Care of pharmaco-resistant absence seizures in childhood.

In childhood absence epilepsy, pharmaco-resistance occurs in 20-30% of patients. In that situation, glucose transporter type 1 deficiency has to be ruled out, especially if absences started before the age of four years and if neurological signs are present. If ethosuximide, valproate and lamotrigine have failed in monotherapy or in association, there are currently no valuable therapeutic options. The same rules apply for epilepsy with myoclonic absences. Importantly, arguments supporting that making the patient seizure-free will improve eventual associated cognitive deficits such as attention deficit are very weak. Therefore, limiting the cognitive side effects of the anti-epileptic drugs has always to be a priority when faced with typical refractory absences in childhood. In epilepsy with eyelid myoclonia, the majority of patients are pharmaco-resistant. However, absence seizures, if present, tend to be very brief, and seizures are limited in many patients to eyelid myoclonia that eventually do not affect their quality of life and are well attenuated by wearing blue lenses. Atypical absences occurring in the course a developmental and/or epileptic encephalopathy are often pharmaco-resistant. In that situation, characterizing the type of epilepsy syndrome and searching for a specific genetic or structural etiology are needed to offer the best therapeutic options to the patient.

[Enoxaparin and tinzaparin in pediatrics: Impact of recommendation on prescription quality and anti-Xa levels]. / Énoxaparine et tinzaparine en pédiatrie : impact de recommandations sur la qualité des prescriptions et l'activité anti-Xa.

OBJECTIVES: A protocol has been written and distributed in May 2017 to all prescribers in a pediatric hospital to standardize and to secure the prescriptions of enoxaparin and tinzaparin considered as two high risk medications. The aim of this study is to evaluate the impact of the protocol on those prescriptions in a pediatric population. METHODS: This is a monocentric retrospective study comparing prescriptions of this two low-molecular-weight heparins for patients under 18 years old in 2016 and 2018, thus before and after the protocol redaction. RESULTS: In 2016, 2246 prescriptions of enoxaparin and tinzaparin were analyzed for 627 patients. Among them, 142 (22.6%) patients have had at least one anti-Xa level dosed. On the other hand, in 2018, 2061 prescriptions were written for 628 patients including 96 (15.3%) who have had at least one anti-Xa level dosed. The conformity rate of the first dose in IU/kg/administration of the first enoxaparin prescription goes from 36.3% before protocol to 52.1% after (P=0.03*). Concerning tinzaparin, the conformity rate goes from 69.2% to 83.3%. (P=0.19). The rate of first anti-Xa level in the range 0.4 to 1.2 IU/ml increase between 2016 and 2018 from 27.7% to 43.8% (P<0.001*). CONCLUSION: This protocol enabled to improve the quality of prescriptions in terms of: dosage written in IU/kg/administration, frequency of administration, dilution conformity, and result of the first anti-Xa level. Some efforts must be made in writing the dose in IU not in mg or ml.

Informing etiologic research priorities for squamous cell esophageal cancer in Africa: A review of setting-specific exposures to known and putative risk factors.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in most Eastern and Southern African countries, but its etiology has been understudied to date. To inform its research agenda, we undertook a review to identify, of the ESCC risk factors which have been established or strongly suggested worldwide, those with a high prevalence or high exposure levels in any ESCC-affected African setting and the sources thereof. We found that for almost all ESCC risk factors known to date, including tobacco, alcohol, hot beverage consumption, nitrosamines and both inhaled and ingested PAHs, there is evidence of population groups with raised exposures, the sources of which vary greatly between cultures across the ESCC corridor. Research encompassing these risk factors is warranted and is likely to identify primary prevention strategies.

Positive variation of the MRI signal via intramolecular inclusion complexation of a C-2 functionalized ß-cyclodextrin.

The synthesis of a new contrast agent based on a ß-cyclodextrin scaffold and bearing a flexible lipophilic spacer arm on its secondary face is reported. Intermolecular host-guest inclusion complexes were known to undergo an enhancement of the contrast imaging. We extend this concept to intramolecular complexation. Inter- and intramolecular interactions are compared by NMR spectroscopy, circular dichroism and magnetic resonance imaging using hydrocinnamic acid and adamantane carboxylic acid as external guests. This positive variation of the observed relaxivity is a key element of new strategies aiming at developing smart molecular MRI probes.

Varroa destructor changes its cuticular hydrocarbons to mimic new hosts.

Varroa destructor (Vd) is a honeybee ectoparasite. Its original host is the Asian honeybee, Apis cerana, but it has also become a severe, global threat to the European honeybee, Apis mellifera. Previous studies have shown that Varroa can mimic a host's cuticular hydrocarbons (HC), enabling the parasite to escape the hygienic behaviour of the host honeybees. By transferring mites between the two honeybee species, we further demonstrate that Vd is able to mimic the cuticular HC of a novel host species when artificially transferred to this new host. Mites originally from A. cerana are more efficient than mites from A. mellifera in mimicking HC of both A. cerana and A. mellifera. This remarkable adaptability may explain their relatively recent host-shift from A. cerana to A. mellifera.

The impact of early pelvic and lower limb reperfusion and attentive peri-operative management on the incidence of spinal cord ischemia during thoracoabdominal aortic aneurysm endovascular repair.

OBJECTIVE/BACKGROUND: Spinal cord ischemia (SCI) is a devastating complication following endovascular thoracoabdominal aortic aneurysm (TAAA) repair. In an attempt to reduce its incidence two peri-procedural changes were implemented by the authors in January 2010: (i) all large sheaths are withdrawn from the iliac arteries immediately after deploying the central device and before cannulation and branch extension to the visceral vessels; (ii) the peri-operative protocol has been modified in an attempt to optimize oxygen delivery to the sensitive cells of the cord (aggressive blood and platelet transfusion, median arterial pressure monitoring >85 mmHg, and systematic cerebrospinal fluid drainage). METHODS: Between October 2004 and December 2013, 204 endovascular TAAA repairs were performed using custom made devices manufactured with branches and fenestrations to maintain visceral vessel perfusion. Data from all of these procedures were prospectively collected in an electronic database. Early post-operative results in patients treated before (group 1, n = 43) and after (group 2, n = 161 patients) implementation of the modified implantation and peri-operative protocols were compared. RESULTS: Patients in groups 1 and 2 had similar comorbidities (median age at repair 70.9 years [range 65.2-77.0 years]), aneurysm characteristics (median diameter 58.5 mm [range 53-65 mm]), and length of procedure (median 190 minutes [range 150-240 minutes]). The 30 day mortality rate was 11.6% in group 1 versus 5.6% in group 2 (p = .09). The SCI rate was 14.0% versus 1.2% (p < .01). If type IV TAAAs were excluded from this analysis, the SCI rate was 25.0% (6/24 patients) in group 1 versus 2.1% (2/95 patients) in group 2 (p < .01). CONCLUSION: The early restoration of arterial flow to the pelvis and lower limbs, and aggressive peri-operative management significantly reduces SCI following type I-III TAAA endovascular repair. With the use of these modified protocols, extensive TAAA endovascular repairs are associated with low rates of SCI.

Renal Outcomes Following Fenestrated and Branched Endografting.

OBJECTIVE: The purpose of this study was to analyze immediate and long-term renal outcomes (renal function and renal events) after fenestrated (FEVAR) and branched endovascular aortic aneurysm repair (BEVAR). METHODS: All FEVAR and BEVAR performed between October 2004 and October 2012 were included in this study. Post-operative acute renal failure (ARF) was defined according to the RIFLE criteria. Renal volume (calculated with a 3D workstation) and estimated glomerular filtration rate (GFR) (estimated with the Modification of Diet in Renal Disease [MDRD] formula) were evaluated before the procedure, before discharge, 12 months after, and yearly thereafter. Renal stent occlusion, dissection, fracture, stenosis, kink, renal stent related endoleak, and renal stent secondary intervention were all considered "renal composite events" and analyzed. A time to event analysis was performed for renal events and secondary renal interventions. RESULTS: 225 patients were treated with FEVAR and BEVAR. Renal target vessels (n = 427) were perfused by fenestrations (n = 374), or branches (n = 53). Median follow up was 3.1 years (2.9-3.3 years). Technical success was achieved in 95.5% of patients. Post-operative ARF was seen in 64 patients (29%). Mean total renal volume and eGFR at 1 year, 2 year, and 3 year follow up were significantly lower when compared with pre-operative levels (after BEVAR and FEVAR); the decrease at 3 years was 14.8% (6.7%; 22.2%) (p = .0006) for total renal volume and 14.3% (3.1%; 24.3%) (p = .02) for eGFR. The 30 day and 5 year freedom from renal composite event was 98.6% (95.8-99.6%) and 84.5% (76.5-89.9%) after FEVAR and BEVAR (NS). The 30 day and 5 year freedom from renal occlusion was 99.5% (96.7-99.9%) and 94.4% (89.3-97.1%) after FEVAR and BEVAR (NS). CONCLUSION: FEVAR and BEVAR are durable options for the treatment of complex aortic aneurysms and are associated with low renal morbidity, without differences between devices types. The clinical impact of decreasing renal volume over time in these patients is yet to be fully understood.

Impact of hybrid rooms with image fusion on radiation exposure during endovascular aortic repair.

OBJECTIVE: To evaluate exposure to radiation during endovascular aneurysm repair (EVAR) performed with intraoperative guidance by preoperative computed tomographic angiogram fusion. METHODS: All consecutive patients who underwent standard bifurcated (BIF) or thoracic (THO), and complex fenestrated (FEN) or branched (BR) EVAR were prospectively enrolled. Indirect dose-area product (DAP), fluoroscopy time (FT), and contrast medium volume were recorded. These data were compared with a previously published prospective EVAR cohort of 301 patients and to other literature. Direct DAP and peak skin dose were measured with radiochromic films. Results are expressed as median (interquartile range). RESULTS: From December 2012 to July 2013, 102 patients underwent standard (56.8%) or complex (43.2%) EVAR. The indirect DAP (Gy.cm(2)) was as follows: BIF 12.2 (8.7-19.9); THO 26.0 (11.9-34.9); FEN 43.7 (24.7-57.5); and BR 47.4 (37.2-108.2). The FT (min) was as follows: BIF 10.6 (9.1-14.7); THO 8.9 (6.0-10.5); FEN 30.7 (20.2-40.5); and BR 39.5 (34.8-51.6). The contrast medium volume (mL) was as follows: BIF 59.0 (50.0-75.0); THO 80.0 (50.0-100.0); FEN 105.0 (70.0-136.0); and BR 120.0 (100.0-170.0). When compared with a previous cohort, there was a significant reduction in DAP during BIF, FEN, and BR procedures, and a significant reduction of iodinated contrast volume during FEN and BR procedures. There was also a significant reduction in DAP during BIF procedures when compared with the literature (p < .01). DAP measurement on radiochromic films was strongly correlated with indirect DAP values (r(2) = .93). CONCLUSION: The exposure of patients and operators to radiation is significantly reduced by routine use of image fusion during standard and complex EVAR.

The effectiveness of the stabilization/solidification process on the leachability and toxicity of the tannery sludge chromium.

A stabilization/solidification (S/S) process by using cement was applied to tannery sludge in order to find a safer way of landfilling this waste. The effects of three parameters on the process effectiveness were analysed in terms of leachate toxicity and chromium retention (%). The parameters studied were the relative amount of added water (30-50 wt.%), cement (10-60 wt.% in the solid components), and the use of three different types of cement (clinker with additions of limestone, with additions of limestone and fly ashes, and with additions of pozzolans). Statistical analysis performed by variance analysis and categorical multifactorial tests reveals that all the studied parameters significantly influence the effectiveness of the process. Results showed that chromium retention decreases as the relative amount of cement and water increases, probably due to additional chromium provided by cement and increased in the porosity of the mixtures. Leachate toxicity showed the same minimum value for mixtures with 30% or 40% cement, depending on the type of cement, showing that clinker is the main material responsible for the process effectiveness, and additives (pozzolans or fly ashes) do not improve it. The volume increase is lower as less sludge is replaced by cement and the relative amount of water decreases, and for the cement without additions of fly ashes or pozzolans. Therefore, the latter seems to be the most appropriate cement in spite of being more expensive. This is due to the fact that the minimum toxicity value is achieved with a lower amount of cement; and moreover, the volume increase in the mixtures is lower, minimizing the disposal cost to a landfill.

An optimal combination for EVAR: low profile endograft body and continuous spiral stent limbs.

AIM: to evaluate the outcomes of EVAR performed with a new generation of bifurcated endografts and limbs. METHODS: prospectively collected data from fifty consecutive patients with abdominal aortic aneurysms (AAA) treated at our institution with a Low Profile Zenith(®) bifurcated body/Zenith(®) Spiral-Z legs combo were analysed. AngioCT scans and Ultrasound exams were performed prior to discharge. Ultrasound examination was repeated 6 months after the procedure to assess endograft patency and to depict endoleaks RESULTS: Median age was 70.6 years [50-88] and median ASA score was 3 [2-4]. Median aortic diameter was 56 mm [49-81]. Of the 100 external iliac access vessels, 14 had a diameter of 6 mm or lower. All endografts were successfully implanted. Post-operative Ultrasound examination and angioCT scan depicted both 1 type Ia, and 10 and 19 type 2 endoleaks respectively. An asymptomatic thrombosis of the left external iliac artery distal to the endograft limb was also depicted. 30-day mortality rate was 0%. Two patients died respectively three and four months after EVAR. Both deaths were not aneurysm related. All patients underwent an ultrasound exam 6-12 months after EVAR. All endografts main bodies and limbs were patent. Five endoleaks were depicted, all were type II endoleaks (the early type Ia endoleak had sealed spontaneously; it was confirmed by an angioCT scan). One patient presented a significant stenosis of the left iliac limb at the level of a narrow and calcified aortic bifurcation. It was successfully treated by bilateral iliac angioplasty and kissing balloon stenting. CONCLUSIONS: EVAR performed with the Zenith LP main body in combination with Spiral-Z Iliac Legs is safe and effective. No limb occlusions were diagnosed at the 6 month follow up even in challenging iliac anatomies usually considered as contra indications for EVAR. Our first results are most satisfying and calling to be completed by a longer follow up.

The benefits of EVAR planning using a 3D workstation.

OBJECTIVES: To evaluate the influence of planning endovascular aneurysm repair (EVAR) with a three-dimensional (3D) workstation on early and midterm outcomes. METHODS: All patients undergoing infrarenal EVAR performed between 2006 and 2009 at our institution were included in the current study. Prior to 2008 (group 1), endograft sizing was performed by interrogation of computed tomography angiography axial images. After 2008 (group 2), endograft sizing was routinely performed using a 3D workstation (Aquarius, Terarecon), allowing for multiplanar reconstruction and centerline analysis. Pre-, peri-, postoperative, and follow-up data were prospectively entered in an electronic database. All postoperative complications and subsequent secondary interventions depicted during the 2-year period following EVAR were compared. Secondary intervention and mortality rates were defined at 2 years and compared. Freedom from secondary intervention and overall survival rates were calculated using the Kaplan-Meier method during follow-up and compared by log-rank test. RESULTS: A total of 295 patients (149 patients in group 1 and 146 patients in group 2) were included. All patients had completed a minimum of 2 years of follow-up. During this 2-year period following EVAR, the type 1 endoleak rate was 8.7% in group 1 and 1.4% in group 2 (p = .004) respectively. Secondary intervention rates related to type 1 endoleak was 5.4% in group 1 and 0 in group 2 (p < .001). No difference was observed regarding all-cause mortality, aneurysm-related death, and freedom from secondary intervention rates during follow-up. CONCLUSION: The routine use of 3D workstations for EVAR planning significantly reduces the rate of type 1 endoleaks and, therefore, the rate of related secondary interventions.

Overexpression of the Small Ubiquitin-Like Modifier protease OTS1 gene enhances drought tolerance in sugarcane (Saccharum spp. hybrid).

Sugarcane is an economically important crop plant across the globe as it is the primary source of sugar and biofuel. Its growth and development are greatly influenced by water availability; therefore, in periods of water scarcity, yields are severely compromised. Small Ubiquitin-Like Modifier (SUMO) proteases play an important role in stress responses by regulating the SUMO-related post-translational modification of proteins. In an attempt to enhance drought tolerance in sugarcane, this crop was genetically transformed with a cysteine protease (OVERLY TOLERANT TO SALT-1; OTS1) from Arabidopsis thaliana using particle bombardment. Transgenic plants were analysed in terms of photosynthetic capacity, oxidative damage, antioxidant accumulation and the SUMO-enrich protein profile was assessed. Sugarcane transformed with the AtOTS1 gene displayed enhanced drought tolerance and delayed leaf senescence under water deficit compared to the untransformed wild type (WT). The AtOTS1 transgenic plants maintained a high relative moisture content and higher photosynthesis rate when compared to the WT. In addition, when the transgene was expressed at high levels, the transformed plants were able to maintain higher stomatal conductance and chlorophyl content under moderate stress compared to the WT. Under severe water deficit stress, the transgenic plants accumulated less malondialdehyde and maintained membrane integrity. SUMOylation of total protein and protease activity was lower in the AtOTS1 transformed plants compared to the WT, with several SUMO-enriched proteins exclusively expressed in the transgenics when exposed to water deficit stress. SUMOylation of proteins likely influenced various mechanisms contributing to enhanced drought tolerance in sugarcane.

Antibiotic susceptibilities and resistance genes of Ureaplasma parvum isolated in South Africa.

OBJECTIVES: There is only limited information on the antimicrobial susceptibilities and resistance genes of Ureaplasma parvum in South Africa. This study was designed to detect and characterize resistance genes in U. parvum. METHODS: Fifteen U. parvum isolates were investigated employing the broth microdilution method (tetracycline, doxycycline, ofloxacin, erythromycin, azithromycin and josamycin). Gene analyses were performed on target regions of: tet(M); gyrA, gyrB, parC and parE; erm(A), erm(B), erm(C) and erm(E); msr(A), msr(B), msr(C) and msr(D); 23S rRNA operons; and L4 and L22 ribosomal proteins. RESULTS: Seven of the U. parvum isolates were fully susceptible to the antibiotics tested. Five strains exhibited resistance to tetracycline (MICs 16-256 mg/L), one strain was resistant to ofloxacin (MIC 128 mg/L) and four strains were resistant to macrolides (MICs 128 mg/L); two strains showed dual resistance to tetracycline and erythromycin. The five tetracycline-resistant strains were found to have mosaic tet(M) genes, with one strain containing different specific regions to those previously described. Mutations in the L22 ribosomal protein were seen in three strains that were resistant to erythromycin (two strains) and erythromycin + azithromycin (one strain). For a further strain that was resistant to erythromycin and azithromycin, possible mechanisms of resistance remained elusive. CONCLUSIONS: This is the first report of quinolone, erythromycin and azithromycin resistance development in U. parvum from South Africa. A point mutation in parC (Pro-57 → Leu) and two novel mutations in parE (Ile-73 → Thr and a methionine insertion at codon 86) were found in an ofloxacin-resistant strain. The study reinforces the adaptability of U. parvum to develop resistance and acquire, modify and maintain transposon-located resistance genes.

An expert curated global legume checklist improves the accuracy of occurrence, biodiversity and taxonomic data.

The Legume Phylogeny Working Group's Taxonomy Working Group was tasked to create a community endorsed global legume checklist that will serve as a primary source of taxa for biodiversity data platforms and legume-related research. The checklist was published in June 2021, recognising 772 genera and 22,360 species. It is disseminated through the new Legume Data Portal as part of the Global Biodiversity Information Facility (GBIF) hosted portal initiative. The process that was followed to publish and disseminate the checklist and its content is described here. The impact of the work by the Taxonomy Working Group are quantified by comparing the published checklist with the GBIF taxonomic backbone. A total of 44,157 names overlapped with the GBIF taxonomic backbone while 30,456 names were added, which enabled more accurate name matching of 61,235 legume occurrences. Continuous improvement to the World Checklist of Vascular Plants (WCVP): Fabaceae checklist will allow the GBIF taxonomic backbone and other checklist managers to converge to a consistent and comprehensive list of legume taxa globally over time.

Effect of methionine and trace minerals (zinc, copper and manganese) supplementation on growth performance of broilers subjected to Eimeria challenge.

Coccidiosis is a major intestinal challenge that causes economic loss to the broiler industry. Two battery cage studies were conducted to evaluate the effect of trace minerals, source and dose of methionine on growth performance and gut health of broilers subjected to Eimeria challenge. Experiment #1 consisted of 9 treatments of 2 × 2 × 2 factorial design + 1 arrangement with main factors of methionine (Met) sources (DL-Met vs. 2-hydroxy-4-(methylthio)-butanoic acid (HMTBa)), total sulfur amino acid (TSAA) levels (high vs. low; ±5% of recommended level), and sources of trace minerals (TM) Zn:Cu:Mn in the form Inorganic trace minerals (ITM) in sulfates (80:20:100ppm) vs. mineral methionine hydroxy-analogue bis-chelate (MMHAC, 40:10:50ppm), each with 8 pens of 10 birds. Experiment #2 consisted of 2 treatments--ITM [ZnSO4:tribasic copper chloride (TBCC):MnSO4 110:125:120ppm] and MMHAC (Zn:Cu:Mn, 40:30:40ppm), each with 36 pens of 10 birds. All birds except for treatment 9 in experiment #1 were orally gavaged with 1x, 4x and 16x recommended dose of coccidiosis vaccine on d0, d7 and d14, respectively. Data were subjected to one-way and/or three-way ANOVA, and means were separated by Fisher's protected LSD test with significance at p ≤ 0.05. In experiment #1, factorial analysis revealed the main effects of TSAA level and TM, but not Met source. High TSAA level improved body weight and cumulative feed intake at 14, 20, and 27d. MMHAC improved body weight at 14, and 27d; feed intake at 14, 20, and 27d; and cumulative FCR at 27d vs. sulfates. One-way ANOVA analysis showed that birds fed MMHAC and high levels of TSAA regardless of Met source had similar body weight as unchallenged birds on d27. In experiment #2, MMHAC improved body weight and cumulative FCR, and reduced jejunal IL-17A gene expression on d28. In summary, in broilers subjected to Eimeria challenge, supplementation of the reduced levels of bis-chelated trace minerals MMHAC improved growth performance compared to high levels of ITM (sulfates or TBCC), which might partially result from better immune response, high levels of TSAA improved growth performance, Met source had no effect. Supplementation of both bis-chelated trace minerals MMHAC and high levels of TSAA could overcome the growth performance challenge issue due to coccidiosis.

Small-scale Arctic charr Salvelinus alpinus fisheries in Canada's Nunavut: management challenges and options.

The Arctic charr Salvelinus alpinus is a diverse and abundant resource in Canada's Nunavut. The anadromous form is primarily targeted by exploitation in small-scale fisheries. The continued importance of subsistence fisheries and growing interest in further developing commercial fisheries underline the need for proper management of S. alpinus in northern Canada. This paper presents the current state of S. alpinus fisheries in Nunavut and related management challenges. An alternate framework for assessment using life-history information as it determines stock productivity and resilience to harvesting is presented. This framework combines (1) a risk assessment tool [productivity-susceptibility analysis (PSA)] to evaluate the relative vulnerability of S. alpinus stocks to harvest and (2) a conceptual model for quantitative assessment to determine sustainable harvest levels. Diversity in S. alpinus life history and contrast in vulnerability scores derived from PSA assessment are demonstrated for a sample of 86 anadromous stocks from throughout Nunavut. These data provide evidence in support of an alternate strategy for assessment permitting to integrate diversity in S. alpinus life history for improved generalization and representativeness. Salvelinus alpinus fisheries in Arctic regions exemplify the need for stock assessment and management alternatives to ensure fish conservation in remote, sensitive ecosystems and in data-poor circumstances.

Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Protection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults. METHODS: This double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70. RESULTS: Among 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 µg (n = 25), Viaskin-PT 50 µg (n = 25), laser + Viaskin-PT 25 µg (n = 5), laser + Viaskin-PT 50 µg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 µg and 50 µg (139.87 (95% CI 87.30-224.10) and 121.76 (95% CI 95.04-156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37-89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 µg (4/5 (80.0%), 95% CI 28.4-99.5) and 50 µg (22/25 (88.0%), 95% CI 68.8-97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0-26.5). CONCLUSIONS: Viaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT03035370) and was funded by DBV Technologies.

Origin of IgA-secreting plasma cells in the mammary gland.

Lymphoblasts from the mesenteric lymph nodes (MN) of mice home to the mammary glands of syngeneic recipients late in pregnancy and during lactation, and within hours of transfer most can be shown to contain IgA. Homing does not occur in virgins, in early pregnancy, or after weaning. Homing MN lymphoblasts are sensitive to antiserum to IgA plus complement, but not to other class-specific antisera. Thus, lymphoblasts in MN with the potential to home to the mammary gland are already committed to IgA synthesis and bear surface IgA before reaching their destination. These results explain observations, made by others, of specific IgA antibodies and IgA plasma cells in milk and colostrum after oral immunization. Under natural conditions it is likely that IgA precursor cells, after stimulation in the gut-associated lymphoid tissue by intestinal antigens, migrate to the mammary gland where they secrete antibodies which constitute an important defense mechanism of the newborn. In the absence of lactation, these cells probably form part of the normal traffic to the lamina propria of the small intestine.