Performance in a Simulated Virtual Reality Anterior Cervical Discectomy and Fusion Task: Disc Residual, Rate of Removal, and Efficiency Analyses.

BACKGROUND AND OBJECTIVES: Anterior cervical discectomy and fusion (ACDF) is among the most common spine procedures. The Sim-Ortho virtual reality simulator platform contains a validated ACDF simulated task for performance assessment. This study aims to develop a methodology to extract three-dimensional data and reconstruct and quantitate specific simulated disc tissues to generate novel metrics to analyze performance metrics of skilled and less skilled participants. METHODS: We used open-source platforms to develop a methodology to extract three-dimensional information from ACDF simulation data. Metrics generated included, efficiency index, disc volumes removed from defined regions, and rate of tissue removal from superficial, central, and deep disc regions. A pilot study was performed to assess the utility of this methodology to assess expertise during the ACDF simulated procedure. RESULTS: The system outlined, extracts data allowing the development of a methodology which accurately reconstructs and quantitates 3-dimensional disc volumes. In the pilot study, data sets from 27 participants, divided into postresident, resident, and medical student groups, allowed assessment of multiple novel metrics, including efficiency index (surgical time spent in actively removing disc), where the postresident group spent 61.8% of their time compared with 53% and 30.2% for the resident and medical student groups, respectively ( P = .01). During the annulotomy component, the postresident group removed 47.4% more disc than the resident groups and 102% more than the medical student groups ( P = .03). CONCLUSION: The methodology developed in this study generates novel surgical procedural metrics from 3-dimensional data generated by virtual reality simulators and can be used to assess surgical performance.

Evaluation of Mycobacterium avium subsp. paratuberculosis isocitrate lyase (IcL) and ABC transporter (BacA) knockout mutants as vaccine candidates.

There has been little success in controlling Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis, due to suboptimal diagnostics and the ineffectiveness of available vaccines. By knocking out BacA and IcL, genes required for MAP survival in dairy calves, two live-attenuated vaccine candidates were created. This study evaluated the host-specific attenuation of MAP IcL and BacA mutants in mouse and calf models, as well as the elicited immune responses. Deletion mutants were generated in MAP strain A1-157 through specialized transduction and found viable in vitro. First, the mutants' attenuation and elicited cytokine secretion were assessed in a mouse model, 3 weeks after intraperitoneal inoculation with MAP strains. Later, vaccine strains were assessed in a natural host infection model where calves received 109CFU oral dose of MAP wild-type or mutant strains at 2 weeks old. Transcription levels of cytokines in PBMCs were evaluated at 12-, 14-, and 16-weeks post-inoculation (WPI) and MAP colonization in tissue was assessed at 4.5 months after inoculation. Whereas both vaccine candidates colonized mouse tissues similarly to wild-type strain, both failed to persist in calf tissues. In either mouse or calf models, gene deletion did not reduce immunogenicity. Instead, inoculation with ΔBacA induced a greater upregulation of proinflammatory cytokines than ΔIcL and wild-type in both models and a greater expansion of cytotoxic and memory T-cells than uninfected control in calves. ΔBacA and wild-type strains significantly increased secretion of IP-10, MIG, TNFα, and RANTES in mice serum compared to uninfected control. This agreed with upregulation of IL-12, IL-17, and TNFα in calves inoculated with ΔBacA at all time points. The ΔBacA also gave rise to greater populations of CD4+CD45RO+, and CD8+ cells than uninfected control calves at 16 WPI. Low survival rate of MAP in macrophages co-incubated with PBMCs isolated from the ΔBacA group indicated that these cell populations are capable of killing MAP. Overall, the immune response elicited by ΔBacA is stronger compared to ΔIcL and it is maintained over two different models and over time in calves. Further investigation is warranted to evaluate the BacA mutant's protection against MAP infection as a live attenuated vaccine candidate.

Povidone-iodine irrigation reduces infection after total hip and knee arthroplasty.

INTRODUCTION: One of the most important challenges faced by orthopedic surgeons is periprosthetic joint infection (PJI). PJI is a common cause for total joint arthroplasty failure with an incidence of 0.3-1.9%. PJI can be devastating for the patient and extremely costly for the healthcare system. There is concern that a major cause of PJI is intra-operative colonization and recent studies have shown a decrease in PJI with the use of dilute povidone-iodine (Betadine®, Avrio Health L.P, Stamford, CT) irrigation prior to wound closure. This study presents our experience with the use of dilute Betadine® irrigation prior to wound closure and its effect on our post-operative hip and knee arthroplasty acute infection rate. MATERIALS AND METHODS: Retrospective chart review performed at our hospital looking at PJI amongst patients who underwent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) between 2013 and 2017 comparing different irrigation methods (n = 3232). The study group (n = 1207) underwent irrigation prior to wound closure with dilute Betadine for 3 min and the control group (n = 1511) underwent irrigation using normal saline (NS). RESULTS: Using a logistic regression model where the following variables were adjusted for; ASA, age, sex, foley insertion, surgical duration and diabetes mellitus status a statistical significant reduction was seen in any infection (OR 0.45 [0.22; 0.89], p value < 0.05) and SSI (OR 0.30 [0.13; 0.70], p value 0.01) with the Betadine group. No significant reduction was seen with deep infections with the Betadine group compared to the NS group. CONCLUSION: PJI is a devastating complication following total joint arthroplasty and we found Betadine compared to NS irrigation provides an inexpensive and simple method to lower any PJI and more specifically SSI in THA and TKA. LEVEL OF EVIDENCE: III.

Oral vaccination stimulates neutrophil functionality and exerts protection in a Mycobacterium avium subsp. paratuberculosis infection model.

Mycobacterium avium subsp. paratuberculosis (Map) causes paratuberculosis (PTB), a granulomatous enteritis in ruminants that exerts high economic impact on the dairy industry worldwide. Current vaccines have shown to be cost-effective against Map and in some cases confer beneficial non-specific effects against other pathogens suggesting the existence of trained immunity. Although Map infection is mainly transmitted by the fecal-oral route, oral vaccination has not been deeply studied. Therefore, the aim of this study was to compare the oral route with a set of mycobacterial and non-mycobacterial vaccines with a subcutaneously administered commercially available vaccine. Training effects on polymorphonuclear neutrophils (PMNs) and homologous and heterologous in vivo protection against Map were investigated in the rabbit infection model. Oral vaccination with inactivated or live vaccines was able to activate mucosal immunity as seen by elevation of serum IgA and the expression of IL4 in peripheral blood mononuclear cells (PBMCs). In addition, peripheral PMN phagocytosis against Map was enhanced by vaccination and extracellular trap release against Map and non-related pathogens was modified by both, vaccination and Map-challenge, indicating trained immunity. Finally, PBMCs from vaccinated animals stimulated in vitro with Map antigens showed a rapid innate activation cytokine profile. In conclusion, our data show that oral vaccination against PTB can stimulate neutrophil activity and both innate and adaptive immune responses that correlate with protection.

Operating Room Educational Environment in Canada: Perceptions of Surgical Residents.

OBJECTIVE: The educational experience in operating rooms (OR) plays a central role in the transformation of a trainee into a surgeon. As Canadian residency programs transition to competency-based medical education, and since most surgical competencies are attained in the OR, we investigated the perceptions of Canadian surgical residents about their OR learning environment. DESIGN: Cross-sectional, national survey. SETTING: An online questionnaire, including the validated 40-item operating room educational environment measure (OREEM) inventory, was sent to residency programs of all surgical specialties in Canada. The OREEM assesses the trainees' perceptions of the "trainer and training," "learning opportunities," "atmosphere in the operating room," "supervision, workload, and support," Each individual item was rated using a 5-point Likert scale ranging from "strongly disagree" (scores 1) to "strongly agree" (scores 5). The mean score of each individual item was measured, and the mean scores of each subscale and an overall score of the questions were also measured. PARTICIPANTS: Surgical residents in Canada. RESULTS: Four hundred thirty residents were included for final analysis. The overall mean OREEM score was 3.72 ± 0.4. "Atmosphere in the OR" was the subscale with the highest mean score (3.87 ± 0.5), while "supervision, workload, and support" had the lowest subscale mean score (3.49 ± 0.5). The overall OREEM mean score for junior and senior residents was 3.67 ± 0.4 and 3.80 ± 0.4, respectively (p = 0.001). No significant differences were seen in the mean OREEM score between males and females or different surgical programs. Nevertheless, general surgery had the lowest "supervision, workload, and support" subscale score (3.27 ± 0.5; p < 0.001). CONCLUSIONS: The overall educational environment in OR may be considered satisfactory as perceived by Canadian surgical residents; however, several areas for potential improvement are identified and suggestions for optimizing the learning environment are described.

X-ray diffraction and in situ pressurization of dentine apatite reveals nanocrystal modulus stiffening upon carbonate removal.

Bone-like materials comprise carbonated-hydroxyapatite nanocrystals (c-Ap) embedding a fibrillar collagen matrix. The mineral particles stiffen the nanocomposite by tight attachment to the protein fibrils creating a high strength and toughness material. The nanometer dimensions of c-Ap crystals make it very challenging to measure their mechanical properties. Mineral in bony tissues such as dentine contains 2~6 wt.% carbonate with possibly different elastic properties as compared with crystalline hydroxyapatite. Here we determine strain in biogenic apatite nanocrystals by directly measuring atomic deformation in pig dentine before and after removing carbonate. Transmission electron microscopy revealed the platy 3D morphology while atom probe tomography revealed carbon inside the calcium rich domains. High-energy X-ray diffraction in combination with in situ hydrostatic pressurization quantified reversible c-Ap deformations. Crystal strains differed between annealed and ashed (decarbonated) samples, following 1 or 10 h heating at 250 °C or 550 °C respectively. Measured bulk moduli (K) and a-/c-lattice deformation ratios (η) were used to generate synthetic Ksyn and ηsyn identifying the most likely elastic constants C33 and C13 for c-Ap. These were then used to calculate the nanoparticle elastic moduli. For ashed samples, we find an average E11=107 GPa and E33 =128 GPa corresponding to ~5% and ~17% stiffening of the a-/c-axes of the nanocrystals as compared with the biogenic nanocrystals in annealed samples. Ashed samples exhibit ~10% lower Poisson's ratios as compared with the 0.25~0.36 range of carbonated apatite. Carbonate in c-Ap may therefore serve for tuning local deformability within bony tissues. STATEMENT OF SIGNIFICANCE: Carbonated apatite nanoparticles, typical for bony tissues, stiffen the network of collagen fibrils. However, it is not known if the biogenic apatite mechanical (elastic) properties differ from those of geologic mineral counterparts. Indeed the tiny dimensions and variable carbonate composition may have strong effects on deformation resistance. The present study provides experimental measurements of the elastic constants which we use to estimate Young's moduli and Poisson's ratio values. Comparison between ashed and annealed dentine samples quantifies the properties of both carbonated and decarbonated apatite nanocrystals. The results reveal fundamental attributes of bony mineral and showcase the additive advantages of combining X-ray diffraction with in situ hydrostatic compression, backed by atom probe and transmission electron microscopy tomography.

Inducing cellular immune responses with a marked Mycobacterium avium subsp. paratuberculosis strain in dairy calves.

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne's disease, a chronic granulomatous enteritis with a high global prevalence in dairy cattle. This disease causes significant economic loss in the dairy industry and has been challenging to control, as current diagnostic assays are low in sensitivity and specificity, and previously developed vaccines do not prevent infection and face regulatory concerns due to interference with bovine tuberculosis diagnostics. To remediate this issue, positive and negative immune markers were created in a MAP strain as a step towards a vaccine capable of differentiating infected from vaccinated animals (DIVA). A gene coding for an immunogenic protein (MAP1693c) in the MAP genome was replaced with a library of epitope-tagged immunogenic genes (pepA) via a stable allelic exchange method. These markers were evaluated in a calf infection trial, where Holstein-Friesian dairy calves were inoculated at two weeks of age with either the marked strain or the parent strain, or remained uninfected controls. Cellular immune responses to the markers were measured using an interferon gamma release assay (IGRA). There were no MAP1693c marker-specific differences in cellular immune responses between infection groups. A scrambled version of the HA (human influenza hemagglutinin) epitope, but not the actual HA epitope, induced a significant IFN-γ response in marker-infected calves compared to WT-infected and uninfected groups at 4.5 months post-inoculation. This scrambled HA epitope thus holds potential as a diagnostic tool as part of a DIVA vaccine for Johne's disease.

Identification of collagen fibrils in cross sections of bone by electron energy loss spectroscopy (EELS).

Transmission electron microscopic (TEM) images of ion-milled bovid cortical bone cut approximately normal to the axes of fibrils show that mineral occurs in the form of plates surrounding and laying between circular or elliptical features about 50 nm in diameter. The classification of these features as either pores or collagen fibrils is highly debated. Electron energy loss spectroscopy (EELS) mapping of these features in ion milled sections shows that they are lacking significant amounts of mineral or collagen, although their appearance suggests that they are cross sections of collagen fibrils. However, analogous sections prepared using an ultramicrotome show that, while these circular features show reduced concentrations of calcium and phosphorus, some of them contain quantities of carbon and nitrogen in bonding states comparable to the composition of collagen. This work demonstrates that the observed circular features are sections of collagen fibrils, but that bombardment by argon ions during broad beam ion milling destroys the collagen and associated gap-zone mineral.

Disparities in hepatitis C virus infection screening among Baby Boomers in the United States.

BACKGROUND: The study objective was to identify potential sociodemographic disparities in hepatitis C virus (HCV) infection screening among Baby Boomers in the United States. METHODS: We analyzed cross-sectional data from the 2013-2016 National Health Interview Survey. The outcome was whether a person had an HCV infection screening (yes/no). Key independent variables were race/ethnicity, geographic region, poverty level, education level, and health insurance status. Multivariate logistic regression was performed to examine the factors associated with the receipt of HCV screening. RESULTS: The study sample included a total of 41,914 United States Baby Boomers, who represented a population size of 69,554,339. In 2016, the HCV screening rate among Baby Boomers was 13.9%. In the multivariate logistic regression, we found that Asians had 27% lower odds of receiving an HCV screening compared to Blacks (odds ratio [OR] = 0.74, P = .02). People who lived in the Northeast, South, and West had a higher likelihood of having an HCV screening than those who lived in the Midwest (OR = 1.33, 1.39, and 1.69, respectively; all P values <.001). Additionally, people with less education, lower income, and private health insurance were significantly less likely to have an HCV screening. CONCLUSION: Future studies or interventions are needed to target these disadvantaged populations to improve HCV screening in Baby Boomers.

Investigation of the ZNF804A gene polymorphism with genetic risk for bipolar disorder in attention deficit hyperactivity disorder.

BACKGROUND: Genome-wide association studies (GWAS) have been conducted on many psychiatric disorders. Evidence from large GWAS indicates that the single nucleotide polymorphism (SNP) rs1344706 in the zinc-finger protein 804A gene (ZNF804A) is associated with psychotic disorders including bipolar disorder and schizophrenia. One study also found significant association between rs1344706 and the executive control network of attention. In this study we examine the role of the rs1344706 polymorphism that previously showed association with BD and is known to alter expression of the gene in two clinical family-based ADHD samples from the UK and Taiwan. FINDINGS: To investigate the association between rs1344706 and ADHD, two family samples of ADHD probands from the United Kingdom (n = 180) and Taiwan (n = 212) were genotyped using TaqMan SNP genotyping assays and analysed using within-family transmission disequilibrium test. No significant associations were found between rs1344706 polymorphism and ADHD in either of the samples from Taiwan (P = 0.91) and UK (P = 0.41). Even combining the two datasets together the A allele of rs1344706 SNP was still not significantly over-transmitted to affected probands (P = 0.50). Furthermore, there was no evidence of association with the specific symptoms subgroups of inattention or hyperactivity-impulsivity. CONCLUSIONS: In this study we used family-based ADHD data in the UK and Taiwanese population to test for an association between rs1344706 SNP in the ZNF804A gene and ADHD. Results showed no significant association of rs1344706 with ADHD in UK and Taiwanese samples.