Participant perspectives of an online co-design process to develop a prevention-focused mental health and well-being platform for primary producers.

OBJECTIVE: To explore participant experiences of an online co-design process to develop a web-based preventative mental health and well-being intervention targeting primary producers in rural Australia. SETTING: Rural Victoria, Australia. PARTICIPANTS: Participants from a primary producer background, including horticulture, fisheries, animal cultivation and farm consultancy, were eligible for the study if they had participated in both the co-design and beta testing processes for a primary producer platform. DESIGN: A qualitative study using semi-structured phone-based interviews was undertaken. A reflexive inductive approach to data analysis was employed to develop themes. RESULTS: Eleven participants were interviewed, with an average age of 51 years, of which 7 were female. Five main themes were developed. These included: (1) participant diversity, (2) impact of online delivery on co-design participation, (3) experiences of the co-design process, (4) maintaining a shared vision and goals and (5) acting on the co-design recommendations. Use of online methods was a clear enabler to engage participants who were geographically dispersed and offers an alternative to more conventional approaches to co-design using face-to-face methods. Some aspects of participant engagement may need a greater focus when conducted online compared with face-to-face. CONCLUSIONS: Using an online co-design method to develop a preventative mental health and well-being web-based platform for primary producers was novel. Findings address a gap in the literature around the experience of participants engaging in a co-design process and identify opportunities to improve participant engagement and experience with the online format.

The Role of the Metzincin Superfamily in Prostate Cancer Progression: A Systematic-Like Review.

Prostate cancer remains a leading cause of cancer-related morbidity in men. Potentially important regulators of prostate cancer progression are members of the metzincin superfamily of proteases, principally through their regulation of the extracellular matrix. It is therefore timely to review the role of the metzincin superfamily in prostate cancer and its progression to better understand their involvement in this disease. A systematic-like search strategy was conducted. Articles that investigated the roles of members of the metzincin superfamily and their key regulators in prostate cancer were included. The extracted articles were synthesized and data presented in tabular and narrative forms. Two hundred and five studies met the inclusion criteria. Of these, 138 investigated the role of the Matrix Metalloproteinase (MMP) subgroup, 34 the Membrane-Tethered Matrix Metalloproteinase (MT-MMP) subgroup, 22 the A Disintegrin and Metalloproteinase (ADAM) subgroup, 8 the A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) subgroup and 53 the Tissue Inhibitor of Metalloproteinases (TIMP) family of regulators, noting that several studies investigated multiple family members. There was clear evidence that specific members of the metzincin superfamily are involved in prostate cancer progression, which can be either in a positive or negative manner. However, further understanding of their mechanisms of action and how they may be used as prognostic indicators or molecular targets is required.

Geographical analysis of evaluated chronic disease programs for Aboriginal and Torres Strait Islander people in the Australian primary health care setting: a systematic scoping review.

BACKGROUND: Targeted chronic disease programs are vital to improving health outcomes for Indigenous people globally. In Australia it is not known where evaluated chronic disease programs for Aboriginal and Torres Strait Islander people have been implemented. This scoping review geographically examines where evaluated chronic disease programs for Aboriginal people have been implemented in the Australian primary health care setting. Secondary objectives include scoping programs for evidence of partnerships with Aboriginal organisations, and use of ethical protocols. By doing so, geographical gaps in the literature and variations in ethical approaches to conducting program evaluations are highlighted. METHODS: The objectives, inclusion criteria and methods for this scoping review were specified in advance and documented in a published protocol. This scoping review was undertaken in accordance with the Joanna Briggs Institute (JBI) scoping review methodology. The search included 11 academic databases, clinical trial registries, and the grey literature. RESULTS: The search resulted in 6894 citations, with 241 retrieved from the grey literature and targeted organisation websites. Title, abstract, and full-text screening was conducted by two independent reviewers, with 314 citations undergoing full review. Of these, 74 citations evaluating 50 programs met the inclusion criteria. Of the programs included in the geographical analysis (n = 40), 32.1% were implemented in Major Cities and 29.6% in Very Remote areas of Australia. A smaller proportion of programs were delivered in Inner Regional (12.3%), Outer Regional (18.5%) and Remote areas (7.4%) of Australia. Overall, 90% (n = 45) of the included programs collaborated with an Aboriginal organisation in the implementation and/or evaluation of the program. Variation in the use of ethical guidelines and protocols in the evaluation process was evident. CONCLUSIONS: A greater focus on the evaluation of chronic disease programs for Aboriginal people residing in Inner and Outer Regional areas, and Remote areas of Australia is required. Across all geographical areas further efforts should be made to conduct evaluations in partnership with Aboriginal communities residing in the geographical region of program implementation. The need for more scientifically and ethically rigorous approaches to Aboriginal health program evaluations is evident.

Balsamin induces apoptosis in breast cancer cells via DNA fragmentation and cell cycle arrest.

Breast cancer is the second most common cancer causing death worldwide with metastasis and disease relapse being the major drawbacks in current treatments. Therefore, development of novel drugs is needed. Balsamin, a 28 kDa Type I ribosome-inactivating protein, is rich in the seeds of Momordica balsamina. In this study, the molecular mechanism and the possible effects of balsamin on the two key hallmarks of cancer were investigated. Firstly, the induction of apoptosis in human breast cancer MCF-7 and BT549 cells showed that balsamin-induced apoptosis involved increases in caspase-3 and caspase-8 activity, upregulation of Bax, Bid, and Bad, and downregulation of BCL-2 and BCL-XL. Furthermore, balsamin inhibited the proliferation of breast cancer cells in a dose-dependent manner with IC50 values of 24.53 and 32.79 µg/ml for MCF-7 and BT549 cells, respectively. Moreover, flow cytometric analysis revealed that balsamin induced S-/G-phase cell cycle arrest. Our studies show that balsamin has anti-tumor activity and could be used as a neutraceutical for the treatment of breast cancer.

The Mortality and Myocardial Effects of Antidepressants Are Moderated by Preexisting Cardiovascular Disease: A Meta-Analysis.

BACKGROUND: Antidepressants (ADs) are commonly prescribed medications, but their long-term health effects are debated. ADs disrupt multiple adaptive processes regulated by evolutionarily ancient biochemicals, potentially increasing mortality. However, many ADs also have anticlotting properties that can be efficacious in treating cardiovascular disease. We conducted a meta-analysis assessing the effects of ADs on all-cause mortality and cardiovascular events in general-population and cardiovascular-patient samples. METHODS: Two reviewers independently assessed articles from PubMed, EMBASE, and Google Scholar for AD-related mortality controlling for depression and other comorbidities. From these articles, we extracted information about cardiovascular events, cardiovascular risk status, and AD class. We conducted mixed-effect meta-analyses testing sample type and AD class as moderators of all-cause mortality and new cardiovascular events. RESULTS: Seventeen studies met our search criteria. Sample type consistently moderated health risks. In general-population samples, AD use increased the risks of mortality (HR = 1.33, 95% CI: 1.14-1.55) and new cardiovascular events (HR = 1.14, 95% CI: 1.08-1.21). In cardiovascular patients, AD use did not significantly affect risks. AD class also moderated mortality, but the serotonin reuptake inhibitors were not significantly different from tricyclic ADs (TCAs) (HR = 1.10, 95% CI: 0.93-1.31, p = 0.27). Only "other ADs" were differentiable from TCAs (HR = 1.35, 95% CI: 1.08-1.69). Mortality risk estimates increased when we analyzed the subset of studies controlling for premedication depression, suggesting the absence of confounding by indication. CONCLUSIONS: The results support the hypothesis that ADs are harmful in the general population but less harmful in cardiovascular patients.

Identifying Factors and Techniques to Decrease the Positive Margin Rate in Partial Mastectomies: Have We Missed the Mark?

Breast conservation therapy (BCT) has a reported incidence of positive margins ranging widely in the literature from 20% to 70%. Efforts have been made to refine standards for partial mastectomy and to predict which patients are at highest risk for incomplete excision. Most have focused on histology and demographics. We sought to further define modifiable risk factors for positive margins and residual disease. A retrospective study was conducted of 567 consecutive partial mastectomies by 21 breast and general surgeons from 2009 to 2012. Four hundred fourteen cases of neoplasm were reviewed for localization, intraoperative assessment, excision technique, rates, and results of re-excision/mastectomy. Histologic margins were positive in 23% of patients, 25% had margins 0.1-0.9 mm, and 7% had tumor within 1-1.9 mm. Residual tumor was identified at-in 61 cases: 38% (disease at margin), 21% (0.1-0.9 mm), and 14% (1-1.9 mm). Ductal carcinoma in situ (DCIS) was present in 85% of residual disease on re-excision and correlated to higher rates of re-excision (p = <0.001), residual disease, and subsequent mastectomy. The use of multiple needles to localize neoplasms was associated with 2-3 times the likelihood for positive margins than when a single needle was required. The removal of additional margins at initial surgery correlated with improved rates of complete excision when DCIS was present. Patients must have careful analysis of specimen margins at the time of surgery and may benefit from additional tissue excision or routine shaving of the cavity of resection. Surgeons should conduct careful patient selection for BCT, in the context of multifocal, and multicentric disease. Patients for whom tumor localization requires bracketing may be at higher risk for positive margins and residual disease and should be counseled accordingly.

A national follow-up survey of UK graduates opinion of undergraduate oral surgery teaching.

INTRODUCTION: A national follow-up survey was undertaken to determine whether dental graduates from 2009 perceived that their undergraduate oral surgery education had equipped them for general dental practice 4 years after graduating. MATERIALS AND METHODS: Graduates from the same 13 United Kingdom dental schools who had taken part in the original survey were invited to take part in this follow-up online survey. Their contact details were identified via the general dental council register, social media and alumni groups. RESULTS: In total, 161 responded (2009b) which represents 16% of the graduates of the original survey in 2009a. A similar percentage of these respondents perceived that the teaching in oral surgery had given them sufficient knowledge to undertake independent practice (83% and 79% in 2009a and 2009b, respectively). Most respondents (99% in both years) reported confidence in undertaking simple forceps exodontia. Confidence in surgical exodontia was poor in both surveys, but one area that appeared improved in the follow-up related to the sectioning of teeth (84% in 2009b compared with 49% in 2009a). Areas of weakness identified in 2009 were reported to be improved in the follow-up. CONCLUSION: This follow-up survey supports the findings of the original survey. Future longitudinal studies would allow institutions to identify possible weaknesses in their curriculum and to track the career development of their graduates and facilitate robust data collection.

The evolutionary conservation of the A Disintegrin-like and Metalloproteinase domain with Thrombospondin-1 motif metzincins across vertebrate species and their expression in teleost zebrafish.

BACKGROUND: The A Disintegrin-like and Metalloproteinase domain with Thrombospondin-1 motifs (ADAMTS) enzymes comprise 19 mammalian zinc-dependent metalloproteinases (metzincins) with homologues in a wide range of invertebrates. ADAMTS enzymes have a broad range of functions in development and diseases due to their extracellular matrix remodelling activity. Here, we report a detailed characterisation of their evolutionary conservation across vertebrates. RESULTS: Using bioinformatics complemented with de novo sequencing, gene sequences for ADAMTS enzymes were obtained from a variety of organisms. Detailed evolutionary analyses revealed a high level of conservation across vertebrates with evidence of ADAMTS gene expansion during two rounds of whole genome duplication (WGD) in vertebrates, while tandem duplication events and gene loss were also apparent. However, the additional round of teleost-specific WGD did not have a significant effect on ADAMTS gene family members suggesting their conserved roles have remained constant in teleost fish. Quantitative reverse-transcriptase polymerase chain reaction analysis revealed dynamic expression of adamts genes throughout zebrafish embryonic development reflecting the key conserved roles they play in vertebrate embryogenesis. Notably, several adamts mRNAs were maternally expressed with a dramatic increase in mRNA levels coinciding with zygotic expression and organogenesis. Broad adamts mRNA expression was also demonstrated in several adult organs indicating potential roles in adult homeostasis. CONCLUSIONS: Our data highlight the evolution of the ADAMTS gene family through duplication processes across metazoans supplemented by a burst of amplification through vertebrate WGD events. It also strongly posits the zebrafish as a potential model species to further elucidate the function of ADAMTS enzymes during vertebrate development.

The prevalence of co-prescription of clinically relevant CYP enzyme inhibitor and substrate drugs in community-dwelling elderly Australians.

WHAT IS KNOWN AND OBJECTIVE: The elderly are at increased risk of adverse effects resulting from drug interactions due to decreased drug clearance and polypharmacy. This study examines the prevalence of the co-administration of clinically relevant cytochrome P450 (CYP) enzyme inhibitors with drugs that are substrates for these enzymes, in the community-dwelling elderly in Australia. METHODS: Participants aged 75 years or older (n = 1045) were recruited via their general practitioners at four Australian sites (Newcastle, Sydney, Melbourne and Adelaide). A research nurse visited the home of each patient to compile a list of all prescription medications (including doses) currently used by the patient, and to complete assessments for depression, quality of life and cognitive status. The medication data were searched for the co-prescription of clinically relevant CYP inhibitor and corresponding substrate drugs. RESULTS AND DISCUSSION: Potentially inappropriate CYP inhibitor-substrate combinations were found in 6·2% (65/1045) of patients. These patients were on significantly more medications (6·1 ± 3·0 vs. 3·9 ± 2·5; P = 0·001) and had a significantly lower physical quality of life (P = 0·047) than those who were not on any CYP inhibitor-substrate combinations. The most commonly prescribed inhibitor-substrate combinations involved the CYP 3A4 inhibitors, diltiazem and verapamil, with the substrates simvastatin or atorvastatin. Only 1 of 41 patients on a CYP3A4 inhibitor and a statin was prescribed a non-CYP 3A4 metabolized statin. Metoprolol was another substrate commonly co-prescribed with a CYP2D6 inhibitor. In many cases, the risks and benefits of potential interactions may have been considered by the GP as the prescribed doses of both the inhibitor and substrate were relatively low. There were, however, some notable exceptions, also involving the substrates simvastatin, atorvastatin and metoprolol. There were no GP factors that were associated with co-prescription of CYP inhibitors and substrates. WHAT IS NEW AND CONCLUSION: There is not a particular GP demographic that should be targeted for education regarding CYP interactions, but a focus on particular medications such as the statins may reduce the potential for clinically significant drug-drug interactions. As CYP drug-drug interactions are more common in patients on higher number of medications, particular vigilance is required at the time of prescribing and dispensing medications for elderly patients with multiple conditions.

Evaluating osteogenic effects associated with the incorporation of ascorbic acid in mineralized collagen scaffolds.

Current treatments for craniomaxillofacial (CMF) defects motivate the design of instructive biomaterials that can promote osteogenic healing of complex bone defects. We report methods to promote in vitro osteogenesis of human mesenchymal stem cells (hMSCs) within a model mineralized collagen scaffold via the incorporation of ascorbic acid (vitamin C), a key factor in collagen biosynthesis and bone mineralization. An addition of 5 w/v% ascorbic acid into the base mineralized collagen scaffold significantly changes key morphology characteristics including porosity, macrostructure, and microstructure. This modification promotes hMSC metabolic activity, ALP activity, and hMSC-mediated deposition of calcium and phosphorous. Additionally, the incorporation of ascorbic acid influences osteogenic gene expression (BMP-2, RUNX2, COL1A2) and delays the expression of genes associated with osteoclast activity and bone resorption (OPN, CTSK), though it reduces the secretion of OPG. Together, these findings highlight ascorbic acid as a relevant component for mineralized collagen scaffold design to promote osteogenic differentiation and new bone formation for improved CMF outcomes.

Rapid Assessment of Biomarkers on Single Extracellular Vesicles Using 'Catch and Display' on Ultrathin Nanoporous Silicon Nitride Membranes.

Extracellular vesicles (EVs) are particles secreted by all cells that carry bioactive cargo and facilitate intercellular communication with roles in normal physiology and disease pathogenesis. EVs have tremendous diagnostic and therapeutic potential and accordingly, the EV field has grown exponentially in recent years. Bulk assays lack the sensitivity to detect rare EV subsets relevant to disease, and while single EV analysis techniques remedy this, they are undermined by complicated detection schemes often coupled with prohibitive instrumentation. To address these issues, we propose a microfluidic technique for EV characterization called 'catch and display for liquid biopsy (CAD-LB)'. CAD-LB rapidly captures fluorescently labeled EVs in the similarly-sized pores of an ultrathin silicon nitride membrane. Minimally processed sample is introduced via pipette injection into a simple microfluidic device which is directly imaged using fluorescence microscopy for a rapid assessment of EV number and biomarker colocalization. In this work, nanoparticles were first used to define the accuracy and dynamic range for counting and colocalization by CAD-LB. Following this, the same assessments were made for purified EVs and for unpurified EVs in plasma. Biomarker detection was validated using CD9 in which Western blot analysis confirmed that CAD-LB faithfully recapitulated differing expression levels among samples. We further verified that CAD-LB captured the known increase in EV-associated ICAM-1 following the cytokine stimulation of endothelial cells. Finally, to demonstrate CAD-LB's clinical potential, we show that EV biomarkers indicative of immunotherapy responsiveness are successfully detected in the plasma of bladder cancer patients undergoing immune checkpoint blockade.

The Metabolic and Endocrine Effects of a 12-Week Allulose-Rich Diet.

The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown to reduce blood glucose, in a rat model of diet-induced obesity and T2D. Over 12 weeks, we hypothesized that allulose supplementation would improve body weight, insulin sensitivity, and glycemic control. Our results showed that allulose mitigated the adverse effects of high-fat, high-sugar diets, including reduced body weight gain and improved insulin resistance. The allulose group exhibited lower food consumption and increased levels of glucagon-like peptide-1 (GLP-1), enhancing glucose regulation and appetite control. Additionally, allulose prevented liver triglyceride accumulation and promoted mitochondrial uncoupling in adipose tissue. These findings suggest that allulose supplementation can improve metabolic health markers, making it a promising dietary component for managing obesity and T2D. Further research is needed to explore the long-term benefits and mechanisms of allulose in metabolic disease prevention and management. This study supports the potential of allulose as a safe and effective intervention for improving metabolic health in the context of dietary excess.

Generative design approach to combine architected Voronoi foams with porous collagen scaffolds to create a tunable composite biomaterial.

Regenerative biomaterials for musculoskeletal defects must address multi-scale mechanical challenges. Repairing craniomaxillofacial bone defects, which are often large and irregularly shaped, requires close conformal contact between implant and defect margins to aid healing. While mineralized collagen scaffolds can promote mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo, their mechanical performance is insufficient for surgical translation. We report a generative design approach to create scaffold-mesh composites by embedding a macro-scale polymeric Voronoi mesh into the mineralized collagen scaffold. The mechanics of architected foam reinforced composites are defined by a rigorous predictive moduli equation. We show biphasic composites localize strain during loading. Further, planar and 3D mesh-scaffold composites can be rapidly shaped to aid conformal fitting. Voronoi-based composites overcome traditional porosity-mechanics relationship limits while enabling rapid shaping of regenerative implants to conformally fit complex defects unique for individual patients. STATEMENT OF SIGNIFICANCE: Biomaterial strategies for (craniomaxillofacial) bone regeneration are often limited by the size and complex geometry of the defects. Voronoi structures are open-cell foams with tunable mechanical properties which have primarily been used computationally. We describe generative design strategies to create Voronoi foams via 3D-printing then embed them into an osteogenic mineralized collagen scaffold to form a multi-scale composite biomaterial. Voronoi structures have predictable and tailorable moduli, permit stain localization to defined regions of the composite, and permit conformal fitting to effect margins to aid surgical practicality and improve host-biomaterial interactions. Multi-scale composites based on Voronoi foams represent an adaptable design approach to address significant challenges to large-scale bone repair.

Generative design approach to combine architected Voronoi foams with porous collagen scaffolds to create a tunable composite biomaterial.

Regenerative biomaterials for musculoskeletal defects must address multi-scale mechanical challenges. We are developing biomaterials for craniomaxillofacial bone defects that are often large and irregularly shaped. These require close conformal contact between implant and defect margins to aid healing. While we have identified a mineralized collagen scaffold that promotes mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo, its mechanical performance is insufficient for surgical translation. We report a generative design approach to create scaffold-mesh composites by embedding a macro-scale polymeric Voronoi mesh into the mineralized collagen scaffold. The mechanics of architected foam reinforced composites are defined by a rigorous predictive moduli equation. We show biphasic composites localize strain during loading. Further, planar and 3D mesh-scaffold composites can be rapidly shaped to aid conformal fitting. Voronoi-based composites overcome traditional porosity-mechanics relationship limits while enabling rapid shaping of regenerative implants to conformally fit complex defects unique for individual patients.

Evaluation of bacterial attachment on mineralized collagen scaffolds and addition of manuka honey to increase mesenchymal stem cell osteogenesis.

The design of biomaterials to regenerate bone is likely to increasingly require modifications that reduce bacterial attachment and biofilm formation as infection during wound regeneration can significantly impede tissue repair and typically requires surgical intervention to restart the healing process. Further, much research on infection prevention in bone biomaterials has focused on modeling of non-resorbable metal alloy materials, whereas an expanding direction of bone regeneration has focused on development of bioresorbable materials. This represents a need for the prevention and understanding of infection in resorbable biomaterials. Here, we investigate the ability of a mineralized collagen biomaterial to natively resist infection and examine how the addition of manuka honey, previously identified as an antimicrobial agent, affects gram positive and negative bacterial colonization and mesenchymal stem cell osteogenesis and vasculature formation. We incorporate manuka honey into these scaffolds via either direct fabrication into the scaffold microarchitecture or via soaking the scaffold in a solution of manuka honey after fabrication. Direct incorporation results in a change in the surface characteristics and porosity of mineralized collagen scaffolds. Soaking scaffolds in honey concentrations higher than 10% had significant negative effects on mesenchymal stem cell metabolic activity. Soaking or incorporating 5% honey had no impact on endothelial cell tube formation. Although solutions of 5% honey reduced metabolic activity of mesenchymal stem cells, MSC-seeded scaffolds displayed increased calcium and phosphorous mineral formation, osteoprotegerin release, and alkaline phosphatase activity. Bacteria cultured on mineralized collagen scaffolds demonstrated surfaces covered in bacteria and no method of preventing infection, and using 10 times the minimal inhibitory concentration of antibiotics did not completely kill bacteria within the mineralized collagen scaffolds, indicating bioresorbable scaffold materials may act to shield bacteria from antibiotics. The addition of 5% manuka honey to scaffolds was not sufficient to prevent P. aeruginosa attachment or consistently reduce the activity of methicillin resistant staphylococcus aureus, and concentrations above 7% manuka honey are likely necessary to impact MRSA. Together, our results suggest bioresorbable scaffolds may create an environment conducive to bacterial growth, and potential trade-offs exist for the incorporation of low levels of honey in scaffolds to increase osteogenic potential of osteoprogenitors while high-levels of honey may be sufficient to reduce gram positive or negative bacteria activity but at the cost of reduced osteogenesis.

Biocompatibility and biodistribution of matrix-bound nanovesicles in vitro and in vivo.

Matrix-bound nanovesicles (MBV) are a distinct subtype of extracellular vesicles that are firmly embedded within biomaterials composed of extracellular matrix (ECM). MBV both store and transport a diverse, tissue specific portfolio of signaling molecules including proteins, miRNAs, and bioactive lipids. MBV function as a key mediator in ECM-mediated control of the local tissue microenvironment. One of the most important mechanisms by which MBV in ECM bioscaffolds support constructive tissue remodeling following injury is immunomodulation and, specifically, the promotion of an anti-inflammatory, pro-remodeling immune cell activation state. Recent in vivo studies have shown that isolated MBV have therapeutic efficacy in rodent models of both retinal damage and rheumatoid arthritis through the targeted immunomodulation of pro-inflammatory macrophages towards an anti-inflammatory activation state. While these results show the therapeutic potential of MBV administered independent of the rest of the ECM, the in vitro and in vivo safety and biodistribution profile of MBV remain uncharacterized. The purpose of the present study was to thoroughly characterize the pre-clinical safety profile of MBV through a combination of in vitro cytotoxicity and MBV uptake studies and in vivo toxicity, immunotoxicity, and imaging studies. The results showed that MBV isolated from porcine urinary bladder are well-tolerated and are not cytotoxic in cell culture, are non-toxic to the whole organism, and are not immunosuppressive compared to the potent immunosuppressive drug cyclophosphamide. Furthermore, this safety profile was sustained across a wide range of MBV doses. STATEMENT OF SIGNIFICANCE: Matrix-bound nanovesicles (MBV) are a distinct subtype of bioactive extracellular vesicles that are embedded within biomaterials composed of extracellular matrix (ECM). Recent studies have shown therapeutic efficacy of MBV in models of both retinal damage and rheumatoid arthritis through the targeted immunomodulation of pro-inflammatory macrophages towards an anti-inflammatory activation state. While these results show the therapeutic potential of MBV, the in vitro and in vivo biocompatibility and biodistribution profile of MBV remain uncharacterized. The results of the present study showed that MBV are a well-tolerated ECM-derived therapy that are not cytotoxic in cell culture, are non-toxic to the whole organism, and are not immunosuppressive. Collectively, these data highlight the translational feasibility of MBV therapeutics across a wide variety of clinical applications.

Osteoprotegerin-eluting nanoparticulate mineralized collagen scaffolds improve skull regeneration.

Custom synthesis of extracellular matrix (ECM)-inspired materials for condition-specific reconstruction has emerged as a potentially translatable regenerative strategy. In skull defect reconstruction, nanoparticulate mineralized collagen glycosaminoglycan scaffolds (MC-GAG) have demonstrated osteogenic and anti-osteoclastogenic properties, culminating in the ability to partially heal in vivo skull defects without the addition of exogenous growth factors or progenitor cell loading. In an effort to reduce catabolism during early skull regeneration, we fabricated a composite material (MCGO) of MC-GAG and recombinant osteoprotegerin (OPG), an endogenous anti-osteoclastogenic decoy receptor. In the presence of differentiating osteoprogenitors, MCGO demonstrated an additive effect with endogenous OPG limited to the first 14 days of culture with total eluted and scaffold-bound OPG exceeding that of MC-GAG. Functionally, MCGO exhibited similar osteogenic properties as MC-GAG, however, MCGO significantly reduced maturation and resorptive activities of primary human osteoclasts. In a rabbit skull defect model, MCGO scaffold-reconstructed defects displayed higher mineralization as well as increased hardness and microfracture resistance compared to non-OPG functionalized MC-GAG scaffolds. The current work suggests that MCGO is a development in the goal of reaching a materials-based strategy for skull regeneration.

Next-generation sequencing of microbial communities in the Athabasca River and its tributaries in relation to oil sands mining activities.

The Athabasca oil sands deposit is the largest reservoir of crude bitumen in the world. Recently, the soaring demand for oil and the availability of modern bitumen extraction technology have heightened exploitation of this reservoir and the potential unintended consequences of pollution in the Athabasca River. The main objective of the present study was to evaluate the potential impacts of oil sands mining on neighboring aquatic microbial community structure. Microbial communities were sampled from sediments in the Athabasca River and its tributaries as well as in oil sands tailings ponds. Bacterial and archaeal 16S rRNA genes were amplified and sequenced using next-generation sequencing technology (454 and Ion Torrent). Sediments were also analyzed for a variety of chemical and physical characteristics. Microbial communities in the fine tailings of the tailings ponds were strikingly distinct from those in the Athabasca River and tributary sediments. Microbial communities in sediments taken close to tailings ponds were more similar to those in the fine tailings of the tailings ponds than to the ones from sediments further away. Additionally, bacterial diversity was significantly lower in tailings pond sediments. Several taxonomic groups of Bacteria and Archaea showed significant correlations with the concentrations of different contaminants, highlighting their potential as bioindicators. We also extensively validated Ion Torrent sequencing in the context of environmental studies by comparing Ion Torrent and 454 data sets and by analyzing control samples.

A national survey of UK final year students' opinion of undergraduate oral surgery teaching.

BACKGROUND: A national survey was undertaken to establish a baseline of our final year students' perception of how their undergraduate oral surgery education has equipped them for key areas of general dental practice. MATERIALS AND METHODS: Questionnaires were distributed to the 13 UK schools with final year students, towards the end of the academic year in 2009. The questionnaires were completed anonymously and were optically scanned. RESULTS: In total, 632 questionnaires were returned, which represents 66% of the students of the graduating year. The majority (83%) of the respondents perceived that the teaching in oral surgery had given them sufficient knowledge to undertake independent practise. Most respondents (99%) felt confident to perform forceps exodontia, but confidence in the various aspects of surgical exodontia was lower. A majority (83%) had experience of an outreach scheme performing forceps exodontia (75%) and surgical exodontia (16%) in this environment. Twenty per cent indicated a desire to undertake a career in oral surgery, 6% in oral and maxillofacial surgery and 35% in another speciality. CONCLUSION: This survey suggests that the majority of the students perceive that the oral surgery education has prepared them well for key areas of general practice. It also suggests that there is, however, a need to provide further improvement in the delivery of surgical skills and knowledge.

Transitioning into the workforce during the COVID-19 pandemic: Understanding the experiences of student diagnostic radiographers.

INTRODUCTION: The COVID-19 pandemic, with associated pressures on healthcare services and workforce, had implications for final year Diagnostic Radiography students completing their training and transitioning into employment. The aim of this study was to explore their experience as novice practitioners starting work and integrating into the workforce during a time of national crisis. METHODS: Five early career Diagnostic Radiographers, eligible to join the temporary HCPC register, were recruited. One to one interviews were completed online exploring their thoughts, feelings and experiences. Participants had the option of using photographs to aid communication. RESULTS: Interviews were transcribed, emerging themes identified and coded. Four main themes emerged specifically related to the COVID-19 pandemic, (i) perceived challenges associated with joining the workforce, (ii) managing expectations and unexpected outcomes during transition, (iii) adapting to changes in systems and structures, (iv) sense of uncertainty relating to professional identity. The impacts were experienced beyond the work environment into social and personal lives. Participants demonstrated resilience as they adapted to their shifting lives and drew on the support of clinical colleagues and University academics for help. They did report feelings of concern and anxiety. The participants all expressed a sense of feeling valued and supported in their new roles. CONCLUSION: The Pandemic was unprecedented and created uncertainty in terms of workforce requirements. This study highlights the personal impact and professional responses of novice practitioners, who felt a sense of duty and care to help support the NHS and others. IMPLICATIONS FOR PRACTICE: This will help in the understanding of the transition of student into employment and what wider support needs to be in place prior, during and after this phase.