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Background: We investigated whether a computed tomography (CT)-based score could predict a large infarct (≥ 80 mL) on early diffusion-weighted magnetic resonance imaging (DWI)., Methods: Acute stroke patients considered for endovascular therapy within 8 hours of the onset of symptoms were included. The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was determined on noncontrast CT and computed tomography angiography source images (CTA-SI). Limited collateral flow was defined as less than 50% collateral filling on CTA-SI., Results: Fifty-six patients were analyzed. National Institutes of Health Stroke Scale score was 20 (15-24) in the large infarct group and 16 (11-20) in the small infarct group (P = .049). ASPECTS on noncontrast CT and CTA-SI was 5 (3-8) and 3 (2-6) in the large infarct group and 9 (8-10) and 8 (7-9) in the small infarct group (both P < .001), respectively. Limited collateral flow was frequent in the large infarct group than in the small infarct group (92% vs. 11%, P < .001). Multivariate analysis found that CTA-SI ASPECTS less than or equal to 5 (odds ratio [OR], 40.55; 95% confidence interval [CI], 1.10-1493.44; P = .044) and limited collateral flow (OR, 114.64; 95% CI, 1.93-6812.79; P = .023) were associated with a large infarct. Absence of ASPECTS less than or equal to 5 and limited collateral flow on CTA-SI predicted absence of a large infarct with a sensitivity of .89, specificity of 1.00, positive predictive value of 1.00, and negative predictive value of .71., Conclusions: Assessment of ASPECTS and collateral flow on CTA-SI may be able to exclude a patient with large infarct on early DWI., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Advanced age, arbitrarily defined as over 80 years, has been an exclusion criterion in many clinical trials for the treatment of acute ischemic stroke. The oldest person, to our knowledge, treated for acute ischemic stroke with intra-arterial therapy is presented and, importantly, this patient was excluded from intravenous tissue plasminogen activator due to an advanced age of 100 years and arrival in our emergency department within the 3-4.5 h time window. Utilizing an MRI based protocol to assess the risk-benefit ratio, treatment by intra-arterial mechanical embolectomy was commenced resulting in middle cerebral artery recanalization at 6 h 30 min. The patient improved, and ultimately returned to a baseline modified Rankin Scale score of 3. With careful selection, elderly patients may benefit from acute stroke therapies and may be considered on a case by case basis.

GATA4 is a transcription factor that plays a role in regulating the normal development of many mesoderm and endoderm derived tissues, including the pancreas. Silencing of GATA4 mRNA expression by promoter methylation has been implicated in carcinogenesis of the ovary, lung and colorectum. By contrast, GATA4 mRNA expression is upregulated in pancreatic cancer cell lines and tissues. To further clarify the relationship of GATA4 to pancreatic cancer, we immunolabeled 90 samples of pancreatic ductal adenocarcinoma using a GATA4 specific monoclonal antibody. Both the intensity and percent of labeling was recorded for each carcinoma and correlated to the clinic opathologic features available for each patient. Samples of normal adult (n=26) and fetal pancreatic tissue (n=8) were also immunolabeled for comparison to expression patterns in pancreatic carcinoma tissues. Immunolabeling for GATA4 indicated robust nuclear expression in developing acini in fetal pancreatic tissues, consistent with the role of GATA4 in embryologic development, and in mature pancreatic acinar epithelium. Immunolabeling for GATA4 was also noted within normal duct epithelial cells, although it was always lesser in intensity than for acinar cell nuclei in the same section. Positive GATA4 immunolabeling was seen in 61/90 (68%) infiltrating pancreatic cancers of which 27/90 (30%) showed strong positive labeling. While there was no relationship among GATA4 and patient age, race or pathologic features, we did find a significant association among strong positive labeling and female gender (p=0.01). These findings support previous studies implicating GATA4 in pancreatic cancer and offer new avenues for investigation into this aggressive tumor type.

The development of small molecules that disrupt protein-protein interactions is a key goal in addressing a number of disease states. The alpha-helix is commonly found at protein interaction interfaces and has been the focus of substantial small molecule mimetic efforts. One of the primary drawbacks of many small molecule alpha-helix mimetics is their hydrophobic core structures. To address this problem we have developed a novel scaffold based on a more water soluble 5-6-5 imidazole-phenyl-thiazole core. An inhibitor of this class has been shown to disrupt the Cdc42/Dbs protein-protein interaction at micromolar concentrations and may be useful in overcoming Cdc42-induced tumor resistance to anticancer therapies.

New chemotherapeutics are urgently needed to combat malaria. We previously reported on a novel series of antimalarial, ethylenediamine-based inhibitors of protein farnesyltransferase (PFT). In the current study, we designed and synthesized a series of second generation inhibitors, wherein the core ethylenediamine scaffold was varied in order to examine both the homology model of Plasmodium falciparum PFT (PfPFT) and our predicted inhibitor binding mode. We identified several PfPFT inhibitors (PfPFTIs) that are selective for PfPFT versus the mammalian isoform of the enzyme (up to 136-fold selectivity), that inhibit the malarial enzyme with IC50 values down to 1 nM, and that block the growth of P. falciparum in infected whole cells (erythrocytes) with ED50 values down to 55 nM. The structure-activity data for these second generation, ethylenediamine-inspired PFT inhibitors were rationalized by consideration of the X-ray crystal structure of mammalian PFT and the homology model of the malarial enzyme.