Study of the effect of bacterial lipopolysaccharide on the structure and dynamics on mouse tubulin polymerization

Background and aims: In recent decades, there has been much research on the microtubule dynamics as well as on factors affecting it. According to different studies, lipopolysaccharide (LPS) is thought to play an indirect role in neurodegenerative diseases through enzymatic pathways which hyperphosphorylate Tau protein and dissociate it from microtubules. In the present study, it was aimed to assess the direct effect of LPS on the structure and dynamics of tubulin polymerization in vitro. Methods: In this study, mouse tubulins were purified through two cycles of temperature-dependent polymerization-depolymerization. Cellulose-phosphate chromatography was used to further purify tubulins. SDS-PAGE was used to analyze the purity of the tubulins. Circular dichroism (CD), intrinsic fluorescence and turbidity assays were used to assess the changes in secondary and tertiary structures, and the dynamics of tubulin polymerization in the presence of different concentrations of LPS (5pM, 5nM, 50nM, 0.5µM and 5µM), respectively. Results: SDS-PAGE analysis confirmed the purity of tubulins. The intrinsic fluorescence analysis and CD assay revealed the changes in the secondary and tertiary structures of tubulins in the presence of LPS. The results of turbidity assay indicated that LPS could reduce the polymerization of tubulins. Conclusion: Our results indicate that LPS is able to change the secondary and tertiary structures of tubulin and decreases tubulin polymerization. According to our results, lipopolysaccharide in addition to an indirect effect on the microtubules stability, as well as by decreases in tubulin polymerization could result in neurodegenerative diseases specially Alzheimer's diseases

Hydrogel nanoparticle encapsulated plasmid as a suitable gene delivery system

To facilitate the delivery of genetic material, the use of appropriate carriers such as polymers is necessary. Nanoparticles comprising of chitosan-alginate polymers were formed through pregel preparation method. Chi/Alg nanoparticles had a mean Z-Average diameter of 161.8 nm and mean zeta 29.3 mV, respectively. The ability of plasmid-complex in preventing DNA migration showed Chi/Alg nanoparticles have great capacity to maintain plasmid. The efficiency of nanoparticles for transfection of pEGFP-N1 plasmid in the cultured HEK 293 cells was measured by flow cytometry. Cell viability assays indicated that nanoparticles had no toxic effect on HEK 293 cells after 4 or 24 h. Our suitable candidate for gene delivery would be alg/chi nanoparticles.Для облегчения доставки генетического материала необходимо использование подходящих носителей, таких как полимеры. Наночастицы, состоящие из хитозан-альгинатных полимеров, были получены методом подготовки прегеля. Chi/Alg наночастицы имели средний диаметр 161.8 нм (Z-Average) и средний zeta-потенциал 29.3 mV. Отсутствие миграции ДНК во время электрофореза комплексов плазмиды с наночастицами показало, что Chi/Alg наночастицы могут удерживать плазмидную ДНК внутри комплекса. Эффективность наночастиц для трансфекции плазмиды pEGFP-N1 в культивируемые клетки HEK 293 была измерена с помощью жидкостной цитометрии. Тесты на жизнеспособ-ность клеток показали, что наночастицы не имели токсичного эффекта на клетки HEK 293 через 4 ч или 24 ч. Наночастицы Alg/Chi являются подходящим кандидатом для доставки генов

How is rehabilitation with and without an integrated self-management approach perceived by UK community-dwelling stroke survivors? A qualitative process evaluation to explore implementation and contextual variations.

OBJECTIVE: Self-management programmes could support long-term needs after stroke and using methods integrated into rehabilitation is one option. To explore theoretical assumptions and possible mechanisms of implementation a process evaluation was delivered alongside a cluster trial which has demonstrated feasibility of an integrated self-management programme (Bridges SMP) in community-dwelling stroke survivors. This paper aims to show the extent to which experiences from stroke survivors receiving rehabilitation in control (usual care) and intervention (integrated self-management) sites reflected the differences in rehabilitation received and whether their understandings aligned with the self-management approach employed. DESIGN: Semistructured qualitative interviews carried out as part of a process evaluation analysed thematically. SETTING: Study was based in South London; all interviews were carried out in participants' home setting. PARTICIPANTS: 22 stroke participants recruited; 12 from integrated self-management sites and 10 from usual care sites. RESULTS: All participants revealed shared appreciation of knowledge and support from therapists but subtle differences emerged between sites in respect to perceptions about responsibility, control and how previous experiences were used. Accounts depicted a variance regarding who had structured and planned their rehabilitation, with greater flexibility about content and involvement perceived by participants from the integrated self-management sites. They also provided accounts and experiences which aligned with principles of the intervention, such as self-discovery and problem-solving. CONCLUSIONS: The findings reflect our theoretical assumptions and possible mechanisms of implementation that rehabilitation with a focus on supporting self-management is reflected in accounts and understandings of stroke survivors. Taken together with our previous research this justifies evaluating the effectiveness of Bridges SMP in a larger sample to further contribute to an understanding of the functioning of the intervention, implementation, contextual factors and mechanisms of impact. TRIAL REGISTRATION NUMBER: ISRCTN42534180; Post-results

Characteristics and efficacy of play therapy interventions in visually impaired children and adolescents: A systematic review study

Background: Visual impairment can hinder achieving developmental markers in children. Various studies have examined the effectiveness of play therapy in children with visual impairment. However, lack of a comprehensive review study that examined the characteristics and overall effectiveness of these interventions, led to conducting of the present study. Objectives: This study aimed to provide strong evidence on the characteristics and efficacy of play therapy interventions in children and adolescents (0-21 years) with visual impairment. Methods: Our literature searching was done with English and Persian keywords obtained from Mesh in the Cochrane, PubMed, Scopus,Web of Science, Magiran, Iran Medex, Iranian Archive for Scientific Documents Center (IASD), Iranian National Library (INL), Google and Google Scholar, until 2020. The selection process of articles was according to PRISMA. Text data was analyzed by convention content analysis. Additionally, the modified Downs and Black Checklist was used to assess the quality of primary studies. Results: From 1763 articles, finally nine were analyzed which met the inclusion criteria. The major findings were presented in the categories of on participants, implementation, measurements, and efficacy of interventions. All subjects were with visual impairment, without severe physical or cognitive impairment. Play interventions were done by children, or with operational children and their caregivers or parents. Play therapy interventions were in two forms of computer/video based game and child-therapist/parent based game, which were conducted in different settings resembling home, school, or sport camp conditions. Data were gathered by observation of researchers and reports of children using different questionnaires. All of the interventions were effective in improving cognitive, visual, physical, communicative and vestibular skills of the children. Conclusions: Despite the comprehensive efficacy of play therapy intervention in children with visual impairment, few studies have been conducted in this field. Considering multi-biases such as missing control of confounders, more high quality standard studies are needed to further evaluate the effectiveness of play therapy in children with visual impairments. © 2020, Author(s)

Inhomogeneous Gravity

We study the inhomogeneous cosmological evolution of the Newtonian gravitational 'constant' G in the framework of scalar-tensor theories. We investigate the differences that arise between the evolution of G in the background universes and in local inhomogeneities that have separated out from the global expansion. Exact inhomogeneous solutions are found which describe the effects of masses embedded in an expanding FRW Brans-Dicke universe. These are used to discuss possible spatial variations of G in different regions. We develop the technique of matching different scalar-tensor cosmologies of different spatial curvature at a boundary. This provides a model for the linear and non-linear evolution of spherical overdensities and inhomogeneities in G. This allows us to compare the evolution of G and \dot{G} that occurs inside a collapsing overdense cluster with that in the background universe. We develop a simple virialisation criterion and apply the method to a realistic lambda-CDM cosmology containing spherical overdensities. Typically, far slower evolution of \dot{G} will be found in the bound virialised cluster than in the cosmological background. We consider the behaviour that occurs in Brans-Dicke theory and in some other representative scalar-tensor theories.Comment: 15 pages, 15 figures. Submitted to MNRAS. References adde

The psychological impact of prolonged disorders of consciousness on caregivers:a systematic review of quantitative studies

Objective: Systematic review of the nature, frequency and severity of psychological experiences of people who have a close relationship with a person with a prolonged disorder of consciousness. Data sources: Cochrane Library, Web of Science, PsycINFO, PubMed, Embase®, MEDLINE®, Allied and Complementary Medicine™, were searched from inceptions until December 2016 with additional hand searching of reference lists of included articles. Review methods: Studies were included that used quantitative methodologies and psychological measures to investigate experiences. The PRISMA statement was followed with inclusion criteria set a priori. A data synthesis summarized psychological constructs studied. Results: A total of 18 studies (ranging between n = 16–487 participants) met the inclusion criteria with 15 of 18 studies focused on the primary caregiver. A total of 23 standardized psychological measures were identified to assess four primary psychological constructs: Loss and grief, psychological wellbeing changes, burden and use of coping strategies. Conclusions: Small sample sizes, limited variables and reliance on observational methods affected quality. Caregivers do find ways to manage independently, but some exhibit clinically significant psychological distress that does not change over time alone and may get worse

Rasch analysis of the Multiple Sclerosis Impact Scale (MSIS-29)

<p>Abstract</p> <p>Background</p> <p>Multiple Sclerosis (MS) is a degenerative neurological disease that causes impairments, including spasticity, pain, fatigue, and bladder dysfunction, which negatively impact on quality of life. The Multiple Sclerosis Impact Scale (MSIS-29) is a disease-specific health-related quality of life (HRQoL) instrument, developed using the patient's perspective on disease impact. It consists of two subscales assessing the physical (MSIS-29-PHYS) and psychological (MSIS-29-PSYCH) impact of MS. Although previous studies have found support for the psychometric properties of the MSIS-29 using traditional methods of scale evaluation, the scale has not been subjected to a detailed Rasch analysis. Therefore, the objective of this study was to use Rasch analysis to assess the internal validity of the scale, and its response format, item fit, targeting, internal consistency and dimensionality.</p> <p>Methods</p> <p>Ninety-two persons with definite MS residing in the community were recruited from a tertiary hospital database. Patients completed the MSIS-29 as part of a larger study. Rasch analysis was undertaken to assess the psychometric properties of the MSIS-29.</p> <p>Results</p> <p>Rasch analysis showed overall support for the psychometric properties of the two MSIS-29 subscales, however it was necessary to reduce the response format of the MSIS-29-PHYS to a 3-point response scale. Both subscales were unidimensional, had good internal consistency, and were free from item bias for sex and age. Dimensionality testing indicated it was not appropriate to combine the two subscales to form a total MSIS score.</p> <p>Conclusion</p> <p>In this first study to use Rasch analysis to fully assess the psychometric properties of the MSIS-29 support was found for the two subscales but not for the use of the total scale. Further use of Rasch analysis on the MSIS-29 in larger and broader samples is recommended to confirm these findings.</p

Electroretinogram changes following sequential panretinal photocoagulation for proliferative diabetic retinopathy

Purpose: To evaluate changes in electroretinogram (ERG) response over the course of multiple sessions of panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PRP). Methods: A prospective cohort study of 11 patients with PDR who required PRP was conducted. PRP was completed over three sessions. Each patient had five ERGs done: baseline, 1 week after each PRP session, and 6 weeks after the last session of PRP. Dark-adapted 0.01 ERG, Dark-adapted 3 ERG, Dark-adapted 10 ERG, Light-adapted 3 ERG, and Light-adapted 30 Hz flicker ERG were done. The mean change in a-and b-wave amplitudes as well as implicit times compared to baseline was analyzed. Results: A significant reduction in peak amplitudes of both a-and b-waves and delay in latencies were observed in all responses (p<0.05). The absolute amplitude reduction and delay in latency were higher for scotopic b-waves (p<0.05). The root mean square (RMS) of Dark-adapted 10.0 ERG (p<0.05) and total mean amplitude changes of a-and b-waves (p<0.001) were reduced after each laser session; however, the magnitude of change was not different between the first, second, or third sessions of PRP, and each session showed a similar deterioration rate of ERG parameters comparing to each other (p=0.4 for RMS and p=0.2 for total mean amplitude changes). In addition, the results indicated recovery of the amplitude and latency of ERG waves after 6 weeks from the final treatment (p<0.001) although not to baseline levels. Conclusion: ERG findings following PRP show reduced retinal function after each session which partially recovers by 6 weeks after the completion of therapy. Clinicians should be mindful of these changes when planning the treatment course for patients with PDR. © 2020 Khojasteh et al

A Predictive Model for Corticosteroid Response in Individual Patients with MS Relapses

<div><p>Objectives</p><p>To derive a simple predictive model to guide the use of corticosteroids in patients with relapsing remitting MS suffering an acute relapse.</p><p>Materials and Methods</p><p>We analysed individual patient randomised controlled trial data (n=98) using a binary logistic regression model based on age, gender, baseline disability scores [physician-observed: expanded disability status scale (EDSS) and patient reported: multiple sclerosis impact scale 29 (MSIS-29)], and the time intervals between symptom onset or referral and treatment.</p><p>Results</p><p>Based on two a priori selected cut-off points (improvement in EDSS ≥ 0.5 and ≥ 1.0), we found that variables which predicted better response to corticosteroids after 6 weeks were younger age and lower MSIS-29 physical score at the time of relapse (model fit 71.2% - 73.1%).</p><p>Conclusions</p><p>This pilot study suggests two clinical variables which may predict the majority of the response to corticosteroid treatment in patients undergoing an MS relapse. The study is limited in being able to clearly distinguish factors associated with treatment response or spontaneous recovery and needs to be replicated in a larger prospective study.</p></div