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

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

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

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

Structured request form in musculoskeletal radiology examinations (CONCERTO): results of an expert Delphi consensus—structured radiology request form for correct classification of patients to undergo radiological examinations of the Italian Society of Medical and Interventional Radiology (SIRM), the Italian Society of Rheumatology (SIR) and the Italian Society of Orthopedics and Traumatology (SIOT)

Purpose: To describe a Delphi consensus for the realization of a structured radiology request form for patients undergoing musculoskeletal imaging. Methods: A steering committee (four radiologists, a rheumatologist and an orthopedic surgeon) proposed a form to an expert panel (30 members, ten radiologists, ten rheumatologists and ten orthopedic surgeons). Through an online survey, the panelists voted on their level of agreement with the statements of the form using a 10-point Likert scale (1: no agreement; 10: total agreement) in a three-round process. A combination of two distinct criteria, a mean agreement level ≥ 8 and a percentage of at least 75% of responses with a value ≥ 8, was deemed as acceptable. Results: The form achieved high median ratings in all the assessed key features. During the first round, all items met the threshold to be advanced as unmodified in the next round. Additional proposed items were considered and introduced in the next round (six items in Section 1, five items in Section 2, ten items in Section 3, 11 items in Section 4, six items in Section 5, eight items in Section 6, ten items in Section 7 and eight items in Section 8). Of these items, in round 3, only six reached the threshold to be integrated into the final form. Conclusions: Implementation of a structured radiology request form can improve appropriateness and collaboration between clinicians and radiologists in musculoskeletal imaging

The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis

Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases

A network model of Italy shows that intermittent regional strategies can alleviate the COVID-19 epidemic

The COVID-19 epidemic hit Italy particularly hard, yielding the implementation of strict national lockdown rules. Previous modelling studies at the national level overlooked the fact that Italy is divided into administrative regions which can independently oversee their own share of the Italian National Health Service. Here, we show that heterogeneity between regions is essential to understand the spread of the epidemic and to design effective strategies to control the disease. We model Italy as a network of regions and parameterize the model of each region on real data spanning over two months from the initial outbreak. We confirm the effectiveness at the regional level of the national lockdown strategy and propose coordinated regional interventions to prevent future national lockdowns, while avoiding saturation of the regional health systems and mitigating impact on costs. Our study and methodology can be easily extended to other levels of granularity to support policy- and decision-makers

An analysis of IL-36 signature genes and individuals with IL1RL2 knockout mutations validates IL-36 as a psoriasis therapeutic target

Interleukin (IL)-36a, IL-36b, and IL-36g are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (TH17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. This enabled us to demonstrate a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associatedwith the disease in genome-wide studies. Next, we investigated the impact of in vivo and ex vivo IL-36 receptor blockade using a neutralizing antibody or a recombinant antagonist. Both inhibitors had marked anti-inflammatory effects on psoriatic skin, demonstrated by statistically significant reductions in IL-17 expression, keratinocyte activation, and leukocyte infiltration. Finally, we explored the potential safety profile associated with IL-36 blockade by phenotyping 12 individuals carrying knockout mutations of the IL-36 receptor gene. We found that normal immune function was broadly preserved in these individuals, suggesting that IL-36 signaling inhibition would not substantially compromise host defenses. These observations, which integrate the results of transcriptomics and model system analysis, pave the way for early-stage clinical trials of IL-36 antagonists