Outpatient Management of COVID-19: Rapid Evidence Review.

Common presenting symptoms of coronavirus disease 2019 include fever, dry cough, shortness of breath, and fatigue. However, patients may have a wide range of symptoms representing a spectrum of mild to severe illness. Symptoms in children tend to be milder and may include fever, cough, and feeding difficulty. The incubation period is two to 14 days, although symptoms typically appear within five days of exposure. Multiple testing modalities exist, but infection should be confirmed by polymerase chain reaction testing using a nasopharyngeal swab. There are no evidence- based treatments appropriate for use in the outpatient setting; management is supportive and should include education about isolation. In hospitalized patients, remdesivir should be considered to reduce time to recovery, and low-dose dexamethasone should be considered in patients who require supplemental oxygen. Overall, 85% of patients have mild illness, whereas 14% have severe disease requiring hospitalization, including 5% who require admission to an intensive care unit. Predictors of severe disease include increasing age, comorbidities, lymphopenia, neutrophilia, leukocytosis, low oxygen saturation, and increased levels of C-reactive protein, d-dimer, transaminases, and lactate dehydrogenase.

Effects of 7 days on an ad libitum low-fat vegan diet: the McDougall Program cohort.

BACKGROUND: Epidemiologic evidence, reinforced by clinical and laboratory studies, shows that the rich Western diet is the major underlying cause of death and disability (e.g, from cardiovascular disease and type 2 diabetes) in Western industrialized societies. The objective of this study is to document the effects that eating a low-fat (≤10% of calories), high-carbohydrate (~80% of calories), moderate-sodium, purely plant-based diet ad libitum for 7 days can have on the biomarkers of cardiovascular disease and type 2 diabetes. METHODS: Retrospective analysis of measurements of weight, blood pressure, blood sugar, and blood lipids and estimation of cardiovascular disease risk at baseline and day 7 from 1615 participants in a 10-day residential dietary intervention program from 2002 to 2011. Wilcoxon's signed-rank test was used for testing the significance of changes from baseline. RESULTS: The median (interquartile range, IQR) weight loss was 1.4 (1.8) kg (p < .001). The median (IQR) decrease in total cholesterol was 22 (29) mg/dL (p < .001). Even though most antihypertensive and antihyperglycemic medications were reduced or discontinued at baseline, systolic blood pressure decreased by a median (IQR) of 8 (18) mm Hg (p < .001), diastolic blood pressure by a median (IQR) of 4 (10) mm Hg (p < .001), and blood glucose by a median (IQR) of 3 (11) mg/dL (p < .001). For patients whose risk of a cardiovascular event within 10 years was >7.5% at baseline, the risk dropped to 5.5% (>27%) at day 7 (p < .001). CONCLUSIONS: A low-fat, starch-based, vegan diet eaten ad libitum for 7 days results in significant favorable changes in commonly tested biomarkers that are used to predict future risks for cardiovascular disease and metabolic diseases.

Self-reported benefits and risks of open water swimming to health, wellbeing and the environment: Cross-sectional evidence from a survey of Scottish swimmers.

Engaging with natural environments benefits human health by providing opportunities for social interactions, enhancing mental wellbeing and enabling outdoor spaces for physical exercise. Open water swimming has seen a rapid increase in popularity, partly due to the physical health benefits it can provide but also with the growing interest in (re)connecting with nature for environment-health interactions. Using a national-scale online survey of 717 open water swimmers, the aim of this study was to investigate patterns and trends in the perceived benefits and risks of open water swimming to both public health and the environment; and to understand whether these perceived risks and benefits vary across different typologies of swimmers and open water, or 'blue space', environments. Strong associations were found between the most important self-reported benefit associated with open water swimming and both participant age and the categorisation of their typical swim style. All but one of the age-groups surveyed perceived mental wellbeing benefits to be the most important benefit of open water swimming; whilst those aged over 65 identified physical rather than mental wellbeing benefits to be the most important outcome. Participants who preferred lake swimming reported greater concern regarding possible environmental damage caused by the increasing popularity of open water swimming compared to those engaging in river or sea swimming. However, the majority of participants perceived the risks to the environment from open water swimming to be minimal. Our study adds to the growing evidence that open water swimming is perceived by participants as benefitting their mental and physical wellbeing. Improved understanding of the benefits and risks of engaging with blue spaces used for open water swimming can contribute to co-designed policy development to promote safer, healthier and more sustainable outdoor recreation opportunities associated with this increasingly popular outdoor pursuit.

What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.

BACKGROUND: There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits. METHODS: An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed. DISCUSSION: The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.

Hybrid gold-iron oxide nanoparticles as a multifunctional platform for biomedical application.

BACKGROUND: Iron oxide nanoparticles (IONPs) have increasing applications in biomedicine, however fears over long term stability of polymer coated particles have arisen. Gold coating IONPs results in particles of increased stability and robustness. The unique properties of both the iron oxide (magnetic) and gold (surface plasmon resonance) result in a multimodal platform for use as MRI contrast agents and as a nano-heater. RESULTS: Here we synthesize IONPs of core diameter 30 nm and gold coat using the seeding method with a poly(ethylenimine) intermediate layer. The final particles were coated in poly(ethylene glycol) to ensure biocompatibility and increase retention times in vivo. The particle coating was monitored using FTIR, PCS, UV-vis absorption, TEM, and EDX. The particles appeared to have little cytotoxic effect when incubated with A375M cells. The resultant hybrid nanoparticles (HNPs) possessed a maximal absorbance at 600 nm. After laser irradiation in agar phantom a ΔT of 32°C was achieved after only 90 s exposure (50 µg mL-1). The HNPs appeared to decrease T2 values in line with previously clinically used MRI contrast agent Feridex(®). CONCLUSIONS: The data highlights the potential of these HNPs as dual function MRI contrast agents and nano-heaters for therapies such as cellular hyperthermia or thermo-responsive drug delivery.

Launching a Statewide COVID-19 Primary Care Hotline and Telemedicine Service.

To respond to the COVID-19 pandemic and recover from its aftermath, primary care teams will face waves of overwhelming demand for information and the need to significantly transform care delivery. INNOVATION: Oregon Health & Science University's primary care team envisioned and implemented the COVID-19 Connected Care Center, a statewide telephone "hotline" service. RESULTS: The hotline has taken more than 5825 calls from patients in 33 of Oregon's 36 counties in less than 3 months. In preliminary survey data, 86% of patients said their questions were answered during the call, 90% would recommend this service, and 70% reported a reduction in stress levels about coronavirus. In qualitative interviews, patients reported their questions answered, short wait times, nurses spent time as needed, and appropriate follow-up was arranged. CONCLUSION: Academic health centers may have the capacity to leverage their extensive resources to rapidly launch a multiphased pandemic response that meets peoples' need for information and access to primary care, while minimizing risk of infection and emergency department use and rapidly supporting primary care teams to make the necessary operational changes to do the same in their communities. Such efforts require external funding in a fee-for-service payment model.

Freshwater blue space and population health: An emerging research agenda.

Growing evidence suggests that access and exposure to water bodies or blue spaces can provide a variety of health and well-being benefits. Attempts to quantify these 'blue-health' benefits have largely focused on coastal environments, with freshwater blue spaces receiving far less attention despite over 50% of the global population living within 3 km of a body of freshwater and populations living in landlocked areas having limited coastal access. This critical review identifies opportunities to improve our understanding of the relationship between freshwater blue space and health and well-being and outlines key recommendations to broaden the portfolio of emerging research needs associated with the field of blue-health. Recognising fundamental distinctions in relationships between health outcomes and access and exposure to freshwater versus coastal blue space is critical and further research is required to determine the mechanisms that link exposure to freshwater blue space with tangible health outcomes and to understand how such mechanisms vary across a range of freshwater environments. Furthermore, methodological improvements are necessary as spatial approaches adopted to quantify access and exposure to freshwater blue space often fail to account for the unique physical characteristics of freshwater and come with a variety of limitations. Based on the findings of this review, a suite of research needs are proposed, which can be categorised into three broad themes: (i) establishing a freshwater blue-health methodological framework; (ii) advancing the empirical freshwater blue-health evidence base; and (iii) promoting freshwater blue-health opportunities. When taken together, these research themes offer opportunities to advance current understanding and better integrate freshwater blue space into the wider nature-health research agenda.

Valuing inland blue space: A contingent valuation study of two large freshwater lakes.

Water bodies, or blue spaces, offer a range of health and well-being benefits. Many of these benefits occur in waterside spaces and do not require direct water contact. For example, non-water based physical activity (e.g. walking and running) and reduced stress as a result of viewing water from a distance. However, research dedicated to understanding the economic impact of changes to freshwater ecosystems predominantly focuses on water-based recreation and water quality. As a result, the economic impacts of changes to waterside space are often overlooked. This study used the contingent valuation method to determine public preference for the protection of lakeside quality, in terms of lake views, path quality and lakeside access, at two large freshwater lakes in Scotland (Loch Lomond and Loch Leven). The aim of the study was to estimate willingness to pay among a sample of adults in Scotland (n = 1056) for the protection of lakeside quality. Results indicate that the majority of respondents are willing to pay for the preservation of lakeside quality at each lake. Based upon the most conservative estimates obtained, mean willingness to pay for the protection of lakeside quality was £12.06 per household per year at Loch Lomond and £8.44 at Loch Leven. These findings provide valuable economic data and suggest that changes to waterside space at destination water bodies have nationally important economic impacts. Greater consideration of the economic impact of changes to lakeside space is recommended in order to develop cost-effective and socially optimal water resource management policies at large freshwater lakes.

Synthesis, photolysis studies and in vitro photorelease of caged TRPV1 agonists and antagonists.

The synthesis of a range of caged TRPV1 agonists and antagonists is reported. The photolysis characteristics of these compounds, when irradiated with a 355 nm laser, have been studied and in all cases the desired compound was produced. Photolysis of a caged TRPV1 agonist in cultured trigeminal neurons produced responses that were consistent with the activation of TRPV1 receptors.

Rethinking the influence of hydroelectric development on gene flow in a long-lived fish, the Lake Sturgeon Acipenser fulvescens.

Many hydroelectric dams have been in place for 50 - >100 years, which for most fish species means that enough generations have passed for fragmentation induced divergence to have accumulated. However, for long-lived species such as Lake Sturgeon, Acipenser fulvescens, it should be possible to discriminate between historical population structuring and contemporary gene flow and improve the broader understanding of anthropogenic influence. On the Winnipeg River, Manitoba, two hypotheses were tested: 1) Measureable quantities of former reservoir dwelling Lake Sturgeon now reside downstream of the Slave Falls Generating Station, and 2) genetically differentiated populations of Lake Sturgeon occur upstream and downstream, a result of historical structuring. Genetic methods based on ten microsatellite markers were employed, and simulations were conducted to provide context. With regards to contemporary upstream to downstream contributions, the inclusion of length-at-age data proved informative. Both pairwise relatedness and Bayesian clustering analysis substantiated that fast-growing outliers, apparently entrained after residing in the upstream reservoir for several years, accounted for ~15% of the Lake Sturgeon 525-750 mm fork length captured downstream. With regards to historical structuring, upstream and downstream populations were found to be differentiated (FST = 0.011, and 0.013-0.014 when fast-growing outliers were excluded), and heterozygosity metrics were higher for downstream versus upstream juveniles. Historical asymmetric (downstream) gene flow in the vicinity of the generating station was the most logical explanation for the observed genetic structuring. In this section of the Winnipeg River, construction of a major dam does not appear to have fragmented a previously panmictic Lake Sturgeon population, but alterations to habitat may be influencing upstream to downstream contributions in unexpected ways.

Acoustic force mapping in a hybrid acoustic-optical micromanipulation device supporting high resolution optical imaging.

Many applications in the life-sciences demand non-contact manipulation tools for forceful but nevertheless delicate handling of various types of sample. Moreover, the system should support high-resolution optical imaging. Here we present a hybrid acoustic/optical manipulation system which utilizes a transparent transducer, making it compatible with high-NA imaging in a microfluidic environment. The powerful acoustic trapping within a layered resonator, which is suitable for highly parallel particle handling, is complemented by the flexibility and selectivity of holographic optical tweezers, with the specimens being under high quality optical monitoring at all times. The dual acoustic/optical nature of the system lends itself to optically measure the exact acoustic force map, by means of direct force measurements on an optically trapped particle. For applications with (ultra-)high demand on the precision of the force measurements, the position of the objective used for the high-NA imaging may have significant influence on the acoustic force map in the probe chamber. We have characterized this influence experimentally and the findings were confirmed by model simulations. We show that it is possible to design the chamber and to choose the operating point in such a way as to avoid perturbations due to the objective lens. Moreover, we found that measuring the electrical impedance of the transducer provides an easy indicator for the acoustic resonances.

Wavelength-orthogonal photolysis of neurotransmitters in vitro.

Irradiation of a mixture of 4-methoxyphenacyl-caged (S)-glutamate and 4,5-dimethoxy-2-nitrobenzyl-caged γ-amino butyric acid (GABA) on neurons, at ~260 nm, evokes selective photorelease of (S)-glutamate (Glu) whereas photolysis at 405 nm causes selective photorelease of GABA.

Laser-nucleated acoustic cavitation in focused ultrasound.

Acoustic cavitation can occur in therapeutic applications of high-amplitude focused ultrasound. Studying acoustic cavitation has been challenging, because the onset of nucleation is unpredictable. We hypothesized that acoustic cavitation can be forced to occur at a specific location using a laser to nucleate a microcavity in a pre-established ultrasound field. In this paper we describe a scientific instrument that is dedicated to this outcome, combining a focused ultrasound transducer with a pulsed laser. We present high-speed photographic observations of laser-induced cavitation and laser-nucleated acoustic cavitation, at frame rates of 0.5×10(6) frames per second, from laser pulses of energy above and below the optical breakdown threshold, respectively. Acoustic recordings demonstrated inertial cavitation can be controllably introduced to the ultrasound focus. This technique will contribute to the understanding of cavitation evolution in focused ultrasound including for potential therapeutic applications.

Combining rails and anchors with laser forcing for selective manipulation within 2D droplet arrays.

We demonstrate the combination of a rails and anchors microfluidic system with laser forcing to enable the creation of highly controllable 2D droplet arrays. Water droplets residing in an oil phase can be pinned to anchor holes made in the base of a microfluidic channel, enabling the creation of arrays by the appropriate patterning of such holes. The introduction of laser forcing, via laser induced thermocapillary forces to anchored droplets, enables the selective extraction of particular droplets from an array. We also demonstrate that such anchor arrays can be filled with multiple, in our case two, droplets each and that if such droplets have different chemical contents, the application of a laser at their interface triggers their merging and a chemical reaction to take place. Finally by adding guiding rails within the microfluidic structure we can selectively fill large scale arrays with monodisperse droplets with significant control over their contents. In this way we make a droplet array filled with 96 droplets containing different concentrations of fluorescent microparticles.

Targeted optical injection of gold nanoparticles into single mammalian cells.

We present an all optical technique for the targeted delivery of single 100 nm diameter gold nanoparticles into a specified region of the interior of an individual mammalian cell through a combination of optical tweezing and optical injection. The internalisation of the nanoparticle is verified by confocal laser scanning microscopy and confocal laser scanning reflectance microscopy. This represents the first time that nano sized particles have been tweezed and optically injected into mammalian cells using only light, and provides a novel methodology for internalising nanosphere based biosensors within specific intracellular regions of a mammalian cell.

Caged AG10: new tools for spatially predefined mitochondrial uncoupling.

The study of mitochondria and mitochondrial Ca2+ signalling in localised regions is hampered by the lack of tools that can uncouple the mitochondrial membrane potential (DeltaPsi(m)) in a spatially predefined manner. Although there are a number of existing mitochondrial uncouplers, these compounds are necessarily membrane permeant and therefore exert their actions in a spatially unselective manner. Herein, we report the synthesis of the first caged (photolabile protected) mitochondrial uncouplers, based on the tyrphostin AG10. We have analysed the laser photolysis of these compounds, using (1)H NMR and HPLC, and demonstrate that the major product of caged AG10 photolysis is AG10. It is shown that photolysis within single smooth muscle cells causes a collapse of DeltaPsi(m) consistent with photorelease of AG10. Furthermore, the effect of the photoreleased AG10 is localised to a subcellular region proximal to the site of photolysis, demonstrating for the first time spatially predefined mitochondrial uncoupling.

Enhanced operation of femtosecond lasers and applications in cell transfection.

In this work we present a review and discussion on the enhancement of femtosecond (fs) lasers for use within biophotonics with a particular focus on their use in optical transfection techniques. We describe the broad range of source options now available for the generation of femtosecond pulses before briefly reviewing the application of fs laser in optical transfection studies. We show that major performance enhancements may be obtained by optimising the spatial and temporal performance of the laser source before considering possible future directions in this field. In relation to optical transfection we describe how such laser sources initiate a multiphoton process to permeate the cell membrane in a transient fashion. We look at aspects of this technique including the ability to combine transfection with optical trapping. For future implementation of such transfection we explore the role of new sources and "nondiffracting" light fields.