Inhibition of glyoxylate conversion to oxalate in cultured human cells by the carbonyl-scavenging drug, aminoguanidine

Calcium oxalate is the most frequent cause of kidney stones, and is responsible for the damage to kidneys and other organs observed in inherited disorders of oxalate metabolism. Most oxalate produced in the body is derived from its metabolic precursor, glyoxylate. Thus, any means of scavenging glyoxylate to a non-toxic product, thereby diverting it away from oxalate synthesis, has considerable therapeutic implications. Here we show that aminoguanidine, a compound with a proven safety record and used for many years to prevent long-term complications of diabetes, binds glyoxylate covalently and reduces its conversion to oxalate by human liver- and lymphocyte-derived cell lines by >90%. We propose that scavenging glyoxylate with aminoguanidine or its congeners may provide a means of reducing oxalate production in vivo, and advocate the tissue culture system described here as a convenient means for testing such agents in vitro. A serendipitous finding to emerge from our study was the abiotic and strongly pH-dependent formation of oxalate from ascorbate, which has implications for the contribution of ascorbate to urine oxalate excretion

Steering Resilience in Nursing Practice: Examining the impact of Digital Innovations and Enhanced Emotional Training on Nurse Competencies

The phenomenal development of healthcare practice in the past few decades has reinforced the view that technology could potentially be the third healing triad element. This study, using data from Australia and the United Kingdom, explores resilience in nursing education through the lens of emerging digital technologies and enhanced emotional training. The study employed a mixed-method approach. A pretest-posttest was used to collect data from 54 nursing students during the lectures and tutorials, whilst the qualitative consisted of interviews with 20 health professionals, including nurse teachers and doctors. We found that students’ confidence in mental health nursing practice improved substantially after mental health placement. Besides, the effectiveness of the training offered was not compromised by variances in the demographic groups (e.g. age and gender) amongst the participants. The interview findings revealed that nurses could develop more outstanding modern capabilities with exposure to increasingly used technologies in the healthcare sector; thus, AI and digital technology and health-related engineering equipment can help reduce stress in the profession as machines become critical aid. Technology is, thus, not a threat but a necessary complement that can upskill nurses for contemporary practice

Who’s more vulnerable? A generational investigation of COVID-19 perceptions’ effect on Organisational citizenship Behaviours in the MENA region: job insecurity, burnout and job satisfaction as mediators

Background This paper is an empirical investigation that examines a path model linking COVID-19 perceptions to organisational citizenship behaviour (OCBs) via three mediators: job insecurity, burnout, and job satisfaction. The research examines the path model invariance spanning Generations X, Y, and Z. Three countries in the Middle East and North Africa (MENA) were the focus of the study. Methods The data was collected from a sample of employees in service companies (n = 578). We used a Partial Least Square Structural Equation Modelling (PLS-SEM) to analyse the data. Results Our findings reveal that COVID-19 perceptions positively predict job insecurity, which positively impacts burnout levels. Burnout negatively predicts job satisfaction. The findings established that job satisfaction positively predicts OCBs. The mediation analysis determined that job insecurity, burnout and job satisfaction convey the indirect effects of COVID-19 perceptions onto OCBs. Finally, our hypothesised model is non-equivalent across Generations X, Y and Z. In that regard, our multi-group analysis revealed that the indirect effects of COVID-19 perceptions on OCBs were only valid amongst younger generations, i.e., Generation Y and Generation Z. Specifically, younger generations are substantially more vulnerable to the indirect effects of COVID-19 perceptions on their engagement in OCBs than Generation X whose job satisfaction blocks the effects of COVID-19 perceptions on OCBs. Conclusions The present study extends our knowledge of workplace generational differences in responding to the perceptions of crises or pandemics. It offers evidence that suggests that burnout, job attitudes and organisational outcomes change differently across generations in pandemic times

Pandemic pains to Instagram gains! COVID-19 perceptions effects on behaviours towards fashion brands on Instagram in Sub-Saharan Africa: Tech-native vs non-native generations

This study represents a novel attempt to investigate the cascading effects of COVID-19 perceptions onto behavioural patterns towards fashion brands on Instagram and across two generations tech-native vs tech non-native) in a Sub-Saharan African context. We drew our study on a sample of 338 Instagram users that experienced fashion brands on Instagram in two Sub-Saharan African countries: Uganda and Nigeria. We used partial least square structural equation modelling (PLS-SEM) to test the hypothetical model. We found that COVID-19 perception positively predicted enjoyment and usefulness, leading to more satisfaction with fashion brand accounts on Instagram and hence greater intention to follow and recommend those accounts. Finally, running a multigroup analysis (MGA), we found the effects of COVID-19 perceptions pronounced into both intentions to follow and intention to recommend via the sequence of mediators: enjoyment and satisfaction were only valid amongst the tech-native generational cohort. Our research suggested a new generational categorisation based on technology nativity – offering a new direction of generational studies in digital marketing communications

Cellular Models for River Networks

A cellular model introduced for the evolution of the fluvial landscape is revisited using extensive numerical and scaling analyses. The basic network shapes and their recurrence especially in the aggregation structure are then addressed. The roles of boundary and initial conditions are carefully analyzed as well as the key effect of quenched disorder embedded in random pinning of the landscape surface. It is found that the above features strongly affect the scaling behavior of key morphological quantities. In particular, we conclude that randomly pinned regions (whose structural disorder bears much physical meaning mimicking uneven landscape-forming rainfall events, geological diversity or heterogeneity in surficial properties like vegetation, soil cover or type) play a key role for the robust emergence of aggregation patterns bearing much resemblance to real river networks.Comment: 7 pages, revtex style, 14 figure

Local minimal energy landscapes in river networks

The existence and stability of the universality class associated to local minimal energy landscapes is investigated. Using extensive numerical simulations, we first study the dependence on a parameter $\gamma$ of a partial differential equation which was proposed to describe the evolution of a rugged landscape toward a local minimum of the dissipated energy. We then compare the results with those obtained by an evolution scheme based on a variational principle (the optimal channel networks). It is found that both models yield qualitatively similar river patterns and similar dependence on $\gamma$. The aggregation mechanism is however strongly dependent on the value of $\gamma$. A careful analysis suggests that scaling behaviors may weakly depend both on $\gamma$ and on initial condition, but in all cases it is within observational data predictions. Consequences of our resultsComment: 12 pages, 13 figures, revtex+epsfig style, to appear in Phys. Rev. E (Nov. 2000

Integer Vector Addition Systems with States

This paper studies reachability, coverability and inclusion problems for Integer Vector Addition Systems with States (ZVASS) and extensions and restrictions thereof. A ZVASS comprises a finite-state controller with a finite number of counters ranging over the integers. Although it is folklore that reachability in ZVASS is NP-complete, it turns out that despite their naturalness, from a complexity point of view this class has received little attention in the literature. We fill this gap by providing an in-depth analysis of the computational complexity of the aforementioned decision problems. Most interestingly, it turns out that while the addition of reset operations to ordinary VASS leads to undecidability and Ackermann-hardness of reachability and coverability, respectively, they can be added to ZVASS while retaining NP-completness of both coverability and reachability.Comment: 17 pages, 2 figure

HV 11423: The Coolest Supergiant in the SMC

We call attention to the fact that one of the brightest red supergiants in the SMC has recently changed its spectral type from K0-1 I (December 2004) to M4 I (December 2005) and back to K0-1 I (September 2006). An archival spectrum from the Very Large Telescope reveals that the star was even cooler (M4.5-M5 I) in December 2001. By contrast, the star was observed to be an M0 I in both October 1978 and October 1979. The M4-5 I spectral types is by far the latest type seen for an SMC supergiant, and its temperature in that state places it well beyond the Hayashi limit into a region of the H-R diagram where the star should not be in hydrostatic equilibrium. The star is variable by nearly 2 mag in V, but essentially constant in K. Our modeling of its spectral energy distribution shows that the visual extinction has varied during this time, but that the star has remained essentially constant in bolometric luminosity. We suggest that the star is currently undergoing a period of intense instability, with its effective temperature changing from 4300 K to 3300 K on the time-scale of months. It has one of the highest 12-micron fluxes of any RSG in the SMC, and we suggest that the variability at V is due primarily to changes in effective temperature, and secondly, due to changes in the local extinction due to creation and dissipation of circumstellar dust. We speculate that the star may be nearing the end of its life.Comment: Accepted by the Astrophysical Journa

Exploring a combined biomarker for tuberculosis treatment response: protocol for a prospective observational cohort study.

INTRODUCTION: An improved understanding of factors explaining tuberculosis (TB) treatment response is urgently needed to help clinicians optimise and personalise treatment and assist scientists undertaking novel treatment regimen trials. Promising outcome proxy measures, including sputum bacillary load and host immune response, are widely reported with variable results. However, they have not been studied together in combination with antibiotic exposure. The aim of this observational cohort study is to investigate which antibiotic exposures correlate with sputum bacillary load and which with the host immune response. Subsequently, we will explore if these correlations can be used to inform a candidate combined biomarker predicting cure. METHODS AND ANALYSIS: All patients aged ≥ 18, diagnosed with drug-sensitive pulmonary TB (culture or molecular test), eligible for standard anti-TB treatment, at selected London, UK TB Services, will be invited to participate in this observational cohort study (target sample size=210). Patients will be asked to give blood for host transcriptomics and antibiotic plasma exposure, in addition to standard of care sputum samples for bacillary load. Antibiotic plasma concentrations will be quantified using a validated liquid chromatograph triple quadrupole mass spectrometer (LC-MS/MS) assay and sputum bacillary load by mycobacterial growth incubator tube time to positivity. Expression from a total of 35 prespecified host blood genes will be quantified using NanoString®. Antibiotic exposure, sputum bacillary load and host blood transcriptomic time series data will be analysed using nonlinear mixed-effects models. Correlations between combinations of longitudinal biomarkers and microbiological cure at the end of treatment and remaining relapse free for 1 year thereafter will be analysed using logistic regression and Cox proportional hazard models. ETHICS AND DISSEMINATION: The observational cohort study has been approved by the UK's HRA REC (20/SW/0007). Written informed consent will be obtained. Results will be disseminated via publication, presentation and through engagement with institutes/companies developing novel anti-TB treatment combinations