Psychological interventions in asthma

Asthma is a multifactorial chronic respiratory disease characterised by recurrent episodes of airway obstruction. The current management of asthma focuses principally on pharmacological treatments, which have a strong evidence base underlying their use. However, in clinical practice, poor symptom control remains a common problem for patients with asthma. Living with asthma has been linked with psychological co-morbidity including anxiety, depression, panic attacks and behavioural factors such as poor adherence and suboptimal self-management. Psychological disorders have a higher-than-expected prevalence in patients with difficult-to-control asthma. As psychological considerations play an important role in the management of people with asthma, it is not surprising that many psychological therapies have been applied in the management of asthma. There are case reports which support their use as an adjunct to pharmacological therapy in selected individuals, and in some clinical trials, benefit is demonstrated, but the evidence is not consistent. When findings are quantitatively synthesised in meta-analyses, no firm conclusions are able to be drawn and no guidelines recommend psychological interventions. These inconsistencies in findings may in part be due to poor study design, the combining of results of studies using different interventions and the diversity of ways patient benefit is assessed. Despite this weak evidence base, the rationale for psychological therapies is plausible, and this therapeutic modality is appealing to both patients and their clinicians as an adjunct to conventional pharmacological treatments. What are urgently required are rigorous evaluations of psychological therapies in asthma, on a par to the quality of pharmaceutical trials. From this evidence base, we can then determine which interventions are beneficial for our patients with asthma management and more specifically which psychological therapy is best suited for each patient

High-utilizing Crohn's disease patients under psychosomatic therapy*

<p>Abstract</p> <p>Objective</p> <p>Few studies have been published on health care utilization in Crohn's disease and the influence of psychological treatment on high utilizers.</p> <p>Methods</p> <p>The present sub study of a prospective multi center investigation conducted in 87 of 488 consecutive Crohn's disease (CD) patients was designed to investigate the influence of the course of Crohn's disease on health care utilization (hospital days (HD) and sick leave days (SLD) collected by German insurance companies) and to examine the conditions of high-utilizing patients. Predictors of health care utilization should be selected. Based on a standardized somatic treatment, high health care utilizing patients of the psychotherapy and control groups should be compared before and after a one-year treatment.</p> <p>Results</p> <p>Multivariate regression analysis identified disease activity at randomization as an important predictor of the clinical course (r²= 0.28, p < 0.01). Health care utilization correlated with duration of disease (p < 0.04), but the model was not significant (r²= 0.15, p = 0.09). The patients' level of anxiety, depression and lack of control at randomization predicted their health-related quality of life at the end of the study (r²= 0.51, p < 0.00001). Interestingly, steroid intake and depression (t1) predicted the combined outcome measure (clinical course, HRQL, health care utilization) of Crohn's disease at the end of the study (r²= 0.22, p < 0.001).</p> <p>Among high utilizers, a significantly greater drop in HD (p < 0.03) and in mean in SLD were found in the treatment compared to the control group.</p> <p>Conclusion</p> <p>The course of Crohn's disease is influenced by psychological as well as somatic factors; especially depression seems important here. A significant drop of health care utilization demonstrates the benefit of psychological treatment in the subgroup of high-utilizing CD patients. Further studies are needed to replicate the findings of the clinical outcome in this CD subgroup.</p

Enamel growth rates of anterior teeth in males and females from modern and ancient British populations

Objectives: This study explored biological sex differences in the regional daily growth rates of human anterior enamel from modern and ancient populations in Britain.Methods: Maxillary permanent incisors (n=80) and canines (n=69) from Roman, Anglo-Saxon, Medieval, and Modern day populations were analysed using histological methods. Daily secretion rates (DSRs) were collected for inner, mid, and outer regions of cuspal and lateral enamel. Modern day samples were of known sex, archaeological individuals had sex determined using standard osteological methods. Variation in DSRs between the sexes, both between and within populations, was sought using parametric and non-parametric tests.Results: When all samples were pooled, there was no significant difference between males and females. Similarly no significant differences in DSRs were identified between male and females within each population. When DSRs were compared between the populations, DSRs decreased from the more ancient to the more recent populations for males, and for females. More inter-population differences were observed in males.Discussion: This study presents evidence for the relative consistency of enamel DSRs between male and female groups within each British population. Inter-population analyses found DSRs slowed significantly between Roman and modern day populations for both sexes, with male DSRs showing the greatest variation between populations

Regulation of Amyloid Precursor Protein Processing by the Beclin 1 Complex

Autophagy is an intracellular degradation pathway that functions in protein and organelle turnover in response to starvation and cellular stress. Autophagy is initiated by the formation of a complex containing Beclin 1 (BECN1) and its binding partner Phosphoinositide-3-kinase, class 3 (PIK3C3). Recently, BECN1 deficiency was shown to enhance the pathology of a mouse model of Alzheimer Disease (AD). However, the mechanism by which BECN1 or autophagy mediate these effects are unknown. Here, we report that the levels of Amyloid precursor protein (APP) and its metabolites can be reduced through autophagy activation, indicating that they are a substrate for autophagy. Furthermore, we find that knockdown of Becn1 in cell culture increases the levels of APP and its metabolites. Accumulation of APP and APP C-terminal fragments (APP-CTF) are accompanied by impaired autophagosomal clearance. Pharmacological inhibition of autophagosomal-lysosomal degradation causes a comparable accumulation of APP and APP-metabolites in autophagosomes. Becn1 reduction in cell culture leads to lower levels of its binding partner Pik3c3 and increased presence of Microtubule-associated protein 1, light chain 3 (LC3). Overexpression of Becn1, on the other hand, reduces cellular APP levels. In line with these observations, we detected less BECN1 and PIK3C3 but more LC3 protein in brains of AD patients. We conclude that BECN1 regulates APP processing and turnover. BECN1 is involved in autophagy initiation and autophagosome clearance. Accordingly, BECN1 deficiency disrupts cellular autophagy and autophagosomal-lysosomal degradation and alters APP metabolism. Together, our findings suggest that autophagy and the BECN1-PIK3C3 complex regulate APP processing and play an important role in AD pathology

Insights into the Complex Associations Between MHC Class II DRB Polymorphism and Multiple Gastrointestinal Parasite Infestations in the Striped Mouse

Differences in host susceptibility to different parasite types are largely based on the degree of matching between immune genes and parasite antigens. Specifically the variable genes of the major histocompatibility complex (MHC) play a major role in the defence of parasites. However, underlying genetic mechanisms in wild populations are still not well understood because there is a lack of studies which deal with multiple parasite infections and their competition within. To gain insights into these complex associations, we implemented the full record of gastrointestinal nematodes from 439 genotyped individuals of the striped mouse, Rhabdomys pumilio. We used two different multivariate approaches to test for associations between MHC class II DRB genotype and multiple nematodes with regard to the main pathogen-driven selection hypotheses maintaining MHC diversity and parasite species-specific co-evolutionary effects. The former includes investigations of a ‘heterozygote advantage’, or its specific form a ‘divergent-allele advantage’ caused by highly dissimilar alleles as well as possible effects of specific MHC-alleles selected by a ‘rare allele advantage’ ( = negative ‘frequency-dependent selection’). A combination of generalized linear mixed models (GLMMs) and co-inertia (COIA) analyses made it possible to consider multiple parasite species despite the risk of type I errors on the population and on the individual level. We could not find any evidence for a ‘heterozygote’ advantage but support for ‘divergent-allele’ advantage and infection intensity. In addition, both approaches demonstrated high concordance of positive as well as negative associations between specific MHC alleles and certain parasite species. Furthermore, certain MHC alleles were associated with more than one parasite species, suggesting a many-to-many gene-parasite co-evolution. The most frequent allele Rhpu-DRB*38 revealed a pleiotropic effect, involving three nematode species. Our study demonstrates the co-existence of specialist and generalist MHC alleles in terms of parasite detection which may be an important feature in the maintenance of MHC polymorphism

Observations of trace gases and aerosols over the Indian Ocean during the monsoon transition period

Characteristics of trace gases (O3, CO, CO2, CH4 and N2O) and aerosols (particle size of 2.5 micron) were studied over the Arabian Sea, equatorial Indian Ocean and southwest part of the Bay of Bengal during the monsoon transition period (October-November, 2004). Flow of pollutants is expected from south and southeast Asia during the monsoonal transition period due to the patterns of wind flow which are different from the monsoon period. This is the first detailed report on aerosols and trace gases during the sampled period as the earlier Bay of Bengal Experiment (BOBMEX), Arabian Sea Monsoon Experiment (ARMEX) and Indian Ocean Experiments (INDOEX) were during monsoon seasons. The significant observations during the transition period include: (i) low ozone concentration of the order of 5 ppbv around the equator, (ii) high concentrations of CO2, CH4 and N2O and (iii) variations in PM2.5 of 5-20&#956;g/m3

Immunological Mechanisms Mediating Hantavirus Persistence in Rodent Reservoirs

Hantaviruses, similar to several emerging zoonotic viruses, persistently infect their natural reservoir hosts, without causing overt signs of disease. Spillover to incidental human hosts results in morbidity and mortality mediated by excessive proinflammatory and cellular immune responses. The mechanisms mediating the persistence of hantaviruses and the absence of clinical symptoms in rodent reservoirs are only starting to be uncovered. Recent studies indicate that during hantavirus infection, proinflammatory and antiviral responses are reduced and regulatory responses are elevated at sites of increased virus replication in rodents. The recent discovery of structural and non-structural proteins that suppress type I interferon responses in humans suggests that immune responses in rodent hosts could be mediated directly by the virus. Alternatively, several host factors, including sex steroids, glucocorticoids, and genetic factors, are reported to alter host susceptibility and may contribute to persistence of hantaviruses in rodents. Humans and reservoir hosts differ in infection outcomes and in immune responses to hantavirus infection; thus, understanding the mechanisms mediating viral persistence and the absence of disease in rodents may provide insight into the prevention and treatment of disease in humans. Consideration of the coevolutionary mechanisms mediating hantaviral persistence and rodent host survival is providing insight into the mechanisms by which zoonotic viruses have remained in the environment for millions of years and continue to be transmitted to humans