Mediators of Metabolism: An Unconventional Role for NOD1 and NOD2.

In addition to their classical roles as bacterial sensors, NOD1 and NOD2 have been implicated as mediators of metabolic disease. Increased expression of NOD1 and/or NOD2 has been reported in a range of human metabolic diseases, including obesity, diabetes, non-alcoholic fatty liver disease, and metabolic syndrome. Although NOD1 and NOD2 share intracellular signaling pathway components, they are differentially upregulated on a cellular level and have opposing impacts on metabolic disease development in mouse models. These NOD-like receptors may directly mediate signaling downstream of cell stressors, such as endoplasmic reticulum stress and calcium influx, or in response to metabolic signals, such as fatty acids and glucose. Other studies suggest that stimulation of NOD1 or NOD2 by their bacterial ligands can result in inflammation, altered insulin responses, increased reactive oxygen signaling, and mitochondrial dysfunction. The activating stimuli for NOD1 and NOD2 in the context of metabolic disease are controversial and may be a combination of both metabolic and circulating bacterial ligands. In this review, we will summarize the current knowledge of how NOD1 and NOD2 may mediate metabolism in health and disease, as well as highlight areas of future investigation.

Sequestered Alkaloid Defenses in the Dendrobatid Poison Frog Oophaga pumilio Provide Variable Protection from Microbial Pathogens.

Most amphibians produce their own defensive chemicals; however, poison frogs sequester their alkaloid-based defenses from dietary arthropods. Alkaloids function as a defense against predators, and certain types appear to inhibit microbial growth. Alkaloid defenses vary considerably among populations of poison frogs, reflecting geographic differences in availability of dietary arthropods. Consequently, environmentally driven differences in frog defenses may have significant implications regarding their protection against pathogens. While natural alkaloid mixtures in dendrobatid poison frogs have recently been shown to inhibit growth of non-pathogenic microbes, no studies have examined the effectiveness of alkaloids against microbes that infect these frogs. Herein, we examined how alkaloid defenses in the dendrobatid poison frog, Oophaga pumilio, affect growth of the known anuran pathogens Aeromonas hydrophila and Klebsiella pneumoniae. Frogs were collected from five locations throughout Costa Rica that are known to vary in their alkaloid profiles. Alkaloids were isolated from individual skins, and extracts were assayed against both pathogens. Microbe subcultures were inoculated with extracted alkaloids to create dose-response curves. Subsequent spectrophotometry and cell counting assays were used to assess growth inhibition. GC-MS was used to characterize and quantify alkaloids in frog extracts, and our results suggest that variation in alkaloid defenses lead to differences in inhibition of these pathogens. The present study provides the first evidence that alkaloid variation in a dendrobatid poison frog is associated with differences in inhibition of anuran pathogens, and offers further support that alkaloid defenses in poison frogs confer protection against both pathogens and predators.

Population-Tailored Care for Homeless Veterans and Acute Care Use, Cost, and Satisfaction: A Prospective Quasi-Experimental Trial.

INTRODUCTION: Although traditional patient-centered medical homes (PCMHs) are effective for patients with complex needs, it is unclear whether homeless-tailored PCMHs work better for homeless veterans. We examined the impact of enrollment in a Veterans Health Administration (VHA) homeless-tailored PCMH on health services use, cost, and satisfaction compared with enrollment in a traditional, nontailored PCMH. METHODS: We conducted a prospective, multicenter, quasi-experimental, single-blinded study at 2 VHA medical centers to assess health services use, cost, and satisfaction during 12 months among 2 groups of homeless veterans: 1) veterans receiving VHA homeless-tailored primary care (Homeless-Patient Aligned Care Team [H-PACT]) and 2) veterans receiving traditional primary care services (PACT). A cohort of 266 homeless veterans enrolled from June 2012 through January 2014. RESULTS: Compared with PACT patients, H-PACT patients had more social work visits (4.6 vs 2.7 visits) and fewer emergency department (ED) visits for ambulatory care-sensitive conditions (0 vs 0.2 visits); a significantly smaller percentage of veterans in H-PACT were hospitalized (23.1% vs 35.4%) or had mental health-related ED visits (34.1% vs 47.6%). We found significant differences in primary care provider-specific visits (H-PACT, 5.1 vs PACT, 3.6 visits), mental health care visits (H-PACT, 8.8 vs PACT, 13.4 visits), 30-day prescription drug fills (H-PACT, 40.5 vs PACT, 58.8 fills), and use of group therapy (H-PACT, 40.1% vs PACT, 53.7%). Annual costs per patient were significantly higher in the PACT group than the H-PACT group ($37,415 vs $28,036). In logistic regression model of acute care use, assignment to the H-PACT model was protective as was rating health "good" or better. CONCLUSION: Homeless veterans enrolled in the population-tailored primary care approach used less acute care and costs were lower. Tailored-care models have implications for care coordination in the US Department of Veterans Affairs VA and community health systems.

Persistent Super-Utilization of Acute Care Services Among Subgroups of Veterans Experiencing Homelessness.

BACKGROUND: Acute health care utilization often occurs among persons experiencing homelessness. However, knowing which individuals will be persistent super-utilizers of acute care is less well understood. OBJECTIVE: The objective of the study was to identify those more likely to be persistent super-utilizers of acute care services. RESEARCH DESIGN: We conducted a latent class analysis of secondary data from the Veterans Health Administration Corporate Data Warehouse, and Homeless Operations Management and Evaluation System. The study sample included 16,912 veterans who experienced homelessness and met super-utilizer criteria in any quarter between July 1, 2014 and December 31, 2015. The latent class analysis included veterans' diagnoses and acute care utilization. RESULTS: Medical, mental health, and substance use morbidity rates were high. More than half of the sample utilized Veterans Health Administration Homeless Programs concurrently with their super-utilization of acute care. There were 7 subgroups of super-utilizers, which varied considerably on the degree to which their super-utilization persisted over time. Approximately a third of the sample met super-utilizer criteria for ≥3 quarters; this group was older and disproportionately male, non-Hispanic white, and unmarried, with lower rates of post-9/11 service and higher rates of rural residence and service-connected disability. They were much more likely to be currently homeless with more medical, mental health, and substance use morbidity. CONCLUSION: Only a subset of homeless veterans were persistent super-utilizers, suggesting the need for more targeted interventions.

Screening for Food Insecurity in Six Veterans Administration Clinics for the Homeless, June-December 2015.

OBJECTIVE: We assessed findings from a food-insecurity screening of a national sample of Veterans Administration clinics for homeless and formerly homeless veterans. METHODS: We reviewed results from initial screenings administered at 6 Veterans Administration primary care clinics for the homeless and responses from clinic staff members interviewed about the screening program. RESULTS: A total of 270 patients were screened. The average age was 53 years, and most were male (93.1%). Screening showed a high prevalence of food insecurity. Of the 270, 48.5% reported they experienced food insecurity in the previous 3 months, 55.0% reported averaging 2 meals a day, and 27.3% averaged 1 meal a day. Eighty-seven percent prepared their own meals, relying on food they bought (54.2%), help from friends and family (19.1%), and soup kitchens and food pantries (22%); 47.3% received Supplemental Nutrition Assistance Program benefits (food stamps). Additionally, of those who screened positive for food insecurity 19.8% had diabetes or prediabetes, and 43.5% reported hypoglycemia symptoms when without food. Clinic staff members responded positively to the screening program and described it as a good rapport builder with patients. CONCLUSIONS: Integrating screening for food insecurity among patients in clinical settings was well received by both patients and health care providers. Addressing these positive findings of food insecurity requires a multidisciplinary health care approach.

Which Homeless Veterans Benefit From a Peer Mentor and How?

OBJECTIVE: Veterans Affairs (VA) is expanding peer support. Research is limited on Veterans' perspective on benefits from peer services. We describe homeless Veteran perceptions of value and examine characteristics associated with benefit. METHOD: From a sample of Veterans in a multisite randomized control trial, we studied addition of peers in VA Primary Care and homeless-oriented primary care clinics. We used qualitative methods to study the perceptions of peer services among a subsample of homeless Veterans. Quantitative methods were used to validate findings in both samples. RESULTS: Sixty-five percent of the subsample and 83% of the full sample benefited from a peer mentor. Participants who benefited had more peer visits and minutes of intervention (p<.05), were more likely to be minority, and were less likely to have posttraumatic stress disorder. CONCLUSION: The majority of Veteran participants in this study benefited from receiving peer mentor intervention. African American Veterans were more likely to benefit and Veterans with PTSD were less likely to benefit. Client endorsement of the peer's role influenced outcomes.

Tailoring Care to Vulnerable Populations by Incorporating Social Determinants of Health: the Veterans Health Administration's "Homeless Patient Aligned Care Team" Program.

INTRODUCTION: Although the clinical consequences of homelessness are well described, less is known about the role for health care systems in improving clinical and social outcomes for the homeless. We described the national implementation of a "homeless medical home" initiative in the Veterans Health Administration (VHA) and correlated patient health outcomes with characteristics of high-performing sites. METHODS: We conducted an observational study of 33 VHA facilities with homeless medical homes and patient- aligned care teams that served more than 14,000 patients. We correlated site-specific health care performance data for the 3,543 homeless veterans enrolled in the program from October 2013 through March 2014, including those receiving ambulatory or acute health care services during the 6 months prior to enrollment in our study and 6 months post-enrollment with corresponding survey data on the Homeless Patient Aligned Care Team (H-PACT) program implementation. We defined high performance as high rates of ambulatory care and reduced use of acute care services. RESULTS: More than 96% of VHA patients enrolled in these programs were concurrently receiving VHA homeless services. Of the 33 sites studied, 82% provided hygiene care (on-site showers, hygiene kits, and laundry), 76% provided transportation, and 55% had an on-site clothes pantry; 42% had a food pantry and provided on-site meals or other food assistance. Six-month patterns of acute-care use pre-enrollment and post-enrollment for 3,543 consecutively enrolled patients showed a 19.0% reduction in emergency department use and a 34.7% reduction in hospitalizations. Three features were significantly associated with high performance: 1) higher staffing ratios than other sites, 1) integration of social supports and social services into clinical care, and 3) outreach to and integration with community agencies. CONCLUSION: Integrating social determinants of health into clinical care can be effective for high-risk homeless veterans.

Tailoring Outreach Efforts to Increase Primary Care Use Among Homeless Veterans: Results of a Randomized Controlled Trial.

BACKGROUND: Homeless individuals often have significant unmet health care needs that are critical to helping them leave homelessness. However, engaging them in primary and mental health care services is often elusive and difficult to achieve. OBJECTIVE: We aimed to increase health-seeking behavior and receipt of health care among homeless Veterans. DESIGN: This was a multi-center, prospective, community-based, two-by-two randomized controlled trial of homeless Veterans. PARTICIPANTS: Homeless Veterans not receiving primary care participated in the study. INTERVENTIONS: An outreach intervention that included a personal health assessment and brief intervention (PHA/BI), and/or a clinic orientation (CO) was implemented. MAIN MEASURE: We measured receipt of primary care within 4 weeks of study enrollment. KEY RESULTS: Overall, 185 homeless Veterans were enrolled: the average age was 48.6 years (SD 10.8), 94.6% were male, 43.0% were from a minority population, 12.0% were unsheltered, 25.5% were staying in a dusk-to-dawn emergency shelter, 26.1% were in transitional housing, while 27.7% were in an unstable, doubled-up arrangement. At one month, 77.3% of the PHA/BI plus CO group accessed primary care and by 6 months, 88.7% had been seen in primary care. This was followed by the CO-only group, 50.0% of whom accessed care in the first 4 weeks, the PHI/BI-only arm at 41.0% and the Usual Care arm at 30.6%. Chi-squared tests by group were significant (p < 0.001) at both 4 weeks and 6 months. There was no difference in attitudes about care at baseline and 6 months or in use patterns once enrolled in care. CONCLUSIONS: Our findings suggest that treatment-resistant/avoidant homeless Veterans can be effectively engaged in primary and other clinical care services through a relatively low intensity, targeted and tailored outreach effort.

Effects of experimentally elevated traffic noise on nestling white-crowned sparrow stress physiology, immune function and life history.

Roads have been associated with behavioral and physiological changes in wildlife. In birds, roads decrease reproductive success and biodiversity and increase physiological stress. Although the consequences of roads on individuals and communities have been well described, the mechanisms through which roads affect birds remain largely unexplored. Here, we examine one mechanism through which roads could affect birds: traffic noise. We exposed nestling mountain white-crowned sparrows (Zonotrichia leucophrys oriantha) to experimentally elevated traffic noise for 5 days during the nestling period. Following exposure to traffic noise we measured nestling stress physiology, immune function, body size, condition and survival. Based on prior studies, we expected the traffic noise treatment to result in elevated stress hormones (glucocorticoids), and declines in immune function, body size, condition and survival. Surprisingly, nestlings exposed to traffic noise had lower glucocorticoid levels and improved condition relative to control nests. These results indicate that traffic noise does affect physiology and development in white-crowned sparrows, but not at all as predicted. Therefore, when evaluating the mechanisms through which roads affect avian populations, other factors (e.g. edge effects, pollution and mechanical vibration) may be more important than traffic noise in explaining elevated nestling stress responses in this species.

New to care: demands on a health system when homeless veterans are enrolled in a medical home model.

OBJECTIVES: We compared service use among homeless and nonhomeless veterans newly enrolled in a medical home model and identified patterns of use among homeless veterans associated with reductions in emergency department (ED) use. METHODS: We used case-control matching with a nested cohort analysis to measure 6-month health services use, new diagnoses, and care use patterns in veterans at the Providence, Rhode Island, Veterans Affairs Medical Center from 2008 to 2011. RESULTS: We followed 127 homeless and 106 nonhomeless veterans. Both groups had similar rates of chronic medical and mental health diagnoses; 25.4% of the homeless and 18.1% of the nonhomeless group reported active substance abuse. Homeless veterans used significantly more primary, mental health, substance abuse, and ED care during the first 6 months. Homeless veterans who accessed primary care at higher rates (relative risk ratio [RRR] = 1.46; 95% confidence interval [CI] = 1.11, 1.92) or who used specialty and primary care (RRR = 10.95; 95% CI = 1.58, 75.78) had reduced ED usage. Homeless veterans in transitional housing or doubled-up at baseline (RRR = 3.41; 95% CI = 1.24, 9.42) had similar reductions in ED usage. CONCLUSIONS: Homeless adults had substantial health needs when presenting for care. High-intensity primary care and access to specialty care services could reduce ED use.

A novel murine model of pyoderma gangrenosum reveals that inflammatory skin-gut crosstalk is mediated by IL-1ß-primed neutrophils.

Pyoderma gangrenosum (PG) is a debilitating skin condition often accompanied by inflammatory bowel disease (IBD). Strikingly, ~40% of patients that present with PG have underlying IBD, suggesting shared but unknown mechanisms of pathogenesis. Impeding the development of effective treatments for PG is the absence of an animal model that exhibits features of both skin and gut manifestations. This study describes the development of the first experimental drug-induced mouse model of PG with concomitant intestinal inflammation. Topical application of pyrimidine synthesis inhibitors on wounded mouse skin generates skin ulcers enriched in neutrophil extracellular traps (NETs) as well as pro-inflammatory cellular and soluble mediators mimicking human PG. The mice also develop spontaneous intestinal inflammation demonstrated by histologic damage. Further investigations revealed increased circulating low density IL-1ß primed neutrophils that undergo enhanced NETosis at inflamed tissue sites supported by an increase in circulatory citrullinated histone 3, a marker of aberrant NET formation. Granulocyte depletion dampens the intestinal inflammation in this model, further supporting the notion that granulocytes contribute to the skin-gut crosstalk in PG mice. We anticipate that this novel murine PG model will enable researchers to probe common disease mechanisms and identify more effective targets for treatment for PG patients with IBD.

Enhancing teen pregnancy prevention in local communities: capacity building using the interactive systems framework.

Getting To Outcomes (GTO), an innovative framework for planning, implementing, evaluating, and sustaining interventions has been shown to be effective in helping community-based organizations (CBOs) introduce science-based approaches into their prevention work. However, the Interactive Systems Framework (ISF) suggests that adopting innovations like GTO requires a significant amount of capacity building through training and technical assistance (T/TA). In this study, 11 CBOs and three schools in South Carolina entered into a 3 year program of intense and proactive T/TA based on the ISF to learn how to apply an adaptation of GTO (Promoting Science-Based Approaches-Getting To Outcomes, PSBA-GTO) to their teen pregnancy prevention programs. Using semi-structured interviews, the partnering organizations were assessed at three points in time, pre-T/TA, 12 months, and post T/TA (30 months) for their performance of the steps of GTO in their work. The seven organizations which participated in T/TA until the end of the project received an average of 76 h of TA and 112 h of training per organization. Interview results showed increased performance of all 10 steps of PSBA-GTO by these organizations when conducting their teen pregnancy programs. These results suggest targeted and proactive T/TA can successfully bridge the gap between research and practice by using a three part delivery system, as prescribed in the ISF, which relies on an intermediary prevention support system to ensure accurate and effective translation of research to the everyday work of community-based practitioners.

Development of a reproducible porcine model of infected burn wounds.

Severe burns are traumatic and physically debilitating injuries with a high rate of mortality. Bacterial infections often complicate burn injuries, which presents unique challenges for wound management and improved patient outcomes. Currently, pigs are used as the gold standard of pre-clinical models to study infected skin wounds due to the similarity between porcine and human skin in terms of structure and immunological response. However, utilizing this large animal model for wound infection studies can be technically challenging and create issues with data reproducibility. We present a detailed protocol for a porcine model of infected burn wounds based on our experience in creating and evaluating full thickness burn wounds infected with Staphylococcus aureus on six pigs. Wound healing kinetics and bacterial clearance were measured over a period of 27 d in this model. Enumerated are steps to achieve standardized wound creation, bacterial inoculation, and dressing techniques. Systematic evaluation of wound healing and bacterial colonization of the wound bed is also described. Finally, advice on animal housing considerations, efficient bacterial plating procedures, and overcoming common technical challenges is provided. This protocol aims to provide investigators with a step-by-step guide to execute a technically challenging porcine wound infection model in a reproducible manner. Accordingly, this would allow for the design and evaluation of more effective burn infection therapies leading to better strategies for patient care.

Role of ferroportin in macrophage-mediated immunity.

Perturbations in iron metabolism have been shown to dramatically impact host response to infection. The most common inherited iron overload disorder results from defects in the HFE gene product, a major histocompatibility complex class I-like protein that interacts with transferrin receptors. HFE-associated hemochromatosis is characterized by abnormally high levels of the iron efflux protein ferroportin. In this study, J774 murine macrophages overexpressing ferroportin were used to investigate the influence of iron metabolism on the release of nitric oxide (NO) in response to infection. Overexpression of ferroportin significantly impaired intracellular Mycobacterium tuberculosis growth during early stages of infection. When challenged with lipopolysaccharide (LPS) or M. tuberculosis infection, control macrophages increased NO synthesis, but macrophages overexpressing ferroportin had significantly impaired NO production in response to LPS or M. tuberculosis. Increased NO synthesis in control cells was accompanied by increased iNOS mRNA and protein, while upregulation of iNOS protein was markedly reduced when J744 cells overexpressing ferroportin were challenged with LPS or M. tuberculosis, thus limiting the bactericidal activity of these macrophages. The proinflammatory cytokine gamma interferon reversed the inhibitory effect of ferroportin overexpression on NO production. These results suggest a novel role for ferroportin in attenuating macrophage-mediated immune responses.

Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation.

Disturbances of iron homeostasis are associated with altered susceptibility to infectious disease, but the underlying molecular mechanisms are poorly understood. To study this phenomenon, we examined innate immunity to oral Salmonella infection in Hfe knockout (Hfe(-/-)) mice, a model of the human inherited disorder of iron metabolism type I hemochromatosis. Salmonella- and LPS-induced inflammatory responses were attenuated in the mutant animals, with less severe enterocolitis observed in vivo and reduced macrophage TNF-alpha and IL-6 secretion measured in vitro. The macrophage iron exporter ferroportin (FPN) was up-regulated in the Hfe(-/-) mice, and correspondingly, intramacrophage iron levels were lowered. Consistent with the functional importance of these changes, the abnormal cytokine production of the mutant macrophages could be reproduced in wild-type cells by iron chelation, and in a macrophage cell line by overexpression of FPN. The results of analyzing specific steps in the biosynthesis of TNF-alpha and IL-6, including intracellular concentrations, posttranslational stability and transcript levels, were consistent with reduced translation of cytokine mRNAs in Hfe(-/-) macrophages. Polyribosome profile analysis confirmed that elevated macrophage FPN expression and low intracellular iron impaired the translation of specific inflammatory cytokine transcripts. Our results provide molecular insight into immune function in type I hemochromatosis and other disorders of iron homeostasis, and reveal a novel role for iron in the regulation of the inflammatory response.

Active ras triggers death in glioblastoma cells through hyperstimulation of macropinocytosis.

Expression of activated Ras in glioblastoma cells induces accumulation of large phase-lucent cytoplasmic vacuoles, followed by cell death. This was previously described as autophagic cell death. However, unlike autophagosomes, the Ras-induced vacuoles are not bounded by a double membrane and do not sequester organelles or cytoplasm. Moreover, they are not acidic and do not contain the autophagosomal membrane protein LC3-II. Here we show that the vacuoles are enlarged macropinosomes. They rapidly incorporate extracellular fluid-phase tracers but do not sequester transferrin or the endosomal protein EEA1. Ultimately, the cells expressing activated Ras detach from the substratum and rupture, coincident with the displacement of cytoplasm with huge macropinosome-derived vacuoles. These changes are accompanied by caspase activation, but the broad-spectrum caspase inhibitor carbobenzoxy-Val-Ala-Asp-fluoromethylketone does not prevent cell death. Moreover, the majority of degenerating cells do not exhibit chromatin condensation typical of apoptosis. These observations provide evidence for a necrosis-like form of cell death initiated by dysregulation of macropinocytosis, which we have dubbed "methuosis." An activated form of the Rac1 GTPase induces a similar form of cell death, suggesting that Ras acts through Rac-dependent signaling pathways to hyperstimulate macropinocytosis in glioblastoma. Further study of these signaling pathways may lead to the identification of other chemical and physiologic triggers for this unusual form of cell death.

Modulation of intracellular iron levels by oxidative stress implicates a novel role for iron in signal transduction.

Reactive oxygen species (ROS) display cytotoxicity that can be exacerbated by iron. Paradoxically, HeLa cells treated with the ROS-generators menadione and 2,3-dimethoxy-1,4-naphthoquinone display increased free labile iron. HeLa cells exposed to ROS undergo apoptosis but iron chelation limits the extent of cell death suggesting the rise in intracellular iron plays a signaling role in this pathway. This idea is supported by the fact that iron chelation also alters the pattern of ROS-induced phosphorylation of stress-activated protein kinases SAPK/JNK and p38 MAPK. Thus, ROS-induced increases in cellular free iron contribute to signaling events triggered during oxidative stress response.

Alterations in nucleotide-binding oligomerization domain-2 expression, pathway activation, and cytokine production in Yao syndrome.

Yao syndrome (YAOS) is a systemic autoinflammatory disease (SAID), formerly termed nucleotide-binding oligomerization domain-2 (NOD2)-associated autoinflammatory disease. Due to the recent identification of YAOS, the molecular mechanisms underlying its disease pathogenesis are unclear. With specific NOD2 variants as characteristic genotypic features of YAOS, our study examined NOD2 expression, transcript splicing, signaling pathway activation, and cytokine profiles in peripheral blood mononuclear cells (PBMCs) from 10 YAOS patients and six healthy individuals. All participants were genotyped for NOD2 variants; all YAOS patients were heterozygous for the NOD2 IVS8+158 variant (IVS8+158) and four patients also carried a concurrent NOD2 R702W variant (IVS8+158/R702W haplotype). Resembling other SAIDs, plasma levels of TNFα, IL-1ß, IL-6, IFNγ, and S100A12 were unaltered in YAOS patients. Intron-8 splicing of NOD2 transcripts was unaffected by carriage of NOD2 IVS8+158. However, NOD2 transcript level and basal p38 mitogen-activated protein kinase (MAPK) activity were significantly elevated in PBMCs from IVS8+158 YAOS patients. Moreover, these patients' cells had elevated basal IL-6 secretion that was enhanced by muramyl dipeptide (MDP) stimulation. Tocilizumab treatment of a YAOS IVS8+158 patient resulted in marked clinical improvement. In contrast, MDP-stimulated NF-κB activity was uniquely suppressed in haplotype IVS8+158/R702W patients, as was TNFα secretion. Our study demonstrates for the first time that NOD2 expression and pathway activation are aberrant in YAOS, and specific NOD2 genotypes result in distinct NOD2 expression and cytokine profiles. These findings may also help select therapeutic strategies in the future.

Dual Use and Hospital Admissions among Veterans Enrolled in the VA's Homeless Patient Aligned Care Team.

OBJECTIVE: To examine the association between reliance on VA outpatient care and hospital admissions among Medicare-eligible Veterans enrolled in the Homeless Patient Aligned Care Team (H-PACT). DATA SOURCES/STUDY SETTING: Registry of H-PACT enrollees linked to VA and Medicare utilization data for 2013. STUDY DESIGN: After assigning Veterans to two groups according to whether they received >90 percent of outpatient care in VA (higher reliance) or <90 percent of outpatient care in VA (lower reliance), generalized linear models with inverse probability of treatment weights were used to estimate the association of reliance with Medicare and VA-financed hospital admissions. PRINCIPAL FINDINGS: Compared with higher reliance Veterans, lower reliance Veterans had an equivalent number of annual VA hospitalizations (0.63 vs. 0.50; p = .14) but substantially greater Medicare hospitalizations (0.85 vs. 0.08; p < .001). Among Veterans in the highest tertile of outpatient visits, we observed statistically similar rates of VA hospital use but over 10-fold greater rates of Medicare-financed hospitalizations (1.31 for lower reliance vs. 0.15 for high reliance; p < .001). CONCLUSIONS: Among Veterans receiving integrated care in VA's H-PACT, dual use of Medicare and VA outpatient care is strongly associated with acute hospitalizations financed by Medicare. Linking VA and non-VA data may identify a subset of homeless Veterans with fragmented outpatient care who are at increased risk of poor outcomes.

Stress-Induced Hyperglycemia in White-Throated and White-Crowned Sparrows: A New Technique for Rapid Glucose Measurement in the Field.

Organisms experience stressors, and the physiological response to these stressors is highly conserved. Acute stress activates both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, increasing epinephrine, norepinephrine, and glucocorticoids, collectively promoting glucose mobilization. While this is well characterized in mammals, the hyperglycemic response to stress in avian and nonavian reptiles has received less attention. A number of factors, ranging from time of day to blood loss, are reported to influence the extent to which acute stress leads to hyperglycemia in birds. Here we characterized the glycemic response to acute handling stress in two species of free-living sparrows: white-throated sparrows (WTSPs: Zonotrichia albicollis) in St. Mary's County, Maryland, and white-crowned sparrows (WCSPs: Zonotrichia leucophrys) in Tioga Pass Meadow, California. We validated a novel technique for rapid field measurement of glucose using a human blood glucose meter, FreeStyle Lite. As expected, acute handling stress elevated blood glucose at both 15 and 30 min postcapture as compared to baseline for both WTSPs and WCSPs. In addition, handling for 30 min without bleeding had the same hyperglycemic effect as handling with serial bleeds in WCSPs. Finally, body condition that was measured as abdominal fat score predicted stress-induced blood glucose in WTSPs but not in WCSPs. Our results are consistent with the mammalian literature on acute stress and energy mobilization, and we introduce a new field technique for avian field biologists.