Perception of PrEP-related stigma in PrEP users: Results from the ANRS-PREVENIR cohort.

INTRODUCTION: Since the advent of HIV pre-exposure prophylaxis (PrEP), stigma has been shown to be a major barrier to its uptake and adherence. It is therefore essential to define the proportion of users who consider that PrEP can negatively impact their image and the factors associated with this perception. METHOD: We performed a multivariable logistic regression on data from the 2567 participants in the ANRS-PREVENIR study who answered the outcome question. RESULTS: Almost one-third of the sample (comprising mostly cisgender men who have sex with men [94.3%]) considered that taking PrEP could give others a negative image of them. Younger participants (adjusted odds ratio [aOR] 0.98; 95% confidence interval [CI] 0.97-0.99) and more psychologically vulnerable participants (i.e., lower self-esteem score [aOR 0.98; 95% CI 0.96-0.99] and higher depression score [aOR 1.02; 95% CI 1.00-1.03]) were also more likely to have this perception. In contrast, participants encouraged to take PrEP by their main partner (aOR 0.67; 95% CI 0.51-0.88) and friends (aOR 0.79; 95% CI 0.66-0.95), and those who protected themselves more because they had knowledge of their most recent sexual partner's HIV status (aOR 0.83; 95% CI 0.69-0.99) and systematic use of PrEP and/or condoms during intercourse in the previous 3 months (aOR 0.80; 95% CI 0.67-0.96) were less likely to have this perception. DISCUSSION: Given the strong interrelation between stigmatization (real or perceived), risky behaviours and adherence, our results emphasize the need for HIV prevention campaigns to promote a positive image of PrEP users. They also show that stigmatization and its effects need to be fully considered to improve HIV prevention offers to current and potential PrEP users who are most likely to be psychologically vulnerable.

[Perinatal care for extremely preterm infants. Considerations of the "risks in pregnancy" department]. / Prise en charge de la prématurité extrême. Réflexions du département hospitalo-universitaire (DHU) « risques et grossesse ¼.

Decisions regarding whether to initiate or forgo intensive care for extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients and must be taken into account. After a short review of these factors, we present the thoughts and proposals of the Risks and Pregnancy department. The proposals are to limit emergency decisions, to better take into account other factors than gestational age and prenatal predicted fetal weight in assessing the prognosis, to introduce multidisciplinary consultation in the evaluation and proposals that will be discussed with the parents, and to separate prenatal steroid therapy from decision-making regarding whether or not to administer intensive care.

Phase I randomized study of KHK4083, an anti-OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis.

BACKGROUND: OX40 (CD134) is expressed in lesional but not healthy skin of patients with psoriasis. KHK4083 is a fully human monoclonal antibody against OX40. OBJECTIVE: The primary aim of this first-in-human phase 1 study was to determine the safety and tolerability of ascending single doses of KHK4083 in patients with mild to moderate plaque psoriasis. Secondary aims were to determine the pharmacokinetics and immunogenicity of KHK4083, and an exploratory objective was to assess clinical activity. METHODS: In phase 1a, single doses of KHK4083 0.003 and 0.001 mg/kg IV were administered open label in two cohorts (each n = 6). Phase 1b had a multicentre, randomized, double-blind, placebo-controlled, ascending single-dose design in seven cohorts. Randomization was performed 3 : 1 to KHK4083 (n = 6) or placebo (n = 2) within each cohort. Ascending doses of KHK4083 were 0.03, 0.1, 0.3, 1.0, 3.0 and 10 mg/kg IV, and 1.0 mg/kg SC. RESULTS: There were no severe or serious adverse events (AEs), or discontinuations because of AEs. The most frequent treatment-related AEs in the 55 patients who received KHK4083 were mild or moderate chills (9.1%), and infusion/injection site reactions (7.3%). No clinically meaningful or dose-related changes from baseline in laboratory values, vital signs, ECG recordings or physical examinations were observed. Some KHK4083 recipients (10/54) developed anti-KHK4083 antibodies following treatment. Mean elimination half-life (t1/2 ) increased with dose, maximum serum concentration increased in a dose-proportional manner, and area under the serum concentration-time curve increased in a more than dose-proportional manner with increasing IV dose. Absolute bioavailability following SC administration was 73%. There was some indication of improvement in Psoriasis Area Severity Index (PASI) and sPGA scores at the highest IV doses (1.0 and 10 mg/kg) and the SC dose (1.0 mg/kg). The largest PASI 50 response and improvement in sPGA score ≥2 occurred with KHK4083 1.0 mg/kg SC. CONCLUSION: KHK4083 administration as a single dose up to 10 mg/kg IV or 1.0 mg/kg SC was generally safe and well tolerated in patients with mild to moderate plaque psoriasis with no dose-limiting AEs.

[Inter-observer variability of decision concerning the route of delivery in case of one previous cesarean section and abnormal pelvic measures]. / Étude de la variabilité inter-observateur de la décision de la voie d'accouchement en cas d'utérus uni-cicatriciel et bassin anormal.

OBJECTIVES: To study inter-observer variability of decision concerning the route of delivery using pelvimetry in case of one previous cesarean section and abnormal pelvic measures. MATERIALS AND METHOD: Observational study conducted in 2014 in 4 university maternity units among 36 obstetricians. Two groups of obstetricians - as they practiced in a center where pelvimetry was routinely performed (n=12) or not (n=24) - had to choose a route of delivery for 10 clinical cases of women with a single uterine scar and a tight pelvis. The "routine pelvimetry" group had pelvimetry results. The group "no pelvimetry" became aware of pelvimetry results as a second step and had to indicate whether this information changed or not their management. The measurement of the inter-observer variability was estimated by estimating the proportion of agreement according to Grant method. RESULTS: The proportion of agreements of an attempted vaginal delivery between obstetricians in the group "routine pelvimetry" was 64.7% (95% CI [61-68.5]) and 97.3% (95% CI [96.4 to 98.3]) in the group "no pelvimetry", prior knowledge of pelvimetry results. An attempted vaginal delivery was decided in 77.5% versus 98.7% (P<0.001). After knowledge of pelvimetry results in the group "no pelvimetry" had, the number of attempted vaginal deliver was not different (77.5% vs. 78%, P=0.920). CONCLUSION: In women with one previous cesarean section, in case of tight pelvis discovered after pelvimetry, inter-observer variability of decision concerning the route of delivery is increased. Centers that choose to continue using the routine pelvimetry should develop procedures to limit this variability.

Improving Fiber Alignment in HARDI by Combining Contextual PDE Flow with Constrained Spherical Deconvolution.

We propose two strategies to improve the quality of tractography results computed from diffusion weighted magnetic resonance imaging (DW-MRI) data. Both methods are based on the same PDE framework, defined in the coupled space of positions and orientations, associated with a stochastic process describing the enhancement of elongated structures while preserving crossing structures. In the first method we use the enhancement PDE for contextual regularization of a fiber orientation distribution (FOD) that is obtained on individual voxels from high angular resolution diffusion imaging (HARDI) data via constrained spherical deconvolution (CSD). Thereby we improve the FOD as input for subsequent tractography. Secondly, we introduce the fiber to bundle coherence (FBC), a measure for quantification of fiber alignment. The FBC is computed from a tractography result using the same PDE framework and provides a criterion for removing the spurious fibers. We validate the proposed combination of CSD and enhancement on phantom data and on human data, acquired with different scanning protocols. On the phantom data we find that PDE enhancements improve both local metrics and global metrics of tractography results, compared to CSD without enhancements. On the human data we show that the enhancements allow for a better reconstruction of crossing fiber bundles and they reduce the variability of the tractography output with respect to the acquisition parameters. Finally, we show that both the enhancement of the FODs and the use of the FBC measure on the tractography improve the stability with respect to different stochastic realizations of probabilistic tractography. This is shown in a clinical application: the reconstruction of the optic radiation for epilepsy surgery planning.

[Prenatal management of the risk of maternofetal infection in cases of PPROM]. / Gestion anténatale du risque d'infection amnio-choriale en cas de rupture prématurée des membranes avant 37 semaines d'aménorrhée.

Preterm premature rupture of membranes (PPROM) occurs in 3 % of pregnancies and is responsible for 30 % of premature births. The risks described in cases of PPROM are those of prematurity, acute maternal-fetal infection, cord prolapse, and abruptio placentae. The main objective of prenatal care is to reduce and anticipate the risk of perinatal infection and morbidity superimposed, but the predictive value of prenatal monitoring for the maternal-fetal infection prediction is low. Antibiotics are recommended routinely in PPROM cases. Tocolysis should not be continued more than 48h before 32 weeks gestation. Before 32 or 34 WG, a gain of 1 week of gestational age significantly reduces mortality and neonatal morbidity, and expectant management is usually preferred. French recommendations for clinical practice for expectant management or labor induction leave open either expectant management or labor induction after 34 WG. Between 34 and 37 weeks, the risk of rare severe morbidity related to prematurity are to be balanced against those of an acute infection or a maternal-fetal placental abruption. A large randomized trial comparing expectant and labor induction in cases of PPROM between 33 and 37 weeks showed no benefit of labor induction but did not have the power to explore rare and severe complications.

Electrochemical and physicochemical properties of small phosphonium cation ionic liquid electrolytes with high lithium salt content.

Electrolytes of a room temperature ionic liquid (RTIL), trimethyl(isobutyl)phosphonium (P111i4) bis(fluorosulfonyl)imide (FSI) with a wide range of lithium bis(fluorosulfonyl)imide (LiFSI) salt concentrations (up to 3.8 mol kg(-1) of salt in the RTIL) were characterised using a combination of techniques including viscosity, conductivity, differential scanning calorimetry (DSC), electrochemical impedance spectroscopy (EIS), nuclear magnetic resonance (NMR) and cyclic voltammetry (CV). We show that the FSI-based electrolyte containing a high salt concentration (e.g. 1 : 1 salt to IL molar ratio, equivalent to 3.2 mol kg(-1) of LiFSI) displays unusual transport behavior with respect to lithium ion mobility and promising electrochemical behavior, despite an increase in viscosity. These electrolytes could compete with the more traditionally studied nitrogen-based ionic liquids (ILs) in lithium battery applications.

Factors predictive of macrosomia in pregnancies with a positive oral glucose challenge test: importance of fasting plasma glucose.

AIM: The study aimed to determine the factors associated with fetal macrosomia following a positive oral glucose challenge test (OGCT). METHODS: In this retrospective single-centre study of 1268 pregnancies with positive 50-g OGCTs (plasma glucose≥130mg/dL, or 7.2mmol/L), gestational diabetes mellitus (GDM) was defined as fasting plasma glucose (FPG)≥95mg/dL (5.3mmol/L) and/or postprandial glucose (PPG)≥120mg/dL (6.7mmol/L). RESULTS: In GDM pregnancies, the odds ratios adjusted for confounders (age, BMI, ethnicity, parity and weight gain) were 2.02 for macrosomia (Z score≥1.28) and 2.62 for severe macrosomia (Z score≥1.88). For each 10-mg/dL increase in FPG, the mean birth-weight increase was 60g. Macrosomia risk did not differ between GDM patients with normal FPG (<95mg/dL, or 5.3mmol/L) and non-diabetics, but increased significantly in cases of FPG≥95mg/dL and regardless of the level of PPG. CONCLUSION: In our study population, birth-weight and macrosomia risk were strongly correlated with FPG, suggesting that it is a simple and efficient marker for the risk of macrosomia.

[Specific particularities of uterine scars and their impact on the risk of uterine rupture in case of trial of labor]. / Critères d'acceptation de la voie vaginale selon les caractéristiques de la cicatrice utérine.

OBJECTIVE: To assess the risk of uterine rupture in case of uterine scar in specific situations. To investigate whether ultrasonographic measurement of the lower uterine segment is predictive of the risk of uterine rupture. METHODS: French and English publications were identified through PubMed and Cochrane databases. RESULTS: Trial of labor after cesarean (TOLAC) is possible in cases of uterine mullerian anomalies, segmental vertical or unknown uterine incision, postpartum fever, cesarean delivery before 37 weeks during the previous cesarean (professional agreement). TOLAC can be considered if obstetrical conditions are favorable even if the delay is less than 6 months between the previous cesarean delivery and the date of conception of the following pregnancy (professional agreement). TOLAC can be considered after a previous myomectomy, depending on technical conditions under which the intervention was conducted (gradeC). TOLAC is possible even after previous hysteroscopic metroplasty for uterine septa or in cases of uterine perforation with monopolar coagulation (professional agreement). The type of uterine suture during the previous cesarean should not influence the choice of the route of delivery (professional agreement). TOLAC can be considered in cases of two previous cesarean sections if obstetrical conditions are favorable (professional agreement). Planned cesarean section is recommended from history of three previous cesarean sections (professional agreement). A planned cesarean section is recommended in cases of previous corporeal incision during cesarean (gradeC). There is not enough data to recommend ultrasonographic measurement of the lower uterine segment during pregnancy to help to determine the route of delivery (professional agreement). CONCLUSIONS: TOLAC can be considered, depending on obstetric conditions, in all situations studied, except in cases of previous obstetric corporeal incision or previous history of at least three cesareans.

Flexibility of mobile laboratory unit in support of patient management during the 2007 Ebola-Zaire outbreak in the Democratic Republic of Congo.

The mobile laboratory provides a safe, rapid and flexible platform to provide effective diagnosis of Ebola virus as well as additional differential diagnostic agents in remote settings of equatorial Africa. During the 2007 Democratic Republic of Congo outbreak of Ebola-Zaire, the mobile laboratory was set up in two different locations by two separate teams within a day of equipment arriving in each location. The first location was in Mweka where our laboratory took over the diagnostic laboratory space of the local hospital, whereas the second location, approximately 50 km south near Kampungu at the epicentre of the outbreak, required local labour to fabricate a tent structure as a suitable pre-existing structure was not available. In both settings, the laboratory was able to quickly set up, providing accurate and efficient molecular diagnostics (within 3 h of receiving samples) for 67 individuals, including four cases of Ebola, seven cases of Shigella and 13 cases of malaria. This rapid turn-around time provides an important role in the support of patient management and epidemiological surveillance.

[Postpartum diabetes screening following gestational diabetes mellitus: practices in a university hospital and focus on the role of the general practitioner]. / Dépistage du diabète de type 2 après un diabète gestationnel : rôle du médecin traitant.

OBJECTIVES: Following pregnancies with gestational diabetes mellitus (GDM), to assess: the perception by women of the risk of subsequent type 2 diabetes, the rate of screening for diabetes in the postpartum, and identify the factors leading women to undergo screening, in particular with respect to the information given to the general practitioner (GP) by the obstetrical team. METHODS: A cohort study of all women with GDM who delivered in a single academic hospital between 1st June 2008 and 31st May 2009, based on data extracted from files and from phone interviews made 6 to 12 months after the delivery. RESULTS: Out of 152 GDM cases, 147 medical files were consulted and 124 phone interviews were performed. Fifty-one percent of the interviewed women were aware of the risk of type 2 diabetes. Eighty patients (65%) underwent postpartum glucose testing, out of which 69 were prescribed by the maternity and 27 women (22%) did not get any prescription. The compliance rate was 78% (53/69) for the hospital prescriptions and 100% (18/18) for the GP's prescriptions, a significant difference in uptake (P<0.05). Although it appears that the information given to the GP is the only factor improving patient awareness about type 2 diabetes (P=0.01), as well as their compliance to postpartum glucose testing (P=0.02), only 41 reports (28%) were sent to the GP out of the 63 reports (43%) mentioning the GDM. CONCLUSION: Postpartum testing for type 2 diabetes following a GDM was not optimal in this study. In view of the key role played by the GP in the postpartum period, it appears that cooperation between maternity and GPs needs to be reinforced in order to maximise both proper screening and diabetes primary prevention following GDM.

[Screening of gestational diabetes mellitus: a new consensus?]. / Dépistage du diabète gestationnel: vers un nouveau consensus?

The choice of thresholds to diagnose gestational diabetes mellitus (GDM) is a topic of ongoing controversy. In 2008, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study showed continuous graded relationships between increasing maternal plasma glucose and increasing frequency of adverse perinatal outcomes. Macrosomia (birth weight>90th percentile for gestational age), primary cesarean delivery, clinical neonatal hypoglycemia and hyperinsulinemia (cord serum C peptide>90th percentile) were all related to each of the 3 glucose values (fasting plasma glucose and at 1 and 2 hours after the 75 g oral glucose test). The associations were continuous with no obvious thresholds at which risks increased. The International Association of Diabetes and Pregnancy Study Group (IADPSG) recently issued recommendations that the diagnosis of GDM be made when any of the following thresholds are met or exceeded: fasting plasma glucose: 0,92 g/L; 1 hour: 1,80 g/L; or 2 hours: 1,53 g/L after the 75 g oral glucose test. These criteria were chosen to identify pregnancy with increased risk of adverse perinatal outcomes. By the new criteria, the total incidence of gestational diabetes in the HAPO population was 17, 8%. Fasting plasma glucose (FPG) in early pregnancy appears as an important predictive factor. Higher first trimester FPG (lower than those diagnostic of diabetes) are associated with increased risks of later diagnosis of gestational diabetes and adverse pregnancy outcomes. Whether this new consensus will be adopted by public health bodies and professionals remains to be seen.

Intravaginal dehydroepiandrosterone (prasterone), a highly efficient treatment of dyspareunia.

OBJECTIVE: To examine the effect of intravaginal dehydroepiandrosterone (DHEA) on pain at sexual activity (dyspareunia) identified as the most bothersome symptom of vaginal atrophy in postmenopausal women at both screening and day 1. METHODS: This prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of prasterone (DHEA) applied locally in the vagina on the severity of dyspareunia in 114 postmenopausal women who had identified dyspareunia as their most bothersome symptom of vaginal atrophy, while meeting the criteria for superficial cells ≤ 5% and pH > 5.0 at both screening and day 1. RESULTS: At the standard duration of 12 weeks of treatment, increasing doses of 0.25%, 0.5% and 1.0% DHEA decreased the percentage of parabasal cells by 48.6  ±â€Š 6.78%, 42.4  ±  7.36% and 54.9  ±â€Š 6.60% (p < 0.0001 vs. placebo for all) with no change with placebo (p = 0.769). The effects on superficial cells and pH were also highly significant compared to placebo at all DHEA doses. The severity score of pain at sexual activity decreased by 0.5, 1.4, 1.6 and 1.4 units in the placebo and 0.25%, 0.5% and 1.0% DHEA groups, respectively, with the p value of differences from placebo ranging from 0.0017 to < 0.0001. CONCLUSIONS: Intravaginal DHEA, through local estrogen and androgen formation, causes a rapid and highly efficient effect on pain at sexual activity without systemic exposure of the other tissues, thus avoiding the recently reported systemic effects of estrogens.

[Screening for gestational diabetes mellitus: Is it time to revise the recommendations?]. / Dépistage du diabète gestationnel : le temps est-il venu de revoir les recommandations ?

Universal screening for gestational diabetes mellitus (GDM) has been a topic of ongoing controversy for many years. In 2005, the French Health Authority concluded that no recommendation could be issued because of insufficient evidence. Recently, several studies have clarified the issues. It is now clearly established that women with GDM, including mild forms, are at increased risk of perinatal complications. Randomized controlled trials demonstrate that treatment to reduce maternal glucose levels improves perinatal outcomes. Today, the rationale for screening appears unquestionable. There are simple screening tests. However, it remains difficult to define threshold values because there is a strong, continuous association of maternal glucose levels with increased risks of adverse pregnancy outcomes.

[A comparison of maternal and fetal complications during operative vaginal delivery using Thierry's spatulas and the vacuum extractor]. / Etude comparative de la morbidité maternofoetale immédiate des extractions par spatules de Thierry et par ventouses.

OBJECTIVE: To compare short-term maternal and fetal morbidities between Thierry's spatules and the vacuum extractor. MATERIAL AND METHODS: A retrospective study of all assisted vaginal deliveries using spatules or the vacuum extractor between January 1, 2005 and December 31, 2007 in a single, university hospital maternity. RESULTS: There were 385 deliveries with the vacuum extractor and 332 with spatulas, among a total number of 6941 deliveries. The obstetrical conditions did not differ between the two groups (indication, level or type of presentation, duration of the second stage before extraction). The rate of episiotomy was higher in the spatules than in the vacuum extractor group (80.3 % vs 54.8 %, p < 0.0001), whereas there was a lower rate of first-to-second degree perineal lacerations (18.8 % vs 35.2 %, p < 0.0001). There was no statistically significant difference in the rate of third-to-fourth degree perineal lacerations (2.1 % vs 0.7 %, respectively, p = 0.31). Neonatal outcomes did not differ significantly between the two groups (5-minute Apgar score < 7 in 0.3 % vs 1.8 %, respectively, p = 0.75). CONCLUSION: There were few differences in maternal and neonatal outcomes according to the type of instrument used, except for a lower episiotomy rate with vacuum extraction.

Translational control by delayed RNA folding: identification of the kinetic trap.

The maturation or A-protein gene of single-stranded RNA phage MS2 is preceded by a 130-nt long untranslated leader. When MS2 RNA folding is at equilibrium, the gene is untranslatable because the leader adopts a well-defined cloverleaf structure in which the Shine-Dalgarno (SD) sequence of the maturation gene is taken up in long-distance base pairing with an upstream complementary sequence (UCS). Synthesis of the A-protein takes place transiently while the RNA is synthesized from the minus strand. This requires that formation of the inhibitory cloverleaf is slow. In vitro, the folding delay was on the order of minutes. Here, we present evidence that this postponed folding is caused by the formation of a metastable intermediate. This intermediate is a small local hairpin that contains the UCS in its loop, thereby preventing or slowing down its pairing with the SD sequence. Mutants in which the small hairpin could not be formed made no detectable amounts of A-protein and were barely viable. Apparently, here the cloverleaf formed quicker than ribosomes could bind. On the other hand, mutants in which the small intermediary hairpin was stabilized produced more A-protein than wild type and were viable. One hardly growing mutant that could not form the metastable hairpin and did not make detectable amounts of A-protein was evolved. The emerging pseudo-revertant had selected two second site repressor mutations that allowed reconstruction of a variant of the metastable intermediate. The pseudo-revertant had also regained the capacity to produce the A-protein.

[Humus functioning types in evergreen coniferous forests of the French Inner Alps]. / Modes de fonctionnement d'humus des forêts sempervirentes des Alpes internes françaises.

Three humus forms that are widespread in the Inner Alps, a dysmull below Pinus sylvestris, an oligomull below Abies alba and a mor below Pinus cembra, were studied by following mineral nitrogen production and uptake and by a characterization of the pedofauna. Due to the production and uptake of nitrogen, mainly as nitrates and also due to the dominance of Lumbricids versus Arthropods, the oligomull was the sole humus form that functioned as a mull. Nevertheless relatively weak mineral nitrogen production and the dominance of endogeic soil-dwelling earthworms versus anecic earthworms demonstrated the moderate activity of this mull, which is representative of humus forms of old growth forests and cold climates. There was a discrepancy between the very low biological activity of the dysmull and its status of mull, while an observed bifunctioning between the different layers of this humus also differentiated it from the mor.