Incidental diagnosis of diseases on un-enhanced helical computed tomography performed for ureteric colic

BACKGROUND: Patients presenting in the emergency room with flank pain suggestive of acute ureteric colic may have alternative underlying conditions mimicking ureteric stones. An early diagnosis and appropriate treatment for other causes of flank pain is important. The majority of centers around the world are increasingly using un-enhanced helical CT (UHCT) for evaluation of ureteric colic. This study was conducted to determine the incidence and spectrum of significant incidental diagnoses established or suggested on UHCT performed for suspected renal/ureteric colic. METHODS: Urologist and radiologist reviewed 233 consecutive UHCT, performed for suspected renal/ureteral colic along with assessment of the medical records. Radiological diagnoses of clinical entities not suspected otherwise were analyzed. All other relevant radiological, biochemical and serological investigations and per-operative findings were also noted. RESULTS: Ureteral calculi were identified in 148 examinations (64%), findings of recent passage of calculi in 10 (4%) and no calculus in 75 examinations (32%). Overall the incidental findings (additional or alternative diagnosis) were found in 28 (12%) CT scans. Twenty (71%) of these diagnoses were confirmed by per-operative findings, biopsy, and other radiological and biochemical investigations or on clinical follow up. CONCLUSION: A wide spectrum of significant incidental diagnoses can be identified on UHCT performed for suspected renal/ureteral colic. In the present series of 233 consecutive CT examinations, the incidence of incidental diagnosis was 12%

Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

<p>Abstract</p> <p>Background</p> <p>Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders.</p> <p>Methods</p> <p>CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.</p> <p>Results</p> <p>Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (<it>P </it>= 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (<it>P </it>= 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (<it>P </it>= 0.0124) and IL-21 (<it>P </it>= 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (<it>P </it>= 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (<it>P </it>= 0.0325) and CD patients (<it>P </it>= 0.0293).</p> <p>Conclusions</p> <p>This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.</p

Hexagonal boron nitride on transition metal surfaces

We validate a computational setup based on density functional theory to investigate hexagonal boron nitride (h-BN) monolayers grown on different transition metals exposing hexagonal surfaces. An extended assessment of our approach for the characterization of the geometrical and electronic structure of such systems is performed. Due to the lattice mismatch with the substrate, the monolayers can form Moire-type superstructures with very long periodicities on the surface. Thus, proper models of these interfaces require very large simulation cells (more than 1,000 atoms) and an accurate description of interactions that are modulated with the specific registry of h-BN on the metal. We demonstrate that efficient and accurate calculations can be performed in such large systems using Gaussian basis sets and dispersion corrections to the (semi-)local density functionals. Four different metallic substrates, Rh(111), Ru(0001), Cu(111), and Ni(111), are explicitly considered, and the results are compared with previous experimental and computational studies

Identification of ALK as a major familial neuroblastoma predisposition gene

Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23-24 using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate germline missense mutations in the tyrosine kinase domain of ALK that segregated with the disease in eight separate families. Resequencing in 194 high-risk neuroblastoma samples showed somatically acquired mutations in the tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to critical regions of the kinase domain and were predicted, with high probability, to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth in all cell lines harbouring mutant or amplified ALK, as well as in two out of six wild-type cell lines for ALK. Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy