Isometric agonist and antagonist muscle activation interacts differently with 140-Hz transcranial alternating current stimulation aftereffects at different intensities.

During transcranial electric stimulation, increasing intracellular Ca2+ levels beyond those needed for inducing long term potentiation (LTP) may collapse aftereffects. State-dependent plastic aftereffects are reduced when applied during muscle activation as compared with rest. Cortical surround inhibition by antagonistic muscle activation inhibits the center-innervated agonist. The objective of this study is to determine the interaction of state dependency of transcranial alternating current stimulation (tACS) aftereffects at rest and under activation of agonist and antagonist muscles during stimulation with different intensities. In 13 healthy participants, we measured motor-evoked potential (MEP) amplitudes before and after applying tACS at 140 Hz over the motor cortex in nine single-blinded sessions using sham, 1 mA, and 2 mA stimulation intensities during rest and activation of agonist and antagonist muscles. During rest, only 1 mA tACS produced a significant MEP increase, whereas the 2 mA stimulation produced no significant MEP size shift. During agonist activation 1 mA did not induce MEP changes; after 2 mA, first a decrease and later an increase of MEPs were observed. Antagonist activation under sham tACS led to an inhibition, which was restored to baseline by 1 and 2 mA tACS. Increasing stimulation intensity beyond 1 mA does not increase excitability, compatible with too strong intracellular Ca2+ increase. Antagonist innervation leads to MEP inhibition, supporting the concept of surround inhibition, which can be overcome by tACS at both intensities. During agonist innervation, a tACS dose-dependent relationship exists. Our results integrate concepts of "leaky membranes" under activation, surround inhibition, intracellular Ca2+ increase, and their role in the aftereffects of tACS.NEW & NOTEWORTHY Stimulation intensity and activation of center versus surround muscles affect cortical excitability alterations generated by 140-Hz tACS. At rest, excitatory aftereffects were induced by tACS with 1 mA, but not 2 mA stimulation intensity. With agonistic muscle activation, excitability first decreases, and then increases with 2 mA. For antagonist activation, the MEP amplitude reduction observed in the sham condition is counteracted upon by 1 and 2 mA tACS. This reflects the relation of LTP-like aftereffects to Ca2+ concentration alterations.

Patient-reported experiences of mealtime care and food access in acute and rehabilitation hospital settings: a cross-sectional survey.

BACKGROUND: Nutrition and mealtime interventions can improve nutritional intake amongst hospital inpatients; however, patient-reported experience is rarely considered in their development and evaluation. The present study aimed to measure patient-reported food and mealtime experience to evaluate and inform continuous quality improvement of hospital nutrition care. METHODS: A cross-sectional survey with inpatients in seven acute care and rehabilitation wards was conducted. A 27-item validated questionnaire measured five domains of patient experience: food choices, organisational barriers, feeling hungry, physical barriers to eating and food quality. Responses were summarised descriptively and compared between settings (acute versus rehabilitation), patient demographics (age, gender) and time in hospital. RESULTS: Responses from 143 participants (mean age 67 years, 57% male, 28% rehabilitation, median 6 days into hospitalisation) showed that 10% or fewer respondents reported difficulties with food choices, feeling hungry or food quality. The most common difficulties were opening packets (36%), insufficient menu information provided (29%), being interrupted by staff when eating (28%), being disturbed when eating (27%), being in an uncomfortable position when eating (24%) and difficulty reaching food (21%). There were no significant differences in domain patterns by sex, age group or time in hospital. Organisational barriers were reported less frequently amongst rehabilitation participants compared to acute care (P = 0.01). CONCLUSIONS: This survey highlights areas of positive patient-reported experience with nutrition care and suggests that local improvement efforts should focus on physical assistance needs and organisational barriers, especially in acute care wards. The questionnaire may be useful for informing and evaluating systematic nutrition care improvements.

Improved correlation between animal and human potency of non-steroidal anti-inflammatory drugs using quantitative structure-activity relationships (QSARs).

Animal models are known not to predict human responses well, in general. However, we have been able to demonstrate that, for a series of non-steroidal anti-inflammatory drugs that are or were in clinical use, the incorporation of two simple physicochemical properties results in excellent correlations between human and rodent potencies for anti-inflammatory, analgesic and anti-pyretic activities. This has the potential to allow the use of historical data to improve drug development.

Parasite community similarity in Athabasca River trout-perch (Percopsis omiscomaycus) varies with local-scale land use and sediment hydrocarbons, but not distance or linear gradients.

Parasite communities have been shown to be structured by processes at scales ranging from continental to microhabitat, but few studies have simultaneously considered spatial and environmental variables, measured at different scales, to assess their relative influences on parasite abundance, species richness, and community similarity. Parasite abundance, diversity, and community similarity in Athabasca River trout-perch (Percopsis omiscomaycus) were examined in relation to water quality, substrate profile, metal and organic compound levels in water and sediment, and landscape use patterns at different scales, as well as distance among sites and upstream-downstream position along the river. Although species richness did not differ among sites, there were significant differences in abundance of individual taxa and community structure. We observed a shift from communities dominated by larval trematodes Diplostomum spp. to domination by gill monogeneans Urocleidus baldwini, followed by a reversion further downstream. Variations in the abundance of these taxa and of overall community similarity were strongly correlated with sediment hydrocarbons (alkanes and polycyclic aromatic hydrocarbons (PAHs)) as well as landscape use within 5 km of study sites. No correlations were noted with any other predictors, indicating that parasite populations and communities in this system were likely primarily influenced by habitat level and landscape-scale filters, rather than larger-scale processes such as distance decay or river continuum effects.

Da Vinci robot emergency undocking protocol.

The role of robot-assisted surgery across gynaecology is evolving with increasing numbers of procedures being undertaken with varying degrees of complexity. While the risk of conversion is low at approximately 1 %, the reasons for conversion are variable. These range from technical issues with the robot, surgical complications such as haemorrhage and anaesthetics issues such as an inability to ventilate the patient adequately. While many conversions to open or laparoscopic approach are not due to life-threatening indications, it is important that the theatre staff are aware of the indication and can perform an emergency undocking as effectively, efficiently and safely as possible when the need arises. Unfortunately, there is a paucity of the literature available outlining such protocols. For this reason, we developed an emergency undocking protocol clearly outlining the role of each theatre staff member and the need for clear concise communication.

Steer by ear: Myoelectric auricular control of powered wheelchairs for individuals with spinal cord injury.

PURPOSE: Providing mobility solutions for individuals with tetraplegia remains challenging. Existing control devices have shortcomings such as varying or poor signal quality or interference with communication. To overcome these limitations, we present a novel myoelectric auricular control system (ACS) based on bilateral activation of the posterior auricular muscles (PAMs). METHODS: Ten able-bodied subjects and two individuals with tetraplegia practiced PAM activation over 4 days using visual feedback and software-based training for 1 h/day. Initially, half of these subjects were not able to voluntarily activate their PAMs. This ability was tested with regard to 8 parameters such as contraction rate, lateralized activation, wheelchair speed and path length in a virtual obstacle course. In session 5, all subjects steered an electric wheelchair with the ACS. RESULTS: Performance of all subjects in controlling their PAMs improved steadily over the training period. By day 5, all subjects successfully generated basic steering commands using the ACS in a powered wheelchair, and subjects with tetraplegia completed a complex real-world obstacle course. This study demonstrates that the ability to activate PAM on both sides together or unilaterally can be learned and used intuitively to steer a wheelchair. CONCLUSIONS: With the ACS we can exploit the untapped potential of the PAMs by assigning them a new, complex function. The inherent advantages of the ACS, such as not interfering with oral communication, robustness, stability over time and proportional and continuous signal generation, meet the specific needs of wheelchair users and render it a realistic alternative to currently available assistive technologies.

Laparoscopic Adjustable Gastric Band Slippage Rates Following Laparoscopic Gastric Band Insertion: a Single Centre Experience.

INTRODUCTION: Laparoscopic adjustable gastric bands (LAGB) are placed around the superior aspect of the stomach to aid weight loss and co-morbidity resolution in morbidly obese patients. Slippage of the LAGB from its original position to lower in the fundus of the stomach leads to gastric obstruction, and sometimes ischaemia or perforation, necessitating LAGB repositioning or removal. This study aimed to identify the incidence of LAGB slippage, as well as predisposing factors that may influence its development. METHODS: All LAGBs inserted at one centre, via a pars flaccida technique, by four Bariatric specialist consultants, were reviewed utilising a prospectively maintained Bariatric database, computer records and case notes review. RESULTS: Seven hundred nineteen LAGBs were inserted and 33 slips treated; however, only 22 slips had their LAGB inserted at our centre (local slip rate 3.1 %). Multivariate analysis demonstrated a significant association between LAGB slip and younger median age at LAGB insertion (41 years slip vs. 45 years non-slip; p = 0.027), higher median total excess weight loss (64 % slip vs. 36 % non-slip; p < 0.001) and higher mean excess weight loss per month (2.41 % slip vs. 1.00 % non-slip; p < 0.001). There was no significant effect by sex, BMI at insertion or band type. CONCLUSIONS: Band slips are associated with greater excess weight loss and younger age. Larger studies may be necessary to further elucidate the risk factors contributing to, and mechanisms of, band slippage.

Mechanism-Based QSAR Modeling of Skin Sensitization.

Many chemicals can induce skin sensitization, and there is a pressing need for non-animal methods to give a quantitative indication of potency. Using two large published data sets of skin sensitizers, we have allocated each sensitizing chemical to one of 10 mechanistic categories and then developed good QSAR models for the seven categories that have a sufficient number of chemicals to allow modeling. Both internal and external validation checks showed that each model had good predictivity.

QSAR study of some anti-hyperglycaemic sulphonylurea drugs.

Sulphonylureas are widely used anti-hyperglycaemic drugs for the treatment of type 2 diabetes. The only published quantitative structure-activity relationship (QSAR) models for sulphonylurea drugs have been found to be questionable, for a number of reasons. We have re-analysed the human anti-hyperglycaemic potencies, acute mouse intraperitoneal toxicities (LD50) and plasma protein-binding abilities of the 15 drugs using multiple linear regression and obtained good QSAR models for each endpoint. The obtained QSARs all comply well with the Organisation for Economic Co-operation and Development (OECD) Guidelines for the Validation of (Q)SARs. We could not carry out external validation of our models for acute toxicity and plasma protein-binding because of the very small datasets available.

Hepatotoxicity: a scheme for generating chemical categories for read-across, structural alerts and insights into mechanism(s) of action.

The ability of a compound to cause adverse effects to the liver is one of the most common reasons for drug development failures and the withdrawal of drugs from the market. Such adverse effects can vary tremendously in severity, leading to an array of possible drug-induced liver injuries (DILIs). As a result, it is not surprising that drug development has evolved into a complex and multifaceted process including methods aiming to identify potential liver toxicities. Unfortunately, hepatotoxicity remains one of the most complex and poorly understood areas of human toxicity; thus it is a significant challenge to identify potential hepatotoxins. The performance of existing methods to identify hepatotoxicity requires improvement. The current study details a scheme for generating chemical categories and the development of structural alerts able to identify potential hepatotoxins. The study utilized a diverse 951-compound dataset and used structural similarity methods to produce a number of structurally restricted categories. From these categories, 16 structural alerts associated with observed human hepatotoxicity were developed. Furthermore, the mechanism(s) by which these compounds cause hepatotoxicity were investigated and a mechanistic rationale was proposed, where possible, to yield mechanistically supported structural alerts. Alerts of this nature have the potential to be used in the screening of compounds to highlight potential hepatotoxicity, whilst the chemical categories themselves are important in applying read-across approaches. The scheme presented in this study also has the potential to act as a knowledge generator serving as an excellent starting platform from which to conduct additional toxicological studies.

Endoscopic ultrasound guided fine needle aspiration for the diagnosis of pancreatic cystic neoplasms: a meta-analysis.

BACKGROUND AND OBJECTIVES: Mucinous cystic neoplasms and intraductal papillary mucinous tumours have greater malignant potential than serous cystic neoplasms. EUS alone is inadequate for characterising these lesions but the addition of FNA may significantly improve diagnostic accuracy. The performance of EUS-FNA is highly variable in published studies. AIM: To determine the diagnostic accuracy of EUS-FNA to differentiate mucinous versus non-mucinous cystic lesions with cyst fluid analysis for cytology and carcinoembryonic antigen (CEA) by performing a meta-analysis of published studies. METHODS: Relevant studies were identified via structured database search and included if they used a reference standard of definitive surgical histology or clinical follow-up of at least 6 months. Data from selected studies were pooled to give summary sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio and Receiver Operating Characteristic (ROC) curve. Pre-defined subgroup analysis was performed. RESULTS: Eighteen studies (published 2002-2011) were included, with a total of 1438 patients. For cytology, pooled sensitivity was 54(95%CI 49-59)% and specificity 93(90-95)%. The diagnostic odds ratio (DOR) was 13.3 (4.37-49.43), with I(2) of 77.1%. For CEA sensitivity was 63(59-67)% and specificity 88(83-91)%. The DOR was 10.76(6.29-18.41) with an I(2) of 25.4%. The diagnostic accuracy of EUS-FNA was enhanced in prospective studies and studies of <36 months duration. No impact of publication bias on our results was demonstrated. CONCLUSIONS: Fine-needle aspiration has moderate sensitivity but high specificity for mucinous lesions. EUS-FNA, when used in conjunction with cross sectional imaging, is a useful diagnostic tool for the correct identification of mucinous cysts.

Effects of feed-borne Fusarium mycotoxins on performance, serum chemistry, and intestinal histology of New Zealand White fryer rabbits.

The objective of the present study was to determine the effects of feeding diets containing grains naturally contaminated with Fusarium mycotoxins to fryer rabbits. The efficacy of a glucomannan mycotoxin adsorbent (GMA) was also examined. Thirty 5-wk-old male New Zealand White rabbits were fed a control diet, a contaminated diet, or a contaminated diet + 0.2% GMA for 21 d. Experimental diets contained deoxynivalenol (DON; vomitoxin) at a concentration of 0.25, 4.3, and 4.9 µg/g, respectively. Feed intake was measured daily and water intake was measured every 3 d. At the end of the feeding period, blood was collected for evaluation of serum chemistry and hematology. Visceral organs were excised, weighed, and processed for histopathological examination. Body weight gain and water intake were greater in rabbits fed the contaminated diet (P = 0.075 and 0.020, respectively) and those fed the contaminated + GMA diet (P = 0.026 and 0.002, respectively) compared with controls. Rabbits fed the contaminated + GMA diet had significantly increased serum urea concentrations (P = 0.023) and decreased serum alkaline phosphatase activity (P = 0.020) compared with controls. Increase in BW gain of rabbits fed the contaminated diets was caused by increased water consumption. There was no effect (P > 0.05) of diet on relative organ weights, but decreased infiltrations with eosinophilic granulocytes were observed in different regions of the intestine in rabbits fed the contaminated or the contaminated + GMA diet. It was concluded that rabbits could be adversely affected by feed-borne Fusarium mycotoxins but appear to be less sensitive than other mammalian species. Supplementation with GMA did not reduce many of the effects of feed-borne mycotoxins.

Assessing toxicological data quality: basic principles, existing schemes and current limitations.

Existing toxicological data may be used for a variety of purposes such as hazard and risk assessment or toxicity prediction. The potential use of such data is, in part, dependent upon their quality. Consideration of data quality is of key importance with respect to the application of chemicals legislation such as REACH. Whether data are being used to make regulatory decisions or build computational models, the quality of the output is reflected by the quality of the data employed. Therefore, the need to assess data quality is an important requirement for making a decision or prediction with an appropriate level of confidence. This study considers the biological and chemical factors that may impact upon toxicological data quality and discusses the assessment of data quality. Four general quality criteria are introduced and existing data quality assessment schemes are discussed. Two case study datasets of skin sensitization data are assessed for quality providing a comparison of existing assessment methods. This study also discusses the limitations and difficulties encountered during quality assessment, including the use of differing quality schemes and the global versus chemical-specific assessments of quality. Finally, a number of recommendations are made to aid future data quality assessments.

Remote monitoring of lower-limb prosthetic socket fit using wireless technologies.

Accurate fitting of a lower-limb prosthetic socket is the most important factor affecting amputee satisfaction and rehabilitation. The technology is now available to allow real-time monitoring of in-service pressure distribution of prosthetic limbs. This paper proposes a remote interfacial pressure monitoring system necessary for the assessment of fit. The suitability of a wireless ZigBee network due to its relevant technical specification is investigated. The system enables remote monitoring of a prosthetic socket and its fit under different operating conditions thereby improving design, efficiency and effectiveness. The data can be used by prosthetists and may also be recorded for future training or for patient progress monitoring. This can minimize the number of iterations by getting it right first time, thereby minimizing the number of replacement prostheses.

An examination of the toxic properties of water extracts in the vicinity of an oil sand extraction site.

The industrial extraction of oil sands (OS) in northern Alberta, Canada, has raised concerns about the quality of the Athabasca River. The purpose of this study was to examine the toxic properties of various water extracts on Oncorhynchus mykiss trout hepatocytes. The water samples were fractionated on a reverse-phase C(18) cartridge and the levels of light-, medium- and heavy-weight polycyclic aromatic hydrocarbons (PAHs) were determined by fluorescence spectroscopy. Primary cultures of trout hepatocytes were exposed for 48 h at 15 °C to increasing concentrations of the C(18) extract corresponding to 0.02, 0.1, 0.5 and 2.5X concentrations from upstream/downstream sites in the Athabasca River, lake and groundwater samples, OS tailings and interceptor well-water samples. Changes in cell viability, phase I and phase II biotransformation enzymes (cytochrome P4501A and glutathione S-transferase activities), oxidative damage (lipid peroxidation LPO) and genotoxicity (single and double DNA strand breaks) were monitored in post-exposure cells. The water samples decreased cell viability and increased all the above endpoints at thresholds of between 0.02 and 0.1X the water concentration. The most responsive biomarker was DNA damage but it also offered the least discrimination among sites. LPO was higher at sites downstream of the industrial operations compared to upstream sites. A decision tree analysis was performed to formulate a set of rules by which to identify the distinctive properties of each type of water samples. The analysis revealed that OS tailings and interceptor waters were characterized by an increased concentration in light PAHs (>42 µg L(-1)) and this fraction represented more than 85% of the total PAHs. These samples also inhibited GST activity, which could compromise the elimination of genotoxic PAHs present in the system. An analysis of groundwater samples revealed a contamination pattern similar to that for OS tailings. There is a need for more research into specific biomarkers of toxicity from OS tailings compounds such as naphthenic acids, light PAHs among others, which are a characteristic fingerprint of OS extraction activities.

Repeatability analysis of the Tetrahymena pyriformis population growth impairment assay.

Assessments necessary to ensure the safety of both humans and the environment are challenged by the sheer number of chemicals in use today. Chemical legislation, such as REACH, aims to use alternative methods to reduce the reliance on in vivo animal testing. Consequently, databases such as the TETRATOX database, containing data from the Tetrahymena pyriformis population growth impairment assay, have been used extensively to develop computational models which aid in priority setting and initial hazard assessments. To use any toxicological data, an assessment of quality is required. One important aspect of quality is the repeatability of the assay. This study considered TETRATOX assay data for 85 structurally and mechanistically diverse compounds. The repeatability of replicate determinations was assessed and factors relating to repeatability are discussed. Despite the majority of compounds demonstrating excellent repeatability, it was found that the mechanism of action is likely to be a modulating factor, with compounds acting via electrophilic mechanisms being more likely to exhibit reduced repeatability than those acting via narcotic mechanisms. It is evident from this study that the TETRATOX assay is a robust and highly repeatable assay, suitable for use in toxicological modelling studies and priority setting.

QSAR modelling of bioconcentration factor using hydrophobicity, hydrogen bonding and topological descriptors.

Bioconcentration factor (BCF) is an important step in the uptake of environmental pollutants in the food chain. It is expensive and time-consuming to measure, so predictive methods are of value. We have used an artificial neural network QSAR approach involving descriptors for hydrophobicity, hydrogen bonding and molecular topology, obtained from commercially available software, to predict the fish BCF values of a diverse data set of 624 chemicals. The training set statistics were: r²= 0.765, q²= 0.763, s = 0.610, and those of the external test set were: r²= 0.739, s = 0.627. The model complies with the OECD Principles for the Validation of (Q)SARs.

Parental involvement in paediatric cancer treatment decisions.

This study investigated parents' information needs and involvement in decision-making processes affecting the care of children diagnosed with cancer. Interviews and questionnaires were used to assess parental satisfaction in 50 mothers and 16 fathers responsible for 58 children in an English Paediatric Oncology Unit. Parents reported that doctors contributed almost twice as much to the decision-making process as they did, but parental satisfaction was positively correlated with the amount of information provided when giving informed consent. Satisfaction about their involvement in this process relied heavily upon the level of support received from others. Parents consenting to their child's involvement in non-randomised trials perceived themselves to be under greater pressure from others during the decision-making process while those whose children were further along the treatment trajectory were more uncertain about decisions previously made. Findings indicate that the accessibility, support, information and degree of control afforded to parents by healthcare professionals impacts upon their satisfaction with both the decision-making process and their confidence in the decisions thus made. Information and support tailored to parents' specific needs may therefore enhance satisfaction with clinical decision making and reassure parents about decisions made in the long-term interest of their child's health.