MRI ankle and subtalar characteristics in haemochromatosis arthropathy: a case-control study.

AIM: To examine the magnetic resonance imaging (MRI) features of the ankle and subtalar joints that might distinguish genetic haemochromatosis (GH). MATERIALS AND METHODS: The present study was a retrospective case-control study comparing 30 MRI studies of GH patients with ankle or subtalar arthropathy with 30 matched controls with ankle pain. Anonymised images were scored using a semi-quantative tool adapted from the MRI osteoarthritis knee score. Scores were generated for bone marrow lesions size, number, and distinguishing the proportion of each lesion consisting of subchondral cyst versus oedema. Articular cartilage loss and osteophytes were documented. The primary comparator was bone marrow lesion size. Paired Student's t-test and the chi-squared test were utilised to compare outcomes. RESULTS: Bone marrow lesion/cyst size and number, presence and extent of full-thickness cartilage loss, and osteophyte scores were significantly higher in ankle joints of GH cases (p<0.01). In the middle subtalar articulation, there were significantly higher scores for full-thickness cartilage loss and extent and osteophytes in GH cases (p<0.05). There were no significant differences in the posterior subtalar articulation. CONCLUSION: The finding of both numerous and large cysts on ankle MRI should raise suspicion of GH. Other MRI features of potential diagnostic value include large osteophytes and the presence of extensive full-thickness cartilage loss in the ankle joint and middle subtalar articulation.

Mutant p53: a novel target for the treatment of patients with triple-negative breast cancer?

The identification and validation of a targeted therapy for patients with triple-negative breast cancer (TNBC) is currently one of the most urgent needs in breast cancer therapeutics. One of the key reasons for the failure to develop a new therapy for this subgroup of breast cancer patients has been the difficulty in identifying a highly prevalent, targetable molecular alteration in these tumors. Recently however, the p53 gene was found to be mutated in approximately 80% of basal/TNBC, raising the possibility that targeting the mutant p53 protein product might be a new approach for the treatment of this form of breast cancer. In this study, we investigated the anti-cancer activity of PRIMA-1 and PRIMA-1MET (APR-246), two compounds which were previously reported to reactivate mutant p53 and convert it to a form with wild-type (WT) properties. Using a panel of 18 breast cancer cell lines and 2 immortalized breast cell lines, inhibition of proliferation by PRIMA-1 and PRIMA-1MET was found to be cell-line dependent, but independent of cell line molecular subtype. Although response was independent of molecular subtype, p53 mutated cell lines were significantly more sensitive to PRIMA-1MET than p53 WT cells (p = 0.029). Furthermore, response (measured as IC50 value) correlated significantly with p53 protein level as measured by ELISA (p = 0.0089, r=-0.57, n = 19). In addition to inhibiting cell proliferation, PRIMA-1MET induced apoptosis and inhibited migration in a p53 mutant-dependent manner. Based on our data, we conclude that targeting mutant p53 with PRIMA-1MET is a potential new approach for treating p53-mutated breast cancer, including the subgroup with triple-negative (TN) disease.

Anti-HCV immunoblot indeterminate results in blood donors: non-specific reactivity or past exposure to HCV?

BACKGROUND AND OBJECTIVE: The significance of anti-HCV immunoblot (IB) indeterminate results can be difficult to determine. We analysed results for blood donors tested on the MP Diagnostics HCV Blot 3.0 IB assay to determine whether indeterminate results representing past exposure to HCV could be distinguished from those due to non-specific reactivity. MATERIALS AND METHODS: Results for all donors tested by IB during the study period (July 2010 to December 2013) were included in this study. RESULTS: Of 131 donors tested by IB, 34 (26.0%) were negative, 38 (29.0%) were indeterminate, and 59 (45.0%) were positive. There was no significant difference in IB band reactivity strength between indeterminate and positive donors. The PRISM HCV chemiluminescent immunoassay (ChLIA) sample to cut-off (s/co) ratio distribution for the indeterminate donors was significantly higher than for those with biological false reactivity (P = 0·037), but significantly lower than for donors who were IB positive/HCV RNA negative (P < 0·001) or IB not tested/HCV RNA positive (P < 0·001). Of donors available for follow-up, 53.1% of the indeterminate group disclosed a putative risk factor for HCV infection compared to 39.4% (P < 0·001) for the IB-negative group, 76.6% (P = 0·065) for the IB-positive group and 83.4% (P < 0·001) for the HCV RNA-positive group. CONCLUSION: The results of this study indicate that PRISM ChLIA s/co ratios >2·00 with IB indeterminate results predict exposure to HCV, particularly in the presence of putative risk factors for HCV infection. These findings may be applied to optimizing counselling of donors with indeterminate HCV results.

Refining the risk estimate for transfusion-transmission of occult hepatitis B virus.

BACKGROUND AND OBJECTIVES: We previously published a model to estimate the residual risk (RR) for occult hepatitis B infection (OBI) in the absence of universal anti-HBc testing. To incorporate new information on the epidemiology of OBI, we describe model refinements and estimate a more accurate HBV RR due to OBI in Australia. MATERIALS AND METHODS: In our original model, the OBI risk, p(OBI), was defined by the rate of 'non-detection' by the HBV DNA screening test in use, p(NAT non-detection), and the average infectivity of blood components from OBI donors, p(transmission). We revised the model by integrating three refinements: that donations with anti-HBs levels of >10 IU/l, or donations solely for manufactured plasma products, be excluded from the risk calculation, and an updated estimate of p(transmission). RESULTS: Refining our OBI RR model resulted in a more than 10-fold reduction in the reported RR risk to recipients from OBI in our donor population. Based on the use of a common data set, the mean OBI RR risk decreased from 1 in 374 354 donations (95% CI: 1 in 191 940-1 072 681) to 1 in 3 984 033 (95% CI: 1 in 1 146 188-65 268 257) for the refined model. CONCLUSION: Our model refinements provide a more realistic measure of the HBV RR in the donor population. Unlike the previous model, the new model demonstrates that the risk of HBV due to OBI in the Australian blood donor population is negligible, and further potentially cost-ineffective risk management strategies are not currently warranted.

Hepatitis E virus RNA in Australian blood donors: prevalence and risk assessment.

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is a known transfusion-transmissible agent. HEV infection has increased in prevalence in many developed nations with RNA detection in donors as high as 1 in 600. A high proportion of HEV infections are asymptomatic and therefore not interdicted by donor exclusion criteria. To manage the HEV transfusion-transmission (TT) risk some developed nations have implemented HEV RNA screening. In Australia, HEV is rarely notified; although locally acquired infections have been reported, and the burden of disease is unknown. The purpose of this study was to determine the frequency of HEV infection in Australian donors and associated TT risk. MATERIALS AND METHODS: Plasma samples (n = 74 131) were collected from whole blood donors during 2016 and screened for HEV RNA by transcription-mediated amplification (TMA) in pools of six. Individual TMA reactive samples were confirmed by RT-PCR and, if positive, viral load determined. Prevalence data from the study were used to model the HEV-TT risk. RESULTS: One sample in 74 131 (95% CI: 1 in 1 481 781 to 1 in 15 031) was confirmed positive for HEV RNA, with an estimated viral load of 180 IU/ml, which is below that typically associated with TT. Using a transmission-risk model, we estimated the risk of an adverse outcome associated with TT-HEV of approximately 1 in 3·5 million components transfused. CONCLUSION: Hepatitis E virus viremia is rare in Australia and lower than the published RNA prevalence estimates of other developed countries. The risk of TT-HEV adverse outcomes is negligible, and HEV RNA donor screening is not currently indicated.

Haemochromatosis: unexplained metacarpophalangeal or ankle arthropathy should prompt diagnostic tests: findings from two UK observational cohort studies.

OBJECTIVES: To examine demographic and clinical features leading to the diagnosis of hereditary haemochromatosis and assess factors that might enhance earlier diagnosis, with particular attention to arthritic symptoms. METHOD: Diagnostic features were captured directly from patients with haemochromatosis attending a specialist rheumatology clinic (group 1) and from analysis of a specifically designed questionnaire circulated to members of the UK Haemochromatosis Society (group 2). RESULTS: In groups 1 (n = 62) and 2 (n = 470), respectively, the diagnosis of haemochromatosis was made at a mean age of 52.8 and 56.4 years with 77% and 76% reporting joint symptoms with a mean duration of 8.3 and 8.1 years. The first joints to be affected in group 1 were the metacarpophalangeal (MCP; 38.5%) and ankle (29.5%) followed by the knee, hip, and proximal interphalangeal (PIP) joints. At the time of clinical assessment or questionnaire completion, the most prevalent regions with arthropathy in group 1 were PIP (64.5%), knee (64%), ankle (61%), and MCP (60%) and in group 2 the most prevalent joint regions self-reported were the first carpometacarpal (CMC; 59%), wrist (52%), PIP (47%), MCP (46%), knee (42%), and ankle (35%). CONCLUSIONS: Data from both cohorts confirm the high prevalence of joint symptoms in haemochromatosis predating the diagnosis by many years. Discriminatory features of the arthropathy include the involvement of MCP joints and ankles at a relatively young age in the absence of trauma, all of which are unusual features of primary osteoarthritis (OA). The finding of this presentation should prompt diagnostic tests for haemochromatosis.

The fate of verocytotoxigenic Escherichia coli C600φ3538(Δvtx2 ::cat) and its vtx2 prophage during grass silage preparation.

AIMS: Silage is grass, preserved by fermentation and used as winter feed for cattle. The impact of a range of current grass silage preparation practices on the survival of Escherichia coli C600φ3538(Δvtx2 ::cat) and on the induction, release and infectivity of free phage were investigated. METHODS AND RESULTS: Wilted and fresh grass samples, from plots with and without slurry application, were ensiled with or without formic acid. Each treatment combination was inoculated with approximately 6 log10 CFU per g E. coli C600φ3538(Δvtx2 ::cat) (donor strain) and E. coli C600::kanamycinR (recipient strain) in test-tube model silos and incubated in the dark at 15°C. The physico-chemical (pH, ammonia, ethanol, lactic acid and volatile fatty acids) and microbiological (total viable counts, TVC, total Enterobacteriaceae counts, TEC, E. coli counts, ECC and lactic acid bacteria, LAB) properties of each fermentation were monitored throughout the experiment as were the concentrations of E. coli C600φ3538(Δvtx2 ::cat), E. coli C600::kanamycinR , free phage and transductants, using culture and PCR-based methods. Over the course of the experiment the pH of the grass samples typically decreased by 2 pH units. TVC, TEC and ECC decreased by up to 2·3, 6·4 and 6·2 log10 CFU per g, respectively, while the LAB counts remained relatively stable at 5·2-7·1 log10 CFU per g. Both donor and recipient strains decreased by approximately 5 log10 CFU per g. Free phages were detected in all treatments and transductants were detected and confirmed by PCR in the silo containing wilted grass, pretreated with slurry and ensiled without formic acid. CONCLUSIONS: Verocytotoxigenic E. coli may survive the ensiling process and the conditions encountered are sufficient to induce vtx2 bacteriophage leading to low levels of phage-mediated vtx2 gene transfer. SIGNIFICANCE AND IMPACT OF THE STUDY: These studies suggest that the ensiling of grass may create an environment which facilitates the emergence of new verocytotoxigenic E. coli.

Particulate and non-particulate steroids in spinal epidurals: a systematic review and meta-analysis.

BACKGROUND: Steroids in transforaminal epidural injections are widely used to ease radicular pain in both cervical and lumbar radiculopathy. Concerns have been articulated about the use of particulate steroids for this intervention, as a number of case reports have been published linking them with post procedural paralysis, possibly due to spinal ischaemia secondary to a steroid particulate embolism. Non-particulate, or soluble steroids, are mooted as an alternative; however, their effectiveness relative to particulate steroids has not been conclusively proven. STUDY DESIGN: We review the evidence in the published literature regarding the efficacy of non-particulate steroids in epidural injections compared to particulate steroids, and synthesise it to gauge the qualitative outcomes from level one evidence (visual analogue scales, numerical pain scores and Oswestry Disability Index) from baseline to specified follow up. METHODS: The PRISMA guidelines were utilised for this review. An internet search was performed to collate the available literature from medical databases PubMed, EMBASE, Web of Science and the Cochrane library. We used a broad search term [epidural (and) steroid] to ensure a wide capture of articles. No limitations in terms of language or date of publication were implemented. The reference lists of articles included for full text review were searched for any additional primary or review publications. RESULTS: Four online libraries were searched, with a combined total of 11,353 titles reviewed, not excluding duplicates. Post title abstract and full text review, nine articles were identified as suitable for inclusion for qualitative synthesis. Four of these were suitable for quantitative synthesis, with a total of 300 participants, 147 in the particulate group and 153 in the non-particulate group. Using a random effects model, the pooled standard mean difference of VAS score diminution was not significant between groups (0.31 in favour of particulates, 95 % CI -0.68 to 1.30). From our qualitative synthesis, there was a trend for greater improvement in pain scores within the particulate group. The type of steroid used did not appear to have an effect on the disability score given by patients. CONCLUSION: Particulate steroids are not demonstrably better in relieving pain compared to their non-particulate counterparts. In view of the concerns over the safety profile of particulate steroids, it may be prudent to switch to non particulates, or at the very least the dangers and alternatives should be flagged with the patient group as part of a shared decision making process.

Re-evaluating the residual risk of transfusion-transmitted Ross River virus infection.

BACKGROUND AND OBJECTIVES: Ross River virus (RRV) is an enveloped, RNA alphavirus in the same antigenic group as chikungunya virus. Australia records an annual average of 5000 laboratory-confirmed RRV infections. While RRV is currently geographically restricted to the Western Pacific, the capacity of arboviruses for rapid expansion is well established. The first case of RRV transfusion-transmission was recently described prompting a comprehensive risk assessment. MATERIALS AND METHODS: To estimate the RRV residual risk, we applied laboratory-confirmed RRV notifications to two published models. This modelling generated point estimates for the risk of viraemia in the donor population, the risk of collecting a viraemic donation and the predicted number of infected components. RESULTS: The EUFRAT model estimated the risk of infection in donors as one in 95 039 (one in 311 328 to one in 32 399) to one in 14 943 (one in 48 593 to one in 5094). The point estimate for collecting a RRV viraemic donation varied from one in 166 486 (one in 659 078 to one in 49 158) (annualized national risk) to one in 26 117 (one in 103 628 to one in 7729) (area of high transmission). The modelling predicted 8-11 RRV-infected labile blood components issued in Australia during a 1-year period. CONCLUSION: Considering the uncertainty in the modelled estimates, the unknown rate of RRV donor viraemia and the low severity of any recipient RRV infection, additional risk management for RRV in Australia will initially be restricted to strengthening the messaging to donors regarding prompt reporting of any postdonation illnesses.

Infectivity of blood components from donors with occult hepatitis B infection - results from an Australian lookback programme.

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that transfused blood components from donors with occult hepatitis B virus infection (OBI) are potentially infectious. This study reports the results of an Australian lookback programme for the period subsequent to the commencement of individual donation HBV NAT in July 2010 and estimates the HBV transmission rate for components from two categories of donors, confirmed OBI and HBV inconclusive (anti-HBc reactive with non-discriminated NAT result). MATERIALS AND METHODS: Using the results of lookback investigations, we estimated HBV transmission rates by donor category and type of component transfused based on the prevalence of antibodies to HBV core antigen (anti-HBc) in recipients adjusted for the estimated prevalence in the general population. RESULTS: After subtracting the background anti-HBc rate, we derived an adjusted transmission rate (all components) with lower and upper bounds as follows: 0·85% (0·00-2·35%) for OBI donors, 2·83% (1·23-4·33%) for inconclusive donors and 1·81% (0·21-3·31%) for total (OBI and inconclusive) donors. The median adjusted transmission rate for total donors was higher (but not statistically) for plasma (3·01%) than RCCs (2·86%), but there was no evidence of transmission for cryoprecipitate or platelets (0% for both components). CONCLUSION: Our lookback study suggests a low (0·2-3·3%) but measurable rate of HBV transmission in Australia associated with donors with OBI and supports published evidence that at least some blood component types from OBI donors, including a proportion undetectable by ID-NAT can transmit HBV by transfusion.

Changes in chemical composition and digestibility of three maize stover components digested by white-rot fungi.

Maize stover (total stem and leaves) is not considered a ruminant feed of high nutritive value. Therefore, an improvement in its digestibility may increase the viability of total forage maize production systems in marginal growth regions. The objective of this study was to describe the changes in chemical composition during the storage of contrasting components of maize stover (leaf, upper stem and lower stem) treated with either of two lignin degrading white-rot fungi (WRF; Pleurotus ostreatus, Trametes versicolor). Three components of maize stover (leaf, upper stem and lower stem), harvested at a conventional maturity for silage production, were digested with either of two WRF for one of four digestion durations (1-4 months). Samples taken prior to fungal inoculation were used to benchmark the changes that occurred. The degradation of acid detergent lignin was observed in all sample types digested with P. ostreatus; however, the loss of digestible substrate in all samples inoculated with P. ostreatus was high, and therefore, P. ostreatus-digested samples had a lower dry matter digestibility than samples prior to inoculation. Similarly, T. veriscolor-digested leaf underwent a non-selective degradation of the rumen-digestible components of fibre. The changes in chemical composition of leaf, upper stem and lower stem digested with either P. ostreatus or T. veriscolor were not beneficial to the feed value of the forage, and incurred high DM losses.

Mycophenolate mofetil-induced erythroid hypoplasia in a patient with systemic lupus erythematosus.

Anaemia is prevalent in patients with systemic lupus erythematosus (SLE). The anaemia is often a consequence of the disease itself but may also be secondary to drug treatments. Mycophenolate mofetil (MMF) is increasingly used in the management of patients with SLE and its associated anaemia. We describe the case of a 19-year-old girl, who presented acutely with SLE and renal involvement. Her disease was controlled with immunosuppression but she later developed severe transfusion-dependent anaemia. Several causes were considered before a bone marrow biopsy led to the diagnosis of erythroid hypoplasia. In the absence of clinical or laboratory markers of active lupus, MMF was implicated as the cause. Its discontinuation led to a rapid and sustained correction of the anaemia. Red cell aplasia linked to the use of MMF is uncommon and the manufacturers are aware of fewer than 50 cases. This is the first case report of evolving red cell aplasia induced by MMF in SLE.

A method for estimating the residual risk of transfusion-transmitted HBV infection associated with occult hepatitis B virus infection in a donor population without universal anti-HBc screening.

BACKGROUND AND OBJECTIVES: This report describes a method for estimating the risk of transfusion-transmitted HBV infection attributable to blood components from donors with occult hepatitis B virus infection (OBI) applicable where universal anti-HBc screening is not performed. MATERIALS AND METHODS: In the context of parallel HBsAg and individual donation HBV DNA testing, we developed a mathematical function p(OBI) to estimate the probability of failing to detect [p(NAT nondetection)] a potentially infectious [p(transmission)] donation from a donor with OBI. RESULTS: Among 1 312 451 donations tested for HBsAg and HBV DNA, 29 (from 17 anti-HBc reactive donors classified as OBI) were individual donation NAT negative, giving a p(NAT nondetection) of 2·2096 (95 CI: 1·538-3·173) × 10(-5) . To date, lookback on OBI donors has identified 35 (8·2%) recipients with evidence of current or past HBV infection among 427 tested recipients. After correcting for the background anti-HBc rate in recipients, this results in a p(transmission) of 0·0384 (0·0167-0·0601). The product, pOBI is 1 in 981 920 (95% CI: 437 181-3 223 701). When this is summed with the WP risk for the 2011-2012 period, the overall HBV residual risk estimate is 1 in 538 224 (95% CI: 209 732-1 552 443). CONCLUSION: We estimate the OBI residual risk in Australia is approximately 1 in 982 000 per unit transfused, and this risk represents 55% of the total HBV residual risk and is declining as consequence of ID-NAT identifying repeat donors with OBI.

Large-scale characterization of hospital wastewater system microbiomes and clinical isolates from infected patients: profiling of multi-drug-resistant microbial species.

BACKGROUND: Hospital-acquired infections (HAIs) and infectious agents exhibiting antimicrobial resistance (AMR) are challenges globally. Environmental patient-facing wastewater apparatus including handwashing sinks, showers and toilets are increasingly identified as sources of infectious agents and AMR genes. AIM: To provide large-scale metagenomics analysis of wastewater systems in a large teaching hospital in the Republic of Ireland experiencing multi-drug-resistant HAI outbreaks. METHODS: Wastewater pipe sections (N=20) were removed immediately prior to refurbishment of a medical ward where HAIs had been endemic. These comprised toilet U-bends, and sink and shower drains. Following DNA extraction, each pipe section underwent metagenomic analysis. FINDINGS: Diverse taxonomic and resistome profiles were observed, with members of phyla Proteobacteria and Actinobacteria dominating (38.23 ± 5.68% and 15.78 ± 3.53%, respectively). Genomes of five clinical isolates were analysed. These AMR bacterial isolates were from patients >48 h post-admission to the ward. Genomic analysis determined that the isolates bore a high number of antimicrobial resistance genes (ARGs). CONCLUSION: Comparison of resistome profiles of isolates and wastewater metagenomes revealed high degrees of similarity, with many identical ARGs shared, suggesting probable acquisition post-admission. The highest numbers of ARGs observed were those encoding resistance to clinically significant and commonly used antibiotic classes. Average nucleotide identity analysis confirmed the presence of highly similar or identical genomes in clinical isolates and wastewater pipes. These unique large-scale analyses reinforce the need for regular cleaning and decontamination of patient-facing hospital wastewater pipes and effective infection control policies to prevent transmission of nosocomial infection and emergence of AMR within potential wastewater reservoirs.

Conservation characteristics of corn ears and stover ensiled with the addition of Lactobacillus plantarum MTD-1, Lactobacillus plantarum 30114, or Lactobacillus buchneri 11A44.

The aim of this study was to investigate the effects of inoculating 3 contrasting lactic acid bacteria on the fermentation profile, estimated nutritive value, and aerobic stability of corn ears and stover produced under marginal growing conditions. Ears and stover were separated from whole-crop corn plants obtained from 3 replicate field blocks. Representative subsamples were precision chopped and allocated to 1 of the following treatments: an uninoculated control, Lactobacillus plantarum MTD-1 (LP1), L. plantarum 30114 (LP2), or Lactobacillus buchneri 11A44 (LB). Each bacterial additive was applied at a rate of 1 × 10(6) cfu/g of fresh herbage. Triplicate samples of each treatment were ensiled in laboratory silos at 15°C for 3, 10, 35, or 130 d. No difference was observed between the dry matter recoveries of uninoculated ear or stover silages and silages made with LP1, and the aerobic stability of uninoculated ear and stover silages did not differ from silages made with LB. Stover silages made with LP2 and ensiled for 35 d had a lower proportion of lactic acid in total fermentation products compared with LP1. The aerobic stability and dry matter recovery of ear and stover silages in this study were not improved when made with LB, LP1, or LP2, due to the indigenous highly heterolactic fermentation that prevailed in the uninoculated ear and stover during 130-d ensilage.

Assessing the impact of various ensilage factors on the fermentation of grass silage using conventional culture and bacterial community analysis techniques.

AIMS: Grass silage is an important ruminant feedstuff on farms during winter. The ensilage of grass involves a natural lactic acid bacterial fermentation under anaerobic conditions, and numerous factors can influence the outcome of preservation. The aim of this study was to investigate the effect of dry matter concentration, ensiling system, compaction and air infiltration on silage bacterial community composition. METHODS AND RESULTS: The impact of these factors was examined using conventional methods of microbial analysis and culture-independent Terminal Restriction Fragment Length Polymorphism (T-RFLP). Silage fermentation was restricted in herbage with a high dry matter concentration, and this was reflected in a shift in the bacterial population present. In contrast, ensiling system had little effect on bacterial community composition. Air infiltration, in the absence of compaction, altered silage bacterial community composition and silage pH. CONCLUSIONS: Dry matter concentration and the absence of compaction were the main factors affecting silage microbial community composition, and this was reflected in both the conventional culture-based and T-RFLP data. SIGNIFICANCE AND IMPACT OF THE STUDY: T-RFLP proved a useful tool to study the factors affecting ensilage. Apart from monitoring the presence or absence of members of the population, shifts in the relative presence of members could be monitored.

Conservation characteristics of wilted perennial ryegrass silage made using biological or chemical additives.

The effects of 7 additive treatments on the fermentation and aerobic stability characteristics of wilted grass silage were studied under laboratory conditions. Treatments included no additive applied (untreated control), ammonium tetraformate at 3 and 6 L/t, homofermentative lactic acid bacteria alone ((ho)LAB), a mixture of Lactobacillus buchneri plus homofermentative lactic acid bacteria ((he+ho)LAB), and an antimicrobial mixture of sodium benzoate, sodium propionate, sodium nitrite, and hexamethylenetetramine at 2.5 and 5 L/t. Additives were compared across 3 consecutive harvests of 2 perennial ryegrass cultivars (AberDart and Fennema) following a 24-h wilt. Silos were opened after at least 100 d of ensilage and aerobic stability was assessed. Season of harvest had a large effect on grass composition at ensiling, producing herbages of relatively low (approximately 145g/kg), medium (approximately 250g/kg), and high (approximately 365g/kg) dry matter (DM) concentrations. Within harvests there were lesser differences between cultivars. The untreated control and (ho)LAB additive produced badly fermented silage from the low-DM herbages and well-fermented silage from the medium- and high-DM herbages. The ammonium tetraformate treatments produced both well-fermented and badly fermented silage from the low-DM herbages depending on cultivar, and consistently well-fermented silage from the medium- and high-DM herbages. The (he+ho)LAB silages had similar or slightly lower standard of fermentation than the untreated and (ho)LAB silages. The antimicrobial mixture produced more silages of lower standard of fermentation than the untreated control and ammonium tetraformate and (ho)LAB additives. All additive treatments, including the untreated control, failed to consistently increase residual water-soluble carbohydrate concentrations at silo opening. Ammonium tetraformate at 6 L/t was the most successful and (he+ho)LAB the least successful additive at increasing residual WSC concentrations. The (ho)LAB silages were generally the least aerobically stable. Silages treated with ammonium tetraformate at 6 L/t were relatively stable under aerobic conditions. The (he+ho)LAB additive and antimicrobial mixture had an inconsistent effect on aerobic stability. Overall, ammonium tetraformate at 6 L/t was the most effective additive evaluated in this study, producing generally well-fermented silage with the highest concentrations of residual WSC and an intermediate to long duration of aerobic stability.

The relationship between post-surgery infection and breast cancer recurrence.

Breast cancer is the second most prevalent form of cancer in women worldwide, with surgery remaining the standard treatment. The adverse impact of the surgery remains controversial. It has been suggested that systemic factors during the postoperative period may increase the risk of recurrence, specifically surgical site infection (SSI). The aim of this review was to critically appraise current published literature regarding the influence of SSIs, after primary breast cancer surgery, on breast cancer recurrence, and to delve into potential links between these. This systematic review adopted two approaches: to identify the incidence rates and risk factors related to SSI after primary breast cancer surgery; and, secondly, to examine breast cancer recurrence following SSI occurrence. Ninety-nine studies with 484,605 patients were eligible in the SSI-focused searches, and 53 studies with 17,569 patients for recurrence-focused. There was a 13.07% mean incidence of SSI. Six-hundred and thirty-eight Gram-positive and 442 Gram-negative isolates were identified, with methicillin-susceptible Staphylococcus aureus and Escherichia coli most commonly identified. There were 2077 cases of recurrence (11.8%), with 563 cases of local recurrence, 1186 cases of distant and 25 cases which recurred both locally and distantly. Five studies investigated the association between SSI and breast cancer recurrence with three concluding that an association did exist. In conclusion, there is association between SSI and adverse cancer outcomes, but the cellular link between them remains elusive. Confounding factors of retrospective study design, surgery type and SSI definition make results challenging to compare and interpret. A standardized prospective study with appropriate statistical power is justified.

The Presence of a High Peak Feature Within Low-Average Shear Stimuli Induces Quiescence in Venous Endothelial Cells.

Wall shear stress (WSS) is an important stimulus in vascular remodelling and vascular lesion development. The current methods to assess and predict the risk associated with specific unsteady WSS consider the WSS mean values or the presence of reverse phases described by the oscillatory shear index. Recent evidence has shown that the accuracy of these methods is limited, especially with respect to the venous environment. Unsteady WSS are characterised by several features that may individually affect endothelial cells. Consequently, we assessed the effects of averaged WSS (TAWSS), temporal WSS gradient (TWSSG), maximum WSS (WSS peak) and reverse phase (OSI) by applying different WSS profiles to venous EC in-vitro, using a real-time controlled cone-and-plate cell-shearing device for 24 h. We found that TWSSG and WSS peak affect cell elongation and alignment respectively. We also found that the WSS waveforms with a peak of 1.5 Pa or higher significantly correlate with the induction of a protective phenotype. Cell phenotype induced by these high peak waveforms does not correlate to what is predicted by the hemodynamic indices currently used. The definition of reliable hemodynamic indices can be used to inform the computational models aimed at estimating the hemodynamic effects on vascular remodelling.