Craniocervical instability in patients with Ehlers-Danlos syndromes: outcomes analysis following occipito-cervical fusion.

Craniocervical instability (CCI) is increasingly recognized in hereditary disorders of connective tissue and in some patients following suboccipital decompression for Chiari malformation (CMI) or low-lying cerebellar tonsils (LLCT). CCI is characterized by severe headache and neck pain, cervical medullary syndrome, lower cranial nerve deficits, myelopathy, and radiological metrics, for which occipital cervical fusion (OCF) has been advocated. We conducted a retrospective analysis of patients with CCI and Ehlers-Danlos syndrome (EDS) to determine whether the surgical outcomes supported the criteria by which patients were selected for OCF. Fifty-three consecutive subjects diagnosed with EDS, who presented with severe head and neck pain, lower cranial nerve deficits, cervical medullary syndrome, myelopathy, and radiologic findings of CCI, underwent open reduction, stabilization, and OCF. Thirty-two of these patients underwent suboccipital decompression for obstruction of cerebral spinal fluid flow. Questionnaire data and clinical findings were abstracted by a research nurse. Follow-up questionnaires were administered at 5-28 months (mean 15.1). The study group demonstrated significant improvement in headache and neck pain (p < 0.001), decreased use of pain medication (p < 0.0001), and improved Karnofsky Performance Status score (p < 0.001). Statistically significant improvement was also demonstrated for nausea, syncope (p < 0.001), speech difficulties, concentration, vertigo, dizziness, numbness, arm weakness, and fatigue (p = 0.001). The mental fatigue score and orthostatic grading score were improved (p < 0.01). There was no difference in pain improvement between patients with CMI/LLCT and those without. This outcomes analysis of patients with disabling CCI in the setting of EDS demonstrated significant benefits of OCF. The results support the reasonableness of the selection criteria for OCF. We advocate for a multi-center, prospective clinical trial of OCF in this population.

A pilot study of dietary fibres on pathogen growth in an ex vivo colonic model reveals their potential ability to limit vancomycin-resistant Enterococcus expansion.

Aim: Dietary fibre is important for shaping gut microbiota. The aim of this pilot study was to investigate the impact of dietary fibres on pathogen performance in the presence of gut microbiota. Methods: In an ex vivo gut model, pooled faecal samples were spiked with a cocktail of representative gastrointestinal pathogens and fermented with yeast ß-glucan for 24 hours, after which 16S rRNA amplicon sequencing and short-chain and branched-chain fatty acid (SCFA and BCFA) analyses were performed. In addition, oat ß-glucan, arabinoxylan, yeast ß-glucan, and galactooligosaccharides were each tested against individual representative pathogens and pathogen growth was assessed via qPCR. Glucose served as a control carbon source. Results: Based on 16S rRNA amplicon sequencing, yeast ß-glucan selected for higher proportions of Bacteroides (P = 0.0005, ~6 fold) and Clostridia (P = 0.005, ~3.6 fold) while species of Escherichia/Shigella (P = 0.021, ~2.8 fold) and Lactobacillus (P = 0.007, ~ 15.7-fold) were higher in glucose. Pathogen relative abundance did not differ between glucose and yeast ß-glucan. In the absence of pathogens, higher production of BCFAs (P = 0.002) and SCFAs (P = 0.002) fatty acids was observed for fibre group(s). For individual pathogens, yeast ß-glucan increased growth of Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes (P < 0.05), arabinoxylan increased S. typhimurium (P < 0.05). Tested fibres decreased vancomycin-resistant Enterococcus faecium (P < 0.05), with yeast ß-glucan causing a 1-log reduction (P < 0.01), while galactooligosaccharides decreased L. monocytogenes (P < 0.05). Conclusion: Tested fibres differentially influenced the growth of pathogens, but yeast ß-glucan could represent a dietary strategy to help limit vancomycin-resistant enterococci (VRE) expansion in the gut.

Interplay between inflammatory bowel disease therapeutics and the gut microbiome reveals opportunities for novel treatment approaches.

Inflammatory bowel disease (IBD) is a complex heterogeneous disorder defined by recurring chronic inflammation of the gastrointestinal tract, attributed to a combination of factors including genetic susceptibility, altered immune response, a shift in microbial composition/microbial insults (infection/exposure), and environmental influences. Therapeutics generally used to treat IBD mainly focus on the immune response and include non-specific anti-inflammatory and immunosuppressive therapeutics and targeted therapeutics aimed at specific components of the immune system. Other therapies include exclusive enteral nutrition and emerging stem cell therapies. However, in recent years, scientists have begun to examine the interplay between these therapeutics and the gut microbiome, and we present this information here. Many of these therapeutics are associated with alterations to gut microbiome composition and functionality, often driving it toward a "healthier profile" and preclinical studies have revealed that such alterations can play an important role in therapeutic efficacy. The gut microbiome can also improve or hinder IBD therapeutic efficacy or generate undesirable metabolites. For certain IBD therapeutics, the microbiome composition, particularly before treatment, may serve as a biomarker of therapeutic efficacy. Utilising this information and manipulating the interactions between the gut microbiome and IBD therapeutics may enhance treatment outcomes in the future and bring about new opportunities for personalised, precision medicine.

Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-ß monoclonal antibodies in dominantly inherited Alzheimer's disease.

PURPOSE: Pittsburgh Compound-B (11C-PiB) and 18F-florbetapir are amyloid-ß (Aß) positron emission tomography (PET) radiotracers that have been used as endpoints in Alzheimer's disease (AD) clinical trials to evaluate the efficacy of anti-Aß monoclonal antibodies. However, comparing drug effects between and within trials may become complicated if different Aß radiotracers were used. To study the consequences of using different Aß radiotracers to measure Aß clearance, we performed a head-to-head comparison of 11C-PiB and 18F-florbetapir in a Phase 2/3 clinical trial of anti-Aß monoclonal antibodies. METHODS: Sixty-six mutation-positive participants enrolled in the gantenerumab and placebo arms of the first Dominantly Inherited Alzheimer Network Trials Unit clinical trial (DIAN-TU-001) underwent both 11C-PiB and 18F-florbetapir PET imaging at baseline and during at least one follow-up visit. For each PET scan, regional standardized uptake value ratios (SUVRs), regional Centiloids, a global cortical SUVR, and a global cortical Centiloid value were calculated. Longitudinal changes in SUVRs and Centiloids were estimated using linear mixed models. Differences in longitudinal change between PET radiotracers and between drug arms were estimated using paired and Welch two sample t-tests, respectively. Simulated clinical trials were conducted to evaluate the consequences of some research sites using 11C-PiB while other sites use 18F-florbetapir for Aß PET imaging. RESULTS: In the placebo arm, the absolute rate of longitudinal change measured by global cortical 11C-PiB SUVRs did not differ from that of global cortical 18F-florbetapir SUVRs. In the gantenerumab arm, global cortical 11C-PiB SUVRs decreased more rapidly than global cortical 18F-florbetapir SUVRs. Drug effects were statistically significant across both Aß radiotracers. In contrast, the rates of longitudinal change measured in global cortical Centiloids did not differ between Aß radiotracers in either the placebo or gantenerumab arms, and drug effects remained statistically significant. Regional analyses largely recapitulated these global cortical analyses. Across simulated clinical trials, type I error was higher in trials where both Aß radiotracers were used versus trials where only one Aß radiotracer was used. Power was lower in trials where 18F-florbetapir was primarily used versus trials where 11C-PiB was primarily used. CONCLUSION: Gantenerumab treatment induces longitudinal changes in Aß PET, and the absolute rates of these longitudinal changes differ significantly between Aß radiotracers. These differences were not seen in the placebo arm, suggesting that Aß-clearing treatments may pose unique challenges when attempting to compare longitudinal results across different Aß radiotracers. Our results suggest converting Aß PET SUVR measurements to Centiloids (both globally and regionally) can harmonize these differences without losing sensitivity to drug effects. Nonetheless, until consensus is achieved on how to harmonize drug effects across radiotracers, and since using multiple radiotracers in the same trial may increase type I error, multisite studies should consider potential variability due to different radiotracers when interpreting Aß PET biomarker data and, if feasible, use a single radiotracer for the best results. TRIAL REGISTRATION: ClinicalTrials.gov NCT01760005. Registered 31 December 2012. Retrospectively registered.

Efficacy of Bifidobacterium longum alone or in multi-strain probiotic formulations during early life and beyond.

The significance of Bifidobacterium to human health can be appreciated from its early colonization of the neonatal gut, where Bifidobacterium longum represents the most abundant species. While its relative abundance declines with age, it is further reduced in several diseases. Research into the beneficial properties of B. longum has unveiled a range of mechanisms, including the production of bioactive molecules, such as short-chain fatty acids, polysaccharides, and serine protease inhibitors. From its intestinal niche, B. longum can have far-reaching effects in the body influencing immune responses in the lungs and even skin, as well as influencing brain activity. In this review, we present the biological and clinical impacts of this species on a range of human conditions beginning in neonatal life and beyond. The available scientific evidence reveals a strong rationale for continued research and further clinical trials that investigate the ability of B. longum to treat or prevent a range of diseases across the human lifespan.

A qualitative study of pain and related symptoms experienced by people with Ehlers-Danlos syndromes.

Introduction: Individuals with Ehlers-Danlos syndromes (EDS) often have complex and multi-faceted symptoms across the lifespan. Pain and the related symptoms of fatigue and sleep disorders are common. The objective of this qualitative study was to understand how participants manage their pain and related symptoms. Methods: The design was a qualitative thematic content analysis. Twenty-eight interviews were conducted to collect data from individuals who were participants in a prior quantitative longitudinal study. A semi-structured interview guide was designed to focus on and understand the trajectory of pain, sleep, fatigue, and general function. The interview continued with questions about coping mechanisms and obstacles to maintaining a sense of well-being. Results: Symptoms reported by participants were widespread and often interwoven. Pain was universal and often resulted in fatigue and disordered sleep which impacted physical function. Most participants reported that their symptoms worsened over time. Participants reported a wide range of effective interventions and most reported developing self-care strategies to adapt to their disabilities/limitations. Solutions included complementary interventions discovered when conventional medicine was unsuccessful. Very few relied on a "system" of health care and instead developed their own strategies to adapt to their disabilities/limitations. Discussion: EDS symptoms are often debilitating, and their progression is unknown. For most participants, symptoms worsened over the time. Even though participants in our study, by experience, were self-reliant, the importance of knowledgeable medical providers to help guide self-care should be emphasized.

Evaluation of dose-dependent treatment effects after mid-trial dose escalation in biomarker, clinical, and cognitive outcomes for gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

Introduction: While the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) was ongoing, external data suggested higher doses were needed to achieve targeted effects; therefore, doses of gantenerumab were increased 5-fold, and solanezumab was increased 4-fold. We evaluated to what extent mid-trial dose increases produced a dose-dependent treatment effect. Methods: Using generalized linear mixed effects (LME) models, we estimated the annual low- and high-dose treatment effects in clinical, cognitive, and biomarker outcomes. Results: Both gantenerumab and solanezumab demonstrated dose-dependent treatment effects (significant for gantenerumab, non-significant for solanezumab) in their respective target amyloid biomarkers (Pittsburgh compound B positron emission tomography standardized uptake value ratio and cerebrospinal fluid amyloid beta 42), with gantenerumab demonstrating additional treatment effects in some downstream biomarkers. No dose-dependent treatment effects were observed in clinical or cognitive outcomes. Conclusions: Mid-trial dose escalation can be implemented as a remedy for an insufficient initial dose and can be more cost effective and less burdensome to participants than starting a new trial with higher doses, especially in rare diseases. Highlights: We evaluated the dose-dependent treatment effect of two different amyloid-specific immunotherapies.Dose-dependent treatment effects were observed in some biomarkers.No dose-dependent treatment effects were observed in clinical/cognitive outcomes, potentially due to the fact that the modified study may not have been powered to detect such treatment effects in symptomatic subjects at a mild stage of disease exposed to high (or maximal) doses of medication for prolonged durations.

Longitudinal analysis of symptoms in the Ehlers-Danlos syndromes.

Our study extends a cross-sectional dataset on the Ehlers-Danlos syndromes (EDS) assembled by the National Institute on Aging (NIA), under a protocol entitled Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue. We were successful in contacting 171 of the original 252 participants with EDS. Our study cohort included 91 participants who completed at least one of the following surveys: Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory (MFI-20), and Short Form (SF-36) Health Survey, at both baseline and follow-up. Follow-up surveys occurred a median of 11.6 years after the baseline survey. We used mixed effects linear regression models to examine the change in scores for multiple indices reported by participants. There were small mean changes reflected in our estimates for the EDS population as a whole. There was wide heterogeneity between reported individual experiences, with some participants markedly improved and some dramatically worse. Men had a greater increase in mean pain severity over time than women. This is the first study to report a decade of longitudinal data in EDS.

Colliding and interacting microbiomes and microbial communities - consequences for human health.

Living 'things' coexist with microorganisms, known as the microbiota/microbiome that provides essential physiological functions to its host. Despite this reliance, the microbiome is malleable and can be altered by several factors including birth-mode, age, antibiotics, nutrition, and disease. In this minireview, we consider how other microbiomes and microbial communities impact the host microbiome and the host through the concept of microbiome collisions (initial exposures) and interactions. Interactions include changes in host microbiome composition and functionality and/or host responses. Understanding the impact of other microbiomes and microbial communities on the microbiome and host are important considering the decline in human microbiota diversity in the developed world - paralleled by the surge of non-communicable, inflammatory-based diseases. Thus, surrounding ourselves with rich and diverse beneficial microbiomes and microbial communities to collide and interact with should help to diminish the loss in microbial diversity and protect from certain diseases. In the same vein, our microbiomes not only influence our health but potentially the health of those close to us. We also consider strategies for enhanced host microbiome collisions and interactions through the surrounding environment that ensure increased microbiome diversity and functionality contributing to enhanced symbiotic return to the host in terms of health benefit.

Larvae of Deep-Sea Invertebrates Harbor Low-Diversity Bacterial Communities.

AbstractMicrobial symbionts are a common life-history character of marine invertebrates and their developmental stages. Communities of bacteria that associate with the eggs, embryos, and larvae of coastal marine invertebrates tend to be species specific and correlate with aspects of host biology and ecology. The richness of bacteria associated with the developmental stages of coastal marine invertebrates spans four orders of magnitude, from single mutualists to thousands of unique taxa. This understanding stems predominately from the developmental stages of coastal species. If they are broadly representative of marine invertebrates, then we may expect deep-sea species to associate with bacterial communities that are similar in diversity. To test this, we used amplicon sequencing to profile the bacterial communities of invertebrate larvae from multiple taxonomic groups (annelids, molluscs, crustaceans) collected from 2500 to 3670 m in depth in near-bottom waters near hydrothermal vents in 3 different regions of the Pacific Ocean (the East Pacific Rise, the Mariana Back-Arc, and the Pescadero Basin). We find that larvae of deep-sea invertebrates associate with low-diversity bacterial communities (~30 bacterial taxa) that lack specificity between taxonomic groups. The diversity of these communities is estimated to be ~7.9 times lower than that of coastal invertebrate larvae, but this result depends on the taxonomic group. Associating with a low-diversity community may imply that deep-sea invertebrate larvae do not have a strong reliance on a microbiome and that the hypothesized lack of symbiotic contributions would differ from expectations for larvae of coastal marine invertebrates.

A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years. The primary outcome was a cognitive end point; secondary outcomes included clinical, cognitive, imaging and fluid biomarker measures. Fifty-two participants carrying a mutation were assigned to receive gantenerumab, 52 solanezumab and 40 placebo. Both drugs engaged their Aß targets but neither demonstrated a beneficial effect on cognitive measures compared to controls. The solanezumab-treated group showed a greater cognitive decline on some measures and did not show benefits on downstream biomarkers. Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain. Amyloid-related imaging abnormalities edema was observed in 19.2% (3 out of 11 were mildly symptomatic) of the gantenerumab group, 2.5% of the placebo group and 0% of the solanezumab group. Gantenerumab and solanezumab did not slow cognitive decline in symptomatic DIAD. The asymptomatic groups showed no cognitive decline; symptomatic participants had declined before reaching the target doses.

Functional traits provide new insight into recovery and succession at deep-sea hydrothermal vents.

Investigation of communities in extreme environments with unique conditions has the potential to broaden or challenge existing theory as to how biological communities assemble and change through succession. Deep-sea hydrothermal vent ecosystems have strong, parallel gradients of nutrients and environmental stress, and present unusual conditions in early succession, in that both nutrient availability and stressors are high. We analyzed the succession of the invertebrate community at 9°50' N on the East Pacific Rise for 11 yr following an eruption in 2006 in order to test successional theories developed in other ecosystems. We focused on functional traits including body size, external protection, provision of habitat (foundation species), and trophic mode to understand how the unique nutritional and stress conditions influence community composition. In contrast to established theory, large, fast-growing, structure-forming organisms colonized rapidly at vents, while small, asexually reproducing organisms were not abundant until later in succession. Species in early succession had high external protection, as expected in the harsh thermal and chemical conditions after the eruption. Changes in traits related to feeding ecology and dispersal potential over succession agreed with expectations from other ecosystems. We also tracked functional diversity metrics over time to see how they compared to species diversity. While species diversity peaked at 8 yr post-eruption, functional diversity was continuing to increase at 11 yr. Our results indicate that deep-sea hydrothermal vents have distinct successional dynamics due to the high stress and high nutrient conditions in early succession. These findings highlight the importance of extending theory to new systems and considering function to allow comparison between ecosystems with different species and environmental conditions.

Determining a reliably visible and inexpensive surface fiducial marker for use in MRI: a research study in a busy Australian Radiology Department.

OBJECTIVES: Single-use commercial surface fiducial markers are used in clinical imaging for a variety of applications. The current study sought to find a new, reliably visible, easily sourced and inexpensive fiducial marker alternative for use with MRI. DESIGN: Five commonly requested MRI sequences were determined (three-dimensional (3D) T1-weighted, T1 coronal, 3D T2-weighted, T2 fat suppressed, proton density), to examine the visibility of 18 items (including a commercial fiducial marker). SETTING: Clinical 3T MRI scanner in an Australian Tertiary Hospital and an Australian University Biomedical Engineering research group. INTERVENTIONS: 18 marker alternatives were scanned using five common MRI sequences. Images were reformatted to obtain both an image through the mid-height of each marker and a maximum intensity z-projection image over the volume of the marker. Variations in marker intensity were profiled across each visible marker and a visibility rating defined. MAIN OUTCOME MEASURES: Outcome measures were based on quantitative assessment of a clear intensity contrast ratio between the marker and the adjacent tissue and a qualitative assessment of visibility via a 3-point scale. RESULTS: The fish oil capsule, vitamin D capsule, paint ball pellet, soy sauce sushi tube and commercial markers were typically visible to a high quality on all the imaging sequences and demonstrated a clear differential in intensity contrast against the adjacent tissue. Other common items, such as plasticine 'play doh' and a soft 'Jelly baby' sweet, were surprise candidates, demonstrating high-quality visibility and intensity contrast for the 3D T1-weighted sequence. CONCLUSIONS: Depending on the basis for referral and MRI sequence chosen, four alternative fiducial markers were determined to be inexpensive, easily sourced and consistently visible. Of these, the vitamin D capsule provided an excellent balance between availability, size, cost, usability and quality of the visualised marker for all the commonly used MRI sequences analysed.

Precision Nutrition and the Microbiome Part II: Potential Opportunities and Pathways to Commercialisation.

Modulation of the human gut microbiota through probiotics, prebiotics and dietary fibre are recognised strategies to improve health and prevent disease. Yet we are only beginning to understand the impact of these interventions on the gut microbiota and the physiological consequences for the human host, thus forging the way towards evidence-based scientific validation. However, in many studies a percentage of participants can be defined as 'non-responders' and scientists are beginning to unravel what differentiates these from 'responders;' and it is now clear that an individual's baseline microbiota can influence an individual's response. Thus, microbiome composition can potentially serve as a biomarker to predict responsiveness to interventions, diets and dietary components enabling greater opportunities for its use towards disease prevention and health promotion. In Part I of this two-part review, we reviewed the current state of the science in terms of the gut microbiota and the role of diet and dietary components in shaping it and subsequent consequences for human health. In Part II, we examine the efficacy of gut-microbiota modulating therapies at different life stages and their potential to aid in the management of undernutrition and overnutrition. Given the significance of an individual's gut microbiota, we investigate the feasibility of microbiome testing and we discuss guidelines for evaluating the scientific validity of evidence for providing personalised microbiome-based dietary advice. Overall, this review highlights the potential value of the microbiome to prevent disease and maintain or promote health and in doing so, paves the pathway towards commercialisation.

Precision Nutrition and the Microbiome, Part I: Current State of the Science.

The gut microbiota is a highly complex community which evolves and adapts to its host over a lifetime. It has been described as a virtual organ owing to the myriad of functions it performs, including the production of bioactive metabolites, regulation of immunity, energy homeostasis and protection against pathogens. These activities are dependent on the quantity and quality of the microbiota alongside its metabolic potential, which are dictated by a number of factors, including diet and host genetics. In this regard, the gut microbiome is malleable and varies significantly from host to host. These two features render the gut microbiome a candidate 'organ' for the possibility of precision microbiomics - the use of the gut microbiome as a biomarker to predict responsiveness to specific dietary constituents to generate precision diets and interventions for optimal health. With this in mind, this two-part review investigates the current state of the science in terms of the influence of diet and specific dietary components on the gut microbiota and subsequent consequences for health status, along with opportunities to modulate the microbiota for improved health and the potential of the microbiome as a biomarker to predict responsiveness to dietary components. In particular, in Part I, we examine the development of the microbiota from birth and its role in health. We investigate the consequences of poor-quality diet in relation to infection and inflammation and discuss diet-derived microbial metabolites which negatively impact health. We look at the role of diet in shaping the microbiome and the influence of specific dietary components, namely protein, fat and carbohydrates, on gut microbiota composition.

Heritable disorders of connective tissue: Description of a data repository and initial cohort characterization.

We describe a data repository on heritable disorders of connective tissue (HDCT) assembled by the National Institutes of Health's National Institute on Aging (NIA) Intramural Research Program between 2001 and 2013. Participants included affected persons with a wide range of heritable connective tissue phenotypes, and unaffected family members. Elements include comprehensive history and physical examination, standardized laboratory data, physiologic measures and imaging, standardized patient-reported outcome measures, and an extensive linked biorepository. The NIA made a commitment to make the repository available to extramural investigators and deposited samples at Coriell Tissue Repository (N = 126) and GenTAC registry (N = 132). The clinical dataset was transferred to Penn State University College of Medicine Clinical and Translational Science Institute in 2016, and data elements inventoried. The consented cohort of 1,009 participants averaged 39 ± 18 years (mean ± SD, range 2-95) at consent; gender distribution is 71% F and 83% self-report Caucasian ethnicity. Diagnostic categories include Ehlers-Danlos syndrome (classical N = 50, hypermobile N = 99, vascular N = 101, rare types and unclassified N = 178), Marfan syndrome (N = 33), Stickler syndrome (N = 60), fibromuscular dysplasia (N = 135), Other HDCT (N = 72). Unaffected family members (N = 218) contributed DNA for the molecular archive only. We aim to develop further discrete data from unstructured elements, analyze multisymptom HDCT manifestations, encourage data use by other researchers and thereby better understand the complexity of these high-morbidity conditions and their multifaceted effects on affected persons.

Improving Biomedical Engineering Education Through Continuity in Adaptive, Experiential, and Interdisciplinary Learning Environments.

This study reports our experience of developing a series of biomedical engineering (BME) courses having active and experiential learning components in an interdisciplinary learning environment. In the first course, BME465: biomechanics, students were immersed in a simulation laboratory setting involving mannequins that are currently used for teaching in the School of Nursing. Each team identified possible technological challenges directly related to the biomechanics of the mannequin and presented an improvement overcoming the challenge. This approach of exposing engineering students to a problem in a clinical learning environment enhanced the adaptive and experiential learning capabilities of the course. In the following semester, through BME448: medical devices, engineering students were partnered with nursing students and exposed to simulation scenarios and real-world clinical settings. They were required to identify three unmet needs in the real-world clinical settings and propose a viable engineering solution. This approach helped BME students to understand and employ real-world applications of engineering principles in problem solving while being exposed to an interdisciplinary collaborative environment. A final step was for engineering students to execute their proposed solution from either BME465 or BME448 courses by undertaking it as their capstone senior design project (ENGR401-402). Overall, the inclusion of clinical immersions in interdisciplinary teams in a series of courses not only allowed the integration of active and experiential learning in continuity but also offered engineers more practice of their profession, adaptive expertise, and an understanding of roles and expertise of other professionals involved in enhancement of healthcare and patient safety.

Viromes of one year old infants reveal the impact of birth mode on microbiome diversity.

Establishing a diverse gut microbiota after birth is being increasingly recognised as important for preventing illnesses later in life. It is well established that bacterial diversity rapidly increases post-partum; however, few studies have examined the infant gut virome/phageome during this developmental period. We performed a metagenomic analysis of 20 infant faecal viromes at one year of age to determine whether spontaneous vaginal delivery (SVD) or caesarean section (CS) influenced viral composition. We find that birth mode results in distinctly different viral communities, with SVD infants having greater viral and bacteriophage diversity. We demonstrate that CrAssphage is acquired early in life, both in this cohort and two others, although no difference in birth mode is detected. A previous study has shown that bacterial OTU's (operational taxonomic units) identified in the same infants could not discriminate between birth mode at 12 months of age. Therefore, our results indicate that vertical transmission of viral communities from mother to child may play a role in shaping the early life microbiome, and that birth mode should be considered when studying the early life gut virome.

Phages & antibiotic resistance: are the most abundant entities on earth ready for a comeback?

Bacteriophages, which lost out to antibiotic therapy in the past, may be poised to make a comeback. Once discarded because of their narrow activity spectrum, it can now be viewed as a major advantage that these intracellular, self-replicating entities can exert their killing effect with minimal damage to the commensal microbiome. In eastern Europe, phages continue to be used both prophylactically and therapeutically to treat infections. More recently, much needed regulated clinical trials are underway with a view to restoring phage therapy as a tool for mainstream medicine, although current regulations may impede their full potential. One hundred years after their discovery, and amid an antibiotic resistance crisis, we must ask, what can be done to harness their full antibacterial potential?

Intercountry Consensus Building: Lessons From Developing a Chronic-Conditions Self-Management Support Framework.

Self-management support initiatives that aim to improve the self-care of chronic conditions are considered a key part of a health promotion strategy for addressing the impacts of long-term illness. Given the growth of these activities and still evolving evidence base, thoughtful intercountry collaborations with subject matter experts can be an effective way to expedite building self-management support capacity, promoting the advancement of evidence, and developing effective policies and programs. The challenge is to find an effective consensus building process that promotes linkages between researchers and health promotion decisions makers across vast geographical boundaries and limited resources. This paper describes the international, multistage, face-to-face, and online process that was used for developing an international framework for self-management support by researchers, educators, health care providers, policy makers, program managers/directors, program planners, consultants, patient group representatives, and consumers in 16 countries. We reflect on key lessons from this international initiative and discuss how this type of process may be useful for other health promotion groups trying to exchange knowledge and build consensus on how to move a field of research, policy, and/or practice forward, and advance the evidence-base of practice and the relevance of research.