Narrative exposure therapy for survivors of human trafficking: feasibility randomised controlled trial

Background Human trafficking is a grave human rights violation and a major public health concern. Survivors present with high rates of mental health problems including post-traumatic stress disorder (PTSD). Studies of effective treatments for PTSD in survivors of human trafficking are lacking. Narrative exposure therapy (NET) is an effective PTSD treatment for multiple, prolonged and complex trauma, but its efficacy has not been rigorously tested in survivors of human trafficking. Aims To test the feasibility and acceptability of a randomised controlled trial (RCT) offering NET as a treatment for PTSD in trafficking survivors with a history of multiple traumatic events, as well as providing preliminary evidence regarding its efficacy (trial registration: ISRCTN95136302). Method A single-blind RCT compared NET with a wait-list control in survivors of trafficking with PTSD (n = 25). In the NET arm of the study, participants attended a mean of 17 sessions. Results NET was well tolerated by participants. There were significant reductions in PTSD, depression and anxiety symptoms post-treatment in the NET group but no significant change in the wait-list group. Conclusions The results indicate that NET is a promising and acceptable treatment for trafficking survivors. Psychological therapy in an RCT design can be safely delivered to this vulnerable group, although modifications are required to ensure their holistic needs are properly addressed

Narrative exposure therapy for survivors of human trafficking: feasibility randomised controlled trial

BACKGROUND: Human trafficking is a grave human rights violation and a major public health concern. Survivors present with high rates of mental health problems including post-traumatic stress disorder (PTSD). Studies of effective treatments for PTSD in survivors of human trafficking are lacking. Narrative exposure therapy (NET) is an effective PTSD treatment for multiple, prolonged and complex trauma, but its efficacy has not been rigorously tested in survivors of human trafficking. AIMS: To test the feasibility and acceptability of a randomised controlled trial (RCT) offering NET as a treatment for PTSD in trafficking survivors with a history of multiple traumatic events, as well as providing preliminary evidence regarding its efficacy (trial registration: ISRCTN95136302). METHOD: A single-blind RCT compared NET with a wait-list control in survivors of trafficking with PTSD (n = 25). In the NET arm of the study, participants attended a mean of 17 sessions. RESULTS: NET was well tolerated by participants. There were significant reductions in PTSD, depression and anxiety symptoms post-treatment in the NET group but no significant change in the wait-list group. CONCLUSIONS: The results indicate that NET is a promising and acceptable treatment for trafficking survivors. Psychological therapy in an RCT design can be safely delivered to this vulnerable group, although modifications are required to ensure their holistic needs are properly addressed

Activated platelets retain and protect most of their factor XIII-A cargo from proteolytic activation and degradation

The authors thank László Muszbek for the polyclonal anti-FXIII-Aantibody,Abigail R. Ballardfor technical support, Pablo Ariel for help with the immunofluorescence imaging and analysis, Marina Sokolsky for help with nanoparticle tracking analysis,and Nigel Mackman and Kadri Kangro for reading the manuscript.The Microscopy Services Laboratory, Department of Pathology and Laboratory Medicine, is supported in part by a Cancer Center Core Support Grant to the UNC Lineberger Comprehensive Cancer Center(P30 CA016086).Peer reviewe

STABILON, a Novel Sequence Motif That Enhances the Expression and Accumulation of Intracellular and Secreted Proteins

The dynamic balance of transcriptional and translational regulation together with degron-controlled proteolysis shapes the ever-changing cellular proteome. While a large variety of degradation signals has been characterized, our knowledge of cis-acting protein motifs that can in vivo stabilize otherwise short-lived proteins is very limited. We have identified and characterized a conserved 13-mer protein segment derived from the p54/Rpn10 ubiquitin receptor subunit of the Drosophila 26S proteasome, which fulfills all the characteristics of a protein stabilization motif (STABILON). Attachment of STABILON to various intracellular as well as medically relevant secreted model proteins resulted in a significant increase in their cellular or extracellular concentration in mammalian cells. We demonstrate that STABILON acts as a universal and dual function motif that, on the one hand, increases the concentration of the corresponding mRNAs and, on the other hand, prevents the degradation of short-lived fusion proteins. Therefore, STABILON may lead to a breakthrough in biomedical recombinant protein production

Communications Biophysics

Contains research objectives and reports on two research projects.National Institutes of Health (Grant 2 PO1 GM-14941-01)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 28-043-AMC-02536(E)National Aeronautics and Space Administration (Grant NsG-496)National Institutes of Health (Grant 2 RO1 NB-05462-04)National Institutes of Health (Grant 1 TO1 GM-01555-01

Communications Biophysics

Contains research objectives, summary of research and reports on two research projects.National Institutes of Health (Grant 5 PO1 GM-14940-02)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E)National Aeronautics and Space Administration (Grant NGL 22-009-304)National Institutes of Health (Grant 5 TO1 GM-01555-02)National Institutes of Health (Grant NB-08082-01

High-Density Real-Time PCR-Based in Vivo Toxicogenomic Screen to Predict Organ-Specific Toxicity

Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage. In the present study our objective was to extend in vivo toxicogenomic screening from analyzing one or a few tissues to multiple organs, including heart, kidney, brain, liver and spleen. Nanocapillary quantitative real-time PCR (QRT-PCR) was used in the study, due to its higher throughput, sensitivity and reproducibility, and larger dynamic range compared to DNA microarray technologies. Based on previous data, 56 gene markers were selected coding for proteins with different functions, such as proteins for acute phase response, inflammation, oxidative stress, metabolic processes, heat-shock response, cell cycle/apoptosis regulation and enzymes which are involved in detoxification. Some of the marker genes are specific to certain organs, and some of them are general indicators of toxicity in multiple organs. Utility of the nanocapillary QRT-PCR platform was demonstrated by screening different references, as well as discovery of drug-like compounds for their gene expression profiles in different organs of treated mice in an acute experiment. For each compound, 896 QRT-PCR were done: four organs were used from each of the treated four animals to monitor the relative expression of 56 genes. Based on expression data of the discovery gene set of toxicology biomarkers the cardio- and nephrotoxicity of doxorubicin and sulfasalazin, the hepato- and nephrotoxicity of rotenone, dihydrocoumarin and aniline, and the liver toxicity of 2,4-diaminotoluene could be confirmed. The acute heart and kidney toxicity of the active metabolite SN-38 from its less toxic prodrug, irinotecan could be differentiated, and two novel gene markers for hormone replacement therapy were identified, namely fabp4 and pparg, which were down-regulated by estradiol treatment

Two-way communication with neural networks in vivo using focused light

Neuronal networks process information in a distributed, spatially heterogeneous manner that transcends the layout of electrodes. In contrast, directed and steerable light offers the potential to engage specific cells on demand. We present a unified framework for adapting microscopes to use light for simultaneous in vivo stimulation and recording of cells at fine spatiotemporal resolutions. We use straightforward optics to lock onto networks in vivo, to steer light to activate circuit elements and to simultaneously record from other cells. We then actualize this 'free' augmentation on both an 'open' two-photon microscope and a leading commercial one. By following this protocol, setup of the system takes a few days, and the result is a noninvasive interface to brain dynamics based on directed light, at a network resolution that was not previously possible and which will further improve with the rapid advance in development of optical reporters and effectors. This protocol is for physiologists who are competent with computers and wish to extend hardware and software to interface more fluidly with neuronal networks.National Institutes of Health (U.S.) (Postdoctoral Fellowship)Simons Foundation (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Predoctoral Fellowship)National Institutes of Health (U.S.)Simons Foundatio

PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons

Dipeptide repeat proteins are a major pathogenic feature of C9orf72 amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated C9orf72 dipeptide repeat knock-in mouse models characterized by expression of 400 codon-optimized polyGR or polyPR repeats, and heterozygous C9orf72 reduction. (GR)400 and (PR)400 knock-in mice recapitulate key features of C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction. Quantitative proteomics revealed an increase in extracellular matrix (ECM) proteins in (GR)400 and (PR)400 spinal cord, with the collagen COL6A1 the most increased protein. TGF-β1 was one of the top predicted regulators of this ECM signature and polyGR expression in human induced pluripotent stem cell neurons was sufficient to induce TGF-β1 followed by COL6A1. Knockdown of TGF-β1 or COL6A1 orthologues in polyGR model Drosophila exacerbated neurodegeneration, while expression of TGF-β1 or COL6A1 in induced pluripotent stem cell-derived motor neurons of patients with C9ALS/FTD protected against glutamate-induced cell death. Altogether, our findings reveal a neuroprotective and conserved ECM signature in C9ALS/FTD.</p