The LIFR Inhibitor EC359 Effectively Targets Type II Endometrial Cancer by Blocking LIF/LIFR Oncogenic Signaling.

Endometrial cancer (ECa) is the most common female gynecologic cancer. When comparing the two histological subtypes of endometrial cancer, Type II tumors are biologically more aggressive and have a worse prognosis than Type I tumors. Current treatments for Type II tumors are ineffective, and new targeted therapies are urgently needed. LIFR and its ligand, LIF, have been shown to play a critical role in the progression of multiple solid cancers and therapy resistance. The role of LIF/LIFR in the progression of Type II ECa, on the other hand, is unknown. We investigated the role of LIF/LIFR signaling in Type II ECa and tested the efficacy of EC359, a novel small-molecule LIFR inhibitor, against Type II ECa. The analysis of tumor databases has uncovered a correlation between diminished survival rates and increased expression of leukemia inhibitory factor (LIF), suggesting a potential connection between altered LIF expression and unfavorable overall survival in Type II ECa. The results obtained from cell viability and colony formation assays demonstrated a significant decrease in the growth of Type II ECa LIFR knockdown cells in comparison to vector control cells. Furthermore, in both primary and established Type II ECa cells, pharmacological inhibition of the LIF/LIFR axis with EC359 markedly decreased cell viability, long-term cell survival, and invasion, and promoted apoptosis. Additionally, EC359 treatment reduced the activation of pathways driven by LIF/LIFR, such as AKT, mTOR, and STAT3. Tumor progression was markedly inhibited by EC359 treatment in two different patient-derived xenograft models in vivo and patient-derived organoids ex vivo. Collectively, these results suggest LIFR inhibitor EC359 as a possible new small-molecule therapeutics for the management of Type II ECa.

The Utility and Diagnostic Accuracy of Transient Elastography in Adults with Morbid Obesity: A Prospective Study.

Patients with morbid obesity are at high risk for nonalcoholic fatty liver disease (NAFLD) complicated by liver fibrosis. The clinical utility of transient elastography (TE) by Fibroscan in patients with morbid obesity (body mass index (BMI) ≥ 40 kg/m2) is not well-defined. We examined the diagnostic accuracy of Fibroscan in predicting significant liver fibrosis (fibrosis stage ≥2) in morbidly obese patients (BMI ≥ 40 kg/m2). Patients scheduled for bariatric surgery were prospectively enrolled. Intraoperative liver biopsy, liver-stiffness measurement (LSM) by Fibroscan (XL probe), and biochemical evaluation were all performed on the same day. The endpoint was significant liver fibrosis defined as fibrosis stage ≥2 based on the Nonalcoholic Steatohepatitis Clinical Research Network. The optimal LSM cutoff value for detecting significant fibrosis was determined by using the Youden Index method. Routine clinical, laboratory, and elastography data were analyzed by stepwise logistic regression analysis to identify predictors of significant liver fibrosis and build a predictive model. An optimal cutoff point of the new model's regression formula for predicting significant fibrosis was determined by using the Youden index method. One hundred sixty-seven patients (mean age, 46.4 years) were included, of whom 83.2% were female. Histological assessment revealed the prevalence of steatohepatitis and significant fibrosis of 40.7% and 11.4%, respectively. The median LSM was found to be significantly higher in the significant fibrosis group compared to those in the no or non-significant fibrosis group (18.2 vs. 7.7 kPa, respectively; p = 0.0004). The optimal LSM cutoff for predicting significant fibrosis was 12.8 kPa, with an accuracy of 71.3%, sensitivity of 73.7%, specificity of 70.9%, positive predictive value of 24.6%, negative predictive value of 95.5%, and ROC area of 0.723 (95% CI: 0.62-0.83). Logistic regression analysis identified three independent predictors of significant fibrosis: LSM, hemoglobin A1c, and alkaline phosphatase. A risk score was developed by using these three variables. At an optimal cutoff value of the regression formula, the risk score had an accuracy of 79.6% for predicting significant fibrosis, sensitivity of 89.5%, specificity of 78.4%, positive predictive value of 34.7%, negative predictive value of 98.3%, and ROC area of 0.855 (95% CI: 0.76-0.95). Fibroscan utility in predicting significant liver fibrosis in morbidly obese subjects is limited with accuracy of 71.3%. A model incorporating hemoglobin A1c and alkaline phosphatase with LSM improves accuracy in detecting significant fibrosis in this patient population.

Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD.

BACKGROUND AND AIMS: NAFLD and its more-advanced form, steatohepatitis (NASH), is associated with obesity and is an independent risk factor for cardiovascular, liver-related, and all-cause mortality. Available human data examining hepatic mitochondrial fatty acid oxidation (FAO) and hepatic mitochondrial turnover in NAFLD and NASH are scant. APPROACH AND RESULTS: To investigate this relationship, liver biopsies were obtained from patients with obesity undergoing bariatric surgery and data clustered into four groups based on hepatic histopathological classification: Control (CTRL; no disease); NAFL (steatosis only); Borderline-NASH (steatosis with lobular inflammation or hepatocellular ballooning); and Definite-NASH (D-NASH; steatosis, lobular inflammation, and hepatocellular ballooning). Hepatic mitochondrial complete FAO to CO2 and the rate-limiting enzyme in ß-oxidation (ß-hydroxyacyl-CoA dehydrogenase activity) were reduced by ~40%-50% with D-NASH compared with CTRL. This corresponded with increased hepatic mitochondrial reactive oxygen species production, as well as dramatic reductions in markers of mitochondrial biogenesis, autophagy, mitophagy, fission, and fusion in NAFL and NASH. CONCLUSIONS: These findings suggest that compromised hepatic FAO and mitochondrial turnover are intimately linked to increasing NAFLD severity in patients with obesity.

Body checking in non-elite adolescent ice hockey leagues: it is never too late for policy change aiming to protect the health of adolescents.

OBJECTIVES: The objective of this study is to evaluate the effect of policy change disallowing body checking in adolescent ice hockey leagues (ages 15-17) on reducing rates of injury and concussion. METHODS: This is a prospective cohort study. Players 15-17 years-old were recruited from teams in non-elite divisions of play (lower 40%-70% by division of play depending on year and city of play in leagues where policy permits or prohibit body checking in Alberta and British Columbia, Canada (2015-18). A validated injury surveillance methodology supported baseline, exposure-hours and injury data collection. Any player with a suspected concussion was referred to a study physician. Primary outcomes include game-related injuries, game-related injuries (>7 days time loss), game-related concussions and game-related concussions (>10 days time loss). RESULTS: 44 teams (453 player-seasons) from non-body checking and 52 teams (674 player-seasons) from body checking leagues participated. In body checking leagues there were 213 injuries (69 concussions) and in non-body checking leagues 40 injuries (18 concussions) during games. Based on multiple multilevel mixed-effects Poisson regression analyses, policy prohibiting body checking was associated with a lower rate of injury (incidence rate ratio (IRR): 0.38 (95% CI 0.24 to 0.6)) and concussion (IRR: 0.49; 95% CI 0.26 to 0.89). This translates to an absolute rate reduction of 7.82 injuries/1000 game-hours (95% CI 2.74 to 12.9) and the prevention of 7326 injuries (95% CI 2570 to 12083) in Canada annually. CONCLUSIONS: The rate of injury was 62% lower (concussion 51% lower) in leagues not permitting body checking in non-elite 15-17 years old leagues highlighting the potential public health impact of policy prohibiting body checking in older adolescent ice hockey players.

Heterogeneity in Patient Characteristics and Differences in Treatment Across 4 Canadian Rheumatoid Arthritis Cohorts.

OBJECTIVE: To compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts. METHODS: The 4 longitudinal cohorts included the following: the Canadian Early Arthritis Cohort (CATCH; n = 2878), Ontario Best Practices Research Initiative (OBRI; n = 3734), RHUMADATA (Quebec, n = 2890), and the Rheum4U Precision Health Registry (Calgary, Alberta, n = 709). Data were from cohort inception (range 1998-2016) to 2020. Clinical characteristics and drug treatments were summarized descriptively. RESULTS: In total, 10,211 patients with RA were included. The percentage of patients who entered the cohort with early RA (2 yrs of disease at enrollment) ranged from 29% (Rheum4U) to 100% (CATCH). Mean age (55 yrs), sex (74% female), and seropositivity (69%) were similar between cohorts. At the time of initial disease-modifying antirheumatic drug (DMARD) use, median Disease Activity Score in 28 joints (DAS28) varied, ranging from 2.99 (Rheum4U) to 5.19 (CATCH), but were more similar at the time of the first DMARD switch (range 3.57-5.03), first biologic (bDMARD) or targeted synthetic DMARD (tsDMARD) use (range 4.01-4.67), and second bDMARD or tsDMARD (range 3.71-4.39). The initial DMARD was most commonly methotrexate, either in monotherapy (32%, range 18-40%) or dual therapy (34%, range 29-42%). The first DMARD switch was to another DMARD monotherapy in 20% (range 10-32%), dual therapy in 49% (range 39-56%), and bDMARD or tsDMARD in 24% (range 15-28%). The first bDMARD was an anti-tumor necrosis factor in 79% (range 78-82%). CONCLUSION: Canadian RA cohorts demonstrate some heterogeneity in treatment, which could reflect differences in inclusion criteria, calendar year, or regional differences. This project is a first step toward conducting harmonized analyses across Canadian RA cohorts.

A Model Incorporating Serum Alkaline Phosphatase for Prediction of Liver Fibrosis in Adults with Obesity and Nonalcoholic Fatty Liver Disease.

We assessed the relationship between serum alkaline phosphatase (ALP) and liver fibrosis by histology, in addition to other noninvasive parameters, in obese patients undergoing metabolic surgery. Patients scheduled for elective bariatric surgery were prospectively recruited from a bariatric clinic. An intraoperative liver biopsy was performed, and liver histology was evaluated by a pathologist blinded to the patients' data. The endpoint was significant fibrosis defined as fibrosis stage ≥ 2. Independent predictors of fibrosis were identified by logistic regression. Two hundred ten patients were recruited. Liver histology revealed steatosis in 87.1%, steatohepatitis in 21.9%, and significant fibrosis in 10%. Independent predictors of significant fibrosis were ALP (Odds Ratio (OR) 1.03; 95% Confidence interval (CI), 1.01-1.05), alanine aminotransferase (OR 1.02; 95% CI, 1.01-1.03), HbA1c (OR 1.58; 95% CI, 1.20-2.09), and body mass index (OR 1.06; 95% CI, 1.00-1.13). A tree-based model was developed to predict significant fibrosis, with a receiver operating characteristic (ROC) area of 0.845, sensitivity of 0.857, specificity of 0.836, and accuracy of 0.931. The applicability of serum ALP as an independent biomarker of liver fibrosis should be considered in obesity surgery patients, and in the broader context of obese patients with nonalcoholic fatty liver disease.

Scoping review of balanced scorecards for use in healthcare settings: development and implementation.

OBJECTIVE: Balanced scorecards (BSCs) were developed in the early 1990s in corporate settings as a strategic performance management tool that emphasised measurement from multiple perspectives. Since their introduction, BSCs have been adapted for a variety of industries, including to healthcare settings. The aim of this scoping review was to describe the application of BSCs in healthcare. METHODS: Medline, Embase and CINHAL databases were searched using keywords and medical subject headings for 'balanced scorecard' and related terms from 1992 to 17/04/2020. Title and abstract screening and full text review were conducted in duplicate by two reviewers. Studies describing the development and/or implementation of a BSC in a healthcare setting were included. Data were abstracted using pilot-tested forms and reviewed for key themes and findings. RESULTS: 8129 records were identified and 841 underwent a full text review. 87 articles were included. Over 26 countries were represented and the majority of BSCs were applied at a local level (54%) in hospital settings (41%). While almost all discussed Kaplan and Norton's original BSC (97%), only 69% described alignment with a strategic plan. Patients/family members were rarely involved in development teams (3%) which typically were comprised of senior healthcare leaders/administrators. Only 21% of BSCs included perspectives using identical formatting to the original BSC description. Lessons learnt during development addressed three main themes: scorecard design, stakeholder engagement and feasibility. CONCLUSIONS: BSC frameworks have been used in various healthcare settings but frequently undergo adaptation from the original description in order to suit a specific healthcare context. Future BSCs should aim to include patients/families to promote patient-centred healthcare systems. Considering the heterogeneity evident in development approaches, methodological guidance in this area is warranted.

Improving compliance with guidelines for hypertensive disorders of pregnancy through an electronic health record alert: A retrospective chart review.

OBJECTIVES: Improve appropriate and timely administration of rapid acting antihypertensive medication for the management of hypertensive emergency in pregnancy with utilization of an automated electronic health record (EHR) alert in an academic birthplace. STUDY DESIGN: An automated alert was incorporated into an existing EHR that notified providers of a documented severe range blood pressure, defined as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 110 mmHg. Retrospective chart review was utilized to evaluate appropriate intervention before and after implementation of the alert (referred to as pre-implementation and post-implementation cohorts). MAIN OUTCOME MEASURES: The primary outcome was appropriate administration of rapid-acting antihypertensive medication for the management of hypertensive emergency. Secondary outcomes included: appropriate administration of intravenous (IV) magnesium sulfate for seizure prophylaxis, initiation of oral antihypertensive medication postpartum, and appropriate timing of follow up for blood pressure evaluation following discharge. RESULTS: Of 98 patients identified as having hypertensive emergency in the pre-implementation cohort, 34 (35%) received treatment with a rapid acting antihypertensive medication within one hour compared with 54 of 104 (55%) of patients in the post-implementation cohort (35% vs 55%, RR 1.40 95% CI 1.07-1.82). Significantly more patients followed up for a blood pressure check within one week of discharge (41% vs 31%; p = 0.02). There was not a significant effect on the administration of IV magnesium sulfate or initiation of oral medications postpartum. CONCLUSION: An automated EHR alert improved timely administration of rapid-acting antihypertensive medications for hypertensive emergency and has the potential to improve compliance with national preeclampsia guidelines.

Development of an Implementation Strategy for Patient Decision Aids in Rheumatoid Arthritis Through Application of the Behavior Change Wheel.

OBJECTIVE: Decision aids are being developed to support guideline-based rheumatology care in Canada. The study objective was to identify barriers to decision aid use in rheumatoid arthritis (RA) within a behavior change model to inform an implementation strategy. METHODS: Perspectives from Canadian health care providers (HCPs) and patients living with RA were obtained on an early RA decision aid and on perceived facilitators and barriers to decision aid implementation. Data were collected through semistructured interviews, transcribed, and then analyzed by inductive thematic analysis. The lessons learned were then mapped to the behavior change wheel COM-B system (C = capability, O = opportunity, and M = motivation interact to influence B = behavior) to inform key elements of a national implementation strategy. RESULTS: Fifteen HCPs and fifteen patients participated. The analysis resulted in five lessons learned: 1) paternalistic decision-making is a dominant practice in early RA, 2) patients need emotional support and access to educational tools to facilitate participation in shared decision-making (SDM), 3) there are many logistical barriers to decision aid implementation in current care models, 4) flexibility is necessary for successful implementation, and 5) HCPs have limited interest in further training opportunities about decision aids. Implementation recommendations included the following: 1) making the decision aids directly available to patients (O) and providing SDM education (C/M), 2) creating an SDM rheumatology curriculum (C/O/M), 3) using "decision coaches" or patient partners as peer support (C/O/M), 4) linking decision aids to "living" rheumatology guidelines (M), and 5) designing trials of patient decision aid/SDM interventions to evaluate patient-important outcomes (O/M). CONCLUSION: A multifaceted strategy is suggested to improve uptake of decision aids.

Role of bacterial infections in extracellular vesicles release and impact on immune response.

Extracellular vesicle (EV) biology involves understanding the cellular and molecular mechanisms of cell communication. Studies conducted so far with various bacterial infection models demonstrate the release of various types of EVs that include exosomes and microvesicles. Depending upon the infection and cell type, EV cargo composition changes and ultimately might impact the host immune response and bacterial growth. The mechanisms behind the EVs release, cargo composition, and impact on the immune system have not been fully investigated. Future research needs to include in vivo models to understand the relevance of EVs in host immune function during bacterial infection, and to determine aspects that are shared or species-specific in the host. This would aid in the development of EVs as therapeutics or as markers of disease.

Implementation and Evaluation of Audit and Feedback for Monitoring Treat-to-Target (T2T) Strategies in Rheumatoid Arthritis Using Performance Measures.

INTRODUCTION: In collaboration with the Alberta Medical Association's Physician Learning Program we developed individualized physician reports and held a group feedback session on rheumatoid arthritis (RA) performance measures (PM) to facilitate treat-to-target (T2T) strategies and evaluated physician experiences with this process. METHODS: 5 PMs addressing T2T concepts from an established Canadian quality framework were operationalized for physician practice reports at 2 university-affiliated rheumatology clinics. Rheum4U, a quality improvement and research platform, was the data source. The audit results were reviewed in a facilitated group feedback session. Rheumatologists provided experiential feedback on the process through survey and/or an interview. Transcripts from interviews were analyzed using a 6-step thematic analysis. RESULTS: 11 of 12 eligible rheumatologists consented to receive practice reports and provided feedback through surveys (n = 5) and interviews (n = 6). The practice reports from Rheum4U (n = 448 patients) revealed high rates of yearly follow-up (> 85%, PM1) and 100% performance on documentation of disease activity at ≥ 50% of visits (PM2). Only 34% of patients were seen within 3 months if not in remission (PM3) with 62% (2017) and 69% (2018) of those with active RA achieving a LDA state within 6 months (PM4). Approximately 70% of patients were in remission at any time point (PM5). All survey respondents agreed or strongly agreed comparison to peers was valuable and helped them reflect on their practice. Several strategies for improvement were identified, including but not limited to, leveraging of electronic records for future audit and feedback reports, providing additional granularity of results, additional stratification of results, and using high-performing peers as the comparator rather than the group mean. CONCLUSIONS: Audit and feedback was perceived by clinicians as a useful strategy for evaluating T2T efforts in RA. Future work will focus on longitudinal evaluation of the clinical impact of this quality improvement initiative.

Age, Sex, and Depot-Specific Differences in Adipose-Tissue Estrogen Receptors in Individuals with Obesity.

OBJECTIVE: The aim of this study was to examine the effects of sex and menopausal status on depot-specific estrogen signaling in white adipose tissue (AT) in age-matched men and women with morbid obesity. METHODS: A total of 28 premenopausal women, 16 postmenopausal women, and 27 age-matched men undergoing bariatric surgery were compared for omental (OM) AT (OMAT) and abdominal subcutaneous (SQ) AT (SQAT) genes and proteins. RESULTS: With the exception of fasting nonesterified fatty acids being higher in women (P < 0.01), no differences were found in other indicators of glucose and lipid metabolism. In OMAT, estrogen receptor (ER) beta (ERß) levels were higher in older women than in younger women and older men (sex-age interaction, P < 0.01), and aromatase expression was higher in older men than in older women (P < 0.05). In SQAT, women had lower expression of ERß than men (P < 0.05). Protein content of ER alpha and ERß was highly correlated with the mitochondrial protein uncoupling protein 1 across sexes and ages (P < 0.001). Age increased SQ inflammatory gene expression in both sexes. CONCLUSIONS: In morbid obesity, sex and age affect AT ERs, lipid metabolism, mitochondrial uncoupling protein 1, and inflammatory expression in an AT depot-dependent manner. The SQAT immunometabolic profile is heavily influenced by age and menopause status, more so than OMAT.

Endocervical miRNA Expression Profiles in Women Positive for Chlamydia trachomatis with Clinical Signs and/or Symptoms Are Distinct from Those in Women Positive for Chlamydia trachomatis without Signs and Symptoms.

Chlamydia trachomatis is the leading cause of sexually transmitted infections that may progress to pelvic inflammatory disease and infertility. No effective vaccine exists for Chlamydia, nor are there biomarkers available that readily predict disease progression. In this cross-sectional pilot study, we recruited symptomatic and asymptomatic women with C. trachomatis (CT) infection and asymptomatic, uninfected control women from an urban sexually transmitted disease clinic to determine if there were differences in microRNA (miRNA) expression. Infected women with signs and/or symptoms (CTSS) have distinct miRNA profiles compared to asymptomatic infected women (CTNS). In the CTSS group, miR-142 and -147 showed 2.2- to 6.9-fold increases in expression. In the CTNS group, miR-449c, -6779, -519d, -449a, and -2467 showed 3.9- to 9.0-fold increases in expression. In the CTNS group, cyclins and cell cycle regulation and IL-17 pathways were likely downregulated, while the same signaling pathways were upregulated in the CTSS group. In addition, in the CTSS group, additional inflammatory pathways associated with TNFR1 and IL-8 appear to be upregulated. The miRNA expression patterns differ between CT-infected symptomatic and asymptomatic women, and these differences may warrant further study.

LIMK (LIM Kinase) Inhibition Prevents Vasoconstriction- and Hypertension-Induced Arterial Stiffening and Remodeling.

Increased arterial stiffness and vascular remodeling precede and are consequences of hypertension. They also contribute to the development and progression of life-threatening cardiovascular diseases. Yet, there are currently no agents specifically aimed at preventing or treating arterial stiffening and remodeling. Previous research indicates that vascular smooth muscle actin polymerization participates in the initial stages of arterial stiffening and remodeling and that LIMK (LIM kinase) promotes F-actin formation and stabilization via cofilin phosphorylation and consequent inactivation. Herein, we hypothesize that LIMK inhibition is able to prevent vasoconstriction- and hypertension-associated arterial stiffening and inward remodeling. We found that small visceral arteries isolated from hypertensive subjects are stiffer and have greater cofilin phosphorylation than those from nonhypertensives. We also show that LIMK inhibition prevents arterial stiffening and inward remodeling in isolated human small visceral arteries exposed to prolonged vasoconstriction. Using cultured vascular smooth muscle cells, we determined that LIMK inhibition prevents vasoconstrictor agonists from increasing cofilin phosphorylation, F-actin volume, and cell cortex stiffness. We further show that localized LIMK inhibition prevents arteriolar inward remodeling in hypertensive mice. This indicates that hypertension is associated with increased vascular smooth muscle cofilin phosphorylation, cytoskeletal stress fiber formation, and heightened arterial stiffness. Our data further suggest that pharmacological inhibition of LIMK prevents vasoconstriction-induced arterial stiffening, in part, via reductions in vascular smooth muscle F-actin content and cellular stiffness. Accordingly, LIMK inhibition should represent a promising therapeutic means to stop the progression of arterial stiffening and remodeling in hypertension.

Utilizing multi-user virtual reality to bring clinical therapy into stroke survivors' homes.

INTRODUCTION: Lifespans after the occurrence of a stroke have been lengthening, but most stroke survivors will experience chronic impairment. Directed, repetitive practice may reduce deficits, but clinical access is often limited by a variety of factors, such as transportation. PURPOSE OF THE STUDY: To introduce a multiuser virtual reality platform that can be used to promote therapist-client interactions when the client is at home. METHODS: The Virtual Environment for Rehabilitative Gaming Exercises encourages exploration of the hand workspace by enabling multiple participants, located remotely and colocated virtually, to interact with the same virtual objects in the shared virtual space. Each user controls an avatar by corresponding movement of his or her own body segments. System performance with stroke survivors was evaluated during longitudinal studies in a laboratory environment and in participants' homes. Active arm movement was tracked throughout therapy sessions for both studies. RESULTS: Stroke survivors achieved considerable arm movement while using the system. Mean voluntary hand displacement, after accounting for trunk displacement, was greater than 350 m per therapy session for the Virtual Environment for Rehabilitative Gaming Exercises system. Compliance for home-based therapy was quite high, with 94% of all scheduled sessions completed. Having multiple players led to longer sessions and more arm movement than when the stroke survivors were trained alone. CONCLUSIONS: Multiuser virtual reality offers a relatively inexpensive means of extending clinical therapy into home and enabling family and friends to support rehabilitation efforts, even when physically remote from each other.

Does disallowing body checking in non-elite 13- to 14-year-old ice hockey leagues reduce rates of injury and concussion? A cohort study in two Canadian provinces.

OBJECTIVE: To compare rates of injury and concussion among non-elite (lowest 60% by division of play) Bantam (ages 13-14 years) ice hockey leagues that disallow body checking to non-elite Bantam leagues that allow body checking. METHODS: In this 2-year cohort study, Bantam non-elite ice hockey players were recruited from leagues where policy allowed body checking in games (Calgary/Edmonton 2014-2015, Edmonton 2015-2016) and where policy disallowed body checking (Kelowna/Vancouver 2014-2015, Calgary 2015-2016). All ice hockey game-related injuries resulting in medical attention, inability to complete a session and/or time loss from hockey were identified using valid injury surveillance methodology. Any player suspected of having concussion was referred to a study physician for diagnosis and management. RESULTS: 49 body checking (608 players) and 33 non-body checking teams (396 players) participated. There were 129 injuries (incidence rate (IR)=7.98/1000 hours) and 54 concussions (IR=3.34/1000 hours) in the body checking teams in games. After policy change, there were 31 injuries (IR=3.66/1000 hours) and 17 concussions (IR=2.01/1000 hours) in games. Policy disallowing body checking was associated with a lower rate of all injury (adjusted incidence rate ratio (IRR)=0.44; 95% CI: 0.27 to 0.74). The point estimate showed a lower rate of concussion (adjusted IRR=0.6; 95% CI: 0.31 to 1.18), but this was not statistically significant. CONCLUSION: Policy change disallowing body checking in non-elite Bantam ice hockey resulted in a 56% lower rate of injury. There is growing evidence that disallowing body checking in youth ice hockey is associated with fewer injuries.

Formula diet alters small intestine morphology, microbial abundance and reduces VE-cadherin and IL-10 expression in neonatal porcine model.

BACKGROUND: Breastfeeding is associated with a variety of positive health outcomes in children and is recommended exclusively for the first 6 months of life; however, 50-70 % of infants in the US are formula-fed. To test the hypothesis that immune system development and function in neonates and infants are significantly influenced by diet, 2-day old piglets were fed soy or milk formula (n = 6/group/gender) until day 21 and compared to a sow-fed group (n = 6/gender). METHODS: Histomorphometric analyses of ileum, jejunum and Peyer's patches were carried out, to determine the inflammation status, mRNA and protein expression of pro-inflammatory, anti-inflammatory and growth-related chemokines and cytokines. RESULTS: In formula-fed animals, increases in ileum and jejunum villus height and crypt depth were observed in comparison to sow-fed animals (jejunum, p < 0.01 villus height, p < 0.04 crypt depth; ileum p < 0.001 villus height, p < 0.002 crypt depth). In formula-fed the lymphoid follicle size (p < 0.01) and germinal centers (p < 0.01) with in the Peyer's patch were significantly decreased in comparison to sow-fed, indicating less immune education. In ileum, formula diet induced significant up-regulation of AMCFII, IL-8, IL-15, VEGFA, LIF, FASL, CXCL11, CCL4, CCL25 and down-regulation of IL-6, IL-9, IL-10, IL-27, IFNA4, CSF3, LOC100152038, and LOC100736831 at the transcript level. We have confirmed some of the mRNA data by measuring protein, and significant down-regulation of anti-inflammatory molecule IL-10 in comparison to sow-fed piglets was observed. To further determine the membrane protein expression in the ileum, VE-cadherin, occludin, and claudin-3, Western blot analyses were conducted. Sow fed piglets showed significantly more VE-Cadherin, which associated with levels of calcium, and putrescine measured. It is possible that differences in GI tract and immune development are related to shifts in the microbiome; notably, there were 5-fold higher amounts of Lactobacillaceae spp and 3 fold higher Clostridia spp in the sow fed group in comparison to milk formula-fed piglets, whereas in milk formula-fed pigs Enterobacteriaceae spp was 5-fold higher. CONCLUSION: In conclusion, formula diet alters GI morphology, microbial abundance, intestinal barrier protein VE-cadherin and anti-inflammatory molecule IL-10 expression. Further characterization of formula effects could lead to modification of infant formula to improve immune function, reduce inflammation and prevent conditions such as allergies and infections.