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Vibrio parahaemolyticus is a food-borne pathogen that poses a serious threat to seafood safety and human health. An efficient, nontoxic, and sustainable disinfection material with a stable structure is urgently needed. Herein, silver (Ag)-hydroxyapatite (HAP) composite catalysts were prepared using HAP derived from waste fish bones. The Ag 2.50% -HAP showed a 100% disinfection rate against V. parahaemolyticus, disinfecting nearly 7.0 lg CFU mL -1 within 15 min at a low concentration of 300 μg mL -1 . This efficient disinfection activity could be attributed to the double-synergistic effect of Ag and superoxide radicals, which resulted in the destruction of bacterial cell structures and the leakage of intracellular proteins. Importantly, the composite also exhibited high activity in controlling the growth of pathogens during the storage process of Penaeus vannamei. These findings provided sustainable composite catalysts for disinfecting V. parahaemolyticus in seafood and a high-value utilization strategy for waste fish bones., 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Osteoporosis (OP) is characterized by decreased bone mineral density (BMD) and increased fracture risk, poses a significant global health burden. Recent research has shed light on the bidirectional relationship between gut microbiota (GM) and bone health, presenting a novel avenue for understanding OP pathogenesis and developing targeted therapeutic interventions. This review provides a comprehensive overview of the GM-bone axis, exploring the impact of GM on OP development and management. We elucidate established risk factors and pathogenesis of OP, delve into the diversity and functional changes of GM in OP. Furthermore, we examine experimental evidence and clinical observations linking alterations in GM composition or function with variations in BMD and fracture risk. Mechanistic insights into microbial mediators of bone health, such as microbial metabolites and products, are discussed. Therapeutic implications, including GM-targeted interventions and dietary strategies, are also explored. Finally, we identify future research directions and challenges in translating these findings into clinical practice., 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 © 2024 Hao, Yan, Huang and Li.)

Objective: Here we investigate infectious diseases that potentially contribute to osteological lesions in individuals from the early medieval necropolis of La Olmeda (6th-11th c. CE) in North Iberia., Materials and Methods: We studied a minimum number of 268 individuals (33 adult females; 38 adult males, 77 unknown/indeterminate sex; and 120 non-adults), including articulated and commingled remains. Individuals with differential diagnoses suggesting chronic systemic infectious diseases were sampled and bioinformatically screened for ancient pathogen DNA., Results: Five non-adults (and no adults) presented skeletal evidence of chronic systemic infectious disease (1.87% of the population; 4.67% of non-adults). The preferred diagnoses for these individuals included tuberculosis, brucellosis, and malaria. Ancient DNA fragments assigned to the malaria-causing pathogen, Plasmodium spp., were identified in three of the five individuals. Observed pathology includes lesions generally consistent with malaria; however, additional lesions in two of the individuals may represent hitherto unknown variation in the skeletal manifestation of this disease or co-infection with tuberculosis or brucellosis. Additionally, spondylolysis was observed in one individual with skeletal lesions suggestive of infectious disease., Conclusions: This study sheds light on the pathological landscape in Iberia during a time of great social, demographic, and environmental change. Genetic evidence challenges the hypothesis that malaria was absent from early medieval Iberia and demonstrates the value of combining osteological and archaeogenetic methods. Additionally, all of the preferred infectious diagnoses for the individuals included in this study (malaria, tuberculosis, and brucellosis) could have contributed to the febrile cases described in historical sources from this time., (© 2024 The Author(s). American Journal of Biological Anthropology published by Wiley Periodicals LLC.)

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of S ubdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium , and Clostridium sensu stricto&#95;1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto&#95;1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy., 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.

Determining the burial time of skeletal remains is one of the most important issues of forensic medicine. We speculated that the microbiome of gravesoil may be a promising method to infer burial time by virtue of time-dependent. As we know, forensic scientists have established various models to predict the postmortem interval of a decedent based on the changes in body and soil microbiome communities. However, limited data are available on the burial time prediction for bones, especially dismembered bones. In this exploratory study, we initially conducted 16S rRNA amplicon high-throughput sequencing on the burial soil of 10 porcine femurs within a 120-day period and analyzed the changes in soil microbial communities. Compared with the control soil, a higher Shannon index in the microbial diversity of burial soil containing bones was observed. Correlation analysis identified 61 time-related bacterial families and the best subset selection method obtained best subset, containing Thermomonosporaceae, Clostridiaceae, 0319-A21, and Oxalobacteraceae, which were used to construct a simplified multiple linear regression model with a mean absolute error (MAE) of 56.69 accumulated degree day (ADD). An additional random forest model was established based on indicators for the minimum cross-validation error of Thermomonosporaceae, Clostridiaceae, 0319-A21, Oxalobacteraceae, and Syntrophobacteraceae, with an MAE of 55.65 ADD. The produced empirical data in this pilot study provided the evidence of feasibility that the microbial successional changes of burial soil will predict the burial time of dismembered bones and may also expand the current knowledge of the effects of bone burial on soil bacterial communities., (© 2024 Wiley‐VCH GmbH.)

Background: The bacterial persistence, responsible for therapeutic failures, can arise from the biofilm formation, which possesses a high tolerance to antibiotics. This threat often occurs when a bone and joint infection is diagnosed after a prosthesis implantation. Understanding the biofilm mechanism is pivotal to enhance prosthesis joint infection (PJI) treatment and prevention. However, little is known on the characteristics of Cutibacterium acnes biofilm formation, whereas this species is frequently involved in prosthesis infections., Methods: In this study, we compared the biofilm formation of C. acnes PJI-related strains and non-PJI-related strains on plastic support and textured titanium alloy by (i) counting adherent and viable bacteria, (ii) confocal scanning electronic microscopy observations after biofilm matrix labeling and (iii) RT-qPCR experiments., Results: We highlighted material- and strain-dependent modifications of C. acnes biofilm. Non-PJI-related strains formed aggregates on both types of support but with different matrix compositions. While the proportion of polysaccharides signal was higher on plastic, the proportions of polysaccharides and proteins signals were more similar on titanium. The changes in biofilm composition for PJI-related strains was less noticeable. For all tested strains, biofilm formation-related genes were more expressed in biofilm formed on plastic that one formed on titanium. Moreover, the impact of C. acnes internalization in osteoblasts prior to biofilm development was also investigated. After internalization, one of the non-PJI-related strains biofilm characteristics were affected: (i) a lower quantity of adhered bacteria (80.3-fold decrease), (ii) an increase of polysaccharides signal in biofilm and (iii) an activation of biofilm gene expressions on textured titanium disk., Conclusion: Taken together, these results evidenced the versatility of C. acnes biofilm, depending on the support used, the bone environment and the strain., (© 2024. The Author(s).)

Bone homeostasis in physiology depends on the balance between bone formation and resorption, and in pathology, this homeostasis is susceptible to disruption by different influences, especially under ageing condition. Gut microbiota has been recognized as a crucial factor in regulating host health. Numerous studies have demonstrated a significant association between gut microbiota and bone metabolism through host-microbiota crosstalk, and gut microbiota is even an important factor in the pathogenesis of bone metabolism-related diseases that cannot be ignored. This review explores the interplay between gut microbiota and bone metabolism, focusing on the roles of gut microbiota in bone ageing and aging-related bone diseases, including osteoporosis, fragility fracture repair, osteoarthritis, and spinal degeneration from different perspectives. The impact of gut microbiota on bone metabolism during aging through modification of endocrinology system, immune system and gut microbiota metabolites are summarized, facilitating a better grasp of the pathogenesis of aging-related bone metabolic diseases. This review offers innovative insights into targeting the gut microbiota for the treatment of bone ageing-related diseases as a clinical therapeutic strategy., 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 © 2024 Fu, Zhang, Wang and Liu.)

Introduction: Extensive research efforts have been dedicated to elucidating the intricate pathways by which gastrointestinal microbiota and their metabolites exert influence on the processes of bone formation. Nonetheless, a notable gap exists in the literature concerning a bibliometric analysis of research trends at the nexus of gastrointestinal microbiota and bone metabolism., Methods: To address this scholarly void, the present study employs a suite of bibliometric tools including online platforms, CiteSpace and VOSviewer to scrutinize the pertinent literature in the realm of gastrointestinal microbiota and bone metabolism., Results and Discussion: Examination of the temporal distribution of publications spanning from 2000 to 2023 reveals a discernible upward trajectory in research output, characterized by an average annual growth rate of 19.2%. Notably, China and the United States emerge as primary contributors. Predominant among contributing institutions are Emory University, Harvard University, and the University of California. Pacifici R from Emory University contributed the most research with 15 publications. In the realm of academic journals, Nutrients emerges as the foremost publisher, followed closely by Frontiers in Microbiology and PLOS One . And PLOS One attains the highest average citations of 32.48. Analysis of highly cited papers underscores a burgeoning interest in the therapeutic potential of probiotics or probiotic blends in modulating bone metabolism by augmenting host immune responses. Notably, significant research attention has coalesced around the therapeutic interventions of probiotics, particularly Lactobacillus reuteri , in osteoporosis, as well as the role of gastrointestinal microbiota in the etiology and progression of osteoarthritis. Keyword analysis reveals prevalent terms including gut microbiota, osteoporosis, bone density, probiotics, inflammation, SCFAs, metabolism, osteoarthritis, calcium absorption, obesity, double-blind, prebiotics, mechanisms, postmenopausal women, supplementation, risk factors, oxidative stress, and immune system. Future research endeavors warrant a nuanced exploration of topics such as inflammation, obesity, SCFAs, postmenopausal osteoporosis, skeletal muscle, oxidative stress, double-blind trials, and pathogenic mechanisms. In summary, this study presents a comprehensive bibliometric analysis of global research on the interplay between gastrointestinal microbiota and bone metabolism, offering valuable insights for scholars, particularly nascent researchers, embarking on analogous investigations within this domain., 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 © 2024 Wu, Sun, Guo and Li.)

Background: Corynebacterium spp. are widely disseminated in the environment, and they are part of the skin and mucosal microbiota of animals and humans. Reports of human infections by Corynebacterium spp. have increased considerably in recent years and the appearance of multidrug resistant isolates around the world has drawn attention., Objectives: To describe a new species of Corynebacterium from human tissue bone is described after being misidentified using available methods., Methods: For taxonomic analyses, phylogenetic analysis of 16S rRNA and rpoB genes, in silico DNA-DNA hybridization, average nucleotide and amino acid identity, multilocus sequence analysis, and phylogenetic analysis based on the complete genome were used., Findings: Genomic taxonomic analyzes revealed values of in silico DNA-DNA hybridization, average nucleotide and amino acids identity below the values necessary for species characterization between the analyzed isolates and the closest phylogenetic relative Corynebacterium aurimucosum DSM 44532 T ., Main Conclusions: Genomic taxonomic analyzes indicate that the isolates analyzed comprise a new species of the Corynebacterium genus, which we propose to name Corynebacterium hiratae sp. nov. with isolate 332 T (= CBAS 826 T  = CCBH 35,014 T ) as the type strain., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: Postmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known as the gut-bone axis, has garnered widespread attention., Methods: We employed a two-sample Mendelian randomization approach to assess the associations between gut microbiota with osteoclasts and postmenopausal osteoporosis, respectively. Single nucleotide polymorphisms associated with the composition of gut microbiota were used as instrumental variables. By analyzing large-scale multi-ethnic GWAS data from the international MiBioGen consortium, and combining data from the eQTLGen consortium and the GEFOS consortium, we identified microbiota related to osteoclasts and postmenopausal osteoporosis. Key genes were further identified through MAGMA analysis, and validation was performed using single-cell data GSE147287., Results: The outcomes of this study have uncovered significant associations within the gut microbiome community, particularly with the Burkholderiales order, which correlates with both an increase in osteoclasts and a reduced risk of postmenopausal osteoporosis. with an odds ratio (OR) of 0.400, and a P-value of 0.011. Further analysis using single-cell data allowed us to identify two key genes, FMNL2 and SRBD1, that are closely linked to both osteoclasts and osteoporosis., Conclusion: This study utilizing Mendelian randomization and single-cell data analysis, provides new evidence of a causal relationship between gut microbiota and osteoclasts, as well as postmenopausal osteoporosis. It was discovered that the specific microbial group, the Burkholderiales order, significantly impacts both osteoporosis and osteoclasts. Additionally, key genes FMNL2 and SRBD1 were identified, offering new therapeutic strategies for the treatment of postmenopausal osteoporosis., 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 © 2024 Xiao, Wang, Chen, Chen, Yang, Geng and Xia.)

The interplay between the human microbiome and the musculoskeletal system represents a burgeoning field of research with profound implications for understanding and treating musculoskeletal disorders. This review articulates the pivotal role of the microbiome in modulating bone health, highlighting the gut-bone axis as a critical nexus for potential therapeutic intervention. Through a meticulous analysis of recent clinical research, we underscore the microbiome's influence on osteoporosis, sarcopenia, osteoarthritis, and rheumatoid arthritis, delineating both the direct and indirect mechanisms by which microbiota could impact musculoskeletal integrity and function. Our investigation reveals novel insights into the microbiota's contribution to bone density regulation, hormone production, immune modulation, and nutrient absorption, laying the groundwork for innovative microbiome-based strategies in musculoskeletal disease management. Significantly, we identify the challenges hindering the translation of research into clinical practice, including the limitations of current microbial sequencing techniques and the need for standardized methodologies in microbiome studies. Furthermore, we highlight promising directions for future research, particularly in the realm of personalized medicine, where the microbiome's variability offers unique opportunities for tailored treatment approaches. This review sets a new agenda for leveraging gut microbiota in the diagnosis, prevention, and treatment of musculoskeletal conditions, marking a pivotal step toward integrating microbiome science into clinical musculoskeletal care.

Objectives: This study aims to determine the contamination incidence rate of bone fragments that have been dropped on the floor of the operating theatre, as well as how effective antimicrobial solutions are at decontaminating them., Methods: Bone fragments obtained after 30 total knee arthroplasties were used in the study. Inert pieces of bone emerging after the bone cuts during total knee arthroplasty were divided into 1 × 1 cm fragments. The bone fragments were first left in free fall on the floor of the operating theatre and then were kept in a number of antimicrobial solutions for 15 s. Subsequently, they were microbiologically and histopathologically examined. A swab culture was also taken from the floor of the operating theatre., Results: It was determined that 63.3% of osteochondral fragments in the non-intervened group were contaminated. Growth was likewise detected in all swab cultures. Microorganisms growing in the swab culture and the non-intervened group were similar and mostly Staphylococcus epidermidis and Klebsiella pneumoniae. When the growth rates of the 10% povidone-iodine and 4% chlorhexidine gluconate groups were compared with the growth rate of the non-intervened group, a statistical difference was found. No difference was determined between the growth rates of the sodium hypochlorite and the non-intervened groups. The histopathological analysis revealed no statistical difference between the groups in terms of bone marrow, vascular structure, fat tissue, and osteoblastic activity results in the osteochondral fragments CONCLUSION: Bone tissues dropped from a sterile area on the floor of the operating theatre are highly contaminated. An effective decontamination without bone cell toxicity was achieved using povidone-iodine. Although chlorhexidine gluconate solution had an effective decontamination effect compared to the non-intervened group, it was not 100% effective. Sodium hypochlorite solution was not effective in the decontamination of grafts under our working conditions., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

This paper aims to provide a first glimpse into the genomic characterization of individuals buried in Casal Bertone (Rome, first-third centuries AD) to gain preliminary insight into the genetic makeup of people who lived near a tannery workshop, fullonica. Therefore, we explored the genetic characteristics of individuals who were putatively recruited as fuller workers outside the Roman population. Moreover, we identified the microbial communities associated with humans to detect microbes associated with the unhealthy environment supposed for such a workshop. We examined five individuals from Casal Bertone for ancient DNA analysis through whole-genome sequencing via a shotgun approach. We conducted multiple investigations to unveil the genetic components featured in the samples studied and their associated microbial communities. We generated reliable whole-genome data for three samples surviving the quality controls. The individuals were descendants of people from North African and the Near East, two of the main foci for tannery and dyeing activity in the past. Our evaluation of the microbes associated with the skeletal samples showed microbes growing in soils with waste products used in the tannery process, indicating that people lived, died, and were buried around places where they worked. In that perspective, the results represent the first genomic characterization of fullers from the past. This analysis broadens our knowledge about the presence of multiple ancestries in Imperial Rome, marking a starting point for future data integration as part of interdisciplinary research on human mobility and the bio-cultural characteristics of people employed in dedicated workshops.

The treatment of infected bone defects in complex anatomical structures, such as oral and maxillofacial structures, remains an intractable clinical challenge. Therefore, advanced biomaterials that have excellent anti-infection activity and allow convenient delivery are needed. We fabricated an innovative injectable gellan gum (GG)-based hydrogel loaded with nanohydroxyapatite particles and chlorhexidine (nHA/CHX). The hydrogel has a porous morphology, suitable swelling ratio, and good biocompatibility. It exerts strong antibacterial activity against Staphylococcus aureus growth and biofilm formation in vitro . We successfully established an infected calvarial defect rat model. Bacterial colony numbers were significantly lower in tissues surrounding the bone in rats of the GG/nHA/CHX group after debride surgery and hydrogel implantation in the defect regions than in rats of the blank group. Rats in the GG/nHA/CHX group exhibited significantly increased new bone formation compared to those in the blank group at 4 and 8 weeks. These findings indicate that gellan gum-based hydrogel with nHA/CHX can accelerate the repair of infected bone defects.

Antibiotic treatment of native osteomyelitis caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) is a challenge. Limited epidemiological and outcome data are available. This retrospective cohort study included osteomyelitis patients with ESBL-PE infections treated in a reference centre for bone and joint infections (BJIs) between 2011-2019. Twenty-nine patients with native BJI (mean age, 44.4 ± 15.7 years) were analysed. Fifteen cases were paraplegic patients with ischial pressure sores breaching the hip capsule. Other cases included eight other hip infections, four tibial infections and two foot infections. Infections were mostly polymicrobial (n = 23; 79.3%), including Staphylococcus aureus (n = 13; 8 methicillin-resistant). Klebsiella pneumoniae (n = 13) was the most frequent ESBL-producing species identified, followed by Escherichia coli (n = 10), including 3 E. coli/K. pneumoniae co-infections, and Enterobacter spp. (n = 9). ESBL-PE were rarely susceptible to fluoroquinolones (n = 4; 13.8%). Most therapies were based on carbapenems (n = 22) and combination therapies (n = 19). The median duration of treatment was 41 (5-60) days. Primary control of the infection was achieved in 62.1% (18/29) of cases and up to 86.2% after second look surgeries, after a median follow-up of 6 (1-36) months. Infection with ESBL-producing K. pneumoniae was associated with failure (P = 0.001), whereas age, infection location, prior colonisation and antimicrobial therapy were not found to be predictors of outcome. ESBL-PE native BJIs are often polymicrobial and fluoroquinolone-resistant infections caused by K. pneumoniae, highlighting the need for expert centres with pluridisciplinary meetings with experienced surgeons., Competing Interests: Competing interests None declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Today's eating patterns are characterized by the consumption of unbalanced diets (UBDs) resulting in a variety of health consequences on the one hand, and the consumption of dietary supplements in order to achieve overall health and wellness on the other. Balanced nutrition is especially crucial during childhood and adolescence as these time periods are characterized by rapid growth and development of the skeleton. We show the harmful effect of UBD on longitudinal bone growth, trabecular and cortical bone micro-architecture and bone mineral density; which were analyzed by micro-CT scanning. Three point bending tests demonstrate the negative effect of the diet on the mechanical properties of the bone material as well. Addition of Spirulina algae or Pleurotus eryngii or Agaricus bisporus mushrooms, to the UBD, was able to improve growth and impaired properties of the bone. 16SrRNA Sequencing identified dysbiosis in the UBD rats' microbiota, with high levels of pro-inflammatory associated bacteria and low levels of bacteria associated with fermentation processes and bone related mechanisms. These results provide insight into the connection between diet, the skeletal system and the gut microbiota, and reveal the positive impact of three chosen dietary supplements on bone development and quality presumably through the microbiome composition.

The gastrointestinal tract is colonized by trillions of microorganisms, consisting of bacteria, fungi, and viruses, known as the "second gene pool" of the human body. In recent years, the microbiota-gut-bone axis has attracted increasing attention in the field of skeletal health/disorders. The involvement of gut microbial dysbiosis in multiple bone disorders has been recognized. The gut microbiota regulates skeletal homeostasis through its effects on host metabolism, immune function, and hormonal secretion. Owing to the essential role of the gut microbiota in skeletal homeostasis, novel gut microbiota-targeting therapeutics, such as probiotics and prebiotics, have been proven effective in preventing bone loss. However, more well-controlled clinical trials are still needed to evaluate the long-term efficacy and safety of these ecologic modulators in the treatment of bone disorders., (©2021 Society for Leukocyte Biology.)

An expanding body of research asserts that the gut microbiota has a role in bone metabolism and the pathogenesis of osteoporosis. This review considers the human gut microbiota composition and its role in osteoclastogenesis and the bone healing process, specifically in the case of osteoporosis. Although the natural physiologic processes of bone healing and the pathogenesis of osteoporosis and bone disease are now relatively well known, recent literature suggests that a healthy microbiome is tied to bone homeostasis. Nevertheless, the mechanism underlying this connection is still somewhat enigmatic. Based on the literature, a relationship between the microbiome, osteoblasts, osteoclasts, and receptor activator of nuclear factor-kappa-Β ligand (RANKL) is contemplated and explored in this review. Studies have proposed various mechanisms of gut microbiome interaction with osteoclastogenesis and bone health, including micro-RNA, insulin-like growth factor 1, and immune system mediation. However, alterations to the gut microbiome secondary to pharmaceutical and surgical interventions cannot be discounted and are discussed in the context of clinical therapeutic consideration. The literature on probiotics and their mechanisms of action is examined in the context of bone healing. The known and hypothesized interactions of common osteoporosis drugs and the human gut microbiome are examined. Since dysbiosis in the gut microbiota can function as a biomarker of bone metabolic activity, it may also be a pharmacological and nutraceutical (i.e., pre- and probiotics) therapeutic target to promote bone homeostasis.

Large bone defects face a high risk of infection, which can also lead to bone homeostasis disorders. This seriously hinders the bone healing process; therefore, the help of a dual-functional scaffold that has both anti-infection and bone-homeostasis-regulating capacities is needed in the treatment of infected bone defects. In this study, a 3D printed dual-functional scaffold composed of poly-ε-caprolactone (PCL), mesoporous bioactive glasses (MBG), and gallium (Ga) was produced. In vitro experiments demonstrated the excellent antibacterial ability of the PCL/MBG/Ga scaffold against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). The scaffold also significantly inhibited osteoclastic activity and promoted osteogenic differentiation. Furthermore, a rabbit model with an infected bone defect in the radius was used to evaluate the in vivo bone healing capability of PCL/MBG/Ga. The results demonstrate that the PCL/MBG/Ga scaffold can significantly accelerate bone healing and prevent bone resorption, suggesting its potential for application in repairing infected bone defects.

The development of disseminated cryptococcosis has historically occurred in patients living with advanced human immunodeficiency virus or other immunosuppressive conditions affecting T-cell function. Recently, patients with anti-cytokine neutralising autoantibodies have been recognised to be at risk for disseminated infections by opportunistic intracellular pathogens, including Cryptococcus species. Herein, we present a previously healthy 26-year-old man who was evaluated with disseminated cryptococcosis involving the bone, lung, mediastinum and brain. The patient's serum cryptococcal antigen titres were >1:1,100,000, and evaluation for an underlying immunodeficiency revealed high titres for anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies. We also review the literature of all published cases of disseminated cryptococcosis associated with the presence of anti-GM-CSF autoantibodies. Clinicians should have a heightened awareness of anti-cytokine autoantibodies in patients without a known immunodeficiency and development disseminated infections by opportunistic intracellular pathogens., (© 2021 Wiley-VCH GmbH.)

The Republic of Congo (RoC) is one of the African countries with the most histoplasmosis cases reported. This review summarizes the current status regarding epidemiology, diagnostic tools, and treatment of histoplasmosis in the RoC. A computerized search was performed from online databases Medline, PubMed, HINARI, and Google Scholar to collect literature on histoplasmosis in the RoC. We found 57 cases of histoplasmosis diagnosed between 1954 and 2019, corresponding to an incidence rate of 1-3 cases each year without significant impact of the AIDS epidemic in the country. Of the 57 cases, 54 (94.7%) were cases of Histoplasma capsulatum var. duboisii (Hcd) infection, African histoplasmosis. Three cases (5.3%) of Histoplasma capsulatum var. capsulatum infection were recorded, but all were acquired outside in the RoC. The patients' ages ranged between 13 months to 60 years. An equal number of cases were observed in adults in the third or fourth decades (n = 14; 24.6%) and in children aged ≤15 years. Skin lesions (46.3%), lymph nodes (37%), and bone lesions (26%) were the most frequent clinical presentations. Most diagnoses were based on histopathology and distinctive large yeast forms seen in tissue. Amphotericin B (AmB) was first line therapy in 65% of the cases and itraconazole (25%) for maintenance therapy. The occurrence of African histoplasmosis in apparently normal children raises the possibility that African histoplasmosis is linked to environmental fungal exposure., Competing Interests: The authors have declared that no competing interests exist.

It is well-known that the use of high-speed burring devices with irrigation used in bone surgery produces aerosols, and can toss tissue particles into space. The aim of this study was to assess the spatial vertical contamination in the sterile operation field while using a high-speed cutting device at various locations. A fresh porcine knee was resected for 10 min with a high-speed burring device. To determine the spatial contamination distribution bacteria were used as a tracer. In this novel method for detecting environmental contamination droplets of the contaminated irrigation solution were collected on vertically mounted Petri dishes and the number of colony-forming units was counted. Contamination of varying intensity was observed throughout the room. The highest contamination was found perpendicular to the bur rotation axis in a distance 0.5 m from the bur, at a height of 1.4 m. Around this spot, colony-forming units count isotropically drops to less than 100 CFUs at an area of 0.5 m in diameter. The contamination decreases with increasing distance to the bur head and a main direction of contamination was identified. Placing critical sterile objects in the highly contaminated space during and after bone resection procedures should be avoided whenever possible., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Infection and delayed wound healing are two major serious complications related to traumatic injuries and cause a significant burden to patients and society. Most currently available drug delivery materials typically carry a single drug, lack protection from drug loading, and face challenges in on-demand and precisely controlled drug release. Here, we report a flower ( Cirsium arvense )-inspired capsule-integrated multilayer nanofilm (FICIF), synthesized using a layer-by-layer self-assembly, for programmed multiple drug co-delivery for trauma (open fracture as an example) treatments. Our approach allows polypeptide multilayer nanofilms and innovative impregnated capsules to assemble hierarchical reservoirs with specific drug binding sites, shielding protection capability, and ordered packing structures. The resultant FICIF nanocarriers enable sustained and on-demand co-delivery of a unique immune-tuning cytokine (interleukin 12p70) and a growth factor (bone morphogenetic protein 2) in clinical use, resulting in extraordinary anti-infection (3 orders of magnitude improved bacterial killing) and bone regeneration (5 times enhanced bone healing) in treating infected rat femur fractures. The successful synthesis of these biomimetic high-performance delivery nanocoatings is expected to serve as a source of inspiration for the development of biomaterials for various clinical applications.

Background: Bone and joint infections (BJIs) due to Streptococcus agalactiae are rare but has been described to increase in the past few years. The objective of this study was to describe clinical features and outcomes of cases of S. BJIs., Methods: We conducted a retrospective analysis of adult cases of S. agalactiae BJIs that occurred between January 2009 and June 2015 in a French university hospital. The treatment success was assessed until 24 months after the end of antibiotic treatment., Results: Among the 26 patients included, 20 (77%) were male, mean age was 62 years ± 13 and mean Charlson comorbidity index score was 4.9 ± 3.2. Diabetes mellitus was the most common comorbidity (n = 14, 54%). Six had PJI (Prosthetic Joint Infections), five osteosynthesis-associated infections, 11 osteomyelitis and four native septic arthritis. Eleven patients had a delayed or late infection: six with a prosthetic joint infection and five with an internal fixation device infection. Sixteen patients (62%) had a polymicrobial BJI, most commonly with Gram-positive cocci (75%) notably Staphylococcus aureus (44%). Polymicrobial infections were more frequently found in foot infections (90% vs 44%, p = 0.0184). During the two-year follow-up, three patients died (3/25, 12%) and seven (7/25, 28%) had treatment failure., Conclusion: Diabetes mellitus was the most common comorbidity. We observed an heterogenous management and a high rate of relapse., Competing Interests: The authors have declared that no competing interests exist.

Parasitism is inherent to life and observed in all species. Extinct animals have been studied to understand what they looked like, where and how they lived, what they fed on, and the reasons they became extinct. Paleoparasitology helps to clarify these questions based on the study of the parasites and microorganisms that infected those animals, using as a source material coprolites, fossils in rock, tissue, bone, mummy, and amber, analyses of ancient DNA, immunodiagnosis, and microscopy., (© American Society of Parasitologists 2021.)

The key to evolution is reproduction. Pathogens can either kill the human host or can invade the host without causing death, thus ensuring their own survival, reproduction and spread. Tuberculosis, treponematoses and leprosy are widespread chronic infectious diseases whereby the host is not immediately killed. These diseases are examples of the co-evolution of host and pathogen. They can be well studied as the paleopathological record is extensive, spanning over 200 human generations. The paleopathology of each disease has been well documented in the form of published synthetic analyses recording each known case and case frequencies in the samples they were derived from. Here the data from these synthetic analyses were re-analysed to show changes in the prevalence of each disease over time. A total of 69,379 skeletons are included in this study. There was ultimately a decline in the prevalence of each disease over time, this decline was statistically significant (Chi-squared, p<0.001). A trend may start with the increase in the disease's prevalence before the prevalence declines, in tuberculosis the decline is monotonic. Increase in skeletal changes resulting from the respective diseases appears in the initial period of host-disease contact, followed by a decline resulting from co-adaptation that is mutually beneficial for the disease (spread and maintenance of pathogen) and host (less pathological reactions to the infection). Eventually either the host may become immune or tolerant, or the pathogen tends to be commensalic rather than parasitic., Competing Interests: The Authors have declared that no competing interests exist.

Osteomyelitis is a devastating complication of orthopaedic surgery and commonly caused by Staphylococcus aureus (S. aureus) and Group B Streptococcus (GBS, S. agalactiae). Clinically, S. aureus osteomyelitis is associated with local inflammation, abscesses, aggressive osteolysis, and septic implant loosening. In contrast, S. agalactiae orthopaedic infections generally involve soft tissue, with acute life-threatening vascular spread. While preclinical models that recapitulate the clinical features of S. aureus bone infection have proven useful for research, no animal models of S. agalactiae osteomyelitis exist. Here, we compared the pathology caused by these bacteria in an established murine model of implant-associated osteomyelitis. In vitro scanning electron microscopy and CFU quantification confirmed similar implant inocula for both pathogens (~10 5 CFU/pin). Assessment of mice at 14 days post-infection demonstrated increased S. aureus virulence, as S. agalactiae infected mice had significantly greater body weight, and fewer CFU on the implant and in bone and adjacent soft tissue (p < 0.05). X-ray, µCT, and histologic analyses showed that S. agalactiae induced significantly less osteolysis and implant loosening, and fewer large TRAP + osteoclasts than S. aureus without inducing intraosseous abscess formation. Most notably, transmission electron microscopy revealed that although both bacteria are capable of digesting cortical bone, S. agalactiae have a predilection for colonizing blood vessels embedded within cortical bone while S. aureus primarily colonizes the osteocyte lacuno-canalicular network. This study establishes the first quantitative animal model of S. agalactiae osteomyelitis, and demonstrates a vasculotropic mode of S. agalactiae infection, in contrast to the osteotropic behavior of S. aureus osteomyelitis., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Recent breakthroughs in our understanding of orthopaedic infections have come from advances in transmission electron microscopy (TEM) imaging of murine models of bone infection, most notably Staphylococcus aureus invasion and colonization of osteocyte-lacuno canalicular networks of live cortical bone during the establishment of chronic osteomyelitis. To further elucidate this microbial pathogenesis and evaluate the mechanism of action of novel interventions, additional advances in TEM imaging are needed. Here we present detailed protocols for fixation, decalcification, and epoxy embedment of bone tissue for standard TEM imaging studies, as well as the application of immunoelectron microscopy to confirm S. aureus occupation within sub-micron canaliculi. We also describe the first application of the novel Automated-Tape-UltraMicrotome system with three-dimensional reconstruction and volumetric analyses to quantify S. aureus occupation within the osteocyte-lacuno canalicular networks. Reconstruction of the three-dimensional volume broadened our perspective of S. aureus colonization of the canalicular network and, surprisingly, revealed adjacent noninfected canaliculi. This observation has led us to hypothesize that viable osteocytes of the osteocyte-lacuno canalicular networks respond and resist infection, opening future research directions to explain the paradox of adjacent uninfected canaliculi and life-long deep bone infection in patients with chronic osteomyelitis., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Bone related-bacterial diseases including wound infections and osteomyelitis (OM) remain a serious problem accompanied with amputation in most severe cases. In this work, we report an exceptional effective antibacterial alginate aerogel, which consists of tigecycline (TGC) and octahedral Cu crystal as an organo-inorganic synergy platform for antibacterial and local infection therapy applications. The alginate aerogel could greatly prolong the release of copper ions and maintain effective antibacterial concentration over 18 days. The result of in-vitro experiments demonstrated that the alginate aerogel has an exceptional effective function on antibacterial activity. Cytotoxicity tests indicated that the alginate aerogel has low biological toxicity (average cell viability >75%). These remarkable results suggested that the alginate aerogel exhibits great potential for the treatment of OM, and has a prosperous future of application in bone tissue engineering., (Copyright © 2020. Published by Elsevier B.V.)

The objective of this study was to evaluate the clinical outcomes and safety of clindamycin combination antibiotherapy for the treatment of erythromycin-resistant, lincosamide-susceptible bone and joint infections caused by Staphylococcus spp. Between January 2010 and September 2018, 46 patients with Staphylococcus spp. erythromycin-resistant, lincosamide-susceptible bone and joint infections were treated with clindamycin combination antibiotherapy for 6 to 12 weeks. The type of infection was prosthetic in 20 cases (43.5%), osteosynthetic device in 15 cases (32.6%), chronic osteomyelitis in 7 cases (15.2%), and arthritis in 4 cases (8.7%). The cure rate was 67.4% by intention to treat and 84.6% per protocol, with a median follow-up of 398 days (range 86-843). Only 2 relapses (5.1%) were observed in patients with chronic osteomyelitis; an acquired resistance to lincosamides developed in 1 case. Clindamycin combination therapy appears to be effective for the treatment of bone and joint infection caused by erythromycin-resistant, lincosamide-susceptible Staphylococcus spp., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The present study aimed to evaluate the feasibility of percutaneous bone biopsy in an ambulatory setting as part of the management of diabetic foot osteomyelitis (DFO) on an outpatient basis. DFO may complicate some cases of apparently nonsevere foot infections in patients with diabetes and greatly increase the risk of a lower extremity amputation. It has been suggested that bone culture-based antibiotic therapy is a predictive factor of success in patients with diabetes treated nonsurgically for osteomyelitis of the foot. It is recommended to identify the causative microorganism(s) by the means of either a surgical or percutaneous bone biopsy taken appropriately to select the proper antibiotic therapy. Percutaneous bone biopsy in patients not requiring surgery is, however, not performed in everyday practice as it should be according to the current recommendations. In the present retrospective study, we report a series of 23 consecutive patients with a suspicion of DFO in whom 28 bone samples were collected by percutaneous biopsy at the bedside in an outpatient setting. The percentage of positive cultures was in accordance with that reported in the literature. The mean number of isolates per specimen was 1.04. After a mean 12-month follow-up, the remission was almost of 78%. No adverse event related to the bone biopsy was noted. After a 1-year follow-up, no recurrence was recorded among the patients in remission. The results of the present study suggest that bedside percutaneous bone biopsy performed in the ambulatory setting is a valuable and safe tool in the management of DFO on an outpatient basis.

The Mycobacterium tuberculosis complex (MTC) has affected South American populations since ca. 200 years BCE. In Argentina, possible cases date from ca. 1000-1400 Common Era (CE). This paper describes the oldest (905-1030 CE) confirmed case of tuberculosis (TB) in a young adult male from Lomitas de Saujil (Tinogasta, Catamarca, Argentina). Osteolytic lesions on the bodies of the lower spine were macroscopically and radiographically identified. Bilateral new bone formation was seen on the visceral vertebral third of several ribs and in long bones, compatible with hypertrophic osteoarthropathy. Representative rib and hand bones gave profiles for MTC-specific C 27 -C 32 mycocerosic acid lipid biomarkers; these were strongest in one heavily-lesioned lower rib, which also had MTC-diagnostic C 76 -C 89 mycolic acids and positive amplification of MTC-typical IS6110 aDNA fragments. During the first millennium CE, the intense social interaction, the spatial circumscription of villages among the pre-Hispanic societies in the mesothermal valleys of Catamarca and the fluid contacts with the Eastern lowlands, valleys and puna, were factors likely to favor disease transmission. It is proposed that TB arrived from northern Chile and dispersed towards the northeast into the Yocavil valley, where several cases of TB infection were macroscopically identified for a later chronology., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.

Objective: Xpert MTB/RIF is recommended to detect pulmonary tuberculosis; however, there is insufficient data on its utility for bone samples. This study aimed to assess the accuracy of Xpert MTB/RIF compared with conventional histopathology in diagnosing spinal tuberculosis (STB) based on bone specimens in high burden settings., Materials and Methods: Totally, 128 suspected STB participants were enrolled into this study. The bone specimens were obtained through puncture or operation for histological and Xpert MTB/RIF analyses, so as to compare their accuracy in diagnosing STB by the composite reference standard (CRS)., Results: Finally, 106 subjects with suspected STB were recruited into the analysis, including 27 confirmed and 33 clinically diagnosed STB patients. Relative to histopathology, Xpert MTB/RIF achieved a 86.7% sensitivity, and 12 out of 30 STB patients were positive, while the negative results in them were obtained upon histopathology. Based on CRS, Xpert MTB/RIF yielded a 63.3% sensitivity, which significantly elevated relative to that obtained upon histopathological test (50.0%, p < 0.001). In addition, the pooled sensitivity obtained using the above 2 approaches was as high as 95.0%, which was higher than that of any of the 2 approaches alone. The pooled specificity was 97.8%. Moreover, the area under the curve (AUC) value was 0.75 for Xpert MTB/RIF and 0.81 for histopathology, with no statistical significance. The two methods showed moderate concordance in the diagnosis of STB., Conclusions: The Xpert MTB/RIF test achieves superior specificity and fair sensitivity, which can not be recommended to replace the conventional examinations for the diagnosis of STB. The combined application of these 2 approaches can improve the pooled diagnostic sensitivity and accuracy for STB., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Bacteria play an important role in the degradation of bone material. However, much remains to be learnt about the structure of their communities in degrading bone, and how the depositional environment influences their diversity throughout the exposure period. We genetically profiled the bacterial community in an experimental series of pig bone fragments (femur and humeri) deposited at different well-defined environments in Denmark. The bacterial community in the bone fragments and surrounding depositional environment were studied over one year, and correlated with the bioerosion damage patterns observed microscopically in the bones. We observed that the bacterial communities within the bones were heavily influenced by the local microbial community, and that the general bone microbial diversity increases with time after exposure. We found the presence of several known collagenase producing bacterial groups, and also observed increases in the relative abundance of several of these in bones with tunneling. We anticipate that future analyses using shotgun metagenomics on this and similar datasets will be able to provide insights into mechanisms of microbiome driven bone degradation., Competing Interests: The authors have declared that no competing interests exist.

Bone infections, also known as infectious osteomyelitis, are accompanied by significant inflammation, osteolysis, and necrosis. Osteoclasts (OCs) are the bone-resorbing cells that work in concert with osteoblasts and osteocytes to properly maintain skeletal health and are well known to respond to inflammation by increasing their resorptive activity. OCs have typically been viewed merely as effectors of pathologic bone resorption, but recent evidence suggests they may play an active role in the progression of infections through direct effects on pathogens and via the immune system. This review discusses the host- and pathogen-derived factors involved in the in generation of OCs during infection, the crosstalk between OCs and immune cells, and the role of OC lineage cells in the growth and survival of pathogens, and highlights unanswered questions in the field.

Background [ 18 F]FDG Positron Emission Tomography cannot differentiate between sterile inflammation and infection. Therefore, we, aimed to develop more specific radiotracers fitted for differentiation between sterile and septic infection to improve the diagnostic accuracy. Consequently, the clinicians can refine the treatment of, for example, prosthesis-related infection., Methods: We examined different target points; Staphylococcus aureus biofilm ( 68 Ga-labeled DOTA-K-A9 and DOTA-GSGK-A11), bone remodeling ([ 18 F]NaF), bacterial cell membranes ([ 68 Ga]Ga-Ubiquicidin), and leukocyte trafficking ([ 68 Ga]Ga-DOTA-Siglec-9). We compared them to the well-known glucose metabolism marker [ 18 F]FDG, in a well-established juvenile S. aureus induced osteomyelitis (OM) pig model., Results: [ 18 F]FDG accumulated in the OM lesions seven days after bacterial inoculation, but disappointingly we were not able to identify any tracer accumulation in OM with any of the supposedly more specific tracers., Conclusion: These negative results are, however, relevant to report as they may save other research groups from conducting the same animal experiments and provide a platform for developing and evaluating other new potential tracers or protocol instead.

Aim: This paper was mainly aimed at synthesis of Ce-containing nano-Mg-phosphate ceramic as a multifunctional material., Materials and Methods: Two ceramics based on Mg 3 (PO 4 ) 2 and Ce 0.2 Mg 2.8 (PO 4 ) 2 formulas (MP and MP-C, respectively) were synthesized. The synthesized powders were characterized by XRD, TEM, Zeta potential, and FTIR. Also, their dissolution behavior was tested in Tris-HCl buffer solution. Moreover, the antimicrobial efficacy was evaluated against gram-positive bacteria (Bacillus sphaericus MTCC 511 &Staphylococcus aureus MTCC 87) and gram-negative bacteria (Enterobacter aerogenes MTCC 111 &Pseudomonas aeruginosa MTCC 1034) using dick diffusion assay and microdilution method. Furthermore, the cell viability test was performed for the ceramics on Vero cells (African green monkey kidney cells), and their antitumor activity was determined by PC3 cell line (prostatic cancer). Also, the cellular uptake was determined by the flow cytometry., Key Findings: The results showed that the substitution of Mg by Ce decreased the particle size from 40 to 90 nm for MP sample to 2-10 nm for MP-C sample and increased the degradation rate. Both samples showed excellent antimicrobial activities. Moreover, MP demonstrated more cell viability than MP-C on Vero cells at high concentrations, whereas, MP-C showed more antitumor activity on PC3 cells than MP sample. Moreover, MP-C showed a higher cell uptake than MP due to its smaller size and more negative charge., Significance: Mg-phosphate ceramic can be used in this study successfully as a delivery system for cerium ions and showed a high antitumor activity, which makes it highly recommended as safe and effective cancer treatment materials., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Surgical site infections after orthopaedic surgery using fracture fixation devices or endosseous implants create major surgical challenges with severe adverse effects, such as osteomyelitis. These infections are frequently caused by Staphylococcus aureus, often with high resistance to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). Due to the formation of impenetrable biofilms on implant surfaces, systemic antibiotic treatment has become exceedingly difficult. New solutions are pursued by combining several drugs using a controlled delivery system from specifically engineered implant surfaces. A sol-gel coating on titanium implants was previously developed with 20 wt % vancomycin and 30 wt % farnesol, with suppression of MRSA in vitro. The present study investigated the efficacy of sol-gel film coatings for controlled dual local delivery over 4 weeks utilising a rat infection model. The findings confirmed the viability of this new concept in vivo based on the differences observed between coatings containing vancomycin alone (SGV) and the dual-drug-containing coating with vancomycin and farnesol (SGVF). While both the SGVF and SGV coatings facilitated excellent preservation of the osseous microarchitecture, SGVF coating displayed a slightly higher potency for suppressing MRSA infiltration than SGV, in combination with a lower reactive bone remodelling activity, most likely by disturbing biofilm formation. The next step for advancing the concept of dual-drug delivery from sol-gel coatings to the clinic and confirming the promising effect of the SGVF coatings on reactive bone remodelling and suppressing MRSA infiltration is a study in a larger animal species with longer time points.

Microbial colonization of bone is an important mechanism of postmortem skeletal degradation. However, the types and distributions of bone and tooth colonizing microbes are not well characterized. It is unknown if microbial communities vary in abundance or composition between bone element types, which could help explain differences in human DNA preservation. The goals of the present study were to (1) identify the types of microbes capable of colonizing different human bone types and (2) relate microbial abundances, diversity, and community composition to bone type and human DNA preservation. DNA extracts from 165 bone and tooth samples from three skeletonized individuals were assessed for bacterial loading and microbial community composition and structure. Random forest models were applied to predict operational taxonomic units (OTUs) associated with human DNA concentration. Dominant bacterial bone colonizers were from the phyla Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, and Planctomycetes. Eukaryotic bone colonizers were from Ascomycota, Apicomplexa, Annelida, Basidiomycota, and Ciliophora. Bacterial loading was not a significant predictor of human DNA concentration in two out of three individuals. Random forest models were minimally successful in identifying microbes related to human DNA concentration, which were complicated by high variability in community structure between individuals and body regions. This work expands on our understanding of the types of microbes capable of colonizing the postmortem human skeleton and potentially contributing to human skeletal DNA degradation., Competing Interests: This project was supported by Award No. 2010-DN-BX-K229, awarded by the National Institute of Justice, Office of Justice Programs, U.S. Department of Justice (DOJ) to AZM, JMD, and JD and Award 1549726, awarded by the National Science Foundation (NSF), to JMD. DOJ and NSF had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Bode Cellmark Forensics provided support in the form of salary for JD, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The opinions, findings, and conclusions or recommendations expressed in this manuscript are those of the authors and do not necessarily reflect those of the DOJ, NSF or Bode Cellmark Forensics.

Groundbreaking studies conducted in the mid-1980s demonstrated the possibility of sequencing ancient DNA (aDNA), which has allowed us to answer fundamental questions about the human past. Microbiologists were thus given a powerful tool to glimpse directly into inscrutable bacterial history, hitherto inaccessible due to a poor fossil record. Initially plagued by concerns regarding contamination, the field has grown alongside technical progress, with the advent of high-throughput sequencing being a breakthrough in sequence output and authentication. Albeit burdened with challenges unique to the analysis of bacteria, a growing number of viable sources for aDNA has opened multiple avenues of microbial research. Ancient pathogens have been extracted from bones, dental pulp, mummies and historical medical specimens and have answered focal historical questions such as identifying the aetiological agent of the black death as Yersinia pestis . Furthermore, ancient human microbiomes from fossilized faeces, mummies and dental plaque have shown shifts in human commensals through the Neolithic demographic transition and industrial revolution, whereas environmental isolates stemming from permafrost samples have revealed signs of ancient antimicrobial resistance. Culminating in an ever-growing repertoire of ancient genomes, the quickly expanding body of bacterial aDNA studies has also enabled comparisons of ancient genomes to their extant counterparts, illuminating the evolutionary history of bacteria. In this review we summarize the present avenues of research and contextualize them in the past of the field whilst also pointing towards questions still to be answered.

Intestinal microbiota are considered a sensor for molecular pathways, which orchestrate energy balance, immune responses, and cell regeneration. We previously reported that microbiota restriction promoted higher levels of systemic radiation-induced genotoxicity, proliferative lymphocyte activation, and apoptotic polarization of metabolic pathways. Restricted intestinal microbiota (RM) that harbors increased abundance of Lactobacillus johnsonii (LBJ) has been investigated for bacterial communities that correlated radiation-induced genotoxicity. Indicator phylotypes were more abundant in RM mice and increased in prevalence after whole body irradiation in conventional microbiota (CM) mice, while none of the same ten most abundant phylotypes were different in abundance between CM mice before and after heavy ion irradiation. Muribaculum intestinale was detected highest in female small intestines in RM mice, which were lacking Ureaplasma felinum compared with males, and thus these bacteria could be contributing to the differential amounts of radiation-induced systemic genotoxicity between the CM and RM groups. Helicobacter rodentium and M.intestinale were found in colons in the radiation-resistant CM phenotype. While the expression of interferon-γ was elevated in the small intestine, and lower in blood in CM mice, high-linear energy transfer radiation reduced transforming growth factor-β with peripheral interleukin (IL)-17 in RM mice, particularly in females. We found that female RM mice showed improved micro-architectural bone structure and anti-inflammatory radiation response compared with CM mice at a delayed phase 6 weeks postexposure to particle radiation. However, microbiota restriction reduced inflammatory markers of tumor necrosis factor in marrow, when IL-17 was reduced by intraperitoneal injection of IL-17 neutralizing antibody., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

To analyze host and pathogen factors related to disease severity of community-acquired bone and joint infections in children, a cohort of pediatric patients was prospectively recruited from 13 centers in 7 European countries. A total of 85 children were included, 11 (13%) had a severe infection. Panton-Valentine leukocidin-positive isolates were 17%, and 6% of the isolates were methicillin-resistant Staphylococcus aureus. Multivariate analysis identified Panton-Valentine leukocidin presence (adjusted odds ratio, 12.6; P = 0.01) as the only factor independently associated with severe outcome, regardless of methicillin resistance.