Diabetes Impairs the Aldehyde Detoxifying Capacity of the Retina

Purpose: We studied whether the accumulation of advanced lipoxidation end-products (ALEs) in the diabetic retina is linked to the impairment of lipid aldehyde detoxification mechanisms.

Methods: Retinas were collected from nondiabetic and diabetic rats and processed for conventional and quantitative RT-PCR (qRT-PCR), Western blotting, immunohistochemistry, and aldehyde dehydrogenase (ALDH) activity assays. The effect of the ALDH1a1 inhibitor, NCT-501, on ALE accumulation and cell viability in cultured Müller glia also was investigated.

Results: The rat retina expressed a range of lipid aldehyde detoxifying ALDH and aldo-keto reductase (AKR) genes. In diabetes, mRNA levels were reduced for 5 of 9 transcripts tested. These findings contrasted with those in the lens and cornea where many of these enzymes were upregulated. We have reported previously accumulation of the acrolein (ACR)-derived ALE, FDP-lysine, in retinal Müller glia during diabetes. In the present study, we show that the main ACR-detoxifying ALDH and AKR genes expressed in the retina, namely, ALDH1a1, ALDH2, and AKR1b1, are principally localized to Müller glia. Diabetes-induced FDP-lysine accumulation in Müller glia was associated with a reduction in ALDH1a1 mRNA and protein expression in whole retina and a decrease in ALDH1a1-immunoreactivity specifically within these cells. No such changes were detected for ALDH2 or AKR1b1. Activity of ALDH was suppressed in the diabetic retina and blockade of ALDH1a1 in cultured Müller glia triggered FDP-lysine accumulation and reduced cell viability.

Conclusions: These findings suggest that downregulation of ALDH and AKR enzymes, particularly ALDH1a1, may contribute ALE accumulation in the diabetic retina.

Essential scientific mapping of the value chain of thermochemical converted second-generation bio-fuels

As the largest contributor to renewable energy, biomass (especially lignocellulosic biomass) has significant potential to address atmospheric emission and energy shortage issues. The bio-fuels derived from lignocellulosic biomass are popularly referred to as second-generation bio-fuels. To date, several thermochemical conversion pathways for the production of second-generation bio-fuels have shown commercial promise; however, most of these remain at various pre-commercial stages. In view of their imminent commercialization, it is important to conduct a profound and comprehensive comparison of these production techniques. Accordingly, the scope of this review is to fill this essential knowledge gap by mapping the entire value chain of second-generation bio-fuels, from technical, economic, and environmental perspectives. This value chain covers i) the thermochemical technologies used to convert solid biomass feedstock into easier-to-handle intermediates, such as bio-oil, syngas, methanol, and Fischer-Tropsch fuel; and ii) the upgrading technologies used to convert intermediates into end products, including diesel, gasoline, renewable jet fuels, hydrogen, char, olefins, and oxygenated compounds. This review also provides an economic and commercial assessment of these technologies, with the aim of identifying the most adaptable technology for the production of bio-fuels, fuel additives, and bio-chemicals. A detailed mapping of the carbon footprints of the various thermochemical routes to second-generation bio-fuels is also carried out. The review concludes by identifying key challenges and future trends for second-generation petroleum substitute bio-fuels.

Nurses' experiences of pain management for people with advanced dementia approaching the end of life: a qualitative study

AIMS AND OBJECTIVES: To explore hospice, acute care and nursing home nurses' experiences of pain management for people with advanced dementia in the final month of life. To identify the challenges, facilitators and practice areas requiring further support.

BACKGROUND: Pain management in end-stage dementia is a fundamental aspect of end of life care; however, it is unclear what challenges and facilitators nurses experience in practice, whether these differ across care settings, and whether training needs to be tailored to the context of care.

DESIGN: A qualitative study using semi-structured interviews and thematic analysis to examine data.

METHODS: 24 registered nurses caring for people dying with advanced dementia were recruited from ten nursing homes, three hospices, and two acute hospitals across a region of the United Kingdom. Interviews were conducted between June 2014 and September 2015.

RESULTS: Three core themes were identified: challenges administering analgesia, the nurse-physician relationship, and interactive learning and practice development. Patient-related challenges to pain management were universal across care settings; nurse- and organisation-related barriers differed between settings. A need for interactive learning and practice development, particularly in pharmacology, was identified.

CONCLUSIONS: Achieving pain management in practice was highly challenging. A number of barriers were identified; however, the manner and extent to which these impacted on nurses differed across hospice, nursing home and acute care settings. Needs-based training to support and promote practice development in pain management in end-stage dementia is required.

RELEVANCE TO CLINICAL PRACTICE: Nurses considered pain management fundamental to end of life care provision; however, nurses working in acute care and nursing home settings may be under-supported and under-resourced to adequately manage pain in people dying with advanced dementia. Nurse-to-nurse mentoring and ongoing needs-assessed interactive case-based learning could help promote practice development in this area. Nurses require continuing professional development in pharmacology. This article is protected by copyright. All rights reserved.

“There’s a Catch-22”. The complexities of pain management for people with advanced dementia nearing the end of life: a qualitative exploration of physicians’ perspectives

Background: Pain management is a cornerstone of palliative care. The clinical issues encountered by physicians when managing pain in patients dying with advanced dementia, and how these may impact on prescribing and treatment, are unknown. Aim: To explore physicians’ experiences of pain management for patients nearing the end of life, the impact of these on prescribing and treatment approaches, and the methods employed to overcome these challenges. Design: Qualitative, semi-structured interview study exploring: barriers to and facilitators of pain management, prescribing and treatment decisions, and training needs. Thematic analysis was used to elicit key themes. Settings/Participants: Twenty-three physicians, responsible for treating patients with advanced dementia approaching the end of life, were recruited from primary care (n=9), psychiatry (n=7) and hospice care (n=7). Results: Six themes emerged: diagnosing pain, complex prescribing and treatment approaches, side-effects and adverse events, route of administration, importance of sharing knowledge and training needs. Knowledge exchange was often practised through liaison with physicians from other specialties. Cross-specialty mentoring, and the creation of knowledge networks were believed to improve pain management in this patient population. Conclusions: Pain management in end-stage dementia is complex, requiring cross-population of knowledge between palliative care specialists and non-specialists, in addition to collateral information provided by other health professionals and patients’ families. Regular, cost- and time-effective mentoring and ongoing professional development are perceived to be essential in empowering physicians to meet clinical challenges in this area.