Biliary Dyskinesia: Fact or fiction?

Nearly 20,000 pediatric patients undergo cholecystectomy annually, and abnormal gallbladder emptying ("biliary dyskinesia") has replaced cholelithiasis as the leading indication for this operation in the USA. Nonetheless, patients with abnormal gallbladder emptying nuclear medicine scans do not uniformly benefit from cholecystectomy. This article reviews the available data on presentation, workup and treatment of patients with abnormally low and high rates of gallbladder emptying.

Kinetic Rate Constants of Gold Nanoparticle Deposition on Silicon.

We fabricated gold nanoparticles on nanoporous silicon microparticles using electroless deposition in a hydrofluoric acid solution containing gold chloride. The reaction was followed by UV spectrometer analysis of the absorbance of the solution (proportional to the nanoparticle concentration) for two temperatures (20 and 50 °C). The results indicate that the process is autocatalytic, described by a pseudo-first-order reaction, the apparent rate constant kobs of which was determined by utilizing UV spectrometer data. We found that the reaction rate constant at 20 °C is 7 × 10-3 s-1 and that at 50 °C is 2.9 × 10-2 s-1. Scanning electron microscope (SEM) analysis of samples and diffusion-limited aggregation (DLA) simulations were used to validate the results. This study aims to resolve the kinetics of the electroless deposition of gold on silicon at the nanoscale, in the present state of art missing a quantitative characterization, for certain conditions of growth and given values of temperature and concentration of the reagents. Results may have applications to the synthesis of gold nanoparticles and their use as nanosensors, drug delivery systems, or metal nanometamaterials with advanced optical properties.

Relating the rate of growth of metal nanoparticles to cluster size distribution in electroless deposition.

Electroless deposition on patterned silicon substrates enables the formation of metal nanomaterials with tight control over their size and shape. In the technique, metal ions are transported by diffusion from a solution to the active sites of an autocatalytic substrate where they are reduced as metals upon contact. Here, using diffusion limited aggregation models and numerical simulations, we derived relationships that correlate the cluster size distribution to the total mass of deposited particles. We found that the ratio ξ between the rates of growth of two different metals depends on the ratio γ between the rates of growth of clusters formed by those metals through the linearity law ξ = 14(γ - 1). We then validated the model using experiments. Different from other methods, the model derives k using as input the geometry of metal nanoparticle clusters, decoded by SEM or AFM images of samples, and a known reference.

Superhydrophobic lab-on-chip measures secretome protonation state and provides a personalized risk assessment of sporadic tumour.

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual's diagnosis and/or help clarify risk in healthy populations.

Silica diatom shells tailored with Au nanoparticles enable sensitive analysis of molecules for biological, safety and environment applications.

Diatom shells are a natural, theoretically unlimited material composed of silicon dioxide, with regular patterns of pores penetrating through their surface. For their characteristics, diatom shells show promise to be used as low cost, highly efficient drug carriers, sensor devices or other micro-devices. Here, we demonstrate diatom shells functionalized with gold nanoparticles for the harvesting and detection of biological analytes (bovine serum albumin-BSA) and chemical pollutants (mineral oil) in low abundance ranges, for applications in bioengineering, medicine, safety, and pollution monitoring.

Nano-topography Enhances Communication in Neural Cells Networks.

Neural cells are the smallest building blocks of the central and peripheral nervous systems. Information in neural networks and cell-substrate interactions have been heretofore studied separately. Understanding whether surface nano-topography can direct nerve cells assembly into computational efficient networks may provide new tools and criteria for tissue engineering and regenerative medicine. In this work, we used information theory approaches and functional multi calcium imaging (fMCI) techniques to examine how information flows in neural networks cultured on surfaces with controlled topography. We found that substrate roughness S a affects networks topology. In the low nano-meter range, S a = 0-30 nm, information increases with S a . Moreover, we found that energy density of a network of cells correlates to the topology of that network. This reinforces the view that information, energy and surface nano-topography are tightly inter-connected and should not be neglected when studying cell-cell interaction in neural tissue repair and regeneration.

In vitro expansion of tumour cells derived from blood and tumour tissue is useful to redefine personalized treatment in non-small cell lung cancer patients.

The clinical development of locally and advanced non-small cell lung cancer (NSCLC) suffers from a lack of biomarkers as a guide in the selection of optimal prognostic prediction. Circulating Tumour Cells (CTCs) are correlated to prognosis and show efficacy in cancer monitoring in patients. However, their enumeration alone might be inadequate; it might also be critical to understand the viability, the apoptotic state and the kinetics of these cells. Here, we report what we believe to be a new and selective approach to visually detect tumour specific CTCs. Firstly, using labelled human lung cancer cells, we detected a specific density interval in which NSCL-CTCs were concentrated. Secondly, to better characterize CTCs in respect to their heterogeneous composition and tumour reference, blood and tumour biopsy were performed on specimens taken from the same patient. The approach consisted in comparing phenotype profile of CTCs, and their progenitor Tumour Stem Cells, (TSCs). Moreover, NSCL-CTCs were cultivated in short-time human cultures to provide response to drug sensitivity. Our bimodal approach allowed to reveal two items. Firstly, that one part of a tumour, proximal to the bronchial structure, displays a predominance of CD133+. Secondly, specific NSCL-CTCs Epithelial Cell Adhesion Molecule (EpCAM)+CD29+ can be used as a negative prognostic factor as well the high expression of CTCs EpCAM+. These data were confirmed by drug-sensitivity tests, in vitro, and by the survival curves, in vivo.

Emerging fabrication techniques for 3D nano-structuring in plasmonics and single molecule studies.

The application of new methods and techniques to fields such as biology and medicine is becoming more and more demanding since the request of detailed information down to single molecules is a scientific necessity and a technical realistic possibility. In this effort a key role is played by emerging fabrication techniques. One of the hardest challenges is to incorporate the third dimension in the design and fabrication of novel devices. Significantly, this means that conventional nano-fabrication methods, intrinsically useful for planar structuring, have to be substituted or complemented with new approaches. In this paper we show how emerging techniques can be used for 3D structuring of noble metals down to nanoscale. In particular, the paper deals with electroless deposition of silver, ion and electron beam induced deposition, focused ion beam milling, and two-photon lithography. We exploited these techniques to fabricate different plasmonics nanolenses, nanoprobes and novel beads for optical tweezers. In the future these devices will be used for the manipulation and chemical investigation of single cells with sensitivity down to a few molecules in label free conditions and native environment. Although this paper is only devoted to nanofabrication, we foresee that the fields of biology and medicine will directly gain substantial advantages from this approach.

Genetic mapping of natural variation in a shade avoidance response: ELF3 is the candidate gene for a QTL in hypocotyl growth regulation.

When plants become shaded by neighbouring plants, they perceive a decrease in the red/far-red (R/FR) ratio of the light environment, which provides an early and unambiguous warning of the presence of competing vegetation. The mechanistic bases of the natural genetic variation in response to shade signals remain largely unknown. This study demonstrates that a wide range of genetic variation for hypocotyl elongation in response to an FR pulse at the end of day (EOD), a light signal that simulates natural shade, exists between Arabidopsis accessions. A quantitative trait locus (QTL) mapping analysis was done in the Bayreuth×Shahdara recombinant inbred line population. EODINDEX1 is the most significant QTL identified in response to EOD. The Shahdara alleles at EODINDEX1 caused a reduced response to shade as a consequence of an impaired hypocotyl inhibition under white light, and an accelerated leaf movement rhythm, which correlated positively with the pattern of circadian expression of clock genes such as PRR7 and PRR9. Genetic and quantitative complementation analyses demonstrated that ELF3 is the most likely candidate gene underlying natural variation at EODINDEX1. In conclusion, ELF3 is proposed as a component of the shade avoidance signalling pathway responsible for the phenotypic differences between Arabidopsis populations in relation to adaptation in a changing light environment.

Cross-linked ionomeric materials from poly(styrene-alt-maleic anhydride) and poly(ethylene glycol) for biomedical applications: a preliminary investigation.

Two ionomeric materials, cross-linked through the formation of polyoxyethylene bridges, were synthesized by the reaction of poly(styrene-alt-maleic anhydride) (PSMA) with poly(ethylene glycol) (PEG), carried out in the absence of external catalysts. The reaction was carried out at room temperature, both in bulk with excess glycol, and in acetone solution with a 20:1 ratio of anhydride rings to hydroxyl groups. The materials were characterized by scanning electron microscopy (SEM), total reflection Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The SEM showed a quite uniform porous structure for the material synthesized in bulk, and two distinct phases for that synthesized in acetone solution, a sponge-like structure and a denser one. The FTIR spectra showed that the first material underwent the cross-linking reaction to a greater extent than the second one. Both TGA and DSC confirmed the formation of cross-linked structures. Such tri-dimensional networks, owing to the presence of the carboxyl groups, could easily entrap either cationic drugs, in view of a possible controlled release, or poisonous metal cations, when they must be removed from blood. The second use can be made easier by the hemocompatibility, ascertained in preceding studies on other materials, synthesized by the reaction between maleic anhydride copolymers and hydroxyl-containing macromolecules. Another possible use is the production of ion exchanging gels, as fillers for both ion exchange and liquid chromatography columns, which could be easily regenerated.

Release of proteinic and non-proteinic compounds from novel ionizable hydrogels: Effect of pH on swelling and drug delivery behavior.

Ionizable hydrogels were prepared from new copolymers, poly(vinylalcohol-co-acrylic acid) indicated as P(VA-co-AA), by freezing-thawing processes. These materials are designed as potential controlled delivery devices with specific properties to respond to chemical environment stimuli. The swelling behavior of the P(VA-co-AA) hydrogels was evaluated in response to pH changes in release medium demonstrating a strong dependence with the environmental pH. The release of theophylline (THO) and bovine serum albumin (BSA) incorporated into the hydrogels before freezing-thawing cycles were examined by varying the pH. The release curves of the two different solutes showed a very similar trend depending on the hydrogel porosity and the medium pH. The dependence of THO and BSA release on their size and ionic nature was detected.

Transport properties of EVAl-starch-alpha amylase membranes.

We investigated the influence of various physicochemical parameters on the morphology and time-porosity formation of membranes composed of ethylene-vinyl alcohol, starch, and alpha-amylase. In particular, we determined that (1) it is possible to obtain a membrane with desired porosity by phase inversion in an appropriate water-ethanol mixture and (2) the enzymatic bioerosion is controlled by the amount of alpha-amylase present in the blend. Although no experiments involving drugs were carried out, the delivery properties of the film were determined by measuring the Darcy permeability, the effective diffusivity, and the mean reaction rate of the membranes, relating them to the modality of membrane preparation, the amount of enzyme present within the membrane, and the incubation time of the samples in a buffer solution. Simple theoretical models of the delivery properties of the membranes were developed, leading to predictions that were in good agreement with the experimental results.

Shared leadership in a newly merged medical center.

Mergers of new health care entities require visionary leadership in forming effective partnerships. Shared leadership was one key ingredient in blending two major health care competitors in the Northwest. Building a successful foundation for shared leadership required formation of a common vision, definition of core values, and establishment of guiding principles. Honoring respective cultures, recognizing achievements, and inviting participation led to the design of the shared leadership model focused on the primary objective for the merger: Enhancing health care services to the community.

Transformational partnership for delivery of R.N. baccalaureate education: a service/education leadership model.

A transformational partnership model between a consortium of rural community hospitals and a private Christian university reflects a shared vision for R.N. baccalaureate degree completion. The model includes a community-wide system to promote and sustain accessible, high-quality education for the place-bound R.N. who desires to achieve a B.S.N. Stakeholders, experiencing the current climate of change in health care, benefit from this innovative service/education leadership model. The collaboration built on a commitment to common goals and shared resources seeks to prepare individuals who apply critical thinking to practice settings along with the continuum of care.