How PrEP users constitute a community in the MSM population through their specific experience and management of stigmatization. The example of the French ANRS-PREVENIR study.

The ANRS-PREVENIR (2017-2020) prospective cohort study aims to reduce the number of new HIV infections in the "Ile-de-France" region in France, by enrolling individuals at high risk of HIV infection and proposing daily and on-demand pre-exposure prophylaxis (PrEP). The qualitative component of the ANRS-PREVENIR study aimed to investigate social and relational evolutions associated with PrEP use in men who have sex with men (MSM). In 2018, 12 focus groups with MSM (n = 68) were conducted by a social sciences researcher in Paris. A thematic analysis was performed. Results showed that stigma concerning PrEP use is a complex issue, with various kinds of stigmatization being practiced, sometimes even by the wider MSM population and PrEP users themselves. All types of stigma identified were expressed in forms of verbal abuse which made PrEP use taboo. Inside the wider MSM population a PrEP-user "community" was identified which shared a certain complicity in terms of values and a positive attitude towards PrEP. The emergence of new intragroup and intergroup social norms should be taken into account by policy makers to promote a more positive image of PrEP users.

Imaging of dense cell cultures by multiwavelength lens-free video microscopy.

They present results for lens-free microscopy for the imaging of dense cell culture. With this aim, they use a multiwavelength LED illumination with well separated wavelengths, together with the implementation of an appropriate holographic reconstruction algorithm. This allows for a fast and efficient reconstruction of the phase image of densely packed cells (up to 700 cells/mm2 ) over a large field of view of 29.4 mm2 . Combined with the compactness of the system which fits altogether inside an incubator, lens-free microscopy becomes a unique tool to monitor cell cultures over several days. The high contrast phase shift images provide robust cell segmentation and tracking, and enable high throughput monitoring of individual cell dimensions, dry mass, and motility. They tested the multiwavelength lens-free video-microscope over a broad range of cell lines, including mesenchymal, endothelial, and epithelial cells. © 2017 International Society for Advancement of Cytometry.

Superoxide production pathways in aortas of diabetic rats: beneficial effects of insulin therapy and endurance training.

Superoxide (O 2 (·-) ) overproduction, by decreasing the nitric oxide ((·)NO) bioavailability, contributes to vascular complications in type 1 diabetes. In this disease, the vascular O 2 (·-) can be produced by the NADPH oxidase (NOX), nitric oxide synthase (NOS), and xanthine oxidase (XO). This study aimed to determine the contribution of each enzymatic pathway in hyperglycemia-induced O 2 (·-) overproduction, and the effects of an endurance training program and insulin therapy, associated or not, on the O 2 (·-) production (amount and related enzymes) in diabetic rats. Forty male Wistar rats were divided into diabetic (D), diabetic treated with insulin (D-Ins), diabetic trained (D-Tr), or diabetic insulin-treated and trained (D-Ins + Tr) groups. An additional healthy group was used as control. Insulin therapy (Glargine Lantus, Sanofi) and endurance training (treadmill run: 60 min/day, 25 m/min, 5 days/week) started 1 week after diabetes induction by streptozotocin (45 mg/kg), and lasted for 8 weeks. At the end of the protocol, the O 2 (·-) production in aorta rings was evaluated by histochemical analyses (DHE staining). Each production pathway was studied by inhibiting NOX (apocynin), NOS (L-Name), or XO (allopurinol) before DHE staining. Diabetic rats exhibited hyperglycemia-induced O 2 (·-) overproduction, resulting from NOX, NOS, and XO activation. Insulin therapy and endurance training, associated or not, decreased efficiently and similarly the O 2 (·-) overproduction. Insulin therapy reduced the hyperglycemia and decreased the three enzymatic pathways implicated in the O 2 (·-) production. Endurance training decreased directly the NOS and XO activity. While both therapeutic strategies activated different pathways, their association did not reduce the O 2 (·-) overproduction more significantly.

The building blocks of planets within the 'terrestrial' region of protoplanetary disks.

Our Solar System was formed from a cloud of gas and dust. Most of the dust mass is contained in amorphous silicates, yet crystalline silicates are abundant throughout the Solar System, reflecting the thermal and chemical alteration of solids during planet formation. (Even primitive bodies such as comets contain crystalline silicates.) Little is known about the evolution of the dust that forms Earth-like planets. Here we report spatially resolved detections and compositional analyses of these building blocks in the innermost two astronomical units of three proto-planetary disks. We find the dust in these regions to be highly crystallized, more so than any other dust observed in young stars until now. In addition, the outer region of one star has equal amounts of pyroxene and olivine, whereas the inner regions are dominated by olivine. The spectral shape of the inner-disk spectra shows surprising similarity with Solar System comets. Radial-mixing models naturally explain this resemblance as well as the gradient in chemical composition. Our observations imply that silicates crystallize before any terrestrial planets are formed, consistent with the composition of meteorites in the Solar System.

Thyroid and gastric autoimmune diseases.

OBJECTIVES: Autoimmune thyroid disease (AITD) is frequently accompanied by other organ-specific diseases. We investigated the frequency of the association AITD-Biermer's disease (BD) in patients with AITD by investigating the prevalence of intrinsic factor antibodies (IF-Ab). DESIGN AND METHODS: Sera from 113 patients with AITD (hypo- or hyperthyroidism) were screened for the presence of type I IF-Ab with a competitive automated immunoassay based. Matched sera from 113 patients with dysthyroidism (not AITD) were tested. RESULTS: Four IF-Ab positive patients suffered from AITD. BD was known for two of them and strongly suspected in the two others. All patients with no AITD tested IF-Ab negative. B12 levels were often low whatever the etiology. CONCLUSION: The prevalence of IF-AbI is higher (3.5%) in patients with AITD. Prospective studies should investigate whether correcting thyroid dysfunction improves vitamin B12 levels, and establish whether routine screening for gastric autoimmunity is clinically useful or purely academic.

Vitamin D nutritional status and bone turnover markers in childhood acute lymphoblastic leukemia survivors: A PETALE study.

BACKGROUND: The remarkable progress in the treatment of childhood acute lymphoblastic leukemia (cALL) has led to a survival rate reaching 90%. This success story is unfortunately linked to increased risk of impaired skeletal mass accumulation during childhood and adolescence, predisposing the patients to osteoporosis and pathological fractures at adulthood. OBJECTIVE: This study aims at characterizing the vitamin D status and bone health biomarkers in a well-characterized cohort of cALL survivors. RESULTS: Food frequency questionnaires reveal that (i) the total vitamin D intake varies greatly (44-2132 IU/d), (ii) only 16.8% of the participants consume vitamin D supplements, and (iii) 74% of survivors' intakes are below the Recommended Daily Intakes (400 IU/d). For the 42 participants taking vitamin D supplements, the median (2.5-97.5%iles) intake is 600 IU/d (21.2-1972 IU/d). Sixteen participants are vitamin D deficient (<30 nM) and 66 insufficient (≥30 - <50 nM). Serum 24,25(OH)2D3 concentrations are directly related to those of 25OHD3, and those of 3-epi-25OHD3 below the Lower Limit of Quantification in most samples. The participants' serum concentrations of cross-linked C-telopeptide of type-I collagen and intact amino-terminal pro-peptide of type-I collagen decrease steadily with age, leveling at adulthood, and are at all times higher in males. CONCLUSION: The present study shows that the prevalence of vitamin D insufficiency or deficiency is not greater in cALL survivors compared to the general Canadian population despite low vitamin D food and supplement intakes. Furthermore, there seem to be no overt imbalance in the gender- and age-adjusted serum bone turnover marker concentrations.

Differential processing of class-I-restricted epitopes by the standard proteasome and the immunoproteasome.

Upon exposure to IFN-gamma, the standard proteasome is replaced by the immunoproteasome, which contains LMP2, LMP7 and MECL1, and is considered more efficient at producing antigenic peptides presented to CD8(+) T cells. This view has been challenged this year by reports showing that some epitopes, mainly of self origin, are not processed by the immunoproteasome and that mature dendritic cells constitutively express immunoproteasomes and therefore cannot efficiently present such epitopes.

In vivo chemical investigation of human skin using a confocal Raman fiber optic microprobe.

To evaluate the potential of a new in vivo confocal Raman microprobe, we undertake a pilot study in human skin. A fiber optic probe is operated with a 633-nm laser and trials are conducted in healthy volunteers. We examine changes in molecular composition and structure of the stratum corneum, from different volunteers, from different anatomical sites and skin layers. Main spectral variations are detected in the following regions: 800 to 900 cm(-1) (amino acids); 1200 to 1290 cm(-1) (proteins); and 1030 to 1130 cm(-1), 1300 to 1450 cm(-1), and 2800 to 2900 cm(-1) (lipids). Curve fitting of the amide 1 region performs in detail protein secondary structural variations of the amide 1 band. Protein conformation is also found to vary depending on the anatomical site and volunteer. Similar analysis of the 730- to 1170-cm(-1) spectral window reveals a different organization of lamellar lipids: gel for forearm and palm, and liquid-crystalline phase for fingertips. All these variations result from changes in the stratum corneum components such as natural moisturizing factor (NMF), lipids (namely ceramides), and water. Hierarchical clustering classification is also performed to sort out Raman data obtained from different subjects. Further improvement of the confocal probe would be to adapt a 360-deg configuration enabling access to other anatomical sites.

Cysteinyl leukotrienes modulate angiotensin II constrictor effects on aortas from streptozotocin-induced diabetic rats.

Angiotensin II (Ang II) is a vasopressor peptide involved in the pathogenesis of cardiovascular diseases associated with diabetes mellitus. We have previously reported that the 5-lipoxygenase-derived products, particularly the cysteinyl leukotrienes (CysLTs), are involved in Ang II-induced contraction. In this study, we demonstrated that CysLTs contribute to the contraction elicited by Ang II in isolated aortas from streptozotocin-induced diabetic (SS) rats but not from insulin-treated diabetic rats, fructose-fed rats, or control rats. In an organ bath, pretreatment with the 5-lipoxygenase inhibitor (AA861, 10 micromol/L) reduced by 37.6+/-8.2% and 30.1+/-10.9% the Ang II-induced contractions in intact and endothelium-denuded aortic rings, respectively, from SS rats. In contrast, the CysLT(1) receptor antagonist (MK571, 1 micromol/L) or the dual CysLT(1)/CysLT(2) receptor antagonist (BAY-u9773, 0.1 micromol/L) did not affect Ang II-induced contraction. In addition, Ang II induced a 6.2+/-1.5-fold increase in CysLT release through the stimulation of the Ang II type 1 receptor. Furthermore, the urinary excretion of leukotriene E(4) was increased in SS rats (leukotriene E(4), 13.7+/-2.9 ng/24 h [SS rats, n=10] versus 1.5+/-0.5 ng/24 h [control rats, n=6]; P<0.0004). These data suggest the activation of the 5-lipoxygenase pathway in SS rats and the involvement of 5-lipoxygenase-derived products, particularly the CysLTs, in Ang II-induced contraction in aortas from SS rats through stimulation of CysLT receptors different from the well-characterized CysLT(1) or CysLT(2) receptor.

Functional role of a polymorphism in the Pannexin1 gene in collagen-induced platelet aggregation.

Pannexin1 (Panx1) forms ATP channels that play a critical role in the immune response by reinforcing purinergic signal amplification in the immune synapse. Platelets express Panx1 and given the importance of ATP release in platelets, we investigated Panx1 function in platelet aggregation and the potential impact of genetic polymorphisms on Panx1 channels. We show here that Panx1 forms ATP release channels in human platelets and that inhibiting Panx1 channel function with probenecid, mefloquine or specific (10)Panx1 peptides reduces collagen-induced platelet aggregation but not the response induced by arachidonic acid or ADP. These results were confirmed using Panx1-/- platelets. Natural variations have been described in the human Panx1 gene, which are predicted to induce non-conservative amino acid substitutions in its coding sequence. Healthy subjects homozygous for Panx1-400C, display enhanced platelet reactivity in response to collagen compared with those bearing the Panx1-400A allele. Conversely, the frequency of Panx1-400C homozygotes was increased among cardiovascular patients with hyper-reactive platelets compared with patients with hypo-reactive platelets. Exogenous expression of polymorphic Panx1 channels in a Panx-deficient cell line revealed increased basal and stimulated ATP release from cells transfected with Panx1-400C channels compared with Panx1-400A expressing transfectants. In conclusion, we demonstrate a specific role for Panx1 channels in the signalling pathway leading to collagen-induced platelet aggregation. Our study further identifies for the first time an association between a Panx1-400A>C genetic polymorphism and collagen-induced platelet reactivity. The Panx1-400C variant encodes for a gain-of-function channel that may adversely affect atherothrombosis by specifically enhancing collagen-induced ATP release and platelet aggregation.

Cardiac toxicity of singlet oxygen: implication in reperfusion injury.

Oxygen-derived free radicals (O2.-, H2O2, and .OH) that are produced during postischemic reperfusion are currently suspected to be involved in the pathogenesis of tissue injury. Another reactive oxygen species, the electronically excited molecular oxygen (1O2), is of increasing interest in the area of experimental research in cardiology. In this review are discussed the main potential sources of singlet oxygen in the organism, particularly in the myocardium, the various cardiovascular cytotoxic effects induced by this reactive oxygen intermediate, and the growing evidence of its involvement in ischemia/reperfusion injury.

Scaling of crack surfaces and implications for fracture mechanics

The scaling laws describing the roughness development of crack surfaces are incorporated into the Griffith criterion. We show that, in the case of a Family-Vicsek scaling, the energy balance leads to a purely elastic brittle behavior. On the contrary, it appears that an anomalous scaling reflects an R-curve behavior associated with a size effect of the critical resistance to crack growth in agreement with the fracture process of heterogeneous brittle materials exhibiting a microcracking damage.

Determinants of nurses' adherence to universal precautions for venipunctures.

OBJECTIVES: The aim of this study was to predict and explain nurses' adherence to Universal Precautions (UPs) when performing venipunctures. METHODS: Data were gathered from 156 registered nurses working at a regional hospital. A self-administered questionnaire assessing the psychosocial variables (intention, attitude, subjective norm, perceived control, etc) was completed at baseline, and behavior was self-reported 3 months later. RESULTS: The regression of intention on the variables yielded an adjusted R(2) of 0.68, with perceived barriers (beta =.62, P <.001), social norm (beta =.17, P <.01), and personal normative belief (beta =.19, P <.01) being the significant variables. With respect to the 3-month follow-up, 28% of the variance associated with UPs adherence was explained by intention (beta =.37, P <.001) and perceived behavioral control (beta =.23, P <.05). Moreover, high (n = 116) and low intenders (n = 40) differed on several normative beliefs (P =.0003) and perceived barriers (P =.0001). CONCLUSIONS: It is suggested that perception of control, assessed either globally or by means of a belief-based measure, is a key factor in adherence. Specifically, the perceived difficulties associated with adherence to UPs appear to be related to a nurse's training on UPs and to the existence of suboptimal working conditions.

Emulsions containing partially water-miscible solvents for the preparation of drug nanosuspensions.

The aim of this study was to investigate the feasibility of partially water-miscible solvents, such as benzyl alcohol, butyl lactate and triacetin, to prepare drug nanosuspensions by a solvent quenching technique. Mitotane, which possesses very poor water solubility and low bioavailability, was used as model drug. Preparation was by emulsifying an organic solution of the drug in an aqueous solution of a stabilising agent followed by rapid displacement of the solvent from the internal into the external phase, provoking solid particle formation. To verify the influence of emulsion droplet size on the drug particle size, 0.1 or 0.2% of different emulsifiers (Tween 80, caprylyl-capryl glucoside or lecithin) and different homogenisation conditions (Ultra Turrax or a high pressure homogenizer at 200 or 1000 bar for three cycles) were used. In general, emulsion droplet size decreased with high pressure homogenization and on increasing the number of cycles. The size of drug particles, obtained after adding water at a constant rate, was dependent on the droplet size in the emulsion. Drug particles of approximately 80 nm were obtained using butyl lactate, supporting the hypothesis that drug particle formation by the emulsification diffusion process involves generating regions of local supersaturation. Because of the increase in available surface area, the dissolution rate of diaultrafiltrated suspensions increased greatly compared to commercial product.

Cholesteryl butyrate in solid lipid nanospheres as an alternative approach for butyric acid delivery.

BACKGROUND: Cholesteryl-butyrate chosen as lipid matrix of solid lipid nanospheres (SLNs) could be a suitable pro-drug to deliver butyric acid and overcome one of the most limiting disadvantages of the compound: the short half-life due to a rapid metabolism. METHODS: We evaluated the antiproliferative effect, with respect to that of sodium butyrate, of four SLNs (SLN1, SLN2, SLN3 and SLN4) characterized by a different concentration of cholesteryl-butyrate (range, 1.7-30 mM) on NIH-H460, a non-small cell lung carcinoma cell line. RESULTS: After 6 days of treatment, all SLN preparations induced a dose-dependent inhibition of NHI-H460 cell growth: the most effective SLN preparation (SLN1) was able to induce a complete growth inhibition already at 0.25 mM, a concentration at which sodium butyrate induced only a 55% inhibition. Fluorescence microscopy showed that 6-coumarin-tagged SLNs were almost completely internalized by cells after 5 min of treatment. CONCLUSIONS: The present results indicate that owing to their peculiar characteristics, SLNs could be an interesting alternative approach for butyric acid delivery into tumor cells.

NMR relaxometric investigations of solid lipid nanoparticles (SLN) containing gadolinium(III) complexes.

This work deals with the preparation and relaxometric investigations of solid lipid nanoparticles (SLN) containing [Gd-DTPA(H2O)]2- and [Gd-DOTA(H2O)]-. These paramagnetic chelates are commonly used as contrast agents (CA) for magnetic resonance imaging (MRI) owing to their ability to strongly increase the tissue water proton relaxation rate. The amount of gadolinium(III) (Gd(III)) complex included in the SLN has been evaluated and, on this basis, it has been found that the longitudinal relaxivity of these Gd(III) chelates apparently does not vary, at physiological pH, following their inclusion in SLN. We are unable to establish whether this is due to the free exchange of water from the inner compartment containing the Gd(III) chelate to the bulk water or whether the observed relaxation rate is essentially determined by a fraction of the complex which is close to the surface of the SLN in a region easily accessible to the bulk water. At acidic pH values, the relaxivity of the paramagnetic SLN containing the less thermodynamically and kinetically stable [Gd-DTPA(H2O)]2- markedly increases. This effect may be ascribed to an increased immobilization and/or to an enhanced hydration of the complex on SLN.

Iron oxide-enhanced MR lymphography: initial experience.

The detection of nodal metastases is of utmost importance in oncologic imaging. Ultrasmall superparamagnetic iron oxide particles (USPIO) are novel contrast agents specifically developed for MR lymphography. After intravenous administration, they are taken up by the macrophages of the lymph nodes, where they accumulate. They reduce the signal intensity (SI) of normally functioning nodes on postcontrast T2-and T2*-weighted images through the magnetic susceptibility effects on iron oxide. Metastatic nodes, in which macrophages are replaced by tumor cells, show no significant change in SI on postcontrast T2-and T2*-weighted images. Early clinical experience suggests that USPIO-enhanced MR lymphography improves the sensitivity and specificity for the detection of nodal metastases. It also suggests that micrometastases could be detected in normal-sized nodes. This article reviews the physiochemical properties of USPIO contrast agents, their enhancement patterns, and early clinical experience.

Pertechnetate release from a water/oil microemulsion and an aqueous solution after subcutaneous injection in rabbits.

A water-oil microemulsion and an aqueous solution, both carrying pertechnetate, were injected subcutaneously in rabbits; release was observed by imaging the administration sites with a gamma-camera. Disappearance from the injection site of pertechnetate in aqueous solution was about ten times faster than that of pertechnetate in a microemulsion.

[Post-radiation injury of the ileal small bowel: clinical and pathological report of 12 cases (author's transl)]. / Lésions iléales graves post-irradiation. A propos de 12 observations anatomo-cliniques.

At the Institut Gustave-Roussy we have collected a series of 12 cases studied both on clinical and patological grounds. These patients underwent ileal resection for acute abdominal symptoms occuring after radiation therapy for genital cancer. Ileal lesions after radiation of gynecological cancer are rare: one per cent at the Institut Gustave-Roussy. These complications occur when certain technical types of radiation therapy are employed, and especially when dose exceeds 50 Gy or when a particular clinical condition is present. Gross examination of the bowel segment shows a stiffness of the digestive wall with frequent stenosis, sometimes in association with perforation or fistula. Histological lesions of radiated bowel are essentially located in the submucosa. They are nonspecific, mainly represented by obliterative angiopathy and fibrosis of the ileal wall.

Effect of oil phase composition on the skin permeation of felodipine from o/w microemulsions.

Oil/water microemulsions containing benzyl alcohol or different ratios of benzyl alcohol and isopropyl myristate as oil phase were prepared and used as vehicles for the transdermal absorption of felodipine. Skin permeation from the microemulsions was compared with that from a drug suspension in an apparent external phase of a microemulsion and with an aqueous drug suspension. The highest flux was from the microemulsion with the highest solubility of felodipine, while the permeation rate decreased over time from the suspension in the apparent external phase. The flux from the aqueous suspension was 10-50 times lower than that from the microemulsions. These results indicate that microemulsions containing benzyl alcohol may be interesting vehicles for transdermal administration of felodipine.