Conditioned place preference reveals ongoing pain in calves 3 weeks after disbudding.

Hot-iron disbudding, a routine procedure that prevents horn bud growth through cauterization, is painful for calves. The resulting burns remain sensitive to touch for weeks, but it is unknown whether calves experience ongoing, non-evoked pain. We evaluated conditioned place preference for analgesia in 44 calves disbudded or sham-disbudded 6 hours (Day 0) or 20 days (Day 20) before testing (n = 11/treatment). Calves were conditioned to associate the effects of a lidocaine cornual nerve block with the location and pattern of a visual stimulus, and a control injection of saline with the contrasting stimulus. On Day 0, disbudded calves tended to prefer the lidocaine-paired stimulus over the saline-paired one, suggesting that they found analgesia rewarding. On Day 20, sham calves avoided the lidocaine-paired stimulus, consistent with humans' experience of this drug being painful. Disbudded calves on Day 20 did not show this aversion, suggesting that they traded off the short-term pain of the lidocaine with the longer-term analgesia provided. Day 0 sham calves did not avoid the lidocaine-paired stimulus, likely because they received less than half the dose of Day 20 calves during conditioning. Thus, higher doses of lidocaine are aversive to uninjured animals, but disbudded calves are willing to engage in this cost. We conclude that calves experience ongoing pain 3 weeks after disbudding, raising additional welfare concerns about this procedure

Effect of gas diffusion layer properties on water distribution across air-cooled, open-cathode polymer electrolyte fuel cells: A combined ex-situ X-ray tomography and in-operando neutron imaging study

In-operando diagnostic techniques provide a means of understanding the internal workings of fuel cells under normal operating conditions so that improved designs and operating regimes can be identified. Here, an approach is used which combines ex‐situ characterisation of two anode gas diffusion/microporous layers (GDL-A and GDL-B) with X-ray computed tomography (CT) and in-operando analysis using neutron imaging of operating fuel cells. The combination of TGA, SEM and X-ray CT reveals that GDL-A has a thin microporous layer with ∼26% PTFE covering a thick diffusion layer composed of ‘spaghetti’-shaped fibres. GDL-B is covered by two microporous media (29% and 6.6% PTFE) penetrating deep within the linear fibre network. The neutron imaging reveals two pathways for water transport underneath the cooling channel, either diffusing through the cathode GDL to the active channels, or diffusing through the membrane and towards the anode. The behaviour of water in the GDL is directly affected by the anode gas diffusion, PTFE content and porosity

The Angiotensin Converting Enzyme Insertion/Deletion polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

BACKGROUND: The ACE gene contains a polymorphism consisting of either the presence (insertion, I) or absence (deletion, D) of a 287 bp alu repeat in intron 16. The D allele is associated with increased ACE activity in both tissue and plasma. The DD genotype is associated with risk of developing ARDS and mortality. The frequency of the D allele is higher in patients with pulmonary fibrosis, sarcoidosis and berylliosis. The role of this polymorphism has not been studied in the development of BPD in the premature newborn. METHODS: ACE I/D genotype was determined in 245 (194 African-American, 47 Caucasian and 4 Hispanic) mechanically ventilated infants weighing less than 1250 grams at birth and compared to outcome (death and/or development of BPD). RESULTS: The incidence of the D allele in the study population was 0.58. Eighty-eight (35.9%) infants were homozygous DD, 107 (43.7%) were heterozygous ID and 50 (20.4%) were homozygous II. There were no significant differences between genotype groups with respect to ethnic origin, birth weight, gestation, or gender. There was no effect of the ACE I/D polymorphism on mortality or development of BPD (O(2 )on 28 days or 36 weeks PCA). Secondary outcomes (intraventricular hemorrhage and periventricular leukomalacia) similarly were not influenced by the ACE ID polymorphism. CONCLUSIONS: The ACE I/D polymorphism does not significantly influence the development of BPD in ventilated infants less than 1250 grams

Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep

<p>Abstract</p> <p>Background</p> <p>Initiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia.</p> <p>Objective</p> <p>To test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury.</p> <p>Methods</p> <p>129 d gestational age lambs (n = 5-8/gp; term = 150 d) were operatively delivered and ventilated after exposure to either 1) no medication, 2) antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3) 0.5 mg/kg Dexamethasone IV at delivery or 4) Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (<it>V</it>_T) to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with <it>V</it>_T8 mL/kg and PEEP 5 cmH₂0 for 2 h 45 min.</p> <p>Results</p> <p>High V_Tventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids.</p> <p>Conclusions</p> <p>Antenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury.</p

Elevated platelet-derived growth factor-BB concentrations in premature neonates who develop chronic lung disease

BACKGROUND: Chronic lung disease (CLD) in the preterm newborn is associated with inflammation and fibrosis. Platelet-derived growth factor-BB (PDGF-BB), a potent chemotactic growth factor, may mediate the fibrotic component of CLD. The objectives of this study were to determine if tracheal aspirate (TA) concentrations of PDGF-BB increase the first 2 weeks of life in premature neonates undergoing mechanical ventilation for respiratory distress syndrome (RDS), its relationship to the development of CLD, pulmonary hemorrhage (PH) and its relationship to airway colonization with Ureaplasma urealyticum (Uu). METHODS: Infants with a birth weight less than 1500 grams who required mechanical ventilation for RDS were enrolled into this study with parental consent. Tracheal aspirates were collected daily during clinically indicated suctioning. Uu cultures were performed on TA collected in the first week of life. TA supernatants were assayed for PDGF-BB and secretory component of IgA concentrations using ELISA techniques. RESULTS: Fifty premature neonates were enrolled into the study. Twenty-eight infants were oxygen dependent at 28 days of life and 16 infants were oxygen dependent at 36 weeks postconceptual age. PDGF-BB concentrations peaked between 4 and 6 days of life. Maximum PDGF-BB concentrations were significantly higher in infants who developed CLD or died from respiratory failure. PH was associated with increased risk of CLD and was associated with higher PDGF-BB concentrations. There was no correlation between maximum PDGF-BB concentrations and Uu isolation from the airway. CONCLUSIONS: PDGF-BB concentrations increase in TAs of infants who undergo mechanical ventilation for RDS during the first 2 weeks of life and maximal concentrations are greater in those infants who subsequently develop CLD. Elevation in lung PDGF-BB may play a role in the development of CLD

Role of HPV Genotype, Multiple Infections, and Viral Load on the Risk of High-Grade Cervical Neoplasia

Background:HPV testing provides a much more sensitive method of detection for high-grade lesions than cytology, but specificity is low. Here we explore the extent to which full HPV genotyping, viral load and multiplicity of types can be used to improve specificity. Methods:A population-based sample of 47,120 women undergoing cervical screening were tested for 13 high-risk HPV genotypes. Positive predictive values (PPV) for CIN grade 2 or worse (CIN2+; N=3449) and CIN3 or worse (CIN3+; N=1475) over three years of follow-up were estimated for HPV genotype and viral load. Weighted multivariate logistic regression models were used to estimate the odds of CIN2+ or CIN3+ according to genotype, multiplicity of types and viral load. Results:High-risk HPV was detected in 15.4% of women. A hierarchy of HPV genotypes based on sequentially maximizing PPVs for CIN3+ found HPV16>33>31 to be the most predictive, followed sequentially by HPV18>35>58>45>52>59>51>39>56>68. After adjusting for higher ranked genotypes, multiple HPV infections added little to risk prediction. High viral loads for HPV18, 35, 52 and 58 carried more risk than low viral loads for HPV16, 31 and 33. High viral load for HPV16 was significantly more associated with CIN3+ than low viral load. Conclusions:HPV genotype and viral load, but not multiplicity of HPV infections, are important predictors of CIN2+ and CIN3+. Impact:The ability to identify women at higher risk of CIN2+ and CIN3+ based on both HPV genotype and viral load could be important for individualising triage plans, particularly as HPV becomes the primary screening test

Suppression of GATA-3 Nuclear Import and Phosphorylation: A Novel Mechanism of Corticosteroid Action in Allergic Disease

Peter Barnes and colleagues show that corticosteroids have a potent inhibitory effect on GATA-3 via two interacting mechanisms that suppress Th2 cytokine expression. This novel mechanism of corticosteroid action may help explain the efficacy of corticosteroids in allergic diseases

Immune Response to Mycobacterium tuberculosis Infection in the Parietal Pleura of Patients with Tuberculous Pleurisy

The T lymphocyte-mediated immune response to Mycobacterium tuberculosis infection in the parietal pleura of patients with tuberculous pleurisy is unknown. The aim of this study was to investigate the immune response in the parietal pleura of tuberculous pleurisy compared with nonspecific pleuritis. We have measured the numbers of inflammatory cells particularly T-cell subsets (Th1/Th2/Th17/Treg cells) in biopsies of parietal pleura obtained from 14 subjects with proven tuberculous pleurisy compared with a control group of 12 subjects with nonspecific pleuritis. The number of CD3+, CD4+ and CCR4+ cells and the expression of RORC2 mRNA were significantly increased in the tuberculous pleurisy patients compared with the nonspecific pleuritis subjects. The number of toluidine blue+ cells, tryptase+ cells and GATA-3+ cells was significantly decreased in the parietal pleura of patients with tuberculous pleurisy compared with the control group of nonspecific pleuritis subjects. Logistic regression with receiver operator characteristic (ROC) analysis for the three single markers was performed and showed a better performance for GATA-3 with a sensitivity of 75%, a specificity of 100% and an AUC of 0.88. There was no significant difference between the two groups of subjects in the number of CD8, CD68, neutrophil elastase, interferon (IFN)-γ, STAT4, T-bet, CCR5, CXCR3, CRTH2, STAT6 and FOXP3 positive cells. Elevated CD3, CD4, CCR4 and Th17 cells and decreased mast cells and GATA-3+ cells in the parietal pleura distinguish patients with untreated tuberculous pleurisy from those with nonspecific pleuritis