Simple sonochemical synthesis of novel grass-like vanadium disulfide: A viable non-enzymatic electrochemical sensor for the detection of hydrogen peroxide.

Design and fabrication of novel inorganic nanomaterials for the low-level detection of food preservative chemicals significant is of interest to the researchers. In the present work, we have developed a novel grass-like vanadium disulfide (GL-VS2) through a simple sonochemical method without surfactants or templates. As-prepared VS2 was used as an electrocatalyst for reduction of hydrogen peroxide (H2O2). The crystalline nature, surface morphology, elemental compositions and binding energy of the as-prepared VS2 were analyzed by X-ray diffraction, Raman spectroscopy, field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The electrochemical studies show that the GL-VS2 modified glassy carbon electrode (GL-VS2/GCE) has a superior electrocatalytic activity and lower-reduction potential than the response observed for unmodified GCE. Furthermore, the GL-VS2/GCE displayed a wide linear response range (0.1-260 µM), high sensitivity (0.23 µA µM-1 cm-2), lower detection limit (26 nM) and excellent selectivity for detection of H2O2. The fabricated GL-VS2/GCE showed excellent practical ability for detection of H2O2 in milk and urine samples, revealing the real-time practical applicability of the sensor in food contaminants.

Synchronous or metachronous lymphoma and metastatic cutaneous squamous cell carcinoma in the head and neck region: a diagnostic and management dilemma.

OBJECTIVE: To review our experience of managing patients with a dual diagnosis of metastatic cutaneous squamous cell carcinoma in the head and neck region and low-grade non-Hodgkin lymphoma. The secondary aim was to evaluate the utility of 18F-fluorodeoxyglucose positron emission tomography during diagnosis. METHODS: Patients diagnosed with metastatic cutaneous squamous cell carcinoma of the head and neck and low-grade non-Hodgkin lymphoma, in a five-year period, were identified. Patient, tumour and treatment characteristics were identified. 18F-fluorodeoxyglucose positron emission tomography imaging was reviewed and correlated with histopathology findings. RESULTS: Eight patients were identified. There was a delay in diagnosis of metastatic squamous cell carcinoma in two patients. 18F-fluorodeoxyglucose positron emission tomography differentiated metastatic squamous cell carcinoma from low-grade non-Hodgkin lymphoma with a sensitivity of 88.2 per cent and a specificity of 94.7 per cent. In 38 per cent of patients, compromises in management had to be made. CONCLUSION: The management of metastatic squamous cell carcinoma can be challenging in patients with low-grade non-Hodgkin lymphoma. 18F-fluorodeoxyglucose positron emission tomography can be useful in the diagnosis of metastatic squamous cell carcinoma in patients with low-grade non-Hodgkin lymphoma.

Phase 1 in the development of a patient-reported measure to quantify perceived inconvenience of radiotherapy: generation of issues.

AIMS: Current patient-reported measures (PROMs) do not specifically address radiotherapy (RT) related inconvenience. We conducted, as per guidelines of the European Organization for Research and Treatment of Cancer (EORTC), the initial (issue generation) phase of development of a RT inconvenience PROM. Specifically, we aimed to develop a conceptual framework for RT inconvenience and generate a comprehensive list of issues pertaining to it. METHODS: We reviewed existing PROMs and literature and gathered qualitative and quantitative data from consumers and health professionals, in order to generate a comprehensive list of issues pertaining to RT inconvenience. A framework for the consideration of RT inconvenience was defined and used to ensure all possible issues were explored and to list the issues into conceptual domains. RESULTS: Qualitative data from 26 consumers and 30 health professionals, and quantitative data from 1191 consumers and 253 health professionals resulted in the identification of 38 issues grouped into five conceptual domains: (1) inconvenience of RT opportunity, (2) inconvenience of decision-making, (3) inconvenience of treatment, (4) inconvenience of side effects, and (5) inconvenience of follow-up. CONCLUSIONS: This list of RT inconvenience issues will, in future work, be operationalized into a set of items for pretesting and then large-scale field testing as per the EORTC guidelines.

Engaging Future Clinical Oncology Researchers: An Initiative to Integrate Teaching of Biostatistics and Research Methodology into Specialty Training.

AIMS: To evaluate the learner's perspectives on a novel workshop programme designed to improve skills in biostatistics, research methodology and critical appraisal in oncology. MATERIALS AND METHODS: Trainees were surveyed anonymously at the completion of each annual workshop from 2012 to 2015. In total, 103 trainees in years 2-4 of training in radiation oncology responded, giving a 94% survey response rate. A 1 day workshop, designed by biostatisticians and radiation oncologist facilitators, is the central component of a programme teaching skills in biostatistics, research methods and critical appraisal. This links short didactic lectures about statistical concepts to interactive trainee discussions around discipline-related publications. RESULTS: The workshop was run in conjunction with the major radiation oncology clinical trials group meeting with alternating programmes (A and B). Most of the participants (44-47/47 for A and 48-55/56 for B), reported that their understanding of one or more individual topics improved as a result of teaching. Refinement of the workshop over time led to a more favourable perception of the 'optimal' balance between didactic/interactive teaching: nine of 27 (33%) 'optimal' responses seen in 2013 compared with 23 of 29 (79%) in 2015 (P < 0.001). Commonly reported themes were: clinician facilitators and access to biostatisticians helped contextualise learning and small group, structured discussions provided an environment conducive to learning. CONCLUSIONS: Overall, radiation oncology trainees reported positive perceptions of the educational value of this programme, with feedback identifying areas where this resource might be improved. This model could readily be adapted to suit other medical disciplines and/or other training environments, using specialty-specific research to illuminate key statistical concepts.

Examining Determinants of Radiotherapy Access: Do Cost and Radiotherapy Inconvenience Affect Uptake of Breast-conserving Treatment for Early Breast Cancer?

AIMS: Radiotherapy utilisation is likely affected by multiple factors pertaining to radiotherapy access. Radiotherapy is an integral component of breast-conserving treatment (BCT) for early breast cancer. We aimed to determine if stepwise improvements in radiotherapy access in regional Australia affected the uptake of BCT and thus radiotherapy. MATERIALS AND METHODS: Breast cancer operations in the Central Coast of New South Wales between January 2010 and March 2014 for T1-2N0-1M0 invasive or in situ (≤5 cm) disease in female patients eligible for BCT were examined. BCT uptake was calculated for three 1 year periods: period 1 (local radiotherapy available at cost to user or out of area radiotherapy with travel cost and inconvenience); period 2 (as per period 1 + publicly funded transport and radiotherapy at out of area facilities at no cost to user); period 3 (as per period 1 + publicly funded local radiotherapy at no cost to user). RESULTS: In total, 574 cases met eligibility criteria. BCT declined with increasing distance to publicly funded radiotherapy (P = 0.035). BCT rates for periods 1, 2 and 3 were 63% (113/180), 61% (105/173) and 71% (156/221). There were no statistically significant differences in BCT between periods 1 and 2 in the whole cohort or within age, histology or tumour size subgroups. Overall, there was a 9% increase in BCT in the whole cohort in period 3 compared with periods 1 and 2 (P = 0.031). This increase was statistically significant for women over 70 years (19% increase, P = 0.034), for women with ductal carcinoma in situ (25% increase, P = 0.013) and for women with primary tumours that were ≤10 mm (21% increase, P = 0.016). CONCLUSIONS: Improving the affordability of radiotherapy through publicly funded transport and radiotherapy at out of area facilities did not improve BCT uptake in a region where radiotherapy was locally available, albeit at cost to the user. Improving both affordability and convenience through the provision of local publicly funded radiotherapy increased BCT uptake. Service availability and affordability have long been recognised as important determinants of radiotherapy access. Our findings suggest that inconvenience may also influence radiotherapy utilisation.

Patients' perceptions of health-related quality of life during and after adjuvant radiotherapy for T1N0M0 breast cancer.

AIMS: The effects of radiotherapy on health-related quality of life (HRQOL) may influence decisions about adjuvant radiotherapy after breast-conserving surgery. We sought women's ratings of HRQOL during and after radiotherapy. MATERIALS AND METHODS: Women completed HRQOL measures before, during and after adjuvant radiotherapy for node-negative, hormone receptor-positive breast cancers that were less than 2 cm in size. Acute and late toxicities were rated by clinicians. RESULTS: There were 161 participants with a median age of 58 years (range 34-82). Mean scores for most aspects of HRQOL worsened only slightly during radiotherapy and improved to baseline levels or better within a few months. The symptoms rated as most distressing were: difficulty sleeping (29%), fatigue (23%), breast discolouration (21%), uncertainty about the future (18%), feeling sad or depressed (18%), feeling anxious or worried (19%). Most rated their experience as better (39%) or much better (28%) than expected. Grade 3 toxicities were rare (5% acute, 1% late) with no grade 4 toxicities. CONCLUSIONS: Radiotherapy was associated with transient and generally mild impairments in a few aspects of HRQOL. Concerns about adverse effects on HRQOL should not weigh heavily on decisions about adjuvant breast radiotherapy.

Do screening trial recruitment logs accurately reflect the eligibility criteria of a given clinical trial? Early lessons from the RAVES 0803 trial.

AIMS: Maintaining clinical trial screening logs and reporting data from such logs are given importance due to the relevance of a trial's patient population to the generalisability of its findings. However, screening logs may not always reflect a clinical trial's true target population. The aim of the present study was to define and compare 'apparent recruitment' to a trial as captured in a clinical trial screening log with 'true recruitment', which considers all potentially eligible patients. The Trans Tasman Radiation Oncology Group (TROG) 0803 RAVES clinical trial was used to examine the above. MATERIALS AND METHODS: A prospective, surgical database was interrogated for the 12 month period to identify patients potentially eligible for the TROG 0803 RAVES trial. Information on whether patients were referred to a RAVES trial recruitment site and reasons for non-referral were obtained. RESULTS: Of 92 men undergoing radical prostatectomy, 28 met the RAVES clinical trial eligibility criteria. Fifteen of the 28 eligible men were assessed at a RAVES trial site, with five being ultimately recruited to RAVES (33% 'apparent recruitment fraction' as captured by the site's trial screening log). The 'true recruitment fraction' was 5/28 (18%). CONCLUSION: Screening logs at a recruiting trial site may underestimate the trial's target population and overestimate recruitment. Only a subpopulation of all eligible patients may be captured in trial screening logs and subsequently reported on. This may affect the generalisability of the trial's reported findings.

Definitive radiotherapy or chemoradiotherapy in the treatment of Merkel cell carcinoma.

AIMS: Merkel cell carcinoma (MCC) is a radiosensitive tumour. Radiotherapy has an important role in its treatment, including definitive management. This study aimed to determine the in-field control achieved with definitive radiotherapy or chemoradiotherapy (CRT) and to examine patterns of relapse. MATERIALS AND METHODS: Patients treated with definitive radiotherapy or CRT for biopsy-confirmed MCC were identified from records of the Royal Prince Alfred Hospital and Melanoma Institute Australia. Definitive treatment was defined as treatment delivered to macroscopic or residual microscopic disease at the primary site or in regional nodes. Patients with distant metastatic disease at presentation and those treated electively or adjuvantly (i.e. after microscopically clear excision) were excluded. RESULTS: Of 26 patients treated with definitive radiotherapy (n = 18) or CRT (n = 8), 20 were disease free at last follow-up (median follow-up 23.5 months). Five of the six patients who recurred did so at distant sites, with two experiencing simultaneous in-field failure at treated nodal sites where there had been macroscopic disease at presentation. Eighty-nine per cent of all patients and 85% of those with macroscopic disease were free of in-field recurrence at 2 years. CONCLUSION: Definitive radiotherapy or CRT produces excellent in-field disease control in the treatment of primary and regionally metastatic MCC.

Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer.

Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks ('early death') may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of 'early death'. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with 'early death'. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of 'early death'. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for 'early death'. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.

Polymorphisms in an intronic region of the myocilin gene associated with primary open-angle glaucoma--a possible role for alternate splicing.

PURPOSE: To examine the possible role of alternate splicing leading to aggregation of myocilin in primary open-angle glaucoma. METHODS: Several single nucleotide variations found in the myocilin (MYOC) genomic region were collected and examined for their possible role in causing splice-site alterations. A model for myocilin built using a knowledge-based consensus method was used to map the altered protein products. A total of 150 open-angle glaucoma patients and 50 normal age-matched control subjects were screened for the predicted polymorphisms, and clustering was performed. RESULTS: A total of 124 genomic variations were screened, and six polymorphisms that lead to altered protein products were detected as possible candidates for the alternative splicing mechanism. Five of these lay in the intronic regions, and the one that lay in the exon region corresponded to the previously identified polymorphism (Tyr347Tyr) implicated in primary open-angle glaucoma. Experimentally screening the intronic region of the MYOC gene showed the presence of the predicted g.14072G>A polymorphism, g.1293C/T heterozygous polymorphism, instead of our predicted g.1293C/- polymorphism. Other than the prediction, two novel SNPs (g.1295G>T and g.1299T>G) and two reported SNPs (g.1284G>T and g.1286G>T) were also identified. Cluster analysis showed the g.14072G>A homozygous condition was more common in this cohort than the heterozygous condition. CONCLUSIONS: We previously proposed that the disruption of dimer or oligomer formation by the C-term region allows greater chances of nucleation for aggregation. Here we suggest that polymorphisms in the myocilin genomic region that cause synonymous codon changes or those that occur in the intron regions can possibly lead to altered myocilin protein products through altered intron-exon splicing.

The mutations and potential targets of the forkhead transcription factor FOXL2.

Mutations of FOXL2, a gene encoding a forkhead transcription factor, have been shown to cause the blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). This genetic disorder is characterized by eyelid and mild craniofacial abnormalities that can appear associated with premature ovarian failure. FOXL2 is one of the earliest ovarian markers and it offers, along with its targets, an excellent model to study ovarian development and function in normal and pathological conditions. In this review we summarize recent data concerning FOXL2, its mutations and its potential targets. Indeed, many mutations have been described in the coding sequence of FOXL2. Among them, polyalanine expansions and premature nonsense mutations have been shown to induce protein aggregation. In the context of the ovary, FOXL2 has been suggested to be involved in the regulation of cholesterol and steroid metabolism, apoptosis, reactive oxygen species detoxification and inflammation processes. The elucidation of the impact of FOXL2 mutations on its function will allow a better understanding of the pathogenic mechanisms underlying the BPES phenotype.

Stereotactic radiotherapy for the treatment of neurosarcoidosis involving the pituitary gland and hypothalamus.

We report the case of a 38-year-old, female patient with neurosarcoidosis involving the pituitary gland and hypothalamus, who was treated with stereotactic radiotherapy (24 Gy in 12 fractions) with an excellent result. The purpose of this case report was to illustrate and discuss the diagnostic and therapeutic challenges faced in the management of neurosarcoidosis, as well as document our experience with the use of stereotactic radiotherapy in the treatment of neurosarcoidosis.

Isolation and characterisation of selected germander diterpenoids from authenticated Teucrium chamaedrys and T. canadense by HPLC, HPLC-mS and NMR.

Teucrium species, such as germander, are rich in neo-clerodane diterpenoids and have been used in traditional folk medicine for their stimulant, diuretic, antipyretic and antiseptic properties. However, the furano neo-clerodane diterpenoids present in germander have been implicated in the in vivo hepatotoxicity of this botanical. In this study, authenticated germander (Teucrium chamaedrys L. and Teucrium canadense L.) was used as the source material. Methanol extracts of powdered plant mate rial were prepared and analysed by HPLC using Synergi Max-RP columns with monitoring at 220 nm. Limited amounts of teucrin A and other diterpenoid standards were analysed on a Synergi Max-RP column in order to determine their retention times and to generate calibration curves. The same standards were subjected to concurrent mass spectral analysis. Teucrin A and diterpenoids such as dihydroteugin, teuflin, teuflidin and teucvidin were tentatively identified in the plant extracts by HPLC-MS and 1H-NMR experiments. For the isolation of teucrium diterpenoids on a semipreparative scale, a solid-phase extraction method was developed for the first time using styrene divinylbenzene and strata-X sorbents for teucrin A and teuflin, respectively. Semi-preparative HPLC of the methanol extract of the powdered aerial parts of Teucrium plants was carried out on a semipreparative Synergi Max-RP column with photodiode array detection in order to confirm the identities of some diterpenoids by HPLC-MS and NMR.

Effects of dietary taurocholate, fat and protein on the storage and metabolism of dietary beta-carotene and alpha-tocopherol in ferrets.

Dietary factors affecting tissue storage of beta-carotene (BC), alpha-tocopherol (alpha-T), and retinol (ROL) in mammals include taurocholate, protein, and fat. Few studies have examined the effects of these factors on the storage of BC, retinyl esters, and alpha-T in a mammalian system that is similar to humans. The main objective of the study was to investigate the effects of taurocholate (TC), fat, and protein on the absorption and metabolism of BC and alpha-T in ferret tissues. Three 4-week experiments were conducted using groups of 5-6 ferrets per treatment. All diets contained 0.2% BC. In Experiment 1, taurocholate was fed at concentrations of 0, 0.5, or 1%. Effects of two concentrations of dietary fat (6 and 23%) and three concentrations of protein (10, 20, and 40%) were also studied in Experiments 2 and 3, respectively. Tissues were analyzed for BC, retinoids, and alpha-T by high-pressure liquid chromatography (HPLC). Taurocholate enhanced hepatic and plasma concentrations of BC (2.3- to 3-fold), retinyl palmitate [(RP) 3.2- to 9.5-fold], retinyl stearate [(RS) 2.9- to 6- fold], and hepatic alpha-T (6- to 13- fold) at p < 0.05. High-fat diets elevated hepatic BC, RP, RS, and retinyl linoleate (RL) concentrations (2- to 3.6-fold, p < 0.05). In contrast, high-protein diets lowered hepatic RL 1.8-fold and alpha-T 8-fold (p < 0.05). Our results indicate the importance of taurocholate, fat, and protein in achieving adequate levels of vitamins A and E in mammals.

Simultaneous determination of vitamin A and beta-carotene in dietary supplements by liquid chromatography.

Several liquid chromatography (LC) methods for analysis of vitamin A in foods and feeds have been previously reported but only a few have been applied in non-food matrixes. A validated LC method is needed for determination of vitamin A and beta-carotene in the various matrixes presented by dietary supplements. The performance of a reversed-phase method with methanol-isopropanol gradient elution was evaluated with standard retinyl derivatives and beta-carotene. The reversed-phase method is capable of separating retinol from other derivatives such as retinyl acetate, retinyl palmitate, and beta-carotene. Two types of extraction were used to extract the analytes from the dietary supplements: a hexane-methylene chloride extraction for soft-gel capsules containing beta-carotene, and a direct solvent extraction for dietary supplements in tablet form. The direct solvent extraction consisted of treatment with ethanol and methylene chloride following addition of hot water (55 degrees C). Results with the reversed-phase method for vitamin A and beta-carotene in the products examined (n = 8) indicated excellent method performance. The main form of vitamin A or beta-carotene in dietary supplements was the all-trans isomer. The reversed-phase method avoids saponification and is rapid, accurate, precise, and suitable for simultaneous determination of retinyl derivatives and beta-carotene in dietary supplements.

Phase I trial of the matrix metalloproteinase inhibitor BAY12-9566 in patients with advanced solid tumors.

PURPOSE: Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that are believed to be involved in primary and metastatic tumor growth by degrading the basement membrane and changing the extracellular matrix to facilitate invasion of malignant cells and angiogenesis. Overexpression of MMPs has been documented in various solid tumors. BAY12-9566 is a selective inhibitor of MMPs, in particular MMP-2, -3. and -9. The purpose of this trial was to define the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, pharmacokinetics and pharmacodynamics of orally administered BAY12-9566 in patients with incurable solid tumors. METHODS: The starting dose of BAY12-9566 for this single institution, outpatient phase I study was 100 mg/day orally. Patients were allowed to receive drug for up to 12 months. A total of 27 patients with various solid malignancies including colorectal, breast, lung, cervical and ovarian cancers were enrolled at doses from 100 to 1,600 mg/day. Patients were evaluated weekly while on treatment. Relevant radiologic examination was performed every 8 weeks to document and follow sites of measurable or evaluable disease. RESULTS: Toxicities from BAY12-9566 included liver injury test abnormalities, anemia, shoulder and back pain. thrombocytopenia, mild nausea and fatigue, diarrhea, rash and deep vein thrombosis. No toxicity greater than grade III was observed. As doses were increased from 100 to 400 to 1,600 mg/day, even in divided doses, less than proportional increases in AUC were observed. At the highest dose level of 1600 mg/day, the day 29 AUC (3778.00 mg x h/l) remained similar to the day 29 AUC (3312.60 mg x h/l) at the dose level of 1200 mg/day. No responses were seen, but 14 patients remained on study with stable disease for 4 to 26 months. CONCLUSIONS: BAY12-9566 was well tolerated at doses as high as 800 mg orally twice daily. Although mild alterations in liver injury tests, platelet count and hematocrit were noted, these were not dose-limiting. The drug was well absorbed. However, the absence of proportional increases in AUC with doses greater than 800 mg and the achievement of Css in the range associated with biologic activity in preclinical models led to the selection of 800 mg twice daily for further evaluation in phase III trials.