The preparation of HEMA-MPC films for ocular drug delivery

There is a need to prolong drug residence time using a biocompatible formulation in the subconjunctival space after surgery to treat glaucoma. Drug releasing discs were prepared with 2-(hydroxyethyl)methacrylate (HEMA) and 2-methacryloyl-oxyethyl phosphorylcholine (MPC). The ratio of bound water (Wb) to free water (Wf) ratio increased from 1:0.3 to 1:6.8 with increasing MPC (0 to 50%, w/w). The optimal balance between water content, SR and mechanical strength were obtained with 10% MPC (w/w) hydrogels. Water-alcohol mixtures were examined to facilitate loading of poorly soluble drugs, and they showed greater hydrogel swelling than either water or alcohol alone. The SR was 1.2 ± 0.02 and 3.3 ± 0.1 for water and water:ethanol (1:1) respectively. HEMA-MPC (10%) discs were loaded with dexamethasone using either water:ethanol (1:1) or methanol alone. Drug release was examined in an outflow rig model that mimics the subconjunctival space in the eye. Dexamethasone loading increased from 0.3 to 1.9 mg/disc when the solvent was changed from water:ethanol (1:1) to methanol with the dexamethasone half-life (t½) increasing from 1.9 to 9.7 days respectively. These encouraging results indicate that HEMA-MPC hydrogels have the potential to sustain the residence time of a drug in the subconjunctival space of the eye

Optimisation of biomass, exopolysaccharide and intracellular polysaccharide production from the mycelium of an identified Ganoderma lucidum strain QRS 5120 using response surface methodology

Wild-cultivated medicinal mushroom Ganoderma lucidum was morphologically identified and sequenced using phylogenetic software. In submerged-liquid fermentation (SLF), biomass, exopolysaccharide (EPS) and intracellular polysaccharide (IPS) production of the identified G. lucidum was optimised based on initial pH, starting glucose concentration and agitation rate parameters using response surface methodology (RSM). Molecularly, the G. lucidum strain QRS 5120 generated 637 base pairs, which was commensurate with related Ganoderma species. In RSM, by applying central composite design (CCD), a polynomial model was fitted to the experimental data and was found to be significant in all parameters investigated. The strongest effect (p lt 0.0001) was observed for initial pH for biomass, EPS and IPS production, while agitation showed a significant value (p lt 0.005) for biomass. By applying the optimized conditions, the model was validated and generated 5.12 g/L of biomass (initial pH 4.01, 32.09 g/L of glucose and 102 rpm), 2.49 g/L EPS (initial pH 4, 24.25 g/L of glucose and 110 rpm) and 1.52 g/L of IPS (and initial pH 4, 40.43 g/L of glucose, 103 rpm) in 500 mL shake flask fermentation. The optimized parameters can be upscaled for efficient biomass, EPS and IPS production using G. lucidum

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Use of the Internet for health information by physicians for patient care in a teaching hospital in Ibadan, Nigeria

BACKGROUND: The Internet is the world's largest network of information, communication and services. Although the Internet is widely used in medicine and has made significant impact in research, training and patient care, few studies had explored the extent to which Nigerian physicians use Internet resources for patient care. The objective of this study was to assess physicians' use of the Internet for health information for patient care. METHOD: 172 physicians at the University College hospital (UCH) Ibadan, Nigeria; completed a 31-item, anonymous, standardized questionnaire. The Epi-Info software was used for data analysis. RESULTS: The mean age of the respondents was 31.95 years (SD 4.94). Virtually all (98%) the respondents had used the Internet; 76% accessed it from cyber cafes. E-mail was the most commonly used Internet service (64%). Ninety percent of the respondents reported they had obtained information from the Internet for patient care; of this number, 76.2% had searched a database. The database most recently searched was MEDLINE/PubMed in 99% of cases. Only 7% of the respondents had ever searched the Cochrane Library. More than half (58.1%) perceived they had no confidence to download full-text articles from online sources such as the Health Internetwork Access to Research Initiative (HINARI). Multiple barriers to increased use of the Internet were identified including poor availability of broadband (fast connection speed) Internet access, lack of information searching skills, cost of access and information overload. CONCLUSION: Physicians' use of the Internet for health information for patient care was widespread but use of evidenced-based medicine resources such as Cochrane Library, Up-to-date and Clinical Evidence was minimal. Awareness and training in the use of EBM resources for patient care is needed. Introduction of EBM in the teaching curriculum will enhance the use of EBM resources by physicians for patient care

Regional differences in portion size consumption behaviour: Insights for the global food industry

Abstract: Given the influence of globalization on consumer food behaviour across the world, the purpose of this paper is to contribute to the theoretical discourse around food portion size as a global consumption-related symbol and its underlying socio-economic drivers for food industry strategy. Overall, 25,000 global food consumers were surveyed across 24 countries to elicit insight on portion size consumption behaviour as well as consumer perception on eating and drinking small portion size within selected socio-economic classes. The data was quantitatively analysed to answer the pertinent research objectives. In 20 out of the 24 global markets surveyed, large food portion size was statistically established as a prevalent consumption-related symbol. The paper found that there are regional differences in portion size food consumption behaviour, and further disparities exist across age, gender and income status in 24 countries covering all regions, including Australia, China, Mexico, South Africa, United Kingdom and United States of America. The outlined food industry implications reveal that adaptation and standardisation strategies are still relevant in global food and nutrition strategy as revealed by the variations in the preference for food portion sizes across various countries of the world

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Structured and Standardized Education or Advice for Chronic Primary low back pain in Adults

PURPOSE: Evaluate benefits and harms of education/advice for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing education/advice compared with placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of education/advice could be isolated). We conducted meta-analyses and graded the certainty of evidence. RESULTS: We screened 2514 citations and 86 full text RCTs and included 15 RCTs. Most outcomes were assessed 3 to 6 months post-intervention. Compared with no intervention, education/advice improved pain (10 RCTs, MD = -1.1, 95% CI -1.63 to -0.56), function (10 RCTs, SMD = -0.51, 95% CI -0.89 to -0.12), physical health-related quality of life (HRQoL) (2 RCTs, MD = 24.27, 95% CI 12.93 to 35.61), fear avoidance (5 RCTs, SMD = -1.4, 95% CI -2.51 to -0.29), depression (1 RCT; MD = 2.10, 95% CI 1.05 to 3.15), and self-efficacy (1 RCT; MD = 4.4, 95% CI 2.77 to 6.03). Education/advice conferred less benefit than sham Kinesio taping for improving fear avoidance regarding physical activity (1 RCT, MD = 5.41, 95% CI 0.28 to 10.54). Compared with usual care, education/advice improved pain (1 RCT, MD = -2.10, 95% CI -3.13 to -1.07) and function (1 RCT, MD = -7.80, 95% CI -14.28 to -1.32). There was little or no difference between education/advice and comparisons for other outcomes. For all outcomes, the certainty of evidence was very low. CONCLUSION: Education/advice in adults with CPLBP was associated with improvements in pain, function, HRQoL, and psychological outcomes, but with very low certainty

Effective CP-violating operators of the tau lepton and some of their phenomenologies

The dimension-six CP-violating SU_L(2)\times U_Y(1) invariant operators involving the tau lepton are studied. The constraints from the available experimental data on tau dipole moments are derived. Under the current constraints, the induced CP-violating effects could possibly be observed in tau -> 3\pi \nu_{\tau} at the future tau-charm factory.Comment: comments added, refs corrected, version to appear in PR

Synthetic Lethal Screen Identifies NF-κB as a Target for Combination Therapy with Topotecan for patients with Neuroblastoma

<p>Abstract</p> <p>Background</p> <p>Despite aggressive multimodal treatments the overall survival of patients with high-risk neuroblastoma remains poor. The aim of this study was to identify novel combination chemotherapy to improve survival rate in patients with high-risk neuroblastoma.</p> <p>Methods</p> <p>We took a synthetic lethal approach using a siRNA library targeting 418 apoptosis-related genes and identified genes and pathways whose inhibition synergized with topotecan. Microarray analyses of cells treated with topotecan were performed to identify if the same genes or pathways were altered by the drug. An inhibitor of this pathway was used in combination with topotecan to confirm synergism by <it>in vitro </it>and <it>in vivo </it>studies.</p> <p>Results</p> <p>We found that there were nine genes whose suppression synergized with topotecan to enhance cell death, and the NF-κB signaling pathway was significantly enriched. Microarray analysis of cells treated with topotecan revealed a significant enrichment of NF-κB target genes among the differentially altered genes, suggesting that NF-κB pathway was activated in the treated cells. Combination of topotecan and known NF-κB inhibitors (NSC 676914 or bortezomib) significantly reduced cell growth and induced caspase 3 activity <it>in vitro</it>. Furthermore, in a neuroblastoma xenograft mouse model, combined treatment of topotecan and bortezomib significantly delayed tumor formation compared to single-drug treatments.</p> <p>Conclusions</p> <p>Synthetic lethal screening provides a rational approach for selecting drugs for use in combination therapy and warrants clinical evaluation of the efficacy of the combination of topotecan and bortezomib or other NF-κB inhibitors in patients with high risk neuroblastoma.</p

A global reptile assessment highlights shared conservation needs of tetrapods

Comprehensive assessments of species’ extinction risks have documented the extinction crisis and underpinned strategies for reducing those risks. Global assessments reveal that, among tetrapods, 40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction. Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods. Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs. Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened—confirming a previous extrapolation and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods—agriculture, logging, urban development and invasive species—although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles—including most species of crocodiles and turtles—require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles.Neil Cox, Bruce E. Young, Philip Bowles, Miguel Fernandez, Julie Marin, Giovanni Rapacciuolo, Monika Böhm, Thomas M. Brooks, S. Blair Hedges, Craig Hilton-Taylor, Michael Hoffmann, Richard K. B. Jenkins, Marcelo F. Tognelli, Graham J. Alexander, Allen Allison, Natalia B. Ananjeva, Mark Auliya, Luciano Javier Avila, David G. Chapple, Diego F. Cisneros-Heredia, Harold G. Cogger, Guarino R. Colli, Anslem de Silva, Carla C. Eisemberg, Johannes Els, Ansel Fong G., Tandora D. Grant, Rodney A. Hitchmough, Djoko T. Iskandar, Noriko Kidera, Marcio Martins, Shai Meiri, Nicola J. Mitchell, Sanjay Molur, Cristiano de C. Nogueira, Juan Carlos Ortiz, Johannes Penner, Anders G. J. Rhodin, Gilson A. Rivas, Mark-Oliver Rödel, Uri Roll, Kate L. Sanders, Georgina Santos-Barrera, Glenn M. Shea, Stephen Spawls, Bryan L. Stuart, Krystal A. Tolley, Jean-François Trape, Marcela A. Vidal, Philipp Wagner, Bryan P. Wallace, Yan Xi