The biomolecules of Euglena gracilis: Harnessing biology for natural solutions to future problems.

Over the past decade, the autotrophic and heterotrophic protist Euglena gracilis (E. gracilis) has gained popularity across the studies of environmental science, biosynthesis experiments, and nutritional substitutes. The unique physiology and versatile metabolism of E. gracilis have been a recent topic of interest to many researchers who continue to understand the complexity and possibilities of using E. gracilis biomolecule production. In this review, we present a comprehensive representation of recent literature outlining the various uses of biomolecules derived from E. gracilis across the fields of natural product biosynthesis, as a nutritional substitute, and as bioremediation tools. In addition, we highlight effective strategies for altering metabolite production using abiotic stressors and growth conditions. To better understand metabolite biosynthesis and its role in E. gracilis, integrated studies involving genomics, metabolomics, and proteomics should be considered. Together, we show how the ongoing advancements in E. gracilis related research continue to broaden applications in the biosynthetic sector and highlight future works that would strengthen our understanding of overall Euglena metabolism.

Private groundwater contamination and risk management: A comparative scoping review of similarities, drivers and challenges across two socio-economically developed regions.

Consolidation of multi-domain risk management research is essential for strategies facilitating the concerted government (educational) and population-level (behavioural) actions required to reduce microbial private groundwater contamination. However, few studies to date have synthesised this literature or sought to ascertain the causal generality and extent of supply contamination and preventive responses. In light of the Republic of Ireland (ROI) and Ontario's high reliance and research focus on private wells and consequent utility for empirical comparison, a scoping review of pertinent literature (1990-2022) from both regions was undertaken. The SPICE (Setting, Perspective, Intervention, Comparison, Evaluation) method was employed to inform literature searches, with Scopus and Web of Science selected as primary databases for article identification. The review identified 65 relevant articles (Ontario = 34, ROI = 31), with those investigating well user actions (n = 22) and groundwater quality (n = 28) the most frequent. A markedly higher pooled proportion of private supplies in the ROI exhibited microbial contamination (38.3 % vs. 4.1 %), despite interregional similarities in contamination drivers (e.g., weather, physical supply characteristics). While Ontarian well users demonstrated higher rates of historical (≥ 1) and annual well testing (90.6 % vs. 71.1 %; 39.1 % vs. 8.6 %) and higher rates of historical well treatment (42.3 % vs. 24.3 %), interregional levels of general supply knowledge were analogous (70.7 % vs. 71.0 %). Financial cost, organoleptic properties and residence on property during supply construction emerged as predictors of cognition and behaviour in both regions. Review findings suggest broad interregional similarities in drivers of supply contamination and individual-level risk mitigation, indicating that divergence in contamination rates may be attributable to policy discrepancies - particularly well testing incentivisation. The paucity of identified intervention-oriented studies further highlights the importance of renewed research and policy agendas for improved, targeted well user outreach and incentivised, convenience-based services promoting routine supply maintenance.

Digital transformation of peatland eco-innovations ('Paludiculture'): Enabling a paradigm shift towards the real-time sustainable production of 'green-friendly' products and services.

The world is heading in the wrong direction on carbon emissions where we are not on track to limit global warming to 1.5 °C; Ireland is among the countries where overall emissions have continued to rise. The development of wettable peatland products and services (termed 'Paludiculture') present significant opportunities for enabling a transition away from peat-harvesting (fossil fuels) to developing 'green' eco-innovations. However, this must be balanced with sustainable carbon sequestration and environmental protection. This complex transition from 'brown to green' must be met in real time by enabling digital technologies across the full value chain. This will potentially necessitate creation of new green-business models with the potential to support disruptive innovation. This timely paper describes digital transformation of paludiculture-based eco-innovation that will potentially lead to a paradigm shift towards using smart digital technologies to address efficiency of products and services along with future-proofing for climate change. Digital transform of paludiculture also aligns with the 'Industry 5.0 - a human-centric solution'. However, companies supporting peatland innovation may lack necessary standards, data-sharing or capabilities that can also affect viable business model propositions that can jeopardize economic, political and social sustainability. Digital solutions may reduce costs, increase productivity, improve produce develop, and achieve faster time to market for paludiculture. Digitisation also enables information systems to be open, interoperable, and user-friendly. This constitutes the first study to describe the digital transformation of paludiculture, both vertically and horizontally, in order to inform sustainability that includes process automation via AI, machine learning, IoT-Cloud informed sensors and robotics, virtual and augmented reality, and blockchain for cyber-physical systems. Thus, the aim of this paper is to describe the applicability of digital transformation to actualize the benefits and opportunities of paludiculture activities and enterprises in the Irish midlands with a global orientation.

Behcet's Disease (BD) Presenting as a Cerebral Venous Sinus Thrombosis (CVST).

Presentation 20 year old Caucasian male presented to eye casualty 4 weeks post initial diagnosis of bilateral acute anterior uveitis (AAU), with a three-week history of a progressively worsening headache associated with nausea and vomiting. Diagnosis Non-contrast Computed Topography of the head and Magnetic Resonance venogram revealed a cerebral venous sinus thrombosis (CVST). He had a long-standing history of intermittent oral ulceration, and was diagnosed with Neuro Behcet's Disease (NBD). Treatment The patient was commenced on a therapeutic dose of enoxaparin and prednisolone, and was discharged on enoxaparin, warfarin, tapering prednisolone and azathioprine. Discussion/Conclusion NBD is a rare, but serious manifestation of BD. BD is an important differential diagnosis in a young patient presenting with CVST or bilateral AAU.

Effects of climate and environmental variance on the performance of a novel peatland-based integrated multi-trophic aquaculture (IMTA) system: Implications and opportunities for advancing research and disruptive innovation post COVID-19 era.

Advancing wet peatland 'paludiculture' innovation present enormous potential to sustain carbon-cycles, reduce greenhouse-gas (GHG) gas emissions and to transition communities to low-carbon economies; however, there is limited scientific-evidence to support and enable direct commercial viability of eco-friendly products and services. This timely study reports on a novel, paludiculture-based, integrated-multi-trophic-aquaculture (IMTA) system for sustainable food production in the Irish midlands. This freshwater IMTA process relies on a naturally occurring ecosystem of microalgae, bacteria and duckweed in ponds for managing waste and water quality that is powered by wind turbines; however, as it is recirculating, it does not rely upon end-of-pipe solutions and does not discharge effluent to receiving waters. This constitutes the first report on the effects of extreme weather events on the performance of this IMTA system that produces European perch (Perca fluviatilis), rainbow trout (Oncorhynchus mykiis) during Spring 2020. Sampling coincided with lockdown periods of worker mobility restriction due to COVID-19 pandemic. Observations revealed that the frequency and intensity of storms generated high levels of rainfall that disrupted the algal and bacterial ecosystem in the IMTA leading to the emergence and predominance of toxic cyanobacteria that caused fish mortality. There is a pressing need for international agreement on standardized set of environmental indicators to advance paludiculture innovation that addresses climate-change and sustainability. This study describes important technical parameters for advancing freshwater aquaculture (IMTA), which can be future refined using real-time monitoring-tools at farm level to inform management decision-making based on evaluating environmental indicators and weather data. The relevance of these findings to informing global sustaining and disruptive research and innovation in paludiculture is presented, along with alignment with UN Sustainable Development goals. This study also addresses global challenges and opportunities highlighting a commensurate need for international agreement on resilient indicators encompassing linked ecological, societal, cultural, economic and cultural domains.

National Guidelines on the Provision of Outpatient Parenteral Antimicrobial Therapy (OPAT).

Aim Outpatient parenteral antimicrobial therapy (OPAT) is an option in patients who require parenteral antimicrobial administration and are clinically well enough for hospital discharge. This is an update of the Irish National OPAT guidelines which were last reviewed in 2011. Methods The guideline was devised through a collaborative process with the national OPAT Working Group and a review of the literature. It is intended for clinicians who prescribe any intravenous (IV) antimicrobials outside of the inpatient setting in the Republic of Ireland. Results Patient care while on OPAT should be provided by a designated OPAT service, with clear managerial and clinical governance lines of responsibility. It should be conducted using a team approach with a clinical lead on each site either as an infection specialist, or a general medical physician with infection specialist input and an OPAT nurse. An antimicrobial pharmacist is also desirable. Several factors must be considered when assessing patient's suitability for OPAT including exclusion criteria, infection-specific factors, and patient specific factors such as physical, social and logistic criteria. Conclusion This updated guideline advocates a more individualised OPAT approach, with the recognition that specific antimicrobials and/or specific delivery models may be more appropriate for certain patient groups. Full guidelines are available through www.opat.ie.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

Assessment of two behavioural models (HBM and RANAS) for predicting health behaviours in response to environmental threats: Surface water flooding as a source of groundwater contamination and subsequent waterborne infection in the Republic of Ireland.

Extreme weather events (EWEs) are increasing in frequency, posing a greater risk of adverse human health effects. As such, developing sociological and psychological based interventions is paramount to empowering individuals and communities to actively protect their own health. Accordingly, this study compared the efficacy of two established social-cognitive models, namely the Health Beliefs Model (HBM) and Risks-Attitudes-Norms-Abilities-Self-regulation (RANAS) framework, in predicting health behaviours following EWEs. Surface water flooding was used as the exemplar EWE in the current study, due to the increasing incidence of these events in the Republic of Ireland over the past decade. Levels of prior experience with flooding were considered for analyses and comparative tools included a number of variables predicting health behaviours and intervention potential scores (i.e. measure of impact of targeting each model element). Results suggest that the RANAS model provides a robust foundation for designing interventions for any level of experience with an extreme weather event, however, use of the simpler HBM may be more cost-effective among participants unacquainted with an EWE and in relatively infrequent health threat scenarios. Results provide an evidence base for researchers and policymakers to appropriately engage with populations about such threats and successfully promote spatiotemporally appropriate health behaviours in a changing climate.

One-year parasitological screening of stray dogs and cats in County Dublin, Ireland.

To date, there are no recent studies identifying the prevalence of parasites of human and veterinary importance in dogs and cats in Ireland. The interaction between pets and wildlife species in the environment is an important source of parasite exposure to canids and felines, and one likely to be heightened in the stray animal population. This study aimed to establish the prevalence of endoparasites in unowned dogs and cats in County Dublin, Ireland. Feces from stray dogs (n = 627) and cats (n = 289) entering a rehoming centre were collected immediately after defecation. The main parasitic agents detected were ascarids (15.52 and 30.26%), Cystoisospora (3.27 and 3.69%), Giardia spp. (6.02 and 1.84%) and lungworms (0.64 and 2.08%), in dogs and cats respectively. Animals younger than 3 months of age were more likely to be infected with ascarids (P < 0.001) and Cystoisospora spp. (P = 0.008 and P = 0.014) than older animals. All lungworms were morphologically identified and dogs were infected with Angiostrongylus vasorum (0.48%) and Crenosoma vulpis (0.16%) whereas cats were only infected with Aelurostrongylus abstrusus (2.08%). This represents the first prevalence study of stray animals in Ireland. Data collected will inform the treatment and in addition, the future monitoring and control studies of parasite populations.

Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix.

Citrullination of proteins, a post-translational conversion of arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented in cancer. Here we show that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer (CRC). Using proteomics, we demonstrate that liver metastases exhibit higher levels of citrullination and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance for citrullination in metastatic growth is evident in murine models where inhibition of citrullination substantially reduces liver metastatic burden. Additionally, citrullination of a key matrix component collagen type I promotes greater adhesion and decreased migration of CRC cells along with increased expression of characteristic epithelial markers, suggesting a role for citrullination in promoting mesenchymal-to-epithelial transition and liver metastasis. Overall, our study reveals the potential for PAD4-dependant citrullination to drive the progression of CRC liver metastasis.

Surface water flooding, groundwater contamination, and enteric disease in developed countries: A scoping review of connections and consequences.

Significant volumes of research over the past four decades has sought to elucidate the social, infrastructural, economic, and human health effects of climate change induced surface flooding. To date, epidemiological and public health studies of flooding events have focused on mental health effects, vector-borne diseases, and infectious enteric disease due to floodwater contact (i.e. typically low consumption rates). The inherent nature of groundwater (i.e. out of sight, out of mind) and the widely held belief that aquifers represent a pristine source of drinking water due to natural attenuation may represent the "perfect storm" causing direct consumption of relatively large volumes of surface flood-contaminated groundwater. Accordingly, the current study sought to systematically identify and synthesize all available peer-reviewed literature pertaining to the nexus between surface flooding, groundwater contamination and human gastroenteric outcomes. Just 14 relevant studies were found to have been published during the period 1980-2017, thus highlighting the fact that this potentially significant source of climate-related exposure to environmental infection has remained understudied to date. Studies differed significantly in terms of type and data reporting procedures, making it difficult to discern clear trends and patterns. Approximately 945 confirmed cases of flood-related enteric disease were examined across studies; these concurred with almost 10,000 suspected cases, equating to approximately 20 suspected cases per confirmed case. As such, no regional, national or global estimates are available for the human gastrointestinal health burden of flood-related groundwater contamination. In light of the demonstrable public health significance of the concurrent impacts of groundwater susceptibility and climate change exacerbation, strategies to increase awareness about potential sources of contamination and motivate precautionary behaviour (e.g. drinking water testing and treatment, supply interruptions) are necessary. Mainstreaming climate adaptation concerns into planning policies will also be necessary to reduce human exposure to waterborne sources of enteric infection.

Novel Treatment of Staphylococcus aureus Device-Related Infections Using Fibrinolytic Agents.

Staphylococcal infections involving biofilms represent a significant challenge in the treatment of patients with device-related infections. Staphylococcus aureus biofilms have been shown to be SaeRS regulated and dependent on the coagulase-catalyzed conversion of fibrinogen into fibrin on surfaces coated with human plasma. Here we investigated the treatment of staphylococcal biofilm device-related infections by digesting the fibrin biofilm matrix with and without existing antimicrobials. The fibrinolytic agents plasmin, streptokinase, and nattokinase, and TrypLE, a recombinant trypsin-like protease, were used to digest and treat S. aureus biofilms grown in vitro using in vivo-like static biofilm assays with and without antimicrobials. Cytotoxicity, the potential to induce a cytokine response in whole human blood, and the risk of induction of tolerance to fibrinolytic agents were investigated. A rat model of intravascular catheter infection was established to investigate the efficacy of selected fibrinolytic agents in vivo Under biomimetic conditions, the fibrinolytic agents effectively dispersed established S. aureus biofilms and, in combination with common antistaphylococcal antimicrobials, effectively killed bacterial cells being released from the biofilm. These fibrinolytic agents were not cytotoxic and did not affect the host immune response. The rat model of infection successfully demonstrated the activity of the selected fibrinolytic agents alone and in combination with antimicrobials on established biofilms in vivo TrypLE and nattokinase most successfully removed adherent cells from plasma-coated surfaces and significantly improved the efficacy of existing antimicrobials against S. aureus biofilms in vitro and in vivo These biofilm dispersal agents represent a viable future treatment option for S. aureus device-related infections.

A template for reducing ophthalmology outpatient waiting times: community ophthalmic care.

BACKGROUND: Through an Irish Health Service Executive (HSE) initiative to tackle excessive hospital outpatient waiting times, 996 patients referred to the Ophthalmology Outpatient Department (OPD) of the Mater Misericordiae University Hospital (MMUH), Eccles Street, Dublin 7, Ireland, were outsourced to a community medical eye clinic (CMEC) for consultation with specialist-registered ophthalmologists. AIMS: The study aims to determine if patients referred as routine to the OPD department could be managed in a community setting. METHODS: 996 patients were reviewed in the CMEC, and their data was collected and placed into a spreadsheet for analysis. RESULTS: 61.2% of patients referred to the OPD were fully managed in the community clinic, and 34.9% required ophthalmic surgery in hospital. CONCLUSIONS: By facilitating direct listing of some of the surgical patients to the hospital theatre list, 89.8% of the 996 referrals received treatment without needing to attend the hospital outpatients department.

Apheresis technology correlates with bacterial contamination of platelets and reported septic transfusion reactions.

BACKGROUND: Apheresis technology to collect platelet (PLT) components differs among devices. We evaluated the relationship of the plateletpheresis device with bacterial contamination and reported septic transfusion reactions. STUDY DESIGN AND METHODS: Plateletpheresis was performed using Amicus (Fenwal, a Fresenius Kabi Company) or Trima (Trima Accel, TerumoBCT) from 2010 to 2014. All donations used inlet-line sample diversion and were tested by quality control (QC; Day 1) aerobic culture. Rates of bacterial contamination and septic reactions to PLTs were calculated for both devices. RESULTS: During the 5-year study period, plateletpheresis collections using Amicus and Trima devices totaled 1,486,888 and 671,955 donations, respectively. The rate of confirmed-positive bacterial cultures of apheresis PLT donations was significantly higher with Amicus than with Trima (252 vs. 112 per 106 donations [odds ratio {OR}, 2.3; 95% confidence interval {CI}, 1.8-2.9]). Septic transfusion reactions were caused by 30 apheresis PLT units from 25 contaminated Amicus procedures and three apheresis PLT units from three contaminated Trima procedures. The overall rate of septic reactions was significantly higher with apheresis PLT components collected with Amicus than with Trima (16.8 vs. 4.5 per 106 donations [OR, 3.8; 95% CI, 1.1-12.5]). All apheresis PLT components implicated in septic transfusion reactions had negative QC culture results incubated through Day 5 (i.e., false negatives). CONCLUSION: Apheresis technology affects bacterial contamination of plateletpheresis collections. The device-specific, higher rate of confirmed-positive bacterial culture results also correlated with a significantly higher rate of reported septic transfusion reactions to apheresis PLTs.

A cobalt(ii) complex with unique paraSHIFT responses to anions.

ParaSHIFT agents have shown promise in detecting chemical targets in biological systems by magnetic resonance, but few studies have used transition metal complexes for this purpose. Here we report our investigations into CoMe6trenCl (tren = tris(2-aminoethyl)amine) as a paraSHIFT agent. The paramagnetic region of the 1H NMR spectrum shows characteristic spectral profiles in the presence of fluoride, acetate, lactate and citrate in aqueous solution. These distinctive NMR shifts of each anion are maintained even in mixtures of anions.

Potential use of targeted enzymatic agents in the treatment of Staphylococcus aureus biofilm-related infections.

Staphylococcus aureus is a leading cause of healthcare-associated infections. The ability of S. aureus to attach and subsequently accumulate on the surfaces of implanted medical devices and in host tissues makes infections caused by this pathogen difficult to treat. Current treatments have been shown to have limited effect on surface-associated S. aureus, and may be enhanced by the addition of a dispersal agent. This study assessed the enzymatic agents dispersin B, lysostaphin, alpha amylase, V8 protease and serrapeptase, alone and in combination with vancomycin and rifampicin, against biofilms formed by meticillin-resistant and -susceptible strains of S. aureus. The efficacy of both antibiotics was enhanced when combined with any of the dispersal agents. Lysostaphin and serrapeptase were the most effective dispersal agents against all strains tested. These data indicate that combinations of biofilm dispersal agents and antibiotics may extend the therapeutic options for the treatment of S. aureus biofilm-associated infections.

Gene Discovery for Synthetic Biology: Exploring the Novel Natural Product Biosynthetic Capacity of Eukaryotic Microalgae.

Eukaryotic microalgae are an incredibly diverse group of organisms whose sole unifying feature is their ability to photosynthesize. They are known for producing a range of potent toxins, which can build up during harmful algal blooms causing damage to ecosystems and fisheries. Genome sequencing is lagging behind in these organisms because of their genetic complexity, but transcriptome sequencing is beginning to make up for this deficit. As more sequence data becomes available, it is apparent that eukaryotic microalgae possess a range of complex natural product biosynthesis capabilities. Some of the genes concerned are responsible for the biosynthesis of known toxins, but there are many more for which we do not know the products. Bioinformatic and analytical techniques have been developed for natural product discovery in bacteria and these approaches can be used to extract information about the products synthesized by algae. Recent analyses suggest that eukaryotic microalgae produce many complex natural products that remain to be discovered.

Eradication of Staphylococcus aureus Catheter-Related Biofilm Infections Using ML:8 and Citrox.

Staphylococci are a leading cause of catheter-related infections (CRIs) due to biofilm formation. CRIs are typically managed by either device removal or systemic antibiotics, often in combination with catheter lock solutions (CLSs). CLSs provide high concentrations of the antimicrobial agent at the site of infection. However, the most effective CLSs against staphylococcal biofilm-associated infections have yet to be determined. The purpose of this study was to evaluate the efficacy and suitability of two newly described antimicrobial agents, ML:8 and Citrox, as CLSs against Staphylococcus aureus biofilms. ML:8 (1% [vol/vol]) and Citrox (1% [vol/vol]), containing caprylic acid and flavonoids, respectively, were used to treat S. aureus biofilms grown in vitro using newly described static and flow biofilm assays. Both agents reduced biofilm viability >97% after 24 h of treatment. Using a rat model of CRI, ML:8 was shown to inactivate early-stage S. aureus biofilms in vivo, while Citrox inactivated established, mature in vivo biofilms. Cytotoxicity and hemolytic activity of ML:8 and Citrox were equivalent to those of other commercially available CLSs. Neither ML:8 nor Citrox induced a cytokine response in human whole blood, and exposure of S. aureus to either agent for 90 days was not associated with any increase in resistance. Taken together, these data reveal the therapeutic potential of these agents for the treatment of S. aureus catheter-related biofilm infections.