Cerebellar stroke presenting with isolated dizziness: Brain MRI in 136 patients.

OBJECTIVE: To evaluate occurrence of cerebellar stroke in Emergency Department (ED) presentations of isolated dizziness (dizziness with a normal exam and negative neurological review of systems). METHODS: A 5-year retrospective study of ED patients presenting with a chief complaint of "dizziness or vertigo", without other symptoms or signs in narrative history or on exam to suggest a central nervous system lesion, and work-up included a brain MRI within 48h. Patients with symptoms commonly peripheral in etiology (nystagmus, tinnitus, gait instability, etc.) were included in the study. Patient demographics, stroke risk factors, and gait assessments were recorded. RESULTS: One hundred and thirty-six patients, who had a brain MRI for isolated dizziness, were included. There was a low correlation of gait assessment between ED physician and Neurologist (49 patients, Spearman's correlation r2=0.17). Based on MRI DWI sequence, 3.7% (5/136 patients) had acute cerebellar strokes, limited to or including, the medial posterior inferior cerebellar artery vascular territory. In the 5 cerebellar stroke patients, mean age, body mass index (BMI), hemoglobin A1c, gender distribution, and prevalence of hypertension were similar to the non-cerebellar stroke patient group. Mean LDL/HDL ratio was 3.63±0.80 and smoking prevalence was 80% in the cerebellar stroke group compared to 2.43±0.79 and 22% (respectively, p values<0.01) in the non-cerebellar stroke group. CONCLUSIONS: Though there was preselection bias for stroke risk factors, our study suggests an important proportion of cerebellar stroke among ED patients with isolated dizziness, considering how common this complaint is.

Cancer development, progression, and therapy: an epigenetic overview.

Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell-cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.

Recent speciation and limited phylogeographic structure in Mixophyes frogs from the Australian Wet Tropics.

Through a combination of macroecological, paleoecological, and phylogeographical analyses, the rainforests of the Australian Wet Tropics (AWT) have emerged as a useful model for understanding sensitivity of species to past climatic change and, hence, for predicting vulnerability to future change. To extend the ecological breadth of comparative phylogeographic analyses, we investigate a clade of myobatrachid frogs, Mixophyes, a genus of large, stream-breeding but terrestrial frogs, three species of which are endemic to rainforests of the AWT. Here we (i) combine mtDNA, allozyme, and morphological data to refine knowledge of the geographic and environmental distribution of each taxon, (ii) resolve relationships among species, and (iii) use mtDNA phylogeography to infer responses of the three taxa to late-Pleistocene and Holocene climatic change. Each of the three species (Mixophyes carbinensis, Mixophyes coggeri, and Mixophyes schevilli) is effectively diagnosed by mtDNA, with the two small-bodied, allopatric species (M. carbinensis and M. schevilli) being sister-taxa. Mixophyes have a very different history from other AWT amphibians, with more recent speciation (net divergences <5%) and much lower and geographically unstructured mtDNA diversity within each species. The combination of low diversity (θ(Π)<0.36%) and strong signals of recent population expansion (Fu's Fs<0) suggests very high sensitivity to climate-driven rainforest dynamics, perhaps due to their large body size, low population density, and their requirement for both wet forest-floor litter and streams suitable for breeding. The results further emphasize the heterogeneity of species' responses to climate change and suggest that species dependent on multiple habitat types could be especially vulnerable.

The Effects of Histone Deacetylase Inhibitor and Calpain Inhibitor Combination Therapies on Ovarian Cancer Cells.

BACKGROUND: Ovarian cancer is difficult to treat due to absence of selective drugs and tendency of platinum drugs to promote resistance. Combination therapy using epigenetic drugs is predicted to be a beneficial alternative. MATERIALS AND METHODS: This study investigated the effects of combination therapies using two structurally different histone deacetylase (HDAC) inhibitors (HDACi), sodium butyrate and suberanilohydroxamic acid (SAHA), with the calpain inhibitor calpeptin on two characteristically different ovarian cancer cell lines, CAOV-3 and SKOV-3. RESULTS: Suboptimal doses of HDACi and calpeptin produced several effects. Growth inhibition was enhanced and the epigenetically silenced tumor suppressor genes ARHI, p21 and RARß2 were re-expressed. Methylation of specific CpG residues in ARHI were reduced. Cell-cycle progression was inhibited and apoptosis, as well as autophagy, were induced. The phosphorylation of ERK and Akt were differentially effected by these inhibitors. CONCLUSION: The re-expression of tumor suppressors may sensitize ovarian cancer cells, which then undergo apoptosis and autophagy for cell death.