Acceleration of infectious disease drug discovery and development using a humanized model of drug metabolism.

A key step in drug discovery, common to many disease areas, is preclinical demonstration of efficacy in a mouse model of disease. However, this demonstration and its translation to the clinic can be impeded by mouse-specific pathways of drug metabolism. Here, we show that a mouse line extensively humanized for the cytochrome P450 gene superfamily ("8HUM") can circumvent these problems. The pharmacokinetics, metabolite profiles, and magnitude of drug-drug interactions of a test set of approved medicines were in much closer alignment with clinical observations than in wild-type mice. Infection with Mycobacterium tuberculosis, Leishmania donovani, and Trypanosoma cruzi was well tolerated in 8HUM, permitting efficacy assessment. During such assessments, mouse-specific metabolic liabilities were bypassed while the impact of clinically relevant active metabolites and DDI on efficacy were well captured. Removal of species differences in metabolism by replacement of wild-type mice with 8HUM therefore reduces compound attrition while improving clinical translation, accelerating drug discovery.

Self-Control in Pediatric Migraine Management: A Topical Review.

OBJECTIVE : This review examines the role that two types of self-control may play in youth's self-management of migraine. Although traditionally conceptualized from an inhibitory lens, self-control has both initiatory and inhibitory functions, and the authors suggest the distinction is important in relation to youth's ability to adhere to different components of migraine treatment regimens. METHODS : A topical review of the literature was conducted to identify evidence-based interventions to treat pediatric migraine and conceptualize the role self-control (both initiatory and inhibitory) may play in adherence to its regimen. Both PsycInfo and PubMed databases were used to identify relevant articles. RESULTS : Existing evidence-based interventions and recommendations for pediatric migraine require inhibitory self-control (e.g., avoiding caffeine, tobacco) and initiatory self-control (e.g., taking medication). Formal intervention programs (e.g., cognitive behavioral therapy) tend to employ initiatory self-control (e.g., modifying physical reactions in response to biofeedback). CONCLUSIONS : Understanding the distinct types of self-control required for adherence to different interventions allows for a better conceptualization of self-management of pediatric migraine. Individuals may struggle with adherence when they have deficits in one or both types of self-control skills. Future research should consider whether self-control is associated with differential adherence patterns in pediatric migraine management.

Giving adolescents with cystic fibrosis a voice: Predicting cystic fibrosis nutritional adherence from their decision-making involvement.

OBJECTIVE: Suboptimal nutritional adherence in adolescents with cystic fibrosis (awCF) has been associated with lower lung function. AwCF often have more independence in dietary decisions than younger children, yet little research has examined how adolescent decision-making relates to nutritional adherence. This study explored whether components of adolescent decision-making involvement facilitate enzyme and caloric adherence in awCF. METHODS: 37 families participated and completed study procedures. AwCF and caregivers completed electronic surveys, including the Decision-Making Involvement Scale (DMIS). The DMIS evaluated awCF behaviors during nutrition-related decision-making/discussions with caregivers using DMIS subscales: Child Seek (asking for help/advice from caregivers), Child Express (awCF stating opinions) and Joint/Options (awCF participating in joint decision-making or caregiver providing options). AwCF completed 2, 24-hr diet recalls via videoconferencing/phone to estimate adherence. Chart reviews collected medical information. DMIS subscales were regressed onto enzyme and caloric adherence. RESULTS: 43% of awCF met calorie recommendations; 48.6% took all enzymes as prescribed. Caloric adherence was positively correlated with adolescent- and parent-reported Child Seek (r = 0.53; r = 0.36) and adolescent-reported Joint/Options (r = 0.41). Per adolescent-report, the caloric adherence regression model was significant, with Child Seek contributing unique variance in caloric adherence (ß = .62, p = .03). Parent-reported adolescent-decision-making involvement significantly predicted caloric adherence, but none of the subscales contributed unique variance. No other regressions were significant. CONCLUSIONS: When awCF participated in nutrition-related discussions with a caregiver, especially with questions, caloric adherence was better. Future research should examine whether family factors influence these results. AwCF are encouraged to ask questions in nutrition discussions.

Transition readiness and coping styles in adolescents with type 1 diabetes.

PURPOSE: Although promoting positive coping and reducing negative coping improves health, little research has examined how types of coping relate to transition readiness in adolescents with type 1 diabetes (T1D). This study aimed to clarify the direct and indirect relations between coping style and transition readiness. We first examined which coping styles predict transition readiness in adolescents with T1D and then explored whether diabetes distress mediates the relation between disengagement coping and transition readiness. DESIGN AND METHODS: Using a cross-sectional observational design, 68 families with an adolescent with T1D were recruited during routine clinic appointments. Surveys on family demographics, coping styles, transition readiness, and diabetes distress were completed electronically. Medical information was extracted from electronic health records. RESULTS: Neither primary control, secondary control, nor disengagement coping had a direct significant association with transition readiness after controlling for HbA1c. There was a significant indirect effect of disengagement coping on transition readiness through greater diabetes distress (adolescent report ß = -0.13; 95% CI, LL = -0.27, UL = -0.02; parent report ß = -0.12; 95% CI, LL = -0.26, UL = -0.02). CONCLUSIONS: Coping style did not have a direct effect on transition readiness. However, disengagement coping was associated with diabetes distress, which in turn was significantly related to transition readiness. PRACTICE IMPLICATIONS: Clinicians and researchers should consider incorporating coping strategies within transition readiness interventions to decrease distress and improve transition readiness. Disease-specific psychosocial screening may enhance routine diabetes transition education.

Pictorial versus written asthma action plans for youth: initial impact on regimen knowledge, medication adherence, symptom control, and family satisfaction.

OBJECTIVE: Asthma action plans (AAP) are recommended to guide asthma management. Written AAPs (WAAPs) are under-utilized and can be difficult to understand. Our study designed and tested a simplified pictorial AAP (PAAP). We hypothesized that better outcomes would be obtained for youth with the PAAP. METHODS: One hundred and sixty-nine (169) youth (aged 8-17; AAP-naïve) were screened for this pilot, 2-arm randomized controlled trial. Feasibility, usability and preliminary efficacy of PAAP compared to a WAAP, for improving outcomes (inhaled corticosteroid (ICS) adherence, symptom control, AAP knowledge, AAP satisfaction) were assessed quantitatively. Youth received an AAP from their physician after completing baseline measures and completed measures at three additional time points (1-, 3-, and 6-month). RESULTS: Forty-five youth were recruited (PAAP = 22; WAAP = 23). Youth AAP knowledge was higher for the PAAP group compared to the WAAP group (p = .017). ICS adherence did not differ between groups, over time, or based on prescribed dosing; however, for WAAP participants, adherence was lower with a higher daily prescription (4 puffs) relative to a lower dose (p = .006). Symptom control improved with both AAPs, but the change was not statistically significant. Lung function did not change significantly by AAP type or time, and literacy variables were not related significantly to outcomes. Youth satisfaction with AAP improved significantly for the PAAP group compared to the WAAP group (p = .03). CONCLUSIONS: Higher AAP knowledge and satisfaction among youth in the PAAP group suggests that structured education from a physician using a PAAP is beneficial. Intervention and study design insights gained will guide future research.

Predicting Adolescent Electronic Cigarette Use: Differences by Never, Ever, and Current Users.

OBJECTIVE: Rising rates of adolescent electronic cigarette (ECIG) use is concerning because it can lead to adverse health outcomes and increased risk behavior. There are known predictors of ever versus never ECIG use, but less are known about risk factors for ever versus current use of ECIGs. Problem behavior theory (PBT) was used to evaluate possible risk factors for different ECIG use status. METHODS: Participants were 573 high school students who completed questionnaires measuring ECIG use, as well as constructs within the Social Environment, Perceived Environment, Personality, and Behavior domains of PBT. Multinomial logistic regression was used to evaluate how predictor variables differentiated between participants who reported (a) never use, (b) ever ECIG use, or (c) current ECIG use. RESULTS: Adolescents were more likely to endorse ever ECIG use than never use if they reported peer ECIG use, perceived more benefits and fewer costs (e.g., health) of ECIG use, higher extraversion, alcohol and cigarette use (never vs. ever vs. past 30 days), or attended a school with a higher percentage of socioeconomically disadvantaged students. Adolescents were more likely to report current ECIG use than ever ECIG use if they perceived fewer costs of ECIG use or used cannabis in their lifetime (yes/no). CONCLUSIONS: PBT variables differentiated between ever ECIG use and never ECIG use. However, these variables did not differentiate between ever and current ECIG use. Identifying unique risk factors for current versus ever ECIG use is important to understanding persistent ECIG use and subsequent targeted prevention and intervention programs.

Validation of the Electronic Cigarette Expectancy Scale for Adolescents.

INTRODUCTION: Expectancies of costs and benefits can be predictive of tobacco use, as well as cessation attempts and success. Measuring electronic cigarette (ECIG) expectancies is in its infancy, particularly among adolescents. However, the popularity of adolescent ECIG use demonstrates the need to understand better these contributing factors. Our aim was to evaluate the factor structure and initial psychometric properties of an ECIG expectancies questionnaire adapted from an existing validated scale for conventional cigarette smoking (Smoking Expectancy Scale for Adolescents; SESA). METHODS: Five-hundred sixty-nine adolescents (14-18 years; 60.1% female; 84.1% White) were recruited from high schools and an adolescent medicine clinic. Participants completed a battery of self-report measures, including the ECIG Expectancies Scale for Adolescents (EESA). Exploratory factor analyses were used to examine the underlying factor structure, and convergent validity was evaluated using variables conceptually related to ECIG expectancies. RESULTS: A three-factor solution was chosen based on statistical evidence and conceptual relevance. All three factors - Costs, Social Benefits, and Affective/Weight Benefits - had strong internal consistencies and demonstrated convergent validity via significant associations with peer ECIG use and Conscientiousness. The Costs and Affective/Weight Benefits factors also demonstrated convergent validity with sensation-seeking, intention to use ECIGs, and ECIG use status (current, lifetime, nonuser). CONCLUSION: Results support the initial reliability and validity of the EESA scores. This factor structure is related to, yet different from, that observed not only for the SESA but also for other ECIG-expectancy measures among adult populations.

The Cyclical Relation Between Chronic Pain, Executive Functioning, Emotional Regulation, and Self-Management.

OBJECTIVE: To propose a new model outlining a hypothesized cyclical relation between executive functioning, emotional regulation, and chronic pain in adolescence and to highlight the likely importance of such a relation for self-management behavior and pain-related disability. METHODS: A review of the existing literature that critically explores the role of executive functioning in understanding chronic pain experiences and self-management in adolescence in order to develop the Cyclical model Of Pain, Executive function, emotion regulation, and Self-management (COPES). RESULTS: Growing evidence points towards a potential cyclical relation between chronic pain and impaired executive functioning, which forms the basis of COPES. The COPES model proposes that the relative immaturity of executive functioning in adolescence negatively influences their ability to engage with self-management, which in turn increases adolescents' disability due to pain and contributes to the maintenance of chronic pain, which perpetuates the reduced capacity of executive functioning. The moderating influence of flexible parental support is hypothesized to offset some of these influences. However, the available evidence is limited due to methodological shortcomings such as large variety in executive functioning operationalization, reliance on self-report and cross-sectional designs. CONCLUSIONS: It is anticipated that the COPES model will stimulate more systematic, theory-driven research to further our understanding of the links between executive functioning, chronic pain, self-management, and wellbeing. Such enhanced understanding has the potential to drive forward intervention development and refinement aimed at improving self-management uptake and adherence amongst adolescents with chronic pain.

Associations Between Peer Use, Costs and Benefits, Self-Efficacy, and Adolescent E-cigarette Use.

OBJECTIVE: Prior research identified peer use as a salient risk factor of adolescent electronic cigarette (e-cigarette) use, but has not expanded on the mechanisms of this association. METHODS: Participants were 562 adolescents recruited from rural and suburban public high schools and an adolescent medicine clinic in the mid-Atlantic United States. Participants completed a packet of questionnaires that assessed demographics, substance use, expectations about the consequences of e-cigarette use, and perceptions of their own self-efficacy to resist using e-cigarettes. We estimated a series of mediation models using the MODEL INDIRECT command in MPLUS statistical software. In all models, significance of indirect effects from peer e-cigarette use to self-reported e-cigarette use were tested via two variables: (a) expected costs, (b) benefits of e-cigarette use, and (c) the perceived self-efficacy of the individual to refrain from e-cigarette use. RESULTS: Adolescents with more peers using e-cigarettes were more likely to have ever used an e-cigarette and perceived greater benefits and fewer costs, which was associated with a reduced self-efficacy to refrain from e-cigarette smoking (Model 1). Those with more peers using e-cigarettes were more likely to be currently using e-cigarettes themselves because they perceived greater benefits and fewer costs, which was associated with a reduced self-efficacy to refrain from e-cigarette smoking (Model 2). CONCLUSION: Peer use, self-efficacy to resist use, and expectations of cost and benefits of e-cigarette use should be considered as possible targets when devising tailored interventions and policies to prevent or reduce negative health consequences of long-term e-cigarette use.

Accuracy of Body Size Estimation in Youth with Cystic Fibrosis and Association with Health-Related Quality of Life.

Accuracy of body size estimation may impact motivation to adhere to treatment recommendations and health-related quality of life (HRQOL) in youth with cystic fibrosis (CF), but this has not yet been investigated. Thus, the goal of the current study was to examine accuracy of body size estimation in youth with CF, and associations with HRQOL, lung functioning, and dietary intake. Fifty-four youth diagnosed with CF (M = 13.61 years) completed the Figure Rating Scale, the Cystic Fibrosis Questionnaire-Revised, and a 24-h diet recall interview. Cohen's Weighted Kappa Coefficient evaluated agreement between body size estimation and BMI percentile. Binary logistic regression analyses examined associations between body size accuracy and HRQOL, lung functioning, and dietary intake. A less than adequate agreement was found between youth body size estimation and BMI percentile. Most participants overestimated body size (69.8%). Body Image HRQOL, but neither lung functioning nor dietary intake, was significantly associated with body size estimation accuracy. Working with patients to improve perceptions of body size may also improve HRQOL scores and allow for discussion about treatment goals related to body size.

Developing pictorial asthma action plans to promote self-management and health in rural youth with asthma: A qualitative study.

OBJECTIVE: Asthma action plans (AAPs) provide asthma management instructions to families; however, AAPs typically are written at a 7th-9th grade reading level, making them less useful in lower literacy families. There is a need to develop simpler AAP formats and content to optimize their utility across all families, including those who are rural and may be at a risk for literacy concerns. Because using pictures can simplify and enhance health education, our study's aim was to develop a pictorial AAP through a series of focus groups with key stakeholders - youth with asthma, caregivers, and physicians. METHODS: Fourteen caregiver/youth dyads and four physicians participated in separate focus groups where their preferences for pictorial AAP structure and content were obtained. Focus groups were audio recorded, transcribed, coded with ATLAS.ti, and analyzed for themes. RESULTS: Youth and their caregivers prefer that the AAPs include simple, cartoon-like pictures customized to the patient. Physicians emphasized AAP's capability to display pictures of controller medication given its importance in preventing asthma exacerbations. A stoplight format, currently used in most written AAPs, received positive reviews. Specific suggestions for pictures showing symptoms, medications, and how to take medication were suggested. Words and short phrases accompanying the pictures were thought to add clarity. CONCLUSIONS: Key stakeholders viewed pictorial AAPs as positive and potentially effective alternatives to standard written AAPs. It is expected that low literacy youth and caregivers would more easily understand a pictorial AAP presentation, which should facilitate better medication adherence and asthma outcomes in these children.

A Quality Improvement Initiative to Improve Patient Adherence to Vitamin Supplementation in Cystic Fibrosis.

OBJECTIVES: Patients with cystic fibrosis (CF) and pancreatic insufficiency are prescribed fat-soluble vitamins, although compliance remains low. Our objective was to identify patient and caregiver knowledge deficits regarding vitamin supplementation, provide targeted education, and examine serum vitamin levels pre-and posteducation. METHODS: This prospective quality improvement study involved 118 patients. A vitamin knowledge survey was given to patients/caregivers during a clinic visit, education was provided targeting knowledge deficits, and the survey was re-administered at the next clinic visit. Serum vitamin levels were collected at pre- and postsurvey. RESULTS: Results showed significant pre-post increases for patient and caregiver knowledge scores, and significant decreases in self-reported nonadherence to vitamin use and number of reported barriers affecting adherence. A significant change in vitamin E level to therapeutic range post-education was demonstrated. CONCLUSIONS: Our brief, targeted educational interventions regarding vitamin supplementation showed utility in a routine clinic setting.

A Pilot Study of the Efficacy of Active Leptospermum Honey for the Treatment of Partial-Thickness Facial Burns.

OBJECTIVE: Research suggests that active Leptospermum honey (ALH) improves outcomes in patients with partial-thickness burns by enhancing healing and reepithelialization rates, as well as by protecting against antibiotic-resistant microorganisms. This study assessed the effectiveness of ALH gel on healing time, bacterial growth, patient satisfaction, and cost of treatment. DESIGN: Single-arm, prospective case series. SETTING AND PATIENTS: Seven patients (aged 7-64 years) with partial-thickness facial burns were recruited from a northeastern US burn center. INTERVENTION: All patients cleansed their wounds daily with soap and water, after which they applied ALH gel. MAIN OUTCOME MEASURES: Three physicians independently rated healing using wound photography and daily tests for the presence of exudate. Wound cultures on days 1 and 7 (±2 days) assessed bacterial growth. Patients completed a satisfaction survey at the end of treatment, and cost of treatment was calculated. MAIN RESULTS: Healing time ranged from 3 to 14 days (mean, 8.1 days). Wound cultures revealed normal bacterial growth on days 1 and 7 for all patients. Patients rated ALH gel favorably, with the most common complaint of stickiness in 5 patients. One patient experienced transient burning on application that did not interrupt treatment. Average hospital-based cost of treatment was $26.15 per patient. CONCLUSIONS: Healing time was congruent with or better than what would have been expected with standard treatment. Furthermore, despite no antibiotic treatment, wound culture results yielded no abnormal bacterial growth. Finally, patients overall reported satisfaction with treatment. The findings of this study suggest that ALH is a clinically and economically valuable treatment for partial-thickness facial burns.

Factors related to the psychosocial functioning of youth with neonatal brachial plexus injuries.

OBJECTIVE: Owing to the possible visible nature and functional impairments associated with neonatal brachial plexus injuries (NBPI), the current study investigated the relations of injury severity, social support, and coping strategies to social difficulties and self-concept in youth with NBPI. METHODS: 88 children (aged 10-17 years) with NBPI and their parent(s) were recruited from a national organization and two brachial plexus clinics. Participants completed a variety of questionnaires during their scheduled clinic visits. RESULTS: More social support from classmates was associated with better self-concept and fewer social difficulties. Less frequent use of negative coping strategies was associated with better self-concept and fewer social difficulties and was a significant moderator of the relation between injury severity and self-concept. CONCLUSIONS: Clinicians who work with children with NBPI should consider peer support and coping strategies when promoting the psychosocial functioning of these youth.

Association of caregiver health beliefs and parenting stress with medication adherence in preschoolers with asthma.

OBJECTIVE: This study examined the associations of parenting stress and caregiver negative health beliefs with medication adherence in a sample of preschool-aged children with asthma. METHODS: Participants included 43 caregivers and their child with asthma, aged 2-5 years, who were prescribed a preventative or controller medication. Assessment included parent report of parenting stress associated with parental characteristics and difficult child behavior, health-related beliefs, and adherence to inhaled corticosteroids (ICS). Pharmacy refill records were reviewed to measure medication adherence objectively. Statistical analyses included paired samples t-test and Pearson's correlation coefficients. RESULTS: Parent-report and objective measures of adherence to ICS were significantly different, with parents reporting significantly higher rates of medication adherence (p < 0.001). Also, increased caregiver negative health beliefs, but not parenting stress, were significantly and negatively associated with an objective measure of ICS adherence (p < 0.01). CONCLUSIONS: Because the findings for parenting stress are not consistent with that of the literature on school-aged children with asthma, our results may suggest that preschool children are a unique developmental group. A review of endorsed health beliefs also highlights strengths and concerns for caregivers of these very young children. Overall, our study findings underscore the importance of caregivers' health-related beliefs in promoting adherence to ICS in young children with asthma.

Adherence in young people living with juvenile arthritis: A systematic review.

Objective: Juvenile idiopathic arthritis (JIA) is one of the leading causes of chronic pain in pediatric patients. Treatment regimens, which are critical to symptom management, can be burdensome, involving medication with potentially aversive side effects and exercise that can cause joint pain. Thus, it is important to examine the barriers and facilitators to adherence in JIA. While systematic reviews exist for rheumatic disease in adults, there has not yet been a synthesis of the literature examining adherence in JIA. Methods: PsychINFO, PubMed and MEDLINE databases were systematically searched to identify qualitative and quantitative empirical studies that investigate adherence for JIA. Keywords included: patient compliance OR adherence OR persistence; youth OR children OR juvenile OR pediatric OR teen OR child OR adolescent; and rheumatoid arthritis OR idiopathic arthritis OR arthritis. Articles were excluded from the review if they involved non-human or adult samples, were non-experimental (e.g., practice recommendations), were not peer-reviewed, or were not written in English. After abstract selection, 32 articles were included in the analyses. Results: Adherence to exercise regimens was consistently lower than adherence to medication. Researchers relied heavily on self-report of adherence, which suggests a need for additional research with more objective measures of adherence. Across studies, psychological treatment was not included, so adherence to this treatment component in JIA remains understudied. Conclusions: Results suggest that future research should target devising and evaluating interventions to improve adherence to exercise and perhaps psychological treatment. Implications for Impact: To facilitate adherence in JIA, behavioral health providers should focus on building a strong therapeutic alliance between provider and child, fostering positive coping skills in parents and children, and monitoring the parent-child relationship.

Sleep Patterns, Pain, and Emotional Functioning in Youth with Inflammatory Bowel Disease.

Objective: Youth with inflammatory bowel disease (IBD) may be at increased risk for sleep difficulties due to the painful and inflammatory nature of their disease. Moreover, children and adolescents with IBD experience impairment across a variety of psychosocial domains. However, researchers have yet to investigate the complex interplay between sleep, disease-related symptoms, and psychosocial factors in this population. The purpose of this study was to examine sleep patterns, pain, and mood in pediatric IBD. Methods: A sample of 25 children and adolescents with IBD (Mage = 14.24, Range = 10-18 years; 56% male) were recruited from a pediatric gastroenterology clinic. Youth wore an actigraphy watch and completed daily measures of affect and pain over the course of 14 days. Statistical analyses involved repeated measures general estimating equations. Results: No significant association for sleep with negative affect was demonstrated. Despite majority of this sample being in disease remission, results revealed that increased sleep onset latency was associated with presence of next day pain and pain was associated with better next night sleep efficiency. Conclusions: Findings of the current study suggest youth with IBD experience poor sleep quality, which is significantly related to the pain they experience. Consequently, healthcare providers should screen for and address sleep quality to optimize outcomes in their pediatric patients. Objectively assessing sleep patterns (e.g., actigraphy) may prove useful for pediatric IBD samples; however, additional research is needed to determine actigraphy's feasibility and efficacy in assessing sleep patterns in real world settings (e.g., pediatric medical clinics).

Comparing the effects of various fluid resuscitative strategies on Glycocalyx damage in a canine hemorrhage model.

Hemorrhagic shock and subsequent resuscitation can cause significant dysregulation of critical systems, including the vascular endothelium. Following hemorrhage, the endothelial lining (glycocalyx) can shed, causing release of glycocalyx components, endothelial activation, and systemic inflammation. A canine model of hemorrhagic shock was used to evaluate five resuscitation fluids, including Lactated Ringers+Hetastarch, Whole Blood (WB), Fresh Frozen Plasma+packed Red Blood Cells (FFP+pRBC), and two hemoglobin-based oxygen carrier (HBOC) fluids, for their impact on glycocalyx shedding. Under anesthesia, purpose-bred adult canines were instrumented and subjected to a controlled hemorrhage with blood being drawn until a mean arterial pressure of <50 mmHg was reached or 40 % of the estimated blood volume was removed. Canines were left in shock for 45 mins before being resuscitated with one of the resuscitation fluids over 30 mins. Following resuscitation, the dogs were monitored up to 2 weeks. Following an additional 3-4 weeks for washout, the canines repeated the protocol, undergoing each resuscitation fluid individually. Blood samples were collected during each round at various timepoints for serum isolation, which was used for detection of glycocalyx biomarker. Comparison of baseline and post-hemorrhage alone showed a significant reduction in serum protein (p<0.0001), heparan sulfate (p<0.001), and syndecan-1 (p<0.0001) concentrations, and a significant increase in hyaluronan (p<0.0001) concentration. Intercomparisons of resuscitation fluids indicated minimal differences in glycocalyx markers over time. Comparisons within each fluid showed dynamic responses in glycocalyx biomarkers over time. Relative to individual baselines, syndecan-1 was significantly reduced after resuscitation in most cases (p<0.0001), excluding WB and FFP+pRBC. In all cases, VE-cadherin was significantly elevated at 24 hr compared to baseline (p<0.001). Hyaluronan was significantly elevated by 3 hr in all cases (p<0.01), except for HBOC fluids. Total glycosaminoglycans were significantly reduced only at 3 hr (p<0.001) for non-HBOC fluids. Similarly, heparan sulfate was significantly reduced with all fluids between resuscitation and 24 hr (p<0.01), except WB. The temporal changes in canine glycocalyx biomarkers were atypical of hemorrhage response in other species. This suggests that the hemorrhage lacked severity and/or typical glycocalyx biomarkers do not reflect the canine endothelium compared to other species. Further research is needed to characterize the canine endothelium and the response to resuscitation fluids.