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.

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'.

Enabling children with Developmental Coordination Disorder to self-regulate through the use of Dynamic Performance Analysis: evidence from the CO-OP approach.

Anecdotal evidence suggests that Dynamic Performance Analysis (DPA) is learned by children with Developmental Coordination Disorder (DCD) during Cognitive Orientation to Occupational Performance (CO-OP) intervention. DPA is a tool used by therapists during the CO-OP approach to identify performance breakdowns and strategies for skill acquisition. This suggests that the self-regulation difficulties experienced by these children are amenable to intervention. The purpose of this proof of principle study was to determine: if school-aged children with DCD carry out DPAs, if DPA use was positively affected by intervention, and whether CO-OP had a larger effect on DPA use. Previously recorded videos of 13 children with DCD undergoing CO-OP, contemporary treatment or task-specific training were analyzed for evidence of DPA use. It was found that children in all three groups used simple DPAs before intervention; those receiving CO-OP intervention dramatically increased the number and quality of DPAs and could spontaneously apply it to the performance of another child. These findings indicate that, despite issues of self-regulation, children with DCD do self-monitor performance. More importantly, this ability can improve with CO-OP intervention as it guides the discovery of self-identified performance solutions, thereby enabling skill acquisition, generalization and transfer.

Dalfampridine in multiple sclerosis.

Dalfampridine (4-aminopyridine or 4-AP) is a potassium channel blocker that is historically known in the literature as fampridine (INN). This review begins with an outline of the pharmacology and pharmacokinetics. Early clinical trials are highlighted, followed by a review of the more recent phase II and III placebo-controlled clinical trials that have examined dalfampridine in multiple sclerosis patients. In these trials, extended-release dalfampridine was shown to result in an average 25% increase in the walking speed in more than one-third of the patients who received the drug and met the prescribed criteria for consistent responders. The safety profile of dalfampridine is also reviewed, with a focus on the risk for epileptic seizures as an adverse effect.

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 relation between measures of health status and quality of life in COPD.

Because quality of life (QoL) and health status (HS) scales contain different kinds of items and are shown not to be equivalent, there is a recommendation to use both types of scales. We investigated the relationship between either type of scale but focusing on the subscales of HS measures. A sample of chronic obstructive pulmonary disease (COPD) patients completed two QoL scales and two HS scales (BPQ and SGRQ), neuroticism, six-minute walk test and FEV1. Factor analysis revealed a two-factor structure (consistent with previous research), and showed that one type of HS subscale is different from QoL but another is equivalent to QoL. If total HS scores are used then it is valuable to include a QoL measure, but if HS subscales are reported, then these cover both latent variables, with the BPQ providing a clearer separation of the latent variables than the SGRQ.

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.

Physical and emotional aspects of self-reported health status: a two-factor model of the short-form Breathing Problems Questionnaire.

The short version of the Breathing Problems Questionnaire (BPQ) is used as an outcome tool in pulmonary assessment. The aim of the study was to establish the validity of scoring BPQ with two subscales, reflecting emotional and physical components of health-related quality of life (HRQoL). Two subscales were suggested by exploratory factor analysis conducted on a data set of 97 patients with chronic obstructive pulmonary disease (COPD). Both subscales were significantly associated with the 6 minute walk test, total quality of life, and emotional stability. Only the physical subscale was significantly associated with FEV1, and only the emotional subscale was significantly associated with happiness. Overall, the sizes of the different correlations are consistent with the conceptual differentiation of the two subscales. We suggest that evaluation of rehabilitation can be made with the two subscales as well as an overall score of the BPQ.

Entanglement and some heretical thoughts about homeopathy.

This paper proposes the emergent entanglement theory of homeopathy. This is based on the lack of evidence that choice of homeopathic medicine is important and predicts links between effectiveness of homeopathic medicines and their manufacturers. It predicts that there will be a consistent variation, in terms of outcome, between homeopaths, and between medicines made by different manufacturers, but not the specific homeopathic medicines prescribed. This theory is potentially testable.

Positivity in illness: self-delusion or existential growth?

OBJECTIVES: This study investigated the relationship between a measure of positivity in illness, the Silver Lining Questionnaire (SLQ), and measures of personality and spirituality/religious beliefs as a way of determining whether positivity in illness is a delusion or existential growth. METHOD: This is a cross-sectional study comparing response to the SLQ, to the Eysenck Personality Questionnaire (EPQ-R), breathlessness, illness type, and spiritual and religious beliefs in a final total sample of 194 respiratory outpatients. RESULTS: The SLQ was associated positively with extraversion (r =.16, p<.05), unrelated to neuroticism (r =.11, n.s.) and repression (r =.10, n.s.) and was positively associated with spiritual and religious beliefs, F(2; 187) = 7.12, p < 001, as predicted by the existential growth but not the delusion interpretation. There was no relationship between positivity and age, r(194) =.09, n.s., or between positivity and gender t(192) = -1.27, n.s., and nor were there relationships with type of illness, F(4, 188) = 2.17, n.s., or breathlessness, F (5, 173) = 0.42, n.s. CONCLUSIONS: The results suggest that positivity in illness is associated with existential growth, though the cross-sectional nature of the study precludes a conclusion of causal direction. The non-significant correlation between the SLQ and neuroticism is in the opposite direction predicted by the delusion explanation, but the non-significant relationship between the SLQ and repression is in the predicted direction. We cannot rule out the possibility that some positivity is delusion.

Methodology for the scientific evaluation of complementary and alternative medicine.

It has been suggested that CAM research should establish efficacy before examining mechanism. This paper shows that the efficacy-mechanism distinction is a false one, as any test of efficacy assumes a particular mechanism and is a test of the theory underlying that mechanism. The term RCT is currently used in medicine for two different sorts of study. The randomised controlled trial (RConT) requires an experimental manipulation that can 'control' for the mechanism under consideration, and therefore tests the efficacy of that mechanism. The randomised comparison trial (RComT) requires only an experimental manipulation creating a therapeutically relevant comparison, and tests the effectiveness of that therapy. The ability to achieve control coupled with an assumed implausibility of hidden moderating variables characterises drug therapy and some CAM therapies where the RConT can be used. However, other CAM researchers assume a variety of holistic mechanisms, where control is necessarily poor and the hypothesis of complex interactions suggest the existence of multiple moderators. In these cases other experimental (e.g. RComT), quasi-experimental or non-experimental designs are needed to evaluate therapeutic practice. Researchers from both communities should make explicit their underlying assumptions and the mechanisms they seek to evaluate when carrying out empirical studies. Research design needs to be appropriate for the mechanism under test.

A brief guide to extended network entanglement theory as a theory of healing and its empirical predictions.

Extended network entanglement theory (ENET) derives from a combination of two theoretical ideas: complexity theory and weak quantum theory. The theory suggests that generalized entanglement evolved initially as a form of communication within the body needed to enable the body to self-organize according to genetically specified patterns, and then as a form of communication between organisms which form social groups. This latter form of communication is at the heart of healing mechanisms. This paper sets out the theory in the form of 16 propositions and then describes 11 research ideas. ENET theory suggests that researchers should focus more on the patient-therapist dyad rather than the technical aspects of the therapy.

Developing a measure of attitudes: the holistic complementary and alternative medicine questionnaire.

We have developed an 11-item scale, the Holistic Complementary and Alternative Medicine Questionnaire (HCAMQ). Six of the HCAMQ items relate to beliefs about the scientific validity of complementary and alternative medicine (CAM), and five to beliefs about holistic health (HH). The HCAMQ was completed by 50 patients attending a CAM clinic and 50 attending rheumatology outpatients; the former completed it twice. Factor analysis (oblique rotation) showed that the CAM and HH items measured distinct but related constructs. The HCAMQ has good test retest reliability (r=0.86, 0.82 and 0.77 for the total, CAM subscale and HH subscale, respectively). The individuals attending CAM clinics were significantly more positive on the CAM but not the HH subscale of the HCAMQ and also used less antibiotics than those attending rheumatology outpatients. Positivity towards CAM on the total HCAMQ and subscales was significantly associated with lower age, increased vitamin use, reduced painkiller use, and, other than on the HH subscale, less antibiotic use. The reason why the HH subscale failed to distinguish between the two patient groups or predict less antibiotic use is unknown. The HCAMQ appears to have good internal validity, but its external validity remains to be established.

Testing cognitive function in elderly populations: the PROSPER study. PROspective Study of Pravastatin in the Elderly at Risk.

OBJECTIVES: For large scale follow up studies with non-demented patients in which cognition is an endpoint, there is a need for short, inexpensive, sensitive, and reliable neuropsychological tests that are suitable for repeated measurements. The commonly used Mini-Mental-State-Examination fulfils only the first two requirements. METHODS: In the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5804 elderly subjects aged 70 to 82 years were examined using a learning test (memory), a coding test (general speed), and a short version of the Stroop test (attention). Data presented here were collected at dual baseline, before randomisation for active treatment. RESULTS: The tests proved to be reliable (with test/retest reliabilities ranging from acceptable (r=0.63) to high (r=0.88) and sensitive to detect small differences in subjects from different age categories. All tests showed significant practice effects: performance increased from the first measurement to the first follow up after two weeks. CONCLUSION: Normative data are provided that can be used for one time neuropsychological testing as well as for assessing individual and group change. Methods for analysing cognitive change are proposed.

Oscillatory effects in a homeopathic clinical trial: an explanation using complexity theory, and implications for clinical practice.

Four double-blind, randomised, placebo-controlled clinical trials of asthma or rhinitis treated with homeopathic immunotherapy (HIT) at a 30C potency have been published. The most recent study, involving house dust mite allergic asthmatics, failed to confirm a therapeutic improvement at the end of the study, but did provide preliminary evidence for an oscillation in outcome (both physiological and subjective) in with verum treatment to placebo. In this paper we show how such an oscillation is consistent with a complexity theory interpretation of how the body functions as a whole, and speculate on why different studies have produced different results. If the complexity theory interpretation is correct, then this will have a significant impact on the design of clinical trials in homeopathy and, possibly, other complementary medical interventions.

Oscillatory effects in a homeopathic clinical trials: an explanation using complexity theory, and implications for clinical practice

Four double-blind, randomised, placebo-controlled clinical trials of asthma or rhinitis treated with homeopathic immunotherapy (HIP) at a 30C potency have been published. The most recent study, involving... (AU)

New onset seizures in the elderly: aetiology and prognosis.

Late onset epilepsy is increasing in incidence. These patients often have significant underlying morbidity. This retrospective study in a tertiary referral centre identified 68 patients aged 65 years or older, with new onset seizures over a four-year period. 81% of patients (n = 55) were followed up at an average of 2.7 years post diagnosis. 38% of patients had evidence of cerebrovascular disease (CT visualised focal infarction, haemorrhage or small vessel ischaemia in 32%, clinical diagnosis with normal CT brain in 6%). No patient was found to have a space-occupying lesion. Of the 55 patients followed up, 45% of these had died at a mean age of 82 years old and 1.9 years post diagnosis (range 12 hours to 5 years). Three patients died as a direct result of seizures (trauma and sepsis). 14 patients died of clearly unrelated causes. Eight patients died from underlying vascular disease or Alzheimer's dementia. Patients who died during follow-up were on average 3.4 years older at the time of diagnosis than survivors (p< 0.05). Patients with atrial fibrillation at the time of diagnosis, had increased mortality (relative risk 2.53; 95% C.I. 1.19 - 5.36), but they were older than those without atrial fibrillation. At the time of follow up, 92% of those taking anti-convulsants were maintained seizure free on anticonvulsant monotherapy.

Use of ultramolecular potencies of allergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial.

OBJECTIVE: To evaluate the efficacy of homoeopathic immunotherapy on lung function and respiratory symptoms in asthmatic people allergic to house dust mite. DESIGN: Double blind randomised controlled trial. SETTING: 38 general practices in Hampshire and Dorset. PARTICIPANTS: 242 people with asthma and positive results to skin prick test for house dust mite; 202 completed clinic based assessments, and 186 completed diary based assessments. INTERVENTION: After a four week baseline assessment, participants were randomised to receive oral homoeopathic immunotherapy or placebo and then assessed over 16 weeks with three clinic visits and diary assessments every other week. OUTCOME MEASURE: Clinic based assessments: forced expiratory volume in one second (FEV(1)), quality of life, and mood. DIARY BASED ASSESSMENTS: morning and evening peak expiratory flow, visual analogue scale of severity of asthma, quality of life, and daily mood. RESULTS: There was no difference in most outcomes between placebo and homoeopathic immunotherapy. There was a different pattern of change over the trial for three of the diary assessments: morning peak expiratory flow (P=0.025), visual analogue scale (P=0.017), and mood (P=0.035). At week three there was significant deterioration for visual analogue scale (P=0.047) and mood (P=0.013) in the homoeopathic immunotherapy group compared with the placebo group. Any improvement in participants' asthma was independent of belief in complementary medicine. CONCLUSION: Homoeopathic immunotherapy is not effective in the treatment of patients with asthma. The different patterns of change between homoeopathic immunotherapy and placebo over the course of the study are unexplained.