Near-field optical power transmission of dipole nano-antennas

Nano-antennas in functional plasmonic applications require high near-field optical power transmission. In this study, a model is developed to compute the near-field optical power transmission in the vicinity of a nano-antenna. To increase the near-field optical power transmission from a nano-antenna, a tightly focused beam of light is utilized to illuminate a metallic nano-antenna. The modeling and simulation of these structures is performed using 3-D finite element method based full-wave solutions of Maxwell’s equations. Using the optical power transmission model, the interaction of a focused beam of light with plasmonic nanoantennas is investigated. In addition, the tightly focused beam of light is passed through a band-pass filter to identify the effect of various regions of the angular spectrum to the near-field radiation of a dipole nano-antenna. An extensive parametric study is performed to quantify the effects of various parameters on the transmission efficiency of dipole nano-antennas, including length, thickness, width, and the composition of the antenna, as well as the wavelength and half-beam angle of incident light. An optimal dipole nanoantenna geometry is identified based on the parameter studies in this work. In addition, the results of this study show the interaction of the optimized dipole nano-antenna with a magnetic recording medium when it is illuminated with a focused beam of light

A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s

At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4-6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism

Clinical impact of real-time evaluation of the biological activity and degradation of hepatocyte growth factor

Hepatocyte growth factor (HGF) is essential for injury repair. Despite high HGF levels in chronic ulcers, up-regulation of HGF receptor in ulcer tissue and decreased biological activity of HGF in ulcer secretions have been observed. With a surface plasmon resonance-based method, we assessed the binding of HGF to antibodies, receptors, and the basement membrane and identified binding interactions that are indispensable for the biological activity of HGF. Recombinant HGF (rHGF) lots were tested for activity, structural integrity, and degradation, and the results were verified in an in vitro model of cell injury. Biologically active rHGF, as well as plasma from healthy volunteers, bound to heparan sulphate proteoglycan (HSPG) and to anti-HGF antibodies. Decreased binding to HSPG was the first event in rHGF degradation. This study established the feasibility of identifying patients with chronic inflammation who need exogenous HGF and of using ligand-binding assessment to evaluate rHGF lots for biological activity

Alcohol consumption and risk of urothelial cell bladder cancer in the European Prospective Investigation into Cancer and Nutrition cohort

Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition cohort. We included 476,160 individuals mostly aged 35-70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 incident cases) were calculated using Cox proportional hazards models. Alcohol consumption at baseline and over the life course was analyzed, as well as different types of beverages (beer, wine, spirits). Baseline alcohol intake was associated with a statistically non-significant increased risk of UCC (HR 1.03; 95% confidence interval (CI) 1.00-1.06 for each additional 12 grams/day). HR in smokers was 1.04 (95% CI 1.01-1.07). Men reporting high baseline intakes of alcohol (>96 grams/day) had an increased risk of UCC (HR 1.57; 95% CI 1.03-2.40) compared to those reporting moderate intakes (6 to 24 grams/day). Average lifelong alcohol intake was not associated with the risk of UCC, however intakes of spirits > 24 grams/day were associated with an increased risk of UCC in men (1.38; 95% CI 1.01-1.91) and smokers (1.39; 95% CI 1.01-1.92), compared to moderate intakes. We found no association between alcohol and UCC in women and never smokers. In conclusion, we observed some associations between alcohol and UCC in men and in smokers, possibly due to residual confounding by tobacco smoking. This article is protected by copyright. All rights reserved

Oynophagia in patients after dental extraction: surface electromyography study

OBJECTIVES: Surface electromyographic (sEMG) studies were performed on 40 adult patients following extraction of lower third and second molars to research the approach and limitations of sEMG evaluation of their odynophagia complaints. METHODS: Parameters evaluated during swallowing and drinking include the timing, number of swallows per 100 cc of water, and range (amplitude) of EMG activity of m. masseter, infrahyoid and submental-submandibular group. The above mentioned variables (mean + standard deviation) were measured for the group of dental patients (n = 40) and control group of healthy adults (n = 40). RESULTS: The duration of swallows and drinking in all tests showed increase in dental patients' group, in which this tendency is statistically significant. There was no statistically significant difference between male and female adults' duration and amplitude of muscle activity during continuous drinking in both groups (p = 0.05). The mean of electric activity (in μV) of m. masseter was significantly lower in the dental patients' group in comparison with control group. The electric activity of submental-submandimular and infrahyoid muscle groups was the same in both groups. CONCLUSION: Surface EMG of swallowing is a simple and reliable noninvasive method for evaluation of odynophagia/dysphagia complaints following dental extraction with low level of discomfort of the examination. The surface EMG studies prove that dysphagia following dental extraction and molar surgery has oral origin, does not affect pharingeal segment and submental-submandibular muscle group. This type of dysphagia has clear EMG signs: increased duration of single swallow, longer drinking time, low range of electric activity of m. masseter, normal range of activity of submental-submandibular muscle group, and the "dry swalow" aftereffect. The data can be used for evaluation of complaints and symptoms, as well as for comparison purposes in pre- and postoperative stages and in EMG monitoring during treatment of post-surgical oral cavity discomfort and dysphagia

Integrated Genomic and Gene Expression Profiling Identifies Two Major Genomic Circuits in Urothelial Carcinoma

Similar to other malignancies, urothelial carcinoma (UC) is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes were included in the amplified regions, including known oncogenes like E2F3, CCND1, and CCNE1, as well as new candidate genes, such as SETDB1 (1q21), and BCL2L1 (20q11). We next combined genome profiling with global gene expression, gene mutation, and protein expression data and identified two major genomic circuits operating in urothelial carcinoma. The first circuit was characterized by FGFR3 alterations, overexpression of CCND1, and 9q and CDKN2A deletions. The second circuit was defined by E3F3 amplifications and RB1 deletions, as well as gains of 5p, deletions at PTEN and 2q36, 16q, 20q, and elevated CDKN2A levels. TP53/MDM2 alterations were common for advanced tumors within the two circuits. Our data also suggest a possible RAS/RAF circuit. The tumors with worst prognosis showed a gene expression profile that indicated a keratinized phenotype. Taken together, our integrative approach revealed at least two separate networks of genomic alterations linked to the molecular diversity seen in UC, and that these circuits may reflect distinct pathways of tumor development

Do diagnostic delays in cancer matter?

background: The United Kingdom has poorer cancer outcomes than many other countries due partly to delays in diagnosing symptomatic cancer, leading to more advanced stage at diagnosis. Delays can occur at the level of patients, primary care, systems and secondary care. There is considerable potential for interventions to minimise delays and lead to earlier-stage diagnosis. methods: Scoping review of the published studies, with a focus on methodological issues. results: Trial data in this area are lacking and observational studies often show no association or negative ones. This review offers methodological explanations for these counter-intuitive findings. conclusion: While diagnostic delays do matter, their importance is uncertain and must be determined through more sophisticated methods

A Systematic Study of Gene Mutations in Urothelial Carcinoma; Inactivating Mutations in TSC2 and PIK3R1

Abstract BACKGROUND: Urothelial carcinoma (UC) is characterized by frequent gene mutations of which activating mutations in FGFR3 are the most frequent. Several downstream targets of FGFR3 are also mutated in UC, e.g., PIK3CA, AKT1, and RAS. Most mutation studies of UCs have been focused on single or a few genes at the time or been performed on small sample series. This has limited the possibility to investigate co-occurrence of mutations. METHODOLOGY/PRINCIPAL FINDINGS: We performed mutation analyses of 16 genes, FGFR3, PIK3CA, PIK3R1 PTEN, AKT1, KRAS, HRAS, NRAS, BRAF, ARAF, RAF1, TSC1, TSC2, APC, CTNNB1, and TP53, in 145 cases of UC. We show that FGFR3 and PIK3CA mutations are positively associated. In addition, we identified PIK3R1 as a target for mutations. We demonstrate a negative association at borderline significance between FGFR3 and RAS mutations, and show that these mutations are not strictly mutually exclusive. We show that mutations in BRAF, ARAF, RAF1 rarely occurs in UC. Our data emphasize the possible importance of APC signaling as 6% of the investigated tumors either showed inactivating APC or activating CTNNB1 mutations. TSC1, as well as TSC2, that constitute the mTOR regulatory tuberous sclerosis complex were found to be mutated at a combined frequency of 15%. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a significant association between FGFR3 and PIK3CA mutations in UC. Moreover, the identification of mutations in PIK3R1 further emphasizes the importance of the PI3-kinase pathway in UC. The presence of TSC2 mutations, in addition to TSC1 mutations, underlines the involvement of mTOR signaling in UC

Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma

Molecular changes occurring during invasion and clinical progression of cancer are difficult to study longitudinally in patient-derived material. A unique feature of urothelial bladder cancer (UBC) is that patients frequently develop multiple nonmuscle invasive tumors, some of which may eventually progress to invade the muscle of the bladder wall. Here, we use a cohort of 73 patients that experienced a total of 357 UBC diagnoses to study the stability or change in detected molecular alterations during cancer progression. The tumors were subtyped by gene expression profiling and analyzed for hotspot mutations in FGFR3, PIK3CA and TERT, the most frequent early driver mutations in this tumor type. TP53 alterations, frequent in advanced UBC, were inferred from p53 staining pattern, and potential genomic alterations were inferred by gene expression pattern