Neurodegenerative Diseases – Is Metabolic Deficiency the Root Cause?

Coatings are applied to appliances, instruments and automobiles for a variety of reasons including corrosion protection and enhancement of market value. Automobile finishes are a highly complex blend of polymeric materials which have a definite impact on the eventual ability of a car to sell. Consumers report that the gloss of the finish is one of the major items they look for in an automobile.With the finish being such an important part of the automobile, there is a zero tolerance for paint defects by auto assembly plant management. Owing to the increased complexity of the paint matrix and its inability to be “forgiving” when foreign materials are introduced into a newly applied finish, the analysis of paint defects has taken on unparalleled importance. Scanning electron microscopy with its attendant x-ray analysis capability is the premier method of examining defects and attempting to identify their root cause.Defects are normally examined by cutting out a coupon sized portion of the autobody and viewing in an SEM at various angles.

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Autophagy and ageing: implications for age-related neurodegenerative diseases

Essays in Biochemistry ◽

10.1042/bse0550119 ◽

2013 ◽

Vol 55 ◽

pp. 119-131 ◽

Cited By ~ 37

Author(s):

Bernadette Carroll ◽

Graeme Hewitt ◽

Viktor I. Korolchuk

Keyword(s):

Neurodegenerative Diseases ◽

Energy Availability ◽

Future Studies ◽

Intracellular Degradation ◽

Age Related ◽

Autophagy Induction ◽

Social Importance ◽

Cellular Dysfunction ◽

Autophagy Activity ◽

Intense Research

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our ‘ageing’ world.

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Nanotheranostic agents for neurodegenerative diseases

Emerging Topics in Life Sciences ◽

10.1042/etls20190141 ◽

2020 ◽

Vol 4 (6) ◽

pp. 645-675

Author(s):

Parasuraman Padmanabhan ◽

Mathangi Palanivel ◽

Ajay Kumar ◽

Domokos Máthé ◽

George K. Radda ◽

...

Keyword(s):

Drug Delivery ◽

Neurodegenerative Diseases ◽

Cell Types ◽

Specific Cell ◽

Ageing Population ◽

Target Tissue ◽

Therapeutic Approaches ◽

Surface Receptors ◽

Theranostic Agents ◽

Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

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Root Cause Analyses of Suicides of Mental Health Clients

Crisis ◽

10.1027/0227-5910/a000328 ◽

2015 ◽

Vol 36 (5) ◽

pp. 316-324 ◽

Cited By ~ 6

Author(s):

Donna Gillies ◽

David Chicop ◽

Paul O'Halloran

Keyword(s):

Mental Health ◽

Suicide Prevention ◽

Common Factor ◽

Data Collection Tool ◽

Related Factors ◽

Root Cause ◽

Communication Problems ◽

The Individual ◽

Mental Health Clients ◽

Imminent Risk

Abstract. Background: The ability to predict imminent risk of suicide is limited, particularly among mental health clients. Root cause analysis (RCA) can be used by health services to identify service-wide approaches to suicide prevention. Aims: To (a) develop a standardized taxonomy for RCAs; (b) to quantitate service-related factors associated with suicides; and (c) to identify service-related suicide prevention strategies. Method: The RCAs of all people who died by suicide within 1 week of contact with the mental health service over 5 years were thematically analyzed using a data collection tool. Results: Data were derived from RCAs of all 64 people who died by suicide between 2008 and 2012. Major themes were categorized as individual, situational, and care-related factors. The most common factor was that clients had recently denied suicidality. Reliance on carers, recent changes in medication, communication problems, and problems in follow-through were also commonly identified. Conclusion: Given the difficulty in predicting suicide in people whose expressions of suicidal ideation change so rapidly, services may consider the use of strategies aimed at improving the individual, stressor, support, and care factors identified in this study.

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