in infants with laryngomalacia显示文摘 | Vijayasekaran D Gowrishankar N C Kalpans S | 2010 | Indian J Pediatr2010，77，4： | 1 |
| 15 | Production and applica-tions of esterases显示文摘 | PANDA T GOWRISHANKAR B S | 2005 | Applied Microbiology and Biotechnolo-gy2005，67，： | 1 |
| 16 | Fi- beroptic bronchoscopy in unresolved atelectasis in infants 显示文摘 | Vijayasekaran D Gowrishankar NC Nedunchelian K | 2010 | Indian Pediatr2010，47，7： | 1 |
| 17 | Cell shape-dependent rectification of surface receptor transport in a sinusoidal electric field显示文摘 | Lee RC Gowrishankar TR Basch RM | 1993 | J Biophysical1993，64，： | 1 |
| 18 | Transport lattice approach to describing cell electroporation: use of a local asymptotic model显示文摘 | Stewart D A Gowrishankar T R Weaver J C | 2004 | IEEE Transactions on Plasma Science2004，32，4： | 1 |
| 19 | Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma 显示文摘 | HERSEY P GOWRISHANKAR K | 2015 | Future Oncol2015，11，1： | 1 |
| 20 | Mierodosimetry for conventional and supra-electroporation in cells with organelles 显示文摘 | Gowrishankar T R Esser A T Vasilkoski Z | 2006 | Biochemical and Biophysical Research Communications2006，341，4： | 1 |
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