Mind and body exercises : associations with mental health, antidepressant medication, autonomic functioning and inflammatory biomarkers

Stress, depression and stress-related mental ill-health are common in societies all over the world, and people tend to use both conventional care within the health care system and complementary treatment methods to handle the related symptoms. Still, there is sparse information on whether, how and when to combine these different treatment modalities, in spite of their relatively widespread use. There is thus a need for increased knowledge on complementary treatment methods among conventional health care professionals, patients, policy- and decision makers, and the general public. An example of complementary methods is so called mind and body exercises (MBE), which include e.g. mindfulness based interventions (MBIs). Aims: The overall aim of this thesis was to map the use of MBE and its associations with health and markers of disease, i.e. prescriptions of psychotropics, and to study if there are any robust effects of MBIs on biomarkers of stress. The findings were thus aimed to enable evidence-based recommendations and personalized treatment strategies. The specific aims were: To identify differential associations regarding gender, age, socioeconomic status, health behaviors, perceived stress, self-rated health, and the purchase of prescribed drugs among people who practice MBE extensively, compared to people who do not practice MBE (study I); To further investigate the temporal relationship between MBE, depressive symptoms, purchase of antidepressant drugs and physical exercise, based on the cross-sectional findings in study I (study II); To evaluate existing data on the effect of standardized mindfulness based interventions on inflammatory biomarkers and autonomic nervous system functioning (assessed by measurements of heart rate variability, HRV), through a systematic review and meta-analysis (study III); To investigate the effects of a Mindfulness Based Childbirth and Parenting intervention on HRV and serum inflammatory marker levels among pregnant women, through an RCT study with an active control group comparison (study IV). Methods: Studies I and II were based on responses from the Swedish Longitudinal Occupational Survey of Health (SLOSH). Measures regarding MBE practice, health behaviors, perceived stress, self-rated health and illnesses were drawn from the SLOSH questionnaire, while data on antidepressant drug purchase for all respondents was obtained from the Swedish Prescribed Drug Register. In study III, a literature search was conducted in collaboration with two experienced university librarians. Literature screening and data extraction were performed independently by two researchers. The methodological quality of included studies was assessed independently by two researchers using the Cochrane Collaboration’s tool for assessing risk of bias. In study IV, first time pregnant women at risk of perinatal depression were randomized to MBCP or an active control treatment. At baseline and post-intervention, participants filled out questionnaires and measures on HRV and inflammatory biomarkers were collected. Results: MBE practice was found to have significant cross-sectional associations with high levels of depressive symptoms and prescribed antidepressant purchases (study I). The temporal investigations of these relationships revealed a more complex picture, where MBE practice itself was not associated with either subsequent antidepressant medication or with subsequent depressive symptoms (study II). No significant effect of standardized MBIs on inflammatory biomarkers or HRV, when compared to active controls, treatment as usual or wait-list controls, was found – neither in the meta-analysis (study III) nor in the randomized controlled study (study IV). Conclusions: The findings from study I and II demonstrate the use MBE among the general population as well as in clinical populations like patients suffering from mental ill-health. In order to gain a deeper understanding of the temporality of these correlations, and to delineate possible beneficial or harmful combinations of psychotropics, MBE and other treatment strategies, further research is needed. The findings from study III and IV highlight the necessity of larger, more rigorously conducted RCTs with standardized MBIs being compared to various forms of active controls, also including more long-term follow-ups, in order to provide evidence-based recommendations, both for self-help use and clinical practices

Expression of 5-lipoxygenase and 15-lipoxygenase in rheumatoid arthritis synovium and effects of intraarticular glucocorticoids

The past years have witnessed tremendous progress in the treatment of rheumatoid arthritis, a chronic debilitating autoimmune disease mainly characterized by joint inflammation with progressive tissue destruction and loss of function. This condition affects 0.5-1% of the population, is associated with important co-morbidities and represents a heavy economical burden. New strategies, employing early and aggressive therapies with classical drugs or new agents, have resulted in impressive improvements in controlling disease activity. In some cases they even lead to clinical remission. Despite potent and efficient biological agents that specifically modulate distinct pathological pathways a large proportion of patients remain unresponsive to these therapies; drug-free remission is also difficult to achieve since attempting discontinuation of treatment usually results in disease flare. In rheumatoid arthritis joints there is a constant activation of complex networks of cytokines and factors mediating immune interactions and inflammation, in which prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are important players and contributors to pathogenesis. Our research aimed to investigate the synovial expression of enzymes controlling prostaglandin E2 synthesis and degradation – cyclooxygenase (COX) 1 and 2, microsomal prostaglandin E2 synthase 1 (MPGES1) and 15-prostaglandin dihydrogenase (15-PGDH) as well as enzymes involved in leukotriene synthesis, such as 5-lipoxygenase (LO) and 15-LO. In addition, we evaluated how traditional and new therapies influence these pathways, by analyzing enzyme expression before and after systemic treatment with tumor necrosis factor (TNF) antagonists, rituximab or methotrexate, as well as before and after intra-articular treatment with glucocorticoids. We also evaluated the in vitro effects of TNF antagonists and glucocorticoids on synovial fluid cells and that of methotrexate on synovial fibroblasts. We demonstrated that synovial tissue from RA patients displayed an important expression of enzymes involved in the metabolism of PGE2, as well as 5-LO and 15-LO. MPGES1 and COX-2, the inflammation-inducible enzymes co-localized mainly in fibroblasts and macrophage-like cells and accounted for the local PGE2 production. Intra-articular glucocorticoids significantly reduced all enzymes involved in the PGE2 cascade – COX-1 and COX-2, MPGES1 and 15-PGDH, but also 5-LO, responsible for leukotriene formation. However, they did not influence the expression of 15-LO, an enzyme involved in the formation of both pro-and anti-inflammatory lipid mediators. Regarding the effects of TNF blockers, rituximab or methotrexate, they did not alter the expression profile of enzymes involved in PGE2 metabolism despite showing clinical efficiency in improving disease activity. Although anti-TNF agents reduced the in vitro expression of MPGES1 and COX-2 in synovial fluid cells, the lack of effect ex vivo in biopsies emphasized once again the differences between synovial compartments and possibly the difficulty in mimicking the micro-environment at the site of inflammation in vitro. In conclusion, this thesis demonstrates that potent anti-rheumatic drugs currently used in the clinic with good efficiency also leave inflammatory pathways un-affected, which may account for subclinical ongoing disease activity. Blocking the PGE2 pathway by using MPGES1 inhibitors as combination therapy may show benefit in dampening ongoing local inflammation

Heralded generation of entangled photon pairs

Entangled photons are a crucial resource for quantum communication and linear optical quantum computation. Unfortunately, the applicability of many photon-based schemes is limited due to the stochastic character of the photon sources. Therefore, a worldwide effort has focused in overcoming the limitation of probabilistic emission by generating two-photon entangled states conditioned on the detection of auxiliary photons. Here we present the first heralded generation of photon states that are maximally entangled in polarization with linear optics and standard photon detection from spontaneous parametric down-conversion. We utilize the down-conversion state corresponding to the generation of three photon pairs, where the coincident detection of four auxiliary photons unambiguously heralds the successful preparation of the entangled state. This controlled generation of entangled photon states is a significant step towards the applicability of a linear optics quantum network, in particular for entanglement swapping, quantum teleportation, quantum cryptography and scalable approaches towards photonics-based quantum computing

Modulation of microRNA processing by 5‐lipoxygenase

The miRNA biogenesis is tightly regulated to avoid dysfunction and consequent disease development. Here, we describe modulation of miRNA processing as a novel noncanonical function of the 5‐lipoxygenase (5‐LO) enzyme in monocytic cells. In differentiated Mono Mac 6 (MM6) cells, we found an in situ interaction of 5‐LO with Dicer, a key enzyme in miRNA biogenesis. RNA sequencing of small noncoding RNAs revealed a functional impact, knockout of 5‐LO altered the expression profile of several miRNAs. Effects of 5‐LO could be observed at two levels. qPCR analyses thus indicated that (a) 5‐LO promotes the transcription of the evolutionarily conserved miR‐99b/let‐7e/miR‐125a cluster and (b) the 5‐LO‐Dicer interaction downregulates the processing of pre‐let‐7e, resulting in an increase in miR‐125a and miR‐99b levels by 5‐LO without concomitant changes in let‐7e levels in differentiated MM6 cells. Our observations suggest that 5‐LO regulates the miRNA profile by modulating the Dicer‐mediated processing of distinct pre‐miRNAs. 5‐LO inhibits the formation of let‐7e which is a well‐known inducer of cell differentiation, but promotes the generation of miR‐99b and miR‐125a known to induce cell proliferation and the maintenance of leukemic stem cell functions

Quantum degrees of polarization

We discuss different proposals for the degree of polarization of quantum fields. The simplest approach, namely making a direct analogy with the classical description via the Stokes operators, is known to produce unsatisfactory results. Still, we argue that these operators and their properties should be basic for any measure of polarization. We compare alternative quantum degrees and put forth that they order various states differently. This is to be expected, since, despite being rooted in the Stokes operators, each of these measures only captures certain characteristics. Therefore, it is likely that several quantum degrees of polarization will coexist, each one having its specific domain of usefulness.Comment: 9 pages, 3 figures. v2: Minor corrections and improvement

Quantum polarization tomography of bright squeezed light

We reconstruct the polarization sector of a bright polarization squeezed beam starting from a complete set of Stokes measurements. Given the symmetry that underlies the polarization structure of quantum fields, we use the unique SU(2) Wigner distribution to represent states. In the limit of localized and bright states, the Wigner function can be approximated by an inverse three-dimensional Radon transform. We compare this direct reconstruction with the results of a maximum likelihood estimation, finding an excellent agreement.Comment: 15 pages, 5 figures. Contribution to New Journal of Physics, Focus Issue on Quantum Tomography. Comments welcom

Pulmonary sarcoidosis is associated with exosomal vitamin D-binding protein and inflammatory molecules

BACKGROUND: Sarcoidosis is an inflammatory granulomatous disorder characterized by accumulation of TH1-type CD4+T cells and immune effector cells within affected organs, most frequently the lungs. Exosomes are extracellular vesicles conveying intercellular communication with possible diagnostic and therapeutic applications.OBJECTIVES: Weaimed to provide an understanding of the proinflammatory role of bronchoalveolar lavage fluid (BALF) exosomes in patients with sarcoidosis and to find candidates for disease biomarkers.METHODS: Weperformed a mass spectrometric proteomics characterization of BALF exosomes from 15 patients with sarcoidosis and 5 healthy control subjects and verified the most interesting results with flow cytometry, ELISA, and Western blot analyses in an additional 39 patients and 22 control subjects.RESULTS: Morethan 690 proteins were identified in the BALF exosomes, several of which displayed significant upregulation in patients, including inflammation-associated proteins, such as leukotriene A4 hydrolase. Most of the complement-activating factors were upregulated, whereas the complement regulator CD55 was seen less in patients comparedwith healthy control subjects. In addition, for the first time, we detected vitamin D-binding protein in BALF exosomes, which was more abundant in patients. To evaluate exosome-associated vitamin D-binding protein as a biomarker for sarcoidosis, we investigated plasma exosomes from 23 patients and 11 healthy control subjects and found significantlyhigher expression in patients.CONCLUSION: Together,these data contribute to understanding the role of exosomes in lung disease and provide suggestions for highly warranted sarcoidosis biomarkers. Furthermore, the validation of an exosome-associated biomarker in the blood of patients provides novel, and less invasive, opportunities for disease diagnosis.</h4