Implementation of a Budo group therapy for psychiatric in- and outpatients: a feasibility study.

Introduction: Physical exercise has been shown to have numerous health benefits on co-morbid somatic conditions in psychiatry and can also enhance mental health. Thus, it is not difficult to recommend physical training programs as part of an integrated and holistic treatment approach for mental health disorders. However, getting patients to participate and keeping them engaged is a major challenge. Programs based on martial arts training could be interventions improving physical and mental health with higher attachment rates. The structured discipline, holistic approach integrating physical and mental elements, and empowering activities, may explain higher participant attachment rates. Methods: Thus, the main objective of this feasibility study is to describe a newly established group therapy program incorporating interventions from martial arts training with its physical and philosophical parts including mindfulness and breath work. Results: During the 14-month study period from April 2021 to May 2022, a Budo group therapy was used by 215 individual persons with a total of 725 group therapy participations. Retention in the program was good across all settings and very good for persons who participated as outpatients. The mean age of the participants was 33.5 years with a range from 14 to 69 years of age, and about 41% of the participants were female. The therapy program was able to address patients over the whole spectrum of psychiatric diagnoses. Satisfaction and motivation were uniformly self-reported as very good. Patients self-reported improved mental and physical health after participating in a Budo session compared to pre-session. Discussion: Budo group therapy thus can be seen as a feasible, well-accepted and promising new transdiagnostic treatment approach, combining physical activation with resilience enhancement. With minimal contraindications, a broad spectrum of individuals seeking mental health support can engage in this group therapy.

COVID-19-related consultation-liaison (CL) mental health services in general hospitals: A perspective from Europe and beyond.

OBJECTIVE: The COVID-19 pandemic posed new challenges for integrated health care worldwide. Our study aimed to describe newly implemented structures and procedures of psychosocial consultation and liaison (CL) services in Europe and beyond, and to highlight emerging needs for co-operation. METHODS: Cross-sectional online survey from June to October 2021, using a self-developed 25-item questionnaire in four language versions (English, French, Italian, German). Dissemination was via national professional societies, working groups, and heads of CL services. RESULTS: Of the participating 259 CL services from Europe, Iran, and parts of Canada, 222 reported COVID-19 related psychosocial care (COVID-psyCare) in their hospital. Among these, 86.5% indicated that specific COVID-psyCare co-operation structures had been established. 50.8% provided specific COVID-psyCare for patients, 38.2% for relatives, and 77.0% for staff. Over half of the time resources were invested for patients. About a quarter of the time was used for staff, and these interventions, typically associated with the liaison function of CL services, were reported as most useful. Concerning emerging needs, 58.1% of the CL services providing COVID-psyCare expressed wishes for mutual information exchange and support, and 64.0% suggested specific changes or improvements that they considered essential for the future. CONCLUSION: Over 80% of participating CL services established specific structures to provide COVID-psyCare for patients, their relatives, or staff. Mostly, resources were committed to patient care and specific interventions were largely implemented for staff support. Future development of COVID-psyCare warrants intensified intra- and inter-institutional exchange and co-operation.

The nanotopography of SiO2 particles impacts the selectivity and 3D fold of bound allergens.

A detailed description of the changes that occur during the formation of protein corona represents a fundamental question in nanoscience, given that it not only impacts the behaviour of nanoparticles but also affects the bound proteins. Relevant questions include whether proteins selectively bind particles, whether a specific orientation is preferred for binding, and whether particle binding leads to a modulation of their 3D fold. For allergens, it is important to answer these questions given that all these effects can modify the allergenic response of atopic individuals. These potential impacts on the bound allergen are closely related to the specific properties of the involved nanoparticles. One important property influencing the formation of protein corona is the nanotopography of the particles. Herein, we studied the effect of nanoparticle porosity on allergen binding using mesoporous and non-porous SiO2 NPs. We investigated (i) the selectivity of allergen binding from a mixture such as crude pollen extract, (ii) whether allergen binding results in a preferred orientation, (iii) the influence of binding on the conformation of the allergen, and (iv) how the binding affects the allergenic response. Nanotopography was found to play a major role in the formation of protein corona, impacting the physicochemical and biological properties of the NP-bound allergen. The porosity of the surface of the SiO2 nanoparticles resulted in a higher binding capacity with pronounced selectivity for (preferentially) binding the major birch pollen allergen Bet v 1. Furthermore, the binding of Bet v 1 to the mesoporous rather than the non-porous SiO2 nanoparticles influenced the 3D fold of the protein, resulting in at least partial unfolding. Consequently, this conformational change influenced the allergenic response, as observed by mediator release assays employing the sera of patients and immune effector cells. For an in-depth understanding of the bio-nano interactions, the properties of the particles need to be considered not only regarding the identity and morphology of the material, but also their nanotopography, given that porosity may greatly influence the structure, and hence the biological behaviour of the bound proteins. Thus, thorough structural investigations upon the formation of protein corona are important when considering immunological outcomes, as particle binding can influence the allergenic response elicited by the bound allergen.

Hydrogen/deuterium exchange memory NMR reveals structural epitopes involved in IgE cross-reactivity of allergenic lipid transfer proteins.

Identification of antibody-binding epitopes is crucial to understand immunological mechanisms. It is of particular interest for allergenic proteins with high cross-reactivity as observed in the lipid transfer protein (LTP) syndrome, which is characterized by severe allergic reactions. Art v 3, a pollen LTP from mugwort, is frequently involved in this cross-reactivity, but no antibody-binding epitopes have been determined so far. To reveal human IgE-binding regions of Art v 3, we produced three murine high-affinity mAbs, which showed 70-90% coverage of the allergenic epitopes from mugwort pollen-allergic patients. As reliable methods to determine structural epitopes with tightly interacting intact antibodies under native conditions are lacking, we developed a straightforward NMR approach termed hydrogen/deuterium exchange memory (HDXMEM). It relies on the slow exchange between the invisible antigen-mAb complex and the free 15N-labeled antigen whose 1H-15N correlations are detected. Due to a memory effect, changes of NH protection during antibody binding are measured. Differences in H/D exchange rates and analyses of mAb reactivity to homologous LTPs revealed three structural epitopes: two partially cross-reactive regions around α-helices 2 and 4 as well as a novel Art v 3-specific epitope at the C terminus. Protein variants with exchanged epitope residues confirmed the antibody-binding sites and revealed strongly reduced IgE reactivity. Using the novel HDXMEM for NMR epitope mapping allowed identification of the first structural epitopes of an allergenic pollen LTP. This knowledge enables improved cross-reactivity prediction for patients suffering from LTP allergy and facilitates design of therapeutics.

Could Animal-Assisted Therapy Help to Reduce Coercive Treatment in Psychiatry?

For psychiatric patients, compulsory admission and coercive measures can constitute distressing and sometimes traumatizing experiences. As a consequence, clinicians aim at minimizing such procedures. At the same time, they need to ensure high levels of safety for patients, staff and the public. In order to prevent compulsory measures and to favor the use of less restrictive alternatives, innovative interventions improving the management of dangerous situations are needed. Animal-assisted therapy (AAT) is being applied in a variety of diagnoses and treatment settings, and could have the potential to reduce aggression and psychopathology. Therefore, AAT might be of use in the prevention and early treatment of aggression, and might constitute a promising component of treatment alternatives to forced interventions. To our knowledge, no study evaluating the effect of AAT on compulsory measures in persons with psychiatric diseases has been published up to date. This narrative expert review including a systematic literature search examines the published literature about the use of AAT in psychiatry. Studies report reduced anxiety and aggressiveness as well as positive effects on general wellbeing, self-efficacy, quality of life and mindfulness. Although literature on the applicability of AAT as a component of preventive or de-escalating treatment settings is sparse, beneficial effects of AAT have been reported. Therefore, we encourage examining AAT as a promising new treatment approach to prevent compulsory measures.

Boiling down the cysteine-stabilized LTP fold - loss of structural and immunological integrity of allergenic Art v 3 and Pru p 3 as a consequence of irreversible lanthionine formation.

BACKGROUND: Non-specific lipid transfer proteins (LTPs) are important allergens in fruits, pollen, vegetables, nuts and latex. Due to their compact structure, LTPs are highly resistant to heat treatment. Here, Art v 3 from mugwort pollen and Pru p 3 from peach were used as model allergens to in-depth investigate structural and immunological properties upon thermal treatment at different buffer conditions. METHODS: Recombinant Art v 3 and Pru p 3 were purified from E. coli and incubated at 95 °C up to 120 min using sodium phosphate buffer pH 3.4 or 7.3. Physicochemical properties of allergens were analyzed in circular dichroism spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering, size exclusion chromatography, and mass spectrometry. The crystal structure of Art v 3.0201 was determined to 1.9 Šresolution. IgG and IgE binding was investigated in ELISA using murine and LTP allergic patients' sera. RESULTS: Highly pure and homogenous recombinant allergens were obtained from bacterial production. The crystal structure of Art v 3.0201 revealed an antiparallel four helix bundle with a C-terminal extension mediating an asymmetric, transient dimer interface and differently sized cavities. Both allergens showed high thermal stability at acidic conditions. In contrast, extensive heat treatment in neutral buffer induced irreversible structural changes due to lanthionine-based cysteine rearrangement. This fostered loss of the typical α-helical structure, increased molecular size and abrogation of IgG and IgE binding epitopes. Pru p 3 lost its structural integrity at shorter heat stress duration than Art v 3, which did however only partially affect the molecule's IgE binding epitopes. CONCLUSION: During thermal treatment, susceptibility to structural changes of the LTP-fold is highly dependent on the surrounding environment but also on intrinsic features of individual LTPs. This is a crucial fact to consider when processing LTP-containing food or food products as this will directly influence their allergenic potential.

Untargeted Metabolomics Reveals Molecular Effects of Ketogenic Diet on Healthy and Tumor Xenograft Mouse Models.

The application of ketogenic diet (KD) (high fat/low carbohydrate/adequate protein) as an auxiliary cancer therapy is a field of growing attention. KD provides sufficient energy supply for healthy cells, while possibly impairing energy production in highly glycolytic tumor cells. Moreover, KD regulates insulin and tumor related growth factors (like insulin growth factor-1, IGF-1). In order to provide molecular evidence for the proposed additional inhibition of tumor growth when combining chemotherapy with KD, we applied untargeted quantitative metabolome analysis on a spontaneous breast cancer xenograft mouse model, using MDA-MB-468 cells. Healthy mice and mice bearing breast cancer xenografts and receiving cyclophosphamide chemotherapy were compared after treatment with control diet and KD. Metabolomic profiling was performed on plasma samples, applying high-performance liquid chromatography coupled to tandem mass spectrometry. Statistical analysis revealed metabolic fingerprints comprising numerous significantly regulated features in the group of mice bearing breast cancer. This fingerprint disappeared after treatment with KD, resulting in recovery to the metabolic status observed in healthy mice receiving control diet. Moreover, amino acid metabolism as well as fatty acid transport were found to be affected by both the tumor and the applied KD. Our results provide clear evidence of a significant molecular effect of adjuvant KD in the context of tumor growth inhibition and suggest additional mechanisms of tumor suppression beyond the proposed constrain in energy supply of tumor cells.

Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction.

Nitration of the birch pollen allergen Bet v 1.0101: efficiency and site-selectivity of liquid and gaseous nitrating agents.

Nitration of the major birch pollen allergen Bet v 1 alters the immune responses toward this protein, but the underlying chemical mechanisms are not yet understood. Here we address the efficiency and site-selectivity of the nitration reaction of recombinant protein samples of Bet v 1.0101 with different nitrating agents relevant for laboratory investigations (tetranitromethane, TNM), for physiological processes (peroxynitrite, ONOO(-)), and for the health effects of environmental pollutants (nitrogen dioxide and ozone, O3/NO2). We determined the total tyrosine nitration degrees (ND) and the NDs of individual tyrosine residues (NDY). High-performance liquid chromatography coupled to diode array detection and HPLC coupled to high-resolution mass spectrometry analysis of intact proteins, HPLC coupled to tandem mass spectrometry analysis of tryptic peptides, and amino acid analysis of hydrolyzed samples were performed. The preferred reaction sites were tyrosine residues at the following positions in the polypeptide chain: Y83 and Y81 for TNM, Y150 for ONOO(-), and Y83 and Y158 for O3/NO2. The tyrosine residues Y83 and Y81 are located in a hydrophobic cavity, while Y150 and Y158 are located in solvent-accessible and flexible structures of the C-terminal region. The heterogeneous reaction with O3/NO2 was found to be strongly dependent on the phase state of the protein. Nitration rates were about one order of magnitude higher for aqueous protein solutions (∼20% per day) than for protein filter samples (∼2% per day). Overall, our findings show that the kinetics and site-selectivity of nitration strongly depend on the nitrating agent and reaction conditions, which may also affect the biological function and adverse health effects of the nitrated protein.

Religiosity, magical ideation, and paranormal beliefs in anxiety disorders and obsessive-compulsive disorder: a cross-sectional study.

The relation between religiosity/spirituality (R/S), personal beliefs, and mental health has been extensively studied. However, concerning anxiety disorders (ADs), empirical evidence is scarce. This study investigated the differences in R/S and magical/paranormal ideation among obsessive-compulsive disorder patients (OCD; n = 49), patients with other ADs (n = 36), and healthy controls (HCs; n = 35). Our results suggest negative religious coping as being the only parameter showing significantly higher scores in OCD and AD participants in comparison with HCs. Negative religious coping reflects negative functional expressions of R/S in stressful situations. Logistic regression also suggested negative religious coping as the strongest predictor of group affiliation to the nonhealthy group. Further results show no significant differences between other R/S, magical, and paranormal ideation traits among groups. This study underlines an important role of negative religious coping in ADs yet does not clearly indicate a specific causality. Religious-sensitive treatment targeting cognitive aspects of negative religious coping are discussed.

The role of melatonin in glaucoma: implications concerning pathophysiological relevance and therapeutic potential.

Glaucoma is a frequent ophthalmologic condition leading to chronic progressive optic neuropathy, which can result in visual impairment and blindness. In addition, glaucoma is associated with a dysregulation of circadian rhythms, as well as with a high incidence of sleep disorders, depression, and anxiety. However, because of their high comorbidity in older age, these conditions have not received much scientific attention and are often undertreated. In the current paper, we review the available literature on the role of melatonergic mechanisms in glaucoma, regulation of circadian rhythms, and depression. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. Recently, there has been evidence for a progressive loss of intrinsically photosensitive retinal ganglion cells (ipRGC) because of oxidative stress in glaucoma. As ipRGC are responsible for the photic transduction to the circadian system and subsequent melatonin secretion, and melatonin is involved in the pathophysiology of circadian desynchronization, sleep disorder, and depression, an impairment of photo-dependent melatonergic signaling may be a common pathway connecting glaucoma with these comorbidities. This fact, as well as the proven retinal neuroprotective role of melatonin, suggests that melatonergic drugs provide a potentially promising treatment strategy supplementing the management of intraocular pressure by pharmacological and surgical measures. Additionally, multidisciplinary treatment focusing on depression and normalization of circadian rhythms might be beneficial for glaucoma patients. Furthermore, glaucoma might be a useful model for studying the pathophysiological interactions between the melatonergic, circadian, and mood systems.