Integration Is Correlated With Mental Health Help-Seeking From the General Practitioner: Syrian Refugees' Preferences and Perceived Barriers

Despite a seemingly higher need, refugees in Europe tend to underuse mental health (MH) services. To better understand this underuse, it is important to understand refugees' willingness and ability to seek help from their general practitioner (GP) when experiencing MH problems. We employed a combined vignette and survey design to explore how the GP fits into the larger context of help-seeking preferences among a sample of Syrian refugees in Norway (n = 92), and what barriers they perceive in accessing help from the GP. We also examined how indicators of integration relate to seeking help from the GP. We take an exploratory approach. Participants were presented a vignette of an individual with symptoms in line with ICD-10 and DSM-5 criteria for depression. Participants were somewhat likely to seek help from the GP; however, seeking help from one's relationship with Allah/God and one's partner was preferred. Furthermore, while the GP was rated a somewhat likely help-seeking source, most participants indicated an average of two barriers to seeking help from the GP. Finally, social ties to the majority population in the form of social integration and feelings of connectedness with the host country (psychological integration) were positively correlated with likelihood of seeking help from the GP. Taken together, these findings suggest that the GP is considered a viable source of help among Syrians with a refugee background in the current sample, but that this may be influenced by perceived barriers and social as well as psychological integration. Addressing these barriers and promoting psychosocial integration with the host country are key to facilitating access and usage amongst refugees in need of MH services.publishedVersio

Conformational equilibria in monomeric alpha-synuclein at the single molecule level

Natively unstructured proteins defy the classical "one sequence-one structure" paradigm of protein science. Monomers of these proteins in pathological conditions can aggregate in the cell, a process that underlies socially relevant neurodegenerative diseases such as Alzheimer and Parkinson. A full comprehension of the formation and structure of the so-called misfolded intermediates from which the aggregated states ensue is still lacking. We characterized the folding and the conformational diversity of alpha-synuclein (aSyn), a natively unstructured protein involved in Parkinson disease, by mechanically stretching single molecules of this protein and recording their mechanical properties. These experiments permitted us to directly observe directly and quantify three main classes of conformations that, under in vitro physiological conditions, exist simultaneously in the aSyn sample, including disordered and "beta-like" structures. We found that this class of "beta-like" structures is directly related to aSyn aggregation. In fact, their relative abundance increases drastically in three different conditions known to promote the formation of aSyn fibrils: the presence of Cu2+, the occurrence of the pathogenic A30P mutation, and high ionic strength. We expect that a critical concentration of aSyn with a "beta-like" structure must be reached to trigger fibril formation. This critical concentration is therefore controlled by a chemical equilibrium. Novel pharmacological strategies can now be tailored to act upstream, before the aggregation process ensues, by targeting this equilibrium. To this end, Single Molecule Force Spectroscopy can be an effective tool to tailor and test new pharmacological agents.Comment: 37 pages, 9 figures (including supplementary material

Effectiveness of nutritional countermeasures in microgravity and its ground-based analogues to ameliorate musculoskeletal and cardiopulmonary deconditioning – A Systematic Review

A systematic review was performed to evaluate the effectiveness of nutrition as a standalone countermeasure to ameliorate the physiological adaptations of the musculoskeletal and cardiopulmonary systems associated with prolonged exposure to microgravity. A search strategy was developed to find all astronaut or human space flight bed rest simulation studies that compared individual nutritional countermeasures with non-intervention control groups. This systematic review followed the guidelines of the Cochrane Handbook for Systematic Reviews and tools created by the Aerospace Medicine Systematic Review Group for data extraction, quality assessment of studies and effect size. To ensure adequate reporting this systematic review followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses. A structured search was performed to screen for relevant articles. The initial search yielded 4031 studies of which 10 studies were eligible for final inclusion. Overall, the effect of nutritional countermeasure interventions on the investigated outcomes revealed that only one outcome was in favor of the intervention group, whereas six outcomes were in favor of the control group, and 43 outcomes showed no meaningful effect of nutritional countermeasure interventions at all. The main findings of this study were: (1) the heterogeneity of reported outcomes across studies, (2) the inconsistency of the methodology of the included studies (3) an absence of meaningful effects of standalone nutritional countermeasure interventions on musculoskeletal and cardiovascular outcomes, with a tendency towards detrimental effects on specific muscle outcomes associated with power in the lower extremities. This systematic review highlights the limited amount of studies investigating the effect of nutrition as a standalone countermeasure on operationally relevant outcome parameters. Therefore, based on the data available from the included studies in this systematic review, it cannot be expected that nutrition alone will be effective in maintaining musculoskeletal and cardiopulmonary integrity during space flight and bed rest

Epigenetic reversion of breast carcinoma phenotype is accompanied by DNA sequestration

The importance of microenvironment and context in regulation of tissue-specific genes is finally well established. DNA exposure to, or sequestration from, nucleases can be used to detect differences in higher order chromatin structure in intact cells without disturbing cellular or tissue architecture. To investigate the relationship between chromatin organization and tumor phenotype, we utilized an established 3-D assay where normal and malignant human breast cells can be easily distinguished by the morphology of the structures they make (acinus-like vs tumor-like, respectively). We show that these phenotypes can be distinguished also by sensitivity to AluI digestion where the malignant cells are resistant to digestion relative to non-malignant cells. Reversion of the T4-2 breast cancer cells by either cAMP analogs, or a phospatidylinositol 3-kinase (P13K) inhibitor not only reverted the phenotype, but also the chromatin sensitivity to AluI. By using different cAMP-analogs, we show that the cAMP-induced phenotypic reversion, polarization, and shift in DNA organization act through a cAMP-dependent-protein-kinase A-coupled signaling pathway. Importantly, inhibitory antibody to fibronectin also reverted the malignant phenotype, polarized the acini, and changed chromatin sequestration. These experiments show not only that modifying the tumor microenvironment can alter the organization of tumor cells but also that architecture of the tissues and the global chromatin organization are coupled and yet highly plastic

Elevated CRP and TNF-α Levels are Associated with Blunted Neural Oscillations Serving Fluid Intelligence

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf. METHODS: Seventy adults between the ages of 20-66 years (Mean = 45.17 years, SD = 16.29, 21.4% female) completed an abstract reasoning task that probes Gf during magnetoencephalography (MEG) and provided a blood sample for inflammatory marker analysis. MEG data were imaged in the time-frequency domain, and whole-brain regressions were conducted using each individual\u27s plasma CRP and TNF-α concentrations per oscillatory response, controlling for age, BMI, and education. RESULTS: CRP and TNF-α levels were significantly associated with region-specific neural oscillatory responses. In particular, elevated CRP concentrations were associated with altered gamma activity in the right inferior frontal gyrus and right cerebellum. In contrast, elevated TNF-α levels scaled with alpha/beta oscillations in the left anterior cingulate and left middle temporal, and gamma activity in the left intraparietal sulcus. DISCUSSION: Elevated inflammatory markers such as CRP and TNF-α were associated with aberrant neural oscillations in regions important for Gf. Linking inflammatory markers with regional neural oscillations may hold promise in identifying mechanisms of cognitive and psychiatric disorders

Efficient unfolding pattern recognition in single molecule force spectroscopy data

BackgroundSingle-molecule force spectroscopy (SMFS) is a technique that measures the force necessary to unfold a protein. SMFS experiments generate Force-Distance (F-D) curves. A statistical analysis of a set of F-D curves reveals different unfolding pathways. Information on protein structure, conformation, functional states, and inter- and intra-molecular interactions can be derived.ResultsIn the present work, we propose a pattern recognition algorithm and apply our algorithm to datasets from SMFS experiments on the membrane protein bacterioRhodopsin (bR). We discuss the unfolding pathways found in bR, which are characterised by main peaks and side peaks. A main peak is the result of the pairwise unfolding of the transmembrane helices. In contrast, a side peak is an unfolding event in the alpha-helix or other secondary structural element. The algorithm is capable of detecting side peaks along with main peaks.Therefore, we can detect the individual unfolding pathway as the sequence of events labeled with their occurrences and co-occurrences special to bR\u27s unfolding pathway. We find that side peaks do not co-occur with one another in curves as frequently as main peaks do, which may imply a synergistic effect occurring between helices. While main peaks co-occur as pairs in at least 50% of curves, the side peaks co-occur with one another in less than 10% of curves. Moreover, the algorithm runtime scales well as the dataset size increases.ConclusionsOur algorithm satisfies the requirements of an automated methodology that combines high accuracy with efficiency in analyzing SMFS datasets. The algorithm tackles the force spectroscopy analysis bottleneck leading to more consistent and reproducible results

The growing story of (ARABIDOPSIS) CRINKLY 4

Receptor kinases play important roles in plant growth and development, but only few of them have been functionally characterized in depth. Over the past decade CRINKLY 4 (CR4)-related research has peaked as a result of a newly discovered role of ARABIDOPSIS CR4 (ACR4) in the root. Here, we comprehensively review the available (A)CR4 literature and describe its role in embryo, seed, shoot, and root development, but we also flag an unexpected role in plant defence. In addition, we discuss ACR4 domains and protein structure, describe known ACR4-interacting proteins and substrates, and elaborate on the transcriptional regulation of ACR4. Finally, we address the missing knowledge in our understanding of ACR4 signalling