Energy of the quasi-free electron in CO and HD: Probing intermolecular potentials within the local Wigner-Seitz model.

We present the quasi-free electron energy V0(ρ) in the weakly polar fluids CO and HD from gas to liquid densities ρ, on noncritical isotherms, and at a temperature near the critical isotherm. These results represent the first systematic investigation of V0(ρ) in polar fluids across a broad density range and illustrate that field enhanced photoemission can be used to obtain data in such systems. We show that the local Wigner-Seitz model for V0(ρ), when coupled with thermodynamic data for the fluids, can yield optimized intermolecular potential parameters, as well as the magnitude of the zero kinetic energy electron scattering length.

Energy of the quasi-free electron in H2, D2, and O2: Probing intermolecular potentials within the local Wigner-Seitz model.

We present for the first time the quasi-free electron energy V0(ρ) for H2, D2, and O2 from gas to liquid densities, on noncritical isotherms and on a near critical isotherm in each fluid. These data illustrate the ability of field enhanced photoemission (FEP) to determine V0(ρ) accurately in strongly absorbing fluids (e.g., O2) and fluids with extremely low critical temperatures (e.g., H2 and D2). We also show that the isotropic local Wigner-Seitz model for V0(ρ)--when coupled with thermodynamic data for the fluid--can yield optimized parameters for intermolecular potentials, as well as zero kinetic energy electron scattering lengths.

Universal use of surgical masks is tolerated and prevents respiratory viral infection in stem cell transplant recipients.

Prevention of respiratory viral infection in stem cell transplant patients is important due to its high risk of adverse outcome. This single-centre, mixed methods study, conducted before the severe acute respiratory syndrome coronavirus-2 pandemic, explored the barriers and facilitators to a policy of universal mask use by visitors and healthcare workers, and examined the impact of the first year of introduction of the policy on respiratory viral infection rates compared with preceding years, adjusted for overall incidence. Education around universal mask use was highlighted as being particularly important in policy implementation. A significant decrease in respiratory viral infection was observed following introduction.

Noxa/HSP27 complex delays degradation of ubiquitylated IkBα in airway epithelial cells to reduce pulmonary inflammation.

IFN-γ is known as a pro-inflammatory cytokine, but can also block inflammation in certain chronic diseases although the underlying mechanisms are poorly understood. We found that IFN-γ rapidly induced Noxa expression and that extent of inflammation by repeated house dust mite exposure was enhanced in noxa-/- compared with noxa+/+ mice. Noxa expression blocked transforming necrosis factor alpha (TNF-α)-induced nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the production of pro-inflammatory cytokines. Noxa did not affect TNF-α-induced IκBα phosphorylation but the degradation of 48-chain-ubiquitylated IκBα. The Cys25 of Noxa was cross-linked with Cys137 of phospho-HSP27 and both proteins were required for blocking the degradation of ubiquitylated IκBα. Because phospho-HSP27 is present in airway epithelial cells and not in fibroblasts or thymocytes, we generated transgenic mice that inducibly expressed Noxa in airway epithelia. These mice showed protection from allergen-induced inflammation and mucous cell metaplasia by blocking nuclear translocation of NF-κB. Further, we identified a Noxa-derived peptide that prolonged degradation of 48-chain-ubiquitylated IκBα, blocked nuclear translocation of NF-κB, and reduced allergen-induced inflammation in mice. These results suggest that the anti-inflammatory role of the Noxa protein may be restricted to airway epithelial cells and the use of Noxa for therapy of chronic lung diseases may be associated with reduced side effects.

Pretreatment with antibody to eosinophil major basic protein prevents hyperresponsiveness by protecting neuronal M2 muscarinic receptors in antigen-challenged guinea pigs.

In antigen-challenged guinea pigs there is recruitment of eosinophils into the lungs and to airway nerves, decreased function of inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in the lungs, and airway hyperresponsiveness. A rabbit antibody to guinea pig eosinophil major basic protein was used to determine whether M2 muscarinic receptor dysfunction, and the subsequent hyperresponsiveness, are due to antagonism of the M2 receptor by eosinophil major basic protein. Guinea pigs were sensitized, challenged with ovalbumin and hyperresponsiveness, and M2 receptor function tested 24 h later with the muscarinic agonist pilocarpine. Antigen-challenged guinea pigs were hyperresponsive to electrical stimulation of the vagus nerves compared with controls. Likewise, loss of M2 receptor function was demonstrated since the agonist pilocarpine inhibited vagally-induced bronchoconstriction in control but not challenged animals. Pretreatment with rabbit antibody to guinea pig eosinophil major basic protein prevented hyperresponsiveness, and protected M2 receptor function in the antigen-challenged animals without inhibiting eosinophil accumulation in the lungs or around the nerves. Thus, hyperresponsiveness is a result of inhibition of neuronal M2 muscarinic receptor function by eosinophil major basic protein in antigen-challenged guinea pigs.

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis.

Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface. To address this hypothesis, we combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the Adora2b receptor. Adora2b(-/-) mice experienced a significantly heightened severity of colitis, associated with a more acute onset of disease and loss of intestinal epithelial barrier function. Comparison of mice with Adora2b deletion on vascular endothelial cells (Adora2b(fl/fl)VeCadCre(+)) or intestinal epithelia (Adora2b(fl/fl)VillinCre(+)) revealed a selective role for epithelial Adora2b signaling in attenuating colonic inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair response. Similarly, in vivo studies in genetic mouse models or treatment studies with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken together, our results suggest that intestinal epithelial Adora2b signaling provides protection during intestinal inflammation via enhancing mucosal barrier responses.

Traffic of lymphocytes in the thoracic duct and renal lymph after allotransplantation and in immunosuppression.

A marked rise is seen in the number of white blood cells in the lymph leaving the sheep kidney after allografting; the number of lymphocytes leaving the kidney rising in direct relation to the degree of damage from acute rejection. No such rise is demonstrable in the number of lymphocytes in the thoracic duct lymph of sheep with rejecting kidney allografts. Indeed, there is an apparent decrease in the number of lymphocytes in the thoracic duct lymph of sheep with rejecting kidney allografts. Indeed, there is an apparent decrease in the number of circulating lymphocytes in the body when acute rejection is fully developed. Animals on immunosuppressive regimens show no alteration in the number of lymphocytes collected on thoracic duct cannulation, but immunosuppression appears to reduce the lymphocyte traffic through the kidney.

Production of tolerance and physical dependence in the rat by simple administration of morphine in drinking water.

1 Rats are capable of consuming solutions of morphine sulphate in drinking water ad libitum in the absence of taste-masking chemicals and without the need for scheduled provision or prior parenteral administration of the drug. 2 The success of this method depends on the initial provision of a 0.1 mg/ml solution of morphine sulphate. 3 When the drug concentration is increased to 0.4 mg/ml, the rats achieve an average daily intake of 50 mg/kg body wt. each. 4 Daily intake of morphine may be increased by at least about three fold by increasing the drug concentration to 1.2 mg/ml. 5 Oral morphine administration causes only a moderate loss in body weight. 6 Rats whose daily intake of the drug is 50 mg/kg exhibit tolerance to the analgesic action of morphine and show a drastic loss in body weight at 24 h after withdrawal and most of the behavioural symptoms of the naloxone-precipitated withdrawal syndrome. 7 It is suggested that this simple method of morphine administration is suitable for further biochemical and behavioural studies of the actions of the drug.

A controlled trial of different treatment regimens in patients with urinary tract infections after lower urinary tract surgery.

One hundred and four patients who developed urinary tract infections after catheterization for acute retention of urine and surgery of the bladder or urethra were randomly allocated to four treatment groups. Analysis of the results in 65 patients showed that co-trimoxazole and 1 g cephradine administered twice daily for 1 week were successful in eradicating the urinary tract infections in 93% and 88% of the patients, respectively. The same dose of cephradine administered 4-times a day eradicated 64% of the infections. In patients for whom no treatment was given, the original infection did not clear in 65%. Escherichia coli and coagulase-negative staphylococci were the commonest infecting organisms. The in vitro sensitivity testing of antibiotics did not correlate well with the successful eradication of the infecting organism.

Screening impotence by home nocturnal tumescence self-monitoring.

Twenty subjects complaining of impotence were assessed using nocturnal penile tumescence (NPT), neurological, vascular and hormonal analysis. Subjects undertook NPT in both home and hospital environments: 10 hospital first and 10 home first. There were high levels of agreement between diagnosis using NPT in the two conditions and diagnosis from the physiological tests. There was a high correlation of frequency of erections between the home and hospital conditions, together with a high consecutive night reliability when using the monitor in the home condition (r = .94, p = .001).

Stingray hickey.

A large number of injuries from stingrays are reported each year in the United States. Usually these injuries are inflicted by the stingray's tail, after the resting stingray is stepped on. The tail has a stinger that can cause puncture wounds with envenomation. We report a case in which an injury from a stingray was due to its bite.

Detrimental role of the airway mucin Muc5ac during ventilator-induced lung injury.

Acute lung injury (ALI) is associated with high morbidity and mortality in critically ill patients. At present, the functional contribution of airway mucins to ALI is unknown. We hypothesized that excessive mucus production could be detrimental during lung injury. Initial transcriptional profiling of airway mucins revealed a selective and robust induction of MUC5AC upon cyclic mechanical stretch exposure of pulmonary epithelia (Calu-3). Additional studies confirmed time- and stretch-dose-dependent induction of MUC5AC transcript or protein during cyclic mechanical stretch exposure in vitro or during ventilator-induced lung injury in vivo. Patients suffering from ALI showed a 58-fold increase in MUC5AC protein in their bronchoalveolar lavage. Studies of the MUC5AC promoter implicated nuclear factor κB in Muc5ac induction during ALI. Moreover, mice with gene-targeted deletion of Muc5ac⁻/⁻ experience attenuated lung inflammation and pulmonary edema during injurious ventilation. We observed that neutrophil trafficking into the lungs of Muc5ac⁻/⁻ mice was selectively attenuated. This implicates that endogenous Muc5ac production enhances pulmonary neutrophil trafficking during lung injury. Together, these studies reveal a detrimental role for endogenous Muc5ac production during ALI and suggest pharmacological strategies to dampen mucin production in the treatment of lung injury.

Lessons from a large norovirus outbreak: impact of viral load, patient age and ward design on duration of symptoms and shedding and likelihood of transmission.

BACKGROUND: Hospital norovirus outbreaks cause significant financial and operational disruption which should be minimised by optimal handling of affected areas and use of isolation facilities. AIM: To identify factors associated with increased duration of symptoms and viral excretion and increased probability of transmission. METHODS: Retrospective observational study of a large norovirus outbreak at a UK teaching hospital in the winter of 2009-2010 where patients were diagnosed using a real-time polymerase chain reaction (PCR) assay. FINDINGS: Symptom duration was significantly associated with patient age (Spearman rank correlation coefficient: 0.197; P = 0.002) but not with PCR cycle threshold (C(T)) value. Duration of viral excretion was found to be longer in patients with higher viral loads. Transmission within a ward bay was not significantly associated either with age or with C(T) value but was more likely to occur in some ward blocks than others, which may relate to differences in ward design. Transfer of patients into isolation rooms or cohorted area within two days of symptom onset did not significantly influence probability of onward transmission (52% vs 47%; P = 0.67). CONCLUSIONS: The presented data suggest that C(T) value may guide timing of repeat sample collection if ongoing gastrointestinal symptoms may relate to other pathologies, and that patients developing symptoms of norovirus may remain in their current bay rather than being moved into isolation facilities. The bay or ward should be closed to new admissions but it should be anticipated that duration of symptoms and therefore closure will be longer when the outbreak involves elderly patients.

A stochastic mathematical model of the within-herd transmission dynamics of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): fade-out and persistence.

A stochastic, mathematical model of a farrow-finish pig herd was developed and used to investigate the within-herd transmission dynamics of PRRSV, and to examine patterns of on-farm persistence and fade-out. The model was structured to represent the management of a typical European pig herd. Three parameters determining the natural history of infection were derived from the literature. Transmission parameters were chosen using PRRSV antibody data from a cross-sectional study of 103 pig herds (Evans et al., 2008). The seroprevalence by age was generated from the model at 21-day intervals and was compared to the cross-sectional field data using log-likelihood, accounting for the accuracy of the ELISA test used. The model was run for various isolation practices of purchased gilts, contact structure, herd size and the frequency of re-introduction of infectious gilts. The time-dependent log-likelihood patterns varied between herds in a similar way to patterns observed from serological values from the 103 farms. Essentially they indicated two patterns of seroprevalence: herds in which PRRSV was stably persistent, and herds in which PRRSV was unstable, either recently introduced or recently faded-out. With a herd size of 327 sows with identical management, fade-out of virus occurred within 4 weeks in 21.9% of simulations. Without isolation of gilts from sows, fade-out within 250 days decreased from 81.6% to 14.3% and for herd sizes of 75, 150, 300 and 600, the probability of persistence of virus for >1200 days was 4%, 13.4%, 20.4% and 18.2%, respectively. Introduction of virus at a rate of approximately 0.37 times per year resulted in virus persisting for >1200 days in 32.4% of simulations, compared with 17.6% for no re-introduction. Fade-out of virus was most likely to occur within breeding females before virus reached young stock. Persistence was more likely once PRRSV was present in piglets which in turn infected rearing-pigs. The probability of persistence was higher with increased herd size, increased contact between different age groups and increased re-introduction of infectious gilts. The ability of the model to capture the variability in cross-sectional, age-related serological patterns suggests that the processes of re-introduction, persistence and fade-out of PRRSV play critical roles in PRRSV epidemiology. The potential importance to pig production and transmission of virus between herds is discussed.