Composite bi-layered erodible films for potential ocular drug delivery

Bi-layered hydroxypropylmethylcellulose and Eudragit based films were formulated as potential ocular drug delivery systems using chloramphenicol as a model antibiotic. Films were plasticized with polyethylene glycol 400 present in the Eudragit layer or both Eudragit and hydroxypropylmethylcellulose layers, and loaded with chloramphenicol (0.5% w/v in solution) in the hydroxypropylmethylcellulose layer. The weight, thickness and folding endurance optimized formulations were measured and further characterized for transparency, tensile, mucoadhesive, swelling and in vitro drug dissolution properties. The physical form of chloramphenicol within the films was evaluated using differential scanning calorimetry (DSC), and X-ray diffraction (XRD), complimented with scanning electron microscopy and energy dispersive X-ray spectroscopy. Fourier transform infrared spectroscopy was used to assess the interactions between the drug and the film components and confirm chloramphenicol’s presence within the sample. Optimum films showed high transparency (≥ 80% transmittance), ease of peeling from Petri dish and folding endurance above 250. Average thickness was lower than contact lenses (0.4 - 1mm), confirming them as thin ocular films. The tensile properties showed a good balance between toughness and flexibility and mucoadhesivity showed that they could potentially adhere to the ocular surface for prolonged periods. The drug loaded films showed swelling capacity which was greater than 300% of their original weight. The physical form of chloramphenicol within the films was amorphous (DSC and XRD) whilst in vitro drug dissolution showed sustained drug release from the films for four hours, before complete erosion. The chloramphenicol loaded films represent a potential means of treating common eye infections

Zwavel in de rwzi: Autotrofe denitrificatie en zwavelterugwinning als zuiveringstechniek voor rwzi’s - een haalbaarheidsstudie

Aanvullende nitraatverwijdering vraagt om extra CZV of een efficiënter gebruik van het beschikbare CZV. De inzet van autotrofe denitrificatie maakt dit mogelijk. Bij autotrofe denitrificatie kan zwavel als elektrondonor worden gebruikt. Voor aanvullende heterotrofe denitrificatie is het gangbaar om een externe C-bron zoals methanol te doseren. De nadelen hiervan zijn veiligheidsrisico’s en kosten. Voor zwavel gelden deze nadelen minder. Ook is zwavel, zeker wanneer een interne stroom kan worden gebruikt, duurzamer. Dit onderzoek is uitgevoerd om de zwavelstromen op een rwzi in kaart te brengen en de haalbaarheid van autotrofe denitrificatie in de rwzi te verkennen. Daarnaast is onderzocht of het zwavelgehalte in slib en daarmee de aan zwavel gerelateerde slibverwerkingskosten kunnen worden verlaagd

Harmony and discord:Development of political parties and social fragmentation in Hong Kong, 1980-2017

This paper seeks to examine why political parties in Hong Kong are fragmented and how the development of political parties in Hong Kong leads to social discord. Political parties started to emerge in Hong Kong in the 1980s. They had a golden opportunity to develop in the 1990s due to political reform, but why are political parties in Hong Kong still small, weak, with poor reputations and weak support? The author points out five factors that lead to the malfunction of political parties in Hong Kong. Although some factors are caused by the political parties themselves, the author argues that they are, all in all, constitutional or institutional factors, as they are long-term restraints directly set by the government since the colonial era. Due to the failure of party development in Hong Kong caused by constitutional and institutional restraints, the author will also discuss how this failure has lead to the political and social discord in the past two decades since the handover and the future

New ways to turn on NKT cells

Godfrey and Rossjohn discuss the varied ways to turn on NKT cells in the context of recent findings

Longitudinal investigation of wandering behavior in department of veterans affairs nursing home care units

Objectives To explore the extent of and factors associated with male residents who change wandering status post nursing home admission. Design Longitudinal design with secondary data analyses. Admissions over a 4-year period were examined using repeat assessments with the Minimum Data Set (MDS) to formulate a model understanding the development of wandering behavior. Setting One hundred thirty-four Veterans Administration (VA) nursing homes throughout the United States. Participants Included 6673 residents admitted to VA nursing homes between October 2000 and October 2004. Measurements MDS variables (cognitive impairment, mood, behavior problems, activities of daily living and wandering) included ratings recorded at residents' admission to the nursing home and a minimum of two other time points at quarterly intervals. Results The majority (86%) of the sample were classified as non-wanderers at admission and most of these (94%) remained non-wanderers until discharge or the end of the study. Fifty-one per cent of the wanderers changed status to non-wanderers with 6% of these residents fluctuating in status more than two times. Admission variables associated with an increased risk of changing status from non-wandering to wandering included older age, greater cognitive impairment, more socially inappropriate behavior, resisting care, easier distractibility, and needing less help with personal hygiene. Requiring assistance with locomotion and having three or more medical comorbidities were associated with a decreased chance of changing from non-wandering to wandering status. Conclusion A resident's change from non-wandering to wandering status may reflect an undetected medical event that affects cognition, but spares mobility. Copyright © 2009 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64919/1/2316_ftp.pd

Does transient increase in axial length during accommodation attenuate with age?

Background: The aim was to profile transient accommodative axial length (AXL) changes from early adulthood to advanced presbyopia and to determine whether any differences exist between the responses of myopic and emmetropic individuals. Methods: Ocular biometry was measured by the LenStar biometer (Haag-Streit, Switzerland) in response to 0.00, 3.00 and 4.50 D accommodative stimuli in 35 emmetropes and 37 myopes, aged 18 to 60 years. All results were corrected to reduce errors arising from the increase in crystalline lens thickness with accommodation. Accommodative responses were measured sequentially by the WAM 5500 Auto Ref/Keratometer (Grand Seiko, Japan). Results: AXL increased significantly with accommodation (p<0.001), with a mean corrected AXL elongation of 2 ± 18 µm and 8 ± 16 µm observed at 3.00 D and 4.50 D, respectively. The magnitude of accommodative AXL change was not dependent on refractive error classification (p=0.959), however a significant reduction in the magnitude and variance of AXL change was evident after 43-44 years of age (p<0.002). Conclusion: The negative association between transient AXL elongation and age, in combination with reduced variance of data after age 43-44 years, is consistent with a significant increase in posterior ocular rigidity, which may be influential in the development of presbyopia

Putative DHHC-Cysteine-Rich Domain S-Acyltransferase in Plants

Protein S-acyltransferases (PATs) containing Asp-His-His-Cys within a Cys-rich domain (DHHC-CRD) are polytopic transmembrane proteins that are found in eukaryotic cells and mediate the S-acylation of target proteins. S-acylation is an important secondary and reversible modification that regulates the membrane association, trafficking and function of target proteins. However, little is known about the characteristics of PATs in plants. Here, we identified 804 PATs from 31 species with complete genomes. The analysis of the phylogenetic relationships suggested that all of the PATs fell into 8 groups. In addition, we analysed the phylogeny, genomic organization, chromosome localisation and expression pattern of PATs in Arabidopsis, Oryza sative, Zea mays and Glycine max. The microarray data revealed that PATs genes were expressed in different tissues and during different life stages. The preferential expression of the ZmPATs in specific tissues and the response of Zea mays to treatments with phytohormones and abiotic stress demonstrated that the PATs play roles in plant growth and development as well as in stress responses. Our data provide a useful reference for the identification and functional analysis of the members of this protein family

The NOX toolbox: validating the role of NADPH oxidases in physiology and disease

Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are the only known enzyme family with the sole function to produce ROS. Of the catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed isoform. We provide here a critical review of the currently available experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo, its specificity, selectivity, and possible mechanism of action. Finally, we discuss the validation of NOX4 as a potential therapeutic target for indications including stroke, heart failure, and fibrosis

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events