Performance of neuroretinal rim thickness measurement by Cirrus high-definition optical coherence tomography in myopic eyes.

Neuroretinal rim (NRR) measurement can aid the diagnosis of glaucoma. A few studies reported that Cirrus optical coherence tomography (OCT) had NRR segmentation errors. The current study investigated segmentation success of NRR in myopic eyes using the Cirrus built-in software and to determine the number of acquisitions required to identify NRR thinning. Right eye of 87 healthy adult myopes had an optic disc scanned using Cirrus HD-OCT for five successive acquisitions. A masked examiner evaluated 36 radial line images of each scan to screen for segmentation errors using the built-in software at the Bruch's membrane opening (BMO) and/or internal limiting membrane (ILM). Participants with three accurate NRR acquisitions had their average NRR thickness determined. This result was compared with average of the two acquisitions and the first acquisition. Among 435 OCT scans of the optic disc (87 eyes × 5 acquisitions), 129 (29.7%) scans had segmentation errors that occurred mainly at the ILM. The inferior-temporal and superior meridians had slightly more segmentation errors than other meridians, independent of axial length, amount of myopia, or presence of peripapillary atrophy. Sixty-five eyes (74.7%) had at least three accurate NRR measurements. The three acquisitions had high reliability in NRR thickness in the four quadrants (intraclass correlation coefficient > 0.990, coefficient of variation < 3.9%). NRR difference between the first acquisition and the average of three acquisitions was small (mean difference 2 ± 13 µm, 95% limits of agreement within ± 30 µm) among the four quadrants. Segmentation errors in NRR measurements appeared regardless of axial length, amount of myopia, or presence of peripapillary atrophy. Cirrus segmentation lines should be manually inspected when measuring NRR thickness.

Development of workplace-based assessments of non-technical skills in anaesthesia.

Non-technical skills are recognised as crucial to good anaesthetic practice. We designed and evaluated a specialty-specific tool to assess non-technical aspects of trainee performance in theatre, based on a system previously found reliable in a recruitment setting. We compared inter-rater agreement (multir-ater kappa) for live assessments in theatre with that in a selection centre and a video-based rater training exercise. Twenty-seven trainees participated in the first in-theatre assessment round and 40 in the second. Round- 1 scores had poor inter-rater agreement (mean kappa = 0.20) and low reliability (generalisability coefficient G = 0.50). A subsequent assessor training exercise showed good inter-rater agreement, (mean kappa = 0.79) but did not improve performance of the assessment tool when used in round 2 (mean kappa = 0.14, G = 0.42). Inter-rater agreement in two selection centres (mean kappa = 0.61 and 0.69) exceeded that found in theatre. Assessment tools that perform reliably in controlled settings may not do so in the workplace.

Predictive validity of a selection centre testing non-technical skills for recruitment to training in anaesthesia.

BACKGROUND: Assessment centres are an accepted method of recruitment in industry and are gaining popularity within medicine. We describe the development and validation of a selection centre for recruitment to speciality training in anaesthesia based on an assessment centre model incorporating the rating of candidate's non-technical skills. METHODS: Expert consensus identified non-technical skills suitable for assessment at the point of selection. Four stations-structured interview, portfolio review, presentation, and simulation-were developed, the latter two being realistic scenarios of work-related tasks. Evaluation of the selection centre focused on applicant and assessor feedback ratings, inter-rater agreement, and internal consistency reliability coefficients. Predictive validity was sought via correlations of selection centre scores with subsequent workplace-based ratings of appointed trainees. RESULTS: Two hundred and twenty-four candidates were assessed over two consecutive annual recruitment rounds; 68 were appointed and followed up during training. Candidates and assessors demonstrated strong approval of the selection centre with more than 70% of ratings 'good' or 'excellent'. Mean inter-rater agreement coefficients ranged from 0.62 to 0.77 and internal consistency reliability of the selection centre score was high (Cronbach's α=0.88-0.91). The overall selection centre score was a good predictor of workplace performance during the first year of appointment. CONCLUSIONS: An assessment centre model based on the rating of non-technical skills can produce a reliable and valid selection tool for recruitment to speciality training in anaesthesia. Early results on predictive validity are encouraging and justify further development and evaluation.

The challenge of developing green tea polyphenols as therapeutic agents.

The health benefits of green tea and its main constituent (-)-epigallocatechin gallate [(-)-EGCG] have been widely supported by results from epidemiological, cell culture, animal and clinical studies. On the other hand, there are a number of issues, such as stability, bioavailability and metabolic transformations under physiological conditions, facing the development of green tea polyphenols into therapeutic agents. We previously reported that the synthetic peracetate of (-)-EGCG has improved stability and better bioavailability than (-)-EGCG itself and can act as pro-drug under both in vitro and in vivo conditions. Analogs of catechins have been synthesized and their structure activity relationship provides an understanding to the mechanism of proteasome inhibition. Metabolic methylation of catechins leading to methylated (-)-EGCG may alter the biological activities of these compounds.

Tea polyphenols, their biological effects and potential molecular targets.

Tea is the most popular beverage in the world, second only to water. Tea contains an infusion of the leaves from the Camellia sinensis plant rich in polyphenolic compounds known as catechins, the most abundant of which is (-)-EGCG. Although tea has been consumed for centuries, it has only recently been studied extensively as a health-promoting beverage that may act to prevent a number of chronic diseases and cancers. The results of several investigations indicate that green tea consumption may be of modest benefit in reducing the plasma concentration of cholesterol and preventing atherosclerosis. Additionally, the cancer-preventive effects of green tea are widely supported by results from epidemiological, cell culture, animal and clinical studies. In vitro cell culture studies show that tea polyphenols potently induce apoptotic cell death and cell cycle arrest in tumor cells but not in their normal cell counterparts. Green tea polyphenols were shown to affect several biological pathways, including growth factor-mediated pathway, the mitogen-activated protein (MAP) kinase-dependent pathway, and ubiquitin/proteasome degradation pathways. Various animal studies have revealed that treatment with green tea inhibits tumor incidence and multiplicity in different organ sites such as skin, lung, liver, stomach, mammary gland and colon. Recently, phase I and II clinical trials have been conducted to explore the anticancer effects of green tea in humans. A major challenge of cancer prevention is to integrate new molecular findings into clinical practice. Therefore, identification of more molecular targets and biomarkers for tea polyphenols is essential for improving the design of green tea trials and will greatly assist in a better understanding of the mechanisms underlying its anti-cancer activity.

Trace organic contaminants, including toxaphene and trifluralin, in cotton field soils from Georgia and South Carolina, USA.

Residues of organic contaminants--including toxaphene, DDT, trifluralin, hexachlorocyclohexanes, polychlorinated biphenyls, polycyclic aromatic hydrocarbons (PAHs) and nonylphenol--were measured in 32 cotton field soils collected from South Carolina and Georgia in 1999. Toxaphene, trifluralin, DDT and PAHs were the major contaminants found in these soils. The maximum concentration of toxaphene measured was 2,500 ng/g dry weight. Trifluralin was detected in all the soils at concentrations ranging from 1 to 548 ng/g dry weight. Pesticide residues were not proportional to soil organic carbon content, indicating that their concentrations were a reflection of application history and dissipation rates rather than air-soil equilibrium. Soil extracts were also subjected to in vitro bioassays to assess dioxinlike, estrogenic, and androgenic/glucocorticoid potencies. Relatively more polar fractions of the soils elicited estrogenic and androgenic/glucocorticoid activities, but the magnitude of response was much less than those found in coastal marine sediments from industrialized locations.

Antiproliferative activity of the extract of Gleditsia sinensis fruit on human solid tumour cell lines.

BACKGROUND: The fruit extract of Gleditsia sinensis Lam. (GSE) is a traditional herbal medicine that is saponin-rich. However, its activity on solid tumour cell lines has never been demonstrated. METHODS: The activity of GSE was demonstrated in four cancer cell lines (breast cancer MCF-7, MDA-MB231, hepatoblastoma HepG2 and oesophageal squamous carcinoma cell line SLMT-1) using MTT assay, anchorage-independent clonogenicity assay, DNA laddering and in situ cell death detection. RESULTS: The mean MTT(50) (the mean concentration of GSE to reduce MTT activity by 50%) ranged from 16 to 20 microg/ml of GSE. An anchorage-independent clonogenicity assay showed that all of the four solid tumour cell lines gradually lost their regeneration potential after treatment with GSE, DNA fragmentation and TUNEL analysis demonstrated that the action of GSE is both dose- and time course-dependent. CONCLUSIONS: Our results suggest that GSE has a cytotoxic activity and can induce apoptosis in human solid tumour cell lines.

Identification of a common protein association region in the neuronal Cdk5 activator.

Cyclin-dependent protein kinase 5 (Cdk5) depends on the association with neuronal Cdk5 activator (Nck5a) for kinase activity. A variety of cellular proteins have been shown to undergo high affinity association with Nck5a, including three novel proteins, C42, C48, and C53 found by a yeast two-hybrid screen (Ching, Y. P., Qi, Z., and Wang, J. H. (2000) Gene 242, 285-294). The three proteins show competitive binding to Nck5a suggesting that they bind at a common site. The binding site has been mapped to a region of 26 amino acid residues (residues 145 to 170) at the N-terminal boundary of the kinase activation domain of Nck5a. This region of Nck5a contains an amphipathic alpha-helix whose hydrophobic face is involved in Cdk5 activation (Chin, K. T., Ohki, S, Tang, D., Cheng, H. C., Wang, J. H. , and Zhang, M. (1999) J. Biol. Chem. 274, 7120-7127). Several lines of evidence suggest that Nck5a interacts with the binding proteins at the hydrophilic face of the amphipathic alpha-helix. First, the Nck5a-(145-170) peptide can bind Cdk5 and Nck5a-binding proteins simultaneously. Second, the association of Nck5a-(145-170) to C48 can be markedly reduced by high ionic strength whereas the interaction between Nck5a and Cdk5 is not affected. Third, substitution of Glu(157) by glutamine in Nck5a-(145-170) abolishes the peptide's ability to bind to the three Nck5a-binding proteins without diminishing its Cdk5 binding activity.

Paediatric head injury: incidence, aetiology and management.

Trauma is the commonest cause of hospital admission in children. Head injuries are present in 75% of children with trauma and 70% of all traumatic deaths are due to the head injury. The mechanism of brain injury is examined, resulting from the effects of the primary insult and secondary ischaemic damage. Therapeutic interventions will be discussed with specific emphasis on outcome studies. However, institution of adequate oxygen delivery and haemodynamic stability in the child at the earliest moment remains the most important aspect of the management plan.

Peri-operative silent myocardial ischaemia in patients undergoing lower limb joint replacement surgery: an indicator of postoperative morbidity or mortality?

One hundred and twenty-seven patients undergoing major lower limb joint replacement surgery were studied to determine the incidence of silent myocardial ischemia and to ascertain any link between pre-operative cardiac risk factors, silent myocardial ischaemia and postoperative morbidity. Patients underwent ambulatory ECG monitoring for 4 days (on the pre-operative night and for 3 days postoperatively). Postoperative cardiorespiratory symptomatology and morbidity was assessed by questionnaire at 3 months. Eighty-seven patients had risk factors for silent myocardial ischaemia; 42 patients (30 with risk factors) had peri-operative silent myocardial ischaemia. The median ischaemic loads (range) were 1.04 (0.32-13.31) min.h-1 pre-operatively and 5.53 (0.26-56.39), 6.69 (0.04-42.71) and 1.23 (0.1-53.74) min.h-1 on postoperative days 1-3, respectively. Risk factors did not predict the occurrence of silent myocardial ischaemia or an increased ischaemic load pre-operatively or overall postoperatively. New symptoms (chest pain, palpitations, breathlessness or fatigue) were associated with both silent myocardial ischaemia and ischaemic load (p < 0.05). Thus cardiac risk factors do not predict the occurrence of silent myocardial ischaemia or adverse outcome. Peri-operative silent myocardial ischaemia was associated with increased postoperative fatigue.