The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.Peer reviewe

Prothrombin time is predictive of low plasma prothrombin concentration and clinical outcome in patients with trauma hemorrhage: analyses of prospective observational cohort studies

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Analyses of data previously generated through ACIT and DIA-TRE-TIC studies was funded by AstraZeneca R&D Gothenburg, Sweden

Two distinct populations of Bovine IL-17+ T-cells can be induced and WC1+IL-17+γδ T-cells are effective killers of protozoan parasites

IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-β1, IL-6 and/or IL-1β. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4+ and WC1+ γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17+ T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses

Study protocol for the translating research in elder care (TREC): building context – an organizational monitoring program in long-term care project (project one)

<p>Abstract</p> <p>Background</p> <p>While there is a growing awareness of the importance of organizational context (or the work environment/setting) to successful knowledge translation, and successful knowledge translation to better patient, provider (staff), and system outcomes, little empirical evidence supports these assumptions. Further, little is known about the factors that enhance knowledge translation and better outcomes in residential long-term care facilities, where care has been shown to be suboptimal. The project described in this protocol is one of the two main projects of the larger five-year Translating Research in Elder Care (TREC) program.</p> <p>Aims</p> <p>The purpose of this project is to establish the magnitude of the effect of organizational context on knowledge translation, and subsequently on resident, staff (unregulated, regulated, and managerial) and system outcomes in long-term care facilities in the three Canadian Prairie Provinces (Alberta, Saskatchewan, Manitoba).</p> <p>Methods/Design</p> <p>This study protocol describes the details of a multi-level – including provinces, regions, facilities, units within facilities, and individuals who receive care (residents) or work (staff) in facilities – and longitudinal (five-year) research project. A stratified random sample of 36 residential long-term care facilities (30 urban and 6 rural) from the Canadian Prairie Provinces will comprise the sample. Caregivers and care managers within these facilities will be asked to complete the TREC survey – a suite of survey instruments designed to assess organizational context and related factors hypothesized to be important to successful knowledge translation and to achieving better resident, staff, and system outcomes. Facility and unit level data will be collected using standardized data collection forms, and resident outcomes using the Resident Assessment Instrument-Minimum Data Set version 2.0 instrument. A variety of analytic techniques will be employed including descriptive analyses, psychometric analyses, multi-level modeling, and mixed-method analyses.</p> <p>Discussion</p> <p>Three key challenging areas associated with conducting this project are discussed: sampling, participant recruitment, and sample retention; survey administration (with unregulated caregivers); and the provision of a stable set of study definitions to guide the project.</p

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

&lt;b&gt;Background&lt;/b&gt;: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. &lt;b&gt;Methods/design&lt;/b&gt;: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

Immune adjuvant effect of V. cholerae O1 derived Proteoliposome coadministered by intranasal route with Vi polysaccharide from Salmonella Typhi

Proteoliposome derived from Vibrio cholerae O1 (PLc) is a nanoscaled structure obtained by detergent extraction process. Intranasal (i.n) administration of PLc was immunogenic at mucosal and systemic level vs. V. cholerae; however the adjuvant potential of this structure for non-cholera antigens has not been proven yet. The aim of this work was to evaluate the effect of coadministering PLc with the Vi polysaccharide antigen (Poli Vi) of S. Typhi by i.n route. The results showed that Poli Vi coadministered with PLc (PLc+Poli Vi) induce higher IgA response in saliva (p0.05) to that induced in a group of mice immunised by parenteral route with the Cuban anti-typhoid vaccine vax-TyVi®, although this vaccine did not induce mucosal response. In conclusion, this work demonstrates that PLc can be used as mucosal adjuvant to potentiate the immune response against a polysaccharide antigen like Poli Vi

Measuring the impact and distress of health problems from the individual's perspective: development of the Perceived Impact of Problem Profile (PIPP)

BACKGROUND: The aim of this study was to develop and conduct preliminary validation of the Perceived Impact of Problem Profile (PIPP). Based on the biopsychosocial model of health and functioning, the PIPP was intended as a generic research and clinical measurement tool to assess the impact and distress of health conditions from the individuals' perspective. The ICF classification system was used to guide the structure of the PIPP with subscales included to assess impact on self-care, mobility, participation, relationships and psychological well-being. While the ICF focuses on the classification of objective health and health related status, the PIPP broadens this focus to address the individuals' subjective experience of their health condition. METHODS: An item pool of 23 items assessing both impact and distress on five key domains was generated. These were administered to 169 adults with mobility impairment. Rasch analysis using RUMM2020 was conducted to assess the psychometric properties of each set of items. Preliminary construct validation of the PIPP was performed using the EQ5D. RESULTS: For both the Impact and Distress scales of the PIPP, the five subscales (Self-care, Mobility, Participation, Relationships, and Psychological Well-being) showed adequate psychometric properties, demonstrating fit to the Rasch model. All subscales showed adequate person separation reliability and no evidence of differential item functioning for sex, age, educational level or rural vs urban residence. Preliminary validity testing using the EQ5D items provided support for the subscales. CONCLUSION: This preliminary study, using a sample of adults with mobility impairment, provides support for the psychometric properties of the PIPP as a potential clinical and research measurement tool. The PIPP provides a brief, but comprehensive means to assess the key ICF components, focusing on the individuals' perspective of the impact and distress caused by their health condition. Further validation of its use across different health conditions and varying cultural settings is required

Translating research in elder care: an introduction to a study protocol series

<p>Abstract</p> <p>Background</p> <p>The knowledge translation field is undermined by two interrelated gaps – underdevelopment of the science and limited use of research in health services and health systems decision making. The importance of context in theory development and successful translation of knowledge has been identified in past research. Additionally, examination of knowledge translation in the long-term care (LTC) sector has been seriously neglected, despite the fact that aging is increasingly identified as a priority area in health and health services research.</p> <p>Aims</p> <p>The aims of this study are: to build knowledge translation theory about the role of organizational context in influencing knowledge use in LTC settings and among regulated and unregulated caregivers, to pilot knowledge translation interventions, and to contribute to enhanced use of new knowledge in LTC.</p> <p>Design</p> <p>This is a multi-level and longitudinal program of research comprising two main interrelated projects and a series of pilot studies. An integrated mixed method design will be used, including sequential and simultaneous phases to enable the projects to complement and inform one another. Inferences drawn from the quantitative and qualitative analyses will be merged to create meta-inferences.</p> <p>Outcomes</p> <p>Outcomes will include contributions to (knowledge translation) theory development, progress toward resolution of major conceptual issues in the field, progress toward resolution of methodological problems in the field, and advances in the design of effective knowledge translation strategies. Importantly, a better understanding of the contextual influences on knowledge use in LTC will contribute to improving outcomes for residents and providers in LTC settings.</p

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Self-Reported Functional Status as Predictor of Observed Functional Capacity in Subjects with Early Osteoarthritis of the Hip and Knee: A Diagnostic Study in the CHECK Cohort

Objectives Patients with hip or knee osteoarthritis (OA) may experience functional limitations in work settings. In the Cohort Hip and Cohort Knee study (CHECK) physical function was both self-reported and measured performance-based, using Functional Capacity Evaluation (FCE). Relations between self-reported scores on SF-36 and WOMAC (Western Ontario and McMaster Arthritis Index, function scales) and FCE performance were studied, and their diagnostic value for clinicians in predicting observed physical work limitations was assessed. Methods Ninety-two subjects scored physical function on SF-36 (scale 0–100, 100 indicating the best health level) and WOMAC (scale 0–68, 68 indicates maximum restriction) and performed the FCE. Correlations were calculated between all scores. Cross-tables were constructed using both questionnaires as diagnostic tests to identify work limitations. Subjects lifting <22.5 kg on the FCE-test ‘lifting-low’ were labeled as having physical work limitations. Diagnostic aspects at different cut-off scores for both questionnaires were analysed. Results Statistically significant correlations (Spearman’s ρ 0.34–0.49) were found between questionnaire scores and lifting and carrying tests. Results of a diagnostic cross-table with cut-off point <60 on SF-36 ‘physical functioning’ were: sensitivity 0.34, specificity 0.97 and positive predictive value (PV+) 0.95. Cut-off point ≥21 on WOMAC ‘function’ resulted in sensitivity 0.51, specificity 0.88 and PV+ 0.88. Conclusion Low self-reported function scores on SF-36 and WOMAC diagnosed subjects with limitations on the FCE. However, high scores did not guarantee performance without physical work limitations. These results are specific to the tested persons with early OA, in populations with a different prevalence of limitations, different diagnostic values will be found. FCE may be indicated to help clinicians to assess actual work capacity