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Significance: The integrity of the intestinal barrier is gaining recognition as a significant contributor to various pathophysiological conditions, including inflammatory bowel disease, celiac disease, environmental enteric dysfunction (EED), and malnutrition. EED, for example, manifests as complex structural and functional changes in the small intestine leading to increased intestinal permeability, inflammation, and reduced absorption of nutrients. Despite the importance of gut function, current techniques to assess intestinal permeability (such as endoscopic biopsies or dual sugar assays) are either highly invasive, unreliable, and/or difficult to perform in certain patient populations (e.g., infants). Aim: We present a portable, optical sensor based on transcutaneous fluorescence spectroscopy to assess gut function (in particular, intestinal permeability) in a fast and noninvasive manner. Approach: Participants receive an oral dose of a fluorescent contrast agent, and a wearable fiber-optic probe detects the permeation of the contrast agent from the gut into the blood stream by measuring the fluorescence intensity noninvasively at the fingertip. We characterized the performance of our compact optical sensor by comparing it against an existing benchtop spectroscopic system. In addition, we report results from a human study in healthy volunteers investigating the impact of skin tone and contrast agent dose on transcutaneous fluorescence signals. Results: The first study with eight healthy participants showed good correlation between our compact sensor and the existing benchtop spectroscopic system [correlation coefficient ðr Þ > 0.919, p < 0.001]. Further experiments in 14 healthy participants revealed an approximately linear relationship between the ingested contrast agent dose and the collected signal intensity. Finally, a parallel study on the impact of different skin tones showed no significant differences in signal levels between participants with different skin tones (p > 0.05). Conclusions: In this paper, we demonstrate the potential of our compact transcutaneous fluorescence sensor for noninvasive monitoring of intestinal health. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive hydrogels have attracted much attention owing to the versatility of their programmed response in offering intelligent solutions for biomimicry applications, such as soft robotics, tissue engineering, and drug delivery. To achieve the complexity of biomimetic structures, two photon polymerization (2PP) has provided a means of fabricating intricate 3D structures from stimuli‐responsive hydrogels. Rapid swelling hydrogel microstructures are advantageous for osmotically driven stimuli‐response, where actuation speed, that is reliant on the diffusion of analytes or bioanalytes, can be optimized. Herein, the flexibility of 2PP is exploited to showcase a novel sugar‐responsive, phenylboronic acid‐based photoresist. This offers a remarkable solution for achieving fast response hydrogel systems that have been often hindered by the volume‐dependent diffusion times of analytes to receptor sites. A phenylboronic acid‐based photoresist compatible with 2PP is presented to fabricate stimuli‐responsive microstructures with accelerated response times. Moreover, microstructures with programmable actuation (i.e., bending and opening) are fabricated using the same photoresist within a one‐step fabrication process. By combining the flexibility of 2PP with an easily adaptable photoresist, an accessible fabrication method is showcased for sophisticated and chemo‐responsive 3D hydrogel actuators. [ABSTRACT FROM AUTHOR]

HBV RNA is used as a marker of cccDNA transcription and is applicable in the setting of nucleos(t)ide analog (NA) treatment, which suppresses HBV DNA. Traditional assays for quantification of HBV RNA rely on labor‐intensive 3′RACE assays targeting the polyA tail. In this study, the high‐throughput Roche cobas®HBV RNA investigational assay was assessed on the Roche cobas® 6800 automated platform. Of 969 samples collected for a NA treatment cessation trial, and tested on the cobas assay, 249 were analyzed for sensitivity, reproducibility, sample type applicability, and results were compared to a RACE‐based assay. Results of 97 paired serum and plasma samples demonstrated an excellent correlation of 0.98. However, 14.5% of plasma samples yielded detectable (below the limit of quantification) results, when the paired serum was undetectable, and plasma was shown to yield a statistically significant (p < 0.001) greater mean 0.119 log10copies/ml. Quantification of 152 samples showed good correlation (0.91) between the cobas and RACE assays. The cobas assay demonstrated superior lower limit of quantification, 10 copies/ml, which resulted in detection of 13.2% more samples than the RACE assay. Reproducibility and linear range of the automated assay were also confirmed. The Roche cobas assay for HBV RNA is sensitive and highly recommended. [ABSTRACT FROM AUTHOR]

Microfluidic artificial lungs (μALs) are being investigated for their ability to closely mimic the size scale and cellular environment of natural lungs. Researchers have developed μALs with small artificial capillary diameters (10–50 µm; to increase gas exchange efficiency) and with large capillary diameters (~100 µm; to simplify design and construction). However, no study has directly investigated the impact of capillary height on μAL properties. Here, we use Murray's law and the Hagen-Poiseuille equation to design single-layer, small-scale μALs with capillary heights between 10 and 100 µm. Each µAL contained two blood channel types: capillaries for gas exchange; and distribution channels for delivering blood to/from capillaries. Three designs with capillary heights of 30, 60, and 100 µm were chosen for further modeling, implementation and testing with blood. Flow simulations were used to validate and ensure equal pressures. Designs were fabricated using soft lithography. Gas exchange and pressure drop were tested using whole bovine blood. All three designs exhibited similar pressure drops and gas exchange; however, the μAL with 60 µm tall capillaries had a significantly higher wall shear rate (although physiologic), smaller priming volume and smaller total blood contacting surface area than the 30 and 100 µm designs. Future μAL designs may need to consider the impact of capillary height when optimizing performance. [ABSTRACT FROM AUTHOR]

Tumour hypoxia is the inevitable consequence of a tumour's rapid growth and disorganized, inefficient vasculature. The compensatory mechanisms employed by tumours, and indeed the absence of oxygen itself, hinder the ability of all treatment modalities. The clinical consequence is poorer overall survival, disease-free survival, and locoregional control. Recognizing this, clinicians have been attenuating the effect of hypoxia, primarily with hypoxic modification or with hypoxia-activated pro-drugs, and notable success has been demonstrated. However, in the case of colorectal cancer (CRC), there is a general paucity of knowledge and evidence surrounding the measurement and modification of hypoxia, and this is possibly due to the comparative inaccessibility of such tumours. We specifically review the role of hypoxia in CRC and focus on the current evidence for the existence of hypoxia in CRC, the majority of which originates from indirect positron emission topography imaging with hypoxia selective radiotracers; the evidence correlating CRC hypoxia with poorer oncological outcome, which is largely based on the measurement of hypoxia inducible factor in correlation with clinical outcome; the evidence of hypoxic modification in CRC, of which no direct evidence exists, but is reflected in a number of indirect markers; the prognostic and monitoring implications of accurate CRC hypoxia quantification and its potential in the field of precision oncology; and the present and future imaging tools and technologies being developed for the measurement of CRC hypoxia, including the use of blood-oxygen-level-dependent magnetic resonance imaging and diffuse reflectance spectroscopy. [ABSTRACT FROM AUTHOR]

A dual-flow continuous culture system was used to evaluate the effects of laidlomycin propionate and bacitracin zinc on fermentation, nutrient digestibility, and microbial efficiency. Factors were laidlomycin propionate (LP; 2 mg/L of culture volume) and bacitracin zinc (BAC; 1.4 mg/L), and treatments were as follows: (1) no BAC or LP (CON), (2) LP without BAC (LP), (3) BAC without LP (BAC), and (4) LP and BAC (LP/BAC). A fifth treatment was supplemented with monensin sodium (MON; 6 mg/L) to act as a positive control. Both LP and LP/BAC had significantly greater pH than MON (P < 0.05). Antibiotic treatment did not affect NH 3-N concentration (P = 0.62), but did influence total VFA production (P = 0.02). Monensin fermenters had a greater proportion of total VFA than did LP fermenters (P < 0.05), and improved VFA production by 7.2% compared to CON. Laidlomycin suppressed the production of both acetate (P < 0.01) and butyrate (P = 0.05), and acetate was further reduced when LP was fed in combination with BAC (P = 0.01). Laidlomycin numerically reduced the acetate:propionate ratio (P = 0.12). These results suggest that bacitracin may produce ionophore-like effects on pH and VFA production in vitro. [ABSTRACT FROM AUTHOR]

Myocardial strain offers new insights into ventricular performance, There are software packages from several different companies used to ascertain this, and little data is available in patients with single right ventricle (sRV) physiology. We aimed to compare the analysis of two strain software applications using a cohort of patients with sRV for both inter-vendor and inter-observer variability. Echocardiograms from 85 patients with sRV (122 separate studies) were prospectively evaluated. All had Glenn and/or Fontan palliation. Longitudinal 4-chamber (4LS), inflow/outflow (IO), circumferential, and radial strain were assessed using Velocity Vector Imaging (VVI, Seimens, Munich) and Automated Functional Imaging (AFI, General Electric, Boston) software. In a subset of 45 patients (61 separate studies), strain measurements were obtained by two sonographers so a paired "inter-observer" analysis could be performed. A moderate correlation between measurements made by the two systems was observed. Circumferential strain assessment had the highest R value (0.77) with all others having R values < 0.6. Both software packages showed modest inter-observer reproducibility for longitudinal and circumferential strain. VVI intraclass correlation coefficients (ICC) for 4LS and average circumferential strain (ACS) were 0.6 and 0.58, compared to 0.68 and 0.59 for AFI. Other than radial strain and VVI IO inferior strain, mean strain differences between AFI and VVI were ≤ 1%. Inter-observer variability is modest, however, mean differences are minimal suggesting reasonable clinical reliability. Inter-vendor variability is greater and not as clinically reliable. In patients with sRV, serial assessments with strain should be performed using the same software. [ABSTRACT FROM AUTHOR]

Urinary tract infection is one of the most common bacterial infections leading to increased morbidity, mortality and societal costs. Current diagnostics exacerbate this problem due to an inability to provide timely pathogen identification. Surface enhanced Raman spectroscopy (SERS) has the potential to overcome these issues by providing immediate bacterial classification. To date, achieving accurate classification has required technically complicated processes to capture pathogens, which has precluded the integration of SERS into rapid diagnostics. This work demonstrates that gold-coated membrane filters capture and aggregate bacteria, separating them from urine, while also providing Raman signal enhancement. An optimal gold coating thickness of 50 nm was demonstrated, and the diagnostic performance of the SERS-active filters was assessed using phantom urine infection samples at clinically relevant concentrations (105 CFU/ml). Infected and uninfected (control) samples were identified with an accuracy of 91.1%. Amongst infected samples only, classification of three bacteria (Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae) was achieved at a rate of 91.6%. [ABSTRACT FROM AUTHOR]

Background and Objectives: Pre-donation screening of potential blood donors is critical for ensuring the safety of the donor blood supply, and donor deferral as a result of risk factors is practised worldwide. This systematic review was conducted in the context of an expert review convened by the Australian Red Cross Lifeblood in 2013 to consider Lifeblood's injecting drug use (IDU)-related policies and aimed to identify studies assessing interventions to improve compliance with deferral criteria in blood donation settings. Materials and Methods: MEDLINE/PubMed, OVID Medline, OVID Embase, LILACS, and the Cochrane Library (CENTRAL and DARE) databases were searched for studies conducted within blood donation settings that examined interventions to increase blood donor compliance with deferral criteria. Observational and experimental studies from all geographical areas were considered. Results: Ten studies were identified that tested at least one intervention to improve blood donor compliance with deferral criteria, including computerized interviews or questionnaires, direct and indirect oral questioning, educational materials, and a combination of a tickbox questionnaire and a personal donor interview. High-quality evidence from a single study was provided for the effectiveness of a computerized interview in improving detection of HIV risk behaviour. Low-quality evidence for the effectiveness of computerized interviews was provided by 3 additional studies. Two studies reported a moderate effect of direct questioning in increasing donor deferral, but the quality of the evidence was low. Conclusion: This review identified several interventions to improve donor compliance that have been tested in blood donation settings and provided evidence for the effectiveness of computerized interviews in improving detection of risk factors. [ABSTRACT FROM AUTHOR]

Increased bacterial translocation (BT) across the gut barrier due to greater intestinal permeability (IP) is seen across a range of conditions, including alcohol-related liver disease (ArLD). The phenomenon of BT may contribute to both the pathogenesis and the development of complications in ArLD. There are a number of methods available to assess IP and in this review we look at their various advantages and limitations. The knowledge around BT and IP in ArLD is also reviewed, as well as the therapeutic strategies currently in use and in development. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of increasing concentrations of Cr propionate (CrP) on feedlot performance, blood parameters, carcass characteristics, and skeletal muscle fiber properties in feedlot steers. Crossbred steers (n = 32; 367 ± 2.5 kg; 16 pens; 2 hd/pen) were blocked by body weight (BW), and treatment was randomly assigned to pen: (1) 0 mg added Cr/kg diet dry matter (DM) (control), (2) 0.15 mg added Cr/kg diet DM (CrP; KemTRACE Chromium 0.04%, Kemin Industries, Des Moines, IA), (3) 0.30 mg added Cr/kg diet DM, and (4) 0.45 mg added Cr/kg diet DM. Steers were fed ad libitum, and the treatment was top-dressed at the time of feeding. Body weights, blood samples, and longissimus biopsies were collected before feeding on days 0, 28, 56, 91, 119, and 147. Blood sera were harvested for analysis of glucose, insulin, sera urea nitrogen, and non-esterified fatty acid concentrations. Longissimus biopsies were collected for gene expression, protein expression, and immunohistochemical (IHC) analysis. Pen was the experimental unit for live and carcass data, and steer was the experimental unit with day as a repeated measure for sera and IHC analyses. For the entire duration of the trial, a linear increase in average daily gain (ADG) (P = 0.01) and improvement in G:F was observed (P = 0.01) with no change in DMI (P = 0.11) with increasing CrP. A linear increase in hot carcass weight (HCW) (P ≤ 0.01) with no other changes in carcass composition were noted (P ≥ 0.38) as the level of dietary CrP increased. There was no effect of treatment on any sera parameters measured (P ≥ 0.10). No difference was detected for gene or protein expression of glucose transporter type 4 (GLUT4) due to CrP supplementation (P ≥ 0.10). For skeletal muscle fiber distribution and cross-sectional area, there was no effect of treatment (P ≥ 0.10). Density of total GLUT4 did not change due to CrP (P ≥ 0.10). Internalization of GLUT4 was increased in the 0.30 and 0.45 mg/kg treatments (P < 0.01). For total nuclei density and myonuclei density, there were treatment × day interaction tendencies (P ≤ 0.08). Supplementation of CrP did not alter density of satellite cells (P ≥ 0.10). The number of transporters located in the sarcolemma of skeletal muscle fibers did decrease, implying fewer proteins were needed to transport extracellular glucose into the muscle fiber. Therefore, CrP may augment cellular function and growth via increased efficiency of GLUT4 function. These results indicated CrP increases BW, ADG, and HCW, without changes in circulating sera parameters or total GLUT4 expression. [ABSTRACT FROM AUTHOR]

This study presents a novel fiber‐optic surface‐enhanced Raman spectroscopy (SERS) probe (SERS‐on‐a‐tip) fabricated using a simple, two‐step protocol based on off‐the‐shelf components and materials, with a high degree of controllability and repeatability. Two‐photon polymerization and subsequent metallization are adopted to fabricate a range of SERS arrays on both planar substrates and end‐facets of optical fibers. For the SERS‐on‐a‐tip probes, a limit of detection of 10−7m (Rhodamine 6G) and analytical enhancement factors of up to 1300 are obtained by optimizing the design, geometry, and alignment of the SERS arrays on the tip of the optical fiber. Furthermore, strong repeatability and consistency are achieved for the fabricated SERS arrays, demonstrating that the technique may be suitable for large‐scale fabrication procedures in the future. Finally, rapid SERS detection of live Escherichia coli cells is demonstrated using integration times in the milliseconds to seconds range. This result indicates strong potential for in vivo diagnostic use, particularly for detection of infections. Moreover, to the best of our knowledge, this represents the first report of detection of live, unlabeled bacteria using a fiber‐optic SERS probe. [ABSTRACT FROM AUTHOR]

Background Dual sugar testing for gut permeability is time-consuming and complex. We explored the utility of fluorescein as a simple and inexpensive alternative method. Methods We used a confocal laser endomicroscopy probe placed at the fingertip of participants who had ingested sodium fluorescein to measure the fluorescence at various time points. Results In 10 patients with diarrhoea, but not in 10 controls, fluorescence was detected quickly. By 6 min fluorescence was detected in all diarrhoea patients but only 1 control (p=0.0004). After 15 min there was no difference between the groups. Conclusions This simple oral fluorescein test may be useful to study gut permeability in low-resource settings. [ABSTRACT FROM AUTHOR]

Background and objective In Australia, over a third of individuals living with chronic hepatitis B (CHB) remain undiagnosed. Evidence suggests general practitioners (GPs) can be uncertain regarding whom to test. The aim of this study was to evaluate an educational resource for improving GPs’ knowledge about whom to test for CHB. Methods Following a 2014 baseline survey that identified gaps in CHB knowledge among GPs in Victoria, an educational resource package was developed. Using a follow-up survey, the resource was evaluated by comparing the before-andafter CHB-related knowledge. Results Sixty-five GPs responded to both the baseline and follow-up survey. Their knowledge of populations at high risk of CHB who require testing was significantly greater following the intervention than at baseline. Discussion Concise, clear and practical resources can support GPs when identifying whom to test for hepatitis B. [ABSTRACT FROM AUTHOR]

Objective: Microfluidic artificial lungs (μALs) are being researched for future clinical use due to the potential for increased gas exchange efficiency, small blood contacting surface area, small priming volume, and biomimetic blood flow paths. However, a current roadblock to clinical use is the need to stack hundreds to thousands of these small-scale μALs in parallel to reach clinically relevant blood flows. The need for so many layers not only increases the complexity and projected cost to manufacture a μAL, but also could result in devices which are cumbersome, and, therefore, not suitable for portable artificial lung systems. Methods: Here, we describe the design analysis and optimization of a single-layer μAL that simultaneously calculates rated blood flow, blood contacting surface area, blood volume, pressure drop, and shear stress as a function of blood channel height using previously developed closed-form mathematical equations. A μAL designed using this procedure is then implemented and tested. Results: The resulting device exhibits a rated flow of 17 mL/min and reduces the number of layers required for clinically relevant μAL devices by a factor of up to 32X compared to previous work. Conclusion: This procedure could significantly reduce manufacturing complexity as well as eliminate a barrier to the clinical application of these promising devices. Significance: The described method results in the highest rated flow for any single-layer μAL to date. [ABSTRACT FROM AUTHOR]

Crossbred beef steers (n = 240; 12 pens/treatment; initial BW = 305 ± 17.7 kg) were used in a randomized block design feedlot study to evaluate the influence of coated trenbolone acetate (TBA) and estradiol-17ß (E2) implants (Merck Animal Health, Madison, NJ) on gain performance, carcass traits, and sera metabolites. The five treatments were no implant (NI), Revalor-XR on d 0 [200 mg TBA + 20 mg E2 (coated); XR], Revalor-XS on d 0 [200 mg TBA + 40 mg E2 (total): 80 mg TBA + 16 mg E2 (noncoated) and 120 mg TBA + 24 mg E2 (coated); XS], Revalor-200 on d 0 [200 mg TBA + 20 mg E2 (noncoated); E200], or Revalor-200 on d 70 (D200). Interim BW and blood were collected on d 0, 14, 35, 70, 105, 140, and 175 prior to feeding and on d 213 prior to shipping. Following a 24 h clot at 4 °C, sera was harvested to quantify circulating E2, IGF-I, NEFA, serum urea-N (SUN), and 17ß-trenbolone (17ß-TbOH). Implanted steers had greater (P = 0.05) ADG, G:F, and final BW than NI controls. Implants increased (P < 0.05) HCW by 8%, 366 vs. 391, 414, 380, and 396 ± 6.4 kg, for NI vs. XR, XS, E200, and D200, respectively. The greatest (P = 0.05) dressing percentage, yield grade, and calculated empty body fat occurred in XS, which had greater (P < 0.05) rib fat than NI, XR, and D200. Marbling scores in NI were greater (P < 0.05) than E200 and D200; steers in XR and XS were intermediate (P > 0.10), not differing from NI, E200, or D200. An implant × day interaction (P = 0.01) was noted for circulating E2, IGF-I, SUN, and 17ß-TbOH. Implanted steers had elevated (P = 0.05) sera E2, IGF-I, and 17ß-TbOH, and decreased (P < 0.05) SUN following implantation compared to NI controls. Serum NEFA differed (P < 0.01) over time, but did not differ (P > 0.10) due to implant treatment. These data indicated that the polymer coating applied to the XR implant delayed release of steroidal hormones congruently to D200, with no negative impact on marbling. The greatest dose of E2, contained in XS, provided improvements in gain and carcass weight without detriment to marbling scores compared to NI. [ABSTRACT FROM AUTHOR]

Introduction: Commercial membrane lungs are designed to transfer a specific amount of oxygen per unit of venous blood flow. Membrane lungs are much more efficient at removing CO2 than adding oxygen, but the range of CO2 transfer is rarely reported. Methods: Commercial membrane lungs were studied with the goal of evaluating CO2removal capacity. CO2 removal was measured in 4 commercial membrane lungs under standardized conditions. Conclusion: CO2 clearance can be greater than 4 times that of oxygen at a given blood flow when the gas to blood flow ratio is elevated to 4:1 or 8:1. The CO2 clearance was less dependent on surface area and configuration than oxygen transfer. Any ECMO system can be used for selective CO2 removal. [ABSTRACT FROM AUTHOR]

Plasmo-thermo-electrophoresis (PTEP) involves using plasmonic microstructures to generate both a large-scale convection current and a near-field attraction force (thermo-electrophoresis). These effects facilitate the collective locomotion (i.e., swarming) of microscale particles in suspension, which can be utilized for numerous applications, such as particle/cell manipulation and targeted drug delivery. However, to date, PTEP for ensemble manipulation has not been well characterized, meaning its potential is yet to be realized. Our study aims to provide a characterization of PTEP on the motion and swarming effect of various particles and bacterial cells to allow rational design for bacteria-based microrobots and drug delivery applications. Plasmonic optical fibers (POFs) were fabricated using two-photon polymerization. The particle motion and swarming behavior near the tips of optical fibers were characterized by image-based particle tracking and analyzing the spatiotemporal concentration variation. These results were further correlated with the shape and surface charge of the particles defined by the zeta potential. The PTEP demonstrated a drag force ranging from a few hundred fN to a few tens of pN using the POFs. Furthermore, bacteria with the greater (negative) zeta potential (| ζ | > 10 mV) and smoother shape (e.g., Klebsiella pneumoniae and Escherichia coli) exhibited the greatest swarming behavior. The characterization of PTEP-based bacteria swarming behavior investigated in our study can help predict the expected swarming behavior of given particles/bacterial cells. As such, this may aid in realizing the potential of PTEP in the wide-ranging applications highlighted above. [ABSTRACT FROM AUTHOR]

Background: Access to direct-acting antiviral agents (DAAs) is restricted in some settings; thus, the European Association for the Study of the Liver recommends dual peginterferon/ribavirin (PegIFN/RBV) therapy wherever DAAs are unavailable. HCV genotype (GT) 3 infection is now the most difficult genotype to eradicate and PegIFN/RBV remains an effective option. The goal of this study was to devise a simple predictive score to identify GT3 patients with a high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV therapy. Methods: Relationships between baseline characteristics and SVR were explored by multiple logistic regression models and used to develop a simple scoring system to predict SVR using data from 1239 treatment-naive GT3 patients who received PegIFN alfa-2a/RBV for 24 weeks in two large observational cohort studies. Results: The score was validated using a database of 473 patients. Scores were assigned for six factors as follows: age (years) (≤40: 2 points; >40 but ≤55: 1); bodyweight (kg) (<70: 2; ≥70 but <90: 1); no cirrhosis/transition to cirrhosis (2); ALT ≤2.5 x ULN (1); platelets (109/L) (>200: 2; ≥100 but <200: 1); HCV RNA (<400,000 IU/mL: 1). The points are summed to arrive at a score ranging from 0‒10 where higher scores indicate higher chances of SVR; 141, 123, 203, 249, 232, and 218 patients had total scores of 0‒4, 5, 6, 7, 8, and 9–10, respectively, among whom SVR rates were 45%, 62%, 72%, 76%, 84%, and 89%. Among 622 patients who had scores of 6‒10 and HCV RNA <50 IU/mL by treatment week 4 the SVR rate was 86% (532/622). Conclusions: A simple baseline scoring system involving age, bodyweight, cirrhosis status, ALT level, platelet count and HCV RNA level can be used to identify treatment-naive Caucasian patients with HCV GT3 infection with a high probability of SVR with PegIFN alfa-2a/RBV therapy. [ABSTRACT FROM AUTHOR]

Background: In athletes, ECG changes from physiological cardiac remodelling are common but can overlap with findings from a pathological disorder. We compared ECG findings in a group of elite high school athletes to a cohort of adolescents with hypertrophic cardiomyopathy (HCM).Methods/results: We prospectively performed 15-lead ECGs and echocardiograms in 147 elite high school athletes. Student-athlete ECGs were compared in blinded fashion to ECGs of 148 adolescents with HCM of similar age and ethnicity. Standard ECG hypertrophy criteria and established expert opinion guidelines (European Society of Cardiology, ESC and Seattle criteria) were analysed. All student-athletes had normal echocardiograms. Overall, 77/147 (52%) of student-athletes met standard ECG criteria for ventricular hypertrophy compared to 126/148 (85%) adolescents with HCM (p<0.0001). There were 112/148 (76%) adolescents with HCM who had pathological Q-waves, T-wave inversion and/or ST-segment depression compared to 1/147 (1%) athletes (p<0.0001). Most patients with HCM (84%, 124/148) had ≥1 abnormal ECG finding(s) according to Seattle criteria, compared to 1% of student-athletes (2/147). Similarly, 130/148 (88%) patients with HCM met group-2 ESC criteria (abnormal), compared to 36/147 (24%) student-athletes (p<0.0001).Conclusions: Over 50% of elite high school athletes with echocardiographically confirmed normal hearts satisfied standard voltage criteria for ventricular hypertrophy. Pathological Q-waves, T-wave inversion or ST-segment depression were most helpful in distinguishing adolescents with HCM from normals. Both ESC and Seattle criteria successfully stratified the student-athlete and HCM cohorts, however each had a false-negative rate >10% for the HCM cohort. The Seattle criteria demonstrated a significantly lower false-positive rate (1%) than the ESC criteria (24%). [ABSTRACT FROM AUTHOR]

Chronic hepatitis C infection causes cirrhosis, liver failure and hepatocellular carcinoma, and is the most common indication for liver transplantation. Hepatitis C is curable and complications can be prevented. Until recently, treatment regimens involved peginterferon alfa. Although effective, their widespread use is limited by treatmentrelated toxicity. A number of direct-acting drugs for hepatitis C, such as sofosbuvir, have recently been developed and target multiple steps in the viral life cycle. These drugs are used in combination in interferonfree regimens. Short courses are highly effective with minimal toxicity. [ABSTRACT FROM AUTHOR]

For vascular-targeting carrier (VTC) systems to be effective, carriers must be able to localize and adhere to the vascular wall at the target site. Research suggests that neutrally buoyant nanoparticles are limited by their inability to localize to the endothelium, making them sub-optimal as carriers. This study examines whether particle density can be exploited to improve the targeting (localization and adhesion) efficiency of nanospheres to the vasculature. Silica spheres with 500 nm diameter, which have a density roughly twice that of blood, exhibit improved adhesion to inflamed endothelium in an in vitro model of human vasculature compared to neutrally buoyant polystyrene spheres of the same size. Silica spheres also display better near-wall localization in the presence of red blood cells than they do in pure buffer, likely resulting in the observed improvement in adhesion. Titania spheres (4 times more dense than blood) adhere at levels higher than polystyrene, but only in conditions when gravity or centrifugal force acts in the direction of adhesion. In light of the wide array of materials proposed for use as carrier systems for drug delivery and diagnostics, particle density may be a useful tool for improving the targeting of diseased tissues. [ABSTRACT FROM AUTHOR]

The importance of the size of targeted, spherical drug carriers has been previously explored and reviewed. Particle shape has emerged as an equally important parameter in determining the in vivo journey and efficiency of drug carrier systems. Researchers have invented techniques to better control the geometry of particles of many different materials, which have allowed for exploration of the role of particle geometry in the phases of drug delivery. The important biological processes include clearance by the immune system, trafficking to the target tissue, margination to the endothelial surface, interaction with the target cell, and controlled release of a payload. The review of current literature herein supports that particle shape can be altered to improve a system's targeting efficiency. Nonspherical particles can harness the potential of targeted drug carriers by enhancing targeted site accumulation while simultaneously decreasing side effects and mitigating some limitations faced by spherical carriers. [ABSTRACT FROM AUTHOR]

The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid) (PLGA) spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer) is seen with ∼60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases. [ABSTRACT FROM AUTHOR]