Psychotherapy and Mental Retardation: What\u27s the Use?

The lack of adequate treatment opportunities for mentally retarded people with emotional disturbances has been well documented (11,14,9,16,8,2 1,10,19). A high prevalence of psychopathology, estimated at 4- 5 times that of the non-retarded population (8,10) identifies a population extremely vulnerable to emotional problems. Although advocates from many disciplines, including psychiatry, (15) have worked diligently since the early 20th Century to eliminate massive institutionalization, sterilization, and isolation of the retarded from society\u27s defensive arsenal, the mental healthfield, especially psychiatry, has failed to meet current needs with appropriate clinical services

The influence of intrapersonal sensorimotor experiences on the corticospinal responses during action-observation

The coupling of perception and action has been strongly indicated by evidence that the observation of an action primes a response in the observer. It has been proposed that these primed responses may be inhibited when the observer is able to more closely distinguish between self- and other-generated actions – the greater the distinction, then the greater the inhibition of the primed response. This self–other distinction is shown to be enhanced following a period of visual feedback of self-generated action. The present study was designed to examine how sensorimotor experiences pertaining to self-generated action affect primed responses from observed actions. Single-pulse transcranial magnetic stimulation was used to investigate corticospinal activity elicited during the observation of index- and little-finger actions before and after training (self-generated action). For sensorimotor training, participants executed finger movements with or without visual feedback of their own movement. Results showed that the increases in muscle-specific corticospinal activity elicited from action–observation persisted after training without visual feedback, but did not emerge following training with visual feedback. This inhibition in corticospinal activity during action–observation following training with vision could have resulted from the refining of internal models of self-generated action, which then led to a greater distinction between “self” and “other” actions

The modulation of motor contagion by intrapersonal sensorimotor experience

Sensorimotor experiences can modify the internal models for action. These modifications can govern the discrepancies between predicted and actual sensory consequences, such as distinguishing self- and other-generated actions. This distinction may also contribute toward the inhibition of movement interference, which is strongly associated with the coupling of observed and executed actions. Therefore, movement interference could be mediated by the sensorimotor experiences underlying the self-other distinction. The present study examined the impact of sensorimotor experiences on involuntary movement interference (motor contagion). Participants were required to complete a motor contagion paradigm in which they executed horizontal arm movements while observing congruent (horizontal) or incongruent (vertical) arm movements of a model. This task was completed before and after a training protocol in which participants executed the same horizontal arm movements in the absence of the model stimuli. Different groups of participants trained with or without vision of their moving limb. Analysis of participants who were predisposed to motor contagion (involuntary movement interference during the observation of incongruent movements) revealed that the no vision group continued to demonstrate contagion at post-training, although the vision group did not. We propose that the vision group were able to integrate the visual afferent information with an internal model for action, which effectively refines the ability to match self-produced afferent and efferent sources of information during response-execution. This enhanced matching allows for a better distinction between self and other, which in turn, mediates the inhibition of motor contagion

Control of TCF-4 Expression by VDR and Vitamin D in the Mouse Mammary Gland and Colorectal Cancer Cell Lines

BACKGROUND: The vitamin D receptor (VDR) pathway is important in the prevention and potentially in the treatment of many cancers. One important mechanism of VDR action is related to its interaction with the Wnt/beta-catenin pathway. Agonist-bound VDR inhibits the oncogenic Wnt/beta-catenin/TCF pathway by interacting directly with beta-catenin and in some cells by increasing cadherin expression which, in turn, recruits beta-catenin to the membrane. Here we identify TCF-4, a transcriptional regulator and beta-catenin binding partner as an indirect target of the VDR pathway. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we show that TCF-4 (gene name TCF7L2) is decreased in the mammary gland of the VDR knockout mouse as compared to the wild-type mouse. Furthermore, we show 1,25(OH)2D3 increases TCF-4 at the RNA and protein levels in several human colorectal cancer cell lines, the effect of which is completely dependent on the VDR. In silico analysis of the human and mouse TCF7L2 promoters identified several putative VDR binding elements. Although TCF7L2 promoter reporters responded to exogenous VDR, and 1,25(OH)2D3, mutation analysis and chromatin immunoprecipitation assays, showed that the increase in TCF7L2 did not require recruitment of the VDR to the identified elements and indicates that the regulation by VDR is indirect. This is further confirmed by the requirement of de novo protein synthesis for this up-regulation. CONCLUSIONS/SIGNIFICANCE: Although it is generally assumed that binding of beta-catenin to members of the TCF/LEF family is cancer-promoting, recent studies have indicated that TCF-4 functions instead as a transcriptional repressor that restricts breast and colorectal cancer cell growth. Consequently, we conclude that the 1,25(OH)2D3/VDR-mediated increase in TCF-4 may have a protective role in colon cancer as well as diabetes and Crohn's disease

Patient perspectives of managing fatigue in ankylosing spondylitis, and views on potential interventions: a qualitative study

<p>Background: Fatigue is a major component of living with ankylosing spondylitis (AS), though it has been largely over-looked, and currently there are no specific agreed management strategies.</p> <p>Methods: This qualitative exploratory study involved participants who are members of an existing population-based ankylosing spondylitis (PAS) cohort. Participants residing in South West Wales were invited to participate in a focus group to discuss; (1) effects of fatigue, (2) self-management strategies and (3) potential future interventions. The focus groups were audio-recorded and the transcripts were analysed using thematic analysis.</p> <p>Results: Participants consisted of 3 males/4 females (group 1) and 4 males/3 females (group 2), aged between 35 and 73 years (mean age 53 years). Three main themes were identified: (1) The effects of fatigue were multi-dimensional with participants expressing feelings of being ‘drained’ (physical), ‘upset’ (emotional) and experiencing ‘low-mood’ (psychological); (2) The most commonly reported self-management strategy for fatigue was a balanced combination of activity (exercise) and rest. Medication was reluctantly taken due to side-effects and worries over dependency; (3) Participants expressed a preference for psychological therapies rather than pharmacological for managing fatigue. Information on Mindfulness-Based Stress Reduction (MBSR) was received with interest, with recommendations for delivery in a group format with the option of distance-based delivery for people who were not able to attend a group course.</p> <p>Conclusions: Patients frequently try and manage their fatigue without any formal guidance or support. Our research indicates there is a need for future research to focus on psychological interventions to address the multi-faceted aspects of fatigue in AS.</p&gt

The c-Met receptor tyrosine kinase inhibitor MP470 radiosensitizes glioblastoma cells

<p>Abstract</p> <p>Purpose</p> <p>Glioblastoma multiforme (GBM) is resistant to current cytotoxic therapies, in part because of enhanced DNA repair. Activation of the receptor tyrosine kinase c-Met has been shown to protect cancer cells from DNA damage. We hypothesized that inhibiting c-Met would decrease this protection and thus sensitize resistant tumor cells to the effects of radiation therapy.</p> <p>Materials and methods</p> <p>Eight human GBM cell lines were screened for radiosensitivity to the small-molecule c-Met inhibitor MP470 with colony-count assays. Double-strand (ds) DNA breaks was quantified by using antibodies to gamma H2AX. Western blotting demonstrate expression of RAD51, glycogen synthase kinase (GSK)-3β, and other proteins. A murine xenograft tumor flank model was used for <it>in vivo </it>radiosensitization studies.</p> <p>Results</p> <p>MP470 reduced c-Met phosphorylation and enhanced radiation-induced cell kill by 0.4 logs in SF767 cells. Cells pretreated with MP470 had more ds DNA damage than cells treated with radiation alone. Mechanistically, MP470 was shown to inhibit dsDNA break repair and increase apoptosis. MP470 influences various survival and DNA repair related proteins such as pAKT, RAD51 and GSK3β. <it>In vivo</it>, the addition of MP470 to radiation resulted in a tumor-growth-delay enhancement ratio of 2.9 over radiation alone and extended survival time.</p> <p>Conclusions</p> <p>GBM is a disease site where radiation is often used to address both macroscopic and microscopic disease. Despite attempts at dose escalation outcomes remain poor. MP470, a potent small-molecule tyrosine kinase inhibitor of c-Met, radiosensitized several GBM cell lines both <it>in vitro </it>and <it>in vivo</it>, and may help to improve outcomes for patients with GBM.</p

Acute Ethanol Effects on Focal Cerebral Ischemia in Nonfasted Rats

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66417/1/j.1530-0277.1997.tb03832.x.pd

Freshwater shrimp (Palaemonetes australis) as a potential bioindicator of crustacean health

Palaemonetes australis is a euryhaline shrimp found in south-western Australian estuaries. To determine if P. australis is a suitable bioindicator species for monitoring the health of estuarine biota, they were exposed to measured concentrations of the polycyclic aromatic hydrocarbon, benzo[a]pyrene (B[a]P) at 0.01, 0.1 or 1 ppm for 14 days under laboratory conditions. At the end of exposure the shrimp were sacrificed for biomarker [ethoxycoumarin O-deethylase (ECOD), 8-oxo-dG concentration, and sorbitol dehydrogenase (SDH) activity] analyses. Gender did not appear to influence biomarker responses of the shrimp in this study. ECOD activity was induced in the treatment groups in a linear fashion from 3 (0.01 ppm) times to 12 (1 ppm) times the negative controls. 8-oxo-dG concentration was reduced 3 times in treatment groups below the controls suggesting impaired DNA repair pathways. There was no increase in SDH, signifying hepatopancreatic cell damage had not occurred in any treatment group. The response of P australis to B[a]P exposure indicates that this crustacean is suitable bioindicator species for both laboratory studies and field monitoring. A combination of ECOD and SDH activities and 8-oxo-dG concentration represent a suitable suite of biomarkers for environmental monitoring of the sublethal effects of organic pollution to crustaceans from an estuarine environment

Dental therapists in general dental practice. A literature review and case study analysis to determine what works, why, how and in what circumstances

Introduction In the United Kingdom, policy and guidance changes regarding the role of Dental Therapists (DTs) were implemented in recent years with a view to changing dental care to a more preventive‐focussed, teamwork approach. However, success in the adoption of this model of working has been varied. Aims Adopting a realist approach, our aim was, to examine the use of DTs in general dental practices in Wales, exploring what works, why, how and in what circumstances. Materials and Methods The research comprised two stages. (i) A structured literature search, dual‐coding papers for high‐level factors describing the conditions or context(s) under which the mechanisms operated to produce outcomes. From this, we derived theories about how skill‐mix operates in the general dental service. (ii) Six case studies of general dental practices (three with a Dental Therapist/three without a Dental Therapist) employing a range of skill‐mix models incorporating semi‐structured interviews with all team members. We used the case studies/interviews to explore and refine the theories derived from the literature. Results Eighty‐four papers were coded. From this coding, we identified seven theories which reflected factors influencing general dental practices within three broad contexts: the dental practice as a business, as a healthcare provider, and as a workplace. We tested these theories in interviews with 38 dental team members across the six care studies. As a result, we amended five of the theories. Conclusion Our analysis provides theory about outcomes that DTs may facilitate and the mechanisms that may assist the work of DTs within different contexts of general dental practice

Error Rates, Decisive Outcomes and Publication Bias with Several Inferential Methods

Correction to this article published Hopkins, W.G. & Batterham, A.M. Sports Med (2016) 46: 923. doi:10.1007/s40279-016-0530-