Producing multi-coloured bunches through beam-induced ionization injection in plasma wakefield accelerator.

This paper discusses the properties of electron beams formed in plasma wakefield accelerators through ionization injection. In particular, the potential for generating a beam composed of co-located multi-colour beamlets is demonstrated in the case where the ionization is initiated by the evolving charge field of the drive beam itself. The physics of the processes of ionization and injection are explored through OSIRIS simulations. Experimental evidence showing similar features are presented from the data obtained in the E217 experiment at the FACET facility of the SLAC National Laboratory. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Betatron radiation and emittance growth in plasma wakefield accelerators.

Beam-driven plasma wakefield acceleration (PWFA) has demonstrated significant progress during the past two decades of research. The new Facility for Advanced Accelerator Experimental Tests (FACET) II, currently under construction, will provide 10 GeV electron beams with unprecedented parameters for the next generation of PWFA experiments. In the context of the FACET II facility, we present simulation results on expected betatron radiation and its potential application to diagnose emittance preservation and hosing instability in the upcoming PWFA experiments. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Prevalence and Outcomes of Achromobacter Species Infections in Adults with Cystic Fibrosis: a North American Cohort Study.

Achromobacter species are increasingly being detected in cystic fibrosis (CF) patients, with an unclear epidemiology and impact. We studied a cohort of patients attending a Canadian adult CF clinic who had positive sputum cultures for Achromobacter species in the period from 1984 to 2013. Infection was categorized as transient or persistent (≥50% positive cultures for 1 year). Those with persistent infection were matched 2:1 with age-, sex-, and time-matched controls without a history of Achromobacter infection, and mixed-effects models were used to assess pulmonary exacerbation (PEx) frequency and lung function decline. Isolates from a biobank were retrospectively assessed, identified to the species level by nrdA sequencing, and genotyped using pulsed-field gel electrophoresis (PFGE). Thirty-four patients (11% of those in our clinic), with a median age of 24 years (interquartile range [IQR], 20.3 to 29.8 years), developed Achromobacter infection. Ten patients (29%) developed persistent infection. Persistence did not denote permanence, as most patients ultimately cleared infection, often after years. Patients were more likely to experience PEx at incident isolation than at prior or subsequent visits (odds ratio [OR], 2.7 [95% confidence interval {CI}, 1.2 to 6.7]; P = 0.03). Following persistent infection, there was no difference in annual lung function decline (-1.08% [95% CI, -2.73 to 0.57%] versus -2.74% [95% CI, -4.02 to 1.46%]; P = 0.12) or the odds of PEx (OR, 1.21 [95% CI, 0.45 to 3.28]; P = 0.70). Differential virulence among Achromobacter species was not observed, and no cases of transmission occurred. We demonstrated that incident Achromobacter infection was associated with a greater risk of PEx; however, neither transient nor chronic infection was associated with a worsened long-term prognosis. Large, multicenter studies are needed to clarify the clinical impact, natural history, and transmissibility of Achromobacter.

Development and Validation of a PCR Assay To Detect the Prairie Epidemic Strain of Pseudomonas aeruginosa from Patients with Cystic Fibrosis.

The monitoring of epidemic Pseudomonas aeruginosa is important for cystic fibrosis (CF) infection control. The prairie epidemic strain (PES) is common in western Canadian CF clinics. Using whole-genome sequencing, we identified a novel genomic island and developed a PCR assay for PES. Against a collection of 186 P. aeruginosa isolates, the assay had 98% sensitivity and 100% specificity.

Cancer treatment-related neuropathic pain: proof of concept study with menthol--a TRPM8 agonist.

PURPOSE: Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol. PATIENTS AND METHODS: Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4-6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4-6 weeks. Secondary outcomes included changes in function, mood and skin sensation. RESULTS: Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood (P = 0.0004), catastrophising (P = 0.001), walking ability (P = 0.008) and sensation (P < 0.01) were also observed. CONCLUSION: This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required.

Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin.

BACKGROUND: The different perception and assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) between healthcare providers and patients has not yet been fully addressed, although these two approaches might eventually lead to inconsistent, possibly conflicting interpretation, especially regarding sensory impairment. PATIENTS AND METHODS: A cohort of 281 subjects with stable CIPN was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC v. 2.0) sensory scale, the clinical Total Neuropathy Score (TNSc©), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (mISS) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). RESULTS: Patients' probability estimates showed that the EORTC QLQ-CIPN20 sensory score was overall more highly related to the NCI-CTC sensory score. However, the vibration perception item of the TNSc had a higher probability to be scored 0 for EORTC QLQ-CIPN20 scores lower than 35, as vibration score 2 for EORTC QLQ-CIPN20 scores between 35 and 50 and as grade 3 or 4 for EORTC QLQ-CIPN20 scores higher than 50. The linear models showed a significant trend between each mISS item and increasing EORTC QLQ-CIPN20 sensory scores. CONCLUSION: None of the clinical items had a perfect relationship with patients' perception, and most of the discrepancies stood in the intermediate levels of CIPN severity. Our data indicate that to achieve a comprehensive knowledge of CIPN including a reliable assessment of both the severity and the quality of CIPN-related sensory impairment, clinical and PRO measures should be always combined.

The quality of impressions for crowns and bridges: an assessment of the work received at three commercial dental laboratories. assessing qualities of impressions that may lead to occlusal discrepancies with indirect restorations.

There are few published studies that directly assess the quality of impressions for crowns and bridges in the UK. This paper considers aspects of impression quality with particular attention to factors causing potential occlusal discrepancies in the final restoration. To this end three dental laboratories were visited over a 3-month period. All impressions for conventional crown and bridgework that arrived on the days of the visits were examined and assessed against criteria defined on a custom-designed assessment form. A total of 206 impression cases were considered in this study. Flexible impression trays were used for 65% of working impressions. Their use was more common for NHS work than for private work. 31.9% of all alginate impressions examined were not adequately fixed to the tray. Visible contamination of impressions was not uncommon.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS: After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION: Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

The quality of impressions for crowns and bridges: an assessment of the work received at three commercial dental laboratories. assessing the quality of the impressions of prepared teeth.

The literature is limited in studies directly assessing the quality of impressions for crowns and bridges in the UK. The aim of the study was to assess the quality of impressions for conventional crown and bridgework received by commercial dental laboratories. Three dental laboratories were visited over a 3-month period. All impressions for conventional crowns and bridges that arrived on the days of the visits were examined prior to any laboratory processing. A total of 206 impression cases were examined and assessed against criteria laid out in a custom-designed assessment form. Defects were commonly found in the recording of prepared teeth. Overall, 44.2% of impression cases were unsatisfactory. NHS impressions were more than twice as likely to be unsatisfactory compared to private impressions. If the results of this survey are typical then the general quality of impressions for fixed crown and bridgework is unacceptable. This is particularly true for work completed under the NHS contract.

Clinically relevant fatigue in recurrence-free prostate cancer survivors.

BACKGROUND: Little is known about the prevalence and associations of clinically relevant fatigue (CRF) in recurrence-free prostate cancer survivors. PATIENTS AND METHODS: Four hundred and sixteen recurrence-free prostate cancer survivors who were >1 year post-radiotherapy or radical prostatectomy were surveyed. The prevalence of CRF (defined as Brief Fatigue Inventory >3) was determined and compared with a noncancer control group. Other measures included the Hospital Anxiety and Depression Scale, International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Relationships between these factors and CRF were explored in univariate and multivariate analyses. RESULTS: Analyzable data were obtained from 91% (377/416) of patients. The prevalence of CRF was 29% (108/377) versus 16% (10/63) in the controls (P=0.031). CRF was more common in post-radiotherapy than in post-prostatectomy 33% (79/240) versus 22% (29/133), P=0.024. However, when other factors (current depression, anxiety, urinary symptoms, medical comorbidities, pain and insomnia) were controlled for, previous treatment did not predict CRF. Current depression [Hospital Anxiety and Depression Scale≥8 was by far the strongest association [odds ratio 9.9, 95% confidence interval 4.2-23.5)]. CONCLUSIONS: Almost one-third of recurrence-free prostate cancer survivors report CRF. Depression, anxiety, urinary symptoms, pain and insomnia measured at outcome are more strongly associated than type of cancer treatment previously received.

Clinically relevant fatigue in men with hormone-sensitive prostate cancer on long-term androgen deprivation therapy.

BACKGROUND: The purpose of the study was to determine the prevalence and associations of clinically relevant fatigue (CRF) in men with biochemically controlled prostate cancer on long-term androgen deprivation therapy (ADT). PATIENTS AND METHODS: One hundred and ninety-eight men were surveyed and the prevalence of CRF (Brief Fatigue Inventory score >3) determined. Associations with other measures (Hospital Anxiety and Depression Scale; International Prostate Symptom Score; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; Brief Pain Inventory worst pain; clinical and demographic information) were explored in univariate and multivariate analyses. RESULTS: Eight-one per cent (160 of 198) of questionnaires were analysable. CRF prevalence was 43% (68 of 160). CRF associations included moderate/severe urinary symptoms, anxiety and medical co-morbidities; the strongest associations were depression [odds ratio (OR) 9.8, 95% confidence interval (CI) 4.3-22.8] and pain (OR 9.2, 95% CI 4.0-21.5). After controlling for other factors, the independent associations were depression (OR 4.7, 95% CI 1.6-14.0) and pain (OR 3.1, 95% CI 1.0-8.9). There was no association with age, disease burden or treatment duration. CONCLUSIONS: Two-fifths of men with biochemically controlled prostate cancer on long-term ADT report CRF that interferes with function. Management aimed at improving CRF should address depression and pain.

Prevention of artificial dental plaque formation in vitro by plant extracts.

AIMS: A number of previous studies have shown that plant extracts can inhibit formation of dental plaque. The ability of extracts of Rosmarinus officianalis L., Salvia officianalis L., unfermented cocoa, red grape seed and green tea to inhibit plaque bacteria, glucosyltransferase activity, glucan and plaque formation in an in vitro model using bovine teeth was examined. METHODS AND RESULTS: The antimicrobial activity of the plant extracts against oral bacteria was determined using a standard susceptibility agar dilution technique. Inhibition of growth and acid production from glucose and sucrose by Streptococcus mutans in liquid culture was investigated. Prevention of plaque formation on bovine teeth initiated by Strep. mutans was studied using an artificial mouth. The plant extracts inhibited the growth of oral bacteria and prevented acid production by Strep. mutans. Extracts inhibited glucosyltransferase activity and glucan production and inhibited adhesion to glass. Extracts of R. officianalis L. and S. officianalis L. at 0·25 mg ml(-1) reduced plaque growth by >80%. Green tea extract completely inhibited plaque formation but resulted in a greenish discolouration of the teeth which could not be removed by scrubbing. CONCLUSIONS: The plant extracts, particularly those from R. officianalis L. and S. officianalis L., inhibited glucosyltranferase activity, glucan production and plaque formation in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the extracts of R. officianalis L. and S. officianalis L. may be useful as antiplaque agents in foods and dental preparations. Bovine teeth can be used as an alternative to hydroxyapatite for studies of plaque formation, but they need to be carefully sterilized before use.

Capecitabine combined with oxaliplatin (CapOx) in clinical practice: how significant is peripheral neuropathy?

BACKGROUND: There is speculation that peripheral neuropathy (PN) with capecitabine and oxaliplatin (CapOx; 130 mg/m(2), day 1, every 21 days) may be more common than with FOLFOX4 (5-fluorouracil and oxaliplatin 85 mg/m(2), day 1, every 14 days). We aimed to determine PN incidence and associations during CapOx, and 6 and 12 months after CapOx. PATIENTS AND METHODS: Retrospective audit of 188 oxaliplatin-naive colorectal cancer patients (87 adjuvant, 101 palliative) who received at least one cycle of CapOx. Neurosensory Common Toxicity Criteria Adverse Events version 3 were applied. RESULTS: Overall, 94% experienced acute PN. Worst severities for adjuvant and palliative patients, respectively, were grade 1, 44% and 54%; grade 2, 35% and 32%; grade 3, 16% and 3%; grade 4, 0% and 1% and grade unclear 1% and 1%. Two patients developed PN after CapOx completion despite no symptoms during treatment. Chronic PN at 6 months affected 57% and 18% of adjuvant and palliative patients, respectively. At 12 months, 35% and 16% were affected. Chronic PN at 12 months was associated with cumulative oxaliplatin dose but not age, gender, acute myotonia, pseudolaryngospasm or grade 2 or more PN during treatment. CONCLUSION: Incidence of acute PN during CapOx appears similar to FOLFOX4 but chronic PN in adjuvant patients may be more common with CapOx.

Clinical Outcomes Associated With Escherichia coli Infections in Adults With Cystic Fibrosis: A Cohort Study.

BACKGROUND: Analysis of "emerging" pathogens in cystic fibrosis (CF) lung disease has focused on unique pathogens that are rare in other human diseases or are drug resistant. Escherichia coli is recovered in the sputum of up to 25% of patients with CF, yet little is known about the epidemiology or clinical impact of infection. METHODS: We studied patients attending a Canadian adult CF clinic who had positive sputum cultures for E coli from 1978 to 2016. Infection was categorized as transient or persistent (≥3 positive sputum cultures, spanning >6 months). Those with persistent infection were matched 2:1 with age, sex, and time-period controls without history of E coli infection, and mixed-effects models were used to assess pulmonary exacerbation (PEx) frequency, lung function decline, hospitalization, and intravenous antibiotic days. RESULTS: Forty-five patients (12.3%) had E coli recovered from sputum samples between 1978 and 2016, and 18 patients (40%) developed persistent infection. Nine patients (24%) had PEx at incident infection, and increased bioburden was predictive of exacerbation (P = .03). Risk factors for persistent infection included lower nutritional status (P < .001) and lower lung function (P = .009), but chronic infection with Pseudomonas aeruginosa was protective. There was no difference in annual lung function decline, need for hospitalization or intravenous antibiotics, or risk of PEx in patients with persistent infection. CONCLUSIONS: Persistent E coli infection was frequent and was more common in CF patients with low nutritional status and lung function. However, this does not predict clinical decline. Multicenter studies would allow better characterization of the epidemiology and clinical impact of E coli infection.

A longitudinal characterization of the Non-Cystic Fibrosis Bronchiectasis airway microbiome.

A diverse microbiota exists within the airways of individuals with non-cystic fibrosis bronchiectasis (nCFB). How the lung microbiome evolves over time, and whether changes within the microbiome correlate with future disease progression is not yet known. We assessed the microbial community structure of 133 serial sputa and subsequent disease course of 29 nCFB patients collected over a span of 4-16 years using 16S rRNA paired-end sequencing. Interestingly, no significant shifts in the microbial community of individuals were observed during extended follow-up suggesting the microbiome remains relatively stable over prolonged periods. Samples that were Pseudomonas aeruginosa culture positive displayed markedly different microbial community structures compared to those that were positive for Haemophilus influenzae. Importantly, patients with sputum of lower microbial community diversity were more likely to experience subsequent lung function decline as defined by annual change in ≥-1 FEV1% predicted. Shannon diversity values <1 were more prevalent in patients with FEV1 decline (P = 0.002). However, the relative abundance of particular core microbiota constituents did not associate with risk of decline. Here we present data confirming that the microbiome of nCFB individuals is generally stable, and that microbiome-based measurements may have a prognostic role as biomarkers for nCFB.

Venom Complexity in a Pitviper Produced by Facultative Parthenogenesis.

Facultative parthenogenesis (FP) is asexual reproduction in plant and animal species that would otherwise reproduce sexually. This process in vertebrates typically results from automictic development (likely terminal fusion) and is phylogenetically widespread. In squamate reptiles and chondrichthyan fishes, FP has been reported to occur in nature and can result in the production of reproductively viable offspring; suggesting that it is of ecological and evolutionary significance. However, terminal fusion automixis is believed to result in near genome-wide reductions in heterozygosity; thus, FP seems likely to affect key phenotypic characters, yet this remains almost completely unstudied. Snake venom is a complex phenotypic character primarily used to subjugate prey and is thus tightly linked to individual fitness. Surprisingly, the composition and function of venom produced by a parthenogenetic pitviper exhibits a high degree of similarity to that of its mother and conspecifics from the same population. Therefore, the apparent loss of allelic diversity caused by FP appears unlikely to have a significant impact on the prey-capturing ability of this snake. Accordingly, the pitviper offspring produced by FP retained complex phenotypic characteristics associated with fitness. This result reinforces the potential ecological and evolutionary importance of FP and questions our understanding of the inheritance of venom-associated genes.

Clinically relevant fatigue in cancer outpatients: the Edinburgh Cancer Centre symptom study.

BACKGROUND: Fatigue is associated with cancer and its treatment but we know little about how many and which patients suffer fatigue of clinical severity. We aimed to determine the prevalence of clinically relevant fatigue (CRF) and its associations in outpatients with various cancer diagnoses. PATIENTS AND METHODS: A survey of outpatients with colorectal, breast, gynaecological, genitourinary, sarcoma, melanoma and miscellaneous tumours at a regional cancer centre. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) fatigue subscale and the Hospital Anxiety and Depression Scale (HADS). These self-report data were linked to demographic and clinical variables. Data were available on 2867 outpatients. RESULTS: The prevalence of CRF (EORTC fatigue subscale > or =40) was 32% (95% confidence interval 31-34%). The variables independently associated with CRF were primary cancer site, having disease present, type of cancer treatment and emotional distress (total HADS score > or =15). Emotional distress had the strongest association with fatigue but half the cases of CRF were not distressed. CONCLUSION: CRF is common in cancer outpatients and is associated with type of disease and treatment, as well as with emotional distress. The association between CRF and emotional distress is strong but they are not equivalent conditions.

Gastrointestinal tolerance of erythritol and xylitol ingested in a liquid.

OBJECTIVES: To determine and compare the gastrointestinal (GI) responses of young adults following consumption of 45 g sucrose, 20, 35 and 50 g xylitol or erythritol given as a single oral, bolus dose in a liquid. DESIGN: The study was a randomized, double-blind, placebo-controlled study. SUBJECTS: Seventy healthy adult volunteers aged 18-24 years were recruited from the student population of the University of Salford. Sixty-four subjects completed the study. INTERVENTIONS: Subjects consumed at home without supervision and in random order, either 45 g sucrose or 20, 35 and 50 g erythritol or xylitol in water on individual test days, while maintaining their normal diet. Test days were separated by 7-day washout periods. Subjects reported the prevalence and magnitude of flatulence, borborygmi, bloating, colic, bowel movements and the passage of faeces of an abnormally watery consistency. RESULTS: Compared with 45 g sucrose, consumption of a single oral, bolus dose of 50 g xylitol in water significantly increased the number of subjects reporting nausea (P<0.01), bloating (P<0.05), borborygmi (P<0.005), colic (P<0.05), watery faeces (P<0.05) and total bowel movement frequency (P<0.01). Also 35 g of xylitol increased significantly bowel movement frequency to pass watery faeces (P<0.05). In contrast, 50 g erythritol only significantly increased the number of subjects reporting nausea (P<0.01) and borborygmi (P<0.05). Lower doses of 20 and 35 g erythritol did not provoke a significant increase in GI symptoms. At all levels of intake, xylitol produced significantly more watery faeces than erythritol: resp. 50 g xylitol vs 35 g erythritol (P<0.001), 50 g xylitol vs 20 g erythritol (P<0.001) and 35 g xylitol vs 20 g erythritol (P<0.05). CONCLUSIONS: When consumed in water, 35 and 50 g xylitol was associated with significant intestinal symptom scores and watery faeces, compared to the sucrose control, whereas at all levels studied erythritol scored significantly less symptoms. Consumption of 20 and 35 g erythritol by healthy volunteers, in a liquid, is tolerated well, without any symptoms. At the highest level of erythritol intake (50 g), only a significant increase in borborygmi and nausea was observed, whereas xylitol intake at this level induced a significant increase in watery faeces.

Gastrointestinal responses following acute and medium term intake of retrograded resistant maltodextrins, classified as type 3 resistant starch.

DESIGN: Study part 1 was executed as a randomized double-blind placebo-controlled crossover study and study part 2 as a longitudinal study. SUBJECTS: Forty-one healthy adult volunteers aged 18-24 years were recruited from the student population of the University of Salford. All subjects enrolled and completed study part 1 and 39 subjects enrolled and completed study part 2. INTERVENTIONS: In study part 1, individuals consumed, in random order 0, 20, 40, 60, 80, 100 or 120 g of a RRM containing starch product incorporated in pre-prepared foods on individual test days. Assuming a minimum content of 50% RRM in the starch product this delivered respectively 0, 10, 20, 30, 40, 50 or 60 g of RRM. All foods were prepared and coded by personnel not involved in carrying out the tests. Test days were separated by 7 day washout periods. In study part 2, consumption of RRM was increased from 3.6 g at day 1 in incremental doses up to each subject's MNED as determined in study 1, to be achieved at day 14. Subsequently, RRM intake was from day 15-21 in a way that the final intake at day 21 was at least 10 g above the individual MNED. In both parts of the study, subjects reported the prevalence and magnitude of GI symptoms. RESULTS: No significant change was observed in either defecation frequency and faecal consistency or the number of subjects experiencing any GI symptoms, following consumption of foods containing 0-60 g RRM. The individual MNED at which an increase in symptoms did not occur was determined as 60 g RRM for 71% of the subjects who participated in study part 1. Regression analysis showed that consumption of gradually increasing doses of RRM in food products over 21 days was associated with a significant increase in the mean symptom score for flatulence (P=1.5 x 10(-4)), total bowel movement frequency (P=0.023) and bowel movement frequency to pass watery faeces (P=0.0157). Increasing the ingested dose of RRM by 10 g above the predetermined MNED, however, did not provoke significant increases in GI symptoms. In both studies, the majority of symptom responses were classified by the subjects as 'little more than usual'. CONCLUSIONS: Consumption of up to 60 g RRM is tolerated well by most individuals with no evidence of any significant dose-dependent increase in the magnitude of symptoms or the occurrence of multiple GI symptoms. However, a mild laxative effect when consuming >60 g RRM is suggested. Although there was no change in GI responses following consumption of increasing doses of RRM over 21 days, generally a dose of 10 g RRM above the MNED level was tolerated well during medium term intake.

The antibacterial activity of plant extracts containing polyphenols against Streptococcus mutans.

The minimum inhibitory concentrations (MIC) of commercially available and 70% aqueous propanone (P70) extracts from plants chosen for polyphenol content on Streptococcus mutans and other bacteria were determined using a standard susceptibility agar dilution technique to investigate their potential use as anticariogenic agents. The effects on adhesion of S. mutans to glass were also studied. The lowest MICs were for the P70 extracts of red grape skin (0.5 mg ml(-1)) and green tea and sloe berry skin (2 mg ml(-1)). The commercial extracts generally had a lower activity with a minimum MIC of 2 mg ml(-1) for tea extracts, grape seed extracts and Pynogenol (extract of maritime pine). All other extracts had MICs of > or = 4 mg ml(-1). Unfermented cocoa had greater antimicrobial activity than fermented cocoa and the activity of the fractionated extract increased with the extent of epicatechin polymerization. Epicatechin polymer had an MIC of 1 mg ml(-1) and an MBC of 64 mg ml(-1). Selected extracts were tested against other oral bacteria and showed activity against gram-positive organisms. P70 extracts of unfermented cocoa, epicatechin polymer fraction, green tea and red grape seed were bacteriostatic and prevented acid production when added at the MIC to cultures of S. mutans grown in a chemically defined medium supplemented with either glucose or sucrose. There was a reduction in viability which was greater when added to washed cells, but there were some viable cells after 24 h. The extracts also reduced adherence of S. mutans to glass.