Yeast Pro- and Paraprobiotics Have the Capability to Bind Pathogenic Bacteria Associated With Animal Disease

Live yeast probiotics and yeast cell wall components (paraprobiotics) may serve as an alternative to the use of antibiotics in prevention and treatment of infections caused by pathogenic bacteria. Probiotics and paraprobiotics can bind directly to pathogens, which limits binding of the pathogens to the intestinal cells and also facilitates removal from the host. However, knowledge of bacterial binding, specificity, and/or capability is limited with regard to probiotics or paraprobiotics. The goal of this study was to characterize the qualitative and quantitative nature of two Saccharomyces cerevisiae probiotics and three S. cerevisiae paraprobiotics to adhere to thirteen different pathogenic bacteria using scanning electron miscroscopy and filtration assays. On average, the yeast probiotics (LYA and LYB) exhibited overall greater (P \u3c 0.05) adhesion to the pathogenic bacteria tested (41% and 34%) in comparison to paraprobiotics (23%, 21%, and 22%), though variations were observed between pathogens tested. The ability of Salmonella and Listeriato utilize components of the yeast as a nutrient source was also tested. Bacteria were cultured in media with limited carbon and supplemented with cell free extracts of the probiotics and paraprobiotics. Salmonella exhibited growth, indicating these pathogens could utilize the yeast lysates as a carbon source. Listeria monocytogenes had limited growth in only one of the lysates tested. Together, these data indicate that the interaction between probiotics and paraprobiotics occurs in a strain dependent mechanism. Administration of probiotics and paraprobiotics as therapeutics therefore needs to be specific against the bacterial pathogen target

Effect of Citrus Byproducts on Survival of O157:H7 and Non-O157 \u3ci\u3eEscherichia coli\u3c/i\u3e Serogroups within \u3ci\u3eIn Vitro\u3c/i\u3e Bovine Ruminal Microbial Fermentations

Citrus byproducts (CBPs) are utilized as a low cost nutritional supplement to the diets of cattle and have been suggested to inhibit the growth of both Escherichia coli O157:H7 and Salmonella. The objective of this study was to examine the effects in vitro that varying concentrations of CBP in the powdered or pelleted variety have on the survival of Shiga-toxin Escherichia coli (STEC) serotypes O26:H11, O103:H8, O111:H8, O145:H28, and O157:H7 in bovine ruminal microorganism media. The O26:H11, O111:H8, O145:H28, and O157:H7 serotypes did not exhibit a change in populations in media supplemented with CBP with either variety. The O103:H8 serotype displayed a general trend for an approximate 1 log10 reduction in 5% powdered CBP and 20% pelleted CBP over 6 h. There was a trend for reductions in populations of a variant form of O157:H7 mutated in the stx1 and stx2 genes in higher concentrations of CBP. These results suggest that variations exist in the survival of these serotypes of STEC within mixed ruminal microorganism fluid media when supplemented with CBP. Further research is needed to determine why CBPs affect STEC serotypes differently

The effects of administering different metaphylactic antimicrobials on growth performance and health outcomes of high-risk, newly received feedlot steers

Bovine respiratory disease (BRD) is the primary animal health concern facing feedlot producers. Many antimicrobial mitigation strategies are available, but few studies have compared feedlot performance during both the receiving and finishing periods following application of different antimicrobials used as metaphylaxis at arrival. The objective of this study was to compare antimicrobial metaphylaxis methods on clinical health and growth performance across both the receiving and finishing periods. A total of 238 multiple-sourced steers in two source blocks were used in a generalized complete block design. The four treatments included: 1) a negative control, 5 mL of sterile saline injected subcutaneously (CON); 2) subcutaneous administration of florfenicol at 40 mg/kg of BW (NUF); 3) subcutaneous administration of ceftiofur in the posterior aspect of the ear at 6.6 mg/kg of BW (EXC); and 4) subcutaneous administration of tulathromycin at 2.5 mg/kg of BW (DRA). The morbidity rate for the first treatment of BRD was decreased for the DRA and EXC treatments compared to CON and NUF (P \u3c 0.01). Additionally, average daily gain (ADG), dry matter intake (DMI), and gain-to-feed (G:F) were greater (P ≤ 0.02) in the DRA treatment during the receiving period compared to all other treatments. The ADG was also greater (P \u3c 0.05) for EXC than the CON treatment throughout the finishing period. Nonetheless, other growth performance variables did not differ among metaphylactic treatments during the finishing period (P ≥ 0.14). Likewise, no differences in carcass characteristics or liver abscess score were observed (P ≥ 0.18). All complete blood count (CBC) variables were affected by day (P ≤ 0.01) except mean corpuscular hemoglobin concentration (P = 0.29). Treatment × time interactions were observed for platelet count, white blood cell (WBC) count, monocyte count and percentage, and lymphocyte percentage (P ≤ 0.03). However, there were no observed hematological variables that differed among treatment (P ≥ 0.10). The results indicate that some commercially available antimicrobials labeled for metaphylactic use are more efficacious than others in decreasing morbidity rate

A Common Glaucoma-risk Variant of SIX6 Alters Retinal Nerve Fiber Layer and Optic Disc Measures in a European Population: The EPIC-Norfolk Eye Study.

PURPOSE: A common missense variant in the SIX6 gene (rs33912345) is strongly associated with primary open-angle glaucoma (POAG). We aimed to examine the association of rs33912345 with optic disc and retinal nerve fiber layer (RNFL) measures in a European population. METHODS: We examined participants of the population-based EPIC-Norfolk Eye Study. Participants underwent confocal laser scanning tomography (Heidelberg Retina Tomograph II, HRT) to estimate optic disc rim area and vertical cup-disc ratio (VCDR). Scanning laser polarimetry (GDxVCC) was used to estimate average RNFL thickness. The mean of right and left eye values was considered for each participant. Genotyping was performed using the Affymetrix UK Biobank Axiom Array. Multivariable linear regression with the optic nerve head parameter as outcome variable and dosage of rs33912345 genotype as primary explanatory variable was used, adjusted for age, sex, disc area, axial length, and intraocular pressure. We further repeated analyses stratified into age tertiles. RESULTS: In total, 5433 participants with HRT data and 3699 participants with GDxVCC data were included. Each "C" allele of rs33912345 was associated with a smaller rim area (-0.030 mm [95% CI -0.040, -0.020]; P=5.4×10), a larger VCDR (0.025 [95% CI 0.017, 0.033]; P=3.3×10) and a thinner RNFL (-0.39 μm [95% CI -0.62, -0.15]; P=0.001). The RNFL association was strongest in the oldest age tertile, whereas rim area and VCDR associations were strongest in the youngest and oldest age tertiles. CONCLUSIONS: The protein-coding SIX6 variant rs33912345, previously associated with POAG, has a functional effect on glaucoma-associated optic nerve head traits in Europeans.EPIC-Norfolk infrastructure and core functions are supported by grants from the Medical Research Council (G1000143) and Cancer Research UK (C864/A14136). The clinic for the third health examination was funded by Research into Ageing (262). Genotyping was funded by the Medical Research Council (MC_PC_13048). Mr Khawaja is supported by a Moorfields Eye Charity grant. Miss Chan is a joint Medical Research Council/Royal College of Ophthalmologists Research Fellow, and received additional support from the International Glaucoma Association. Professor Foster has received additional support from the Richard Desmond Charitable Trust (via Fight for Sight) and the Department for Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital and the UCL Institute of Ophthalmology for a specialist Biomedical Research Centre for Ophthalmology

Influence of Market Type and Time of Purchase on Bacterial Counts and Salmonella and Listeria Prevalence in Whole Chickens in Vietnam

The objective of the current study was to determine the influence of market type and sampling time on Salmonella and Listeria prevalence and bacterial counts of 180 whole chicken carcasses collected from 6 supermarkets (SM), 6 indoor markets (IM), and 6 open markets (OM) in Vietnam, at opening (T0) and 4 h after the opening (T4). Salmonella and Listeria prevalence was at least 25.6% and 42.7%, respectively. Whole birds in IM had greater Salmonella prevalence than birds from both SM and OM by 28.4% and 23.0% (P = 0.006 and 0.022, respectively). Listeria prevalence was lower in whole chickens from SM, at 56.6%, than those in IM and OM (78.6% and 73.2%, P = 0.024 and 0.089, respectively). Whole chicken carcasses had more than 10.1, 7.5, and 9.4 log colony-forming units (CFU)/g of aerobic bacteria, Escherichia coli (E. coli), and coliforms, respectively. Both E. coli and coliform counts were greater in IM than in SM (P = 0.002 and 0.006). However, only E. coli counts differed between SM (7.7 log CFU/g) and OM (8.3 log CFU/g; P = 0.024). These results highlighted high levels of bacteria and high prevalence of Salmonella and Listeria in whole chickens in retail establishments in Vietnam, posing potential food safety and public health risks

Metaphylactic antimicrobial effects on occurrences of antimicrobial resistance in \u3ci\u3eSalmonella enterica, Escherichia coli\u3c/i\u3e and \u3ci\u3eEnterococcus\u3c/i\u3e spp. measured longitudinally from feedlot arrival to harvest in high-risk beef cattle

Aims: Our objective was to determine how injectable antimicrobials affected populations of Salmonella enterica, Escherichia coli and Enterococcus spp. in feedlot cattle. Methods and Results: Two arrival date blocks of high-risk crossbred beef cattle (n = 249; mean BW = 244 kg) were randomly assigned one of four antimicrobial treatments administered on day 0: sterile saline control (CON), tulathromycin (TUL), ceftiofur (CEF) or florfenicol (FLR). Faecal samples were collected on days 0, 28, 56, 112, 182 and study end (day 252 for block 1 and day 242 for block 2). Hide swabs and subiliac lymph nodes were collected the day before and the day of harvest. Samples were cultured for antimicrobial-resistant Salmonella, Escherichia coli and Enterococcus spp. The effect of treatment varied by day across all targeted bacterial populations (p ≤ 0.01) except total E. coli. Total E. coli counts were greatest on days 112, 182 and study end (p ≤ 0.01). Tulathromycin resulted in greater counts and prevalence of Salmonella from faeces than CON at study end (p ≤ 0.01). Tulathromycin and CEF yielded greater Salmonella hide prevalence and greater counts of 128ERYR E. coli at study end than CON (p ≤ 0.01). No faecal Salmonella resistant to tetracyclines or third-generation cephalosporins were detected. Ceftiofur was associated with greater counts of 8ERYR Enterococcus spp. at study end (p ≤ 0.03). By the day before harvest, antimicrobial use did not increase prevalence or counts for all other bacterial populations compared with CON (p ≥ 0.13). Conclusions: Antimicrobial resistance (AMR) in feedlot cattle is not caused solely by using a metaphylactic antimicrobial on arrival, but more likely a multitude of environmental and management factors

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

Background: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. Methods: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. Findings: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28–0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. Interpretation: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Live Yeast and Yeast Cell Wall Supplements Enhance Immune Function and Performance in Food-Producing Livestock: A Review †,‡

More livestock producers are seeking natural alternatives to antibiotics and antimicrobials, and searching for supplements to enhance growth performance, and general animal health and well-being. Some of the compounds currently being utilized and studied are live yeast and yeast-based products derived from the strain Saccharomyces cerevisiae. These products have been reported to have positive effects both directly and indirectly on the immune system and its subsequent biomarkers, thereby mitigating negative effects associated with stress and disease. These yeast-based products have also been reported to simultaneously enhance growth and performance by enhancing dry matter intake (DMI) and average daily gain (ADG) perhaps through the establishment of a healthy gastrointestinal tract. These products may be especially useful in times of potential stress such as during birth, weaning, early lactation, and during the receiving period at the feedlot. Overall, yeast supplements appear to possess the ability to improve animal health and metabolism while decreasing morbidity, thereby enhancing profitability of these animals

Effect of Citrus Byproducts on Survival of O157:H7 and Non-O157 Escherichia coli Serogroups within In Vitro Bovine Ruminal Microbial Fermentations

Citrus byproducts (CBPs) are utilized as a low cost nutritional supplement to the diets of cattle and have been suggested to inhibit the growth of both Escherichia coli O157:H7 and Salmonella. The objective of this study was to examine the effects in vitro that varying concentrations of CBP in the powdered or pelleted variety have on the survival of Shiga-toxin Escherichia coli (STEC) serotypes O26:H11, O103:H8, O111:H8, O145:H28, and O157:H7 in bovine ruminal microorganism media. The O26:H11, O111:H8, O145:H28, and O157:H7 serotypes did not exhibit a change in populations in media supplemented with CBP with either variety. The O103:H8 serotype displayed a general trend for an approximate 1log10 reduction in 5% powdered CBP and 20% pelleted CBP over 6 h. There was a trend for reductions in populations of a variant form of O157:H7 mutated in the stx1 and stx2 genes in higher concentrations of CBP. These results suggest that variations exist in the survival of these serotypes of STEC within mixed ruminal microorganism fluid media when supplemented with CBP. Further research is needed to determine why CBPs affect STEC serotypes differently