The pro-resolving mediator, annexin A1 regulates blood pressure, and age-associated changes in cardiovascular function and remodeling.

Aging is associated with chronic, low-level inflammation which may contribute to cardiovascular pathologies such as hypertension and atherosclerosis. This chronic inflammation may be opposed by endogenous mechanisms to limit inflammation, for example, by the actions of annexin A1 (ANXA1), an endogenous glucocorticoid-regulated protein that has anti-inflammatory and pro-resolving activity. We hypothesized the pro-resolving mediator ANXA1 protects against age-induced changes in blood pressure (BP), cardiovascular structure and function, and cardiac senescence. BP was measured monthly in conscious mature (4-month) and middle-aged (12-month) ANXA1-deficient (ANXA1-/- ) and wild-type C57BL/6 mice. Body composition was measured using EchoMRI, and both cardiac and vascular function using ultrasound imaging. Cardiac hypertrophy, fibrosis and senescence, vascular fibrosis, elastin, and calcification were assessed histologically. Gene expression relevant to structural remodeling, inflammation, and cardiomyocyte senescence were also quantified. In C57BL/6 mice, progression from 4 to 12 months of age did not affect the majority of cardiovascular parameters measured, with the exception of mild cardiac hypertrophy, vascular calcium, and collagen deposition. Interestingly, ANXA1-/- mice exhibited higher BP, regardless of age. Additionally, age progression had a marked impact in ANXA1-/- mice, with markedly augmented vascular remodeling, impaired vascular distensibility, and body composition. Consistent with vascular dysfunction, cardiac dysfunction, and hypertrophy were also evident, together with markers of senescence and inflammation. These findings suggest that endogenous ANXA1 plays a critical role in regulating BP, cardiovascular function, and remodeling and delays cardiac senescence. Our findings support the development of novel ANXA1-based therapies to prevent age-related cardiovascular pathologies.

A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms.

The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping. Both cis and trans isomers interact with transcriptional regulators, suggesting that isomerization could serve a role in assembling regulatory complexes in vivo. Toward this end, we show that locking the switch into the trans isomer leads to shortened circadian periods. Furthermore, isomerization is regulated by the cyclophilin family of peptidyl-prolyl isomerases, highlighting the potential for regulation of BMAL1 protein dynamics in period determination.

Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Biodiversity increases and decreases ecosystem stability.

Losses and gains in species diversity affect ecological stability1-7 and the sustainability of ecosystem functions and services8-13. Experiments and models have revealed positive, negative and no effects of diversity on individual components of stability, such as temporal variability, resistance and resilience2,3,6,11,12,14. How these stability components covary remains poorly understood15. Similarly, the effects of diversity on overall ecosystem stability16, which is conceptually akin to ecosystem multifunctionality17,18, remain unknown. Here we studied communities of aquatic ciliates to understand how temporal variability, resistance and overall ecosystem stability responded to diversity (that is, species richness) in a large experiment involving 690 micro-ecosystems sampled 19 times over 40 days, resulting in 12,939 samplings. Species richness increased temporal stability but decreased resistance to warming. Thus, two stability components covaried negatively along the diversity gradient. Previous biodiversity manipulation studies rarely reported such negative covariation despite general predictions of the negative effects of diversity on individual stability components3. Integrating our findings with the ecosystem multifunctionality concept revealed hump- and U-shaped effects of diversity on overall ecosystem stability. That is, biodiversity can increase overall ecosystem stability when biodiversity is low, and decrease it when biodiversity is high, or the opposite with a U-shaped relationship. The effects of diversity on ecosystem multifunctionality would also be hump- or U-shaped if diversity had positive effects on some functions and negative effects on others. Linking the ecosystem multifunctionality concept and ecosystem stability can transform the perceived effects of diversity on ecological stability and may help to translate this science into policy-relevant information.

Subcellular Transcriptomics and Proteomics: A Comparative Methods Review.

The internal environment of cells is molecularly crowded, which requires spatial organization via subcellular compartmentalization. These compartments harbor specific conditions for molecules to perform their biological functions, such as coordination of the cell cycle, cell survival, and growth. This compartmentalization is also not static, with molecules trafficking between these subcellular neighborhoods to carry out their functions. For example, some biomolecules are multifunctional, requiring an environment with differing conditions or interacting partners, and others traffic to export such molecules. Aberrant localization of proteins or RNA species has been linked to many pathological conditions, such as neurological, cancer, and pulmonary diseases. Differential expression studies in transcriptomics and proteomics are relatively common, but the majority have overlooked the importance of subcellular information. In addition, subcellular transcriptomics and proteomics data do not always colocate because of the biochemical processes that occur during and after translation, highlighting the complementary nature of these fields. In this review, we discuss and directly compare the current methods in spatial proteomics and transcriptomics, which include sequencing- and imaging-based strategies, to give the reader an overview of the current tools available. We also discuss current limitations of these strategies as well as future developments in the field of spatial -omics.

Functional diversity can facilitate the collapse of an undesirable ecosystem state.

Biodiversity may increase ecosystem resilience. However, we have limited understanding if this holds true for ecosystems that respond to gradual environmental change with abrupt shifts to an alternative state. We used a mathematical model of anoxic-oxic regime shifts and explored how trait diversity in three groups of bacteria influences resilience. We found that trait diversity did not always increase resilience: greater diversity in two of the groups increased but in one group decreased resilience of their preferred ecosystem state. We also found that simultaneous trait diversity in multiple groups often led to reduced or erased diversity effects. Overall, our results suggest that higher diversity can increase resilience but can also promote collapse when diversity occurs in a functional group that negatively influences the state it occurs in. We propose this mechanism as a potential management approach to facilitate the recovery of a desired ecosystem state.

A high-sucrose diet exacerbates the left ventricular phenotype in a high fat-fed streptozotocin rat model of diabetic cardiomyopathy.

Left ventricular (LV) dysfunction is an early, clinically detectable sign of cardiomyopathy in type 2 diabetes mellitus (T2DM) that precedes the development of symptomatic heart failure. Preclinical models of diabetic cardiomyopathy are essential to develop therapies that may prevent or delay the progression of heart failure. This study examined the molecular, structural, and functional cardiac phenotype of two rat models of T2DM induced by a high-fat diet (HFD) with a moderate- or high-sucrose content (containing 88.9 or 346 g/kg sucrose, respectively), plus administration of low-dose streptozotocin (STZ). At 8 wk of age, male Sprague-Dawley rats commenced a moderate- or high-sucrose HFD. Two weeks later, rats received low-dose STZ (35 mg/kg ip for 2 days) and remained on their respective diets. LV function was assessed by echocardiography 1 wk before end point. At 22 wk of age, blood and tissues were collected postmortem. Relative to chow-fed sham rats, diabetic rats on a moderate- or high-sucrose HFD displayed cardiac reactive oxygen species dysregulation, perivascular fibrosis, and impaired LV diastolic function. The diabetes-induced impact on LV adverse remodeling and diastolic dysfunction was more apparent when a high-sucrose HFD was superimposed on STZ. In conclusion, a high-sucrose HFD in combination with low-dose STZ produced a cardiac phenotype that more closely resembled T2DM-induced cardiomyopathy than STZ diabetic rats subjected to a moderate-sucrose HFD.NEW & NOTEWORTHY Left ventricular dysfunction and adverse remodeling were more pronounced in diabetic rats that received low-dose streptozotocin (STZ) and a high-sucrose high-fat diet (HFD) compared with those on a moderate-sucrose HFD in combination with STZ. Our findings highlight the importance of sucrose content in diet composition, particularly in preclinical studies of diabetic cardiomyopathy, and demonstrate that low-dose STZ combined with a high-sucrose HFD is an appropriate rodent model of cardiomyopathy in type 2 diabetes.

Failures to disagree are essential for environmental science to effectively influence policy development.

While environmental science, and ecology in particular, is working to provide better understanding to base sustainable decisions on, the way scientific understanding is developed can at times be detrimental to this cause. Locked-in debates are often unnecessarily polarised and can compromise any common goals of the opposing camps. The present paper is inspired by a resolved debate from an unrelated field of psychology where Nobel laureate David Kahneman and Garry Klein turned what seemed to be a locked-in debate into a constructive process for their fields. The present paper is also motivated by previous discourses regarding the role of thresholds in natural systems for management and governance, but its scope of analysis targets the scientific process within complex social-ecological systems in general. We identified four features of environmental science that appear to predispose for locked-in debates: (1) The strongly context-dependent behaviour of ecological systems. (2) The dominant role of single hypothesis testing. (3) The high prominence given to theory demonstration compared investigation. (4) The effect of urgent demands to inform and steer policy. This fertile ground is further cultivated by human psychological aspects as well as the structure of funding and publication systems.

Forecasting in the face of ecological complexity: Number and strength of species interactions determine forecast skill in ecological communities.

The potential for forecasting the dynamics of ecological systems is currently unclear, with contrasting opinions regarding its feasibility due to ecological complexity. To investigate forecast skill within and across systems, we monitored a microbial system exposed to either constant or fluctuating temperatures in a 5-month-long laboratory experiment. We tested how forecasting of species abundances depends on the number and strength of interactions and on model size (number of predictors). We also tested how greater system complexity (i.e. the fluctuating temperatures) impacted these relations. We found that the more interactions a species had, the weaker these interactions were and the better its abundance was predicted. Forecast skill increased with model size. Greater system complexity decreased forecast skill for three out of eight species. These insights into how abundance prediction depends on the connectedness of the species within the system and on overall system complexity could improve species forecasting and monitoring.

Biodiversity promotes ecosystem functioning despite environmental change.

Three decades of research have demonstrated that biodiversity can promote the functioning of ecosystems. Yet, it is unclear whether the positive effects of biodiversity on ecosystem functioning will persist under various types of global environmental change drivers. We conducted a meta-analysis of 46 factorial experiments manipulating both species richness and the environment to test how global change drivers (i.e. warming, drought, nutrient addition or CO2 enrichment) modulated the effect of biodiversity on multiple ecosystem functions across three taxonomic groups (microbes, phytoplankton and plants). We found that biodiversity increased ecosystem functioning in both ambient and manipulated environments, but often not to the same degree. In particular, biodiversity effects on ecosystem functioning were larger in stressful environments induced by global change drivers, indicating that high-diversity communities were more resistant to environmental change. Using a subset of studies, we also found that the positive effects of biodiversity were mainly driven by interspecific complementarity and that these effects increased over time in both ambient and manipulated environments. Our findings support biodiversity conservation as a key strategy for sustainable ecosystem management in the face of global environmental change.

Predicting the effects of multiple global change drivers on microbial communities remains challenging.

Microbial communities in many ecosystems are facing a broad range of global change drivers, such as nutrient enrichment, chemical pollution, and temperature change. These drivers can cause changes in the abundance of taxa, the composition of communities, and the properties of ecosystems. While the influence of single drivers is already described in numerous studies, the effect and predictability of multiple drivers changing simultaneously is still poorly understood. In this study, we used 240 highly replicable oxic/anoxic aquatic lab microcosms and four drivers (fertilizer, glyphosate, metal pollution, antibiotics) in all possible combinations at three different temperatures (20, 24, and 28°C) to shed light into consequences of multiple drivers on different levels of organization, ranging from species abundance to community and ecosystem parameters. We found (i) that at all levels of ecological organization, combinations of drivers can change the biological consequence and direction of effect compared to single drivers, (ii) that effects of combinations are further modified by temperature, (iii) that a larger number of drivers occurring simultaneously is often quite closely related to their effect size, and (iv) that there is little evidence that any of these effects are associated with the level of ecological organization of the state variable. These findings suggest that, at least in this experimental ecosystem approximating a stratified aquatic ecosystem, there may be relatively little scope for predicting the effects of combinations of drivers from the effects of individual drivers, or by accounting for the level of ecological organization in question, though there may be some scope for prediction based on the number of drivers that are occurring simultaneous. A priority, though also a considerable challenge, is to extend such research to consider continuous variation in the magnitude of multiple drivers acting together.

Behavioral Intervention Components Associated With Cost-effectiveness: A Comparison of Six Domains.

BACKGROUND: To help implement behavior change interventions (BCIs) it is important to be able to characterize their key components and determine their effectiveness. PURPOSE: This study assessed and compared the components of BCIs in terms of intervention functions identified using the Behaviour Change Wheel Framework (BCW) and in terms of their specific behavior change techniques (BCTs) identified using the BCT TaxonomyV1, across six behavioral domains and the association of these with cost-effectiveness. METHODS: BCIs in 251 studies targeting smoking, diet, exercise, sexual health, alcohol and multiple health behaviors, were specified in terms of their intervention functions and their BCTs, grouped into 16 categories. Associations with cost-effectiveness measured in terms of incremental cost-effectiveness ratio (ICER) upper and lower estimates were determined using regression analysis. RESULTS: The most prevalent functions were increasing knowledge through education (72.1%) and imparting skills through training (74.9%). The most prevalent BCT groupings were shaping knowledge (86.5%), changing behavioral antecedents (53.0%), supporting self-regulation (47.7%), and providing social support (44.6%). Intervention functions associated with better cost-effectiveness were those based on training (ßlow = -15044.3; p = .002), persuasion (ßlow = -19384.9; p = .001; ßupp = -25947.6; p < .001) and restriction (ßupp = -32286.1; p = .019), and with lower cost-effectiveness were those based on environmental restructuring (ß = 15023.9low; p = .033). BCT groupings associated with better cost-effectiveness were goals and planning (ßlow = -8537.3; p = .019 and ßupp = -12416.9; p = .037) and comparison of behavior (ßlow = -13561.9, p = .047 and ßupp = -30650.2; p = .006). Those associated with lower cost-effectiveness were natural consequences (ßlow = 7729.4; p = .033) and reward and threat (ßlow = 20106.7; p = .004). CONCLUSIONS: BCIs that focused on training, persuasion and restriction may be more cost-effective, as may those that encourage goal setting and comparison of behaviors with others.

Warming and top predator loss drive direct and indirect effects on multiple trophic groups within and across ecosystems.

The interspecific interactions within and between adjacent ecosystems strongly depend on the changes in their abiotic and biotic components. However, little is known about how climate change and biodiversity loss in a specific ecosystem can impact the multiple trophic interactions of different biological groups within and across ecosystems. We used natural microecosystems (tank-bromeliads) as a model system to investigate the main and interactive effects of aquatic warming and aquatic top predator loss (i.e. trophic downgrading) on trophic relationships in three integrated food web compartments: (a) aquatic micro-organisms, (b) aquatic macro-organisms and (c) terrestrial predators (i.e. via cross-ecosystem effects). The aquatic top predator loss substantially impacted the three food web compartments. In the aquatic macrofauna compartment, trophic downgrading increased the filter feeder richness and abundance directly and indirectly via an increase in detritivore richness, likely through a facilitative interaction. For the microbiota compartment, aquatic top predator loss had a negative effect on algae richness, probably via decreasing the input of nutrients from predator biological activities. Furthermore, the more active terrestrial predators responded more to aquatic top predator loss, via an increase in some components of aquatic macrofauna, than more stationary terrestrial predators. The aquatic trophic downgrading indirectly altered the richness and abundance of cursorial terrestrial predators, but these effects had different direction according to the aquatic functional group, filter feeder or other detritivores. The web-building predators were indirectly affected by aquatic trophic downgrading due to increased filter feeder richness. Aquatic warming did not affect the aquatic micro- or macro-organisms but did positively affect the abundance of web-building terrestrial predators. These results allow us to raise a predictive framework of how different anthropogenic changes predicted for the next decades, such as aquatic warming and top predator loss, could differentially affect multiple biological groups through interactions within and across ecosystems.

As interações interespecíficas dentro e entre ecossistemas adjacentes dependem fortemente das mudanças de seus componentes abióticos e bióticos. Entretanto, pouco se sabe sobre como mudanças climáticas e a perda de biodiversidade em um ecossistema específico pode impactar as múltiplas interações tróficas de diferentes grupos biológicos dentro e entre ecossistemas. Nós utilizamos micro ecossistemas naturais (bromélias-tanque) como sistema modelo para investigar os efeitos individuais e interativos do aquecimento e da perda de predadores aquáticos (simplificação trófica) nas relações tróficas em três compartimentos integrados da teia alimentar: i) micro-organismos aquáticos, ii) macroorganismos aquáticos e iii) predadores terrestres (via efeito entre ecossistemas). A perda de predadores de topo aquáticos afetou substancialmente os três compartimentos da rede trófica. No compartimento da macrofauna aquática, a simplificação trófica aumentou a riqueza e abundância de filtradores, direta e indiretamente, por meio de um aumento da riqueza de espécies de detritívoros, provavelmente através de uma interação de facilitação. Para o compartimento da microbiota, a perda de predadores de topo aquáticos teve um efeito negativo sobre a riqueza de espécies de algas, provavelmente por meio da diminuição da entrada de nutrientes provenientes das atividades biológicas dos predadores. Além disso, os predadores terrestres mais ativos responderam mais à perda de predadores de topo aquáticos, por meio de um aumento de alguns componentes da macrofauna aquática, do que predadores terrestres mais estacionários. A simplificação trófica aquática alterou indiretamente a riqueza e abundância de predadores cursoriais terrestres, mas esses efeitos tiveram direção diferente de acordo com o grupo funcional aquático, filtradores ou outros detritívoros. Os predadores construtores de teias foram indiretamente afetados pela simplificação trófica aquática devido ao aumento da riqueza de filtradores. O aquecimento aquático não afetou os micro ou macro organismos aquáticos, mas afetou positivamente a abundância de predadores terrestres construtores de teias. Esses resultados nos permitem levantar um quadro preditivo de como diferentes mudanças antropogênicas preditas para as próximas décadas, como o aquecimento e a perda de predadores de topo aquáticos, podem afetar diferencialmente vários grupos biológicos por meio de interações dentro e entre os ecossistemas.

Survival of Clostridioides difficile spores in thermal and chemo-thermal laundering processes and influence of the exosporium on their adherence to cotton bed sheets.

Clostridioides difficile spores were previously demonstrated to survive industrial laundering. Understanding interactions between heat, disinfectants and soiling (e.g. bodily fluids) affecting C. difficile spore survival could inform the optimization of healthcare laundry processes. Reducing spore attachment to linen could also enhance laundering efficacy. This study aimed to compare the sensitivity of C. difficile spores to heat and detergent, with and without soiling and to investigate adherence to cotton. Survival of C. difficile spores exposed to industrial laundering temperatures (71-90°C), reference detergent and industrial detergent was quantified with and without soiling. The adherence to cotton after 0 and 24 h air drying was determined with the exosporium of C. difficile spores partially or fully removed. Clostridioides difficile spores were stable at 71°C for 20 min (≤0·37 log10 reduction) while 90°C was sporicidal (3 log10 reduction); soiling exerted a protective effect. Industrial detergent was more effective at 71°C compared to 25°C (2·81 vs 0·84 log10 reductions), however, specifications for sporicidal activity (>3 log10 reduction) were not met. Clostridioides difficile spores increasingly adhered to cotton over time, with 49% adherence after 24 h. Removal of the exosporium increased adherence by 19-23% compared to untreated spores. Further understanding of the role of the exosporium in attachment to cotton could enhance spore removal and aid decontamination of linen.

Trophic downgrading decreases species asynchrony and community stability regardless of climate warming.

Theory and some evidence suggest that biodiversity promotes stability. However, evidence of how trophic interactions and environmental changes modulate this relationship in multitrophic communities is lacking. Given the current scenario of biodiversity loss and climate changes, where top predators are disproportionately more affected, filling these knowledge gaps is crucial. We simulated climate warming and top predator loss in natural microcosms to investigate their direct and indirect effects on temporal stability of microbial communities and the role of underlying stabilising mechanisms. Community stability was insensitive to warming, but indirectly decreased due to top predator loss via increased mesopredator abundance and consequent reduction of species asynchrony and species stability. The magnitude of destabilising effects differed among trophic levels, being disproportionally higher at lower trophic levels (e.g. producers). Our study unravels major patterns and causal mechanisms by which trophic downgrading destabilises large food webs, regardless of climate warming scenarios.

A semi-supervised Bayesian approach for simultaneous protein sub-cellular localisation assignment and novelty detection.

The cell is compartmentalised into complex micro-environments allowing an array of specialised biological processes to be carried out in synchrony. Determining a protein's sub-cellular localisation to one or more of these compartments can therefore be a first step in determining its function. High-throughput and high-accuracy mass spectrometry-based sub-cellular proteomic methods can now shed light on the localisation of thousands of proteins at once. Machine learning algorithms are then typically employed to make protein-organelle assignments. However, these algorithms are limited by insufficient and incomplete annotation. We propose a semi-supervised Bayesian approach to novelty detection, allowing the discovery of additional, previously unannotated sub-cellular niches. Inference in our model is performed in a Bayesian framework, allowing us to quantify uncertainty in the allocation of proteins to new sub-cellular niches, as well as in the number of newly discovered compartments. We apply our approach across 10 mass spectrometry based spatial proteomic datasets, representing a diverse range of experimental protocols. Application of our approach to hyperLOPIT datasets validates its utility by recovering enrichment with chromatin-associated proteins without annotation and uncovers sub-nuclear compartmentalisation which was not identified in the original analysis. Moreover, using sub-cellular proteomics data from Saccharomyces cerevisiae, we uncover a novel group of proteins trafficking from the ER to the early Golgi apparatus. Overall, we demonstrate the potential for novelty detection to yield biologically relevant niches that are missed by current approaches.

Development of a silver-based dual-function antimicrobial laundry additive and textile coating for the decontamination of healthcare laundry.

AIMS: To repurpose a silver-based antimicrobial textile coating product (Micro-Fresh 1911) as a dual-function antimicrobial laundry additive and textile coating. METHODS AND RESULTS: Survival of Escherichia coli or Staphylococcus aureus type and clinical isolates in a domestic 40°C wash was assessed with and without soiling and biological detergent. Washing with 2% w/v silver additive (wash phase) reduced E. coli and S. aureus by 7·14-8·08 log10 and no cross-contamination was observed. Under dirty conditions, 0·5% silver additive in the rinse phase of a wash with biological detergent reduced E. coli and S. aureus by 7·98-8·40 log10 (0·00-1·42 log10 cross contamination). BS EN ISO 20645:2004 and BS EN ISO 20743:2013 methods were used to assess the antimicrobial activity of polycotton washed with 2% w/v silver additive against S. aureus and E. coli. The treated polycotton was antimicrobial against E. coli and S. aureus type and clinical isolates and remains active after at least one further wash cycle at 40 or 73°C. CONCLUSIONS: The silver additive exhibits antimicrobial activity in a 40°C domestic wash, preventing cross contamination onto clean textiles and depositing an antimicrobial coating onto polycotton. SIGNIFICANCE AND IMPACT OF THE STUDY: The survival of micro-organisms on healthcare uniforms during domestic laundering presents a potential risk of contaminating the home, cross-contamination of other clothing within the wash and transmitting potential pathogens back into healthcare settings via contaminated uniforms. Silver may be useful as an antimicrobial laundry additive to decontaminate healthcare laundry washed at low temperatures in domestic and industrial settings, to therefore reduce the potential risk of transmitting micro-organisms within the domestic and clinical environments.

Microemulsification of essential oils for the development of antimicrobial and mosquito repellent functional coatings for textiles.

AIMS: To develop an essential oil (EO)-loaded textile coating using an environmentally friendly microemulsion technique to achieve both antimicrobial and mosquito repellent functionalities. METHODS AND RESULTS: Minimum inhibitory concentrations and fractional inhibitory concentrations of litsea, lemon and rosemary EOs were determined against Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, Pseudomonas aeruginosa and Trichophyton rubrum. A 1 : 2 mixture of litsea and lemon EOs inhibited all the microorganisms tested and was incorporated into a chitosan-sodium alginate assembly by a microemulsification process. The EO-loaded microemulsions were applied to cotton and polyester fabrics using a soak-pad-dry method. The textile challenge tests demonstrated 7-8 log10 reductions of S. epidermidis, S. aureus and E. coli after 24 h and T. rubrum after 48 h. Aedes aegypti mosquito repellency was also assessed which demonstrated 71·43% repellency compared to 52·94% by neat EO-impregnated cotton. CONCLUSIONS: Textiles treated with the litsea and lemon EO microemulsion showed strong antimicrobial activity against the skin associated microorganisms E. coli, S. aureus, S. epidermidis and T. rubrum and potential mosquito repellent properties. SIGNIFICANCE AND IMPACT OF THE STUDY: EOs could be useful for the development of natural, environmentally friendly functional textiles to protect textiles and users from microbial contamination in addition to possessing other beneficial properties such as mosquito repellency.

Physiological insights into electrodiffusive maintenance of gastric mucus through sensitivity analysis and simulations.

It is generally accepted that the gastric mucosa and adjacent mucus layer are critical in the maintenance of a pH gradient from stomach lumen to stomach wall, protecting the mucosa from the acidic environment of the lumen and preventing auto-digestion of the epithelial layer. No conclusive study has shown precisely which physical, chemical, and regulatory mechanisms are responsible for maintaining this gradient. However, experimental work and modeling efforts have suggested that concentration dependent ion-exchange at the epithelial wall, together with hydrogen ion/mucus network binding, may produce the enormous pH gradients seen in vivo. As of yet, there has been no exhaustive study of how sensitive these modeling results are with respect to variation in model parameters, nor how sensitive such a regulatory mechanism may be to variation in physical/biological parameters. In this work, we perform sensitivity analysis (using Sobol' Indices) on a previously reported model of gastric pH gradient maintenance. We quantify the sensitivity of mucosal wall pH (as a proxy for epithelial health) to variations in biologically relevant parameters and illustrate how variations in these parameters affects the distribution of the measured pH values. In all parameter regimes, we see that the rate of cation/hydrogen exchange at the epithelial wall is the dominant parameter/effect with regards to variation in mucosal pH. By careful sensitivity analysis, we also investigate two different regimes representing high and low hydrogen secretion with different physiological interpretations. By complementing mechanistic modeling and biological hypotheses testing with parametric sensitivity analysis we are able to conclude which biological processes must be tightly regulated in order to robustly maintain the pH values necessary for healthy function of the stomach.

The effect of climbing chalk powder on the infectivity of human coronavirus OC43.

There does not appear to be any studies in the published literature on the stability of SARS-CoV-2 in climbing chalk powder (magnesium carbonate and/or calcium carbonate), which has been hypothesized to pose a potential risk of fomite transmission of coronavirus disease 2019 (COVID-19) within climbing gyms. The aim of this study was to determine the infectivity of a model human coronavirus HCoV-OC43 in the presence of climbing chalk powder on a dry plastic surface. The stability of HCoV-OC43 on a plastic surface dusted with climbing chalk powders (magnesium carbonate, calcium carbonate or a blended chalk) was determined by titration on BHK-21 fibroblast cells. No chalk and no virus controls were included. HCoV-OC43 was stable on the plastic surface for 48 h. The stability of HCoV-OC43 was significantly (P ≤ 0·05) reduced in the presence of magnesium carbonate, calcium carbonate and the chalk blend; the infectivity was reduced by ≥2·29 log10 50% tissue culture infective dose (TCID50 ) immediately upon on contact and by ≥2·46 log10 TCID50 within 1 h of contact. These findings suggest that the infectivity of coronaviruses is reduced by climbing chalk, limiting the risk of potential fomite transmission.