Cognitive Assessment in Grappling Athletes Following Choke Versus Non-Choke Submissions.

PURPOSE: Participation in Brazilian jiu-jitsu (BJJ) and mixed martial arts has increased over the last 3 decades. These sports feature submission attacks, including strangles. These strangles, termed "chokes" in this context, primarily limit blood flow to the brain via compression of neck vasculature. There has been discussion in literature of the possibility of measurable cognitive effects following transient choking episodes. The present study used the King-Devick test (KDT) platform, a tablet-based reaction time and accuracy task designed to measure participants' number recognition, cognition, and verbal expression. This task requires functional vision, saccadic eye movements, comprehension and expression. METHODS: Volunteer participants were screened for exclusion (prior brain injury) criteria and survey information prior to testing. Athletes were tested with the KDT immediately prior to a BJJ training session, again immediately after succumbing to either a choke ("Choke" arm) or non-choke ("Non-Choke" arm) submission while sparring, and again after a 10-minute rest period following the post-submission test. Analysis was done on Test Failures, Total Test Times, and Individual Difference Scores between baseline and subsequent testing. RESULTS: 62 (32 Choke, 30 Non-Choke) participants were analyzed. There was no significant difference between Choke and Non-Choke in Test failures (X2(1,62) = 1.25, p = 0.263), Total Times (t(60) = 0.62, p = 0.540, 95% CI [-3.44, 6.51]), and Individual Difference Scores (t(60) = 0.29, p = 0.776, 95% CI [-2.41, 3.21]). CONCLUSIONS: There were no significant differences between study arms in any of the 3 analyzed measures. This suggests that cognitive functioning, as measured by the King-Devick test, is not affected by transient choking episodes.

The patient experience of peripheral intravenous therapy: development of a patient survey, initial findings, and next steps.

Peripheral intravenous cannulation (PIVC) is one of the most commonly performed invasive procedures in healthcare and can be a stressful experience for patients. Co-creating a patient journey map of intravenous therapy (IVT) together with patients highlighted the need to better understand patient experiences of IVT and informed the development of a patient-reported experience measure of intravenous therapy (IVT). The British Columbia (BC) Lower Mainland IVT Working Group, the BC Office of Patient-Centred Measurement and the provincial supplier of IVT products, hypothesized patient feedback about their IVT experiences would garner new insights to improve both patient experiences and outcomes related to IVT. Leveraging BC's province-wide, coordinated, scientifically rigorous patient-centred measurement program (BCPCM), a module of eight questions were developed, tested and fielded with the 2018 BC Emergency Department patient survey (n=14 076). Weekly monitoring of patient responses, through the BCPCM's web-based Dynamic Analysis and Reporting Tool (the DART), showed key themes and opportunities for improvement, leading to a test of change that introduced a patient information card (Why do I need an IV, What will happen when I get an IV, Tell a nurse if the following happens). This paper outlines the development of the IVT patient experience survey, and presents initial findings and the next steps to take action on the results. Additional data collection is now underway to solicit patient feedback of IVT across BC in outpatient cancer care and acute care hospital settings.

Women's Experiences of Pornography: A Systematic Review of Research Using Qualitative Methods.

Given the proliferation of pornography in personal, relational, and social realms, it is vital to understand women's experiences of this accessible, stimulating, and versatile sexual material. We therefore conducted the first systematic review of research using qualitative methods published in English in peer-reviewed journals. Our search of five databases yielded 22 eligible articles. Thematic analysis of results revealed four broad themes: women encountering pornography, pornography and the self, pornography in the context of relationships, and making sense of pornography. Discussion of themes and subthemes included reflections on women's explanations of intentional and unintentional encounters with pornography, conflicted perceptions of themselves in relation to female pornography actors, diverse perceived effects of pornography on intimate relationships, and tensions between women's arousal to pornography and their values. It was evident that women's experiences of pornography are complex and nuanced, often paradoxical, varying among and within individuals. Our synthesis of results and assessment of limitations suggest (a) that researchers need to define what they mean by pornography and specify any content used in their research and (b) that understanding would be enriched by research that is culturally contextualized and acknowledges public discourses about pornography.

End of life discussion in an academic family health team in kingston, ontario, Canada.

BACKGROUND: End-of-life (EOL) discussions remain difficult in non-terminal patients as death is often perceived as a taboo and uncertainty. However, the call for proper EOL discussions has recently received public attention and media coverage. Evidence also reveals that non-terminal patients are more satisfied with health-care encounters when EOL has been discussed. OBJECTIVES AND METHODS: The objective of this study was to explore the prevalence of EOL discussions in non-terminal adult patients, the perceived barriers to such discussions and suggested methods for improvement. A study mixed-methods study was performed by a group of PGY1 family medicine residents in an academic health team in Kingston, Ontario. RESULTS: EOL discussion was performed in a very small proportion of non-terminal patient encounters. Compared with attending physicians, residents were less likely to discuss EOL issues and reported more perceived barriers. CONCLUSION: Our findings reflect the need for an early and open approach in conducting EOL discussion for non-terminal healthy patients.

Beneficial effect of a CXCR4 agonist in murine models of systemic inflammation.

The chemokine CXC receptor 4 (CXCR4) is activated by stromal cell-derived factor (SDF-1α). CXCR4 may be part of a lipopolysaccharide (LPS) sensing co-clustering complex that modulates TLR4 activation and evidence suggest that SDF-1α can activate anti-inflammatory signaling pathways and suppress inflammation. In the present study we examined the hypothesis that the SDF-1α peptide analog and CXCR4 agonist CTCE-0214 is anti-inflammatory in three distinct models of murine systemic inflammation. Our findings demonstrate that CTCE-0214 in vivo significantly suppressed plasma tumor necrosis factor alpha (TNF-α) increases in acute endotoxemia and following zymosan-induced multiple organ dysfunction syndrome (MODS). In both models, CTCE-0214 did not suppress plasma increases in the anti-inflammatory cytokine interleukin (IL)-10. CTCE-0214 improved survival without antibiotics in a model of severe sepsis induced by cecal ligation and puncture (CLP). CTCE-0214 also decreased plasma increases in IL-6 but not TNF-α and IL-10 in response to CLP-induced inflammation. We demonstrated in a moderately severe model of CLP (one puncture) that IL-6 levels at 24 h were similar to sham controls. However in severe CLP (two punctures) plasma IL-6 levels were markedly elevated. Plasma SDF-1α levels varied inversely with the plasma IL-6. In addition to the beneficial effect of CTCE-0214 in these models of systemic inflammation in vivo, we also demonstrated that the analog dose dependently suppressed LPS-induced IL-6 production in bone marrow-derived macrophages. CTCE-0214 therefore may be beneficial in controlling inflammation sepsis and systemic inflammatory syndromes.

Peroxisome proliferator activated receptor gamma is not necessary for the development of LPS-induced tolerance in macrophages.

Peroxisome proliferator activated receptor-gamma (PPARgamma) has been reported to exert anti-inflammatory properties in endotoxic shock and sepsis. One phenomenon that alters the inflammatory response to endotoxin [lipopolysaccharide (LPS)] is endotoxin tolerance, which is caused by previous exposure to endotoxin. Here, we investigate whether changes in endogenous PPARgamma function regulate this phenomenon using three different models of LPS-induced tolerance in macrophages. In a first in vitro model, previous LPS exposure of murine J774.2 macrophages suppressed tumour necrosis factor-alpha (TNF-alpha) release in response to subsequent LPS challenge. Treatment of J774.2 cells with the PPARgamma inhibitor GW9662 did not alter tolerance induction because these cells were still hyporesponsive to the secondary LPS challenge. In a second ex vivo model, primary rat peritoneal macrophages from LPS-primed rats exhibited suppression of thromboxane B2 and TNF-alpha production, while maintaining nitrite production in response to in vitro LPS challenge. Pretreatment of rats with the PPARgamma inhibitor GW9662 in vivo failed to alter the tolerant phenotype of these primary macrophages. In a third ex vivo model, primary peritoneal macrophages with conditional deletion of PPARgamma were harvested from LPS-primed Cre-lox mice (Cre+/+ PPARgamma-/-) and exhibited significant suppression of TNF-alpha production in response to in vitro LPS challenge. Furthermore, both LPS-primed PPARgamma-deficient Cre+/+ PPARgamma-/- mice and wild-type Cre-/- PPARgamma+/+ mice exhibited reduced plasma TNF-alpha levels in response to a high dose of LPS in vivo. These data demonstrate that PPARgamma does not play a role in the LPS-induced tolerant phenotype in macrophages.

Involvement of G(i) proteins and Src tyrosine kinase in TNFalpha production induced by lipopolysaccharide, group B Streptococci and Staphylococcus aureus.

Previous studies have suggested that heterotrimeric G(i) proteins, Src tyrosine kinase and phosphatidylinositol-3 kinase (PI3 Kinase) are involved in signaling events induced by lipopolysaccharide (LPS) leading to pro-inflammatory cytokines gene expression. To investigate the involvement of these mediators in Gram-positive bacteria induced pro-inflammatory cytokine expression, LPS (10 ng/ml), heat killed group B Streptococci (GBS 1 microg/ml) and Staphylococcus aureus (SA 10 microg/ml) were used to induce TNFalpha production in the murine J774A.1 macrophage (MØ) cell line and human promonocytic THP-1 cell line. Pertussis toxin (PTx, 1 microg/ml), an inhibitor of G(i) protein; pyrazolopyrimidine-2 (PP2, 1 or 25 microM), a Src tyrosine kinase inhibitor; and LY294002 (100 nM), an inhibitor of PI3 Kinase were used to examine the involvement of G(i), Src tyrosine kinase and PI3 Kinase, respectively, in TNFalpha production. In J774A.1 cells, pretreatment with PTx and PP2 attenuated TNFalpha production induced by LPS (60+/-9% and 81+/-11% inhibition, n=3, p<0.05, respectively), GBS (95+/-1% and 80+/-6% inhibition, n=3, p<0.05, respectively) and SA (51+/-18% and 68+/-16% inhibition, n=4, p<0.05, respectively). However, pretreatment with LY 294002 inhibited LPS induced TNFalpha production (82+/-13% inhibition, n=3, p<0.05), but did not inhibit GBS or SA induced TNFalpha production. In THP-1 cells, pretreatment with PTx, PP2 and LY 294002 inhibited TNFalpha production induced by LPS (84+/-3%, 59+/-12% and 84+/-4% inhibition, n=3, p<0.05, respectively) and SA (56+/-7%, 87+/-1% and 35+/-6% inhibition, n=3, p<0.05, respectively). These data support our hypothesis that G(i)-coupled and Src tyrosine kinase-coupled signaling pathways are involved in both Gram-negative and Gram-positive bacteria induced pro-inflammatory cytokine expression. However, unlike LPS, involvement of PI3 Kinase in Gram-positive bacteria induced signaling pathways are species dependent.

Peroxisome proliferator-activated receptor-gamma agonists modulate macrophage activation by gram-negative and gram-positive bacterial stimuli.

Bacterial products, such as lipopolysaccharide (LPS) or heat-killed Escherichia coli (EC), and heat-killed Staphylococcus aureus (SA) are potent activators of macrophages (MØ). When stimulated by these bacterial components, MØ produce inflammatory mediators, such as nitric oxide (NO) and thromboxane (Tx) B(2). Bacterial mediator production is preceded by the activation of various signal transduction pathways. Agonists that activate the peroxisome proliferator-activated receptor-gamma (PPARgamma) have been shown to block MØ mediator production by LPS and other stimuli. However, very little is known about the effects of PPARgamma agonists on SA- or EC-induced MØ activation. Therefore, we investigated whether the PPARgamma agonists 15-deoxy-Delta12,14 prostaglandin J(2) (15-PGJ(2)) and troglitazone block LPS-, EC-, or SA-induced mediator production. Rat peritoneal MØ were stimulated with LPS, EC, or SA (10 microg/mL) with or without increasing concentrations (0.1 to 10 microM) of each PPARgamma agonist and NO and TxB(2) production were measured. 15-PGJ(2) decreased LPS-, EC-, and SA-induced NO and TxB(2) production. However, troglitazone only inhibited the production of TxB(2) by each stimuli. In parallel studies, the effects of PPARgamma agonists on signaling pathways were evaluated. Rat peritoneal MØ were pretreated for 1 h with 15-PGJ(2) or troglitazone (1 or 10 microM) and then stimulated for 40 min with LPS, EC, or SA (10 microg/mL). Western blot analysis demonstrated that 15-PGJ(2) significantly inhibited LPS-, EC-, and SA-induced ERK (1/2) activation and blocked IkappaBalpha degradation. Troglitazone had no significant effect on either signaling protein. The data demonstrate that although both 15-PGJ(2) and troglitazone are considered PPARgamma agonists, they differentially affect mediator production and cell signaling events. PPARgamma-independent effects of 15-PGJ(2) may contribute to its more potent anti-inflammatory effects compared with troglitazone.

Implication of Galpha i proteins and Src tyrosine kinases in endotoxin-induced signal transduction events and mediator production.

Previous studies have suggested that heterotrimeric G proteins and tyrosine kinases may be involved in lipopolysacchaide (LPS) signaling events. Signal transduction pathways activated by LPS we examined in human pomonocytic THP-l cells. We hypothesized that Gi proteins and Src tyrosine kinase differentially affect mitogen-activated protein (MAP) kinases (MAPK) and nuclear factor kappa(NF-kappaB) activation. Post-receptor coupling to Ga, proteins were examined using pertussis toxin (PTx),which inhibits Galpha i receptor-coupling. The involvement of the Src family of tyrosine kinases was examined using the selective Src tyrosine kinase inhibitor pyrazolopyrimidine-2 (PP2). Pretreatment of THP-1 cells with PTx attenuated LPS-induced activation of c-Jun-N-terminal kinase (JNK) and p38 kinase, and production of tumor necrosis factor-alpha (TN-alpha) and thromboxane B2 (TXB2). Pretreatment with PP2 inhibited TNF-alpha and TxB2 production, but had no effect on p38 kinase or JNK signaling. Therefore, the Ga i-coupled signaling pathways and Src tyrosine kinase-coupled signaling pathways are necessary for LPS-induced TNF-alpha and TxB2 production, but differ in their effects on MAPK activation. Neither PTx nor PP2 inhibited LPS-induced activation of interleukin receptor activated kinase (IRAK) or inhibited translocation of NF-kappaB. However, PP2 inhibited LPS-induced NF-kappaB transactivation of a luciferase reporter gene construct in a concentration-dependent manner. Thus, LPS induction of Src tyrosine kinases may be essential in downstream NF-kappaB tansactivation of genes following DNA binding. PTx had no effect on NF-kaapaB activation of the reporter construct. These data suggest upstream divergence in signaling through Galpha i,pathways leading to MAPK activation and other signaling events leading to IkappaBalpha degradation and NF-kaapaB DNA binding.