Hepatic hemangiomas: Factors associated with T2 shine-through effect on diffusion-weighted MR sequences.

PURPOSE: To determine the frequency and factors associated with the presence of T2 shine-through effect in hepatic hemangiomas on diffusion-weighted (DW) magnetic resonance (MR) sequences. MATERIALS AND METHODS: This retrospective study was approved by institutional review board with waiver of informed consent. One hundred forty-nine consecutive patients with 388 hepatic hemangiomas who underwent a liver MR between January 2010 and November 2011 were included. MR analysis evaluated the lesion characteristics (signal intensities and enhancement patterns (classical, rapidly filling, delayed filling)), the presence of T2 shine-through effect on DW sequences (b values of 0, 150, and 600s/mm(2)), and apparent diffusion coefficient (ADC) values. Multivariate analysis was performed to study the factors associated with the T2 shine-through effect. RESULTS: T2 shine-through effect was observed in 204/388 (52.6%) of hepatic hemangiomas and in 100 (67.1%) patients. Mean ADC value of hemangiomas with T2 shine-through effect was significantly lower than hemangiomas without (2.0±0.48 vs 2.38±0.45, P<.0001). On multivariate analysis, high signal intensity on fat-suppressed T2-weighted fast spin-echo images, hemangiomas with classical or delayed enhancement, and the ADC of the liver were the only significant factors associated with T2 shine-through effect. CONCLUSION: T2 shine-through effect is commonly observed in hepatic hemangiomas and is related to hemangiomas characteristics. Radiologists should be aware of this phenomenon which could lead to misdiagnosis. Its presence should not question the diagnosis of hemangiomas when typical MR findings are found.

Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population.

PURPOSE: To describe the weight gain-related side-effects of psychotropic drugs and their consequences on metabolic complications (hypercholesterolemia, obesity) in a Swiss cohort of psychiatric patients. METHOD: This cross-sectional observational study was performed in an out-patient psychiatric division with patients having received for more than 3 months the following drugs: clozapine, olanzapine, quetiapine, risperidone, lithium, and/or valproate. Clinical measures and lifestyle information (smoking behaviour, physical activity) were recorded. RESULTS: 196 inclusions were completed. Weight gain (≥10% of initial weight) following drug treatment was reported in 47% of these patients. Prevalence of obesity (BMI ≥ 30), hypercholesterolemia (≥6.2 mmol/L) and low HDL-cholesterol (<1.0 mmol/L in men, <1.3 mmol/L in women) were present in 38%, 21%, and 27% of patients, respectively. A higher standardised dose, an increase of appetite following medication introduction, the type of medication (clozapine or olanzapine > quetiapine or risperidone > lithium or valproate), and the gender were shown to be significantly associated with evolution of BMI. CONCLUSION: High prevalence of obesity and hypercholesterolemia was found in an out-patient psychiatric population and confirms drug-induced weight gain complications during long-term treatment. The results support the recently published recommendations of monitoring of metabolic side-effects during treatment with atypical antipsychotics. Moreover, the weight gain predictors found in the present study could help to highlight patients with special health care management requirement.

Congenital ataxia and hemiplegic migraine with cerebral edema associated with a novel gain of function mutation in the calcium channel CACNA1A.

Mutations in the CACNA1A gene, encoding the α1 subunit of the voltage-gated calcium channel CaV2.1 (P/Q-type), have been associated with three neurological phenotypes: familial and sporadic hemiplegic migraine type 1 (FHM1, SHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 (SCA6). We report a child with congenital ataxia, abnormal eye movements and developmental delay who presented severe attacks of hemiplegic migraine triggered by minor head traumas and associated with hemispheric swelling and seizures. Progressive cerebellar atrophy was also observed. Remission of the attacks was obtained with acetazolamide. A de novo 3bp deletion was found in heterozygosity causing loss of a phenylalanine residue at position 1502, in one of the critical transmembrane domains of the protein contributing to the inner part of the pore. We characterized the electrophysiology of this mutant in a Xenopus oocyte in vitro system and showed that it causes gain of function of the channel. The mutant CaV2.1 activates at lower voltage threshold than the wild type. These findings provide further evidence of this molecular mechanism as causative of FHM1 and expand the phenotypic spectrum of CACNA1A mutations with a child exhibiting severe SHM1 and non-episodic ataxia of congenital onset.

Novel acid phosphatase in Candida glabrata suggests selective pressure and niche specialization in the phosphate signal transduction pathway.

Evolution through natural selection suggests unnecessary genes are lost. We observed that the yeast Candida glabrata lost the gene encoding a phosphate-repressible acid phosphatase (PHO5) present in many yeasts including Saccharomyces cerevisiae. However, C. glabrata still had phosphate starvation-inducible phosphatase activity. Screening a C. glabrata genomic library, we identified CgPMU2, a member of a three-gene family that contains a phosphomutase-like domain. This small-scale gene duplication event could allow for sub- or neofunctionalization. On the basis of phylogenetic and biochemical characterizations, CgPMU2 has neofunctionalized to become a broad range, phosphate starvation-regulated acid phosphatase, which functionally replaces PHO5 in this pathogenic yeast. We determined that CgPmu2, unlike ScPho5, is not able to hydrolyze phytic acid (inositol hexakisphosphate). Phytic acid is present in fruits and seeds where S. cerevisiae grows, but is not abundant in mammalian tissues where C. glabrata grows. We demonstrated that C. glabrata is limited from an environment where phytic acid is the only source of phosphate. Our work suggests that during evolutionary time, the selection for the ancestral PHO5 was lost and that C. glabrata neofunctionalized a weak phosphatase to replace PHO5. Convergent evolution of a phosphate starvation-inducible acid phosphatase in C. glabrata relative to most yeast species provides an example of how small changes in signal transduction pathways can mediate genetic isolation and uncovers a potential speciation gene.

Early parenteral lipids and growth velocity in extremely-low-birth-weight infants.

BACKGROUND & AIMS: Whether early parenteral lipids improve postnatal growth of preterm neonates remains unclear. We aimed to assess the effects of parenteral lipids on growth velocity in extremely-low-birth-weight infants. METHODS: This retrospective cohort study included 121 extremely-low-birth-weight infants. The associations between parenteral lipids (cumulative intakes during the first week and delays in their introduction) and growth velocities (weight, head circumference and length) up to 28 days of life and to 36 weeks of corrected age were analysed using uni- and multivariate linear regression. RESULTS: Univariate analyses showed a significant positive association between the cumulative intakes of parenteral lipids during the first week and i) weight gain up to day 28; ii) weight gain up to 36 weeks of corrected age; iii) head circumference growth up to day 28. There was a negative correlation between the delay in parenteral lipid introduction and weight gain up to day 28. In multivariate analyses, the association between the cumulative intakes of parenteral lipids and weight gain up to 28 days was independent of gestational age at birth, birth weight, sex, smallness for gestational age, and enteral intakes (regression coefficient: 0.19; 95% CI: 0.01-0.38) and, up to 36 weeks, independent of gestational age, birth weight, sex, smallness for gestational age and parenteral glucose and amino acids (0.16; 95% CI: 0.04-0.27). CONCLUSIONS: Parenteral lipids during the first week were positively associated with weight gain in extremely-low-birth-weight infants and could improve early nutritional support of preterm neonates.

Validation de la mesure de l'oedème postopératoire par bioimpédance chez les patients opérés d'une prothèse totale du genou : une expérience de collaboration entre physiothérapeutes et ingénieurs

Fondements : La recherche sur l'oedème postopératoire consécutif à la chirurgie prothétique du genou est peu développée, notamment en raison de l'absence d'une méthode de mesure adaptée. Une collaboration entre physiothérapeutes et ingénieurs a permis de développer et valider une méthode de mesure innovante et facilement applicable. Les physiothérapeutes ont identifié un besoin clinique, les ingénieurs ont apporté leur savoir technologique, et l'équipe a conjointement élaboré le protocole de mesure et effectué l'étude de validation. Introduction : La bioimpédance est fréquemment utilisée pour évaluer l'oedème par l'analyse d'un signal électrique passant au travers du corps, en extrapolant la résistance théorique à une fréquence égale à zéro (R0). La mesure s'avère fiable et rapide, mais n'a jamais été appliquée et validée pour l'évaluation de l'oedème en chirurgie orthopédique. Objectif : L'objectif de l'étude est de valider la mesure de l'oedème du membre inférieur par bioimpédance, chez des patients ayant bénéficié d'une prothèse totale de genou (PTG). Questionnement : Après nous être assurés de l'absence d'influence de l'implant métallique de la PTG sur la mesure, nous nous questionnions sur la validité et la fiabilité des mesures de bioimpédance dans ce contexte. Méthodes : Deux évaluateurs ont mesuré à tour de rôle et à deux reprises successives l'oedème chez 24 patients opérés d'une PTG, à trois temps différents (préopératoire, J+2, J+8). L'oedème a été évalué par bioimpédance (R0) et par conversion en volume de mesures centimétriques du membre inférieur (MI). Nous avons calculé le ratio moyen des MI pour chaque méthode. Nous avons évalué la reproductibilité intra- et inter-observateurs de la bioimpédance (coefficient de corrélation intraclasse, CCI) et la corrélation entre méthodes (Spearman). Résultats : Le ratio moyen opéré/sain du volume des MI est de 1.04 (SD ± 0.06) en préopératoire, 1.18 (SD ± 0.09) à J+2 et 1.17 (SD ± 0.10) à J+8. Le ratio sain/opéré des MI de R0 est de 1.04 (SD ± 0.07) en préopératoire, 1.51 (SD ± 0.22) à J+2 et 1.65 (SD ± 0.21) à J+8. En préopératoire, à J+2 et J+8, les CCI tous supérieurs à 0.95 pour la reproductibilité intra- et inter-observateurs de la bioimpédance. La corrélation entre méthodes est de 0.71 en préopératoire, 0.61 à J2 et 0.33 à J8. Analyse et conclusion : La variation du ratio des MI entre les temps préopératoire, J+2 et J+8 est plus marquée pour R0. La mesure de bioimpédance bénéficie d'une excellente reproductibilité intra- et inter-observateurs. L'évolution dans le temps de la corrélation entre méthodes peut être expliquée par l'influence potentielle de facteurs confondants sur R0 (modification de la composition liquidienne) et par l'influence de l'atrophie musculaire postopératoire sur la mesure de volume. La collaboration physiothérapeutes-ingénieurs a permis le développement et l'évaluation d'une nouvelle méthode de mesure.

A conserved transcript pattern in response to a specialist and a generalist herbivore.

Transcript patterns elicited in response to attack reveal, at the molecular level, how plants respond to aggressors. These patterns are fashioned both by inflicted physical damage as well as by biological components displayed or released by the attacker. Different types of attacking organisms might therefore be expected to elicit different transcription programs in the host. Using a large-scale DNA microarray, we characterized gene expression in damaged as well as in distal Arabidopsis thaliana leaves in response to the specialist insect, Pieris rapae. More than 100 insect-responsive genes potentially involved in defense were identified, including genes involved in pathogenesis, indole glucosinolate metabolism, detoxification and cell survival, and signal transduction. Of these 114 genes, 111 were induced in Pieris feeding, and only three were repressed. Expression patterns in distal leaves were markedly similar to those of local leaves. Analysis of wild-type and jasmonate mutant plants, coupled with jasmonate treatment, showed that between 67 and 84% of Pieris-regulated gene expression was controlled, totally or in part, by the jasmonate pathway. This was correlated with increased larval performance on the coronatine insensitive1 glabrous1 (coi1-1 gl1) mutant. Independent mutations in COI1 and GL1 led to a faster larval weight gain, but the gl1 mutation had relatively little effect on the expression of the insect-responsive genes examined. Finally, we compared transcript patterns in Arabidopis in response to larvae of the specialist P. rapae and to a generalist insect, Spodoptera littoralis. Surprisingly, given the complex nature of insect salivary components and reported differences between species, almost identical transcript profiles were observed. This study also provides a robustly characterized gene set for the further investigation of plant-insect interaction.

Estimating the apparent transverse relaxation time (R2(*)) from images with different contrasts (ESTATICS) reduces motion artifacts.

Relaxation rates provide important information about tissue microstructure. Multi-parameter mapping (MPM) estimates multiple relaxation parameters from multi-echo FLASH acquisitions with different basic contrasts, i.e., proton density (PD), T1 or magnetization transfer (MT) weighting. Motion can particularly affect maps of the apparent transverse relaxation rate R2(*), which are derived from the signal of PD-weighted images acquired at different echo times. To address the motion artifacts, we introduce ESTATICS, which robustly estimates R2(*) from images even when acquired with different basic contrasts. ESTATICS extends the fitted signal model to account for inherent contrast differences in the PDw, T1w and MTw images. The fit was implemented as a conventional ordinary least squares optimization and as a robust fit with a small or large confidence interval. These three different implementations of ESTATICS were tested on data affected by severe motion artifacts and data with no prominent motion artifacts as determined by visual assessment or fast optical motion tracking. ESTATICS improved the quality of the R2(*) maps and reduced the coefficient of variation for both types of data-with average reductions of 30% when severe motion artifacts were present. ESTATICS can be applied to any protocol comprised of multiple 2D/3D multi-echo FLASH acquisitions as used in the general research and clinical setting.

Segmentation of Head and Neck Lymph Node Regions for Radiotherapy Planning Using Active Contour-Based Atlas Registration

In this paper, we present the segmentation of the headand neck lymph node regions using a new active contourbased atlas registration model. We propose to segment thelymph node regions without directly including them in theatlas registration process; instead, they are segmentedusing the dense deformation field computed from theregistration of the atlas structures with distinctboundaries. This approach results in robust and accuratesegmentation of the lymph node regions even in thepresence of significant anatomical variations between theatlas-image and the patient's image to be segmented. Wealso present a quantitative evaluation of lymph noderegions segmentation using various statistical as well asgeometrical metrics: sensitivity, specificity, dicesimilarity coefficient and Hausdorff distance. Acomparison of the proposed method with two other state ofthe art methods is presented. The robustness of theproposed method to the atlas selection, in segmenting thelymph node regions, is also evaluated.

Metabolic predictors of obesity. Contribution of resting energy expenditure, thermic effect of food, and fuel utilization to four-year weight gain of post-obese and never-obese women.

This prospective study was designed to identify abnormalities of energy expenditure and fuel utilization which distinguish post-obese women from never-obese controls. 24 moderately obese, postmenopausal, nondiabetic women with a familial predisposition to obesity underwent assessments of body composition, fasting and postprandial energy expenditure, and fuel utilization in the obese state and after weight loss (mean 12.9 kg) to a post-obese, normal-weight state. The post-obese women were compared with 24 never-obese women of comparable age and body composition. Four years later, without intervention, body weight was reassessed in both groups. Results indicated that all parameters measured in the post-obese women were similar to the never-obese controls: mean resting energy expenditure, thermic effect of food, and fasting and postprandial substrate oxidation and insulin-glucose patterns. Four years later, post-obese women regained a mean of 10.9 kg while control subjects remained lean (mean gain 1.7 kg) (P < 0.001 between groups). Neither energy expenditure nor fuel oxidation correlated with 4-yr weight changes, whereas self-reported physical inactivity was associated with greater weight regain. The data suggest that weight gain in obesity-prone women may be due to maladaptive responses to the environment, such as physical inactivity or excess energy intake, rather than to reduced energy requirements.

Targeting Notch signaling in pancreatic cancer.

IMPORTANCE OF THE FIELD: With some 220,000 new cases/year in the world, pancreatic adenocarcinoma is the fourth highest cause of death by cancers. Among newly diagnosed patients about 210,000 will die within 9 months following diagnosis. Therefore, effective adjuncts to current treatment strategies are necessary. Because embryological signaling pathways are upregulated in pancreatic adenocarcinoma, they represent potential targets for future therapies. AREAS COVERED IN THIS REVIEW: Our aim is to present the Notch pathway, and to describe its involvement in pancreatic pathophysiology/carcinogenesis. This pathway appeared as a prime target for pancreatic cancer therapy. In the light of the crosstalk of Notch with other survival/embryologic pathways, drugs affecting more than one pathway may have to be combined. WHAT THE READER WILL GAIN: Drugs against gamma-secretases could thus serve in cancer treatment and can be combined with drugs targeting survival pathways interplaying with Notch such as Hedgehog. TAKE HOME MESSAGE: Downregulation of Notch contributes to the inhibition and apoptosis of pancreatic cancer cells whereas Hedgehog inhibition will allow for enhanced delivery of drugs to the tumor. Both pathway inhibitors appear to have synergistic effects for future therapeutics for pancreatic adenocarcinoma, once safety issues of compounds are overcome.

Hepatic hemangiomas : factors associated with T2 shine-through effect on diffusion-weighted MR sequences

Objectifs: Déterminer la fréquence et les facteurs prédictifs de l'effet T2 shine-through dans l'hémangiome hépatique. Matériels et méthodes: Entre janvier 2010 et novembre 2011, l'imagerie par résonance magnétique du foie de 149 patients avec 388 hémangiomes hépatiques a été revue rétrospectivement. Les caractéristiques lésionnelles: la taille, la localisation, le signal et l'aspect en T1, T2 et en diffusion, l'effet T2 shine-through, le coefficient apparent de diffusion des hémangiomes hépatiques et du foie et type de rehaussement ont été évalués. Résultats: L'effet T2 shine-through était observé dans 204/388 (52.6%) des hémangiomes hépatiques et 100 (67.1%) patients. L'ADC moyen des hémangiomas avec T2 shine-through effect était significativement plus bas que les hémangiomas sans T2 shine-through effect (2.0 +/- 0.48 vs 2.38 +/- 0.45 10"3 mm2/s, P < .0001). L'analyse multivariée retrouvait comme facteurs indépendants de la présence d'un effet T2 shine-through un hypersignal sur les images fat- suppressed T2-weighted fast spin-echo, les hémangiomes avec un rehaussement classique et retardé, et l'ADC du foie. Conclusion: Le T2 shine-through effect est fréquemment observé dans les hémangiomes hépatiques et dépend des caractéristiques lésionnelles. Sa présence ne remet pas en question le diagnostic lorsque les signes IRM typiques sont présents.