Examining the Role of Microbiota in Emotional Behavior: Antibiotic Treatment Exacerbates Anxiety in High Anxiety-Prone Male Rats.

Intestinal microbiota are essential for healthy gastrointestinal function and also broadly influence brain function and behavior, in part, through changes in immune function. Gastrointestinal disorders are highly comorbid with psychiatric disorders, although biological mechanisms linking these disorders are poorly understood. The present study utilized rats bred for distinct emotional behavior phenotypes to examine relationships between emotionality, the microbiome, and immune markers. Prior work showed that Low Novelty Responder (LR) rats exhibit high levels of anxiety- and depression-related behaviors as well as myriad neurobiological differences compared to High Novelty Responders (HRs). Here, we hypothesized that the divergent HR/LR phenotypes are accompanied by changes in fecal microbiome composition. We used next-generation sequencing to assess the HR/LR microbiomes and then treated adult HR/LR males with an antibiotic cocktail to test whether it altered behavior. Given known connections between the microbiome and immune system, we also analyzed circulating cytokines and metabolic factors to determine relationships between peripheral immune markers, gut microbiome components, and behavioral measures. There were no baseline HR/LR microbiome differences, and antibiotic treatment disrupted the microbiome in both HR and LR rats. Antibiotic treatment exacerbated aspects of HR/LR behavior, increasing LRs' already high levels of anxiety-like behavior while reducing passive stress coping in both strains. Our results highlight the importance of an individual's phenotype to their response to antibiotics, contributing to the understanding of the complex interplay between gut microbes, immune function, and an individual's emotional phenotype.

Sentiment Analysis in Children with Neurodevelopmental Disorders in an Ingroup/Outgroup Setting.

People punish transgressors with different intensity depending if they are members of their group or not. We explore this in a cross-sectional analytical study with paired samples in children with developmental disorders who watched two videos and expressed their opinion. In Video-1, a football-player from the participant's country scores a goal with his hand. In Video-2, a player from another country does the same against the country of the participant. Each subject watched the two videos and their answers were compared. The autism spectrum disorder (ASD) group showed negative feelings in Video 1 (M = - .1; CI 95% - .51 to .31); and in Video 2 (M = - .43; CI 95% .77 to - .09; t(8) = 1.64, p = .13), but the attention deficit hyperactivity disorder, learning disabilities, intellectual disability groups showed positive opinion in Video-1 and negative in Video-2. This suggests that children with ASD respect rules regardless of whether those who break them belong or not to their own group, possibly due to lower degrees of empathy.

Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: the PROSPER study.

Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), are implicated in the development of atherosclerosis. The role of anti-inflammatory cytokines, like IL-10, is largely unknown. We investigated the association of four single nucleotide polymorphisms (SNPs) in the promoter region of the IL-10 gene (4259AG, -1082GA, -592CA, and -2849GA), with coronary and cerebrovascular disease in participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. All associations were assessed with Cox proportional hazards models adjusted for sex, age, pravastatin use, and country. Haplotype analysis of the four SNPs showed a significant association between haplotype 4 (containing the -592A variant allele) and risk of coronary events (P = 0.019). Moreover, analysis of separate SNPs found a significant association between -2849AA carriers with incident stroke (HR (95%CI) 1.50 (1.04-2.17), P value = 0.02). Our study suggests that not only proinflammatory processes contribute to atherosclerosis, but that also anti-inflammatory cytokines may play an important role.

The 67P/Churyumov-Gerasimenko observation campaign in support of the Rosetta mission.

We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit. Comparison between this large collection of telescopic observations and the in situ results from Rosetta will allow us to better understand comet coma chemistry and structure. This work is just beginning as the mission ends-in this paper, we present a summary of the ground-based observations and early results, and point to many questions that will be addressed in future studies.This article is part of the themed issue 'Cometary science after Rosetta'.

The Lung Information Needs Questionnaire: Development, preliminary validation and findings.

STUDY OBJECTIVES: Many chronic obstructive pulmonary disease (COPD) patients are dissatisfied with the information they are given. A brief questionnaire completed prior to the clinical encounter would assist health professionals identify areas of information need. DESIGN: Ten focus groups of 59 patients assisted in the process of questionnaire construction. Three hundred and four patients (return rate 63%) responded to a postal questionnaire. RESULTS: Twenty-one per cent did not know the name of their disease, 3% reported medication non-compliance and 8% were confused with medicines. Fifty-five per cent of patients were exercising inappropriately, 8% did not know what to do when breathing worsened and 36% did not know when to call an ambulance. All six of the Lung Information Needs Questionnaire domains discriminated significantly as a function of health professional contact. Retest reliability for the six domains varied between .66 and .98, and for the total score was .89. alpha was .62. CONCLUSIONS: Patients can act as experts during the process of questionnaire construction. Information needs vary between patients but tend to be high for non-drug related aspects of self-management COPD. This questionnaire can be used to guide the clinical encounter.

Acute inflammation, acute phase serum amyloid A and cholesterol metabolism in the mouse.

Acute inflammation results in a profound change in the apolipoprotein composition of high density lipoprotein (HDL). Several isoforms of the serum amyloid A (SAA) family, SAA1 and SAA2, become major components of HDL. This structural relationship has suggested that acute phase SAA plays some as yet unidentified role in HDL function, possibly related to cholesterol transport, during the course of acute inflammation. Using subcutaneous AgNO3 to induce a sterile abscess changes in plasma cholesterol and SAA were monitored over the subsequent 144 h. Total plasma cholesterol began to increase within 12 h of the induction of inflammation and reached a peak in 24 h. Thereafter its plasma levels fell returning to normal values by 96-120 h. The bulk of the increase in plasma cholesterol was found in the free cholesterol fraction of HDL. This pattern of cholesterol increase corresponds to the established temporal changes for acute phase SAA (AP-SAA). AP-SAA levels increased within 8 h of the induction of inflammation and reached a peak at 24 h. They began to decrease by 48 h with small quantites still present 120 h later. In concert, but inversely, with the changes in AP-SAA the apoA-I, apoA-II, and apo-E, content of HDL decreased during the AP-SAA increases and increased as AP-SAA levels fell. The plasma appearance of cholesterol from the periphery, and central parts of the inflammatory site was assessed by the use of radiolabelled cholesterol. The peripherally placed cholesterol rapidly reached a peak plasma concentration within 24 h of injection. Cholesterol placed in the central part of the sterile abscess, a site relatively inaccessible to the vasculature required 48 h to reach its peak and was 5-times lower than that placed peripherally. The influence of AP-SAA on neutral cholesterol ester hydrolase (nCEH) activity in mouse liver homogenates, mouse peritoneal macrophage homogenates, and a purified porcine pancreatic enzyme with nCEH activity was also assessed. Following optimization with regard to pH, bile salt concentration, protein concentration and incubation time, mouse peritoneal macrophages had a significantly higher nCEH specific activity than that found in liver (7-8 fold). Purified AP-SAA, assessed over a concentration range of 0-10 microg/ml, enhanced nCEH activity at concentrations above 2 microg/ml. The nCEH activity, regardless of its source, increased by 3-7 fold in the presence of AP-SAA. Equivalent concentrations of apolipoprotein A-I (apo A-I) and bovine serum albumin (BSA) failed to alter the activity of nCEH. The effect of AP-SAA on a purified form of nCEH suggests that AP-SAA may have a direct effect on the activity of this enzyme. The temporal correlation of circulating AP-SAA and plasma cholesterol and the significant stimulation of nCEH by AP-SAA (but not apoA-I or BSA) provides further evidence that AP-SAA plays a role in cholesterol metabolism during the course of acute inflammation.

The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.

Rationale for once-daily therapy in asthma: compliance issues.

Compliance in asthma is known to be poor. Once-daily treatment provides an additional therapeutic option for the clinician whose treatment aims include maximising treatment satisfaction and compliance. Once-daily treatment is preferred by some but not all patients and may lead to greater compliance in patients who are concerned about the effect of corticosteroids on their health. When switching to once-daily treatment, patients should be given a choice as to the time of treatment to minimise the impact of forgetting a dose.

The validity of health assessments: resolving some recent differences.

The purpose of this paper is to examine what is meant by a valid measure of health. Guyatt, Kirshner and Jaeschke propose that health tests should be designed so as to have one of several kinds of validity: "longitudinal construct validity" for those which are used for longitudinal research designs, and "cross-sectional construct validity" for those which are used for cross-sectional designs. Williams and Naylor argue that this approach to test classification and validation confuses what a test purports to measure with the purpose for which it is used, and that some tests have multiple uses. A review of the meanings of validity in the psychological test literature shows that both sets of authors use the term validity in an idiosyncratic way. Although the use of a test (evaluated by content validity) should not be conflated with whether the test actually measures a specified construct (evaluated by construct validity), if health is actually made up of several constructs (as suggested in Hyland's interactional model) then there may be an association between types of construct and types of purpose. Evidence is reviewed that people make several, independent judgements about their health: cognitive perceptions of health problems are likely to be more sensitive to change in a longitudinal research design, whereas emotional evaluations of health provide less bias in cross-sectional designs. Thus, a classification of health measures in terms of the purpose of the test may parallel a classification in terms of what tests purport to measure.

Lichtenstein patch or Perfix plug-and-patch in inguinal hernia: a prospective double-blind randomized controlled trial of short-term outcome.

BACKGROUND: Open mesh used in anterior inguinal hernia repair can be configured as a flat patch (Lichtenstein operation) or as a cone-shaped preformed plug and supplementary patch (plug-and-patch operation; Perfix Plug; Davol Inc, Cranston, RI). METHODS: One hundred forty-one patients were randomly allocated and blinded to receive either a Lichtenstein patch or a Perfix plug-and-patch. Information before the operation and on postoperative days 3 and 14 was recorded by an independent blinded observer to include operating time, postoperative pain, analgesic medication, return to activity and work, and quality of life assessment. RESULTS: Operating time (32 vs 37.6 minutes) was significantly shorter in the plug-and-patch group (P = .01). During days 1 through 8, patients who had undergone the plug-and-patch operation experienced less pain, and their physical functioning on day 3 was significantly better (P = .013). Days of analgesic medication (4.0 vs 4.6 days), return to normal activity (2.8 vs 3.6 days), return to work (17.0 vs 20.8 days), and total days of work missed (14.3 vs 16.1 days) were similar in both groups (P = NS for all comparisons). CONCLUSIONS: Compared with patients who received the Lichtenstein patch for ambulatory inguinal hernia repair, patients who underwent the Perfix plug-and-patch operation experienced less postoperative pain in the first 8 days after the operation but consumed similar postoperative analgesic medication. The rate of return to normal activity and work is similar in both groups, which indicates no superiority for the plug-and-patch operation in overall rehabilitation and societal costs. Overall hospital costs are greater for the plug-and-patch operation ($120 [US]) compared with the Lichtenstein patch ($20 [US]), with a negligible (5.6 minutes) saving of operating room time for the plug-and-patch operation.

The Living with Asthma Questionnaire.

The 'Living with Asthma Questionnaire' is an asthma-specific quality of life scale for assessing patients' own subjective experiences of asthma. The purpose of the questionnaire is to assist individual patient management and to provide an outcome measure for use in clinical trials. The scale has 68 items and covers 11 domains of asthma experience which were derived from focus group discussions amongst asthma sufferers. The initial item set was refined through standard psychometric techniques using a total of 783 patients and there is no statistical evidence for independent, domain-specific subscales. Validation studies are described.

Associations between an asthma morbidity index and ideas of fright and bother in a community population.

There is a need for simple asthma outcome measures for primary care which are not only valid in terms of their relationship with lung function but also in terms of pragmatic psychological constructs. This study assesses the usefulness of adding items on the degree of 'bother' and 'fright' caused by the condition to a previously validated simple asthma morbidity index. A postal questionnaire survey comprising a simple asthma morbidity index and questions on 'fright' and 'bother' was conducted in one general practice in the north-east of England. Responses were obtained from 570 individuals. Of these, 184 (32%) reported low, 133 (23%) medium and 253 (44%) high morbidity. Twenty-nine per cent of respondents had felt frightened by their asthma in the previous 4 weeks. Both the 'fright' and 'bother' items were significantly associated with the morbidity index. The addition of 'bother' and/or 'fright' questions may improve both the content, construct and predictive validity of the morbidity index, but this needs to be established prospectively.

A short outpatient pulmonary rehabilitation programme: immediate and longer-term effects on exercise performance and quality of life.

Pulmonary rehabilitation is widely available in North America and parts of Europe for patients with chronic obstructive pulmonary disease (COPD). Here, we describe the feasibility and benefits of providing a comprehensive but cost effective pulmonary rehabilitation programme in a U.K. district general hospital. Two hundred and sixty-seven patients with respiratory disability were referred for pulmonary rehabilitation. Patients were assessed and recruited onto a 7 week outpatient-based pulmonary rehabilitation programme including elements of exercise and education without longer term maintenance. Exercise performance was measured by the shuttle walking test and a treadmill endurance test, and quality of life as measured by two disease specific questionnaires, the Breathing Problems Questionnaire and the Chronic Respiratory Disease Questionnaire. Of 267 patients referred between 1993 and 1996, 132 (110 with COPD) have completed rehabilitation and could be evaluated. For all graduates, shuttle distance increased by 58 m (27%) and treadmill endurance time increased by 15.9 min (294%). The Breathing Problems Questionnaire proved sensitive to changes in quality of life in some domains. The Chronic Respiratory Disease Questionnaire showed significant improvements in all domains in a sub-set of 57 patients who completed it. Longer term follow-up of 49 patients at a mean of 10.3 months following pulmonary rehabilitation revealed that previous gains in exercise performance and quality of life were maintained with improvements in shuttle walking distance of 33 m (14% over baseline) and endurance time of 16 min (280% over baseline). The Breathing Problems Questionnaire showed no overall change but the Chronic Respiratory Disease Questionnaire showed continued improvement in a small number of patients. We therefore concluded that a short outpatient based pulmonary rehabilitation programme without a maintenance element has produced significant gains in exercise performance and quality of life for 132 patients at a district general hospital in the U.K.

A comparison of three disease-specific and two generic health-status measures to evaluate the outcome of pulmonary rehabilitation in COPD.

The use of health status as an outcome measure is becoming more widespread in pulmonary rehabilitation. There are a number of health status measures but the choice remains uncertain. Three disease specific measures and two generic measures of health status were employed to observe their relative sensitivity to a 7-week course of pulmonary rehabilitation. Patients with stable chronic obstructive pulmonary disease (COPD) were recruited into a rehabilitation programme. They completed a shuttle-walking test and three disease-specific questionnaires: the Chronic Respiratory Questionnaire (CRQ), the St. George's Hospital Respiratory Questionnaire (SGRQ) and the Breathing Problems Questionnaire (BPQ). Patients also completed two generic questionnaires: a global quality-of-life scale and an activity checklist. Ninety-seven patients [58 male mean (SD) age 67 (8.7) years] completed the course over a 12-month period. The mean pre-rehabilitation (SD) FEV1 was 1.06 (0.59) l. The shuttle-walking test and the treadmill-endurance test increased significantly after rehabilitation (P<0.001). All three disease-specific questionnaires improved significantly (the CRQ and SGRQ improved beyond minimum clinically important difference). The global score improved significantly whilst the 'things people do' decreased. All three disease-specific measures were responsive to pulmonary rehabilitation. However the operator-led CRQ appears to be the most sensitive short-term outcome measure.

Antiasthma drugs: quality-of-life rating scales and sensitivity to longitudinal change.

The causal hypothesis of quality of life predicts that questionnaire items measuring the construct of problems are more sensitive to change in a clinical trial compared with those measuring the construct of evaluations. This prediction was confirmed in 2 clinical trials of patients with asthma who were administered salmeterol in comparison with another treatment. These and other data show that whether a significant effect is obtained in a clinical trial, and the size of any effect, depend on the properties of the questionnaire used to assess quality of life. Quantitative assessments of improvement in quality of life should be treated with caution in economic evaluations.

Quality-of-life measures as providers of information on value-for-money of health interventions. Comparison and recommendations for practice.

Three different approaches to measuring quality of life have been developed. Global scales (e.g. time trade-off, visual analogue), multi-attribute utility scales and multidimensional scales (which may be generic or disease-specific). Each of these approaches to measurement provides different kinds of information about quality of life and each can be used to provide information to healthcare purchasers concerning the relative value-for-money of health interventions. The value-for-money of health interventions, in terms of quality of life, can be demonstrated in 2 ways: a formula-driven approach based on cost-utility analysis, which uses scales generating the unit of a quality-adjusted life-year (i.e. global and multi-attribute utility); and a non-formula-driven approach, which uses scales generating multidimensional profiles of quality of life (i.e. multi-attribute utility and multidimensional). Analysis shows that no single approach is sufficient, and that healthcare purchasers should use a variety of types of information in their decision-making, including both cost-utility and informal approaches. Healthcare resource allocation is inevitably a value-dependent activity.

Quality-of-life assessment in respiratory disease: an examination of the content and validity of four questionnaires.

Four recent questionnaires for measuring the quality of life of patients with respiratory disease (Chronic Respiratory Disease Questionnaire, St George's Respiratory Questionnaire, Living with Asthma Questionnaire, and Asthma Quality of Life Questionnaire) differ in the content and style of the items used. Differences in content arise over the use or emphasis on symptom items, functional limitation (activity) items, and emotion items. These differences stem in part from the different methods used for item selection and refinement, which include selecting the most 'important' items, qualitative analysis for clarity, ratings of distress, and psychometric analysis. Despite these differences, there is considerable evidence for content validity of all four questionnaires. Because quality of life is so poorly developed as a theoretical construct, the demonstrable statement that all 4 questionnaires have construct validity provides little information about the questionnaires.

Selection of items and avoidance of bias in quality of life scales.

The total score of a quality of life (QOL) questionnaire reflects the items that make up the questionnaire. Although different questionnaires have strikingly similar items, the balance between types of items can affect research outcomes. Four general quality of life (QOL) scales and one specific scale may be compared to show how the balance of items can bias the results to: (a) increase or decrease the chance of obtaining a significant result in a clinical trial; (b) make one treatment appear better or worse compared with that of a competitor; (c) make the QOL of one disease category appear better or worse than that of another disease category. Healthcare decision-making should be based on relatively unaggregated measures of health.

A scale for assessing quality of life in adult asthma sufferers.

The Asthma Questionnaire is a 68-item quality of life scale designed to be sensitive to quality of life changes in clinical trials. The questionnaire covers 11 domains of life experience, the initial domain and item sets being derived from six qualitative focus groups of asthma patients. Psychometric analysis of responses of 101 asthma patients to the initial 101-item set showed the scale to be unidimensional despite being multi-domain, and the finding of unidimensionality was replicated during the further three stages of item refinement using 783 patients. The scale compensates for acquiescence bias as well as allowing a 'not applicable' response category. Validity of the scale was demonstrated by confirmation of expected group differences and the retest reliability was 0.948.

A method to obtain maternal-fetal plasma samples using a microsampling technique in the rat: transplacental passage of cefoxitin.

A microsampling technique that allows taking blood samples from the umbilical vein of the pregnant rat is described. Such techniques are needed in order to allow pharmacokinetic and embryo exposure to be correlated with teratogenic endpoints. Cefoxitin was administered intravenously (300 mg/kg) into tracheotomized, pentobarbital anesthetized dams on day 21 in gestation. Blood samples were collected via the carotid artery from the dam and the umbilical vein of the fetus at designated times. Up to three samples of 20 to 30 microliters each, were taken from individual fetuses at 20-min intervals. With few exceptions, fetal cefoxitin concentrations were homogeneous at each sampling period. Fetal concentrations were low compared to maternal concentrations as seen by the small fetal/maternal area under the curve ratio (0.053 +/- 0.006).