The oldest carers : a narrative review and synthesis of the experiences of carers aged over 75 years

As populations age, numbers of older carers are increasing. These carers play a vital role in supporting others, often partners or spouses with dementia. This narrative review synthesised peer-reviewed evidence published over the last two decades concerning the experiences of carers aged over 75 years, specifically exploring whether their experiences differ from those of younger carers. Four electronic databases were searched and 4102 publications were identified. Eighteen studies involving over one thousand carer participants were included (11 quantitative, 6 qualitative, and 1 mixed-methods study). Most studies came from Europe or North America and almost all were cross-sectional, but few directly compared younger and older carers, making it difficult to determine whether carers’ experiences vary with age. Quantitative studies generally emphasised the challenges of caring and frequently highlighted, for example, relationships between carer characteristics and negative outcomes such as burden. Qualitative studies were often more positive, emphasising carers’ active responses and the rewards of caring. The normality of caring was highlighted, with some suggesting that caring may be less challenging for older than for younger carers. As with younger carers, being an older carer can be both rewarding and difficult. Our understanding of the experiences of these older carers would be enhanced with more research specifically comparing older and younger carers or comparing older carers and those not in a caring role. Carers are diverse and future research should explore the experiences of carers from different demographic groups. More longitudinal research perhaps focusing on caring dyads and mutual caring is needed

On the Cost of Modularity in Atomic Broadcast

Modularity is a desirable property of complex software systems, since it simplifies code reuse, verification, maintenance, etc. However, the use of loosely coupled modules introduces a performance overhead. This overhead is often considered negligible, but this is not always the case. This paper aims at casting some light on the cost, in terms of performance, that is incurred when designing a relevant group communication protocol with modularity in mind: atomic broadcast. We conduct our experiments using two versions of atomic broadcast: a modular version and a monolithic one. We then measure the performance of both implementations under different system loads. Our results show that the overhead introduced by modularity is strongly related to the level of stress to which the system is subjected, and in the worst cases, reaches approximately 50%

Biological Effects of Clinically Relevant CoCr Nanoparticles in the Dura Mater: An Organ Culture Study

Medical interventions for the treatment of spinal disc degeneration include total disc replacement and fusion devices. There are, however, concerns regarding the generation of wear particles by these devices, the majority of which are in the nanometre sized range with the potential to cause adverse biological effects in the surrounding tissues. The aims of this study were to develop an organ culture model of the porcine dura mater and to investigate the biological effects of CoCr nanoparticles in this model. A range of histological techniques were used to analyse the structure of the tissue in the organ culture. The biological effects of the CoCr wear particles and the subsequent structural changes were assessed using tissue viability assays, cytokine assays, histology, immunohistochemistry, and TEM imaging. The physiological structure of the dura mater remained unchanged during the seven days of in vitro culture. There was no significant loss of cell viability. After exposure of the organ culture to CoCr nanoparticles, there was significant loosening of the epithelial layer, as well as the underlying collagen matrix. TEM imaging confirmed these structural alterations. These structural alterations were attributed to the production of MMP-1, -3, -9, -13, and TIMP-1. ELISA analysis revealed that there was significant release of cytokines including IL-8, IL-6, TNF-α, ECP and also the matrix protein, tenascin-C. This study suggested that CoCr nanoparticles did not cause cytotoxicity in the dura mater but they caused significant alterations to its structural integrity that could lead to significant secondary effects due to nanoparticle penetration, such as inflammation to the local neural tissue

Morphological features of lipid droplet transition during porcine oocyte fertilisation and early embryonic development to blastocyst in vivo and in vitro

Lipid content in mammalian oocytes or embryos differs among species, with bovine and porcine oocytes and embryos showing large cytoplasmic droplets. These droplets are considered to play important roles in energy metabolism during oocyte maturation, fertilisation and early embryonic development, and also in the freezing ability of oocytes or embryos; however, their detailed distribution or function is not well understood. In the present study, changes in the distribution and morphology of porcine lipid droplets during in vivo and in vitro fertilisation, in contrast to parthenogenetic oocyte activation, as well as during their development to blastocyst stage, were evaluated by transmission electron microscopy (TEM). The analysis of semi-thin and ultra-thin sections by TEM showed conspicuous, large, electron-dense lipid droplets, sometimes associated with mitochondrial aggregates in the oocytes, irrespective of whether the oocytes had been matured in vivo or in vitro. Immediately after sperm penetration, the electron density of the lipid droplets was lost in both the in vivo and in vitro oocytes, the reduction being most evident in the oocytes developed in vitro. Density was restored in the pronculear oocytes, fully in the in vivo specimens but only partially in the in vitro ones. The number and size of the droplets seemed, however, to have decreased. At 2- to 4-cell and blastocyst stages, the features of the lipid droplets were almost the same as those of pronuclear oocytes, showing a homogeneous or saturated density in the in vivo embryos but a marbled or partially saturated appearance in the in vitro embryos. In vitro matured oocytes undergoing parthenogenesis had lipid droplets that resembled those of fertilised oocytes until the pronuclear stage. Overall, results indicate variations in both the morphology and amount of cytoplasmic lipid droplets during porcine oocyte maturation, fertilisation and early embryo development as well as differences between in vivo and in vitro development, suggesting both different energy status during preimplantation development in pigs and substantial differences between in vitro and in vivo development.</p

The role of Schizosaccharomyces pombe SUMO ligases in genome stability

SUMOylation is a post-translational modification that affects a large number of proteins, many of which are nuclear. While the role of SUMOylation is beginning to be elucidated, it is clear that understanding the mechanisms that regulate the process is likely to be important. Control of the levels of SUMOylation is brought about through a balance of conjugating and deconjugating activities, i.e. of SUMO (small ubiquitin-related modifier) conjugators and ligases versus SUMO proteases. Although conjugation of SUMO to proteins can occur in the absence of a SUMO ligase, it is apparent that SUMO ligases facilitate the SUMOylation of specific subsets of proteins. Two SUMO ligases in Schizosaccharomyces pombe, Pli1 and Nse2, have been identified, both of which have roles in genome stability. We report here on a comparison between the properties of the two proteins and discuss potential roles for the proteins

Factors That Promote H3 Chromatin Integrity during Transcription Prevent Promiscuous Deposition of CENP-A(Cnp1) in Fission Yeast

Specialized chromatin containing CENP-A nucleosomes instead of H3 nucleosomes is found at all centromeres. However, the mechanisms that specify the locations at which CENP-A chromatin is assembled remain elusive in organisms with regional, epigenetically regulated centromeres. It is known that normal centromeric DNA is transcribed in several systems including the fission yeast, Schizosaccharomyces pombe. Here, we show that factors which preserve stable histone H3 chromatin during transcription also play a role in preventing promiscuous CENP-A(Cnp1) deposition in fission yeast. Mutations in the histone chaperone FACT impair the maintenance of H3 chromatin on transcribed regions and promote widespread CENP-A(Cnp1) incorporation at non-centromeric sites. FACT has little or no effect on CENP-A(Cnp1) assembly at endogenous centromeres where CENP-A(Cnp1) is normally assembled. In contrast, Clr6 complex II (Clr6-CII; equivalent to Rpd3S) histone deacetylase function has a more subtle impact on the stability of transcribed H3 chromatin and acts to prevent the ectopic accumulation of CENP-A(Cnp1) at specific loci, including subtelomeric regions, where CENP-A(Cnp1) is preferentially assembled. Moreover, defective Clr6-CII function allows the de novo assembly of CENP-A(Cnp1) chromatin on centromeric DNA, bypassing the normal requirement for heterochromatin. Thus, our analyses show that alterations in the process of chromatin assembly during transcription can destabilize H3 nucleosomes and thereby allow CENP-A(Cnp1) to assemble in its place. We propose that normal centromeres provide a specific chromatin context that limits reassembly of H3 chromatin during transcription and thereby promotes the establishment of CENP-A(Cnp1) chromatin and associated kinetochores. These findings have important implications for genetic and epigenetic processes involved in centromere specification

Supply Chain Security – Threats and Solutions

In recent years, the cargo transport process has improved mainly in the areas of logistics efficiency and documentation handling. The World Trade Centre terror attack in 2001 changed the world and with it the conditions for logistics world-wide. The logistics consequences were according to[1]: It is instructive to note that these disruptions were not caused by the attack itself, but rather by the governmentâs response to the attack: closing borders, shutting down air traffic and evacuating buildings throughout the country. The aftermath to the attack brought needed attention to the vulnerability of modern supply chains. Supply chain vulnerability reflects sensitivity of the supply chain to disruption [2]. This vulnerability can in many cases be described as âunwanted effectsâ in the supply chain caused either by internal or external forces that create disturbances larger than the supply chain is designed to handle. The objective of Supply chain security is to prevent antagonistic threats from affecting the supply chain performance. Antagonistic threats and other risks and uncertainties are demarcated by three key words: deliberate (caused), illegal (defined by law), and hostile (negative impact for transport network activities) [3]. This chapter presents first the major antagonistic threats to the supply chain and secondly how these threats should be prevented. This leads to the current development of different supply chain security programs

A Method for Describing the Problem of Physician Distrbution in Rural AreasRalph Ekwall

In recent years much attention has been given to the problem of physician shortage and physician maldistribution. The first is con­troversial and not all the experts believe that it exists except as a part of the maldistribution problem. There is a fundamental agreement that a problem of maldistribution exists. The general nature of the problem is that physicians are dis­tributed too densely in small cities and large city suburbs and too sparsely in the inner city and rural areas. It is not the intent of this presen­tation to offer a solution to the problem, but to offer a method for a better analysis and definition of physician distribution in rural areas so that when solutions are for­mulated, they will reflect a more exact definition and analysis of the proble

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

Altered expression of autoimmune regulator in infant down syndrome thymus, a possible contributor to an autoimmune phenotype.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageDown syndrome (DS), caused by trisomy of chromosome 21, is associated with immunological dysfunctions such as increased frequency of infections and autoimmune diseases. Patients with DS share clinical features, such as autoimmune manifestations and specific autoantibodies, with patients affected by autoimmune polyendocrine syndrome type 1. Autoimmune polyendocrine syndrome type 1 is caused by mutations in the autoimmune regulator (AIRE) gene, located on chromosome 21, which regulates the expression of tissue-restricted Ags (TRAs) in thymic epithelial cells. We investigated the expression of AIRE and TRAs in DS and control thymic tissue using quantitative PCR. AIRE mRNA levels were elevated in thymic tissue from DS patients, and trends toward increased expression of the AIRE-controlled genes INSULIN and CHRNA1 were found. Immunohistochemical stainings showed altered cell composition and architecture of the thymic medulla in DS individuals with increased frequencies of AIRE-positive medullary epithelial cells and CD11c-positive dendritic cells as well as enlarged Hassall's corpuscles. In addition, we evaluated the proteomic profile of thymic exosomes in DS individuals and controls. DS exosomes carried a broader protein pool and also a larger pool of unique TRAs compared with control exosomes. In conclusion, the increased AIRE gene dose in DS could contribute to an autoimmune phenotype through multiple AIRE-mediated effects on homeostasis and function of thymic epithelial cells that affect thymic selection processes.Swedish Research Council 80409601 Marianne and Marcus Wallenberg Foundation Region Vastra Gotaland ALFGBG-771712 Arbetsmarknadens Forsakringsaktiebolag 100258 IngaBritt and Arne Lundbergs Research Foundation AnnMari and Per Ahlqvists Foundation Gothenburg Medical Society Wilhelm and Martina Lundgrens Research Foundatio