Antimicrobial resistance in rural rivers: Comparative study of the Coquet (Northumberland) and Eden (Cumbria) River catchments.

Many studies have characterised resistomes in river microbial communities. However, few have compared resistomes in parallel rural catchments that have few point-source inputs of antimicrobial genes (ARGs) and organisms (i.e., AMR) - catchments where one can contrast more nebulous drivers of AMR in rural rivers. Here, we used quantitative microbial profiling (QMP) to compare resistomes and microbiomes in two rural river catchments in Northern England, the Coquet and Eden in Northumberland and Cumbria, respectively, with different hydrological and geographical conditions. The Eden has higher flow rates, higher annual surface runoff, and longer periods of soil saturation, whereas the Coquet is drier and has lower flowrates. QMP analysis showed the Eden contained significantly more abundant microbes associated with soil sources, animal faeces, and wastewater than the Coquet, which had microbiomes like less polluted rivers (Wilcoxon test, p < 0.01). The Eden also had greater ARG abundances and resistome diversity (Kruskal Wallis, p < 0.05), and higher levels of potentially clinically relevant ARGs. The Eden catchment had greater and flashier runoff and more extensive agricultural land use in its middle reach, which explains higher levels of AMR in the river. Hydrological and geographic factors drive AMR in rural rivers, which must be considered in environmental monitoring programmes.

Environmental surveillance of antimicrobial resistance (AMR), perspectives from a national environmental regulator in 2023.

The development, and in some cases increasing prevalence, of resistance to antimicrobials used in clinical and veterinary settings has long been recognised. In recent years, the concept of 'One Health' has added recognition of the role that the environment plays in health protection along with the need for protection of the health of the environment itself. Organisations including the World Health Organization, United Nations Environment Programme, and national governments have identified a need for surveillance of antimicrobial resistance in the environment to sit alongside the surveillance carried out in clinical, veterinary and food sectors. However, having recognised the need for environmental surveillance there are multiple challenges in deciding what this should entail. For example, what pathogens or genes to monitor, who or what we wish to protect and what measures we wish to enable to decrease infection risks. That might include sampling near a source of resistant organisms entering the environment or conversely sampling where the exposure actually occurs. Choices need to be made at both policy and technical levels based on the detailed purposes of surveillance. This paper discusses these issues from the perspective of a national environmental regulator.

The cultural specificity of parent-infant interaction: Perspectives of urban middle-class and rural indigenous families in Costa Rica.

Caregiver-infant interactions in Western middle class often take place in dyadic play settings, engaged in infant-initiated object stimulation, and surrounded by a positive emotional tone, reflecting a distal parenting style. With this study we aim to investigate whether the same conception of caregiver-infant interaction is embodied in the proximal parenting style. For this purpose, we compare the context and pattern of caregiver-infant interactions in two cultural groups in Costa Rica: Urban middle-class families in San José and rural indigenous Bribri families. Naturalistic observations and caregiver interviews revealed significant differences between the groups, with San José families resembling the Western middle-class interaction pattern. Among the Bribris, adult-child play is uncommon so that children interact with adults in primary care settings and with older siblings in play settings. Bribri interactions are further characterized by emotional neutrality. The groups did not differ in terms of body contact. Also, caregivers in both samples took the lead in interactions more often than infants. The results are discussed in the context of an autonomous-relational style as combining psychological autonomy and hierarchical relatedness. We argue that early childhood theories and intervention programs need to abandon the assumption that Western middle-class strategies are universal and recognize locally relevant patterns of caregiver-infant interaction.

Antifungal Exposure and Resistance Development: Defining Minimal Selective Antifungal Concentrations and Testing Methodologies.

This scoping review aims to summarise the current understanding of selection for antifungal resistance (AFR) and to compare and contrast this with selection for antibacterial resistance, which has received more research attention. AFR is an emerging global threat to human health, associated with high mortality rates, absence of effective surveillance systems and with few alternative treatment options available. Clinical AFR is well documented, with additional settings increasingly being recognised to play a role in the evolution and spread of AFR. The environment, for example, harbours diverse fungal communities that are regularly exposed to antifungal micropollutants, potentially increasing AFR selection risk. The direct application of effect concentrations of azole fungicides to agricultural crops and the incomplete removal of pharmaceutical antifungals in wastewater treatment systems are of particular concern. Currently, environmental risk assessment (ERA) guidelines do not require assessment of antifungal agents in terms of their ability to drive AFR development, and there are no established experimental tools to determine antifungal selective concentrations. Without data to interpret the selective risk of antifungals, our ability to effectively inform safe environmental thresholds is severely limited. In this review, potential methods to generate antifungal selective concentration data are proposed, informed by approaches used to determine antibacterial minimal selective concentrations. Such data can be considered in the development of regulatory guidelines that aim to reduce selection for AFR.

Development in context: What we need to know to assess children's attachment relationships.

Attachment studies mostly follow the Western middle-class model in theory and methods. To demonstrate that the assessment of children's caregiving context is an often neglected, but crucial prerequisite for attachment studies, we (a) conducted a literature analysis of attachment research in non-Western contexts and (b) empirically investigated the caregiving arrangements and cultural concepts of attachment figures in three cultural groups in Costa Rica: rural Guanacaste, urban San José, and rural indigenous Bribri. All persons involved in caring for 65 infants (7-20 months) participated in the study, resulting in a total of 179 semistructured interviews. The samples showed differences in caregiving practices, with the urban sample resembling Western middle-class contexts emphasizing the maternal importance; the two rural samples showing extensive caregiving networks; however, differently composed. Moreover, the three samples revealed culturally specific concepts of potential attachment figures. The study emphasizes the need for culturally sensitive conceptual and methodological approaches in attachment research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Evaluation of Norovirus Reduction in Environmentally Contaminated Pacific Oysters During Laboratory Controlled and Commercial Depuration.

Norovirus contamination of oysters is the lead cause of non-bacterial gastroenteritis and a significant food safety concern for the oyster industry. Here, norovirus reduction from Pacific oysters (Crassostrea gigas), contaminated in the marine environment, was studied in laboratory depuration trials and in two commercial settings. Norovirus concentrations were measured in oyster digestive tissue before, during and post-depuration using the ISO 15216-1 quantitative real-time RT-PCR method. Results of the laboratory-based studies demonstrate that statistically significant reductions of up to 74% of the initial norovirus GII concentration was achieved after 3 days at 17-21 °C and after 4 days at 11-15 °C, compared to 44% reduction at 7-9 °C. In many trials norovirus GII concentrations were reduced to levels below 100 genome copies per gram (gcg-1; limit of quantitation; LOQ). Virus reduction was also assessed in commercial depuration systems, routinely used by two Irish oyster producers. Up to 68% reduction was recorded for norovirus GI and up to 90% for norovirus GII reducing the geometric mean virus concentration close to or below the LOQ. In both commercial settings there was a significant difference between the levels of reduction of norovirus GI compared to GII (p < 0.05). Additionally, the ability to reduce the norovirus concentration in oysters to < LOQ differed when contaminated with concentrations below and above 1000 gcg-1. These results indicate that depuration, carried out at elevated (> 11 °C) water temperatures for at least 3 days, can reduce the concentration of norovirus in oysters and therefore consumer exposure providing a practical risk management tool for the shellfish industry.

Neural Correlates of Hypokinetic Dysarthria and Mechanisms of Effective Voice Treatment in Parkinson Disease.

BACKGROUND: Hypokinetic dysarthria is highly prevalent in idiopathic Parkinson disease (PD), and effectiveness of high-intensity voice treatment is well established. However, the neural correlates remain largely unknown. OBJECTIVE: We aimed to specify cerebral pathophysiology of hypokinetic dysarthria and treatment-induced changes using functional magnetic resonance imaging (fMRI). METHODS: We used fMRI to investigate healthy controls (HCs) and patients with idiopathic PD-associated dysarthria before and after treatment according to the Lee Silverman Voice Treatment LOUD (LSVT). During fMRI, participants covertly read sentences with normal (eg, conversation in a quiet room) or high (eg, shouting on a windy beach) intensity. In addition, we tested LSVT effects on intelligibility and different speech features (intensity, pitch, articulation). RESULTS: LSVT effectively improved intelligibility, articulation, and pitch in patients. Covert high-intensity speech compared with covert normal-intensity speech led to increased activation of mainly secondary motor areas and bilateral superior and medial temporal regions. Prior to LSVT, patients showed less activity in several speech-associated areas compared with HCs. As a neural correlate of effective LSVT, increased right-sided superior temporal activity correlated with improved intelligibility. CONCLUSION: This is the first brain imaging study using a covert speech paradigm in PD, which revealed cortical hypoactivation as correlate of hypokinetic dysarthria. Furthermore, cortical correlates of effective LSVT treatment colocalized with the neuronal network, showing increased activation during high- versus normal-intensity speech generation.

A generic approach for the development of short-term predictions of Escherichia coli and biotoxins in shellfish.

Microbiological contamination or elevated marine biotoxin concentrations within shellfish can result in temporary closure of shellfish aquaculture harvesting, leading to financial loss for the aquaculture business and a potential reduction in consumer confidence in shellfish products. We present a method for predicting short-term variations in shellfish concentrations of Escherichia coli and biotoxin (okadaic acid and its derivates dinophysistoxins and pectenotoxins). The approach was evaluated for 2 contrasting shellfish harvesting areas. Through a meta-data analysis and using environmental data (in situ, satellite observations and meteorological nowcasts and forecasts), key environmental drivers were identified and used to develop models to predict E. coli and biotoxin concentrations within shellfish. Models were trained and evaluated using independent datasets, and the best models were identified based on the model exhibiting the lowest root mean square error. The best biotoxin model was able to provide 1 wk forecasts with an accuracy of 86%, a 0% false positive rate and a 0% false discovery rate (n = 78 observations) when used to predict the closure of shellfish beds due to biotoxin. The best E. coli models were used to predict the European hygiene classification of the shellfish beds to an accuracy of 99% (n = 107 observations) and 98% (n = 63 observations) for a bay (St Austell Bay) and an estuary (Turnaware Bar), respectively. This generic approach enables high accuracy short-term farm-specific forecasts, based on readily accessible environmental data and observations.

Design and operation of a low-cost and compact autonomous buoy system for use in coastal aquaculture and water quality monitoring.

The need to ensure future food security and issues of varying estuarine water quality is driving the expansion of aquaculture into near-shore coastal waters. It is prudent to fully evaluate new or proposed aquaculture sites, prior to any substantial financial investment in infrastructure and staffing. Measurements of water temperature, salinity and dissolved oxygen can be used to gain insight into the physical, chemical and biological water quality conditions within a farm site, towards identifying its suitability for farming, both for the stock species of interest and for assessing the potential risk from harmful or toxic algae. The latter can cause closure of shellfish harvesting. Unfortunately, commercial scientific monitoring systems can be cost prohibitive for small organisations and companies to purchase and operate. Here we describe the design, construction and deployment of a low cost (<£ 5000) monitoring buoy suitable for use within a near-shore aquaculture farm or bathing waters. The mooring includes a suite of sensors designed for supporting and understanding variations in near-shore physical, chemical and biological water quality. The system has been designed so that it can be operated and maintained by non-scientific staff, whilst still providing good quality scientific data. Data collected from two deployments totalling 14 months, one in a coastal bay location, another in an estuary, have illustrated the robust design and provided insight into the suitability of these sites for aquaculture and the potential occurrence of a toxin causing algae (Dinophysis spp.). The instruments maintained good accuracy during the deployments when compared to independent in situ measurements (e.g. RMSE 0.13-0.16 °C, bias 0.03-0.08 °C) enabling stratification and biological features to be identified, along with confirming that the waters were suitable for mussel (Mytilus spp.) and lobster (Homarus gammarus) aquaculture, whilst sites showed conditions agreeable for Dinophysis spp.

The Weather and Ménière's Disease: A Longitudinal Analysis in the UK.

HYPOTHESIS: Changes in the weather influence symptom severity in Ménière's disease (MD). BACKGROUND: MD is an unpredictable condition that significantly impacts on quality of life. It is suggested that fluctuations in the weather, especially atmospheric pressure may influence the symptoms of MD. However, to date, limited research has investigated the impact of the weather on MD. METHODS: In a longitudinal study, a mobile phone application collected data from 397 individuals (277 females and 120 males with an average age of 50 yr) from the UK reporting consultant-diagnosed MD. Daily symptoms (vertigo, aural fullness, tinnitus, hearing loss, and attack prevalence) and GPS locations were collected; these data were linked with Met Office weather data (including atmospheric pressure, humidity, temperature, visibility, and wind speed). RESULTS: Symptom severity and attack prevalence were reduced on days when atmospheric pressure was higher. When atmospheric pressure was below 1,013 hectopascals, the risk of an attack was 1.30 (95% confidence interval: 1.10, 1.54); when the humidity was above 90%, the risk of an attack was 1.26 (95% confidence interval 1.06, 1.49). CONCLUSION: This study provides the strongest evidence to date that changes in atmospheric pressure and humidity are associated with symptom exacerbation in MD. Improving our understanding of the role of weather and other environmental triggers in Ménière's may reduce the uncertainty associated with living with this condition, significantly contributing to improved quality of life.

Evaluation of biological endpoints in crop plants after exposure to non-steroidal anti-inflammatory drugs (NSAIDs): implications for phytotoxicological assessment of novel contaminants.

Human pharmaceuticals have been detected in the terrestrial environment at µg to mg kg(-1) concentrations. Repeated application of sewage sludge (biosolids) and increasing reclaimed wastewater use for irrigation could lead to accumulation of these novel contaminants in soil systems. Despite this, potential phytotoxicological effects on higher plants have rarely been evaluated. These studies aimed to test effects upon germination, development, growth and physiology of two crop plants, namely radish (Raphanus sativus Spakler 3) and lettuce (Lactuca sativa All Year Around), after exposure to different, but structurally related non-steroidal anti-inflammatory drugs (NSAIDs) at environmentally relevant concentrations. A range of biological endpoints comprising biomass, length, water content, specific root and shoot length, root to shoot ratio, daily progress of stages of cell elongation and organ emergence (primary root, hypocotyl elongation, cotyledon emergence, cotyledon opening, and no change), as well as photosynthetic measurements were evaluated. Compounds from the fenamic acid class were found to affect R. sativus root endpoints (root length and water content), while ibuprofen affected early root development of L. sativa. In general, phytotoxicological effects on root endpoints demonstrated that impacts upon higher plants are not only compound specific, but also differ between plant species. It was found that the usage of a wide range of biological endpoints (all simple, cost-effective and ecologically relevant) were beneficial in detecting differences in plant responses to NSAID exposure. Due to paucity and discrepancy within the few previously available phytotoxicological studies with pharmaceuticals, it is now essential to allocate time and resources to consider development of suitable chronic toxicity tests, and some suggestions regarding this are presented.

A proteomic evaluation of the effects of the pharmaceuticals diclofenac and gemfibrozil on marine mussels (Mytilus spp.): evidence for chronic sublethal effects on stress-response proteins.

Human pharmaceuticals (e.g. the lipid regulator gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac) are an emerging environmental threat in the aquatic environment. This study aimed to evaluate sublethal effects of these two commonly found pharmaceuticals on the protein profiles of marine mussels (Mytilus spp.). Mytilus spp. was exposed to environmentally relevant and elevated concentrations (1 and 1000 µg/l respectively) of both drugs for 14 days. In addition, mussels were maintained for seven days post treatment to examine the potential of blue mussels to recover from such an exposure. Differential protein expression signatures (PES) in the digestive gland of mussels were obtained using two-dimensional gel electrophoresis after 7, 14, and 21 days of exposure. Twelve spots were significantly increased or decreased by gemfibrozil and/or diclofenac, seven of which were successfully identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. These proteins were involved in energy metabolism, oxidative stress response, protein folding, and immune responses. Changes in the PES over time suggested that mussels were still experiencing oxidative stress for up to seven days post exposure. In addition, a suite of biomarkers comprising glutathione transferase, lipid peroxidation, and DNA damage were studied. An oxidative stress response was confirmed by biomarker responses. To our knowledge, this is the first investigation using proteomics to assess the potential effects of human pharmaceuticals on a non-target species in an environmentally-relevant model. The successful application of this proteomic approach supports its potential use in pollution biomonitoring and highlights its ability to aid in the discovery of new biomarkers.

Seasonal variations of biomarker responses in the marine blue mussel (Mytilus spp.).

Biomarkers, which can detect changes at the biochemical level, have been used for many years as early warning tools in environmental monitoring. In order to distinguish between natural variability and the potential effects of anthropogenic pollution, it is essential to identify background levels and establish the potential influence of abiotic (season, temperature and salinity) and biotic (gametogenesis) factors. In this study, we examined various biomarkers of stress (glutathione S-transferase (GST)), reproduction (vitellin-like proteins) and damage (lipid peroxidation (LPO) and DNA damage (DNA)) in marine mussels (Mytilus spp.) from a known pristine hybrid zone. Levels of all biomarker expression varied between seasons and appeared to be linked to the reproductive cycle. Oxidative stress in winter, with low GST expression and a higher expression of LPO and DNA damage displayed could be explained by low food availability. These data provide vital baseline information for future ecotoxicological and environmental monitoring studies.

The effect of shore location on biomarker expression in wild Mytilus spp. and its comparison with long line cultivated mussels.

Biomarkers are a common tool in the assessment of potential effects of contaminants in aquatic organisms. In order to identify the effects of anthropogenic pollution it is essential to identify background levels and to know the range of natural variability in the biomarker response. In this study, we examined various biomarkers of stress (glutathione S-transferase and metallothionein), damage (lipid peroxidation (LPO) and DNA damage (DNA)) and reproduction (vitellin-like proteins) in marine mussels (Mytilus spp.) from four locations along a vertical transect from high to low shore and compared them with cultivated long line mussels. High shore and cultivated mussels showed significantly higher LPO and DNA damage expression than the low shore mussels indicating a level of oxidative stress resulting from mussel location. Significant effects in physiological endpoints were also found. This study highlights the need to consider the diversity of natural environmental stress factors when using biomarkers in environmental assessment.

Effects of the pharmaceuticals gemfibrozil and diclofenac on the marine mussel (Mytilus spp.) and their comparison with standardized toxicity tests.

Human pharmaceuticals, like the lipid lowering agent gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac are causing environmental concern. In this study, the marine mussel (Mytilus spp.) was exposed by injection to environmentally relevant and elevated (1 µg/L and 1000 µg/L) concentrations of both compounds and biomarker expression was observed. Gemfibrozil exposure induced biomarkers of stress (glutathione S-transferase and metallothionein) at both concentrations 24h and 96 h after exposure, respectively. Biomarkers of damage (lipid peroxidation (LPO) and DNA damage) were significantly affected, as well as the biomarker for reproduction, alkali-labile phosphate assay, indicating the potential oxidative stress and endocrine disrupting effect of gemfibrozil. Diclofenac significantly induced LPO after 96 h indicating tissue damage. Additionally standard toxicity tests using the marine species Vibrio fischeri, Skeletonema costatum and Tisbe battagliai showed differences in sensitivity to both drugs in the mg/L range. Results indicate a suite of tests should be used to give accurate information for regulation.

Intratympanic dexamethasone/hyaluronic acid mix as an adjunct to intravenous steroid and vasoactive treatment in patients with severe idiopathic sudden sensorineural hearing loss.

OBJECTIVE: To evaluate differences in effectiveness (hearing recovery rates) between idiopathic sudden sensorineural hearing loss (ISSNHL) patients treated with intravenous therapy alone and patients treated with a combination of intravenous and intratympanic therapy. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital center. PATIENTS AND INTERVENTIONS: Ninety-four patients with moderate ISSNHL treated with an intravenous steroid and vasoactive regimen (duration of therapy, 9 ± 2.76 d) and 76 patients with severe ISSNHL treated with a combination regimen of intravenous and intratympanic therapy (duration of therapy, 10 ± 2.71 d) were reviewed. In the latter patients' group, a series of 3 intratympanic injections of a dexamethasone/hyaluronic acid mix solution were applied every 2 days. MAIN OUTCOME MEASURE: Pure-tone audiometric thresholds at 0.5, 1, 2, 4, and 8 kHz were compared between groups using the Wilcoxon test. RESULTS: Combination therapy in severe ISSNHL did not show any statistically significant difference in effectiveness to intravenous therapy in moderate ISSNHL (p > 0.05). CONCLUSION: In patients with severe ISSNHL, starting intratympanic steroid therapy as an adjunct early in the course of intravenous steroid and vasoactive therapy improves hearing to a level which is obtained in patients with less severe (moderate) ISSNHL treated with intravenous therapy alone.

Effects of the pharmaceuticals gemfibrozil and diclofenac on biomarker expression in the zebra mussel (Dreissena polymorpha) and their comparison with standardised toxicity tests.

Pharmaceuticals, including the lipid regulator gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac have been identified in waste water treatment plant effluents and receiving waters throughout the western world. The acute and chronic toxicity of these compounds was assessed for three freshwater species (Daphnia magna, Pseudokirchneriella subcapitata, Lemna minor) using standardised toxicity tests with toxicity found in the non-environmentally relevant mid mg L(-1) concentration range. For the acute endpoints (IC(50) and EC(50)) gemfibrozil showed higher toxicity ranging from 29 to 59 mg L(-1) (diclofenac 47-67 mg L(-1)), while diclofenac was more toxic for the chronic D. magna 21 d endpoints ranging from 10 to 56 mg L(-1) (gemfibrozil 32-100 mg L(-1)). These results were compared with the expression of several biomarkers in the zebra mussel (Dreissena polymorpha) 24 and 96 h after exposure by injection to concentrations of 21 and 21,000 µg L(-1) corresponding to nominal concentrations of 1 and 1000 µg L(-1). Exposure to gemfibrozil and diclofenac at both concentrations significantly increased the level of lipid peroxidation, a biomarker of damage. At the elevated nominal concentration of 1000 µg L(-1) the biomarkers of defence glutathione transferase and metallothionein were significantly elevated for gemfibrozil and diclofenac respectively, as was DNA damage after 96 h exposure to gemfibrozil. No evidence of endocrine disruption was observed using the alkali-labile phosphate technique. Results from this suite of biomarkers indicate these compounds can cause significant stress at environmentally relevant concentrations acting primarily through oxidation pathways with significant destabilization of the lysosomal membrane and that biomarker expression is a more sensitive endpoint than standardised toxicity tests.