Priority setting: Development of the South Australian Aboriginal Chronic Disease Consortium RoadMap for Action.

ISSUES ADDRESSED: Aboriginal and Torres Strait Islander (Aboriginal) people in South Australia are overburdened by cardiovascular disease, diabetes and cancer. The South Australian Aboriginal Chronic Disease Consortium (Consortium) was established in June 2017 as a collaborative partnership to lead the implementation of three state-wide chronic disease plans using a strategic approach to identifying key priority areas for action. METHODS: In 2017-2018, the Consortium Coordinating Centre facilitated a priority setting process, which involved extensive consultation, including a prioritisation survey and stakeholder workshops. The Consortium's Aboriginal Community Reference Group was instrumental in leading the identification of priorities for action. RESULTS: The Consortium RoadMap for Action identified seven across-plan priorities and six condition-specific priorities. It acknowledged that: strengthening social and emotional well-being is central to improving health outcomes; prevention and early detection, acute management and ongoing management are all components of the continuum of care; and improving access to services, strengthening the workforce, and monitoring and evaluation are required across the continuum of care. CONCLUSION: Widespread implementation failure in the past across the health system and health services implementation and research translation highlights the value of the Consortium approach and its commitment to implementing the state-wide chronic disease plans in a collaborative manner. The Consortium relies on and fosters cross-sectoral alignment, with all key players including all public, private and Aboriginal Community Controlled health services, to progress its priorities and aspirations to improve health outcomes for Aboriginal people using evidence-based strategies. SO WHAT?: Rigorous and transparent priority setting processes that bring together research, clinical practice, health services operations, policy and community perspectives can foster intersectoral collaboration and partnership and support the implementation of shared priorities.

The ancestry and geographical origins of St Helena's liberated Africans.

The island of St Helena played a crucial role in the suppression of the transatlantic slave trade. Strategically located in the middle of the South Atlantic, it served as a staging post for the Royal Navy and reception point for enslaved Africans who had been "liberated" from slave ships intercepted by the British. In total, St Helena received approximately 27,000 liberated Africans between 1840 and 1867. Written sources suggest that the majority of these individuals came from West Central Africa, but their precise origins are unknown. Here, we report the results of ancient DNA analyses that we conducted as part of a wider effort to commemorate St Helena's liberated Africans and to restore knowledge of their lives and experiences. We generated partial genomes (0.1-0.5×) for 20 individuals whose remains had been recovered during archaeological excavations on the island. We compared their genomes with genotype data for over 3,000 present-day individuals from 90 populations across sub-Saharan Africa and conclude that the individuals most likely originated from different source populations within the general area between northern Angola and Gabon. We also find that the majority (17/20) of the individuals were male, supporting a well-documented sex bias in the latter phase of the transatlantic slave trade. The study expands our understanding of St Helena's liberated African community and illustrates how ancient DNA analyses can be used to investigate the origins and identities of individuals whose lives were bound up in the story of slavery and its abolition.

An Aboriginal-led consortium approach to chronic disease action for health equity and holistic wellbeing.

ISSUE ADDRESSED: The Wellbeing Economy, which places human and ecological wellbeing at the centre of policy making, aligns with holistic Aboriginal and Torres Strait Islander conceptualisations of health and wellbeing. In order to address chronic diseases in South Australian Aboriginal and Torres Strait Islander populations, the South Australian Aboriginal Chronic Disease Consortium (Consortium) is fostering action in ways that align both with the Wellbeing Economy and with Health in All Policies (HiAP) approaches. METHODS: In June 2017, the Consortium was established as a collaborative partnership between government and non-government organisations, researchers, Aboriginal organisations and communities to lead the effective implementation of three state-wide chronic disease plans. A coordinating centre was funded to support and progress the work of the Consortium. RESULTS: During its first 5 years, the Consortium has developed a foundation for sustained system reform through partnering with stakeholders, leading projects and initiatives, advocating for key priorities, leveraging existing infrastructure and funding, supporting services, and coordinating delivery of priority actions using innovative approaches. CONCLUSIONS: Through the Consortium governance structure, Aboriginal and Torres Strait Islander community members, policy actors, service providers and researchers oversee, drive, influence and support the implementation of priority action initiatives. Sustained funding, competing priorities of partner organisations and project evaluation are constant challenges. SO WHAT?: A consortium approach provides direction and shared priorities, which foster collaboration across and between organisations, service providers and the Aboriginal community. Aligning with HiAP approaches and the Wellbeing Economy, it harnesses knowledge, networks and partnerships that support project implementation and reduce duplication.

Hip fractures.

In the UK the incidence of hip fractures is nearly 76 000 cases per year, with the vast majority of these fractures occurring in patients over the age of 70 years. Most patients who sustain a hip fracture will have significant comorbidities and up to 40% will have cognitive impairment. For patients, sustaining a hip fracture can potentially be a devastating event. This article provides an overview of the presentation, assessment and management of hip fractures for core surgical, acute care common stem and emergency medicine trainees.

The impact of COVID-19 on the future of orthopaedic training in the UK.

The COVID-19 pandemic has had a major impact on global healthcare systems, has drastically affected patient care, and has had widespread effects upon medical education. As plans are being devised to reinstate elective surgical services, it is important to consider the impact that the pandemic has had and will continue to have on surgical training. We describe the effect COVID-19 has had at all levels of training in the UK within trauma and orthopaedics and evaluate how training might change in the future. We found that the COVID-19 pandemic has significantly impacted trainees within trauma and orthopaedics at all levels of training. It had led to reduced operative exposure, cancellations of examinations and courses, and modifications to speciality recruitment and annual appraisals. This cohort of trainees is witnessing novel methods of delivering orthopaedic services, which will continue to develop and become part of routine practice even once the pandemic has resolved. It will be important to observe the extent to which the rapid changes currently being introduced will impact the personal health, safety, and career progression of current trainees.

Impact of the COVID-19 pandemic on paediatric orthopaedic trauma workload in central London: a multi-centre longitudinal observational study over the "golden weeks".

Background and purpose - The COVID-19 pandemic has been recognised as an unprecedented global health crisis. This study assesses the impact on a large acute paediatric hospital service in London, evaluating the trends in the acute paediatric orthopaedic trauma referral caseload and operative casemix before (2019) and during (2020) COVID-19 lockdown. Patients and methods - A longitudinal retrospective observational prevalence study of both acute paediatric orthopaedic trauma referrals and operative caseload was performed for the first 6 "golden weeks" of lockdown. These data were compared with the same period in 2019. Statistical analyses included median (± median absolute deviation), risk and odds ratios as well as Fisher's exact test to calculate the statistical significance, set at p ≤ 0.05. Results - Acute paediatric trauma referrals in 2020 were reduced by two-thirds compared with 2019 (n = 302 vs. 97) with a halving risk (RR 0.55) and odds ratios (OR 0.43) of sporting-related mechanism of injuries (p = 0.002). There was a greater use of outpatient telemedicine in the COVID-19 period with more Virtual Fracture Clinic use (OR 97, RR 84, p < 0.001), and fewer patients being seen for consultation and followed up face to face (OR 0.55, RR 0.05, p < 0.001). Interpretation - The impact of the COVID-19 pandemic has led to a decline in the number of acute paediatric trauma referrals, admissions, and operations during the COVID period. There has also been a significant change in the patient pathway with more being reviewed via the means of telemedicine to reduce the risk of COVID-19 transmission and exposure. More work is required to observe for similar trends nationwide and globally as the pandemic has permanently affected the entire healthcare infrastructure.

Clavicle fractures.

Clavicle fractures account for approximately 2-5% of all fractures in adults and 10-15% in children. There is a bimodal distribution, with two peaks occurring in patients <25 years of age as a result of direct trauma and in those >55 years of age secondary to a fall onto an outstretched arm. Approximately two-thirds of all clavicle fractures occur in men. This article provides an overview of the presentation, assessment and management of clavicle fractures for both core surgical trainees and acute care common stem/emergency medicine trainees.

Clinical outcomes in elective total hip arthroplasty in Parkinson's disease: a systematic review of the literature.

Parkinson's disease (PD) poses a significant challenge for the arthroplasty surgeon, owing to excessive muscle tone, higher fracture risk and poor bone quality. Several studies have reported high mortality, early failure and perioperative complications associated with hip fracture surgery in PD; however, no higher-level evidence exists regarding elective hip arthroplasty.The aim of our study was to perform a systematic review to evaluate the evidence basis and clinical outcomes pertaining to patients with underlying Parkinson's disease undergoing elective total hip arthroplasty (THA).We searched MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials to identify studies evaluating the safety and clinical outcomes of THA in patients suffering from Parkinson's. Our review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Ten studies encompassing 49,730 patients were included in our systematic review. Qualitative synthesis demonstrated comparable results between PD patients and controls with respect to one-year mortality and surgical site infections. PD patients experienced more medical complications, had a longer hospital stay and worse long-term implant survival. Some studies also reported a higher rate of dislocation, periprosthetic fractures and aseptic loosening.Decisions about the optimal articulation, the utilization of cemented components, dual-mobility cups or constrained liners were not uniform among included studies.THA in patients with Parkinson's disease can offer significant functional gains and pain relief. Surgical considerations pertain to the approach and ways to address instability, whereas emphasis should be placed on appropriate counselling and exploring whether potential improvement of life quality outweighs the risks. Cite this article: EFORT Open Rev 2020;5:856-865. DOI: 10.1302/2058-5241.5.200034.

Procedural injustice, police legitimacy, and officer gender: A vignette-based test of the invariance thesis.

Role congruity theory suggests that gender-based stereotypes can result in female police officers paying a higher price (i.e., viewed as less legitimate) relative to male officers for mistreating people. The invariance thesis posits that the effect of (un)fair treatment by legal authorities on legal attitudes and beliefs is stable across situations, time, and space. This study tested the invariance thesis by assessing whether the effect of procedural injustice on police legitimacy differed across officer gender. A factorial vignette survey that consisted of two types of citizen-initiated police encounters was administered to a university-based sample (N = 525). The results showed that the effect of procedural injustice had a powerful and significant influence on participants' legitimacy perceptions. These effects were consistent regardless of whether the treatment was doled out by a male or a female police officer. The findings provide support for the invariance thesis.

Honey bee Royalactin unlocks conserved pluripotency pathway in mammals.

Royal jelly is the queen-maker for the honey bee Apis mellifera, and has cross-species effects on longevity, fertility, and regeneration in mammals. Despite this knowledge, how royal jelly or its components exert their myriad effects has remained poorly understood. Using mouse embryonic stem cells as a platform, here we report that through its major protein component Royalactin, royal jelly can maintain pluripotency by activating a ground-state pluripotency-like gene network. We further identify Regina, a mammalian structural analog of Royalactin that also induces a naive-like state in mouse embryonic stem cells. This reveals an important innate program for stem cell self-renewal with broad implications in understanding the molecular regulation of stem cell fate across species.

Live Imaging Reveals that the First Division of Differentiating Human Embryonic Stem Cells Often Yields Asymmetric Fates.

How do stem cells respond to signals to initiate differentiation? Here, we show that, despite uniform exposure to differentiation-inducing extracellular signals, individual human embryonic stem cells (hESCs) respond heterogeneously. To track how hESCs incipiently exit pluripotency, we established a system to differentiate hESCs as single cells and conducted live imaging to track their very first cell division. We followed the fate of their earliest daughters as they remained undifferentiated or differentiated toward the primitive streak (the earliest descendants of pluripotent cells). About 30%-50% of the time, hESCs divided to yield one primitive streak and one undifferentiated daughter. The undifferentiated daughter cell was innately resistant to WNT signaling and could not respond to this primitive-streak-specifying differentiation signal. Hence, the first division of differentiating hESCs sometimes yields daughters with diverging fates, with implications for the efficiency of directed differentiation protocols and the underlying rules of lineage commitment.

Defects of the vertebral end plate: implications for disc degeneration depend on size.

BACKGROUND CONTEXT: Bony vertebral end plates must be porous to allow metabolite transport into the disc, and yet strong to resist high intradiscal pressure (IDP). End plate defects may therefore have nutritional and mechanical consequences for the disc, depending on their size and type. We hypothesize that broad, diffuse defects are more closely associated with disc decompression and degeneration than are focal Schmorl's node-type defects. PURPOSE: This study aimed to determine how the size and type of end plate defects are related to decompression and degeneration in the adjacent intervertebral disc. STUDY DESIGN: Mechanical, histologic, and micro-computed tomographic investigations were carried out in cadaver spines. METHODS: The study involved 40 motion segments (T8-T9 to L4-L5) dissected from 23 cadavers aged 48-98 years. Intradiscal stresses were measured, under 1 kN compression, by pulling a pressure transducer along the disc's midsagittal diameter. The resulting "stress profiles" revealed nucleus pressure (IDP) and maximum stresses in the anterior and posterior annulus. Micro-computed tomography was then used to examine all 40 discs, with 5 mm of adjacent bone on either side, so that end plate defects could be characterized at a resolution of 35 µm. Cross-sectional area (in the transverse plane), volume, location, and morphologic type were determined for all bony defects in the 80 end plates. Finally, discs from each motion segment (with hyaline cartilage and bone attached) were sectioned (undecalcified) at 7 µm for histology to allow degeneration to be assessed. RESULTS: Substantial defects were identified in 24 of 40 specimens (35 of 80 end plates). Of these, 83% was centrally located, and 17% was laterally located. Defects occurred more frequently in male than female specimens (p=.043), and were more common in thoracic than lumbar end plates (p=.002), although lumbar defects were greater in volume (p=.05). Defect area and volume increased with decreasing IDP, with decreasing peak stress in the annulus, and with increasing tissue degeneration. Stepwise multiple regression showed that average defect area depended most strongly on IDP, whereas maximum defect area and volume depended most strongly on peak stress in the anterior annulus. Multiple end plate defects were associated with lower values of IDP and higher degeneration scores when compared with erosions and Schmorl's nodes. CONCLUSIONS: Disc degeneration has a stronger association with large or multiple end plate defects than with small or single defects (of any type). Large end plate defects probably allow greater volume changes within the disc, leading to greater nucleus decompression.

Early Trabecular Development in Human Vertebrae: Overproduction, Constructive Regression, and Refinement.

Early bone development may have a significant impact upon bone health in adulthood. Bone mineral density (BMD) and bone mass are important determinants of adult bone strength. However, several studies have shown that BMD and bone mass decrease after birth. If early development is important for strength, why does this reduction occur? To investigate this, more data characterizing gestational, infant, and childhood bone development are needed in order to compare with adults. The aim of this study is to document early vertebral trabecular bone development, a key fragility fracture site, and infer whether this period is important for adult bone mass and structure. A series of 120 vertebrae aged between 6 months gestation and 2.5 years were visualized using microcomputed tomography. Spherical volumes of interest were defined, thresholded, and measured using 3D bone analysis software (BoneJ, Quant3D). The findings showed that gestation was characterized by increasing bone volume fraction whilst infancy was defined by significant bone loss (≈2/3rds) and the appearance of a highly anisotropic trabecular structure with a predominantly inferior-superior direction. Childhood development progressed via selective thickening of some trabeculae and the loss of others; maintaining bone volume whilst creating a more anisotropic structure. Overall, the pattern of vertebral development is one of gestational overproduction followed by infant "sculpting" of bone tissue during the first year of life (perhaps in order to regulate mineral homeostasis or to adapt to loading environment) and then subsequent refinement during early childhood. Comparison of early bone developmental data in this study with adult bone volume values taken from the literature shows that the loss in bone mass that occurs during the first year of life is never fully recovered. Early development could therefore be important for developing bone strength, but through structural changes in trabecular microarchitecture rather than bone mass.

Pathogenesis of Vertebral Anterior Wedge Deformity: A 2-Stage Process?

STUDY DESIGN: Biomechanical and radiographical study on cadaveric spines. OBJECTIVE: To explain the pathogenesis of vertebral "anterior wedge" deformity, which causes senile kyphosis. SUMMARY OF BACKGROUND DATA: This deformity arises with minimal trauma and is difficult to reproduce in cadaveric spines. We hypothesize that wedging is created by a 2-stage process. First, excessive loading damages a vertebral endplate and decompresses the adjacent intervertebral disc. This alters load sharing between the vertebral body cortex and trabeculae so that subsequent cyclic loading causes progressive collapse of the unsupported anterior cortex. METHODS: Thirty-four cadaveric thoracolumbar "motion segments," aged 70 to 98 years, were positioned in flexion and overloaded in compression. Physiologically reasonable cyclic compressive loading was then applied to each flexed specimen, at progressively higher loads, for up to 2 hours. Before and after initial overload and again after cyclic loading, the distribution of loading on the vertebra was assessed from measurements of compressive stress within the adjacent disc. These "stress profiles" were repeated in the neutral, flexed, and extended postures. Progressive vertebral body deformity was assessed radiographically. RESULTS: Compressive overload induced endplate fracture at an average force of 2.31 kN. There was minimal anterior wedging, but pressure in the adjacent disc nucleus (in flexion) fell by an average of 55% and neural arch load bearing increased by 166%. Subsequent cyclic loading exaggerated these changes and concentrated compressive stress within the anterior annulus. After both stages, height of the anterior and posterior vertebral cortexes was reduced by 32% and 12%, respectively, so that anterior wedging of the vertebral body increased from 5.0° to 11.4° on average. All changes were highly significant (P < 0.001). CONCLUSION: Anterior wedge deformities can be created consistently by a 2-stage process involving initial endplate damage, followed by progressive collapse of the anterior cortex. Detecting initial endplate damage may be important to minimize vertebral deformity in patients with osteoporosis. LEVEL OF EVIDENCE: N/A.

Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging.

Deterioration of adult stem cells accounts for much of aging-associated compromised tissue maintenance. How stem cells maintain metabolic homeostasis remains elusive. Here, we identified a regulatory branch of the mitochondrial unfolded protein response (UPR(mt)), which is mediated by the interplay of SIRT7 and NRF1 and is coupled to cellular energy metabolism and proliferation. SIRT7 inactivation caused reduced quiescence, increased mitochondrial protein folding stress (PFS(mt)), and compromised regenerative capacity of hematopoietic stem cells (HSCs). SIRT7 expression was reduced in aged HSCs, and SIRT7 up-regulation improved the regenerative capacity of aged HSCs. These findings define the deregulation of a UPR(mt)-mediated metabolic checkpoint as a reversible contributing factor for HSC aging.

SIRT7 represses Myc activity to suppress ER stress and prevent fatty liver disease.

Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD(+)-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7-deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease.

Protein post-translational modification analyses using on-chip immunoprobed isoelectric focusing.

Post-translational modifications play a critical role in regulating protein function. Increasingly, determination of protein identity, estimation of abundance, and characterization of post-translational modifications are required for analysis of protein-mediated cell signaling networks. As such, we report an integrated and rapid multispectral immunoprobed isoelectric focusing technique for identifying specific proteins bearing post-translational modifications. Immunoprobed isoelectric focusing is composed of isoelectric focusing in a large pore-size polyacrylamide gel to determine protein pI followed by immobilization of pI-resolved proteins. Proteins are immobilized via covalent attachment to a channel-filling benzophenone-functionalized polyacrylamide gel via brief UV exposure (photoblot), followed by multispectral antibody-based detection. The assay correlates observed post-translational modifications to pI shifts relative to the unmodified protein of interest. During the electrokinetically driven antibody probing stage, we observed nonuniform electrophoretic probe mobility along the channel axis. The spatially varying mobility is attributed to nonuniform charge arising from covalent attachment of ampholytes to the benzophenone-functionalized gel matrix during the photoblotting step. Using the multistep microfluidic assay, phosphorylated and acetylated forms of heat shock protein 27 and superoxide dismutase 2 were detected, respectively. The assay reported protein isoforms in immune-purified sample and raw cell lysate in 2 hours with sample volume requirements of 2 µL. This new assay is well-matched to systems biology frameworks for study of protein post-translational modifications.

SIRT3 reverses aging-associated degeneration.

Despite recent controversy about their function in some organisms, sirtuins are thought to play evolutionarily conserved roles in lifespan extension. Whether sirtuins can reverse aging-associated degeneration is unknown. Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces oxidative stress, is highly enriched in hematopoietic stem cells (HSCs) where it regulates a stress response. SIRT3 is dispensable for HSC maintenance and tissue homeostasis at a young age under homeostatic conditions but is essential under stress or at an old age. Importantly, SIRT3 is suppressed with aging, and SIRT3 upregulation in aged HSCs improves their regenerative capacity. Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process and shows that aging-associated degeneration can be reversed by a sirtuin.

Morphogenesis of an extended phenotype: four-dimensional ant nest architecture.

Animals produce a variety of structures to modify their environments adaptively. Such structures represent extended phenotypes whose development is rarely studied. To begin to rectify this, we used micro-computed tomography (CT) scanning and time-series experiments to obtain the first high-resolution dataset on the four-dimensional growth of ant nests. We show that extrinsic features within the environment, such as the presence of planes between layers of sediment, influence the architecture of Lasius flavus nests, with ants excavating horizontal tunnels along such planes. Intrinsically, the dimensions of the tunnels are associated with individual colonies, the dynamics of excavation can be explained by negative feedback and the angular distribution of tunnels is probably a result of local competition among tunnels for miners. The architecture and dynamics of ant nest excavation therefore result from local interactions of ants with one another and templates inherent in the environment. The influence of the environment on the form of structures has been documented across both biotic and abiotic domains. Our study opens up the utility of CT scanning as a technique for observing the morphogenesis of such structures.