Impedimetric Biosensors for Detecting Vascular Endothelial Growth Factor (VEGF) Based on Poly(3,4-ethylene dioxythiophene) (PEDOT)/Gold Nanoparticle (Au NP) Composites

In advanced forms of diabetic retinopathy, retinal vascular occlusive disease and exudative age-related macular degeneration, vision loss is associated with elevated levels or extravasation of vascular endothelial-derived growth factor (VEGF) into the retina, vitreous, and anterior chamber of the eye. We hypothesize that point-of-care biosensors, capable of rapidly and precisely measuring VEGF levels within the eye will assist clinicians in assessing disease severity, and in establishing individualized dosing intervals for intraocular anti-VEGF injection therapy. An impedance biosensor based on a poly(3,4-ethylenedioxythiophene) (PEDOT)/gold nanoparticle (Au NP) composite was developed for detecting VEGF. PEDOT with Au NP was electrochemically deposited on three different medical electrode sensor designs: free-standing pads, screen printed dots, and interdigitated micro-strip electrodes. Anti-VEGF antibody was covalently immobilized on the surface of the polymer films through attachment to citrate-functionalized Au NPs, and the resulting composites were used to detect VEGF-165 by electrochemical impedance spectroscopy (EIS). The PEDOT-Au NP composite materials were characterized using optical microscopy, SEM/EDS, FIB, TEM, and STEM techniques. Among the different micro-electrodes, the interdigitated strip shape showed the best overall film stability and reproducibility. A linear relationship was established between the charge transfer resistance (Rct) and VEGF concentration. The detection limit of VEGF was found to be 0.5 pg/mL, with a correlation coefficient of 0.99 ± 0.064%. These results indicate that the proposed PEDOT/Au NP composites can be used in designing low-cost and accurate VEGF biosensors for applications such as clinical diagnosis of VEGF-mediated eye disease

A Case of Green Urine after Ingestion of Herbicides

The development of discolored urine may have many possible causes. Here we present the case of a 76-year-old woman who was admitted after ingesting the inorganic herbicides, mefenacet and imazosulfuron. Her urine color changed to green almost immediately. Since the patient had no specific medication or medical history we considered that the most likely cause of the change in urine color was the ingestion of the herbicides. Spectrophotometric analysis of the urine was conducted and a peak was observed in the green area of the wavelength spectrum. These findings show that mefenacet and imazosulfuron should be considered in the differential diagnosis of green discolored urine

A One Health Framework for the Evaluation of Rabies Control Programmes: A Case Study from Colombo City, Sri Lanka

<div><p>Background</p><p>One Health addresses complex challenges to promote the health of all species and the environment by integrating relevant sciences at systems level. Its application to zoonotic diseases is recommended, but few coherent frameworks exist that combine approaches from multiple disciplines. Rabies requires an interdisciplinary approach for effective and efficient management.</p><p>Methodology/Principal Findings</p><p>A framework is proposed to assess the value of rabies interventions holistically. The economic assessment compares additional monetary and non-monetary costs and benefits of an intervention taking into account epidemiological, animal welfare, societal impact and cost data. It is complemented by an ethical assessment. The framework is applied to Colombo City, Sri Lanka, where modified dog rabies intervention measures were implemented in 2007. The two options included for analysis were the control measures in place until 2006 (“baseline scenario”) and the new comprehensive intervention measures (“intervention”) for a four-year duration. Differences in control cost; monetary human health costs after exposure; Disability-Adjusted Life Years (DALYs) lost due to human rabies deaths and the psychological burden following a bite; negative impact on animal welfare; epidemiological indicators; social acceptance of dogs; and ethical considerations were estimated using a mixed method approach including primary and secondary data. Over the four years analysed, the intervention cost US $1.03 million more than the baseline scenario in 2011 prices (adjusted for inflation) and caused a reduction in dog rabies cases; 738 DALYs averted; an increase in acceptability among non-dog owners; a perception of positive changes in society including a decrease in the number of roaming dogs; and a net reduction in the impact on animal welfare from intermediate-high to low-intermediate.</p><p>Conclusions</p><p>The findings illustrate the multiple outcomes relevant to stakeholders and allow greater understanding of the value of the implemented rabies control measures, thereby providing a solid foundation for informed decision-making and sustainable control.</p></div

Electric field and exciton structure in CdSe nanocrystals

Quantum Stark effect in semiconductor nanocrystals is theoretically investigated, using the effective mass formalism within a $4\times 4$ Baldereschi-Lipari Hamiltonian model for the hole states. General expressions are reported for the hole eigenfunctions at zero electric field. Electron and hole single particle energies as functions of the electric field ($\mathbf{E}_{QD}$) are reported. Stark shift and binding energy of the excitonic levels are obtained by full diagonalization of the correlated electron-hole Hamiltonian in presence of the external field. Particularly, the structure of the lower excitonic states and their symmetry properties in CdSe nanocrystals are studied. It is found that the dependence of the exciton binding energy upon the applied field is strongly reduced for small quantum dot radius. Optical selection rules for absorption and luminescence are obtained. The electric-field induced quenching of the optical spectra as a function of $\mathbf{E}_{QD}$ is studied in terms of the exciton dipole matrix element. It is predicted that photoluminescence spectra present anomalous field dependence of the emission lines. These results agree in magnitude with experimental observation and with the main features of photoluminescence experiments in nanostructures.Comment: 9 pages, 7 figures, 1 tabl

Upregulation of Glutamate Receptors in Rat Cerebral Cortex with Neuronal Migration Disorders

Neuronal migration disorders (NMDs) constitute the main pathologic substrate of medically intractable epilepsy in human. This study is designed to investigate the changes in expression of glutamate receptor subtypes on radiation-induced NMD in rats. The lesion was produced by intrauterine irradiation (240 cGy) on E17 rats, and then 10 weeks old rats were used for the study. The pathologic and immunohistochemical findings for glutamate receptor subunit proteins on NMD cortex were correlated with development of behavioral seizures and EEG abnormality. Spontaneous seizures uncommonly occurred in NMD rats (5%); however, clinical stages of seizures were significantly increased in NMD rats by an administration of kainic acid. Brains taken from irradiated rats revealed gross and histopathologic features of NMD. Focal cortical dysplasia was identified by histopathology and immunohistochemistry with neurofilament protein (NF-M/H). Significantly strong NR1 and NR2A/B immunoreactivities were demonstrated in cytomegalic and heterotopic neurons of NMD rats. The results of the present study indicate that epileptogenesis of NMD might be caused by upregulation of glutamate receptor expression in dysplastic neurons of the rat cerebral cortex with NMDs

Transforaminal endoscopic surgery for symptomatic lumbar disc herniations: a systematic review of the literature

The study design includes a systematic literature review. The objective of the study was to evaluate the effectiveness of transforaminal endoscopic surgery and to compare this with open microdiscectomy in patients with symptomatic lumbar disc herniations. Transforaminal endoscopic techniques for patients with symptomatic lumbar disc herniations have become increasingly popular. The literature has not yet been systematically reviewed. A comprehensive systematic literature search of the MEDLINE and EMBASE databases was performed up to May 2008. Two reviewers independently checked all retrieved titles and abstracts and relevant full text articles for inclusion criteria. Included articles were assessed for quality and outcomes were extracted by the two reviewers independently. One randomized controlled trial, 7 non-randomized controlled trials and 31 observational studies were identified. Studies were heterogeneous regarding patient selection, indications, operation techniques, follow-up period and outcome measures and the methodological quality of these studies was poor. The eight trials did not find any statistically significant differences in leg pain reduction between the transforaminal endoscopic surgery group (89%) and the open microdiscectomy group (87%); overall improvement (84 vs. 78%), re-operation rate (6.8 vs. 4.7%) and complication rate (1.5 vs. 1%), respectively. In conclusion, current evidence on the effectiveness of transforaminal endoscopic surgery is poor and does not provide valid information to either support or refute using this type of surgery in patients with symptomatic lumbar disc herniations. High-quality randomized controlled trials with sufficiently large sample sizes are direly needed to evaluate if transforaminal endoscopic surgery is more effective than open microdiscectomy

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)