Metabolomics Profiling for Identification of Novel Potential Markers in Early Prediction of Preeclampsia

Objective

The first aim was to investigate specific signature patterns of metabolites that are significantly altered in first-trimester serum of women who subsequently developed preeclampsia (PE) compared to healthy pregnancies. The second aim of this study was to examine the predictive performance of the selected metabolites for both early onset [EO-PE] and late onset PE [LO-PE].

Methods

This was a case-control study of maternal serum samples collected between 8+0 and 13+6 weeks of gestation from 167 women who subsequently developed EO-PE n = 68; LO-PE n = 99 and 500 controls with uncomplicated pregnancies. Metabolomics profiling analysis was performed using two methods. One has been optimized to target eicosanoids/oxylipins, which are known inflammation markers and the other targets compounds containing a primary or secondary biogenic amine group. Logistic regression analyses were performed to predict the development of PE using metabolites alone and in combination with first trimester mean arterial pressure (MAP) measurements.

Results

Two metabolites were significantly different between EO-PE and controls (taurine and asparagine) and one in case of LO-PE (glycylglycine). Taurine appeared the most discriminative biomarker and in combination with MAP predicted EO-PE with a detection rate (DR) of 55%, at a false-positive rate (FPR) of 10%.

Conclusion

Our findings suggest a potential role of taurine in both PE pathophysiology and first trimester screening for EO-PE.     

Metabolomic Derangements Are Associated with Mortality in Critically Ill Adult Patients

Objective

To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU) mortality in adults.

Rationale

Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasible.

Methods

We performed metabolomic profiling of plasma from 90 ICU subjects enrolled in the BWH Registry of Critical Illness (RoCI). We tested individual metabolites and a Bayesian Network of metabolites for association with 28-day mortality, using logistic regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites and the network were tested for replication in an independent cohort of 149 adults enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD) study.

Results

We tested variable metabolites for association with 28-day mortality. In RoCI, nearly one third of metabolites differed among ICU survivors versus those who died by day 28 (N = 57 metabolites, p<.05). Associations with 28-day mortality replicated for 31 of these metabolites (with p<.05) in the CAPSOD population. Replicating metabolites included lipids (N = 14), amino acids or amino acid breakdown products (N = 12), carbohydrates (N = 1), nucleotides (N = 3), and 1 peptide. Among 31 replicated metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine, 1-arachidonoylGPC(20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine). This network achieved a 91% AUC predicting 28-day mortality in RoCI, and 74% of the AUC in CAPSOD (p<.001 in both populations).

Conclusion

Both individual metabolites and a metabolomic network were associated with 28-day mortality in two independent cohorts. Metabolomic profiling represents a valuable new approach for identifying novel biomarkers in critically ill patients.     

Metabolome-Wide Association Study of Neovascular Age-Related Macular Degeneration

Purpose

To determine if plasma metabolic profiles can detect differences between patients with neovascular age-related macular degeneration (NVAMD) and similarly-aged controls.

Methods

Metabolomic analysis using liquid chromatography with Fourier-transform mass spectrometry (LC-FTMS) was performed on plasma samples from 26 NVAMD patients and 19 controls. Data were collected from mass/charge ratio (m/z) 85 to 850 on a Thermo LTQ-FT mass spectrometer, and metabolic features were extracted using an adaptive processing software package. Both non-transformed and log2 transformed data were corrected using Benjamini and Hochberg False Discovery Rate (FDR) to account for multiple testing. Orthogonal Partial Least Squares-Discriminant Analysis was performed to determine metabolic features that distinguished NVAMD patients from controls. Individual m/z features were matched to the Kyoto Encyclopedia of Genes and Genomes database and the Metlin metabolomics database, and metabolic pathways associated with NVAMD were identified using MetScape.

Results

Of the 1680 total m/z features detected by LC-FTMS, 94 unique m/z features were significantly different between NVAMD patients and controls using FDR (q = 0.05). A comparison of these features to those found with log2 transformed data (n = 132, q = 0.2) revealed 40 features in common, reaffirming the involvement of certain metabolites. Such metabolites included di- and tripeptides, covalently modified amino acids, bile acids, and vitamin D-related metabolites. Correlation analysis revealed associations among certain significant features, and pathway analysis demonstrated broader changes in tyrosine metabolism, sulfur amino acid metabolism, and amino acids related to urea metabolism.

Conclusions

These data suggest that metabolomic analysis can identify a panel of individual metabolites that differ between NVAMD cases and controls. Pathway analysis can assess the involvement of certain metabolic pathways, such as tyrosine and urea metabolism, and can provide further insight into the pathophysiology of AMD.     

Search Query Data to Monitor Interest in Behavior Change: Application for Public Health

There is a need for effective interventions and policies that target the leading preventable causes of death in the U.S. (e.g., smoking, overweight/obesity, physical inactivity). Such efforts could be aided by the use of publicly available, real-time search query data that illustrate times and locations of high and low public interest in behaviors related to preventable causes of death.

Objectives

This study explored patterns of search query activity for the terms ‘weight’, ‘diet’, ‘fitness’, and ‘smoking’ using Google Insights for Search.

Methods

Search activity for ‘weight’, ‘diet’, ‘fitness’, and ‘smoking’ conducted within the United States via Google between January 4^th, 2004 (first date data was available) and November 28^th, 2011 (date of data download and analysis) were analyzed. Using a generalized linear model, we explored the effects of time (month) on mean relative search volume for all four terms.

Results

Models suggest a significant effect of month on mean search volume for all four terms. Search activity for all four terms was highest in January with observable declines throughout the remainder of the year.

Conclusions

These findings demonstrate discernable temporal patterns of search activity for four areas of behavior change. These findings could be used to inform the timing, location and messaging of interventions, campaigns and policies targeting these behaviors.     

A Biomarker Panel (Bioscore) Incorporating Monocytic Surface and Soluble TREM-1 Has High Discriminative Value for Ventilator-Associated Pneumonia: A Prospective Observational Study

Introduction

Ventilator-associated pneumonia (VAP) increases mortality in critical illness. However, clinical diagnostic uncertainty persists. We hypothesised that measuring cell-surface and soluble inflammatory markers, incorporating Triggering Receptor Expressed by Myeloid cells (TREM)-1, would improve diagnostic accuracy.

Methods

A single centre prospective observational study, set in a University Hospital medical-surgical intensive Care unit, recruited 91 patients into 3 groups: 27 patients with VAP, 33 ventilated controls without evidence of pulmonary sepsis (non-VAP), and 31 non-ventilated controls (NVC), without clinical infection, attending for bronchoscopy. Paired samples of Bronchiolo-alveolar lavage fluid (BALF) and blood from each subject were analysed for putative biomarkers of infection: Cellular (TREM-1, CD11b and CD62L) and soluble (IL-1β, IL-6, IL-8, sTREM-1, Procalcitonin). Expression of cellular markers on monocytes and neutrophils were measured by flow cytometry. Soluble inflammatory markers were determined by ELISA. A biomarker panel (‘Bioscore’), was constructed, tested and validated, using Fisher’s discriminant function analysis, to assess its value in distinguishing VAP from non VAP.

Results

The expression of TREM-1 on monocytes (mTREM-1) and neutrophils (nTREM-1) and concentrations of IL-1β, IL-8, and sTREM-1 in BALF were significantly higher in VAP compared with non-VAP and NVC (p<0.001). The BALF/blood mTREM-1 was significantly higher in VAP patients compared to non-VAP and NVC (0.8 v 0.4 v 0.3 p<0.001). A seven marker Bioscore (BALF/blood ratio mTREM-1 and mCD11b, BALF sTREM-1, IL-8 and IL-1β, and serum CRP and IL-6) correctly identified 88.9% of VAP cases and 100% of non-VAP cases.

Conclusion

A 7-marker bioscore, incorporating cellular and soluble TREM-1, accurately discriminates VAP from non-pulmonary infection.     

The Association between Race and Crohn's Disease Phenotype in the Western Cape Population of South Africa,Defined by the Montreal Classification System

Background

Inter-racial differences in disease characteristics and in the management of Crohn''s disease (CD) have been described in African American and Asian subjects, however for the racial groups in South Africa, no such recent literature exists.

Methods

A cross sectional study of all consecutive CD patients seen at 2 large inflammatory bowel disease (IBD) referral centers in the Western Cape, South Africa between September 2011 and January 2013 was performed. Numerous demographic and clinical variables at diagnosis and date of study enrolment were identified using an investigator administered questionnaire as well as clinical examination and patient case notes. Using predefined definitions, disease behavior was stratified as ‘complicated’ or ‘uncomplicated’.

Results

One hundred and ninety four CD subjects were identified; 35 (18%) were white, 152 (78%) were Cape Coloured and 7(4%) were black. On multiple logistic regression analysis Cape Coloureds were significantly more likely to develop ‘complicated’ CD (60% vs. 9%, p = 0.023) during the disease course when compared to white subjects. In addition, significantly more white subjects had successfully discontinued cigarette smoking at study enrolment (31% vs. 7% reduction, p = 0.02). No additional inter-racial differences were found. A low proportion of IBD family history was observed among the non-white subjects.

Conclusions

Cape Coloured patients were significantly more likely to develop ‘complicated’ CD over time when compared to whites.     

Communicating and Dealing with Uncertainty in General Practice: The Association with Neuroticism

Background

Diagnostic reasoning in primary care setting where presented problems and patients are mostly unselected appears as a complex process. The aim was to develop a questionnaire to describe how general practitioners (GPs) deal with uncertainty to gain more insight into the decisional process. The association of personality traits with medical decision making was investigated additionally.

Methods

Raw items were identified by literature research and focus group. Items were improved by interviewing ten GPs with thinking-aloud-method. A personal case vignette related to a complex and uncertainty situation was introduced. The final questionnaire was administered to 228 GPs in Germany. Factorial validity was calculated with explorative and confirmatory factor analysis. The results of the Communicating and Dealing with Uncertainty (CoDU) – questionnaire were compared with the scales of the ‘Physician Reaction to Uncertainty’ (PRU) questionnaire and with the personality traits which were determined with the Big Five Inventory (BFI-K).

Results

The items could be assigned to four scales with varying internal consistency, namely ‘communicating uncertainty’ (Cronbach alpha 0.79), ‘diagnostic action’ (0.60), ‘intuition’ (0.39) and ‘extended social anamnesis’ (0.69). Neuroticism was positively associated with all PRU scales ‘anxiety due to uncertainty’ (Pearson correlation 0.487), ‘concerns about bad outcomes’ (0.488), ‘reluctance to disclose uncertainty to patients’ (0.287), ‘reluctance to disclose mistakes to physicians’ (0.212) and negatively associated with the CoDU scale ‘communicating uncertainty’ (−0.242) (p<0.01 for all). ‘Extraversion’ (0.146; p<0.05), ‘agreeableness’ (0.145, p<0.05), ‘conscientiousness’ (0.168, p<0.05) and ‘openness to experience’ (0.186, p<0.01) were significantly positively associated with ‘communicating uncertainty’. ‘Extraversion’ (0.162), ‘consciousness’ (0.158) and ‘openness to experience’ (0.155) were associated with ‘extended social anamnesis’ (p<0.05).

Conclusion

The questionnaire allowed describing the diagnostic decision making process of general practitioners in complex situations. Personality traits are associated with diagnostic reasoning and communication with patients, which might be important for medical education and quality improvement purposes.     

Standardized Handwriting to Assess Bradykinesia,Micrographia and Tremor in Parkinson's Disease

Objective

To assess whether standardized handwriting can provide quantitative measures to distinguish patients diagnosed with Parkinson''s disease from age- and gender-matched healthy control participants.

Design

Exploratory study. Pen tip trajectories were recorded during circle, spiral and line drawing and repeated character ‘elelelel’ and sentence writing, performed by Parkinson patients and healthy control participants. Parkinson patients were tested after overnight withdrawal of anti-Parkinsonian medication.

Setting

University Medical Center Groningen, tertiary care, the Netherlands.

Participants

Patients with Parkinson''s disease (n = 10; mean age 69.0 years; 6 male) and healthy controls (n = 10; mean age 68.1 years; 6 male).

Interventions

Not applicable.

Main Outcome Measures

Movement time and velocity to detect bradykinesia and the size of writing to detect micrographia. A rest recording to investigate the presence of a rest-tremor, by frequency analysis.

Results

Mean disease duration in the Parkinson group was 4.4 years and the patients were in modified Hoehn-Yahr stages 1–2.5. In general, Parkinson patients were slower than healthy control participants. Median time per repetition, median velocity and median acceleration of the sentence task and median velocity of the elel task differed significantly between Parkinson patients and healthy control participants (all p<0.0014). Parkinson patients also wrote smaller than healthy control participants and the width of the ‘e’ in the elel task was significantly smaller in Parkinson patients compared to healthy control participants (p<0.0014). A rest-tremor was detected in the three patients who were clinically assessed as having rest-tremor.

Conclusions

This study shows that standardized handwriting can provide objective measures for bradykinesia, tremor and micrographia to distinguish Parkinson patients from healthy control participants.     

Beyond a Dichotomous View of the Concepts of ‘Sex’ and ‘Gender’ Focus Group Discussions among Gender Researchers at a Medical Faculty

Introduction

The concepts of ‘sex’ and ‘gender’ are both of vital importance in medicine and health sciences. However, the meaning of these concepts has seldom been discussed in the medical literature. The aim of this study was to explore what the concepts of ‘sex’ and ‘gender’ meant for gender researchers based in a medical faculty.

Methods

Sixteen researchers took part in focus group discussions. The analysis was performed in several steps. The participating researchers read the text and discussed ideas for analysis in national and international workshops. The data were analysed using qualitative content analysis. The authors performed independent preliminary analyses, which were further developed and intensively discussed between the authors.

Results

The analysis of meanings of the concepts of ‘sex’ and ‘gender’ for gender researchers based in a medical faculty resulted in three categories; “Sex as more than biology”, with the subcategories ‘sex’ is not simply biological, ‘sex’ as classification, and ‘sex’ as fluid and changeable; ”Gender as a multiplicity of power-related constructions”, with the subcategories: ‘gender’ as constructions, ‘gender’ power dimensions, and ‘gender’ as doing femininities and masculinities; “Sex and gender as interwoven”, with the subcategories: ‘sex’ and ‘gender’ as inseparable and embodying ‘sex’ and ‘gender’.

Conclusions

Gender researchers within medicine pointed out the importance of looking beyond a dichotomous view of the concepts of ‘sex’ and ‘gender’. The perception of the concepts was that ‘sex’ and ‘gender’ were intertwined. Further research is needed to explore how ‘sex’ and ‘gender’ interact.     

Placebo Use in the United Kingdom: Results from a National Survey of Primary Care Practitioners

Objectives

Surveys in various countries suggest 17% to 80% of doctors prescribe ‘placebos’ in routine practice, but prevalence of placebo use in UK primary care is unknown.

Methods

We administered a web-based questionnaire to a representative sample of UK general practitioners. Following surveys conducted in other countries we divided placebos into ‘pure’ and ‘impure’. ‘Impure’ placebos are interventions with clear efficacy for certain conditions but are prescribed for ailments where their efficacy is unknown, such as antibiotics for suspected viral infections. ‘Pure’ placebos are interventions such as sugar pills or saline injections without direct pharmacologically active ingredients for the condition being treated. We initiated the survey in April 2012. Two reminders were sent and electronic data collection closed after 4 weeks.

Results

We surveyed 1715 general practitioners and 783 (46%) completed our questionnaire. Our respondents were similar to those of all registered UK doctors suggesting our results are generalizable. 12% (95% CI 10 to 15) of respondents used pure placebos while 97% (95% CI 96 to 98) used impure placebos at least once in their career. 1% of respondents used pure placebos, and 77% (95% CI 74 to 79) used impure placebos at least once per week. Most (66% for pure, 84% for impure) respondents stated placebos were ethical in some circumstances.

Conclusion and implications

Placebo use is common in primary care but questions remain about their benefits, harms, costs, and whether they can be delivered ethically. Further research is required to investigate ethically acceptable and cost-effective placebo interventions.     

Predictors of Viral Pneumonia in Patients with Community-Acquired Pneumonia

Background

Viruses are increasingly recognized as major causes of community-acquired pneumonia (CAP). Few studies have investigated the clinical predictors of viral pneumonia, and the results have been inconsistent. In this study, the clinical predictors of viral pneumonia were investigated in terms of their utility as indicators for viral pneumonia in patients with CAP.

Methods

Adult patients (≥18 years old) with CAP, tested by polymerase chain reaction (PCR) for respiratory virus, at two teaching hospitals between October 2010 and May 2013, were identified retrospectively. Demographic and clinical data were collected by reviewing the hospital electronic medical records.

Results

During the study period, 456 patients with CAP were identified who met the definition, and 327 (72%) patients were tested using the respiratory virus PCR detection test. Viral pneumonia (n = 60) was associated with rhinorrhea, a higher lymphocyte fraction in the white blood cells, lower serum creatinine and ground-glass opacity (GGO) in radiology results, compared to non-viral pneumonia (n = 250) (p<0.05, each). In a multivariate analysis, rhinorrhea (Odd ratio (OR) 3.52; 95% Confidence interval (CI), 1.58–7.87) and GGO (OR 4.68; 95% CI, 2.48–8.89) were revealed as independent risk factors for viral pneumonia in patients with CAP. The sensitivity, specificity, positive- and negative-predictive values (PPV and NPV) of rhinorrhea were 22, 91, 36 and 83%: the sensitivity, specificity, PPV and NPV of GGO were and 43, 84, 40 and 86%, respectively.

Conclusion

Symptom of rhinorrhea and GGO predicted viral pneumonia in patients with CAP. The high specificity of rhinorrhea and GGO suggested that these could be useful indicators for empirical antiviral therapy.     

Visual information without thermal energy may induce thermoregulatory-like cardiovascular responses

Background

Human core body temperature is kept quasi-constant regardless of varying thermal environments. It is well known that physiological thermoregulatory systems are under the control of central and peripheral sensory organs that are sensitive to thermal energy. If these systems wrongly respond to non-thermal stimuli, it may disturb human homeostasis.

Methods

Fifteen participants viewed video images evoking hot or cold impressions in a thermally constant environment. Cardiovascular indices were recorded during the experiments. Correlations between the ‘hot-cold’ impression scores and cardiovascular indices were calculated.

Results

The changes of heart rate, cardiac output, and total peripheral resistance were significantly correlated with the ‘hot-cold’ impression scores, and the tendencies were similar to those in actual thermal environments corresponding to the impressions.

Conclusions

The present results suggest that visual information without any thermal energy can affect physiological thermoregulatory systems at least superficially. To avoid such ‘virtual’ environments disturbing human homeostasis, further study and more attention are needed.     

Sex Differences in Itch Perception and Modulation by Distraction – an fMRI Pilot Study in Healthy Volunteers

Background

Even though itch is a common syndrome of many diseases there is only little knowledge about sex and gender differences in pruritus, especially in central itch perception and modulation. To our knowledge, this is the first fMRI study examining sex differences in perception and its modulation by distraction.

Methods

Experimental itch was induced by application of histamine (0.1 mM) via microdialysis fibers twice at the left forearm and twice at the left lower leg in 33 healthy volunteers (17 females, 16 males). The brain activation patterns were assessed by fMRI during itch without and with distraction (Stroop task). Between the various conditions, subjects were asked to rate itch intensity, desire to scratch and pain intensity. In a second experiment in 10 of the 33 volunteers histamine was replaced by saline solution to serve as control for the ‘Stroop’ condition.

Results

Women generally presented higher itch intensities compared to men during itch over the course of the experiment. A more specific analysis revealed higher itch intensities and desire to scratch in women during experimental induced itch that can be reduced by distraction at the lower legs when itch is followed by ‘Stroop’. In contrast, men depicted significant reduction of ‘itch’ by ‘Stroop’ at the forearms. Women depicted higher brain activation of structures responsible for integration of sensory, affective information and motor integration/planning during ‘itch’ and ‘Stroop’ condition when compared to men. No sex differences were seen in the saline control condition.

Conclusion

Women and men exhibited localisation dependent differences in their itch perception with women presenting higher itch intensities and desire to scratch. Our findings parallel clinical observations of women reporting higher itch intensities depending on itch localisation and suffering more from itch as compared to men.     

Psychological and physiological effect in humans of touching plant foliage - using the semantic differential method and cerebral activity as indicators

Background

Numerous studies have reported on the healing powers of plants and nature, but there have not been so many instances of experimental research. In particular, there are very few psychological and physiological studies using tactile stimuli. This study examines the psychological and physiological effects of touching plant foliage by using an evaluation profile of the subjects’ impressions and investigating cerebral blood flow.

Methods

The subjects were 14 young Japanese men aged from 21 to 27 years (mean ± standard deviation: 23.6 ± 2.4). With their eyes closed, the subjects touched four different tactile samples including a leaf of natural pothos (Epipremnum aureum). The physiological indices were compared before and after each stimulus. Psychological indices were obtained using a ‘semantic differential’ method.

Results

The fabric stimulus gave people ‘soft’ and ‘rough’ impressions, ‘kind’, ‘peaceful’ and ‘pleasant’ feelings psychologically, and a sense of physiological calm. On the other hand, the metal stimulus gave people ‘cold’, ‘smooth’ and ‘hard’ impressions and an image of something ‘artificial’. The metal stimulus caused a stress response in human cerebral blood flow although its evaluation in terms of ‘pleasant or unpleasant’ was neutral. There were no remarkable differences between the stimuli of natural and artificial pothos compared with other types of stimulus psychologically. However, only the natural pothos stimulus showed a sense of physiological calm in the same appearance as the fabric stimulus.

Conclusions

This study shows that people experience an unconscious calming reaction to touching a plant. It is to be concluded that plants are an indispensable element of the human environment.     

Detection of Subclinical Atherosclerosis in Asymptomatic Subjects Using Ultrasound Radiofrequency-Tracking Technology

Objective

Atherosclerosis is a chronic and systemic disease and its developmental process involves the synergism of multiple risk factors such as hypertension, dyslipidemia, diabetes, obesity and smoking. The diagnosis of subclinical atherosclerosis is essential for strategic guidance towards suitable treatments and efficient prevention against acute cardiovascular events. This study employed ultrasound radiofrequency (RF) tracking technology to characterize human carotid arteries in vivo in terms of intima-media thickness (IMT) and artery stiffness, and evaluated the statistical correlation between carotid IMT and stiffness, and the number of risk factors for atherosclerosis.

Methods

A total of 160 asymptomatic subjects were enrolled. Ultrasound RF-tracking technology was employed to acquire carotid IMT and stiffness parameters: maximum IMT (^MAXIMT), RF Quality IMT (^RFQIMT), distensibility coefficient (), compliance coefficient (), index, index and local pulse wave velocity (). The subjects were categorized in four groups in terms of the number of risk factors: ‘zero’, ‘single’, ‘double’, and ‘multiple’, and statistical analyses of carotid IMT and stiffness parameters were performed between these different groups.

Results

The subjects (n = 145) with ^MAXIMT smaller than 1.0 mm matched the IMT criteria for non-atherosclerosis and were named as NA-subjects. Spearman’s rho correlation analysis of the whole group and the NA-subjects both showed that ^MAXIMT correlated positively with ^RFQIMT, , , and , and negatively with and (p<0.01). The analysis of covariance of NA-subjects showed significant differences between subjects with and without risk factors, and also showed significant differences between the ‘zero’, ‘single’, ‘double’, and ‘multiple’ groups.

Conclusions

The carotid IMT and stiffness parameters obtained by the ultrasound RF-tracking technology were demonstrated to possess significant statistical correlation with the number of risk factors from 160 subjects, and these anatomical and mechanical parameters may potentially be used together with the IMT criteria to support subclinical atherosclerosis diagnosis.     

Accuracy of the Interpretation of Chest Radiographs for the Diagnosis of Paediatric Pneumonia

Introduction

World Health Organization (WHO) radiological classification remains an important entry criterion in epidemiological studies of pneumonia in children. We report inter-observer variability in the interpretation of 169 chest radiographs in children suspected of having pneumonia.

Methods

An 18-month prospective aetiological study of pneumonia was undertaken in Northern England. Chest radiographs were performed on eligible children aged ≤16 years with clinical features of pneumonia. The initial radiology report was compared with a subsequent assessment by a consultant cardiothoracic radiologist. Chest radiographic changes were categorised according to the WHO classification.

Results

There was significant disagreement (22%) between the first and second reports (kappa = 0.70, P<0.001), notably in those aged <5 years (26%, kappa = 0.66, P<0.001). The most frequent sources of disagreement were the reporting of patchy and perihilar changes.

Conclusion

This substantial inter-observer variability highlights the need for experts from different countries to create a consensus to review the radiological definition of pneumonia in children.     

Fasting for 24 Hours Heightens Reward from Food and Food-Related Cues

Introduction

We examined the impact of a 24 hour complete fast (vs. fed state) on two measures of food reward: 1) ‘wanting’, as measured by response to food images and by the relative-reinforcing value of food (RRV), and 2) ‘liking’, as measured by response to food images and the hedonic evaluation of foods consumed.

Methods

Utilizing a randomized crossover design, 15 subjects (9 male; 6 female) aged 28.6±4.5 yrs with body mass index 25.3±1.4 kg/m² were randomized and counterbalanced to normal feeding (FED) and 24-hour fast (FASTED) conditions. Trait characteristics were measured with the Three Factor Eating Questionnaire. Two computer tasks measured food reward: 1) RRV progressive ratio task, 2) explicit ‘liking’ and ‘wanting’ (Leeds Food Preference Questionnaire, LFPQ). Also measured were ad libitum energy intake (EI; buffet) and food ‘liking’ (visual analogue scale) of personalized stimuli.

Results

There were no significant anthropometric changes between conditions. Appetite scores, hedonic ratings of ‘liking’, and ad libitum EI all significantly increased under the FASTED condition (p<0.05). Under the FASTED condition there were significant increases in the RRV of snack foods; similarly, explicit ‘wanting’ and ‘liking’ significantly increased for all food categories. ‘Liking’ of sweet foods remained high across-meals under FASTED, but savory foods decreased in hedonic saliency.

Conclusion

Relative to a fed state, we observed an increase in hedonic ratings of food, the rewarding value of food, and food intake after a 24 hr fast. Alliesthesia to food and food cues is suggested by heightened hedonic ratings under the FASTED condition relative to FED.     

Retinal Thickness Measurement Obtained with Spectral Domain Optical Coherence Tomography Assisted Optical Biopsy Accurately Correlates with Ex Vivo Histology

Background

This study determines ‘correlation constants’ between the gold standard histological measurement of retinal thickness and the newer spectral-domain optical coherence tomography (SD-OCT) technology in adult C57BL/6 mice.

Methods

Forty-eight eyes from adult mice underwent SD-OCT imaging and then were histologically prepared for frozen sectioning with H&E staining. Retinal thickness was measured via 10x light microscopy. SD-OCT images and histological sections were standardized to three anatomical sites relative to the optic nerve head (ONH) location. The ratios between SD-OCT to histological thickness for total retinal thickness (TRT) and six sublayers were defined as ‘correlation constants’.

Results

Mean (± SE) TRT for SD-OCT and histological sections was 210.95 µm (±1.09) and 219.58 µm (±2.67), respectively. The mean ‘correlation constant’ for TRT between the SD-OCT and histological sections was 0.96. The retinal thickness for all sublayers measured by SD-OCT vs. histology were also similar, the ‘correlation constant’ values ranged from 0.70 to 1.17. All SD-OCT and histological measurements demonstrated highly significant (p<0.01) strong positive correlations.

Conclusion

This study establishes conversion factors for the translation of ex vivo data into in vivo information; thus enhancing the applicability of SD-OCT in translational research.     

Unhealthy Days and Quality of Life in Irish Patients with Diabetes

Objectives

To study the determinants of health-related quality of life (HRQoL) in Irish patients with diabetes using the Centres for Disease Controls'' (CDC''s) ‘Unhealthy Days’ summary measure and to assesses the agreement between this generic HRQoL measure and the disease-specific Audit of Diabetes Dependant Quality of Life (ADDQoL) measure.

Research Design and Methods

Data were analysed from the Diabetes Quality of Life Study, a cross-sectional study of 1,456 people with diabetes in Ireland (71% response rate). Unhealthy days were assessed using the CDC''s ‘Unhealthy days’ summary measure. Quality of life (QoL) was also assessed using the ADDQoL measure. Analyses were conducted primarily using logistic regression. The agreement between the two QoL instruments was measured using the kappa co-efficient.

Results

Participants reported a median of 2 unhealthy days per month. In multivariate analyses, female gender (P = 0.001), insulin use (P = 0.030), diabetes complications (P = <0.001) were significantly associated with more unhealthy days. Older patients had fewer unhealthy days per month (P = 0.003). Agreement between the two measures of QoL (unhealthy days measure and ADDQoL) was poor, Kappa = 0.234

Conclusions

The findings highlight the determinants of HRQoL in patients with diabetes using a generic HRQoL summary measure. The ‘Unhealthy Days’ and the ADDQoL have poor agreement, therefore the ‘Unhealthy Days’ summary measure may be assessing a different construct. Nonetheless, this study demonstrates that the generic ‘Unhealthy Days’ summary measure can be used to detect determinants of HRQoL in patients with diabetes.     

Lower Fetuin-A,Retinol Binding Protein 4 and Several Metabolites after Gastric Bypass Compared to Sleeve Gastrectomy in Patients with Type 2 Diabetes

Background

Bypass of foregut secreted factors promoting insulin resistance is hypothesized to be one of the mechanisms by which resolution of type 2 diabetes (T2D) follows roux-en-y gastric bypass (GBP) surgery.

Aim

To identify insulin resistance-associated proteins and metabolites which decrease more after GBP than after sleeve gastrectomy (SG) prior to diabetes remission.

Methods

Fasting plasma from 15 subjects with T2D undergoing GBP or SG was analyzed by proteomic and metabolomic methods 3 days before and 3 days after surgery. Subjects were matched for age, BMI, metformin therapy and glycemic control. Insulin resistance was calculated using homeostasis model assessment (HOMA-IR). For proteomics, samples were depleted of abundant plasma proteins, digested with trypsin and labeled with iTRAQ isobaric tags prior to liquid chromatography-tandem mass spectrometry analysis. Metabolomic analysis was performed using gas chromatography-mass spectrometry. The effect of the respective bariatric surgery on identified proteins and metabolites was evaluated using two-way analysis of variance and appropriate post-hoc tests.

Results

HOMA-IR improved, albeit not significantly, in both groups after surgery. Proteomic analysis yielded seven proteins which decreased significantly after GBP only, including Fetuin-A and Retinol binding protein 4, both previously linked to insulin resistance. Significant decrease in Fetuin-A and Retinol binding protein 4 after GBP was confirmed using ELISA and immunoassay. Metabolomic analysis identified significant decrease of citrate, proline, histidine and decanoic acid specifically after GBP.

Conclusion

Greater early decrease was seen for Fetuin-A, Retinol binding protein 4, and several metabolites after GBP compared to SG, preceding significant weight loss. This may contribute to enhanced T2D remission observed following foregut bypass procedures.