Despite advances in monitoring spatiotemporal expression patterns of genes and proteins with fluorescent probes, direct detection of metabolites and small molecules remains challenging. A technique for spatially resolved detection of small molecules would benefit the study of redox-active metabolites produced by microbial biofilms, which can drastically affect colony development. Here we present an integrated circuit-based electrochemical sensing platform featuring an array of working electrodes and parallel potentiostat channels. “Images” over a 3.25 × 0.9 mm area can be captured with a diffusion-limited spatial resolution of 750 μm. We demonstrate that square wave voltammetry can be used to detect, identify, and quantify (for concentrations as low as 2.6 μM) four distinct redox-active metabolites called phenazines. We characterize phenazine production in both wild-type and mutant Pseudomonas aeruginosa PA14 colony biofilms, and find correlations with fluorescent reporter imaging of phenazine biosynthetic gene expression.

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The function of microRNAs (miRNAs) during alcoholic liver disease (ALD) has recently become of great interest in biological research. Studies have shown that ALD associated miRNAs play a crucial role in the regulation of liver-inflammatory agents such as tumour necrosis factor-alpha (TNF-α), one of the key inflammatory agents responsible for liver fibrosis (liver scarring) and the critical contributor of alcoholic liver disease. Lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, is responsible for TNF-α release by Kupffer cells. miRNAs are the critical mediators of LPS signalling in Kupffer cells, hepatocytes and hepatic stellate cells. Certain miRNAs, in particular miR-155 and miR-21, show a positive correlation in up-regulation of LPS signalling when they are exposed to ethanol. ALD is related to enhanced gut permeability that allows the levels of LPS to increase, leads to increased secretion of TNF-α by the Kupffer cells and subsequently promotes alcoholic liver injury through specific miRNAs. Meanwhile, two of the most frequently dysregulated miRNAs in steatohepatitis, miR-122 and miR-34a are the critical mediators in ethanol/LPS activated survival signalling during ALD. In this review, we summarize recent findings regarding the experimental and clinical aspects of functions of specific microRNAs, focusing mainly on inflammation and cell survival after ethanol/LPS treatment, and advances on the role of circulating miRNAs in human alcoholic disorders.

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Records of 100 consecutive hospitalized cancer patients referred for psychiatric consultation were reviewed. These patients constituted only 5% of those seen by the Psychiatry Consultation Service during the study period. Fifty-six percent of the referred patients were diagnosed as depressed and 40% as having organic brain disease. Twenty-six of the 100 patients were misdiagnosed by the referring physician as depressed but were classified by the staff psychiatrist as suffering from organic brain syndrome. When referral was studied by primary site of cancer, only patients with breast cancer were referred at a significantly higher than expected rate (p less than .001). The importance of the mental status examination as a routine procedure in all cancer patients is stressed so that an organic brain syndrome will not be missed. Suggestions for patient management are given.

Cellular senescence is a state of irreversible cell cycle arrest that has been involved in many gastrointestinal diseases, including human cholestatic liver disorders. Senescence may play a role in biliary atresia, primary sclerosing cholangitis, cellular rejection, and primary biliary cirrhosis, four liver diseases affecting cholangiocytes and the biliary system. In this review, we examine proposed mechanisms of senescence-related biliary diseases, including hypotheses associated with the senescence-associated phenotype, induction of senescence in nearby cells, and the depletion of stem cell subpopulations. Current evidence for the molecular mechanisms of senescence in the previously mentioned diseases is discussed in detail, with attention to recent advances on the role of pathways associated with senescence-associated phenotype, stress-induced senescence, telomere dysfunction, and autophagy.

Multiple coagulation studies were carried out in eight healthy young men at sea level (SL) and after 1, 24, and 48 h at a simulated altitude of 4,400 m. Platelet aggregation, as induced by ADP, epinephrine, and collagen, was not significantly altered by high-altitude (HA) exposure. Mean 2,3-diphosphoglycerate, a physiological inhibitor of platelet aggregation, rose (P less than 0.001) after 24 h at HA and remained elevated while no changes in circulating catecholamines were observed. Platelet count, factor 3 availability, and membrane lipid peroxide formation were likewise unaltered at HA, as were prothrombin and thrombin times and protamine paracoagulation test. However, mean partial thromboplastin time was significantly shortened (P less than 0.01) after 1 and 24 h at HA, recovering to SL control by 48 h. Fibrinogen and factor VIII levels also fell (P less than 0.01 and P less than 0.02) after 1 h at HA but returned to the preexposure values by 24 h. Fibrin degradation products were transiently detectable in three subjects at HA. Thus, although normal platelet function did not appear to be modified by short-term exposure to simulated high altitude, evidence for a coagulopathy was obtained.

Optical biosensing based on fluorescence detection has arguably become the standard technique for quantifying extents of hybridization between surface-immobilized probes and fluorophore-labeled analyte targets in DNA microarrays. However, electrochemical detection techniques are emerging which could eliminate the need for physically bulky optical instrumentation, enabling the design of portable devices for point-of-care applications. Unlike fluorescence detection, which can function well using a passive substrate (one without integrated electronics), multiplexed electrochemical detection requires an electronically-active substrate to analyze each array site and benefits from the addition of integrated electronic instrumentation to further reduce platform size and eliminate the electromagnetic interference that can result from bringing non-amplified signals off chip. We report on an active electrochemical biosensor array, constructed with a standard complementary metaloxide-semiconductor (CMOS) technology, to perform quantitative DNA hybridization detection on chip using targets conjugated with ferrocene redox labels. A 4×4 array of gold working electrodes and integrated potentiostat electronics, consisting of control amplifiers and current-input analog-todigital converters, on a custom-designed 5×3 mm 2 CMOS chip drive redox reactions using cyclic voltammetry, sense DNA binding, and transmit digital data off chip for analysis. We demonstrate multiplexed and specific detection of DNA targets as well as real-time monitoring of hybridization, a task that is difficult, if not impossible, with traditional fluorescence-based microarrays.