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The Zebrafish Posterior Lateral Line primordium migrates in a channel between the skin and somites. Its migration depends on the coordinated movement of its mesenchymal-like leading cells and trailing cells, which form epithelial rosettes, or protoneuromasts. We describe a superficial population of flat primordium cells that wrap around deeper epithelialized cells and extend polarized lamellipodia to migrate apposed to the overlying skin. Polarization of lamellipodia extended by both superficial and deeper protoneuromast-forming cells depends on Fgf signaling. Removal of the overlying skin has similar effects on superficial and deep cells: lamellipodia are lost, blebs appear instead, and collective migration fails. When skinned embryos are embedded in Matrigel, basal and superficial lamellipodia are recovered; however, only the directionality of basal protrusions is recovered, and migration is not rescued. These observations support a key role played by superficial primordium cells and the skin in directed migration of the Posterior Lateral Line primordium.

The non-cooperative moving targets typically appear defocused in synthetic aperture radar (SAR) images as they are non-stationary during the coherent processing interval. Typically, the problem of refocusing the moving targets in SAR scenes is addressed as a problem of the target's motion estimation and compensation. In this study, the problem is addressed as a problem of non-cooperative target imaging and the authors propose a solution based on the use of inverse synthetic aperture radar (ISAR) processing to solve this problem. Taking into consideration the advantages of SAR processing, the problem is tackled starting from formed SAR images, where non-cooperative targets images are firstly detected, then, backprojected to the received data domain and reprocessed as ISAR data. The effectiveness of the proposed method is then tested on Cosmo-Skymed spotlight SAR data of maritime targets.

Bardet-Biedl Syndrome (BBS, MIM#209900) is a genetically heterogeneous disorder with pleiotropic phenotypes that include retinopathy, mental retardation, obesity and renal abnormalities. Of the 15 genes identified so far, seven encode core proteins that form a stable complex called BBSome, which is implicated in trafficking of proteins to cilia. Though BBS9 (also known as PTHB1) is reportedly a component of BBSome, its direct function has not yet been elucidated. Using zebrafish as a model, we show that knockdown of bbs9 with specific antisense morpholinos leads to developmental abnormalities in retina and brain including hydrocephaly that are consistent with the core phenotypes observed in syndromic ciliopathies. Knockdown of bbs9 also causes reduced number and length of cilia in Kupffer's vesicle. We also demonstrate that an orthologous human BBS9 mRNA, but not one carrying a missense mutation identified in BBS patients, can rescue the bbs9 morphant phenotype. Consistent with these findings, knockdown of Bbs9 in mouse IMCD3 cells results in the absence of cilia. Our studies suggest a key conserved role of BBS9 in biogenesis and/or function of cilia in zebrafish and mammals.

Increased rates of sexually transmitted infections (STIs) have been reported among men who have sex with men. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of STIs. All participants attending their scheduled visit in the open-label extension of the ANRS IPERGAY trial in France (men aged 18 years or older having condomless sex with men and using pre-exposure prophylaxis for HIV with tenofovir disoproxil fumarate plus emtricitabine) were eligible for inclusion in this open-label randomised study. Participants were randomly assigned (1:1) at a central site to take a single oral dose of 200 mg doxycycline PEP within 24 h after sex or no prophylaxis. The primary endpoint was the occurrence of a first STI (gonorrhoea, chlamydia, or syphilis) during the 10-month follow-up. The cumulative probability of occurrence of the primary endpoint was estimated in each group with the Kaplan-Meier method and compared with the log-rank test. The primary efficacy analysis was done on the intention-to-treat population, comprising all randomised participants. All participants received risk-reduction counselling and condoms, and were tested regularly for HIV. This trial is registered with ClinicalTrials.gov number, NCT01473472. Between July 20, 2015, and Jan 21, 2016, we randomly assigned 232 participants (n=116 in the doxycycline PEP group and n=116 in the no-PEP group) who were followed up for a median of 8·7 months (IQR 7·8–9·7). Participants in the PEP group used a median of 680 mg doxycycline per month (IQR 280–1450). 73 participants presented with a new STI during follow-up, 28 in the PEP group (9-month probability 22%, 95% CI 15–32) and 45 in the no-PEP group (42%, 33–53; log-rank test p=0·007). The occurrence of a first STI in participants taking PEP was lower than in those not taking PEP (hazard ratio [HR] 0·53; 95% CI 0·33–0·85; p=0·008). Similar results were observed for the occurrence of a first episode of chlamydia (HR 0·30; 95% CI 0·13–0·70; p=0·006) and of syphilis (0·27; 0·07–0·98; p=0·047); for a first episode of gonorrhoea the results did not differ significantly (HR 0·83; 0·47–1·47; p=0·52). No HIV seroconversion was observed, and 72 (71%) of all 102 STIs were asymptomatic. Rates of serious adverse events were similar in the two study groups. Gastrointestinal adverse events were reported in 62 (53%) participants in the PEP group and 47 (41%) in the no-PEP group (p=0·05). Doxycycline PEP reduced the occurrence of a first episode of bacterial STI in high-risk men who have sex with men. France Recherche Nord & Sud Sida-HIV Hépatites (ANRS) and Bill & Melinda Gates Foundation.

Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery are a therapeutic alternative in peritoneal carcinomatosis, colorectal cancer and in evaluation for ovarian carcinomatosis. However HIPEC is frequently associated with significant morbidity. The aim of this study was to investigate morbidity according to the Clavien-Dindo classification, in 21 patients treated by HIPEC. This is a review of all patients treated for peritoneal disease by HIPEC between 2006 and 2013. They had laparotomy with or without cytoreductive surgery and heated fluid with chemotherapy irrigated with a temperature of 41-43[degrees]. One man and 20 female were included. The median age was 60 years [37-71]. 57 % were obese (BMI>30) and 5 % were morbidly obese (BMI>40). The PS was 0 (n=17), 1 (n=3) and unknown for one person. 52 % had preoperative albumin<30 g/l. 38 % had first recurrence of ovarian carcinomatosis, 62 % had peritoneal mesothelioma or pseudomyxoma. 43 % had received a first line chemotherapy before HIPEC. Although some complications may be related to the surgery, this study has identified high toxicity due to HIPEC including febrile aplasia, severe renal failure and thrombocytopenia.

An outbreak of gastroenteritis occurred in Italy among 39 persons who had attended a private supper. All guests were previously healthy, young, non-pregnant adults; 18 (46%) had symptoms, mostly gastrointestinal (78%), with a short incubation period. Four were hospitalized with acute febrile gastroenteritis, two of whom had blood cultures positive for Listeria monocytogenes. No other microorganisms were recovered from the hospitalized patients' specimens. Epidemiological investigation identified rice salad as the most likely vehicle of the food-borne outbreak. L. monocytogenes was isolated from three leftover foods, the kitchen freezer and blender. Isolates from the patients, the foods and the freezer were indistinguishable: serotype l/2b, same phage type and multilocus enzyme electrophoretic type. Eight (36%) of 22 guests tested were found to have antibodies against L. monocytogenes, compared with none of 11 controls from the general population. This point source outbreak was probably caused by infection with L. monocytogenes. Unusual features included the high attack rate among immunocompetent adults and the predominance of gastrointestinal symptoms.

Neuronal Na+ and K+ channels elicit currents in opposing directions and thus have opposing effects on neuronal excitability. Mutations in genes encoding Na+ or K+ channels often interact genetically, leading to either phenotypic suppression or enhancement for genes with opposing or similar effects on excitability, respectively. For example, the effects of mutations in Shaker (Sh), which encodes a K+ channel subunit, are suppressed by loss-of-function mutations in the Na+ channel structural gene para, but enhanced by loss-of-function mutations in a second K+ channel encoded by eag. Here we identify two novel mutations that suppress the effects of a Sh mutation on behavior and neuronal excitability. We used recombination mapping to localize both mutations to the eag locus, and we used sequence analysis to determine that both mutations are caused by a single amino acid substitution (G297E) in the S2–S3 linker of Eag. Because these novel eag mutations confer opposite phenotypes to eag loss-of-function mutations, we suggest that eagG297E causes an eag gain-of-function phenotype. We hypothesize that the G297E substitution may cause premature, prolonged, or constitutive opening of the Eag channels by favoring the “unlocked” state of the channel.

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended in men who have sex with men (MSM). We assessed HAV and HBV vaccine uptake in the non-immune participants and their immunisation during follow-up of the ANRS IPERGAY (Intervention Préventive de l'Exposition aux Risques avec et pour les Gays) pre-exposure prophylaxis (PrEP) trial.During the ANRS IPERGAY trial among MSM (NCT 01473472), vaccination against HAV and HBV was offered free of charge to all non-immune participants at baseline. We assessed anti-HAV IgGs and anti-hepatitis B surface (HBs) antibodies (Abs) at baseline, 1–3 months after each vaccine dose and on the last follow-up visit. Vaccination uptake and immunisation were analysed in non-immune participants with at least 6 months of follow-up after the 1st vaccine dose.A total of 427 MSM with a median age of 34.8 years were analysed. Median follow-up was 2.2 years (Q1–Q3, 1.6–2.9). Absence of anti-HAV IgG at baseline (50.4%, 215/427) was associated with younger age (p=0.0001). Among HAV non-immune participants, 96.1% (197/205) received one or more vaccine doses and 91.0% (172/189) received two vaccine doses. Among HBV non-immune participants, 97.6 % (81/83) received one or more vaccine doses and 78.4% (58/74) received three doses. On the last-visit sample, anti-HAV IgG and anti-HBs Abs were respectively detected in 94.8% (95% CI 90.0% to 97.7%) and 79.6% (95% CI 66.5% to 89.4%) of participants with complete vaccination and in 80.0% (95% CI 51.9% to 95.7%) and 40.0% (95% CI 16.3% to 67.7%) of participants with incomplete vaccination.Vaccine acceptability against HAV and HBV infections was very high in MSM starting PrEP. Immunisation was high in participants with a full vaccination scheme. Physicians must consider PrEP visits as major opportunities to propose and complete HAV and HBV vaccination in at-risk non-immune subjects.

Background: The zebrafish posterior lateral line primordium (PLLp) is a group of ~150 cells which spearheads the development of the lateral line by migrating along the length of the embryo, periodically depositing epithelial rosettes which serve as sense organ precursors. The PLLp is patterned by juxtaposed and mutually inhibitory Wnt and FGF signalling systems. Wnt in leading cells drives the expression of both FGF ligands and FGF signalling inhibitors. FGF ligand therefore activates receptors in more trailing cells, promoting rosette formation. However, the mechanisms by which this polarity is established and then maintained are incompletely understood. Methods: We used high resolution imaging in live zebrafish embryos mosaically labelled with a membrane GFP to characterize the formation and release of extracellular vesicles during the development of the PLLp. Results: Using high resolution timelapse imaging, we show that leading cells extend long vesicle-bearing fillopodial protrusions, similar to cytonemes, towards trailing cells. Small extracellular vesicles released by these protrusions are taken up by trailing cells and rapidly transported apically, where FGF is known to accumulate in a microlumenal compartment of the epithelial rosette. The extension of these protrusions is sensitive to inhibition of HSPG sulfation, a manipulation also known to prevent an effective FGF response in trailing cells. Furthermore, we show that the direction of extension of these protrusions is highly correlated with the direction and speed of cell migration. Summary/Conclusion: We propose that extracellular-vesicle mediated signalling is, at least in part, responsible for delivering signals from leading cells to trailing cells to in a manner intrinsically tied to the directionality of PLLp movement.

ObjectivesWe aimed to assess among men who have sex with men (MSM) risk factors for HIV infection, to identify those who require urgent pre-exposure prophylaxis (PrEP) prescription.MethodsAll participants enrolled in the placebo arm of the ANRS IPERGAY trial, or infected between screening and day 0, were included. Baseline characteristics were described and HIV incidence rate ratios (RRs) were estimated with their 95% CIs.Results203 MSM were included with a median follow-up of 9 months. During the study period, 16 participants acquired HIV infection while not receiving tenofovir disoproxil and emtricitabin (TDF/FTC) over 212.4 person-years (PYs) of follow-up (incidence rate 7.5/100 PYs, 95% CI: 4.3 to 12.2). Being enrolled in Paris was associated with a significant increased risk of HIV infection (RR: 4.1; 95% CI: 1.1 to 28.3). A high number of sexual partners in prior 2 months (≥10 vs <5) and of condomless receptive anal sex episodes in prior 12 months (>5 vs <5) were strong predictors for HIV acquisition (RR: 10.6 (2 to 260.2) and 3.3 (1.2 to 10.2), respectively). Those who reported more often or only receptive sexual practices were also at increased risk (RR: 9.8 (2.0 to 246.6)). The use of recreational drugs in prior 12 months, especially gamma hydroxybutarate/gamma butyrolactone (RR: 5.9; 95% CI: 2 to 21.7), was associated with a significantly increased risk of HIV acquisition even after adjustment for sexual practices.ConclusionsMSM who have frequent condomless receptive anal sex and multiple partners, or use recreational drugs should be targeted in priority for PrEP prescription especially if they live in an area with a high prevalence of HIV infection.