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Objectives The authors had a unique opportunity to study the early impacts of occupational and recreational exposures on the development of noise-induced hearing loss (NIHL) in a cohort of 392 young workers. The objectives of this study were to estimate strength of associations between occupational and recreational exposures and occurrence of early-stage NIHL and to determine the extent to which relationships between specific noise exposures and early-stage NIHL were mitigated through the use of hearing protection. Methods Participants were young adults who agreed to participate in a follow-up of a randomised controlled trial. While the follow-up study was designed to observe long-term effects (up to 16 years) of a hearing conservation intervention for high school students, it also provided opportunity to study the potential aetiology of NIHL in this worker cohort. Study data were collected via exposure history questionnaires and clinical audiometric examinations. Results Over the 16-year study period, the authors documented changes to hearing acuity that exceeded 15 dB at high frequencies in 42.8% of men and 27.7% of women. Analyses of risk factors for NIHL were limited to men, who comprised 68% of the cohort, and showed that risks increased in association with higher levels of the most common recreational and occupational noise sources, as well as chemical exposures with ototoxic potential. Use of hearing protection and other safety measures, although not universal and sometimes modest, appeared to offer some protection. Conclusions Early-stage NIHL can be detected in young workers by measuring high-frequency changes in hearing acuity. Hearing conservation programmes should focus on a broader range of exposures, whether in occupational or non-occupational settings. Priority exposures include gunshots, chainsaws, power tools, smoking and potentially some chemical exposures. [ABSTRACT FROM AUTHOR]

Background and purpose The outcome of modern resurfacing remains to be determined. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) started collection of data on hip resurfacing at a time when modern resurfacing was started in Australia. The rate of resurfacing has been higher in Australia than in many other countries. As a result, the AOANJRR has one of the largest series of resurfacing procedures. This study was undertaken to determine the results of this series and the risk factors associated with revision. Patients and methods Data from the AOANJRR were used to analyze the survivorship of 12,093 primary resurfacing hip replacements reported to the Joint Replacement Registry between September 1999 and December 2008. This was compared to the results of primary conventional total hip replacement reported during the same period. The Kaplan-Meier method and proportional hazards models were used to determine risk factors such as age, sex, femoral component size, primary diagnosis, and implant design. Results Female patients had a higher revision rate than males; however, after adjusting for head size, the revision rates were similar. Prostheses with head sizes of less than 50 mm had a higher revision rate than those with head sizes of 50 mm or more. At 8 years, the cumulative per cent revision of hip resurfacing was 5.3 (4.6-6.2), as compared to 4.0 (3.8-4.2) for total hip replacement. However, in osteoarthritis patients aged less than 55 years with head sizes of 50 mm or more, the 7-year cumulative per cent revision for hip resurfacing was 3.0 (2.2-4.2). Also, hips with dysplasia and some implant designs had an increased risk of revision. Interpretation Risk factors for revision of resurfacing were older patients, smaller femoral head size, patients with developmental dysplasia, and certain implant designs. These results highlight the importance of patient and prosthesis selection in optimizing the outcome of hip resurfacing. [ABSTRACT FROM AUTHOR]

There is a growing debate about the question of equity of access to hospice and palliative care services. Even countries with relatively well developed palliative care systems are considered to have problems of access and inequity of provision. Despite these concerns, we still lack a relevant evidence base to serve as a guide to action. We present an analysis of access to adult hospice inpatient provision in the north-west region of England that employs Geographical Information Systems (GIS). Measures of the possible demand for, and supply of, hospice inpatient services are used to determine the potential accessibility of cancer patients, assessed at the level of small areas (electoral wards). Further, the use of deprivation scores permits an analysis of the equity of access to adult inpatient hospice care, leading to the identification of areas where additional service provision may be warranted. Our research is subject to a number of caveats - it is limited to inpatient hospice provision and does not include other kinds of inpatient and community-based palliative care services. Likewise, we recognise that not everyone with cancer will require palliative care and also that palliative care needs exist among those with nonmalignant conditions. Nevertheless, our methodology is one that can also be applied more generally. [ABSTRACT FROM AUTHOR]

Background: The management of the patella in total knee arthroplasty is still problematic. We aimed to identify differences in the clinical outcome of total knee arthroplasty according to whether or not patellar resurfacing had been performed in a prospective, randomized study of 220 osteoarthritic knees.Methods: Two hundred and twenty total knee arthroplasties in 201 patients were randomly assigned to be performed with either resurfacing or retention of the patella, and the results were followed for a mean of forty-eight months (range, thirty-six to seventy-nine months) in a double-blind (both patient and clinical evaluator blinded), prospective study. Evaluation was performed annually by an independent observer and consisted of assessment with the Knee Society clinical rating system, specific evaluation of anterior knee pain, a stair-climbing test, and radiographic examination.Results: Fifteen (12%) of the 128 knees without patellar resurfacing and nine (10%) of the ninety-two knees with patellar resurfacing underwent a revision or another type of reoperation related to the patellofemoral articulation. This difference was not significant (chi square with one degree of freedom = 0.206, p = 0.650). At the time of the latest follow-up, there was a significantly higher incidence of anterior pain (chi square with one degree of freedom = 5.757, p = 0.016) in the knees that had not had patellar resurfacing.Conclusions: Patients who underwent patellar resurfacing had superior clinical results in terms of anterior knee pain and stair descent. However, anterior knee pain still occurred in patients with patellar resurfacing, and nine (10%) of the ninety-two patients in that group underwent a revision or another type of reoperation involving the patellofemoral joint. Weight but not body mass index was associated with the development of anterior knee pain in the patients without patellar resurfacing, a finding that suggests that patellofemoral dysfunction may be a function of joint loading rather than obesity. [ABSTRACT FROM AUTHOR]

This paper presents the results of an intervention programme designed to promote the communication skills of a group of children with moderate learning difficulties. Thirty children were involved in a 12-week programme of supported peer-communication activities which aimed to improve the children's regulatory skills during peer interaction. By the end of the programme, the children were talking more, asking more appropriate questions and responding to ambiguous utterances more effectively. The results of the study demonstrate that a programme for children with learning difficulties in which pairs of children working together are encouraged to use and reflect on regulatory strategies can provide an effective context for intervention. [ABSTRACT FROM AUTHOR]

The oculocephalic response (OCR) is a simple office maneuver that assesses the vestibulo-ocular reflex (VOR). An abnormal response is manifested clinically as refixation saccades following a rapid horizontal head movement. Because little attention has been given to the OCR in the literature, a prospective study was undertaken with 112 consecutive patients who presented with dizziness and underwent OCR testing followed by caloric evaluation. Agreement was good between the OCR and caloric evaluation (kappa = 0.44). Specificity was quite high (97%); sensitivity was found to be less (39%). Positive (68%) and negative (90%) predictive values of the OCR illustrate that the clinician can often anticipate the results of caloric testing based on this response. This easily performed test of the VOR is a useful tool in the evaluation of the dizzy patient. [ABSTRACT FROM AUTHOR]

This study addressed the question of whether shear and tensile loads applied 15 minutes after bonding metal brackets to enamel affected the shear/peel bond strength of the adhesive. Ninety standard 0.022-inch stainless steel edgewise premolar mesh-backed brackets were bonded using a no-mix chemical-cured adhesive to 90 teeth, which had been prepared in a standardized manner. After 15 minutes three groups of 30 teeth were subjected to the following regimes: no applied load, tensile static load of 0.77 N (78 g), and shear static load of 0.77 N. After 14 days storage in 100 per cent relative humidity at 37°C, the shear/peel strength of the adhesive bond was measured using a purpose built jig mounted on a universal testing machine. Shear/peel bond strengths were analysed using Weibull statistics. The Weibull moduli of the three groups indicated that the adhesive performed consistently despite early static loading. Characteristic strengths were 9.22, 9.27, and 9.05 MPa for the control, tensile, and shear groups, respectively. The findings indicate that static loads (such as tying in or archwires) can be placed on brackets 15 minutes after cementation, without a clinically significant reduction in bond strength of the tested adhesive. [ABSTRACT FROM AUTHOR]

BACKGROUND: Progressive weight-bearing is recommended following autologous chondrocyte implantation. This weight-bearing program assumes that increasing external loads experienced at the foot during gait are closely related to external-knee-joint moments. We investigated this relationship, and examined other variables that may contribute to knee-joint kinetics of which the clinician can modify using practical instruction within a clinical setting. METHODS: Gait analysis was performed in 51 patients following autologous chondrocyte implantation, during various partial- and full-weight-bearing conditions. The contribution of ground-reaction force, kinematic and spatio-temporal gait parameters to external-knee moments was investigated within weight-bearing levels less than 60%, between 60% and 90% and more than 90% of individual body weight. FINDINGS: There was no association between peak-ground-reaction force and the knee-adduction moment within the 60-90% and more than 90% weight-bearing conditions, nor the peak-knee-flexion moment at less than 60% weight-bearing. Peak-ground-reaction force accounted for no more than 21.4% and 18.6% of the variance in the knee-adduction and flexion moments, respectively, within any weight-bearing condition, while the combination of peak-ground-reaction force, kinematic and spatio-temporal parameters investigated accounted for no more than 39.7% and 52.2%, respectively. Foot-progression angle and knee-flexion during weight acceptance accounted for a significant (P<0.05) portion of the variance in external-knee moments, particularly at higher levels of weight-bearing. INTERPRETATION: A large amount of variance in knee moments may be attributed to variables other than external loads, some of which can be modified by the clinician. Clinically, this is important for any therapist implementing progressive weight-bearing protocols. [ABSTRACT FROM AUTHOR]

Abstract: Previous published research has shown promising results with flexion splinting post total knee arthroplasty. Before instituting this practice, we conducted a randomised controlled trial to confirm any benefits over splinting in extension. Five patients were recruited into the trial. 5 were excluded. The flexion group consisted of 49 patients who had their knee placed in 70° of flexion over an inactive CPM machine for 24 h post operation. The extension group consisted of 46 patients who were splinted in full extension for the first 24 h post operation. We assessed post-operative day 1 drain volume, haemoglobin and haematocrit, blood transfusions, duration of inpatient stay, range of motion and complications within 6 weeks of surgery. There was no significant difference between the two groups among any of the outcomes measured. As such, we have been unable to demonstrate any benefit with splintage in flexion post total knee arthroplasty and have not adopted it as part of our post-operative management. [Copyright &y& Elsevier]

Objective Extensive WHO collaborative studies were performed to evaluate the suitability of transgenic mice susceptible to poliovirus (TgPVR mice, strain 21, bred and provided by the Central Institute for Experimental Animals, Japan) as an alternative to monkeys in the neurovirulence test (NVT) of oral poliovirus vaccine (OPV). Methods Nine laboratories participated in the collaborative study on testing neurovirulence of 94 preparations of OPV and vaccine derivatives of all three serotypes in TgPVR21 mice. Findings Statistical analysis of the data demonstrated that the TgPVR21 mouse NVT was of comparable sensitivity and reproducibility to the conventional WHO NVT in simians. A statistical model for acceptance/rejection of OPV lots in the mouse test was developed, validated, and shown to be suitable for all three vaccine types. The assessment of the transgenic mouse NVT is based on clinical evaluation of paralysed mice. Unlike the monkey NVT, histological examination of central nervous system tissue of each mouse offered no advantage over careful and detailed clinical observation. Conclusions Based on data from the collaborative studies the WHO Expert Committee for Biological Standardization approved the mouse NVT as an alternative to the monkey test for all three OPV types and defined a standard implementation process for laboratories that wish to use the test. This represents the first successful introduction of transgenic animals into control of biologicals. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic had extensive influence on dental education. UK dental schools were compelled to respond with substantial adaptations to clinical training approaches and environments to mitigate educational impact., Materials and Methods: The Surveying Pandemic Education Response in Higher Education Dental Schools (SPEARHEAD) study aimed to retrospectively evaluate the diverse responses of UK dental schools to the COVID-19 pandemic. All UK dental schools were invited to participate in semi-structured interviews to ascertain institutional responses, with transcripts subjected to thematic framework analysis., Results and Discussion: Ten UK dental schools contributed to the study and three main themes were identified: student education, environment, and procedures and equipment. The most common approach to student education was the reduction of student numbers in clinical areas; however, this increased supervisory demands. While there was widespread acknowledgement of the need for enhanced ventilation, implementing the necessary modifications was frequently constrained by building configurations and financial implications. Numerous procedural adjustments were implemented, accompanied by widespread adoption of enhanced personal protective equipment. Fallow periods were common, although differing durations underscored the need for data-driven guidance. Many schools transitioned towards electric speed-controlled handpieces, but the need to reflect real-world scenarios often led to a reversion to air turbines., Conclusion: UK dental schools showed initiative, resilience, and ingenuity in safeguarding students from enduring irretrievable educational setbacks amidst the challenges posed by the COVID-19 pandemic. Validating a data-driven strategy for addressing future threats would facilitate a unified response, minimising the educational repercussions and bolstering the resilience of dental training., (© 2024 The Author(s). European Journal of Dental Education published by John Wiley & Sons Ltd.)

Emotional experiences often evoke neural plasticity that supports adaptive changes in behavior, including maladaptive plasticity associated with mood and substance use disorders. These adaptations are supported in part by experience-dependent activation of immediate-early response genes, such as Npas4 (neuronal PAS domain protein 4). Here we show that a conserved long noncoding enhancer RNA (lnc-eRNA), transcribed from an activity-sensitive enhancer, produces DNA:RNA hybrid R-loop structures that support three-dimensional chromatin looping between enhancer and proximal promoter and rapid Npas4 gene induction. Furthermore, in mouse models, Npas4 lnc-eRNA and its R-loop are required for the development of behavioral adaptations produced by chronic psychosocial stress or cocaine exposure, revealing a potential role for this regulatory mechanism in the transmission of emotional experiences.

Powerful associations that link drugs of abuse with cues in the drug-paired environment often serve as prepotent relapse triggers. Drug-associated contexts and cues activate ensembles of nucleus accumbens (NAc) neurons, including D1-class medium spiny neurons (MSNs) that typically promote, and D2-class MSNs that typically oppose, drug seeking. We found that in mice, cocaine conditioning upregulated transiently the activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), in a small subset of NAc neurons. The NPAS4+ NAc ensemble was required for cocaine conditioned place preference. We also observed that NPAS4 functions within NAc D2-, but not D1-, MSNs to support cocaine-context associations and cue-induced cocaine, but not sucrose, seeking. Together, our data show that the NPAS4+ ensemble of NAc neurons is essential for cocaine-context associations in mice, and that NPAS4 itself functions in NAc D2-MSNs to support cocaine-context associations by suppressing drug-induced counteradaptations that oppose relapse-related behaviour., (© 2024. The Author(s).)

Repeated cocaine use produces adaptations in brain function that contribute to long-lasting behaviors associated with cocaine use disorder (CUD). In rodents, the activity-regulated cytoskeleton-associated protein (Arc) can regulate glutamatergic synaptic transmission, and cocaine regulates Arc expression and subcellular localization in multiple brain regions, including the nucleus accumbens (NAc)-a brain region linked to CUD-related behavior. We show here that repeated, non-contingent cocaine administration in global Arc KO male mice produced a dramatic hypersensitization of cocaine locomotor responses and drug experience-dependent sensitization of conditioned place preference (CPP). In contrast to the global Arc KO mice, viral-mediated reduction of Arc in the adult male, but not female, NAc (shArc NAc ) reduced both CPP and cocaine-induced locomotor activity, but without altering basal miniature or evoked glutamatergic synaptic transmission. Interestingly, cell type-specific knockdown of Arc in D1 dopamine receptor-expressing NAc neurons reduced cocaine-induced locomotor sensitization, but not cocaine CPP; whereas, Arc knockdown in D2 dopamine receptor-expressing NAc neurons reduced cocaine CPP, but not cocaine-induced locomotion. Taken together, our findings reveal that global, developmental loss of Arc produces hypersensitized cocaine responses; however, these effects cannot be explained by Arc's function in the adult mouse NAc since Arc is required in a cell type- and sex-specific manner to support cocaine-context associations and locomotor responses., (© 2024 The Author(s). Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in the treatment of knee cartilage defects, although limited research is available on its longer term (≥10 years) sustainability in the patellofemoral joint., Purpose: To report the clinical and radiological outcomes at ≥10 years in a prospectively recruited cohort of patients undergoing MACI in the patellofemoral joint and compare outcomes in patients undergoing MACI on the patella versus the trochlea., Study Design: Case series; Level of evidence, 4., Methods: The current study prospectively enrolled 95 patients who underwent patellofemoral MACI, of whom 29 (13 patella, 16 trochlea) underwent concomitant tibial tubercle osteotomy. Patients were assessed preoperatively and at 2, 5, and ≥10 years using a range of patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score, the 36-item Short Form Health Survey, and the frequency and severity of knee pain as well as patient satisfaction, full active knee flexion and extension, and peak isokinetic knee extensor and flexor torques. High-resolution magnetic resonance imaging (MRI) was performed to assess pertinent graft parameters, as well as determine an overall MRI composite score, per the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results were analyzed according to the graft location (patella or trochlea)., Results: Of the 95 patients recruited, 82 patients (41 patella, 41 trochlea) were available for a clinical review at ≥10 years after surgery (mean follow-up, 11.9 years [range, 10-15 years]). For the whole patellofemoral MACI cohort, all PROMs significantly improved over time ( P < .05), with no significant changes ( P > .05) observed in any MRI-based score from 2 to ≥10 years after surgery. At ≥10 years, 90.2% (n = 74) were satisfied with MACI in relieving their knee pain, and 85.4% (n = 70) were satisfied with the improvement in their ability to participate in sports. No differences ( P > .05) were observed in PROMs between those undergoing patellar MACI and those undergoing trochlear MACI, although a significant group effect was observed for limb symmetry indices of knee extensor ( P = .009) and flexor ( P = .041) strength, which were greater in those undergoing patellar (vs trochlear) MACI. No statistically significant differences ( P > .05) were observed between patellar and trochlear grafts on any MRI-based measure. In the cohort assessed at ≥10 years after surgery, 4 patients (2 patella, 2 trochlea) demonstrated graft failure on MRI scans, although a further 3 patients (all trochlea) were omitted from the ≥10-year review for having already progressed to total knee arthroplasty., Conclusion: Good clinical scores, high levels of patient satisfaction, and adequate graft survivorship were observed at ≥10 years after MACI on the patella and trochlea., Competing Interests: Presented as a poster at the annual meeting of the AOSSM, Denver, Colorado, July 2024.One or more of the authors has declared the following potential conflict of interest or source of funding: This research has received funding from the National Health and Medical Research Council (ID254622 and ID1003452) and an independent research grant from Vericel that assisted with later-stage follow-up of patients. G.C.J. owns shares in Orthocell. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Childhood and adolescent stress increase the risk of postpartum depression (PPD), often providing an increased probability of treatment refractoriness. Nevertheless, the mechanisms linking childhood/adolescent stress to PPD remain unclear. Our study investigated the longitudinal effects of adolescent stress on the hypothalamic-pituitary-adrenal (HPA) axis and postpartum behaviors in mice and humans. Adolescent social isolation prolonged glucocorticoid elevation, leading to long-lasting postpartum behavioral changes in female mice. These changes were unresponsive to current PPD treatments but improved with post-delivery glucocorticoid receptor antagonist treatment. Childhood/adolescent stress significantly impacted HPA axis dysregulation and PPD in human females. Repurposing glucocorticoid receptor antagonists for some cases of treatment-resistant PPD may be considered., Competing Interests: Competing Interests Statement The authors declare no competing interests.

Background: Long-term outcomes in larger cohorts after matrix-induced autologous chondrocyte implantation (MACI) are required. Furthermore, little is known about the longer-term clinical and radiological outcomes of MACI performed in the tibiofemoral versus patellofemoral knee joint., Purpose: To present the 10-year clinical and radiological outcomes in patients after MACI and compare outcomes in patients undergoing tibiofemoral versus patellofemoral MACI., Study Design: Case series; Level of evidence, 4., Methods: Between September 2002 and December 2012, 204 patients who underwent MACI were prospectively registered into a research program and assessed preoperatively and at 2, 5, and 10 years postoperatively. Of these patients, 168 were available for clinical review at 10 years, with 151 (of a total of 182) grafts also assessed via magnetic resonance imaging (MRI). Patients were evaluated using the Knee injury and Osteoarthritis Outcome Score, a visual analog scale for pain frequency and severity, satisfaction, and peak isokinetic knee extensor and flexor strength. Limb symmetry indices (LSIs) were calculated for strength measures. Grafts were scored on MRI scans via the MOCART (magnetic resonance observation of cartilage repair tissue) system, with a focus on tissue infill and an overall MRI graft composite score., Results: All patient-reported outcome measures improved ( P < .0001) up to 2 years after surgery. Apart from the significant increase ( P = .004) in the peak isokinetic knee extensor LSI, no other patient-reported outcome measure or clinical score had changed significantly from 2 to 10 years. At the final follow-up, 92% of patients were satisfied with MACI to provide knee pain relief, with 76% satisfied with their ability to participate in sports. From 2 to 10 years, no significant change was seen for any MRI-based MOCART variable nor the overall MRI composite score. Of the 151 grafts reviewed via MRI at 10 years, 14 (9.3%) had failed, defined by graft delamination or no graft tissue on MRI scan. Furthermore, of the 36 patients (of the prospectively recruited 204) who were not available for longer-term review, 7 had already proceeded to total knee arthroplasty, and 1 patient had undergone secondary MACI at the same medial femoral condylar site because of an earlier graft failure. Therefore, 22 patients (10.8%) essentially had graft failure over the period. At the final follow-up, patients who underwent MACI in the tibiofemoral (vs patellofemoral) joint reported significantly better Knee injury and Osteoarthritis Outcome Score subscale scores for Quality of Life ( P = .010) and Sport and Recreation ( P < .001), as well as a greater knee extensor strength LSI ( P = .002). Even though the tibiofemoral group demonstrated better 10-year MOCART scores for tissue infill ( P = .027), there were no other MRI-based differences ( P > .05)., Conclusion: This study reports the long-term review of a prospective series of patients undergoing MACI, demonstrating good clinical scores, high levels of patient satisfaction, and acceptable graft survivorship at 10 years. Patients undergoing tibiofemoral (vs patellofemoral) MACI reported better long-term clinical outcomes, despite largely similar MRI-based outcomes., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This research has received some funding from the National Health and Medical Research Council (ID254622 and ID1003452) and the Hollywood Private Hospital Research Foundation (RF31 and RF050). This research was approved by the Hollywood Private Hospital (HPH145) Human Research Ethics Committee. J.R.E. has received support for education and research support from Vericel. G.C.J. has shares in Orthocell. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

While there is a lot of emphasis on the need for good infection prevention and control practices and acute care, the increasing complexity of patients being cared for in their own homes means that there is an increased risk for infection. Good practice is required by community nurses to minimise this risk. Patients' own homes can present particular challenges in complying with good practice and this article looks at some of the barriers to optimum infection prevention and control precautions in this setting.

A growing body of evidence exists supporting the role that genetic variation plays in athletic performance and injury. This study sought to identify genetic variants associated with performance and lower limb musculoskeletal injury in a high-level athletic cohort. A total of 126 Estonian National Team members (Olympic athletes and participants of International Championships) (104 males, 82.5%) underwent a genome-wide association analysis between 2017 and 2018, to identify single-nucleotide polymorphisms (SNPs) associated with performance and/or injury. The athletic cohort was stratified within each sport based on performance and whether they were a medalist ( n  = 29) or not ( n  = 97), whether they sustained an injury ( n  = 47) or not ( n  = 79), and the type of injury (patella tendinopathy n  = 22, Achilles tendinopathy n  = 17, hamstring injury n  = 3, anterior cruciate ligament rupture n  = 6). Three SNPs demonstrated strong genome-wide association with athletic performance (podium/medalist versus not), including DSG1 (rs10502567, OR 14.3) and DSG4 (rs73410248, OR 17.4), while 76 SNPs demonstrated suggestive significance. Overall, 37 SNPs gave genome-wide suggestive association with any type of injury, including PAPPA2 (rs11580456, OR 13.8) and MAS1 (rs220735, rs170219, OR 3.1) which demonstrated positive signal with multiple SNPs. Several genes demonstrated positive association for the specific injury types, including COL22A1 (rs3924862) and PLXNA2 (rs11799530), as well as PAPPA2 (rs11580456), DOK5 (rs73142922), GNG12 (rs28435277), and DAP (rs267959, rs2930047, rs1080440, rs267939). The current study identified genetic variants associated with high-level athletic performance and musculoskeletal injury. Further work is required to permit integration of this and future knowledge into individualized training practices, as well as injury mitigation and rehabilitation programs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To assess the marginal and internal misfit of endocrowns fabricated from a resin matrix ceramic (CS), a partially crystallized (EMC), and a fully crystallized (ILS) lithium disilicate glass-ceramic., Methods and Materials: Thirty human premolar teeth restored with endocrowns were investigated. Three CAD/CAM materials were used (n=10 per group): CS, EMC, and ILS. Two-dimensional (2D) analysis of marginal and internal misfit was performed on micro-computed tomography scans before and after adhesive bonding. Further, three-dimensional (3D) analysis was performed to determine the total internal volume discrepancy. Surface roughness of the fitting surfaces of endocrowns was characterized using optical profilometry and scanning electron microscopy., Results: Adhesive bonding did not significantly affect marginal or internal misfit (p≥0.093). Differences in marginal misfit among the experimental groups were not statistically significant (p≥0.221). However, differences in 2D internal misfit were statistically significant; the CS group exhibited the largest internal misfit (p=0.001), while no significant difference was found between other groups (p=0.123). The largest discrepancies were observed at the pulpal floor and cervical region of all investigated specimens. No statistically significant difference was found in 3D misfit between ILS and EMC groups (p=0.711); however both exhibited statistically lower 3D misfit values compared to the CS group (p≤0.037). ILS endocrowns exhibited the smoothest and most homogenous fitting surface profile (p<0.001). However, there was no significant correlation between 2D internal misfit and the surface roughness (p≥0.082)., Conclusions: The choice of CAD/CAM material may influence the fitting accuracy of endocrowns. The investigated lithium disilicate glass-ceramics conferred superior internal fit for endocrowns compared to resin matrix ceramic., (© Operative Dentistry, 2023.)

This study assessed the impact of increased speed of high-speed contra-angle handpieces (HSCAHs) on the aerosolization of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surrogate virus and any concomitant thermal impact on dental pulp. A bacteriophage phantom-head model was used for bioaerosol detection. Crown preparations were performed with an NSK Z95L Contra-Angle 1:5 (HSCAH-A) and a Bien Air Contra-Angle 1:5 Nova Micro Series (HSCAH-B) at speeds of 60,000, 100,000, and 200,000 revolutions per minute (rpm), with no air coolant. Bioaerosol dispersal was measured with Φ6-bacteriophage settle plates, air sampling, and particle counters. Heating of the internal walls of the pulp chambers during crown preparation was assessed with an infrared camera with HSCAH-A and HSCAH-B at 200,000 rpm (water flows ≈15 mL min -1 and ≈30 mL min -1 ) and an air-turbine control (≈23.5 mL min -1 ) and correlated with remaining tissue thickness measurements. Minimal bacteriophage was detected on settle or air samples with no notable differences observed between handpieces or speeds ( P > 0.05). At all speeds, maximum settled aerosol and average air detection was 1.00 plaque-forming units (pfu) and 0.08 pfu/m 3 , respectively. Irrespective of water flow rate or handpiece, both maximum temperature (41.5°C) and temperature difference (5.5°C) thresholds for pulpal health were exceeded more frequently with reduced tissue thickness. Moderate and strong negative correlations were observed based on Pearson's correlation coefficient, between remaining dentine thickness and either differential ( r = -0.588) or maximum temperature ( r = -0.629) measurements, respectively. Overall, HSCAH-B generated more thermal energy and exceeded more temperature thresholds compared to HSCAH-A. HSCAHs without air coolant operating at speeds of 200,000 rpm did not increase bioaerosolization in the dental surgery. Thermal risk is variable, dependent on handpiece design and remaining dentine thickness.

The development of ligands for biological targets is critically dependent on the identification of sites on proteins that bind molecules with high affinity. A set of compounds, called FragLites, can identify such sites, along with the interactions required to gain affinity, by X-ray crystallography. We demonstrate the utility of FragLites in mapping the binding sites of bromodomain proteins BRD4 and ATAD2 and demonstrate that FragLite mapping is comparable to a full fragment screen in identifying ligand binding sites and key interactions. We extend the FragLite set with analogous compounds derived from amino acids (termed PepLites) that mimic the interactions of peptides. The output of the FragLite maps is shown to enable the development of ligands with leadlike potency. This work establishes the use of FragLite and PepLite screening at an early stage in ligand discovery allowing the rapid assessment of tractability of protein targets and informing downstream hit-finding.

Purpose: To report 10-year outcomes and survivorship in patients undergoing bicompartmental knee arthroplasty (BCKA) using the Journey-Deuce prosthesis in a consecutive prospective case series., Methods: Between November 2006 and November 2009, 41 patients with a mean age of 69.6 years (range 51-86) underwent 51 bicompartmental knee arthroplasties with the Journey-Deuce knee prosthesis. All patients presented with symptomatic medial and patellofemoral compartment osteoarthritis, with intact cruciate ligaments and a preserved lateral compartment on plain radiographs and Magnetic Resonance Imaging. Clinical assessment was undertaken pre-surgery and at 1, 2, 5 and 10 years post-surgery using the Oxford Knee Score (OKS), EuroQol Group 5-Dimension self-reported questionnaire (EQ-5D) and maximal active range of motion (ROM)., Results: 30 patients (37 knees) were followed-up at a mean time of 11.4 years (SD 1.1; range 10.5-14.0). Eight patients (ten knees) were deceased and three could not be contacted at final review. No major component revision was performed. Pre-operative OKS 25.4 (SD 5.2; range 15-40), knee flexion 116.4° (SD 10.3°; range 100°-140°) and EQ-5D 70.5 (SD 19.9; range 25-95). 10-year OKS 43.5 (SD 4.1; range 32-48), knee flexion 127.3° (SD 11.1°; range 105°-144°) and EQ-5D 77.4 (SD 9.3; range 60-100). The OKS (p < 0.0001), EQ-5D (p = 0.024) and active knee flexion ROM (p < 0.0001) all significantly improved from pre-surgery to 1-year post-surgery, with no further significant changes in these scores between any post-operative time period up until 10 years. 32% (7/22) of tibial and 45% (10/22) of femoral components showed progressive radiolucencies between 2 and 5-year and 10-year follow-up., Conclusions: This is the largest cohort of patients having undergone BCKA (with the Journey-Deuce prosthesis) with longest follow-up described in the literature. At 10 years, patients presented with significantly improved clinical outcomes, comparable to other surgical arthroplasty options. No major component revision was performed. Progressive radiolucencies were noted in 32% of tibial and 45% of femoral components without corresponding clinical signs of loosening., Level of Evidence: Level III., (© 2021. Crown.)

Purpose: For real-world evidence, it is convenient to use routinely collected data from the electronic medical record (EMR) to measure survival outcomes. However, patients can become lost to follow-up, causing incomplete data and biased survival time estimates. We quantified this issue for patients with metastatic cancer seen in an academic health system by comparing survival estimates from EMR data only and from EMR data combined with high-quality cancer registry data., Materials and Methods: Patients diagnosed with metastatic cancer from 2008 to 2014 were included in this retrospective study. Patients who were diagnosed with cancer or received their initial treatment within our system were included in the institutional cancer registry and this study. Overall survival was calculated using the Kaplan-Meier method. Survival curves were generated in two ways: using EMR follow-up data alone and using EMR data supplemented with data from the Stanford Cancer Registry/California Cancer Registry., Results: Four thousand seventy-seven patients were included. The median follow-up using EMR + Cancer Registry data was 19.9 months, and the median follow-up in surviving patients was 67.6 months. There were 1,301 deaths recorded in the EMR and 3,140 deaths recorded in the Cancer Registry. The median overall survival from the date of cancer diagnosis using EMR data was 58.7 months (95% CI, 54.2 to 63.2); using EMR + Cancer Registry data, it was 20.8 months (95% CI, 19.6 to 22.3). A similar pattern was seen using the date of first systemic therapy or date of first hospital admission as the baseline date., Conclusion: Using EMR data alone, survival time was overestimated compared with EMR + Cancer Registry data.

Background: Total hip arthroplasty (THA) is common though the investigation of new prostheses requires a practical, step-wise introduction. This study reports the 2-year clinical results and periprosthetic bone mineral density (BMD) changes, along with a subset undergoing Radiostereometric analysis (RSA), in patients undergoing primary cemented THA using a new highly polished, double tapered, collarless femoral stem (Absolut)., Methods: Between August 2013 and December 2016, 47 patients with a mean age of 74.2 years (range 36-89) underwent 51 THAs with the Absolut. All patients underwent clinical assessment pre-surgery and at 6 weeks, 3, 12 and 24 months using the Oxford and Harris Hip Scores, as well as Dual Energy X-ray Absorptiometry (DEXA) to assess BMD within 2-4 weeks post-surgery, 12 and 24 months. RSA was undertaken in a patient subset (the first n = 30) early post-surgery (1-2 days) and 3, 12 and 24 months., Results: All clinical scores significantly improved (p < 0.05). RSA revealed a mean subsidence of 0.78 mm at 3 months, 1.23 mm at 12 months and 1.51 mm at 24 months. Anterior-posterior and medial-lateral translation was negligible. A significant increase (p = 0.020) in BMD was observed in Gruen zone 1, though no significant changes were observed for any other zone up until 2 years. Two patients acquired an early post-operative deep vein thrombosis that were treated accordingly and resolved, with no further complications or re-operations., Conclusion: The Absolut cemented femoral stem demonstrated good outcomes, BMD changes consistent with sound prosthesis integration and patterns of post-operative micromotion observed in other successful cemented stems., (© 2022 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

The fast degradation of collagen-based membranes in the biological environment remains a critical challenge, resulting in underperforming Guided Bone Regeneration (GBR) therapy leading to compromised clinical results. Photoactive atelocollagen (AC) systems functionalised with ethylenically unsaturated monomers, such as 4-vinylbenzyl chloride (4VBC), have been shown to generate mechanically competent materials for wound healing, inflammation control and drug delivery, whereby control of the molecular architecture of the AC network is key. Building on this platform, the sequential functionalisation with 4VBC and methacrylic anhydride (MA) was hypothesised to generate UV-cured AC hydrogels with reduced swelling ratio, increased proteolytic stability and barrier functionality for GBR therapy. The sequentially functionalised atelocollagen precursor (SAP) was characterised via TNBS and ninhydrin colourimetric assays, circular dichroism and UV-curing rheometry, which confirmed nearly complete consumption of collagen's primary amino groups, preserved triple helices and fast (< 180 s) gelation kinetics, respectively. Hydrogel's swelling ratio and compression modulus were adjusted depending on the aqueous environment used for UV-curing, whilst the sequential functionalisation of AC successfully generated hydrogels with superior proteolytic stability in vitro compared to both 4VBC-functionalised control and the commercial dental membrane Bio-Gide®. These in vitro results were confirmed in vivo via both subcutaneous implantation and a proof-of-concept study in a GBR calvarial model, indicating integrity of the hydrogel and barrier defect, as well as tissue formation following 1-month implantation in rats. STATEMENT OF SIGNIFICANCE: Collagen-based membranes remain a key component in Guided Bone Regeneration (GBR) therapy, but their properties, e.g. proteolytic stability and soft tissue barrier functionality, are still far from optimal. This is largely attributed to the complex molecular configuration of collagen, which makes chemical accessibility and structure-function relations challenging. Here, we fabricated a UV-cured hydrogel network of atelocollagen, whereby triple helices were sequentially functionalised with two distinct ethylenically unsaturated monomers. The effects of the sequential functionalisation and UV-curing on the macroscopic properties, degradation behaviour and GBR capability were investigated in vitro and in vivo. The results highlight the key role of the sequential functionalisation and provide important insights for the design of future, longer-lasting resorbable membranes for GBR therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. G. Tronci, S.J. Russell and D.J. Wood are named inventors on a patent related to the fabrication of collagen-based materials., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Like most legumes, chickpeas form specialized organs called root nodules. These nodules allow for a symbiotic relationship with rhizobium bacteria. The rhizobia provide fixed atmospheric nitrogen to the plant in a usable form. It is of both basic and practical interest to understand the host plant genetics of legume root nodulation. Chickpea lines PM233 and PM405, which harbor the mutationally identified nodulation genes rn1 and rn4, respectively, both display nodulation-deficient phenotypes. Previous investigators identified the rn1 mutation with the chickpea homolog of Medicago truncatula nodulation gene NSP2, but were unable to define the mutant rn1 allele. We used Illumina and Nanopore sequencing reads to attempt to identify and characterize candidate mutation sites responsible for the PM233 and PM405 phenotypes., Results: We aligned Illumina reads to the available desi chickpea reference genome, and did a de novo contig assembly of Nanopore reads. In mutant PM233, the Nanopore contigs allowed us to identify the breakpoints of a ~ 35 kb deleted region containing the CaNSP2 gene, the Medicago truncatula homolog of which is involved in nodulation. In mutant PM405, we performed variant calling in read alignments and identified 10 candidate mutations. Genotyping of a segregating progeny population narrowed that pool down to a single candidate gene which displayed homology to M. truncatula nodulation gene NIN., Conclusions: We have characterized the nodulation mutation sites in chickpea mutants PM233 and PM405. In mutant PM233, the rn1 mutation was shown to be due to deletion of the entire CaNSP2 nodulation gene, while in mutant PM405 the rn4 mutation was due to a single base deletion resulting in a frameshift mutation between the predicted RWP-RK and PB1 domains of the NIN nodulation gene. Critical to characterization of the rn1 allele was the generation of Nanopore contigs for mutant PM233 and its wild type parent ICC 640, without which the deletional boundaries could not be defined. Our results suggest that efforts of prior investigators were hampered by genomic misassemblies in the CaNSP2 region of both the desi and kabuli reference genomes., (© 2022. The Author(s).)

Limiting infection transmission is central to the safety of all in dentistry, particularly during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Aerosol-generating procedures (AGPs) are crucial to the practice of dentistry; it is imperative to understand the inherent risks of viral dispersion associated with AGPs and the efficacy of available mitigation strategies. In a dental surgery setting, crown preparation and root canal access procedures were performed with an air turbine or high-speed contra-angle handpiece (HSCAH), with mitigation via rubber dam or high-volume aspiration and a no-mitigation control. A phantom head was used with a 1.5-mL min -1 flow of artificial saliva infected with Φ6-bacteriophage (a surrogate virus for SARS-CoV-2) at ~10 8 plaque-forming units mL -1 , reflecting the upper limits of reported salivary SARS-CoV-2 levels. Bioaerosol dispersal was measured using agar settle plates lawned with the Φ6-bacteriophage host, Pseudomonas syringae . Viral air concentrations were assessed using MicroBio MB2 air sampling and particle quantities using Kanomax 3889 GEOα counters. Compared to an air turbine, the HSCAH reduced settled bioaerosols by 99.72%, 100.00%, and 100.00% for no mitigation, aspiration, and rubber dam, respectively. Bacteriophage concentrations in the air were reduced by 99.98%, 100.00%, and 100.00% with the same mitigations. Use of the HSCAH with high-volume aspiration resulted in no detectable bacteriophage, both on nonsplatter settle plates and in air samples taken 6 to 10 min postprocedure. To our knowledge, this study is the first to report the aerosolization in a dental clinic of active virus as a marker for risk determination. While this model represents a worst-case scenario for possible SARS-CoV-2 dispersal, these data showed that the use of HSCAHs can vastly reduce the risk of viral aerosolization and therefore remove the need for clinic fallow time. Furthermore, our findings indicate that the use of particle analysis alone cannot provide sufficient insight to understand bioaerosol infection risk.

Purpose: To investigate the mid-term outcomes of an accelerated return to full weight bearing (WB) after matrix-induced autologous chondrocyte implantation (MACI)., Methods: This randomized study allocated 35 patients (37 knees) to a 6 week (n = 18) or 8 week (n = 19) return to full WB after MACI. Patients were evaluated pre-operatively and at 1, 2 and minimum 5 years (range 5.5-7 years), using the KOOS, SF-36, visual analogue pain scale, 6-min walk test and active knee range of motion (ROM). Peak isokinetic knee extensor and flexor strength was assessed, with limb symmetry indices (LSIs) calculated. Magnetic resonance imaging (MRI) was undertaken to evaluate the repair tissue, and an MRI composite score was calculated., Results: While no group differences (n.s.) were observed, significant improvement was observed for all patient-reported outcome measures (p < 0.05), 6-min walk distance (p = 0.040), active knee flexion (p = 0.002) and extension (p < 0.0001) ROM, and the LSI for peak knee extensor strength (p < 0.0001). At final review, 87.5% (6 weeks) and 82.4% (8 weeks) of patients were satisfied overall. A non-significant decline (n.s.) was observed for the MRI composite score from 1-year post-surgery to final review, with no significant MRI-based differences (n.s.) between groups. At final review, two grafts (6-week n = 1, 8-week n = 1) demonstrated MRI-based graft failure, while an additional patient had progressed toward knee arthroplasty (8.1% failure rate at minimum 5 years)., Conclusions: The 6-week return to full WB after MACI provided comparable clinical and MRI-based outcomes beyond 5 years post-surgery, without jeopardizing the graft. This 6-week WB protocol is faster than those previously proposed and studied., Level of Evidence: II., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Wet spinning is an established fibre manufacturing route to realise collagen fibres with preserved triple helix architecture and cell acceptability for applications in biomedical membranes. However, resulting fibres still need to be chemically modified post-spinning to ensure material integrity in physiological media, with inherent risks of alteration of fibre morphology and with limited opportunities to induce fibrillogenesis following collagen fixation in the crosslinked state. To overcome this challenge, we hypothesised that a photoactive type I collagen precursor bearing either single or multiple monomers could be employed to accomplish hierarchically assembled fibres with improved processability, macroscopic properties and nanoscale organisation via sequential wet spinning and UV-curing. In-house-extracted type I rat tail collagen functionalised with both 4-vinylbenzyl chloride (4VBC) and methacrylate residues generated a full hydrogel network following solubilisation in a photoactive aqueous solution and UV exposure, whereby ~85 wt.% of material was retained following 75-day hydrolytic incubation. Wide-angle X-ray diffraction confirmed the presence of typical collagen patterns, whilst an averaged compression modulus and swelling ratio of more than 290 kPa and 1500 wt.% was recorded in the UV-cured hydrogel networks. Photoactive type I collagen precursors were subsequently wet spun into fibres, displaying the typical dichroic features of collagen and regular fibre morphology. Varying tensile modulus ( E = 5 ± 1 - 11 ± 4 MPa) and swelling ratio ( SR = 1880 ± 200 - 3350 ± 500 wt.%) were measured following post-spinning UV curing and equilibration with phosphate-buffered saline (PBS). Most importantly, 72-h incubation of the wet spun fibres in PBS successfully induced renaturation of collagen-like fibrils, which were fixed following UV-induced network formation. The whole process proved to be well tolerated by cells, as indicated by a spread-like cell morphology following a 48-h culture of L929 mouse fibroblasts on the extracts of UV-cured fibres.