Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?

Background: The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake. Method: A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS). Results: One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS. Conclusion: This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies

Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery

Holographic Vitrification

We establish the existence of stable and metastable stationary black hole bound states at finite temperature and chemical potentials in global and planar four-dimensional asymptotically anti-de Sitter space. We determine a number of features of their holographic duals and argue they represent structural glasses. We map out their thermodynamic landscape in the probe approximation, and show their relaxation dynamics exhibits logarithmic aging, with aging rates determined by the distribution of barriers.Comment: 100 pages, 25 figure

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

B-cell lymphoma in retrieved femoral heads: a long term follow up

<p>Abstract</p> <p>Background</p> <p>A relatively high incidence of pathological conditions in retrieved femoral heads, including a group of patients having low grade B-cell lymphoma, has been described before. At short term follow up none of these patients with low-grade B-cell lymphoma showed evidence of systemic disease. However, the long term follow up of these patients is not known.</p> <p>Methods</p> <p>From November 1994 up to and including December 2005 we screened all femoral heads removed at the time of primary total hip replacement histopathologically and included them in the bone banking protocol according to the guidelines of the American Associations of Tissue Banks (AATB) and the European Association of Musculo-Skeletal Transplantation (EAMST). We determined the percentage of B-cell lymphoma in all femoral heads and in the group that fulfilled all criteria of the bone banking protocol and report on the long-term follow-up.</p> <p>Results</p> <p>Of 852 femoral heads fourteen (1.6%) were highly suspicious for low-grade B-cell lymphoma. Of these 852 femoral heads, 504 were eligible for bone transplantation according to the guidelines of the AATB and the EAMST. Six femoral heads of this group of 504 were highly suspicious for low-grade B-cell lymphoma (1.2%). At long term follow up two (0.2%) of all patients developed systemic malignant disease and one of them needed medical treatment for her condition.</p> <p>Conclusion</p> <p>In routine histopathological screening we found variable numbers of low-grade B-cell lymphoma throughout the years, even in a group of femoral heads that were eligible for bone transplantation. Allogenic transmission of malignancy has not yet been reported on, but surviving viruses are proven to be transmissible. Therefore, we recommend the routine histopathological evaluation of all femoral heads removed at primary total hip arthroplasty as a tool for quality control, whether the femoral head is used for bone banking or not.</p

Relationships between paranoid thinking, self-esteem and the menstrual cycle.

This study aimed to investigate whether paranoid experiences and levels of self-esteem fluctuate over the menstrual cycle and whether levels of self-esteem are lower when perceived persecution is felt to be deserved. Measures of anxiety, depression, persecution, deservedness and self-esteem were completed on-line by 278 women over their menstrual cycle. Responses were compared at the paramenstrual (3 days before and after menses onset) and mid-cycle phase. At the paramenstrual phase persecution, negative self-esteem, anxiety and depression were higher and positive self-esteem was lower than at mid-cycle. A greater proportion of women experienced persecution as deserved at the paramenstrual phase. This was associated with higher depression and negative self-esteem scores. Increased levels of deservedness significantly strengthened the relationship between persecution and negative, but not positive, self-esteem. These findings suggest that the paramenstrual phase is a time of vulnerability to increased paranoid experiences, an increased likelihood that feelings of persecution will feel deserved and lowered self-esteem. The findings support the view that interpersonal sensitivities may be key to menstrual cycle symptoms and have an impact on relationships. Further, the study illustrated that ideas developed for psychosis could make a valuable contribution to understanding and managing this aspect of menstruation-related distress

"You've got a friend in me": can social networks mediate the relationship between mood and MCI?

engagement is beneficial to both mental health and cognition, and represents a potentially modifiable factor. Consequently this study explored this association and assessed whether the relationship between mild cognitive impairment (MCI) and mood problems was mediated by social networks. Methods: This study includes an analysis of data from the Cognitive Function and Ageing Study Wales (CFAS Wales). CFAS Wales Phase 1 data were collected from 2010-2013 by conducting structured interviews with older people aged over 65 years of age living in urban and rural areas of Wales, and included questions that assessed cognitive functioning, mood, and social networks. Regression analyses were used to investigate the associations between individual variables and the mediating role of social networks. Results: Having richer social networks was beneficial to both mood and cognition. Participants in the MCI category had weaker social networks than participants without cognitive impairment, whereas stronger social networks were associated with a decrease in the odds of experiencing mood problems, suggesting that they may offer a protective effect against anxiety and depression. Regression analyses revealed that social networks are a significant mediator of the relationship between MCI and mood problems. Conclusions: These findings are important, as mood problems are a risk factor for progression from MCI to dementia, so interventions that increase and strengthen social networks may have beneficial effects on slowing the progression of cognitive decline

Differences in the signaling pathways of α1A- and α1B-adrenoceptors are related to different endosomal targeting

Aims: To compare the constitutive and agonist-dependent endosomal trafficking of α1A- and α1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype. Methods: Using CypHer5 technology and VSV-G epitope tagged α1A- and α1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot). Results and Conclusions: Constitutive as well as agonist-induced trafficking of α1A and α1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: α1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to β-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. α1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-β-cyclodextrin

Inclusive search for same-sign dilepton signatures in pp collisions at root s=7 TeV with the ATLAS detector

An inclusive search is presented for new physics in events with two isolated leptons (e or mu) having the same electric charge. The data are selected from events collected from p p collisions at root s = 7 TeV by the ATLAS detector and correspond to an integrated luminosity of 34 pb(-1). The spectra in dilepton invariant mass, missing transverse momentum and jet multiplicity are presented and compared to Standard Model predictions. In this event sample, no evidence is found for contributions beyond those of the Standard Model. Limits are set on the cross-section in a fiducial region for new sources of same-sign high-mass dilepton events in the ee, e mu and mu mu channels. Four models predicting same-sign dilepton signals are constrained: two descriptions of Majorana neutrinos, a cascade topology similar to supersymmetry or universal extra dimensions, and fourth generation d-type quarks. Assuming a new physics scale of 1 TeV, Majorana neutrinos produced by an effective operator V with masses below 460 GeV are excluded at 95% confidence level. A lower limit of 290 GeV is set at 95% confidence level on the mass of fourth generation d-type quarks