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QUESTION: How do parents recognise and make judgements about respiratory signs and symptoms in their young children? Design Qualitative study using semistructured interviews. Setting Leicester, UK. Participants Parents of 19 [...]

Sunlight has the potential to induce DNA damage in the skin. If these photolesions are left unrepaired, they can greatly increase the risk of skin cancer. This process is facilitated by another UV-induced insult, photoimmune suppression. Vitamin D metabolites have demonstrated a marked ability to mitigate these negative effects. The photoprotective pathway still remains elusive. Recent research, however, points to the important role of the vitamin D receptor and the endoplasmic reticulum protein ERp57 in mediating the actions of vitamin D compounds. Determining the functional relationship between vitamin D metabolites, the VDR/ERp57 complex, and downstream DNA repair mechanisms will contribute to the greater understanding of this photoprotective system. Furthermore, in light of evidence suggesting that CYP27B1 is not necessary for photoprotection, strong emphasis must now be placed on examining other vitamin D metabolic pathways and the actions of new metabolites in photoprotection. Recent literature points to 20(OH)D3 as a possible alternative to 1,25(OH)2D3. However, further work must be conducted to determine the photoprotective pathway of this vitamin D derivative.

One-bead one-compound combinatorial chemistry together with a high-throughput screen based on fluorescently labeled enzyme allowed the identification of slow binding inhibitors of human serine racemase (hSR). A peptide library of topographically segregated encoded resin beads was synthesized, and several hSR-binding compounds were isolated, identified, and resynthesized for further kinetic study. Of these, several showed inhibitory effects with moderate potency (high micromolar KIs) toward hSR. A clear structural motif was identified consisting of 3-phenylpropionic acid and histidine moieties. Importantly, the inhibitors identified showed no structural similarities to the natural substrate, l-serine. Detailed kinetic analyses of the properties of selected inhibitors show that the screening protocol used here selectively identifies slow binding inhibitors. They provide a pharmacophore for the future isolation of more potent ligands that may prove useful in probing and understanding the biological role of hSR.

BACKGROUND: Despite intensive research into the molecular abnormalities associated with colorectal cancer (CRC), no diagnostic tests have emerged which usefully complement standard histopathological assessments. AIMS: To assess the feasibility of using immunohistochemistry to detect replication error (RER) positive CRCs and determine the incidence of RER positivity within distinct patient subgroups. METHODS: 502 CRCs were analysed for RER positivity (at least two markers affected) and/or expression of hMSH2 and hMLH1. RESULTS: There were 15/30 (50%) patients with metachronous CRCs, 16/51 (31%) with synchronous CRCs, 14/45 (31%) with a proximal colon carcinoma, and 4/23 (17%) who developed a CRC under the age of 50 showed RER positivity. However, 0/54 patients who developed a solitary carcinoma of the rectum/left colon over the age of 50 showed RER positivity. Immunohistochemical analysis revealed that 66/66 (100%) RER positive carcinomas were associated with complete lack of expression of either hMSH2 or hMLH1. This correlation was confirmed using a further 101 proximal colon carcinomas. Patients with a mismatch repair defective carcinoma showed improved survival but a 5.54 times relative risk of developing a metachronous CRC. A prospective immunohistochemical study revealed 13/117 (11%) patients had a mismatch repair defective carcinoma. A fivefold excess of hMLH1 defective cases was noted. CONCLUSIONS: All RER positive carcinomas were identified by the immunohistochemical test. This is the first simple laboratory test which can be performed routinely on all CRCs. It will provide a method for selecting patients who should be investigated for HNPCC, offered long term follow up, and who may not respond to standard chemotherapy regimens.

Consulting skills can be developed and improved through the use of a unique case format and method of case analysis. The format and methodology, developed by Argyris, is based in his theory of action. Argyris argues that consultants function out of two theories, one which they espouse and another which actually guides their words and actions, their theory‐in‐use. A consultant's theory‐in‐use is often tacit and thus unavailable for self‐examination or correction. The analysis is conducted in a small group using a case which the consultant has constructed from an actual dialogue he or she has had with a client. The dialogue provides the means to examine possible contradictions between the consultant's theory‐in‐use and the espoused theory. In addition the analysis provides insight into inferences the consultant makes about the client's words and actions which may be incorrect.

Correlation between cleavage formation and growth of syntectonic fibrous minerals is used to show that superposition of crenulation cleavages in Lower Ordovician rocks from the Eastern Townships of Quebec, Canada, resulted from overprinting during progressive deformation. Fibres of calcite, quartz and chlorite in pressure shadows adjacent to pyrite curve through almost 90°, from parallelism with the first to parallelism with the second, superposed crenulation cleavage. Whereas the cleavages mark only the initial and final orientations of the flattening plane, the fibres record the gradual rotation of this plane in the interval between formation of the cleavages. The continuity of the undeformed fibres suggests a single progressive deformation rather than two separate tectonic events.