Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Slaapgerelateerde ademhalingsstoornissen

In dit hoofdstuk wordt achtereenvolgens aandacht besteed aan verschillende slaapgerelateerde ademhalingsstoornissen (obstructief slaapapneusyndroom, centraal slaapapneusyndroom en obesitas-hypoventilatiesyndroom), hun prevalenties, gevolgen, comorbiditeit (in het bijzonder psychiatrische stoornissen) en mogelijke behandelingen. Slaapgerelateerde ademhalingsstoornissen zijn, na insomnie, de meest voorkomende groep slaapstoornissen. Er zijn aanwijzingen dat de prevalentie nog hoger is bij mensen met een ernstige psychiatrische aandoening. Echter, in tegenstelling tot bij insomnie, is er tot nu toe weinig wetenschappelijk onderzoek gedaan naar de wisselwerking tussen slaapapneu en psychiatrische stoornissen. Er is enige evidentie dat slaapapneu het risico op een depressie vergroot en psychiatrische symptomen kan verergeren. Omdat de kennis over mogelijke interacties nog zo beperkt is, wordt geadviseerd zowel de slaapgerelateerde ademhalingsstoornis als de psychiatrische aandoening te behandelen

Review of delirium in patients with Parkinson’s disease

Parkinson’s disease (PD) is common and has a number of associated neuropsychiatric disturbances. Of these, delirium has historically been under-recognised. Delirium is an acute disturbance of attention and awareness that fluctuates, and is accompanied by an additional disturbance of cognition. As delirium is known to carry a particularly poor prognosis in terms of morbidity and mortality, and the relationship between delirium and dementia is becoming better defined, we completed a literature review of delirium in the context of PD. A literature search was completed using the databases PubMed, Embase and Ovid Medline. PubMed (1945–2014) was searched in September 2014; Embase (1974–2014); and Ovid Medline (1946–2014) in October 2014. The search terms ‘delirium’ and ‘Parkinsons’ in combination were used. Large studies using a robust definition of delirium were lacking in PD. There is the suggestion that PD is a risk factor for delirium and that delirium negatively impacts upon the motor symptom trajectory. Deficits in the neurotransmitters dopamine and acetylcholine are implicated in the pathophysiology of delirium in PD. Systemic inflammation also appears to have a role. Treatment of delirium in PD should include medication review and cautious use of atypical antipsychotics where pharmacological treatment is indicated. Of the atypical antipsychotics studied, quetiapine has the least extrapyramidal side effects. Evidence suggests a specific link between delirium and PD but well-designed clinical studies to evaluate the prevalence, impact and treatment of delirium in PD are required. Given the potential to improve outcomes through delirium prevention we conclude that delirium in PD is an area worthy of further study.No Full Tex