Peripheral blood stem cells collection on spectra optia apheresis system using the continuous mononuclear cell collection protocol: A single center report of 39 procedures.

BACKGROUND: The aim of the study was to assess the performance of the new Continuous Mononuclear Cell Collection (CMNC) protocol on the Spectra Optia Apheresis System for collecting autologous Peripheral Blood Stem Cells (PBSC) in adult patients with respect to collection variables, CD34+ cells harvest prediction and engraftment data. In this retrospective study, 39 CMNC procedures on 23 mobilized patients with multiple myeloma and lymphoma were analyzed. CD34+ cells and blood cells yields, collection efficiencies (CE1 and CE2), cell losses were calculated. Engraftment data of 17 autologous transplantations were collected. RESULTS: Apheresis duration was 239 min for a product volume of 220 mL. Cell product haematocrit, MNC and platelets counts were acceptable (respectively 2.4%, 65%, 834 x 109/L). Median platelet loss was 27.3%. Median CD34+ CE1 and CE2 were 64.6% and 48.5% respectively. We harvested 2.92 × 106 CD34+ cells/kg, with a CD34 dose ≥ 2 × 106 /kg for 67% of the procedures. Linear correlation between preapheresis CD34 count and the CP CD34 dose/kg allowed a prediction model with a decrease trend for high WBC precount. Procedures were well tolerated. For 17 autologous transplantations, median time to neutrophils and platelets reconstitutions were 12 and 13 days respectively. CONCLUSIONS: Spectra Optia CMNC protocol successfully collected CD34+ cells with yields permitting the harvest of sufficient enriched grafts for autologous transplantation. The CD34+ cell yield prediction was excellent. PBSC collection with CMNC protocol had advantages of high processing rate, low product volume, and acceptable contamination by platelets. J. Clin. Apheresis 32:182-190, 2017. © 2016 Wiley Periodicals, Inc.

Anatomical basis of the coordination between smooth and striated urethral and anal sphincters: loops of regulation between inferior hypogastric plexus and pudendal nerve. Immuno-histological study with 3D reconstruction.

PURPOSE: (1) Describe both nervous pathways to the sphincters, and highlight the anatomical support of their coordination. (2) Obtain a 3D representation of this complex innervation system. METHODS: A computer-assisted anatomical dissection technique was used. Serial histological sections were cut in the pelvis of four female human foetuses (aged 19-32 weeks of gestation). The sections were treated with conventional staining, and with seven different immunostainings. The sections were digitalized and, finally, a 3D representation was built from the corresponding images. RESULTS: Myelinated and sensory fibres were detected at the inferior hypogastric plexus (IHP) level. Our analysis showed that most of the afferent sensory fibres come from the urinary and anal sphincters through the anterior and posterior branches of the IHP respectively. A highly positive nitrergic (anti-NOS1) and sensitive (anti-CGRP) labelling was found in the external layer of the urethral sphincter. The 3D representation allowed describing the two components of the innervation system. A sensory-motor regulation loop was found for both sphincters. CONCLUSION: A 3D description of the components of both nervous pathways to the sphincters has been established. Our findings on the innervation of the sphincters tend to question the classical infra/supra levatorian muscle description. The coordinated work of the internal and external layers of the anal and urethral sphincter is probably mediated by multiple roles regulation.

Dual-modulation fiber Fabry-Perot interferometer with double reflection for slowly-varying displacements.

This Letter describes a dual-amplitude modulation technique incorporated into a double reflection extrinsic-type fiber Fabry-Perot interferometer to measure periodic, nonperiodic as well as quasi-static displacements. The modulation scheme simultaneously maintains the interference signal pair in quadrature and provides a reference signal for displacements inferior to a quarter of the source wavelength. The control and phase demodulation of the interferometer carried out via software enable quasi-real-time measurement and facilitates sensor alignment. The sensor system can be exploited in the low frequency range from 10(-3) to ∼500 Hz and has a resolution better than 2.2 nm, targeting applications in geophysics.

Posterior urethral injuries associated with pelvic injuries in young adults: computerized finite element model creation and application to improve knowledge and prevention of these lesions.

INTRODUCTION: Young adult males involved in motorcycle accidents are particularly at risk for posterior urethral injury whenever pelvic injury occurs. Posterior urethral injuries remain problematic because their diagnosis may be missed, and during the initial treatment response the urethral injury can be aggravated by urethral catheterization. Few anatomical and clinical tools exist that establish a correlation between injuries and fractures of the pelvic ring and the risk of posterior urethral injury. METHOD: Based on experience with traffic accident modeling, a computerized finite element model was conceived integrating the specific anatomic structures concerned. This model was extrapolated from a CAT scan of a young adult. The anatomic structures concerned in urethral and pelvic ring trauma (PRT) were isolated, placed in 3D and given biomechanical properties. The model was verified according to available experiments on PRT. RESULTS: To apply the model, we recreated a lateral impact mechanism on the pelvic ring. Stretching between the prostatic and membranous portions of the urethra (before and after visualization of a pelvic fracture) as well as timing of injury was studied. CONCLUSION: The model's application permitted us to analyze precisely the link between lateral impact trauma of the pelvic ring and lesions of the posterior urethra and to identify an urethra stretching prior to visualization of a pelvic fracture. Utilization of the model with other mechanisms of injury should allow for better comprehension of this associated trauma, improved prevention, iatrogenic aggravation of, and care for, these serious injuries.

Structural and photochemical properties of organosilver reactive intermediates MeAg2(+) and PhAg2(+).

Although there is growing interest in silver promoted carbon-carbon bond formation, a key challenge in developing robust and reliable organosilver reagents is that thermal and photochemical decomposition reactions can compete with the desired coupling reaction. These undesirable reactions have been poorly understood due to complications arising from factors such as solvent effects and aggregation. Here the unimolecular decomposition reactions of organosilver cations, RAg(2)(+), where R = methyl (Me) and phenyl (Ph), are examined in the gas phase using a combination of mass spectrometry based experiments and theoretical calculations to explore differences between thermal and photochemical decompositions. Under collision-induced dissociation conditions, which mimic thermal decomposition, both PhAg(2)(+) and MeAg(2)(+) fragment via formation of Ag(+). The new ionic products, RAg(+•) and Ag(2)(+•), which arise via bond homolysis, are observed when RAg(2)(+) is subject to photolysis using a UV-vis tunable laser OPO. Furthermore, comparisons between the theoretical and experimental UV-vis spectra allow us to unambiguously determine the most stable structures of PhAg(2)(+) and MeAg(2)(+) and to identify the central role of the silver part in the optical absorption of these species. The new photoproducts result from fragmentation in electronic excited states. In particular, potential energy surface calculations together with the fragment charges highlight the role of triplet states in these new fragmentation schemes.

Hemispherical differences in the shape and topography of asteroid (101955) Bennu.

We investigate the shape of near-Earth asteroid (101955) Bennu by constructing a high-resolution (20 cm) global digital terrain model from laser altimeter data. By modeling the northern and southern hemispheres separately, we find that longitudinal ridges previously identified in the north extend into the south but are obscured there by surface material. In the south, more numerous large boulders effectively retain surface materials and imply a higher average strength at depth to support them. The north has fewer large boulders and more evidence of boulder dynamics (toppling and downslope movement) and surface flow. These factors result in Bennu's southern hemisphere being rounder and smoother, whereas its northern hemisphere has higher slopes and a less regular shape. We infer an originally asymmetric distribution of large boulders followed by a partial disruption, leading to wedge formation in Bennu's history.

Controlling the composition of a confined fluid by an electric field.

Starting from a generic model of a pore/bulk mixture equilibrium, we propose a novel method for modulating the composition of the confined fluid without having to modify the bulk state. To achieve this, two basic mechanisms-sensitivity of the pore filling to the bulk thermodynamic state and electric field effect-are combined. We show by Monte Carlo simulation that the composition can be controlled both in a continuous and in a jumpwise way. Near the bulk demixing instability, we demonstrate a field induced population inversion in the pore. The conditions for the realization of this method should be best met with colloids, but being based on robust and generic mechanisms, it should also be applicable to some molecular fluids.

Structure of highly confined fluids: mixture of polar and nonpolar macroparticles in an external field.

In this paper we study the structure of highly confined mixtures of polar and nonpolar macroparticles in an external field by Monte Carlo simulation in the canonical ensemble. Without attempting a systematic investigation of the model, several effects including confinement, polarization, and solvation forces are considered. In particular, we show that layering at different length scales can be obtained in mixtures of differently sized particles subject to an external electric field.

Nefopam hydrochloride compatibility and stability with selected proton pump inhibitors in bionolyte G5 injection for intravenous infusion.

BACKGROUND: The use of extemporaneously prepared admixtures of drugs must be supported by documentation of their chemical stability. OBJECTIVE: To assess the physical compatibility and the chemical stability of nefopam hydrochloride, a centrally acting non-opioid analgesic, when admixed with selected proton pump inhibitors (omeprazole, esomeprazole or pantoprazole), in bionolyte G5 injection for intravenous infusion. METHOD: Admixtures were assessed for periods of up to 72 h after storage at ambient temperature without protection from light and at +4 degrees C protected from light. A preparation was considered stable if the compounds of the mixture retained at least 90% of their original potency during the storage. Triplicate samples of nefopam and the selected proton pump inhibitors as well as the following mixtures (nefopam/omeprazole, nefopam/esomeprazole and nefopam/pantoprazole) were prepared in the concentrations required, in polypropylene bottles of bionolyte G5 injection. The physical compatibility was assessed by visual observation at each sampling interval. The chemical stability of the drugs was evaluated by high-performance liquid chromatography and by measurement of pH values. RESULTS: During refrigerated storage, nefopam as well as the selected proton pump inhibitors, when prepared separately in bionolyte G5 injection maintained chemical stability for up to 7 days. At ambient storage conditions, the protons pump inhibitors maintained chemical stability for 24 h, but thereafter their concentrations decreased significantly at day 1. Nefopam maintained chemical stability for up to 72 h at +25 degrees C. Nefopam/omeprazole and nefopam/esomeprazole mixtures in bionolyte were physically incompatible with the mixtures exhibiting a black colour. They underwent rapid and extensive loss, making the combination unacceptable within minutes of mixing. However, the nefopam/pantoprazole mixture was compatible over the study period, but with a reduced duration of the stability. CONCLUSION: Within the limits defined above, nefopam and the selected proton pump inhibitors may be prepared separately in advance in bionolyte G5 injection. The nefopam/pantoprazole mixture was stable for a short period, while the nefopam/omeprazole and the nefopam/esomeprazole mixtures were incompatible and unusable, immediately upon admixture.

Experience of two trauma-centers with pancreatic injuries requiring immediate surgery.

BACKGROUND/AIMS: Pancreatic injury from blunt trauma is infrequent. The aim of the present study was to evaluate a simplified approach of management of pancreatic trauma injuries requiring immediate surgery consisting of either drainage in complex situation or pancreatectomy in the other cases. METHODOLOGY: From January 1986 to December 2006, 40 pancreatic traumas requiring immediate surgery were performed. Mechanism of trauma, clinical and laboratories findings were noted upon admission, classification of pancreatic injury according to Lucas' classification were considered. Fifteen (100%) drainages were performed for stage I (n=15), 60% splenopancreatectomies and 40% drainage was achieved for stage II (n=18), 3 Pancreaticoduonectomies and 2 exclusion of duodenum with drainage and 2 packing were performed for stage IV (n=7). RESULTS: There were 30 men and 10 women with mean age of 29+/-13 years (15-65). Thirty-eight patients had multiple trauma. Overall, mortality and global morbidity rate were 17% and 65% respectively, and the rates increased with Lucas' pancreatic trauma stage. CONCLUSIONS: Distal pancreatectomy is indicated for distal injuries with duct involvement, and complex procedures such as pancreaticoduodenectomy should be performed in hemodynamically stable patients.

Liver injuries in frontal crash situations a coupled numerical - experimental approach.

From clinical knowledge, it has been established that hepatic traumas frequently lead to lethal injuries. In frontal or lateral crash situations, these injuries can be induced by pure deceleration effects or blunt trauma due to belt or steering wheel impact. Concerning the liver under frontal decelerations, how could one investigate organ behaviour leading to the injury mechanisms? This work couples experimental organ decelerations measurements (with 19 tests on cadaver trunks) and finite element simulation, provides a first analysis of the liver behaviour within the abdomen. It shows the influence of the liver attachment system that leads to liver trauma and also torsion effects between the two lobes of the liver. Injury mechanisms were evaluated through the four phases of the liver kinematics under frontal impact: (1) postero-anterior translation, (2) compression and sagittal rotation, (3) rotation in the transverse plane and (4) relaxation.

[Endoscopic management of postoperative pancreatic collections]. / Prise en charge endoscopique des collections pancréatiques postopératoires.

INTRODUCTION: Treatment of pancreatic postoperative collections are usually managed with a multidisciplinary team. Different managements are possible: abstention, external drainage, endoscopic treatment or surgery. METHODS: We report on a case series of five patients with a postoperative pancreatic collection, endoscopically managed. Patients underwent all a CT scan associated or not with endoscopic ultrasonography. RESULTS: An endoscopic cystenterosotomy was performed in all the cases, with two double pig tail stents sometimes associated with nasocystic drainage for clearing the cyst lumen and with transpapillary drainage in one case. All the procedures were successful and patients healed in all the cases with the disappearance of the radiological image within a 33 days to three months range with one complication due to superinfection of the drained cyst, endoscopically managed with a nasocystic catheter. CONCLUSION: Therapeutic endoscopy, with a multidisciplinary approach, is a promising way to manage postoperative pancreatic collections.

[Pregnant woman and road safety: a numerical approach. Application to a restrained third trimester pregnant woman in frontal impact]. / Femme enceinte et accidentologie routière: intérêt de l'approche numérique. Application à un choc frontal au troisième trimestre de la grossesse avec analyse de l'effet de la ceinture de sécurité

OBJECTIVES: The goal of our work is the development of a numerical model of pregnant woman in driving position. We present an application to the study of injury mechanisms during a frontal car crash for a seat belt restrained pregnant woman in driving position. MATERIALS AND METHODS: We integrated a digital representation of a pregnant uterus, foetus and placenta in a previous existing numerical model of non pregnant Human body in driving position, the Humos model. The realization of a numerical simulation of a frontal car crash enabled us to analyze the part played by the safety belt in the organic traumatisms. RESULTS: Three phases were highlighted. The first phase consists of a translation forwards of the pregnant uterus during the impact. The second phase is a rotation forwards in the sagittal plan of the pregnant uterus with for axis of rotation the posterior wall of the pubis. The third phase is a vertical adjustment coupled to a translation of the uterus towards the back. This translation leads the uterus to impact the spine. CONCLUSION: The development of a pregnant numerical model in the field of accidentology allows the analysis of organic traumatisms. That makes it possible to study the role played by the existing safety systems. This model might make it possible to develop safety systems specific to the pregnant woman.

Rheumatologic Manifestations of Hematologic Neoplasms.

BACKGROUND: The rheumatologic manifestations of hematologic neoplasms are a collection of diverse syndromes. This review aims to describe the most common syndromes in the context of potential mechanisms of pathogenesis. METHODS: We undertook a structured search of the available peer-reviewed literature describing paraneoplastic phenomena associated with hematologic neoplasms and the most current literature on the biology of inflammation and neoplasm. RESULTS: This review describes the common rheumatologic manifestations and discusses their possible underlying pathogenesis. CONCLUSIONS: This review describes common clinical features of paraneoplastic phenomena prevalent in hematologic malignancies that may help differentiate them from primary rheumatologic disease and discusses the most current understanding of underlying pathogenesis with a specific focus on the biology of inflammation in neoplastic transformation.

Monitoring CD27+ memory B-cells in neuromyelitis optica spectrum disorders patients treated with rituximab: Results from a bicentric study.

BACKGROUND: Rituximab (RTX) is increasingly used in the treatment of neuromyelitis optica spectrum disorder (NMO-SD). Administration regimen is not consensual as there is no reliable biomarker of RTX efficacy. In most cases, after induction, RTX is administered systematically every 6months. OBJECTIVE: To assess efficacy and safety of a maintenance regimen based on CD19+ CD27+ memory B-cell (mBc) detection. METHODS: We conducted a study in two French centers, including patients with NMO-SD who received an induction therapy with RTX. We compared the number of administered infusions, relapses and EDSS depending on two maintenance schemes (S1: administration of 1g RTX infusion every 6months or S2: a scheme based on regular mBc detection. 1g RTX was administered if mBc was >0.05%) RESULTS: 40 patients were included (mean age: 40.2years, F/M sex ratio: 5/1). Aquaporin-4 antibodies were positive in 75% patients. Under S1 regimen, all patients received 2 infusions per year, whereas under S2, they received 1.62 infusion per year. The mean interval between infusions under S2 was 7.4months, without decrease of clinical efficacy. CONCLUSION: In our study, mBc-based administration of RTX allowed personalizing treatment administration and in several cases to lower the cumulative dose without loss of efficacy.

Hollow viscus injury due to blunt trauma: A review.

Blunt abdominal trauma results in injury to the bowel and mesenteries in 3-5% of cases. The injuries are polymorphic including hematoma, seromuscular tear, perforation, and ischemia. They preferentially involve the small bowel and may result in bleeding and/or peritonitis. An urgent laparotomy is necessary if there is evidence of active bleeding or peritonitis at the initial examination, but these situations are uncommon. The main diagnostic challenge is to promptly and correctly identify lesions that require surgical repair. Diagnostic delay exceeding eight hours before surgical repair is associated with increased morbidity and probably with mortality. Because of this risk, the traditional therapeutic approach has been to operate on all patients with suspected bowel or mesenteric injury. However, this approach leads to a high rate of non-therapeutic laparotomy. A new approach of non-operative management (NOM) may be applicable to hemodynamically stable patients with no signs of perforation or peritonitis, and is being increasingly employed. This attitude has been described in several recent studies, and can be applied to nearly 40% of patients. However, there is no consensual agreement on which criteria or combination of clinical and radiological signs can insure the safety of NOM. When NOM is decided upon at the outset, very close monitoring is mandatory with repeated clinical examinations and interval computerized tomography (CT). Larger multicenter studies are needed to better define the selection criteria and modalities for NOM.

[Antenatal palliative plan following diagnosis of fetal lethal condition: Rennes Teaching Hospital experience]. / Projet palliatif anténatal après diagnostic de malformation fœtale létale : expérience du CHU de Rennes de 2006 à 2012.

OBJECTIVES: To study the pregnancies followed at Rennes University Hospital from 2006 to 2012, after prenatal diagnosis of lethal fetal condition and prenatal project of palliative care at birth consisting of comfort care emphasizing parent-child encounters and bonding. MATERIAL AND METHODS: Retrospective study of 20 pregnancies with diagnosis of lethal fetal condition where parents accepted antenatally the proposal or sought for palliative care at birth. RESULTS: Diagnosis was made at a median age of 20 weeks gestation (12-33). Birth occurred at 37.4 WG, 6 caesarean sections were performed for maternal conditions. Six cases of hypoplastic left heart syndrome (HLHS) share common characteristics: good Apgar score, prolonged survival (26hours to 159days) transfer to neonatology ward (6) or later at home (4). In four multiple pregnancies, the choice of SP mainly contributed to protect healthy twins during pregnancy. In birth room, there was no need for invasive procedure or drugs. Death: one occurred during labor, 8 in birth room before H2, others in neonatal ward before d4 (excluding HLHS). CONCLUSION: These data will enable better antenatal preparation of both teams and parents. Lifetime, however short, allowed parents to meet with their child alive this permitting collection of memory traces and bonding.

Circulating microRNAs in follicular fluid, powerful tools to explore in vitro fertilization process.

Circulating or "extracellular" microRNAs (miRNAs) detected in biological fluids, could be used as potential diagnostic and prognostic biomarkers of several disease, such as cancer, gynecological and pregnancy disorders. However, their contributions in female infertility and in vitro fertilization (IVF) remain unknown. This study investigated the expression profiles of five circulating miRNAs (let-7b, miR-29a, miR-30a, miR-140 and miR-320a) in human follicular fluid from 91 women with normal ovarian reserve and 30 with polycystic ovary syndrome (PCOS) and their ability to predict IVF outcomes. The combination of FF miR-30a, miR-140 and let-7b expression levels discriminated between PCOS and normal ovarian reserve with a specificity of 83.8% and a sensitivity of 70% (area under the ROC curve, AUC = 0.83 [0.73-0.92]; p < 0.0001). FF samples related to low number of mature oocytes (≤2) contained significant less miR-320a levels than those related to a number of mature oocytes >2 (p = 0.04). Moreover, FF let-7b predicted the development of expanded blastocysts with 70% sensitivity and 64.3% specificity (AUC = 0.67 [0.54-0.79]; p = 0.02) and FF miR-29a potential to predict clinical pregnancy outcome reached 0.68 [0.55-0.79] with a sensitivity of 83.3% and a specificity of 53.5% (p = 0.01). Therefore, these miRNAs could provide new helpful biomarkers to facilitate personalized medical care during IVF.

Aldehyde dehydrogenases inhibition eradicates leukemia stem cells while sparing normal progenitors.

The vast majority of patients with acute myeloid leukemia (AML) achieve complete remission (CR) after standard induction chemotherapy. However, the majority subsequently relapse and die of the disease. A leukemia stem cell (LSC) paradigm has been invoked to explain this failure of CR to reliably translate into cure. Indeed, LSCs are highly enriched in CD34+CD38- leukemic cells that exhibit positive aldehyde dehydrogenase activity (ALDH+) on flow cytometry, these LSCs are resistant to currently existing treatments in AML such as cytarabine and anthracycline that, at the cost of great toxicity on normal cells, are highly active against the leukemic bulk, but spare the LSCs responsible for relapse. To try to combat the LSC population selectively, a well-characterized ALDH inhibitor by the trivial name of dimethyl ampal thiolester (DIMATE) was assessed on sorted CD34+CD38- subpopulations from AML patients and healthy patients. ALDH activity and cell viability were monitored by flow cytometry. From enzyme kinetic studies DIMATE is an active enzyme-dependent, competitive, irreversible inhibitor of ALDH1. On cells in culture, DIMATE is a powerful inhibitor of ALDHs 1 and 3, has a major cytotoxic activity on human AML cell lines. Moreover, DIMATE is highly active against leukemic populations enriched in LSCs, but, unlike conventional chemotherapy, DIMATE is not toxic for healthy hematopoietic stem cells which retained, after treatment, their self-renewing and multi-lineage differentiation capacity in immunodeficient mice, xenografted with human leukemic cells. DIMATE eradicates specifically human AML cells and spares healthy mouse hematologic cells.