Evaluation of basal ganglia haemodynamic changes with perfusion-weighted magnetic resonance imaging in patients with Parkinson's disease

The aim of our study was to assess the regional cerebral blood flow (rCBF) of basal ganglia and thalami in patients with Parkinson’s disease (PD) using perfusion–weighted magnetic resonance imaging (PW–MRI)

Differences in client and therapist views of the working alliance in drug treatment

Background - There is growing evidence that the therapeutic alliance is one of the most consistent predictors of retention and outcomes in drug treatment. Recent psychotherapy research has indicated that there is a lack of agreement between client, therapist and observer ratings of the therapeutic alliance; however, the clinical implications of this lack of consensus have not been explored. Aims - The aims of the study are to (1) explore the extent to which, in drug treatment, clients and counsellors agree in their perceptions of their alliance, and (2) investigate whether the degree of disagreement between clients and counsellors is related to retention in treatment. Methods - The study recruited 187 clients starting residential rehabilitation treatment for drug misuse in three UK services. Client and counsellor ratings of the therapeutic alliance (using the WAI-S) were obtained during weeks 1-12. Retention was in this study defined as remaining in treatment for at least 12 weeks. Results - Client and counsellor ratings of the alliance were only weakly related (correlations ranging from r = 0.07 to 0.42) and tended to become more dissimilar over the first 12 weeks in treatment. However, whether or not clients and counsellors agreed on the quality of their relationship did not influence whether clients were retained in treatment. Conclusions - The low consensus between client and counsellor views of the alliance found in this and other studies highlights the need for drug counsellors to attend closely to their clients' perceptions of the alliance and to seek regular feedback from clients regarding their feelings about their therapeutic relationship

Decrease in n-acetylaspartate following concussion may be coupled to decrease in creatine

Objectives: To assess the time course changes in brain N-acetylaspartate (NAA) and creatine (Cr) in athletes who suffered a sport-related concussion. Participants: Eleven non-consecutive concussed athletes and 11 sex and age-matched control volunteers. Main outcome measures: At 3, 15, 30 and 45 days post-injury, athletes were examined by proton Magnetic Resonance Spectroscopy (1H-MRS) for the determination of NAA,(Cr) and choline (Cho). 1H-MRS data recorded in the control group were used for comparison. Results: Compared to controls (2.18 ± 0.19), athletes showed an NAA/Cr increase at 3 (2.71 ± 0.16; p < 0.01) and 15 days (2.54 ± 0.21; p < 0.01), followed by a decrease and subsequent normalization at 30 (1.95 ± 0.16, p < 0.05) and 45 days(2.17 ± 0.20; p <0.05) post-concussion. NAA/Cho decreased at 3, 15 and 30 days post-injury (p < 0.01 compared to controls), with no differences from controls at 45 days post-concussion. Significant increase in the Cho/Cr after 3 (+33%, p < 0.01) and 15 (+31.5%, p < 0.01) days post-injury was observed, whilst no differences compared to controls were recorded at 30 and 45 days post-impact. Conclusions: This cohort of athletes indicates that concussion may cause concomitant decrease in cerebral NAA and Cr. This occurrence provokes longer time of metabolism normalization, as well as longer resolution time of concussion-associated clinical symptoms

Differences between Proximal versus Distal Intraorbital Optic Nerve Diffusion Tensor Magnetic Resonance Imaging Properties in Glaucoma Patients

Purpose. To analyze in vivo the diffusion tensor magnetic resonance imaging (DT-MRI) properties of the intraorbital optic nerve at two different levels: Proximal to the optic nerve head (ONH) and distal to the ONH at the level of the orbital apex in glaucoma patients. Methods. Twenty-four patients with primary open-angle glaucoma were examined. The categorization into early and severe glaucoma was performed by Hodapp's classification. Fifteen healthy individuals served as controls. DT-MRI was performed with a 3T-MR unit. Results. At early stage mean diffusivity (MD) values were higher at the proximal site with respect to the distal site. On the contrary, a decrease in fractional anisotropy (FA) was observed only relative to patient stage, independent of optic nerve site. Moreover, at early disease stage an increase in overall diffusivities, was evident at the proximal site, whereas at the distal site a decrease of the largest diffusivity and an increase in both the intermediate and smallest diffusivities were observed. FA and MD measured at the proximal site, had, respectively, the highest sensitivity and specificity in discriminating between healthy and glaucomatous eyes. Conclusions. Our study represents the first attempt to evaluate in vivo fiber integrity changes along the optic nerve with DT-MRI. Optic nerve degeneration appears to be a process that affects differently the proximal and the distal segments of the optic nerve. The complementary high sensitivity of FA with the high specificity of MD at the proximal site may provide reliable indexes for the identification of glaucomatous patients at early stages

Winnowing DNA for Rare Sequences: Highly Specific Sequence and Methylation Based Enrichment

Rare mutations in cell populations are known to be hallmarks of many diseases and cancers. Similarly, differential DNA methylation patterns arise in rare cell populations with diagnostic potential such as fetal cells circulating in maternal blood. Unfortunately, the frequency of alleles with diagnostic potential, relative to wild-type background sequence, is often well below the frequency of errors in currently available methods for sequence analysis, including very high throughput DNA sequencing. We demonstrate a DNA preparation and purification method that through non-linear electrophoretic separation in media containing oligonucleotide probes, achieves 10,000 fold enrichment of target DNA with single nucleotide specificity, and 100 fold enrichment of unmodified methylated DNA differing from the background by the methylation of a single cytosine residue

Providing web-based mental health services to at-risk women

<p>Abstract</p> <p>Background</p> <p>We examined the feasibility of providing web-based mental health services, including synchronous internet video conferencing of an evidence-based support/education group, to at-risk women, specifically poor lone mothers. The objectives of this study were to: (i) adapt a face-to-face support/education group intervention to a web-based format for lone mothers, and (ii) evaluate lone mothers' response to web-based services, including an online video conferencing group intervention program.</p> <p>Methods</p> <p>Participating mothers were recruited through advertisements. To adapt the face-to-face intervention to a web-based format, we evaluated participant motivation through focus group/key informant interviews (n = 7), adapted the intervention training manual for a web-based environment and provided a computer training manual. To evaluate response to web-based services, we provided the intervention to two groups of lone mothers (n = 15). Pre-post quantitative evaluation of mood, self-esteem, social support and parenting was done. Post intervention follow up interviews explored responses to the group and to using technology to access a health service. Participants received $20 per occasion of data collection. Interviews were taped, transcribed and content analysis was used to code and interpret the data. Adherence to the intervention protocol was evaluated.</p> <p>Results</p> <p>Mothers participating in this project experienced multiple difficulties, including financial and mood problems. We adapted the intervention training manual for use in a web-based group environment and ensured adherence to the intervention protocol based on viewing videoconferencing group sessions and discussion with the leaders. Participant responses to the group intervention included decreased isolation, and increased knowledge and confidence in themselves and their parenting; the responses closely matched those of mothers who obtained same service in face-to-face groups. Pre-and post-group quantitative evaluations did not show significant improvements on measures, although the study was not powered to detect these.</p> <p>Conclusions</p> <p>We demonstrated that an evidence-based group intervention program for lone mothers developed and evaluated in face-to-face context transferred well to an online video conferencing format both in terms of group process and outcomes.</p

Deregulated expression of the imprinted DLK1-DIO3 region in glioblastoma stemlike cells: Tumor suppressor role of lncRNA MEG3

Background: Glioblastoma (GBM) stemlike cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted delta-like homolog 1 gene type III iodothyronine deiodinase gene (DLK-DIO3) region on chromosome 14q32 in GBM pathogenesis. Methods: Real-time PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression, and reverse-phase protein array profiles were used to investigate the tumor suppressor function of the maternally expressed 3 gene (MEG3). Results: Loss of expression of genes and noncoding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared with normal brain. This downregulation is mainly mediated by epigenetic silencing. Kaplan-Meier analysis indicated that low expression of MEG3 and MEG8 long noncoding (lnc)RNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration, and colony formation and decreases in vivo tumor growth, reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and epithelial-to-mesenchymal transition (EMT). Conclusion: In GBM, MEG3 acts as a tumor suppressor mainly regulating cell adhesion, EMT, and cell proliferation, thus providing a potential candidate for novel GBM therapies

The tailored activity program (TAP) to address behavioral disturbances in frontotemporal dementia: a feasibility and pilot study

Purpose: To explore the feasibility of implementing the Tailored Activity Program with a cohort of people with frontotemporal dementia and their carers (dyads). Methods: The Tailored Activity Program is an occupational therapy based intervention that involves working collaboratively with family carers and prescribes personalized activities for behavioral management in people with dementia. Twenty dyads randomized into the study (Tailored Activity Program: n = 9; Control: n = 11) were assessed at baseline and 4-months. Qualitative analyzes evaluated feasibility and acceptability of the program for the frontotemporal dementia cohort, and quantitative analyzes (linear mixed model analyzes, Spearman’s rho correlations) measured the impact of the program on the dyads. Results: The Tailored Activity Program was an acceptable intervention for the frontotemporal dementia dyads. Qualitative analyses identified five themes: “carer perceived benefits”, “carer readiness to change”, “strategies used by carer to engage person with dementia”, “barriers to the Tailored Activity Program uptake/implementation”, and “person with dementia engagement”. Quantitative outcomes showed an overall reduction of behavioral symptoms (F 18.34 = 8.073, p = 0.011) and maintenance of functional performance in the person with dementia (F 18.03 = 0.375, p = 0.548). Conclusions: This study demonstrates the potential for using an activity-based intervention such as the Tailored Activity Program in frontotemporal dementia. Service providers should recognize that while people with frontotemporal dementia present with challenging issues, tailored therapies may support their function and reduce their behavioral symptoms.Implications for rehabilitation The Tailored Activity Program is an occupational therapy based intervention that involves prescribing personalized activities for behavioral management in dementia. The Tailored Activity Program is an acceptable and feasible intervention approach to address some of the unique behavioral and functional impairments inherent in frontotemporal dementia

Downregulation of ETS Rescues Diabetes-Induced Reduction of Endothelial Progenitor Cells

Transplantation of vasculogenic progenitor cells (VPC) improves neovascularization after ischemia. However, patients with type 2 diabetes mellitus show a reduced VPC number and impaired functional activity. Previously, we demonstrated that p38 kinase inhibition prevents the negative effects of glucose on VPC number by increasing proliferation and differentiation towards the endothelial lineage in vitro. Moreover, the functional capacity of progenitor cells is reduced in a mouse model of metabolic syndrome including type 2 diabetes (Lepr(db)) in vivo.The aim of this study was to elucidate the underlying signalling mechanisms in vitro and in vivo. Therefore, we performed DNA-protein binding arrays in the bone marrow of mice with metabolic syndrome, in blood-derived progenitor cells of diabetic patients as well as in VPC ex vivo treated with high levels of glucose. The transcriptional activation of ETS transcription factors was increased in all samples analyzed. Downregulation of ETS1 expression by siRNA abrogated the reduction of VPC number induced by high-glucose treatment. In addition, we observed a concomitant suppression of the non-endothelial ETS-target genes matrix metalloproteinase 9 (MMP9) and CD115 upon short term lentiviral delivery of ETS-specific shRNAs. Long term inhibition of ETS expression by lentiviral infection increased the number of cells with the endothelial markers CD144 and CD105.These data demonstrate that diabetes leads to dysregulated activation of ETS, which blocks the functional activity of progenitor cells and their commitment towards the endothelial cell lineage