The contribution of fatigue and sleepiness to depression in patients attending the sleep laboratory for evaluation of obstructive sleep apnea

Purpose: A high prevalence of depressive symptomatology has been reported amongst sufferers of obstructive sleep apnea (OSA), but it remains unclear as to whether this is due to their OSA or other factors associated with the disorder. The current study aimed to assess the incidence and aetiology of depression in a community sample of individuals presenting to the sleep laboratory for diagnostic assessment of OSA. Methods: Forty-five consecutive individuals who presented to the sleep laboratory were recruited; of those, 34 were diagnosed with OSA, and 11 were primary snorers with no clinical or laboratory features of OSA. Nineteen control subjects were also recruited. Patients and controls completed the Beck Depression Inventory, the Profile of Mood States (POMS), and the Epworth Sleepiness Scale to assess their mood and sleepiness, prior to their polysomnography. Results: All patients reported significantly more depressive symptoms compared with healthy controls, regardless of their degree of OSA. There were no significant differences between OSA patients and primary snorers on any of the mood and self-rated sleepiness measures. Depression scores were not significantly associated with any of the nocturnal variables. Regression analysis revealed that the POMS fatigue subscale explained the majority of the variance in subjects' depression scores. Conclusions: Fatigue was the primary predictor of the level of depressive symptoms in patients who attended the sleep laboratory, regardless of the level of severity of sleep disordered breathing. When considering treatment options, practitioners should be aware of the concomitant occurrence of depressive symptoms and fatigue in patients presenting with sleep complaints, which may not be due to a sleep disorder

CydDC-mediated reductant export in Escherichia coli controls the transcriptional wiring of energy metabolism and combats nitrosative stress

The glutathione/cysteine exporter CydDC maintains redox balance in Escherichia coli. A cydD mutant strain was used to probe the influence of CydDC upon reduced thiol export, gene expression, metabolic perturbations, intracellular pH homeostasis, and tolerance to nitric oxide (NO). Loss of CydDC was found to decrease extracytoplasmic thiol levels, whereas overexpression diminished the cytoplasmic thiol content. Transcriptomic analysis revealed a dramatic up-regulation of protein chaperones, protein degradation (via phenylpropionate/phenylacetate catabolism), ?-oxidation of fatty acids, and genes involved in nitrate/nitrite reduction. 1H NMR metabolomics revealed elevated methionine and betaine and diminished acetate and NAD+ in cydD cells, which was consistent with the transcriptomics-based metabolic model. The growth rate and ?pH, however, were unaffected, although the cydD strain did exhibit sensitivity to the NO-releasing compound NOC-12. These observations are consistent with the hypothesis that the loss of CydDC-mediated reductant export promotes protein misfolding, adaptations to energy metabolism, and sensitivity to NO. The addition of both glutathione and cysteine to the medium was found to complement the loss of bd -type cytochrome synthesis in a cydD strain (a key component of the pleiotropic cydDC phenotype), providing the first direct evidence that CydDC substrates are able to restore the correct assembly of this respiratory oxidase. These data provide an insight into the metabolic flexibility of E. coli , highlight the importance of bacterial redox homeostasis during nitrosative stress, and report for the first time the ability of periplasmic low molecular weight thiols to restore haem incorporation into a cytochrome complex

A method for identifying associations between seizures and possible trigger events in adults with intellectual disability.

OBJECTIVES: Precipitants of seizures are often reported by patients and carers, but the accuracy of these claims remains unknown. Focusing on epilepsy in people with intellectual disability (ID), the aims of this work were to (1) identify a set of methods for assessing the validity of reported seizure triggers in individual patients; and (2) undertake an initial assessment of the ease of implementation and acceptability of the method by applying it to a series of cases. METHODS: Data collection materials (developed with carer involvement) consisted primarily of carer diaries of seizure and trigger occurrences. Statistical analysis of diary data was using the self-controlled case series method. Unlike previously used methods, the analysis method included a means of choosing the time window, following trigger exposure, during which changes in seizure likelihood are to be assessed. RESULTS: The method developed was trialed in five adults with ID and epilepsy, who had a range of ID severities and living circumstances. Examples of the application of the method in two of the five cases are presented for illustrative purposes. The method was acceptable to participants and most aspects successfully implemented. SIGNIFICANCE: This method may be useful for clinicians and researchers wishing to investigate possible triggers in individual patients with epilepsy and ID. It also supports the identification of a statistically defined time window following exposure to a precipitant, during which the risk of developing a seizure is increased. The identification of such a window has value not just in contributing to clinical management, but also in guiding future work into the mechanisms of seizure precipitation.This study was funded by a grant to HR from Epilepsy Action: The Epilepsy Association. (Registered Charity in England (No. 234343)). SX was supported by NIH/NCRR Colorado CTSI Grant Number UL1 RR025780. HR is a member of the NIHR’s Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East of England at Cambridgeshire & Peterborough NHS Foundation Trust. JI also received funding from CLAHRC East of England during preparation of the manuscript. This article presents independent research with funding from the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health (UK). We would also like to thank Elizabeth Blake-Palmer for her assistance with patient recruitment, and Professor Paddy Farrington for statistical advice.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/epi.1313

Energy and water use in Arizona agriculture: Working paper series--08-08

Increasing energy and water concerns in Arizona are the driving forces to improve the efficiency of agricultural production within the state. In this article we address the energy and water uses in growing a variety of crops in Arizona. The goal of the research project is to identify and quantify all energy and water uses from the production of the initial seed, through the treatments of the soil and various chemical introductions, all the way until the crop is harvested in the field. Thus, the analysis is "from seed to the edge of the field." Using a series of secondary data sources, the paper provides ranges for the energy and water consumption for the predominant crops grown in the major agriculture areas of the state

Understanding the implementation and adoption of an information technology intervention to support medicine optimisation in primary care: qualitative study using strong structuration theory

Objectives: Using strong structuration theory, we aimed to understand the adoption and implementation of an electronic clinical audit and feedback tool to support medicine optimisation for patients in primary care. Design: This is a qualitative study informed by strong structuration theory. The analysis was thematic, using a template approach. An a priori set of thematic codes, based on strong structuration theory, was developed from the literature and applied to the transcripts. The coding template was then modified through successive readings of the data. Setting: Clinical commissioning group in the south of England. Participants: Four focus groups and five semi-structured interviews were conducted with 18 participants purposively sampled from a range of stakeholder groups (general practitioners, pharmacists, patients and commissioners). Results: Using the system could lead to improved medication safety, but use was determined by broad institutional contexts; by the perceptions, dispositions and skills of users; and by the structures embedded within the technology. These included perceptions of the system as new and requiring technical competence and skill; the adoption of the system for information gathering; and interactions and relationships that involved individual, shared or collective use. The dynamics between these external, internal and technological structures affected the adoption and implementation of the system. Conclusions: Successful implementation of information technology interventions for medicine optimisation will depend on a combination of the infrastructure within primary care, social structures embedded in the technology and the conventions, norms and dispositions of those utilising it. Future interventions, using electronic audit and feedback tools to improve medication safety, should consider the complexity of the social and organisational contexts and how internal and external structures can affect the use of the technology in order to support effective implementation

Functional genomics to identify the factors contributing to successful persistence and global spread of an antibiotic resistance plasmid

Background: The spread of bacterial plasmids is an increasing global problem contributing to the widespread dissemination of antibiotic resistance genes including β-lactamases. Our understanding of the details of the biological mechanisms by which these natural plasmids are able to persist in bacterial populations and are able to establish themselves in new hosts via conjugative transfer is very poor. We recently identified and sequenced a globally successful plasmid, pCT, conferring β-lactam resistance. Results: Here, we investigated six plasmid encoded factors (tra and pil loci; rci shufflon recombinase, a putative sigma factor, a putative parB partitioning gene and a pndACB toxin-antitoxin system) hypothesised to contribute to the 'evolutionary success' of plasmid pCT. Using a functional genomics approach, the role of these loci was investigated by systematically inactivating each region and examining the impact on plasmid persistence, conjugation and bacterial host biology. While the tra locus was found to be essential for all pCT conjugative transfer, the second conjugation (pil) locus was found to increase conjugation frequencies in liquid media to particular bacterial host recipients (determined in part by the rci shufflon recombinase). Inactivation of the pCT pndACB system and parB did not reduce the stability of this plasmid. Conclusions: Our findings suggest the success of pCT may be due to a combination of factors including plasmid stability within a range of bacterial hosts, a lack of a fitness burden and efficient transfer rates to new bacterial hosts rather than the presence of a particular gene or phenotype transferred to the host. The methodology used in our study could be applied to other 'successful' globally distributed plasmids to discover the role of currently unknown plasmid backbone genes or to investigate other factors which allow these elements to persist and spread