Langerhans cell histiocytosis presenting as a blueberry muffin rash

Langerhans cells, often referred to as the “macrophages of the skin”, are dendritic cells that normally reside in the epidermis and papillary dermis. Just like macrophages, they function as antigen-presenting cells that activate naive T cells. Certain mutations such as those involving the BRAF gene can cause unopposed production of Langerhans Cells, which is known as Langerhans Cell Histiocytosis (LCH). LCH triggers an inflammatory immune response that causes systemic manifestations such as fever and fatigue, as well as other manifestations depending on the affected organs. The pathogenesis behind LCH remains poorly understood. It is still unknown whether it is a neoplastic process or a reactive cancer-mimicking illness. Diagnosis of LCH is confirmed by biopsy, and treatment is largely dependent on the extent and severity of the disease. Common treatments include corticosteroids, excision, radiation, and chemotherapy. We present a case of a 1-year-old Saudi male with LCH

Childhood cancer and hematological disorders negatively affect spermatogonial quantity at diagnosis : a retrospective study of a male fertility preservation cohort

Peer reviewe

Essential Oils from Artemisia herba alba Asso., Maticaria Recutita L., and Dittrichia Viscosa L. (Asteraceae): A Promising Source of Eco-Friendly Agents to Control Callosobruchus maculatus Fab. Warehouse Pest

Callosobruchus maculatus (Fab.) (C. maculatus) is one of the major pests of legume seeds in storage causing significant damage, leading to food insecurity and low income for farmers. This work was planned to develop eco-friendly agents from essential oils of Artemisia herba alba Asso. (AEO), Maticaria Recutita L. (MEO), and Dittrichia Viscosa L. (DEO) to control C. maculatus. To achieve this goal, essential oils (EOs) were extracted by hydro-distillation using Clevenger apparatus before being characterized by GC-MS. EOs were used for testing purposes using three different tests, namely, inhalation toxicity, contact toxicity, and repellency tests. GC-MS analysis of EOs showed the presence of 16 potentially active compounds in AEO and 38 in MEO, whilst 15 compounds were identified in DEO. AEO was higher in thujone (57.6%) and chrysanthenone (11.8%). Santolina alcohol (40.7%) and germacrene D (8.9%) were the major compounds identified in MEO, whereas isocostic acid (72.3%) was the chief compound of DEO. The obtained findings showed that the studied EOs showed considerable insecticidal activity against C. maculatus with a lethal dose (LC50) of 3.78, 8.86, and 14.34 μL/1 liter of air by AEO, MEO, and DEO, respectively. At 1 μL/1 liter of air, the oviposition reduction rate was 90.02%, 70.65%, and 48.23% by AEO, MEO, and DEO, respectively, whereas the emergence reduction rate was 87.32%, 60.08%, and 32.24% by AEO, MEO, and DEO, respectively. With increasing doses up to 20 μL/L, the reduction of individual emergence reached 98.8% by AEO of 24 h after treatment. AEO, MEO, and DEO showed significant repellent effects against adults of C. maculatus with repulsion percentages of 60.83%, 50.83%, and 72.5%, respectively. The outcome of this work suggests that the essential oils of the studied plants, particularly Artemisia herba alba Asso. oils, can constitute a natural and environmentally friendly alternative to develop new bioinsecticides for the control of C. maculatus.</jats:p

Effect of parental and ART treatment characteristics on perinatal outcomes

Funding This study was funded by Foreest Medical School, Alkmaar, the Netherlands (grants: FIO 1307 and FIO 1505). Acknowledgements We thank the Foundation of the Netherlands Perinatal Registry for permission to use their registry data (approval number 12.43). We thank G.P. Kroon and H.W.W. van Leeuwen for their assistance in collecting the necessary IVF data. Furthermore, we thank the medical informatics students A. Wong for the first deterministic data linkage and S. Wortel for assisting in the database validation process. In addition, we thank all care providers for the registration of the perinatal data as well as the IVF laboratory data.Peer reviewedPublisher PD

Altered gene expression of Staphylococcus aureus upon interaction with human endothelial cells

Staphylococcus aureus is isolated from a substantial number of patients with infective endocarditis who are not known to have predisposing heart abnormalities. It has been suggested that the infection is initiated by the direct binding of S. aureus to human vascular endothelium. To determine the mutual response of the endothelial cells and the bacteria, we studied the interaction between S. aureus and human vascular endothelium. Scanning electron microscopic analyses showed that binding of S. aureus to human umbilical vein endothelial cells (HUVEC) mainly occurred via thread-like protrusions extending from the cell surface. Bound bacteria appeared to be internalized via retraction of the protrusions into newly formed invaginations of the endothelial cell surface. The growth phase of S. aureus had a major impact on the interaction with HUVEC. Logarithmically growing bacteria showed increased binding to, and were more readily internalized by, HUVEC compared to stationary-phase bacteria. To assess the bacterial response to the cellular environments an expression library of S. aureus was used to identify genes whose expression was induced after 4 h of exposure to HUVEC. The identified genes could be divided into different categories based on the functions of the encoded proteins (transport, catabolism, biosynthesis, and DNA repair). Further analyses of five of the S. aureus transposon clones showed that HUVEC as well as human serum are stimuli for triggering gene expression in S. aureus

Development of the Pulmonary Vein and the Systemic Venous Sinus: An Interactive 3D Overview

Knowledge of the normal formation of the heart is crucial for the understanding of cardiac pathologies and congenital malformations. The understanding of early cardiac development, however, is complicated because it is inseparably associated with other developmental processes such as embryonic folding, formation of the coelomic cavity, and vascular development. Because of this, it is necessary to integrate morphological and experimental analyses. Morphological insights, however, are limited by the difficulty in communication of complex 3D-processes. Most controversies, in consequence, result from differences in interpretation, rather than observation. An example of such a continuing debate is the development of the pulmonary vein and the systemic venous sinus, or “sinus venosus”. To facilitate understanding, we present a 3D study of the developing venous pole in the chicken embryo, showing our results in a novel interactive fashion, which permits the reader to form an independent opinion. We clarify how the pulmonary vein separates from a greater vascular plexus within the splanchnic mesoderm. The systemic venous sinus, in contrast, develops at the junction between the splanchnic and somatic mesoderm. We discuss our model with respect to normal formation of the heart, congenital cardiac malformations, and the phylogeny of the venous tributaries

Comprehensive Gene-Expression Survey Identifies Wif1 as a Modulator of Cardiomyocyte Differentiation

During chicken cardiac development the proepicardium (PE) forms the epicardium (Epi), which contributes to several non-myocardial lineages within the heart. In contrast to Epi-explant cultures, PE explants can differentiate into a cardiomyocyte phenotype. By temporal microarray expression profiles of PE-explant cultures and maturing Epi cells, we identified genes specifically associated with differentiation towards either of these lineages and genes that are associated with the Epi-lineage restriction. We found a central role for Wnt signaling in the determination of the different cell lineages. Immunofluorescent staining after recombinant-protein incubation in PE-explant cultures indicated that the early upregulated Wnt inhibitory factor-1 (Wif1), stimulates cardiomyocyte differentiation in a similar manner as Wnt stimulation. Concordingly, in the mouse pluripotent embryogenic carcinoma cell line p19cl6, early and late Wif1 exposure enhances and attenuates differentiation, respectively. In ovo exposure of the HH12 chicken embryonic heart to Wif1 increases the Tbx18-positive cardiac progenitor pool. These data indicate that Wif1 enhances cardiomyogenesis

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

Optimizing Yield and Quality of Silage and Hay for Pea–Barley Mixtures Ratio under Irrigated Arid Environments

The changing climate, water scarcity, reduction in the land area under forage crops, expanding ruminant population, burgeoning demands for milk and meat production and food security concerns all insist on a necessary increase in forage production and quality. Cereal–legume mixed intercropping offers a biologically superior option to boost herbage yield and quality of preserved fodder (hay and silage), provided that rationalization of the component crop’s proportional ratio is performed. Therefore, the current study was conducted to determine the forage yield and quality of barley (Hordeum vulgare L.) and pea (Pisum sativum L.) mixtures at the ratios 100:0, 75:25, 50:50, 25:75 and 0:100. The experiment was laid out in the regular arrangement of a randomized complete block design with three replicates. The results exhibited that forage quality was significantly affected by the mixture ratio. There was a significant improvement in protein, fiber rate and digestibility from the mixture. The ratios of barley and pea with 50:50 and 25:75 produced the maximum productivity and the best quality of forage. Regarding forage preservation, silage recorded higher contents of crude protein, ash and lower fiber contents than hay. Among seed mixtures, 0:100 ratio of barley–pea yielded the highest quality of silage with the maximum crude protein, ash and digestibility with lowest fiber contents