The Role of Imaging in Patient Selection, Preoperative Planning, and Postoperative Monitoring in Human Upper Extremity Allotransplantation

Objective. To describe the role of imaging in vascular composite allotransplantation based on one institution’s experience with upper extremity allotransplant patients. Methods. The institutional review board approved this review of HIPAA-compliant patient data without the need for individual consent. A retrospective review was performed of imaging from 2008 to 2011 on individuals undergoing upper extremity transplantation. This demonstrated that, of the 19 patients initially considered, 5 patients with a mean age of 37 underwent transplantation. Reports were correlated clinically to delineate which preoperative factors lead to patient selection versus disqualification and what concerns dictated postoperative imaging. Findings were subdivided into musculoskeletal and vascular imaging criterion. Results. Within the screening phase, musculoskeletal exclusion criterion included severe shoulder arthropathy, poor native bone integrity, and marked muscular atrophy. Vascular exclusion criterion included loss of sufficient arterial or venous supply and significant distortion of the native vascular architecture. Postoperative imaging was used to document healing and hardware integrity. Postsurgical angiography and ultrasound were used to monitor for endothelial proliferation or thrombosis as signs of rejection and vascular complication. Conclusion. Multimodality imaging is an integral component of vascular composite allotransplantation surgical planning and surveillance to maximize returning form and functionality while minimizing possible complications

Inkjet-based biopatterning of bone morphogenetic protein-2 to spatially control calvarial bone formation

The purpose of this study was to demonstrate spatial control of osteoblast differentiation in vitro and bone formation in vivo using inkjet bioprinting technology and to create three-dimensional persistent bio-ink patterns of bone morphogenetic protein-2 (BMP-2) and its modifiers immobilized within microporous scaffolds. Semicircular patterns of BMP-2 were printed within circular DermaMatrix™ human allograft scaffold constructs. The contralateral halves of the constructs were unprinted or printed with BMP-2 modifiers, including the BMP-2 inhibitor, noggin. Printed bio-ink pattern retention was validated using fluorescent or 125I-labeled bio-inks. Mouse C2C12 progenitor cells cultured on patterned constructs differentiated in a dose-dependent fashion toward an osteoblastic fate in register to BMP-2 patterns. The fidelity of spatial restriction of osteoblastic differentiation at the boundary between neighboring BMP-2 and noggin patterns improved in comparison with patterns without noggin. Acellular DermaMatrix constructs similarly patterned with BMP-2 and noggin were then implanted into a mouse calvarial defect model. Patterns of bone formation in vivo were comparable with patterned responses of osteoblastic differentiation in vitro. These results demonstrate that three-dimensional biopatterning of a growth factor and growth factor modifier within a construct can direct cell differentiation in vitro and tissue formation in vivo in register to printed patterns. © 2010 Mary Ann Liebert, Inc

Teixobactin kills bacteria by a two-pronged attack on the cell envelope

Antibiotics that use novel mechanisms are needed to combat antimicrobial resistance1–3. Teixobactin4 represents a new class of antibiotics with a unique chemical scaffold and lack of detectable resistance. Teixobactin targets lipid II, a precursor of peptidoglycan5. Here we unravel the mechanism of teixobactin at the atomic level using a combination of solid-state NMR, microscopy, in vivo assays and molecular dynamics simulations. The unique enduracididine C-terminal headgroup of teixobactin specifically binds to the pyrophosphate-sugar moiety of lipid II, whereas the N terminus coordinates the pyrophosphate of another lipid II molecule. This configuration favours the formation of a β-sheet of teixobactins bound to the target, creating a supramolecular fibrillar structure. Specific binding to the conserved pyrophosphate-sugar moiety accounts for the lack of resistance to teixobactin4. The supramolecular structure compromises membrane integrity. Atomic force microscopy and molecular dynamics simulations show that the supramolecular structure displaces phospholipids, thinning the membrane. The long hydrophobic tails of lipid II concentrated within the supramolecular structure apparently contribute to membrane disruption. Teixobactin hijacks lipid II to help destroy the membrane. Known membrane-acting antibiotics also damage human cells, producing undesirable side effects. Teixobactin damages only membranes that contain lipid II, which is absent in eukaryotes, elegantly resolving the toxicity problem. The two-pronged action against cell wall synthesis and cytoplasmic membrane produces a highly effective compound targeting the bacterial cell envelope. Structural knowledge of the mechanism of teixobactin will enable the rational design of improved drug candidates

Teixobactin kills bacteria by a two-pronged attack on the cell envelope

Antibiotics that use novel mechanisms are needed to combat antimicrobial resistance1–3. Teixobactin4 represents a new class of antibiotics with a unique chemical scaffold and lack of detectable resistance. Teixobactin targets lipid II, a precursor of peptidoglycan5. Here we unravel the mechanism of teixobactin at the atomic level using a combination of solid-state NMR, microscopy, in vivo assays and molecular dynamics simulations. The unique enduracididine C-terminal headgroup of teixobactin specifically binds to the pyrophosphate-sugar moiety of lipid II, whereas the N terminus coordinates the pyrophosphate of another lipid II molecule. This configuration favours the formation of a β-sheet of teixobactins bound to the target, creating a supramolecular fibrillar structure. Specific binding to the conserved pyrophosphate-sugar moiety accounts for the lack of resistance to teixobactin4. The supramolecular structure compromises membrane integrity. Atomic force microscopy and molecular dynamics simulations show that the supramolecular structure displaces phospholipids, thinning the membrane. The long hydrophobic tails of lipid II concentrated within the supramolecular structure apparently contribute to membrane disruption. Teixobactin hijacks lipid II to help destroy the membrane. Known membrane-acting antibiotics also damage human cells, producing undesirable side effects. Teixobactin damages only membranes that contain lipid II, which is absent in eukaryotes, elegantly resolving the toxicity problem. The two-pronged action against cell wall synthesis and cytoplasmic membrane produces a highly effective compound targeting the bacterial cell envelope. Structural knowledge of the mechanism of teixobactin will enable the rational design of improved drug candidates

Teixobactin kills bacteria by a two-pronged attack on the cell envelope

Antibiotics that use novel mechanisms are needed to combat antimicrobial resistance1–3. Teixobactin4 represents a new class of antibiotics with a unique chemical scaffold and lack of detectable resistance. Teixobactin targets lipid II, a precursor of peptidoglycan5. Here we unravel the mechanism of teixobactin at the atomic level using a combination of solid-state NMR, microscopy, in vivo assays and molecular dynamics simulations. The unique enduracididine C-terminal headgroup of teixobactin specifically binds to the pyrophosphate-sugar moiety of lipid II, whereas the N terminus coordinates the pyrophosphate of another lipid II molecule. This configuration favours the formation of a β-sheet of teixobactins bound to the target, creating a supramolecular fibrillar structure. Specific binding to the conserved pyrophosphate-sugar moiety accounts for the lack of resistance to teixobactin4. The supramolecular structure compromises membrane integrity. Atomic force microscopy and molecular dynamics simulations show that the supramolecular structure displaces phospholipids, thinning the membrane. The long hydrophobic tails of lipid II concentrated within the supramolecular structure apparently contribute to membrane disruption. Teixobactin hijacks lipid II to help destroy the membrane. Known membrane-acting antibiotics also damage human cells, producing undesirable side effects. Teixobactin damages only membranes that contain lipid II, which is absent in eukaryotes, elegantly resolving the toxicity problem. The two-pronged action against cell wall synthesis and cytoplasmic membrane produces a highly effective compound targeting the bacterial cell envelope. Structural knowledge of the mechanism of teixobactin will enable the rational design of improved drug candidates

Comprehensive cleft care., Volume one // edited by Joseph E. Losee, Richard E. Kirschner.

Includes bibliographical references and index.1 online resourc

Reconstruction of Osteomyelitis Defects of the Craniofacial Skeleton

Osteomyelitis of the craniofacial skeleton closely resembles osteomyelitis elsewhere in the body in its pathophysiology and medical management; subsequent reconstruction after debridement remains distinctly challenging. The goals of reconstruction must include the restoration of the complex and readily visible morphology of the cranium and face, as well as the adequate return of vital sensory, expressive, and digestive functions. In this article, the various reconstructive modalities will be discussed including pedicled and nonpedicled flaps with or without an osseous component, nonvascularized bone grafts, alloplastic implants, and bone regeneration using protein therapy. Although reconstruction of craniofacial defects after osteomyelitis commonly proves formidable, the satisfactory return of form and function remains a plausible reconstructive goal

The history of surgical education in the United States: Past, present, and future

In just over 100 years, surgical education in the United States has evolved from a disorganized practice to a refined system esteemed worldwide as one of the premier models for the training of physicians and surgeons. But in the changing environment of health care, new challenges have arisen that could warrant a reform. To design our future, we must understand our past. The present work is not intended to be a comprehensive account of the history of American surgery. Instead, it tells the abridged history of surgical education in our country: the evolution from apprenticeships to residencies; the birth of hospital-based teaching; the impact of key historical events on training; the marks left by some preeminent characters; the conception of regulatory entities that steer our education; and, finally, how our process of training surgeons might need to be refined for the continued progress of our profession. Told in chronological order in a manner that will be memorable to readers, this story weaves together the key events that explain how our current surgical training models came to be. We conclude with a timely invitation to draw from these past lessons to redesign the future of graduate medical education, making a case for the transition to time-variable, competency-based medical education for surgical residency programs in America

Video. Diagnostic laparoscopy and preoperative planning in ischiopagus tripus conjoined twins: a surgical first, with detailed demonstration of the complex anatomical relationships.

Diagnosis and management of conjoined twins are constantly evolving. New imaging techniques provide important anatomic details and help in planning the separation procedure. Despite these technological advances, however, the complex arrangement of conjoined organs is somewhat difficult to interpret, leaving unresolved questions at time of surgery. The authors present a video demonstrating laparoscopy as an adjunct in the preoperative planning of separation of ischiopagus tripus conjoined twins as well as illustrating the complex anatomy in a combination of video, drawings, and radiologic imaging. To date, this is the first time that laparoscopy has been used in preoperative assessment of conjoined twins. After elective cesarean delivery, ischiopagus tripus conjoined twins were thoroughly evaluated with conventional imaging, including plain radiographs and computed tomography scan with three-dimensional (3-D) reconstruction images. The anatomy of the gastrointestinal and genitourinary tracts was further defined with barium enema, retrograde pyelography, and cystoscopy. In addition to these tests, diagnostic laparoscopy was performed at time of tissue expander placement. An angled scope, introduced through a 5-mm umbilical port, was used to visualize the intraperitoneal organs as well as all accessible retroperitoneal structures. Laparoscopy provided useful information regarding the bowel distribution between the twins. In addition, it helped demonstrate the relationship of shared solid organs with other intra-abdominal structures and identify anatomic landmarks used in the subsequent separation of the twins. Finally, laparoscopy helped confirm the presence, number, and morphology of the internal female genitalia. Diagnostic laparoscopy is a useful tool in evaluation of ischiopagus tripus conjoined twins. It is an important adjunct to preoperative studies in preparing for an expeditious and safe separation procedure

Circadian Clock Mutation Disrupts Estrous Cyclicity and Maintenance of Pregnancy

AbstractClassic experiments have shown that ovulation and estrous cyclicity are under circadian control and that surgical ablation of the suprachiasmatic nuclei (SCN) results in estrous acyclicity in rats [1–3]. Here, we characterized reproductive function in the circadian Clock mutant mouse [4, 5] and found that the circadian Clock mutation both disrupts estrous cyclicity and interferes with the maintenance of pregnancy. Clock mutant females have extended, irregular estrous cycles, lack a coordinated luteinizing hormone (LH) surge on the day of proestrus, exhibit increased fetal reabsorption during pregnancy, and have a high rate of full-term pregnancy failure. Clock mutants also show an unexpected decline in progesterone levels at midpregnancy and a shortened duration of pseudopregnancy, suggesting that maternal prolactin release may be abnormal. In a second set of experiments, we interrogated the function of each level of the hypothalamic-pituitary-gonadal (HPG) axis in order to determine how the Clock mutation disrupts estrous cyclicity. We report that Clock mutants fail to show an LH surge following estradiol priming in spite of the fact that hypothalamic levels of gonadotropin-releasing hormone (GnRH), pituitary release of LH, and serum levels of estradiol and progesterone are all normal in Clock/Clock females. These data suggest that Clock mutants lack an appropriate circadian daily-timing signal required to coordinate hypothalamic hormone secretion. Defining the mechanisms by which the Clock mutation disrupts reproductive function offers a model for understanding how circadian genes affect complex physiological systems