Investigation on the self-assembly of the NFL-TBS.40-63 peptide and its interaction with gold nanoparticles as a delivery agent for glioblastoma.

NFL-TBS.40-63 peptide is a recently discovered peptide derived from the light neurofilament chain (NFL). In this study, we demonstrated that the Biotinylated-NFL-peptide (BIOT-NFL) can spontaneously self-assemble into well-organized nanofibers (approximately 5 nm width and several micrometers in length) in several solutions, whereas the typical self-assembly was not systematically observed from other peptides with or without coupling. The critical aggregation concentration that allows the BIOT-NFL-peptide to aggregate and auto associate was determined at 10-4 mol/L by surface tension measurements. X-ray scattering of BIOT-NFL-peptide also demonstrated its beta-sheet structure that can facilitate the intermolecular interactions involved in the self-assembly process. The possible disassembly of self-assembled BIOT-NFL-peptide-nanofibers was examined via a dialysis membrane study. We further investigated the interaction between nanofibers formed by BIOT-NFL-peptide and gold nanoparticles. Interestingly, a strong interaction was demonstrated between these nanoparticles and BIOT-NFL-peptide resulted in the formation of BIOT-NFL-peptide-nanofibers grandly decorated by gold nanoparticles. Finally, we investigated the internalization of gold nanoparticles coupled with BIOT-NFL-nanofibers into F98 rat glioblastoma cells, which was increased compared to the non-coupled control gold nanoparticles. All these results indicate that this peptide could be a promising therapeutic agent for targeted delivery.

[Expert consensus from the College of French Gynecologists and Obstetricians: Management of nausea and vomiting of pregnancy and hyperemesis gravidarum]. / Consensus formalisé d'experts du Collège national des gynécologues et obstétriciens français : prise en charge des nausées et vomissements gravidiques et de l'hyperémèse gravidique.

OBJECTIVE: To determine the management of patients with 1st trimester nausea and vomiting and hyperemesis gravidarum. METHODS: A panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. RESULTS: Hyperemesis gravidarum is distinguished from nausea and vomiting during pregnancy by weight loss≥5 % or signs of dehydration or a PUQE score≥7. Hospitalization is proposed when there is, at least, one of the following criteria: weight loss≥10%, one or more clinical signs of dehydration, PUQE (Pregnancy Unique Quantification of Emesis and nausea) score≥13, hypokalemia<3.0mmol/L, hyponatremia<120mmol/L, elevated serum creatinine>100µmol/L or resistance to treatment. Prenatal vitamins and iron supplementation should be stopped without stopping folic acid supplementation. Diet and lifestyle should be adjusted according to symptoms. Aromatherapy is not to be used. If the PUQE score is<6, even in the absence of proof of their benefit, ginger, pyridoxine (B6 vitamin), acupuncture or electrostimulation can be used, even in the absence of proof of benefit. It is proposed that drugs or combinations of drugs associated with the least severe and least frequent side effects should always be chosen for uses in 1st, 2nd or 3rd intention, taking into account the absence of superiority of a class over another to reduce the symptoms of nausea and vomiting of pregnancy and hypermesis gravidarum. To prevent Gayet Wernicke encephalopathy, Vitamin B1 must systematically be administered for hyperemesis gravidarum needing parenteral rehydration. Patients hospitalized for hyperemesis gravidarum should not be placed in isolation (put in the dark, confiscation of the mobile phone or ban on visits, etc.). Psychological support should be offered to all patients with hyperemesis gravidarum as well as information on patient' associations involved in supporting these women and their families. When returning home after hospitalization, care will be organized around a referring doctor. CONCLUSION: This work should contribute to improving the care of women with hyperemesis gravidarum. However, given the paucity in number and quality of the literature, researchers must invest in the field of nausea and vomiting in pregnancy, and HG to identify strategies to improve the quality of life of women with nausea and vomiting in pregnancy or hyperemesis gravidarum.

[Normal childbirth: physiologic labor support and medical procedures. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynaecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF) -- Text of the Guidelines (short text)]. / Accouchement normal : accompagnement de la physiologie et interventions médicales. Recommandations de la Haute Autorité de Santé (HAS) avec la collaboration du Collège National des Gynécologues Obstétriciens Français (CNGOF) et du Collège National des Sages-Femmes de France (CNSF) ­ Texte des recommandations (texte court).

OBJECTIVE: The objective of these guidelines is to define for women at low obstetric risk modalities that respect the physiology of delivery and guarantee the quality and safety of maternal and newborn care. METHODS: These guidelines were made by a consensus of experts based on an analysis of the scientific literature and the French and international recommendations available on the subject. RESULTS: It is recommended to conduct a complete initial examination of the woman in labor at admission (consensus agreement). The labor will be monitored using a partogram that is a useful traceability tool (consensus agreement). A transvaginal examination may be offered every two to four hours during the first stage of labor and every hour during the second stage of labor or before if the patient requests it, or in case of a warning sign. It is recommended that if anesthesia is required, epidural or spinal anesthesia should be used to prevent bronchial inhalation (grade A). The consumption of clear fluids is permitted throughout labor in patients with a low risk of general anesthesia (grade B). It is recommended to carry out a "low dose" epidural analgesia that respects the experience of delivery (grade A). It is recommended to maintain the epidural analgesia through a woman's self-administration pump (grade A). It is recommended to give the woman the choice of continuous (by cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring if the conditions of maternity organization and the permanent availability of staff allow it and, after having informed the woman of the benefits and risks of each technique (consensus agreement). In the active phase of the first stage of labor, the dilation rate is considered abnormal if it is less than 1cm/4h between 5 and 7cm or less than 1cm/2h above 7cm (level of Evidence 2). It is then recommended to propose an amniotomy if the membranes are intact or an oxytocin administration if the membranes are already ruptured, and the uterine contractions considered insufficient (consensus agreement). It is recommended not to start expulsive efforts as soon as complete dilation is identified, but to let the presentation of the fetus drop (grade A). It is recommended to inform the gynecologist-obstetrician in case of nonprogression of the fetus after two hours of complete dilation with sufficient uterine dynamics (consensus agreement). It is recommended not to use abdominal expression (grade B). It is recommended to carry out preventive administration of oxytocin at 5 or 10 IU to prevent PPH after vaginal delivery (grade A). In the case of placental retention, it is recommended to perform a manual removal of the placenta (grade A). In the absence of bleeding, it should be performed 30minutes but not more than 60minutes after delivery (consensus agreement). It is recommended to assess at birth the breathing or screaming, and tone of the newborn to quickly determine if resuscitation is required (consensus agreement). If the parameters are satisfactory (breathing present, screaming frankly, and normal tonicity), it is recommended to propose to the mother that she immediately place the newborn skin-to-skin with her mother if she wishes, with a monitoring protocol (grade B). Delayed cord clamping is recommended beyond the first 30seconds in neonates, not requiring resuscitation (grade C). It is recommended that the first oral dose (2mg) of vitamin K (consensus agreement) be given systematically within two hours of birth. CONCLUSION: These guidelines allow women at low obstetric risk to benefit from a better quality of care and optimal safety conditions while respecting the physiology of delivery.

Perineal prevention and protection in obstetrics: CNGOF clinical practice guidelines.

INTRODUCTION: The objective of these clinical practice guidelines was to analyse all of the interventions during pregnancy and childbirth that might prevent obstetric anal sphincter injuries (OASIS) and postnatal pelvic floor symptoms. MATERIAL AND METHODS: These guidelines were developed in accordance with the methods prescribed by the French Health Authority (HAS). RESULTS: A prenatal clinical examination of the perineum is recommended for women with a history of Crohn's disease, OASIS, genital mutilation, or perianal lesions (professional consensus). Just after delivery, a perineal examination is recommended to check for OASIS (Grade B); if there is doubt about the diagnosis, a second opinion should be requested (Grade C). In case of OASIS, the injuries (including their severity) and the technique for their repair should be described in detail (Grade C). Perineal massage during pregnancy must be encouraged among women who want it (Grade B). No intervention conducted before the start of the active phase of the second stage of labour has been shown to be effective in reducing the risk of perineal injury. The crowning of the baby's head should be manually controlled and the posterior perineum manually supported to reduce the risk of OASIS (Grade C). The performance of an episiotomy during normal deliveries is not recommended to reduce the risk of OASIS (Grade A). In instrumental deliveries, episiotomy may be indicated to avoid OASIS (Grade C). When an episiotomy is performed, a mediolateral incision is recommended (Grade B). The indication for episiotomy should be explained to the woman, and she should consent before its performance. Advising women to have a caesarean delivery for primary prevention of postnatal urinary or anal incontinence is not recommended (Grade B). During pregnancy and again in the labour room, obstetrics professionals should focus on the woman's expectations and inform her about the modes of delivery.

[Perineal prevention and protection in obstetrics: CNGOF Clinical Practice Guidelines (short version)]. / Prévention et protection périnéale en obstétrique : Recommandations pour la Pratique Clinique du CNGOF (texte court).

INTRODUCTION: The objective of these clinical practice guidelines was to analyse all of the interventions during pregnancy and childbirth that might prevent obstetric anal sphincter injuries (OASIS) and postnatal pelvic floor symptoms. MATERIAL AND METHODS: These guidelines were developed in accordance with the methods prescribed by the French Health Authority (HAS). RESULTS: A prenatal clinical examination of the perineum is recommended for women with a history of Crohn's disease, OASIS, genital mutilation, or perianal lesions (professional consensus). Just after delivery, a perineal examination is recommended to check for OASIS (Grade B); if there is doubt about the diagnosis, a second opinion should be requested (GradeC). In case of OASIS, the injuries (including their severity) and the technique for their repair should be described in detail (GradeC). Perineal massage during pregnancy must be encouraged among women who want it (Grade B). No intervention conducted before the start of the active phase of the second stage of labour has been shown to be effective in reducing the risk of perineal injury. The crowning of the baby's head should be manually controlled and the posterior perineum manually supported to reduce the risk of OASIS (GradeC). The performance of an episiotomy during normal deliveries is not recommended to reduce the risk of OASIS (Grade A). In instrumental deliveries, episiotomy may be indicated to avoid OASIS (GradeC). When an episiotomy is performed, a mediolateral incision is recommended (Grade B). The indication for episiotomy should be explained to the woman, and she should consent before its performance. Advising women to have a caesarean delivery for primary prevention of postnatal urinary or anal incontinence is not recommended (Grade B). During pregnancy and again in the labour room, obstetrics professionals should focus on the woman's expectations and inform her about the modes of delivery.

Order-Disorder Structural Transitions in Mazes Built by Evaporating Drops.

We show that the evaporation of surfactant solutions confined in quasi-two-dimensional porous media creates micron-sized labyrinthine patterns composing the walls of a centimeter-sized maze. These walls are made of solid deposits formed during drying via a sequence of individual Haines jumps occurring at the pore scale. We rationalize this process driven by simple iterative rules with a cellular automaton that acts as a maze generator. This model well describes the formation dynamics and final structure of an experimental maze as functions of the wettability heterogeneities of a porous medium and its geometry. Also, our findings unveil the crucial role of two geometric dimensionless quantities that control the structural order of a maze.

Physical Properties and Hydrogen-Bonding Network of Water-Ethanol Mixtures from Molecular Dynamics Simulations.

While many numerical and experimental works were focused on water-ethanol mixtures at low ethanol concentration, this work reports predictions of a few physical properties (thermodynamical, interfacial, dynamical, and dielectrical properties) of water-ethanol mixture at high alcohol concentrations by means of molecular dynamics simulations. By using a standard force field a good agreement was found between experiment and molecular simulation. This was allowed us to explore the dynamics, structure, and interplay between both hydrogen-bonding networks of water and ethanol.

Replacement of CTAB with peptidic ligands at the surface of gold nanorods and their self-assembling properties.

Herein, we describe the self-assembling of gold nanorods (GNRs) induced during the ligand exchange at their surface. An exchange reaction between tricysteine PEGylated peptidic ligands and cetyltrimethylammonium bromide (CTAB)-protected gold nanorods is conducted. We demonstrated that the terminal group charge (positively or negatively charged) and the hydrophobicity of the peptidic ligands (bearing or not an undecanoyl chain) strongly affects the self-organization of the GNRs occurring in solution. Adjusting the amount of short PEGylated peptides causes a self-organization of the gold nanorods in solution, resulting in a red- or blue-shift of the plasmon bands. The decrease of their surface charge and the self-assembling in solution were first shown by zetametry, by Dynamic Light Scattering and UV-spectroscopy. Thanks to Small Angle X-ray Scattering experiments and Transmission Electron Microscopy images, the self-organization of the nanorods in solution was clearly demonstrated and correlated to the spectroscopic change in absorbance. Conversely, in the case of longer PEGylated peptidic ligands including an undecanoyl chain, the GNRs are particularly stable against aggregation for several days after purification. By controlled drying on a substrate, we showed their ability to self-organize into well-defined ordered structures making them very attractive as building blocks to design optical materials.

Ordered stacking of F-actin layers and mixed lipid bilayers: a columnar liquid crystal.

In this Letter, we show how the grooved helical structure of actin microfilaments (F-actin) interacting with mixed fluid lipid bilayers leads to handedness-independent 1D lipid bilayer undulations coupled to longitudinal in-plane ordering of the microfilaments. This longitudinal ordering is forced by the emerging in-plane compression and curvature energy terms of the straight 1D bilayer undulation wave fronts. Thereby, adjacent helices are set into registry along their long axis in their monolayer and π shifted between adjacent monolayers. An ordered composite multilamellar structure emerges by alternate stacking of these lipid bilayers and monolayers of F-actin. This two-dimensionally ordered system has the symmetries of a centered rectangular columnar liquid crystal, the straight 1D wave fronts playing the role of the classical molecular columns.

Galactosyl headgroup interactions control the molecular packing of wheat lipids in Langmuir films and in hydrated liquid-crystalline mesophases.

The behavior of the two major galactolipids of wheat endosperm, mono- (MGDG) and di-galactosyldiacylglycerol (DGDG) was studied in aqueous dispersion and at the air/liquid interface. The acyl chains of the pure galactolipids and their binary equimolar mixture are in the fluid or liquid expanded phase. SAXS measurements on liquid-crystalline mesophases associated with the electron density reconstructions show that the DGDG adopts a lamellar phase L(alpha) with parallel orientation of the headgroups with respect to the plane of the bilayer, whereas MGDG forms an inverse hexagonal phase H(II) with a specific organization of galactosyl headgroups. The equimolar mixture shows a different behavior from those previously described with formation of an Im3m cubic phase. In comparing monolayers composed of the pure galactolipids and their equimolar mixtures, PM-IRRAS spectra show significant differences in the optical properties and orientation of galactosyl groups with respect to the interface. Furthermore, Raman and FTIR spectroscopies show that the acyl chains of the galactolipid mixture are more ordered compared to those of the pure components. These results suggest strong interactions between MGDG and DGDG galactosyl headgroups and these specific physical properties of galactolipids are discussed in relation to their biological interest in wheat seed.

Water-soluble pegylated quantum dots: from a composite hexagonal phase to isolated micelles.

We present a simple method based on the dispersion of fluorescent quantum dots (QD) into a liquid crystal phase that provides either nanostructured material or isolated QD micelles depending on water concentration. The liquid-crystal phase was obtained by using a gallate amphiphile with a poly(ethylene glycol) chain as the polar headgroup, named I. The hydration of QD/I mixtures resulted in the formation of a composite hexagonal phase identified by small-angle X-ray scattering and by polarized light and fluorescence optical microscopy, showing a homogeneous distribution of fluorescence within hexagonal phase. This composite mesophase can be converted into isolated QD-I micelles by dilution in water. The fluorescent QD-I micelles, purified by size exclusion chromatography, are well monodisperse with a hydrodynamic diameter of 20-30 nm. Moreover, these QD do not show any nonspecific adsorption on lipid or cell membranes. By simply adjusting the water content, the PEG gallate amphiphile I provides a simple method to prepare a self-organized composite phase or pegylated water soluble QD micelles for biological applications.

Self-association process of a peptide in solution: from beta-sheet filaments to large embedded nanotubes.

Lanreotide is a synthetic octapeptide used in the therapy against acromegaly. When mixed with pure water at 10% (w/w), Lanreotide (acetate salt) forms liquid crystalline and monodisperse nanotubes with a radius of 120 A. The molecular and supramolecular organization of these structures has been determined in a previous work as relying on the lateral association of 26 beta-sheet filaments made of peptide noncovalent dimers, the basic building blocks. The work presented here has been devoted to the corresponding self-association mechanisms, through the characterization of the Lanreotide structures formed in water, as a function of peptide (acetate salt) concentration (from 2% to 70% (w/w)) and temperature (from 15 degrees C to 70 degrees C). The corresponding states of water were also identified and quantified from the thermal behavior of water in the Lanreotide mixtures. At room temperature and below 3% (w/w) Lanreotide acetate in water, soluble aggregates were detected. From 3% to 20% (w/w) long individual and monodisperse nanotubes crystallized in a hexagonal lattice were evidenced. Their molecular and supramolecular organizations are identical to the ones characterized for the 10% (w/w) sample. Heating induces the dissolution of the nanotubes into soluble aggregates of the same structural characteristics as the room temperature ones. The solubilization temperature increases from 20 degrees C to 70 degrees C with the peptide concentration and reaches a plateau between 15% and 25% (w/w) in peptide. These aggregates are proposed to be the beta-sheet filaments that self-associate to build the walls of the nanotubes. Above 20% (w/w) of Lanreotide acetate in water, polydisperse embedded nanotubes are formed and the hexagonal lattice is lost. These embedded nanotubes exhibit the same molecular and supramolecular organizations as the individual monodisperse nanotubes formed at lower peptide concentration. The embedded nanotubes do not melt in the range of temperature studied indicating a higher thermodynamic stability than individual nanotubes. In parallel, the thermal behaviors of water in mixtures containing 2-80% (w/w) in peptide have been studied by differential scanning calorimetry, and three different types of water were characterized: 1), bulk water melting at 0 degrees C, 2), nonfreezing water, and 3), interfacial water melting below 0 degrees C. The domains of existence and coexistence of these different water states are related to the different Lanreotide supramolecular structures. All these results were compiled into a binary Lanreotide-water phase diagram and allowed to propose a self-association mechanism of Lanreotide filaments into monodisperse individual nanotubes and embedded nanotubes.

Lipid-DNA and lipid-polyelectrolyte mesophases: structure and exchange kinetics.

Cationic lipid-DNA complexes are used as gene transfer vehicles in molecular biology and potentially in human gene therapy. In recent synchrotron X-ray scattering studies the molecular structure of such self-assembling aggregates was elucidated. A rich polymorphism of lamellar, hexagonal, lamellar-columnar and micellar mesophases was found. In this article we describe composite phases of cationic lipid mixed with hyaluronic acid and dextran sulfate which likewise form intercalated lamellar complexes. Heterogeneous phases of lipid/dextran sulfate mixed with lipid/DNA exhibit macroscopic phase separation. When dextran sulfate is added to preformed cationic lipid DNA complexes the latter are dissolved in favor of the lipid-polyelectrolyte phases. We investigated the kinetics of the DNA replacement by dextran sulfate. The experiments are intended to mimic the interaction of cationic lipid gene delivery complexes with highly charged extracellular matrix components.