1. There is huge emphasis in veterinary and agricultural science in understanding the basics of processes and exploiting them for benefits to the economy and human and animal welfare. It is always ...valuable to be able to step back from existing or favourite hypotheses and paradigms to look at an area of work or problem and see whether a different approach might be productive particularly by drawing parallels with other sometimes unrelated problems.
2. This approach has been used to explore (i) the use of live, attenuated Salmonella vaccines to generate a new form of competitive exclusion, (ii) gene expression technology for the design of improved inactivated vaccines (iii) use of cytokine therapy to reduce persistent carriage by Salmonella, (iv) using bacteriophages to reduce carcass contamination by food-borne pathogens and reduce carriage of antibiotic resistance plasmids.
3. The potential for extending virus therapy to parasite infections is also discussed.
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Salmonella enterica remains an important avian and human pathogen. Control has been effective in some countries but the hygiene and biosecurity required may not be possible everywhere. Antibiotic ...resistance is an increasing problem for both veterinary and human medicine. This short review commentary highlights existing and potential new control measures including legislation, hygiene and biosecurity, use of live and inactivated vaccines, and bacteriophages to tackle intestinal colonization, reduce the prevalence of antibiotic resistance and improve carcass decontamination.
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Fowl typhoid and pullorum disease are two distinct septicaemic diseases largely specific to avian species and caused by Salmonella Gallinarum and Salmonella Pullorum, respectively. They were first ...described more than one century ago. Since their discovery, many efforts have been made to control and prevent their occurrence in commercial farming of birds. However, they remain a serious economic problem to livestock in countries where measures of control are not efficient or in those where the climatic conditions favour the environmental spread of these microorganisms. During the past 15 to 20 years there has been an explosion of genetic and immunological information on the biology of these two organisms, which is beginning to contribute to a better understanding of the organisms and their interaction with the host. However, it is not enough simply to understand the pathology in greater and greater detail. What is needed, in addition to this increase in basic knowledge, is creative thinking to challenge existing paradigms and to develop really novel approaches to infection control.
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Background
The British Society of Gastroenterology recommends that all familial adenomatous polyposis (FAP) and Lynch syndrome (LS) families are screened in the context of a registry. This systematic ...review was performed to appraise the published evidence for registration and screening in relation to colorectal cancer (CRC) incidence and mortality.
Methods
Five electronic databases were searched using a combination of medical subject heading terms and free‐text keywords. Titles and s were scrutinized by two independent reviewers. Inclusion criteria were English‐language studies describing CRC incidence and/or mortality in patients with FAP or LS, with comparison of either: screened and unscreened patients, or time periods before and after establishment of the registry.
Results
Of 4668 s identified, 185 full‐text articles were selected; 43 studies fulfilled the inclusion criteria. No randomized clinical trial evidence was identified. For FAP, 33 of 33 studies described a significant reduction of CRC incidence and mortality with registration and screening. For LS, nine of ten studies described a reduction of CRC incidence and mortality with registration and screening. Five studies (FAP, 2; LS, 3) provided evidence for complete prevention of CRC‐related deaths during surveillance. Clinical and statistical heterogeneity prevented pooling of data for meta‐analysis.
Conclusion
Studies consistently report that registration and screening result in a reduction of CRC incidence and mortality in patients with FAP and LS (level 2a evidence, grade B recommendation). Funding and managerial support for hereditary CRC registries should be made available.
Presented to the Association of Surgeons of Great Britain and Ireland 2013 Congress, Glasgow, UK, May 2013, and to the Annual Meeting of the Association of Coloproctology of Great Britain and Ireland, Liverpool, UK, July 2013; published in form as Br J Surg 2013; 100(Suppl 7): 123–124 and as Colorectal Dis 2013; 15(Suppl 1): 4
Registration and screening of benefit
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Lytic bacteriophages, applied to chicken skin that had been experimentally contaminated with Salmonella enterica serovar Enteritidis or Campylobacter jejuni at a multiplicity of infection (MOI) of 1, ...increased in titer and reduced the pathogen numbers by less than 1 log10 unit. Phages applied at a MOI of 100 to 1,000 rapidly reduced the recoverable bacterial numbers by up to 2 log10 units over 48 h. When the level of Salmonella contamination was low (< log10 2 per unit area of skin) and the MOI was 10(5), no organisms were recovered. By increasing the number of phage particles applied (i.e., MOI of 10(7)), it was also possible to eliminate other Salmonella strains that showed high levels of resistance because of restriction but to which the phages were able to attach.
Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H₂S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the ...cardiovascular system and elsewhere. The chemical basis of this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators of H₂S/sulfide signaling, but their biosynthesis and relationship to NO remain enigmatic. We sought to characterize the nature, chemical biology, and bioactivity of key reaction products formed in the NO/sulfide system. At physiological pH, we find that NO and sulfide form a network of cascading chemical reactions that generate radical intermediates as well as anionic and uncharged solutes, with accumulation of three major products: nitrosopersulfide (SSNO⁻), polysulfides, and dinitrososulfite N-nitrosohydroxylamine-N-sulfonate (SULFI/NO), each with a distinct chemical biology and in vitro and in vivo bioactivity. SSNO⁻ is resistant to thiols and cyanolysis, efficiently donates both sulfane sulfur and NO, and potently lowers blood pressure. Polysulfides are both intermediates and products of SSNO⁻ synthesis/decomposition, and they also decrease blood pressure and enhance arterial compliance. SULFI/NO is a weak combined NO/nitroxyl donor that releases mainly N₂O on decomposition; although it affects blood pressure only mildly, it markedly increases cardiac contractility, and formation of its precursor sulfite likely contributes to NO scavenging. Our results unveil an unexpectedly rich network of coupled chemical reactions between NO and H₂S/sulfide, suggesting that the bioactivity of either transmitter is governed by concomitant formation of polysulfides and anionic S/N-hybrid species. This conceptual framework would seem to offer ample opportunities for the modulation of fundamental biological processes governed by redox switching and sulfur trafficking.
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Objective/Hypothesis
To describe clinically relevant between‐group differences in MD Anderson Dysphagia Inventory (MDADI) scores among head and neck cancer (HNC) patients.
Study Design
Retrospective ...cross‐sectional study was conducted in 1,136 HNC patients seen for modified barium swallow (MBS) studies.
Methods
The MDADI was administered by written questionnaire at the MBS appointment. MD Anderson Dysphagia Inventory global, composite, and subscale scores were calculated. Anchor‐based methods were employed to determine clinically meaningful between‐group differences by feeding tube status, aspiration status (per MBS study), and diet level.
Results
Mean MDADI scores for the 1,136 patients were: emotional 65.8 ± 17.3, functional 68.1 ± 19.6, physical 60.1 ± 18.6, global 59.3 ± 28.3, and composite 64.0 ± 17.1. Three hundred seventy‐eight patients (33%) were feeding tube‐dependent; 395 (34.8%) were aspirators; 122 (11%) were nothing per oral (Performance Status Scale‐Head and Neck PSS‐HN diet = 0); and 249 (22%) ate unrestricted, regular diets (PSS‐HN diet = 100). Statistically significant (P < 0.0001) between‐group differences (feeding tube vs. no feeding tube, aspirator vs. nonaspirator, oral vs. nonoral diet, PSS‐HN diet levels) were observed for all mean MDADI scores (global, composite, and subscales). A mean difference of 10 points in composite MDADI scores differentiated feeding tube‐dependent from nontube‐dependent patients, aspirators from nonaspirators, and distinct PSS‐HN diet levels.
Conclusions
We identify that a 10‐point between‐group difference in composite MDADI scores was associated with clinically meaningful between‐group differences in swallowing function.
Level of Evidence
4. Laryngoscope, 126:1108–1113, 2016
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As a part of the 40th anniversary celebrations of Avian Pathology we review the last four decades of Salmonella research which has led to major progress in our understanding of the bacteriology and ...infection biology of the organism through the huge advances in molecular biology and immunology that have accompanied technical advances in biology generally. In many countries combinations of improvements in management, sometimes under legislative pressure and supported by a number of basic biological interventions, have resulted in reductions in incidence in the Salmonella serovars that are commonly associated with food-poisoning to unprecedented low levels in parent flocks, broilers and layers. Utilisation of the information generated during the past few decades should improve the efficacy of surveillance and biological interventions both for the intestinal carriage that is associated most frequently with human infection and also for systemic diseases, including fowl typhoid and pullorum disease. These two diseases continue to be major economic problems in many countries where the possibilities for improvements in hygiene may be limited but which, nevertheless, are increasingly a significant part of the global economy in poultry meat.
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Salmonella enterica in poultry remains a major political issue. S. enterica serovar Enteritidis, particularly, remains a world-wide problem. Control in poultry by immunity, whether acquired or ...innate, is a possible means of containing the problem. Widespread usage of antibiotics has led to the emergence of multiple antibiotic-resistant bacteria. This problem has indicated an increasing requirement for effective vaccines to control this important zoonotic infection. An attempt is made in the present review to explain the relatively poor success in immunizing food animals against these non-host-specific Salmonella serotypes that usually produce food-poisoning, compared with the success obtained with the small number of serotypes that more typically produce systemic "typhoid-like" diseases. New examinations of old problems such as the carrier state and vertical transmission, observed with S. Pullorum, is generating new information of relevance to immunity. Newer methods of attenuation are being developed. Live vaccines, if administered orally, demonstrate non-specific and rapid protection against infection that is of biological and practical interest. However, from the point of view of consumer safety, there is a school of thought that considers inactivated or sub-unit vaccines to be the safest. The benefits of developing effective killed or sub-unit vaccines over the use of live vaccines are enormous. Recently, there have been significant advances in the development of adjuvants (e.g. microspheres) that are capable of potent immuno-stimulation, targeting different arms of the immune system. The exploitation of such technology in conjunction with the ongoing developments in identifying key Salmonella virulence determinants should form the next generation of Salmonella sub-unit vaccines for the control of this important group of pathogens. There are additional areas of concern associated with the use of live vaccines, particularly if these are generated by genetic manipulation.
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