Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response.

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.

Statin Adherence Is Associated With Reduced Recurrent Stroke Risk in Patients With or Without Atrial Fibrillation.

BACKGROUND AND PURPOSE: Outpatient statin use reduces the risk of recurrent ischemic stroke among patients with stroke of atherothrombotic cause. It is not known whether statins have similar effects in ischemic stroke caused by atrial fibrillation (AFib). METHODS: We studied outpatient statin adherence, measured by percentage of days covered, and the risk of recurrent ischemic stroke in patients with or without AFib in a 21-hospital integrated healthcare delivery system. RESULTS: Among 6116 patients with ischemic stroke discharged on a statin over a 5-year period, 1446 (23.6%) had a diagnosis of AFib at discharge. The mean statin adherence rate (percentage of days covered) was 85, and higher levels of percentage of days covered correlated with greater degrees of low-density lipoprotein suppression. In multivariable survival models of recurrent ischemic stroke over 3 years, after controlling for age, sex, race/ethnicity, medical comorbidities, and hospital center, higher statin adherence predicted reduced stroke risk both in patients without AFib (hazard ratio, 0.78; 95% confidence interval, 0.63-0.97) and in patients with AFib (hazard ratio, 0.59; 95% confidence interval, 0.43-0.81). This association was robust to adjustment for the time in the therapeutic range for international normalized ratio among AFib subjects taking warfarin (hazard ratio, 0.61; 95% confidence interval, 0.41-0.89). CONCLUSIONS: The relationship between statin adherence and reduced recurrent stroke risk is as strong among patients with AFib as it is among patients without AFib, suggesting that AFib status should not be a reason to exclude patients from secondary stroke prevention with a statin.

Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review.

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of symptoms. Diet modification and nutritional supplements could be used to improve patient outcomes, such fatigue and quality of life. We reviewed and discussed the evidence for nutritional interventions that may assist in alleviating symptoms of CFS/ME. METHODS: Medline, Cinahl and Scopus were systematically searched from 1994 to May 2016. All studies on nutrition intervention were included where CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing). RESULTS: Seventeen studies were included that meet the inclusion criteria. Of these, 14 different interventions were investigated on study outcomes. Many studies did not show therapeutic benefit on CFS/ME. Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10. CONCLUSIONS: This review identified insufficient evidence for the use of nutritional supplements and elimination or modified diets to relieve CFS/ME symptoms. Studies were limited by the number of studies investigating the interventions, small sample sizes, study duration, variety of instruments used, and studies not reporting dietary intake method. Further research is warranted in homogeneous CFS/ME populations.

Impact of Increased Early Statin Administration on Ischemic Stroke Outcomes: A Multicenter Electronic Medical Record Intervention.

BACKGROUND: Statin administration early in ischemic stroke may influence outcomes. Our aim was to determine the clinical impact of increasing statin administration early in ischemic stroke hospitalization. METHODS AND RESULTS: This is a retrospective analysis of a multicenter electronic medical record (EMR) intervention to increase early statin administration in ischemic stroke across all 20 hospitals of an integrated healthcare delivery system. A stroke EMR order set was modified from an "opt-in" to "opt-out" mode of statin ordering. Outcomes were mortality by 90 days, discharge disposition, and increase in stroke severity. We examined the relationship between intervention and outcome using autoregressive integrated moving average (ARIMA) time-series modeling. The EMR intervention increased both overall in-hospital statin administration (from 87.2% to 90.7%, P<0.001) and early statin administration (from 16.9% to 26.3%, P<0.001). ARIMA models showed a small increase in the rate of survival (difference in probability [Pdiff]=0.02, P=0.016) and discharge to home or rehabilitation facility (Pdiff=0.04, P=0.034) associated with the intervention. The increase in statin administration <8 hours was associated with much larger increases in survival (Pdiff=0.17, P=0.033) and rate of discharge to home or rehabilitation (Pdiff=0.29, P=0.011), as well as a decreased rate of neurological deterioration in-hospital (Pdiff=-0.14, P=0.026). CONCLUSIONS: A simple EMR change increased early statin administration in ischemic stroke and was associated with improved clinical outcomes. This is, to our knowledge, the first EMR intervention study to show that a modification of an electronic order set resulted in improved clinical outcomes.

fMRI neurofeedback of higher visual areas and perceptual biases.

The self-regulation of brain activation via neurofeedback training offers a method to study the relationship between brain areas and perception in a more direct manner than the conventional mapping of brain responses to different types of stimuli. The current proof-of-concept study aimed to demonstrate that healthy volunteers can self-regulate activity in the parahippocampal place area (PPA) over the fusiform face area (FFA). Both areas are involved in higher order visual processing and are activated during the imagery of scenes and faces respectively. Participants (N=9) were required to upregulate PPA relative to FFA activity, and all succeeded at the task, with imagery of scenes being the most commonly reported mental strategy. A control group (N=8) underwent the same imagery and testing procedure, albeit without neurofeedback, in a mock MR scanner to account for any non-specific training effects. The upregulation of PPA activity occurred concurrently with activation of prefrontal and parietal areas, which have been associated with ideation and mental image generation. We tested whether successful upregulation of the PPA relative to FFA had consequences on perception by assessing bistable perception of faces and houses in a binocular rivalry task (before and after the scanning sessions) and categorisation of faces and scenes presented in transparent composite images (during scanning, interleaved with the self-regulation blocks). Contrary to our expectations, upregulation of the PPA did not alter the duration of face or house perception in the rivalry task and response speed and accuracy in the categorisation task. This conclusion was supported by the results of another control experiment (N=10 healthy participants) that involved intensive exposure to category-specific stimuli and did not show any behavioural or perceptual changes. We conclude that differential self-regulation of higher visual areas can be achieved, but that perceptual biases under conditions of stimulus rivalry are relatively robust against such internal modulation of localised brain activity. This study sets the basis for future investigations of perceptual and behavioural consequences of localised self-regulation of neural activity.

Effect of statin use during hospitalization for intracerebral hemorrhage on mortality and discharge disposition.

IMPORTANCE: Statin use during hospitalization is associated with improved survival and a better discharge disposition among patients with ischemic stroke. It is unclear whether inpatient statin use has a similar effect among patients with intracerebral hemorrhage (ICH). OBJECTIVE: To determine whether inpatient statin use in ICH is associated with improved outcomes and whether the cessation of statin use is associated with worsened outcomes. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 3481 patients with ICH admitted to any of 20 hospitals in a large integrated health care delivery system over a 10-year period. Detailed electronic medical and pharmacy records were analyzed to explore the association between inpatient statin use and outcomes. MAIN OUTCOMES AND MEASURES: The primary outcome measures were survival to 30 days after ICH and discharge to home or inpatient rehabilitation facility. We used multivariable logistic regression, controlling for demographics, comorbidities, initial severity, and code status. In addition, we used instrumental variable modeling to control for confounding by unmeasured covariates at the individual patient level. RESULTS: Among patients hospitalized for ICH, inpatient statin users were more likely than nonusers to be alive 30 days after ICH (odds ratio [OR], 4.25 [95% CI, 3.46-5.23]; P < .001) and were more likely than nonusers to be discharged to their home or an acute rehabilitation facility (OR, 2.57 [95% CI, 2.16-3.06]; P < .001). Patients whose statin therapy was discontinued were less likely than statin users to survive to 30 days (OR, 0.16 [95% CI, 0.12-0.21]; P < .001) and were less likely than statin users to be discharged to their home or an acute rehabilitation facility (OR, 0.26 [95% CI, 0.20-0.35]; P < .001). Instrumental variable models of local treatment environment (to control for confounding by unmeasured covariates) confirmed that a higher probability of statin therapy was associated with a higher probability of 30-day survival (with an increase in probability of 0.15 [95% CI, 0.04-0.25]; P = .01) and a better chance of being discharged to home or an acute rehabilitation facility (with an increase in probability of 0.13 [95% CI, 0.02-0.24]; P = .02). CONCLUSIONS AND RELEVANCE: Inpatient statin use is associated with improved outcomes after ICH, and the cessation of statin use is associated with worsened outcomes after ICH. Given the association between statin cessation and substantially worsened outcomes, the risk-benefit balance of discontinuing statin therapy in the acute setting of ICH should be carefully considered.

Radiation-induced morphoea treated with UVA-1 phototherapy.

Morphoea is a localized inflammatory disorder of the dermis and subcutaneous fat and radiotherapy is a rarely reported cause (estimated incidence of 2 per 1000). Morphoea is commonly mistaken for an inflammatory recurrence of breast cancer, resulting in unnecessary investigations and treatment. We report the case of a 40-year-old woman who developed radiation-induced morphoea of the breast 7 months following adjuvant radiotherapy. She was treated with topical and systemic steroids as well as psoralen plus ultraviolet (UV)A before proceeding to UVA1 phototherapy. We also review the literature and discuss other management options.

Assessment of microtubule-associated protein (MAP)-Tau expression as a predictive and prognostic marker in TACT; a trial assessing substitution of sequential docetaxel for FEC as adjuvant chemotherapy for early breast cancer.

The TACT trial is the largest study assessing the benefit of taxanes as part of adjuvant therapy for early breast cancer. The goal of this translational study was to clarify the predictive and prognostic value of Tau within the TACT trial. Tissue microarrays (TMA) were available from 3,610 patients. ER, PR, HER2 from the TACT trial and Tau protein expression was determined by immunohistochemistry on duplicate TMAs. Two parallel scoring systems were generated for Tau expression ('dichotomised' vs. 'combined' score). The positivity rate of Tau expression was 50 % in the trial population (n = 2,483). Tau expression correlated positively with ER (p < 0.001) and PR status (p < 0.001); but negatively with histological grade (p < 0.001) and HER2 status (p < 0.001). Analyses with either scoring systems for Tau expression demonstrated no significant interaction between Tau expression and efficacy of docetaxel. Contrary to the hypothesis that taxane benefit would be enriched in Tau negative/low patients, the only groups with a suggestion of a reduced event rate in the taxane group were the HER2-positive, Tau positive subgroups. Tau expression was seen to be a prognostic factor on univariate analysis associated with an improved DFS, independent of the treatment group (p < 0.001). It had no prognostic value in ER-negative tumours and the weak prognostic effect of Tau in ER-positive tumours (p = 0.02) diminished, when considering ER as an ordinal variable. On multivariable analyses, Tau had no prognostic value in either group. In addition, no significant interaction between Tau expression and benefit from docetaxel in patients within the PR-positive and negative subsets was seen. This is now the second large adjuvant study, and the first with quantitative analysis of ER and Tau expression, failing to show an association between Tau and taxane benefit with limited utility as a prognostic marker for Tau in ER-positive early breast cancer patients.

Toxicity of increasing aflatoxin B1 concentrations from contaminated corn with or without clay adsorbent supplementation in ducklings.

A total of 1,280 1-d-old ducks were used in a study to investigate the effects of increasing aflatoxin B1 (AFB1) concentrations from naturally contaminated corn on young ducklings, and the effectiveness of a clay adsorbent (CA) to protect against those effects. Ducks were randomly allotted to 8 treatments (TRT) in a 4 × 2 factorial arrangement with 4 levels of AFB1 (0, 25, 50, and 100 µg/kg) and 2 levels of CA (0 and 0.1%) with 8 pens per TRT and 20 ducks per pen. All ducks were allowed ad libitum access to feed and water during the 21-d experiment. The ADG, ADFI, feed conversion rate, mortality, bill color, and CV of BW of each replicate were measured at the end of the study. Blood and tissue samples from 8 ducks per TRT were obtained on d 21 of the experiment to determine the serum immunoglobulin and protein concentrations, relative organ weights, and intestinal morphology. Average daily gain and relative weights of the liver, spleen, thymus, and bursa of Fabricius decreased linearly (P < 0.05) as dietary AFB1 increased. Serum proteins and intestinal villi heights and villus/crypt ratio followed the same pattern. Bill decolorization ratio, CV of BW, and mortality increased linearly (P < 0.05) as dietary AFB1 increased. Adding 0.1% CA to the diet improved (P < 0.05) the relative weights of the small intestine, spleen, and thymus, and the villus height and villus/crypt ratio of the duodenum and jejunum, as well as the serum IgG and IgM concentrations. Adding CA also reduced (P < 0.05) bill decolorization ratio, CV of BW, mortality, and serum IgA concentration. Therefore, duck performance was negatively affected by increasing AFB1 concentrations in diets. But the addition of 0.1% CA can protect against the detrimental effects caused by AFB1-contaminated corn in diets for ducks.

High critical care usage due to pediatric stroke: results of a population-based study.

OBJECTIVES: To measure intensive care unit (ICU) admission, intubation, decompressive craniotomy, and outcomes at discharge in a large population-based study of children with ischemic and hemorrhagic stroke. METHODS: In a retrospective study of all children enrolled in a Northern Californian integrated health care plan (1993-2003), we identified cases of symptomatic childhood stroke (age >28 days through 19 years) from inpatient and outpatient electronic diagnoses and radiology reports, and confirmed them through chart review. Data regarding stroke evaluation, management, and outcomes at discharge were abstracted. Intensive care unit (ICU) admission, intubation, and decompressive neurosurgery rates were measured, and multivariate logistic regression was used to identify predictors of critical care usage and outcomes at discharge. RESULTS: Of 256 cases (132 hemorrhagic and 124 ischemic), 61% were admitted to the ICU, 32% were intubated, and 11% were treated with a decompressive neurosurgery. Rates were particularly high among children with hemorrhagic stroke (73% admitted to the ICU, 42% intubated, and 19% received a decompressive neurosurgery). Altered mental status at presentation was the most robust predictor for all 3 measures of critical care utilization. Neurologic deficits at discharge were documented in 57%, and were less common after hemorrhagic than ischemic stroke: 48% vs 66% (odds ratio 0.5, 95% confidence interval 0.3-0.8). Case fatality was 4% overall, 7% among children admitted to the ICU, and was similar between ischemic and hemorrhagic stroke. CONCLUSIONS: ICU admission is frequent after childhood stroke and appears to be justified by high rates of intubation and surgical decompression.

Practice variation in neuroimaging to evaluate dizziness in the ED.

BACKGROUND: The appropriate role of neuroimaging to evaluate emergency department (ED) patients with dizziness is not established by guidelines or evidence. METHODS: We identified all adults with a triage complaint of dizziness who were evaluated at 20 EDs of a large Northern California integrated health care program in 2008. Using comprehensive medical records, we captured all head computed tomographies (CTs) or brain magnetic resonance images (MRIs) completed at presentation or within 2 days and all stroke diagnoses within 1 week. We assessed variation in neuroimaging use by site using a random-effects logistic model to account for differences in patient- (demographic and vascular risk factors) and site-level factors (volume, % patients with dizziness, and % patients with dizziness admitted) and linear regression to assess the relationship between neuroimaging rates and stroke diagnosis rates by site. RESULTS: Of 378 992 patients seen in 2008, 20 795 (5.5%) had at least one ED visit for dizziness. Overall, 5585 patients (26.9%) had a head CT and 652 (3.1%) had a brain MRI. Between 21.8% and 32.8% of ED patients with dizziness at each site had a head CT (P<.001). For brain MRI, the range was 0.8% to 6.2%-a nearly 8-fold variation (P<.001) that persisted after adjustment for patient- and site-level factors. Higher neuroimaging rates did not translate into higher stroke diagnoses rates, with 0.7% to 2.5% of patients with dizziness diagnosed with stroke by site. CONCLUSION: The use of neuroimaging for ED patients with dizziness varies substantially without an associated improvement in stroke diagnosis, which is identified only rarely.

Effect on hepatonephric organs, serum metabolites and oxidative stress in post-weaning piglets fed purified zearalenone-contaminated diets with or without Calibrin-Z.

The objectives of this study were to investigate the toxicity of zearalenone (ZEA) on hepatonephric organs, serum metabolites and oxidative stress of piglets and to evaluate the efficacy of Calibrin-Z (CAZ) in preventing ZEA-induced adverse effects. The experiment was conducted for 22 days using 36 piglets weaned at 21 days of age (Landrace × Yorkshire × Duroc, 18 females and 18 males; 8.84 ± 0.21 kg average body weight). Piglets of each gender were randomly allocated to the following six dietary treatments: (i) Control (basal diet only); (ii) Control + 1 g/kg CAZ; (iii) Control + 1 mg/kg ZEA; (iv) Control + 1 mg/kg ZEA + 1 g/kg CAZ; (v) Control + 1 mg/kg ZEA + 2 g/kg CAZ; (vi) Control + 1 mg/kg ZEA + 4 g/kg CAZ. Piglets were housed and fed individually for the entire experimental period. Blood samples were taken, and piglets were killed at the end of the experiment to obtain organs for physiological assessment. Results showed that piglets fed the ZEA-contaminated diet had increased (p < 0.05) activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltransferase (GGT), creatine kinase and cholinesterase, concentrations of urea, and creatinine in serum, and malondialdehyde (MDA) in serum and liver. Pigs fed the ZEA-only diet also showed reductions in serum (p < 0.05) globulin, triglycerides and high-density lipoproteins (HDL), and reductions in total superoxide dismutase (TSOD) and glutathione peroxidase (GSHPx) activity in both serum and liver. Supplementation of CAZ at the dosages of 1-4 g/kg to the diet containing 1.05 mg/kg ZEA linearly increased (p < 0.05) concentrations of triglycerides and HDL in serum, activity of TSOD and GSHPx in serum and liver, but linearly reduced (p < 0.05) all tested serum enzymes and lowered (p < 0.05) the elevated concentrations of urea, and creatinine in serum, and MDA in serum and liver caused by dietary ZEA. Piglets fed the ZEA-contaminated diet showed increased (p < 0.05) relative weight of liver and kidney compared with the control, whereas only numerical improvement on relative weight of liver and kidney was observed with simultaneous addition of CAZ at 4 g/kg diet and ZEA. However, feeding the diet with CAZ alone at 1 g/kg had no impact on any of the measured parameters when compared to the control. It is suggested that feeding ZEA at 1.05 mg/kg exerted a deleterious effect on piglets, which was totally or partly ameliorated by dietary supplementation of CAZ at concentrations between 1 and 4 g/kg diet.

Recent trauma and acute infection as risk factors for childhood arterial ischemic stroke.

OBJECTIVE: Trauma and acute infection have been associated with stroke in adults, and are prevalent exposures in children. We hypothesized that these environmental factors are independently associated with childhood arterial ischemic stroke (AIS). METHODS: In a case-control study nested within a cohort of 2.5 million children (≤19 years old) enrolled in an integrated health care plan (1993-2007), childhood AIS cases (n = 126) were identified from electronic records and confirmed through chart review. Age- and facility-matched controls (n = 378) were randomly selected from the cohort. Exposures were determined from review of medical records prior to the stroke diagnosis, or the same date for the paired controls; time windows were defined a priori. RESULTS: A medical encounter for head or neck trauma within the prior 12 weeks was an independent risk factor for childhood AIS (odds ratio [OR], 7.5; 95% confidence interval [CI], 2.9-19.3), present in 12% of cases (1.6% of controls). Median time from trauma to stroke was 0.5 days (interquartile range, 0-2 days); post hoc redefinition of trauma exposure (prior 1 week) was more strongly associated with AIS: OR, 39; 95% CI, 5.1-298. A medical encounter for a minor acute infection (prior 4 weeks) was also an independent risk factor (OR, 4.6; 95% CI, 2.6-8.2), present in 33% of cases (13% of controls). No single infection type predominated. Only 2 cases had exposure to trauma and infection. INTERPRETATION: Trauma and acute infection are common independent risk factors for childhood AIS, and may be targets for stroke prevention strategies.

Statin use during ischemic stroke hospitalization is strongly associated with improved poststroke survival.

BACKGROUND AND PURPOSE: Statins reduce infarct size in animal models of stroke and have been hypothesized to improve clinical outcomes after ischemic stroke. We examined the relationship between statin use before and during stroke hospitalization and poststroke survival. METHODS: We analyzed records from 12 689 patients admitted with ischemic stroke to any of 17 hospitals in a large integrated healthcare delivery system between January 2000 and December 2007. We used multivariable survival analysis and grouped-treatment analysis, an instrumental variable method that uses treatment differences between facilities to avoid individual patient-level confounding. RESULTS: Statin use before ischemic stroke hospitalization was associated with improved survival (hazard ratio, 0.85; 95% CI, 0.79-0.93; P<0.001), and use before and during hospitalization was associated with better rates of survival (hazard ratio, 0.59; 95% CI, 0.53-0.65; P<0.001). Patients taking a statin before their stroke who underwent statin withdrawal in the hospital had a substantially greater risk of death (hazard ratio, 2.5; 95% CI, 2.1-2.9; P<0.001). The benefit was greater for high-dose (>60 mg/day) statin use (hazard ratio, 0.43; 95% CI, 0.34-0.53; P<0.001) than for lower dose (<60 mg/day) statin use (hazard ratio, 0.60; 95% CI, 0.54-0.67; P<0.001; test for trend P<0.001), and earlier treatment in-hospital further improved survival. Grouped-treatment analysis showed that the association between statin use and survival cannot be explained by patient-level confounding. CONCLUSIONS: Statin use early in stroke hospitalization is strongly associated with improved poststroke survival, and statin withdrawal in the hospital, even for a brief period, is associated with worsened survival.

Azithromycin induces anti-viral responses in bronchial epithelial cells.

The majority of asthma exacerbations are caused by rhinovirus. Currently the treatment of asthma exacerbations is inadequate. Previous evidence suggests that macrolide antibiotics have anti-inflammatory and antiviral effects; however, the mechanism is unknown. We investigated the anti-rhinoviral potential of macrolides through the induction of antiviral gene mRNA and protein. Primary human bronchial epithelial cells were pre-treated with the macrolides azithromycin, erythromycin and telithromycin, and infected with minor-group rhinovirus 1B and major-group rhinovirus 16. The mRNA expression of the antiviral genes, type I interferon-ß and type III interferon-λ1, interferon-λ2/3, and interferon-stimulated genes (retinoic acid inducible gene I, melanoma differentiation associated gene 5, oligoadenylate synthase, MxA and viperin) and pro-inflammatory cytokines (interleukin (IL)-6 and IL-8), and rhinovirus replication and release were measured. Azithromycin, but not erythromycin or telithromycin, significantly increased rhinovirus 1B- and rhinovirus 16-induced interferons and interferon-stimulated gene mRNA expression and protein production. Furthermore, azithromycin significantly reduced rhinovirus replication and release. Rhinovirus induced IL-6 and IL-8 protein and mRNA expression were not significantly reduced by azithromycin pre-treatment. In conclusion, the results demonstrate that azithromycin has anti-rhinoviral activity in bronchial epithelial cells and, during rhinovirus infection, increases the production of interferon-stimulated genes.

Neurofeedback: A promising tool for the self-regulation of emotion networks.

Real-time functional magnetic resonance imaging (fMRI) affords the opportunity to explore the feasibility of self-regulation of functional brain networks through neurofeedback. We localised emotion networks individually in thirteen participants using fMRI and trained them to upregulate target areas, including the insula and amygdala. Participants achieved a high degree of control of these networks after a brief training period. We observed activation increases during periods of upregulation of emotion networks in the precuneus and medial prefrontal cortex and, with increasing training success, in the ventral striatum. These findings demonstrate the feasibility of fMRI-based neurofeedback of emotion networks and suggest a possible development into a therapeutic tool.

The effect of chromium as chromium propionate on growth performance, carcass traits, meat quality, and the fatty acid profile of fat from pigs fed no supplemented dietary fat, choice white grease, or tallow.

The purpose of this research was to investigate the effect of Cr as chromium propionate (CrProp) on growth performance, carcass traits, meat quality, and the fatty acid profile of fat from pigs fed no supplemented dietary fat, choice white grease (CWG), or tallow. An experiment was conducted with 108 crossbred Yorkshire gilts assigned in a randomized complete block design based on BW (average initial and final BW were 29 +/- 3 and 109 +/- 7 kg, respectively) and allotted within block to a 2 x 3 factorial arrangement of treatments. The treatment arrangement consisted of 2 levels of Cr supplementation (0 and 200 microg/kg in the form of CrProp) and 3 dietary fat sources (no added fat, CWG, or tallow). Each treatment was replicated 6 times with 3 pigs per replicate pen. The experiment was conducted over time with 3 replicates in each of 2 trials. A 4-phase grower-finisher feeding program was used. Dietary treatments were 1) a corn-soybean meal (C-SBM) diet with no added fat; 2) a C-SBM diet with 4% added tallow; 3) a C-SBM diet with 4% added CWG; 4) diet 1 + 200 microg/kg of Cr as CrProp; and 5) diet 2 + 200 microg/kg of Cr; 6) diet 3 + 200 microg/kg of Cr. Addition of Cr did not affect (P > 0.10) growth performance, but did decrease (P = 0.05) 10th-rib backfat and increase (P = 0.03) percentage of muscle. Gain:feed was increased (P = 0.003) and ADFI was decreased (P = 0.03) by fat addition. Fat addition increased HCW (P = 0.05) and dressing percent (P = 0.03). Average backfat, 9th-rib LM cook loss, and 10th-rib LM drip loss and total loss were decreased (P = 0.02 to 0.04) by tallow. Belly bending on both the teatline and scribe side were increased (P = 0.01 to 0.03) by CWG. Iodine values on belly fat samples were decreased (P = 0.02) by Cr supplementation. In addition, iodine values on belly and loin fat samples were increased (P = 0.001) by CWG. Overall, Cr supplementation decreased backfat and the iodine value of belly fat and increased the percentage of muscle.

The development of a testosterone stimulation test in the Virginia opossum (Didelphis virginiana) and its use in evaluating deslorelin contraception.

The aims of the present study were to examine the variability of testosterone secretion in the Virginia Opossum over a 24 h period and to develop a testosterone stimulation test that would provide an index of the prevailing testosterone biosynthetic capacity of the testes; the latter was used to clinically evaluate the efficacy of a gonadotrophin-releasing hormone agonist contraceptive. Sexually-mature captive opossums (n = 12) located in Africam Safari (Mexico) sampled every 12 h over 24 h consistently showed basal (<0.21 ng mL(-1)) blood testosterone concentrations. Intra-muscular injection of buserelin (2 microg mL(-1)) and human chorionic gonadotrophin (hCG; 1000 IU) resulted in an increase (P < 0.05) of plasma testosterone concentrations with maximal concentrations (3.9 ng mL(-1) and 5.8 ng mL(-1) respectively) occurring 120 min after injection. Plasma testosterone declined relatively rapidly to basal concentrations after 240 min with hCG but remained elevated after the same period of time with buserelin. Male opossums treated with (n = 6) and without (n = 6) a controlled-release deslorelin implant (Suprelorin; 4.7 mg deslorelin) were evaluated over a 10-week period for changes in testosterone secretion (hCG stimulation test) and sperm production (spermatorrhea). At the end of this period, the animals were hemi-castrated and their relative testicular quantitative histology compared. Testosterone concentration decreased over the course of the study in both treated and control animals (P < 0.0001) but there was no apparent effect of deslorelin on testosterone secretion, testicular histology (relative proportions of testicular cell types and seminiferous tubule diameter), or sperm production (presence of sperm in the cauda epididymis or urine).