Prospective assessment of Y-chromosome microdeletions and reproductive outcomes among infertile couples of Japanese and African origin

BACKGROUND: To compare the frequency of Y-chromosome microdeletions in Japanese and African azoospermic and oligozoospermic men and describe embryo characteristics and reproductive outcome following in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). METHODS: Our study was performed prospectively at two centers, a private IVF clinic and a university hospital. Japanese and African (Tanzanian) men with nonobstructive azoospermia (NOA) and oligozoospermia (concentration < 5 × 10(6 )/ml) were evaluated for Y-chromosome microdeletions (n = 162). Of the 47 men with NOA, 26 were Japanese and 21 were Africans. Of the 115 men with oligozoospermia, 87 were Japanese and 28 were Africans. Reproductive outcomes of patients with Y-chromosome microdeletions were then compared with those of 19 IVF+ICSI cycles performed on couples with Y-chromosome intact males/tubal factor infertility which served as a control group. RESULTS: Seven azoospermic and oligozoospermic patients had Y-chromosome deletions; the total number of deletions in the AZFc region was five. There was only one deletion in the AZFa region and one complete deletion involving all three regions (AZFa, b, and c) within AZF. In our study population, microdeletion frequency among Japanese men was 6.2% (95% CI, 4.25% – 14.45%), whereas no deletions were identified in the African group (95% CI, 0.0% – 7.27%). The difference between the two groups was not statistically significant, however. Embryos derived from ICSI utilizing sperm with Y-chromosome microdeletion showed reduced rates of fertilization, blastocyst development, implantation, and pregnancy compared to the Y-chromosome intact group, although these observed differences were not statistically significant. CONCLUSION: The observed frequency of Y-chromosome microdeletion was 6.2% among Japanese azoospermic and oligozoospermic males; no microdeletions were identified among our African study patients. In this population of couples undergoing IVF+ICSI, there was no statistically significant difference in embryo characteristics or pregnancy outcome between patients with Y-chromosome microdeletion and those with an intact Y-chromosome

EPR of radicals in primitive organic matter: a tool for the research of biosignatures of the most ancient traces of life

acceptéInternational audienceIn this paper we report on electron paramagnetic resonance (EPR) of paramagnetic centers in the carbonaceous matter of primitive siliceous rocks, known to contain the most ancient traces of life. The EPR lines observed are attributed to pi-radicals stabilized by the aromatic structure of this matter. It is found that the line widths and the line shapes vary continuously during geological periods and show a progressive pattern evolution from Gaussian-Lorentzian (recent) to purely Lorentzian (ca. 2000 million years [Myr]), and to supra-Lorentzian (ca. 3500 Myr). Artificial ageing experiments allowed us to define four stages of maturation of the organic matter according to the evolution of g-factors, EPR intensity, peak-to-peak line width and line shape. We suggest that the peculiar supra-Lorentzian line shape observed for organic matter older than 2000 Myr should be related to a low-dimensional (two- or one-dimensional) spatial distribution of electron spins. From these results, we derive a relationship between the line shape and the age of the organic matter, valid for ages ranging from about 600 Myr to about 3500 Myr

Acquired immune responses to the seasonal trivalent influenza vaccination in COPD

International audienceEpidemiological data suggest that influenza vaccination protects against all-cause mortality in chronic obstructive pulmonary disease (COPD) patients. However, recent work has suggested there is a defect in the ability of some COPD patients to mount an adequate humoral response to influenza vaccination. The aim of our study was to investigate humoral and cell-mediated vaccine responses to the seasonal trivalent influenza vaccination (TIV) in COPD subjects and healthy controls. Forty-seven subjects were enrolled into the study; 23 COPD patients, 13 age-matched healthy controls (HC ≥ 50) and 11 young healthy control subjects (YC ≤ 40). Serum and peripheral blood mononuclear cells (PBMC) were isolated pre-TIV vaccination and at days 7 and 28 and 6 months post-vaccine for haemagglutinin inhibition (HAI) titre, antigen-specific T cell and antibody-secreting cell analysis. The kinetics of the vaccine response were similar between YC, HC and COPD patients and there was no significant difference in antibody titres between these groups at 28 days post-vaccine. As we observed no disease-dependent differences in either humoral or cellular responses, we investigated if there was any association of these measures with age. H1N1 (r = -0·4253, P = 0·0036) and influenza B (r = -0·344, P = 0·0192) antibody titre at 28 days negatively correlated with age, as did H1N1-specific CD4+ T helper cells (r = -0·4276, P = 0·0034). These results suggest that age is the primary determinant of response to trivalent vaccine and that COPD is not a driver of deficient responses per se. These data support the continued use of the yearly trivalent vaccine as an adjunct to COPD disease management

Interleukin-32 promotes detachment and activation of human Langerhans cells in a human skin explant model

International audienceBACKGROUND: Cross-talk between skin keratinocytes (KCs) and Langerhans cells (LCs) plays a fundamental role in the body's first line of immunological defences. However, the mechanism behind the interaction between these two major epidermal cells is unknown. Interleukin (IL)-32 is produced in inflammatory skin disorders. We questioned the role of IL-32 in the epidermis.OBJECTIVES: We aimed to determine the role of IL-32 produced by KCs on surrounding LCs.METHODS: We used an ex vivo human explant model from healthy donors and investigated the role of IL-32 on LC activation using imaging, flow cytometry, reverse transcriptase quantitative polymerase chain reaction and small interfering (si)RNA treatment.RESULTS: Modified vaccinia virus ankara (MVA) infection induced KC death alongside the early production of the proinflammatory cytokine IL-32. We demonstrated that IL-32 produced by MVA-infected KCs induced modest but significant morphological changes in LCs and downregulation of adhesion molecules, such as epithelial cell adhesion molecule and very late antigen-4, and CXCL10 production. The treatment of KCs with IL-32-specific siRNA, and anti-IL-32 blocking antibody significantly inhibited LC activation, demonstrating the role of IL-32 in LC activation. We also found that some Toll-like receptor ligands induced a very high level of IL-32 production by KCs, which initiated LC activation.CONCLUSIONS: We propose, for the first time, that IL-32 is a molecular link between KCs and LCs in healthy skin, provoking LC migration from the epidermis to the dermis prior to their migration to the draining lymph nodes

Transoral robotic surgery for squamous cell carcinomas of the posterior pharyngeal wall

International audiencePosterior pharyngeal wall squamous cell carcinomas (SCCs) are rare and have an associated poor prognosis. Progress in transoral resection techniques, in particular, transoral robotic surgery (TORS), have renewed the role of surgery in their treatment. This article presents the oncological and functional results obtained by the French Group of Head and Neck Robotic Surgery for TORS for posterior pharyngeal wall SCC-curative surgery. This retrospective, multicentre study presents data collected between September 2009 and November 2013 for patients treated with TORS for posterior pharyngeal wall SCCs. Analysis of patient characteristics, tumour and treatment details were completed. Kaplan-Meier analysis was used to calculate overall survival rates and recurrence-free survival rates. Student's t test and Chi2 test were also calculated. 23 patients were included (mean age of 62 years). 12 patients had a prior HNSCC. Ten patients had pT1 cancers. The overall two-year survival rate was 59%, but 89% for pT1 compared to 28% for pT2-T3 (p = 0.01). It was noted that TORS was simple to perform, but generated significant post-operative dysphagia. Two cases of spondylodiscitis were reported as specific post-operative complications of TORS. In conclusion, TORS is a treatment solution for selected posterior pharyngeal wall SCCs. It provides a possible alternative to medical treatment for early pT1 lesions and is often the only remaining curative solution in patients previously treated with radiotherapy. In cases of bulky resection, or when there is a past medical history of radiotherapy, a tissue reconstruction by forearm free-flap may be indicated