High throughput fabrication of plasmonic nanostructures in nanofluidic pores for biosensing applications.

One of the primary advantages of nanoscale sensors is that they often can provide conceptually new ways of performing sensing that are not feasible with their large-scale analogs. For example, the small size of nanoscale sensor elements, such as plasmonic metal nanoparticles, allows them to be combined with nanofluidic systems. Among the potential applications of such a combination is the efficient delivery of analyte to the sensor surface. With this in mind, in this work we look to address the challenge of creating and positioning nanoplasmonic sensor elements within nanofluidic pores. A scheme is presented that allows for the production of arrays of pores in a thin (220 nm) silicon nitride membrane with one plasmonic nanoparticle sensor element in each pore. The high throughput fabrication protocol is parallel and enables multiple sensor chips to be produced simultaneously, yet with accurate tuning of the dimension and shape of the nanoparticles. The presented system is shown to possess polarization-sensitive plasmonic resonances that can be tuned significantly in the visible wavelength range by just varying one process parameter. The thickness of the membrane could be optimized to minimize the influence of the optical membrane interference on the plasmonic readout. The sensitivity of the plasmon resonances to changes in refractive index, which forms the basis for using the system for biosensing, was found to be competitive with other nanoplasmonic sensors.

Pegylated interferon α plus ribavirin for the treatment of chronic hepatitis C: a multicentre independent study supported by the Italian Drug Agency.

BACKGROUND: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in "real world" chronic hepatitis C patients in Italy. METHODS: Independent observational multicentre study including consecutive patients receiving Peg-interferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. RESULTS: 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase: 325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) during the prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%). During multivariate analysis genotypes 2/3 were significantly associated with higher sustained virological response rates; cirrhosis and γ-glutamil-transpeptidase >2 times the normal limit were associated with poorer response. CONCLUSIONS: The response to Peg-interferon/ribavirin therapy in "real world" clinical practice is distinctly lower than in registration trials. The difference in response rates was more pronounced among easy-to-treat than among difficult-to-treat hepatitis C virus genotypes.

Recommendations for the management of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients.

OBJECTIVE: The objective of this review was to define a core set of recommendations for the treatment of HCV-associated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. METHODS: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. RESULTS: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigen-content diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. CONCLUSION: Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.