Electrospun pH-sensitive core-shell polymer nanocomposites fabricated using a tri-axial process

A modified tri-axial electrospinning process was developed for the generation of a new type of pH-sensitive polymer/lipid nanocomposite. The systems produced are able to promote both dissolution and permeation of a model poorly water-soluble drug. First, we show that it is possible to run a tri-axial procress with only one of the three fluids being electrospinnable. Using an electrospinnable middle fluid of Eudragit S100 (ES100) with pure ethanol as the outer solvent and an unspinnable lecithin-diclofenac sodium (PL-DS) core solution, nanofibers with linear morphology and clear core/shell structures can be fabricated continuously and smoothly. X-ray diffraction proved that these nanofibers are structural nanocomposites with the drug present in an amorphous state. In vitro dissolution tests demonstrated that the formulations could preclude release in acidic conditions, and that the drug was released from the fibers in two successive steps at neutral pH. The first step is the dissolution of the shell ES100 and the conversion of the core PL-DS into sub-micron sized particles. This frees some DS into solution, and later the remaining DS is gradually released from the PL-DS particles through diffusion. Ex vivo permeation results showed that the composite nanofibers give a more than two-fold uplift in the amount of DS passing through the colonic membrane as compared to pure DS; 74% of the transmitted drug was in the form of PL-DS particles. The new tri-axial electrospinning process developed in this work provides a platform to fabricate structural nanomaterials, and the core-shell polymer-PL nanocomposites we have produced have significant potential applications for oral colon-targeted drug delivery. STATEMENT OF SIGNIFICANCE: A modified tri-axial electrospinning is demonstrated to create a new type of core-shell pH-sensitive polymer/lipid nanocomposites, in which an electrospinnable middle fluid is exploited to support the un-spinnable outer and inner fluids. The structural nanocomposites are able to provide a colon-targeted sustained release and an enhanced permeation performance of diclofenac sodium. The developed tri-axial process can provide a platform for fabricating new structural nanomaterials with high quality. The strategy of a combined usage of polymeric excipients and phosphilipid in a core-shell format should provide new possibilities of developing novel drug delivery systems for efficacious oral administration of poorly-water soluble drugs

Discovery of a ROCK inhibitor, FPND, which prevents cerebral hemorrhage through maintaining vascular integrity by interference with VE-cadherin

published_or_final_versio

Pay-it-forward dual gonorrhea/chlamydia test uptake among men who have sex with men in China: a pragmatic, quasi-experimental study

Background: Chinese men who have sex with men (MSM) rarely receive gonorrhea/chlamydia testing. The purpose of this pilot study was to evaluate a pay-it-forward strategy to increase gonorrhea/chlamydia testing among MSM. Pay-it-forward has one person receive a gift, then asks the same person if they would like to give a gift to another person. Methods: We used a quasi-experimental pragmatic study to compare a pay-it-forward model to standard of care at two HIV testing sites for MSM. A pay-it-forward program was implemented for three months, during which men were offered free gonorrhea/chlamydia testing and given the option of donating money toward testing for future participants. Both sites then switched to standard of care for three months, offering dual testing at the standard price. We compared test uptake and financial costs in the two groups. Findings: 408 men were included in this study. 203 men were offered pay-it-forward, and 205 were offered standard of care. Overall, 109 (109/203, 53·7%) men received gonorrhea/chlamydia testing in the pay-it-forward group and 12 (12/205, 5·9%) men received gonorrhea/chlamydia testing in the standard of care group (adjusted odds ratio 19·73, 95%CI 10·02-38·85). This was a first gonorrhea or chlamydia test for 86% (104/121) of men. 89% (97/109) of men in the pay-it-forward group donated some amount. The incremental unit cost per test in the pay-it-forward group was 67 USD, compared to 503 USD in the standard of care group. Interpretation: Pay-it-forward may be a sustainable model for expanding integrated HIV testing services among MSM in China

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

Gender differences in the association between adiposity and probable major depression: a cross-sectional study of 140,564 UK Biobank participants

<b>Background</b><p></p> Previous studies on the association between adiposity and mood disorder have produced contradictory results, and few have used measurements other than body mass index (BMI). We examined the association between probable major depression and several measurements of adiposity: BMI, waist circumference (WC), waist-hip-ratio (WHR), and body fat percentage (BF%).<p></p> <b>Methods</b><p></p> We conducted a cross-sectional study using baseline data on the sub-group of UK Biobank participants who were assessed for mood disorder. Multivariate logistic regression models were used, adjusting for potential confounders including: demographic and life-style factors, comorbidity and psychotropic medication.<p></p> <b>Results</b><p></p> Of the 140,564 eligible participants, evidence of probable major depression was reported by 30,145 (21.5%). The fully adjusted odds ratios (OR) for obese participants were 1.16 (95% confidence interval (CI) 1.12, 1.20) using BMI, 1.15 (95% CI 1.11, 1.19) using WC, 1.09 (95% CI 1.05, 1.13) using WHR and 1.18 (95% CI 1.12, 1.25) using BF% (all p <0.001). There was a significant interaction between adiposity and gender (p = 0.001). Overweight women were at increased risk of depression with a dose response relationship across the overweight (25.0-29.9 kg/m2), obese I (30.0-34.9 kg/m2), II (35.0-39.9 kg/m2) and III (≥40.0 kg/m2) categories; fully adjusted ORs 1.14, 1.20, 1.29 and 1.48, respectively (all p < 0.001). In contrast, only obese III men had significantly increased risk of depression (OR 1.29, 95% CI 1.08, 1.54, p = 0.006).<p></p> <b>Conclusion</b><p></p> Adiposity was associated with probable major depression, irrespective of the measurement used. The association was stronger in women than men. Physicians managing overweight and obese women should be alert to this increased risk

East London’s Homeless: a retrospective review of an eye clinic for homeless people

Background There is very little published work on the visual needs of homeless people. This paper is the first study to investigate the visual needs of homeless people in the UK. Although similar work has been done in other countries, this study is unique because the United Kingdom is the only country with a National Health Service which provides free healthcare at the point of access. This study analysed the refractive status of the sample used, determined the demographics of homeless people seeking eye care and established if there is a need for community eye health with access to free spectacle correction in East London. Methods This retrospective case study analysed the clinical records of 1,141 homeless people using the Vision Care for Homeless People services at one of their clinics in East London. All eye examinations were carried out by qualified optometrists and, where appropriate, spectacles were dispensed to patients. Data captured included age, gender, ethnicity and refractive error. Results were analysed using two-sample t-tests with Excel and Minitab. Results Demographics of age, gender and ethnicity are described. Spherical equivalents (SE) were calculated from prescription data available for 841 clinic users. Emmetropia was defined as SE–0.50DS to +1DS, myopia as SE  +1DS. The majority of clinic users were male (79.2 %, n = 923). Approximately 80 % (n = 583) of clinic users were white, 10 % (n = 72) were ‘black’, 4 % (n = 29) ‘Asian’ and the remaining 5.6 % (n = 40) were of ‘mixed ethnicity’ and ‘other’ groups. The mean age of females attending the clinic was significantly lower than that of males (45.9 years, SD = 13.8 vs’ 48.4 years, SD = 11.8) when analysed using a two-sample t-test (t (317) = 2.44, p = 0.02). One third of service users were aged between 50–59 years. Myopia and hyperopia prevalence rates were 37.0 % and 21.0 % respectively. A total of 34.8 % of homeless people were found to have uncorrected refractive error, and required spectacle correction. Conclusions This study has identified a high proportion of uncorrected refractive error in this sample and therefore a need for regular eye examinations and provision of refractive correction for homeless people

Cyclic Behavior of HPFRCC Coupling Beams with Bundled Diagonal Bars

Coupled shear walls are efficient in resisting lateral forces induced by winds and earthquakes. However, it is difficult to construct coupled shear walls particularly because current design codes require complex reinforcing details within coupling beams. The objective of this study was to develop simple reinforcement details for diagonally reinforced coupling beams; reducing transverse steel by use of high-performance fiber-reinforced cementitious composites (HPFRCCs) and bundling diagonal bars are explored. Four coupling beam specimens with length-to-depth aspect ratios of 2.0 or 3.5 were fabricated and tested under cyclic lateral displacements. The test results revealed that HPFRCC coupling beams with bundled diagonal bars and widely spaced transverse reinforcement (one-half the amount of reinforcement required by current seismic codes) exhibited excellent seismic performance compared with ordinary concrete coupling beams having code-required distributed diagonal reinforcement and transverse reinforcement

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Increased Mobility of Metal Oxide Nanoparticles Due to Photo and Thermal Induced Disagglomeration

Significant advances have been made on our understanding of the fate and transport of engineered nanomaterials. One unexplored aspect of nanoparticle aggregation is how environmental stimuli such as light exposure and temperature variations affect the mobility of engineered nanoparticles. In this study, TiO2, ZnO, and CeO2 were chosen as model materials for investigating the mobility of nanoparticles under three external stimuli: heat, light and sonication. Sunlight and high power sonication were able to partially disagglomerate metal oxide clusters, but primary particles bonded by solid state necks were left intact. A cycle of temperature increase from 25°C to 65°C and then decrease back was found to disagglomerate the compact clusters in the heating phase and reagglomerate them as more open fractal structures during the cooling phase. A fractal model summing the pair-wise DLVO interactions between primary particles within two fractal agglomerates predicts weak attractions on the order of a few kT. Our study shows that common environmental stimuli such as light exposure or temperature variation can disagglomerate nanoparticle clusters and enhance their mobility in open waters. This phenomenon warrants attention since it is likely that metal oxide nanoparticles will experience these natural stimuli during their transport in the environment