MOLECULAR STRUCTURE OF THE EPIDERMAL EXTRACELLULAR SPACES

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65966/1/j.1365-4362.1979.tb01946.x.pd

Early phase clinical trials of anticancer agents in children and adolescents — an ITCC perspective

In the past decade, the landscape of drug development in oncology has evolved dramatically; however, this paradigm shift remains to be adopted in early phase clinical trial designs for studies of molecularly targeted agents and immunotherapeutic agents in paediatric malignancies. In drug development, prioritization of drugs on the basis of knowledge of tumour biology, molecular 'drivers' of disease and a drug's mechanism of action, and therapeutic unmet needs are key elements; these aspects are relevant to early phase paediatric trials, in which molecular profiling is strongly encouraged. Herein, we describe the strategy of the Innovative Therapies for Children with Cancer (ITCC) Consortium, which advocates for the adoption of trial designs that enable uninterrupted patient recruitment, the extrapolation from studies in adults when possible, and the inclusion of expansion cohorts. If a drug has neither serious dose-related toxicities nor a narrow therapeutic index, then studies should generally be started at the adult recommended phase II dose corrected for body surface area, and act as dose-confirmation studies. The use of adaptive trial designs will enable drugs with promising activity to progress rapidly to randomized studies and, therefore, will substantially accelerate drug development for children and adolescents with cancer

Convergent functional genomic studies of omega-3 fatty acids in stress reactivity, bipolar disorder and alcoholism

Omega-3 fatty acids have been proposed as an adjuvant treatment option in psychiatric disorders. Given their other health benefits and their relative lack of toxicity, teratogenicity and side effects, they may be particularly useful in children and in females of child-bearing age, especially during pregnancy and postpartum. A comprehensive mechanistic understanding of their effects is needed. Here we report translational studies demonstrating the phenotypic normalization and gene expression effects of dietary omega-3 fatty acids, specifically docosahexaenoic acid (DHA), in a stress-reactive knockout mouse model of bipolar disorder and co-morbid alcoholism, using a bioinformatic convergent functional genomics approach integrating animal model and human data to prioritize disease-relevant genes. Additionally, to validate at a behavioral level the novel observed effects on decreasing alcohol consumption, we also tested the effects of DHA in an independent animal model, alcohol-preferring (P) rats, a well-established animal model of alcoholism. Our studies uncover sex differences, brain region-specific effects and blood biomarkers that may underpin the effects of DHA. Of note, DHA modulates some of the same genes targeted by current psychotropic medications, as well as increases myelin-related gene expression. Myelin-related gene expression decrease is a common, if nonspecific, denominator of neuropsychiatric disorders. In conclusion, our work supports the potential utility of omega-3 fatty acids, specifically DHA, for a spectrum of psychiatric disorders such as stress disorders, bipolar disorder, alcoholism and beyond

Soemmering's ring, an aspect of secondary cataract:A morphological description by SEM

A Soemmering's ring attached to a patient's I.O.L. was removed and processed for SEM-examination. The enveloping structure of the Soemmering's ring was clearly of capsular origin, adherent along a single line and forming an envelope around the inner material. The envelope had a membranous character. The contents of the ring varied from the outside to the centre. Close to the capsule envelope a more or less amorphous material was found. Most of the contents of the ring was made up of lens-fibre material. Sometimes clear lens fibres were visible with densely packed lens-fibre proteins, sometimes with clusters of recrystallized proteins, rod-shaped or spherical, surrounded by what appeared to be amorphous material. The recrystallized and the amorphous lens-fibre material are similar to material found in cataractous lenses

Secondary cataract material collected with a glass cannula:A SEM study

Secondary cataract material from three patients, collected with a glass cannula approx. 18, 24 and 30 months respectively after operation, was prepared for SEM examination. For the soft samples this was done by filtration through a millipore filter followed by fixation and drying. The more solid material was suspended in a fixation solution, followed by centrifuging, suspension in 70% ethanol and drying on a specimen-holder. The short residence samples (18 months) showed mainly erythrocytes, some (inflammatory) cells and degenerated lens-fibre material. Most of the more solid material, which was collected more than 20 months after operation, showed fragments of (regenerated) capsule epithelium and pieces of solid lens-fibre material with fragments of capsule epithelium attached