Proteasome inhibition alleviates prolonged moderate compression-induced muscle pathology

Background: The molecular mechanism initiating deep pressure ulcer remains to be elucidated. The present study tested the hypothesis that the ubiquitin proteasome system is involved in the signalling mechanism in pressure-induced deep tissue injury. Methods. Adult Sprague Dawley rats were subjected to an experimental compression model to induce deep tissue injury. The tibialis region of the right hind limb was subjected to 100 mmHg of static pressure for six hours on each of two consecutive days. The compression pressure was continuously monitored by a three-axial force transducer within the compression indentor. The left hind limb served as the intra-animal control. Muscle tissues underneath the compressed region were collected and used for analyses. Results: Our results demonstrated that the activity of 20S proteasome and the protein abundance of ubiquitin and MAFbx/atrogin-1 were elevated in conjunction with pathohistological changes in the compressed muscle, as compared to control muscle. The administration of the proteasome inhibitor MG132 was found to be effective in ameliorating the development of pathological histology in compressed muscle. Furthermore, 20S proteasome activity and protein content of ubiquitin and MAFbx/atrogin-1 showed no apparent increase in the MG132-treated muscle following compression. Conclusion: Our data suggest that the ubiquitin proteasome system may play a role in the pathogenesis of pressure-induced deep tissue injury. © 2011 Siu et al; licensee BioMed Central Ltd.Link_to_subscribed_fulltex

Little evidence of systemic and adipose tissue inflammation in overweight individuals†

Context: The effect of weight loss by diet alone or diet in conjunction with exercise on low-grade inflammation in non-obese (overweight) individuals is not known. Objective: Test the hypothesis that 24 weeks of moderate calorie restriction (CR; 25%) by diet only or with aerobic exercise would reduce markers of systemic inflammation and attenuate inflammation gene expression in subcutaneous adipose tissue. Design: Randomized controlled trial. Setting: Institutional Research Center. Participants: Thirty-five overweight (body mass index: 27.8 ± 0.7 kg/m2) but otherwise healthy participants (16M/19F) completed the study. Intervention: Participants were randomized to either CR (25% reduction in energy intake, n = 12), caloric restriction + exercise (CR + EX: 12.5% reduction in energy intake + 12.5% increase in exercise energy expenditure, n = 12), or control (healthy weight-maintenance diet, n = 11) for 6 months. Main outcome measures: Fasting serum markers of inflammation [leptin, highly sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), adiponectin] and inflammation-related genes [CD68, IL-6, TNF-α, macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1), adiponectin, plasminogen activator inhibitor-1 (PAI-1)] in subcutaneous adipose tissue. Results: CR and CR + EX lost similar amounts of body weight (–10 ± 1%), fat mass (–24 ± 3%), visceral fat (–27 ± 3%), and had increased insulin sensitivity (CR: 40 ± 20%, CR + EX: 66 ± 22%). Leptin was significantly decreased from baseline (p < 0.001) in both groups however TNF-α and IL-6 were not changed. hsCRP was decreased in CR + EX. There was no change in the expression of genes involved in macrophage infiltration (CD68, MIF MCP-1, PAI-1) or inflammation (IL-6, TNF-α, adiponectin) in either CR or CR + EX. Conclusion: A 10% weight loss with a 25% CR diet alone or with exercise did not impact markers of systemic inflammation or the expression of inflammation-related adipose genes in overweight individuals

Chandra Monitoring of the Candidate Anomalous X-ray Pulsar AX J1845.0-0258

The population of clearly identified anomalous X-ray pulsars has recently grown to seven, however, one candidate anomalous X-ray pulsar (AXP) still eludes re-confirmation. Here, we present a set of seven Chandra ACIS-S observations of the transient pulsar AX J1845.0-0258, obtained during 2003. Our observations reveal a faint X-ray point source within the ASCA error circle of AX J1845.0-0258's discovery, which we designate CXOU J184454.6-025653 and tentatively identify as the quiescent AXP. Its spectrum is well described by an absorbed single-component blackbody (kT~2.0 keV) or power law (Gamma~1.0) that is steady in flux on timescales of at least months, but fainter than AX J1845.0-0258 was during its 1993 period of X-ray enhancement by at least a factor of 13. Compared to the outburst spectrum of AX J1845.0-0258, CXOU J184454.6-025653 is considerably harder: if truly the counterpart, then its spectral behaviour is contrary to that seen in the established transient AXP XTE J1810-197, which softened from kT~0.67 keV to ~0.18 keV in quiescence. This unexpected result prompts us to examine the possibility that we have observed an unrelated source, and we discuss the implications for AXPs, and magnetars in general.Comment: 4 pages, 3 figures. To be published in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 24-28, 2006, London, UK), eds. D. Page, R. Turolla, & S. Zan

Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation

Rationale: Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation. Objectives: We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice. Methods: Male mice received paroxetine (10 mg/kg/day, s.c.) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system. Results Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation. Conclusions: This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms

The Transmission Dynamics of Tuberculosis in a Recently Developed Chinese City

BACKGROUND: Hong Kong is an affluent subtropical city with a well-developed healthcare infrastructure but an intermediate TB burden. Declines in notification rates through the 1960s and 1970s have slowed since the 1980s to the current level of around 82 cases per 100 000 population. We studied the transmission dynamics of TB in Hong Kong to explore the factors underlying recent trends in incidence. METHODOLOGY/PRINCIPAL FINDINGS: We fitted an age-structured compartmental model to TB notifications in Hong Kong between 1968 and 2008. We used the model to quantify the proportion of annual cases due to recent transmission versus endogenous reactivation of latent infection, and to project trends in incidence rates to 2018. The proportion of annual TB notifications attributed to endogenous reactivation increased from 46% to 70% between 1968 and 2008. Age-standardized notification rates were projected to decline to approximately 56 per 100 000 in 2018. CONCLUSIONS/SIGNIFICANCE: Continued intermediate incidence of TB in Hong Kong is driven primarily by endogenous reactivation of latent infections. Public health interventions which focus on reducing transmission may not lead to substantial reductions in disease burden associated with endogenous reactivation of latent infections in the short- to medium-term. While reductions in transmission with socio-economic development and public health interventions will lead to declines in TB incidence in these regions, a high prevalence of latent infections may hinder substantial declines in burden in the longer term. These findings may therefore have important implications for the burden of TB in developing regions with higher levels of transmission currently.published_or_final_versio

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

Bonding between π-Conjugated Polycations and Monolayer Graphene: Decisive Role of Anions

Functionalization and precise modulation of the electronic properties of graphene are key processes in the development of new applications of this promising material. This study examines the potential of using organic polycations as p-dopants and/or anchoring motifs for non-covalent functionalization. A library of hybrid materials was prepared through wet-chemical non-covalent functionalization. Both chemical vapor deposition graphene and reduced graphene oxide were functionalized with a series of neutral and polycationic benzimidazole-based systems. We report on how both the number of anions and the size, shape, and magnitude of the positive charge of the benzimidazole-based systems cooperatively affect the redox properties as well as the affinity for and the nature of bonding to graphene. The redox properties of the benzimidazole-based systems were studied by cyclic voltammetry. The functionalized graphene materials were characterized by Raman spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry. Density functional theory calculations were performed to make contact between the experimental results obtained for molecular samples and hybrid materials. No universal dependence of the binding affinity on a single parameter, such as the amount of positive charge or the size of the system, was found. Instead, the cooperative effect of the three-dimensional structure of the benzimidazole-based systems and the number of anions was found to play a pivotal role. Together, these parameters determine the degree of partial electron sharing and magnitude of dispersion forces involved in the binding of members of this family of benzimidazole-based systems to graphene

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

ROMA (Rank-Ordered Multifractal Analysis) for intermittent fluctuations with global crossover behavior

Rank-Ordered Multifractal Analysis (ROMA), a recently developed technique that combines the ideas of parametric rank ordering and one parameter scaling of monofractals, has the capabilities of deciphering the multifractal characteristics of intermittent fluctuations. The method allows one to understand the multifractal properties through rank-ordered scaling or non-scaling parametric variables. The idea of the ROMA technique is applied to analyze the multifractal characteristics of the auroral zone electric field fluctuations observed by SIERRA. The observed fluctuations span across contiguous multiple regimes of scales with different multifractal characteristics. We extend the ROMA technique such that it can take into account the crossover behavior -- with the possibility of collapsing probability distributions functions (PDFs) -- over these contiguous regimes.Comment: 24 pages, 18 figure