Treatment of osteochondral injuries of the humeral head using fresh osteochondral allograft transplantation.

Background: Large osteochondral lesions of the humeral head can result from locked posterior dislocations, avascular necrosis, and osteochondritis dissecans. Fresh osteochondral allograft (OCA) transplantation is a treatment option for young patients with focal osteochondral defects of the humeral head. The purpose of this case series was to assess graft survivorship, subjective patient-reported outcomes, and satisfaction among 7 patients who underwent OCA transplantation of the humeral head. Methods: We identified 7 patients who underwent humeral head OCA transplantation between 2008 and 2017. A custom questionnaire including the American Shoulder and Elbow Surgeons score, Quick Disabilities of the Arm, Shoulder, and Hand score (QuickDash), Likert satisfaction, and reoperations was mailed to each patient. Clinical failure was defined as further surgery that involved removal of the allograft. Results: Median follow-up duration was 10 years (range, 4.6 to 13.5 years) with a median age of 21.6 years (range, 18.5 to 43.5 years). Most patients (86%) reported improved function and reduced pain. At the final follow-up, 71% of patients reported ongoing problems with their shoulder including pain, stiffness, clicking/grinding, limited range of motion, and instability. Return to recreational activities was high at 86% but 43% expressed limitations with activity due to their shoulder. Overall satisfaction was high at 71% with mean American Shoulder and Elbow Surgeons and QuickDASH scores at 62.4 and 29.2, respectively. Reoperation after OCA occurred in 1 patient (14%). Conclusion: Among this case series of 7 patients who underwent OCA transplantation of the humeral head, patient satisfaction was high at 10-year follow-up and most returned to recreational activity although most also had persistent shoulder symptoms.

Development of Melioidosis Subunit Vaccines Using an Enzymatically Inactive Burkholderia pseudomallei AhpC.

Burkholderia pseudomallei, the causative agent of melioidosis, is a facultative intracellular, Gram-negative pathogen that is highly infectious via the respiratory route and can cause severe, debilitating, and often fatal diseases in humans and animals. At present, no licensed vaccines for immunization against this CDC Tier 1 select agent exist. Studies in our lab have previously demonstrated that subunit vaccine formulations consisting of a B. pseudomallei capsular polysaccharide (CPS)-based glycoconjugate (CPS-CRM197) combined with hemolysin-coregulated protein (Hcp1) provided C57BL/6 mice with high-level protection against an acute inhalational challenge of B. pseudomallei. In this study, we evaluated the immunogenicity and protective capacity of B. pseudomallei alkyl hydroperoxide reductase subunit C (AhpC) in combination with CPS-CRM197. AhpC is a peroxiredoxin involved in oxidative stress reduction and is a potential protective antigen. To facilitate our studies and maximize safety in animals, recombinant B. pseudomallei AhpC harboring an active site mutation (AhpCC57G) was expressed in Escherichia coli and purified using tandem nickel-cobalt affinity chromatography. Immunization of C57BL/6 mice with CPS-CRM197 combined with AhpCC57G stimulated high-titer IgG responses against the CPS component of the glycoconjugate as well as stimulated high-titer IgG and robust interferon gamma (IFN-γ)-, interleukin-5 (IL-5)-, and IL-17-secreting T cell responses against AhpCC57G. When challenged via an inhalational route with a high dose (~27 50% lethal doses [LD50s]) of B. pseudomallei, 70% of the immunized mice survived 35 days postchallenge. Collectively, our findings demonstrate that AhpCC57G is a potent activator of cellular and humoral immune responses and may be a promising candidate to include in future melioidosis subunit vaccines.

Establishing Task-Relevant MVC Protocols for Modelling Sustained Isometric Force Variability: A Manual Control Study.

The present study examined how prevalent methods for determining maximal voluntary contraction (MVC) impact the experimentally derived functions of graded force-force variability. Thirty-two young healthy subjects performed continuous isometric force tracking (20 s trials) at 10 target percentages (5-95% MVC) normalized to a conventional discrete-point (n = 16), or sustained (n = 16) MVC calculation. Distinct rates and magnitudes of change were observed for absolute variability (standard deviation (SD), root mean squared error (RMSE)), tracking error (RMSE, constant error (CE)), and complexity (detrended fluctuation analysis (DFA)) (all p < 0.05) of graded force fluctuations between the MVC groups. Differential performance strategies were observed beyond ~65% MVC, with the discrete-point group minimizing their SD at force values below that of the criterion target (higher CE/RMSE). Moreover, the sustained group's capacity to minimize SD/RMSE/CE corresponded to a more complex structure in their force fluctuations. These findings reveal that the time component of MVC estimation has a direct influence on the corrective strategies supporting near-maximal manual force control. While discrete MVC protocols predominate in the study of manual strength/endurance/precision, a 1:1 MVC-task mapping appears more to be ecologically valid if visuo-motor precision outcomes are of central importance.

Predicting toxins found in toxin-antitoxin systems with a role in host-induced Burkholderia pseudomallei persistence.

Burkholderia pseudomallei (Bpm) is a bacterial pathogen that causes Melioidosis, a disease with up to 40% mortality and an infection relapse of 15-23% despite antibiotic treatment. Ineffective clearance of Bpm by antibiotics is believed to be due to persistence, a hibernation-like survival mechanism modulated, in part, by toxin-antitoxin systems (TAS). Several organisms possess a repertoire of TASs but defining environmental cues eliciting their activity is hindered by laborious in vitro experiments, especially when there are many toxins with redundant function. Here, we identified which of 103 proteins in Bpm that share features found in toxins of the TAS and repurposed transcriptional data to identify which ones play a role in surviving intracellular host defenses. Putative toxins with the strongest transcriptional response were found to have low conservation between Bpm strains, while toxins that were constitutively expressed were highly conserved. Further examination of highly conserved toxins BPSS0899, BPSS1321, and BPSL1494 showed that they were functional, and their mutation led to reduce survival within macrophages and reduced in vivo persistence-associated pathology (abscesses) during treatment, but did not affect macrophages persistence. These findings highlight the utility of a data-driven approach to select putative toxins and suggests a selective role for some TAS in host survival.