An Innovative Oat‐Based Sterile Emollient Cream in the Maintenance Therapy of Childhood Atopic Dermatitis

Although emollients are recommended in the management of atopic dermatitis (AD), regimens for emollient maintenance therapy are awaiting validation. We conducted an international, multicenter, open‐label trial to assess the effects of a 3‐month maintenance treatment regimen with a sterile, preservative‐free emollient cream containing oat plantlets in children (ages 6 mos–6 yrs) with moderate AD. After a 14‐day run‐in stabilization phase using a topical corticosteroid (TCS) treatment of medium potency, 108 children with a SCORing Atopic Dermatitis (SCORAD) index of 20 or less were included in the study. Emollient was applied twice daily for 3 months. Rescue TCS treatment was used only in cases of flare‐ups. The SCORAD index, Patient‐Oriented SCORAD (PO‐SCORAD) index, number of flares, TCS use, and tolerance were assessed at months 1, 2, and 3 (M1, M2, M3). AD severity improved, with a highly significant decrease in the SCORAD and PO‐SCORAD indexes at M2 and M3 (p < 0.001). Changes from baseline to M3 were 48.6 ± 73.6% for SCORAD and 29.6 ± 125.3% for PO‐SCORAD. The number of flares and TCS use significantly decreased by M3 (both p < 0.001). Very good tolerance was recorded in 100% of children at M2 and M3. Notwithstanding the limitations inherent in open‐label trials, twice daily application of the oat‐based sterile emollient cream led to a significant improvement of clinical symptoms, evidenced by parallel changes in the SCORAD and PO‐SCORAD indexes and fewer flare‐ups. Clinical benefit and less TCS use were maintained at M3. Tolerance was very good.     

Translational screening platform to evaluate chemotherapy in combination with focal therapy for retinoblastoma

Retinoblastoma is the most common pediatric eye cancer. It is currently treated with a limited number of drugs, adapted from other pediatric cancer treatments. Drug toxicity and relapse of the disease warrant new therapeutic strategies for these young patients. In this study, we developed a robust tumoroid-based platform to test chemotherapeutic agents in combination with focal therapy (thermotherapy) – a treatment option widely used in clinical practice – in accordance with clinically relevant trial protocols. The model consists of matrix-embedded tumoroids that retain retinoblastoma features and respond to repeated chemotherapeutic drug exposure similarly to advanced clinical cases. Moreover, the screening platform includes a diode laser (810 nm, 0.3 W) to selectively heat the tumoroids, combined with an on-line system to monitor the intratumoral and surrounding temperatures. This allows the reproduction of the clinical settings of thermotherapy and combined chemothermotherapy treatments. When testing the two main drugs currently used in clinics to treat retinoblastoma in our model, we observed results similar to those clinically obtained, validating the utility of the model. This screening platform is the first system to accurately reproduce clinically relevant treatment methods and should lead to the identification of more efficient drugs to treat retinoblastoma.     

Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure. Part 1: Oral route

Synthetic amorphous silica (SAS) in its nanosized form is now used in food applications although the potential risks for human health have not been evaluated. In this study, genotoxicity and oxidative DNA damage of two pyrogenic (NM‐202 and 203) and two precipitated (NM‐200 and ‐201) nanosized SAS were investigated in vivo in rats following oral exposure. Male Sprague Dawley rats were exposed to 5, 10, or 20 mg/kg b.w./day for three days by gavage. DNA strand breaks and oxidative DNA damage were investigated in seven tissues (blood, bone marrow from femur, liver, spleen, kidney, duodenum, and colon) with the alkaline and the (Fpg)‐modified comet assays, respectively. Concomitantly, chromosomal damage was investigated in bone marrow and in colon with the micronucleus assay. Additionally, malondialdehyde (MDA), a lipid peroxidation marker, was measured in plasma. When required, a histopathological examination was also conducted. The results showed neither obvious DNA strand breaks nor oxidative damage with the comet assay, irrespective of the dose and the organ investigated. Similarly, no increases in chromosome damage in bone marrow or lipid peroxidation in plasma were detected. However, although the response was not dose‐dependent, a weak increase in the percentage of micronucleated cells was observed in the colon of rats treated with the two pyrogenic SAS at the lowest dose (5 mg/kg b.w./day). Additional data are required to confirm this result, considering in particular, the role of agglomeration/aggregation of SAS NMs in their uptake by intestinal cells. Environ. Mol. Mutagen. 56:218–227, 2015. © 2014 Wiley Periodicals, Inc.     

Conditional ligands for Asian HLA variants facilitate the definition of CD8+ T‐cell responses in acute and chronic viral diseases

Conditional ligands have enabled the high‐throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation‐sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA‐A, ‐B, and ‐C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA‐based MHC stability assay. HLA tetramers with redirected specificity could detect antigen‐specific CD8⁺ T‐cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein‐Barr virus (EBV) infections. The potential of this population‐centric HLA library was demonstrated with the characterization of seven novel T‐cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state‐of‐the‐art epitope prediction. This flow cytometry‐based technology therefore holds considerable promise for monitoring clinically relevant antigen‐specific T‐cell responses in populations of distinct ethnicity.