Spinal cord injury (SCI) researchers have predominately utilized rodents and mice for in vivo SCI modeling and experimentation. From these small animal models have come many insights into the biology of SCI, and a growing number of novel treatments that promote behavioral recovery. It has, however, been difficult to demonstrate the efficacy of such treatments in human clinical trials. A large animal SCI model that is an intermediary between rodent and human SCI may be a valuable translational research resource for pre-clinically evaluating novel therapies, prior to embarking upon lengthy and expensive clinical trials. Here, we describe the development of such a large animal model. A thoracic spinal cord injury at T10/11 was induced in Yucatan miniature pigs (20-25 kg) using a weight drop device. Varying degrees of injury severity were induced by altering the height of the weight drop (5, 10, 20, 30, 40, and 50 cm). Behavioral recovery over 12 weeks was measured using a newly developed Porcine Thoracic Injury Behavior Scale (PTIBS). This scale distinguished locomotor recovery among animals of different injury severities, with strong intra-observer and inter-observer reliability. Histological analysis of the spinal cords 12 weeks post-injury revealed that animals with the more biomechanically severe injuries had less spared white matter and gray matter and less neurofilament immunoreactivity. Additionally, the PTIBS scores correlated strongly with the extent of tissue sparing through the epicenter of injury. This large animal model of SCI may represent a useful intermediary in the testing of novel pharmacological treatments and cell transplantation strategies.

TDF-treated patients with chronic hepatitis B have reduced bone mineral density, but the reduction is limited to 1 anatomical site. Age and advanced liver disease are additional contributing factors, underlining the importance of multifactorial fracture risk assessment. FRAX can accurately identify those at greatest risk of osteoporotic fracture.

A large proportion of islets are lost after transplantation partly due to a lack of functional vasculature. Islets revascularize from host tissue but the process takes up to 2 weeks and has been suggested to result in reduced vascular density in engrafted islets. We describe a method for observing and quantifying the revascularization of intraportally transplanted islets that includes number, density, and branching of islet capillaries. Syngeneic islets were transplanted selectively into the two right posterior lobes of the liver of adult Lewis rats. Sections of the livers were dual stained for insulin and Bandeiraea simplicifolia and analyzed for islet morphology, area, and vascular density from day 0 to day 14 posttransplant and compared to native islets. Vascular density was 1431 ± 75.7 vessels/mm 2 in native islets and fell to 325.3 ± 30.8 vessels/mm 2 (p < 0.001) by day 1 posttransplant and subsequently increased until day 14 when it was significantly higher than in native islets (2612.5 ± 107.8 vessels/mm 2 , p < 0.001). The percentage of islet area occupied by vascular space was 9.1 ± 0.9% in native islets. After falling to 2.3 ± 0.3% (p < 0.001) 1 day posttransplant this rose to supranormal levels (21.5 ± 0.8%, p < 0.001) by day 14. The index of capillary branching was 0.771 ± 0.017 in native islets and fell to 0.465 ± 0.02 (p = 0.001) by day 3 but returned to native values by day 7 posttransplantation (0.726 ± 0.03). This technique provides a robust method for tracking and quantifying the revascularization of intraportally transplanted islets, which should enable the comparison of different strategies aimed at accelerating islet revascularization.Key words: Islet transplantation; Vascular density; Endothelium; Quantification INTRODUCTIONRat pancreatic islets are highly vascular and receive 6% of the pancreatic arterial blood flow, despite only accounting for 0.3% of the volume of the pancreas (23). One-year insulin independence rates for clinical islet transplantation have improved but two or more transEach islet is supplied by one to three afferent arterioles that divide at the mantle of the islet into a glomerulusplants are usually required to achieve insulin independence (36). The requirement for multiple donors contrasts like network of capillaries that either coalesce at the edge of the islet or traverse the central β-cell core to with the single donor required for insulin independence after whole pancreas transplantation. This highlights the connect with collecting venules on the other side (5,24). The venules then drain either into the acinar (exocrine) fact that successful islet transplantation is dependent on the number of islets transplanted and, more importantly, venous system or directly into interlobular veins and hence into the portal vein (24). the proportion that survive. In kidney subcapsular experimental models, up to 60% of islet mass is lost in the Normal islet vasculature is disrupted during isolation from the whole pancreas but experimental studies show immediate posttransplant per...

Hepatitis B virus (HBV) infection is estimated to affect 292 million people worldwide, 90% of them are unaware of their HBV status. The Determine HBsAg 2 (Alere Medical Co, Ltd Chiba Japan [Now Abbott]) is a rapid test that meets European Union (EU) regulatory requirements for Hepatitis B surface antigen 2 (HBsAg) analytical sensitivity, detecting the 0.1 IU/mL World Health Organization (WHO) International HBsAg Standard. This prospective, multicentre study was conducted to establish its clinical performance. 351 evaluable subjects were enrolled, 145 HBsAg‐positive. The fingerstick whole blood sensitivity and specificity were 97.2% and 98.5% (15′ reading, reference assay cut‐off 0.05 IU/mL), sensitivity increasing to 97.9% with the prespecified cut‐off 0.13 IU/mL (EU regulations). The venous whole blood, serum and plasma sensitivity was 97.2%, 97.9%, and 98.6%, respectively (15′ reading); reaching 99%, 99.5% and 100% specificity. A testing algorithm following up an initial positive fingerstick test result with plasma/serum test demonstrates 100% specificity. The Determine HBsAg 2 test gives 15‐minute results with high sensitivity and specificity, making it an ideal tool for point‐of‐care testing, with the potential to enable large‐scale population‐wide screening to reach the WHO HBV diagnostic targets. The evaluated test improves the existing methods as most of the reviewed rapid tests do not meet the EU regulatory requirements of sensitivity.

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Introduction Bone Mineral Density (BMD) loss has been reported in chronic liver disease. In Chronic Hepatitis B (CHB) patients, Tenofovir Disoproxil Fumarate (TDF) is recommended as a first line therapy, in accordance with EASL guidelines. Concerns regarding the long-term safety of TDF have been raised, in particular changes in BMD in HIV patients, but limited data exist on similar changes in HBV treated patients. The aim of this study was to determine the impact of TDF on BMD in an ethnically diverse HBV infected population undergoing long-term treatment with this agent. Methods In a single centre, CHB patients treated with TDF for a minimum 12 months were prospectively offered a dual x-ray absorptiometry scan. BMD loss was defined by WHO criteria; T-score <−2.5 (osteoporosis) and between −1 and −2.5 (osteopenia). 83 consecutive patients were included (64 males), median age 45 (range 26–64). A control group, 27 patients with CHB (19 males), median age 32 (range 20–61), with no TDF exposure were also examined. Data on ethnicity, BMI, gender, fibrosis stage, comorbidities and drug history were recorded in all subjects. Results BMD loss was present in 45% of the treatment group (osteopenia 84%, osteoporosis 16%) and in 48% of the control group (osteopenia 85%, osteoporosis 15%). There was no difference in BMD loss when comparing both groups (p=0.45). In the ethnically diverse population studied, there was increased BMD loss in the non-White population (48%, treated group; 50%, controls) compared with the white population (33%, treated group; 40%, controls). By univariate analysis age, gender, fibrosis stage, comorbidities were all significant (p=<0.05, all variables), but particularly ethnicity (p=0.009). At multivariate analysis only ethnicity, BMI and male gender met statistical significance (p<0.015, <0.017 and <0.018 respectively), but not TDF. Conclusion This results demonstrate the prevalence of reduced BMD in CHB patients of diverse ethnicity, independent of TDF treatment. This cross-sectional study does not exclude the potential for BMD loss with TDF and further longitudinal studies are required to determine its effect on bone over time. Other factors also contribute to BMD loss, namely ethnicity and BMI, and should be given due consideration when selecting a treatment option.

Results 10% of prior relapsers and 31e40% of partial responders (shaded cells), had <1 log10 decline in HCV RNA at week 4 in the control and L-I arm, respectively. SVR rates in the T L-I arm among prior relapsers and partial responders were higher (62% and 56%, respectively; combined SVR¼58%) than in prior week 12 NR who experienced <1 log10 decline in HCV RNA (15%). Although patients with À1 log10 response at end of the L-I phase had the highest SVR rates, SVR in T/PR patients with <1 log10 was considerably higher (62615%) than control (0%). Conclusion Poor interferon responders on treatment (<1 log10 decline in HCV RNA at week 4) are not the same as prior PR NR (<2 log10 at week 12). SVR rates in T/PR patients were higher than control irrespective of their response (< or À1 log10) at the end of the L-I phase. Safety findings in the T arm were similar irrespective of week 4 response.