Paris MEM: a study protocol for an effectiveness and efficiency trial on the treatment of traumatic stress in France after the 2015-16 terrorist attacks.

BACKGROUND: The Paris and Nice terrorist attacks affected a thousand of trauma victims and first-line responders. Because there were concerns that this might represent the first of several attacks, there was a need to quickly enhance the local capacities to treat a large number of individuals suffering from trauma-related disorders. Since Reconsolidation Therapy (RT) is brief, relatively easy to learn, well tolerated and effective, it appeared as the ideal first-line treatment to teach to clinicians in this context. METHODS: This study protocol is a two-arm non-randomized, multicenter controlled trial, comparing RT to treatment as usual for the treatment of trauma-related disorders. RT consists of actively recalling one's traumatic event under the influence of the ß-blocker propranolol, once a week, for 10-25 min with a therapist, over 6 consecutive weeks. This protocol evaluates the feasibility, effectiveness, and cost-utility of implementing RT as part of a large multi-center (N = 400) pragmatic trial with a one-year follow-up. DISCUSSION: Paris MEM is the largest trial to date assessing the efficiency of RT in the aftermath of a large-scale man-made disaster. RT could possibly reinforce the therapeutic arsenal for the treatment of patients suffering from trauma-related disorders, not only for communities in western countries but also worldwide for terror- or disaster-stricken communities. TRIAL REGISTRATION: Clinical Trials (ClinicalTrials.gov). June 3, 2016. NCT02789982.

Feather pecking in laying hens housed in free-range or furnished-cage systems on French farms.

1. Beak trimming is currently used in France to avoid the negative consequences of severe feather pecking (SFP). However, this practice is controversial in terms of animal welfare, and forbidden in some European countries.2. This study aimed to assess the prevalence of SFP in French laying hen farms, to describe how farmers manage this behavioural disorder and to better understand the risk factors involved.3. A study was carried out from April 2015 to June 2016. Visits were paid to 79 flocks kept in furnished cages (FC) and 80 flocks in a free-range (FR) system. All the hens had trimmed beaks and were genotypically brown. The information collected included feather cover, skin damage, beak condition, farm and poultry house characteristics, livestock performance and management.4. The prevalence of SFP in FC flocks was estimated at 32.9% (IC = 95%, [22.5; 43.3]) and the prevalence of cannibalism as 2.5% (IC = 95%, [0.7; 8.8]) at 70 weeks of age. The prevalence of SFP in FR flocks was estimated to be 23.8% (IC = 95%, [14.5; 31.1]) and the prevalence of cannibalism was 8.8% (IC = 95%, [4.3; 17.0]) at 61 weeks of age.5. In FC flocks, SFP was associated with the combination of genotype, type and length of perches, cage area per hen, type of lighting, number of hens per cage and farm location. In FR flocks, feather cover was associated with use of the outdoor run, lighting programme, genotype, farm location and date of house construction.

The melting of glucose.

Several sugars are known to undergo a spontaneous liquefaction below their reputed melting point (Tm), but the origin of this apparent melting is not yet clearly understood. In this paper we address this puzzling behavior in the particular case of the crystalline forms of glucose: Gα and Gß, involving respectively the glucose-α and glucose-ß anomers. We show in particular that the spontaneous melting below their reputed melting point Tm (∼151 °C for Gα and ∼156 °C for Gß) corresponds to a horizontal displacement of the system in the eutectic phase diagram of the anomeric mixture glucose-α / glucose-ß. This displacement is associated with mutarotation in the liquid which, in turn, induces additional liquefaction of the remaining crystal. This feedback loop creates a vicious circle which stops when the mixture reaches the liquidus branch, i.e. when the liquefaction is total. It is also shown that this behavior becomes more complex on approaching the eutectic temperature Te (120 °C). Just above Te, the liquefaction process is followed by a recrystallization leading to the crystalline form Gß. On the other hand, just below Te, the spontaneous liquefaction process stops as no melting is expected whatever the anomeric composition.

Mixing effects in glass-forming Lennard-Jones mixtures.

Mixing effects have been investigated from molecular dynamics simulations at constant number of particles, volume, and temperature on the Kob-Andersen glass-forming Lennard-Jones atomic mixture A(x)B(1-x) for 0 < or = x < or = 1 compositions. Upon cooling, crystallization is observed for x < or = 0.5 and x > or = 0.9 compositions. The crystalline states can be described by a quite complex coexistence of voids (x < or = 0.5), point defects, and one or two crystal structures which were characterized and found identical to those reported by Fernandez and Harrowell [Phys. Rev. E 67, 011403 (2003)] from energy minimization. Amorphization is also seen at 0.6 < or = x < or = 0.8 compositions and it is suggested that both crystal structures, CsCl and fcc-hcp, do not compete at these compositions since only one type of crystalline seed is found in the liquid, either fcc/hcp or CsCl. A significant decrease in the diffusion constants for both A and B particles is also seen above x(A) approximately = 0.5. The problem of the extraordinary stability of the model against crystallization is discussed.

Low-frequency vibrational properties of lysozyme in sugar aqueous solutions: a Raman scattering and molecular dynamics simulation study.

The low-frequency (omega<400 cm(-1)) vibrational properties of lysozyme in aqueous solutions of three well-known protecting sugars, namely, trehalose, maltose, and sucrose, have been investigated by means of complementary Raman scattering experiments and molecular dynamics simulations. The comparison of the Raman susceptibility chi(")(omega) of lysozyme/water and lysozyme/sugar/water solutions at a concentration of 40 wt % with the chi(") of dry lysozyme suggests that the protein dynamics mostly appears in the broad peak around 60-80 cm(-1) that reflects the vibrations experienced by atoms within the cage formed by their neighbors, whereas the broad shoulder around 170 cm(-1) mainly stems from the intermolecular O-H...O stretching vibrations of water. The addition of sugars essentially induces a significant high frequency shift and intensity reduction of this band that reveal a slowing down of water dynamics and a distortion of the tetrahedral hydrogen bond network of water, respectively. Furthermore, the lysozyme vibrational densities of states (VDOS) have been determined from simulations of lysozyme in 37-60 wt % disaccharide aqueous solutions. They exhibit an additional broad peak around 290 cm(-1), in line with the VDOS of globular proteins obtained in neutron scattering experiments. The influence of sugars on the computed VDOS mostly appears on the first peak as a slight high-frequency shift and intensity reduction in the low-frequency range (omega<50 cm(-1)), which increase with the sugar concentration and with the exposition of protein residues to the solvent. These results suggest that sugars stiffen the environment experienced by lysozyme atoms, thereby counteracting the softening of protein vibrational modes upon denaturation, observed at high temperature in the Raman susceptibility of the lysozyme/water solution and in the computed VDOS of unfolded lysozyme in water. Finally, the Raman susceptibility of sugar/water solutions and the calculated VDOS of water in the different lysozyme solutions confirm that sugars induce a significant strengthening of the hydrogen bond network of water that may stabilize proteins at high temperatures.

The clinical significance of radiologically detected silent pulmonary nodules in early breast cancer.

BACKGROUND: Increasing numbers of patients with early cancer undergo routine staging using computerized tomography (CT). Those in whom indeterminate pulmonary nodules are visualized without the presence of other metastatic lesions represent a clinical dilemma regarding their management as early breast cancer or metastatic disease. PATIENTS AND METHODS: Medical records of breast cancer patients who underwent thoracic CT scans between the years 2002 and 2008 were analyzed. Those with obvious metastatic disease were excluded. Patients were identified via the radiology database by searching for the terms: 'suspicious lung metastases' and 'indeterminate nodules'. RESULTS: Out of 1578 new patients assessed from 2002 to 2008, we carried out 802 staging CT scans. Thirty-four cases (4.2%) with indeterminate pulmonary nodules were identified. We categorized cases by size and number of nodules. At a median follow-up of 18 months, there were no changes in lesion size in 86% of patients with a solitary nodule <1 cm and 89% with multiple subcentimeter nodules. In contrast, in 100% of cases with pulmonary nodules >1 cm, the nodules had progressed at follow-up (chi(2), P = 0.004). CONCLUSIONS: Breast cancer cases with subcentimeter indeterminate pulmonary lesions and no evidence of metastases elsewhere are unlikely to represent metastatic disease. Treatment with curative intent or entry into clinical trials should not be excluded.

Characterization of molecular motions in biomolecular systems by elastic incoherent neutron scattering.

In the present work the role played by the instrumental resolution function in elastic incoherent neutron scattering (EINS) experiment is discussed. An important result consists in the definition of an equivalent time t(*), which depends both on the characteristic system time and on the resolution time, for which the spatial Fourier transform of EINS intensity profile and the self-distribution function (SDF) evaluated at t=t(*) are proportional. Then the equivalent time t(*) is introduced in the SDF procedure, an operational recipe for the mean square displacement determination. The new revised procedure is applied on data of myoglobin in trehalose dry environment and of hydrated homologous disaccharides (sucrose and trehalose).

Neuroimaging of CNS involvement in HIV.

Central nervous system involvement in HIV-positive patients is common with 40% of patients suffering neurological disease at some point in their lives. Neuroimaging is important to properly diagnose treatable conditions and to monitor response to treatment. In this article, we describe and illustrate the main CNS imaging findings. The following categories of pathology are addressed: direct neurological effects of HIV, opportunistic CNS infections and neoplasms, cerebrovascular complications of HIV and CNS effects of highly active retroviral therapy (HAART). Imaging techniques employed include computed tomography, magnetic resonance imaging, diffusion-weighted imaging, functional magnetic resonance imaging and magnetic resonance spectroscopy.

Association between Salivary Hypofunction and Food Consumption in the Elderlies. A Systematic Literature Review.

OBJECTIVES: This systematic literature review aims to summarize the existing scientific evidence about the association between a reduced salivary function and food consumption in elderly people. METHODS: A validated search strategy in two databases (PubMed and ISI Web of Knowledge) was carried out and retrieved papers together with their reference lists were screened by two independent reviewers. The quality of the included studies was critically appraised via the Quality Assessment Criteria for Evaluating Primary Research Papers. RESULTS: From the originally identified studies (n=391), only 15 articles (all cross-sectional studies) met the pre-fixed inclusion/exclusion criteria. The methodological quality of the included studies was in general good, although only 3 from 15 obtained the maximum score. The control of confounding factors was the quality variable more poorly rated in the selected studies. Salivary hypofunction was associated with a decrease of the objective chewing and swallowing abilities and taste perception. Moreover, most of the selected studies showed a relationship between salivary hypofunction and food consumption (in terms of appetite loss, unbalanced dietary intake and malnutrition), although no causality could be established. CONCLUSIONS: This study highlights the fact that salivary hypofunction definition and measurements are different across the studies. Therefore, future research efforts should focus on establishing a gold standard to define and identify salivary hypofunction throughout life and on performing longitudinal studies controlling for confounding factors to establish causality.

Antibacterial activation of hydroxyapatite (HA) with controlled porosity by different antibiotics.

In order to prevent the increasing frequency of per-operative infections, bioceramics can be loaded with anti-bacterial agents, which will release with respect to their chemical characteristics. A novel hydroxyapatite (HA) was elaborated with specific internal porosities for using as a bone-bioactive antibiotic (ATB) carrier material. UV spectrophotometry and bacteria inhibition tests were performed for testing the ATB adsorption and the microbiological effectiveness after loading with different antibiotics. The impregnation time, ATB impregnating concentration, impregnation condition and other factors, which might influence the ATB loading effect, were studied by exposure to different releasing solvents and different pathogenic bacteria: Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli. It clearly showed that the facility of ATB loading on this porous HA is even possible just under simple non-vacuum impregnation conditions in a not-so-long impregnating interval. The results also showed that, for all three types of ATB (vancomycin, ciprofloxacin and gentamicin), adsorbed amount on the micro-porous HA were hugely higher than that on dense HA. The micro-porosity of test HA had also significantly prolonged the release time of antibiotics even under mimic physiological conditions. Furthermore, it also has primarily proved by a pilot test that the antibacterial efficiency of crude micro-porous HA could be further significantly improved by other methods of functionalization such as cold plasma technique.

Biological and physico-chemical assessment of hydroxyapatite (HA) with different porosity.

HA with specific internal porosities was loaded with different antibiotics (ATBs) and then tested on its microbiological effectiveness. The HA purity was controlled with X-ray diffraction, IR and Raman spectrometry. Varying the sintering temperature and/or adding graphite and PMMA as porogenous agents lead to obtained micro- and meso-porosities. The biological tests concerned cell viability, proliferation and morphology (SEM), and the cytochemical staining of actin and vinculin. The micro- and meso-porous HA samples had an internal pore size of 1-10 microm and 10-50 microm, respectively. X-ray diffraction and FTIR confirmed the high purity of the HA. The cell viability tests with L132 cells confirmed the excellent cytocompatibility of HA, the graphite powder and the ATB vancomycine. Proliferation rate was assessed with MC3T3-E1 osteoblasts. All HA samples produced a higher proliferation than the controls; the micro-porous HA inducing the highest cell growth. The ATB impregnated HA also stimulated cell proliferation but in lower extend. Cytochemical staining of osteoblasts revealed a well-developed cytoskeleton with strong stress fibres. Labelling of the focal adhesion contacts with anti-vinculin showed a less developed adhesion process in the cells on the different HA substrates. It was possible to realize a highly pure hydroxyapatite with different but controlled porosities by varying the sintering temperature and/or addition of a porogenous agents. This purity and the micro-porosity stimulate significantly cell growth.

How do trehalose, maltose, and sucrose influence some structural and dynamical properties of lysozyme? Insight from molecular dynamics simulations.

The influence of three well-known disaccharides, namely, trehalose, maltose, and sucrose, on some structural and dynamical properties of lysozyme has been investigated by means of molecular dynamics computer simulations in the 37-60 wt % concentration range. The effects of sugars on the protein conformation are found to be relatively weak, in agreement with the preferential hydration of lysozyme. Conversely, sugars seem to increase significantly the relaxation times of the protein. These effects are shown to be correlated to the fractional solvent accessibilities of lysozyme residues and further support the slaving of protein dynamics. Moreover, a significant increase in the relaxation times of lysozyme, sugars, and water molecules is observed within the studied concentration range and may result from the percolation of the hydrogen-bond network of sugar molecules. This percolation appears to be of primary importance to explain the influence of sugars on the dynamical properties of lysozyme and water.

Transformation of pharmaceutical compounds upon milling and comilling: the role of T(g).

Milling is a usual process used in the course of drug formulation, which however may change the physical nature of the end product. The diversity of the transformations of organic compounds upon milling has been widely demonstrated in the pharmaceutical literature. However, no effort has still been devoted to study the correlation between the nature of the transformation and the milling conditions. Results clarifying such transformations are shortly reviewed with special attention paid to the temperature of milling. The importance of the position of the glass transition temperature compared with that of milling is demonstrated. It is shown that decreasing the milling temperature leads to an increase of the amorphization tendency whereas milling above T(g) can produce a crystal-to-crystal transformation between polymorphic varieties. These observations contradict the usual suggestion that milling transforms the physical state only by a heating effect which induces a local melting. Equilibrium thermodynamics does not seem appropriate for describing the process. The driven alloys concept offers a more rational framework to interpret the effect of the milling temperature. Other results are also presented, which demonstrate the possibility for milling to form low temperature solid-state alloys that offer new promising ways to stabilize amorphous molecular solids.

Prospective audit of emergency department transit times associated with entonox analgesia for reduction of the acute, traumatic dislocated shoulder.

AIM: To establish current UK practice for the management of the acute traumatic shoulder dislocation with respect to analgesia and reduction manoeuvres. To compare the transit times of patients through an emergency department (ED) after the use of intravenous analgesia and/ or sedation compared to entonox +/- simple oral analgesia. METHODS: A postal questionnaire was sent to 100 UK ED consultants to establish current practice. The treating clinicians were allowed to choose the method of analgesia provided to reduce the patient's dislocated shoulder, provided the patient was happy with it. They administered either (1) traditional intravenous morphine and/or midazolam or (2) entonox +/- simple oral analgesia to facilitate reduction. A prospective audit was conducted to compare the transit times of the two groups of patients. RESULTS: The postal questionnaire revealed that intravenous morphine and midazolam are widely used during reduction of the acute shoulder dislocation in the UK. The audit showed that this was associated with a significantly prolonged transit time through the ED, compared to entonox alone, (mean 77 min versus 177 min, respectively, p<0.001) without compromise in reduction success. CONCLUSION: Entonox +/- simple oral analgesia significantly decreases ED transit times as compared to IV morphine and/or midazolam for the reduction of the acute traumatic dislocated shoulder. Further studies should be done into patient pain scores and into the best combination of oral analgesia and entonox.

Primary sciatic nerve lymphoma: a case report and review of the literature.

A patient with primary B cell non-Hodgkin's lymphoma of the sciatic nerve is described. He presented with neuropathic symptoms in the left leg, initially diagnosed as tarsal tunnel syndrome. Magnetic resonance imaging (MRI) identified the abnormality in the sciatic nerve. A fascicular biopsy of the sciatic nerve showed a diffuse large B cell non-Hodgkin's lymphoma. The patient was treated with chemotherapy and rituximab (anti-CD20 monoclonal antibody). Four months later he was in remission, and remains so 48 months from presentation. Primary lymphoma of single peripheral nerves may be a unique subtype of extranodal lymphoma, which usually follows an aggressive course and has a variable response to current therapeutic strategies. MRI is useful, alongside electrophysiological studies, in patients with atypical peripheral nerve symptoms.

Dynamics of the amorphous and crystalline alpha-, gamma-phases of indomethacin.

Crystallization processes in indomethacin can be observed below Tg leading to different forms depending on the thermal treatment: a rapid and deep quench below Tg leads to the metastable alpha-phase and a slow cooling close to Tg gives rise to the stable gamma-phase. To understand this atypical behavior, we have studied the molecular mobility of the amorphous and crystalline forms of indomethacin by dielectric relaxation and 1H NMR spectroscopy. Two relaxations were detected in the glassy state obtained from the deeply quenched liquid. One, also present in the gamma-phase, was attributed to local rotations. The other one, of very low amplitude, was attributed to the Johari-Goldstein relaxation. The results allowed to discuss the relationship between these two relaxation processes and the crystallization properties of amorphous indomethacin.

Analysis of sugar bioprotective mechanisms on the thermal denaturation of lysozyme from Raman scattering and differential scanning calorimetry investigations.

Sugar-induced thermostabilization of lysozyme was analyzed by Raman scattering and modulated differential scanning calorimetry investigations, for three disaccharides (maltose, sucrose, and trehalose) characterized by the same chemical formula (C(12)H(22)O(11)). This study shows that trehalose is the most effective in stabilizing the folded secondary structure of the protein. The influence of sugars on the mechanism of thermal denaturation was carefully investigated by Raman scattering experiments carried out both in the low-frequency range and in the amide I band region. It was determined that the thermal stability of the hydrogen-bond network of water, highly dependent on the presence of sugars, contributes to the stabilization of the native tertiary structure and inhibits the first stage of denaturation, that is, the transformation of the tertiary structure into a highly flexible state with intact secondary structure. It was found that trehalose exhibits exceptional capabilities to distort the tetra-bonded hydrogen-bond network of water and to strengthen intermolecular O-H interactions responsible for the stability of the tertiary structure. Trehalose was also observed to be the best stabilizer of the folded secondary structure, in the transient tertiary structure, leading to a high-temperature shift of the unfolding process (the second stage of denaturation). This was interpreted from the consideration that the transient tertiary structure is less flexible and inhibits the solvent accessibility around the hydrophobic groups of lysozyme.

Metastability release of the form alpha of trehalose by isothermal solid state vitrification.

Kinetic investigations of the polymorphic form alpha of anhydrous trehalose have been performed below its apparent melting temperature (Tm) by differential scanning calorimetry (DSC) and X-ray diffraction. The results reveal a spontaneous isothermal vitrification process which indicates that the phase alpha is in a very unusual superheating situation. This behavior has been attributed to the fact that the effective melting temperature (Tm(eff)) of the phase alpha is likely to be located far below the glass transition temperature (Tg) of this compound. The high viscosity of the liquid trehalose between Tm(eff) and Tg is thus invoked to explain the long lifetime of the phase alpha in this temperature range.

Perspectives on the amorphisation/milling relationship in pharmaceutical materials.

This paper presents an overview of recent advances in understanding the role of the amorphous state in the physical and chemical transformations of pharmaceutical materials induced by mechanical milling. The following points are addressed: (1) Is milling really able to amorphise crystals?, (2) Conditions for obtaining an amorphisation, (3) Milling of hydrates, (4) Producing amorphous state without changing the chemical nature, (5) Milling induced crystal to crystal transformations: mediation by an amorphous state, (6) Nature of the amorphous state obtained by milling, (7) Milling of amorphous compounds: accelerated aging or rejuvenation, (8) Specific recrystallisation behaviour, and (9) Toward a rationalisation and conceptual framework.

Composition of bone and apatitic biomaterials as revealed by intravital Raman microspectroscopy.

Microcharacterization of biominerals allows a better understanding of the pathophysiological events that occur in calcified tissues and synthetic biomaterials. Different methods have been extensively used to conduct such investigations. A new model for the intravital study of the composition and structure of membranous bone by Raman microspectroscopy is described. Titanium bone chambers equipped with a fused-silica optical window were implanted transcutaneously in the calvaria of New Zealand rabbits. The implanted optical windows were well tolerated, and spectral acquisitions were performed without any additional invasive procedure. Bone and implanted apatitic biomaterials were analyzed at different times after surgery. All Raman bands were unambiguously identified in the bone and biomaterial spectra. The main PO4 and CO3 Raman bands in bone spectra were consistent with those found in the carbonated apatite spectrum. The major collagen bands were always observed around 1200-1300 (amide III) and 1600-1700 (amide I) delta cm(-1) and, 1400-1470 and 2800-3100 delta cm(-1) (bending and stretching modes of CH groups, respectively). The phenylalanine (Phe) band was identified in all spectra at 1003 delta cm(-1) and overlapped that of the weak HPO4(2-) ion. The CH bands frequently overlapped the lipid bands. However a distinct protein and lipid bands were detected at 2950 and 2852 delta cm(-1), respectively. In bone areas close to blood vessels, the Raman signature of hemoglobin was detected with a characteristic band at 754 delta cm(-1). The changes observed in bone varied as a function of time and location. The composition and structure of all of the biomaterials studied--including those that were resorbable--seemed to remain stable over time and location. We report for the first time the complete intravital study of Raman spectra of bone and calcium phosphate biomaterials over a period of 8 months. This new approach does not require specimen preparation and allows simultaneous observation of mineral and organic bone constituents over time, which therefore should provide insightful information about their relationship.