Biological Roles of the O-Methyl Phosphoramidate Capsule Modification in Campylobacter jejuni.

Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, and the capsular polysaccharide (CPS) of this organism is required for persistence and disease. C. jejuni produces over 47 different capsular structures, including a unique O-methyl phosphoramidate (MeOPN) modification present on most C. jejuni isolates. Although the MeOPN structure is rare in nature it has structural similarity to some synthetic pesticides. In this study, we have demonstrated, by whole genome comparisons and high resolution magic angle spinning NMR, that MeOPN modifications are common to several Campylobacter species. Using MeOPN biosynthesis and transferase mutants generated in C. jejuni strain 81-176, we observed that loss of MeOPN from the cell surface correlated with increased invasion of Caco-2 epithelial cells and reduced resistance to killing by human serum. In C. jejuni, the observed serum mediated killing was determined to result primarily from activation of the classical complement pathway. The C. jejuni MeOPN transferase mutant showed similar levels of colonization relative to the wild-type in chickens, but showed a five-fold drop in colonization when co-infected with the wild-type in piglets. In Galleria mellonella waxmoth larvae, the MeOPN transferase mutant was able to kill the insects at wild-type levels. Furthermore, injection of the larvae with MeOPN-linked monosaccharides or CPS purified from the wild-type strain did not result in larval killing, indicating that MeOPN does not have inherent insecticidal activity

Mallard Use of Hen HousesTM in Eastern Ontario

Nesting structures for ground-nesting waterfowl may be an effective technique for increasing nesting success in regions in which nest success is below the 15% threshold needed to maintain a stable population. We studied the occupancy rate of artificial nesting structures called hen housesTM by Mallards (Anas platyrhynchos) nesting in two different wetland habitats, beaver ponds and sewage lagoons, in eastern Ontario during 1999-2001. We hypothesized that, because natural cover was sparse on sewage lagoons, Mallards would occupy hen houses at a higher rate on sewage lagoons than on beaver ponds. However, of the 248 hen houses distributed between beaver ponds and sewage lagoons, none was occupied by waterfowl. Common Grackles (Quiscalus quiscula) were the only avian species that nested in hen houses. However, Mallards successfully nested directly under several structures (n = 6) when water levels were low enough to expose the ground beneath them. Mayfield daily nest survival estimates for Mallards nesting in natural cover were similar on sewage lagoons and beaver ponds for all years (mean = 0.99) and were higher than most published estimates. Factors such as nesting cover, predation pressures, and structure design and material may influence the use of artificial hen houses and should be considered when planning a hen house program outside of the Prairie Pothole Region

Mallard Use of Hen Houses TM in Eastern Ontario Utilisation de nichoirs de type hen house MD par le Canard colvert dans l'est de l'Ontario

ABSTRACT. Nesting structures for ground-nesting waterfowl may be an effective technique for increasing nesting success in regions in which nest success is below the 15% threshold needed to maintain a stable population. We studied the occupancy rate of artificial nesting structures called hen houses TM by Mallards (Anas platyrhynchos) nesting in two different wetland habitats, beaver ponds and sewage lagoons, in eastern Ontario during 1999-2001. We hypothesized that, because natural cover was sparse on sewage lagoons, Mallards would occupy hen houses at a higher rate on sewage lagoons than on beaver ponds. However, of the 248 hen houses distributed between beaver ponds and sewage lagoons, none was occupied by waterfowl. Common Grackles (Quiscalus quiscula) were the only avian species that nested in hen houses. However, Mallards successfully nested directly under several structures (n = 6) when water levels were low enough to expose the ground beneath them. Mayfield daily nest survival estimates for Mallards nesting in natural cover were similar on sewage lagoons and beaver ponds for all years (mean = 0.99) and were higher than most published estimates. Factors such as nesting cover, predation pressures, and structure design and material may influence the use of artificial hen houses and should be considered when planning a hen house program outside of the Prairie Pothole Region. RÉSUMÉ. Des nichoirs conçus pour les espèces de sauvagine nichant sur le sol peuvent s'avérer une technique efficace pour accroître le succès de la reproduction dans les régions où ce succès est inférieur au seuil de 15 % nécessaire au maintien d'une population stable. Pendant la période de 1999 à 2001, nous avons étudié le taux d'occupation de structures de nidification artificielles appelées hen house MD par les Canards colverts (Anas platyrhynchos) nichant dans deux types d'habitats humides de l'est de l'Ontario, soit des étangs de castor et des bassins de stabilisation des eaux usées. Nous avons émis l'hypothèse selon laquelle la proportion de nichoirs occupés par le Canard colvert serait plus élevée dans les bassins de stabilisation que dans les étangs de castor parce que le couvert naturel était plus clairsemé dans les bassins. Cependant, aucun des 248 nichoirs répartis entre les étangs de castor et les bassins de stabilisation des eaux usées n'a été occupé par la sauvagine. Le Quiscale bronzé (Quiscalus quiscula) est la seule espèce aviaire qui a utilisé ces nichoirs. Cependant, le Canard colvert s'est reproduit avec succès sous plusieurs de ces structures (n = 6) quand les niveaux d'eau étaient suffisamment bas pour que le sol sous-jacent soit exposé. Chez les Canards colverts nichant dans des microhabitats naturels, les estimations du taux journalier de survie au nid selon la méthode de Mayfield étaient très similaires dans les bassins de stabilisation et les étangs de castor pour toutes les années (moyenne = 0,99) et supérieures à la plupart des valeurs publiées. Des facteurs comme le degré de couvert végétal au nid, la pression exercée par les prédateurs ainsi que la conception de la structure et les matériaux utilisés peuvent avoir une incidence sur l'utilisation de nichoirs à canard et devraient être pris en compte dans la planification d'un programme d'installation de nichoirs hen house en dehors de la région des cuvettes des Prairies

Update on the management of renal cell carcinoma: The BSMO expert panel recommendations

peer reviewe

Randomized phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer.

peer reviewed[en] OBJECTIVE: Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer. METHODS: Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, β = 80%, one sided. RESULTS: 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms. CONCLUSION: The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed

Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study

Introduction: Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types 1–3 SMA. Here, an analysis was performed after all patients had received at least 1 year of treatment with risdiplam. Methods: Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6 months and 60 years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2 years of treatment. Results: A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0 years (1–60 years) and 39.1 kg (9.2–108.9 kg), respectively. About 63% of patients aged 2–60 years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions: The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients

Rilpivirine in HIV-1-positive women initiating pregnancy: to switch or not to switch?

International audienceBackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.ObjectivesTo describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.MethodsIn the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC.ResultsAmong 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred.ConclusionsIn virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes