Sema6D forward signaling impairs T cell activation and proliferation in head and neck cancer.

Immune checkpoint inhibitors (ICIs) are indicated for a diverse range of cancer types, and characterizing the tumor immune microenvironment is critical for optimizing therapeutic strategies, including ICIs. T cell infiltration and activation status in the tumor microenvironment greatly affects the efficacy of ICIs. Here, we show that semaphorin 6D (Sema6D) forward signaling, which is reportedly involved in coordinating the orientation of cell development and migration as a guidance factor, impaired the infiltration and activation of tumor-specific CD8+ T cells in murine oral tumors. Sema6D expressed by nonhematopoietic cells was responsible for this phenotype. Plexin-A4, a receptor for Sema6D, inhibited T cell infiltration and partially suppressed CD8+ T cell activation and proliferation induced by Sema6D stimulation. Moreover, mouse oral tumors, which are resistant to PD-1-blocking treatment in wild-type mice, showed a response to the treatment in Sema6d-KO mice. Finally, analyses of public data sets of human head and neck squamous cell carcinoma, pan-cancer cohorts, and a retrospective cohort study showed that SEMA6D was mainly expressed by nonhematopoietic cells such as cancer cells, and SEMA6D expression was significantly negatively correlated with CD8A, PDCD1, IFNG, and GZMB expression. Thus, targeting Sema6D forward signaling is a promising option for increasing ICI efficacy.

Staged Bilateral Total Hip Arthroplasty in a Patient With Larsen Syndrome.

Larsen syndrome is a rare genetic disorder characterized by weak connective tissues and various musculoskeletal abnormalities. This is a case report of a 39-year-old patient with Larsen syndrome who presented with over a decade of bilateral hip pain and difficulty ambulating. This patient has a prior history of bilateral congenital hip dislocations that were treated with open reduction and spica casting as a child with good result. Years later, she went on to develop bilateral hip osteoarthritis with significant remodeling of the proximal femur. The goal of this case presentation is to demonstrate the utility of total hip arthroplasty for this patient and discuss surgical challenges and considerations.

Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8+ T cell cytotoxicity and proliferation.

Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms in mice, although the role of human Sema4A in the tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non-small cell lung cancer (NSCLC) responded significantly better to anti-programmed cell death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly, SEMA4A expression in human NSCLC was mainly derived from tumor cells and was associated with T cell activation. Sema4A promoted cytotoxicity and proliferation of tumor-specific CD8+ T cells without terminal exhaustion by enhancing mammalian target of rapamycin complex 1 and polyamine synthesis, which led to improved efficacy of PD-1 inhibitors in murine models. Improved T cell activation by recombinant Sema4A was also confirmed using isolated tumor-infiltrating T cells from patients with cancer. Thus, Sema4A might be a promising therapeutic target and biomarker for predicting and promoting ICI efficacy.

Anatomical Engineering and 3D Printing for Surgery and Medical Devices: International Review and Future Exponential Innovations.

Three-dimensional printing (3DP) has recently gained importance in the medical industry, especially in surgical specialties. It uses different techniques and materials based on patients' needs, which allows bioprofessionals to design and develop unique pieces using medical imaging provided by computed tomography (CT) and magnetic resonance imaging (MRI). Therefore, the Department of Biology and Medicine and the Department of Physics and Engineering, at the Bioastronautics and Space Mechatronics Research Group, have managed and supervised an international cooperation study, in order to present a general review of the innovative surgical applications, focused on anatomical systems, such as the nervous and craniofacial system, cardiovascular system, digestive system, genitourinary system, and musculoskeletal system. Finally, the integration with augmented, mixed, virtual reality is analyzed to show the advantages of personalized treatments, taking into account the improvements for preoperative, intraoperative planning, and medical training. Also, this article explores the creation of devices and tools for space surgery to get better outcomes under changing gravity conditions.

Photoregulation of PRMT-1 Using a Photolabile Non-Canonical Amino Acid.

Protein methyltransferases are vital to the epigenetic modification of gene expression. Thus, obtaining a better understanding of and control over the regulation of these crucial proteins has significant implications for the study and treatment of numerous diseases. One ideal mechanism of protein regulation is the specific installation of a photolabile-protecting group through the use of photocaged non-canonical amino acids. Consequently, PRMT1 was caged at a key tyrosine residue with a nitrobenzyl-protected Schultz amino acid to modulate protein function. Subsequent irradiation with UV light removes the caging group and restores normal methyltransferase activity, facilitating the spatial and temporal control of PRMT1 activity. Ultimately, this caged PRMT1 affords the ability to better understand the protein's mechanism of action and potentially regulate the epigenetic impacts of this vital protein.

A small RNA regulates pprM, a modulator of pleiotropic proteins promoting DNA repair, in Deinococcus radiodurans under ionizing radiation.

Networks of transcriptional and post-transcriptional regulators are critical for bacterial survival and adaptation to environmental stressors. While transcriptional regulators provide rapid activation and/or repression of a wide-network of genes, post-transcriptional regulators, such as small RNAs (sRNAs), are also important to fine-tune gene expression. However, the mechanisms of sRNAs remain poorly understood, especially in less-studied bacteria. Deinococcus radiodurans is a gram-positive bacterium resistant to extreme levels of ionizing radiation (IR). Although multiple unique regulatory systems (e.g., the Radiation and Desiccation Response (RDR)) have been identified in this organism, the role of post-transcriptional regulators has not been characterized within the IR response. In this study, we have characterized an sRNA, PprS (formerly Dsr2), as a post-transcriptional coordinator of IR recovery in D. radiodurans. PprS showed differential expression specifically under IR and knockdown of PprS resulted in reduced survival and growth under IR, suggesting its importance in regulating post-radiation recovery. We determined a number of potential RNA targets involved in several pathways including translation and DNA repair. Specifically, we confirmed that PprS binds within the coding region to stabilize the pprM (DR_0907) transcript, a RDR modulator. Overall, these results are the first to present an additional layer of sRNA-based control in DNA repair pathways associated with bacterial radioresistance.

Onlay Patellofemoral Arthroplasty in Patients With Isolated Patellofemoral Arthritis: A Systematic Review.

BACKGROUND: Patellofemoral arthroplasty (PFA) for isolated patellofemoral osteoarthritis (OA) remains controversial due to variable postoperative outcomes and high failure rates. Second-generation (2G) onlay prostheses have been associated with improved postoperative outcomes. This systematic review was performed to assess the current overall survivorship and functional outcomes of 2G PFA. METHODS: A search was performed using PubMed, Cochrane Library, EMBASE, and Google Scholar. Thirty-three studies published in the last 15 years (2005-2020) were included; of these 22 studies reported patient-reported outcome measures. Operative and nonoperative complications were analyzed. Pooled statistical analysis was performed for survivorship and functional scores using Excel 2016 and Stata 13. RESULTS: The mean age of the patients was 59.7. When analyzing all studies, weighted survival at mean follow-up of 5.52 was 87.72%. Subanalysis of studies with minimum 5 years of follow up showed a survival of 94.24%. Fifteen studies reported Oxford Knee Score with a weighted mean postoperative Oxford Knee Score of 33.59. Mean American Knee Society Score pain was 79.7 while mean American Knee Society Score function was 79.3. The most common operative complication was OA progression for all implants. The percentage of revisions and conversions reported after analyzing all studies was 1.37% and 7.82% respectively. CONCLUSION: Safe and acceptable results of functional outcomes and PFA survivorship can result from 2G PFAs at both short and mid-term follow-up for patients with isolated patellofemoral OA. However, long-term follow-up outcomes are still pending for the newer implants. More extensive studies using standardized functional outcomes and long-term cost benefits should be evaluated.

Predictors of In-Hospital Ambulatory Status Following Low-Energy Hip Fracture Surgery.

Introduction: Twenty-five percent to seventy-five percent of independent patients do not walk independently after hip fracture (HF), and many patients experience functional loss. Early rehabilitation of functional status is associated with better long-term outcomes; however, predictors of early ambulation after HF have not been well described. Purposes: To assess the impact of perioperative and patient-specific variables on in-hospital ambulatory status following low-energy HF surgery. Methods: This is a retrospective analysis of 463 geriatric patients who required HF surgery at a metropolitan level-1 trauma center. The outcomes were time to transfer (out of bed to chair) and time to walk. Results: Three hundred ninety-two (84.7%) patients were able to transfer after surgery with a median time of 43.8 hours (quartile range: 24.7-53.69 hours), while 244 (52.7%) patients were able to walk with a median time of 50.86 hours (quartile range: 40.72-74.56 hours). Preinjury ambulators with aids (hazard ratio [HR]: 0.70, confidence interval [CI]: 0.50-0.99), age >80 years (HR: 0.66, CI: 0.52-0.84), peptic ulcer disease (HR: 0.57, CI: 0.57-0.82), depression (HR: 0.66, CI: 0.49- 0.89), time to surgery >24 hours (HR: 0.77, CI: 0.61-0.98), and surgery on Friday (HR: 0.73, CI: 0.56-0.95) were associated with delayed time to transfer. Delayed time to walk was observed in patients over 80 years old (HR: 0.74, CI: 0.56-0.98), females (HR: 0.67, CI: 0.48-0.94), peptic ulcer disease (HR: 0.23, CI: 0.84-0.66), and depression (HR: 0.51, CI: 0.33-0.77). Conclusions: Operative predictors of delayed time to transfer were surgery on Friday and time to surgery >24 hours after admission. Depression is associated with delayed time to transfer and time to walk. These data suggest that is important to perform surgeries within 24 hours of admission identify deficiencies in care during the weekends, and create rehabilitation programs specific for patient with depression. Improving functional rehabilitation after surgery may facilitate faster patient discharge, decrease inpatient care costs, and better long-term functional outcomes.

A Comparison Between Two Collagen Nerve Conduits and Nerve Autograft: A Rat Model of Motor Nerve Regeneration.

PURPOSE: To compare recovery in a rat model of sciatic nerve injury using a novel polyglycolic acid (PGA) conduit, which contains collagen fibers within the tube, as compared with both a hollow collagen conduit and nerve autograft. We hypothesize that a conduit with a scaffold will provide improved nerve regeneration over hollow conduits and demonstrate no significant differences when compared with autograft. METHODS: A total of 72 Sprague-Dawley rats were randomized into 3 experimental groups, in which a unilateral 10-mm sciatic defect was repaired using either nerve autograft, a hollow collagen conduit, or a PGA collagen-filled conduit. Outcomes were measured at 12 and 16 weeks after surgery, and included bilateral tibialis anterior muscle weight, voltage and force maximal contractility, assessment of ankle contracture, and nerve histology. RESULTS: In all groups, outcomes improved between 12 and 16 weeks. On average, the autograft group outperformed both conduit groups, and the hollow conduit demonstrated improved outcomes when compared with the PGA collagen-filled conduit. Differences in contractile force, however, were significant only at 12 weeks (autograft > hollow collagen conduit > PGA collagen-filled conduit). At 16 weeks, contractile force demonstrated no significant difference but corroborated the same absolute results (autograft > hollow collagen conduit > PGA collagen-filled conduit). CONCLUSIONS: Nerve repair using autograft provided superior motor nerve recovery over the 2 conduits for a 10-mm nerve gap in a murine acute transection injury model. The hollow collagen conduit demonstrated superior results when compared with the PGA collagen-filled conduit. CLINICAL RELEVANCE: The use of a hollow collagen conduit provides superior motor nerve recovery as compared with a PGA collagen-filled conduit.

Radiographic and Clinical Outcomes of Periprosthetic Distal Femur Fractures Treated With Open Reduction Internal Fixation.

OBJECTIVES: To report outcomes and complications of periprosthetic distal femur fractures (PPDFF) treated with open reduction internal fixation (ORIF) using a plate construct, with or without endosteal augmentation. DESIGN: Retrospective Case Series. SETTING: One Level I trauma center and one tertiary care hospital. PATIENTS/PARTICIPANTS: Forty patients with PPDFFs, treated by 3 surgeons, were identified using an institutional trauma registry. Thirty-two patients with 12 months of clinical and radiographic follow-up were included, and 8 patients were lost to follow-up before 12 months. INTERVENTION: All patients underwent ORIF of the PPDFF with lateral locked plating, and 11 received additional endosteal augmentation using allograft fibula. RESULTS: Thirty-two patients were available for the final follow-up. Ninety-four percent of patients achieved union at an average of 6.5 months postoperatively. Twenty-one percent of patients underwent subsequent surgery, with more than half of those being for removal of implants. Anatomic limb alignment was achieved in all cases (no malunions). Almost half of the patients required assistive devices for ambulation in the long term. CONCLUSIONS: ORIF of PPDFF with direct visualization using periarticular locking plates ± endosteal strut allograft resulted in a 94% union rate and no deep infections. There was no difference in outcomes between groups treated with or without additional endosteal fibular allograft. However, these are catastrophic injuries in frail patients, and 20% of patients either died or were lost to follow-up, and almost half required an assistive device for ambulation after surgery despite restoration of limb alignment. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Evaluation of two collagen conduits and autograft in rabbit sciatic nerve regeneration with quantitative magnetic resonance DTI, electrophysiology, and histology.

BACKGROUND: We compared different surgical techniques for nerve regeneration in a rabbit sciatic nerve gap model using magnetic resonance diffusion tensor imaging (DTI), electrophysiology, limb function, and histology. METHODS: A total of 24 male New Zealand white rabbits were randomized into three groups: autograft (n = 8), hollow conduit (n = 8), and collagen-filled conduit (n = 8). A 10-mm segment of the rabbit proximal sciatic nerve was cut, and autograft or collagen conduit was used to bridge the gap. DTI on a 3-T system was performed preoperatively and 13 weeks after surgery using the contralateral, nonoperated nerve as a control. RESULTS: Overall, autograft performed better compared with both conduit groups. Differences in axonal diameter were significant (autograft > hollow conduit > collagen-filled conduit) at 13 weeks (autograft vs. hollow conduit, p = 0.001, and hollow conduit vs. collagen-filled conduit, p < 0.001). Significant group differences were found for axial diffusivity but not for any of the other DTI metrics (autograft > hollow conduit > collagen-filled conduit) (autograft vs. hollow conduit, p = 0.001 and hollow conduit vs. collagen-filled conduit, p = 0.021). As compared with hollow conduit (autograft > collagen-filled conduit > hollow conduit), collagen-filled conduit animals demonstrated a nonsignificant increased maximum tetanic force. CONCLUSIONS: Autograft-treated rabbits demonstrated improved sciatic nerve regeneration compared with collagen-filled and hollow conduits as assessed by histologic, functional, and DTI parameters at 13 weeks.

Synthetic Biology of Small RNAs and Riboswitches.

In bacteria and archaea, small RNAs (sRNAs) regulate complex networks through antisense interactions with target mRNAs in trans, and riboswitches regulate gene expression in cis based on the ability to bind small-molecule ligands. Although our understanding and characterization of these two important regulatory RNA classes is far from complete, these RNA-based mechanisms have proven useful for a wide variety of synthetic biology applications. Besides classic and contemporary applications in the realm of metabolic engineering and orthogonal gene control, this review also covers newer applications of regulatory RNAs as biosensors, logic gates, and tools to determine RNA-RNA interactions. A separate section focuses on critical insights gained and challenges posed by fundamental studies of sRNAs and riboswitches that should aid future development of synthetic regulatory RNAs.

Osseous Vascularity of the Medial Elbow After Ulnar Collateral Ligament Reconstruction: A Comparison of the Docking and Modified Jobe Techniques.

BACKGROUND: Although vascularity plays a critical role in healing after ulnar collateral ligament (UCL) reconstruction, intraosseous blood flow to the medial epicondyle (ME) and sublime tubercle remains undefined. PURPOSE: To quantify vascular disruption caused by tunnel drilling with the modified Jobe and docking techniques for UCL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Eight matched pairs (16 specimens) of fresh-frozen cadaveric upper extremities were randomized to 1 of 2 study groups: docking technique or modified Jobe technique. One elbow in each pair underwent tunnel drilling by the assigned technique, while the contralateral elbow served as a control. Pregadolinium and postgadolinium magnetic resonance imaging were performed to quantify intraosseous vascularity within the ME, trochlea, and proximal ulna. Three-dimensional computed tomography (CT) and gross dissection were performed to assess terminal vessel integrity. RESULTS: Ulnar tunnel drilling had minimal impact on vascularity of the proximal ulna, with maintenance of >95% blood flow for each technique. Perfusion in the ME was reduced 14% (to 86% of baseline) for the docking technique and 60% (to 40% of baseline) for the modified Jobe technique (mean difference, 46%; P = .029). Three-dimensional CT and gross dissection revealed increased disruption of small perforating vessels of the posterior aspect of the ME for the modified Jobe technique. CONCLUSION: Although tunnel drilling in the sublime tubercle appears to have a minimal effect on intraosseous vascularity of the proximal ulna, both the docking and modified Jobe techniques reduce flow in the ME. This reduction was 4 times greater for the modified Jobe technique, and these findings have important implications for UCL reconstruction surgery. CLINICAL RELEVANCE: As the rate of revision UCL reconstructions continues to rise, investigation into causes for failure of primary surgery is needed. One potential cause is poor tendon-to-bone healing due to inadequate vascularity. This study quantifies the amount of vascular insult that is incurred in the ME during UCL reconstruction. While vascular insult is only one of many factors that affects the surgical success rate, surgeons performing this procedure should be mindful of this potential for vascular disruption.

Postoperative CT Is Superior for Acetabular Fracture Reduction Assessment and Reliably Predicts Hip Survivorship.

BACKGROUND: Postoperative pelvic radiographs are routinely used to assess acetabular fracture reduction. We compared radiographs and computed tomography (CT) with regard to their ability to detect residual fracture displacement. We also determined the association between the quality of reduction as assessed on CT and hip survivorship and identified risk factors for conversion to total hip arthroplasty (THA). METHODS: Patients were included in the study who had undergone acetabular fracture fixation between 1992 and 2012, who were followed for ≥2 years (or until early THA), and for whom radiographs and a pelvic CT scan were available. Residual displacement was measured on postoperative radiographs and CT and graded according to Matta's criteria (0 to 1 mm indicating anatomic reduction; 2 to 3 mm, imperfect reduction; and >3 mm, poor reduction) by observers who were blinded to patient outcome. Kaplan-Meier survivorship curves were plotted and log-rank tests were used to assess statistical differences in survivorship curves between adequate (anatomic or imperfect) and inadequate reductions on CT. Cox proportional hazard regression analysis was used to identify risk factors for conversion to THA. Two hundred and eleven patients were included. At mean of 9.0 years (standard deviation [SD], 5.6; median, 7.9; range, 0.5 to 23.3 years) postoperatively, 161 patients (76%) had retained their native hip. RESULTS: Compared with radiographs, CT showed worse reduction in 124 hips (59%), the same reduction in 79 (37%), and better reduction in 8 (4%). Of the 99 patients graded as having adequate reduction on CT, 10% underwent conversion to THA in comparison with 36% of those with inadequate reduction, and there was a significant difference between the survivorship curves (p < 0.001). Mean hip survivorship was shorter in patients ≥50 years of age (p < 0.001) and in those with an inadequate reduction on CT (p < 0.001). Independent risk factors for conversion to THA were age (hazard ratio [HR] = 4.46, 95% confidence interval [CI] = 2.07 to 9.62; p < 0.001), inadequate reduction (HR = 3.57, 95% CI = 1.71 to 7.45; p = 0.001), and posterior wall involvement (HR = 1.81, 95% CI = 1.00 to 3.26; p = 0.049). Sex, fracture type (elementary versus associated), and year of surgery did not influence hip survivorship. CONCLUSIONS: CT is superior to radiographs for detecting residual displacement after acetabular fracture fixation. Hip survivorship is greater in patients with adequate (anatomic or imperfect) reduction on CT. Along with older age and posterior wall involvement, an inadequate reduction on CT is a risk factor for conversion to THA. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Fluorescence Modulation of Green Fluorescent Protein Using Fluorinated Unnatural Amino Acids.

The ability to modulate protein function through minimal perturbations to amino acid structure represents an ideal mechanism to engineer optimized proteins. Due to the novel spectroscopic properties of green fluorescent protein, it has found widespread application as a reporter protein throughout the fields of biology and chemistry. Using site-specific amino acid mutagenesis, we have incorporated various fluorotyrosine residues directly into the fluorophore of the protein, altering the fluorescence and shifting the pKa of the phenolic proton associated with the fluorophore. Relative to wild type GFP, the fluorescence spectrum of the protein is altered with each additional fluorine atom, and the mutant GFPs have the potential to be employed as pH sensors due to the altered electronic properties of the fluorine atoms.

The Hip Fracture Patient on Warfarin: Evaluating Blood Loss and Time to Surgery.

OBJECTIVES: To compare blood loss, delay of surgery, and short-term adverse events in (1) patients admitted on warfarin versus nonanticoagulated controls and (2) warfarin patients with day of surgery (DOS) international normalized ratio (INR) of 1.5 or greater versus below 1.5. DESIGN: Retrospective cohort. SETTING: Academic Level I trauma center. PATIENTS/PARTICIPANTS: One hundred twenty four patients treated surgically for hip fractures including patients presenting on warfarin (n = 62) and matched controls (n = 62). INTERVENTION: Cephalomedullary nailing (CMN), hemiarthroplasty, or total hip arthroplasty. MAIN OUTCOME MEASURES: The primary outcome was transfusion rate. Secondary outcomes included calculated blood loss, 30-day complication rate, and hours from emergency department presentation to surgery. RESULTS: There was no significant difference in blood transfusion rates between the warfarin and control groups (P = 0.86). Blood transfusion was required in 58.1% of patients in the warfarin group (48.3% of arthroplasties and 65.5% of CMNs) compared with 56.6% of controls (41.9% of arthroplasties and 73.3% of CMNs). There were also no significant differences in calculated blood loss or in complication rates. Patients on warfarin had significantly longer time to surgery (P < 0.01). Subanalysis of the warfarin group showed that patients with DOS INR at or above 1.5 had similar transfusion rates, blood loss, and complications compared with patients with INR below 1.5. Treatment with CMN was the only covariate that was found to be a significant independent predictor of transfusion on multivariable analysis (P = 0.048). CONCLUSIONS: Patients with hip fractures admitted on warfarin seem to be at similar risk of transfusion or adverse events compared with nonanticoagulated patients. Awaiting normalization of INR delayed surgery without reducing bleeding or preventing complications. Within reason, surgeons may consider proceeding with surgery in patients with INR above 1.5 if patients are otherwise medically optimized. The upper limit above which surgery causes increased blood loss is currently unknown. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

A Genome-Wide Search for Ionizing-Radiation-Responsive Elements in Deinococcus radiodurans Reveals a Regulatory Role for the DNA Gyrase Subunit A Gene's 5' Untranslated Region in the Radiation and Desiccation Response.

Tight regulation of gene expression is important for the survival of Deinococcus radiodurans, a model bacterium of extreme stress resistance. Few studies have examined the use of regulatory RNAs as a possible contributing mechanism to ionizing radiation (IR) resistance, despite their proffered efficient and dynamic gene expression regulation under IR stress. This work presents a transcriptome-based approach for the identification of stress-responsive regulatory 5' untranslated region (5'-UTR) elements in D. radiodurans R1 that can be broadly applied to other bacteria. Using this platform and an in vivo fluorescence screen, we uncovered the presence of a radiation-responsive regulatory motif in the 5' UTR of the DNA gyrase subunit A gene. Additional screens under H2O2-induced oxidative stress revealed the specificity of the response of this element to IR stress. Further examination of the sequence revealed a regulatory motif of the radiation and desiccation response (RDR) in the 5' UTR that is necessary for the recovery of D. radiodurans from high doses of IR. Furthermore, we suggest that it is the preservation of predicted RNA structure, in addition to DNA sequence consensus of the motif, that permits this important regulatory ability.IMPORTANCEDeinococcus radiodurans is an extremely stress-resistant bacterium capable of tolerating up to 3,000 times more ionizing radiation than human cells. As an integral part of the stress response mechanism of this organism, we suspect that it maintains stringent control of gene expression. However, understanding of its regulatory pathways remains incomplete to date. Untranslated RNA elements have been demonstrated to play crucial roles in gene regulation throughout bacteria. In this work, we focus on searching for and characterizing responsive RNA elements under radiation stress and propose that multiple levels of gene regulation work simultaneously to enable this organism to efficiently recover from exposure to ionizing radiation. The model we propose serves as a generic template to investigate similar mechanisms of gene regulation under stress that have likely evolved in other bacterial species.

Nonunion After Clavicle Osteosynthesis: High Incidence of Propionibacterium acnes.

OBJECTIVE: The objective of this study was to review the etiology of clavicle nonunions after osteosynthesis and investigate the outcomes of a treatment with a single-stage revision. DESIGN: Retrospective case series. SETTING: Orthopaedic specialty hospital. PATIENTS: Twenty cases of nonunion after osteosynthesis of the clavicle were identified. The average age was 44 years (±13 years). In 9 cases, there was catastrophic implant failure that prompted the revision surgery. In the 18 cases in which cultures were taken, 15 of the 18 (83%) were treated as infections with a course of antibiotics. In 14 cases, the cultures were positive for Propionibacterium acnes. RESULTS: Fifteen patients were treated with a prolonged course of antibiotics. Eighteen patients had follow-up, and the average time to radiographic union was 22 weeks. There were no cases of nonunion after revision surgery. CONCLUSIONS: There is a high rate of positive cultures in cases of nonunion after osteosynthesis of the clavicle. This suggests the etiology of midshaft clavicle nonunions may result from a combination of suboptimal mechanical fixation and latent infection. Our treatment protocol of superior and anterior plating, interfragmentary fixation, bone grafting, and appropriate antimicrobial treatment of latent infections has resulted in 100% union rate. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The Role of Patient Characteristics on the Choice of Unicompartmental versus Total Knee Arthroplasty in Patients With Medial Osteoarthritis.

BACKGROUND: Medial unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) are both viable treatment options for medial osteoarthritis (OA). However, it remains unclear when to choose for which arthroplasty treatment. Goals of this study were therefore to (1) compare outcomes after both treatments and (2) assess which treatment has superior outcomes in different patient subgroups. METHODS: In this retrospective cohort study, 166 patients received the RESTORIS MCK Medial UKA and 63 patients the Vanguard TKA and were radiographically matched on isolated medial OA. Western Ontario and McMaster Universities Arthritis Index scores were collected preoperatively and postoperatively (mean: 3.0 years, range: 2.0-5.0 years). RESULTS: Preoperatively, no differences were observed, but medial UKA patients reported better functional outcomes than TKA (89.7 ± 13.6 vs 81.2 ± 18.0, P = .001) at follow-up.Better functional outcomes were noted after medial UKA in patients younger than age 70 years (89.5 ± 14.2 vs 78.6 ± 20.0, P = .001), with body mass index below 30 (90.3 ± 11.4 vs 83.6 ± 14.9, P = .005), with body mass index above 30 (88.3 ± 17.5 vs 78.8 ± 21.0, P = .034) and in females (90.6 ± 11.0 vs 78.1 ± 19.4, P = .001) when compared with TKA. No differences were found in males and older patients between both arthroplasties. CONCLUSION: Superior functional outcomes were noted after medial UKA over TKA in patients presenting with medial OA with these prostheses. Subgroup analyses suggest that medial UKA is the preferred treatment in younger patients and females while no differences were noted in older patients and males after medial UKA and TKA. This might help the orthopedic surgeon in individualizing arthroplasty treatment for patients with medial OA.