Cardiovascular Risk Associated with Methotrexate versus Retinoids in Patients with Psoriasis: A Nationwide Taiwanese Cohort Study.

PURPOSE: Psoriasis is an inflammatory disease associated with cardiovascular disease. Methotrexate (MTX) is a first-line systemic anti-psoriatic agent that may also protect against cardiovascular disease. We examined the cardiovascular risks among patients with psoriasis who were receiving MTX or the comparator, retinoids. PATIENTS AND METHODS: We analysed data from the Taiwanese National Health Insurance database. The primary outcome was a composite of hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality (composite cardiovascular outcome). Propensity score-weighted analyses were used to evaluate patients who were followed from therapy initiation to the earliest instance of outcome occurrence, insurance disenrollment, death or study termination. RESULTS: We identified 13,777 patients who received MTX and 6020 patients who received retinoids from 2000 to 2012. Compared to retinoids, MTX was associated with lower crude incidences of cardiovascular outcomes, hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality. In intention-to-treat analyses, MTX was associated with lower risks of composite cardiovascular outcomes (adjusted hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.76-0.94), ischaemic heart disease (HR: 0.87, 95% CI: 0.71-1.06), ischaemic stroke (HR: 1.06, 95% CI: 0.89-1.27) and all-cause mortality (HR: 0.75, 95% CI: 0.66-0.85). Similar results were found in as-treated analyses. CONCLUSION: In this nationwide cohort of patients with psoriasis, compared to retinoids, MTX was associated with a modestly lower risk of cardiovascular events.

Nanowire transistor-based ultrasensitive virus detection with reversible surface functionalization.

We have applied a reusable silicon nanowire field-effect transistor (SiNW-FET) as a biosensor to conduct ultrasensitive detection of H5N2 avian influenza virus (AIV) in very dilute solution. The reversible surface functionalization of SiNW-FET was made possible using a disulfide linker. In the surface functionalization, 3-mercaptopropyltrimethoxysilane (MPTMS) was first modified on the SiNW-FET (referred to as MPTMS/SiNW-FET), with subsequent dithiothreitol washing to reduce any possible disulfide bonding between the thiol groups of MPTMS. Subsequently, receptor molecules could be immobilized on the MPTMS/SiNW-FET by the formation of a disulfide bond. The success of the reversible surface functionalization was verified with fluorescence examination and electrical measurements. A surface topograph of the SiNW-FET biosensor modified with a monoclonal antibody against H5N2 virus (referred to as mAb(H5)/SiNW-FET) after detecting approximately 10(-17) M H5N2 AIVs was scanned by atomic force microscopy to demonstrate that the SiNW-FET is capable of detecting very few H5N2 AIV particles.

Surface potential variations on a silicon nanowire transistor in biomolecular modification and detection.

Using a silicon nanowire field-effect transistor (SiNW-FET) for biomolecule detections, we selected 3-(mercaptopropyl)trimethoxysilane (MPTMS), N-[6-(biotinamido)hexyl]-3(')-(2(')-pyridyldithio) propionamide (biotin-HPDP), and avidin, respectively, as the designated linker, receptor, and target molecules as a study model, where the biotin molecules were modified on the SiNW-FET to act as a receptor for avidin. We applied high-resolution scanning Kelvin probe force microscopy (KPFM) to detect the modified/bound biomolecules by measuring the induced change of the surface potential (ΔΦ(s)) on the SiNW-FET under ambient conditions. After biotin-immobilization and avidin-binding, the ΔΦ(s) on the SiNW-FET characterized by KPFM was demonstrated to correlate to the conductance change inside the SiNW-FET acquired in aqueous solution. The ΔΦ(s) values on the SiNW-FET caused by the same biotin-immobilization and avidin-binding were also measured from drain current versus gate voltage curves (I(d)-V(g)) in both aqueous condition and dried state. For comparison, we also study the ΔΦ(s) values on a Si wafer caused by the same biotin-immobilization and avidin-binding through KPFM and ζ potential measurements. This study has demonstrated that the surface potential measurement on a SiNW-FET by KPFM can be applied as a diagnostic tool that complements the electrical detection with a SiNW-FET sensor. Although the KPFM experiments were carried out under ambient conditions, the measured surface properties of a SiNW-FET are qualitatively valid compared with those obtained by other biosensory techniques performed in liquid environment.