Intrahepatic persistent fetal right umbilical vein: a retrospective study

Introduction: To appraise the incidence and value of intrahepatic persistent right umbilical vein (PRUV). Methods: This was a single-center study. Records of all women with a prenatal diagnosis of intrahepatic PRUV were reviewed. The inclusion criteria were women with gestational age greater than 13 weeks of gestation. Exclusion criteria were fetuses with situs abnormalities, due to the hepatic venous ambiguity, and extrahepatic PRUV. The primary outcome was the incidence of intrahepatic PRUV in our cohort. The secondary outcomes were associated malformations. Results: 219/57,079 cases (0.38%) of intrahepatic PRUV were recorded. The mean gestational age at diagnosis was 21.8 ± 2.9 weeks of gestations. PRUV was isolated in the 76.7%, while in 23.3% was associated with other major or minor abnormalities. The most common associated abnormalities were cardiovascular abnormalities (8.7%), followed by genitourinary abnormalities (6.4%), skeletal abnormalities (4.6%), and central nervous system abnormalities (4.1%). Within the cardiovascular abnormalities, the most common one was ventricular septal defect (six cases). Conclusion: In most cases PRUV is an isolated finding. Associated minor or major malformations are presented in the 23.3% of the cases, so this finding should prompt detailed prenatal assessment of the fetus, with particular regard to cardiovascular system

The IkB kinase inhibitor nuclear factor-kB essential modulator–binding domain peptide for inhibition of balloon injury-induced neointimal formation

Objective—The activation of nuclear factor-kB (NF-kB) is a crucial step in the arterial wall’s response to injury. The identification and characterization of the NF-kB essential modulator– binding domain (NBD) peptide, which can block the activation of the IkB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-kB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation.<br></br> Methods and Results—In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 microg/site) significantly reduced the number of proliferating cells at day 7 (by 40%; P<0.01) and reduced injury-induced neointimal formation (by 50%; P<0.001) at day 14. These effects were associated with a significant reduction of NF-kB activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 micromol/L) reduced rat smooth muscle cell proliferation, migration, and invasion in vitro. Similar results were observed in apolipoprotein E-/-, mice in which the NBD peptide (150 microg/site) reduced wire-induced neointimal formation at day 28 (by 47%; P<0.01).<br></br> Conclusion—The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-kB activation

UK Breastfeeding Helpline support: An investigation of influences upon satisfaction

Background Incentive or reward schemes are becoming increasingly popular to motivate healthy lifestyle behaviours. In this paper, insights from a qualitative and descriptive study to investigate the uptake, impact and meanings of a breastfeeding incentive intervention integrated into an existing peer support programme (Star Buddies) are reported. The Star Buddies service employs breastfeeding peer supporters to support women across the ante-natal, intra-partum and post-partum period. Methods In a disadvantaged area of North West England, women initiating breastfeeding were recruited by peer supporters on the postnatal ward or soon after hospital discharge to participate in an 8 week incentive (gifts and vouchers) and breastfeeding peer supporter intervention. In-depth interviews were conducted with 26 women participants who engaged with the incentive intervention, and a focus group was held with the 4 community peer supporters who delivered the intervention. Descriptive analysis of routinely collected data for peer supporter contacts and breastfeeding outcomes before and after the incentive intervention triangulated and retrospectively provided the context for the qualitative thematic analysis. Results A global theme emerged of 'incentives as connectors', with two sub-themes of 'facilitating connections' and 'facilitating relationships and wellbeing'. The incentives were linked to discussion themes and gift giving facilitated peer supporter access for proactive weekly home visits to support women. Regular face to face contacts enabled meaningful relationships and new connections within and between the women, families, peer supporters and care providers to be formed and sustained. Participants in the incentive scheme received more home visits and total contact time with peer supporters compared to women before the incentive intervention. Full participation levels and breastfeeding rates at 6-8 weeks were similar for women before and after the incentive intervention. Conclusion The findings suggest that whilst the provision of incentives might not influence women's intentions or motivations to breastfeed, the connections forged provided psycho-social benefits for both programme users and peer supporters

Deformation and flow of a two-dimensional foam under continuous shear

We investigate the flow properties of a two-dimensional aqueous foam submitted to a quasistatic shear in a Couette geometry. A strong localization of the flow (shear banding) at the edge of the moving wall is evidenced, characterized by an exponential decay of the average tangential velocity. Moreover, the analysis of the rapid velocity fluctuations reveals self-similar dynamical structures consisting of clusters of bubbles rolling as rigid bodies. To relate the instantaneous (elastic) and time-averaged (plastic) components of the strain, we develop a stochastic model where irreversible rearrangements are activated by local stress fluctuations originating from the rubbing of the wall. This model gives a complete description of our observations and is also consistent with data obtained on granular shear bands by other groups.Comment: 5 pages, 2 figure

Width distribution of contact lines on a disordered substrate

We have studied the roughness of a contact line of a liquid meniscus on a disordered substrate by measuring its width distribution. The comparison between the measured width distribution and the width distribution calculated in previous works, extended here to the case of open boundary conditions, confirms that the Joanny-de Gennes model is not sufficient to describe the dynamics of contact lines at the depinning threshold. This conclusion is in agreement with recent measurements which determine the roughness exponent by extrapolation to large system sizes.Comment: 4 pages, 3 figure

Callers’ attitudes and experiences of UK breastfeeding helpline support

Background: Breastfeeding peer support, is considered to be a key intervention for increasing breastfeeding duration rates. Whilst a number of national organisations provide telephone based breastfeeding peer support, to date there have been no published evaluations into callers’ experiences and attitudes of this support. In this study we report on the descriptive and qualitative insights provided by 908 callers as part of an evaluation of UK-based breastfeeding helpline(s). Methods: A structured telephone interview, incorporating Likert scale responses and open-ended questions was undertaken with 908 callers over May to August, 2011 to explore callers’ experiences of the help and support received via the breastfeeding helpline(s). Results: Overall satisfaction with the helpline was high, with the vast majority of callers’ recalling positive experiences of the help and support received. Thematic analysis was undertaken on all qualitative and descriptive data recorded during the evaluation, contextualised within the main areas addressed within the interview schedule in terms of ‘contact with the helplines’; ‘experiences of the helpline service’, ‘perceived effectiveness of support provision’ and ‘impact on caller wellbeing’. Conclusion: Callers valued the opportunity for accessible, targeted, non-judgmental and convenient support. Whilst the telephone support did not necessarily influence women’s breastfeeding decisions, the support they received left them feeling reassured, confident and more determined to continue breastfeeding. We recommend extending the helpline service to ensure support can be accessed when needed, and ongoing training and support for volunteers. Further advertising and promotion of the service within wider demographic groups is warranted

Genetic susceptibility to aspergillosis in allogeneic stem-cell transplantation

Invasive aspergillosis (IA) is a major threat to positive outcomes for allogeneic stem-cell transplantation (allo-SCT) patients. Despite presenting similar degrees of immunosuppression, not all individuals at-risk ultimately develop infection. Therefore, the traditional view of neutropenia as a key risk factor for aspergillosis needs to be accommodated within new conceptual advances on host immunity and its relationship to infection. Polymorphisms in innate immune genes, such as those encoding TLRs, cytokines and cytokine receptors, have recently been associated with susceptibility to IA in allo-SCT recipients. This suggests that understanding host-pathogen interactions at the level of host genetic susceptibility will allow the formulation of new targeted and patient-tailored antifungal therapeutics, including improved donor screening.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/65962/2009, SFRH/BPD/46292/2008Specific Targeted Research Projects MANASP (LSHE-CT-2006), contract number 037899 (FP6), Italian Project PRIN2007KLCKP8_004

Proteomic analysis of a filaggrin-deficient skin organoid model shows evidence of increased transcriptional-translational activity, keratinocyte-immune crosstalk and disordered axon guidance

Background: Atopic eczema is an itchy inflammatory disorder characterised by skin barrier dysfunction. Loss-of-function mutations in the gene encoding filaggrin ( FLG) are a major risk factor, but the mechanisms by which filaggrin haploinsufficiency leads to atopic inflammation remain incompletely understood. Skin as an organ that can be modelled using primary cells in vitro provides the opportunity for selected genetic effects to be investigated in detail.Methods: Primary human keratinocytes and donor-matched primary fibroblasts from healthy individuals were used to create skin organoid models with and without siRNA-mediated knockdown of FLG. Biological replicate sets of organoids were assessed using histological, functional and biochemical measurements.Results: FLG knockdown leads to subtle changes in histology and ultrastructure including a reduction in thickness of the stratum corneum and smaller, less numerous keratohyalin granules. Immature organoids showed evidence of barrier impairment with FLG knockdown, but the mature organoids showed no difference in transepidermal water loss, water content or dye penetration. There was no difference in epidermal ceramide content. Mass spectrometry proteomic analysis detected &gt;8000 proteins per sample. Gene ontology and pathway analyses identified an increase in transcriptional and translational activity but a reduction in proteins contributing to terminal differentiation, including caspase 14, dermokine, AKT1 and TGF-beta-1. Aspects of innate and adaptive immunity were represented in both the up-regulated and down-regulated protein groups, as was the term 'axon guidance'.Conclusions: This work provides further evidence for keratinocyte-specific mechanisms contributing to immune and neurological, as well as structural, aspects of skin barrier dysfunction. Individuals with filaggrin deficiency may derive benefit from future therapies targeting keratinocyte-immune crosstalk and neurogenic pruritus.</p

Cellular dissection of psoriasis for transcriptome analyses and the post-GWAS era

Abstract Background Genome-scale studies of psoriasis have been used to identify genes of potential relevance to disease mechanisms. For many identified genes, however, the cell type mediating disease activity is uncertain, which has limited our ability to design gene functional studies based on genomic findings. Methods We identified differentially expressed genes (DEGs) with altered expression in psoriasis lesions (n = 216 patients), as well as candidate genes near susceptibility loci from psoriasis GWAS studies. These gene sets were characterized based upon their expression across 10 cell types present in psoriasis lesions. Susceptibility-associated variation at intergenic (non-coding) loci was evaluated to identify sites of allele-specific transcription factor binding. Results Half of DEGs showed highest expression in skin cells, although the dominant cell type differed between psoriasis-increased DEGs (keratinocytes, 35%) and psoriasis-decreased DEGs (fibroblasts, 33%). In contrast, psoriasis GWAS candidates tended to have highest expression in immune cells (71%), with a significant fraction showing maximal expression in neutrophils (24%, P < 0.001). By identifying candidate cell types for genes near susceptibility loci, we could identify and prioritize SNPs at which susceptibility variants are predicted to influence transcription factor binding. This led to the identification of potentially causal (non-coding) SNPs for which susceptibility variants influence binding of AP-1, NF-κB, IRF1, STAT3 and STAT4. Conclusions These findings underscore the role of innate immunity in psoriasis and highlight neutrophils as a cell type linked with pathogenetic mechanisms. Assignment of candidate cell types to genes emerging from GWAS studies provides a first step towards functional analysis, and we have proposed an approach for generating hypotheses to explain GWAS hits at intergenic loci.http://deepblue.lib.umich.edu/bitstream/2027.42/109537/1/12920_2013_Article_485.pd

Functional and proteomic analysis of a full thickness filaggrin-deficient skin organoid model

Background: Atopic eczema is an itchy inflammatory disorder characterised by skin barrier dysfunction. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a major risk factor, but the mechanisms by which filaggrin haploinsufficiency leads to atopic inflammation remain incompletely understood. Skin as an organ that can be modelled using primary cells in vitro provides the opportunity for selected genetic effects to be investigated in detail. Methods: Primary human keratinocytes and donor-matched primary fibroblasts from healthy individuals were used to create skin organoid models with and without siRNA-mediated knockdown of FLG. Biological replicate sets of organoids were assessed using histological, functional and biochemical measurements. Results: FLG knockdown leads to subtle changes in histology and ultrastructure including a reduction in thickness of the stratum corneum and smaller, less numerous keratohyalin granules. Immature organoids showed some limited evidence of barrier impairment with FLG knockdown, but the mature organoids showed no difference in transepidermal water loss, water content or dye penetration. There was no difference in epidermal ceramide content. Mass spectrometry proteomic analysis detected &gt;8000 proteins per sample. Gene ontology and pathway analyses identified an increase in transcriptional and translational activity but a reduction in proteins contributing to terminal differentiation, including caspase 14, dermokine, AKT1 and TGF-beta-1. Aspects of innate and adaptive immunity were represented in both the up-regulated and down-regulated protein groups, as was the term ‘axon guidance’. Conclusions: This work provides further evidence for keratinocyte-specific mechanisms contributing to immune and neurological, as well as structural, aspects of skin barrier dysfunction. Individuals with filaggrin deficiency may derive benefit from future therapies targeting keratinocyte-immune crosstalk and neurogenic pruritus