The Challenged Sense of Belonging Scale (CSBS) - a validation study in English, Arabic, and Farsi/Dari among refugees and asylum seekers in Germany

This study introduces and investigates the validity of a brief scale measuring a challenged sense of belonging. The sense of belonging as well as challenges to this sense are important, albeit neglected aspects of social integration and of significance to migration and refugee studies as well as to virtually all other social science contexts. Assessing a challenged or eroded sense of belonging provides important insights into how individuals relate to their environment and whether they feel socially connected or disconnected from it. The construct goes beyond national or cultural identity, instead emphasizing the dynamic processes of emotional attachment. Reviewing the substantial theoretical literature on belonging, we identify four of its key elements: connection, participation, identification, and congruence. Drawing on existing measurement instruments, we propose a brief Challenged Sense of Belonging Scale (CSBS) that addresses each of the four elements and investigate its validity in a unique, multi-lingual random sample of 3783 adult refugees in Germany from various national and cultural backgrounds. We provide evidence for the scale's validity separately for three main survey languages (English, Arabic, Farsi/Dari) using confirmatory factor analysis, a test of measurement invariance, item test and rest correlations, and correlation analysis to explore convergent validity. Our findings suggest that the scale is a suitable instrument for the assessment of a challenged sense of belonging in a heterogeneous population of refugees

Mindfulness-Based Interventions for In-Patients With Schizophrenia Spectrum Disorders-A Qualitative Approach

In recent years, mindfulness-based interventions (MBI) have gained clinical relevance in the treatment of patients with schizophrenia spectrum disorders (SSDs). High symptom burden, long durations of hospitalization and high rehospitalization rates demonstrate the severity and cost-intensity of these disorders. MBIs have shown promising treatment outcomes in a small number of trials, primarily taking place in English-speaking countries. The current study aims to explore mechanisms and processes as well as adverse effects of MBIs on in-patients with SSDs in a German university hospital setting. A qualitative design based on inductive thematic analysis accompanied by quantitative assessments was chosen. A semi-structured interview guide was developed by psychiatrists and psychologists to assess patient experiences, perceptions, thoughts, and feelings during and after taking part in a MBI. Twenty-seven interviews were conducted between September 2017 and October 2018 with in-patients who are diagnosed with schizophrenia or schizoaffective disorder. Rater-based questionnaires, such as the Positive and Negative Syndrome Scale (PANSS), Montgomery Asberg Depression Rating Scale (MADRS), and Psychotic Symptom Rating Scales-Auditory Hallucination (PSYRATS-AH) were administered at baseline to collect clinical outcomes. Qualitative analysis revealed two domains: content and function. In the first domain related to content with the core elements "detachment and rumination", "presence and getting lost", "non-judgment and judgment", and effects with "emotions", "cognition", and "symptom changes". A second domain related to function was extracted, including the relevance of perception of context and transfer to everyday life. Overall, improvements concerning cognition, distress, and psychopathology were detected, while no adverse effects, such as increased psychotic symptoms, were revealed. As the first study of its kind, mechanisms, processes, and the safety of MBIs were explored and confirmed in a sample of German in-patients with SSDs. The results of this qualitative study are in line with recent findings on MBIs amongst patients with psychotic disorders from other countries. Results lay the ground for future research to focus on the systematic study of MBIs in large samples, its treatment processes, outcomes, and effectiveness for in-patients with SSDs

Staging and stratifying cognitive dysfunction in multiple sclerosis

BACKGROUND: The sequence in which cognitive domains become impaired in multiple sclerosis (MS) is yet to be formally demonstrated. It is unclear whether processing speed dysfunction temporally precedes other cognitive impairments, such as memory and executive function. OBJECTIVE: Determine the order in which different cognitive domains become impaired in MS and validate these findings using clinical and vocational outcomes. METHODS: In a longitudinal sample of 1073 MS patients and 306 healthy controls, we measured performance on multiple, consensus-standard, neurocognitive tests. We used an event-based staging approach to model the sequence in which cognitive domains become impaired. Linear and logistic mixed-effects models were used to explore associations between stages of impairment, neurological disability, and employment status. RESULTS: Our model suggested that the order of impairments was as follows: processing speed, visual learning, verbal learning, working memory/attention, and executive function. Stage of cognitive impairment predicted greater neurological disability, β = 0.16, SE = 0.02, p < 0.001, and probability of unemployment, β = 1.14, SE = 0.001, p < 0.001. CONCLUSION: This is the first study to introduce a cognitive staging and stratification system for MS. Findings underscore the importance of using the Symbol Digit Modalities Test in routine screening for cognitive impairment and memory testing to assess patients later in disease evolution

Treatment recommendation differences for schizophrenia and major depression: a population-based study in a Vietnamese cohort

Background: In Vietnam, the mental health care infrastructure is on the verge of transformation with an increase in the demand for access to adequate and effective mental health care services. Public attitudes towards mental illness, as well as corresponding treatment options influence help-seeking behaviors of patients and caregivers, affecting the course of their treatment. This study assesses attitudes towards treatment options for depression and schizophrenia, as the two most common psychiatric disorders in Vietnam, accounting for at least 75% of all psychiatric inpatients. Methods: A general population-based survey was conducted in Hanoi, Vietnam between April and August 2013. Participants received a description of a person with symptoms of either depression (n=326) or schizophrenia (n=403) and were asked to give recommendations for adequate sources of mental health support and treatment options. Multiple analyses on a single item level compared the likelihood of recommendation between schizophrenia and depression. Results: Overall, respondents recommended health care services, ranging from seeking mental health care professionals, psychotherapists, and psychiatrists for both disorders. Psychotherapy was the most favored treatment method, whereas further treatment options, such as concentration and relaxation exercises, meditation or yoga and psychotropic medication were also endorsed as helpful. For the schizophrenia vignette condition, psychotherapy, visiting a psychiatrist or psychotherapist received stronger endorsement rates as compared to the depression vignette. Furthermore, ECT, Feng Shui-based practices, praying and visiting natural healers were recommended less by respondents for the depression vignette in comparison with the schizophrenia vignette. Conclusions: The Vietnamese public endorsed evidence-based treatment recommendations from a variety of treatments options. Differences in the treatment recommendations between depression and schizophrenia reflected the perceived severity of each disorder. Further developments of the Vietnamese mental health care system concerning mental health care providers, as well as the legal regulations surrounding the provision of psychotherapy are needed

Coulomb implosion mechanism of negative ion acceleration in laser plasmas

Coulomb implosion mechanism of the negatively charged ion acceleration in laser plasmas is proposed. When a cluster target is irradiated by an intense laser pulse and the Coulomb explosion of positively charged ions occurs, the negative ions are accelerated inward. The maximum energy of negative ions is several times lower than that of positive ions. The theoretical description and Particle-in-Cell simulation of the Coulomb implosion mechanism and the evidence of the negative ion acceleration in the experiments on the high intensity laser pulse interaction with the cluster targets are presented.Comment: 4 page

Developmental Acquisition of a Rapid Calcium-Regulated Vesicle Supply Allows Sustained High Rates of Exocytosis in Auditory Hair Cells

Auditory hair cells (HCs) have the remarkable property to indefinitely sustain high rates of synaptic vesicle release during ongoing sound stimulation. The mechanisms of vesicle supply that allow such indefatigable exocytosis at the ribbon active zone remain largely unknown. To address this issue, we characterized the kinetics of vesicle recruitment and release in developing chick auditory HCs. Experiments were done using the intact chick basilar papilla from E10 (embryonic day 10) to P2 (two days post-hatch) by monitoring changes in membrane capacitance and Ca2+ currents during various voltage stimulations. Compared to immature pre-hearing HCs (E10-E12), mature post-hearing HCs (E18-P2) can steadily mobilize a larger readily releasable pool (RRP) of vesicles with faster kinetics and higher Ca2+ efficiency. As assessed by varying the inter-pulse interval of a 100 ms paired-pulse depolarization protocol, the kinetics of RRP replenishment were found much faster in mature HCs. Unlike mature HCs, exocytosis in immature HCs showed large depression during repetitive stimulations. Remarkably, when the intracellular concentration of EGTA was raised from 0.5 to 2 mM, the paired-pulse depression level remained unchanged in immature HCs but was drastically increased in mature HCs, indicating that the Ca2+ sensitivity of the vesicle replenishment process increases during maturation. Concomitantly, the immunoreactivity of the calcium sensor otoferlin and the number of ribbons at the HC plasma membrane largely increased, reaching a maximum level at E18-P2. Our results suggest that the efficient Ca2+-dependent vesicle release and supply in mature HCs essentially rely on the concomitant engagement of synaptic ribbons and otoferlin at the plasma membrane

Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer

Citrullinated histone H3 (H3Cit) is a central player in the neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs). NETs have been shown to elicit harmful effects on the host, and were recently proposed to promote tumor progression and spread. Here we report significant elevations of plasma H3Cit in patients with advanced cancer compared with age-matched healthy individuals. These elevations were specific to cancer patients as no increase was observed in severely ill and hospitalized patients with a higher non-malignant comorbidity. The analysis of neutrophils from cancer patients showed a higher proportion of neutrophils positive for intracellular H3Cit compared to severely ill patients. Moreover, the presence of plasma H3Cit in cancer patients strongly correlated with neutrophil activation markers neutrophil elastase (NE) and myeloperoxidase (MPO), and the inflammatory cytokines interleukin-6 and -8, known to induce NETosis. In addition, we show that high levels of circulating H3Cit strongly predicted poor clinical outcome in our cohort of cancer patients with a 2-fold increased risk for short-term mortality. Our results also corroborate the association of NE, interleukin-6 and -8 with poor clinical outcome. Taken together, our results are the first to unveil H3Cit as a potential diagnostic and prognostic blood marker associated with an exacerbated inflammatory response in patients with advanced cancer

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Poly-acetylated chromatin signatures are preferred epitopes for site-specific histone H4 acetyl antibodies

Antibodies specific for histone post-translational modifications (PTMs) have been central to our understanding of chromatin biology. Here, we describe an unexpected and novel property of histone H4 site-specific acetyl antibodies in that they prefer poly-acetylated histone substrates. By all current criteria, these antibodies have passed specificity standards. However, we find these site-specific histone antibodies preferentially recognize chromatin signatures containing two or more adjacent acetylated lysines. Significantly, we find that the poly-acetylated epitopes these antibodies prefer are evolutionarily conserved and are present at levels that compete for these antibodies over the intended individual acetylation sites. This alarming property of acetyl-specific antibodies has far-reaching implications for data interpretation and may present a challenge for the future study of acetylated histone and non-histone proteins