Microbial transmission in animal social networks and the social microbiome.

Host-associated microbiomes play an increasingly appreciated role in animal metabolism, immunity and health. The microbes in turn depend on their host for resources and can be transmitted across the host's social network. In this Perspective, we describe how animal social interactions and networks may provide channels for microbial transmission. We propose the 'social microbiome' as the microbial metacommunity of an animal social group. We then consider the various social and environmental forces that are likely to influence the social microbiome at multiple scales, including at the individual level, within social groups, between groups, within populations and species, and finally between species. Through our comprehensive discussion of the ways in which sociobiological and ecological factors may affect microbial transmission, we outline new research directions for the field.

Radiofrequency Microdebridement Versus Surgical Decompression for Achilles Tendinosis: A Randomized Controlled Trial.

Achilles tendinosis is primarily managed nonoperatively with activity modification and physiotherapy, although surgery can be required. This has classically involved surgical decompression of the Achilles tendon, although the use of radiofrequency microdebridement has been suggested as a novel minimally invasive alternative. We present a randomized controlled trial comparing radiofrequency microdebridement using the Topaz® microdebrider wand and traditional surgical decompression. All patients with Achilles tendinosis referred to a single surgeon and meeting the inclusion criteria were invited to participate in our single-blinded, randomized controlled study. The Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire and the visual analog scale were used as measures at baseline and 6 months postoperatively. From 2009 to 2014, 16 patients were randomized to traditional decompression treatment and 20 to Topaz® treatment. All surgical procedures were performed as day-case procedures with the patient under general anesthetic by a single surgeon. No significant differences were found between the groups in demographic data. At 6 months after intervention, both groups demonstrated an improvement in the Victorian Institute of Sports Assessment-Achilles and visual analog scale scores compared with baseline, with no difference found between treatment modalities at 6 months. The Topaz® microdebrider resulted in variable outcomes after surgery and is not without complications. Regarding the patient-reported outcome measures, Topaz® conferred no additional benefit compared with traditional surgical decompression and we have stopped using Topaz® in our treatment of Achilles tendinosis.

Inadequate pre-operative glycaemic control in patients with diabetes mellitus adversely influences functional recovery after total knee arthroplasty : Patients with impaired glycaemic control exhibit poorer functional outcomes at 1-year post-arthroplasty.

PURPOSE: Whilst inadequate glycaemic control is associated with an increase in perioperative complications following total knee arthroplasty, the impact of glycaemic control in this at-risk patient group remains ill-defined. Identification of at-risk patients would allow targeted pre-operative glycaemic control intervention. METHODS: One hundred consecutive patients with a diagnosis of diabetes mellitus and one hundred age, sex and BMI matched patients without diabetes undergoing total knee arthroplasty in a single institution were analysed between 2008 and 2013. Inadequate glycaemic control was defined as having an HbA1c of greater than 64 mmol/mol (8.0 % NGSP) measured within the 3 months before surgery. Patient demographics, diabetes management and complications of diabetes were recorded and used as explanatory variables to deliver a generalised linear model. This allows for relationships to be defined between change in patient-reported function (SF-36, WOMAC) and these explanatory variables. RESULTS: The patient group with concomitant diabetes exhibited smaller improvements in WOMAC and SF-36 physical component summary at 1 year after knee arthroplasty. This effect was most pronounced in the subset of patients with inadequate glycaemic control recorded in the early pre-operative period. CONCLUSION: Patients with diabetes, particularly those with inadequate glycaemic control, exhibit less improvement at 1 year following knee arthroplasty than patients without diabetes mellitus. Clinical focus on modulating this factor in this at-risk group is warranted. LEVEL OF EVIDENCE: III.

Length of stay and its impact upon functional outcomes following lower limb arthroplasty.

PURPOSE: The aim was to investigate the interplay between patient characteristics and (1) length of hospital stay and (2) one-year patient-reported outcome following total knee and hip arthroplasty. METHODS: Event (survival) analysis and structural equation modelling were performed for 1001 patients undergoing knee (n = 566) and hip (n = 435) arthroplasty in a single institution. RESULTS: Age, body mass index and co-morbidities were independent predictors of length of stay in both event analysis and structural equation modelling. These patient characteristics and type of arthroplasty had both small direct and indirect effects on patient-reported outcome measures at one year. Length of stay had a small effect (<2 %) in SF-36 scores at one year. CONCLUSION: Predictors that influence length of stay also impact on one-year post-operative outcome and therefore should be taken into account during patient selection and discharge planning. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Thyroid-like follicular carcinoma of the kidney: one case report and review of the literature.

OBJECTIVES: Thyroid-like follicular carcinoma of the kidney continues to confound the practicing pathologist with its close resemblance to the follicular variant of thyroid carcinoma, as well as other benign and malignant entities. Our goal is to expand the knowledge of this rare renal cell carcinoma subtype, which is morphologically similar to follicular carcinoma of the thyroid but lacks expression of characteristic thyroid immunohistochemical markers such as TTF-1 and thyroglobulin. METHODS: We evaluated the gross, histologic, immunohistochemical, and fluorescence in situ hybridization (FISH) studies of a new case and performed a comprehensive review of the literature. RESULTS: The lesion was spongy and well-circumscribed. Microscopically it showed variably sized follicular structures, filled with abundant, deeply eosinophilic, colloid-like material. At the periphery, it displayed areas resembling metanephric adenoma and early stages of nephrogenesis. The tumor cells strongly expressed CK7, PAX-8, PAX-2, vimentin, EMA, and CK19 immunostains. Other markers, such as CD10, RCC, HBME-1, thyroglobulin, and TTF-1, were not immunoreactive. The tumor was negative for trisomy of both 7 and 17 and showed borderline monosomies (losses) of both chromosomes in FISH studies. CONCLUSIONS: Five years of preoperative observation and lack of recurrence bring further insight into the slow progressive nature of this neoplasm and support a low malignant potential. Proper identification is important to secure adequate treatment and follow-up.

Shorter, rough trunnion surfaces are associated with higher taper wear rates than longer, smooth trunnion surfaces in a contemporary large head metal-on-metal total hip arthroplasty system.

Taper wear at the head-neck junction is a possible cause of early failure in large head metal-on-metal (LH-MoM) hip replacements. We hypothesized that: (i) taper wear may be more pronounced in certain product designs; and (ii) an increased abductor moment arm may be protective. The tapers of 104 explanted LH-MoM hip replacements revised for adverse reaction to metal debris (ARMD) from a single manufacturer were analyzed for linear and volumetric wear using a co-ordinate measuring machine. The mated stem was a shorter 12/14, threaded trunnion (n=72) or a longer, smooth 11/13 trunnion (n=32). The abductor moment arm was calculated from pre-revision radiographs. Independent predictors of linear and volumetric wear included taper angle, stem type, and the horizontal moment arm. Tapers mated with the threaded 12/14 trunnion had significantly higher rates of volumetric wear (0.402 mm3/yr vs. 0.123 mm3/yr [t=-2.145, p=0.035]). There was a trend to larger abductor moment arms being protective (p=0.055). Design variation appears to play an important role in taper-trunnion junction failure. We recommend that surgeons bear these findings in mind when considering the use of a short, threaded trunnion with a cobalt-chromium head.

Short-stretch inelastic compression bandage in knee swelling following total knee arthroplasty study (STICKS): study protocol for a randomised controlled feasibility study.

BACKGROUND: Enhanced recovery programmes in total knee arthroplasty are well established. Post-operative knee swelling is common and impairs early post-operative function. The use of a short-stretch, inelastic compression bandage is hypothesised to reduce knee swelling and improve pain and early function. A study was designed to test feasibility with a view to informing a larger, future trial and to provide preliminary data. METHODS/DESIGN: This is a randomised controlled feasibility study. Fifty consecutive patients selected for primary total knee arthroplasty will be enrolled in the trial. Patients with a BMI >35, latex allergy or neurological or peripheral vascular disease are excluded. Patients are randomised by distance randomisation to receive a compression bandage for 24 hours after surgery or a standard wool and crepe bandage. The bandages are applied by one of two consultant surgeons who have had training with their application. Knee swelling, range of motion and pain scores will be compared pre-operatively and at day 1, day 2 and at 6 weeks between groups. The Oxford knee score and EQ-5D health status will be compared pre-operatively and at 6 months between groups. Recruitment rates, retention rates, resource allocation, completeness of data collection, and tolerance and complications with the compression bandage are recorded. Descriptive statistics are used to calculate a standard deviation for post-operative knee swelling in the groups and to perform a power calculation incorporating anticipated patient retention rates to inform a future trial. Preliminary data will be analysed using the independent samples t-test for equal distributions and the Mann-Whitney U for unequal distributions with the significance denoted at P <0.05. DISCUSSION: Enhanced recovery programmes have revolutionized the management of total knee arthroplasty. There is a paucity of clinical data regarding the efficacy of compression bandages. Large, randomised controlled trials are uncommon in orthopaedic surgery. The results of this study will provide feasibility and preliminary data prior to the construction of a larger, multicentre study. TRIAL REGISTRATION: The study was registered with Current Controlled Trials ( ISRCTN86903140 ) on 30 May 2013.

Three unique presentations of atraumatic spinal cord infarction in the pediatric emergency department.

Nontraumatic spinal cord infarction is especially rare in children. Although diagnosis is easily made with magnetic resonance imaging, the typical presenting signs and symptoms and etiology remain elusive. Evidence-based treatment courses are not available. We assess a series of 3 unique patients with nontraumatic spinal cord infarction who presented to our emergency department over the course of 2 years. We consider their presentation, etiology, and treatment course to provide other emergency department physicians with the ability to better identify and evaluate these patients. We also note the need for further research on nontraumatic spinal cord infarction because these patients' outcomes can be quite devastating.

Low testosterone elevates interleukin family cytokines in a rodent model: a possible mechanism for the potentiation of vascular disease in androgen-deficient males.

BACKGROUND: Androgen deficiency (AD) is associated with increased risk of atherosclerosis, cardiovascular, and peripheral arterial disease. Although the biochemical and molecular mechanisms underlying this risk remain unclear, higher testosterone (TST) levels correlate to significant immunoprotective molecular and cellular responses. Our group has previously demonstrated that female sex hormones influence vascular pathogenesis via inflammatory-modulated matrix metalloproteinase (MMP) regulation. Here we investigated the role of AD and androgen replacement therapy in the modulation of these hormonally responsive pathways that could be playing a role in the development of vascular pathogenesis. METHODS: Aged orchiectomized male rats underwent TST supplementation per controlled release pellet implantation (0-150 mg). Young and aged intact groups served as controls. Serum was collected at 0-4 wk and analyzed by enzyme-linked immunosorbent assays, qualitative cytokine screening, and quantitative multiplex analyses. Human aortic smooth muscle cells were treated with 4,5α-dihydrotestosterone (DHT; 0-3000 nM) before or after interleukin 1ß (IL-1ß; 5 ng/mL) stimulation. Quantitative polymerase chain reaction and in-gel zymography was used to assay the effect on MMP expression and activity. RESULTS: Subphysiological, physiological, and supraphysiological levels of TST were achieved with 0.5, 2.5, and 35 mg TST pellet implants in vivo, respectively. Inflammatory arrays indicated that interleukin cytokines, specifically IL-2, IL-6, IL-10, IL-12, and IL-13, were elevated at subphysiological level of TST, whereas TST supplementation decreased interleukins. Supraphysiological TST resulted in a significant increase in MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in vivo. Pretreatment with IL-1ß slightly increased membrane type 1-MMP (MT1-MMP) and MMP-2 expression at low to mid-level DHT exposure in vitro, although these trends were not statistically significant. CONCLUSIONS: Here we demonstrate AD is a proinflammatory modulator and indicate that MMP-independent mechanisms may play a role downstream of AD-induced inflammatory signaling in dysfunctional vascular remodeling. Future in vivo studies will examine AD and TST supplementation in acute inflammatory response to vascular injury and in MMP-modulated vascular disease.

Taking note of Tinbergen, or: the promise of a biology of behaviour.

In this concluding paper, we revisit Tinbergen's 1963 article and assess its impact on the field of behavioural research in general, and the papers in this volume in particular. We show how Tinbergen's insistence that greater attention should be paid to studies of 'survival value' has yielded immense returns over the past 50 years, allowing an integrative biology of behaviour to emerge and thrive, and that his addition of ontogeny to the 'major problems of biology' was both insightful and prescient.

A Review on the Management of Hip and Knee Osteoarthritis.

Arthritis is the most common chronic condition affecting patients over the age of 70. The prevalence of osteoarthritis increases with age, and with an aging population, the effect of this disease will represent an ever-increasing burden on health care. The knee is the most common joint affected in osteoarthritis, with up to 41% of limb arthritis being located in the knee, compared to 30% in hands and 19% in hips. We review the current concepts with regard to the disease process and risk factors for developing hip and knee osteoarthritis. We then explore the nonsurgical management of osteoarthritis as well as the operative management of hip and knee arthritis. We discuss the indications for surgical treatment of hip and knee arthritis, looking in particular at the controversies affecting young and obese patients in both hip and knee replacements. Patient and implant related outcomes along with survivorships are addressed as well as the experiences and controversies described in national joint registries.

Novel bacterial immobilization compound effectively decreases bacterial counts in healthy volunteers.

Skin flora immobilization technology is similar in efficacy to Iodine-Povidone in healthy volunteers. We did a prospective study in a university clinic with 60 healthy volunteers. Right inguinal skin area on healthy volunteers was used to compare the antimicrobial properties of cyanoacrylate sealant (FloraSeal, Adhesion Biomedical, Wyomissing, PA) versus standard surgical preparation Povidone-iodine (Betadine, Purdue Productions, Stamford, CT). Bacterial counts were measured at different time intervals: 15 minutes, 4 hours, and 24 hours. Bacterial colony forming units were compared between Povidone-iodine and cyanoacrylate sealant. The absolute log reduction was 5.568 for Povidone-iodine (7 absolute CFU); 5.028 for cyanoacrylate (59 absolute CFU); and 5.568 for Povidone-iodine and cyanoacrylate combined (21 absolute CFU). Cyanoacrylate was able to sustain a reduction on bacterial counts at 4 hours and 24 hours of more than 99.8 per cent as compared with the control group. Cyanoacrylate microbial sealant successfully reduces bacterial counts on normal healthy skin. The results were similar to Povidone-iodine alone. We believe this technology may be an excellent means of mitigating incisional surgical site infection by reducing the risk of contamination by skin flora and warrants further testing.

Evidence for a genetic basis of aging in two wild vertebrate populations.

Aging, or senescence, defined as a decline in physiological function with age, has long been a focus of research interest for evolutionary biologists. How has natural selection failed to remove genetic effects responsible for such reduced fitness among older individuals? Current evolutionary theory explains this phenomenon by showing that, as a result of the risk of death from environmental causes that individuals experience, the force of selection inevitably weakens with age. This in turn means that genetic mutations having detrimental effects that are only felt late in life might persist in a population. Although widely accepted, this theory rests on the assumption that there is genetic variation for aging in natural systems, or (equivalently), that genotype-by-age interactions (GxA) occur for fitness. To date, empirical support for this assumption has come almost entirely from laboratory studies on invertebrate systems, most notably Drosophila and C. elegans, whereas tests of genetic variation for aging are largely lacking from natural populations. By using data from two wild mammal populations, we perform quantitative genetic analyses of fitness and provide the first evidence for a genetic basis of senescence to come from a study in the natural environment. We find evidence that genetic differences among individuals cause variation in their rates of aging and that additive genetic variance for fitness increases with age, as predicted by the evolutionary theory of senescence.

Research governance impediments to clinical trials: a retrospective survey.

OBJECTIVE: We sought to evaluate the delays, between-centre variations in practice, and opportunity costs attributable to delays in research governance approval of clinical trials in the United Kingdom. DESIGN: Retrospective survey. SETTING: Research and Development (R&D) departments at 50 UK National Health Service hospital trusts governing 57 hospital sites. PARTICIPANTS: R&D departments participating in four randomized multicentre clinical trials coordinated by our Neurosciences Trials Unit. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Median delay between application and research governance approval. RESULTS: Only half of the R&D departments used the UK online R&D form. Only a single copy of the application was required by 96% of R&D departments. The median delay between application and research governance approval was 44 working days (inter-quartile range 23-80). A delay of >20 working days was incurred by 43 applications (75%), of which 24 (56%) were not explicable and 11 (20%) were attributable to local funding negotiations. Based on the trial randomization rates at each centre, 108 patients (17% of all patients randomized) could have been randomized during the delay, at a crude cost to funding agencies of 53,743 pounds; if a four week delay was deemed acceptable, 75 patients (12% of all patients randomized) could have been randomized during unacceptable delays, at a crude cost to funding agencies of 37,700 pounds. CONCLUSIONS: The UK research governance system incurs unacceptably long and costly delays for clinical trials. Urgent reform is needed, including rapid design and uniform implementation of the 'bureaucracy busting' measures in Best Research for Best Health.

Developmental plasticity and human health.

Many plants and animals are capable of developing in a variety of ways, forming characteristics that are well adapted to the environments in which they are likely to live. In adverse circumstances, for example, small size and slow metabolism can facilitate survival, whereas larger size and more rapid metabolism have advantages for reproductive success when resources are more abundant. Often these characteristics are induced in early life or are even set by cues to which their parents or grandparents were exposed. Individuals developmentally adapted to one environment may, however, be at risk when exposed to another when they are older. The biological evidence may be relevant to the understanding of human development and susceptibility to disease. As the nutritional state of many human mothers has improved around the world, the characteristics of their offspring--such as body size and metabolism--have also changed. Responsiveness to their mothers' condition before birth may generally prepare individuals so that they are best suited to the environment forecast by cues available in early life. Paradoxically, however, rapid improvements in nutrition and other environmental conditions may have damaging effects on the health of those people whose parents and grandparents lived in impoverished conditions. A fuller understanding of patterns of human plasticity in response to early nutrition and other environmental factors will have implications for the administration of public health.