UV responsive quercetin derived and functionalized CuO/ZnO nanocomposite in ameliorating photocatalytic degradation of rhodamine B dye and enhanced biocidal activity against selected pathogenic strains.

Quercetin was investigated for its role as a reducing agent in biosynthesizing CuO/ZnO nanocomposite, its subsequent surface functionalization and influence in Rhodamine B dye degradation and biocidal activity. The as synthesized quercetin functionalized CuO/ZnO nanocomposite (CuO/ZnO@Q) was analyzed using X-ray diffraction (XRD), Fourier transform infra red spectroscopy (FTIR), Transmission electron microscopy (TEM), Energy dispersive spectroscopy (EDS) and Ultraviolet-visible spectroscopy (UV-Vis). XRD showed the formation of crystalline CuO, ZnO phases and FTIR analysis revealed the incorporation of quercetin functional groups in the synthesized nanocomposite. TEM image displayed the formation of quercetin deposited spherical CuO/ZnO nanostructure with the EDAX results confirming the presence of organic carbon composition from quercetin. The UV absorption spectra ascertained the presence and role of quercetin in the enhanced absorption of radiation in the UV range. CuO/ZnO@Q showed improved photocatalysis with complete Rhodamine B dye degradation after 75 min of UV irradiation, as against pure CuO/ZnO, which exhibited incomplete dye degradation even after 90 min of irradiation. Moreover, quercetin surface functionalization effectively ameliorated its antimicrobial activity against E. coli, S. aureus, Shigella, B. subtilis, A. niger and C. albicans, proving its potential in significantly enhancing biocidal activity along with photocatalytic dye degradation in a natural and eco-friendly route.

Tripolyphosphate crosslinked Triticum aestivum (wheatgrass) functionalized antimicrobial chitosan: Ameliorating effect on physicochemical, mechanical, invitro cytocompatibility and cell migration properties.

Polymeric films for various biomedical applications require to be biocompatible and non- toxic. Chemical route of modifications for functionalization of the films for improved properties lead to undesirable effects for biological applications. Hence a natural way to enhancing their properties is by functionalizing them using plant extracts. This report investigates the synthesis of bioactive phytochemical loaded polymer using Triticum aestivum (wheatgrass) extract incorporated in tripolyphosphate crosslinked chitosan. Physical and mechanical properties of the extract functionalized crosslinked chitosan were analyzed and this showed significant changes in thickness, tensile strength and % elongation of the blend. The extract functionalized chitosan was characterized using Fourier transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM) and Energy dispersive spectroscopy (EDAX) confirming the interaction between the functional moieties of the extract and polymer. Antimicrobial analysis showed improved activity against Escherichia coli and Staphylococus aureus and Candida albicans. Presence of the extract in crosslinked chitosan enhanced the cytocompatibility in 3T3 cells carried out by MTT assay and showed improved cell migration properties determined by scratch assay.Communicated by Ramaswamy H. Sarma.

Protein binding and antioxidant studies of diimine based emissive surfactant-ruthenium(II) complexes.

Biophysical interaction of amphiphilic fluorescent surfactant-ruthenium(II) complexes and its precursor ruthenium(II) complexes with drug carrying proteins such as bovine and human serum albumins (BSA and HSA) have been studied through the UV-visible absorption, fluorescence and circular dichroism spectroscopic techniques to correlate the impact of head and tail groups of the metallosurfactants towards the designing of metallodrugs for the biomedical applications. The obtained results showed that both precursor- and surfactant-ruthenium(II) complexes interact with BSA/HSA via ground state protein-complex formation and their quenching follows the static mechanism. The extent of protein quenching and binding parameters resulted that the surfactant-ruthenium(II) complexes effectively interact with protein compared to their precursor-ruthenium(II) complexes, and also those interaction have greatly influenced by the change in the head group size compared to change in the tail group length. Interestingly on increasing the temperature, the protein-complex binding strength was decreased for the precursor-ruthenium(II) complexes, those increased for the surfactant-ruthenium(II) complexes, probably due to the respective involvement of electrostatic and hydrophobic interactions as supported by the thermodynamics of protein-complex interaction. Moreover, the results from UV-visible, synchronous and circular dichroism studies confirmed the occurrence of conformational and micro environmental changes in BSA/HSA upon binding with these complexes. It is also noted that HSA has more binding affinity with surfactant-ruthenium(II) complexes compared to BSA. The free radical scavenging ability against DPPH, ABTS, NO and superoxide free radical assays suggested that surfactant-ruthenium(II) complexes have better free radical scavenging ability compared to precursor-ruthenium(II) complexes.Communicated by Ramaswamy H. Sarma.

Letter--Value-Driven Treatment Decisions: Need of the Hour for Relapsed/Refractory Multiple Myeloma.

DISCLOSURES: No funding was involved in the writing of this letter. Medhekar, Sapra, Majer, Harrison, and Tekle are employees of and stockholders in Amgen.

Factors Associated with Direct Health Care Costs Among Patients with Migraine.

BACKGROUND: Migraine imposes substantial economic burden on patients and the health care system. Approximately 18% of women and 6% of men suffer from migraine in the United States. This is a heterogeneous group, and little data are available to evaluate factors associated with migraine costs. OBJECTIVE: To evaluate characteristics associated with high costs among commercially insured patients with migraine. METHODS: This retrospective analysis identified patients with migraine in the Truven Health MarketScan Research Databases between January 2008 and June 2013. Patients were required to have 12 months continuous enrollment before and after migraine diagnoses and/or migraine-specific medications (index date). Patients with costs greater than the top 25th percentile of all-cause costs during the 12-month post-index period were classified into the upper quartile (UQ) cohort. Multiple logistic regression was used to evaluate demographic and clinical factors associated with being in the UQ cohort, and generalized linear models were used to estimate the incremental costs by select factors after controlling for other covariates. RESULTS: In the total population, 857,073 patients (mean [SD] age: 43.2 [12.5] years), were included, with 83.2% females. Average post-index annual all-cause costs were $13,045 (SD = $25,328) with the top 25th percentile of costs at $14,120. Overall, 44.4% and 54.8% of patients had ≥ 1 pre-index claim for opioids and triptans, respectively. Patients with ≥ 2 migraine-related emergency room visits were twice as likely to be in the UQ cohort (OR = 2.13, 95% CI = 2.02-2.25; P < 0.05) and incurred $3,125 incremental all-cause costs compared with those with < 2 visits. Patients who visited a neurologist were 33.0% more likely to be in the UQ cohort and had significantly higher adjusted all-cause costs ($11,794 vs. $9,868, P < 0.05). Opioid users had a 1.5-3 times increased likelihood of being in the UQ cohort (P < 0.05); adjusted all-cause annual costs ranged from $8,888 (95% CI = $8,862-$8,914) for nonusers to $15,210 (95% CI = $15,113-$15,307) for high users (7+ claims). Patients having 7+ triptan claims were 1.2 times as likely to be in the UQ cohort compared with nonusers, with estimated costs of $11,517 (95% CI = $11,438-$11,596) for high users and $10,753 (95% CI = $10,717-$10,790) for nonusers. CONCLUSIONS: Results suggest that certain modifiable factors, such as increased acute medication use (opioids and triptans) and more migraine-related emergency room visits are associated with higher all-cause health care costs for patients with migraine. These findings could be used to identify patients who require early intervention, enhanced symptoms monitoring, and appropriate disease management. Future studies could examine the effect of disease severity on health resource utilization and costs using survey or medical record data. DISCLOSURES: This study was funded by Amgen and conducted by Truven Health Analytics. Bonafede, Cappell, and Kim are employees of Truven Health Analytics, which received compensation from Amgen for the overall conduct of the study and preparation of the manuscript. Cai was an employee of Truven Health Analytics at the time of this study. Sapra, Shah, and Desai are employees of Amgen. Katherine Widnell was an employee of Amgen when the manuscript draft was developed. Winner reports receiving research support from Allergan, Amgen, A-Z, Teva, Pfizer, Novartis, and Lilly. Study concept and design were contributed by Bonafede, Sapra, Shah, and Desai, along with Widnell and Winner. Kim and Cai took the lead in data collection, assisted by Bonafede and Cappell. Data interpretation was performed by Widnell and Winter, along with the other authors. All authors contributed to the writing and revision of the manuscript.

Health state utilities associated with attributes of treatments for hepatitis C.

BACKGROUND: Cost-utility analyses are frequently conducted to compare treatments for hepatitis C, which are often associated with complex regimens and serious adverse events. Thus, the purpose of this study was to estimate the utility associated with treatment administration and adverse events of hepatitis C treatments. DESIGN: Health states were drafted based on literature review and clinician interviews. General population participants in the UK valued the health states in time trade-off (TTO) interviews with 10- and 1-year time horizons. The 14 health states described hepatitis C with variations in treatment regimen and adverse events. RESULTS: A total of 182 participants completed interviews (50% female; mean age = 39.3 years). Utilities for health states describing treatment regimens without injections ranged from 0.80 (1 tablet) to 0.79 (7 tablets). Utilities for health states describing oral plus injectable regimens were 0.77 (7 tablets), 0.75 (12 tablets), and 0.71 (18 tablets). Addition of a weekly injection had a disutility of -0.02. A requirement to take medication with fatty food had a disutility of -0.04. Adverse events were associated with substantial disutilities: mild anemia, -0.12; severe anemia, -0.32; flu-like symptoms, -0.21; mild rash, -0.13; severe rash, -0.48; depression, -0.47. One-year TTO scores were similar to these 10-year values. CONCLUSIONS: Adverse events and greater treatment regimen complexity were associated with lower utility scores, suggesting a perceived decrease in quality of life beyond the impact of hepatitis C. The resulting utilities may be used in models estimating and comparing the value of treatments for hepatitis C.

A 1-year pilot study of vagus nerve stimulation in treatment-resistant rapid-cycling bipolar disorder.

OBJECTIVE: Vagus nerve stimulation (VNS) appears to be an effective treatment option for patients with treatment-resistant unipolar and bipolar depression. The aim of the present study was to investigate the efficacy of VNS in a group of patients with treatment-resistant rapid-cycling bipolar disorder (RCBD) who were excluded from previous trials. METHOD: Nine outpatients with a DSM-IV-TR diagnosis of treatment-resistant RCBD were treated for 40 weeks with open-label VNS. The first patient was enrolled in June 2001, and the last patient completed the study in July 2005. Patients recorded their depression and mania mood symptoms on a daily basis throughout the study using the National Institute of Mental Health prospective life charting methodology and daily mood ratings. Patients were assessed every 2 weeks during the 2-month baseline period before device activation, every 2 weeks for the remaining 40 weeks of the study, and at the end of the study with the 24-item Hamilton Rating Scale for Depression (HAM-D-24), the 10-item Montgomery-Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Clinical Global Impressions (CGI) scale, the Global Assessment of Functioning (GAF) scale, and the 30-item Inventory of Depressive Symptomatology Self-Report (IDS-SR-30). Any adverse events or device complications were also recorded at each visit. The prospective life charts were analyzed by calculating the area under the curve. Statistical analysis was performed with a mixed-model repeated-measures regression analysis for repeated measures of the various rating scales. Significant p values were < or = .05. RESULTS: Over the 12-month study period, VNS was associated with a 38.1% mean improvement in overall illness as compared to baseline (p = .012), as well as significant reductions in symptoms as measured by the HAM-D-24 (p = .043), MADRS (p = .003), CGI (p = .013), and GAF (p < .001) rating scales. Common adverse events were voice alteration during stimulation and hoarseness. CONCLUSION: These data suggest that VNS may be an efficacious and well-tolerated treatment option for patients with treatment-resistant RCBD. Currently, no comparison is available in the literature. Larger randomized trials are needed to verify these findings.

Tuberculosis screening: usefulness of new KREATECH IgA ELISA test.

A total of 71 sera from 15 proved cases of pulmonary tuberculosis, 2 cases with doubtful radiological report and 54 suspected cases, contacts, donors etc. were subjected to Elisa IgG, IgM and IgA tests for tuberculosis, with a view to comparing the merits of IgA test with those of IgG and IgM. Kreatech IgA test which is claimed to indicate presence of active tuberculosis was positive in 13 of the proved cases and negative in both the doubtful cases. These preliminary results indicate that KREATECH IgA is a promising new ELISA test which can be a useful laboratory aid in the diagnosis of active tuberculosis, both pulmonary and extrapulmonary, for screening of suspected cases, and for monitoring cases undergoing therapy.