Hypertrophic pyloric stenosis: tips and tricks for ultrasound diagnosis

We describe a systematic approach to the ultrasound (US) examination of the antropyloric region in children. US is the modality of choice for the diagnosis of hypertrophic pyloric stenosis (HPS). The imaging features of the normal pylorus and the diagnostic findings in HPS are reviewed and illustrated in this pictorial essay. Common difficulties in performing the examination and tips to help overcome them will also be discussed

Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

Imaging of the urinary tract: the role of CT and MRI

Computed tomography (CT) and magnetic resonance imaging (MRI) are increasingly valuable tools for assessing the urinary tract in adults and children. However, their imaging capabilities, while overlapping in some respects, should be considered as complementary, as each technique offers specific advantages and disadvantages both in actual inherent qualities of the technique and in specific patients and with a specific diagnostic question. The use of CT and MRI should therefore be tailored to the patient and the clinical question. For the scope of this article, the advantages and disadvantages of these techniques in children will be considered; different considerations will apply in adult practice

Care of vision and ocular health in diabetic members of a national diabetes organization: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Regular examination and early treatment of diabetic retinopathy can prevent visual loss. The aim of the study was to describe the care of vision and ocular health in people with diabetes in Norway.</p> <p>Methods</p> <p>A cross-sectional questionnaire survey of a random sample (n = 1,887) of the Norwegian Diabetic Associations' (NDA) members was carried out in 2005. Questions were asked about care of vision and ocular health, history of ocular disease and visual symptoms, general medical history and diabetes management. The study was approved by the Regional Committee for Medical Research Ethics.</p> <p>Results</p> <p>The response rate was 74%. Forty-four questionnaires with incomplete data regarding gender, age or type of diabetes were excluded, leaving 1352 cases (52% females) for analysis. 451 (33%) had type 1 and 901 (67%) had type 2 diabetes, the mean duration of diabetes was respectively, 22 (sd ± 14) and 10 (sd ± 9) years. In all 1,052 (78%) had their eyes examined according to guidelines and 1,169 (87%) confirmed to have received information about regular eye examinations. One in two recalled to have received such information from their general practitioner. To have received information about the importance of eye examinations (PR 3.1, 95% CI 2.4 to 4.0), and diabetes duration > 10 years (PR 1.2, 95% CI 1.2 to 1.3), were independently associated with reporting regular eye examinations. A history of diabetic retinopathy was reported by 178 (13%) responders, of which 101 (57%) reported a history of laser treatment. Responders who had regular eye examinations reported more frequently a history of diabetic retinopathy (19% vs. 5%, p < 0.001). The frequency of retinopathy was significantly higher in responders with reported HbA1c values above treatment target (23% vs. 13%, p = 0.001). However, in responders who were not regularly examined, there was no difference in reported frequency of retinopathy with regard to HbA1c level.</p> <p>Conclusion</p> <p>Eight out of ten diabetic members of the NDA had their eyes examined according to current guidelines and the majority was well informed about the risk of vision loss due to diabetes. The results indicate that the reported history of diabetic retinopathy likely underestimates the prevalence of retinopathy.</p

Quantification of Optic Disc Edema during Exposure to High Altitude Shows No Correlation to Acute Mountain Sickness

BACKGROUND: The study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. METHODOLOGY/PRINCIPAL FINDINGS: A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3®) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO₂) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline (p&lt;0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO₂ or HR. CONCLUSIONS/SIGNIFICANCE: Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO₂ and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS

Combining Computational Prediction of Cis-Regulatory Elements with a New Enhancer Assay to Efficiently Label Neuronal Structures in the Medaka Fish

The developing vertebrate nervous system contains a remarkable array of neural cells organized into complex, evolutionarily conserved structures. The labeling of living cells in these structures is key for the understanding of brain development and function, yet the generation of stable lines expressing reporter genes in specific spatio-temporal patterns remains a limiting step. In this study we present a fast and reliable pipeline to efficiently generate a set of stable lines expressing a reporter gene in multiple neuronal structures in the developing nervous system in medaka. The pipeline combines both the accurate computational genome-wide prediction of neuronal specific cis-regulatory modules (CRMs) and a newly developed experimental setup to rapidly obtain transgenic lines in a cost-effective and highly reproducible manner. 95% of the CRMs tested in our experimental setup show enhancer activity in various and numerous neuronal structures belonging to all major brain subdivisions. This pipeline represents a significant step towards the dissection of embryonic neuronal development in vertebrates

Directed Neural Differentiation of Mouse Embryonic Stem Cells Is a Sensitive System for the Identification of Novel Hox Gene Effectors

The evolutionarily conserved Hox family of homeodomain transcription factors plays fundamental roles in regulating cell specification along the anterior posterior axis during development of all bilaterian animals by controlling cell fate choices in a highly localized, extracellular signal and cell context dependent manner. Some studies have established downstream target genes in specific systems but their identification is insufficient to explain either the ability of Hox genes to direct homeotic transformations or the breadth of their patterning potential. To begin delineating Hox gene function in neural development we used a mouse ES cell based system that combines efficient neural differentiation with inducible Hoxb1 expression. Gene expression profiling suggested that Hoxb1 acted as both activator and repressor in the short term but predominantly as a repressor in the long run. Activated and repressed genes segregated in distinct processes suggesting that, in the context examined, Hoxb1 blocked differentiation while activating genes related to early developmental processes, wnt and cell surface receptor linked signal transduction and cell-to-cell communication. To further elucidate aspects of Hoxb1 function we used loss and gain of function approaches in the mouse and chick embryos. We show that Hoxb1 acts as an activator to establish the full expression domain of CRABPI and II in rhombomere 4 and as a repressor to restrict expression of Lhx5 and Lhx9. Thus the Hoxb1 patterning activity includes the regulation of the cellular response to retinoic acid and the delay of the expression of genes that commit cells to neural differentiation. The results of this study show that ES neural differentiation and inducible Hox gene expression can be used as a sensitive model system to systematically identify Hox novel target genes, delineate their interactions with signaling pathways in dictating cell fate and define the extent of functional overlap among different Hox genes

Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment

Introduction: The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simple epithelium even across species and classes, and can partially restore features of differentiated tissue to mouse mammary tumours in co-culture experiments. Despite these exciting properties, the molecular identity of embryonic mammary cells remains to be fully characterised. Methods: Here, we define the transcriptome of the mammary primordium and the two distinct cellular compartments that comprise it, the mammary primordial bud epithelium and mammary mesenchyme. Pathway and network analysis was performed and comparisons of embryonic mammary gene expression profiles to those of both postnatal mouse and human mammary epithelial cell sub-populations and stroma were made. Results: Several of the genes we have detected in our embryonic mammary cell signatures were previously shown to regulate mammary cell fate and development, but we also identified a large number of novel candidates. Additionally, we determined genes that were expressed by both embryonic and postnatal mammary cells, which represent candidate regulators of mammary cell fate, differentiation and progenitor cell function that could signal from mammary lineage inception during embryogenesis through postnatal development. Comparison of embryonic mammary cell signatures with those of human breast cells identified potential regulators of mammary progenitor cell functions conserved across species. Conclusions: These results provide new insights into genetic regulatory mechanisms of mammary development, particularly identification of novel potential regulators of mammary fate and mesenchymal-epithelial cross-talk. Since cancers may represent diseases of mesenchymal-epithelial communications, we anticipate these results will provide foundations for further studies into the fundamental links between developmental, stem cell and breast cancer biology

Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing

Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes