Impact of cardiac interoception cues and confidence on voluntary decisions to make or withhold action in an intentional inhibition task

Interoceptive signals concerning the internal physiological state of the body influence motivational feelings and action decisions. Cardiovascular arousal may facilitate inhibition to mitigate risks of impulsive actions. Baroreceptor discharge at ventricular systole underpins afferent signalling of cardiovascular arousal. In a modified Go/NoGo task, decisions to make or withhold actions on ‘Choose’ trials were not influenced by cardiac phase, nor individual differences in heart rate variability. However, cardiac interoceptive awareness and insight predicted how frequently participants chose to act, and their speed of action: Participants with better awareness and insight tended to withhold actions and respond slower, while those with poorer awareness and insight tended to execute actions and respond faster. Moreover, self-reported trait urgency correlated negatively with intentional inhibition rates. These findings suggest that lower insight into bodily signals is linked to urges to move the body, putatively by engendering noisier sensory input into motor decision processes eliciting reactive behaviour

Qualitative Environmental Health Research: An Analysis of the Literature, 1991-2008

BACKGROUND. Recent articles have advocated for the use of qualitative methods in environmental health research. Qualitative research uses nonnumeric data to understand people's opinions, motives, understanding, and beliefs about events or phenomena. OBJECTIVE. In this analysis of the literature, I report the use of qualitative methods and data in the study of the relationship between environmental exposures and human health. DATA SOURCES. A primary search on ISI Web of Knowledge/Web of Science for peer-reviewed journal articles dated from 1991 through 2008 included the following three terms: qualitative, environ*, and health. Inclusion and exclusion criteria are described. DATA EXTRACTION. Searches resulted in 3,155 records. Data were extracted and findings of articles analyzed to determine where and by whom qualitative environmental health research is conducted and published, the types of methods and analyses used in qualitative studies of environmental health, and the types of information qualitative data contribute to environmental health. DATA SYNTHESIS. Ninety-one articles met inclusion criteria. These articles were published in 58 different journals, with a maximum of eight for a single journal. The results highlight a diversity of disciplines and techniques among researchers who used qualitative methods to study environmental health, with most studies relying on one-on-one interviews. Details of the analyses were absent from a large number of studies. Nearly all of the studies identified increased scientific understanding of lay perceptions of environmental health exposures. DISCUSSION AND CONCLUSIONS. Qualitative data are published in traditionally quantitative environmental health studies to a limited extent. However, this analysis demonstrates the potential of qualitative data to improve understanding of complex exposure pathways, including the influence of social factors on environmental health, and health outcomes.National Institute of Environmental Health Sciences (R25 ES012084, P42ES007381

Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness.

In the fourth article of a five-part series providing a global perspective on integrating mental health, Sylvia Kaaya and colleagues discuss the importance of integrating mental health interventions into HIV prevention and treatment platforms. Please see later in the article for the Editors' Summary

The combined effect of smoking tobacco and drinking alcohol on cause-specific mortality: a 30 year cohort study

<p><b>Background:</b> Smoking and consuming alcohol are both related to increased mortality risk. Their combined effects on cause-specific mortality were investigated in a prospective cohort study.</p> <p><b>Methods:</b> Participants were 5771 men aged 35-64, recruited during 1970-73 from various workplaces in Scotland. Data were obtained from a questionnaire and a screening examination. Causes of death were all cause, coronary heart disease (CHD), stroke, alcohol-related, respiratory and smoking-related cancer. Participants were divided into nine groups according to their smoking status (never, ex or current) and reported weekly drinking (none, 1-14 units and 15 or more). Cox proportional hazards models were used to obtain relative rates of mortality, adjusted for age and other risk factors.</p> <p><b>Results:</b> In 30 years of follow-up, 3083 men (53.4%) died. Compared with never smokers who did not drink, men who both smoked and drank 15+ units/week had the highest all-cause mortality (relative rate = 2.71 (95% confidence interval 2.31-3.19)). Relative rates for CHD mortality were high for current smokers, with a possible protective effect of some alcohol consumption in never smokers. Stroke mortality increased with both smoking and alcohol consumption. Smoking affected respiratory mortality with little effect of alcohol. Adjusting for a wide range of confounders attenuated the relative rates but the effects of alcohol and smoking still remained. Premature mortality was particularly high in smokers who drank 15 or more units, with a quarter of the men not surviving to age 65. 30% of men with manual occupations both smoked and drank 15+ units/week compared with only 13% with non-manual ones.</p> <p><b>Conclusions:</b> Smoking and drinking 15+ units/week was the riskiest behaviour for all causes of death.</p&gt

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

Use of technology in children's dietary assessment

Background: Information on dietary intake provides some of the most valuable insights for mounting intervention programmes for the prevention of chronic diseases. With the growing concern about adolescent overweight, the need to accurately measure diet becomes imperative. Assessment among adolescents is problematic as this group has irregular eating patterns and they have less enthusiasm for recording food intake. Subjects/Methods: We used qualitative and quantitative techniques among adolescents to assess their preferences for dietary assessment methods.Results: Dietary assessment methods using technology, for example, a personal digital assistant (PDA) or a disposable camera, were preferred over the pen and paper food record. Conclusions: There was a strong preference for using methods that incorporate technology such as capturing images of food. This suggests that for adolescents, dietary methods that incorporate technology may improve cooperation and accuracy. Current computing technology includes higher resolution images, improved memory capacity and faster processors that allow small mobile devices to process information not previously possible. Our goal is to develop, implement and evaluate a mobile device (for example, PDA, mobile phone) food record that will translate to an accurate account of daily food and nutrient intake among adolescents. This mobile computing device will include digital images, a nutrient database and image analysis for identification and quantification of food consumption. Mobile computing devices provide a unique vehicle for collecting dietary information that reduces the burden on record keepers. Images of food can be marked with a variety of input methods that link the item for image processing and analysis to estimate the amount of food. Images before and after the foods are eaten can estimate the amount of food consumed. The initial stages and potential of this project will be described

Bacterial morphotype grading for periodontal disease assessment

BACKGROUND: Listgarten and Hellden (1978) used darkfield microscopy of wet mounts to differentiate between healthy and periodontally diseased sites in the mouth by expressing the different bacterial morphotypes observed as a percentage of the total number of bacteria counted. This method of periodontal disease assessment gained favour as a diagnostic tool but presented with the limitation of immediate examination to determine the number of motile rods present and an inability to distinguish between gingivitis and periodontitis. Grading of bacterial morphotypes into several distinct categories of health or disease (Ison and Hay, 2002), simplified the scoring system of Gram-stained smears for the diagnosis of bacterial vaginosis (Nugent et al. 1991). The application of a similar grading system using stained smears rather than wet mounts could be advantageous to the diagnosis of periodontal disease. OBJECTIVES/AIMS: This study tested the hypothesis that stained smears of dental plaque collected from the gingival crevice of individuals with varying probing pocket depths (PD) may provide a grading system for periodontal disease assessment. MATERIALS AND METHODS: Subgingival plaque samples were collected from 49 patients, stained with a silver stain and the proportions of each bacterial morphotype graded relative to their respective PD measurements. RESULTS: This technique allowed for a grading system of I–IV, with grade I indicating health and grade IV indicating severe periodontal disease. DISCUSSION: Stained smear examination eliminates the time restriction for motile rod enumeration and allows for storage of smears for future reference. CONCLUSION: Standardization of the microscopic areas to be evaluated or examined will facilitate the agreement of cut-off values for the diagnosis of periodontal disease.This material is based on work partially supported financially by the National Research Foundation (NRF) of South Africa

Synthesis and Biological Evaluation of Phenanthrenes as Cytotoxic Agents with Pharmacophore Modeling and ChemGPS-NP Prediction as Topo II Inhibitors

In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC50 0.08–1.66 µg/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a–b and for the carbonyl group of 5-OCOCH3 in 7a–b, important for their cytotoxic properties. The SAR for moderately active 5a–b (5-OCH3), and highly active 6a–b and 7a–b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a–b as topoisomerase II inhibitors

Genetics of callous-unemotional behavior in children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU

Monitoring the initial pulmonary absorption of two different beclomethasone dipropionate aerosols employing a human lung reperfusion model

BACKGROUND: The pulmonary residence time of inhaled glucocorticoids as well as their rate and extend of absorption into systemic circulation are important facets of their efficacy-safety profile. We evaluated a novel approach to elucidate the pulmonary absorption of an inhaled glucocorticoid. Our objective was to monitor and compare the combined process of drug particle dissolution, pro-drug activation and time course of initial distribution from human lung tissue into plasma for two different glucocorticoid formulations. METHODS: We chose beclomethasone dipropionate (BDP) delivered by two different commercially available HFA-propelled metered dose inhalers (Sanasthmax(®)/Becloforte™ and Ventolair(®)/Qvar™). Initially we developed a simple dialysis model to assess the transfer of BDP and its active metabolite from human lung homogenate into human plasma. In a novel experimental setting we then administered the aerosols into the bronchus of an extracorporally ventilated and reperfused human lung lobe and monitored the concentrations of BDP and its metabolites in the reperfusion fluid. RESULTS: Unexpectedly, we observed differences between the two aerosol formulations Sanasthmax(®)/Becloforte™ and Ventolair(®)/Qvar™ in both the dialysis as well as in the human reperfusion model. The HFA-BDP formulated as Ventolair(®)/Qvar™ displayed a more rapid release from lung tissue compared to Sanasthmax(®)/Becloforte™. We succeeded to explain and illustrate the observed differences between the two aerosols with their unique particle topology and divergent dissolution behaviour in human bronchial fluid. CONCLUSION: We conclude that though the ultrafine particles of Ventolair(®)/Qvar™ are beneficial for high lung deposition, they also yield a less desired more rapid systemic drug delivery. While the differences between Sanasthmax(®)/Becloforte™ and Ventolair(®)/Qvar™ were obvious in both the dialysis and lung perfusion experiments, the latter allowed to record time courses of pro-drug activation and distribution that were more consistent with results of comparable clinical trials. Thus, the extracorporally reperfused and ventilated human lung is a highly valuable physiological model to explore the lung pharmacokinetics of inhaled drugs