Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signaling in The Prefrontal Cortex Modulates Cued Fear Learning, But Not Spatial Working Memory, in Female Rats

A genetic polymorphism within the gene encoding the pituitary adenylate cyclase- activating polypeptide (PACAP) receptor type I (PAC1R) has recently been associated with hyper-reactivity to threat-related cues in women, but not men, with post-traumatic stress disorder (PTSD). PACAP is a highly conserved peptide, whose role in mediating adaptive physiological stress responses is well established. Far less is understood about the contribution of PACAP signaling in emotional learning and memory, particularly the encoding of fear to discrete cues. Moreover, a neurobiological substrate that may account for the observed link between PAC1R and PTSD in women, but not men, has yet to be identified. Sex differences in PACAP signaling during emotional learning could provide novel targets for the treatment of PTSD. Here we investigated the contribution of PAC1R signaling within the prefrontal cortex to the acquisition of cued fear in female and male rats. We used a variant of fear conditioning called trace fear conditioning, which requires sustained attention to fear cues and depends on working-memory like neuronal activity within the prefrontal cortex. We found that cued fear learning, but not spatial working memory, was impaired by administration of a PAC1R antagonist directly into the prelimbic area of the prefrontal cortex. This effect was specific to females. We also found that levels of mRNA for the PAC1R receptor in the prelimbic cortex were greater in females compared with males, and were highest during and immediately following the proestrus stage of the estrous cycle. Together, these results demonstrate a sex-specific role of PAC1R signaling in learning about threat-related cues

Whey for Sarcopenia; Can Whey Peptides, Hydrolysates or Proteins Play a Beneficial Role?

peer reviewedAs the human body ages, skeletal muscle loses its mass and strength. It is estimated that in 10% of individuals over the age of 60, this muscle frailty has progressed to sarcopenia. Biomarkers of sarcopenia include increases in inflammatory markers and oxidative stress markers and decreases in muscle anabolic markers. Whey is a high-quality, easily digested dairy protein which is widely used in the sports industry. This review explores the evidence that whey protein, hydrolysates or peptides may have beneficial effects on sarcopenic biomarkers in myoblast cell lines, in aged rodents and in human dietary intervention trials with the older consumer. A daily dietary supplementation of 35 g of whey is likely to improve sarcopenic biomarkers in frail or sarcopenia individuals. Whey supplementation, consumed by an older, healthy adult certainly improves muscle mTOR signaling, but exercise appears to have the greatest benefit to older muscle. In vitro cellular assays are central for bioactive and bioavailable peptide identification and to determine their mechanism of action on ageing muscle.Department of Agriculture, Food and the Marine, Irelan

Consumer and Healthcare Professional Led Priority Setting for Quality Use of Medicines in People with Dementia: Gathering Unanswered Research Questions

Background: Historically, research questions have been posed by the pharmaceutical industry or researchers, with little involvement of consumers and healthcare professionals. Objective: To determine what questions about medicine use are important to people living with dementia and their care team and whether they have been previously answered by research. Methods: The James Lind Alliance Priority Setting Partnership process was followed. A national Australian qualitative survey on medicine use in people living with dementia was conducted with consumers (people living with dementia and their carers including family, and friends) and healthcare professionals. Survey findings were supplemented with key informant interviews and relevant published documents (identified by the research team). Conventional content analysis was used to generate summary questions. Finally, evidence checking was conducted to determine if the summary questions were 'unanswered'. Results: A total of 545 questions were submitted by 228 survey participants (151 consumers and 77 healthcare professionals). Eight interviews were conducted with key informants and four relevant published documents were identified and reviewed. Overall, analysis resulted in 68 research questions, grouped into 13 themes. Themes with the greatest number of questions were related to co-morbidities, adverse drug reactions, treatment of dementia, and polypharmacy. Evidence checking resulted in 67 unanswered questions. Conclusion: A wide variety of unanswered research questions were identified. Addressing unanswered research questions identified by consumers and healthcare professionals through this process will ensure that areas of priority are targeted in future research to achieve optimal health outcomes through quality use of medicines

The effects of bioavailable dairy whey peptides on nerve and muscle health

As we age, we lose skeletal muscle mass and strength. Muscle ageing can be reversed or delayed by a combination of exercise and dietary protein. There is an increasing amount of evidence from intervention trials that consumption of whey has positive benefits on ageing muscle health. Bovine whey proteins (β-Lactoglobulin (β-Lac), α-Lactalbumin (α-Lac), Bovine Serum Albumin (BSA) and Lactoferrin) are high quality dairy proteins that are easily digested contain all essential amino acids and are rich in branched chain amino acids. These proteins are also noted for their bioactive peptides. This thesis examines the effects of up to 5 bioavailable whey peptides, TKIPA (β-Lac), NLPPL (BSA), KVPQ (BSA), VAGT (β-Lac) and VGIN (α-Lac) on redox and inflammatory biomarkers in muscle and microglial cell lines. All five peptides significantly protected C2C12 cells from free radical damage with two peptides NLPPL and VAGT having positive effects in both C2C12 and BV-2 cells. In addition, this study reports on the levels of 3 inflammatory biomarkers of ageing (Interleukin 1-β, Interleukin- 6 and Tumour Necrosis Factor alpha) in a limited number of frail older adults in Ireland. The preliminary results from the bloods indicate that IL-6, IL-1, TNF- are elevated in the older Irish frail population

Controlling wealth from beyond the grave - who controls the distribution and use of a deceased’s estate and who ought to inherit it? : a study of Inheritance Law, introducing and utilising bloodline justice theory to understand the economic, moral and social considerations influencing common law and legislative developments in the last 200 years and contemplating possibilities for reform

The laws of inheritance and succession (“Inheritance Law”) are both a product and means of social and economic change, as well as moral influence. An historical analysis of the law in England and Wales will assist to understand both the founding principles and development of Inheritance Law. By reference to case law and statute it will be possible to identify where Inheritance Law has failed to react and keep pace with social development and to assess how laws of the early nineteenth and twentieth centuries fit within twenty-first century society and property laws more broadly. “Bloodline Justice” is introduced as a theory of, and a lens through which to study, Inheritance Law. It is the theory that one can inherit or may have a right to inherit based on bloodline relationship to the deceased or because one sits within the circles of closeness to the same. It is utilised to analyse how moral and social theories have operated for and against the interests of the living and the dead, critically analysing key areas where there is scope for conflict. Testator control is a convenient way to arrange property transfer on death, but the capacity to challenge also necessary. Consideration will be given to the rationale and morality of allowing the dead testamentary freedom, as regard the distribution of wealth to the living and sometimes also the use of it, with reference to restrictions the law has attempted to place on that freedom. This thesis will therefore critically examine how Inheritance Law is influenced by wider historical, social and moral perceptions of what our laws in this area should be and for whom they should provide, from a starting point of bloodline justice. The main mechanisms to transfer property on death will be considered, and challenges to Inheritance Law and bloodline justice in the twenty-first century will be evaluated. It is recognised that whilst there is a pragmatic need in any system of law to enable property transfer on death, difficulties arise where an historic system of law coalesces with individual testamentary freedom in a rapidly changing environment. Current statutes are numerous and archaic, common law judgments varied, and the make-up of society and familial relationships so diversified since current Inheritance legislation was drafted that Inheritance Law is, at best, in need of holistic review and consolidation, if not reform

Effect of Bioavailable Whey Peptides on C2C12 Muscle Cells

Whey proteins are highly valued food ingredients. This study examines the health benefits to muscle cells of six individual whey peptides known to cross the intestinal barrier. Results indicate that peptides KVPQ, NLPPL, VAGT, VGIN and PVPQ protect undifferentiated C2C12 myoblasts from free radical damage

Process Evaluation of the Integrated Childsmile Programme. Report of the fourth tranche of fieldwork (August 2013 to July 2014)

<p>This report provides findings from the fourth tranche of the process evaluation of the integrated Childsmile programme, covering the period August 2013 to July 2014.</p><p><br></p><p>Childsmile is the national, early years oral health improvement in Scotland. It comprises interacting components (Core: toothbrushing in all nurseries and targeted primary schools, provision of oral health packs at key stages; Nursery & School: fluoride varnishing provided to children in targeted educational establishments; and Practice: support for families with young children to register with and attend dental practices and to engage in protecting their children's oral health).</p><p><br></p><p>The purpose of the process evaluation is to explore implementation of the programme, to aid the interpretation of its outcomes.</p

Process Evaluation of the Integrated Childsmile Programme. Report of the third tranche of fieldwork (August 2012 to July 2013)

<p>This report provides findings from the third tranche of the process evaluation of the integrated Childsmile programme, covering the period August 2012 to July 2013.</p><p><br></p><p>Childsmile is the national, early years oral health improvement in Scotland. It comprises interacting components (Core: toothbrushing in all nurseries and targeted primary schools, provision of oral health packs at key stages; Nursery & School: fluoride varnishing provided to children in targeted educational establishments; and Practice: support for families with young children to register with and attend dental practices and to engage in protecting their children's oral health).</p><p><br></p><p>The purpose of the process evaluation is to explore implementation of the programme, to aid the interpretation of its outcomes.</p