A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling

The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca2+ signaling leading to a parallel increase in the cytosolic Ca2+ pools that activate the Ca2+-dependent NADPH oxidase (NOX) thereby increasing ROS. The inhibition of mitochondrial Ca2+ uptake by TSPO is a consequence of the phosphorylation of the voltage-dependent anion channel (VDAC1) by the protein kinase A (PKA), which is recruited to the mitochondria, in complex with the Acyl-CoA binding domain containing 3 (ACBD3). Notably, the neurotransmitter glutamate, which contributes neuronal toxicity in age-dependent conditions, triggers this TSPO-dependent mechanism of cell signaling leading to cellular demise. TSPO is therefore proposed as a novel OMM-based pathway to control intracellular Ca2+ dynamics and redox transients in neuronal cytotoxicity

Precautionary labelling of foods for allergen content: are we ready for a global framework?

© 2014 Allen et al.; licensee BioMed Central Ltd.Food allergy appears to be on the rise with the current mainstay of treatment centred on allergen avoidance. Mandatory allergen labelling has improved the safety of food for allergic consumers. However an additional form of voluntary labelling (termed precautionary allergen labelling) has evolved on a wide range of packaged goods, in a bid by manufacturers to minimise risk to customers, and the negative impact on business that might result from exposure to trace amounts of food allergen present during cross-contamination during production. This has resulted in near ubiquitous utilisation of a multitude of different precautionary allergen labels with subsequent confusion amongst many consumers as to their significance. The global nature of food production and manufacturing makes harmonisation of allergen labelling regulations across the world a matter of increasing importance. Addressing inconsistencies across countries with regards to labelling legislation, as well as improvement or even banning of precautionary allergy labelling are both likely to be significant steps forward in improved food safety for allergic families. This article outlines the current status of allergen labelling legislation around the world and reviews the value of current existing precautionary allergen labelling for the allergic consumer. We strongly urge for an international framework to be considered to help roadmap a solution to the weaknesses of the current systems, and discuss the role of legislation in facilitating this

The management of behavioural and psychological symptoms of dementia in the acute general medical hospital: A longitudinal cohort study

yesBackground: The acute hospital is a challenging place for a person with dementia. Behavioural and psychological symptoms of dementia (BPSD) are common and may be exacerbated by the hospital environment. Concerns have been raised about how BPSD are managed in this setting and about over reliance on neuroleptic medication. This study aimed to investigate how BPSD are managed in UK acute hospitals. Method(s): A longitudinal cohort of 230 patients with dementia admitted to two acute NHS hospitals. BPSD were measured every four days (Behave-AD scale), as well as documentation of pharmacological prescriptions and non-pharmacological management. Results: The overall prevalence of BPSD was 75%, with aggression and activity disturbance being the most common. Antipsychotics were prescribed for 28 (12%) patients; 70% of these prescriptions were new on admission. Benzodiazepines were prescribed for 27 (12%) patients, antidepressants were prescribed for 37 (16%) patients, and sedatives were prescribed for 14 (3%) patients. Patients who were prescribed antipsychotics, after adjusting for end of life medication, age and dementia severity, were significantly more likely to die (adjusted hazard ratio 5.78, 95% CI 1.57, 21.26, p= 0.008). Nonpharmacological management was used in 55% of participants, most commonly psychosocial interventions (36%) with little evidence of monitoring their effectiveness. A form of restraint was used during 50 (22%) patients’ admissions. Conclusions: Antipsychotic medications and psychosocial interventions were the main methods used to manage BPSD; however, these were not implemented or monitored in a systematic fashion.Alzheimer's Society; BUPA Foundatio

Cardiac-restricted IGF-1Ea overexpression reduces the early accumulation of inflammatory myeloid cells and mediates expression of extracellular matrix remodelling genes after myocardial infarction

Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea) propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9), their inhibitors (TIMP-1 and TIMP-2), and collagen types (Col 1α1 and Col 1α3) in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function

Stability Measurements of Rutherford Cables with Various Treatments

To improve the stability of Rutherford type superconducting cables, various methods of treating cables were considered and tested. These treatments include strand coating, partial soldering, "barber-pole" insulation and "porous $9 metal" solder filling. To study the effect of these treatments, several cables were prepared and MQE (minimum quench energy) values were measured. Coating, partial soldering or "barber-pole insulation" improved the relative stability$9 for some cables. The "porous metal" filled cables showed higher MQE. However the results suggest that the porous metal process needs to be improved. The measured data for cables with various treatments are presented. (8 refs)

A qualitative study exploring the difficulties influencing decision making at the end of life for people with dementia

BACKGROUND: Dementia is a progressive neurodegenerative condition characterized by declining functional and cognitive abilities. The quality of end of life care for people with dementia in the UK can be poor. Several difficult decisions may arise at the end of life, relating to the care of the person with dementia, for example management of comorbidities. OBJECTIVE: To explore difficulties in decision making for practitioners and family carers at the end of life for people with dementia. DESIGN: Qualitative methodology using focus groups and semi-structured interviews and thematic analysis methods. SETTINGS AND PARTICIPANTS: Former (n=4) and current (n=6) family carers of people with experience of end of life care for a person with dementia were recruited from an English dementia voluntary group in 2015. A further 24 health and care professionals were purposively sampled to include a broad range of expertise and experience in dementia end of life care. RESULTS: Four key themes were identified as follows: challenges of delivering coherent care in dynamic systems; uncertainty amongst decision makers; internal and external conflict amongst decision makers; and a lack of preparedness for the end of life. Overarching difficulties such as poor communication, uncertainty and conflict about the needs of the person with dementia as well as the decision maker's own role can characterize decision making at the end of life. CONCLUSIONS: This study suggests that decision making at the end of life for people with dementia has the potential to be improved. More planning earlier in the course of dementia with an on-going approach to conversation may increase preparedness and family carers' expectations of end of life

Naming Game on Adaptive Weighted Networks

We examine a naming game on an adaptive weighted network. A weight of connection for a given pair of agents depends on their communication success rate and determines the probability with which the agents communicate. In some cases, depending on the parameters of the model, the preference toward successfully communicating agents is basically negligible and the model behaves similarly to the naming game on a complete graph. In particular, it quickly reaches a single-language state, albeit some details of the dynamics are different from the complete-graph version. In some other cases, the preference toward successfully communicating agents becomes much more relevant and the model gets trapped in a multi-language regime. In this case gradual coarsening and extinction of languages lead to the emergence of a dominant language, albeit with some other languages still being present. A comparison of distribution of languages in our model and in the human population is discussed.Comment: 22 pages, accepted in Artificial Lif

Addressing Food Insecurity in College: Mapping a Shared Conceptual Framework for Campus Pantries in Michigan

The first known university food pantry started at Michigan State University in 1993. Since then, campus food pantries are more widespread, although little is known about them. The current study examined how college pantries best serve students and foster their success. Twentyâ eight food pantry directors and staff from across sixteen Michigan college campuses engaged in concept mapping, a technique used to examine the interrelationships among concepts understood by stakeholders. Analyses identified six concepts, examined importance of each concept as assigned by participants, and evaluated variation among institutions. Implications for findings and future research directions are discussed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147046/1/asap12161_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147046/2/asap12161.pd