Evaluation of catch-up growth in severe pediatric Hashimoto's hypothyroidism.

BACKGROUND: We aimed to evaluate catch-up growth in children with severe Hashimoto's hypothyroidism (HH) after thyroid hormone replacement therapy (HRT). METHODS: A multicenter retrospective study was conducted including children referred for growth slowdown that led to the diagnosis of HH between 1998 and 2017. RESULTS: A total of 29 patients were included, with a median age of 9.7 years (13-172 months). Median height at diagnosis was -2.7 [-4.6; -0.1] standard deviation score (SDS), with a height loss of 2.5 [0.7; 5.4] SDS compared to height before growth deflection (p<0.0001). At diagnosis, the median TSH level was 819.5 mIU/L [100; 1844], the median FT4 level was 0 pmol/L [undetectable; 5.4], and the median anti-thyroperoxidase antibody level was 1601 UI/L [47; 25,500]. In the 20 patients treated only with HRT, there were significant differences between height at diagnosis and height at 1 year (n = 19, p<0.0001), 2 years (n = 13, p = 0.0005), 3 years (n = 9, p = 0.0039), 4 years (n = 10, p = 0.0078), and 5 years (n = 10, p = 0.0018) of treatment but not in the case of final height (n = 6, p = 0.0625). Median final height was -1.4 [-2.7; 1,5] SDS (n = 6), with a significant difference between height loss at diagnosis and total catch-up growth (p = 0.003). The other nine patients were also given growth hormone (GH). They were smaller at diagnosis (p = 0.01); however, there was no difference in final height between those two groups (p = 0.68). CONCLUSION: Severe HH can lead to a major height deficit, and catch-up growth seems to be insufficient after treatment with HRT alone. In the most severe cases, administration of GH may enhance this catch-up.

Quemaduras profundas en extremidades inferiores. La importancia del factor humano: caso clínico / Deep burns in lower extremities. The importance of the human factor: clinical case

El objetivo de este artículo es exponer el abordaje terapéutico y la importancia del factor humano en la aparición de eventos adversos en lesiones producidas por quemaduras. Para ello presentamos el caso de una mujer de 48 años que sufrió quemaduras dérmicas profundas por exposición a aceite hirviendo en ambas extremidades inferiores con una superficie corporal total quemada del 10%. En atención primaria se estableció un plan de actuación de enfermería con visión holística para evitar la aparición de eventos adversos. Los resultados muestran que, pese a las instrucciones dadas sobre la importancia del reposo, el factor humano de la paciente impidió, a partir de los 15 días, que guardase el reposo necesario. Este hecho produjo la profundización de algunas de las lesiones. Se puede concluir que la aparición de los eventos adversos debidos al factor humano retrasó la curación de las heridas y profundizó las lesiones en ambas extremidades (AU)

The objective is to expose the therapeutic approach and importance of the human factor in the appearance of adverse events in injuries caused by burns. To do this, we present the case of a 48-year-old woman who suffered deep skin burns from exposure to boiling oil in lower extreme embassies with a burned total body surface area of 10%. In Primary Care, a nursing action plan with a holistic vision was established to avoid the appearance of adverse events. The results indicated, despite the instructions given on the importance of rest, that the human factor of the patient prevented, from 15 days, keeping the necessary rest. This fact caused the deepening of some of the injuries. It can be concluded that the appearance of adverse events due to the human factor delayed wound healing and deepened the injuries to both extremities (AU)

[IgG4-Related Disease: A rare cause of severe interstitial lung disease]. / La maladie associée aux IgG4 : une cause rare de pneumopathie infiltrante hypoxémiante sévère.

BACKGROUND: The intrathoracic manifestations of IgG4-related disease include a range of conditions and severity, and can on occasion cause acute respiratory failure as reported in the case described here. OBSERVATION: A 69-year-old male former smoker, was admitted to our hospital with dyspnea, fever, cough, fatigue, and a 3-month history of weight loss. He received high flow oxygen therapy and non-invasive ventilation for severe respiratory failure. Chest computed tomography revealed multifocal condensations and ground glass opacities, accompanied by thickening of the perilymphatic interstitium, mediastinal lymphadenopathy and bilateral pleural effusion. Elevated serum concentrations of IgG4 suggested an IgG4-Related Disease. He developed renal failure and underwent a renal biopsy. Histopathological analysis of which supported the diagnosis by showing dense lymphocytic infiltrate with a count of IgG4+ cells/hpf higher than 60, and storiform fibrosis - a swirling, "cartwheel" pattern of fibrosis which may have a patchy distribution. The patient responded well to steroid therapy. CONCLUSION: Although respiratory symptoms are usually mild in IgG4-relatd disease, thoracic features can evolve into acute respiratory failure with few extra thoracic manifestations.

[Familial pulmonary veno-occlusive disease with a composite biallelic heterozygous EIF2AK4 mutation]. / Une maladie veino-occlusive pulmonaire familiale avec mutation biallélique hétérozygote composite d'EIF2AK4.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Heritable and sporadic forms have been distinguished. Hypoxemia, profound reduction in the diffusion of carbon monoxide and haemodynamic confirmation of pre-capillary pulmonary hypertension are the major diagnostic criteria. Thoracic CT scanning and a response to pharmaceutical therapy provide additional information to confirm the diagnosis. A 52-year-old patient, three of whose siblings had pulmonary hypertension, was admitted with dyspnoea, malaise and palpitations. Right heart catheterisation confirmed pre-capillary pulmonary hypertension. A search for an EIF2AK4 mutation was carried out, and this showed a composite biallelic heterozygous mutation compatible with the diagnosis of familial PVOD, identical to that showed in one of his brothers. Given the signs of severity of the disease and the diagnosis of PVOD, whose response to pharmaceutical therapy is often poor, the patient was placed on a waiting list for lung transplantation. Despite a similar diagnosis in 3 brothers and follow-up proposed 11 years before the diagnosis, pulmonary hypertension appeared within a few weeks and led immediately to a severe clinical situation. Annual clinical and echocardiographic monitoring had been strongly advised to the patient, but had not allowed diagnosis at a mild or moderate stage of the disease. This clinical case shows that the identification of factors predicting the development of heritable PVOD at a pre-symptomatic stage is an important issue for clinical research.

[Eosinophilic pneumonia: A rare complication of sodium divalproate]. / Pneumopathie à éosinophiles : une complication rare du divalproate de sodium.

INTRODUCTION: Eosinophilic pneumonias are characterized by an increase in lung eosinophils. These disorders can be induced by drug reactions. CASE REPORT: A 57-year-old woman suffering from bipolar disorder and treated by sodium divalproate for more than 2 years was hospitalised in the department of respiratory medicine for dyspnoea and cough. The investigations showed severe hypoxaemia, airflow limitation, multiple ground-glass opacities and crazy paving on the chest CT-scan and a blood eosinophilia. A significant alveolar eosinophilia was found in the broncho-alveolar lavage. A complete assessment of possible causes was made. Finally, we made the diagnosis of eosinophilic pneumonia secondary to sodium divalproate. The treatment was stopped and systemic corticosteroid therapy was not introduced. The patient showed an improvement of her dyspnoea in a few days. Lung function and the CT-scan were normal within a few months. CONCLUSIONS: Sodium divalproate, frequently used in the treatment of bipolar disorder, is a rare cause of eosinophilic lung disease, even years after its introduction. Rapid diagnosis and withdrawal of treatment led to complete resolution in the reported case.

[A case of bronchiectasis due to light chain deposition disease]. / Histoire naturelle d'une forme bronchectasiante de la maladie à dépôts de chaînes légères.

INTRODUCTION: The natural history of orphan lung diseases is often unclear. We report the long-term follow-up of a case of bronchiectasis due to pulmonary non amyloid light chain deposition disease (LCDD). CASE REPORT: A 50-year-old woman who was a smoker, was diagnosed with diffuse thin walled bronchiectasis of uncertain origin after presenting with a respiratory tract infection. Ten years later, the combination of bronchiectasis, the appearance of pulmonary cysts and the identification of increased kappa free light chains evoked the diagnosis of pulmonary LCDD. The diagnosis was confirmed by lung biopsy. No immunoproliferative disorder was identified. During the 12 years follow-up, dyspnea worsened progressively and bronchiectasis and lung cysts extended leading to multicystic lung disease. Pulmonary function tests did not show any ventilatory defect but a small decrease in carbon monoxide transfer factor occurred. CONCLUSION: We describe the evolution of a rare presentation of isolated pulmonary LCDD, characterized by cystic diffuse atypical bronchiectasis with thin walls, associated with progressive cystic destruction of the lung parenchyma. The possibility of pulmonary LCDD should be considered in cases of atypical bronchiectasis of unknown etiology.

[Drug-induced interstitial pneumonitis due to avelumab: A case report]. / Pneumopathie interstitielle médicamenteuse à l'avelumab : à propos d'un cas.

INTRODUCTION: The anti programmed death-1 (PD-1) and the programmed death ligand 1 (PD-L1) antibodies are used as immunotherapies in the treatment of many solid tumours. Cases of interstitial pneumonitis induced by anti PD-1 have been widely described, but there are fewer data with anti PD-L1. Avelumab is a new immunotherapy of the anti PD-L1 class. CASE REPORT: A 66-year-old woman, ex-smoker, had been treated with avelumab and axitinib since November 2016 for renal cell cancer. Interstitial pneumonitis was discovered accidentally 4 months after the beginning of the treatment, with ground glass opacities, intra-lobular crosslinking and adenopathy of the 4R zone on the CT scan. An exhaustive assessment did not reveal any respiratory function defect or an infectious or immunological cause. The radiological abnormalities regressed spontaneously after cessation of treatment confirming the diagnosis of drug-induced pneumonitis. CONCLUSION: Avelumab can induce interstitial lung disease. The mechanism is uncertain and requires further studies. Monitoring of respiratory function and CT scanning are necessary for its early management.

[Prophylactic radiotherapy in a single fraction of 10Gy at intervention pleural site in patient with malignant pleural mesothelioma: A retrospective monocentric cohort study]. / Irradiation préventive en une séance de 10Gy des sites d'intervention pleurale des patients atteints de mésothéliome pleural malin : étude de cohorte rétrospective monocentrique.

PURPOSE: Prophylactic radiotherapy to prevent procedure-tracts metastases from malignant pleural mesothelioma remains controversial and clinical practice varies. The purpose was to assess the efficacy of local radiotherapy in a single fraction of 10Gy in preventing malignant seeding at intervention pleural site in patients with malignant pleural mesothelioma. MATERIAL AND METHODS: This is a retrospective cohort study, including patients with histological confirmed malignant pleural mesothelioma treated by prophylactic irradiation to prevent interventional site metastases with a unique fraction of 10Gy with 6 to 18MeV, from January 1990 to December 2013 in the institut de cancérologie de Lorraine (Nancy, France). RESULTS: Ninety-one patients were treated by irradiation in intervention site, involving 120 intervention pleural sites, 91 thoracoscopies, 17 thoracotomies with chest drain and 12 CT or ultrasound guided needle biopsies. The median follow-up was 7 months (interquartile between 3 and 15 months). The overall survival was 43.5% at 12 months. The local progression free survival was 43.7% at 12 month. The incidence of local recurrence was 8% at 12 months. The median interval from radiotherapy to local recurrence was 4 months (2; 32). No grade II or higher toxicity was observed. CONCLUSION: Irradiation of pleural intervention sites with a single fraction of 10Gy is effective, well tolerated, simple, fast and cost effective.

Extensive lymph node dissection during pancreaticoduodenectomy: a risk factor for hepatic steatosis?

PURPOSE: The first reports of hepatic steatosis following pancreaticoduodenectomy (PD) were published several years ago; however, clear risk factors remain to be identified. Therefore, the aim of this study was to identify the risk factors for hepatic steatosis post-PD. METHODS: We studied 90 patients who had undergone PD between September 2005 and January 2015. The inclusion criteria were as follows: available unenhanced CT within one month before PD and at least one unenhanced CT acquisition between PD and chemotherapy initiation. Using scanners, we studied the liver and spleen density as well as the surface areas of visceral (VF) and subcutaneous fat (SCF). These variables were previously identified by univariate and multivariate analyses. RESULTS: Hepatic steatosis occurred in 25.6% of patients at 45.2 days, on average, post-PD. Among the patients with hepatic steatosis, the average liver density was 52 HU before PD and 15.1 HU post-PD (p < 0.001). The Patients with hepatic steatosis lost more VF (mean, 28 vs. 11 cm2) and SCF (28.8 vs. 13.7 cm2) (p < 0.01 and p = 0.01, respectively). Portal vein resection and extensive lymph node dissection were independent risk factors in the multivariate analysis (odds ratio [OR] 5.29, p = 0.009; OR 3.38, p = 0.04, respectively). CONCLUSION: Portal vein resection and extensive lymph node dissection are independent risk factors for post-PD hepatic steatosis.

MDCT features of hepatocellular carcinoma (HCC) in non-cirrhotic liver.

PURPOSE: To describe the multidetector row computed tomography (MDCT) imaging features of HCC that develops in patients who are free from underlying liver cirrhosis and to determine if the MDCT presentation of this specific tumor differs from that of the more common HCC that develops in patients with liver cirrhosis using a retrospective case-control study. PATIENTS AND METHODS: The MDCT examinations of 38 patients with HCC in non-cirrhotic liver (group 1) were quantitatively and qualitatively analyzed and compared to those obtained in 38 patients with HCC in cirrhotic liver (group 2) matched for age and gender. Quantitative and qualitative characteristics of HCC of both groups were compared using univariate analysis. RESULTS: HCCs were significantly larger in group 1 (81.5mm±55.5) than in group 2 (44.5mm±39.1 SD; P=0.0015). In group 1, HCCs were more frequently single tumors (87%) than in group 2 (37%) (P<0.0001), encapsulated (92% vs. 47% respectively; P<0.0001), had more frequently fatty component (24% vs. 8%, respectively; P=0.0279) and internal hemorrhage (29% vs. 3%, respectively; P=0.0033). No significant differences were found between the two groups for location, hyperenhancement of HCC during the arterial phase, washout during the portal phase, endoluminal portal involvement by HCC, endoportal cruoric thrombus, invasion of adjacent organs and underlying liver steatosis. CONCLUSION: HCC in non-cirrhotic liver are larger than those observed in cirrhotic liver and more frequently present as a single encapsulated tumor. They have the same patterns of enhancement than HCC that develops in cirrhotic liver.

Radioembolization with yttrium-90 microspheres work up: Practical approach and literature review.

Radioembolization (RE) is a selective internal radiotherapy technique in which yttrium-90 blended microspheres are infused through the hepatic arteries. It is based on the fact that primary and secondary hepatic tumors are vascularized mostly by arterial blood flow whereas healthy hepatocytes obtain their blood supply mostly from the portal network. This enables high radiation doses to be delivered, sparing the surrounding non-malignant liver parenchyma. Most of the complications are caused by unexpected particles passing into the gastrointestinal tract through branches originating from the main hepatic arterial supply. Knowledge of this hepatic arterial network and of its variations and the technical considerations this raises are required in preparation for treatment. This work describes the specific anatomical features and techniques for this anatomy through recent literature illustrated by cases from our own experience.

CDKN1C mutation affecting the PCNA-binding domain as a cause of familial Russell Silver syndrome.

BACKGROUND: Russell Silver syndrome (RSS) leads to prenatal and postnatal growth retardation. About 55% of RSS patients present a loss-of-methylation of the paternal ICR1 domain on chromosome 11p15. CDKN1C is a cell proliferation inhibitor encoded by an imprinted gene in the 11p15 ICR2 domain. CDKN1C mutations lead to Beckwith Wiedemann syndrome (BWS, overgrowth syndrome) and in IMAGe syndrome which associates growth retardation and adrenal insufficiency. We searched for CDKN1C mutations in a cohort of clinically diagnosed RSS patients with no molecular anomaly. METHOD: The coding sequence and intron-exon boundaries of CDKN1C were analysed in 97 RSS patients. The impact of CDKN1C variants on the cell cycle in vitro were determined by flow cytometry. Stability of CDKN1C was studied by western immunoblotting after inhibition of translation with cycloheximide. RESULTS: We identified the novel c.836G>[G;T] (p.Arg279Leu) mutation in a familial case of intrauterine growth retardation (IUGR) with RSS phenotype and no evidence of IMAGe. All the RSS patients inherited this mutation from their mothers (consistent with monoallelic expression from the maternal allele of the gene). A mutation of this amino acid (p.Arg279Pro) has been reported in cases of IMAGe. Functional analysis showed that Arg279Leu (RSS) did not affect the cell cycle, whereas the Arg279Pro mutation (IMAGe) led to a gain of function. Arg279Leu (RSS) led to an increased stability which could explain an increased activity of CDKN1C. CONCLUSIONS: CDKN1C mutations cause dominant maternally transmitted RSS, completing the molecular mirror with BWS. CDKN1C should be investigated in cases with family history of RSS.

Abnormal neuronal differentiation and mitochondrial dysfunction in hair follicle-derived induced pluripotent stem cells of schizophrenia patients.

One of the prevailing hypotheses suggests schizophrenia as a neurodevelopmental disorder, involving dysfunction of dopaminergic and glutamatergic systems. Accumulating evidence suggests mitochondria as an additional pathological factor in schizophrenia. An attractive model to study processes related to neurodevelopment in schizophrenia is reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and differentiating them into different neuronal lineages. iPSCs from three schizophrenia patients and from two controls were reprogrammed from hair follicle keratinocytes, because of their accessibility and common ectodermal origin with neurons. iPSCs were differentiated into Pax6(+)/Nestin(+) neural precursors and then further differentiated into ß3-Tubulin(+)/tyrosine hydroxylase(+)/DAT(+) dopaminergic neurons. In addition, iPSCs were differentiated through embryonic bodies into ß3-Tubulin(+)/Tbox brain1(+) glutamatergic neurons. Schizophrenia-derived dopaminergic cells showed severely impaired ability to differentiate, whereas glutamatergic cells were unable to maturate. Mitochondrial respiration and its sensitivity to dopamine-induced inhibition were impaired in schizophrenia-derived keratinocytes and iPSCs. Moreover, we observed dissipation of mitochondrial membrane potential (Δψm) and perturbations in mitochondrial network structure and connectivity in dopaminergic along the differentiation process and in glutamatergic cells. Our data unravel perturbations in neural differentiation and mitochondrial function, which may be interconnected, and of relevance to dysfunctional neurodevelopmental processes in schizophrenia.

Diverse p63 and p73 isoforms regulate Δ133p53 expression through modulation of the internal TP53 promoter activity.

In response to stress, p53 binds and transactivates the internal TP53 promoter, thus regulating the expression of its own isoform, Δ133p53α. Here, we report that, in addition to p53, at least four p63/p73 isoforms regulate Δ133p53 expression at transcriptional level: p63ß, ΔNp63α, ΔNp63ß and ΔNp73γ. This regulation occurs through direct DNA-binding to the internal TP53 promoter as demonstrated by chromatin immunoprecipitation and the use of DNA-binding mutant p63. The promoter regions involved in the p63/p73-mediated transactivation were identified using deleted, mutant and polymorphic luciferase reporter constructs. In addition, we observed that transient expression of p53 family members modulates endogenous Δ133p53α expression at both mRNA and protein levels. We also report concomitant variation of p63 and Δ133p53 expression during keratinocyte differentiation of HaCat cells and induced pluripotent stem cells derived from mutated p63 ectodermal dysplasia patients. Finally, proliferation assays indicated that Δ133p53α isoform regulates the anti-proliferative activities of p63ß, ΔNp63α, ΔNp63ß and ΔNp73γ. Overall, this study shows a strong interplay between p53, p63 and p73 isoforms to orchestrate cell fate outcome.

Induced pluripotent stem cells from hair follicles as a cellular model for neurodevelopmental disorders.

Disease-specific induced pluripotent stem cells (iPSC) allow unprecedented experimental platforms for basic research as well as high-throughput screening. This may be particularly relevant for neuropsychiatric disorders, in which the affected neuronal cells are not accessible. Keratinocytes isolated from hair follicles are an ideal source of patients' cells for reprogramming, due to their non-invasive accessibility and their common neuroectodermal origin with neurons, which can be important for potential epigenetic memory. From a small number of plucked human hair follicles obtained from two healthy donors we reprogrammed keratinocytes to pluripotent iPSC. We further differentiated these hair follicle-derived iPSC to neural progenitors, forebrain neurons and functional dopaminergic neurons. This study shows that human hair follicle-derived iPSC can be differentiated into various neural lineages, suggesting this experimental system as a promising in vitro model to study normal and pathological neural developments, avoiding the invasiveness of commonly used skin biopsies.

Metal-on-metal bearings total hip arthroplasty: the cobalt and chromium ions release concern.

With certain concerns recently reported on metal-on-metal bearing couples in total hip arthroplasty, this study's objective is to review the current knowledge concerning release of metal ions and its potential consequences. Each metal-on-metal implant presents different tribological properties. The analytical techniques for metals are accurate and the Co ion rates seem acceptable up to 2 µg/L. A delayed type IV hypersensitivity reaction (atypical lymphocytic vasculitis-associated lesion [ALVAL]) may be the source of arthroplasty failure. Idiosyncratic, it remains unpredictable even using cutaneous tests and apparently is rare (0.3%). Today, there are no scientific or epidemiologic data supporting a risk of carcinogenesis or teratogenesis related to the use of a metal-on-metal bearings couple. Solid pseudotumors nearly exclusively are observed with resurfacing procedures, carrying a high annual revision rate in women under 40 years of age, occurring particularly in cases of acetabular malposition and with use of cast molded Cr-Co alloys. Osteolysis manifests through complete and progressive radiolucent lines or through cavitary lesions stemming from ALVAL-type alterations or impingement problems or implant incompatibility. The formation of wear debris exceeding the biological tolerance is possible with implant malposition, subluxation, and jamming of the femoral head in cases of cup deformity. Moreover, each implant presents different metal ion production; assessment of their performance and safety is required before their clinical use. With the knowledge available today, metal-on-metal bearing couples are contraindicated in cases of metal allergies or end stage renal dysfunction and small size resurfacing should cautiously be used.

Impact of rapid enterovirus molecular diagnosis on the management of infants, children, and adults with aseptic meningitis.

Enteroviruses (EV) are the main etiological agents of aseptic meningitis. Diagnosis is made by detecting the genome using RT-PCR. The aim of the study was to evaluate the impact of a positive diagnosis on the management of infants, children, and adults. During 2005, 442 patients were admitted to hospital with suspected meningitis. Clinical and laboratory data and initial treatment were recorded for all patients with enteroviral meningitis. The turnaround time of tests and the length of hospital stay were analyzed. The results showed that EV-PCR detected EV in 69 patients (16%), 23% (16/69) were adults. About 18% of CSF samples had no pleocytosis. After positive PCR results, 63% of children were discharged immediately (mean 2 hr 30 min) and 95% within 24 hr. Infants and adults were discharged later (after 1.8 and 2 days, respectively). The use of antibiotics was significantly lower in children than in infants and adults. The PCR results allowed discontinuation of antibiotics in 50-60% of all patients treated. Patients received acyclovir in 16% of cases (7% children vs. 50% adults) and 23% (11% vs. 69%) underwent a CT scan. Clinical data were compared between patients whose positive EV-PCR results were available within 24 hr (n = 32) and those whose results were available > 24 hr after collection of CSF (n = 14). Duration of antibiotic treatment (difference: 2.3 days; P = 0.05) was reduced between the two groups. No statistical difference in the length of stay was observed. The EV-PCR assay should be performed daily in hospital laboratory practice and considered as part of the initial management of meningitis.

The CXCR4 antagonist AMD3100 impairs survival of human AML cells and induces their differentiation.

The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, participate in the retention of acute myeloblastic leukemia (AML) cells within the bone marrow microenvironment and their release into the circulation. AML cells also constitutively express SDF-1-dependent elastase, which regulates their migration and proliferation. To study the molecular events and genes regulated by the SDF-1/CXCR4 axis and elastase in AML cells, we examined gene expression profiles of the AML cell line, U937, under treatment with a neutralizing anti-CXCR4 antibody or elastase inhibitor, as compared with non-treated cells, using DNA microarray technology. Unsupervised hierarchical clustering analysis demonstrated similar gene expression profiles of anti-CXCR4 antibody or elastase inhibitor-treated cells, as compared with control. Pathway and functional analysis showed a greater tendency toward differentiation in cells under either one of both treatment modalities. Thus given, we further analyzed the effects of CXCR4 inhibition on AML cell growth and differentiation using the antagonist AMD3100. AMD3100 arrested proliferation in AML cell lines and triggered changes that mimicked differentiation, including morphological changes and the expression of myeloid differentiation antigens. Inhibition of elastase also triggered the differentiation of AML cells. Our study defines a new role for the SDF-1/CXCR4 axis in the regulation of leukemic cell survival and differentiation.

Arthrospira platensis harvesting with membranes: fouling phenomenon with limiting and critical flux.

The present work deals with the harvesting of Arthrospira platensis (Spirulina) from a diluted culture medium. This cyanobacterium was retained by the European Space Agency as food supply for long term manned spatial missions, and integrated in the MELiSSA project: an artificial microecosystem which supports life in space. Membranes techniques seem to be adapted to efficiency, reliability and safety constraints, even if a well-known limitation is the progressive fouling and permeation flux decrease. Among usual solid/liquid separation processes, Arthrospira harvesting is performed by tangential ultrafiltration (tubular inorganic membrane 50 kD Céram-Inside from Tami, Nyons, France). To ensure a reliable separation step with the best biomass quality, a good comprehension of the ultrafiltration progress and fouling phenomenon is needed, in particular, the link between operating parameters, permeation flux and cleanability. Comparative experiments were made between limiting and critical flux with different suspensions: fresh biomass, stressed biomass and a suspension of Arthrospira platensis enriched with exopolysaccharides.