Mechanisms of the intestinal and urinary microbiome in kidney stone disease.

Kidney stone disease affects ~10% of the global population and the incidence continues to rise owing to the associated global increase in the incidence of medical conditions associated with kidney stone disease including, for example, those comprising the metabolic syndrome. Considering that the intestinal microbiome has a substantial influence on host metabolism, that evidence has suggested that the intestinal microbiome might have a role in maintaining oxalate homeostasis and kidney stone disease is unsurprising. In addition, the discovery that urine is not sterile but, like other sites of the human body, harbours commensal bacterial species that collectively form a urinary microbiome, is an additional factor that might influence the induction of crystal formation and stone growth directly in the kidney. Collectively, the microbiomes of the host could influence kidney stone disease at multiple levels, including intestinal oxalate absorption and direct crystal formation in the kidneys.

Physiological effects and subjective tolerability of prone positioning in COVID-19 and healthy hypoxic challenge.

BACKGROUND: Prone positioning has a beneficial role in coronavirus disease 2019 (COVID-19) patients receiving ventilation but lacks evidence in awake non-ventilated patients, with most studies being retrospective, lacking control populations and information on subjective tolerability. METHODS: We conducted a prospective, single-centre study of prone positioning in awake non-ventilated patients with COVID-19 and non-COVID-19 pneumonia. The primary outcome was change in peripheral oxygenation in prone versus supine position. Secondary outcomes assessed effects on end-tidal CO2, respiratory rate, heart rate and subjective symptoms. We also recruited healthy volunteers to undergo proning during hypoxic challenge. RESULTS: 238 hospitalised patients with pneumonia were screened; 55 were eligible with 25 COVID-19 patients and three non-COVID-19 patients agreeing to undergo proning - the latter insufficient for further analysis. 10 healthy control volunteers underwent hypoxic challenge. Patients with COVID-19 had a median age of 64 years (interquartile range 53-75). Proning led to an increase in oxygen saturation measured by pulse oximetry (SpO2) compared to supine position (difference +1.62%; p=0.003) and occurred within 10 min of proning. There were no effects on end-tidal CO2, respiratory rate or heart rate. There was an increase in subjective discomfort (p=0.003), with no difference in breathlessness. Among healthy controls undergoing hypoxic challenge, proning did not lead to a change in SpO2 or subjective symptom scores. CONCLUSION: Identification of suitable patients with COVID-19 requiring oxygen supplementation from general ward environments for awake proning is challenging. Prone positioning leads to a small increase in SpO2 within 10 min of proning though is associated with increased discomfort.

Association of Social Distancing, Population Density, and Temperature With the Instantaneous Reproduction Number of SARS-CoV-2 in Counties Across the United States.

Importance: Local variation in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the United States has not been well studied. Objective: To examine the association of county-level factors with variation in the SARS-CoV-2 reproduction number over time. Design, Setting, and Participants: This cohort study included 211 counties, representing state capitals and cities with at least 100 000 residents and including 178 892 208 US residents, in 46 states and the District of Columbia between February 25, 2020, and April 23, 2020. Exposures: Social distancing, measured by percentage change in visits to nonessential businesses; population density; and daily wet-bulb temperatures. Main Outcomes and Measures: Instantaneous reproduction number (Rt), or cases generated by each incident case at a given time, estimated from daily case incidence data. Results: The 211 counties contained 178 892 208 of 326 289 971 US residents (54.8%). Median (interquartile range) population density was 1022.7 (471.2-1846.0) people per square mile. The mean (SD) peak reduction in visits to nonessential business between April 6 and April 19, as the country was sheltering in place, was 68.7% (7.9%). Median (interquartile range) daily wet-bulb temperatures were 7.5 (3.8-12.8) °C. Median (interquartile range) case incidence and fatality rates per 100 000 people were approximately 10 times higher for the top decile of densely populated counties (1185.2 [313.2-1891.2] cases; 43.7 [10.4-106.7] deaths) than for counties in the lowest density quartile (121.4 [87.8-175.4] cases; 4.2 [1.9-8.0] deaths). Mean (SD) Rt in the first 2 weeks was 5.7 (2.5) in the top decile compared with 3.1 (1.2) in the lowest quartile. In multivariable analysis, a 50% decrease in visits to nonessential businesses was associated with a 45% decrease in Rt (95% CI, 43%-49%). From a relative Rt at 0 °C of 2.13 (95% CI, 1.89-2.40), relative Rt decreased to a minimum as temperatures warmed to 11 °C, increased between 11 and 20 °C (1.61; 95% CI, 1.42-1.84) and then declined again at temperatures greater than 20 °C. With a 70% reduction in visits to nonessential business, 202 counties (95.7%) were estimated to fall below a threshold Rt of 1.0, including 17 of 21 counties (81.0%) in the top density decile and 52 of 53 counties (98.1%) in the lowest density quartile.2. Conclusions and Relevance: In this cohort study, social distancing, lower population density, and temperate weather were associated with a decreased Rt for SARS-CoV-2 in counties across the United States. These associations could inform selective public policy planning in communities during the coronavirus disease 2019 pandemic.

The mindful nurse leader: Key take-away: Go slow before you go fast.

The first and second articles in this three-part series on mindfulness described the production of the video "In the Moment: Stories of Mindfulness in Nursing" as part of the authors' Robert Wood Johnson Foundation Executive Nurse Fellowship program. In this final installment, we discuss our leadership approaches and lessons learned, both as a team and individuals.

The mindful nurse leader: Advancing executive nurse leadership skills through participation in action learning.

In this second installment of a three-part series on mindfulness, we describe the process of producing video vignettes to illustrate how clinical nurses draw on the power of mindfulness to build their own resiliency while delivering compassionate care.

The mindful nurse leader: Improving processes and outcomes; restoring joy to nursing.

In this first installment of a three-part series on mindfulness, we describe a dynamic project aimed at elevating the importance of mindfulness, compassion, and presence as key competencies for professional nurses across the career span in all healthcare settings.

Women's Longitudinal Patterns of Smoking during the Pre-Conception, Pregnancy and Postnatal Period: Evidence from the UK Infant Feeding Survey.

BACKGROUND: An understanding of women's longitudinal patterns of smoking during the pre-conception, pregnancy and postnatal period and the factors associated with these patterns could help better inform smoking cessation services and interventions. METHODS: Latent class analysis (LCA) was used to empirically identify women's smoking patterns in a sample of 10,768 mothers from the 2010 UK Infant Feeding Survey. Multinomial logistic regression was used to identify characteristics associated with these patterns. RESULTS: LCA identified five distinct smoking patterns during the pre-conception, pregnancy and postnatal period: "non-smokers" (74.1% of women); "pregnancy-inspired quitters" (10.2%); "persistent smokers" (10.1%); "temporary quitters" (4.4%); and postnatal quitters (1.1%). Smoking patterns varied markedly according to socio-demographic variables and parity. After adjusting for these variables, mothers who lived during pregnancy with a partner who smoked were more likely to be temporary quitters (aOR 2.64, 95% CI 1.74-3.99) or persistent smokers (aOR 3.32, 95% CI 2.34-4.72) than pregnancy-inspired quitters. Mothers who lived during pregnancy with someone else other than a partner who smoked were more likely to be persistent smokers (aOR 2.34, 95% CI 1.38-3.97) or postnatal quitters (aOR 2.97, 95% CI 1.07-8.24) than pregnancy-inspired quitters. Mothers given information on how their partner could stop smoking if they lived during pregnancy with a smoking partner were less likely to be persistent smokers (aOR 0.42, 95% CI 0.27-0.65) than pregnancy-inspired quitters. CONCLUSION: Health professionals should ask about smoking at every opportunity, and refer women who self-report as current smokers to an evidence based smoking cessation service.

A guide to multi-centre ethics for surgical research in Australia and New Zealand.

BACKGROUND: This paper describes existing inconsistencies as well as the disparate processes and logistics required when obtaining ethics approval in Australia and New Zealand in order to initiate a multi-centre bi-national surgical trial. METHODS: The endovascular aortic aneurysm repair trial is a large multi-centre trial that aims to obtain pre- and post-operative data from patients in hospitals across Australia and New Zealand. As the trial was research based, ethics applications were submitted to all hospitals where surgeons wished to be involved in the trial. RESULTS: Few ethics committees have embraced attempts to simplify the application process for multi-centre trials. There was limited mutual review between Human Research Ethics Committees necessitating the submission of multiple applications. Though the use of the National Ethics Application Form in ethical review is increasing, some Human Research Ethics Committees do not accept it in its entirety; many require site-specific applications or sections of the Common Application Form modules. CONCLUSIONS: Queensland, New South Wales and New Zealand were the easiest systems to prepare, submit and lodge ethics applications because of their understanding and accommodation of reviewing multi-centred trials. The time, expense and complexity of obtaining ethics approval for multi-centre research projects are impediments to their establishment and reduce the time available for research. Australia is working to implement a system named the Harmonisation of Multi-centre Ethical Review to ease the process of obtaining multi-centre ethics clearance. Our experience suggests there will be some teething problems with implementation and acceptance.

Developing tools to predict outcomes following cardiovascular surgery.

BACKGROUND: Surgical decision-making tools may help surgeons achieve better outcomes by providing more personally relevant information to patients. This paper describes approaches to developing statistical tools capable of estimating the probability of morbidity and mortality after cardiovascular surgery. Our aim is to inform surgeons about the important stages that contribute to the development of decision tools. METHODS: The key elements described include study design (data quality, cohort size, etc.) and statistical methodology for developing and testing decision tools. Mention is made of the delivery of decision tools, simplicity of use, ease of interpretation of results and accessibility. Information specific to cardiac and vascular surgery is included. RESULTS: Development of useful and effective decision tools is dependent on robust and reliable data, unambiguous outcome requirements and considerable statistical expertise. Decision tools must also be extensively tested for validity and reliability, both internally and with external data. CONCLUSION: Understanding the development and assumptions that underlie surgical decision tool development will help cardiovascular surgeons appreciate the value of applying such techniques at a clinical level.

Redistribution of boron in leaves reduces boron toxicity.

High soil boron (B) concentrations lead to the accumulation of B in leaves, causing the development of necrotic regions in leaf tips and margins, gradually extending back along the leaf. Plants vary considerably in their tolerance to B toxicity, and it was recently discovered that one of the tolerance mechanisms involved extrusion of B from the root. Expression of a gene encoding a root B efflux transporter was shown to be much higher in tolerant cultivars. In our current research we have shown that the same gene is also upregulated in leaves. However, unlike in the root, the increased activity of the B efflux transporter in the leaves cannot reduce the tissue B concentration. Instead, we have shown that in tolerant cultivars, these transporters redistribute B from the intracellular phase where it is toxic, into the apoplast which is much less sensitive to B. These results provide an explanation of why different cultivars with the same leaf B concentrations can show markedly different toxicity symptoms. We have also shown that rain can remove a large proportion of leaf B, leading to significant improvements of growth of both leaves and roots.

Influence of leaf tolerance mechanisms and rain on boron toxicity in barley and wheat.

Boron (B) toxicity is common in many areas of the world. Plant tolerance to high B varies widely and has previously been attributed to reduced uptake of B, most commonly as a result of B efflux from roots. In this study, it is shown that the expression of genes encoding B efflux transporters in leaves of wheat (Triticum aestivum) and barley (Hordeum vulgare) is associated with an ability of leaf tissues to withstand higher concentrations of B. In tolerant cultivars, necrosis in leaves occurred at B concentrations more than 2-fold higher than in sensitive cultivars. It is hypothesized that this leaf tolerance is achieved via redistribution of B by efflux transporters from sensitive symplastic compartments into the leaf apoplast. Measurements of B concentrations in leaf protoplasts, and of B released following infiltration of leaves, support this hypothesis. It was also shown that under B-toxic conditions, leaching of B from leaves by rain had a strong positive effect on growth of both roots and shoots. Measurements of rates of guttation and the concentration of B in guttation droplets indicated that the impact of guttation on the alleviation of B toxicity would be small.

The involvement of aquaglyceroporins in transport of boron in barley roots.

Boron (B) enters cells as the uncharged boric acid, a small neutral molecule with sufficient lipid solubility to cross cell membranes without the aid of transport proteins. The extent to which the observed uptake rates for B in plants can be explained by this simple physical process was examined by applying treatments expected to inhibit the membrane transporters most likely to be involved in B transport. These experiments established that at least 50% of B uptake could be facilitated by transporters. The B transport characteristics of two barley aquaglyceroporins, HvPIP1;3 and HvPIP1;4, were investigated using yeast complementation assays. Expression of both genes in yeast resulted in increased B sensitivity. Transport assays in yeast confirmed that HvPIP1;3 and HvPIP1;4 are both capable of transporting B. The physiological role of these HvPIP1 genes in B transport is uncertain since their expression was not responsive to B nutritional status, and they continued to be expressed under toxicity conditions.

Molybdate transport through the plant sulfate transporter SHST1.

Molybdenum is an essential micronutrient required by plants. The mechanism of molybdenum uptake in plants is poorly understood, however, evidence has suggested that sulfate transporters may be involved. The sulfate transporter from Stylosanthes hamata, SHST1, restored growth of the sulfate transport yeast mutant, YSD1, on media containing low amounts of molybdate. Kinetic analysis using 99MoO4(2-) demonstrated that SHST1 enhanced the uptake of molybdate into yeast cells at nM concentrations. Uptake was not inhibited by sulfate, but sulfate transport via SHST1 was reduced with molybdate. These results are the first measurement of molybdate transport by a characterised plant sulfate transport protein.