Point-of-care antimicrobial coating protects orthopaedic implants from bacterial challenge.

Implant related infections are the most common cause of joint arthroplasty failure, requiring revision surgeries and a new implant, resulting in a cost of $8.6 billion annually. To address this problem, we created a class of coating technology that is applied in the operating room, in a procedure that takes less than 10 min, and can incorporate any desired antibiotic. Our coating technology uses an in situ coupling reaction of branched poly(ethylene glycol) and poly(allyl mercaptan) (PEG-PAM) polymers to generate an amphiphilic polymeric coating. We show in vivo efficacy in preventing implant infection in both post-arthroplasty infection and post-spinal surgery infection mouse models. Our technology displays efficacy with or without systemic antibiotics, the standard of care. Our coating technology is applied in a clinically relevant time frame, does not require modification of implant manufacturing process, and does not change the implant shelf life.

Hybrid Tongue - Myoelectric Control Improves Functional Use of a Robotic Hand Prosthesis.

OBJECTIVE: This study aims at investigating the functional performance of a novel prosthesis control scheme integrating an inductive tongue interface and myoelectric control. The tongue interface allowed direct selection of the desired grasp while myoelectric signals were used to open and close the robotic hand. METHODS: The novel method was compared to a conventional sequential on/off myoelectric control scheme using functional tasks defined by Assistive Hand Assessment protocol. Ten able-bodied participants were fitted with the SmartHand on their left forearm. They used both the conventional myoelectric control and the Tongue and Myoelectric Hybrid interface (TMH) to accomplish two activities of daily living (i.e., preparing a sandwich and gift wrapping). Sessions were video recorded and the outcome measure was the completion time for the subtasks as well as the full tasks. RESULTS: The sandwich task was completed significantly faster, with 19% decrease in the completion time, using the TMH when compared to the conventional sequential on/off myoelectric control scheme (p < 0.05). CONCLUSION: The results indicate that the TMH control scheme facilitates the active use of the prosthetic device by simplifying grasp selection, leading thereby to faster completion of challenging and relevant tasks involving bimanual activities.

Evading the host response: Staphylococcus "hiding" in cortical bone canalicular system causes increased bacterial burden.

Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss. Debate persists as to the optimal void filler for this "limb salvage" surgery, whether metal or allograft bone. Clinicians focus on optimizing important functional gains for patients, and the risk of devastating implant infection has been thought to be similar regardless of implant material. Recent insights into infection pathophysiology are challenging this equipoise, however, with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus (the most common infecting agent) into the host lacunar-canaliculi network, and also clinical data revealing a higher rate of infection of allograft over metal. The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal. Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal, and both microarchitecture of host implant and presence of host immune response were assessed. An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone. The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection. These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible, contributing to elevated risks of infection in cortical bone. The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.

The Use of a Novel Antimicrobial Implant Coating In Vivo to Prevent Spinal Implant Infection.

STUDY DESIGN: A controlled, interventional animal study. OBJECTIVE: Spinal implant infection (SII) is a devastating complication. The objective of this study was to evaluate the efficacy of a novel implant coating that has both a passive antibiotic elution and an active-release mechanism triggered in the presence of bacteria, using an in vivo mouse model of SII. SUMMARY OF BACKGROUND DATA: Current methods to minimize the frequency of SII include local antibiotic therapy (vancomycin powder), betadine irrigation, silver nanoparticles, and passive release from antibiotic-loaded poly(methyl methacrylate) cement beads, all of which have notable weaknesses. A novel implant coating has been developed to address some of these limitations but has not been tested in the environment of a SII. METHODS: A biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer was designed to deliver antibiotics. The in vivo performance of this coating was tested in the delivery of either vancomycin or tigecycline in a previously established mouse model of SII. Noninvasive bioluminescence imaging was used to quantify the bacterial burden, and implant sonication was used to determine bacterial colony-forming units (CFUs) from the implant and surrounding bone and soft tissue. RESULTS: The PEG-PPS-vancomycin coating significantly lowered the infection burden from postoperative day 3 onwards (P < 0.05), whereas PEG-PPS-tigecycline only decreased the infection on postoperative day 5 to 10 (P < 0.05). CFUs were lower on PEG-PPS-vancomycin pins than PEG-PPS-tigecycline and PEG-PPS pins alone on both the implants (2.4 × 10, 8.5 × 10, and 1.0 × 10 CFUs, respectively) and surrounding bone and soft tissue (1.3 × 10, 4.8 × 10, and 5.4 × 10 CFUs, respectively) (P < 0.05). CONCLUSION: The biodegradable PEG-PPS coating demonstrates promise in decreasing bacterial burden and preventing SII. The vancomycin coating outperformed the tigecycline coating in this model compared to prior work in arthroplasty models, highlighting the uniqueness of the paraspinal infection microenvironment. LEVEL OF EVIDENCE: N/A.

Evaluation of US Orthopaedic Surgery Academic Centers Based on Measurements of Academic Achievement.

INTRODUCTION: Although a variety of agencies have attempted to evaluate the academic achievements of orthopaedic surgery academic centers, most use opaque criteria that are difficult to interpret and do not provide clear targets for improvement. This study leverages a weighted algorithm using objective measurements that has been linked to academic achievement to attempt to provide a comprehensive assessment of scholarly accomplishment for orthopaedic surgery academic centers. METHODS: We examined full-time faculty at 138 US orthopaedic surgery academic centers; part-time or volunteer faculty were excluded. Five metrics of academic achievement were assessed: National Institutes of Health funding (2013), number of publications, Hirschberg-index (ie, a metric of impact of publications), leadership positions held in orthopaedic surgery societies, and editorial board positions of top orthopaedic and subspecialty journals. Academic programs were given a score for every category, and the algorithm was used to calculate an overall score of academic achievement for each program. RESULTS: The five most academically productive programs were Washington University in St. Louis, Hospital for Special Surgery, Mayo Clinic, University of Pennsylvania, and Thomas Jefferson University. CONCLUSION: This algorithm may provide faculty with an assessment tool that can establish benchmarks to help focus efforts toward increasing the academic productivity of their respective programs.

Improved Decoupling for Low Frequency MRI Arrays using Non-conventional Preamplifier Impedance.

OBJECTIVE: In this study, we describe a method to improve preamplifier decoupling in low frequency MRI receive coil arrays, where sample loading is low and coils exhibit a high Q-factor. METHODS: The method relies on the higher decoupling obtained when coils are matched to an impedance higher than 50 Ω. Preamplifiers with inductive (and low resistive) input impedance, increase even further the effectiveness of the method. RESULTS: We show that for poorly sample loaded coils, coupling to other elements in an array is a major source of SNR degradation due to a reduction of the coil Q-factor. An 8-channel 13C array at 32 MHz for imaging of the human head has been designed following this strategy. The improved decoupling even allowed constructing the array without overlapping of neighboring coils. Parallel imaging performance is also evaluated demonstrating a better spatial encoding of the array due to its non-overlapped geometry. CONCLUSION: The proposed design strategy for coil arrays is beneficial for low frequency coils where the coil thermal noise is dominant. The method has been demonstrated on an 8-channel array for the human head for 13C MRI at 3 T (32 MHz), with almost 2-fold SNR enhancement when compared to a traditional array of similar size and number of elements. SIGNIFICANCE: The proposed method is of relevance for low frequency arrays, where sample loading is low, and noise correlation is high due to insufficient coil decoupling.

Is Core Needle Biopsy Reliable in Differentiating Between Aggressive Benign and Malignant Radiolucent Bone Tumors?

BACKGROUND: Although there is widespread acceptance of core needle biopsy (CNB) for diagnosing solid tumors, there is reluctance by some clinicians to use CNB for aneurysmal bone cysts (ABCs) as a result of concerns of safety (bleeding, nerve injury, fracture, readmission, or infection) and reliability, particularly to rule out malignant diagnoses like telangiectatic osteosarcoma. This is especially true when CNB tissue is sent from an outside hospital, where the technique used to obtain the tissue may be spurious. QUESTIONS/PURPOSES: (1) Is CNB effective (provided adequate information to indicate appropriate surgical treatment without further open biopsy) as an initial diagnostic test for ABC? (2) Is CNB accurate (pathology consistent with the subsequent definitive surgical pathologic diagnosis) in differentiating between benign lesions such as primary or secondary ABCs and malignant radiolucent lesions such as telangiectatic osteosarcoma? (3) What are the complications of CNB? (4) Is there any difference in the effectiveness or accuracy of CNB performed at outside institutions when compared with a referral center? METHODS: A retrospective study of our musculoskeletal tumor board pathology database (1990-2016) was performed using search criteria "aneurysmal bone cyst" or "telangiectatic osteosarcoma." Only patients undergoing a CNB who proceeded to definitive surgical resection with final pathology were included. Excluding outside CNBs, CNB was performed after presentation at a musculoskeletal tumor board as a result of atypical features on imaging or history concerning for malignancy. Outside CNB tissue was reviewed by our pathologists. If there was sufficient tissue for diagnosis, the patient proceeded to definitive surgery. If not, the patient underwent open biopsy. CNB diagnosis, open biopsy results, and open surgical resection pathology were reviewed. Complications, including bleeding, infection, nerve injury, readmission, or fracture, between the CNB and definitive open surgical procedure (mean 1.6 months) were documented. CNBs were considered "effective" if they yielded pathology considered sufficient to proceed with appropriate definitive surgery without additional open biopsy. CNBs were considered "accurate" if they were effective and yielded a pathologic diagnosis that matched the subsequent definitive surgical pathology. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of obtaining a malignant diagnosis using CNB were also calculated. RESULTS: A total of 81% (59 of 73) of CNBs were effective. Ninety-three percent (55 of 59) of CNBs were classified as accurate. Diagnostic CNBs had a sensitivity and specificity of 89% (eight of nine) and 100% (51 of 51), respectively. The PPV was 1.00 and the NPV was 0.82. There were no complications. With the numbers available, there was no difference in efficacy (90% [37 of 41 versus 14 of 15]; odds ratio, 0.97 [95% confidence interval {CI}, 0.41-2.27], p = 0.94) or accuracy (92% [34 of 37 versus 13 of 14]; odds ratio, 0.87 [95% CI, 0.08-9.16], p = 0.91) between CNBs performed in house and those referred from outside. CONCLUSIONS: These data suggest that CNBs are useful as an initial diagnostic test for ABC and telangiectatic osteosarcoma. Tissue from outside CNBs can be read reliably without repeat biopsy. If confirmed by other institutions, CNB may be considered a reasonable approach to the diagnosis of aggressive, radiolucent lesions of bone. LEVEL OF EVIDENCE: Level III, diagnostic study.

Cryogenic Preamplifiers for Magnetic Resonance Imaging.

Pursuing the ultimate limit of detection in magnetic resonance imaging (MRI) requires cryogenics to decrease the thermal noise of the electronic circuits. As cryogenic coils for MRI are slowly emerging cryogenic preamplifiers are required to fully exploit their potential. A cryogenic preamplifier operated at 77 K is designed and implemented for C imaging at 3 T (32.13 MHz), using off-the-shelves components. The design is based on a high electron mobility transistor (ATF54143) in a common source configuration. Required auxiliary circuitry for optimal cryogenic preamplifier performance is also presented consisting of a voltage regulator (noise free supply voltage and optimal power consumption), switch, and trigger (for active detuning during transmission to protect the preamplifier). A gain of 18 dB with a noise temperature of 13.7 K is achieved. Performing imaging experiments in a 3 T scanner showed an 8% increased signal-to-noise ratio from 365 to 399 when lowering the temperature of the preamplifier from 296 to 77 K while keeping the coil at room temperature. This paper thus enables the merger of cryogenic coils and preamplifiers in the hopes of reaching the ultimate limit of detection for MRI.

Long-term outcomes of cement in cement technique for revision endoprosthesis surgery.

BACKGROUND AND OBJECTIVE: Cemented endoprosthetic reconstruction after resection of primary bone sarcomas has been a standard-of-care option for decades. With increased patient survival, the incidence of failed endoprostheses requiring revision surgery has increased. Revision of cemented endoprotheses by cementing into the existing cement mantle (CiC) is technically demanding. METHODS: This is a retrospective review of our endoprosthesis database of 512 consecutive cemented endoprosthetic reconstructions performed for oncologic diagnoses between 1980 and 2014. A total of 54 implants (mean patient age 32 years, range 13-81) were revised with a CiC technique. Outcomes evaluated were prosthesis survival, revision surgery categorized according to the Henderson Failure Mode Classification, complications, and functional scores. RESULTS: Fifteen-year Kaplan-Meier survival rate was 34% for initial revision and 39% for subsequent revision implants. Mean revised Musculoskeletal Tumor Society (MSTS) Score was 27 at latest follow-up. Infection rate was 2%, 9%, and 13% for primary endoprostheses, initial revisions, and subsequent revisions, respectively. Limb salvage rate was 87%. CONCLUSIONS: At long-term follow up, endoprostheses revised with the CiC technique showed consistent 15-year survival from initial (34%) to subsequent (39%) revision. Despite a relatively high failure rate, these results are encouraging and demonstrate that this is a conservative, repeatable technique.

Single-Dose, Preoperative Vitamin-D Supplementation Decreases Infection in a Mouse Model of Periprosthetic Joint Infection.

BACKGROUND: Despite recent advances, infection remains the most common etiology of arthroplasty failure. Recent work suggests that 25-hydroxyvitamin D (25D) deficiency correlates with the frequency of periprosthetic joint infection (PJI). We endeavored to examine whether 25D3 deficiency leads to increased bacterial burden in vivo in an established mouse model of PJI and, if so, whether this effect can be reversed by preoperative 25D3 supplementation. METHODS: Mice (lys-EGFP) possessing fluorescent neutrophils were fed a vitamin D3-sufficient (n = 20) or deficient (n = 40) diet for 6 weeks. A group of 25D3-deficient mice (n = 20) were "rescued" with 1 intraperitoneal dose of 25D3 at 3 days before surgery. A stainless steel implant was inserted into the knee joint and the joint space was inoculated with bioluminescent Staphylococcus aureus (1 × 10 colony forming units [CFUs]). In vivo imaging was used to monitor bacterial burden and neutrophil infiltration. Blood was drawn to confirm 25D3 levels 3 days before surgery and on postoperative days (PODs) 0 and 14. Mice were killed at POD 21, and CFUs were quantified after culture. Myeloperoxidase (MPO) and ß-N-acetylglucosaminidase (NAG) were assayed to look at neutrophil infiltration and activated tissue macrophage recruitment, respectively. RESULTS: Serum values confirmed 25D3 deficiency and repletion of the 25D3-rescued group. Bacterial bioluminescence and neutrophil fluorescence were significantly greater (p < 0.05) in the 25D3-deficient group. CFU counts from the joint tissue and implant were also significantly greater in this group (p < 0.05). Rescue treatment significantly decreased bacterial burden and neutrophil infiltration (p < 0.05). Compared with the 25D3-sufficient and 25D3-rescued groups, MPO activity was higher (p < 0.02) and NAG activity was lower (p < 0.03) in the 25D3-deficient group. CONCLUSIONS: This study demonstrated in vivo in a mouse model of PJI that (1) 25D3 deficiency results in increased bacterial burden and neutrophil infiltration, and (2) this effect can be reversed with preoperative repletion of 25D3. CLINICAL RELEVANCE: Considering that >65% of patients undergoing arthroplasty have insufficient or low levels of total 25D and that 25D levels can be replenished with ease using a U.S. Food and Drug Administration (FDA)-approved, oral 25D3 product, 25D deficiency may be an important modifiable risk factor in humans undergoing joint replacement.

The Relationship Between OREF Grants and Future NIH Funding Success.

BACKGROUND: The Orthopaedic Research and Education Foundation (OREF) is the leading specialty-specific nongovernmental organization providing orthopaedic funding in the United States. As extramural research funding has become increasingly difficult to acquire, one mission of the OREF is to support investigators to generate data needed to secure larger extramural funding from agencies such as the National Institutes of Health (NIH). The objectives of this study were to evaluate the rate of translating OREF faculty-level grants into subsequent NIH funding and to determine if there are identifiable factors that increase the rate of converting an OREF grant into NIH funding. METHODS: This is a retrospective review of OREF grants awarded to full-time faculty orthopaedic surgeons between 1994 and 2014. Grants were analyzed on the basis of award type and were categorized as basic science, clinical, or epidemiological. Sex, individual scholarly productivity, and publication experience were evaluated. All awardees were assessed for subsequent NIH funding using the NIH RePORTER web site. RESULTS: One hundred and twenty-six faculty-level OREF grants were awarded to 121 individuals. Twenty-seven OREF grant awardees (22%) received NIH funding at a mean of 6.3 years after OREF funding. Nineteen (46%) of 41 Career Development Grant winners later received NIH funding compared with 10 (12%) of 85 other award winners. OREF grants for basic science projects were awarded more often (58%) and were more than 4 times as likely to result in NIH funding than non-basic science projects (odds ratio, 4.70 [95% confidence interval, 1.66 to 13.33]; p = 0.0036). Faculty who later received NIH funding had higher scholarly productivity and publication experience (p < 0.05). CONCLUSIONS: The OREF grant awardee conversion rate of 22% and, particularly, the 46% for Career Development Grant winners compares favorably with the overall NIH funding success rate (18% in 2014). Faculty-level OREF grants appear to achieve their purpose of identifying and supporting researchers who aim to secure subsequent federal funding. CLINICAL RELEVANCE: The goal of this study is to examine how successful faculty who have obtained OREF grants have been in securing NIH funding later in their careers. Although subsequent accrual of NIH funding is not the only goal of OREF funding, it can be used as an important benchmark to assess the development of orthopaedic clinician-scientists.

Improved costs and outcomes with conscious sedation vs general anesthesia in TAVR patients: Time to wake up?

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become a commonplace procedure for the treatment of aortic stenosis in higher risk surgical patients. With the high cost and steadily increasing number of patients receiving TAVR, emphasis has been placed on optimizing outcomes as well as resource utilization. Recently, studies have demonstrated the feasibility of conscious sedation in lieu of general anesthesia for TAVR. This study aimed to investigate the clinical as well as cost outcomes associated with conscious sedation in comparison to general anesthesia in TAVR. METHODS: Records for all adult patients undergoing TAVR at our institution between August 2012 and June 2016 were included using our institutional Society of Thoracic Surgeons (STS) and American College of Cardiology (ACC) registries. Cost data was gathered using the BIOME database. Patients were stratified into two groups according to whether they received general anesthesia (GA) or conscious sedation (CS) during the procedure. No-replacement propensity score matching was done using the validated STS predicted risk of mortality (PROM) as a propensity score. Primary outcome measure with survival to discharge and several secondary outcome measures were also included in analysis. According to our institution's data reporting guidelines, all cost data is presented as a percentage of the general anesthesia control group cost. RESULTS: Of the 231 patients initially identified, 225 (157 GA, 68 CS) were included for analysis. After no-replacement propensity score matching, 196 patients (147 GA, 49 CS) remained. Overall mortality was 1.5% in the matched population with a trend towards lower mortality in the CS group. Conscious sedation was associated with significantly fewer ICU hours (30 vs 96 hours, p = <0.001) and total hospital days (4.9 vs 10.4, p<0.001). Additionally, there was a 28% decrease in direct cost (p<0.001) as well as significant decreases in all individual all cost categories associated with the use of conscious sedation. There was no difference in composite major adverse events between groups. These trends remained on all subsequent subgroup analyses. CONCLUSION: Conscious sedation is emerging as a safe and viable option for anesthesia in patients undergoing transcatheter aortic valve replacement. The use of conscious sedation was not only associated with similar rates of adverse events, but also shortened ICU and overall hospital stays. Finally, there were significant decreases in all cost categories when compared to a propensity matched cohort receiving general anesthesia.

Combinatory antibiotic therapy increases rate of bacterial kill but not final outcome in a novel mouse model of Staphylococcus aureus spinal implant infection.

BACKGROUND: Management of spine implant infections (SII) are challenging. Explantation of infected spinal hardware can destabilize the spine, but retention can lead to cord compromise and biofilm formation, complicating management. While vancomycin monotherapy is commonly used, in vitro studies have shown reduced efficacy against biofilm compared to combination therapy with rifampin. Using an established in vivo mouse model of SII, we aim to evaluate whether combination therapy has increased efficacy compared to both vancomycin alone and infected controls. METHODS: An L-shaped, Kirschner-wire was transfixed into the L4 spinous process of 12-week-old C57BL/6 mice, and inoculated with bioluminescent Staphylococcus aureus. Mice were randomized into a vancomycin group, a combination group with vancomycin plus rifampin, or a control group receiving saline. Treatment began on post-operative day (POD) 7 and continued through POD 14. In vivo imaging was performed to monitor bioluminescence for 35 days. Colony-forming units (CFUs) were cultured on POD 35. RESULTS: Bioluminescence peaked around POD 7 for all groups. The combination group had a 10-fold decrease in signal by POD 10. The vancomycin and control groups reached similar levels on POD 17 and 21, respectively. On POD 25 the combination group dropped below baseline, but rebounded to the same level as the other groups, demonstrating a biofilm-associated infection by POD 35. Quantification of CFUs on POD 35 confirmed an ongoing infection in all three groups. CONCLUSIONS: Although both therapies were initially effective, they were not able to eliminate implant biofilm bacteria, resulting in a rebound infection after antibiotic cessation. This model shows, for the first time, why histologic-based, static assessments of antimicrobials can be misleading, and the importance of longitudinal tracking of infection. Future studies can use this model to test combinations of antibiotic therapies to see if they are more effective in eliminating biofilm prior to human trials.

Mid- to Long-Term Outcomes of Cervical Disc Arthroplasty versus Anterior Cervical Discectomy and Fusion for Treatment of Symptomatic Cervical Disc Disease: A Systematic Review and Meta-Analysis of Eight Prospective Randomized Controlled Trials.

PURPOSE: This study aimed to investigate the mid- to long-term outcomes of cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) for the treatment of 1-level or 2-level symptomatic cervical disc disease. METHODS: Medline, Embase, and the Cochrane Central Register of Controlled Trials databases were searched to identify relevant randomized controlled trials that reported mid- to long-term outcomes (at least 48 months) of CDA versus ACDF. All data were analyzed by Review Manager 5.3 software. The relative risk (RR) and 95% confidence intervals (CIs) were calculated for dichotomous variables. The weighted mean difference (WMD) and 95%CIs were calculated for continuous variables. A random effect model was used for heterogeneous data; otherwise, a fixed effect model was used. RESULTS: Eight prospective randomized controlled trials (RCTs) were retrieved in this meta-analysis, including 1317 and 1051 patients in CDA and ACDF groups, respectively. Patients after an ACDF had a significantly lower rate of follow-up than that after CDA. Pooled analysis showed patients in CDA group achieved significantly higher rates of overall success, Neck Disability Index (NDI) success, neurological success and significantly lower rates of implant/surgery-related serious adverse events and secondary procedure compared with that in ACDF group. The long-term functional outcomes (NDI, Visual Analog Scale (VAS) neck and arm pain scores, the Short Form 36 Health Survey physical component score (SF-36 PCS)), patient satisfaction and recommendation, and the incidence of superior adjacent segment degeneration also favored patients in CDA group with statistical difference. Regarding inferior adjacent segment degeneration, patients in CDA group had a lower rate without statistical significance. CONCLUSIONS: This meta-analysis showed that cervical disc arthroplasty was superior over anterior discectomy and fusion for the treatment of symptomatic cervical disc disease in terms of overall success, NDI success, neurological success, implant/surgery-related serious adverse events, secondary procedure, functional outcomes, patient satisfaction and recommendation, and superior adjacent segment degeneration.

Control of a Robotic Hand Using a Tongue Control System-A Prosthesis Application.

OBJECTIVE: The aim of this study was to investigate the feasibility of using an inductive tongue control system (ITCS) for controlling robotic/prosthetic hands and arms. METHODS: This study presents a novel dual modal control scheme for multigrasp robotic hands combining standard electromyogram (EMG) with the ITCS. The performance of the ITCS control scheme was evaluated in a comparative study. Ten healthy subjects used both the ITCS control scheme and a conventional EMG control scheme to complete grasping exercises with the IH1 Azzurra robotic hand implementing five grasps. Time to activate a desired function or grasp was used as the performance metric. RESULTS: Statistically significant differences were found when comparing the performance of the two control schemes. On average, the ITCS control scheme was 1.15 s faster than the EMG control scheme, corresponding to a 35.4% reduction in the activation time. The largest difference was for grasp 5 with a mean AT reduction of 45.3% (2.38 s). CONCLUSION: The findings indicate that using the ITCS control scheme could allow for faster activation of specific grasps or functions compared with a conventional EMG control scheme. SIGNIFICANCE: For transhumeral and especially bilateral amputees, the ITCS control scheme could have a significant impact on the prosthesis control. In addition, the ITCS would provide bilateral amputees with the additional advantage of environmental and computer control for which the ITCS was originally developed.

A comparative study of virtual hand prosthesis control using an inductive tongue control system.

This study compares the time required to activate a grasp or function of a hand prosthesis when using an electromyogram (EMG) based control scheme and when using a control scheme combining EMG and control signals from an inductive tongue control system (ITCS). Using a cross-over study design, 10 able-bodied subjects used a computer model of a hand and completed simulated grasping exercises. The time required to activate grasps was recorded and analyzed for both control schemes. End session mean activation times (ATs; seconds) for the EMG control scheme grasps 1 -5 were 0.80, 1.51, 1.95, 2.93, and 3.42; for the ITCS control scheme grasps 1 ‒5 they were 1.19, 1.89, 1.75, 2.26, and 1.80. Mean AT for grasps 1 and 2 was statistically significant in favor of the EMG control scheme (p = 0.030; p = 0.004). For grasp 3 no statistical significance occurred, and for grasps 4 and 5 there was a statistical significance in favour of the ITCS control scheme (p = 0.048; p = 0.004). Based on the amount of training and the achieved level of performance, it is concluded that the proposed ITCS control scheme can be used as a means of enhancing prosthesis control.

Fractal dimension of an intrinsically disordered protein: small-angle X-ray scattering and computational study of the bacteriophage λ N protein.

Small-angle X-ray scattering (SAXS) was used to characterize the bacteriophage λ N protein, a 107 residue intrinsically disordered protein (IDP) that functions as a transcriptional antitermination factor. The SAXS data were used to estimate both the average radius of gyration and the fractal dimension, a measure of the protein's internal scaling properties, under a variety of solution conditions. In the absence of denaturants, the radius of gyration was 38 ± 3.5 Å and the fractal dimension was 1.76 ± 0.05, slightly larger than the value predicted for a well-solvated polymer with excluded volume (1.7). Neither the radius of gyration nor the fractal dimension changed significantly on the addition of urea, further indicating that the protein is extensively unfolded and well solvated in the absence of denaturant. The addition of NaCl or D(2) O was found to promote aggregation, but did not appear to affect the properties of the monomeric form. The experimental SAXS profiles were also compared with those predicted by a computational model for a random-coil polypeptide, with an adjustable solvation energy term. The experimental data were well fit to the model with the solvation energy close to zero. These results indicate that the λ N protein is among the more expanded members of the broad class of IDPs, most likely because of its high content of charged residues and a large net charge (+15 at neutral pH). The expanded nature of the conformational ensemble may play a role in facilitating the interactions of the protein with other components of the dynamic transcriptional complex.

Effects of macromolecular crowding on an intrinsically disordered protein characterized by small-angle neutron scattering with contrast matching.

Small-angle neutron scattering was used to examine the effects of molecular crowding on an intrinsically disordered protein, the N protein of bacteriophage λ, in the presence of high concentrations of a small globular protein, bovine pancreatic trypsin inhibitor (BPTI). The N protein was labeled with deuterium, and the D(2)O concentration of the solvent was adjusted to eliminate the scattering contrast between the solvent and unlabeled BPTI, leaving only the scattering signal from the unfolded protein. The scattering profile observed in the absence of BPTI closely matched that predicted for an ensemble of random conformations. With BPTI added to a concentration of 65 mg/mL, there was a clear change in the scattering profile representing an increase in the mass fractal dimension of the unfolded protein, from 1.7 to 1.9, as expected if crowding favors more compact conformations. The crowding protein also inhibited aggregation of the unfolded protein. At 130 mg/mL BPTI, however, the fractal dimension was not significantly different from that measured at the lower concentration, contrary to the predictions of models that treat the unfolded conformations as convex particles. These results are reminiscent of the behavior of polymers in concentrated melts, suggesting that these synthetic mixtures may provide useful insights into the properties of unfolded proteins under crowding conditions.