Retinaldehyde/hyaluronic acid fragments: a synergistic association for the management of skin aging

Background Retinaldehyde (RAL) was proven effective in treating photodamaged skin. Topical treatments with specific intermediate‐size hyaluronate fragments (HAFi, 50–400 kDa) have been shown to stimulate keratinocytes proliferation and epidermal hyperplasia. The aim of this open, multicentric, international study was to assess the efficacy of the combination RAL–HAFi in the correction of skin photoaging. Patients/Methods Either RAL 0.05%–HAFi 0.5% (Eluage^® cream; group 1) or RAL 0.05%–HAFi 1% (Eluage^® antiwrinkle concentrate; group 2) or both products (group 3) were applied daily to the 1462 subjects during 90 days. Overall photoaging severity was evaluated in the three groups by the dermatologists at D0, D30, and D90 based on the Larnier’s scale. Wrinkles and/or furrows and clinical signs of aging were evaluated using a 4‐point scale. The skin microrelief of the crow’s feet, evaluated by optical profilometry, was performed in subjects from group 3. Results The 3‐month application significantly improved overall photoaging through decrease of the Larnier’s score in the three groups (P < 0.001). At D90, significant improvement of wrinkles was shown in groups 2 and 3 [forehead wrinkles (?19% and ?10%, respectively, P < 0.001), nasolabial folds (?20% and ?16%, P < 0.001), crow’s feet (?27% in the two groups, P < 0.001), and perioral wrinkles (?34% and ?23%, P < 0.001)]. Clinical signs of photoaging on the entire face improved significantly in groups 1 and 3 [elasticity (?32% and ?33%, respectively, P < 0.001), hyperpigmentation (?34% and ?31%, P < 0.001), and ptosis (?18% and ?22%; P < 0.001)]. Results were confirmed using an optical profilometry technique. Products were very well tolerated. Conclusion This clinical study showed the efficacy and value of the RAL–HAFi combination in the management of aging skin in a large cohort of patients.     

The role of the corpus callosum in the perception of reversible figures in children

To test the role of interhemispheric competition through the corpus callosum in the perceptual alternation of reversible figures, we compared children with callosal pathology and typically developing children on a bistable stimulus task. The children with corpus callosum pathology reported significantly less changes of percepts per minute than the age-matched typically developing children. In addition, older typically developing children reported significantly more changes of percepts than the younger ones. These results support the hypothesis that the rate of reversal between two interpretations of a bistable stimulus may be partly mediated by the corpus callosum.     

Plasmodium falciparum malaria and atovaquone-proguanil treatment failure

We noticed overrepresentation of atovaquone-proguanil therapeutic failures among Plasmodium falciparum-infected travelers weighing >100 kg. We report here 1 of these cases, which was not due to resistant parasites or impaired drug bioavailability. The follow-up of such patients should be strengthened.     

The dynamics of soil bacterial community structure in response to yearly repeated agricultural copper treatments

The annual dynamics of soil bacterial community structure, including early, dose-dependent and transient modifications, was observed consecutively at different levels of copper contamination (high: 48 kg Cu ha(-1), low: 16 kg Cu ha(-1)) repeated yearly over a three-year field experiment. Repeated low-level Cu contamination led to an increase in community stability to metal stress without a long-term shift in the population structure, whereas repeated high-level Cu contamination induced a novel and stable bacterial community structure. Furthermore, field experimentation highlighted that episodic climatic stress can modulate copper impact by enhancing community stability.     

Hyaluronan hydrogel: an appropriate three-dimensional model for evaluation of anticancer drug sensitivity

The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation and proliferation, and contributes to the invasiveness of human cancers. In order to investigate the sensitivity of cancer cells to antimitotic agents, we developed a cross-linked HA hydrogel, a three-dimensional matrix in which cells can invade and grow. We have studied three cell lines (SA87, NCI-H460 and H460M), from primary tumors and metastases, that migrated into the HA hydrogel and proliferated giving rise to clusters and colonies. Concurrently, we studied the growth of these cell lines in a usual monolayer culture system. In these two models, increasing concentrations of doxorubicin and 5-fluorouracil were evaluated for their ability to inhibit tumor cell growth and colony formation. Taken together, our data suggest that the cancer cells were more resistant in the three-dimensional model than in monolayer cell systems. The antimitotic drugs were efficient after 24h of treatment in the monolayer cultures, whereas they were significantly efficient only after one week of incubation in the HA hydrogels. Herein, we show that this cross-linked matrix provides a three-dimensional model particularly appropriate for investigating mechanisms involved in cancer cell line sensitivity to antimitotic drugs.     

Detection of exonic copy-number changes using a highly efficient oligonucleotide-based comparative genomic hybridization-array method

Genomic copy-number variations (CNVs) involving large DNA segments are known to cause many genetic disorders. Depending on the changes, they are predicted to lead either to decreased or an increased gene expression. However, the ability to detect smaller exonic copy-number changes has not been explored. Here we describe a new oligonucleotide-based comparative genomic hybridization (CGH)-array approach for high-throughput detection of exonic deletions or duplications and its application to deletion/duplication analyses of the genes encoding CFTR, six sarcoglycans (SGCA, SGCB, SGCG, SGCD, SGCE, and SGCZ), and DMD. In this work we show the successful development of an array format containing 158 exons that collectively span eight genes and its clinical application for the rapid screening of deletions and duplications in a diagnostic setting. We have analyzed a series of 35 DNA samples from patients affected with cystic fibrosis (CF), Duchenne and Becker muscular dystrophies (DMD/BMD), or sarcoglycanopathies, and have characterized exonic copy-number changes that have been validated with other methods. Interestingly, even heterozygous deletions and duplications of only one exon, as well as mosaic deletions, were detected by this CGH approach. Our results showed that the resolution is very high, as abnormalities of about 1.5-2 kb could be detected. Since this approach is completely scalable, this new molecular tool will allow the screening of combinations of genes involved in a particular group of clinically and genetically heterogeneous disorders such as mental retardation, muscular dystrophies and brain malformations.