Modulation of Gut Microbiota Metabolism in Obesity-Related Type 2 Diabetes Reduces Osteomyelitis Severity.

Staphylococcus aureus is an opportunistic pathogen causing osteomyelitis through hematogenous seeding or contamination of implants and open wounds following orthopedic surgeries. The severity of S. aureus-mediated osteomyelitis is enhanced in obesity-related type 2 diabetes (obesity/T2D) due to chronic inflammation impairing both adaptive and innate immunity. Obesity-induced inflammation is linked to gut dysbiosis, with modification of the gut microbiota by high-fiber diets leading to a reduction in the symptoms and complications of obesity/T2D. However, our understanding of the mechanisms by which modifications of the gut microbiota alter host infection responses is limited. To address this gap, we monitored tibial S. aureus infections in obese/T2D mice treated with the inulin-like fructan fiber oligofructose. Treatment with oligofructose significantly decreased S. aureus colonization and lowered proinflammatory signaling postinfection in obese/T2D mice, as observed by decreased circulating inflammatory cytokines (tumor necrosis factor-α [TNF-α]) and chemokines (interferon-γ-induced protein 10 kDa [IP-10], keratinocyte-derived chemokine [KC], monokine induced by interferon-γ [MIG], monocyte chemoattractant protein-1 [MCP-1], and regulated upon activation, normal T cell expressed and presumably secreted [RANTES]), indicating partial reduction in inflammation. Oligofructose markedly shifted diversity in the gut microbiota of obese/T2D mice, with notable increases in the anti-inflammatory bacterium Bifidobacterium pseudolongum. Analysis of the cecum and plasma metabolome suggested that polyamine production was increased, specifically spermine and spermidine. Oral administration of these polyamines to obese/T2D mice resulted in reduced infection severity similar to oligofructose supplementation, suggesting that polyamines can mediate the beneficial effects of fiber on osteomyelitis severity. These results demonstrate the contribution of gut microbiota metabolites to the control of bacterial infections distal to the gut and polyamines as an adjunct therapeutic for osteomyelitis in obesity/T2D. IMPORTANCE Individuals with obesity-related type 2 diabetes (obesity/T2D) are at a five times increased risk for invasive Staphylococcus aureus osteomyelitis (bone infection) following orthopedic surgeries. With increasing antibiotic resistance and limited discoveries of novel antibiotics, it is imperative that we explore other avenues for therapeutics. In this study, we demonstrated that the dietary fiber oligofructose markedly reduced osteomyelitis severity and hyperinflammation following acute prosthetic joint infections in obese/T2D mice. Reduced infection severity was associated with changes in gut microbiota composition and metabolism, as indicated by increased production of natural polyamines in the gut and circulating plasma. This work identifies a novel role for the gut microbiome in mediating control of bacterial infections and polyamines as beneficial metabolites involved in improving the obesity/T2D host response to osteomyelitis. Understanding the impact of polyamines on host immunity and mechanisms behind decreasing susceptibility to severe implant-associated osteomyelitis is crucial to improving treatment strategies for this patient population.

Exploring barriers and facilitators of physical distancing in the context of the COVID-19 pandemic: a qualitative interview study.

Background: Physical distancing measures (e.g., keeping a distance of two metres from others, avoiding crowded areas, and reducing the number of close physical contacts) continue to be among the most important preventative measures used to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID -19). Therefore, it is important to understand barriers and facilitators of physical distancing to help inform future public health campaigns. Methods: The current study aimed to qualitatively explore barriers and facilitators of physical distancing in the context of the COVID-19 pandemic using a qualitative interpretative design. Semi-structured one-to-one phone interviews were conducted with 25 participants aged 18+ years and living in the Republic of Ireland between September and October 2020. A purposive sampling strategy was used to maximise diversity in terms of age, gender, and socioeconomic status. Interviews were transcribed verbatim and analysed using inductive thematic analysis. Results: Analysis resulted in the development of six main themes related to barriers and facilitators of physical distancing: (1) Maintaining and negotiating close relationships; (2) Public environments support or discourage physical distancing; (3) Habituation to threat; (4) Taking risks to maintain well-being; (5) Personal responsibility to control the "controllables"; and (6) Confusion and uncertainty around government guidelines. Conclusions: Our study found that physical distancing measures are judged to be more or less difficult based on a number of internal and external psychosocial factors, including maintaining and negotiating close relationships, habituation to threat, risk compensation, structure of public environments, personal responsibility, and confusion or uncertainty around government guidelines. Given the diversity in our sample, it is clear that the identified barriers and facilitators vary depending on context and life stage. Messaging that targets sub-groups of the population may benefit from considering the identified themes in this analysis.

Outsized nutrient contributions from small tributaries to a Great Lake.

Excessive nitrogen (N) and phosphorus (P) loading is one of the greatest threats to aquatic ecosystems in the Anthropocene, causing eutrophication of rivers, lakes, and marine coastlines worldwide. For lakes across the United States, eutrophication is driven largely by nonpoint nutrient sources from tributaries that drain surrounding watersheds. Decades of monitoring and regulatory efforts have paid little attention to small tributaries of large water bodies, despite their ubiquity and potential local importance. We used a snapshot of nutrient inputs from nearly all tributaries of Lake Michigan-the world's fifth largest freshwater lake by volume-to determine how land cover and dams alter nutrient inputs across watershed sizes. Loads, concentrations, stoichiometry (N:P), and bioavailability (percentage dissolved inorganic nutrients) varied by orders of magnitude among tributaries, creating a mosaic of coastal nutrient inputs. The 6 largest of 235 tributaries accounted for ∼70% of the daily N and P delivered to Lake Michigan. However, small tributaries exhibited nutrient loads that were high for their size and biased toward dissolved inorganic forms. Higher bioavailability of nutrients from small watersheds suggests greater potential to fuel algal blooms in coastal areas, especially given the likelihood that their plumes become trapped and then overlap in the nearshore zone. Our findings reveal an underappreciated role that small streams may play in driving coastal eutrophication in large water bodies. Although they represent only a modest proportion of lake-wide loads, expanding nutrient management efforts to address smaller watersheds could reduce the ecological impacts of nutrient loading on valuable nearshore ecosystems.

Identifying and addressing psychosocial determinants of adherence to physical distancing guidance during the COVID-19 pandemic - project protocol.

Optimising public health physical distancing measures has been a critical part of the global response to the spread of COVID-19. Evidence collected during the current pandemic shows that the transmission rate of the virus is significantly reduced following implementation of intensive physical distancing measures. Adherence to these recommendations has been poorer than adherence to other key transmission reduction behaviours such as handwashing. There are a complex range of reasons that are likely to predict why people do not or only partially adhere to physical distancing recommendations. In the current project we aim to address the following research questions: (1) What are the psychosocial determinants of physical distancing for the general public and for key socio-demographic sub-groups (e.g., young adults, older adults, etc.)?; (2) Do current Government of Ireland COVID-19 physical distancing communications address the determinants of physical distancing?; and (3) How can communications be optimised and tailored to sub-groups to ensure maximum adherence to guidelines? These will be addressed by conducting three work packages (WPs). In WP1, we will work closely with the iCARE international study, which includes a large online survey of public responses to measures established to reduce and slow the spread of COVID-19, including physical distancing. We will analyse Irish data, comparing it to data from other countries, to identify the key psychosocial determinants of physical distancing behaviour. This will be followed by a qualitative study to explore in depth the barriers and facilitators of physical distancing behaviour among the Irish public (WP2). In WP3, we will conduct a content analysis and evidence mapping of current government messaging around physical distancing, to ensure the findings from this research feed into the development of ongoing communication and future messaging about physical distancing.

The Response of nor and nos Contributes to Staphylococcus aureus Virulence and Metabolism.

Staphylococcus aureus causes a wide spectrum of disease, with the site and severity of infection dependent on virulence traits encoded within genetically distinct clonal complexes (CCs) and bacterial responses to host innate immunity. The production of nitric oxide (NO) by activated phagocytes is a major host response to which S. aureus metabolically adapts through multiple strategies that are conserved in all CCs, including an S. aureus nitric oxide synthase (Nos). Previous genome analysis of CC30, a lineage associated with chronic endocardial and osteoarticular infections, revealed a putative NO reductase (Nor) not found in other CCs that potentially contributes to NO resistance and clinical outcome. Here, we demonstrate that Nor has true nitric oxide reductase activity, with nor expression enhanced by NO stress and anaerobic growth. Furthermore, we demonstrate that nor is regulated by MgrA and SrrAB, which modulate S. aureus virulence and hypoxic response. Transcriptome analysis of the S. aureus UAMS-1, UAMS-1 Δnor, and UAMS-1 Δnos strains under NO stress and anaerobic growth demonstrates that Nor contributes to nucleotide metabolism and Nos to glycolysis. We demonstrate that Nor and Nos contribute to enhanced survival in the presence of human human polymorphonuclear cells and have organ-specific seeding in a tail vein infection model. Nor contributes to abscess formation in an osteological implant model. We also demonstrate that Nor has a role in S. aureus metabolism and virulence. The regulation overlap between Nor and Nos points to an intriguing link between regulation of intracellular NO, metabolic adaptation, and persistence in the CC30 lineage.IMPORTANCEStaphylococcus aureus can cause disease at most body sites, and illness spans asymptomatic infection to death. The variety of clinical presentations is due to the diversity of strains, which are grouped into distinct clonal complexes (CCs) based on genetic differences. The ability of S. aureus CC30 to cause chronic infections relies on its ability to evade the oxidative/nitrosative defenses of the immune system and survive under different environmental conditions, including differences in oxygen and nitric oxide concentrations. The significance of this work is the exploration of unique genes involved in resisting NO stress and anoxia. A better understanding of the functions that control the response of S. aureus CC30 to NO and oxygen will guide the treatment of severe disease presentations.

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device-related infection.

Orthopedic device-related infection (ODRI), including both fracture-related infection (FRI) and periprosthetic joint infection (PJI), remain among the most challenging complications in orthopedic and musculoskeletal trauma surgery. ODRI has been convincingly shown to delay healing, worsen functional outcome and incur significant socio-economic costs. To address this clinical problem, ever more sophisticated technologies targeting the prevention and/or treatment of ODRI are being developed and tested in vitro and in vivo. Among the most commonly described innovations are antimicrobial-coated orthopedic devices, antimicrobial-loaded bone cements and void fillers, and dual osteo-inductive/antimicrobial biomaterials. Unfortunately, translation of these technologies to the clinic has been limited, at least partially due to the challenging and still evolving regulatory environment for antimicrobial drug-device combination products, and a lack of clarity in the burden of proof required in preclinical studies. Preclinical in vivo testing (i.e. animal studies) represents a critical phase of the multidisciplinary effort to design, produce and reliably test both safety and efficacy of any new antimicrobial device. Nonetheless, current in vivo testing protocols, procedures, models, and assessments are highly disparate, irregularly conducted and reported, and without standardization and validation. The purpose of the present opinion piece is to discuss best practices in preclinical in vivo testing of antimicrobial interventions targeting ODRI. By sharing these experience-driven views, we aim to aid others in conducting such studies both for fundamental biomedical research, but also for regulatory and clinical evaluation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:271-287, 2019.

How do adults define the treats they give to children? A thematic analysis.

One in four children on the Island of Ireland are overweight or obese. The consumption of energy-dense, nutrient-poor foods such as snacks, contribute to one fifth of children's calorie intake. However the snack food literature has failed to draw firm conclusions between snack food intake and obesity. Within this literature, the word snack and treat are used interchangeably, inconsistently and in differing contexts, which may explain the poor link between snacks or extra foods, and overweight or obesity. There is currently no academic definition of the word 'treat' relevant to an Irish population. Defining how adults perceive the treats they give children is of particular importance in the context of children's diets, and may provide insight into the relative contribution of treats to energy intakes. With ten focus groups of adult caregivers of children, across the Island of Ireland, this study aimed to investigate treat giving behaviour. This research highlights a paradoxical definition of treats: a treat was identified as an energy-dense food that gave pleasure, was deserved and believed to be infrequent; participants perceived this to be the true definition of treats which was coined "real treats". However, in reality, treats were given and consumed frequently, downgrading the status of these treats to "regular treats" which reflected their real-life use. Developing the definition of treats for an adult population, may enhance our understanding of why adults give food treats to children, the role this has on the development of eating habits, the design of interventions and communication strategies to reduce the consumption of non-nutritive foods, labelled by adults as treats.

Is it still a real treat? Adults' treat provision to children.

Consumption of high-energy foods in the absence of hunger has been identified as a key target to address in the area of obesity. For children, such foods are often provided by adults as treats. There is limited understating of adults' treat giving. The present study aimed to understand adults' provision of treats to children on the Island of Ireland. A total of 1039 participants, including parents, grandparents, child minders and education practitioners completed a face-to-face survey in their home. Participants defined their treats for children primarily as 'something nice', 'deserved/earned' and 'something special'. The top three motivations for treat foods provision were 'to reward for good behaviour' (42.3%), 'because the child(ren) ask' (42.2%) and 'to make the child(ren) feel better' (29.4%). Almost all participants would provide treat foods at celebrations and 52.5% always did so. In addition, 68% participants had structured weekly and/or daily treat for children. Treats provided to children were dominated by energy-dense foods. The top three were sweets, chocolates and ice-creams, being used by 45.2%, 45.1% and 38.8% participants. Variations were observed across different adult groups, in terms of their treat giving behaviour. The main observation was that adults' treat foods provision has become habitual. The findings can help develop targeted strategies to encourage the reduction or replacement of food treats for children.

Exacerbated Staphylococcus aureus Foot Infections in Obese/Diabetic Mice Are Associated with Impaired Germinal Center Reactions, Ig Class Switching, and Humoral Immunity.

Obese patients with type 2 diabetes (T2D) are at an increased risk of foot infection, with impaired immune function believed to be a critical factor in the infectious process. In this study, we test the hypothesis that humoral immune defects contribute to exacerbated foot infection in a murine model of obesity/T2D. C57BL/6J mice were rendered obese and T2D by a high-fat diet for 3 mo and were compared with controls receiving a low-fat diet. Following injection of Staphylococcus aureus into the footpad, obese/T2D mice had greater foot swelling and reduced S. aureus clearance than controls. Obese/T2D mice also had impaired humoral immune responses as indicated by lower total IgG levels and lower anti-S. aureus Ab production. Within the draining popliteal lymph nodes of obese/T2D mice, germinal center formation was reduced, and the percentage of germinal center T and B cells was decreased by 40-50%. Activation of both T and B lymphocytes was similarly suppressed in obese/T2D mice. Impaired humoral immunity in obesity/T2D was independent of active S. aureus infection, as a similarly impaired humoral immune response was demonstrated when mice were administered an S. aureus digest. Isolated splenic B cells from obese/T2D mice activated normally but had markedly suppressed expression of Aicda, with diminished IgG and IgE responses. These results demonstrate impaired humoral immune responses in obesity/T2D, including B cell-specific defects in Ab production and class-switch recombination. Together, the defects in humoral immunity may contribute to the increased risk of foot infection in obese/T2D patients.

Targeting the gut microbiome to treat the osteoarthritis of obesity.

Obesity is a risk factor for osteoarthritis (OA), the greatest cause of disability in the US. The impact of obesity on OA is driven by systemic inflammation, and increased systemic inflammation is now understood to be caused by gut microbiome dysbiosis. Oligofructose, a nondigestible prebiotic fiber, can restore a lean gut microbial community profile in the context of obesity, suggesting a potentially novel approach to treat the OA of obesity. Here, we report that - compared with the lean murine gut - obesity is associated with loss of beneficial Bifidobacteria, while key proinflammatory species gain in abundance. A downstream systemic inflammatory signature culminates with macrophage migration to the synovium and accelerated knee OA. Oligofructose supplementation restores the lean gut microbiome in obese mice, in part, by supporting key commensal microflora, particularly Bifidobacterium pseudolongum. This is associated with reduced inflammation in the colon, circulation, and knee and protection from OA. This observation of a gut microbiome-OA connection sets the stage for discovery of potentially new OA therapeutics involving strategic manipulation of specific microbial species inhabiting the intestinal space.

Obesity/type 2 diabetes increases inflammation, periosteal reactive bone formation, and osteolysis during Staphylococcus aureus implant-associated bone infection.

Obese and type 2 diabetic (T2D) patients have a fivefold increased rate of infection following placement of an indwelling orthopaedic device. Though implant infections are associated with inflammation, periosteal reactive bone formation, and osteolysis, the effect of obesity/T2D on these complicating factors has not been studied. To address this question, C57BL/6J mice were fed a high fat diet (60% Kcal from fat) to induce obesity/T2D, or a control diet (10% Kcal from fat) for 3 months, and challenged with a transtibial pin coated with a bioluminescent USA300 strain of S. aureus. In the resulting infected bone, obesity/T2D was associated with increased S. aureus proliferation and colony forming units. RNA sequencing of the infected tibiae on days 7 and 14 revealed an increase in 635 genes in obese/T2D mice relative to controls. Pathways associated with ossification, angiogenesis, and immunity were enriched. MicroCT and histology on days 21 and 35 demonstrated significant increased periosteal reactive bone formation in infected obese/T2D mice versus infected controls (p < 0.05). The enhanced periosteal bone formation was associated with increased osteoblastic activity and robust endochondral ossification, with persistant cartilage on day 21 that was only observed in infected obesity/T2D. Osteolysis and osteoclast numbers in obesity/T2D were also significantly increased versus infected controls (p < 0.05). Consistent with an up-regulated immune transcriptome, macrophages were more abundant within both the periosteum and the new reactive bone of obese/T2D mice. In conclusion, we find that implant-associated S. aureus osteomyelitis in obesity/T2D is associated with increased inflammation, reactive bone formation, and osteolysis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1614-1623, 2018.

Methionine Metabolites in Patients With Sepsis.

OBJECTIVE: Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. METHODS: This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. RESULTS: Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P < .001; SAH: 99 [60-165] vs 35 [28-45] nM, P < .001). In contrast, plasma tHcy concentrations were lower in sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] µM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P < .001, respectively). Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. CONCLUSIONS: Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease for which there are no disease modifying therapies. Thus, strategies that offer chondroprotective or regenerative capability represent a critical unmet need. Recently, oral consumption of a hydrolyzed type 1 collagen (hCol1) preparation has been reported to reduce pain in human OA and support a positive influence on chondrocyte function. To evaluate the tissue and cellular basis for these effects, we examined the impact of orally administered hCol1 in a model of posttraumatic OA (PTOA). In addition to standard chow, male C57BL/6J mice were provided a daily oral dietary supplement of hCol1 and a meniscal-ligamentous injury was induced on the right knee. At various time points post-injury, hydroxyproline (hProline) assays were performed on blood samples to confirm hCol1 delivery, and joints were harvested for tissue and molecular analyses were performed, including histomorphometry, OARSI and synovial scoring, immunohistochemistry and mRNA expression studies. Confirming ingestion of the supplements, serum hProline levels were elevated in experimental mice administered hCol1. In the hCol1 supplemented mice, chondroprotective effects were observed in injured knee joints, with dose-dependent increases in cartilage area, chondrocyte number and proteoglycan matrix at 3 and 12 weeks post-injury. Preservation of cartilage and increased chondrocyte numbers correlated with reductions in MMP13 protein levels and apoptosis, respectively. Supplemented mice also displayed reduced synovial hyperplasia that paralleled a reduction in Tnf mRNA, suggesting an anti-inflammatory effect. These findings establish that in the context of murine knee PTOA, daily oral consumption of hCol1 is chondroprotective, anti-apoptotic in articular chondrocytes, and anti-inflammatory. While the underlying mechanism driving these effects is yet to be determined, these findings provide the first tissue and cellular level information explaining the already published evidence of symptom relief supported by hCol1 in human knee OA. These results suggest that oral consumption of hCol1 is disease modifying in the context of PTOA.

Adaptive Upregulation of Clumping Factor A (ClfA) by Staphylococcus aureus in the Obese, Type 2 Diabetic Host Mediates Increased Virulence.

Obesity and associated type 2 diabetes (T2D) are important risk factors for infection following orthopedic implant surgery. Staphylococcus aureus, the most common pathogen in bone infections, adapts to multiple environments to survive and evade host immune responses. Whether adaptation of S. aureus to the unique environment of the obese/T2D host accounts for its increased virulence and persistence in this population is unknown. Thus, we assessed implant-associated osteomyelitis in normal versus high-fat-diet obese/T2D mice and found that S. aureus infection was more severe, including increases in bone abscesses relative to nondiabetic controls. S. aureus isolated from bone of obese/T2D mice displayed marked upregulation of four adhesion genes (clfA, clfB, bbp, and sdrC), all with binding affinity for fibrin(ogen). Immunostaining of infected bone revealed increased fibrin deposition surrounding bacterial abscesses in obese/T2D mice. In vitro coagulation assays demonstrated a hypercoagulable state in obese/T2D mice that was comparable to that of diabetic patients. S. aureus with an inactivating mutation in clumping factor A (clfA) showed a reduction in bone infection severity that eliminated the effect of obesity/T2D, while infections in control mice were unchanged. In infected mice that overexpress plasminogen activator inhibitor-1 (PAI-1), S. aureusclfA expression and fibrin-encapsulated abscess communities in bone were also increased, further linking fibrin deposition to S. aureus expression of clfA and infection severity. Together, these results demonstrate an adaptation by S. aureus to obesity/T2D with increased expression of clfA that is associated with the hypercoagulable state of the host and increased virulence of S. aureus.

Evaluation of the Finis Swimsense® and the Garmin Swim™ activity monitors for swimming performance and stroke kinematics analysis.

AIMS: The study aims were to evaluate the validity of two commercially available swimming activity monitors for quantifying temporal and kinematic swimming variables. METHODS: Ten national level swimmers (5 male, 5 female; 15.3±1.3years; 164.8±12.9cm; 62.4±11.1kg; 425±66 FINA points) completed a set protocol comprising 1,500m of swimming involving all four competitive swimming strokes. Swimmers wore the Finis Swimsense and the Garmin Swim activity monitors throughout. The devices automatically identified stroke type, swim distance, lap time, stroke count, stroke rate, stroke length and average speed. Video recordings were also obtained and used as a criterion measure to evaluate performance. RESULTS: A significant positive correlation was found between the monitors and video for the identification of each of the four swim strokes (Garmin: X2 (3) = 31.292, p<0.05; Finis:X2 (3) = 33.004, p<0.05). No significant differences were found for swim distance measurements. Swimming laps performed in the middle of a swimming interval showed no significant difference from the criterion (Garmin: bias -0.065, 95% confidence intervals -3.828-6.920; Finis bias -0.02, 95% confidence intervals -3.095-3.142). However laps performed at the beginning and end of an interval were not as accurately timed. Additionally, a statistical difference was found for stroke count measurements in all but two occasions (p<0.05). These differences affect the accuracy of stroke rate, stroke length and average speed scores reported by the monitors, as all of these are derived from lap times and stroke counts. CONCLUSIONS: Both monitors were found to operate with a relatively similar performance level and appear suited for recreational use. However, issues with feature detection accuracy may be related to individual variances in stroke technique. It is reasonable to expect that this level of error would increase when the devices are used by recreational swimmers rather than elite swimmers. Further development to improve accuracy of feature detection algorithms, specifically for lap time and stroke count, would also increase their suitability within competitive settings.

Three novel mutations of ARG1 identified in Chinese patients with argininemia detected by newborn screening.

Argininemia is a rare autosomal recessive genetic disorder caused by deficiency of arginase Ι, resulting from mutations in the ARG1 gene. Few genetic studies of ARG1 mutations in Chinese patients have been reported. In this study, two argininemia patients were initially diagnosed by tandem mass spectrometry in newborn screening. Mutation analysis of the ARG1 gene was performed by direct sequencing. Three novel mutations were identified and in silico methods were used to predict the impact of these mutations on the activity of enzyme. Two missense mutations, p.D100N and p.R71T, in Patient-1 were predicted to lower the stability of arginase Ι by analysis of 3D crystal structure, while two nonsense mutations, p.G12X and p.E42X, in Patient-2 were predicted to lead to truncated protein. Neonatal screening combined with genetic analysis is important for timely diagnosis and initiation of interventions of a potential genetic metabolic disease such as argininemia.

Shoulder arthritis secondary to rotator cuff tear: A reproducible murine model and histopathologic scoring system.

Untreated rotator cuff tears can progress to a distinct form of shoulder arthritis, and the mechanism of this progression is poorly understood. Biomechanical, molecular and genetic factors may be at play, and a reliable animal model is needed to enable further research. The purpose of this study was to create a reproducible model of posttraumatic shoulder arthritis in the mouse, and to develop a scoring system for this model to enable future research on interventions, the role of various gene products, and the development of therapies to alter the natural course of the disease. Forty-five mice underwent operative ligation of the rotator cuff tendons and were followed for 45 weeks following surgery, with free cage activity post-operatively. Mice were sacrificed at various intervals from 2 to 45 weeks post-injury and histopathologic scoring was developed and tested by blinded reviewers using both quantitative computational analysis of coronal sections of the shoulder joint and semi-quantitative grading. The scoring system revealed a progressive, time-dependent set of tissue changes in the shoulder joint with features similar to human cuff tear arthropathy including acetabularization of the acromion and femoralization of the humeral head. This model establishes that osteoarthritis of the shoulder is distinct from osteoarthritis of the knee or hip, with different stages of degeneration and unique histopathologic features. Using the novel grading procedure and quantitative assessments presented here, future research using this model will enable investigators to test established and novel therapies and evaluate the role of inflammatory factors and gene products in shoulder arthritis. This study provides a reproducible mouse model of shoulder arthritis following isolated injury to the rotator cuff which elucidates characteristics of cuff tear arthropathy and provides a scoring system and venue for future research. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:506-514, 2017.

Analysis of swimming performance: perceptions and practices of US-based swimming coaches.

In elite swimming, a broad range of methods are used to assess performance, inform coaching practices and monitor athletic progression. The aim of this paper was to examine the performance analysis practices of swimming coaches and to explore the reasons behind the decisions that coaches take when analysing performance. Survey data were analysed from 298 Level 3 competitive swimming coaches (245 male, 53 female) based in the United States. Results were compiled to provide a generalised picture of practices and perceptions and to examine key emerging themes. It was found that a disparity exists between the importance swim coaches place on biomechanical analysis of swimming performance and the types of analyses that are actually conducted. Video-based methods are most frequently employed, with over 70% of coaches using these methods at least monthly, with analyses being mainly qualitative in nature rather than quantitative. Barriers to the more widespread use of quantitative biomechanical analysis in elite swimming environments were explored. Constraints include time, cost and availability of resources, but other factors such as sources of information on swimming performance and analysis and control over service provision are also discussed, with particular emphasis on video-based methods and emerging sensor-based technologies.

Suppressive Effects of Insulin on Tumor Necrosis Factor-Dependent Early Osteoarthritic Changes Associated With Obesity and Type 2 Diabetes Mellitus.

OBJECTIVE: Obesity is a state of chronic inflammation that is associated with insulin resistance and type 2 diabetes mellitus (DM), as well as an increased risk of osteoarthritis (OA). This study was undertaken to define the links between obesity-associated inflammation, insulin resistance, and OA, by testing the hypotheses that 1) tumor necrosis factor (TNF) is critical in mediating these pathologic changes in OA, and 2) insulin has direct effects on the synovial joint that are compromised by insulin resistance. METHODS: The effects of TNF and insulin on catabolic gene expression were determined in fibroblast-like synoviocytes (FLS) isolated from human OA synovium. Synovial TNF expression and OA progression were examined in 2 mouse models, high-fat (HF) diet-fed obese mice with type 2 DM and TNF-knockout mice. Insulin resistance was investigated in synovium from patients with type 2 DM. RESULTS: Insulin receptors (IRs) were abundant in both mouse and human synovial membranes. Human OA FLS were insulin responsive, as indicated by the dose-dependent phosphorylation of IRs and Akt. In cultures of human OA FLS with exogenous TNF, the expression and release of MMP1, MMP13, and ADAMTS4 by FLS were markedly increased, whereas after treatment with insulin, these effects were selectively inhibited by >50%. The expression of TNF and its abundance in the synovium were elevated in samples from obese mice with type 2 DM. In TNF-knockout mice, increases in osteophyte formation and synovial hyperplasia associated with the HF diet were blunted. The synovium from OA patients with type 2 DM contained markedly more macrophages and showed elevated TNF levels as compared to the synovium from OA patients without diabetes. Moreover, insulin-dependent phosphorylation of IRs and Akt was blunted in cultures of OA FLS from patients with type 2 DM. CONCLUSION: TNF appears to be involved in mediating the advanced progression of OA seen in type 2 DM. While insulin plays a protective, antiinflammatory role in the synovium, insulin resistance in patients with type 2 DM may impair this protective effect and promote the progression of OA.

Inertial Sensor Technology for Elite Swimming Performance Analysis: A Systematic Review.

Technical evaluation of swimming performance is an essential factor of elite athletic preparation. Novel methods of analysis, incorporating body worn inertial sensors (i.e., Microelectromechanical systems, or MEMS, accelerometers and gyroscopes), have received much attention recently from both research and commercial communities as an alternative to video-based approaches. This technology may allow for improved analysis of stroke mechanics, race performance and energy expenditure, as well as real-time feedback to the coach, potentially enabling more efficient, competitive and quantitative coaching. The aim of this paper is to provide a systematic review of the literature related to the use of inertial sensors for the technical analysis of swimming performance. This paper focuses on providing an evaluation of the accuracy of different feature detection algorithms described in the literature for the analysis of different phases of swimming, specifically starts, turns and free-swimming. The consequences associated with different sensor attachment locations are also considered for both single and multiple sensor configurations. Additional information such as this should help practitioners to select the most appropriate systems and methods for extracting the key performance related parameters that are important to them for analysing their swimmers' performance and may serve to inform both applied and research practices.