Value of PET/CT versus contrast-enhanced CT in identifying chest wall invasion (T3) by NSCLC [B-671]

Purpose: To determine the diagnostic value of 18F-FDG PET/CT versus contrastenhanced CT in identifying chest wall invasion by NSCLC. Methods and Materials: The primary selection criterion was a peripheral tumor of any size with contact to the chest wall. A total of 25 patients with pathologically proven NSCLC satisfied these criteria. Chest wall invasion was interpreted upon PET/CT when a frank costal or intercostal 18F-FDG uptake was identified with or without concomitant morphologic alterations. On the other hand, the existence of periosteal rib reaction/erosion, chest wall thickening or obliteration of the pleural fat layer either separately or combined were considered essential diagnostic criteria for disease extension into the chest wall upon contrast-enhanced CT. The results were correlated with the final histological analysis. Results: Among the studied cohort, 13/25 (52%) patients had chest wall invasion consistent with T3 disease. Both PET/CT and contrast-enhanced CT successfully identified 12/13 (92%) of these patients. The single false-negative result was due to parietal pleural invasion. On the other hand, one false-positive result was encountered by PET/CT in a dyspneic patient; whereas, CT analysis revealed false-positive results in six patients. In these patients, periosteal rib reaction (n = 2) or asymmetric enlargement of adjacent chest wall muscles (n = 1) were identified along with an obliterated pleural fat layer (n = 6). The sensitivity, specificity, and accuracy of PET/CT and contrast-enhanced CT were 92, 91 and 92% versus 92, 50 and 72%. Conclusion: 18F-FDG PET/CT is an accurate diagnostic modality in identifying.

Absence of the fourth cranial nerve in congenital Brown syndrome.

PURPOSE: To elucidate the aetiology of congenital Brown syndrome. METHODS: Four consecutive patients diagnosed with unilateral congenital Brown syndrome had a comprehensive standardized ocular motility examination. Any compensatory head posture was measured. Brain magnetic resonance imaging (MRI) with regard for the IV cranial nerve (CN) was performed in all patients. Orbital MRI was performed in 2/4 patients, with images acquired in eight directions of gaze and superior oblique (SO) muscle areas compared. RESULTS: CN IV could not be identified bilaterally in two patients, but was absent only on the side of the Brown syndrome in the two other patients. On the normal side, orbital MRI revealed a smaller SO muscle area in upgaze than in downgaze, demonstrating normal actions of this muscle. On the side of the Brown syndrome, the SO area remained the same in upgaze and in downgaze and approximately symmetric to the area of SO in downgaze on the normal side. CONCLUSIONS: These cases add further anatomical support to the theory of paradoxical innervation in congenital Brown syndrome. CN IV was absent in two patients on the side of the Brown syndrome, but without muscle hypoplasia. SO muscle size did not vary in up- and downgaze, which we interpreted as a sign of constant innervation through branches of CN III.

Correlation between vasoconstrictor roles and mRNA expression of alpha1-adrenoceptor subtypes in blood vessels of genetically engineered mice.

We examined the contribution of each alpha(1)-adrenoceptor (AR) subtype in noradrenaline (NAd)-evoked contraction in the thoracic aortas and mesenteric arteries of mice. Compared with the concentration-response curves (CRCs) for NAd in the thoracic aortas of wild-type (WT) mice, the CRCs of mutant mice showed a significantly lower sensitivity. The pD(2) value in rank order is as follows: WT mice (8.21) > alpha(1B)-adrenoceptor knockout (alpha(1B)-KO) (7.77) > alpha(1D)-AR knockout (alpha(1D)-KO) (6.44) > alpha(1B)- and alpha(1D)-AR double knockout (alpha(1BD)-KO) (5.15). In the mesenteric artery, CRCs for NAd did not differ significantly between either WT (6.52) and alpha(1B)-KO mice (7.12) or alpha(1D)-KO (6.19) and alpha(1BD)-KO (6.29) mice. However, the CRC maximum responses to NAd in alpha(1D)- and alpha(1BD)-KO mice were significantly lower than those in WT and alpha(1B)-KO mice. Except in the thoracic aortas of alpha(1BD)-KO mice, the competitive antagonist prazosin inhibited the contraction response to NAd with high affinity. However, prazosin produced shallow Schild slopes in the vessels of mice lacking the alpha(1D)-AR gene. In the thoracic aorta, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.25 and 8.46, respectively, and in alpha(1B)-KO mice they were 8.49 and 9.13, respectively. In the mesenteric artery, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.34 and 7.47, respectively, and in alpha(1B)-KO mice they were 8.11 and 7.82, respectively. These pharmacological findings were in fairly good agreement with findings from comparison of CRCs, with the exception of the mesenteric arteries of WT and alpha(1B)-KO mice, which showed low affinities to BMY7378. We performed a quantitative analysis of the mRNA expression of each alpha(1)-AR subtype in these vessels in order to examine the correlation between mRNA expression level and the predominance of each alpha(1)-AR subtype in mediating vascular contraction. The rank order of each alpha(1)-AR subtype in terms of its vasoconstrictor role was in fairly good agreement with the level of expression of mRNA of each subtype, that is, alpha(1D)-AR > alpha(1B)-AR > alpha(1A)-AR in the thoracic aorta and alpha(1D)-AR > alpha(1A)-AR > alpha(1B)-AR in the mesenteric artery. No dramatic compensatory change of alpha(1)-AR subtype in mutant mice was observed in pharmacological or quantitative mRNA expression analysis.

Caractéristiques cliniques des leucémies lymphoblastiques aiguës de type T immature (E-rosette négatif) détecté par l'anticorps monoclonal LAU-A1 [Clinical characteristics of immature T-type (negative E-rosette) acute lymphoblastic leukemia detected by LAU-A1 monoclonal antibody]

Immature T-ALL is a newly defined subgroup of ALL in which the blasts lack the receptor for sheep erythrocytes (ER) and the usual T-cell markers, but express the 40 kDa pan-T surface antigen recognized by our monoclonal antibody LAU-A1. Patients with immature T-ALL represent 10% of all cases of adult ALL. Leukocyte counts are lower and spleen, liver and lymph node enlargement is less prominent, but mediastinal enlargement is more frequent than in mature (ER-positive) T-ALL. 7 patients with immature T-ALL (median age 42 years, range 13-73) were treated with intensified chemotherapy regimens, and only one 47-year-old female entered a short-lived complete remission. The overall survival of our patients was poor (median 7.5 months, with only one patient surviving at 15 months) and seemed not to be influenced by age. Our study indicates that immature T-ALL can only be accurately identified by the use of monoclonal antibodies recognizing the 40 kDa pan-T antigen, and that immature T-ALL is a separate disease entity typified by a poor prognosis.

RECHERCHE TRANSLATIONNELLE EN NEUROSCIENCES PSYCHIATRIQUES: DE L'ANIMAL MODELE DE SCHIZOPHRENIE A LA DETECTION D'UNE DESORIENTATION SPATIALE, PRATIQUE OU SYMBOLIQUE CHEZ DES PATIENTS

La modélisation, chez l'animal, de maladies psychiatriques telles que la schizophrénie repose sur différentes démarches visant à induire des perturbations cérébrales similaires à celles observées dans la maladie. Nous avons cherché à étudier chez le rat les effets d'une diminution (50%) transitoire en glutathion (GSH) durant le développement (PND 5 à PND 16) à partir de l'implication, chez des adultes, des conséquences de cette perturbation dans des mécanismes fondamentaux de traitement de l'information sensorielle. Cette thèse évalue et documente les déficits de compétences de navigation spatiale dans ce modèle. Nous avons mis en évidence des effets comportementaux à partir de l'identification de différences particulières dans des tâches d'orientation: des difficultés, chez les rats ayant subi un déficit en GSH, à élaborer une représentation globale de l'environnement dans lequel ils se déplacent, difficultés compensées par une attention particulière aux détails visuels le composant. Cette stratégie réactive compensatoire est efficace lorsque les conditions permettent un ajustement continu aux repères visuels environnementaux. Elle ne permet cependant pas des prédictions et des attentes sur ce qui devrait être rencontré et perçu dans une certaine direction, dès qu'une partie des informations visuelles familières disparaît. Il faudrait pour cela une capacité fondée sur une représentation abstraite, à distance des modalités sensorielles qui en ont permis son élaboration. Notre thèse soutient que les déficits, supposés participer à l'émergence de certains symptômes de la maladie, auraient également des conséquences sur l'élaboration de la représentation spatiale nécessaire à des capacités d'orientation effectives et symboliques. - The study of a psychiatric disease such as schizophrenia in an animal model relies on different approaches attempting to replicate brain perturbations similar to those observed in the illness. In the present work, behavioural consequences of a functional deficit in brain connectivity and coordination were assessed in rats with a transitory glutathione (GSH) deficit induced during the postnatal development (PND 5-PND 16) with daily injections of BSO (1- buthionine-(S,R)- sulfoximine). We searched for a theoretical syndrome associating ecologically relevant behavioural adaptive deficits and resulting from the weakening of sensory integration processes. Our results revealed significant and specific deficit of BSO treated rats in spatial orientation tasks designed to test for cognitive mapping abilities. Treated rats behaved as if impaired in the proactive strategies supported by an abstract representation such as a cognitive map. In contrast their performances were preserved whenever the environmental conditions allowed for adaptative reactive strategies, an equivalent of the visual affordances described by Gibson (1958). This supports our thesis that BSO treated rats expressed difficulties in elaborating a global representation of the environment. This deficit was completely - or - partially compensated by the development of an increased attention to the environment's visual details. This compensatory reactive strategy requires a rich environment allowing for continuous adjustment to visual cues. However, such adjustment doesn't allow to predictions and expectancies about what should be met and perceived in a certain direction, when familiar visual spatial cues are missing. Such competencies require orientation based on the use of an abstract spatial representation, independent from the specific sensory modalities that have participated to its elaboration. The impairment of BSO rats such spatial representation could result from a deficit in the integration and organization of perceptual information. Our model leads to the hypothesis that these fundamental deficits might account for certain symptoms of schizophrenia. They would also interfere with in the capacity to elaborate spatial representation necessary for optimal orientation in natural, artificial or symbolic environment.

Essstörungen bei Adipositas und Diabetes mellitus [Eating disorders associated with obesity and diabetes].

Binge eating disorder is one of the most frequent comorbid mental disorders associated with overweight and obesity. Binge eating disorder patients often suffer from other mental disorders and longitudinal studies indicate a continuous weight gain during the long-term course. As in other eating disorders gender is a risk factor, but the proportion of male binge eating disorder patients is surprisingly high.In young women with type 1 diabetes the prevalence of subclinical types of bulimia nervosa is increased. In addition, insulin purging as a characteristic compensatory behavior in young diabetic women poses a considerable problem. In patients with type 1 diabetes, disturbed eating and eating disorders are characterized by insufficient metabolic control and early development of late diabetic sequelae. Patients with type 2 diabetes are often overweight or obese. Binge eating disorder does not occur more frequently in patients with type 2 diabetes compared to healthy persons. However, the comorbidity of binge eating disorder and diabetes type 2 is associated with weight gain and insulin resistance. Especially in young diabetic patients a screening procedure for disturbed eating or eating disorders seems to be necessary. Comorbid patients should be offered psychotherapy.

Sox genes in C. elegans: sox-2 role in postembryonic development

Report for the scientific sojourn carried out at the Columbia University, United States, from 2010 to 2012. Expression of SoxB genes correlates with the commitment of cells to a neural fate; however, the relevance of SoxB proteins in early vertebrate neurogenesis has been difficult to prove genetically due to embryonic lethality and presumed redundant functions. The nematode C. Elegants has only 5 sox genes: sox-2 and sox-3 form the SoxB group while sem-2, sox-4 and egl-13 belong to other Sox groups. Our results show that sox-2 and sem-2 are the sox genes expressed earliest and in a broader manner during embryogenesis, being expressed in several neuronal progenitors. sox-3, sox-4 and egl-13 are expressed in few cells during late embryogenesis, when most neurons are already born. Both sox-2 and sem-2 null mutants are early larval lethal but do not show neuronal specification defects during embryonic development as indicated by quantification of a panneuronal reporter. Potential redundancy or compensatory mechanisms between different sox genes have been ruled out, strongly suggesting that sox genes are not required for specification of embryonically-derived neurons. However, at the first larval stage there are still several blast cells that will give rise to different postembryonic lineages, which generate several neurons amongst other cell types. nterestingly, sox-2 is expressed in many of these progenitor cells. Using mosaic analysis we have so far identified neurons derived from two different postembryonic lineages which fail to be generated in C. elegans sox-2 mutants. These results support the idea that postembryonic progenitor competence is compromised in the absence of sox-2.

Simultaneous loss of beta- and gamma-catenin does not perturb hematopoiesis or lymphopoiesis.

Hematopietic stem cells (HSCs) maintain life-long hematopoiesis in the bone marrow via their ability to self-renew and to differentiate into all blood lineages. Although a central role for the canonical wnt signaling pathway has been suggested in HSC self-renewal as well as in the development of B and T cells, conditional deletion of beta-catenin (which is considered to be essential for Wnt signaling) has no effect on hematopoiesis or lymphopoiesis. Here, we address whether this discrepancy can be explained by a redundant and compensatory function of gamma-catenin, a close homolog of beta-catenin. Unexpectedly, we find that combined deficiency of beta- and gamma-catenin in hematopoietic progenitors does not impair their ability to self-renew and to reconstitute all myeloid, erythroid, and lymphoid lineages, even in competitive mixed chimeras and serial transplantations. These results exclude an essential role for canonical Wnt signaling (as mediated by beta- and/or gamma-catenin) during hematopoiesis and lymphopoiesis.

Repeated Double-Poling Sprint Training in Hypoxia by Competitive Cross-country Skiers.

PURPOSE: Repeated-sprint training in hypoxia (RSH) was recently shown to improve repeated-sprint ability (RSA) in cycling. This phenomenon is likely to reflect fiber type-dependent, compensatory vasodilation, and therefore, our hypothesis was that RSH is even more beneficial for activities involving upper body muscles, such as double poling during cross-country skiing. METHODS: In a double-blinded fashion, 17 competitive cross-country skiers performed six sessions of repeated sprints (each consisting of four sets of five 10-s sprints, with 20-s intervals of recovery) either in normoxia (RSN, 300 m; FiO2, 20.9%; n = 8) or normobaric hypoxia (RSH, 3000 m; FiO2, 13.8 %; n = 9). Before (pre) and after (post) training, performance was evaluated with an RSA test (10-s all-out sprints-20-s recovery, until peak power output declined by 30%) and a simulated team sprint (team sprint, 3 × 3-min all-out with 3-min rest) on a double-poling ergometer. Triceps brachii oxygenation was measured by near-infrared spectroscopy. RESULTS: From pretraining to posttraining, peak power output in the RSA was increased (P < 0.01) to the same extent (29% ± 13% vs 26% ± 18%, nonsignificant) in RSH and in RSN whereas the number of sprints performed was enhanced in RSH (10.9 ± 5.2 vs 17.1 ± 6.8, P < 0.01) but not in RSN (11.6 ± 5.3 vs 11.7 ± 4.3, nonsignificant). In addition, the amplitude in total hemoglobin variations during sprints throughout RSA rose more in RSH (P < 0.01). Similarly, the average power output during all team sprints improved by 11% ± 9% in RSH and 15% ± 7% in RSN. CONCLUSIONS: Our findings reveal greater improvement in the performance of repeated double-poling sprints, together with larger variations in the perfusion of upper body muscles in RSH compared with those in RSN.

Repercussion of a deficiency in mitochondrial ß-oxidation on the carbon flux of short-chain fatty acids to the peroxisomal ß-oxidation cycle in Aspergillus nidulans.

The fungus Aspergillus nidulans contains both a mitochondrial and peroxisomal ß-oxidation pathway. This work was aimed at studying the influence of mutations in the foxA gene, encoding a peroxisomal multifunctional protein, or in the scdA/echA genes, encoding a mitochondrial short-chain dehydrogenase and an enoyl-CoA hydratase, respectively, on the carbon flux to the peroxisomal ß-oxidation pathway. A. nidulans transformed with a peroxisomal polyhydroxyalkanoate (PHA) synthase produced PHA from the polymerization of 3-hydroxyacyl-CoA intermediates derived from the peroxisomal ß-oxidation of external fatty acids. PHA produced from erucic acid or heptadecanoic acid contained a broad spectrum of monomers, ranging from 5 to 14 carbons, revealing that the peroxisomal ß-oxidation cycle can handle both long and short-chain intermediates. While the ∆foxA mutant grown on erucic acid or oleic acid synthesized 10-fold less PHA compared to wild type, the same mutant grown on octanoic acid or heptanoic acid produced 3- to 6-fold more PHA. Thus, while FoxA has an important contribution to the degradation of long-chain fatty acids, the flux of short-chain fatty acids to peroxisomal ß-oxidation is actually enhanced in its absence. While no change in PHA was observed in the ∆scdA∆echA mutant grown on erucic acid or oleic acid compared to wild type, there was a 2- to 4-fold increased synthesis of PHA in ∆scdA∆echA cells grown in octanoic acid or heptanoic acid. These results reveal that a compensatory mechanism exists in A. nidulans that increases the flux of short-chain fatty acids towards the peroxisomal ß-oxidation cycle when the mitochondrial ß-oxidation pathway is defective.

Delta9-tetrahydrocannabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice

The possible interactions between Delta9-tetrahydrocannabinol (THC) and nicotine remain unclear in spite of the current association of cannabis and tobacco in humans. The aim of the present study was to explore the interactions between these two drugs of abuse by evaluating the consequences of THC administration on the somatic manifestations and the aversive motivational state associated to nicotine withdrawal in mice. Acute THC administration significantly decreased the incidence of several nicotine withdrawal signs precipitated by mecamylamine or naloxone, such as wet-dog-shakes, paw tremor and scratches. In both experimental conditions, the global withdrawal score was also significantly attenuated by acute THC administration. THC also reversed conditioned place aversion associated to naloxone precipitated nicotine withdrawal. We have then evaluated whether this effect of THC was due to possible adaptive changes induced by chronic nicotine on CB1 cannabinoid receptors. The stimulation of GTPS-binding proteins by the cannabinoid agonist WIN 55,212-2 and the density of CB1 cannabinoid receptor binding labelled with [3H] CP-55,940 were not modified by chronic nicotine treatment in the different brain structures investigated. Finally, we evaluated the consequences of THC administration on c-Fos expression in several brain structures after chronic nicotine administration and withdrawal. c-Fos was decreased in the caudate putamen and the dentate gyrus after mecamylamine precipitated nicotine withdrawal. However, acute THC administration did not modify c-Fos expression under these experimental conditions. Taken together, these results indicate that THC administration attenuated somatic signs of nicotine withdrawal and this effect was not associated to compensatory changes on CB1 cannabinoid receptors during chronic nicotine administration. In addition, THC also ameliorated the aversive motivational consequences of nicotine withdrawal.

Benefit of Cup Medialization in Total Hip Arthroplasty is Associated With Femoral Anatomy.

BACKGROUND: Medialization of the cup with a respective increase in femoral offset has been proposed in THA to increase abductor moment arms. Insofar as there are potential disadvantages to cup medialization, it is important to ascertain whether the purported biomechanical benefits of cup medialization are large enough to warrant the downsides; to date, studies regarding this question have disagreed. QUESTIONS/PURPOSES: The purpose of this study was to quantify the effect of cup medialization with a compensatory increase in femoral offset compared with anatomic reconstruction for patients undergoing THA. We tested the hypothesis that there is a (linear) correlation between preoperative anatomic parameters and muscle moment arm increase caused by cup medialization. METHODS: Fifteen patients undergoing THA were selected, covering a typical range of preoperative femoral offsets. For each patient, a finite element model was built based on a preoperative CT scan. The model included the pelvis, femur, gluteus minimus, medius, and maximus. Two reconstructions were compared: (1) anatomic position of the acetabular center of rotation, and (2) cup medialization compensated by an increase in the femoral offset. Passive abduction-adduction and flexion-extension were simulated in the range of normal gait. Muscle moment arms were evaluated and correlated to preoperative femoral offset, acetabular offset, height of the greater trochanter (relative to femoral center of rotation), and femoral antetorsion angle. RESULTS: The increase of muscle moment arms caused by cup medialization varied among patients. Muscle moment arms increase by 10% to 85% of the amount of cup medialization for abduction-adduction and from -35% (decrease) to 50% for flexion-extension. The change in moment arm was inversely correlated (R(2) = 0.588, p = 0.001) to femoral antetorsion (anteversion), such that patients with less femoral antetorsion gained more in terms of hip muscle moments. No linear correlation was observed between changes in moment arm and other preoperative parameters in this series. CONCLUSIONS: The benefit of cup medialization is variable and depends on the individual anatomy. CLINICAL RELEVANCE: Cup medialization with compensatory increase of the femoral offset may be particularly effective in patients with less femoral antetorsion. However, cup medialization must be balanced against its tradeoffs, including the additional loss of medial acetabular bone stock, and eventual proprioceptive implications of the nonanatomic center of rotation and perhaps joint reaction forces. Clinical studies should better determine the relevance of small changes of moment arms on function and joint reaction forces.

Line bisection by eye and by hand reveal opposite biases

The vision-for-action literature favours the idea that the motor output of an action - whether manual or oculomotor - leads to similar results regarding object handling. Findings on line bisection performance challenge this idea: healthy individuals bisect lines manually to the left of centre, and to the right of centre when using eye fixation. In case that these opposite biases for manual and oculomotor action reflect more universal compensatory mechanisms that cancel each other out to enhance overall accuracy, one would like to observe comparable opposite biases for other material. In the present study, we report on three independent experiments in which we tested line bisection (by hand, by eye fixation) not only for solid lines, but also for letter lines; the latter, when bisected manually, is known to result in a rightward bias. Accordingly, we expected a leftward bias for letter lines when bisected via eye fixation. Analysis of bisection biases provided evidence for this idea: manual bisection was more rightward for letter as compared to solid lines, while bisection by eye fixation was more leftward for letter as compared to solid lines. Support for the eye fixation observation was particularly obvious in two of the three studies, for which comparability between eye and hand action was increasingly adjusted (paper-pencil versus touch screen for manual action). These findings question the assumption that ocular motor and manual output are always inter-changeable, but rather suggest that at least for some situations ocular motor and manual output biases are orthogonal to each other, possibly balancing each other out.

Women's work histories in Italy: education as investment in reconciliation and legitimacy?

Within pre-enlargement Europe, Italy records one of the widest employment rate gaps between highly and poorly educated women, as well one of the largest differences in the share, among working women, of public sector employment. Building on these stylized facts and using the Longitudinal Survey of Italian Households (ILFI), we investigate the working trajectories of three cohorts of Italian women born between 1935 and 1964 and observed from their first job until they are in their forties. We use mainly, but not exclusively, event history analysis in order to identify the main factors that influence entry into and exit from paid work over the life course. Our results suggest that in the Italian context, where employment protection policies have also been used as surrogate measures to favour reconciliation between family and work, and where traditional gender norms still persist, education is so important for women's employment decisions because it represents an investment in 'reconciliation' and 'work legitimacy' over and above investment in human capital.

Role of islet microRNAs in diabetes: which model for which question?

MicroRNAs are important regulators of gene expression. The vast majority of the cells in our body rely on hundreds of these tiny non-coding RNA molecules to precisely adjust their protein repertoire and faithfully accomplish their tasks. Indeed, alterations in the microRNA profile can lead to cellular dysfunction that favours the appearance of several diseases. A specific set of microRNAs plays a crucial role in pancreatic beta cell differentiation and is essential for the fine-tuning of insulin secretion and for compensatory beta cell mass expansion in response to insulin resistance. Recently, several independent studies reported alterations in microRNA levels in the islets of animal models of diabetes and in islets isolated from diabetic patients. Surprisingly, many of the changes in microRNA expression observed in animal models of diabetes were not detected in the islets of diabetic patients and vice versa. These findings are unlikely to merely reflect species differences because microRNAs are highly conserved in mammals. These puzzling results are most probably explained by fundamental differences in the experimental approaches which selectively highlight the microRNAs directly contributing to diabetes development, the microRNAs predisposing individuals to the disease or the microRNAs displaying expression changes subsequent to the development of diabetes. In this review we will highlight the suitability of the different models for addressing each of these questions and propose future strategies that should allow us to obtain a better understanding of the contribution of microRNAs to the development of diabetes mellitus in humans.