Anti-methicillin resistance Staphylococcus aureus and in vitro toxicology evaluation of corilagin-loaded gelatin/agar microspheres with potential biotextile applications.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged since the early 1960s. The increasing resistance of pathogens to currently used antibiotics requires the urgent discovery of new antimicrobials effective in combating drug-resistant bacteria. From past to present, medicinal plants are useful to cure human diseases. Corilagin (ß-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), commonly found in Phyllanthus species, exerts potentiating effect on ß-lactams against MRSA. However, its biological effect may not be fully utilized. Therefore, incorporating microencapsulation technology with the delivery of corilagin would be more effective in utilizing the potential effect on biomedical applications. This work reports the development of a safe micro-particulate system which combined agar with gelatin as wall matrix materials for topical delivery of corilagin in order to eliminate the potential toxicity of the crosslinker formaldehyde. The optimal parameters for microsphere preparation were identified and the particle size of optimal microspheres was 20.11 µm ± 3.58. Antibacterial studies revealed that micro-trapped corilagin (minimum bactericidal concentration, MBC = 0.5 mg/mL) possessed a higher potency against MRSA than free corilagin (MBC = 1 mg/mL). The in vitro skin cytotoxicity showed the safety of the corilagin-loaded microspheres for topical applications, with approximately 90 % of HaCaT cell viability. Our results demonstrated the potential of corilagin-loaded gelatin/agar microspheres for the applicable bio-textile products to treat drug-resistant bacterial infections.

Joint effect of defocus blur and spatial attention.

Defocus blur and spatial attention both act on our ability to see clearly over time. However, it is currently unknown how these two factors interact because studies on spatial resolution only focused on the separate effects of attention and defocus blurs. In this study, eleven participants performed a resolution acuity task along the diagonal 135˚/315˚ with horizontal, at 8˚ eccentricity for clear and blurred Landolt C images under various manipulations of covert endogenous attention. All the conditions were interleaved and viewed binocularly on a visual display. We observed that attention not just improves the resolution of clear stimuli, but also modulates the resolution of defocused stimuli for compensating the loss of resolution caused by retinal blur. Our results show, however, that as the degree of attention decreases, the differences between clear and blurred images largely diminish, thus limiting the benefit of an image quality enhancement. It also appeared that attention tends to enhance the resolution of clear targets more than blurred targets, suggesting potential variations in the gain of vision correction with the level of attention. This demonstrates that the interaction between spatial attention and defocus blur can play a role in the way we see things. In view of these findings, the development of adaptive interventions, which adjust the eye's defocus to attention, may hold promise.

Advancing Care for Head and Neck Cancers in a Multidisciplinary Tumour Board in the East.

Managing head and neck cancers is an excellent example of the importance of teamwork, with head and neck surgeons, clinical oncologists, radiologists, pathologists and other allied health professionals specialised in this disease site working together. The reliable imaging and dedicated pretreatment work-up entailing the comprehensive anatomical description of tumour involvement by the radiologists, the expertise of surgeons in performing en-bloc gross tumour resection, the uneventful speedy postoperative rehabilitation and recovery by the speech therapists and nutritionists, as well as the dedicated treatment planning of clinical oncologists in delivering precise preoperative or postoperative (chemo)radiotherapy to maximise the therapeutic potentials are the pillars of treatment success. A multidisciplinary tumour board involving all of these key players is essential to provide the highest level of recommendation based on evidence-based medicine and to bring patients new hopes and the best chance of cure. This review illustrates the seamless collaborative teamwork within a well-established multidisciplinary tumour board in managing one of the most intractable cancers in the East, taking enlightenment and inspiration from the West.

The Application of Non-linear Flow Resistance in Cerebral Artery: Compared with Windkessel Model based on Genetic Algorithm.

Continuous blood pressure is measured from various extracranial body sites, with difference in amplitude and phase with intracranial blood pressure. Consequent influences on the accuracy of Windkessel model need further investigation. Between blood pressure and intracranial flow rate, a model with non-linear flow resistance (R-DT) was proposed and compared with the 3-element Windkessel (RCR) model. From the measured blood flow velocity in middle cerebral artery, the blood pressure was estimated by R-DT and RCR models respectively. The parameters in the models were optimized by genetic algorithm. The accuracies of R-DT and RCR models were compared based on their estimation errors to the measured blood pressure. The capacitance element in RCR model indicated limited ability to take the time shift into account. Compared with RCR model, R-DT model had less error (averaged relative error: 5.19% and 2.49% for RCR and RDT models). The non-linear flow resistance was applicable in simulating cerebral arteries.

Translesional pressure gradient and leptomeningeal collateral status in symptomatic middle cerebral artery stenosis.

BACKGROUND AND PURPOSE: Leptomeningeal collateral (LMC) status governs the prognosis of large artery occlusive stroke, although factors determining LMC status are not fully elucidated. The aim was to investigate metrics affecting LMC status in such patients by using computational fluid dynamics (CFD) models based on computed tomography angiography (CTA). METHODS: In this cross-sectional study, patients with recent ischaemic stroke or transient ischaemic attack attributed to atherosclerotic M1 middle cerebral artery (MCA) stenosis (50%-99%) were recruited. Demographic, clinical and imaging data of these patients were collected. Ipsilesional LMC status was graded as good or poor by assessing the laterality of anterior and posterior cerebral arteries in CTA. A CFD model based on CTA was constructed to reflect focal hemodynamics in the distal internal carotid artery, M1 MCA and A1 anterior cerebral artery. Pressure gradients were calculated across culprit MCA stenotic lesions in CFD models. Predictors for good LMC status were sought in univariate and multivariate analyses. RESULTS: Amongst the 85 patients enrolled (mean age 61.5 ± 10.9 years), 38 (44.7%) had good ipsilesional LMC status. The mean pressure gradient across MCA lesions was 14.8 ± 18.1 mmHg. Advanced age (P = 0.030) and a larger translesional pressure gradient (P = 0.029) independently predicted good LMCs. A lower fasting blood glucose level also showed a trend for good LMCs (P = 0.058). CONCLUSIONS: Our study suggested a correlation between translesional pressure gradient and maturation of LMCs in intracranial atherosclerotic disease. Further studies with more exquisite and dynamic monitoring of cerebral hemodynamics and LMC evolution are needed to verify the current findings.

Good collateral circulation predicts favorable outcomes in intravenous thrombolysis: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Baseline collateral status has been correlated with outcomes of acute ischaemic stroke patients receiving intravenous thrombolysis (IVT) in previous studies. We carried out the current systematic review and meta-analysis to synthesize currently available evidence regarding such correlations. METHODS: Full-text articles published since 2000 were retrieved and screened. The overall effect sizes of good versus poor collateral status over a series of outcomes and certain baseline features were estimated by random-effects models and presented in risk ratios (RRs) or mean differences. RESULTS: Overall, 28 (3057 patients) and 14 (1584 patients) studies were included in qualitative and quantitative synthesis, respectively. Compared with poor pre-treatment collateral status, good collaterals showed a beneficial effect over the primary outcome of a favorable functional outcome at 3 or 6 months [RR, 2.45; 95% confidence interval, 1.94-3.09; P < 0.001] in acute ischaemic stroke patients receiving IVT treatment. However, such an effect tended to be different between studies with prescribed time windows of 3, 4.5 and > 4.5 h (up to 7 h), with the RRs being 2.21, 2.48 and 5.00, respectively (I2  = 53%). Good pre-treatment collaterals were also associated with a smaller infarct size at baseline, and a lower rate of symptomatic intracranial hemorrhage and a higher rate of neurological improvement early after IVT treatment. CONCLUSIONS: The present study has demonstrated the prognostic value of baseline collateral circulation for outcomes of acute ischaemic stroke patients receiving intravenous reperfusion therapies, studied with different time windows of up to 7 h after ictus for IVT therapy.

A design of a DICOM-RT-based tool box for nonrigid 4D dose calculation.

The study was aimed to introduce a design of a DICOM-RT-based tool box to facilitate 4D dose calculation based on deformable voxel-dose registration. The computational structure and the calculation algorithm of the tool box were explicitly discussed in the study. The tool box was written in MATLAB in conjunction with CERR. It consists of five main functions which allow a) importation of DICOM-RT-based 3D dose plan, b) deformable image registration, c) tracking voxel doses along breathing cycle, d) presentation of temporal dose distribution at different time phase, and e) derivation of 4D dose. The efficacy of using the tool box for clinical application had been verified with nine clinical cases on retrospective-study basis. The logistic and the robustness of the tool box were tested with 27 applications and the results were shown successful with no computational errors encountered. In the study, the accumulated dose coverage as a function of planning CT taken at end-inhale, end-exhale, and mean tumor position were assessed. The results indicated that the majority of the cases (67%) achieved maximum target coverage, while the planning CT was taken at the temporal mean tumor position and 56% at the end-exhale position. The comparable results to the literature imply that the studied tool box can be reliable for 4D dose calculation. The authors suggest that, with proper application, 4D dose calculation using deformable registration can provide better dose evaluation for treatment with moving target.

Post-radiation Plasma Epstein-Barr Virus DNA and Local Clinical Remission After Radical Intensity-modulated Radiation Therapy for Nasopharyngeal Carcinoma.

AIMS: We studied if post-radiation plasma Epstein-Barr virus (EBV) DNA predicted local clinical remission after radical intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma. MATERIALS AND METHODS: Patients with non-metastatic nasopharyngeal carcinoma with baseline and serial plasma EBV DNA were treated with radical IMRT ± adjunct chemotherapy. Eight weeks after IMRT, they had plasma EBV DNA and routine six-site random nasopharyngeal biopsies on the same day. A repeat biopsy was carried out every 2 weeks if residual tumours were noted in previous biopsies until 12 weeks after IMRT when local persistence was defined. Correlation of undetectable plasma EBV DNA with local clinical remission was carried out. RESULTS: Two hundred and sixty patients with serial plasma EBV DNA completed IMRT, after a median follow-up of 3.1 years. Only one (0.4%) suffered from local persistence. Area under the curve values of receiver operating characteristics of undetectable plasma EBV DNA for negative biopsy at 8 weeks and local persistence were 0.642 and 0.439, respectively. They increased to 0.856 (P = 0.007) and 0.952 (P = 0.119), respectively, when combined with age <65 years and T1/T2 stage. CONCLUSIONS: Post-treatment plasma EBV DNA was not useful to predict local clinical remission in this study, probably because of excellent local control after IMRT. However, it may serve as a reference for high-risk patients treated with older radiation techniques.

Indications for and pregnancy outcomes of cervical cerclage: 11-year comparison of patients undergoing history-indicated, ultrasound-indicated, or rescue cerclage.

OBJECTIVES: To review and compare pregnancy outcomes of patients undergoing history-indicated, ultrasound-indicated, or rescue cerclage. DESIGN: Case series with internal comparison. SETTING: A regional obstetric unit in Hong Kong. PATIENTS: Women undergoing cervical cerclage at Kwong Wah Hospital between 1 January 2001 and 31 December 2011. INTERVENTIONS: Cervical cerclage. MAIN OUTCOME MEASURES: Pregnancy outcomes including miscarriage, gestational age at delivery, birth weight, and duration of pregnancy prolongation. RESULTS: Overall, 47 patients were included. Nine (19.1%) pregnancies resulted in miscarriage. The median gestational age at delivery was 35.7 weeks. Among the 23 patients who had history-indicated cerclage, only four (17.4%) had three or more previous second-trimester miscarriages or preterm deliveries. Among the 15 patients who had ultrasound-indicated cerclage, preoperative cervical length of ≤1.5 cm was associated with shorter prolongation of pregnancy, compared with that of >1.5 cm (median, 12.1 vs 18.4 weeks; P=0.009). Among the nine women who had rescue cerclage, those who underwent the procedure before 20 weeks of gestation delivered earlier than those underwent cerclage later (median, 22.5 vs 34.1 weeks; P=0.048). CONCLUSIONS: Patients eligible for the Royal College of Obstetricians and Gynaecologists-recommended history-indicated cerclage remain few. The majority of patients may benefit from serial ultrasound monitoring of cervical length with or without ultrasound-indicated cerclage.

Adding computed tomography and transcranial Doppler findings to the ABCD2 score to predict long-term risk of stroke after transient ischaemic attack or minor stroke.

BACKGROUND AND PURPOSE: The ABCD(2) score can predict the early risk of stroke after transient ischaemic attack or minor stroke. However, there is no simple and practical assessment method for the long-term risks. Computed tomography (CT) and transcranial Doppler (TCD) findings were added to the ABCD(2) score to build an ABCD(2) L(2) score and whether the new scoring system could improve the predictive value of the ABCD(2) score for the long-term risk of stroke was determined. METHODS: From January 2004 to December 2005, all patients with a definite diagnosis of transient ischaemic attack or minor stroke at the Prince of Wales Hospital were consecutively enrolled and followed up until August 2008. CT and TCD were performed. The areas under the curve were used to quantify the ABCD(2) and ABCD(2) L(2) scores and related items. RESULTS: All 481 patients completed the follow-up. The shortest follow-up time was 0.17 months (until death), the longest follow-up time was 55.60 months and the mean follow-up time was 40.3 ± 11.0 months. In total, 277 (57.6%) patients showed lesions on CT scans and 195 (40.6%) patients were found with intracranial large artery atherosclerosis. Further strokes occurred in 74 (15.4%) patients, including four (0.83%) patients who died of ischaemic stroke during the follow-up period. The area under the curve increased from 0.650 (0.586-0.715) for the ABCD(2) score to 0.700 (0.637-0.764) for the ABCD(2) L(2) score. CONCLUSION: Adding CT and TCD results to the ABCD(2) score to increase its predictability for long-term risk of stroke recurrence might be a meaningful exploration.

Use of methylphenidate for the management of fatigue in Chinese patients with cancer.

UNLABELLED: REASON FOR THE STUDY: Studies on methylphenidate for cancer-related fatigue showed conflicting results. This prospective study aims to determine whether methylphenidate is useful for relieving fatigue in Chinese patients with cancer. Chinese Version of Brief Fatigue Inventory (BFI-C) was administered on days 1, 8, and 29. Methylphenidate dose on day 1 was 5 mg daily then adjusted after day 8 according to response and side effects tolerance. MAIN FINDINGS: Only 48% of the 25 recruited patients were on methylphenidate by day 29. Overall, no significant improvement in fatigue level was observed after methylphenidate, though benefits were shown in subgroups with age ≤ 65 and higher baseline BFI-C values. PRINCIPAL CONCLUSIONS: Methylphenidate may be useful for management of cancer-related fatigue in selected Chinese patients.

Patients' views on failure to gain expected clinical beneficial outcomes from participation in palliative medicine clinical trials.

UNLABELLED: REASON FOR THE STUDY: This study aims to understand patients' views on failing to gain expected beneficial outcomes from palliative medicine clinical trials. This is a qualitative study involving semistructured interviews. MAIN FINDINGS: Seven patients were interviewed. Despite loss of initial hope in benefiting themselves in terms of better disease or symptom control, patients interviewed still found joining clinical trials meaningful experience in terms of benefiting future patients and being valuable life experience. Experience in interacting with research staff partly formulated final impressions on clinical trial participation experience. PRINCIPAL CONCLUSIONS: Joining well-designed clinical trials unlikely causes harm to patients. Caring attitudes of researchers and maintaining good researcher-patient relationships can help patients in meaning-finding process, especially if they have failed to gain anticipated clinical benefits.

Dosimetric predictors of radiation-induced acute nausea and vomiting in IMRT for nasopharyngeal cancer.

PURPOSE: We wanted to investigate dosimetric parameters that would predict radiation-induced acute nausea and vomiting in intensity-modulated radiation therapy (IMRT) for undifferentiated carcinoma of the nasopharynx (NPC). METHODS AND MATERIALS: Forty-nine consecutive patients with newly diagnosed NPC were treated with IMRT alone in this prospective study. Patients receiving any form of chemotherapy were excluded. The dorsal vagal complex (DVC) as well as the left and right vestibules (VB-L and VB-R, respectively) were contoured on planning computed tomography images. A structure combining both the VB-L and the VB-R, named VB-T, was also generated. All structures were labeled organs at risk (OAR). A 3-mm three-dimensional margin was added to these structures and labeled DVC+3 mm, VB-L+3 mm, VB-R+3 mm, and VB-T+3 mm to account for physiological body motion and setup error. No weightings were given to these structures during optimization in treatment planning. Dosimetric parameters were recorded from dose-volume histograms. Statistical analysis of parameters' association with nausea and vomiting was performed using univariate and multivariate logistic regression. RESULTS: Six patients (12.2%) reported Grade 1 nausea, and 8 patients (16.3%) reported Grade 2 nausea. Also, 4 patients (8.2%) complained of Grade 1 vomiting, and 4 patients (8.2%) experienced Grade 2 vomiting. No patients developed protracted nausea and vomiting after completion of IMRT. For radiation-induced acute nausea, V40 (percentage volume receiving at least 40Gy) to the VB-T and V40>=80% to the VB-T were predictors, using univariate analysis. On multivariate analysis, V40>=80% to the VB-T was the only predictor. There were no predictors of radiation-induced acute vomiting, as the number of events was too small for analysis. CONCLUSIONS: This is the first study demonstrating that a V40 to the VB-T is predictive of radiation-induced acute nausea. The vestibules should be labeled as sensitive OARs, and weightings should be considered for dose sparing during optimization in the treatment planning of IMRT.