High molecular weight hyaluronic acid vectorised with clay provides long-term hydration and reduces skin brightness.

BACKGROUND: Hyaluronic acid (HA) is a widely used active cosmetic ingredient. Its multiple skin care benefits are modulated by its molecular weight. Low molecular weight (LMW) HA can penetrate the skin, but high molecular weight (HMW) HA remains at the surface. Here, we assessed how vectorization of HMW HA with bentonite clay-achieved with an innovative technology-enhances its cosmetic and hydrating properties. MATERIALS AND METHODS: The two HA forms were applied to skin explants; their penetration and smoothing effects were monitored by Raman spectroscopy and scanning electron microscopy. The two forms were biochemically characterised by chromatography, enzyme sensitivity assays, and analysis of Zeta potential. Cosmetics benefits such as, the smoothing effect of vectorised-HA was assessed in ex vivo experiments on skin explants. A placebo-controlled clinical study was finally conducted applying treatments for 28 days to analyse the final benefits in crow's feet area. RESULTS: Raman spectroscopy analysis revealed native HMW HA to accumulate at the surface of skin explants, whereas vectorised HMW HA was detected in deeper skin layers. This innovative vectorisation process changed the zeta potential of vectorised HMW HA, being then more anionic and negative without impacting the biochemical structure of native HA. In terms of cosmetic benefits, following application of vectorised HMW HA ex vivo, the skin's surface was visibly smoother. This smoothing was clinically confirmed, with a significant reduction in fine lines. CONCLUSION: The development of innovative process vectorising HMW HA allowed HMW HA penetration in the skin. This enhanced penetration extends the clinical benefits of this iconic cosmetic ingredient.

[Unrelated donor selection for allogeneic hematopoietic stem cell transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Choix d'un donneur non apparenté en vue d'une allogreffe de cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

The selection of a donor is an essential element in allogeneic hematopoietic stem cell transplantation. In the absence of an HLA-matched related donor, the selection of an unrelated donor is considered, and is currently the most common type of allogenic donor used in practice. Many criteria are considered for the selection when multiple donors are available, particularly in case of partial match. The aim of this workshop is to assist in the selection of an unrelated donor, in keeping with recent data from the literature.

DNA methylation profiling in Trisomy 21 females with and without breast cancer.

Background: Down Syndrome (DS) is the most common chromosome anomaly in humans and occurs due to an extra copy of chromosome 21. The malignancy profile in DS is unique, since DS patients have a low risk of developing solid tumors such as breast cancer however they are at higher risk of developing acute myeloid leukemia and acute lymphoblastic leukemia. Methods: In this study, we investigated DNA methylation signatures and epigenetic aging in DS individuals with and without breast cancer. We analyzed DNA methylation patterns in Trisomy 21 (T21) individuals without breast cancer (T21-BCF) and DS individuals with breast cancer (T21-BC), using the Infinium Methylation EPIC BeadChip array. Results: Our results revealed several differentially methylated sites and regions in the T21-BC patients that were associated with changes in gene expression. The differentially methylated CpG sites were enriched for processes related to serine-type peptidase activity, epithelial cell development, GTPase activity, bicellular tight junction, Ras protein signal transduction, etc. On the other hand, the epigenetic age acceleration analysis showed no difference between T21-BC and T21-BCF patients. Conclusions: This is the first study to investigate DNA methylation changes in Down syndrome women with and without breast cancer and it could help shed light on factors that protect against breast cancer in DS.

Skin Cellular Reprogramming as an Innovative Anti-Aging Strategy for Cosmetic Application: A Clinical Study of Sericoside.

BACKGROUND: While our body ages, skin cells progressively lose their pluripotency and proliferative capacities, as well as remodeling driver role, among other activities. This loss of capacities leads to visible aging signs such as wrinkles, under-eye bags or even aging spots. We studied if the stimulation of cell pluripotency and proliferation by a natural molecule could be an innovative anti-ageing strategy for skin rejuvenation. METHODS: The activity of sericoside, a compound extracted from the bark of Terminalia sericea roots, was evaluated at a concentration of 0.02% in vitro. This assessment involved transcriptomic analysis on fibroblasts after 24 hours, as well as proliferation tests on aged fibroblasts after 72 hours. A clinical study was then conducted on 40 volunteers between the ages of 35 and 55. For four weeks, volunteers applied a cream twice daily containing either sericoside or blank emulsion (control group). Skin elasticity was measured by cutometry with R2 parameter. Skin texture and roughness was analyzed by an in vivo 3D scanner. RESULTS: Transcriptomic analysis showed that sericoside improved the set of gene expressions involved in cell cycle (+85% MKI67), cell proliferation (+250% IGF1), DNA repair (+56% OGG1), pluripotency transcription factors (+36% NANOG) and stem cells maintenance (+200% SOX2). We substantiated a decrease of proliferation factor with aged cells compared to young cells by 50%, while sericoside increased this proliferation factor by +46%, a similar rate to that of a 22-year-old donor. Clinically, the anti-aging effects of sericoside were evident: the use of sericoside resulted in a 17% increase in skin elasticity and a 10% reduction in skin roughness, underscoring the smoothing effect with sericoside. CONCLUSIONS: The study highlighted an innovative anti-aging strategy that involves re-activating cells' memory to reprogram cell pluripotency by stimulating the natural tools available in our DNA.

Autoimmunity in Down's syndrome via cytokines, CD4 T cells and CD11c+ B cells.

Down's syndrome (DS) presents with a constellation of cardiac, neurocognitive and growth impairments. Individuals with DS are also prone to severe infections and autoimmunity including thyroiditis, type 1 diabetes, coeliac disease and alopecia areata1,2. Here, to investigate the mechanisms underlying autoimmune susceptibility, we mapped the soluble and cellular immune landscape of individuals with DS. We found a persistent elevation of up to 22 cytokines at steady state (at levels often exceeding those in patients with acute infection) and detected basal cellular activation: chronic IL-6 signalling in CD4 T cells and a high proportion of plasmablasts and CD11c+TbethighCD21low B cells (Tbet is also known as TBX21). This subset is known to be autoimmune-prone and displayed even greater autoreactive features in DS including receptors with fewer non-reference nucleotides and higher IGHV4-34 utilization. In vitro, incubation of naive B cells in the plasma of individuals with DS or with IL-6-activated T cells resulted in increased plasmablast differentiation compared with control plasma or unstimulated T cells, respectively. Finally, we detected 365 auto-antibodies in the plasma of individuals with DS, which targeted the gastrointestinal tract, the pancreas, the thyroid, the central nervous system, and the immune system itself. Together, these data point to an autoimmunity-prone state in DS, in which a steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation all contribute to a breach in immune tolerance. Our findings also open therapeutic paths, as we demonstrate that T cell activation is resolved not only with broad immunosuppressants such as Jak inhibitors, but also with the more tailored approach of IL-6 inhibition.

Targeting SDF-1 as an efficient strategy to resolve skin hyperpigmentation issues with Himanthalia elongata extract.

BACKGROUND: During aging, human skin is facing hyperpigmentation disorders: senile lentigo (chronobiologic aging) leads to loss of melanogenesis' control while solar lentigo (UV exposure) promotes an increase of oxidized proteins, melanogenesis, and lipofuscin. AIMS: Stromal-cell-derived-factor-1 (SDF-1) was identified as key regulator of hyperpigmentation and its expression is reduced in senescent fibroblasts, highlighting this protein as new target for skin hyperpigmentation. MATERIALS: We developed two skin explant models mimicking of senile and solar lentigo, based on H2 O2 systemic treatment and UV irradiation, respectively. We evaluated Himanthalia elongata extract (HEX) on these models after 5 days of treatment and analyzed SDF-1 expression and skin pigmentation. For solar lentigo, we also analyzed oxidized proteins and lipofuscin accumulation. Finally, we evaluated HEX in vivo on nearly 100 multi ethnicities' volunteers. RESULTS: SDF-1 expression decreased in senile lentigo model, associated with hyperpigmentation. HEX application restored SDF-1 expression, leading to skin pigmentation decrease. For solar lentigo, we showed an impact of UVs on SDF-1 expression linked to hyperpigmentation, while the application of HEX restored SDF-1 expression and reduced skin pigmentation. On same model, HEX reduced oxidized proteins quantity and lipofuscin which increased after UV exposure. Clinically, HEX reduced dark spot pigmentation on Caucasian volunteers' hands and on Asian and African volunteers' face after 28 days. DISCUSSION: We have developed ex vivo models mimetic of senile and solar lentigo and showed for a very first time that SDF-1 can be also a key regulator for UV-induced hyperpigmentation. CONCLUSION: Our ex vivo and clinical studies highlighted the power of HEX with strong reduction of dark spots regardless of volunteers' ethnicities.

UM171 Expansion of Cord Blood Improves Donor Availability and HLA Matching For All Patients, Including Minorities.

Cord blood (CB) stem cell transplantation offers a greater tolerance to HLA mismatches compared to adult-derived stem cell transplants (i.e., bone marrow or peripheral blood stem cells). Indeed, 4/6 or 5/8 HLA-matched CB transplantations are regularly performed for patients lacking a matched unrelated donor. Unfortunately, most banked CB units contain a stem cell dose that is too small to treat adult patients, resulting in only 4% to 5% of available CB units offering an adequate cell dose for prompt engraftment for adult patients. Ex vivo stem cell expansion appears to be an attractive strategy to circumvent this cell dose issue, while also enabling the selection of better HLA-matched CB units. In this study, we retrospectively performed HLA matching simulations to assess how the minimal cell content requirements associated with UM171 CB expansion may improve usability of existing CB unit inventories and donor availability for patients of different races and ethnicities. We analyzed a dataset of 58,971 adults for whom a donor search was initiated through the National Marrow Donor Program Be The Match registry against 142,942 CB units from major U.S. public CB banks listed on the Be The Match registry. Our results show that by enabling selection of smaller CB units, UM171-expanded CB transplantation increases donor availability from 72% to 84% for all patients compared to single unmanipulated CB transplantation. Furthermore, the low cell dose criteria for UM171-expanded CB also increases donor availability compared to double CB transplantation, while enabling better HLA matching between donor and recipient. UM171 expanded CB appears particularly beneficial for racial and ethnic minority patients as CB availability increases from 53% to 78% for African Americans, from 66% to 85% for Hispanics, and from 68% to 84% for Asians and Pacific Islanders, compared to single unmanipulated CB transplantation. In addition, UM171 expansion dramatically improves usability of CB units currently in inventories, as only 4.3% and 0.6% of banked CBs have sufficient cell doses for a 70 kg and 100 kg patient, respectively. UM171 raises this proportion to 53.8% and 20.2%, respectively, making CB banks potentially more cost effective. In conclusion, UM171 expansion allows the use of smaller CB units while also improving access to transplantation for racial and ethnic minorities.

The anti-wrinkles properties of sodium acetylated hyaluronate.

BACKGROUND: Intrinsic aging promotes wrinkles formation by an imbalance between matrix synthesis/degradation in favor of degradation. This is accelerated by the exposome leading to overproduction of protease and fewer remodeling. OBJECTIVE: Protecting the integrity of extracellular matrix appears as the most efficient anti-aging solution. We developed a grafted HA specifically designed to get anti-aging property due to a specific molecular weight and acetylation degree. METHODS: A transcriptomic analysis was performed on fibroblasts, followed by a measurement of MMP secretion and subsequent effect on collagen degradation. MMP expression in skin explants concerned by chronobiological and extrinsic aging was analyzed by immunostaining. A clinical study was conducted on volunteers presenting wrinkles on face to evaluate flash reduction of wrinkles after 6 h of application by profilometry and anti-aging efficacy after 2 months by VISIA® CR2.3. RESULTS: Transcriptomic analysis evidenced an inhibition of MMP gene expression with acetylated HA, confirmed by an inhibition of MMPs release by fibroblasts, and a protection of type I collagen against degradation. We confirmed the reduction of MMPs in mature skin and in skin explants exposed to UV and urban dust. We demonstrated during clinical studies the flash reduction effect of acetylated HA on crow's feet wrinkles and a filling of nasogenian areas 6 h after application, and a wrinkles number reduction on nasogenian area up to 2 months of application. CONCLUSION: We developed a new grafted HA owing protective properties against ECM degradation induced by chronobiological and extrinsic aging, leading to a significant and efficient anti-wrinkles effect.

LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis.

BACKGROUND: LRP-1 is a multifunctional scavenger receptor belonging to the LDLR family. Due to its capacity to control pericellular levels of various growth factors and proteases, LRP-1 plays a crucial role in membrane proteome dynamics, which appears decisive for tumor progression. METHODS: LRP-1 involvement in a TNBC model was assessed using an RNA interference strategy in MDA-MB-231 cells. In vivo, tumorigenic and angiogenic effects of LRP-1-repressed cells were evaluated using an orthotopic xenograft model and two angiogenic assays (Matrigel® plugs, CAM). DCE-MRI, FMT, and IHC were used to complete a tumor longitudinal follow-up and obtain morphological and functional vascular information. In vitro, HUVECs' angiogenic potential was evaluated using a tumor secretome, subjected to a proteomic analysis to highlight LRP-1-dependant signaling pathways. RESULTS: LRP-1 repression in MDA-MB-231 tumors led to a 60% growth delay because of, inter alia, morphological and functional vascular differences, confirmed by angiogenic models. In vitro, the LRP-1-repressed cells secretome restrained HUVECs' angiogenic capabilities. A proteomics analysis revealed that LRP-1 supports tumor growth and angiogenesis by regulating TGF-ß signaling and plasminogen/plasmin system. CONCLUSIONS: LRP-1, by its wide spectrum of interactions, emerges as an important matricellular player in the control of cancer-signaling events such as angiogenesis, by supporting tumor vascular morphology and functionality.

Combining Raman imaging and MCR-ALS analysis for monitoring retinol permeation in human skin.

BACKGROUND: Monitoring the transcutaneous permeation of exogenous molecules using conventional techniques generally requires long pre-analytical preparation or labelling of samples. However, Raman spectroscopy is a label-free and non-destructive method which provides spatial distribution of tracked actives in skin. The aim of our study was to prove the interest of Raman imaging coupled with multivariate curve resolution alternating least square (MCR-ALS) analysis in monitoring retinol penetration into frozen and living human skin. MATERIALS AND METHODS: After topical treatment of skin samples by free or encapsulated retinol, thin cross sections were analysed by Raman imaging (up to 100 µm depth). Mann-Whitney test was used to identify retinol spectroscopic markers in skin. MCR-ALS was used to estimate retinol contribution in Raman spectral images. Heat maps were constructed to compare the distribution of free and encapsulated retinol in skin models. RESULTS: We identified the bands at 1158, 1196 and 1591 cm-1 as specific features for monitoring retinol in skin. Moreover, our MCR-ALS results showed an improvement of retinol penetration (up to 30 µm depth) with the encapsulated form as well as storage reservoir formation in stratum corneum, for each skin model. Finally, greater retinol penetration into living skin was observed. CONCLUSION: This study shows a proof of concept for the evaluation of retinol penetration in skin using Raman imaging coupled with MCR-ALS. This concept needs to be validated on more subjects to include inter-individual variability but also other factors affecting skin permeation (age, sex, pH, etc). Our study can be extended to other actives.

Mannose-6-phosphate complex and improvement in biomechanical properties of the skin.

BACKGROUND: The dermis is composed of a tangle of macromolecules that provides the skin its biomechanical properties. During chronological aging, fibroblasts lose their ability to synthesize collagen and an accumulation of matrix metalloproteinases leads to an increase in collagen degradation. As a result, there is a decline in the biomechanical properties of the skin. Skin aging is accelerated by external factors such as UV radiation and pollution, which induce accumulation of oxidants, and so of oxidized proteins in the skin. AIMS: Atomic force microscopy (AFM) has emerged as an alternative method for studying the biomechanical properties of skin cells and tissues. METHODS/RESULTS: Thus, we identified mannose-6-phosphate complex as a new powerful molecule capable of reversing the visible signs of aging by reorganizing the collagen network of the dermis and by improving the skin biomechanical properties. This effect was correlated with clinical studies that showed a marked antiaging effect through a reduction in the number of crow's feet and in the depth and size of neck wrinkles. CONCLUSION: Mannose-6-phosphate complex appeared to be able to protect proteins in the dermis scaffold against oxidation and degradation, allowing an improvement in the skin biomechanical properties.

Transcriptomic study in women with trisomy 21 identifies a possible role of the GTPases of the immunity-associated proteins (GIMAP) in the protection of breast cancer.

BACKGROUND: People with trisomy 21 (T21) are predisposed to developing hematological tumors, but have significantly lower-than-expected age-adjusted incidence rates of having a solid tumor. MATERIAL AND METHODS: To identify novel genetic factors implicated in the lower breast cancer (BC) frequency observed in women with T21 than in the general population, we compared the transcriptome pattern of women with a homogeneous T21, aged more than 30 years, with or without BC, and tumoral BC tissue of control women with a normal karyotype from the study of Varley et al. (2014). RESULTS: Differential analysis of gene expression between the 15 women in the T21 without BC group and BC patients in the other groups (two women with T21 and fifteen control women, respectively) revealed 154 differentially expressed genes, of which 63 were found to have similar expression profile (up- or downregulated). Of those 63 genes, four were in the same family, namely GIMAP4, GIMAP6, GIMAP7 and GIMAP8, and were strongly upregulated in the T21 without BC group compared to the other groups. A significant decrease in mRNA levels of these genes in BC tissues compared to non-tumor breast tissues was also noted. CONCLUSION: We found that the expression of some GIMAPs is significantly higher in women with T21 without BC than in patients with sporadic BC. Our findings support the hypothesis that GIMAPs may play a tumor-suppressive role against BC, and open the possibility that they may also have the same role for other solid tumors in T21 patients. The search for new prognostic factors and hopefully new therapeutic or preventive strategies against BC are discussed.

Major multilevel molecular divergence between THP-1 cells from different biorepositories.

The THP-1 cell line is broadly used as a model for acute myeloid leukemia (AML) with MLL fusion and to study monocyte differentiation and function. We studied THP-1 cells obtained from two major biorepositories. The two cell lines were closely related with a percentage match of short tandem repeat (STR) profiles ranging from 93.75% to 100%, depending on the algorithm used. Nevertheless, we found that the two cell lines presented discordant HLA type, cytogenetic aberrations and AML-related gene expression (including critical targets of MLL fusion). These discrepancies resulted mainly from loss of heterozygosity (LOH) involving five chromosomal regions. In view of their aberrant expression of key "leukemia" genes (e.g., LIN28B, MEIS1 and SPARC), we argue that one of the THP-1 cell lines may not be a reliable model for studying leukemia. Their defective expression of HLA molecules and abnormal adhesion properties is also a caveat for studies of antigen presentation. In a more general perspective, our findings show that seemingly minor discrepancies in STR profiles among cell lines may be the sign of major genetic drift, of sufficient magnitude to affect the reliability of cell line-based research.

Well-aging: A new strategy for skin homeostasis under multi-stressed conditions.

BACKGROUND: Several studies evidenced significant increase of cortisol is the consequence of UV or emotional stress and leads to various deleterious effects in the skin. AIM: The well-aging, a new concept of lifestyle, procures an alternative to the anti-aging strategy. We demonstrated that Tephrosia purpurea extract is able to stimulate well-being hormones while reducing cortisol release. Furthermore, we hypothesized that the extract could positively influence the global skin homeostasis. METHOD: We evaluated the impact of the extract on cortisol, ß-endorphin, and dopamine, released by normal human epidermal keratinocytes (NHEKs). A gene expression study was realized on NHEKs and NHDFs. The protein over-expression of HMOX1 and NQO1 was evidenced at cellular and tissue level. Finally, we conducted a clinical study on 21 women living in a polluted environment in order to observe the impact of the active on global skin improvement. RESULTS: The extract is able to reduce significantly the cortisol release while inducing the production of ß-endorphin and dopamine. The gene expression study revealed that Tephrosia purpurea extract up-regulated the genes involved in antioxidant response and skin renewal. Moreover, the induction of HMOX and NQO1 expression was confirmed on NHDFs, NHEKs and in RHE. We clinically demonstrated that the extract improved significantly the skin by reducing dark circles, represented by an improvement of L*, a*, and ITA parameters. CONCLUSION: Tephrosia purpurea extract has beneficial effects on skin homeostasis through control of the well-being state and antioxidant defenses leading to an improvement of dark circles, a clinical features particularly impacted by emotional and environmental stress.

From stem cells protection to skin microbiota balance: Orobanche rapum extract, a new natural strategy.

BACKGROUND: Healthy skin is a delicate balance between skin renewal and microbiota homeostasis, and its imbalance promotes premature aging and dermatological disorders. Skin stem cells are key actors in this process but their sensitivity to aging and external stressors such as UV reduces the skin renewal power. The skin microbiota has been recently described as active in the healthy skin, and its imbalance could trigger some disorders. AIMS: We hypothesized that reactivation of stem cells and maintenance of microbiota could be a disruptive strategy for younger and healthier skin. We thus developed a new plant extract that restores the entire skin renewal process by sequential activation from stem cells stimulation to microbiota protection. METHODS: We studied stem cells comportment in the presence of Orobanche rapum extract by survivin immunocytochemistry and caspases 3 and 9 dosages. We also analyzed epidermal differentiation markers by immunohistochemistry and lipids organization by GC/MS At the clinical level, we investigated the impact of O. rapum extract on microbiota and on skin aspect. RESULTS: We demonstrated an active protection of skin stem cells through the maintenance of their clone-forming capacity and resistance to UV through the overexpression of survivin coupled to caspases inhibition. Furthermore, we showed the restoration of epidermal differentiation markers and ceramide biosynthesis favorable to orthorhombic organization. Clinical studies, including microbiota analysis, showed an active skin surface renewal coupled with microbiota protection. CONCLUSION: We evidenced that our active ingredient is able to stimulate skin rejuvenation while protecting the cutaneous microbiota, creating healthier skin and thereby beauty.

A gentle approach to investigate the influence of LRP-1 silencing on the migratory behavior of breast cancer cells by atomic force microscopy and dynamic cell studies.

The aim of the study was to get more insight into the role of LRP-1 in the mechanism of tumor progression in triple negative breast cancer. Atomic force microscopy, videomicroscopy, confocal microscopy and Rho-GTPAse activity assay were used on MDA-MB-231 and LRP-1-silenced cells. Silencing of LRP-1 in MDA-MB-231 cells was shown to led to a dramatic increase in the Young's modulus in parallel to a spectacular drop in membrane extension dynamics as well as a decrease in the cells migration abilities on both collagen I and fibronectin substrates. These results were perfectly correlated to a corresponding change in cell morphology and spreading capacity as well as in Rho-GTPases activity. By a multi-technique approach, it was demonstrated that LRP-1 played a crucial role in the migration of MDA-MB-231 cells by modulating the membrane extension dynamic. The originality of this AFM investigation lies in the non-invasive aspect of the measurements.

Quantitative characterization of single-cell adhesion properties by atomic force microscopy using protein-functionalized microbeads.

A method was developed to characterize the adhesion properties of single cells by using protein-functionalized atomic force microscopy (AFM) probes. The quantification by force spectroscopy of the mean detachment force between cells and a gelatin-functionalized colloidal tip reveals differences in cell adhesion properties that are not within reach of a traditional bulk technique, the washing assay. In this latter method, experiments yield semiquantitative and average adhesion properties of a large population of cells. They are also limited to stringent conditions and cannot highlight disparities in adhesion in the subset of adherent cells. In contrast, this AFM-based method allows for a reproducible and quantitative investigation of the adhesive properties of individual cells in common cell culture conditions and allows for the detection of adhesive subpopulations of cells. These characteristics meet the critical requirements of many fields, such as the study of cancer cell migratory abilities.

Gynecologic follow up of 129 women on dialysis and after kidney transplantation: a retrospective cohort study.

OBJECTIVE: To describe the gynecologic issues and follow-up in our referral center of women on dialysis and after kidney transplantation. STUDY DESIGN: This retrospective cohort study included 129 dialysed women among whom 102 had had transplants. Data on menstrual pattern, pregnancies, contraception, and cervical cytology were retrieved from patients' files. RESULTS: The follow-up started at age 41.6±14.2 years and lasted for 9.5±10.2 years. Of the women, 78.7% had regular menses before dialysis, decreasing to 30.6% on dialysis (p<0.001), when 43.1% were amenorrheic (p<0.001). After transplantation, more patients had regular menstruation and fewer were amenorrheic (respectively 57.1% and 23.1%, p<0.001). On dialysis and after transplantation, 25% and 30.5% of patients suffered from metrorrhagia (compared to 17.1% before, p<0.01). Concerning pregnancies, rates of spontaneous abortions (33.3%, p=0.01), intrauterine growth retardation (28.5%, p<0.001) and prematurity (23.8%, p=0.008) were significantly higher after transplantation than before dialysis. Prescriptions for the combined contraceptive pill and intrauterine device decreased whereas chlormadinone acetate was widely used: it treated metrorrhagia and relieved mastodynia in 80% and 12% of the cases. Smear tests showed more inflammation (33% vs 0.8%, p<0.05), condylomas (13.6% vs 3.1%, p=0.005) and intraepithelial neoplasias (12.6% vs 2.3%, p=0.003) among patients after renal graft than before dialysis. CONCLUSION: Women on dialysis and after kidney transplantation suffered more from irregular menses and metrorrhagia which was improved by chlormadinone acetate. We noted high rates of obstetrical complications and abnormal smear tests. Consequently, this population must have close follow-up to identify and treat gynecologic issues.

Identification of spectral modifications occurring during reprogramming of somatic cells.

Recent technological advances in cell reprogramming by generation of induced pluripotent stem cells (iPSC) offer major perspectives in disease modelling and future hopes for providing novel stem cells sources in regenerative medicine. However, research on iPSC still requires refining the criteria of the pluripotency stage of these cells and exploration of their equivalent functionality to human embryonic stem cells (ESC). We report here on the use of infrared microspectroscopy to follow the spectral modification of somatic cells during the reprogramming process. We show that induced pluripotent stem cells (iPSC) adopt a chemical composition leading to a spectral signature indistinguishable from that of embryonic stem cells (ESC) and entirely different from that of the original somatic cells. Similarly, this technique allows a distinction to be made between partially and fully reprogrammed cells. We conclude that infrared microspectroscopy signature is a novel methodology to evaluate induced pluripotency and can be added to the tests currently used for this purpose.