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Background: Poor physical fitness, stress, and fatigue are factors impacting military readiness, national security, and economic burden for the United States Department of Defense. Improved accuracy of wearable biosensors and remote field biologic sample collection strategies could make critical contributions to understanding how physical readiness and occupational stressors result in on-the-job and environment-related injury, sleep impairments, diagnosis of mental health disorders, and reductions in performance in war-fighters., Objective: This study aimed to evaluate the feasibility and acceptability of intensive biomarker and biometric data collection to understand physiological and psychological stress in Army Reserved Officer Training Corps cadets before, during, and after a 96-hour field training exercise (FTX)., Methods: A prospective pilot study evaluated the feasibility and acceptability of multimodal field data collection using passive drool saliva sampling, sweat sensors, accelerometry, actigraphy, and photoplethysmography. In addition, physical fitness (Army Combat Fitness Test), self-reported injury, and psychological resilience (Brief Resilience Scale) were measured., Results: A total of 22 cadets were included. Two were lost to follow-up due to injury during FTX, for a retention rate of 91%. Assessments of performance and psychological resilience were completed for all remaining participants, resulting in 100% testing adherence. All participants provided saliva samples before the FTX, with 98% adherence at the second time point and 91% at the third. For sweat, data collection was not possible. Average daily wear time for photoplethysmography devices was good to excellent, meeting a 70% threshold with data collected for ≥80% of person-days at all time points. Of the participants who completed the FTX and 12 completed a post-FTX acceptability survey for a response rate of 60%. Overall, participant acceptance was high (≥80%) for all metrics and devices., Conclusions: This study demonstrates that wearable biosensors and remote field biologic sample collection strategies during a military FTX have the potential to be used in higher stakes tactical environments in the future for some, but not all, of the strategies. Overall, real-time biometric and biomarker sampling is feasible and acceptable during field-based training and provides insights and strategies for future interventions on military cadet and active-duty readiness, environmental stress, and recovery., (©Rachele Pojednic, Amy Welch, Margaret Thornton, Meghan Garvey, Tara Grogan, Walter Roberts, Garrett Ash. Originally published in JMIR Formative Research (https://formative.jmir.org), 18.10.2024.)

Neonatal infectious disease continues to result in high rates of infant morbidity and mortality. Early- and late-onset disease represent difficult to detect and difficult to treat illnesses, particularly when antimicrobial resistant pathogens are present. Newborns are immunodeficient and are at increased risk of vertical and horizontal infection, with preterm infants increasingly susceptible. Additional risk factors associated with infection include prolonged use of a central catheter and/or ventilation, congenital abnormalities, admittance to intensive care units, and the use of broad-spectrum antibiotics. There is increasing recognition of the importance of the host microbiome and dysbiosis on neonatal infectious disease, including necrotising enterocolitis and sepsis in patients. Current diagnostic methods rely on blood culture, which is unreliable, time consuming, and can result in false negatives. There is a lack of accurate and reliable diagnostic tools available for the early detection of infectious disease in infants; therefore, efficient triage and treatment remains challenging. The application of biomarkers, machine learning, artificial intelligence, biosensors, and microfluidics technology, may offer improved diagnostic methodologies. Point-of-care devices, such diagnostic methodologies, may provide fast, reliable, and accurate diagnostic aids for neonatal patients. This review will discuss neonatal infectious disease as impacted by antimicrobial resistance and will highlight novel point-of-care diagnostic options.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, commonly associated with nosocomial transmission. Gram-negative bacterial species are particularly problematic due to the release of the lipopolysaccharide toxins upon cell death. The lipopolysaccharide toxin of E. coli has a greater immunogenic potential than that of other Gram-negative bacteria. The resultant dysregulation of the immune system is associated with organ failure and mortality, with pregnant women, ICU patients, and neonates being particularly vulnerable. Additionally, sepsis recovery patients have an increased risk of re-hospitalisation, chronic illness, co-morbidities, organ damage/failure, and a reduced life expectancy. The emergence and increasing prevalence of antimicrobial resistance in bacterial and fungal species has impacted the treatment of sepsis patients, leading to increasing mortality rates. Multidrug resistant pathogens including vancomycin-resistant Enterococcus, beta lactam-resistant Klebsiella , and carbapenem-resistant Acinetobacter species are associated with an increased risk of mortality. To improve the prognosis of sepsis patients, predominantly high-risk neonates, advances must be made in the early diagnosis, triage, and control of sepsis. The identification of suitable biomarkers and biomarker combinations, coupled with machine learning and artificial intelligence, show promise in early detection protocols. Rapid diagnosis of sepsis in patients is essential to inform on clinical treatment, especially with resistant infectious agents. This timely review aims to discuss sepsis prevalence, aetiology, and recent advances towards disease mitigation and control.

Background: Little is known about patients' postoperative week-by-week progress after undergoing posterior approach total hip arthroplasty (THA) with regard to pain, function, return to work, and driving. Purpose : We sought to evaluate a large cohort of patients undergoing posterior approach THA with modified posterior hip precautions to better understand the trajectory of recovery. Methods : Patients at a single institution undergoing primary posterior approach THA by fellowship-trained arthroplasty surgeons were prospectively enrolled. Patient functional status and early rehabilitation recovery milestones were evaluated preoperatively and each week postoperatively for 6 weeks. Results : Of 312 patients who responded to weekly questionnaires, there were varying response rates per question. At 1 week after surgery, 15% (39/256) of respondents had returned to work, increasing to 57% (129/225) at week 6. At 6 weeks, 77% of patients (174/225) had returned to driving; 25% (56/225) were taking pain medication (including prescription opioids or nonsteroidal anti-inflammatory drugs); and 15% (34/225) were using assistive devices (down from 91%, 78%, 56%, 35%, and 27% at weeks 1, 2, 3, 4, and 5, respectively). Average postoperative Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement and Lower Extremity Functional Scale scores were significantly higher than preoperative scores. Respondents reported significantly less pain at each week postoperatively than the previous week. Conclusion : These findings suggest that there may be an expected pathway for recovery after posterior THA using perioperative pain protocols, modified postoperative precautions, and physical therapy protocols to improve patient outcomes after THA, with most patients returning to normal at 4 weeks. Defining the expected recovery timeline may help surgeons in counseling patients preoperatively and guiding their recovery., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Seth A. Jerabek, MD, reports relationships with Stryker and Imagen Technologies. David J. Mayman, MD, reports relationships with Orthalign, Smith and Nephew, Stryker, Imagen, Wishbone, and MiCare Path. Mark P. Figgie, MD, reports relationships with WishBone, Lima, HS2, and the Knee Society nominating committee. Peter K. Sculco, MD, reports relationships with Lima Corporate, Zimmer Biomet, Intellijoint Surgical, Depuy Synthes, ATEC (Eos Imaging), Parvizi Surgical Innovation, and the AAHKS outreach committee and publications committee. The other authors declare no potential conflicts of interest., (© The Author(s) 2023.)

Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause chronic hepatitis with important clinical differences. HCV causes hepatic steatosis and insulin resistance, while HBV confers increased risk of liver cancer. We hypothesised these differences may be due to virus-specific effects on mitochondrial function., Methods: Seahorse technology was utilised to investigate effects of virus infection on mitochondrial function. Cell based assays were used to measure mitochondrial membrane potential and quantify pyruvate and lactate. Mass spectrometry was performed on mitochondria isolated from HBV expressing, HCV infected and control cells cultured with isotope-labelled amino acids, to identify proteins with different abundance. Altered expression of key mitochondrial proteins was confirmed by real time PCR and western blot., Results: Reduced mitochondrial function and ATP production were observed with HCV infection and HBV expression. HCV impairs glycolysis and reduces expression of genes regulating fatty acid oxidation, promoting lipid accumulation. HBV causes lactate accumulation by increasing expression of lactate dehydrogenase A, which converts pyruvate to lactate. In HBV expressing cells there was marked enrichment of pyruvate dehydrogenase kinase, inhibiting conversion of pyruvate to acetyl-CoA and thereby reducing its availability for mitochondrial oxidative phosphorylation., Conclusions: HCV and HBV impair mitochondrial function and reduce ATP production. HCV reduces acetyl-CoA availability for energy production by impairing fatty acid oxidation, causing lipid accumulation and hepatic steatosis. HBV has no effect on fatty oxidation but reduces acetyl-CoA availability by disrupting pyruvate metabolism. This promotes lactic acidosis and oxidative stress, increasing the risk of disease progression and liver cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The human gastrointestinal tract houses a diverse range of microbial species that play an integral part in many biological functions. Several preclinical studies using germ-free mice models have demonstrated that the gut microbiome profoundly influences carcinogenesis and progression. Colorectal cancer appears to be associated with microbial dysbiosis involving certain bacterial species, including F. nucleatum , pks+ E. coli , and B. fragilis , with virome commensals also disrupted in patients. A dysbiosis toward these pro-carcinogenic species increases significantly in CRC patients, with reduced numbers of the preventative species Clostridium butyicum , Roseburia , and Bifidobacterium evident. There is also a correlation between Clostridium infection and CRC. F. nucleatum , in particular, is strongly associated with CRC where it is associated with therapeutic resistance and poor outcomes in patients. The carcinogenic mode of action of pathogenic bacteria in CRC is a result of genotoxicity, epigenetic alterations, ROS generation, and pro-inflammatory activity. The aim of this review is to discuss the microbial species and their impact on colorectal cancer in terms of disease initiation, progression, and metastasis. The potential of anticancer peptides as anticancer agents or adjuvants is also discussed, as novel treatment options are required to combat the high levels of resistance to current pharmaceutical options.

Healthcare-associated infections caused by multi-drug-resistant pathogens are increasing globally, and current antimicrobial options have limited efficacy against these robust species. The WHO details the critically important bacterial and fungal species that are often associated with medical device HAIs. The effective sterilization of medical devices plays a key role in preventing infectious disease morbidity and mortality. A lack of adherence to protocol and limitations associated with each sterilization modality, however, allows for the incidence of disease. Furthermore, issues relating to carcinogenic emissions from ethylene oxide gas (EtO) have motivated the EPA to propose limiting EtO use or seeking alternative sterilization methods for medical devices. The Food and Drug Administration supports the sterilization of healthcare products using low-temperature VH 2 O 2 as an alternative to EtO. With advances in biomaterial and medical devices and the increasing use of combination products, current sterilization modalities are becoming limited. Novel approaches to disinfection and sterilization of medical devices, biomaterials, and therapeutics are warranted to safeguard public health. Bacteriophages, endolysins, and antimicrobial peptides are considered promising options for the prophylactic and meta-phylactic control of infectious diseases. This timely review discusses the application of these biologics as antimicrobial agents against critically important WHO pathogens, including ESKAPE bacterial species.

Background: Non-ventilator healthcare-associated pneumonia (NV-HAP) is an important healthcare-associated infection. This study tested the feasibility of using routine admission data to identify those patients at high risk of NV-HAP who could benefit from targeted, preventive interventions., Methods: Patients aged ≥64 years who developed NV-HAP five days or more after admission to elderly-care wards, were identified by retrospective case note review together with matched controls. Data on potential predictors of NV-HAP were captured from admission records. Multi-variate analysis was used to build a prognostic screening tool (PRHAPs); acceptability and feasibility of the tool was evaluated., Results: A total of 382 cases/381 control patients were included in the analysis. Ten predictors were included in the final model; nine increased the risk of NV-HAP (OR between 1.68 and 2.42) and one (independent mobility) was protective (OR 0.48; 95% CI 0.30-0.75). The model correctly predicted 68% of the patients with and without NV-HAP; sensitivity 77%; specificity 61%. The PRHAPs tool risk score was 60% or more if two predictors were present and over 70% if three were present. An expert consensus group supported incorporating the PRHAPs tool into electronic logic systems as an efficient mechanism to identify patients at risk of NV-HAP and target preventative strategies., Conclusions: This prognostic screening (PRHAPs) tool, applied to data routinely collected when a patient is admitted to hospital, could enable staff to identify patients at greatest risk of NV-HAP, target scarce resources in implementing a prevention care bundle, and reduce the use of antimicrobial agents., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clostridioides species possess many virulence factors and alarming levels of muti-drug resistance which make them a significant risk to public health safety and a causative agent of livestock disease. Clostridioides result in serious systemic and gastrointestinal diseases such as myonecrosis, colitis, food poisoning and gastroenteritis. As foodborne pathogens, Clostridioides species are associated with significant incidences of morbidity and mortality where the application of broad-spectrum antibiotics predisposes patients to virulent Clostridioides colonisation. As part of the One Health approach, there is an urgent need to eliminate the use of antibiotics in food production to safeguard animals, humans and the environment. Alternative options are warranted to control foodborne pathogens at all stages of food production. Antimicrobial peptides and bacteriophages have demonstrated efficacy against Clostridioides species and may offer antimicrobial biocontrol options. The bacteriocin nisin, for example, has been implemented as a biopreservative for the control of Listeria , Staphylococcus and Clostridia species in food. Bacteriophage preparations have also gained recognition for the antibacterial action against highly virulent bacterial species including foodborne pathogens. Studies are warranted to mitigate the formulation and administration limitations associated with the application of such antimicrobials as biocontrol strategies. This review outlines foodborne Clostridioides species, their virulence factors, and potential biocontrol options for application in food production.

The antimicrobial resistance crisis is an ongoing major threat to public health safety. Low- and middle-income countries are particularly susceptible to higher fatality rates and the economic impact of antimicrobial resistance (AMR). As an increasing number of pathogens emerge with multi- and pan-drug resistance to last-resort antibiotics, there is an urgent need to provide alternative antibacterial options to mitigate disease transmission, morbidity, and mortality. As identified by the World Health Organization (WHO), critically important pathogens such as Klebsiella and Pseudomonas species are becoming resistant to last-resort antibiotics including colistin while being frequently isolated from clinical cases of infection. Antimicrobial peptides are potent amino acid sequences produced by many life forms from prokaryotic, fungal, plant, to animal species. These peptides have many advantages, including their multi-hit mode of action, potency, and rapid onset of action with low levels of resistance being evident. These innate defense mechanisms also have an immune-stimulating action among other activities in vivo, thus making them ideal therapeutic options. Large-scale production and formulation issues (pharmacokinetics, pharmacodynamics), high cost, and protease instability hinder their mass production and limit their clinical application. This review outlines the potential of these peptides to act as therapeutic agents in the treatment of multidrug-resistant infections considering the mode of action, resistance, and formulation aspects. Clinically relevant Gram-positive and Gram-negative pathogens are highlighted according to the WHO priority pathogen list.

Emerging, re-emerging and zoonotic viral pathogens represent a serious threat to human health, resulting in morbidity, mortality and potentially economic instability at a global scale. Certainly, the recent emergence of the novel SARS-CoV-2 virus (and its variants) highlighted the impact of such pathogens, with the pandemic creating unprecedented and continued demands for the accelerated production of antiviral therapeutics. With limited effective small molecule therapies available for metaphylaxis, vaccination programs have been the mainstay against virulent viral species. Traditional vaccines remain highly effective at providing high antibody titres, but are, however, slow to manufacture in times of emergency. The limitations of traditional vaccine modalities may be overcome by novel strategies, as outlined herein. To prevent future disease outbreaks, paradigm shift changes in manufacturing and distribution are necessary to advance the production of vaccines, monoclonal antibodies, cytokines and other antiviral therapies. Accelerated paths for antivirals have been made possible due to advances in bioprocessing, leading to the production of novel antiviral agents. This review outlines the role of bioprocessing in the production of biologics and advances in mitigating viral infectious disease. In an era of emerging viral diseases and the proliferation of antimicrobial resistance, this review provides insight into a significant method of antiviral agent production which is key to protecting public health.

The prevalence of neurological conditions which manifest with chronic pain is increasing globally, where the World Health Organisation has now classified chronic pain as a risk factor for death by suicide. While many chronic pain conditions have a definitive underlying aetiology, non-somatic conditions represent difficult-to-diagnose and difficult-to-treat public health issues. The interaction of the immune system and nervous system has become an important area in understanding the occurrence of neuroinflammation, nociception, peripheral and central sensitisation seen in chronic pain. More recently, however, the role of the resident microbial species in the human gastrointestinal tract has become evident. Dysbiosis, an alteration in the microbial species present in favour of non-beneficial and pathogenic species has emerged as important in many chronic pain conditions, including functional somatic syndromes, autoimmune disease and neurological diseases. In particular, a decreased abundance of small chain fatty acid, e.g., butyrate-producing bacteria, including Faecalibacterium , Firmicutes and some Bacteroides spp., is frequently evident in morbidities associated with long-term pain. Microbes involved in the production of neurotransmitters serotonin, GABA, glutamate and dopamine, which mediate the gut-brain, axis are also important. This review outlines the dysbiosis present in many disease states manifesting with chronic pain, where an overlap in morbidities is also frequently present in patients.

Equine influenza virus strains of Florida sublineage clade 1 (Fc1) have been circulating in North America. In this study, virus neutralization assays were performed to evaluate antigenic differences between Fc1 vaccine strains and North American Fc1 strains isolated in 2021-2022, using equine antisera against A/equine/South Africa/4/2003 (a vaccine strain recommended by the World Organisation for Animal Health) and A/equine/Ibaraki/1/2007 (a Japanese vaccine strain). Antibody titers against four North American Fc1 strains isolated in 2021-2022 were comparable to those against the homologous vaccine strains. These results suggest that current Fc1 vaccine strains are effective against North American strains from 2021-2022., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The association between poor performance and respiratory disease in Thoroughbred racehorses that do not have a structural abnormality of the respiratory tract, is often based on anecdotal evidence. The objective of this scoping review was to examine the scientific evidence for such associations. Publications were selected based on a search of three databases (PubMed, Scopus, and CAB Direct), in English and without date restriction, followed by a screening process to exclude non-relevant papers, duplicates, and reviews. This process identified 996 publications of which 20 were analysed using the Quality in Prognosis Studies (QUIPS) tool. The results indicated that the evidence supporting the relationship between proposed diagnostic indicators and poor performance is variable. There is a need for better quality evidence. In particular, there are conflicting reports relating to the impact of equine asthma and EIPH on athletic performance. Furthermore, a lack of standardisation in the measurement of racehorse performance makes it difficult to compare findings from different studies. The industry would benefit from high-level guidance concerning the design of controlled performance studies in Thoroughbred racehorses to collect comprehensive data and facilitate targeted interventions.

Fungal pathogens cause significant human morbidity and mortality globally, where there is a propensity to infect vulnerable people such as the immunocompromised ones. There is increasing evidence of resistance to antifungal drugs, which has significant implications for cutaneous, invasive and bloodstream infections. The World Health Organization (WHO) published a priority list of fungal pathogens in October 2022, thus, highlighting that a crisis point has been reached where there is a pressing need to address the solutions. This review provides a timely insight into the challenges and implications on the topic of antifungal drug resistance along with discussing the effectiveness of established disease mitigation modalities and approaches. There is also a need to elucidate the cellular and molecular mechanisms of fungal resistance to inform effective solutions. The established fungal decontamination approaches are effective for medical device processing and sterilization, but the presence of pathogenic fungi in recalcitrant biofilms can lead to challenges, particularly during cleaning. Future design ideas for implantable and reusable medical devices should consider antifungal materials and appropriates for disinfection, and where it is relevant, sterilization. Preventing the growth of mycotoxin-producing fungi on foods through the use of appropriate end-to-end processes is advisable, as mycotoxins are recalcitrant and challenging to eliminate once they have formed.

Background: Our research showed that patients with alcohol-associated liver disease (ALD) had more severe liver disease than those without a diagnosis of ALD yet were less likely to be selected for transplant listing due to their increased psychosocial vulnerability. This study aims to answer whether this vulnerability translates to worse short-term outcomes after transplant listing., Methods: A total of 187 patients were approved for liver transplant listing and are included in the present retrospective study. We collected dates of transplantation, retransplantation, death, and pathologic data for evidence of rejection, and reviewed alcohol biomarkers and documentation for evidence of alcohol use., Results: The ALD cohort had higher Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) scores (39.4 vs. 22.5, p <0.001) and Model for End-Stage Liver Disease (MELD)-Na scores (25.0 vs. 18.5, p <0.001) compared with the non-ALD cohort. Forty-nine (59.7%) subjects with ALD and 60 (57.1%, p =0.71) subjects without ALD subsequently received a liver transplant. Overall mortality was similar between the 2 groups (20.7% ALD vs. 21.0% non-ALD, p =0.97). Neither the SIPAT score (HR: 0.98, 95% CI: 0.96-1.00, p =0.11) nor MELD-Na score (HR 0.99, 95% CI 0.95-1.02, p =0.40) were associated with mortality. Patients with ALD were more likely to have alcohol biomarkers tested both before (84.1% vs. 24.8% non-ALD, p <0.001) and after liver transplantation (74.0% vs. 16.7% non-ALD, p <0.001). SIPAT score was associated with alcohol use after listing (OR: 1.03, 95% CI: 1.0-1.07, p =0.04), although a return to alcohol use was not associated with mortality (HR: 1.60, 95% CI: 0.63-4.10, p =0.33)., Conclusion: Patients with ALD had higher psychosocial risk compared with patients without a diagnosis of ALD who were placed on the waitlist, but had similar short-term outcomes including mortality, transplantation, and rejection. Although a high SIPAT score was predictive of alcohol use, in the short-term, alcohol use after transplant listing was not associated with mortality., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Fungal pathogens contribute to significant disease burden globally; however, the fact that fungi are eukaryotes has greatly complicated their role in fungal-mediated infections and alleviation. Antifungal drugs are often toxic to host cells and there is increasing evidence of adaptive resistance in animals and humans. Existing fungal diagnostic and treatment regimens have limitations that has contributed to the alarming high mortality rates and prolonged morbidity seen in immunocompromised cohorts caused by opportunistic invasive infections as evidenced during HIV and COVID-19 pandemics. There is a need to develop real-time monitoring and diagnostic methods for fungal pathogens and to create a greater awareness as to the contribution of fungal pathogens in disease causation. Greater information is required on the appropriate selection and dose of antifungal drugs including factors governing resistance where there is commensurate need to discover more appropriate and effective solutions. Popular azole fungal drugs are widely detected in surface water and sediment due to incomplete removal in wastewater treatment plants where they are resistant to microbial degradation and may cause toxic effects on aquatic organisms such as algae and fish. UV has limited effectiveness in destruction of anti-fungal drugs where there is increased interest in the combination approaches such as novel use of pulsed-plasma gas-discharge technologies for environmental waste management. There is growing interest in developing alternative and complementary green eco-biocides and disinfection innovation. Fungi present challenges for cleaning, disinfection and sterilization of reusable medical devices such as endoscopes where they (example, Aspergillus and Candida species) can be protected when harboured in build-up biofilm from lethal processing. Information on the efficacy of established disinfection and sterilization technologies to address fungal pathogens including bottleneck areas that present high risk to patients is lacking. There is a need to address risk mitigation and modelling to inform efficacy of appropriate intervention technologies that must consider all contributing factors where there is potential to adopt digital technologies to enable real-time analysis of big data, such as use of artificial intelligence and machine learning. International consensus on standardised protocols for developing and reporting on appropriate alternative eco-solutions must be reached, particularly in order to address fungi with increasing drug resistance where research and innovation can be enabled using a One Health approach., Competing Interests: Declaration of competing interest The author declares no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Biologics have become an important area of medical research generating therapeutics essential for the treatment of many disease states. Biologics are defined as biologically active compounds manufactured by living cells or through biological processes termed bioprocessing. Compared to small molecules which are chemically synthesised they are relatively complex and therapeutically specific molecules. Biologics include hormones, vaccines, blood products, monoclonal antibodies, recombinant therapeutic proteins, enzymes, gene and cellular therapies amongst others. For biologic production prokaryotic and eukaryotic cells (mammalian and non-mammalian) are used as expression systems. Eukaryotic expression systems offer many advantages over prokaryotic based systems. The manufacture of high-quality proteins for human clinical use via recombinant technologies has been achieved in yeast and filamentous fungal systems. Advances in bioprocessing such as genetic engineering, bioreactor design, continuous processing, and quality by design has allowed for increased productivity and higher yield in in these non-mammalian eukaryotic systems with protein translation similar to mammalian systems. The application of eukaryotic expressions systems for the manufacture of biologics of therapeutic importance are described herein.

Updating vaccine strains is essential to control equine influenza. We evaluated the protective efficacy of an inactivated equine influenza vaccine derived from viruses generated by reverse genetics (RG) in horses in an experimental viral challenge study. Wild-type (WT) virus (A/equine/Tipperary/1/2019) and virus generated by RG (consisting of hemagglutinin and neuraminidase genes from A/equine/Tipperary/1/2019 and six other genes from high-growth A/Puerto Rico/8/34) were inactivated by formalin for vaccine use. Twelve 1-year-old naïve horses with no antibodies against equine influenza virus were assigned to three groups (each n = 4): control, WT, and RG. They were vaccinated twice, 4 weeks apart, and were challenged with A/equine/Tipperary/1/2019 2 weeks after the second vaccination. All four horses in the control group and one horse in the WT group had pyrexia for multiple days and respiratory illness, and one horse in the RG group had pyrexia for 2 days without respiratory illness. The mean rectal temperatures and the mean concentrations of serum amyloid A in the WT and RG groups were significantly lower than those in the control group, with no significant differences between them. The WT and RG vaccines significantly reduced viral shedding relative to the control. The protective efficacy of the RG-derived inactivated vaccine against equine influenza virus is comparable to that of the vaccine derived from WT viruses in horses. The RG technique can make it easy to update equine influenza vaccine strains., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Food safety and sustainable food production is an important part of the Sustainable Development goals aiming to safeguard the health and wellbeing of humans, animals and the environment. Foodborne illness is a major cause of morbidity and mortality, particularly as the global crisis of antimicrobial resistance proliferates. In order to actively move towards sustainable food production, it is imperative that green biocontrol options are implemented to prevent and mitigate infectious disease in food production. Replacing current chemical pesticides, antimicrobials and disinfectants with green, organic options such as biopesticides is a step towards a sustainable future. Bacteriophages, virus which infect and kill bacteria are an area of great potential as biocontrol agents in agriculture and aquaculture. Lytic bacteriophages offer many advantages over traditional chemical-based solutions to control microbiological contamination in the food industry. The innate specificity for target bacterial species, their natural presence in the environment and biocompatibility with animal and humans means phages are a practical biocontrol candidate at all stages of food production, from farm-to-fork. Phages have demonstrated efficacy as bio-sanitisation and bio-preservation agents against many foodborne pathogens, with activity against biofilm communities also evident. Additionally, phages have long been recognised for their potential as therapeutics, prophylactically and metaphylactically. Further investigation is warranted however, to overcome their limitations such as formulation and stability issues, phage resistance mechanisms and transmission of bacterial virulence factors.

Introduction: The importance of ultraclean air in reducing deep infection was studied by Charnley who showed that the rate decreased as the airborne bacterial load was reduced. The effectiveness was shown in a large Medical Research Council (MRC) trial, but registry data have not shown a consistent benefit. Because we treat patients with rheumatoid arthritis, we decided to look at our theatre air quality., Methods: In phase 1 we monitored air quality using settle plates, exposed for one hour after the incision, on the instrument trolleys in a joint replacement theatre. In phase 1 the scrub person did not wear a body exhaust system. In phase 2 all three staff used a body exhaust system, and we played close attention to the orientation and position of the surgical lights and trolleys., Results: In phase 1 we grew 0.24 colonies/plate/hour in the ultraclean zone, which is comparable to the Charnley trial findings. In the second phase we grew 0.03 colonies/plate/hour ( p <0.001). When plates were placed on the trolleys in controlled positions there was a tendency for the colonies to appear on the corners of the trolleys at the edge of the clean zone (NS)., Discussion: The study showed that in phase 1 colony counts comparable to the original Charnley studies were achieved. Colony counts of 0.03 colonies/plate/hour can be achieved in contemporary practice, with all team members using body exhausts.

Functional somatic syndromes are increasingly diagnosed in chronically ill patients presenting with an array of symptoms not attributed to physical ailments. Conditions such as chronic fatigue syndrome, fibromyalgia syndrome, or irritable bowel syndrome are common disorders that belong in this broad category. Such syndromes are characterised by the presence of one or multiple chronic symptoms including widespread musculoskeletal pain, fatigue, sleep disorders, and abdominal pain, amongst other issues. Symptoms are believed to relate to a complex interaction of biological and psychosocial factors, where a definite aetiology has not been established. Theories suggest causative pathways between the immune and nervous systems of affected individuals with several risk factors identified in patients presenting with one or more functional syndromes. Risk factors including stress and childhood trauma are now recognised as important contributors to chronic pain conditions. Emotional, physical, and sexual abuse during childhood is considered a severe stressor having a high prevalence in functional somatic syndrome suffers. Such trauma permanently alters the biological stress response of the suffers leading to neuroexcitatory and other nerve issues associated with chronic pain in adults. Traumatic and chronic stress results in epigenetic changes in stress response genes, which ultimately leads to dysregulation of the hypothalamic-pituitary axis, the autonomic nervous system, and the immune system manifesting in a broad array of symptoms. Importantly, these systems are known to be dysregulated in patients suffering from functional somatic syndrome. Functional somatic syndromes are also highly prevalent co-morbidities of psychiatric conditions, mood disorders, and anxiety. Consequently, this review aims to provide insight into the role of the nervous system and immune system in chronic pain disorders associated with the musculoskeletal system, and central and peripheral nervous systems.

The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a validated interview tool to assess psychosocial well-being in candidates for solid organ transplants, with higher scores indicating greater vulnerability. We hypothesized that patients with alcohol-related liver disease (ALD) undergoing liver transplantation (LT) evaluation would have higher SIPAT scores than candidates with non-ALD, but that only patients with ALD who have low scores would be selected. We analyzed retrospectively consecutive adults undergoing LT evaluation from June 2018 to December 2019. Comparisons between patients with ALD and patients with non-ALD were made using the nonparametric Wilcoxon rank sum test plus a multivariate analysis to determine independent predictors for approval. In the study cohort of 358 patients, there were 199 (56%) patients with ALD with a mean age of 55 years, and 133 (67%) were men. There were 159 (44%) patients with non-ALD with a mean age of 57 years, and 95 (60%) were men. Mean Model for End-Stage Liver Disease-sodium scores were similar for selected versus not selected patients with ALD (25 versus 25.6) and selected versus not selected patients with non-ALD (18.3 versus 17.4), although the ALD group had substantially higher Model for End-Stage Liver Disease scores. Patients with ALD had higher mean SIPAT composite and individual domain scores compared with their non-ALD counterparts. SIPAT scores were not affected by age or sex. Proportionately more candidates with non-ALD were selected compared to candidates with ALD (68% versus 42%; P < 0.001; odds ratio for approval of non-ALD versus ALD, 2.9; 95% confidence interval, 1.8-4.7; P < 0.001). Composite SIPAT scores were lower in the selected versus nonselected in both ALD and non-ALD groups, although the SIPAT scores were significantly higher in selected patients with ALD (median, 39) than selected patients with non-ALD (median, 23; P = 0.001). Psychosocial assessment has a greater influence than acuity of liver failure on the selection of patients with ALD for LT listing, whereas psychosocial assessment has a minor influence on the selection of non-ALD candidates., (© 2021 by the American Association for the Study of Liver Diseases.)

Mushrooms have been used as traditional medicine for millennia, fungi are the main natural source of psychedelic compounds. There is now increasing interest in using fungal active compounds such as psychedelics for alleviating symptoms of mental health disorders including major depressive disorder, anxiety, and addiction. The anxiolytic, antidepressant and anti-addictive effect of these compounds has raised awareness stimulating neuropharmacological investigations. Micro-dosing or acute dosing with psychedelics including Lysergic acid diethylamide (LSD) and psilocybin may offer patients treatment options which are unmet by current therapeutic options. Studies suggest that either dosing regimen produces a rapid and long-lasting effect on the patient post administration with a good safety profile. Psychedelics can also modulate immune systems including pro-inflammatory cytokines suggesting a potential in the treatment of auto-immune and other chronic pain conditions. This literature review aims to explore recent evidence relating to the application of fungal bioactives in treating chronic mental health and chronic pain morbidities.

Antimicrobial resistance (AMR) is recognised globally as one of the greatest threats to human and animal health; thus, discovery of alternative antibacterial agents to address AMR is a priority challenge. This study constitutes the first report of a low-melting temperature, polymer- extrusion process for the smart delivery of thermally-sensitive antimicrobial bioactives, including generally-regarded-as-safe (GRAS) bioactives derived from various sources. Bioactives were assessed before and after extrusion by determining their respective minimum inhibitory concentrations (MIC). WHO-priority AMR-bacterial isolates causing zoonotic infections were evaluated along with use of standard ATCC strains. Findings revealed that this copolymer method was capable of delivering thermally-sensitive bioactives with varying degrees of growth inhibition against the AMR-bacterial strains. The extrusion process was found to increase the effect of nisin against MRSA (4-fold increase) and L. monocytogenes (6.4-fold increase), silver nitrate (AgNO 3 ) against E. coli (3.6-fold increase) and S. epidermidis (1.25-fold increase), and chitosan against S. aureus (1.25-fold). Findings show the potential applicability of this polymer extrusion process for developing future bioactive-loaded polymer compounds; thus, highlighting the potential of converging bio-based industry with novel materials for enabling 'One-Health' solutions., Competing Interests: Declaration of competing interest There is no conflict of interest for authors., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Plant vascular systems can translocate the entomopathogen Bacillus thuringiensis from the soil into plant tissues. However, whether other soil dwelling entomopathogens utilize plant vascular tissue for movement has not yet been fully explored. We used Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV) to evaluate whether baculoviruses, a common entomopathogen and bioinsecticide, can be transported through the plant vascular pathways of Zea mays . We found that our treatments did not allow a sufficient virus translocation into the plant to induce a lethal infection in insects, which was confirmed by a molecular analysis. While other entomopathogens translocate, baculoviruses may not be one of them.

Antimicrobial resistance (AMR) remains one of the greatest public health-perturbing crises of the 21st century, where species have evolved a myriad of defence strategies to resist conventional therapy. The production of extended-spectrum β-lactamase (ESBL), AmpC and carbapenemases in Gram-negative bacteria (GNB) is one such mechanism that currently poses a significant threat to the continuity of first-line and last-line β-lactam agents, where multi-drug-resistant GNB currently warrant a pandemic on their own merit. The World Health Organisation (WHO) has long recognised the need for an improved and coordinated global effort to contain these pathogens, where two factors in particular, international travel and exposure to antimicrobials, play an important role in the emergence and dissemination of antibiotic-resistant genes. Studies described herein assess the resistance patterns of isolated nosocomial pathogens, where levels of resistance were detected using recognised in vitro methods. Additionally, studies conducted extensively investigated alternative biocide (namely peracetic acid, triameen and benzalkonium chloride) and therapeutic options (specifically 1,10-phenanthroline-5,6-dione), where the levels of induced endotoxin from E. coli were also studied for the latter. Antibiotic susceptibility testing revealed there was a significant association between multi-drug resistance and ESBL production, where the WHO critical-priority pathogens, namely E. coli , K. pneumoniae , A. baumannii and P. aeruginosa , exhibited among the greatest levels of multi-drug resistance. Novel compound 1,10-phenanthroline-5,6-dione (phendione) shows promising antimicrobial activity, with MICs determined for all bacterial species, where levels of induced endotoxin varied depending on the concentration used. Tested biocide agents show potential to act as intermediate-level disinfectants in hospital settings, where all tested clinical isolates were susceptible to treatment.

The emergence of severe acute respiratory disease (SARS-CoV-2) variants that cause coronavirus disease is of global concern. Severe acute respiratory disease variants of concern (VOC) exhibiting greater transmissibility, and potentially increased risk of hospitalization, severity and mortality, are attributed to molecular mutations in outer viral surface spike proteins. Thus, there is a reliance on using appropriate counter-disease measures, including non-pharmaceutical interventions and vaccination. The best evidence suggests that the use of frontline biocides effectively inactivate coronavirus similarly, including VOC, such as 202012/01, 501Y.V2 and P.1 that have rapidly replaced the wild-type variant in the United Kingdom, South Africa and Brazil, respectively. However, this review highlights that efficacy of VOC-disinfection will depend on the type of biocide and the parameters governing the activity. VOC are likely to be similar in size to the wild-type strain, thus implying that existing guidelines for use and re-use of face masks post disinfection remain relevant. Monitoring to avoid injudicious use of biocides during the coronavirus disease era is required as prolonged and excessive biocide usage may negatively impact our receiving environments; thus, highlighting the potential for alternative more environmental-friendly sustainable biocide solutions. Traditional biocides may promote cross-antimicrobial resistance to antibiotics in problematical bacteria. The existing filtration efficacy of face masks is likely to perform similarly for VOC due to similar viral size; however, advances in face mask manufacturing by way incorporating new anti-viral materials will potentially enhance their design and functionality for existing and potential future pandemics., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Although widely accepted as a water sterilisation technique, chlorination results in the production of potentially harmful by-products, mainly Trihalomethanes. Furthermore, the chlorination process requires specialised infrastructure, management and high costs. In this research paper a potential alternative sterilisation technique was investigated. This rapid three-step process utilized Goethite Nanoparticles and the photosensitising capabilities of a xanthene dye. Rose Bengal (RB) a compound primarily used as a stain to diagnose damaged tissue in the eye was utilized under visible light excitation to sterilise water containing gram-positive Staphylococcus aureus and Bacillus cereus. Bacterial reductions (cfu/ml) of up to 6log10 are reported at RB concentrations of 0.5 mg/L and 10 mg/L for S. aureus and B. cereus, respectively. Goethite Nanoparticles (GNP's), an iron oxyhydroxide, were synthesised by co-precipitation of iron salts and used to adsorb RB post-sterilisation. Poly-vinyl Alcohol (PVA) functionalised GNP's were synthesised to highlight the adsorbent capabilities of the GNP surface. The adsorption capacity for uncoated GNPs was 476.19 mg/g, this reduced to 170.4 mg/g for PVA-GNP's, highlighting the highly porous nature of the synthesised GNP surface. Adsorption was optimal in slightly acidic conditions (pH5-6). The adsorption parameters best followed Lagergens Pseudo-second order kinetics with correlation coefficients close to unity. At the highest envisaged RB concentration (10 mg/L) approximately 20 mg/L GNP's was required to remove the dye from solution post-treatment. Flame Atomic Absorption analysis of the water post-removal revealed Iron concentrations of 0.058 mg/L. This correlates to removal efficacy of 99.71% with residual iron levels below the EU recommended limit of 0.2 mg/L., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Equine herpesvirus 1 isolates from a 2021 outbreak of neurologic disease in Europe have a mutation, A713G, in open reading frame 11 not detected in 249 other sequences from equine herpesvirus 1 isolates. This single-nucleotide polymorphism could help identify horses infected with the virus strain linked to this outbreak.

The objective of this study was to determine the benefit of pre-milking teat foam disinfection on the prevention of new infections by contagious and environmental bacteria in two spring calving herds managed outdoors (Herd 1 [H1]; 331 cows and Herd 2 [H2]; 142 cows). Four pre-milking teat preparation treatments were applied post calving; with each herd receiving two treatments; using a split udder design (for approx. 15 weeks). These treatments included; (1) 'water wash, foam application and dry wipe (WFD) in H1'; (2) 'water wash and dry wipe (WD)' in H1; (3) 'foam application and dry wipe (FD)' in H2; (4) 'no teat cleaning preparation (NP)' in H2. Individual quarter foremilk samples were collected on four occasions and all clinical and sub-clinical cases were recorded. The mean SCC of quarter foremilk samples was 134 × 10 3 cells/mL and 127 × 10 3 cells/mL for WD and WFD, respectively, and 109 × 10 3 cells/mL and 89 × 10 3 cells/mL for NP and FD, respectively ( p > 0.05). Lower bacterial counts were observed on teat skin that received a foaming treatment. Pre-milking teat disinfection using a foaming product may be of little benefit, in early lactation, for a pasture-based dairy herd.

Objective: To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19., Design: A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19., Setting: University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT)., Participants: 956 healthcare workers were recruited by open invitation via UHBFT trust email and social media between 27 April 2020 and the 8 June 2020., Intervention: Participants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables., Results: Using an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM, respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity in self-isolating individuals a time when Wuhan strain SARS-CoV-2 was predominant., Conclusions and Relevance: Assays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease., Competing Interests: Competing interests: MTD reports personal fees from Abingdon Health, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Functional movement disorders (FMD) are a common and disabling neuropsychiatric condition, part of the spectrum of functional neurological/conversion disorder. FMD represent one of the most enigmatic disorders in the history of medicine. However, in the twenty years after the first report of distinctive abnormal brain activity associated with functional motor symptoms, there have been tremendous advances in the pathophysiologic understanding of these disorders. FMD can be characterized as a disorder of aberrant neurocircuitry interacting with environmental and genetic factors. These developments suggest that research on FMD could be better served by an integrative, neuroscience-based approach focused on functional domains and their neurobiological substrates. This approach has been developed in 'Research Domain Criteria' (RDoC) project, which promotes a dimensional approach to psychiatric disorders. Here, we use the RDoC conceptualization to review recent neuroscience research on FMD, focusing on the domains most relevant to these disorders. We discuss how the adoption of a similar integrative framework may facilitate the identification of the mechanisms underlying FMD and could also have potential clinical applicability., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To provide a standardised approach to the diagnosis of diseases and to facilitate health certification for trade, the World Organisation for Animal Health (OIE) standards, described in the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals (Terrestrial Manual), include internationally agreed laboratory diagnostic techniques. This review examines the type of tests recommended in the disease-specific chapters of the Terrestrial Manual for the six most common purposes of diagnostic techniques, including certification for movement, confirmation of clinical cases and disease surveillance. The most frequently recommended tests for all six purposes are enzyme-linked immunosorbent assay and/or polymerase chain reaction, for which there are detailed validation guidelines in the OIE Terrestrial Manual. This is true for all species and no species-specific barriers to validation related to test type were identified. Classical techniques continue to be well represented in the Terrestrial Manual recommendations whereas novel technologies are slow to gain acceptance. These classical tests can present challenges for validation as there may be a dearth of international standard reagents and harmonised protocols.

Antimicrobial resistance is one of the greatest dangers to public health of the 21st century, threatening the treatment and prevention of infectious diseases globally. Disinfection, the elimination of microbial species via the application of biocidal chemicals, is essential to control infectious diseases and safeguard animal and human health. In an era of antimicrobial resistance and emerging disease, the effective application of biocidal control measures is vital to protect public health. The COVID-19 pandemic is an example of the increasing demand for effective biocidal solutions to reduce and eliminate disease transmission. However, there is increasing recognition into the relationship between biocide use and the proliferation of Antimicrobial Resistance species, particularly multidrug-resistant pathogens. The One Health approach and WHO action plan to combat AMR require active surveillance and monitoring of AMR species; however, biocidal resistance is often overlooked. ESKAPE ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species) pathogens and numerous fungal species have demonstrated drug and biocidal resistance where increased patient mortality is a risk. Currently, there is a lack of information on the impact of biocide application on environmental habitats and ecosystems. Undoubtedly, the excessive application of disinfectants and AMR will merge to result in secondary disasters relating to soil infertility, loss of biodiversity and destruction of ecosystems.

Background: Pseudomonas aeruginosa is a common opportunistic pathogen and molecular typing in outbreaks has linked patient acquisition to contaminated hospital water systems., Aim: To elucidate the role of P. aeruginosa transmission rates in non-outbreak augmented care settings in the UK., Methods: Over a 16-week period, all water outlets in augmented care units of four hospitals were sampled for P. aeruginosa and clinical isolates were collected. Outlet and clinical P. aeruginosa isolates underwent whole-genome sequencing (WGS), which with epidemiological data identified acquisition from water as definite (level 1), probable (level 2), possible (level 3), and no evidence (level 4)., Findings: Outlets were positive in each hospital on all three occasions: W (16%), X (2.5%), Y (0.9%) and Z (2%); and there were 51 persistently positive outlets in total. WGS identified likely transmission (at levels 1, 2 and 3) from outlets to patients in three hospitals for P. aeruginosa positive patients: W (63%), X (54.5%) and Z (26%). According to the criteria (intimate epidemiological link and no phylogenetic distance), approximately 5% of patients in the study 'definitely' acquired their P. aeruginosa from their water outlets in the intensive care unit. This study found extensive evidence of transmission from the outlet to the patients particularly in the newest hospital (W), which had the highest rate of positive outlets., Conclusions: The overall findings suggest that water outlets are the most likely source of P. aeruginosa nosocomial infections in some settings, and that widespread introduction of control measures would have a substantial impact on infections., (Copyright © 2021. Published by Elsevier Ltd.)

Fungal skin infections and iatrogenic disease of companion animals continue to be an ongoing issue for veterinarians, where misdiagnosis or inapt medical treatment result in secondary conditions within animals. The widespread use of antifungals in both modern medicine and agriculture has resulted in concomitant resistance in species, where zoonotic transfer poses a risk to public health. Studies described herein assess the resistance of pathogenic species isolated from companion animals to a battery of conventional antimicrobial agents. Levels of resistance were detected using recognised in vitro methods, where additional novel therapeutic and biocide options were also extensively investigated. Results show high levels of resistance to the three main families of antifungal agents, namely caspofungin, Amp B and fluconazole. Resistance in Candida , Cryptococcal , Aspergillus and Trichophyton species is described herein, highlighting the need for defined species-specific antifungal breakpoints, and for Malassezia and Wickerhamomyces anomalus species which also have zoonotic potential. Novel compound phendione showed promising antimicrobial activity, with MICs determined for both fungal and bacterial species. The biocidal options investigated also showed potential to act as intermediate-level disinfectants, where peracetic acid proved most effective against fungal spore formers.

This study compared concurrent and separate primary vaccination against equid alphaherpesviruses 1 and 4, genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae, and equine influenza A virus, genus Alphainfluenzavirus, family Orthomyxoviridae. Their vernacular names are equine herpesvirus 1 and 4 (EHV1/4) and equine influenza virus (EIV). Infection with these respiratory pathogens is associated with loss of performance, interruption of training schedules, and on occasion, cancellation of equestrian events. Vaccination is highly recommended, and for some activities it is a mandatory requirement of the relevant authority. As there is a dearth of information relating to the impact of concurrent vaccination on the antibody response to EHV and EIV vaccines, they are usually administered separately, often 2 weeks apart. In a previous study of booster vaccination in Thoroughbred racehorses, concurrent vaccination with whole-virus inactivated carbopol-adjuvanted EHV and EIV vaccines did not impact negatively on the antibody response. In this study, investigations were extended to concurrent versus separate primary vaccination of warmblood foals. A field study was conducted to compare the immune response to a carbopol-adjuvanted EHV vaccine and an immune stimulating complex (ISCOM)-adjuvanted EI vaccine administered concurrently and 2 weeks apart. No adverse clinical reactions were observed, the pattern of EI and EHV antibody response was similar for both groups, and there was no evidence that concurrent primary vaccination compromised the humoral response. The results are of relevance to horse owners who wish to decrease veterinary costs, limit handling of young animals, and simplify record keeping by vaccinating concurrently.

Background: Teat disinfection is an important step in the control of mastitis within a dairy herd. The objective of this study was to evaluate the effectiveness of 96 commercially available teat disinfectant products in Ireland against bacterial isolates on teat skin. Teat disinfection products were applied to the teats of seventeen Holstein-Friesian cows. A split-udder model was used where one cow received two different teat disinfection products on each day. A composite swab sample was taken of the left teats and the right teats before and after teat disinfectant application. Swab samples were plated onto 3 different selective agars to enumerate bacterial counts of streptococcal, staphylococcal and coliform isolates., Results: Streptococcal isolates were the most prominent bacterial group recovered on teat swabs taken before the application of a teat disinfection product (55.0%), followed by staphylococcal isolates (41.3%) and coliform isolates (3.7%). Products were reclassified by active ingredients (n = 9) for analysis. These ingredient groups included; chlorhexidine, chlorine dioxide, diamine, iodine, iodine and lactic acid, lactic acid, lactic acid and chlorhexidine, lactic acid and hydrogen peroxide, and lactic acid and salicylic acid. The ingredient group, chlorine dioxide, resulted in comparable reductions to the iodine group for streptococcal isolates. The ingredient group, iodine combined with lactic acid, resulted in the greatest reduction of staphylococcal isolates. When observing products individually, a product containing 1.6% w/w lactic acid combined with hydrogen peroxide was the most effective at reducing streptococcal isolates on the teat skin, whereas a product containing lactic acid combined with 0.6% w/w chlorhexidine was the most effective against staphylococcal isolates. Minor differences were observed regarding the relationship between effectiveness and active ingredient concentration between products., Conclusions: This study suggests that some teat disinfectant products achieve a higher reduction in bacterial levels against different specific bacterial groups on teat skin than other products. Therefore, when choosing a teat disinfectant product, the bacteria in the dairy herds' environment should be considered. Further studies are necessary to evaluate products efficacy against new IMIs and any possible effects on teat skin condition.

Objective: To determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers., Design: A cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020., Setting: University Hospitals Birmingham NHS Foundation Trust (UHBFT), UK., Participants: 545 asymptomatic healthcare workers were recruited while at work. Participants were invited to participate via the UHBFT social media. Exclusion criteria included current symptoms consistent with COVID-19. No potential participants were excluded., Intervention: Participants volunteered a nasopharyngeal swab and a venous blood sample that were tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 spike glycoprotein antibodies, respectively. Results were interpreted in the context of prior illnesses and the hospital departments in which participants worked., Main Outcome Measure: Proportion of participants demonstrating infection and positive SARS-CoV-2 serology., Results: The point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545). The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516). Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%, χ 2 =21.1034, p<0.0001) and quantitatively greater antibody responses than those who had remained asymptomatic. Seroprevalence was greatest among those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%), with lower rates observed in participants working in intensive care (14.8%). BAME (Black, Asian and minority ethnic) ethnicity was associated with a significantly increased risk of seropositivity (OR: 1.92, 95% CI 1.14 to 3.23, p=0.01). Working on the intensive care unit was associated with a significantly lower risk of seropositivity compared with working in other areas of the hospital (OR: 0.28, 95% CI 0.09 to 0.78, p=0.02)., Conclusions and Relevance: We identify differences in the occupational risk of exposure to SARS-CoV-2 between hospital departments and confirm asymptomatic seroconversion occurs in healthcare workers. Further investigation of these observations is required to inform future infection control and occupational health practices., Competing Interests: Competing interests: MTD reports personal fees from Abingdon Health, outside the submitted work. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mycobacterium avium paratuberculosis is responsible for paratuberculosis or Johne's disease in cows, having economic impacts on the dairy industry and a prevalence rate exceeding 50% in dairy herds. The economic burden of Johne's disease relates to decreased milk production and costs of disease prevention, treatment, and management, while having an economic impact on dairy producers, processors, consumers, and stakeholders of the dairy industry. Determining the true economic impact of the disease is difficult at regional and farm level as symptoms are not evident in subclinically infected animals. At present, the virulence, pathogenicity, persistence, and infectious dose of M. avium paratuberculosis are poorly understood, consequently effective paratuberculosis control measures remain obscure. M. avium paratuberculosis is potentially zoonotic with foodborne transmission a public health risk due to a possible causative link with inflammatory bowel disease in humans. A preventive approach is necessary to reduce the presence of this drug-resistant pathogen in dairy herds and subsequently dairy food. The use of inefficient diagnostic tests coupled with the long latency period of infection results in delayed animal culling and trade of asymptomatic animals, leading to regional transmission and increased disease prevalence. To date, there has been limited success at controlling and treating this terminal endemic disease, leading to significant prevalence rates. This study aims to outline the key factors associated with Johne's' disease while outlining its significant impact on the dairy sector.

Incentivized debt conversion is a financing mechanism that can assist countries with a heavy debt burden to bolster their long-term domestic investment in nature conservation. The Nature Conservancy, an international conservation-based nongovernmental organization, is adapting debt conversions to support marine conservation efforts by small island developing states and coastal countries. Prioritizing debt conversion opportunities according to their potential return on investment can increase the impact and effectiveness of this finance mechanism. We developed guidance on how to do so with a decision-support approach that relies on a novel threat-based adaptation of cost-effectiveness analysis. We constructed scenarios by varying parameters of the approach, including enabling conditions, expected benefits, and threat classifications. Incorporating both abatable and unabatable threats affected priorities across planning scenarios. Similarly, differences in scenario construction resulted in unique solution sets for top priorities. We show how environmental organizations, private entities, and investment banks can adopt structured prioritization frameworks for making decisions about conservation finance investments, such as debt conversions. Our guidance can accommodate a suite of social, ecological, and economic considerations, making the approach broadly applicable to other conservation finance mechanisms or investment strategies that seek to establish a transparent process for return-on-investment decision-making., (© 2020 Society for Conservation Biology.)