C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance.

In rheumatoid arthritis, the emergence of anti-citrullinated autoimmunity is associated with HLA-antigen-T cell receptor complexes. The precise mechanisms underpinning this breach of tolerance are not well understood. Porphyromonas gingivalis expresses an enzyme capable of non-endogenous C-terminal citrullination with potential to generate citrullinated autoantigens. Here we document how C-terminal citrullination of ovalbumin peptide323-339 alters the interaction between antigen-presenting cells and OTII T cells to induce functional changes in responding T cells. These data reveal that C-terminal citrullination is sufficient to breach T cell peripheral tolerance in vivo and reveal the potential of C-terminal citrullination to lower the threshold for T cell activation. Finally, we demonstrate a role for the IL-2/STAT5/CD25 signalling axis in breach of tolerance. Together, our data identify a tractable mechanism and targetable pathways underpinning breach of tolerance in rheumatoid arthritis and provide new conceptual insight into the origins of anti-citrullinated autoimmunity.

Serum vitamin D concentrations at dry-off and close-up predict increased postpartum urine ketone concentrations in dairy cattle.

Vitamin D is commonly supplemented to dairy cows as vitamin D3 to support calcium homeostasis and in times of low sunlight exposure. Vitamin D has beneficial immunomodulatory and anti-inflammatory properties. Serum 25-hydroxyvitamin D [25(OH)D] concentrations fluctuated during lactation, with the lowest concentrations measured in healthy cows within 7 d of calving. However, it is unknown if serum 25(OH)D concentrations measured during the previous lactation are associated with transition diseases or health risk factors in dairy cattle. We collected serum samples from 279 dairy cattle from 5 commercial dairy herds in Michigan at dry-off, close-up, and 2-10 d in milk (DIM). Vitamin D concentrations were determined by measuring serum 25(OH)D by radioimmunoassay. Total serum calcium was measured by colorimetric methods. Body condition scores (BCS) were assigned at the time of blood collection. Clinical disease incidence was monitored until 30 d postparturition. Separate bivariable logistic regression analyses were used to determine if serum 25(OH)D at dry-off, close-up, and 2-10 DIM was associated with various clinical diseases including mastitis, lameness, and uterine disorders (classified as metritis, retained placenta, or both) and increased urine ketone concentrations at P < 0.05. Among all significant bivariable analyses, multivariable logistic regression analyses were built to adjust for potential confounding variables including parity, BCS, season, and calcium. Receiver operator characteristic (ROC) curve analyses were used to determine optimal concentrations of serum 25(OH)D. We found that higher serum 25(OH)D concentrations at dry-off and close-up predicted increased urine ketone concentrations in early lactation, even after adjustment for confounders. Alternatively, we found that lower serum 25(OH)D at 2-10 DIM was associated with uterine diseases. Optimal concentrations for serum 25(OH)D at dry-off and close-up for lower risk of increased urine ketone concentrations were below 103.4 and 91.1 ng/mL, respectively. The optimal concentration for serum 25(OH)D at 2-10 DIM for uterine diseases was above 71.4 ng/mL. These results indicate that serum 25(OH)D at dry-off and close-up may be a novel predictive biomarker for increased urine ketone concentrations during early lactation. Increased urine ketone concentrations are not necessarily harmful or diagnostic for ketosis but do indicate development of negative energy balance, metabolic stress, and increased risk of early lactation diseases. Predicting that dairy cattle are at increased risk of disease facilitates implementation of intervention strategies that may lower disease incidence. Future studies should confirm these findings and determine the utility of serum 25(OH)D concentrations as a predictive biomarker for clinical and subclinical ketosis.

Phylogeography of Atlantic Forest glassfrogs (Vitreorana): when geography, climate dynamics and rivers matter.

Recent advances in the field of landscape genetics provide ways to jointly analyze the role of present-day climate and landscape configuration in current biodiversity patterns. Expanding this framework into a phylogeographic study, we incorporate information on historical climatic shifts, tied to descriptions of the local topography and river configuration, to explore the processes that underlie genetic diversity patterns in the Atlantic Forest hotspot. We study two montane, stream-associated species of glassfrogs: Vitreorana eurygnatha and V. uranoscopa. By integrating species distribution modeling with geographic information systems and molecular data, we find that regional patterns of molecular diversity are jointly explained by geographic distance, historical (last 120 ky) climatic stability, and (in one species) river configuration. Mitochondrial DNA genealogies recover significant regional structure in both species, matching previous classifications of the northern and southern forests in the Atlantic Forest, and are consistent with patterns reported in other taxa. Yet, these spatial patterns of genetic diversity are only partially supported by nuclear data. Contrary to data from lowland taxa, historical climate projections suggest that these montane species were able to persist in the southern Atlantic Forest during glacial periods, particularly during the Last Glacial Maximum. These results support generally differential responses to climatic cycling by northern (lowland) and southern (montane) Atlantic Forest species, triggered by the joint impact of regional landscape configuration and climate change.

Oxylipid profiles of dairy cattle vary throughout the transition into early mammary gland involution.

Successful lactation in multiparous dairy cattle relies on a well-managed dry period that allows the mammary gland to remodel and regenerate between lactations. Oxylipids are potent inflammatory mediators that are capable of regulating all aspects of inflammation. Although an oxylipid profile has been documented for periparturient and lactating cattle, little work has been done to define the profile of cows in the early dry period. Therefore, our group aimed to characterize the oxylipid profile in healthy cows during the transition into early mammary gland involution. Plasma samples were collected from 10 healthy Holstein dairy cows via coccygeal venipuncture 6 d before dry-off (d -6), at dry-off (d 0), and 1 (d +1), 2 (d +2), 6 (d +6), and 12 (d +12) d after the dry-off date. Liquid chromatography-mass spectrometry was used to quantify select monounsaturated fatty acids, polyunsaturated fatty acids, and saturated fatty acids, whereas oxylipids were quantified using liquid chromatography-tandem mass spectrometry. The results of this study revealed a unique profile of pro- and anti-inflammatory oxylipids throughout the transition from late lactation into the dry period. Many compounds reached the highest concentrations of the study at d +1, d +2, or d +12, whereas others reached the lowest concentrations at d +12. The characterization of this profile allows for further understanding of the physiology of early mammary involution. Future studies should investigate how the oxylipid profile of early mammary involution may affect the health and productivity of dairy cows.

Changes in biomarkers of nutrient metabolism, inflammation, and oxidative stress in dairy cows during the transition into the early dry period.

Metabolic stress occurs in dairy cows when physiologic homeostasis is disrupted as a consequence of aberrant nutrient metabolism, chronic inflammation, and oxidative stress. Early-lactation cows that suffer from metabolic stress are susceptible to health disorders that cause significant production losses. However, there is little information regarding the occurrence and effect of metabolic stress during involution. Therefore, the purpose of this study was to investigate well-known biomarkers associated with metabolic stress in early-lactation cows at various time points during the early dry period when dairy cows also are subjected to dramatic changes in physiologic homeostasis. Our group conducted a descriptive study by collecting serum and whole-blood samples from the coccygeal vein of 29 healthy dairy cows at a commercial dairy herd. Sampling points included d -6, 0, +1, +2, +6, and +12 relative to dry-off date. Samples were used to quantify biomarkers related to nutrient metabolism, oxidative stress, and inflammation that included calcium, nonesterified fatty acids, ß-hydroxybutyrate, albumin, haptoglobin, cortisol, reactive oxygen and nitrogen species, antioxidant potential, oxidant status index, and isoprostanes. Additionally, whole-blood leukocyte differentials for total leukocyte, neutrophils, lymphocytes, eosinophils, and monocytes were analyzed. Within altered nutrient metabolism biomarkers, calcium and nonesterified fatty acid concentrations changed most from d 0 to d +2 during the sampling period. Indicators of oxidant status, such as reactive oxygen and nitrogen species, antioxidant potential, and oxidant status index, generally increased throughout the sampling period except at d +2, suggesting altered redox status throughout early involution. In contrast, isoprostane concentrations fluctuated throughout the study, demonstrating that indicators of oxidative damage occurred more sporadically during the sampling period. Therefore, many of the biomarkers associated with early-lactation metabolic stress also changed during the transition from late lactation to the early dry period, but not to the same magnitude and duration previously reported in periparturient cows. Future studies should be directed toward assessing whether the magnitude and duration of biomarker expression can affect the health and well-being of cows during the early dry period.

Weekend admission and mortality for gastrointestinal disorders across England and Wales.

BACKGROUND: Little has been reported on mortality following admissions at weekends for many gastrointestinal (GI) disorders. The aim was to establish whether GI disorders are susceptible to increased mortality following unscheduled admission on weekends compared with weekdays. METHODS: Record linkage was undertaken of national administrative inpatient and mortality data for people in England and Wales who were hospitalized as an emergency for one of 19 major GI disorders. RESULTS: The study included 2 254 701 people in England and 155 464 in Wales. For 11 general surgical and medical GI disorders there were little, or no, significant weekend effects on mortality at 30 days in either country. There were large consistent weekend effects in both countries for severe liver disease (England: 26·2 (95 per cent c.i. 21·1 to 31·6) per cent; Wales: 32·0 (12·4 to 55·1 per cent) and GI cancer (England: 21·8 (19·1 to 24·5) per cent; Wales: 25·0 (15·0 to 35·9) per cent), which were lower in patients managed by surgeons. Admission rates were lower at weekends than on weekdays, most strongly for severe liver disease (by 43·3 per cent in England and 51·4 per cent in Wales) and GI cancer (by 44·6 and 52·8 per cent respectively). Both mortality and the weekend mortality effect for GI cancer were lower for patients managed by surgeons. DISCUSSION: There is little, or no, evidence of a weekend mortality effect for most major general surgical or medical GI disorders, but large weekend effects for GI cancer and severe liver disease. Lower admission rates at weekends indicate more severe cases. The findings for severe liver disease may suggest a lack of specialist hepatological resources. For cancers, reduced availability of end-of-life care in the community at weekends may be the cause.

Multilocus phylogenetic and geospatial analyses illuminate diversification patterns and the biogeographic history of Malagasy endemic plated lizards (Gerrhosauridae: Zonosaurinae).

Although numerous studies have attempted to find single unifying mechanisms for generating Madagascar's unique flora and fauna, little consensus has been reached regarding the relative importance of climatic, geologic and ecological processes as catalysts of diversification of the region's unique biota. Rather, recent work has shown that both biological and physical drivers of diversification are best analysed in a case-by-case setting with attention focused on the ecological and life-history requirements of the specific phylogenetic lineage under investigation. Here, we utilize a comprehensive analytical approach to examine evolutionary drivers and elucidate the biogeographic history of Malagasy plated lizards (Zonosaurinae). Data from three genes are combined with fossil information to construct time-calibrated species trees for zonosaurines and their African relatives, which are used to test alternative diversification hypotheses. Methods are utilized for explicitly incorporating phylogenetic uncertainty into downstream analyses. Species distribution models are created for 14 of 19 currently recognized species, which are then used to estimate spatial patterns of species richness and endemicity. Spatially explicit analyses are employed to correlate patterns of diversity with both topographic heterogeneity and climatic stability through geologic time. We then use inferred geographic ranges to estimate the biogeographic history of zonosaurines within each of Madagascar's major biomes. Results suggest constant Neogene and Quaternary speciation with divergence from the African most recent common ancestor ~30 million years ago when oceanic currents and African rivers facilitated dispersal. Spatial patterns of diversity appear concentrated along coastal regions of northern and southern Madagascar. We find no relationship between either topographic heterogeneity or climatic stability and patterns of diversity. Ancestral state reconstructions suggest that western dry forests were important centres of origin with recent invasion into spiny and rain forest. These data highlight the power of combining multilocus phylogenetic and spatially explicit analyses for testing alternative diversification hypotheses within Madagascar's unique biota and more generally, particularly as applied to phylogenetically and biologically constrained systems.

Quantifying the Representation of Black Adolescents in Suicide Intervention Research.

This systematic review aimed to quantify the representation of Black youth in U.S. suicide intervention research. Specifically, we sought to evaluate Black youth representation in terms of (a) equity of inclusion (i.e., the inclusion of Black youth in research study samples at a rate consistent with the overall national rate of Black adolescents in the US) and (b) equity of intervention efficacy (i.e., evaluating the presence of racial disparities in intervention efficacy/effect sizes). In addition, we aimed to evaluate whether an association existed between funding status of research and representation of Black youth in studies, and to provide recommendations for future research in this area. To this end, the present study extracted and analyzed demographic information of studies included in recent meta-analyses conducted by Robinson and colleagues (2018), which were not previously analyzed, in addition to new literature published between September 2017 and January 2021. Results showed that the prevalence of Black youth included in studies was representative (14.67%; ntotal = 4451, nBlack = 664), with a median inclusion rate of 13%; however, absolute sample and group sizes were so small that it precluded comparison of differential treatment outcomes for Black youth. Thus, out of 22 studies identified, only one was able to investigate treatment outcomes for suicide in Black youth specifically. This study points to the conclusion that without adequately powered studies, disparities in treatment efficacy for Black youth cannot be compared or addressed, and the existing disparity in suicidal outcomes for Black youth will grow even larger.

Conservation outside protected areas and the effect of human-dominated landscapes on stress hormones in Savannah elephants.

Biodiversity conservation strategies are increasingly focused on regions outside national protected areas, where animals face numerous anthropogenic threats and must coexist with human settlements, livestock, and agriculture. The effects of these potential threats are not always clear, but they could have profound implications for population viability. We used savannah elephants (Loxodonta africana) as a case study to assess the physiological stress associated with living in a human-livestock-dominated landscape. We collected samples over two 3-month periods in 2007 and 2008. We used fecal DNA to identify 96 individual elephants in a community conservation area (CCA) and measured fecal glucocorticoid metabolite (FGM) concentrations as a proxy for stress. The CCA is community Maasai land managed for livestock and wildlife. We compared the FGM concentrations from the CCA to FGM concentrations of 40 elephants in Amboseli National Park and 32 elephants in the Maasai Mara National Reserve, where human settlements and intense livestock grazing were absent. In the CCA, we found no significant individual differences in FGM concentrations among the elephants in 2007 (p = 0.312) or 2008 (p = 0.412) and no difference between years (p = 0.616). The elephants in the CCA had similar FGM concentrations to the Maasai Mara population, but Amboseli elephants had significantly lower FGM concentrations than those in either Maasai Mara or the CCA (Tukey pairwise test, p < 0.001), due primarily to females excreting significantly lower FGM relative to males (p = 0.025). In the CCA, there was no relation among female group size, average pairwise group relatedness, and average group FGM concentration. We found no clear evidence of chronic stress in elephants living on CCA communal land, which is encouraging for conservation strategies promoting the protection of animals living outside protected areas.

Analyses of fecal and hair glucocorticoids to evaluate short- and long-term stress and recovery of Asiatic black bears (Ursus thibetanus) removed from bile farms in China.

Demand for traditional Chinese medicines has given rise to the practice of maintaining Asiatic black bears (Ursus thibetanus) in captivity to harvest bile. We evaluated hypothalamic-pituitary-adrenal (HPA) activity in Asiatic black bears on a bile farm in China by measuring cortisol in hair. We also monitored hair and fecal glucocorticoid metabolites as bears acclimated to improved husbandry at the Animals Asia Foundation China Bear Rescue Center (CBRC) after removal from other bile farms. Fecal samples were collected twice weekly for ~1 year, and hair was obtained from bears upon arrival at the CBRC and again ≥163 days later. Paired hair samples showed declines in cortisol concentrations of 12-88% in 38 of 45 (84%, p<0.001) bears after arrival and acclimation at the rehabilitation facility. Concentrations of cortisol in hair from bears on the bile farm were similar to initial concentrations upon arrival at the CBRC but were higher than those collected after bears had been at the CBRC for ≥163 days. Fecal glucocorticoid concentrations varied across months and were highest in April and declined through December, possibly reflecting seasonal patterns, responses to the arrival and socialization of new bears at the CBRC, and/or annual metabolic change. Data from segmental analysis of hair supports the first of these explanations. Our findings indicate that bears produced elevated concentrations of glucocorticoids on bile farms, and that activity of the HPA axis declined following relocation. Thus, hair cortisol analyses are particularly well suited to long-term, retrospective assessments of glucocorticoids in ursids. By contrast, fecal measures were not clearly associated with rehabilitation, but rather reflected more subtle endocrine changes, possibly related to seasonality.

Application of audio computer-assisted self-interviews to collect self-reported health data: an overview.

For assessment of sensitive health behaviors (e.g., sexual behavior, violent behaviors, substance use), research is typically limited to an examination of self-reports of past behavior. Audio computer-assisted self-interviews (ACASI) may enhance the validity of self-report data in research and clinical settings by reducing measurement bias. This paper provides an introduction to ACASI for collection of self-reported health data. The potential benefits and cost-effectiveness of ACASI use in research and clinical settings are reviewed. We then review the theoretical underpinnings that may underlie differential reporting of health behaviors between assessment modalities. Next, we highlight studies that have investigated differences in self-reported health behaviors between assessment modalities. Lastly, we summarize potential applications of ACASI assessments within clinical settings.

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

A qualitative and quantitative assessment of the impact of three processing algorithms with halving of study count statistics in myocardial perfusion imaging: filtered backprojection, maximal likelihood expectation maximisation and ordered subset expectation maximisation with resolution recovery.

INTRODUCTION: Ordered subset expectation maximisation with depth-dependent resolution recovery (OSEM-RR) is a processing algorithm reported to improve images with halved tracer activity in myocardial perfusion scintigraphy (MPS) compared to filtered backprojection (FBP) using conventional activities. OSEM-RR has not yet been compared with maximal likelihood expectation maximisation (MLEM). METHODS: 39 patients undergoing MPS and two anthropomorphic phantoms (one with, one without an inferior wall insert) had full-time (FT) and half-time (HT) SPECT datasets acquired simultaneously and processed by FBP, MLEM and OSEM-RR. Two experienced reporters scored images of all clinical studies (n=234) for conspicuity of a perfusion defect, with results being compared using Wilcoxon paired and Kappa tests. A quantitative assessment based on mean segmental pixel counts taken from numbers automatically displayed over the 20 segments of Cedars Sinai Autoquant QPS image were compared using Pearson's correlation and Bland Altman analysis. RESULTS: A small but consistent superior concurrence between FT and HT datasets for OSEM-RR compared to FBP and MLEM was observed for both qualitative and quantitative analyses. OSEM-RR resulted in better definition of the inferior wall defect on the phantom study. CONCLUSION: OSEM-RR appears superior to both FBP and MLEM in terms of handling reduced count statistics.

Evidence that hyperprolactinaemia is associated with ovarian acyclicity in female zoo African elephants.

African elephants of reproductive age in zoos are experiencing high rates of ovarian cycle problems (>40%) and low reproductive success. Previously, our laboratory found that 1/3 of acyclic females exhibit hyperprolactinaemia, a likely cause of ovarian dysfunction. This follow-up study re-examined hyperprolactinaemia in African elephants and found the problem has increased significantly to 71% of acyclic females. Circulating serum progestagens and prolactin were analysed in 31 normal cycling, 13 irregular cycling and 31 acyclic elephants for 12 months. In acyclic females, overall mean prolactin concentrations differed from cycling females (P < 0.05), with concentrations being either higher (n = 22; 54.90 ± 13.31 ngmL(-1)) or lower (n = 9; 6.47 ± 1.73 ngmL(-1)) than normal. No temporal patterns of prolactin secretion were evident in elephants that lacked progestagen cycles. In cycling females, prolactin was secreted in a cyclical manner, with higher concentrations observed during nonluteal (34.38 ± 1.77 and 32.75 ± 2.61 ngmL(-1)) than luteal (10.51 ± 0.30 and 9.67 ± 0.42 ngmL(-1)) phases for normal and irregular females, respectively. Of most concern was that over two-thirds of acyclic females now are hyperprolactinemic, a dramatic increase over that observed 7 years earlier. Furthermore, females of reproductive age constituted 45% of elephants with hyperprolactinaemia. Until the cause of this problem is identified and a treatment is developed, reproductive rates will remain suboptimal and the population nonsustaining.

Social support correlates with glucocorticoid concentrations in wild African elephant orphans.

Social relationships have physiological impacts. Here, we investigate whether loss of the mother/offspring relationship has lasting effects on fecal glucocorticoid metabolite (fGCM) concentrations in wild African elephant orphans several years following their mothers' deaths. We find no difference in fGCM concentrations between orphans and nonorphans, but find lower fGCM concentrations in elephants with more age mates in their family. We also unexpectedly identify lower concentrations in orphans without their natal family versus nonorphans and natal orphans, which we speculate may be due to the development of hypocortisolism following a prolonged period without familial support. An index of plant productivity (i.e. food) shows the largest correlation with fGCM concentrations. Our findings indicate no lasting differences in glucocorticoid concentrations of surviving orphan elephants who are with their family, suggest the presence of age mates may reduce glucocorticoid concentrations in elephants, and emphasize that basic survival needs are the primary regulators of the stress response.

Situational and motivational factors associated with unhealthy alcohol use among Russian women with HIV and hepatitis C Virus co-infection.

Introduction: Alcohol use is prevalent among Russian women with HIV and hepatitis C Virus (HCV) co-infection despite alcohol's known harmful health effects for this population. Identifying factors that facilitate continued unhealthy alcohol use is critical to developing effective alcohol reduction interventions. This study assessed situational and motivational factors associated with unhealthy alcohol use among HIV/HCV co-infected women in clinical care in St. Petersburg, Russia. Methods: Guided by the motivational model for alcohol use, we conducted 30 semi-structured interviews with women living with HIV/HCV co-infection to identify situational and motivational factors associated with unhealthy drinking and barriers and facilitators to abstaining. Interviews were recorded and analyzed using a the-matic analysis approach. Results: Despite awareness of the health risks associated with alcohol use, many women reported heavy episodic drinking, particularly in social situations. A key motive for drinking was coping with negative emotions triggered by stressful situations, such as work- and family-related conflicts. Key situational factors included drinking with family and friends and in social situations. Women who endorsed negative drinking coping motives were the most motivated to stop drinking. Health concerns were also cited as reasons to stop drinking; however, few women reported that their doctors recommended that they abstain. Conclusions: Several situational and motivational facilitators of alcohol use and barriers to alcohol reduction were identified, as well as some opportunities for prevention, among women in care for HIV in Russia. Awareness-raising and training regarding the adverse consequences of alcohol use among persons with HIV/HCV co-infection should include clinicians, patients and relatives.

A compact x-ray diffraction system for dynamic compression experiments on pulsed-power generators.

Pulsed-power generators can produce well-controlled continuous ramp compression of condensed matter for high-pressure equation-of-state studies using the magnetic loading technique. X-ray diffraction (XRD) data from dynamically compressed samples provide direct measurements of the elastic compression of the crystal lattice, onset of plastic flow, strength-strain rate dependence, structural phase transitions, and density of crystal defects, such as dislocations. Here, we present a cost-effective, compact, pulsed x-ray source for XRD measurements on pulsed-power-driven ramp-loaded samples. This combination of magnetically driven ramp compression of materials with a single, short-pulse XRD diagnostic will be a powerful capability for the dynamic materials' community to investigate in situ dynamic phase transitions critical to equation of states. We present results using this new diagnostic to evaluate lattice compression in Zr and Al and to capture signatures of phase transitions in CdS.

Results of the third reproductive assessment survey of North American Asian (Elephas maximus) and African (Loxodonta africana) female elephants.

A written survey assessed reproductive status of female Asian and African elephants in AZA/SSP facilities in 2008, and data were compared to surveys conducted in 2002 and 2005. Results showed that ovarian acyclicity rates across the surveys remained unchanged for Asian (13.3, 10.9 and 11.1%) and African (22.1, 31.2 and 30.5%) elephants, respectively (P > 0.05), but were higher overall for African compared to Asian elephants (P < 0.05). In 2008, the percentages of Asian and African elephants with irregular cycles (14.3 and 15.8%) and irregular + no cycles (25.4 and 46.4%) was similar to 2005 (7.6 and 11.8%; 18.5 and 43.0%), but were increased compared to 2002 (2.6 and 5.2%; 16.0 and 27.3%), respectively (P < 0.05). For both species, ovarian acyclicity increased with age (P < 0.05). Reproductive tract pathologies did not account for the majority of acyclicity, although rates were higher in noncycling females (P < 0.05). Bull presence was associated with increased cyclicity rates (P < 0.05) for Asian (92.5 vs. 58.3%) and African (64.9 vs. 57.8%) elephants compared to females at facilities with no male, respectively. Cyclicity rates were higher for Asian (86.8 vs. 65.2%) and African (67.9 vs. 56.7%) elephants managed in free compared to protected contact programs (P < 0.05), respectively. Geographical facility location had no effect on cyclicity (P > 0.05). In summary, incidence of ovarian cycle problems continues to predominantly affect African elephants. Although percentages of acyclicity did not increase between 2005 and 2008, 42.2% Asian and 30.2% African females were no longer being hormonally monitored; thus, reproductive cycle abnormalities could be worse than current data suggest.

Activity pattern, reproductive behaviors and gonadal hormones in the raccoon dog (Nyctereutes procyonoides).

The objectives of this study were to (1) assess year-round behaviors and activity patterns of captive raccoon dogs (Nyctereutes procyonoides) and (2) characterize the species' reproductive endocrinology. Behaviors and activity patterns of 12 (5.7) animals were recorded over a 1-year period. During that time, fecal samples were collected 2-7 times/week from 16 (7.9) individuals (six of these were included in the behavioral study) for the analysis of testosterone, progesterone and estrogen metabolite concentrations. Activity pattern and excretion of gonadal steroids followed a seasonal pattern. Specifically, dogs were cathemeral in summer, and primarily nocturnal in winter. In the males, testosterone concentrations were at baseline from April through September, began to rise in October and reached peak concentrations in February (P<0.05). In the females, elevated estrogen (P<0.05) was observed in March followed by an increase in progestagen concentrations from March through May (P<0.05) in both pregnant and pseudopregnant animals. Gender significantly influenced monthly testosterone/estrogen ratio (P<0.01); values were higher in males than in females throughout the year with overall percentage of overlapping values between males and females being 28%. In summary, this study characterized cirannual fluctuations in behaviors and gonadal steroid metabolites in the raccoon dog maintained in captivity. Because there is no obvious sexual dimorphism, the differences in testosterone/estrogen ratio may be useful for gender differentiation (72% accuracy), especially among individuals living in the wild.

Peripheral markers of oxidative stress in Labrador retrievers with copper-associated hepatitis.

OBJECTIVES: To evaluate biomarkers of oxidative stress in dogs with copper-associated hepatitis (CAH) as compared with healthy controls, and to evaluate if these markers correlate with hepatic copper concentrations and hepatic histopathologic features. MATERIALS AND METHODS: Prospective study. Plasma reactive metabolite concentrations, plasma antioxidant potential, and plasma and urine isoprostane concentrations were determined in Labrador retrievers with copper-associated hepatitis (n=9) as well as in breed- and sex-matched (n=9) and age- and sex-matched (n=9) healthy control populations. Possible correlations between markers of oxidative stress and hepatic histopathological features also were investigated. RESULTS: Reactive metabolites (median, range) were over twofold greater in dogs with copper-associated hepatitis (87.2 RFU/µL, 60.9 to 185.6 RFU/µL) as compared to breed- and sex-matched (38.2 RFU/µL, 22.4 to 116.8 RFU/µL) and age- and sex-matched controls (32.0 RFU/µL, 18.5 to 127.4 RFU/µL). Antioxidant potential was decreased in copper-associated hepatitis dogs (6.5 TE/µL, 5.1 to 7.7 TE/µL) as compared to breed- and sex-matched controls (8.2 TE/µL, 5.3 to 11.8 TE/µL). Both reactive metabolite concentrations and the reactive metabolite to antioxidant potential ratio were positively correlated with hepatic copper concentrations. Plasma and urine isoprostanes were variable and not significantly different between populations. CLINICAL SIGNIFICANCE: Labrador retrievers with copper-associated hepatitis have altered oxidant status. Plasma reactive metabolite concentrations and the reactive metabolite to antioxidant potential ratio could be useful biomarkers. However, neither plasma nor urine isoprostanes were useful biomarkers for copper-associated hepatitis.