The heritability of Nematodirus battus fecal egg counts.

Although Nematodirus battus is a serious threat to the health and survival of young lambs, there are few options to control this parasite. Bayesian Monte Carlo Markov Chain modelling with a zero-inflated Poisson distribution was used to estimate the heritability of egg counts in both June and July for each of five consecutive cohorts of 200 Scottish Blackface lambs. In one of the 10 analyses, the results failed the diagnostic tests. In seven of the analyses, there was no convincing evidence that the variation in egg counts was heritable. In the 2 years of high infection, the heritability was approximately 0.4 in June but the estimates lacked precision and the 95% highest posterior density credible intervals ranged from just above zero to 0.7. Selective breeding for resistance to N. battus will be difficult because genetically resistant or susceptible lambs cannot be consistently identified by phenotypic markers.

The Plasticity and Stability of Regulatory T Cells during Viral-Induced Inflammatory Lesions.

Ocular infection with HSV causes a chronic T cell-mediated inflammatory lesion in the cornea. Lesion severity is affected by the balance of different CD4 T cell subsets, with greater severity occurring when the activity of regulatory T cells (Tregs) is compromised. In this study, fate-mapping mice were used to assess the stability of Treg function in ocular lesions. We show that cells that were once Foxp3+ functional Tregs may lose Foxp3 and become Th1 cells that could contribute to lesion expression. The instability primarily occurred with IL-2Rlo Tregs and was shown, in part, to be the consequence of exposure to IL-12. Lastly, in vitro-generated induced Tregs (iTregs) were shown to be highly plastic and capable of inducing stromal keratitis when adoptively transferred into Rag1-/- mice, with 95% of iTregs converting into ex-Tregs in the cornea. This plasticity of iTregs could be prevented when they were generated in the presence of vitamin C and retinoic acid. Importantly, adoptive transfer of these stabilized iTregs to HSV-1-infected mice prevented the development of stromal keratitis lesions more effectively than did control iTregs. Our results demonstrate that CD25lo Treg and iTreg instability occurs during a viral immunoinflammatory lesion and that its control may help to avoid lesion chronicity.

Composition of the gut microbiota modulates the severity of malaria.

Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden.

Plasmodium suppresses expansion of T cell responses to heterologous infections.

Plasmodium remains a major pathogen causing malaria and impairing defense against other infections. Defining how Plasmodium increases susceptibility to heterologous pathogens may lead to interventions that mitigate the severity of coinfections. Previous studies proposed that reduced T cell responses during coinfections are due to diminished recruitment of naive T cells through infection-induced decreases in chemokine CCL21. We found that, although Listeria infections reduced expression of CCL21 in murine spleens, lymphocytic choriomeningitis virus (LCMV)-specific T cell responses were not impaired during Listeria + LCMV coinfection, arguing against a major role for this chemokine in coinfection-induced T cell suppression. In our experiments, Plasmodium yoelii infection led to a reduced CD8(+) T cell response to a subsequent Listeria infection. We propose an alternative mechanism whereby P. yoelii suppresses Listeria-specific T cell responses. We found that Listeria-specific T cells expanded more slowly and resulted in lower numbers in response to coinfection with P. yoelii. Mathematical modeling and experimentation revealed greater apoptosis of Listeria-specific effector T cells as the main mechanism, because P. yoelii infections did not suppress the recruitment or proliferation rates of Listeria-specific T cells. Our results suggest that P. yoelii infections suppress immunity to Listeria by causing increased apoptosis in Listeria-specific T cells, resulting in a slower expansion rate of T cell responses.

Evaluation of multiple biomarkers of cardiovascular stress for risk prediction and guiding medical therapy in patients with stable coronary disease.

BACKGROUND: Circulating biomarkers can offer insight into subclinical cardiovascular stress and thus have the potential to aid in risk stratification and tailoring of therapy. METHODS AND RESULTS: We measured plasma levels of 4 cardiovascular biomarkers, midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and copeptin, in 3717 patients with stable coronary artery disease and preserved left ventricular ejection fraction who were randomized to trandolapril or placebo as part of the Prevention of Events With Angiotensin Converting Enzyme (PEACE) trial. After adjustment for clinical cardiovascular risk predictors and left ventricular ejection fraction, elevated levels of MR-proANP, MR-proADM, and CT-proET-1 were independently associated with the risk of cardiovascular death or heart failure (hazard ratios per 1-SD increase in log-transformed biomarker levels of 1.97, 1.48, and 1.47, respectively; P≤0.002 for each biomarker). These 3 biomarkers also significantly improved metrics of discrimination when added to a clinical model. Trandolapril significantly reduced the risk of cardiovascular death or heart failure in patients who had elevated levels of ≥2 biomarkers (hazard ratio, 0.53; 95% confidence interval, 0.36-0.80), whereas there was no benefit in patients with elevated levels of 0 or 1 biomarker (hazard ratio, 1.09; 95% confidence interval, 0.74-1.59; P(interaction)=0.012). CONCLUSIONS: In patients with stable coronary artery disease and preserved left ventricular ejection fraction, our results suggest that elevated levels of novel biomarkers of cardiovascular stress may help identify patients who are at higher risk of cardiovascular death and heart failure and may be useful to select patients who derive significant benefit from angiotensin-converting enzyme inhibitor therapy.

Prognostic utility of neopterin and risk of heart failure hospitalization after an acute coronary syndrome.

Aims There is increasing evidence that immune mechanisms are involved in the pathogenesis of heart failure (HF). The relationship between neopterin and the risk of HF has yet to be investigated on a large scale. We assessed the relationship between neopterin, a novel marker of monocyte activation, and risk of hospitalization for HF. Methods and results Among the subjects of Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial, 3946 had neopterin levels measured at study entry, on average 7 days after acute coronary syndrome (ACS). We assessed the relationship between neopterin and hospitalization for HF, and for death or HF over 2 years mean follow-up in a post hoc analysis using Cox regression models. Unadjusted hospitalization rates for HF increased across quartiles of neopterin, from 0.66 to 3.97 per 100 person-years. Per 1SD increment in log (neopterin), the adjusted risk of HF increased by 34% [hazard ratio (HR) 1.34, CI 1.10-1.64; P = 0.004]. Even after excluding individuals with a prior history of HF or recurrent ischaemic events, the relationship between neopterin and HF hospitalization remained significant. When added to a multivariable Cox model of HF-risk containing traditional risk factors, C-reactive protein and brain natriuretic protein (BNP), the further addition of neopterin significantly improved the HF-risk prediction model by likelihood ratio test analysis (P = 0.005), C-statistic (increasing from 0.743 to 0.773; P = 0.027), integrated discrimination improvement (IDI) analysis (P = 0.001), but not net reclassification improvement (NRI) analysis (P = 0.406). Similar results were obtained for the endpoint of death or HF. Conclusion Neopterin levels are an independent predictor of HF hospitalization, and improve risk prediction over and above conventional biomarkers.

What is the optimal blood pressure in patients after acute coronary syndromes?: Relationship of blood pressure and cardiovascular events in the PRavastatin OR atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial.

BACKGROUND: Aggressive blood pressure (BP) control has been advocated in patients with acute coronary syndrome, but few data exist in this population relative to cardiovascular outcomes. METHODS AND RESULTS: We evaluated 4162 patients enrolled in the PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial (acute coronary syndrome patients randomized to pravastatin 40 mg versus atorvastatin 80 mg). The average follow-up BP (systolic and diastolic) was categorized into 10-mm Hg increments. The primary outcome was a composite of death due to any cause, myocardial infarction, unstable angina requiring rehospitalization, revascularization after 30 days, and stroke. The secondary outcome was a composite of death due to coronary heart disease, nonfatal myocardial infarction, or revascularization. The relationship between BP (systolic or diastolic) followed a J- or U-shaped curve association with primary, secondary, and individual outcomes, with increased events rates at both low and high BP values, both unadjusted and after adjustment for baseline variables, baseline C-reactive protein, and on-treatment average levels of low-density lipoprotein cholesterol. A nonlinear Cox proportional hazards model showed a nadir of 136/85 mm Hg (range 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic) at which the incidence of primary outcome was lowest. The curve was relatively flat for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg. CONCLUSIONS: After acute coronary syndrome, a J- or U-shaped curve association existed between BP and the risk of future cardiovascular events, with lowest event rates in the BP range of approximately 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic and a relatively flat curve for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg, which suggests that too low of a pressure (especially <110/70 mm Hg) may be dangerous. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00382460.

Clinical features and outcomes of women with unstable ischemic heart disease: observations from metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndromes-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36).

BACKGROUND: The pathobiological basis of ischemic heart disease and thus the manifestations and response to therapy can differ between women and men. In prior studies, sex-based treatment differences have been observed with the antiischemic ranolazine, with a possibly diminished effect in women. METHODS AND RESULTS: We conducted a prospectively planned analysis of the clinical, biomarker, angiographic, and continuous ECG features and 1-year outcomes of women with unstable ischemic heart disease randomized to ranolazine or placebo in Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36). Compared with men (n=4269), women (n=2291) were older with more risk factors (P<0.001). On presentation, women were less likely than men to have significant epicardial coronary artery disease (no stenosis >or=50% on angiography, 19.4% versus 8.6%; P<0.001) or elevated troponin (57.1% versus 68.9%; P<0.001). Yet, women were more likely to have an elevated B-type natriuretic peptide (47.0% versus 40.2%; P<0.001), worse median angina frequency scores (80 versus 100; P<0.001), and an ischemic episode on continuous ECG administered during the first 7 days (22.5% versus 19.3%; P=0.0025). Women and men were at similar adjusted risk for the primary end point of cardiovascular death, myocardial infarction, or recurrent ischemia (adjusted hazard ratio, 1.11; 95% confidence interval, 0.96 to 1.29; P=0.15). Ranolazine was associated with a significant reduction in recurrent ischemia in women (13.0% versus 18.2%; hazard ratio, 0.71; 95% confidence interval, 0.57 to 0.88; P=0.002). CONCLUSIONS: Women with a clinical syndrome consistent with unstable ischemic heart disease, despite having less obstructive coronary artery disease, were more likely than men to report anginal episodes and had more recorded ischemic periods on continuous ECG. In this setting, ranolazine may be a particularly useful antiischemic agent in women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00099788.

Prognostic utility of secretory phospholipase A(2) in patients with stable coronary artery disease.

BACKGROUND: Secretory phospholipase A(2) (sPLA(2)) may contribute to atherogenesis. To date, few prospective studies have examined the utility of sPLA(2) for risk stratification in coronary artery disease (CAD). METHODS: We measured plasma sPLA(2) activity at baseline in 3708 subjects in the PEACE randomized trial of trandolapril vs placebo in stable CAD. Median follow-up was 4.8 years. We used Cox regression to adjust for demographics, clinical risk factors, apolipoprotein B, apolipoprotein A1, and medications. RESULTS: After multivariable adjustment, sPLA(2) was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio Q4:Q1 1.55, 95% CI 1.13-2.14) and cardiovascular death or heart failure (1.91, 1.20-3.03). In further multivariable assessment, increased activity levels of sPLA(2) were associated with the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio 1.47, 95% CI 1.06-2.04), independent of lipoprotein-associated phospholipase A(2) mass and C-reactive protein, and modestly improved the area under the curve (AUC) beyond established clinical risk factors (AUC 0.668-0.675, P = 0.01). sPLA(2), N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T all were independently associated with cardiovascular death or heart failure, and each improved risk discrimination (P = 0.02, P < 0.001, P < 0.001, respectively). CONCLUSIONS: sPLA(2) activity provides independent prognostic information beyond established risk markers in patients with stable CAD. These data are encouraging for studies designed to evaluate the role of sPLA(2) as a therapeutic target.

Arginine-vasopressin infusion in a child with cranial diabetes insipidus during hyperhydration therapy with chemotherapy: a therapeutic challenge.

SUMMARY: An 11-year-old girl presented with acute lower limb weakness, dehydration, hypernatraemia and secondary rhabdomyolysis on a background of an 8-month history of polyuria. Radiological investigations revealed a suprasellar tumour which was diagnosed on biopsy as a non-metastatic germinoma. Further endocrinological investigations confirmed panhypopituitarism and she commenced desmopressin, hydrocortisone and thyroxine. Her chemotherapeutic regime consisted of etoposide, carboplatin and ifosfamide, the latter of which required 4 litres of hyperhydration therapy daily. During the first course of ifosfamide, titration of oral desmopressin was trialled but this resulted in erratic sodium control leading to disorientation. Based on limited literature, we then trialled an arginine-vasopressin (AVP) infusion. A sliding scale was developed to adjust the AVP dose, with an aim to achieve a urine output of 3-4 mL/kg/h. During the second course of ifosamide, AVP infusion was commenced at the outset and tighter control of urine output and sodium levels was achieved. In conclusion, we found that an AVP infusion during hyperhydration therapy was required to achieve eunatraemia in a patient with cranial diabetes insipidus. Developing an AVP sliding scale requires individual variation; further reports/case series are required to underpin practice. LEARNING POINTS: Certain chemotherapeutic regimens require large fluid volumes of hyperhydration therapy which can result in significant complications secondary to rapid serum sodium shifts in patients with diabetes insipidus. The use of a continuous AVP infusion and titrating with a sliding scale is more effective than oral desmopressin in regulating plasma sodium and fluid balance during hyperhydration therapy. No adverse effects were found in our patient using a continuous AVP infusion. Adjustment of the AVP infusion rate depends on urine output, fluid balance, plasma sodium levels and sensitivity/response of the child to titrated AVP doses.

Predictors of initial nontherapeutic anticoagulation with unfractionated heparin in ST-segment elevation myocardial infarction.

BACKGROUND: Although weight-based nomograms have improved the efficacy and safety of dosing unfractionated heparin in ST-segment elevation myocardial infarction, achieving therapeutic anticoagulation in practice remains challenging. METHODS AND RESULTS: In the Enoxaparin and Thrombolysis in Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, 20 506 patients with ST-segment elevation myocardial infarction were randomized to enoxaparin or unfractionated heparin, the latter dosed according to the American College of Cardiology/American Heart Association weight-based nomogram with centrally monitored activated partial thromboplastin times (aPTTs). A total of 6055 patients received study unfractionated heparin and a fibrin-specific lytic and had an initial aPTT drawn within 4 to 8 hours of starting therapy. Despite close adherence to recommended dosing, only 33.8% of initial aPTTs were therapeutic (1.50 to 2.00 times control); 13.2% were markedly low (<1.25 times); and 16.3% were markedly high (> or =2.75 times). Markedly high aPTTs were more likely in patients who were older (adjusted risk ratio [RR(adj)], 1.14 per decade; P=0.001), were female (RR(adj), 1.46; P<0.001), were of lower weight (RR(adj), 1.19 per 10-kg decrease; P<0.001) or had renal dysfunction (RR(adj), 1.08 per 0.2-mg/dL increase in serum creatinine; P=0.006). Markedly high aPTTs were associated with increased risk of TIMI major or minor bleeding by 48 hours (odds ratio, 2.11; P=0.004); markedly low aPTTs tended to be associated with increased risk of fatal or nonfatal reinfarction by 48 hours (odds ratio, 2.19; P=0.057). CONCLUSIONS: Despite the use of a standard weight-based unfractionated heparin nomogram in ST-segment elevation myocardial infarction, nontherapeutic anticoagulation is frequent and more likely among certain vulnerable patient groups, with excess anticoagulation associated with increased bleeding and inadequate anticoagulation associated with reinfarction. These findings should be considered when dosing unfractionated heparin in support of fibrinolytic therapy.

Extent of ST-segment resolution after fibrinolysis adds improved risk stratification to clinical risk score for ST-segment elevation myocardial infarction.

BACKGROUND: The TIMI risk score (TRS) for ST-segment elevation myocardial infarction (STEMI) is a convenient validated clinical risk score for predicting mortality. Although not part of the risk score, ST-segment resolution (STRes) may provide a simple method of risk stratification based on the response to reperfusion. We sought to determine whether STRes provides incremental risk stratification to the TIMI risk score. METHODS: The Clopidogrel as Adjunctive Reperfusion Therapy--Thrombolysis in Myocardial Infraction (CLARITY-TIMI 28) trial randomized STEMI patients receiving fibrinolysis to clopidogrel or placebo. A total of 2,340 patients had electrocardiograms (ECGs) valid to calculate STRes at 90 minutes, which was defined as complete (>70%), partial (30%-70%), or no resolution (30%). TRS was defined as low (0-2), medium (3-4), and high (> or =5). Clinical follow-up was through 30 days. Results were validated in 2,743 patients from the ExTRACT-TIMI 25 study. RESULTS: The degree of STRes at 90 minutes after fibrinolysis correlated in a stepwise fashion with death or heart failure (5.1% complete STRes, 8.9% partial STRes, 13.4% no STRes, P < .001). Furthermore, the degree of STRes provided a consistent and significant gradient of risk across all risk score categories (low, medium, or high) and significantly improved the discriminatory ability of TIMI risk score to predict death or heart failure (c-statistic 0.69 for TIMI risk score alone and 0.74 with STRes added to the model, P < .001). With the inclusion of STRes to the TIMI risk score, 913 patients (39%) were reclassified to higher or lower risk groups, and the net reclassification improvement (NRI) was highly significant (P < .001). In the ExTRACT-TIMI 25 trial, addition of the STRes improved also the c-statistic (P = .012) and NRI (P < .001). CONCLUSIONS: The extent of STRes based on routinely obtained ECGs is an independent predictor of death and heart failure when used together with the TIMI risk score and significantly improves the ability to risk stratify patients after fibrinolysis.

Cathepsin F of Teladorsagia circumcincta is a recently evolved cysteine protease.

Parasitic cysteine proteases are involved in parasite stage transition, invasion of host tissues, nutrient uptake, and immune evasion. The cysteine protease cathepsin F is the most abundant protein produced by fourth-stage larvae (L4) of the nematode Teladorsagia circumcincta, while its transcript is only detectable in L4 and adults. T. circumcincta cathepsin F is a recently evolved cysteine protease that does not fall clearly into either of the cathepsin L or F subfamilies. This protein exhibits characteristics of both cathepsins F and L, and its phylogenetic relationship to its closest homologs is distant, including proteins of closely related nematodes of the same subfamily.

Detection of myocardial injury in patients with unstable angina using a novel nanoparticle cardiac troponin I assay: observations from the PROTECT-TIMI 30 Trial.

BACKGROUND: At least 30% of patients with non-ST-elevation acute coronary syndrome present without evidence of myonecrosis using current generation troponin assays. A new generation of research assays for troponin that offer a >10-fold increase in analytical sensitivity has emerged. METHODS: To perform a pilot study to evaluate the clinical sensitivity of a new ultra-sensitive nanoparticle assay for cardiac troponin I (nano-cTnI), we identified 50 patients with unstable angina (serial negative cTnI) and 50 patients with non-ST-elevation myocardial infarction with an initially negative current generation cTnI result. We measured cTnI using an assay (Nanosphere, Northbrook, IL) that can detect pg/mL concentrations of cTnI (detection-limit 0.0002 microg/L). RESULTS: Measured at 0, 2, and 8 hours with the nano-cTnI assay 44%, 62%, and 82% of patients with unstable angina defined by the current-generation assay had an elevated nano-cTnI result (> or =0.003 microg/L, 99 th percentile decision-limit, coefficient of variation <10%). In patients with definite myocardial injury (current-generation cTnI > or =0.1 microg/L) but an initially negative cTnI, 72% and 98% had a nano-cTnI > or =0.003 microg/L at 0 and 2 hours. No patient had a positive current-generation cTnI without an elevated nano-cTnI level. CONCLUSIONS: In this pilot study using a nanoparticle assay for cTnI, myocardial injury was detectable in a substantial proportion of patients presently classified as having unstable angina, suggesting that ischemia with rest pain without injury is rare. The emergence of a new generation of troponin assays has the potential to lead to new clinical applications based on enhanced analytical performance at very low concentrations of troponin.

The racing pigeon (Columba livia domestica) industry in Victoria, Australia, and epidemiology of a novel Group A rotavirus outbreak.

A novel Group A rotavirus, first identified clinically in racing, feral and fancy pigeons in Western Australia, had spread throughout Australia by March 2017. In December 2016, the putative index case of rotavirus in racing pigeons in the state of Victoria was confirmed at a regional bird sale, with rapid spread to peri-urban Melbourne, the capital city. A survey sent to approximately 400 Victorian pigeon fanciers identified eight (of 85 respondents) with a confirmed rotavirus infection in their loft(s). If a fancier had purchased live birds, either from the regional sale or from another source, there was a 13%-38% increased likelihood of the loft subsequently being confirmed rotavirus-positive. An increased loft-level risk of rotavirus was also positively associated with the number of neighbouring lofts within a 5-km radius of a home loft. It was concluded that rotavirus was primarily transmitted beyond the Victorian index case through the movement of live birds into a loft, either deliberately through bird purchase and/or inadvertently through the entry of pigeons from neighbouring lofts. As pigeon racing inherently requires consistent contact between birds from different lofts, vaccination is recommended as a primary method of rotavirus control in this unique industry.

High seroprevalance of Neospora caninum in dogs in Victoria, Australia, compared to 20 years ago.

BACKGROUND: Canids are definitive hosts of the apicomplexan parasite Neospora caninum, the leading cause of abortion in cattle worldwide. For horizontal transmission from canids to occur, oocysts of N. caninum must be shed by the definitive host into the environment of susceptible intermediate hosts such as cattle. The purpose of this study was to determine the prevalence of N. caninum in canids in Victoria, Australia's leading dairy producing state. RESULTS: Neospora-like oocysts were observed in 8% (18/234) of faecal samples from wild dogs, domestic dogs and red foxes from Victoria, Australia. However, none tested positive for N. caninum DNA using a quantitative PCR. In a separate sample population, blood sera from 483 domestic dogs were tested for anti-N. caninum antibodies using competitive ELISA. A subset of cELISA samples were re-tested using indirect fluorescence antibody test (IFAT). A seroprevalence of 29.8% (144/483; 95% CI: 11.7-47.8%) was calculated when using cELISA; whereas it was 32.9% (27/80; 95% CI: 15.8-51.8%) using IFAT. Potential risk factors were evaluated using univariable analyses and then assessed in separate multivariable models. Using 'aged' dogs as a reference, the seroprevalence of 'adolescent' and 'adult' dogs was 88% (P = 0.05) and 91% (P = 0.08), respectively, indicating seroprevalence increases with age. There was a 19% higher likelihood of infection in rural locations (P = 0.10) relative to urban areas. Jack Russell Terriers had a 22% higher risk of a cELISA-positive result (P = 0.05) regardless of geographical location, age or sex. CONCLUSION: These results demonstrate that exposure to N. caninum in domestic dogs is widespread in Victoria, although faecal oocyst shedding is infrequent. Our results indicate increased N. caninum seroprevalance status in dogs over the past two decades. The results imply that dogs get either exposed to the infected meat more frequently or that vertical dam to foetus transmission is more frequent than previously thought. Our study calls for re-evaluation of historical N. caninum seroprevalance studies, because the attitude to dog diet changes.

Exercising influence: distinct biotic interactions shape root microbiomes.

Root microbiomes are formed from diverse microbial soil settings with extraordinary consistency, suggesting both defined mechanisms of assembly and specific microbial activity. Recent improvements in sequencing technologies, data analysis techniques, and study design, allow definition of the microbiota within these intimate and important relationships with increasing accuracy. Comparing datasets provides powerful insights into the overlap of plant microbiomes, as well as the impacts of surrounding plants and microbes on root microbiomes and long-term soil conditioning. Here we address how recent studies tease apart the impact of various biotic interactions, including: plant-plant, plant-microbe, and microbe-microbe on root microbiome composition.

A qualitative analysis of bariatric patients' post-surgical barriers to exercise.

Research has shown that some bariatric patients overestimate post-surgical exercise levels, while others struggle with negative cognitions and follow-through on intentions to exercise; however, little exists on specific barriers affecting bariatric patients' post-surgical exercise behaviors. Considering that regular exercise is a predictor of weight loss maintenance, further research is warranted. Survey methodology was utilized to assess post-operative exercise barriers as well as beneficial post-surgical exercise services among a sample of bariatric patients solicited from an online support website. Qualitative assessment of responses was completed using inductive content analysis. Higher-order themes for exercise barriers included internal, external, and no barriers; generic categories determined for internal barriers included motivational and physical barriers. Of the participants, 78% reported at least one internal motivational barrier, and the most frequently reported subcategorical barrier was time (28%); physical barriers were reported related to surgery (9%) or other chronic conditions (19%). Higher-order themes for exercise services included positive descriptions such as benefits from exercise prescription as well as the importance of facilities and individuals, while negative descriptions included no services available or services that were unhelpful. Participants cited the benefit of community-based facilities, so providers might consider partnering with local professionals to deliver exercise services. Staff should be aware of physical barriers specific to bariatric populations including issues with post-surgical stamina and chronic comorbid conditions in order to provide appropriate exercise prescription. In addition, as motivational and time barriers occur frequently, providers should be well-trained on how to help patients overcome these impediments to exercise maintenance.

Clinical implications and correlates of Q waves in patients with ST-elevation myocardial infarction treated with fibrinolysis: observations from the CLARITY-TIMI 28 trial.

BACKGROUND: The relationships between Q waves that appear during the acute phase of ST-elevation myocardial infarction (STEMI), clinical characteristics, ST-segment resolution (STRes), and clopidogrel therapy in patients treated with fibrinolysis are not well described. HYPOTHESIS: We hypothesized that Q waves would be associated with less successful reperfusion and increased cardiovascular events. METHODS: In the CLARITY-TIMI 28 trial, 3491 STEMI patients treated with fibrinolysis were randomized to clopidogrel or placebo. Electrocardiograms were evaluated for STRes post-fibrinolysis and the presence of pathologic Q waves during the index hospitalization in 3322 patients. RESULTS: Q waves were identified in 2045 patients (61.6%) prior to discharge and were associated with increased odds of congestive heart failure (CHF) (adjusted odds ratio [ORadj ]: 2.10, P = 0.002) or the composite of cardiovascular death/CHF at 30 days (ORadj : 2.08, P ≤ 0.001). Q waves were associated with lower odds of Thrombolysis in Myocardial Infarction [TIMI] flow grade 2 to 3 (ORadj : 0.78, P = 0.028), TIMI myocardial perfusion grade 3 (ORadj : 0.83, P = 0.029), and complete STRes at 90 minutes (ORadj : 0.80, P = 0.030). Patients with both a Q wave and incomplete STRes 90 minutes after fibrinolysis were at higher risk for cardiovascular death or CHF (11.1%) than patients with no Q wave and at least partial STRes (1.9%). Overall, clopidogrel tended to be equally or more effective in patients without Q waves compared to those with Q waves. CONCLUSIONS: Among STEMI patients treated with fibrinolysis, evaluating for Q waves prior to discharge is a simple method of assessing for less successful reperfusion and an increased risk of adverse 30-day cardiovascular outcomes. The combination of Q waves and 90-minute STRes allows additional risk refinement.

Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin-converting enzyme inhibition in stable ischemic heart disease.

OBJECTIVES: This study sought to test 2 hypotheses: 1) fibroblast growth factor (FGF)-23 identifies patients with stable ischemic heart disease (SIHD) at high risk of cardiovascular events independent of clinical factors, renal function, and established cardiovascular biomarkers; and 2) FGF-23 identifies patients who derive greater clinical benefit from angiotensin-converting enzyme inhibitor therapy. BACKGROUND: FGF-23 is an endocrine regulator of mineral metabolism and markedly elevated levels are associated with cardiovascular events in patients with chronic kidney disease. Data in patients with SIHD are more sparse. METHODS: FGF-23 levels were measured in 3,627 patients with SIHD randomly assigned to trandolapril or placebo within the PEACE (Prevention of Events With Angiotensin-Converting Enzyme) trial and followed up for a median of 5.1 years. RESULTS: After adjustment for clinical risk predictors, left ventricular ejection fraction, markers of renal function, and established cardiovascular biomarkers, FGF-23 concentration was independently associated with an increased risk of cardiovascular death or heart failure among patients allocated to placebo (quartile 4 hazard ratio: 1.73; 95% confidence interval, 1.09 to 2.74; p = 0.02) and significantly improved metrics of discrimination. Furthermore, among patients in the top quartile of FGF-23 levels, trandolapril significantly reduced cardiovascular death or incident heart failure (hazard ratio: 0.45; 95% confidence interval: 0.28 to 0.72), whereas there was no clinical benefit in the remaining patients (hazard ratio: 1.07; 95% confidence interval: 0.75 to 1.52; p interaction = 0.0039). This interaction was independent of and additive to stratification based on renal function. CONCLUSIONS: Elevated levels of FGF-23 are associated with cardiovascular death and incident heart failure in patients with SIHD and identify patients who derive significant clinical benefit from angiotensin-converting enzyme inhibitor therapy regardless of renal function. (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy [PEACE]: NCT00000558).