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International audience; The purpose of this study was to examine the association between young players’ perception of mother’s and father’s responsiveness with their self-esteem, anxiety (i.e., worry), and thriving (i.e., positive affect, vitality, and life satisfaction). In total, 314 male British rugby players with a mean age of 16.23 years (SD = 0.26) completed the study in two phases: n = 124 (first dataset), and n = 192 (second dataset). Participants trained on average 3.14 times/week (SD = 0.94) and had been involved in rugby for an average of 8.21 years (SD = 2.89). Participants completed questionnaires measuring perceived parental responsiveness (PPR) for their mother and father, self-esteem, worry about sport performance, and thriving indicators (i.e., positive affect, vitality, and life satisfaction). The results consistently indicated that participants’ perceptions of their mother’s and father’s responsiveness positively related to thriving, and negatively related to their worry about sport performance, mediated by their self-esteem. Overall, the study highlights the need for parents to be provided with insights into the value of being responsive to their child and being encouraged to regularly talk with their child regarding their needs and desires, and seeking to understand how their child perceives the support they currently receive.

The purpose of this study was to examine temporally distal influence at a three-month interval of perceived parental responsiveness on athletes’ goal accomplishment, trait cognitive sport anxiety, and thriving. Young players (154 males, 51 females, M = 12.50 years, SD = 0.65) involved in rugby, basketball, and handball participated in the study. Initially, participants set three goals to accomplish over the next three months and completed questionnaires assessing their perceptions of their parents’ responsiveness, perceived self-efficacy, and self-esteem. Three months later, participants completed questionnaires assessing their goal accomplishment, worry about sport performance, and thriving. The results showed that athletes’ perceptions of their mother’s/father’s responsiveness, mediated by perceived athletes’ self-efficacy to accomplish their goals, influenced their goal accomplishment and trait cognitive sport anxiety three months later. The results also showed that athletes’ perceptions of their mother’s/father’s responsiveness, mediated by athletes’ self-esteem, influenced athletes’ thriving and trait cognitive sport anxiety three months later. Overall, the present study uniquely contributes to the understanding of parent-athlete relationships by showing that athletes’ perceptions of their mother’s and father’s responsiveness influence certain distal outcomes three months later (i.e., goal accomplishment, sports anxiety, and thriving) while mediated by self-efficacy and self-esteem.

Background Chronic periprosthetic joint infection (PJI) is a devastating complication that can occur following total joint replacement. Patients with chronic PJI report a substantially lower quality of life and face a higher risk of short-term mortality. Establishing a diagnosis of chronic PJI is challenging because of conflicting guidelines, numerous tests, and limited evidence. Delays in diagnosing PJI are associated with poorer outcomes and morbid revision surgery. The purpose of this systematic review was to compare the diagnostic accuracy of serum, synovial, and tissue-based tests for chronic PJI. Methods This review adheres to the Cochrane Collaboration's diagnostic test accuracy methods for evidence searching and syntheses. A detailed search of MEDLINE, Embase, the Cochrane Library, and the grey literature was performed to identify studies involving the diagnosis of chronic PJI in patients with hip or knee replacement. Eligible studies were assessed for quality and bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Meta-analyses were performed on tests with sufficient data points. Summary estimates and hierarchical summary receiver operating characteristic (HSROC) curves were obtained using a bivariate model. Results A total of 12,616 citations were identified, and 203 studies met the inclusion criteria. Of these 203 studies, 170 had a high risk of bias. Eighty-three unique PJI diagnostic tests were identified, and 17 underwent meta-analyses. Laboratory-based synovial alpha-defensin tests and leukocyte esterase reagent (LER) strips (2+) had the best performance, followed by white blood-cell (WBC) count, measurement of synovial C-reactive protein (CRP) level, measurement of the polymorphonuclear neutrophil percentage (PMN%), and the alpha-defensin lateral flow test kit (Youden index ranging from 0.78 to 0.94). Tissue-based tests and 3 serum tests (measurement of interleukin-6 [IL-6] level, CRP level, and erythrocyte sedimentation rate [ESR]) had a Youden index between 0.61 to 0.75 but exhibited poorer performance compared with the synovial tests mentioned above. Conclusions The quality of the literature pertaining to chronic PJI diagnostic tests is heterogeneous, and the studies are at a high risk for bias. We believe that greater transparency and more complete reporting in studies of diagnostic test results should be mandated by peer-reviewed journals. The available literature suggests that several synovial fluid-based tests perform well for diagnosing chronic PJI and their use is recommended in the work-up of any suspected case of chronic PJI. Level of evidence Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Low Molecular Weight Heparins (LMWH) are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal chain length of 18 saccharides units, including an antithrombin (AT) binding pentasaccharide, is mandatory to form the active ternary complex for LMWH obtained by alkaline β-elimination (e.g., enoxaparin). However, the relationship between structure of octadecasaccharides and their thrombin inhibition has not been yet assessed on natural compounds due to technical hurdles to isolate sufficiently pure material. We report the preparation of five octadecasaccharides by using orthogonal separation methods including size exclusion, AT affinity, ion pairing and strong anion exchange chromatography. Each of these octadecasaccharides possesses two AT binding pentasaccharide sequences located at various positions. After structural elucidation using enzymatic sequencing and NMR, in vitro aFXa and aFIIa were determined. The biological activities reveal the critical role of each pentasaccharide sequence position within the octadecasaccharides and structural requirements to inhibit thrombin. Significant differences in potency, such as the twenty-fold magnitude difference observed between two regioisomers, further highlights the importance of depolymerisation process conditions on LMWH biological activity.

Before contacting host tissues, invading pathogens directly or indirectly interact with host microbiota, but the effects of such interactions on the initial stages of infection are poorly understood. Bordetella pertussis is highly infectious among humans but requires large doses to colonize rodents, unlike a closely related zoonotic pathogen, Bordetella bronchiseptica, raising important questions about the contributions of bacterial competition to initial colonization and host selection. We observed that

Perfluorocarbon-based emulsions increase the blood solubility of isoflurane, enflurane, and halothane, with a maximal effect reported for the less soluble isoflurane. Current volatile anesthetics are less soluble and may be more affected by this phenomenon. Perflubron (Oxygent(TM)) is a perfluorocarbon-based emulsion in late-stage clinical testing in surgical patients for use as a temporary oxygen carrier. We tested the hypothesis that perflubron increases the solubility of isoflurane, sevoflurane, and desflurane, as reflected by their blood/gas partition coefficient (lambda(Bl:g)). Fresh whole-blood samples were drawn from eight volunteers and mixed with perflubron to obtain concentrations of 1.2%, 1.8%, and 3.6% by volume (equivalent to in vivo doses of 1.8 to 5.4 g/kg, which represent up to twice the intended clinical dose range). By using the double-extraction method, we demonstrated increased lambda(Bl:g) for isoflurane, sevoflurane, and desflurane. However, the solubility in blood does not really change, because volatile anesthetics are actually partitioning into perflubron. Increasing the amount of emulsion in the blood consequently increases the amount of gas carried, as reflected by the measured linear correlation between the lambda(Bl:g) values of all three volatile anesthetics and perflubron doses. Even though the increase ranges from 0.9 (desflurane) to 2.6 (sevoflurane) times the normal value, the apparent lack of clinical implications in current trials with perflubron may trigger further in vivo experiments.Perflubron increases the in vitro solubility of volatile anesthetics when present in the blood at clinically relevant concentrations. Volatile anesthetics actually partition into the emulsion, but the solubility in the blood does not change. Further studies are needed to assess whether perflubron will affect the pharmacokinetics of volatile anesthetics in vivo.

The incidence of whooping cough, once a common and deadly childhood disease, was greatly reduced following the introduction of whole-cell vaccines in the late 1940s [1]. However, concern about their side effects led to a transition to acellular vaccines in the 1980s [2]. Subsequently, the incidence of whooping cough has increased to levels 50-fold higher than the all-time low in the United States, in 1976 [3]. In many countries, even those with high vaccine coverage, B. pertussis continues to spread and cause periodic epidemics [4–9], raising questions about the effects of vaccines on the spread of disease. Acellular vaccines provide protection against the most severe forms of whooping cough but are less effective against B. pertussis infections associated with milder forms of coughing illness [1, 4]. Consequently, there is debate about whether acellular vaccines induce the most effective type of immune response to protect vaccinated individuals and prevent the spread of disease [10]. Both whole-cell and acellular vaccines are able to generate high levels of antibodies towards the bacterial components present in each. But only the whole-cell vaccine efficiently activates T-helper type 1 (Th1) cells that generate an effective interferon γ (IFN-γ) response that is important in the control and clearance of B. pertussis infection [11, 12]. Acellular vaccination creates a largely Th2 and Th17 response that is less effective in animal models, potentially explaining the increased incidence coinciding with the switch to acellular vaccines [10, 12]. To date, these analyses have been limited to studies within individuals. However, the observed differences in response would also be expected to affect the inflammatory response that could contribute to symptoms such as coughing and sneezing, the primary mechanisms of transmission of B. pertussis. Therefore, the different effects of the 2 vaccines could also contribute to the observed increase in incidence by affecting the transmission of B. pertussis, although these effects have not been measured experimentally. Detailed molecular studies of Bordetella pathogenesis have been performed in the mouse model, because of its simplicity and reproducibility, and findings have been consistent with those from the limited work done in humans and other animals [1, 13]. In many cases, Bordetella bronchiseptica, a closely related subspecies of B. pertussis that naturally infects a wide range of mammalian hosts, including humans and mice, has been used as a model system to study the infectious process [1, 14]. Since B. bronchiseptica naturally infects mice, both interactions between bacterial factors and host immune functions can be probed to the molecular level during the infectious process. These infection models have focused on the interactions between bacteria and an experimentally inoculated host, largely avoiding the defining characteristic of infectious disease: transmission. To overcome this limitation, we have recently developed a transmission system in mice, in which we have demonstrated the importance of innate immune activity regulated by Toll-like receptor 4 (TLR4) in limiting the transmission of B. bronchiseptica [15]. Defects in TLR4 led to an increase in both the infectiousness of the infected individual (ie, shedding) and the susceptibility of the host (ie, colonization of susceptible mice) in this model. Importantly, this work has provided an experimental system in which transmission can be studied experimentally, allowing direct measurement of the effects of vaccines on various aspects that contribute to transmission. In this study, we examine the effects of vaccination on transmission and examine the immune mechanisms involved in these effects. Consistent with expectations, whole-cell vaccines (involving either B. pertussis or B. bronchiseptica) induce an immune response that limits shedding and blocks transmission from inoculated index cases. Both memory CD4+ T cells and antibodies are implicated in the control of shedding. Whole-cell vaccination was effective in limiting the shedding and infectivity of B. bronchiseptica, while acellular vaccination was less effective. Together these results suggest that the resurgence of B. pertussis could be due to 2 deficiencies of the acellular vaccines: failure to protect the vaccinated individual from infection, only blunting the severity of disease, and failure to prevent the transmission of B. pertussis. The different effects of vaccines on individual and herd immunity should be important considerations for the next generation of B. pertussis vaccines.

Transmission of pathogens has been notoriously difficult to study under laboratory conditions leaving knowledge gaps regarding how bacterial factors and host immune components affect the spread of infections between hosts. We describe the development of a mouse model of transmission of a natural pathogen, Bordetella bronchiseptica, and its use to assess the impact of host immune functions. Although B. bronchiseptica transmits poorly between wild-type mice and mice lacking other immune components, it transmits efficiently between mice deficient in Toll-Like Receptor 4 (TLR4). TLR4-mutant mice were more susceptible to initial colonization, and poorly controlled pathogen growth and shedding. Heavy neutrophil infiltration distinguished TLR4-deficient responses, and neutrophil depletion did not affect respiratory CFU load, but decreased bacterial shedding. The effect of TLR4 response on transmission may explain the extensive variation in TLR4 agonist potency observed among closely related subspecies of Bordetella. This transmission model will enable mechanistic studies of how pathogens spread from one host to another, the defining feature of infectious disease.

Perfluorocarbon emulsions (PFEs) appear as platelets in automated cell counters, which may affect samples from thrombocytopenic patients (less than 100,000/mu L). Therefore, we mixed clinically relevant concentrations of perfluorodichlorooctane (Oxyfluor(R); Hemagen, Inc., St. Louis, MO) in vitro with whole blood samples ranging from 0 to 150,000 platelets/mu L and compared a new counter that uses optical platelet recognition (Abbott CellDyn 3200; Santa Clara, CA) with conventional electroimpedance-based counters (Abbott CellDyn 3500 and CellDyn 1700). We found that emulsion particles appear as small-sized platelets either in diluent or in blood. The emulsion results in a reproducible overestimate of the platelet counts, of greater importance as PFE concentration increases, and as the actual platelet count of the blood samples decreases. The new optical technology yields smaller overestimates but, even at low PFE concentrations, gives an unacceptable relative error at platelet counts near the transfusion thresholds recommended by the American Society of Anesthesiologists guidelines for blood component therapy. Unexpected interference in the leukocyte and erythrocyte channels is also reported. Experimental limitations preclude extrapolation of these findings to other automated cell counters, because differences in technology or software may affect their capacity to separate PFE particles from platelets. Implications: Perfluorocarbons are being investigated under conditions in which thrombocytopenia is likely to occur. In this in vitro study, we demonstrate significant overestimates in platelet counts from automated cell counters at clinically relevant perfluorocarbon concentrations in thrombocytopenic blood samples.

Background . We developed a prosthetic left ventricle (LV) to coronary sinus (CS) shunt (LVCSS) that is autoregulating and provides LV-powered retrograde perfusion of the coronary sinus. Methods . Each of 20 Yorkshire pigs underwent 1 hour of left anterior descending diagonal artery occlusion followed by 3 hours of reperfusion. The controls (n = 5) did not have shunt treatment. The LVCSS group (n = 9) underwent shunt treatment during the ischemic period. The LVCSS with partial coronary sinus occlusion (PCSO) group (LVCSS+PCSO, n=6) underwent shunt treatment and PCSO during the ischemic period. Vital staining and planimetry techniques were used to determine the area at risk for infarction and the area of necrosis. Results . The area at risk was not significantly different among groups. The area of necrosis was decreased by 53% in the LVCSS group and by 73% in the LVCSS+PCSO group when compared to controls ( p Conclusions . The LVCSS reduces infarct size in pigs after acute coronary artery occlusion. The addition of PCSO to LVCSS further improves myocardial salvage.

Heparin and low-molecular-weight heparins (LMWHs) are anticoagulant drugs that mainly inhibit the coagulation cascade by indirectly interacting with factor Xa and factor IIa (thrombin). Inhibition of factor Xa by antithrombin (AT) requires the activation of AT by specific pentasaccharide sequences containing 3-O-sulfated glucosamine. Activated AT also inhibits thrombin by forming a stable ternary complex of AT, thrombin, and a polysaccharide (requires at least an 18-mer/octadeca-mer polysaccharide). The full structure of any naturally occurring octadecasaccharide sequence has yet to be determined. In the context of the development of LMWH biosimilars, structural data on such important biological mediators could be helpful for better understanding and regulatory handling of these drugs. Here we present the isolation and identification of an octadecasaccharide with very high anti-factor Xa activity (∼3 times higher than USP [U.S. Pharmacopeia] heparin). The octadecasaccharide was purified using five sequential chromatographic methods with orthogonal specificity, including gel permeation, AT affinity, strong anion exchange, and ion-pair chromatography. The structure of the octadecasaccharide was determined by controlled enzymatic sequencing and nuclear magnetic resonance (NMR). The isolated octadecasaccharide contained three consecutive AT-binding sites and was tested in coagulation assays to determine its biological activity. The isolation of this octadecasaccharide provides new insights into the modulation of thrombin activity.

Heparin is a highly sulfated hetero polysaccharide mixture found and extracted from mammalian tissues. It has been widely used as an anticoagulant drug during the past decades. In the new proposed USP heparin monograph, the 1 H NMR acceptance criteria to prevent contamination by over sulfated chondroitin sulfate (OSCS), or other persulfated glycosaminoglycans, specifies that no unidentified signals greater than 4% of the mean of signal height of 1 and 2 [1] should be present in the following ranges: 0.10–2.00, 2.10–3.20, and 5.70–8.00 ppm. However, those criteria do not take into account the impact of potential structural modifications generated by the heparin manufacturing processes. In fact, starting from pig mucosa, heparin purification involves oxidizing reagents such as sodium peroxide, potassium permanganate and peracetic acid. In the present work, we demonstrate that potassium permanganate treated heparins show a small but characteristic extra signal at 2.10 ppm. Controlled heparinase I depolymerisation is used to target and excise the oligosaccharide responsible for this extra signal from the polysaccharide backbone. By using orthogonal chromatographic techniques, the fingerprint oligosaccharide was isolated and its structure elucidated. Without the identification of this structural moiety, such purified heparins may have been considered as non-compliant drug substance and not suitable for pharmaceutical use.