1,8-Naphthalimide based fluorescent sensors for enzymes

Fluorescent probes have long been valuable tools in the study of biological systems. With the ever-expanding range of known enzymatic biomarkers for disease, it has never been more important to develop synthetically facile, sensitive, selective, and robust methods for the detection of these analytes. The 1,8-naphthalimide fluorophore presents an ideal scaffold on which to design a range of fluorescent probes for an unknowable diversity of biomarkers. With tuneable photophysical properties, synthetic versatility, photostability and a large Stokes shift, the 1,8-naphthalimide has, and continues to be, exploited for the detection of a wide range of enzymatic conversions. This review will outline the recent progress towards the design and synthesis of 1,8-naphthalimide fluorophores for the detection of selected enzymatic conversions

Bayesian estimation of prevalence of paratuberculosis in dairy herds enrolled in a voluntary Johne’s Disease Control Programme in Ireland

Bovine paratuberculosis is a disease characterised by chronic granulomatous enteritis which manifests clinically as a protein-losing enteropathy causing diarrhoea, hypoproteinaemia, emaciation and, eventually death. Some evidence exists to suggest a possible zoonotic link and a national voluntary Johne’s Disease Control Programme was initiated by Animal Health Ireland in 2013. The objective of this study was to estimate herd-level true prevalence (HTP) and animal-level true prevalence (ATP) of paratuberculosis in Irish herds enrolled in the national voluntary JD control programme during 2013–14. Two datasets were used in this study. The first dataset had been collected in Ireland during 2005 (5822 animals from 119 herds), and was used to construct model priors. Model priors were updated with a primary (2013–14) dataset which included test records from 99,101 animals in 1039 dairy herds and was generated as part of the national voluntary JD control programme. The posterior estimate of HTP from the final Bayesian model was 0.23–0.34 with a 95% probability. Across all herds, the median ATP was found to be 0.032 (0.009, 0.145). This study represents the first use of Bayesian methodology to estimate the prevalence of paratuberculosis in Irish dairy herds. The HTP estimate was higher than previous Irish estimates but still lower than estimates from other major dairy producing countries

The effect of paratuberculosis on milk yield—A systematic review and meta-analysis

peer-reviewedBovine paratuberculosis is a disease characterized by chronic granulomatous enteritis causing protein-losing enteropathy. Adverse effects on animal productivity are key drivers in the attempt to control paratuberculosis at the farm level. Economic models require an accurate estimation of the production effects associated with paratuberculosis. The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of paratuberculosis on milk production. A total of 20 effect estimates from 15 studies were included in the final meta-analysis. Substantial between-study heterogeneity was observed. Subgroup analysis by case definition and study design was carried out to investigate heterogeneity. The majority of between-study variation was attributed to studies that defined cases on serology. Calculation of a pooled effect estimate was only appropriate for studies that defined cases by organism detection. A reduction in milk yield, corrected for lactation number and herd of origin of 1.87 kg/d, equivalent to 5.9% of yield, was associated with fecal culture or PCR positivity in individual cows

AZASPIRACIDS – Toxicological Evaluation, Test Methods and Identifcation of the Source Organisms (ASTOX II)

Since the Irish monitoring program was set up in 2001 azaspiracids (AZAs) have been detected in shellfish above the regulatory limit every year with the exception of 2004. The south west coast of Ireland is especially prone to the onsets of AZA events. Over this period a number of poisoning incidents associated with this toxin group have occurred, all related to Irish shellfish. In 2003 the Marine Institute was awarded funding for a research project named ASTOX. This project was very successful in producing a range of reference materials (RMs, which are essential for accurate detection and monitoring, and which up to this point were unavailable. The project also examined the toxicity of AZAs, primarily using in vitro cell assays but some in vivo studies were also performed. The overall aims of the ASTOX 2 project were to strengthen knowledge on the causative organism and toxicity of AZAs. The project aims were grouped into three areas: ecology, chemical support and toxicology.Marine Institute Marine Research Sub Programme (NDP 2007 - 2013), co financed under the European Regional Development Fund

Potent antimicrobial effect induced by disruption of chloride homeostasis

Artificial transmembrane ion transporters have proposed applicability to medicinal chemistry, where perturbation of normal cellular homeostasis has already been shown to induce apoptosis in mammalian cells; however, this effect has not been observed in bacteria. In this study, we report the synthesis and structural characterization of a new class of fluorescent anionophores that effectively kill Gram-positive bacteria by disrupting normal Na+ and Cl- concentrations.The so-called "squindoles"take advantage of both NH and CH hydrogen-bonding interactions to bind chloride with high affinity and act as efficient anion transporters, as measured by lipid vesicle transport assays. The most active transporter shows potent inhibitory activity against Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA). Cell-based as-says and label-free quantitative proteomic profiling suggest that the mode of action is directly related to the anion-transport ability, whereby an influx of chloride into bacterial cells significantly affects their proteome and induces several known stress responses

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic : an international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes