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Background: Infections following shoulder surgery, particularly periprosthetic joint infection (PJI), are challenging to treat. Cutibacterium acnes is the causative pathogen in 39% to 76% of these cases. This study explores the efficacy of bacteriophage therapy as an alternative to conventional antibiotics for treating such infections. Methods: Nine phages with lytic activity were isolated from the skin of humans using C. acnes ATCC 6919 as the indicator host. These phages were tested individually or in combination to assess host range and antibiofilm activity against clinical strains of C. acnes associated with PJIs. The phage cocktail was optimized for broad-spectrum activity and tested in vitro against biofilms formed on titanium discs to mimic the prosthetic environment. Results: The isolated phages displayed lytic activity against a range of C. acnes clinical isolates. The phage cocktail significantly reduced the bacterial load of C. acnes strains 183, 184, and GG2A, as compared with untreated controls (p < 0.05). Individual phages, particularly CaJIE7 and CaJIE3, also demonstrated significant reductions in bacterial load with respect to specific strains. Moreover, phages notably disrupted the biofilm structure and reduced biofilm biomass, confirming the potential of phage therapy in targeting biofilm-associated infections. Conclusions: Our preclinical findings support the potential of phage therapy as a viable adjunct to traditional antibiotics for treating C. acnes infections in orthopedic device-related infections. The ability of phages to disrupt biofilms may be particularly beneficial for managing infections associated with prosthetic implants. [ABSTRACT FROM AUTHOR]

Glucocorticoids may be given prior to major orthopedic surgery to decrease postoperative nausea, vomiting, and pain. Additionally, many orthopedic patients may be on chronic glucocorticoid therapy. The aim of our study was to investigate whether glucocorticoid administration influences Orthopedic-Device-Related Infection (ODRI) in a rat model. Screws colonized with Staphylococcus epidermidis were implanted in the tibia of skeletally mature female Wistar rats. The treated groups received either a single shot of dexamethasone in a short-term risk study, or a daily dose of dexamethasone in a longer-term interference study. In both phases, bone changes in the vicinity of the implant were monitored with microCT. There were no statistically significant differences in bacteriological outcome with or without dexamethasone. In the interference study, new bone formation was statistically higher in the dexamethasone-treated group (p = 0.0005) as revealed by CT and histopathological analysis, although with relatively low direct osseointegration of the implant. In conclusion, dexamethasone does not increase the risk of developing periprosthetic osteolysis or infection in a pre-clinical model of ODRI. Long-term administration of dexamethasone seemed to offer a benefit in terms of new bone formation around the implant, but with low osseointegration. [ABSTRACT FROM AUTHOR]

Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of the internet vote. Only two questions received a ≥90% consensus vote, emphasizing the disparate approaches and lack of established consensus for in vitro modeling and interpretation of results. Comments on knowledge gaps and the need for further research on these critical MSKI questions are included. [ABSTRACT FROM AUTHOR]

A judicious, well-planned bone and soft tissue debridement remains one of the cornerstones of state-of-the-art treatment of fracture-related infection (FRI). Meticulous surgical excision of all non-viable tissue can, however, lead to the creation of large soft tissue defects. The management of these defects is complex and numerous factors need to be considered when selecting the most appropriate approach. This narrative review summarizes the current evidence with respect to soft tissue management in patients diagnosed with FRI. Specifically we discuss the optimal timing for tissue closure following debridement in cases of FRI, the need for negative microbiological culture results from the surgical site as a prerequisite for definitive wound closure, the optimal type of flap in case of large soft tissue defects caused by FRI and the role of negative pressure wound therapy (NPWT) in FRI. Finally, recommendations are made with regard to soft tissue management in FRI that should be useful for clinicians in daily clinical practice. Level of evidence Level V. [ABSTRACT FROM AUTHOR]

Orthopedic-device-related infection is one of the most severe complications in orthopedic surgery. To reduce the associated morbidity and healthcare costs, new prevention and treatment modalities are continuously under development. Preclinical in vivo models serve as a control point prior to clinical implementation. This study presents a mouse model of subcutaneously implanted titanium discs, infected with Staphylococcus aureus, to fill a gap in the early-stage testing of antimicrobial biomaterials. Firstly, three different inocula were administered either pre-adhered to the implant or pipetted on top of it following implantation to test their ability to reliably create an infection. Secondly, the efficacy of low-dose (25 mg/kg) and high-dose (250 mg/kg) cefazolin administered systemically in infection prevention was assessed. Lastly, titanium implants were replaced by antibiotic-loaded bone cement (ALBC) discs to investigate the efficacy of local antibiotics in infection prevention. The efficacy in infection prevention of the low-dose perioperative antibiotic prophylaxis (PAP) depended on both the inoculum and inoculation method. Bacterial counts were significantly lower in animals receiving the high dose of PAP. ALBC discs with or without the additional PAP proved highly effective in infection prevention and provide a suitable positive control to test other prevention strategies. [ABSTRACT FROM AUTHOR]

Fracture-related infection (FRI) remains a serious complication in open fracture care. Adequate surgical treatment and perioperative antibiotic prophylaxis (PAP) are key factors influencing the outcome. However, data concerning the optimal duration of PAP is scarce. The aim of this systematic review was to provide an overview of current evidence on the association between PAP duration and FRI in open fractures. A comprehensive search on 13 January 2022, in Embase, Medline, Cochrane, Web of Science and Google Scholar revealed six articles. Most studies compared either 1 day versus 5 days of PAP or included a cut-off at 72 h. Although prolonged PAP was not beneficial in the majority of patients, the variety of antibiotic regimens, short follow-up periods and unclear description of outcome parameters were important limitations that were encountered in most studies. This systematic review demonstrates a lack of well-constructed studies investigating the effect of PAP duration on FRI. Based on the available studies, prolonged PAP does not appear to be beneficial in the prevention of FRI in open fractures. However, these results should be interpreted with caution since all included studies had limitations. Future randomized trials are necessary to answer this research question definitively. [ABSTRACT FROM AUTHOR]

Approximately 250 000 children undergo pediatric procedural sedation (PPS) in Emergency Departments (ED) in the United Kingdom and Ireland annually. PPS practice in our setting has not been described as fully as other high-income countries. We aimed to evaluate PPS in EDs in the United Kingdom and Ireland. An online survey was distributed through Paediatric Emergency Research in the UK and Ireland (PERUKI), in June 2020. One respondent per ED completed the survey, including questions on agents, fasting, training, and governance. Of 72 PERUKI sites, 61 (85%) responded, of which PPS was performed in 50 (82%). Internal training packages existed in under half (22/50, 44.0%). Most had a guideline (43/50; 86.0%) and documentation proforma (39/50; 78.0%). Audit databases existed in 24/50 (48.0%). Intravenous ketamine was the most common agent (43/50; 86%), followed by variable concentration nitrous oxide (13/50; 26%). Fasting practices varied widely across sites and agents. We have demonstrated widespread PPS use, but non-standardized practice. This leads to potential issues of risk and variability across agents, highlighting a need for a sedation package in the United Kingdom and Ireland to standardize practice and data collection. We propose development of a prospective ED sedation registry in the United Kingdom and Ireland to facilitate data collection to support research within this area., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Paediatric and Neonatal Pain published by John Wiley & Sons Ltd.)

Sitafloxacin is a 4th generation fluoroquinolone antibiotic with broad activity against a wide range of Gram-negative and Gram-positive bacteria. It is approved in Japan and used to treat pneumonia and urinary tract infections (UTIs) as well as other upper and lower respiratory infections, genitourinary infections, oral infections and otitis media. Compared to other fluoroquinolones, sitafloxacin displays a low minimal inhibitory concentration (MIC) for many bacterial species but also activity against anaerobes, intracellular bacteria, and persisters. Furthermore, it has also shown strong activity against biofilms of P. aeruginosa and S. aureus in vitro, which was recently validated in vivo with murine models of S. aureus implant-associated bone infection. Although limited in scale at present, the published literature supports the further evaluation of sitafloxacin in implant-related infections and other biofilm-related infections. The aim of this review is to summarize the chemical-positioning-based mechanisms, activity, resistance profile, and future clinical potential of sitafloxacin.

Purpose of Review: Sarcopenia, generally characterized by the age-related reduction in muscle strength, lean/muscle mass and functional ability, is also associated with reduced bone mass and strength and impaired brain health and function. One potential intervention which has received much 'hype' over the past few decades to countermeasure these negative consequences of biological aging is creatine monohydrate supplementation., Recent Findings: From a skeletal muscle perspective, the combination of creatine monohydrate supplementation and resistance training provides 'hope' for older adults as it improves measures of lean mass, regional (limb) muscle thickness, upper- and lower-body muscle strength and functional ability. Further, there is some evidence that creatine (supplementation or habitual diet) provides a ray of 'hope' for improving some aspects of cognitive function. The majority of research suggests that creatine is more 'hype' than 'hope' for improving measures of bone mass in older adults. Creatine monohydrate supplementation provides some anti-sarcopenic benefits for older adults., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Phage therapy (PT) continues to attract interest in the fight against fracture-related infection (FRI), particularly for recurring infections that have not been resolved using conventional therapeutic approaches. The journey PT has taken from early clinical application in the pre-antibiotic era to its recent reintroduction to western clinical practice has been accelerated by the increased prevalence of multi-drug resistant (MDR) pathogens in the clinic. This review will present PT's potential as a precise, adaptable, and effective treatment modality, with a focus on patient and phage selection, as well as the various administration protocols currently applied to patients. The challenges for PT, for example the most optimal application technique and dosing, are also discussed and underscore the importance of personalized approaches and the urgent need for more robust clinical evidence. Future perspectives, including phage engineering and innovative delivery systems will be discussed, as they may broaden the applicability of PT to a point where it may become a standard rather than an option of last resort for orthopedic infection management., Competing Interests: Declaration of competing interest No conflict., (Copyright © 2024. Published by Elsevier Ltd.)

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location, and implants used, there are also a wide range of animal models described modeling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to (1) animal model considerations, (2) outcome measurements, and (3) imaging., (© 2024 Orthopaedic Research Society.)

Background: Long bone defects resulting from primary trauma or secondary to debridement of fracture-related infection (FRI) remain a major clinical challenge. One approach often used is the induced membrane technique (IMT). The effectiveness of the IMT in infected versus non-infected settings remains to be definitively established. In this study we present a new rabbit humerus model and compare the IMT approach between animals with prior infection and non-infected equivalents., Methods: A 5 mm defect was created in the humerus of New Zealand White rabbits (n = 53) and fixed with a 2.5 mm stainless steel plate. In the non-infected groups, the defect was either left empty (n = 6) or treated using the IMT procedure (PMMA spacer for 3 weeks, n = 6). Additionally, both approaches were applied in animals that were inoculated with Staphylococcus aureus 4 weeks prior to defect creation (n = 5 and n = 6, respectively). At the first and second revision surgeries, infected and necrotic tissues were debrided and processed for bacteriological quantification. In the IMT groups, the PMMA spacer was removed 3 weeks post implantation and replaced with a beta-tricalcium phosphate scaffold and bone healing observed for a further 10 weeks. Infected groups also received systemic antibiotic therapy. The differences in bone healing between the groups were evaluated radiographically using a modification of the radiographic union score for tibial fractures (RUST) and by semiquantitative histopathology on Giemsa-Eosin-stained sections., Results: The presence of S. aureus infection at revision surgery was required for inclusion to the second stage. At the second revision surgery all collected samples were culture negative confirming successful treatment. In the empty defect group, bone healing was increased in the previously infected animals compared with non-infected controls as revealed by radiography with significantly higher RUST values at 6 weeks (p = 0.0281) and at the end of the study (p = 0.0411) and by histopathology with increased cortical bridging (80% and 100% in cis and trans cortical bridging in infected animals compared to 17% and 67% in the non-infected animals). With the IMT approach, both infected and non-infected animals had positive healing assessments., Conclusion: We successfully developed an in vivo model of bone defect healing with IMT with and without infection. Bone defects can heal after an infection with even better outcomes compared to the non-infected setting, although in both cases, the IMT achieved better healing., (© 2023. The Author(s).)

Globally, coral reefs face increasing disease prevalence and large-scale outbreak events. These outbreaks offer insights into microbial and functional patterns of coral disease, including early indicators of disease that may be present in visually-healthy tissues. Outbreak events also allow investigation of how reef-building corals, typically colonial organisms, respond to disease. We studied Pocillopora damicornis during an acute tissue loss disease outbreak on Guam to determine whether dysbiosis was present in visually-healthy tissues ahead of advancing disease lesions. These data reveal that coral fragments with visual evidence of disease are expectedly dysbiotic with high microbial and metabolomic variability. However, visually-healthy tissues from the same colonies lacked dysbiosis, suggesting disease containment near the affected area. These results challenge the idea of using broad dysbiosis as a pre-visual disease indicator and prompt reevaluation of disease assessment in colonial organisms such as reef-building corals., (© 2023. Springer Nature Limited.)

To determine if creatine (Cr) supplementation could influence cognitive performance and whether any changes were related to changes in prefrontal cortex (PFC) activation during such cognitive tasks, thirty (M = 11, F = 19) participants were evenly randomized to receive supplementation with Cr (CR10:10 g/day or CR20:20 g/day) or a placebo (PLA:10 g/day) for 6 weeks. Participants completed a cognitive test battery (processing speed, episodic memory, and attention) on two separate occasions prior to and following supplementation. Functional near-infrared spectroscopy (fNIRS) was used to measure PFC oxyhemoglobin (O 2 Hb) during the cognitive evaluation. A two-way repeated measures ANOVA was used to determine the differences between the groups and the timepoints for the cognitive performance scores and PFC O 2 Hb. In addition, a one-way ANOVA of % change was used to determine pre- and post-differences between the groups. Creatine (independent of dosage) had no significant effect on the measures of cognitive performance. There was a trend for decreased relative PFC O 2 Hb in the CR10 group versus the PLA group in the processing speed test ( p = 0.06). Overall, six weeks of Cr supplementation at a moderate or high dose does not improve cognitive performance or change PFC activation in young adults.

The COVID-19 pandemic prompted chaotic changes in the daily lives of K-12 teachers, resulting in increased stress and other mental health problems. Limited evidence regarding the relationship between physical activity, sleep, and perceived stress among teachers during the COVID-19 pandemic exists. Therefore, the purpose of this study was to investigate the association between physical activity, sleep quality, and perceived psychological stress among teachers during the COVID-19 pandemic. An online survey measuring physical activity, sleep quality, and perceived psychological stress was distributed across 47 US states between September and October of 2020. Data provided by 635 teachers (mean age: 42 ± 18 years, 74.6% female) were included in the present analysis. Results suggested a negative association between physical activity and perceived psychological stress. Mediation analyses indicated that teachers engaging in high levels of physical activity were more likely to have good quality sleep and, in turn, were less likely to report high levels of perceived stress. Physical activity and sleep-related interventions could help curtail the rising levels of psychological distress amongst K-12 teachers during stressful times such as the COVID-19 pandemic. Teachers, especially those that self-report as female and/or young, report high levels of stress. These high levels of stress are a serious challenge for school districts in terms of attracting and retaining qualified teachers in K-12 classrooms.

Bacterial exopolysaccharides (EPS) are water-soluble polymers consisting of repeating sugar moieties that serve a wide range of functions for the bacterial species that produce them. Their functions include biofilm matrix constituent, nutrient retention, protection from environmental threats and even pathogenicity. EPS have also been exploited for use in various applications in the biomedical field: most notably as viscosupplements, drug delivery vehicles and in tissue engineering constructs. The use of EPS in bone tissue engineering has increased in recent years due to the wide range of compounds available, low cost, and ease of production on an industrial scale. This review discusses the extraction and purification methods employed to produce bacterial EPS. A particular focus is on bone-related tissue engineering applications where EPS is the primary active agent, or as a scaffold matrix, as well as a carrier for osteopromotive agents., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Coral reefs are amongst the most biodiverse ecosystems on earth, and while stony corals create the foundational complexity of these ecosystems, octocorals and anemones contribute significantly to their biodiversity and function. Like stony corals, many octocorals contain Symbiodiniaceae endosymbionts and can bleach when temperatures exceed the species' upper thermal limit. Here, we report octocoral bleaching susceptibility and resistance within the subtropical Lord Howe Island coral reef ecosystem during and after marine heatwaves in 2019. Octocoral and anemone surveys were conducted at multiple reef locations within the Lord Howe Island lagoon during, immediately after, and 7 months after the heatwaves. One octocoral species, Cladiella sp. 1, experienced bleaching and mortality, with some bleached colonies detaching from the reef structure during the heatwave (presumed dead). Those that remained attached to the benthos survived the event and recovered endosymbionts within 7 months of bleaching. Cladiella sp. 1 Symbiodiniaceae density (in cells per µg protein), chlorophyll a and c 2 per µg protein, and photosynthetic efficiency were significantly lower in bleached colonies compared to unbleached colonies, while chlorophyll a and c 2 per symbiont were higher. Interestingly, no other symbiotic octocoral species of the Lord Howe Island lagoonal reef bleached. Unbleached Xenia cf crassa colonies had higher Symbiodiniaceae and chlorophyll densities during the marine heatwave compared to other monitoring intervals, while Cladiella sp. 2 densities did not change substantially through time. Previous work on octocoral bleaching has focused primarily on gorgonian octocorals, while this study provides insight into bleaching variability in other octocoral groups. The study also provides further evidence that octocorals may be generally more resistant to bleaching than stony corals in many, but not all, reef ecosystems. Responses to marine heating events vary and should be assessed on a species by species basis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Steinberg, Ainsworth, Moriarty, Bednarek, Dafforn and Johnston.)

Acute aerobic exercise has been shown to improve fine motor skills and alter activation of the motor cortex (M1). The intensity of exercise may influence M1 activation, and further impact whole-body motor skill performance. The aims of the current study were to compare a whole-body motor skill via a piano task following moderate-intensity training (MIT) and high-intensity interval training (HIIT), and to determine if M1 activation is linked to any such changes in performance. Nine subjects (seven females and two males), aged 18 ± 1 years completed a control, MIT, and HIIT trial followed by administration of a piano performance task. M1 activation was evaluated by measuring oxyhemoglobin (O 2 Hb) and hemoglobin difference (Hbdiff) changes during post-exercise piano performance using functional near-infrared spectroscopy (fNIRS). The results indicate that piano performance scores were higher after the MIT trial, but not HIIT trial, compared to the control trial. A negative relationship was detected between heart rate during HIIT and post-HIIT piano scores. M1 activation (as measured by Hbdiff) was significantly increased after the HIIT trial. M1 activation was also positively associated with piano performance when exercise trials (HIIT + MIT) and all trials (HIIT + MIT + Control) were combined. We found that acute moderate-intensity exercise led to an improvement in complex motor skill performance while higher-intensity exercise increased M1 activation. These results demonstrate that moderate-intensity exercise can prime the nervous system for the acquisition of whole-body motor skills, suggesting that similar exercise protocols may be effective in improving the outcomes of other motor tasks performed during regular routines of daily life (e.g., sporting tasks, activities of daily living or rehabilitation). In addition, it appears that improvements in motor task performance may be driven by M1 activation. Our findings provide new mechanistic insight into the complex relationship between exercise intensity, M1 activation, and whole-body motor skill performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moriarty, Johnson, Thomas, Evers, Auten, Cavey, Dorman and Bourbeau.)