Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn's disease. The ENIGMA study.

Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F. prausnitzii strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of Proteus and/or Veillonellaceae - both implicated in early Crohn's disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn's disease.

Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis.

Mycobacterium tuberculosis remains a leading cause of infectious disease morbidity and mortality for which new drug combination therapies are needed. Mycobacterial bioenergetics has emerged as a promising space for the development of novel therapeutics. Further to this, unique combinations of respiratory inhibitors have been shown to have synergistic or synthetic lethal interactions, suggesting that combinations of bioenergetic inhibitors could drastically shorten treatment times. Realizing the full potential of this unique target space requires an understanding of which combinations of respiratory complexes, when inhibited, have the strongest interactions and potential in a clinical setting. In this review, we discuss (i) chemical-interaction, (ii) genetic-interaction and (iii) chemical-genetic interaction studies to explore the consequences of inhibiting multiple mycobacterial respiratory components. We provide potential mechanisms to describe the basis for the strongest interactions. Finally, whilst we place an emphasis on interactions that occur with existing bioenergetic inhibitors, by highlighting interactions that occur with alternative respiratory components we envision that this information will provide a rational to further explore alternative proteins as potential drug targets and as part of unique drug combinations.

What is the role of surgical simulation on operative opportunity for the trainee ENT surgeon?

OBJECTIVE: This study sought to assess the impact of simulation training in influencing trainees' initial surgical participation as perceived by experienced surgeon trainers. METHODS: Twenty ENT surgeons assessed how much of a given procedure they would expect to allow a trainee to perform for their first time. Responses were provided for trainees who had undergone a relevant simulation course and those who had not, and scored according to the eLogbook levels of involvement in surgery. This was completed for simulated procedures with validated models, across four grades of junior doctors. RESULTS: A total of 1120 judgements on the trainees' intended level of involvement were made. The median involvement score was higher in the simulation group versus the non-simulation group (Mann-Whitney U, p = 0.0001), corresponding to a translation in surgical opportunity from a primarily assisting role to an active role. CONCLUSION: Trainer perception of a relevant ENT simulation course appears to positively impact on the initial surgical opportunities afforded to the trainee.

Balloon sinuplasty: our first year.

INTRODUCTION: Balloon sinuplasty is a new technology which has only recently been introduced in the UK. We review the current literature, and we present our first year's results for the technique together with a description of indications, outcomes and problems. METHODS: Retrospective case note review of 27 consecutive patients undergoing sinuplasty alone in the first year in which this procedure was performed. The main outcome measures used were subjective improvement and Sino-Nasal Outcome Test (SNOT-22) score. RESULTS: Dilatation was successful in 98 per cent of sinuses in which it was attempted; however, subjective improvement was noted in only 62 per cent of patients thus treated. CONCLUSION: We believe that balloon sinuplasty has a place in routine rhinology practice but that its applications are limited, and that its additional costs must be considered. We present advantages and possible limitations of the technique.

Significant differences in UK and US female bone density reference ranges.

UNLABELLED: In the United Kingdom (UK), T- and Z-scores are usually calculated using reference ranges derived from United States (US) populations. In the UK arm of a recent randomised trial (International Breast Cancer Intervention Study II (IBIS-II)), substantially, fewer women than expected were recruited into the osteopenic (-2.545 years with a typical body mass index of 28 kg m(-2) have spine and hip bone mineral density (BMD) 0.6 standard deviation higher than their US counterparts. INTRODUCTION: Dual energy X-ray absorptiometry (DXA) is widely used for the diagnosis of osteoporosis and to investigate the effect of pharmacological treatments on BMD. In both routine and research settings, it is important that DXA results are correctly interpreted. METHODS: T- and Z-scores for the first 650 UK Caucasian women enrolled in the IBIS-II study were compared with data from two independent studies of unrelated, unselected UK Caucasian women: (1) 2,382 women aged 18 to 79 recruited to the Twins UK Adult Twin Registry; (2) 431 women aged 21 to 84 with no risk factors for osteoporosis recruited at Guy's Hospital. All DXA measurements were performed on Hologic densitometers. Subjects were divided into six age bands, and T- and Z-scores were calculated using the manufacturer's US reference range for the spine and the National Health and Nutrition Examination Survey III reference range for the femoral neck and total hip. RESULTS: The overall mean Z-scores for the IBIS-II, Twin, and Guy's groups were: spine: +0.61, +0.29, +0.33; femoral neck: +0.42, +0.36, +0.45; total hip: +0.65, +0.38, +0.39 (all p<0.001 compared with the expected value of 0). The mean body weight of subjects in the three studies was 74.4, 65.5, and 65.4 kg, respectively. Analysis revealed a highly significant relationship between Z-score and weight at each BMD site with a slope of 0.03 kg(-1). CONCLUSIONS: In general, US spine and hip reference ranges are not suitable for the calculation of Z-scores in UK women. For some research study designs, the differences may significantly influence the pattern of subject recruitment.

Joint action of disease control measures: a case study of alternaria leaf blight of carrot.

ABSTRACT The efficacy of chemical (i.e., foliar fungicide sprays), genetic (i.e., moderately resistant cultivars), and cultural (i.e., drip-irrigation system) control measures was quantified individually and in combination in the management of Alternaria dauci, the causal agent of Alternaria leaf blight of carrot. Whereas host resistance and drip irrigation affected both the time of disease onset and the rate of disease progression, chemical control affected only the latter. In all cases, a single control measure did not provide an acceptable level of disease suppression. Control efficacy values (based on the relative area under the disease progress curve) for chemical, genetic, and cultural control were 58 +/- 11, 39 +/- 20, and 60 +/- 22%, respectively (values are means +/- standard error). By contrast, implementing two control measures concurrently always improved disease suppression significantly compared with the individual measures. Control efficacy values were 91 +/- 8% for the integration of chemical and genetic measures and 82 +/- 23% for the integration of chemical and cultural measures. Moreover, yields in plots protected by two control measures simultaneously were higher by 10.1 to 28.6 t/ha than those in the respective plots protected by single measures. The joint effect of chemical control and host resistance was additive, whereas that of chemical control and drip irrigation was synergistic in most cases. A literature review was performed to determine if these findings represent a general relationship between chemical and genetic, and chemical and cultural measures. Based on 19 reviewed cases, it was concluded that additive effects are the rule and synergistic or antagonistic effects are the exception. Synergistic effects of two control measures were observed when one control measure improved the efficacy of the other directly or when one control measure induced host resistance or predisposed the pathogen to increased susceptibility. These results may enable a more effective selection of candidate control measures for integration in the future.

First Report of Leaf Blight Caused by Alternaria longipes on Carrots in Israel.

Alternaria leaf blight, caused by Alternaria dauci (Köhn) Groves & Skolko, is one of the most devastating foliar pathogens of carrots (Daucus carota L.). Lesions appear as minute, necrotic, dark brown spots often initiated on the edge of the leaflet blade. They later enlarge in size and may merge into a large necrotic area, causing shriveling of the entire leaflet (1). In summer 2000, observations made in several carrot fields in the northwestern part of the Negev Region in Israel revealed infections that were atypical for A. dauci because they were initiated primarily in the middle section of the leaflet blade and were surrounded by a large yellowish area. A. longipes (Ellis & Everh.) E. Mason was consistently isolated from the lesions. Occasionally both A. longipes and A. dauci developed on the same leaves. The two pathogens differed in conidial morphology (size and shape of spore and beak) when cultured on potato dextrose agar medium. One hundred conidia of each species were measured. A. dauci conidia were 100 to 450 µm long and 6 to 15 µm wide, with a beak of up to 3 times the length of the conidium; A. longipes conidia were 35 to 110 µm long and 11 to 21 µm wide, and the beak measured one-third to one-half the length of the conidium. These measurements corresponded to the sizes listed previously (2). Inoculation of greenhouse-grown plants and completion of Koch's postulates confirmed that A. longipes is pathogenic to carrots. Conidia of both species germinated at temperatures from 5 to 36°C. In vitro tests revealed that A. longipes was less sensitive than A. dauci to fungicides commonly used in Israel in carrot fields. A fifty percent effective dose of chlorothalonil and difenoconazole was 3.0 and 0.2 µg a.i./ml, respectively, for mycelia growth of A. dauci, whereas the corresponding values for A. longipes were 10.5 and 3.0 µg a.i./ml, respectively. The prevalence of A. longipes in carrot fields and the influence of this pathogen on yields are currently not known. References: (1) I. Barash et al. Physiol. Plant Pathol. 19:7, 1981. (2) M. B. Ellis. Dematiaceous Hyphomycetes. CMI. Kew, Surrey, England, 1971.

Optimization of Chemical Suppression of Alternaria dauci, the Causal Agent of Alternaria Leaf Blight in Carrots.

Alternaria leaf blight, caused by Alternaria dauci, is a major constraint to carrot production in Israel. Israeli carrot growers apply prophylactic sprays at 3- to 10-day intervals throughout the season until harvest, up to 30 sprays in a growing season. In this study, we attempted to optimize the chemical suppression of the disease, in order to reduce fungicide use. The efficacy of nine fungicides was determined in two field experiments. All fungicides reduced disease severity, but there were significant differences in efficacy among them. The most effective were difenoconazole and chlorothalonil; less effective were copper hydroxide, tebuconazole, trifloxystrobin, and mancozeb; the least effective in our experiments were flutrifol, propineb, and iprodione. The effect of the time of spray initiation on fungicide efficacy was determined in three field experiments. Qualitative (analysis of variance) and quantitative (regression) analyses of the data revealed that initiating sprays after disease onset reduced control efficacy. Thus, an action threshold model could not be developed for A. dauci in carrots. The time before harvest at which sprays could be terminated was tested in two field experiments and it was found that terminating sprays 14 days before harvest did not significantly affect the overall control efficacy. The main conclusions derived from these experiments were tested and corroborated in two additional field experiments.