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Background. Subdural collections of cerebrospinal fluid (CSF) with associated hydrocephalus have been described by several different and sometimes inaccurate terms. It has been proposed that a subdural effusion with hydrocephalus (SDEH) can be treated effectively with a ventriculoperitoneal shunt (V-P shunt). In this study, we present our experience treating patients with SDEH without directly treating the subdural collection. Methods. We treated three patients with subdural effusions and hydrocephalus as a result of a head injury. All the patients were treated with a V-P shunt despite the fact that there was an extra-axial CSF collection withmidline shift. Results. In all of the patients, the subdural effusions subsided and the ventricular dilatation improved in the postoperative period. The final clinical outcome remains difficult to predict and depends not only on the successful CSF diversion but also on the primary and secondary brain insult. Conclusion. Subdural effusions with hydrocephalus can be safely and effectively treated with V-P shunting, without directly treating the subdural effusion which subsides along with the treatment of hydrocephalus. However, it is extremely important to make an accurate diagnosis of an SDEH and differentiate this condition from other subdural collections which require different management. [ABSTRACT FROM AUTHOR]

The circadian clock controls many aspects of mammalian physiology and behaviour with a periodicity of approximately 24 h. These include the anticipation of, and adaptation to, daily environmental changes such as the light–dark cycle, temperature fluctuations and the availability of food. The toxicity of many drugs is dependent on the circadian phase at which they are administered, and recent work has begun to unravel the molecular basis for circadian variations in sensitivity to xenobiotic exposure. Between 2 and 10% of the transcriptome is expressed in a circadian manner, including many key genes associated with the metabolism and transport of xenobiotics. Furthermore, a number of xenobiotics may directly alter the expression of genes that control circadian rhythms. This review discusses the emerging evidence for the regulation of circadian rhythm genes having an important impact on molecular response to xenobiotics. [ABSTRACT FROM AUTHOR]

Abstract Background Colorectal cancer (CRC) is a heterogeneous and biologically poorly understood disease. To tailor CRC treatment, it is essential to first model this heterogeneity by defining subtypes of patients with homogeneous biological and clinical characteristics and second match these subtypes to cell lines for which extensive pharmacological data is available, thus linking targeted therapies to patients most likely to respond to treatment. Methods We applied a new unsupervised, iterative approach to stratify CRC tumor samples into subtypes based on genome-wide mRNA expression data. By applying this stratification to several CRC cell line panels and integrating pharmacological response data, we generated hypotheses regarding the targeted treatment of different subtypes. Results In agreement with earlier studies, the two dominant CRC subtypes are highly correlated with a gene expression signature of epithelial-mesenchymal-transition (EMT). Notably, further dividing these two subtypes using iNMF (iterative Non-negative Matrix Factorization) revealed five subtypes that exhibit activation of specific signaling pathways, and show significant differences in clinical and molecular characteristics. Importantly, we were able to validate the stratification on independent, published datasets comprising over 1600 samples. Application of this stratification to four CRC cell line panels comprising 74 different cell lines, showed that the tumor subtypes are well represented in available CRC cell line panels. Pharmacological response data for targeted inhibitors of SRC, WNT, GSK3b, aurora kinase, PI3 kinase, and mTOR, showed significant differences in sensitivity across cell lines assigned to different subtypes. Importantly, some of these differences in sensitivity were in concordance with high expression of the targets or activation of the corresponding pathways in primary tumor samples of the same subtype. Conclusions The stratification presented here is robust, captures important features of CRC, and offers valuable insight into functional differences between CRC subtypes. By matching the identified subtypes to cell line panels that have been pharmacologically characterized, it opens up new possibilities for the development and application of targeted therapies for defined CRC patient sub-populations.