Endurance Sporting Events.

Endurance sports encompass a broad range of events from marathons and triathlons to ultramarathons, long-distance cycling, skiing, and swimming. As these events have experienced a surge in popularity, we have a greater need to understand the associated medical risks. This article reviews the history of endurance races, reviews the most critical and common causes of cardiovascular, heat, electrolyte, and musculoskeletal injuries/illnesses, and discusses considerations for medical directors/personnel associated with such events.

Photodynamic Inactivation in agriculture: combating fungal phytopathogens resistant to conventional treatment.

Botrytis cinerea is a severe threat in agriculture, as it can infect over 200 different crop species with gray mold affecting food yields and quality. The conventional treatment using fungicides lead to emerging resistance over the past decades. Here, we introduce Photodynamic Inactivation (PDI) as a strategy to combat B. cinerea infections, independent of fungicide resistance. PDI uses photoactive compounds, which upon illumination create reactive oxygen species toxic for killing target organisms. This study focuses on different formulations of sodium-magnesium-chlorophyllin (Chl, food additive E140) as photoactive compound in combination with EDTA disodium salt dihydrate (Na2EDTA) as cell-wall permeabilizer and a surfactant. In an in vitro experiment, three different photosensitizers (PS) with varying Chl and Na2EDTA concentrations were tested against five B. cinerea strains with different resistance mechanisms. We showed that all B. cinerea mycelial spheres of all tested strains were eradicated with concentrations as low as 224 µM Chl and 3.076 mM Na2EDTA (LED illumination with main wavelength of 395 nm, radiant exposure 106 J cm-2). To further test PDI as a Botrytis treatment strategy in agriculture a greenhouse trial was performed on B. cinerea infected bell pepper plants (Capsicum annum L). Two different rates (560 or 1120 g Ha-1) of PS formulation (0.204 M Chl and 1.279 M Na2EDTA) and a combination of PS formulation with 0.05% of the surfactant BRIJ L4 (560 g Ha-1) were applied weekly for 4 weeks by spray application. Foliar lesions, percentage of leaves affected, percentage of leaf area diseased and AUDPC were significantly reduced, while percentage of marketable plants were increased by all treatments compared to a water treated control, however, did not statistically differ from each other. No phytotoxicity was observed in any treatment. These results add to the proposition of employing PDI with the naturally sourced PS Chl in agricultural settings aimed at controlling B. cinerea disease. This approach seems to be effective regardless of the evolving resistance mechanisms observed in response to conventional antifungal treatments.

Preventing multi-resistance: New insights for managing fungal adaptation.

Sustainable crop protection is vital for food security, yet it is under threat due to the adaptation of a diverse and evolving pathogen population. Resistance can be managed by maximising the diversity of selection pressure through dose variation and the spatial and temporal combination of active ingredients. This study explores the interplay between operational drivers for maximising the sustainability of management strategies in relation to the resistance status of fungal populations. We applied an experimental evolution approach to three artificial populations of Zymoseptoria tritici, an economically significant wheat pathogen, each differing in initial resistance status. Our findings reveal that diversified selection pressure curtails the selection of resistance in naïve populations and those with low frequencies of single resistance. Increasing the number of modes of action most effectively delays resistance development, surpassing the increase in the number of fungicides, fungicide choice based on resistance risk, and temporal variation in fungicide exposure. However, this approach favours generalism in the evolved populations. The prior presence of multiple resistant isolates and their subsequent selection in populations override the effects of diversity in management strategies, thereby invalidating any universal ranking. Therefore, the initial resistance composition must be specifically considered in sustainable resistance management to address real-world field situations.

Improving the standardisation, timeliness and efficiency of the occupational therapy admission process in an older adult inpatient service.

Occupational therapists (OTs) are at the forefront of providing recovery-oriented care for older people through timely assessments of patient's engagement in daily living activities among many other interventions. This aids a timely, safe and successful discharge from hospital.This project built on the foundations of previous work while considering the context and requirements of two older adult wards, the rates of admission and staff retention. The specific aim agreed was for 90% of patients admitted to the older adults' inpatient units to be assessed by the occupational therapy (OTY) team within days of admission by December 2022.The OTs worked in collaboration to initiate two tests of change with a total of five PDSA cycles.Our tests of change resulted in an increase of patients engaging in OTY initial assessments within seven days of admission from 47.65% (May to November 2021) to 78% (December 2021 to December 2022).Our team embarked on a quality improvement project to improve standardisation, efficiency and timeliness of the OTY process in an older adult inpatient service by using a pragmatic measure and tests of change evidenced in a previous study. This evidenced the generalisability of the findings of this study. While we were able to improve the timeliness of OTY initial assessments, we concluded that the overall impact on outcomes such as timely discharge was also dependent on other clinical and social factors.

Defect-Promoted Ni-Based Layer Double Hydroxides with Enhanced Deprotonation Capability for Efficient Biomass Electrooxidation.

Ni-based hydroxides are promising electrocatalysts for biomass oxidation reactions, supplanting the oxygen evolution reaction (OER) due to lower overpotentials while producing value-added chemicals. The identification and subsequent engineering of their catalytically active sites are essential to facilitate these anodic reactions. Herein, the proportional relationship between catalysts' deprotonation propensity and Faradic efficiency of 5-hydroxymethylfurfural (5-HMF)-to-2,5 furandicarboxylic acid (FDCA, FEFDCA ) is revealed by thorough density functional theory (DFT) simulations and atomic-scale characterizations, including in situ synchrotron diffraction and spectroscopy methods. The deprotonation capability of ultrathin layer-double hydroxides (UT-LDHs) is regulated by tuning the covalency of metal (M)-oxygen (O) motifs through defect site engineering and selection of M3+ co-chemistry. NiMn UT-LDHs show an ultrahigh FEFDCA of 99% at 1.37 V versus reversible hydrogen electrode (RHE) and retain a high FEFDCA of 92.7% in the OER-operating window at 1.52 V, about 2× that of NiFe UT-LDHs (49.5%) at 1.52 V. Ni-O and Mn-O motifs function as dual active sites for HMF electrooxidation, where the continuous deprotonation of Mn-OH sites plays a dominant role in achieving high selectivity while suppressing OER at high potentials. The results showcase a universal concept of modulating competing anodic reactions in aqueous biomass electrolysis by electronically engineering the deprotonation behavior of metal hydroxides, anticipated to be translatable across various biomass substrates.

Antifungal alternation can be beneficial for durability but at the cost of generalist resistance.

The evolution of resistance to pesticides is a major burden in agriculture. Resistance management involves maximizing selection pressure heterogeneity, particularly by combining active ingredients with different modes of action. We tested the hypothesis that alternation may delay the build-up of resistance not only by spreading selection pressure over longer periods, but also by decreasing the rate of evolution of resistance to alternated fungicides, by applying an experimental evolution approach to the economically important crop pathogen Zymoseptoria tritici. Our results show that alternation is either neutral or slows the overall resistance evolution rate, relative to continuous fungicide use, but results in higher levels of generalism in evolved lines. We demonstrate that the nature of the fungicides, and therefore their relative intrinsic risk of resistance may underly this trade-off, more so than the number of fungicides and the rhythm of alternation. This trade-off is also dynamic over the course of resistance evolution. These findings open up new possibilities for tailoring resistance management effectively while optimizing interplay between alternation components.

Intergenerational programming during the pandemic: Transformation during (constantly) changing times.

Intergenerational programs have long been employed to reduce ageism and optimize youth and older adult development. Most involve in-person meetings, which COVID-19 arrested. ​​Needs for safety and social contact were amplified during COVID-19, leading to modified programming that engaged generations remotely rather than eliminating it. Our collective case study incorporates four intergenerational programs in five US states prior to and during COVID-19. Each aims to reduce ageism, incorporating nutrition education, technology skills, or photography programming. Authors present case goals, participants, implementation methods, including responses to COVID-19, outcomes, and lessons learned. Technology afforded opportunities for intergenerational connections; non-technological methods also were employed. Across cases, programmatic foci were maintained through adaptive programming. Community partners' awareness of immediate needs facilitated responsive programming with universities, who leveraged unique resources. While new methods and partnerships will continue post-pandemic, authors concurred that virtual contact cannot fully substitute for in-person relationship-building. Remote programming maintained ties between groups ready to resume shared in-person programming as soon as possible; they now have tested means for responding to routine or novel cancellations of in-person programming. Able to implement in-person and remote intergenerational programming, communities can fight ageism and pursue diverse goals regardless of health, transportation, weather, or other restrictions.

Outcomes of non-cystic fibrosis-related bronchiectasis post-lung transplantation.

BACKGROUND: Lung transplantation is a recognised treatment for end-stage lung disease due to bronchiectasis. Non-cystic fibrosis (CF) bronchiectasis and CF are often combined into one cohort; however, outcomes for non-CF bronchiectasis patients vary between centres, and in comparison with those for CF. AIMS: To compare lung transplantation mortality and morbidity of bronchiectasis (non-CF) patients with those with CF and other indications. METHODS: Retrospective analysis of patients undergoing lung transplantation between 1 January 2008 and 31 December 2013. Time to and cause of lung allograft loss was censored on 1 April 2018. A case-note review was conducted on a subgroup of 78 patients, to analyse hospital admissions as a marker of morbidity. RESULTS: A total of 341 patients underwent lung transplantation; 22 (6%) had bronchiectasis compared with 69 (20%) with CF. The 5-year survival for the bronchiectasis group was 32%, compared with CF (69%), obstructive lung disease (OLD) (64%), pulmonary hypertension (62%) and ILD (55%) (P = 0.008). Lung allograft loss due to chronic lung allograft dysfunction with predominant infection was significantly higher in the bronchiectasis group at 2 years. The rate of acute admissions was 2.24 higher in the bronchiectasis group when compared with OLD (P = 0.01). Patients with bronchiectasis spent 45.81 days in hospital per person year after transplantation compared with 18.21 days for CF. CONCLUSIONS: Bronchiectasis patients in the present study had a lower 5-year survival and poorer outcomes in comparison with other indications including CF. Bronchiectasis should be considered a separate entity to CF in survival analysis.

Directed evolution predicts cytochrome b G37V target site modification as probable adaptive mechanism towards the QiI fungicide fenpicoxamid in Zymoseptoria tritici.

Acquired resistance is a threat to antifungal efficacy in medicine and agriculture. The diversity of possible resistance mechanisms and highly adaptive traits of pathogens make it difficult to predict evolutionary outcomes of treatments. We used directed evolution as an approach to assess the resistance risk to the new fungicide fenpicoxamid in the wheat pathogenic fungus Zymoseptoria tritici. Fenpicoxamid inhibits complex III of the respiratory chain at the ubiquinone reduction site (Qi site) of the mitochondrially encoded cytochrome b, a different site than the widely used strobilurins which inhibit the same complex at the ubiquinol oxidation site (Qo site). We identified the G37V change within the cytochrome b Qi site as the most likely resistance mechanism to be selected in Z. tritici. This change triggered high fenpicoxamid resistance and halved the enzymatic activity of cytochrome b, despite no significant penalty for in vitro growth. We identified negative cross-resistance between isolates harbouring G37V or G143A, a Qo site change previously selected by strobilurins. Double mutants were less resistant to both QiIs and quinone outside inhibitors compared to single mutants. This work is a proof of concept that experimental evolution can be used to predict adaptation to fungicides and provides new perspectives for the management of QiIs.

Are Efficient-Dose Mixtures a Solution to Reduce Fungicide Load and Delay Evolution of Resistance? An Experimental Evolutionary Approach.

Pesticide resistance poses a critical threat to agriculture, human health and biodiversity. Mixtures of fungicides are recommended and widely used in resistance management strategies. However, the components of the efficiency of such mixtures remain unclear. We performed an experimental evolutionary study on the fungal pathogen Z. tritici to determine how mixtures managed resistance. We compared the effect of the continuous use of single active ingredients to that of mixtures, at the minimal dose providing full control of the disease, which we refer to as the "efficient" dose. We found that the performance of efficient-dose mixtures against an initially susceptible population depended strongly on the components of the mixture. Such mixtures were either as durable as the best mixture component used alone, or worse than all components used alone. Moreover, efficient dose mixture regimes probably select for generalist resistance profiles as a result of the combination of selection pressures exerted by the various components and their lower doses. Our results indicate that mixtures should not be considered a universal strategy. Experimental evaluations of specificities for the pathogens targeted, their interactions with fungicides and the interactions between fungicides are crucial for the design of sustainable resistance management strategies.

Microcapillary Reactors via Coaxial Electrospinning: Fabrication of Small Poly(Acrylic Acid) Gel Beads and Thin Threads of Biological Cell Dimensions.

Poly(acrylic acid) (PAA) bulk gels and threads, typically derived via free-radical polymerization, are of interest as anionic polyelectrolyte mimics of cellular cytosol and as models for early protocells. The thread dimensions have been limited by the diameters of readily-available glass or plastic capillaries, and threads with diameters of less than 50 µm have been difficult to achieve. Here, we report a useful approach for achieving crosslinked, partially neutralized PAA, namely poly(acrylate), gel threads with diameters of a few microns when dry. This technique utilizes coaxial electrospinning to effectively produce capillaries (shells) of polystyrene loaded with a gel-forming precursor mixture composed of 3 M acrylic acid, methylene-bisacrylamide, potassium persulfate and 2.2 M NaOH in the core, followed by thermally-induced polymerization and then the removal of the polystyrene shell. Relatively long (up to 5 mm), continuous PAA threads with thicknesses of 5-15 µm are readily obtained, along with a multitude of PAA gel particles, which result from the occasional break-up of the fluid core prior to gel formation during the electrospinning process. The threads and beads are of the sizes of interest to model ancient protocells, certain functional aspects of excitable cells, such as myocytes and neurons, and various membraneless organelles.

Population Genomics Reveals Molecular Determinants of Specialization to Tomato in the Polyphagous Fungal Pathogen Botrytis cinerea in France.

Many fungal plant pathogens encompass multiple populations specialized on different plant species. Understanding the factors underlying pathogen adaptation to their hosts is a major challenge of evolutionary microbiology, and it should help to prevent the emergence of new specialized pathogens on novel hosts. Previous studies have shown that French populations of the gray mold pathogen Botrytis cinerea parasitizing tomato and grapevine are differentiated from each other, and have higher aggressiveness on their host of origin than on other hosts, indicating some degree of host specialization in this polyphagous pathogen. Here, we aimed at identifying the genomic features underlying the specialization of B. cinerea populations to tomato and grapevine. Based on whole genome sequences of 32 isolates, we confirmed the subdivision of B. cinerea pathogens into two genetic clusters on grapevine and another, single cluster on tomato. Levels of genetic variation in the different clusters were similar, suggesting that the tomato-specific cluster has not recently emerged following a bottleneck. Using genome scans for selective sweeps and divergent selection, tests of positive selection based on polymorphism and divergence at synonymous and nonsynonymous sites, and analyses of presence and absence variation, we identified several candidate genes that represent possible determinants of host specialization in the tomato-associated population. This work deepens our understanding of the genomic changes underlying the specialization of fungal pathogen populations.

Depression scores improve with continuous positive airway pressure in specialized sleep clinics: real-world data.

STUDY OBJECTIVES: To assess changes in Hospital Anxiety and Depression Scale (HADS) scores after continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea. METHODS: Consecutive patients attending the Alfred Health sleep clinic, diagnosed with obstructive sleep apnea, and prescribed CPAP were recruited. The primary outcome was a change in the HADS depression (HADS-D) and anxiety (HADS-A) subscales from the time of diagnosis to follow-up. Secondary analysis compared high (> 4 hours) and low (< 4 hours) CPAP adherence groups and change in depression cases, defined by HADS-D ≥ 8, and anxiety cases, defined by HADS-A ≥ 11. RESULTS: We included 108 participants in the final analysis. Adherence groups were well matched in baseline mood, sleepiness, and apnea variables. Overall age (mean ± standard deviation) was 56.1 ± 12.8 years, and there was a median (interquartile ratio) apnea-hypopnea-index of 42.7 (27.5-58.1) or median (interquartile ratio) oxygen-desaturation-index of 43.0 (26.0-74.0). The median duration of CPAP therapy was 1.3 years. The HADS-D decreased after CPAP by -1.4 (adjusted 95% confidence interval, -2.1 to -0.6; P = .001). Patients with high-CPAP adherence (n = 84) had a tendency towards a greater reduction in HADS-D (-1.5) compared with those with low-CPAP adherence (n = 24; -0.3; adjusted P = .19). Depression cases (HADS-D ≥ 8) decreased by 13.1% in the high-CPAP-adherence group (P = .03) and increased by 4.1% in the low-CPAP-adherence group (P = .71). The HADS-A decreased after CPAP by -1.8 (adjusted 95% confidence interval, -1.8 to -0.4; P = .004). There was no significant difference between adherence groups or anxiety cases (HADS-A > 11). CONCLUSIONS: Specialized obstructive sleep apnea treatment with CPAP reduces depression scores, with a trend toward greater reduction in those with high CPAP adherence.

Effect of Sodium Supplements and Climate on Dysnatremia During Ultramarathon Running.

OBJECTIVE: Analyze the effect of sodium supplementation, hydration, and climate on dysnatremia in ultramarathon runners. DESIGN: Prospective observational study. SETTING: The 2017 80 km (50 mile) stage of the 250 km (150 mile) 6-stage RacingThePlanet ultramarathon in 2017 Chilean, Patagonian, and 2018 Namibian, Mongolian, and Chilean deserts. PARTICIPANTS: All race entrants who could understand English were invited to participate, with 266 runners enrolled, mean age of 43 years (± 9), 61 (36%) females, average weight 74 kg (± 12.5), and average race time 14.5 (± 4.1) hours. Post-race sodium collected on 174 (74%) and 164 (62%) participants with both the blood sample and post-race questionnaire. INTERVENTION: Weight change and finish line serum sodium levels were gathered. MAIN OUTCOME MEASURES: Incidence of exercise-associated hyponatremia (EAH; <135 mmol·L-1) and hypernatremia (>145 mmol·L-1) by sodium ingestion and climate. RESULTS: Eleven (6.3%) runners developed EAH, and 30 (17.2%) developed hypernatremia. Those with EAH were 14 kg heavier at baseline, had significantly less training distances, and averaged 5 to 6 hours longer to cover 50 miles (80 km) than the other participants. Neither rate nor total ingested supplemental sodium was correlated with dysnatremia, without significant differences in drinking behaviors or type of supplement compared with normonatremic runners. Hypernatremic runners were more often dehydrated [8 (28%), -4.7 kg (± 9.8)] than EAH [4 (14%), -1.1 kg (± 3.8)] (P < 0.01), and EAH runners were more frequently overhydrated (6, 67%) than hypernatremia (1, 11%) (P < 0.01). In the 98 (56%) runners from hot races, there was EAH OR = 3.5 [95% confidence interval (CI), 0.9-25.9] and hypernatremia OR = 8.8 (95% CI, 2.9-39.5) compared with cold races. CONCLUSIONS: This was the first study to show that hot race climates are an independent risk factor for EAH and hypernatremia. Sodium supplementation did not prevent EAH nor cause hypernatremia. Longer training distances, lower body mass, and avoidance of overhydration were shown to be the most important factors to prevent EAH and avoidance of dehydration to prevent hypernatremia.

Large-scale study validates that regional fungicide applications are major determinants of resistance evolution in the wheat pathogen Zymoseptoria tritici in France.

In modern cropping systems, the near-universal use of plant protection products selects for resistance in pest populations. The emergence and evolution of this adaptive trait threaten treatment efficacy. We identified determinants of fungicide resistance evolution and quantified their effects at a large spatiotemporal scale. We focused on Zymoseptoria tritici, which causes leaf blotch in wheat. Phenotypes of qualitative or quantitative resistance to various fungicides were monitored annually, from 2004 to 2017, at about 70 sites throughout 22 regions of France (territorial units of 25 000 km2 on average). We modelled changes in resistance frequency with regional anti-Septoria fungicide use, yield losses due to the disease and the regional area under organic wheat. The major driver of resistance dynamics was fungicide use at the regional scale. We estimated its effect on the increase in resistance and relative apparent fitness of each resistance phenotype. The predictions of the model replicated the spatiotemporal patterns of resistance observed in field populations (R2 from 0.56 to 0.82). The evolution of fungicide resistance is mainly determined at the regional scale. This study therefore showed that collective management at the regional scale could effectively complete local actions.

Investigating the mechanism of impact and differential effect of the Quality Premium scheme on antibiotic prescribing in England: a longitudinal study.

BACKGROUND: In 2017, approximately 73% of antibiotics in England were prescribed from primary care practices. It has been estimated that 9%-23% of antibiotic prescriptions between 2013 and 2015 were inappropriate. Reducing antibiotic prescribing in primary care was included as one of the national priorities in a financial incentive scheme in 2015-2016. AIM: To investigate whether the effects of the Quality Premium (QP), which provided performance-related financial incentives to clinical commissioning groups (CCGs), could be explained by practice characteristics that contribute to variations in antibiotic prescribing. DESIGN & SETTING: Longitudinal monthly prescribing data were analysed for 6251 primary care practices in England from April 2014 to March 2016. METHOD: Linear generalised estimating equations models were fitted, examining the effect of the 2015-2016 QP on the number of antibiotic items per specific therapeutic group age-sex related prescribing unit (STAR-PU) prescribed, adjusting for seasonality and months since implementation. Consistency of effects after further adjustment for variations in practice characteristics were also examined, including practice workforce, comorbidities prevalence, prescribing rates of non-antibiotic drugs, and deprivation. RESULTS: Antibiotics prescribed in primary care practices in England reduced by -0.172 items per STAR-PU (95% confidence interval [CI] = -0.180 to -0.171) after 2015-2016 QP implementation, with slight increases in the months following April 2015 (+0.014 items per STAR-PU; 95% CI = +0.013 to +0.014). Adjusting the model for practice characteristics, the immediate and month-on-month effects following implementation remained consistent, with slight attenuation in immediate reduction from -0.172 to -0.166 items per STAR-PU. In subgroup analysis, the QP effect was significantly greater among the top 20% prescribing practices (interaction p<0.001). Practices with low workforce and those with higher diabetes prevalence had greater reductions in prescribing following 2015-2016 QP compared with other practices (interaction p<0.001). CONCLUSION: In high-prescribing practices, those with low workforce and high diabetes prevalence had more reduction following the QP compared with other practices, highlighting the need for targeted support of these practices and appropriate resourcing of primary care.

The polyphagous plant pathogenic fungus Botrytis cinerea encompasses host-specialized and generalist populations.

The host plant is often the main variable explaining population structure in fungal plant pathogens, because specialization contributes to reduce gene flow between populations associated with different hosts. Previous population genetic analysis revealed that French populations of the grey mould pathogen Botrytis cinerea were structured by hosts tomato and grapevine, suggesting host specialization in this highly polyphagous pathogen. However, these findings raised questions about the magnitude of this specialization and the possibility of specialization to other hosts. Here we report specialization of B. cinerea populations to tomato and grapevine hosts but not to other tested plants. Population genetic analysis revealed two pathogen clusters associated with tomato and grapevine, while the other clusters co-occurred on hydrangea, strawberry and bramble. Measurements of quantitative pathogenicity were consistent with host specialization of populations found on tomato, and to a lesser extent, populations found on grapevine. Pathogen populations from hydrangea and strawberry appeared to be generalist, while populations from bramble may be weakly specialized. Our results suggest that the polyphagous B. cinerea is more accurately described as a collection of generalist and specialist individuals in populations. This work opens new perspectives for grey mould management, while suggesting spatial optimization of crop organization within agricultural landscapes.

Enhanced elasticity in poly(acrylic acid) gels via synthesis in the presence of high concentrations of select salts.

Poly(acrylic acid) (PAA) gels synthesized via free-radical polymerization of acrylic acid, N,N'-methylenebisacrylamide and high molarities of salts in water exhibit properties markedly different from PAA gels synthesized without salt, even when the latter are incubated in high-molarity salt solutions after gelation. Particularly noteworthy is unusual mechanical behaviour that includes substantially increased elongation, increased modulus, and rapid recovery after strain. The greatest enhancement in viscoelastic behaviour is evident in 2 M LiCl and ZnCl2 samples, with LiCl samples having a modulus of 39 kPa and reaching an extension ratio of 10 and a fracture stress of 135 kPa, and ZnCl2 samples having a modulus of 43 kPa and reaching an extension ratio of 8.5 and a fracture stress of 175 kPa. This enhanced elasticity is thought to be brought about by a combination of coiled but only weakly-entangled PAA chains with phase-separated regions of salt acting as a plasticizer and modulating intermolecular interactions among AA units.