Maternal Mid-Gestation Cytokine Dysregulation in Mothers of Children with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a developmental disorder characterised by deficits in social interactions and communication, with stereotypical and repetitive behaviours. Recent evidence suggests that maternal immune dysregulation may predispose offspring to ASD. Independent samples t-tests revealed downregulation of IL-17A concentrations in cases, when compared to controls, at both 15 weeks (p = 0.02), and 20 weeks (p = 0.02), which persisted at 20 weeks following adjustment for confounding variables. This adds to the growing body of evidence that maternal immune regulation may play a role in foetal neurodevelopment

Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes is a risk factor for Alzheimer's disease (AD), most likely linked to an impairment of insulin signalling in the brain. Therefore, drugs that enhance insulin signalling may have therapeutic potential for AD. Liraglutide (Victoza) and exenatide (Byetta) are novel long-lasting analogues of the GLP-1 incretin hormone and are currently available to treat diabetes. They facilitate insulin signalling via the GLP-1 receptor (GLP-1R). Numerous <it>in vitro </it>and <it>in vivo </it>studies have shown that GLP-1 analogues have a range of neuroprotective properties. GLP-1Rs are expressed in the hippocampal area of the brain an important site of adult neurogenesis and maintenance of cognition and memory formation. Therefore, if GLP-1 analogues can cross the blood brain barrier, diffuse through the brain to reach the receptors and most importantly activate them, their neuroprotective effects may be realized.</p> <p>Results</p> <p>In the present study we profiled the GLP-1 receptor agonists liraglutide (Victoza) and lixisenatide (Lyxumia). We measured the kinetics of crossing the blood brain barrier (BBB), activation of the GLP-1R by measuring cAMP levels, and physiological effects in the brain on neuronal stem cell proliferation and neurogenesis. Both drugs were able to cross the BBB. Lixisenatide crossed the BBB at all doses tested (2.5, 25, or 250 nmol/kg bw ip.) when measured 30 min post-injection and at 2.5-25 nmol/kg bw ip. 3 h post-injection. Lixisenatide also enhanced neurogenesis in the brain. Liraglutide crossed the BBB at 25 and 250 nmol/kg ip. but no increase was detectable at 2.5 nmol/kg ip. 30 min post-injection, and at 250 nmol/kg ip. at 3 h post-injection. Liraglutide and lixisenatide enhanced cAMP levels in the brain, with lixisenatide being more effective.</p> <p>Conclusions</p> <p>Our results suggest that these novel incretin analogues cross the BBB and show physiological activity and neurogenesis in the brain, which may be of use as a treatment of neurodegenerative diseases.</p

Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus

<p>Abstract</p> <p>Background</p> <p><it>MCF2L2, ADIPOQ </it>and <it>SOX2 </it>genes are located in chromosome 3q26-27, which is linked to diabetic nephropathy (DN). <it>ADIPOQ </it>and <it>SOX2 </it>genetic polymorphisms are found to be associated with DN. In the present study, we first investigated the association between <it>MCF2L2 </it>and DN, and then evaluated effects of these three genes on the development of DN.</p> <p>Methods</p> <p>A total of 1177 type 1 diabetes patients with and without DN from the GoKinD study were genotyped with TaqMan allelic discrimination. All subjects were of European descent.</p> <p>Results</p> <p>Leu359Ile T/G variant in the <it>MCF2L2 </it>gene was found to be associated with DN in female subjects (P = 0.017, OR = 0.701, 95%CI 0.524-0.938) but not in males. The GG genotype carriers among female patients with DN had tendency decreased creatinine and cystatin levels compared to the carriers with either TT or TG genotypes. This polymorphism <it>MCF2L2-</it>rs7639705 together with SNPs of <it>ADIPOQ</it>-rs266729 and <it>SOX2</it>-rs11915160 had combined effects on decreased risk of DN in females (P = 0.001).</p> <p>Conclusion</p> <p>The present study provides evidence that <it>MCF2L2</it>, <it>ADIPOQ </it>and <it>SOX2 </it>genetic polymorphisms have effects on the resistance of DN in female T1D patients, and suggests that the linkage with DN in chromosome 3q may be explained by the cumulated genetic effects.</p

Home: The place the older adult can not imagine living without

<p>Abstract</p> <p>Background</p> <p>Rapidly aging populations with an increased desire to remain at home and changes in health policy that promote the transfer of health care from formal places, as hospitals and institutions, to the more informal setting of one's home support the need for further research that is designed specifically to understand the experience of home among older adults. Yet, little is known among health care providers about the older adult's experience of home. The aim of this study was to understand the experience of home as experienced by older adults living in a rural community in Sweden.</p> <p>Methods</p> <p>Hermeneutical interpretation, as developed by von Post and Eriksson and based on Gadamer's philosophical hermeneutics, was used to interpret interviews with six older adults. The interpretation included a self examination of the researcher's experiences and prejudices and proceeded through several readings which integrated the text with the reader, allowed new questions to emerge, fused the horizons, summarized main and sub-themes and allowed a new understanding to emerge.</p> <p>Results</p> <p>Two main and six sub-themes emerged. Home was experienced as the place the older adult could not imagine living without but also as the place one might be forced to leave. The older adult's thoughts vacillated between the well known present and all its comforts and the unknown future with all its questions and fears, including the underlying threat of loosing one's home.</p> <p>Conclusions</p> <p>Home has become so integral to life itself and such an intimate part of the older adult's being that when older adults lose their home, they also loose the place closest to their heart, the place where they are at home and can maintain their identity, integrity and way of living. Additional effort needs to be made to understand the older adult's experience of home within home health care in order to minimize intrusion and maximize care. There is a need to more fully explore the older adult's experience with health care providers in the home and its impact on the older adult's sense of "being at home" and their health and overall well-being.</p

Studies of the Decay B+- -> D_CP K+-

We report studies of the decay B+- -> D_CP K+-, where D_CP denotes neutral D mesons that decay to CP eigenstates. The analysis is based on a 29.1/fb data sample of collected at the \Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e+ e- storage ring. Ratios of branching fractions of Cabibbo-suppressed to Cabibbo-favored processes involving D_CP are determined to be B(B- -> D_1 K-)/B(B- -> D_1 pi-)=0.125 +- 0.036 +- 0.010 and B(B- -> D_2 K-)/B(B- -> D_2 pi-)=0.119 +- 0.028 +- 0.006, where indices 1 and 2 represent the CP=+1 and CP=-1 eigenstates of the D0 - anti D0 system, respectively. We also extract the partial rate asymmetries for B+- -> D_CP K+-, finding A_1 = 0.29 +- 0.26 +- 0.05 and A_2 = -0.22 +- 0.24 +- 0.04.Comment: 10 pages, 2 figures, submitted to Physical Review Letter

The Ups and Downs of Mutation Frequencies during Aging Can Account for the Apert Syndrome Paternal Age Effect

Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2). The incidence of this disease increases with the age of the father (paternal age effect), and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features

Sheldon Spectrum and the Plankton Paradox: Two Sides of the Same Coin : A trait-based plankton size-spectrum model

The Sheldon spectrum describes a remarkable regularity in aquatic ecosystems: the biomass density as a function of logarithmic body mass is approximately constant over many orders of magnitude. While size-spectrum models have explained this phenomenon for assemblages of multicellular organisms, this paper introduces a species-resolved size-spectrum model to explain the phenomenon in unicellular plankton. A Sheldon spectrum spanning the cell-size range of unicellular plankton necessarily consists of a large number of coexisting species covering a wide range of characteristic sizes. The coexistence of many phytoplankton species feeding on a small number of resources is known as the Paradox of the Plankton. Our model resolves the paradox by showing that coexistence is facilitated by the allometric scaling of four physiological rates. Two of the allometries have empirical support, the remaining two emerge from predator-prey interactions exactly when the abundances follow a Sheldon spectrum. Our plankton model is a scale-invariant trait-based size-spectrum model: it describes the abundance of phyto- and zooplankton cells as a function of both size and species trait (the maximal size before cell division). It incorporates growth due to resource consumption and predation on smaller cells, death due to predation, and a flexible cell division process. We give analytic solutions at steady state for both the within-species size distributions and the relative abundances across species

Optimization of fixation methods for observation of bacterial cell morphology and surface ultrastructures by atomic force microscopy

Fixation ability of five common fixation solutions, including 2.5% glutaraldehyde, 10% formalin, 4% paraformaldehyde, methanol/acetone (1:1), and ethanol/acetic acid (3:1) were evaluated by using atomic force microscopy in the present study. Three model bacteria, i.e., Escherichia coli, Pseudomonas putida, and Bacillus subtilis were applied to observe the above fixation methods for the morphology preservation of bacterial cells and surface ultrastructures. All the fixation methods could effectively preserve cell morphology. However, for preserving bacterial surface ultrastructures, the methods applying aldehyde fixations performed much better than those using alcohols, since the alcohols could detach the surface filaments (i.e., flagella and pili) significantly. Based on the quantitative and qualitative assessments, the 2.5% glutaraldehyde was proposed as a promising fixation solution both for observing morphology of both bacterial cell and surface ultrastructures, while the methonal/acetone mixture was the worst fixation solution which may obtain unreliable results

Young patients', parents', and survivors' communication preferences in paediatric oncology: Results of online focus groups

Contains fulltext : 51596.pdf ( ) (Open Access)BACKGROUND: Guidelines in paediatric oncology encourage health care providers to share relevant information with young patients and parents to enable their active participation in decision making. It is not clear to what extent this mirrors patients' and parents' preferences. This study investigated communication preferences of childhood cancer patients, parents, and survivors of childhood cancer. METHODS: Communication preferences were examined by means of online focus groups. Seven patients (aged 8-17), 11 parents, and 18 survivors (aged 8-17 at diagnosis) participated. Recruitment took place by consecutive inclusion in two Dutch university oncological wards. Questions concerned preferences regarding interpersonal relationships, information exchange and participation in decision making. RESULTS: Participants expressed detailed and multi-faceted views regarding their needs and preferences in communication in paediatric oncology. They agreed on the importance of several interpersonal and informational aspects of communication, such as honesty, support, and the need to be fully informed. Participants generally preferred a collaborative role in medical decision making. Differences in views were found regarding the desirability of the patient's presence during consultations. Patients differed in their satisfaction with their parents' role as managers of the communication. CONCLUSION: Young patients' preferences mainly concur with current guidelines of providing them with medical information and enabling their participation in medical decision making. Still, some variation in preferences was found, which faces health care providers with the task of balancing between the sometimes conflicting preferences of young cancer patients and their parents

Simple model systems: a challenge for Alzheimer's disease

The success of biomedical researches has led to improvement in human health and increased life expectancy. An unexpected consequence has been an increase of age-related diseases and, in particular, neurodegenerative diseases. These disorders are generally late onset and exhibit complex pathologies including memory loss, cognitive defects, movement disorders and death. Here, it is described as the use of simple animal models such as worms, fishes, flies, Ascidians and sea urchins, have facilitated the understanding of several biochemical mechanisms underlying Alzheimer's disease (AD), one of the most diffuse neurodegenerative pathologies. The discovery of specific genes and proteins associated with AD, and the development of new technologies for the production of transgenic animals, has helped researchers to overcome the lack of natural models. Moreover, simple model systems of AD have been utilized to obtain key information for evaluating potential therapeutic interventions and for testing efficacy of putative neuroprotective compounds