Implementation of a standardised perioperative nutrition care pathway in upper gastrointestinal cancer surgery: A multisite pilot study.

BACKGROUND: Perioperative nutrition support is recommended for patients undergoing upper gastrointestinal (UGI) cancer surgery; however, limited evidence exists regarding implementation of a nutrition care pathway in clinical practice. The aims of this pilot study were to determine whether implementation of a standardised perioperative nutrition pathway for patients undergoing UGI cancer surgery improves access to dietetics care, as well as to evaluate study feasibility, fidelity, resource requirements and effect on clinical outcomes. METHODS: Patients with newly diagnosed UGI cancer from four major metropolitan hospitals in Melbourne, planned for curative intent surgery, were included in the prospective pilot study (n = 35), with historical controls (n = 35) as standard care. Outcomes were dietetics care (dietetics contacts) nutritional status, hand grip strength, weight change, preoperative hospital admissions, complications and length of stay, recruitment feasibility, fidelity and adherence, and resource requirements. Continuous data were analysed using independent samples t test accounting for unequal variances or a Mann-Whitney U test. Dichotomous data were analysed using Fisher's exact test. RESULTS: The percentage of participants receiving preoperative dietetic intervention increased from 55% to 100% (p < 0.001). Mean ± SD dietetics contacts increased from 2.2 ± 3.7 to 5.9 ± 3.9 (p < 0.001). Non-statistically significant decreases in preoperative nutrition-related hospital admissions, and surgical complications were demonstrated in patients who underwent neoadjuvant therapy. Recruitment rate was 81%, and adherence to the nutrition pathway was high (> 70% for all stages of the pathway). The mean ± SD estimated resource requirement for the preoperative period was 3.7 ± 2.8 h per patient. CONCLUSIONS: Implementation of this standardised nutrition pathway resulted in improved access to dietetics care. Recruitment feasibility and high fidelity to the intervention suggest that a larger study would be viable.

Long-Term Outcome of Multidisciplinary Versus Standard Gastroenterologist Care for Functional Gastrointestinal Disorders: A Randomized Trial.

BACKGROUND & AIMS: Functional gastrointestinal disorders are common and costly to the healthcare system. In the Multidisciplinary Treatment of Functional Gastrointestinal Disorders study, we demonstrated that multidisciplinary care resulted in superior clinical and cost outcomes, when compared with standard gastroenterologist-only care at end of treatment. In this study we evaluate the longer-term outcomes. METHODS: In a single-center, pragmatic trial patients with Rome IV criteria-defined functional gastrointestinal disorders were randomized 1:2 to a gastroenterologist-only standard care vs a multidisciplinary clinic comprising gastroenterologists, dietitians, gut hypnotherapists, psychiatrists, and biofeedback physiotherapists. Outcomes in this study were assessed 12 months after the end of treatment. Global symptom improvement was assessed by using a 5-point Likert scale. Symptoms, specific disorder status, psychological state, quality of life, and cost were additional outcomes. A modified intention-to-treat analysis was performed. RESULTS: Of 188 randomized patients, 143 (46 standard care, 97 multidisciplinary) formed the longer-term modified intention-to-treat analysis. Sixty-two percent of multidisciplinary clinic patients saw allied clinicians. Sixty-five percent (30/46) standard care versus 76% (74/97) multidisciplinary clinic patients achieved global symptom improvement 12 months after end of treatment (P = .17), whereas 20% (9/46) versus 37% (36/97) rated their symptoms as "5/5 much better" (P = .04). A ≥50-point reduction in Irritable Bowel Syndrome Severity Scoring System occurred in 38% versus 66% (P = .02), respectively, for irritable bowel syndrome patients. Anxiety and depression were greater in the standard care than multidisciplinary clinic (12 vs 10, P = .19), and quality of life was lower in standard care than the multidisciplinary clinic (0.75 vs 0.77, P =·.03). An incremental cost-effectivness ratio found that for every additional 3555AUD spent in the multidisciplinary clinic, a further quality-adjusted life year was gained. CONCLUSIONS: Twelve months after the completion of treatment, integrated multidisciplinary clinical care achieved a greater proportion of patients with improvement of symptoms, psychological state, quality of life, and cost, compared with gastroenterologist-only care. CLINICAL TRIALS: gov: number NCT03078634.

Parallel Murine and Human Plaque Proteomics Reveals Pathways of Plaque Rupture.

RATIONALE: Plaque rupture is the proximate cause of most myocardial infarctions and many strokes. However, the molecular mechanisms that precipitate plaque rupture are unknown. OBJECTIVE: By applying proteomic and bioinformatic approaches in mouse models of protease-induced plaque rupture and in ruptured human plaques, we aimed to illuminate biochemical pathways through which proteolysis causes plaque rupture and identify substrates that are cleaved in ruptured plaques. METHODS AND RESULTS: We performed shotgun proteomics analyses of aortas of transgenic mice with macrophage-specific overexpression of urokinase (SR-uPA+/0 mice) and of SR-uPA+/0 bone marrow transplant recipients, and we used bioinformatic tools to evaluate protein abundance and functional category enrichment in these aortas. In parallel, we performed shotgun proteomics and bioinformatics studies on extracts of ruptured and stable areas of freshly harvested human carotid plaques. We also applied a separate protein-analysis method (protein topography and migration analysis platform) to attempt to identify substrates and proteolytic fragments in mouse and human plaque extracts. Approximately 10% of extracted aortic proteins were reproducibly altered in SR-uPA+/0 aortas. Proteases, inflammatory signaling molecules, as well as proteins involved with cell adhesion, the cytoskeleton, and apoptosis, were increased. ECM (Extracellular matrix) proteins, including basement-membrane proteins, were decreased. Approximately 40% of proteins were altered in ruptured versus stable areas of human carotid plaques, including many of the same functional categories that were altered in SR-uPA+/0 aortas. Collagens were minimally altered in SR-uPA+/0 aortas and ruptured human plaques; however, several basement-membrane proteins were reduced in both SR-uPA+/0 aortas and ruptured human plaques. Protein topography and migration analysis platform did not detect robust increases in proteolytic fragments of ECM proteins in either setting. CONCLUSIONS: Parallel studies of SR-uPA+/0 mouse aortas and human plaques identify mechanisms that connect proteolysis with plaque rupture, including inflammation, basement-membrane protein loss, and apoptosis. Basement-membrane protein loss is a prominent feature of ruptured human plaques, suggesting a major role for basement-membrane proteins in maintaining plaque stability.

Implementing a standardised perioperative nutrition care pathway in upper gastrointestinal cancer surgery: a mixed-methods analysis of implementation using the Consolidated Framework for Implementation Research.

BACKGROUND: Implementation studies of complex interventions such as nutrition care pathways are important to health services research, as they support translation of research into practice. There is limited research regarding implementation of a nutrition care pathway in an upper gastrointestinal (UGI) cancer population. The aim of this study was to comprehensively evaluate the implementation process of a perioperative nutrition care pathway in UGI cancer surgery using The Consolidated Framework for Implementation Research (CFIR). METHODS: This was a mixed methods implementation study conducted during a pilot study of a standardised nutrition care pathway across four major hospitals between September 2018 to August 2019. Outcome measures included five focus groups among study dietitians (n = 4-8 per group), and quantitative satisfaction surveys from multi-disciplinary team (MDT) members (n = 14) and patients (n = 18). Focus group responses were analysed thematically using the CFIR constructs, which were used as a priori codes. Survey responses were summarised using means and standard deviations. A convergent parallel mixed methods approach according to CFIR domains and constructs was used to integrate qualitative and quantitative data. RESULTS: Qualitative data demonstrated that dietitian perceptions primarily aligned with five CFIR constructs (networks and communications, structural characteristics, adaptability, compatibility and patient needs/resources), indicating a complex clinical and implementation environment. Challenges to implementation mostly related to adapting the pathway, and the compatibility of nutrition coordination to existing aspects of care within each setting. Identified benefits from dietitian qualitative data and MDT survey responses included increased engagement between the dietitian and MDT, and a more proactive approach to nutrition care. Patients were highly satisfied with the service, with the majority of survey items being rated highly (≥4 of a possible 5 points). CONCLUSIONS: The nutrition care pathway was perceived to be beneficial by key stakeholders. Based on the findings, sustainability and compliance to this model of care may be achieved with improved systems level coordination and communication.

Bioprinting and Biofabrication with Peptide and Protein Biomaterials.

The ability to fabricate artificial tissue constructs through the controlled organisation of cells, structures and signals within a biomimetic scaffold offers significant promise to the field of regenerative medicine, drug delivery and tissue engineering. Advances in additive manufacturing technologies have facilitated the printing of spatially defined cell-laden artificial tissue constructs capable of providing biomimetic spatiotemporal presentation of biological and physical cues to cells in a designed multicomponent structure. Despite significant progress in the field of bioprinting, a key challenge remains in developing and utilizing materials that can adequately recapitulate the complexities of the native extracellular matrix on a nanostructured, chemical level during the printing process. This gives rise to the need for suitable materials - particularly in establishing effective control over cell fate, tissue vascularization and innervation. Recently, significant interested has been invested into developing candidate materials using protein and peptide-derived biomaterials. The ability of these materials to form highly printable hydrogels which are reminiscent of the native ECM has seen significant use in a variety of regenative applications, including both organ bioprinting and non-organ bioprinting. Here, we discuss the emerging technologies for peptide-based bioprinting applications, highlighting bioink development and detailing bioprinter processors. Furthermore, this work presents application specific, peptide-based bioprinting approaches, and provides insight into current limitations and future perspectives of peptide-based bioprinting techniques.

The modA10 phasevarion of nontypeable Haemophilus influenzae R2866 regulates multiple virulence-associated traits.

Non-typeable Haemophilus influenzae (NTHi) is a human restricted commensal and pathogen that elicits inflammation by adhering to and invading airway epithelia cells: transcytosis across these cells can result in systemic infection. NTHi strain R2866 was isolated from the blood of a normal 30-month old infant with meningitis, and is unusual for NTHi in that it is able to cause systemic infection. Strain R2866 is able to replicate in normal human serum due to expression of lgtC which mimics human blood group p(k). R2866 contains a phase-variable DNA methyltransferase, modA10 which switches ON and OFF randomly and reversibly due to polymerase slippage over a long tetrameric repeat tract located in its open reading frame. Random gain or loss of repeats during replication can results in expressed (ON), or not expressed (OFF) states, the latter due to a frameshift or transcriptional termination at a premature stop codon. We sought to determine if the unusual virulence of R2866 was modified by modA10 phase-variation. A modA10 knockout mutant was found to have increased adherence to, and invasion of, human ear and airway monolayers in culture, and increased invasion and transcytosis of polarized human bronchial epithelial cells. Intriguingly, the rate of bacteremia was lower in the infant rat model of infection than a wild-type R2866 strain, but the fatality rate was greater. Transcriptional analysis comparing the modA10 knockout to the R2866 wild-type parent strain showed increased expression of genes in the modA10 knockout whose products mediate cellular adherence. We conclude that loss of ModA10 function in strain R2866 enhances colonization and invasion by increasing expression of genes that allow for increased adherence, which can contribute to the increased virulence of this strain.

Postnatal Deletion of the Type II Transforming Growth Factor-ß Receptor in Smooth Muscle Cells Causes Severe Aortopathy in Mice.

OBJECTIVE: Prenatal deletion of the type II transforming growth factor-ß (TGF-ß) receptor (TBRII) prevents normal vascular morphogenesis and smooth muscle cell (SMC) differentiation, causing embryonic death. The role of TBRII in adult SMC is less well studied. Clarification of this role has important clinical implications because TBRII deletion should ablate TGF-ß signaling, and blockade of TGF-ß signaling is envisioned as a treatment for human aortopathies. We hypothesized that postnatal loss of SMC TBRII would cause aortopathy. APPROACH AND RESULTS: We generated mice with either of 2 tamoxifen-inducible SMC-specific Cre (SMC-CreER(T2)) alleles and homozygous floxed Tgfbr2 alleles. Mice were injected with tamoxifen, and their aortas examined 4 and 14 weeks later. Both SMC-CreER(T2) alleles efficiently and specifically rearranged a floxed reporter gene and efficiently rearranged a floxed Tgfbr2 allele, resulting in loss of aortic medial TBRII protein. Loss of SMC TBRII caused severe aortopathy, including hemorrhage, ulceration, dissection, dilation, accumulation of macrophage markers, elastolysis, abnormal proteoglycan accumulation, and aberrant SMC gene expression. All areas of the aorta were affected, with the most severe pathology in the ascending aorta. Cre-mediated loss of SMC TBRII in vitro ablated both canonical and noncanonical TGF-ß signaling and reproduced some of the gene expression abnormalities detected in vivo. CONCLUSIONS: SMC TBRII plays a critical role in maintaining postnatal aortic homeostasis. Loss of SMC TBRII disrupts TGF-ß signaling, acutely alters SMC gene expression, and rapidly results in severe and durable aortopathy. These results suggest that pharmacological blockade of TGF-ß signaling in humans could cause aortic disease rather than prevent it.

Development of a Magnetic Attachment Method for Bionic Eye Applications.

Successful visual prostheses require stable, long-term attachment. Epiretinal prostheses, in particular, require attachment methods to fix the prosthesis onto the retina. The most common method is fixation with a retinal tack; however, tacks cause retinal trauma, and surgical proficiency is important to ensure optimal placement of the prosthesis near the macula. Accordingly, alternate attachment methods are required. In this study, we detail a novel method of magnetic attachment for an epiretinal prosthesis using two prostheses components positioned on opposing sides of the retina. The magnetic attachment technique was piloted in a feline animal model (chronic, nonrecovery implantation). We also detail a new method to reliably control the magnet coupling force using heat. It was found that the force exerted upon the tissue that separates the two components could be minimized as the measured force is proportionately smaller at the working distance. We thus detail, for the first time, a surgical method using customized magnets to position and affix an epiretinal prosthesis on the retina. The position of the epiretinal prosthesis is reliable, and its location on the retina is accurately controlled by the placement of a secondary magnet in the suprachoroidal location. The electrode position above the retina is less than 50 microns at the center of the device, although there were pressure points seen at the two edges due to curvature misalignment. The degree of retinal compression found in this study was unacceptably high; nevertheless, the normal structure of the retina remained intact under the electrodes.

Selection against glycosylation sites in potential target proteins of the general HMWC N-glycosyltransferase in Haemophilus influenzae.

The HMWABC system of non-typeable Haemophilus influenzae (NTHi) encodes the HMWA adhesin glycoprotein, which is glycosylated by the HMWC glycosyltransferase. HMWC is a cytoplasmic N-glycosyltransferase, homologues of which are widespread in the Pasteurellaceae. We developed an assay for nonbiased detection of glycoproteins in NTHi based on metabolic engineering of the Leloir pathway and growth in media containing radiolabelled monosaccharides. The only glycoprotein identified in NTHi by this assay was HMWA. However, glycoproteomic analyses ex vivo in Escherichia coli showed that HMWC of NTHi was a general glycosyltransferase capable of glycosylating selected asparagines in proteins other than its HMWA substrate, including Asn78 in E. coli 30S ribosomal protein S5. The equivalent residue in S5 homologues in H. influenzae or other sequenced Pasteurellaceae genomes is not asparagine, and these organisms also showed significantly fewer than expected potential sites of glycosylation in general. Expression of active HMWC in E. coli resulted in growth inhibition compared with expression of inactive enzyme, consistent with glycosylation by HMWC detrimentally affecting the function of some E. coli proteins. Together, this supports the presence of a selective pressure in the Pasteurellaceae against glycosylation sites that would be modified by the general N-glycosyltransferase activity of HMWC.

Porous structures inspired by porcupine quill: multiscale design optimization approach.

This paper presents a novel approach for designing a freeform bending-resistant structure from the combination of explicit discrete component-based topology optimization (TO) and the porcupine quill-inspired features. To embed the porcupine quill's features into the TO formulations, the method involves constructing discrete components at various scales to imitate features including solid shell, stochastically distributed pores, and graded stiffeners. The components are iteratively updated, and the optimization process allows for the grading of quill-inspired features while achieving optimal structural compliance under bending loads. The proposed approach is demonstrated to be effective through the resolution of Messershmitt-Bolkow-Blohm (MBB) beam designs, parameterized studies of geometric parameters, and numerical validation of long-span and short-span quill-inspired beam designs. By examining the von Mises stress distribution, the study highlights the mitigation of material yielding at the shell region brought by the geometric features of porcupine quills, leading to the potential theory support for the bending resistance. The optimized MBB beams are manufactured using the material extrusion technique, and three-point bending tests are conducted to explore the failure mitigation capability of the quill-inspired beam under large deformation. Consequently, the study concludes that the proposed quill-inspired component-based TO approach can design a structure with excellent bending resistance according to the improved energy absorption as well as increased deformation after reaching 75% peak load.

Control of Neuronal Survival and Development Using Conductive Diamond.

This study demonstrates the control of neuronal survival and development using nitrogen-doped ultrananocrystalline diamond (N-UNCD). We highlight the role of N-UNCD in regulating neuronal activity via near-infrared illumination, demonstrating the generation of stable photocurrents that enhance neuronal survival and neurite outgrowth and foster a more active, synchronized neuronal network. Whole transcriptome RNA sequencing reveals that diamond substrates improve cellular-substrate interaction by upregulating extracellular matrix and gap junction-related genes. Our findings underscore the potential of conductive diamond as a robust and biocompatible platform for noninvasive and effective neural tissue engineering.

Diamond as a scaffold for bone growth.

Diamond is an attractive material for biomedical implants. In this work, we investigate its capacity as a bone scaffold. It is well established that the bioactivity of a material can be evaluated by examining its capacity to form apatite-like calcium phosphate phases on its surface when exposed to simulated body fluid. Accordingly, polycrystalline diamond (PCD) and ultrananocrystalline diamond (UNCD) deposited by microwave plasma chemical vapour deposition were exposed to simulated body fluid and assessed for apatite growth when compared to the bulk silicon. Scanning electron microscopy and X-ray photoelectron spectroscopy showed that both UNCD and PCD are capable of acting as a bone scaffold. The composition of deposited apatite suggests that UNCD and PCD are suitable for in vivo implantation with UNCD possible favoured in applications where rapid osseointegration is essential.

The biosynthesis and role of phosphorylcholine in pathogenic and nonpathogenic bacteria.

Phosphorylcholine (ChoP) can be found in all life forms. Although this molecule was first thought to be uncommon in bacteria, it is now appreciated that many bacteria express ChoP on their surface. ChoP is usually attached to a glycan structure, but in some cases, it is added as a post-translational modification to proteins. Recent findings have demonstrated the role of ChoP modification and phase variation (ON/OFF switching) in bacterial pathogenesis. However, the mechanisms of ChoP synthesis are still unclear in some bacteria. Here, we review the literature and examine the recent developments in ChoP-modified proteins and glycolipids and of ChoP biosynthetic pathways. We discuss how the well-studied Lic1 pathway exclusively mediates ChoP attachment to glycans but not to proteins. Finally, we provide a review of the role of ChoP in bacterial pathobiology and the role of ChoP in modulating the immune response.

Advanced flexible transvaginal mesh with high visibility under computerized tomography (CT) scan.

Pelvic floor disorders, including pelvic organ prolapse (POP) and stress urinary incontinence (SUI), are serious and very common. Surgery is commonly undertaken to restore the strength of the vaginal wall using transvaginal surgical mesh (TVM). However, up to 15% of TVM implants result in long-term complications, including pain, recurrent symptoms, and infection.Clinical Relevance- In this study, a new bioengineered TVM has been developed to address these issues. The TVM is visible using noninvasive imaging techniques such as computed tomography (CT); it has a highly similar structural profile to human tissue and potential to reduce pain and inflammation. These combined technological advances have the potential to revolutionize women's health.

Robot-assisted implantation of additively manufactured patient-specific orthopaedic implants: evaluation in a sheep model.

PURPOSE: Bone tumours must be surgically excised in one piece with a margin of healthy tissue. The unique nature of each bone tumour case is well suited to the use of patient-specific implants, with additive manufacturing allowing production of highly complex geometries. This work represents the first assessment of the combination of surgical robotics and patient-specific additively manufactured implants. METHODS: The development and evaluation of a robotic system for bone tumour excision, capable of milling complex osteotomy paths, is described. The developed system was evaluated as part of an animal trial on 24 adult male sheep, in which robotic bone excision of the distal femur was followed by placement of patient-specific implants with operative time evaluated. Assessment of implant placement accuracy was completed based on post-operative CT scans. RESULTS: A mean overall implant position error of 1.05 ± 0.53 mm was achieved, in combination with a mean orientation error of 2.38 ± 0.98°. A mean procedure time (from access to implantation, excluding opening and closing) of 89.3 ± 25.25 min was observed, with recorded surgical time between 58 and 133 min, with this approximately evenly divided between robotic (43.9 ± 15.32) and implant-based (45.4 ± 18.97) tasks. CONCLUSIONS: This work demonstrates the ability for robotics to achieve repeatable and precise removal of complex bone volumes of the type that would allow en bloc removal of a bone tumour. These robotically created volumes can be precisely filled with additively manufactured patient-specific implants, with minimal gap between cut surface and implant interface.

Recent advances in research applications of nanophase hydroxyapatite.

Hydroxyapatite, the main inorganic material in natural bone, has been used widely for orthopaedic applications. Due to size effects and surface phenomena at the nanoscale, nanophase hydroxyapatite possesses unique properties compared to its bulk-phase counterpart. The high surface-to-volume ratio, reactivities, and biomimetic morphologies make nano-hydroxyapatite more favourable in applications such as orthopaedic implant coating or bone substitute filler. Recently, more efforts have been focused on the possibility of combining hydroxyapatite with other drugs and materials for multipurpose applications, such as antimicrobial treatments, osteoporosis treatments and magnetic manipulation. To build more effective nano-hydroxyapatite and composite systems, the particle synthesis processes, chemistry, and toxicity have to be thoroughly investigated. In this Minireview, we report the recent advances in research regarding nano-hydroxyapatite. Synthesis routes and a wide range of applications of hydroxyapatite nanoparticles will be discussed. The Minireview also addresses several challenges concerning the biosafety of the nanoparticles.

Additive Manufacturing of Sustainable Construction Materials and Form-finding Structures: A Review on Recent Progresses.

Recently, there has been an increasing interest on the sustainability advantage of 3D concrete printing (3DCP), where the original cement-based mixtures used for printing could be replaced or incorporated with environmental-friendly materials. The development in digital modeling and design tools also creates a new realm of form-finding architecture for 3DCP, which is based on topological optimization of volumetric mass and physical performance. This review provides a perspective of using different green cementitious materials, applications of structural optimization, and modularization methods for realizing sustainable construction with additive manufacturing. The fresh and hardened mechanical properties of various sustainable materials for extrusion-based 3D printing are presented, followed by discussions on different topology optimization techniques. The current state of global research and industrial applications in 3DCP, along with the development of sustainable construction materials, is also summarized. Finally, research and practical gaps identified in this review lead to several recommendations on material developments, digital design tool's prospects for 3DCP to achieve the sustainability goal.

Liquid metal polymer composite: Flexible, conductive, biocompatible, and antimicrobial scaffold.

Gallium and its alloys, such as eutectic gallium indium alloy (EGaIn), a form of liquid metal, have recently attracted the attention of researchers due to their low toxicity and electrical and thermal conductivity for biomedical application. However, further research is required to harness EGaIn-composites advantages and address their application as a biomedical scaffold. In this research, EGaIn-polylactic acid/polycaprolactone composites with and without a second conductive filler, MXene, were prepared and characterized. The addition of MXene, into the EGaIn-composite, can improve the composite's electrochemical properties by connecting the liquid metal droplets resulting in electrically conductive continuous pathways within the polymeric matrix. The results showed that the composite with 50% EGaIn and 4% MXene, displayed optimal electrochemical properties and enhanced mechanical and radiopacity properties. Furthermore, the composite showed good biocompatibility, examined through interactions with fibroblast cells, and antibacterial properties against methicillin-resistant Staphylococcus aureus. Therefore, the liquid metal (EGaIn) polymer composite with MXene provides a first proof-of-concept engineering scaffold strategy with low toxicity, functional electrochemical properties, and promising antimicrobial properties.

Phasevarions mediate random switching of gene expression in pathogenic Neisseria.

Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae, the random switching of the modA gene controls expression of a phase-variable regulon of genes (a "phasevarion"), via differential methylation of the genome in the modA ON and OFF states. Phase-variable mod genes are also present in Neisseria meningitidis and Neisseria gonorrhoeae, suggesting that phasevarions may occur in these important human pathogens. Phylogenetic studies on phase-variable mod genes associated with type III restriction modification (R-M) systems revealed that these organisms have two distinct mod genes--modA and modB. There are also distinct alleles of modA (abundant: modA11, 12, 13; minor: modA4, 15, 18) and modB (modB1, 2). These alleles differ only in their DNA recognition domain. ModA11 was only found in N. meningitidis and modA13 only in N. gonorrhoeae. The recognition site for the modA13 methyltransferase in N. gonorrhoeae strain FA1090 was identified as 5'-AGAAA-3'. Mutant strains lacking the modA11, 12 or 13 genes were made in N. meningitidis and N. gonorrhoeae and their phenotype analyzed in comparison to a corresponding mod ON wild-type strain. Microarray analysis revealed that in all three modA alleles multiple genes were either upregulated or downregulated, some of which were virulence-associated. For example, in N. meningitidis MC58 (modA11), differentially expressed genes included those encoding the candidate vaccine antigens lactoferrin binding proteins A and B. Functional studies using N. gonorrhoeae FA1090 and the clinical isolate O1G1370 confirmed that modA13 ON and OFF strains have distinct phenotypes in antimicrobial resistance, in a primary human cervical epithelial cell model of infection, and in biofilm formation. This study, in conjunction with our previous work in H. influenzae, indicates that phasevarions may be a common strategy used by host-adapted bacterial pathogens to randomly switch between "differentiated" cell types.

Diamond in the Rough: Toward Improved Materials for the Bone-Implant Interface.

The ability of an orthopedic implant to integrate successfully with the surrounding bone tissue is imperative for optimal patient outcomes. Here, the recent advances and future prospects for diamond-based coatings of conventional osteo-implant materials (primarily titanium) are explored. The ability of these diamond coatings to enhance integration into existing bone, improved implant mechanical properties, facilitate surface chemical functionalization, and provide anti-microbial properties are discussed in context of orthopedic implants. These diamond-based materials may have the additional benefit of providing an osteo-inductive effect, enabling better integration into existing bone via stem cell recruitment and bone regeneration. Current and timely research is highlighted to support the discussion and suggestions in further improving implant integration via an osseoinductive effect from the diamond composite materials.