Spatial recovery of the murine gut microbiota after antibiotics perturbation.

Bacterial communities are highly complex, with interaction networks dictating ecosystem function. Bacterial interactions are constrained by the spatial organization of these microbial communities, yet studying the spatial organization of microbial communities at the single-cell level has been technically challenging. Here, we use the recently developed high-phylogenetic-resolution microbiota mapping by fluorescence in situ hybridization technology to image the gut microbiota at the species and single-cell level. We simultaneously image 63 different bacterial species to spatially characterize the perturbation and recovery of the gut microbiota to ampicillin and vancomycin in the cecum and distal colon of mice. To decipher the biology in this complex imaging data, we developed an analytical framework to characterize the spatial changes of the gut microbiota to a perturbation. The three-tiered analytical approach includes image-level diversity, pairwise colocalization analysis, and hypothesis-driven neighborhood analysis. Through this workflow, we identify biogeographic and antibiotic-based differences in the spatial organization of the gut microbiota. We demonstrate that the cecal microbiota has increased micrometer-scale diversity than the colon at baseline and recovers better from perturbation. Also, we identify potential foundation and keystone species that have high baseline neighborhood richness and that are associated with recovery from antibiotics. Through this workflow, we add a spatial layer to the characterization of bacterial communities and progress toward a better understanding of bacterial interactions leading to improved microbiome modulation strategies. IMPORTANCE: Antibiotics have broad off-target effects on the gut microbiome. When the microbial community is unable to recover from antibiotics, it can lead to increased susceptibility to gastrointestinal infections and increased risk of immunological and metabolic diseases. In this study, we work to better understand how the gut microbiota recovers from antibiotics by employing a recent technology to image the entire bacterial community at once. Through this approach, we characterize the spatial changes in the gut microbiota after treatment with model antibiotics in both the cecum and colon of mice. We find antibiotic- and biogeographic-dependent spatial changes between bacterial species and that many of these spatial colocalizations do not recover to baseline levels even 35 days after antibiotic administration.

Dysregulated energy metabolism impairs chondrocyte function in osteoarthritis.

OBJECTIVES: Metabolic pathways are a series of chemical reactions by which cells take in nutrient substrates for energy and building blocks needed to maintain critical cellular processes. Details of chondrocyte metabolism and how it rewires during the progression of osteoarthritis (OA) are unknown. This research aims to identify what changes in the energy metabolic state occur in OA cartilage. METHODS: Patient matched OA and non-OA cartilage specimens were harvested from total knee replacement patients. Cartilage was first collected for metabolomics, proteomics, and transcriptomics analyses to study global alterations in OA metabolism. We then determined the metabolic routes by tracking [U-13C] isotope with liquid chromatography-mass spectrometry (LC-MS). We further evaluated cellular bioenergetic profiles by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) and investigated the effects of low-dose and short-term effects of 2-deoxyglucose (2DG) on chondrocytes. RESULTS: OA chondrocytes showed increased basal ECAR and more lactate production compared to non-OA chondrocytes. [U-13C] glucose labelling revealed that less glucose-derived carbon entered the tricarboxylic acid (TCA) cycle. On the other hand, mitochondrial respiratory rates were markedly decreased in the OA chondrocytes compared to non-OA chondrocytes. These changes were accompanied by decreased cellular ATP production, mitochondrial membrane potential and disrupted mitochondrial morphology. We further demonstrated in vitro that short-term inhibition of glycolysis suppressed matrix degeneration gene expression in chondrocytes and bovine cartilage explants cultured under inflammatory conditions. CONCLUSION: This study represents the first comprehensive comparative analysis of metabolism in OA chondrocytes and lays the groundwork for therapeutic targeting of metabolism in OA.

Hemispheric asymmetry in ocean change and the productivity of ecosystem sentinels.

Climate change and other human activities are causing profound effects on marine ecosystem productivity. We show that the breeding success of seabirds is tracking hemispheric differences in ocean warming and human impacts, with the strongest effects on fish-eating, surface-foraging species in the north. Hemispheric asymmetry suggests the need for ocean management at hemispheric scales. For the north, tactical, climate-based recovery plans for forage fish resources are needed to recover seabird breeding productivity. In the south, lower-magnitude change in seabird productivity presents opportunities for strategic management approaches such as large marine protected areas to sustain food webs and maintain predator productivity. Global monitoring of seabird productivity enables the detection of ecosystem change in remote regions and contributes to our understanding of marine climate impacts on ecosystems.

Characterisation of ovine bone marrow-derived stromal cells (oBMSC) and evaluation of chondrogenically induced micro-pellets for cartilage tissue repair in vivo.

Bone marrow stromal cells (BMSC) show promise in cartilage repair, and sheep are the most common large animal pre-clinical model. OBJECTIVE: The objective of this study was to characterise ovine BMSC (oBMSC) in vitro, and to evaluate the capacity of chondrogenic micro-pellets manufactured from oBMSC or ovine articular chondrocytes (oACh) to repair osteochondral defects in sheep. DESIGN: oBMSC were characterised for surface marker expression using flow cytometry and evaluated for tri-lineage differentiation capacity. oBMSC micro-pellets were manufactured in a microwell platform, and chondrogenesis was compared at 2%, 5%, and 20% O2. The capacity of cartilage micro-pellets manufactured from oBMSC or oACh to repair osteochondral defects in adult sheep was evaluated in an 8-week pilot study. RESULTS: Expanded oBMSC were positive for CD44 and CD146 and negative for CD45. The common adipogenic induction ingredient, 3-Isobutyl-1-methylxanthine (IBMX), was toxic to oBMSC, but adipogenesis could be restored by excluding IBMX from the medium. BMSC chondrogenesis was optimal in a 2% O2 atmosphere. Micro-pellets formed from oBMSC or oACh appeared morphologically similar, but hypertrophic genes were elevated in oBMSC micro-pellets. While oACh micro-pellets formed cartilage-like repair tissue in sheep, oBMSC micro-pellets did not. CONCLUSION: The sensitivity of oBMSC, compared to human BMSC, to IBMX in standard adipogenic assays highlights species-associated differences. Micro-pellets manufactured from oACh were more effective than micro-pellets manufactured from oBMSC in the repair of osteochondral defects in sheep. While oBMSC can be driven to form cartilage-like tissue in vitro, the effective use of these cells in cartilage repair will depend on the successful mitigation of hypertrophy and tissue integration.

Attitudes towards risk-reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study.

OBJECTIVE: To determine risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk. DESIGN: Multicentre, cohort, questionnaire study (IRSCTN:12310993). SETTING: United Kingdom (UK). POPULATION: UK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups. METHODS: Participants completed a 39-item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes. MAIN OUTCOMES: RRESDO acceptability, menopausal sequelae, satisfaction/regret. RESULTS: In all, 346 of 683 participants underwent risk-reducing salpingo-oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2-7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2-27.5, P < 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2-0.9, P = 0.025). CONCLUSION: Data show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness. TWEETABLE ABSTRACT: RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction.

Object surveillance with radio-frequency atomic magnetometers.

The capabilities of a radio-frequency atomic magnetometer for object detection based on magnetic induction tomography are explored. The determination of object orientation is demonstrated by utilizing the measurement geometry. The self-compensation configuration of the atomic magnetometer is implemented to address the issue of saturation of the sensor response by the radio-frequency primary field that generates the object signature. Three methods of "covert" detection are investigated as a testbed for exploring the functionalities of this sensor, where (1) the operational frequency of the sensor is continuously changed, (2) the primary field has non-monochromatic frequency distribution, and (3) the sensor operates in the so-called spin maser mode. The results of the measurements are also discussed in terms of possible magnetic field communication.

Quinolone-induced Biceps Tendon Rupture.

Presentation A 76-year-old man presented with acute left upper limb pain and subsequent large ecchymosis. Diagnosis An ultrasound study was performed which showed partial left biceps tendon rupture. Treatment He was managed conservatively with Orthopaedic input. The patient was given analgesia and reassured. Discussion Tendon rupture is an unusual but serious complication of quinolone exposure. This case highlights that this should be included in the differential for acute limb pain in patients who have been prescribed these drugs.

Emergency preparedness: Ionising radiation incidents and medical management.

Military personnel risk being exposed to ionising radiation through a variety of means, including industrial accidents with Ministry of Defence equipment, inadvertent exposure while on operations, terrorist activities and nuclear war. The aim of this review is to outline the possible acute health effects and immediate management of radiation casualties in the context of different exposure scenarios. It emphasises the most important principles for managing irradiated, and/or contaminated casualties, in the operational environment, as well as providing details of key references and other sources of reach-back support.

Deep Learning-Based Femoral Cartilage Automatic Segmentation in Ultrasound Imaging for Guidance in Robotic Knee Arthroscopy.

Knee arthroscopy is a minimally invasive surgery used in the treatment of intra-articular knee pathology which may cause unintended damage to femoral cartilage. An ultrasound (US)-guided autonomous robotic platform for knee arthroscopy can be envisioned to minimise these risks and possibly to improve surgical outcomes. The first necessary tool for reliable guidance during robotic surgeries was an automatic segmentation algorithm to outline the regions at risk. In this work, we studied the feasibility of using a state-of-the-art deep neural network (UNet) to automatically segment femoral cartilage imaged with dynamic volumetric US (at the refresh rate of 1 Hz), under simulated surgical conditions. Six volunteers were scanned which resulted in the extraction of 18278 2-D US images from 35 dynamic 3-D US scans, and these were manually labelled. The UNet was evaluated using a five-fold cross-validation with an average of 15531 training and 3124 testing labelled images per fold. An intra-observer study was performed to assess intra-observer variability due to inherent US physical properties. To account for this variability, a novel metric concept named Dice coefficient with boundary uncertainty (DSCUB) was proposed and used to test the algorithm. The algorithm performed comparably to an experienced orthopaedic surgeon, with DSCUB of 0.87. The proposed UNet has the potential to localise femoral cartilage in robotic knee arthroscopy with clinical accuracy.

Adaptive smartphone-based sensor fusion for estimating competitive rowing kinematic metrics.

Competitive rowing highly values boat position and velocity data for real-time feedback during training, racing and post-training analysis. The ubiquity of smartphones with embedded position (GPS) and motion (accelerometer) sensors motivates their possible use in these tasks. In this paper, we investigate the use of two real-time digital filters to achieve highly accurate yet reasonably priced measurements of boat speed and distance traveled. Both filters combine acceleration and location data to estimate boat distance and speed; the first using a complementary frequency response-based filter technique, the second with a Kalman filter formalism that includes adaptive, real-time estimates of effective accelerometer bias. The estimates of distance and speed from both filters were validated and compared with accurate reference data from a differential GPS system with better than 1 cm precision and a 5 Hz update rate, in experiments using two subjects (an experienced club-level rower and an elite rower) in two different boats on a 300 m course. Compared with single channel (smartphone GPS only) measures of distance and speed, the complementary filter improved the accuracy and precision of boat speed, boat distance traveled, and distance per stroke by 44%, 42%, and 73%, respectively, while the Kalman filter improved the accuracy and precision of boat speed, boat distance traveled, and distance per stroke by 48%, 22%, and 82%, respectively. Both filters demonstrate promise as general purpose methods to substantially improve estimates of important rowing performance metrics.

Feasibility of Transthoracic Echocardiography Evaluation of Pulmonary Arteries Following Arterial Switch Operation.

Pulmonary artery (PA) stenosis is the most common late sequela following arterial switch for d-transposition of the great arteries. The purpose of this study was to assess the effectiveness of transthoracic echocardiography in evaluating the pulmonary arteries following repair. This was a retrospective, cross-sectional analysis of all echocardiograms performed on patients following arterial switch operation. A numerical scoring system was devised and used to quantify PA visualization based on 2D images, color mapping, and spectral Doppler. The study cohort included 150 patients. The ability to visualize at least one PA was poorer in patients who were older [> 10 years (47%) vs ≤ 10 years (89%) (p < 0.001)], and who had larger body surface area (BSA) (> 1.25 m2 (40%) vs ≤ 1.25 m2 (90%) (p < 0.001)]. Regardless of age, 2D visualization of the pulmonary arteries was poor for the entire cohort. Of those with at least one non-visualized PA, only 54% had alternative imaging performed or ordered within the 5 years at or prior to their last echocardiogram. In conclusion, PA visualization following arterial switch is worse in patients who are older and in those with larger BSA. In such patients, alternative forms of imaging are more likely to be necessary.

Temporal change to self-rated health in the Swiss population from 1997 to 2012: the roles of age, gender, and education.

OBJECTIVES: Our study aimed to describe the temporal changes in self-rated health status (SRH) from 1997 to 2012 in adults aged 25 to 84 residing in Switzerland, with a view to identifying groups at risk for declining health. STUDY DESIGN: Secondary analysis of population-based cross-sectional health surveys. METHODS: Data were collected from the cross-sectional, population-based, five-year Swiss Health Survey, from 1997, 2002, 2007 and 2012. A total of 63,861 individuals' data were included. Multilevel mixed-effect logistic regression analysis was employed to estimate the probability of very good and good health within the framework of a hierarchical cross-classified age-period-cohort model (HAPC), adjusting for education level, gender, civil status, smoking status and body mass index. RESULTS: Individuals with higher education were substantially more likely than those with primary education to report good SRH (OR = 2.12; 95% CI = 1.93-2.33 for secondary education and OR = 3.79; 95% CI = 3.39-4.23 for tertiary education). The education effect depended on birth cohort and age: higher proportions of good SRH were reported by secondary (8%-17%) and tertiary (10%-22%) compared with primary educated individuals from the 1940 birth cohort onward; the proportion of secondary/tertiary (compared to primary) educated people reporting good SRH increased with age (by 10/11% at 45-50 years and 25/36% at 80-84 years). Gender health equality was achieved by the 1955 (primary educated) and 1960 (secondary educated) birth cohorts, while these women overtook men in reporting good SRH from the 1975 birth cohort onward. Tertiary educated younger women were significantly less likely to report good SRH than men but parity was achieved at around pension age. Similarly, gender inequality in those with primary and secondary education reduced in the younger ages to not be significant at around age 55, with women overtaking men from age 65. CONCLUSIONS: Younger birth cohorts with lower education levels appear most vulnerable in terms of their SRH. The education effect cumulatively increases when attaining incrementally higher education levels. While women report lower health than men, gender inequality in SRH has declined and even reversed over time and is substantially linked to differences in educational status. Swiss public health strategies should particularly target the younger adults with only primary school education of both genders; for women, to combat health burdens in their early life, and men, to mitigate issues in their later life.

Magnetically controlled growing rods in the treatment of early-onset scoliosis: a note of caution.

The MAGnetic Expansion Control (MAGEC) system is used increasingly in the management of early-onset scoliosis. Good results have been published, but there have been recent reports identifying implant failures that may be associated with significant metallosis surrounding the implants. This article aims to present the current knowledge regarding the performance of this implant, and the potential implications and strategies that may be employed to identify and limit any problems. We urge surgeons to apply caution to patient and construct selection; engage in prospective patient registration using a spine registry; ensure close clinical monitoring until growth has ceased; and send all explanted MAGEC rods for independent analysis. The MAGEC system may be a good instrumentation system for the treatment of early-onset scoliosis. However, it is innovative and like all new technology, especially when deployed in a paediatric population, robust systems to assess long-term outcome are required to ensure that patient safety is maintained. Cite this article: Bone Joint J 2017;99-B:708-13.

Preparing and sharing food: a quantitative analysis of a primary school-based food intervention.

Background: Primary schools are increasingly used as arenas for public health initiatives. The aim of this study was to assess a primary school-based food intervention. Methods: The intervention comprised timetabled kitchen classroom sessions (90 min, fortnightly). Pupils prepared and cooked food, which they then ate together. Children's relationship with food, including food enjoyment, experience and food neophobia, were addressed at the intervention school (baseline n = 154; follow-up n = 164) and at a matched control school (baseline n = 171; follow-up n = 174). Results: Pupils at the intervention school scored significantly higher (M = 3.90, SD = 1.81) for scores on Kitchen Equipment, compared to the control school (M = 3.06, SD = 2.12); and again scored significantly higher (M = 9.34, SD = 3.79) for the overall Cooking Experience Score compared to the control school (M = 7.98, SD = 4.57). Shifts accompanying the intervention in three outcome measures for pupils (taste description, liking for cooking and helping with cooking at home) were also revealed. No main intervention effect for food neophobia and fussiness was found; a close to significant time by intervention interaction (P = 0.053) was evident. Conclusions: The study indicates limited but encouraging changes, and contributes to the growing literature regarding school-based food initiatives.

'Between Combat boots and Birkenstocks'-Lessons from HIV/AIDS, SARS, H1N1 and Ebola.

OBJECTIVES: In late 2013, an Ebola outbreak quickly grew into an epidemic of extraordinary magnitude, killing more people than all previous Ebola outbreaks combined. Although the epidemic was unprecedented, the world had previously experienced several acute public health emergencies requiring global coordination. HIV/AIDS, SARS and H1N1 tested global response, and in each case coordination proved problematic, making the 2013-2015 Ebola epidemic no exception. The purpose of this project was to identify persistent vulnerabilities within global public health emergency response and to identify areas for future research and improvement. STUDY DESIGN: Non-systematic review and qualitative interview study. METHODS: Using PubMed and Google, a comprehensive search of articles connected to the HIV/AIDS, SARS, H1N1 and Ebola responses was conducted. Then, 21 key responders involved in those emergencies, primarily from the US Centers for Disease Control and Prevention, participated in in-depth interviews. The content analysis and in-depth interview data were analysed using MAXQDA analysis software. RESULTS: A number of issues emerged, including cultural and political clashes within relevant agencies and a lack of confidence in those agencies, policy barriers that hinder long-term international response, a shortage of personnel and resources, itemized funding streams that limit flexibility to direct resources, and challenges to deploying responders internationally. CONCLUSIONS: The data suggest that the world remains ill prepared to handle sustained responses and global pandemics. The study identified major vulnerabilities persistent within US-led global public health response and offers recommendations for further focused research to fully understand why these challenges persist.

A valuable technique for femoral stem revision in total hip replacement: The in-cement revision - A case series and technical note.

Revision of a cemented femoral stem can be a challenging procedure. We present a series of cases utilising the "In-cement" revision, whereby the same size stem is introduced into the original cement mantle, without additional cementing. It requires a stable cement mantle in the correct version. We describe the technique and present a review of 23 revision total hip replacements performed over a 5 year period. At average follow-up of 67 months (12-128 months), the overall survivorship was 91.3% with no patient requiring re-revision for stem loosening or mechanical failure. Two patients required re-revision for infection and one of those patients is now deceased. No further operations were required in 21 patients. The "In-cement" revision can be a valuable technique for the revision arthroplasty surgeon. Early results suggest this is a safe and effective technique in the appropriate patient.

Chondromodulin-1 ameliorates osteoarthritis progression by inhibiting HIF-2α activity.

OBJECTIVES: Hypoxia is known to stabilize hypoxia-inducible factor (HIF) and initiate angiogenic signaling cascade. However, cartilage living in hypoxia environment can maintain avascularity. It is well known that abrogation of avascularity is related to cartilage degradation in osteoarthritis (OA). The aims of present study were to investigate the role of chondromodulin-1 (ChM-1), an endogenously anti-angiogenic protein in cartilage, during chondrocyte maturation and OA progression, as well as to explore the molecular mechanisms underlying the function of ChM-1 with a focus on HIF-2α pathway. METHODS: Angiogenic-related markers were evaluated in OA cartilage and different stages of chondrocyte differentiation. Chondrocytes transfected with ChM-1 lentivirus or siRNA was treated with tumor necrosis factor (TNF-α) to investigate the role of ChM-1 in chondrocyte hypertrophic changes. In vivo study was conducted by using a surgical induced OA rat model with intra-articular injection of lentivirus ChM-1 (LV-ChM-1) or mock lentivirus (LV-GFP) control. Transcriptional activity of HIF-2α was determined by chromatin immunoprecipitation (ChIP) assay to unveil the mechanisms of ChM-1. RESULTS: Majority angiogenic factors increased in severe OA cartilage, while anti-angiogenic factors including ChM-1 decreased. ChM-1 expression was strongly related with chondrocyte differentiation and chondrogenesis in vitro. ChM-1 overexpression protected chondrocytes from TNF-α induced hypertrophy, and intra-articular injection of LV-ChM-1 delayed OA progression. ChM-1 delayed HIF-2α nuclear translocation at early time-points and decreased transcriptional activity of HIF-2α on collagen type Ð¥ α1 (COL10A1), vascular endothelial growth factor A (VEGFA) and matrix metallopeptidase-13 (MMP-13). CONCLUSIONS: ChM-1 maintains cartilage homeostasis by inhibiting HIF-2α induced catabolic activity and regulation of ChM-1 in cartilage may be a promising therapeutic strategy for OA.

Age- and Level-Dependence of Fatty Infiltration in Lumbar Paravertebral Muscles of Healthy Volunteers.

BACKGROUND AND PURPOSE: Normative age-related decline in paravertebral muscle quality is important for reference to disease and risk identification in patients. We aimed to establish age- and vertebral level-dependence of paravertebral (multifidus and erector spinae) muscle volume and fat content in healthy adult volunteers. MATERIALS AND METHODS: In this prospective study multifidus and erector spinae fat signal fraction and volume at lumbar levels L1-L5 were measured in 80 healthy volunteers (10 women and men per decade, 20-62 years of age) by 2-point Dixon 3T MR imaging. ANOVA with post hoc Bonferroni correction compared fat signal fraction and volume among subgroups. Pearson and Spearman analysis were used for correlations (P < .05). RESULTS: Fat signal fraction was higher in women (17.8% ± 10.7%) than men (14.7% ± 7.8%; P < .001) and increased with age. Multifidus and erector spinae volume was lower in women (565.4 ± 83.8 cm(3)) than in men (811.6 ± 98.9 cm(3); P < .001) and was age-independent. No differences in fat signal fraction were shown between the right and left paravertebral muscles or among the L1, L2, and L3 lumbar levels. The fat signal fraction was highest at L5 (women, 31.9% ± 9.3%; men, 25.7% ± 8.0%; P < .001). The fat signal fraction at L4 correlated best with total lumbar fat signal fraction (women, r = 0.95; men, r = 0.92, P < .001). Total fat signal fraction was higher in the multifidus compared with erector spinae muscles at L1-L4 for both sexes (P < .001). CONCLUSIONS: Lumbar paravertebral muscle fat content increases with aging, independent of volume, in healthy volunteers 20-62 years of age. Women, low lumbar levels, and the multifidus muscle are most affected. Further study examining younger and older subjects and the functional impact of fatty infiltrated paravertebral muscles are warranted.