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“Although the phenomenology accompanying psychoses is fascinating, hitherto empirical examinations have been qualitative and thus limited in their clinical conclusions regarding

the actual underlying cognitive mechanisms responsible for the formation and maintenance of the delusion. which is often distressing to the patient. We investigated the internal cognitive structure (i.e., connections) of some delusions pertaining to self and others in a patient with psychosis who was very fluent and thus able to provide a lucid account of his phenomenological experiences. To this end we employed a clustering method (HICLAS disjunctive model) in conjunction with standard neuropsychological Belnacasan tests. A well-fitting, but parsimonious solution revealed the absence of unique feature sets associated with certain persons, findings that provide a compelling case underlying the confusion in certain instances between real and delusional selleck inhibitor people. We illustrate the methodology in one patient and suggest that it is sensitive enough to explore the structure of delusions, which in conjunction with standard neuropsychological and clinical assessments promises to be useful in uncovering the mechanisms underlying delusions in psychosis. Published

by Elsevier Ireland Ltd.”
“The interaction of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells (BMSCs) has a positive impact on ALL resistance to chemotherapy. We investigated the modulation of a series of putative asparaginase-resistance/sensitivity genes in B-precursor ALL cells upon coculture with BMSCs. Coculture with stromal cells resulted in increased insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) expression by ALL cells. Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of

recombinant rIGFBP7 (rIGFBP7) to the culture medium, nearly showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase. In these assays, IGFBP7 function occurred mainly in an insulin-and stromal-dependent manner. ALL cells were found to contribute substantially to extracellular IGFBP7 levels in the conditioned coculture medium. Diagnostic BM plasma from children with ALL had higher levels of IGFBP7 than controls. IGFBP7, in an insulin/IGF-dependent manner, enhanced asparagine synthetase expression and asparagine secretion by BMSCs, thus providing a stromal-dependent mechanism by which IGFBP7 protects ALL cells against asparaginase in this coculture system. Importantly, higher IGFBP7 mRNA levels were associated with lower leukemia-free survival (Cox regression model, P = 0.003) in precursor B-cell Ph(-) ALL patients (n = 147) treated with a contemporary polychemotherapy protocol.