A 24-week treatment strategy with pegylated interferon/ribavirin in HIV/hepatitis C virus genotype 3-coinfected patients who achieved a rapid virologic response results in a high sustained virologic response rate.

We designed a study to evaluate the efficacy of a 24-week treatment strategy in HIV/hepatitis C virus (HCV) genotype 3-coinfected patients achieving rapid virologic response for a first HCV treatment with pegylated interferon plus ribavirin (peg-IFN/RBV). Our results suggest that a shorter course of peg-IFN/RBV therapy may be sufficient in this population.

Benefits from sustained virologic response to pegylated interferon plus ribavirin in HIV/hepatitis C virus-coinfected patients with compensated cirrhosis.

BACKGROUND: The objective of this study was to determine the impact of sustained virologic response (SVR) to pegylated interferon (peg-IFN) plus ribavirin (RBV) on the incidence of liver-related complications and overall mortality in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS: We included in this prospective cohort study 166 coinfected patients with compensated cirrhosis, who received peg-IFN plus RBV, to assess the time from the starting date of HCV therapy to the first hepatic decompensation and death due to any cause. RESULTS: SVR was observed in 43 (25%) individuals. Two (4.6%) patients with SVR developed liver decompensation vs 33 (26.8%) individuals without SVR (P = .002). The incidence of liver-related complications was 0.89 cases per 100 person-years (95% confidence interval [CI], .11-3.1) in SVR patients and 6.4 cases per 100 person-years (95% CI, 4.5-8.9) in non-SVR patients. Factors independently associated with liver decompensation were non-SVR (hazard ratio [HR], 8.1; 95% CI, 1.08-61.5; P = .042) and MELD score ≥9 at baseline (HR, 2.9; 95% CI, 1.2-7.2; P = .016). Two (4.6%) patients with SVR died due to any cause compared with 22 (17.9%) individuals without SVR (P = .02). MELD score ≥9 (HR, 3.1; 95% CI, 1.3-7.7; P = .011) and non-SVR (HR, 8.0; 95% CI, 1.07-61; P = .043) were independently associated with overall mortality. CONCLUSIONS: The achievement of SVR following peg-IFN plus RBV markedly reduces the incidence of liver-related decompensation and the overall mortality in HIV/HCV-coinfected patients with compensated cirrhosis.

Ultrahigh-throughput screening in drop-based microfluidics for directed evolution.

The explosive growth in our knowledge of genomes, proteomes, and metabolomes is driving ever-increasing fundamental understanding of the biochemistry of life, enabling qualitatively new studies of complex biological systems and their evolution. This knowledge also drives modern biotechnologies, such as molecular engineering and synthetic biology, which have enormous potential to address urgent problems, including developing potent new drugs and providing environmentally friendly energy. Many of these studies, however, are ultimately limited by their need for even-higher-throughput measurements of biochemical reactions. We present a general ultrahigh-throughput screening platform using drop-based microfluidics that overcomes these limitations and revolutionizes both the scale and speed of screening. We use aqueous drops dispersed in oil as picoliter-volume reaction vessels and screen them at rates of thousands per second. To demonstrate its power, we apply the system to directed evolution, identifying new mutants of the enzyme horseradish peroxidase exhibiting catalytic rates more than 10 times faster than their parent, which is already a very efficient enzyme. We exploit the ultrahigh throughput to use an initial purifying selection that removes inactive mutants; we identify approximately 100 variants comparable in activity to the parent from an initial population of approximately 10(7). After a second generation of mutagenesis and high-stringency screening, we identify several significantly improved mutants, some approaching diffusion-limited efficiency. In total, we screen approximately 10(8) individual enzyme reactions in only 10 h, using < 150 microL of total reagent volume; compared to state-of-the-art robotic screening systems, we perform the entire assay with a 1,000-fold increase in speed and a 1-million-fold reduction in cost.

Bile reflux and marginal ulcers after one-anastomosis gastric bypass (OAGB). A narrative review.

One-anastomosis gastric bypass has now become the third most commonly performed bariatric technique worldwide. However, as a consequence of the configuration of this surgery, it can present some chronic complications (anastomotic mouth ulcers and biliary reflux) that physicians must come to better understand and assess. In this narrative review, we aimed to update our knowledge of both the diagnosis and treatment of these two complications in the context of bariatric surgeries. We concluded that a series of pre-, intra-, and postoperative preventive strategies should be considered by surgeons to help reduce the appearance of these complications.

Response to pegylated interferon plus ribavirin among HIV/hepatitis C virus-coinfected patients with compensated liver cirrhosis.

BACKGROUND: The objective of this study was to determine the efficacy of pegylated interferon (peg-IFN) plus ribavirin (RBV) in human immunodeficiency virus (HIV)-infected patients with hepatitis C virus (HCV)-related compensated liver cirrhosis, as well as the predictors of response in these individuals. METHODS: All subjects enrolled in a prospective cohort of 841 HIV/HCV-coinfected patients who received peg-IFN and RBV and who had a liver biopsy or a liver stiffness measurement within the year before starting peg-IFN plus RBV were included in this study. The sustained virologic response (SVR) rate and predictors of SVR response were analyzed. RESULTS: A total of 629 patients were included in this study; 175 (28%) had cirrhosis. In an intention-to-treat analysis, 44 (25%) patients with cirrhosis and 177 (39%) without cirrhosis achieved SVR (P = .001). Among patients with cirrhosis, SVR was observed in 14%, 47%, and 30% of individuals with HCV genotypes 1, 2-3, and 4, respectively. Discontinuation of therapy owing to adverse events was observed in 30 (17%) individuals with cirrhosis and 37 (8%) subjects without cirrhosis (P = .001). CONCLUSIONS: The efficacy of peg-IFN plus RBV among HIV/HCV-coinfected patients with cirrhosis is lower than in those without cirrhosis, although this antiviral combination still leads to a substantial rate of SVR in those carrying HCV genotype 3. A higher rate of discontinuations of HCV therapy due to adverse events among cirrhotic patients could partially explain the differences in the SVR rate between both populations.

Confined assembly of asymmetric block-copolymer nanofibers via multiaxial jet electrospinning.

Multiaxial (triaxial/coaxial) electrospinning is utilized to fabricate block copolymer (poly(styrene-b-isoprene), PS-b-PI) nanofibers covered with a silica shell. The thermally stable silica shell allows post-fabrication annealing of the fibers to obtain equilibrium self-assembly. For the case of coaxial nanofibers, block copolymers with different isoprene volume fractions are studied to understand the effect of physical confinement and interfacial interaction on self-assembled structures. Various confined assemblies such as co-existing cylinders and concentric lamellar rings are obtained with the styrene domain next to the silica shell. This confined assembly is then utilized as a template to guide the placement of functional nanoparticles such as magnetite selectively into the PI domain in self-assembled nanofibers. To further investigate the effect of interfacial interaction and frustration due to the physically confined environment, triaxial configuration is used where the middle layer of the self-assembling material is sandwiched between the innermost and outermost silica layers. The results reveal that confined block-copolymer assembly is significantly altered by the presence and interaction with both inner and outer silica layers. When nanoparticles are incorporated into PS-b-PI and placed as the middle layer, the PI phase with magnetite nanoparticles migrates next to the silica layers. The migration of the PI phase to the silica layers is also observed for the blend of PS and PS-b-PI as the middle layer. These materials not only provide a platform to further study the effect of confinement and wall interactions on self-assembly but can also help develop an approach to fabricate multilayered, multistructured nanofibers for high-end applications such as drug delivery.

Phosphine polymerization by nitric oxide: experimental characterization and theoretical predictions of mechanism.

A yellow solid material [P(x)H(y)] has been obtained in the reaction of phosphine (PH(3)) and nitric oxide (NO) at room temperature and characterized by thermogravimetric analysis mass spectrometry (TGA-MS) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. In this work using complete basis set (CBS-QB3) methods a plausible mechanism has been investigated for phosphine polymerization in the presence of nitric oxide (NO). Theoretical explorations with the ab initio method suggest (a) instead of the monomer the nitric oxide dimer acts as an initial oxidant, (b) the resulting phosphine oxides (H(3)P=O <--> H(3)P(+)O(-)) in the gas phase draw each other via strong dipolar interactions between the P-O groups, and (c) consequently an autocatalyzed polymerization occurs among the phosphine oxides, forming P-P chemical bonds and losing water. The possible structures of polyhydride phosphorus polymer were discussed. In the calculations a series of cluster models was computed to simulate polymerization.

Photoreactive coating for high-contrast spatial patterning of microfluidic device wettability.

For many applications in microfluidics, the wettability of the devices must be spatially controlled. We introduce a photoreactive sol-gel coating that enables high-contrast spatial patterning of microfluidic device wettability.

Controlling nanoparticle location via confined assembly in electrospun block copolymer nanofibers.

Coaxial nanofibers with poly(styrene-block-isoprene) (PS-b-PI)/magnetite nanoparticles as core and silica as shell are fabricated using electrospinning.1-4 Thermally stable silica helps to anneal the fibers above the glass transition temperature of PS-b-PI and form ordered nanocomposite morphologies. Monodisperse magnetite nanoparticles (NPs; 4 nm) are synthesized and surface coated with oleic acid to provide marginal selectivity towards an isoprene domain. When 4 wt% nanoparticles are added to symmetric PS-b-PI, transmission electron microscopy (TEM) images of microtomed electrospun fibers reveal that NPs are uniformly dispersed only in the PI domain, and that the confined lamellar assembly in the form of alternate concentric rings of PS and PI is preserved. For 10 wt% NPs, a morphology transition is seen from concentric rings to a co-continuous phase with NPs again uniformly dispersed in the PI domains. No aggregates or loss of PI selectivity is found in spite of interparticle attraction. Magnetic properties are measured using a superconducting quantum interference device (SQUID) magnetometer and all nanocomposite fiber samples exhibit superparamagnetic behavior.

Ion-specific and reversible wetting of imidazolium-based minigels.

Cross-linked imidazolium-based [poly(ViEtIm +Br -)] microparticles were synthesized, and their wetting properties were studied by optical microscopy, after addition of aqueous solutions of sodium halides. Particle wetting showed ion specificity due to counterion binding, described by Desnoyer's model. The interaction between anions and the microparticles allowed exchanging halogenides between them in a reversible way. A salt-independent characteristic wetting time was found as well as a decreasing power law with salt concentration, for the network diffusion coefficient. It modified the polymer network elasticity as ion concentration increased, making the network softer.

Poly(methyl methacrylate)s with pendant calixpyrroles: polymeric extractants for halide anion salts.

Poly(methyl methacrylate)s containing pendant octamethylcalix[4]pyrrole subunits were prepared and demonstrated to be capable of extracting tetrabutylammonium chloride and fluoride salts from aqueous media.

Swelling kinetics of poly(N-isopropylacrylamide) minigels.

We synthesize poly(N-isopropylacrylamide) (PNIPAM) gels with different sizes in the micrometer scale by a slight variation of a recent emulsion polymerization method (ref 1). The procedure is different than that typically used for obtaining macroscopic PNIPAM hydrogels. The resultant minigel suspension is polydisperse thus allowing the swelling kinetics for different gel sizes to be studied; we do so at temperatures below the volume-transition temperature by wetting with water previously dried particles. The resultant swelling is followed by optical video microscopy. We find that the characteristic swelling time scales with the inverse of the particle dimension squared, in agreement with theoretical predictions (ref 2). The proportionality constant is the network diffusion coefficient D, which for the minigels under consideration appears to be in between that of PNIPAM macrogels and the self-diffusion coefficient of water.

Scalable liquid shear-driven fabrication of polymer nanofibers.

A simple process for batch or continuous formation of polymer nanofibers and other nanomaterials in the bulk of a sheared fluid medium is introduced. The process may be of high value to commercial nanotechnology, as it can be easily scaled up to the fabrication of staple nanofibers at rates that may exceed tens of kilograms per hour.

Impact of IL28B genotype on first-week response to telaprevir-based therapy in HIV-HCV coinfection.

BACKGROUND: IL28B genotype predicts response to treatment against HCV with pegylated interferon/ribavirin (PR) and impacts on the outcome of therapy including telaprevir (TVR). This study aimed to determine the influence of the favourable IL28B genotype on early viral kinetics during therapy with TVR/PR in HIV-HCV-coinfected patients. METHODS: All HIV-HCV genotype 1 coinfected subjects who received TVR/PR for at least 4 weeks were included from populations prospectively followed in 22 centres throughout Germany, Switzerland and Spain. RESULTS: Of the 129 subjects included, 38 (29.5%) presented with IL28B genotype CC and 94 (72.9%) were treatment-experienced. A total of 96 (73.8%) patients showed undetectable plasma HCV RNA at treatment week (W)4: 30 (78.9%) of the IL28B-CC carriers and 65 (71.4%) of the non-CC carriers (P=0.377). Among treatment-naive patients, proportions of undetectable HCV RNA among IL28B-CC versus non-CC carriers were 8/9 (88.9%) versus 3/9 (33.3%; P=0.016) and 14/17 (82.4%) versus 11/18 (61.1%; P=0.164) at W2 and W4. The decrease of HCV RNA at W2 and W4 was similar among the IL28B carriers. CONCLUSIONS: IL28B genotype does not predict W4 response to TVR/PR in HIV-HCV-coinfected patients, regardless of their treatment history. However, there is evidence of an impact on response during the first weeks in treatment-naive patients.

Hepatitis C virus genotype 4 responds better to pegylated interferon with ribavirin than genotype 1 in HIV-infected patients.

We assess the efficacy of pegylated interferon (peg-IFN) with ribavirin (RBV) and the predictors of sustained virological response (SVR) among HIV/hepatitis C virus genotype 4 (HCV-4)-coinfected patients. Thirty-nine (31.5%) of 124 individuals with HCV-4 achieved SVR compared with 103 (22.7%) of 453 individuals with HCV genotype 1 (P=0.046). Only interleukin-28B (IL28B) genotype CC was independently associated with SVR in HIV/HCV-4-coinfected patients. The efficacy of peg-IFN with RBV in coinfected individuals with genotype 4 is significantly higher than in those with genotype 1. IL28B CC genotype is the main predictor of response in this population.

Target-wave to spiral-wave pattern transition in a discrete Belousov-Zhabotinsky reaction driven by inactive resin beads.

Wave pattern formation and transition in chemical and biochemical reaction systems can reveal the system properties. We investigate the pattern transition from target waves to spiral waves upon the increment of inactive beads in a discrete system model, where ion-exchange resin loaded with Belousov-Zhabotinsky catalyst corresponds to the active beads. The results show that inactive beads slow the propagation speed of target waves and increase the wave frequency. As the population of inactive beads increases, clusters are formed, which then break waves into segments where bounded spiral pairs are generated and separated into individual spirals. From this observation, we conclude that the population of inactive resin beads acts as the bifurcation parameter controlling the wave pattern transition from targets to spirals.

Microwave, photo- and thermally responsive PNIPAm-gold nanoparticle microgels.

Microwave-, photo- and thermo-responsive polymer microgels that range in size from 500 to 800 microm and are swollen with water were prepared by a novel microarray technique. We used a liquid-liquid dispersion technique in a system of three immiscible liquids to prepare hybrid PNIPAm- co-AM core-shell capsules loaded with AuNPs. The spontaneous encapsulation is a result of the formation of double oil-in-water-in-oil (o/w/o) emulsion. It is facilitated by adjusting the balance of the interfacial tensions between the aqueous phase (in which a water-soluble drug may be dissolved), the monomer phase and the continuous phase. The water-in-oil (w/o) droplets containing 26 wt% NIPAm and Am monomers, 0.1 wt% Tween-80 surfactant, FITC fluorescent dye and colloidal gold nanoparticles spontaneously developed a core-shell morphology that was fixed by in situ photopolymerization. The results demonstrate new reversibly swelling and deswelling AuNP/PNIPAm hybrid core-shell microcapsules and microgels that can be actuated by visible light and/or microwave radiation (

Monodisperse thermoresponsive microgels of poly(ethylene glycol) analogue-based biopolymers.

Monodisperse microgels of P(MEO2MA-co-OEGMA) have been synthesized by using free radical polymerization. Microgels with a variety of particle radii ranging from 82 to 412 nm have been obtained with different surfactant concentrations. The particle size distribution is extremely narrow and even better than that for PNIPAM microgels. Pure MEO2MA microgels have an LCST of about 22 degrees C. The LCSTs corresponding to the molar ratio of OEGMA to MEO2MA at 10 and 20% are 31 and 37 degrees C, respectively. Microgels in water self-assemble into various phases, including a crystalline phase with iridescent colors, which are the result of Bragg diffraction from differently oriented crystalline planes. Considering that PEG is nontoxic and anti-immunogenic as proven by the FDA, thermoresponsive P(MEO2MA-co-OEGMA) microgels may have many exciting biomedical applications.

Nucleation rate measurement of colloidal crystallization using microfluidic emulsion droplets.

An emulsion crystallization method has been demonstrated to measure the nucleation rate of a thermoresponsive colloidal poly-N-isopropylacrylamide (PNIPAM) system. The colloidal PNIPAM suspension was injected into a microfluidic flow-focusing device to generate monodispersed droplets in oil. The temperature was controlled to fine tune the volume fraction of the PNIPAM particles, and the microfluidic flow rate was varied to change the droplet sizes, thus altering the nucleation volume. Using independent droplets, we can isolate the nucleation events to eliminate the interactions among crystallites that existed in bulk or large droplet systems. Therefore, we were able to carry out accurate nucleation rate measurements of colloidal crystals. This emulsion crystallization method is promising for bridging the gap among theories, simulations, and experiments for nucleation kinetics studies.