The effect of natural antimicrobials against Campylobacter spp. and its similarities to Salmonella spp, Listeria spp., Escherichia coli, Vibrio spp., Clostridium spp. and Staphylococcus spp.

Publication history: Accepted - 5 November 2020; Published online - 13 November 2020The increased resistance of campylobacters to antibiotics required the identification and isolation of novel antimicrobials able to inhibit its virulence, to cause less or no resistance and display no host toxicity. Acquiring all this knowledge was only possible through a better understanding of their antibacterial potency and of the biological mechanisms involved attenuating the bacterial virulence factors. This review describes the most recent developments in the area by looking at the new antimicrobial interventions aiming to combat the transmission and colonisation of Campylobacter spp. and its commonalities with other pathogenic bacteria. In this review we are also looking into the most recent developments, both in vitro and in vivo, focusing on the biological mechanisms by which natural antimicrobials express their anti-pathogenic effect. Following this extensive literature search we conclude that further studies are essential to elucidate the efficiency of plant, animal, bacteria and marine-derived antimicrobials as well as their role as promising alternatives to antibiotics

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Impact of industrial production system parameters on chicken microbiomes: mechanisms to improve performance and reduce Campylobacter

Publication history: Accepted - 17 August 2020; Published online - 9 September 2020Background The factors affecting host-pathogen ecology in terms of the microbiome remain poorly studied. Chickens are a key source of protein with gut health heavily dependent on the complex microbiome which has key roles in nutrient assimilation and vitamin and amino acid biosynthesis. The chicken gut microbiome may be influenced by extrinsic production system parameters such as Placement Birds/m2 (stocking density), feed type and additives. Such parameters, in addition to on-farm biosecurity may influence performance and also pathogenic bacterial numbers such as Campylobacter. In this study, three different production systems ‘Normal’ (N), ‘Higher Welfare’ (HW) and ‘Omega-3 Higher Welfare’ (O) were investigated in an industrial farm environment at day 7 and day 30 with a range of extrinsic parameters correlating performance with microbial dynamics and Campylobacter presence. Results Our data identified production system N as significantly dissimilar from production systems HW and O when comparing the prevalence of genera. An increase in Placement Birds/m2 density led to a decrease in environmental pressure influencing the microbial community structure. Prevalence of genera, such as Eisenbergiella within HW and O, and likewise Alistipes within N were representative. These genera have roles directly relating to energy metabolism, amino acid, nucleotide and short chain fatty acid (SCFA) utilisation. Thus, an association exists between consistent and differentiating parameters of the production systems that affect feed utilisation, leading to competitive exclusion of genera based on competition for nutrients and other factors. Campylobacter was identified within specific production system and presence was linked with the increased diversity and increased environmental pressure on microbial community structure. Addition of Omega-3 though did alter prevalence of specific genera, in our analysis did not differentiate itself from HW production system. However, Omega-3 was linked with a positive impact on weight gain. Conclusions Overall, our results show that microbial communities in different industrial production systems are deterministic in elucidating the underlying biological confounders, and these recommendations are transferable to farm practices and diet manipulation leading to improved performance and better intervention strategies against Campylobacter within the food chain.OG and NC acknowledge research funding from Moy Park. UZI is funded by NERC Independent Research Fellowship (NE/L011956/1)

Mixtures of natural antimicrobials can reduce Campylobacter jejuni, Salmonella enterica and Clostridium perfringens infections and cellular inflammatory response in MDCK cells

Publication history: Accepted - 1 June 2021; Published online - 7 June 2021Background: The classification of natural antimicrobials as potential antibiotic replacements is still hampered by the absence of clear biological mechanisms behind their mode of action. This study investigated the mechanisms underlying the anti-bacterial effect of a mixture of natural antimicrobials (maltodextrin, citric acid, sodium citrate, malic acid, citrus extract and olive extract) against Campylobacter jejuni RC039, Salmonella enterica SE 10/72 and Clostridium perfringens ATCC® 13124 invasion of Madin–Darby Canine Kidney cells (MDCK). Results: Minimum sub-inhibitory concentrations were determined for Campylobacter jejuni (0.25%), Salmonella enterica (0.50%) and Clostridium perfringens (0.50%) required for the in vitro infection assays with MDCK cells. The antimicrobial mixture significantly reduced the virulence of all three pathogens towards MDCK cells and restored the integrity of cellular tight junctions through increased transepithelial resistance (TEER) and higher expression levels of ZO-1 (zonula occludens 1) and occludin. This study also identified the ERK (external regulated kinase) signalling pathway as a key mechanism in blocking the pro-inflammatory cytokine production (IL-1β, IL-6, IL-8, TNF-α) in infected cells. The reduction in hydrogen peroxide ( H2O2) production and release by infected MDCK cells, in the presence of the antimicrobial mixture, was also associated with less tetrathionate formed by oxidation of thiosulphate (p < 0.0001). Conclusion: The present study describes for the first time that mixtures of natural antimicrobials can prevent the formation of substrates used by bacterial pathogens to grow and survive in anaerobic environments (e.g. tetrathionate).This study was supported by a grant awarded to NC by Environtech, Dublin, Ireland

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice

Cone-rod dystrophy (CRD) is an inherited progressive retinal dystrophy affecting the function of cone and rod photoreceptors. By autozygosity mapping, we identified null mutations in the ADAM metallopeptidase domain 9 (ADAM9) gene in four consanguineous families with recessively inherited early-onset CRD. We also found reduced photoreceptor responses in Adam9 knockout mice, previously reported to be asymptomatic. In 12-month-old knockout mice, photoreceptors appear normal, but the apical processes of the retinal pigment epithelium (RPE) cells are disorganized and contact between photoreceptor outer segments (POSs) and the RPE apical surface is compromised. In 20-month-old mice, there is clear evidence of progressive retinal degeneration with disorganized POS and thinning of the outer nuclear layer (ONL) in addition to the anomaly at the POS-RPE junction. RPE basal deposits and macrophages were also apparent in older mice. These findings therefore not only identify ADAM9 as a CRD gene but also identify a form of pathology wherein retinal disease first manifests at the POS-RPE junction

Vitamin status and cognitive function in a long-term care population

BACKGROUND: Ageing can be associated with poor dietary intake, reduced nutrient absorption, and less efficient utilization of nutrients. Loss of memory and related cognitive function are also common among older persons. This study aimed to measure the prevalence of inadequate vitamin status among long-term care patients and determine if an association exists between vitamin status and each of three variables; cognitive function, vitamin supplementation, and medications which alter gastric acid levels. METHODS: Seventy-five patients in a long-term care hospital in Guelph, Ontario were recruited to a cross-sectional study. 47 were female and the mean age was 80.7 (+/-11.5) years, ranging from 48 to 100 years. Blood was used to measure levels of vitamins B12 (cobalamin), B6 (pyridoxal-5'-phosphate/PLP), erythrocyte folate, vitamin B3 (niacin) and homocysteine (Hcy). The Standardized Mini-Mental State Examination (SMMSE) was administered to measure cognitive function. A list of medications and vitamin supplementation for each patient was provided by the pharmacy. RESULTS: The prevalence of low vitamin (B12, B6, erythrocyte folate, niacin) or high metabolite (homocysteine) levels among 75 patients were as follows: B12 <148 pmol/L in 5/75 (6.7%); B12 between 148 and 221 pmol/L in 26/75 (34.7%); B6 ≤30 nmol/L in 4/75 (5.3%); erythrocyte folate <370 nmol/L in 1/75 (1.3%); niacin ratio ≤1 in 20/75 (26.7%); homocysteine >13.3 μmol/L in 31/75 (41.3%). There was no significant difference among residents grouped into marked (n = 44), mild (n = 14), or normal (n = 9) cognitive function when evaluating the effect of vitamin status. There were no significant differences in mean B12 and homocysteine levels between users and non-users of drug therapy (Losec, Zantac, or Axid). Compared to vitamin supplement non-users, supplemented residents had significantly higher mean B12 (p < 0.0001) and erythrocyte folate (p < 0.05) concentrations and significantly lower mean homocysteine (p < 0.01) levels; 229.1 versus 423.6 pmol/L for B12, 882.9 versus 1043.6 nmol/L for erythrocyte folate and 14.4 versus 12.0 μmol/L for homocysteine. CONCLUSION: Given the prevalence data on vitamin status in this sample population, the possible benefits of vitamin supplementation should be considered in clinical intervention studies using these populations of elderly

Influence of the central-to-peripheral arterial stiffness gradient on the timing and amplitude of wave reflections

In individuals with compliant aortas, peripheral muscular artery stiffness exceeds central elastic artery stiffness. With ageing, central stiffness increases, with little change in peripheral stiffness, resulting in a reversal of the normal stiffness gradient. This reversal may reduce wave reflection amplitude, due to movement of the major “effective” reflection site further from the heart. To test this, we investigated the relationship among arterial stiffness gradients (normal and reversed), wave reflection amplitude and reflection site distance. Subjects aged ≥50years were recruited from the Anglo-Cardiff Collaborative Trial. Central stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). In study 1, peripheral PWV was also measured in the arm (carotid-radial, crPWV), and in study 2 in the leg (femoral- dorsalis pedis, fpPWV). Reflection site distance was calculated from cfPWV and reflected wave travel time. Subjects were dichotomized into those with a normal stiffness gradient (peripheral>central PWV), or a reversed gradient (peripheral<central PWV). In study 1, reflection site distance was greater in subjects with a reversed gradient (P<0.01), whereas time to reflection was lower (P<0.001). Both augmentation pressure (P<0.001) and augmentation index (P<0.05) were greater in subjects with a reversed gradient. In study 2, augmentation pressure, augmentation index and reflection site distance were greater in subjects with a reversed stiffness gradient (P<0.01, P<0.05 and P<0.01, respectively), and time to reflection was not different between groups. A reversed arterial stiffness gradient is associated with increased reflection site distance and a paradoxical increase in reflected wave amplitude, and augmentation index