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Objective To describe two cases of Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) necrotizing pneumonia treated with ECMO, and complete pulmonary evaluation at six months. Methods Retrospective analysis of two patients presenting with severe PVL-SA pneumonia who both underwent complete respiratory function testing and chest CT scan six months after hospital discharge. Results Indications for ECMO were refractory hypoxia and left ventricular dysfunction associated with right ventricular dilatation. Patients were weaned off ECMO after 52 and 5 days. No ECMO-related hemorrhagic complication was observed. Pulmonary function tests performed at six months were normal and the CT scan showed complete regression of pulmonary injuries. Conclusion PVL-SA pneumonia is characterized by extensive parenchymal injuries, including necrotic and hemorrhagic complications. ECMO may be used as a salvage treatment without any associated hemorrhagic complication, provided anticoagulant therapy is carefully monitored, and may lead to complete pulmonary recovery at six months. [ABSTRACT FROM AUTHOR]

10-period Al 0.57 Ga 0.43 N/Al 0.38 Ga 0.62 N multi-quantum wells (MQWs) were grown on a relaxed Al 0.58 Ga 0.42 N buffer on AlN templates on sapphire. The threading dislocations and V-pits were characterized and their origin is discussed. The influence of V-pits on the structural quality of the MQWs and on optical emission at 280 nm was analyzed. It was observed that near-surface V-pits were always associated with grain boundaries consisting of edge threading dislocations originating from the AlN/Al 2 O 3 interface. Although the high density of V-pits disrupted MQWs growth, it did not affect the internal quantum efficiency which was measured to be ~1% at room temperature even when V-pit density was increased from 7×10 7 cm −2 to 2×10 9 cm −2 . The results help to understand the origin, propagation and influences of the typical defects in AlGaN MQWs grown on AlN/Al 2 O 3 templates which may lead to further improvement of the performance of DUV devices. [ABSTRACT FROM AUTHOR]

Haemochromatosis is predominantly associated with the HFE p.C282Y homozygous genotype, which is present in approximately 1 in 200 people of Northern European origin. However, not all p.C282Y homozygotes develop clinical features of haemochromatosis, and not all p.C282Y homozygotes even present abnormal iron parameters justifying venesection therapy. This situation was not apparent from initial genotype/phenotype correlation studies as there was a selection bias of patients. Only those patients with a significant iron burden were included in these early studies. It is now largely accepted that the p.C282Y/p.C282Y genotype is necessary for the development of HFE haemochromatosis. However, this genotype provides few clues as to why certain symptoms are associated with the disease. Expression of iron overload in people with this genotype depends on the complex interplay of environmental factors and modifier genes. In this review, we restrict our discussion to work done in humans giving examples of animal models where this has helped clarify our understanding. We discuss penetrance, explaining that this concept normally does not apply to autosomal recessive disorders, and discuss the usefulness of different biochemical markers in ascertaining iron burden. Hepcidin, a peptide synthesized primarily by the liver, has been identified as the central regulator in iron homeostasis. Consequently, understanding its regulation is the key. We conclude that the main goal now is to identify important modifiers that have a significant and unambiguous effect on iron storage. [ABSTRACT FROM AUTHOR]

The molecular basis of hereditary hemochromatosis (HH) is more complex than previously expected. More than 80% of hemochromatosis probands of Northern European descent are homozygous for the C282Y HFE gene mutation. However, five novel non-related- HFE HH forms have now been identified. The transferrin receptor( TFR2)-linked form is inherited in an autosomal recessive pattern and is considered to be an adult-onset syndrome. Until now, it has been associated with five mutations that have only been detected in Japanese and southern European patients. Here, we report the identification of a novel TFR2 nonsense mutation in two related French adolescents. We discuss the phenotype of this sibling pair from precedent biological and clinical findings as well as the expected role of TFR2 in iron homeostasis. Finally, we suggest that iron overload phenotypes associated with mutations in TFR2 may be intermediate between those related to mutations in HFE and those related to mutations in juvenile hemochromatosis genes. [ABSTRACT FROM AUTHOR]

L’étude EMSAI a été mise en place à la suite de l’APR-EFS 2010 et de l’arrêté du 12 janvier 2009 permettant de proposer une partie des patients atteints d’hémochromatose au don du sang bénévole. Deux faits essentiels supportent cette étude : – aucune donnée ne permet d’apprécier la proportion de patients réellement atteints d’hémochromatose et traités dans les centres de santé au regard des diverses situations possibles d’hyperferritinémie ; – l’utilité des saignées itératives est régulièrement discutée quand l’hyperferritinémie relève d’une cause non génétique, notamment dans le contexte du syndrome métabolique. Avec 1500 patients recrutés sur l’ensemble du territoire, et grâce à la collaboration de 25 ETS, le protocole EMSAI constitue une étude épidémiologique sans précédent. À ce stade, l’analyse des 808 premiers questionnaires médicaux permet de souligner trois points importants : – le syndrome métabolique est rapporté chez près d’un patient traité sur deux (46 %) ; – l’hémochromatose liée au gène HFE est évoquée de manière excessive, puisque sur 339 patients décrits (42 %), seuls 164 sont porteurs du génotype C282Y homozygote (20 %), 73 présentent le génotype C282Y/H63D (9 %) et 102 ne présentent aucun des deux génotypes considérés (13 %) ; – la surcharge en fer est significativement plus importante chez les patients C282Y homozygotes ( Figure 1 ). D’autres aspects du protocole EMSAI pourront être abordés au moment du congrès, tels que la place des autres causes d’hyperferritinémie (alcool, cytolyse, inflammation), la situation particulière des hyperferritinémies multifactorielles et l’efficacité des saignées pour chacun des groupes de patients répertoriés. [ABSTRACT FROM AUTHOR]

Introduction Des études cliniques rétrospectives ont suggéré que les anesthésiques locaux (Als) utilisés lors de chirurgies carcinologiques diminueraient la récidive et la dissémination métastatique [1] . Des études fondamentales sur cellules cancéreuses (poumon, langue, sein) [2] ont montré des résultats similaires. Le carcinome hépatocellulaire (CHC) représente le 6 e rang mondial des cancers et la 2 e cause de décès par cancer, avec un fort taux de récidives (70 % à 5 ans après chirurgie) [3] . Pour les stades très précoces, le premier traitement curatif est la résection chirurgicale au cours de laquelle des Als peuvent être administrés. Le but de cette étude était d’étudier in vitro l’effet des anesthésiques locaux sur les cellules humaines de carcinome hépatocellulaire. Matériel et méthodes Les cellules humaines des lignées de carcinome hépatocellulaire HuH7 et HepaRG progéniteurs ont été utilisées. Le groupe témoin était constitué de cellules humaines de lignées HepaRG différenciées, cellules possédant le phénotype le plus proche des hépatocytes sains. Dans un premier temps, les cellules ont été mises en culture en présence ou non d’Als (lidocaïne et ropivacaïne) à diverses concentrations pendant 48 heures. La migration et la viabilité cellulaire a été étudiée (test MTT). Résultats Les résultats de cette première étape montrent que la lidocaïne et la ropivacaïne diminuent significativement la croissance et la migration cellulaire des lignées HuH7 et HepaRG progéniteurs. Cet effet est dose-dépendant et associé à un blocage en phase G2 du cycle cellulaire. Les Als n’ont pas d’effets sur les HepaRG différenciés (phénotype proche des hépatocytes sains) ( Fig. 1 ). Discussion Ces résultats encourageants ont montré une inhibition spécifique de la croissance des cellules humaines de CHC par les Als. Une étude non supervisée de l’expression génomique par microarray est en cours afin d’identifier les gènes d’intérêts. Finalement, la dérégulation des gènes d’intérêts sera confirmée au niveau ADN par RT–PCR/qPCR et au niveau protéique par western-blot. [ABSTRACT FROM AUTHOR]

Genetic medicine applied to the study of hemochromatosis has identified the systemic loop controlling iron homeostasis, centered on hepcidin-ferroportin interaction. Current challenges are to dissect the molecular pathways underlying liver hepcidin synthesis in response to circulatory iron, HFE, TFR2, HJV, TMPRSS6 and BMP6 functions, and to define the major structural elements of hepcidin-ferroportin interaction. We built a first 3D model of human ferroportin structure, using the crystal structure of EmrD, a bacterial drug efflux transporter of the Major Facilitator Superfamily, as template. The model enabled study of disease-associated mutations, and guided mutagenesis experiments to determine the role of conserved residues in protein stability and iron transport. Results revealed novel amino acids that are critical for the iron export function and the hepcidin-mediated inhibition mechanism: for example, tryptophan 42, localized in the extracellular end of the ferroportin pore and involved in both biological functions. Here, we propose a strategy that is not limited to structure analysis, but integrates information from different sources, including human disease-associated mutations and functional in vitro assays. The first major hypothesis of this PhD thesis is that ferroportin resistance to hepcidin relies on different molecular mechanisms that are critical for ferroportin endocytosis, and include at least three fundamental steps: (i) hepcidin binding to ferroportin, (ii) structural reorganization of the N- and C-ter ferroportin lobes, and (iii) ferroportin ubiquitination. [ABSTRACT FROM AUTHOR]

We demonstrate a method to reduce the mode volume of optical micro/nanocavities by positioning an opaque microtip in close proximity of the structures. This concept is used to blueshift the resonance of an active photonic crystal nanocavity by up to 16 nm. This tuning range is shown to be about 10 times larger than the redshift achieved with a bare dielectric microtip of the same size and shape. By imagining materials or multilayered devices with the ability to become transparent and opaque under external control, the blue and redshifts of the resonance would become possible with a single perturbing device. [ABSTRACT FROM AUTHOR]