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Introduction: At our tertiary orthopaedic centre, mycobacterial cultures are routinely performed on bone and joint samples sent for bacterial culture. Methods: From laboratory records, we ascertained the number of mycobacterial cultures performed, the number positive for Mycobacterium tuberculosis complex (MTBC) and/or non-tuberculous mycobacteria (NTM), and the characteristics of individuals from whom mycobacteria were isolated. We collected the same data from 100 individuals with negative mycobacterial cultures. Results: Excluding sample types that were not bone or joint samples, 6162 mycobacterial cultures were performed between 4 July 2017 and 30 September 2022. A total of 22 patients had MTBC and 6 patients had NTM newly isolated from bone or joint samples placed in mycobacterial culture, while a further 1 patient had both Mycobacterium tuberculosis and Mycobacterium avium isolated. To identify one new mycobacterial infection of bone or joint (MTBC or NTM) that would not have been detected with routine bacterial cultures alone, 229 (95 % CI of 158–347) mycobacterial cultures were needed. Mycobacterial cultures were much less likely to be positive in samples taken from prosthetic joints. They were more likely to be positive in spinal samples and in samples taken from patients with suspected sarcoma. In patients from whom MTBC had been isolated, granulomatous inflammation was reported in 86 % (18 of 21) of contemporaneous histological specimens. Conclusions: Targeted, rather than routine, mycobacterial culture of bone and joint specimens should be considered in settings with a low burden of tuberculosis.

Objectives: To compare prosthetic joint infection (PJI) and acute kidney injury (AKI) rates among cohorts before and after changing our hospital's antimicrobial prophylactic regimen from cefuroxime to teicoplanin plus gentamicin. Methods: We retrospectively studied all patients undergoing primary total joint arthroplasty at our hospital 18 months pre- and post-implementation of the change in practice. All deep infections identified during follow-up were assessed against the European Bone and Joint Infection Society (EBJIS) definitions for PJI. Survival analysis using Cox regression was employed to adjust for differences in baseline characteristics and compare the risk of PJI between the groups. AKIs were identified using pathology records and categorized according to the KDIGO (Kidney Disease – Improving Global Outcomes) criteria. AKI rates were calculated for the pre- and post-intervention periods. Results: Of 1994 evaluable patients, 1114 (55.9 %) received cefuroxime only (pre-intervention group) and 880 (44.1 %) patients received teicoplanin plus gentamicin (post-intervention group). The overall rate of PJI in our study was 1.50 % (30 of 1994), with a lower PJI rate in the post-intervention group (0.57 %; 5 of 880) compared with the pre-intervention group (2.24 %; 25 of 1114). A corresponding risk reduction for PJI of 75.2 % (95 % CI of 35.2–90.5; p=0.004) was seen in the post-intervention group, which was most pronounced for early-onset and delayed infections due to coagulase-negative staphylococci (CoNS) and cefuroxime-resistant Enterobacteriaceae. Significantly higher AKI rates were seen in the post-intervention group; however, 84 % of cases (32 of 38) were stage 1, and there were no differences in the rate of stage-2 or -3 AKI. Conclusions: Teicoplanin plus gentamicin was associated with a significant reduction in PJI rates compared with cefuroxime. Increases in stage-1 AKI were seen with teicoplanin plus gentamicin.

We present the first reported case of prosthetic joint infection caused by Trueperella pyogenes. This animal pathogen rarely causes human infection. Our patient was successfully treated with single-stage exchange and 12 weeks of rifampicin and moxifloxacin.

We report a case of an infected massive endoprosthetic replacement treated successfully with 2 stage surgery and off-label dalbavancin. Dalbavancin was used due to a limited number of antimicrobial options that could be administered safely in an outpatient setting and to avoid the need for daily dosing.

73Ge(n,γ) cross sections were measured at the neutron time-of-flight facility n_TOF at CERN up to neutron energies of 300 keV, providing for the first time experimental data above 8 keV. Results indicate that the stellar cross section at kT=30 keV is 1.5 to 1.7 times higher than most theoretical predictions. The new cross sections result in a substantial decrease of 73Ge produced in stars, which would explain the low isotopic abundance of 73Ge in the solar system. Keywords: Nucleosynthesis, Neutron capture, s process, Germanium, n_TOF

The catalytic properties of LaCoO3 in aqueous oxidation are explored as a function of doping. Both Sr substitution for La and Fe/Ni substitution for Co are studied. The reaction of interest is the aqueous epoxidation of crotyl alcohol with hydrogen peroxide. The reaction products are measured using GC, and the decomposition of hydrogen peroxide is studied using the volume of oxygen evolved during reaction. Strong variations in the activity to epoxide formation are observed, with Fe-doped samples being rather inactive in the reaction. SR VUV photoemission is used to explore the surface reactivity of the ceramic catalysts in aqueous solution, using H2O as a probe molecule. These measurements are complemented by XANES measurements designed to probe the local defect structure and XPS measurements of surface composition. We relate the observed catalytic activity to the defect structure of the doped materials. In Ni-doped materials, oxygen vacancies appear to be the predominant defect, whereas in Fe-doped samples, electron holes are stabilized on Fe, leading to very different catalytic behaviour. Surface studies in combination with AA measurements reveal some dissolution of the catalyst into solution during the reaction. The surface reactivity to water is influenced by the TM d electron count, with water binding more strongly to Fe-doped materials than to those containing Ni. The influence of these factors on the rate of the unwanted hydrogen peroxide decomposition reaction and hence on activity in epoxidation is discussed.

The Connexin43 gap junction gene GJA1 has one coding exon, but its mRNA undergoes internal translation to generate N-terminal truncated isoforms of Connexin43 with the predominant isoform being only 20 kDa in size (GJA1-20k). Endogenous GJA1-20k protein is not membrane bound and has been found to increase in response to ischemic stress, localize to mitochondria, and mimic ischemic preconditioning protection in the heart. However, it is not known how GJA1-20k benefits mitochondria to provide this protection. Here, using human cells and mice, we identify that GJA1-20k polymerizes actin around mitochondria which induces focal constriction sites. Mitochondrial fission events occur within about 45 s of GJA1-20k recruitment of actin. Interestingly, GJA1-20k mediated fission is independent of canonical Dynamin-Related Protein 1 (DRP1). We find that GJA1-20k-induced smaller mitochondria have decreased reactive oxygen species (ROS) generation and, in hearts, provide potent protection against ischemia-reperfusion injury. The results indicate that stress responsive internally translated GJA1-20k stabilizes polymerized actin filaments to stimulate non-canonical mitochondrial fission which limits ischemic-reperfusion induced myocardial infarction.

Anthropogenic landscape modification which leads to the displacement of species, is arguably one of the most profound impacts on animal movement globally. In urban landscapes, animal movement is generally impacted by varying levels of increased urbanization. However, this is species dependent and is mostly guided by the surrounding habitat. Fragmentation and habitat patch isolation must be considered at scales appropriate to the study species. Using telemetry, we test these assumptions investigating movement patterns of flocks of Forest Red-tailed Black Cockatoos (Calyptorhynchus banksii naso; RTBC) between three regions: urban, peri-urban, and forest using GPS and satellite PTT. This species occurs at varying levels of urbanization, however, how this might affect its movements is largely unknown. We did not find evidence that RTBC movement was impaired in the urban region compared with peri-urban or forest regions. It found, however, a significant within-region variation in movement extent among flocks and across regions depending on foraging resource availability and location. Differences in daily movement distance (Av. 4.96 - 16.41 km) and home range size (6.02 - 52.57 km2) between urban flocks appeared to be associated with the proximity of green spaces as roosts and foraging sites, with roadside vegetation providing important foraging resources and movement corridors. Key urban habitats were predominantly located in public nature reserves and private properties, with roadside vegetation connecting these sites for RTBC. The findings of this study highlight that conservation management for this and many other threatened species should regard the urban landscape as a critical habitat for urban adapted species. This would include management of its green spaces with connectivity and offsets from roads in mind. Furthermore, future research should focus on identifying additional key habitat sites (resource selection) and species distribution modeling, which will facilitate an active and adaptive approach towards this species' conservation management.

Metabolic adaption is crucial for the heart to sustain its contractile activity under various physiological and pathological conditions. At the molecular level, the changes in energy demand impinge on the expression of genes encoding for metabolic enzymes. Among the major components of an intricate transcriptional circuitry, peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α) plays a critical role as a metabolic sensor, which is responsible for the fine-tuning of transcriptional responses to a plethora of stimuli. Cumulative evidence suggests that energetic impairment in heart failure is largely attributed to the dysregulation of PGC-1α. In this review, we summarize recent studies revealing how PGC-1α is regulated by a multitude of mechanisms, operating at different regulatory levels, which include epigenetic regulation, the expression of variants, post-transcriptional inhibition, and post-translational modifications. We further discuss how the PGC-1α regulatory cascade can be impaired in the failing heart.

Abstract Background Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. Methods This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. Discussion This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). Trial registration NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.