The discrete path sampling technique is used to calculate folding pathways of the 16-amino acid beta hairpin-forming sequence from residues 41-56 of the B1 domain of protein G. The folding time is ...obtained using master equation dynamics and kinetic Monte Carlo simulations, and the time evolution of different order parameters and occupation probabilities of groups of minima are calculated and used to characterize intermediates on the folding pathway.
Salmonella in cattle herds may behave as epidemic or endemic infections. An intensive longitudinal sampling study across all management groups and ages on six dairy farms in the UK was used to ...examine patterns of Salmonella shedding, following the prior identification of either Salmonella Dublin (SD) (three farms) or Salmonella Typhimurium (ST) (three farms) on the premises in the context of clinical salmonellosis. Individual faeces, pooled faeces and environmental samples (total 5711 samples), taken approximately every six weeks for 15–24 weeks, were cultured for Salmonella. SD was detected at low frequency (on any visit, 0.5–18.3 per cent of samples positive) and most consistently in calves. By contrast, ST was isolated at higher frequency (on any visit, 6.8–75 per cent of samples positive), and in higher numbers, up to 107 cfu/g faeces. Significantly more samples from calves were positive for ST than were positive for SD (50.6 per cent v 3.1 per cent; P < 0.001), which was also true for milking cows (46.3 per cent v 4.4 per cent; P < 0.001). The differences could help to explain the different patterns of bovine infection classically associated with these two serovars in the UK. No consistent effect upon shedding was seen among the ST-infected herds following vaccination.
Abstract
Human noroviruses are the most common viral agents of acute gastroenteritis. Recently, human intestinal enteroids were shown to be permissive for norovirus infection. We tested their ...suitability as a system to study norovirus neutralization. Hyperimmune sera raised against virus-like particles (VLPs) representing different genotypes showed highly specific neutralization activity against GII.4 and GII.6 noroviruses. Carbohydrate blocking assays and neutralization exhibited similar patterns in antibody responses. Notably, sera produced against chimeric VLPs that presented swapped structural shell and protruding (P) domains, from different genotypes showed that neutralization is primarily mediated by antibodies mapping to the P domain of the norovirus capsid protein. This study provides empirical information on the antigenic differences among genotypes as measured by neutralization, which could guide vaccine design.
Lack of a cell culture system for human noroviruses has impacted the study of their antigenic relationships in vivo. Using human intestinal enteroids, we show that 4 viruses, representing 2 norovirus genotypes, are neutralized in a genotype-specific manner.
•Grazing cows fed supplement during milking or as a partial mixed ration on a feedpad.•Ruminal pH and serum haptoglobin (Hp) concentrations were measured.•Supplement feeding method did not affect ...ruminal pH or serum Hp.
Ruminal pH and serum concentrations of haptoglobin (Hp) were measured in order to assess the risk of subacute ruminal acidosis (SARA) in grazing cows offered rolled wheat grain twice daily in the dairy at milking (Control group; n = 64), or as a partial mixed ration (PMR group; n = 64) on a feedpad. Cows were allocated various levels of the supplement (8, 10, 12 or 14 kg dry matter/day). Ruminal pH was measured in 16 rumen-fistulated cows (eight PMR and eight Control group cows), using indwelling pH meters, recording every 10 min for 14 days. Serum Hp was analysed in samples collected from 125 cows. No differences in ruminal pH or serum Hp concentration were found between treatment groups, or levels of feeding. It was concluded that, using ruminal pH patterns and Hp as markers of SARA at the feeding levels used in this study, there were no differences between grazing cows fed the supplement either as grain in the dairy or as a PMR fed on a feedpad.
Enteric bacteria with a demonstrable or potential ability to form attaching-effacing lesions, so-called attaching-effacing (AE) bacteria, have been found in the intestinal tracts of a wide variety of ...warm-blooded animal species, including man. In some host species, for example cattle, pigs, rabbits and human beings, attaching-effacing
Escherichia coli (AEEC) have an established role as enteropathogens. In other host species, AE bacteria are of less certain significance. With continuing advances in the detection and typing of AE strains, the importance of these bacteria for many hosts is likely to become clearer. The pathogenic effects of AE bacteria result from adhesion to the intestinal mucosa by a variety of mechanisms, culminating in the formation of the characteristic intimate adhesion of the AE lesion. The ability to induce AE lesions is mediated by the co-ordinated expression of some 40 bacterial genes organized within a so-called pathogenicity island, known as the “Locus for Enterocyte Effacement”. It is also believed that the production of bacterial toxins, principally Vero toxins, is a significant virulence factor for some AEEC strains. Recent areas of research into AE bacteria include: the use of
Citrobacter rodentium to model human AEEC disease; quorum-sensing mechanisms used by AEEC to modulate virulence gene expression; and the potential role of adhesion in the persistent colonization of the intestine by AE bacteria. This review of AE bacteria covers their molecular biology, their occurrence in various animal species, and the diagnosis, pathology and clinical aspects of animal diseases with which they are associated. Reference is made to human pathogens where appropriate. The focus is mainly on natural colonization and disease, but complementary experimental data are also included.
Logistic regression, supported by other statistical analyses was used to explore the possible association of risk factors with the fluoroquinolone (FQ)-resistance status of 108 pig finisher farms in ...Great Britain. The farms were classified as ‘affected’ or ‘not affected’ by FQ-resistant E. coli or Campylobacter spp. on the basis of isolation of organisms from faecal samples on media containing 1 mg/l FQ. The use of FQ was the most important factor associated with finding resistant E. coli and/or Campylobacter, which were found on 79% (FQ-resistant E. coli) and 86% (FQ-resistant Campylobacter) of farms with a history of FQ use. However, resistant bacteria were also found on 19% (FQ-resistant E. coli) and 54% (FQ-resistant Campylobacter) of farms with no history of FQ use. For FQ-resistant E. coli, biosecurity measures may be protective and there was strong seasonal variation, with more farms found affected when sampled in the summer. For FQ-resistant Campylobacter, the buying-in of grower stock may increase risk and good on-farm hygiene may be protective. The findings suggest that resistant organisms, particularly Campylobacter, may spread between pig farms.
A survey of salmonella infection on 454 commercial layer flock holdings in the uk was carried out between October 2004 and September 2005. Fifty-four (11·7 per cent, 95 per cent confidence interval ...9·3 to 14·0 per cent) were salmonella positive. The most common serovar identified was Salmonella Enteritidis at a prevalence of 5·8 per cent, and 70 per cent of these isolates were phage types 4, 6, 7 and 35. Salmonella Typhimurium was the second most prevalent serovar, found in 1·8 per cent of the farms. Of the three other serovars given top priority by the eu because of their public health significance, Salmonella Virchow and Salmonella Infantis were each isolated from one holding, but Salmonella Hadar was not isolated from any of the holdings. Analysis of antimicrobial resistance patterns revealed that over 76 per cent of the isolates were sensitive to all of the 16 drugs tested, and all the isolates were sensitive to ciprofloxacin, gentamicin, ceftazidime, apramycin, amikacin, amoxicillin/clavulanic acid, neomycin and cefotaxime.
Eight pig breeding units previously associated with Salmonella Typhimurium were visited during a period of up to seven years. Samples from voided faeces, surfaces, fomites and wildlife were cultured. ...Certain serovars (Derby, Stanley, Give, Bredeney, Mbandaka and Manhattan) were isolated repeatedly on certain units, while others (Agona, Ajiobo, Heidelberg, Meleagridis, Muenchen, Montevideo, Rissen and Senftenberg) were detected only once or intermittently. Serovars Kedougou, Newport and Typhimurium were isolated consistently on some units but only intermittently on others. There was an association between the Salmonella serovar in pens and in the immediate environment of the pens. Pens holding breeding stock destined for production herds were frequently positive for Salmonella. Herds under common ownership showed similar serovar combinations. Serovars from wildlife were typical of the associated premises. Cleaning and disinfection was frequently ineffective. On one unit, a low level of Salmonella was attributed to a small herd size, good cleaning and disinfection, and good rodent control. Breeding herds are therefore susceptible to endemic infections with multiple Salmonella serovars, and cleaning, disinfection and vector control may be inadequate in many cases. The prevalence of S Typhimurium was greater in youngstock, which may have important implications for public health.
Objectives In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional ...characteristics associated with enteral autonomy. Study design A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. Results A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. Conclusions A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.
In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12-26 years. Following notification of 7 ...presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings.
We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine.
Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0-5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003-0.7) for conjugated meningococcal C vaccination in a 2003 school-based program.
Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae.
PDF
