Engram-specific transcriptome profiling of contextual memory consolidation

Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24 h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P = 6.2 × 10−13), including Atf3 (P = 2.4 × 10−41), Penk (P = 1.3 × 10−15), and Kcnq3 (P = 3.1 × 10−12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory

Within-trial economic evaluation of diabetes-specific cognitive behaviour therapy in patients with type 2 diabetes and subthreshold depression

<p>Abstract</p> <p>Background</p> <p>Despite the high prevalence of subthreshold depression in patients with type 2 diabetes, evidence on cost-effectiveness of different therapy options for these patients is currently lacking.</p> <p>Methods/Design</p> <p>Within-trial economic evaluation of the diabetes-specific cognitive behaviour therapy for subthreshold depression. Patients with diabetes and subthreshold depression are randomly assigned to either 2 weeks of diabetes-specific cognitive behaviour group therapy (n = 104) or to standard diabetes education programme only (n = 104). Patients are followed for 12 months. During this period data on total health sector costs, patient costs and societal productivity costs are collected in addition to clinical data. Health related quality of life (the SF-36 and the EQ-5D) is measured at baseline, immediately after the intervention, at 6 and at 12 months after the intervention. Quality adjusted life years (QALYs), and cumulative costs will be estimated for each arm of the trial. Cost-effectiveness of the diabetes-specific cognitive behaviour group therapy will be analysed from the perspective of the German statutory health insurance and from the societal perspective. To this end, incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained will be calculated.</p> <p>Discussion</p> <p>Some methodological issues of the described economic evaluation are discussed.</p> <p>Trial registration</p> <p>The trial has been registered at the Clinical Trials Register (NCT01009138).</p

EMDR Effects on Pursuit Eye Movements

This study aimed to objectivize the quality of smooth pursuit eye movements in a standard laboratory task before and after an Eye Movement Desensitization and Reprocessing (EMDR) session run on seven healthy volunteers. EMDR was applied on autobiographic worries causing moderate distress. The EMDR session was complete in 5 out of the 7 cases; distress measured by SUDS (Subjective Units of Discomfort Scale) decreased to a near zero value. Smooth pursuit eye movements were recorded by an Eyelink II video system before and after EMDR. For the five complete sessions, pursuit eye movement improved after their EMDR session. Notably, the number of saccade intrusions—catch-up saccades (CUS)—decreased and, reciprocally, there was an increase in the smooth components of the pursuit. Such an increase in the smoothness of the pursuit presumably reflects an improvement in the use of visual attention needed to follow the target accurately. Perhaps EMDR reduces distress thereby activating a cholinergic effect known to improve ocular pursuit

Cost-effectiveness analysis of cognitive behaviour therapy for treatment of minor or mild-major depression in elderly patients with type 2 diabetes: study protocol for the economic evaluation alongside the MIND-DIA randomized controlled trial (MIND-DIA CEA)

<p>Abstract</p> <p>Background</p> <p>Depression and elevated depression symptoms are more prevalent in patients with type 2 diabetes than in those without diabetes and are associated with adverse health outcomes and increased total healthcare utilization. This suggests that more effective depression treatment might not only improve health outcome, but also reduce costs. However, there is a lack of evidence on (cost-) effectiveness of treatment options for minor and mild-major depression in patients with type 2 diabetes. In this paper we describe the design and methods of the economic evaluation, which will be conducted alongside the MIND-DIA trial (Cognitive behaviour therapy in elderly type 2 diabetes patients with minor or mild-major depression). The objective of the economic evaluation (MIND-DIA CEA) is to examine incremental cost-effectiveness of a diabetes specific cognitive behaviour group therapy (CBT) as compared to intensified treatment as usual (TAU) and to a guided self-help group intervention (SH).</p> <p>Methods/Design</p> <p>Patients will be followed for 15 months. During this period data on health sector costs, patient costs and societal productivity/time costs will be collected in addition to clinical data. Person-years free of moderate/severe major depression, quality adjusted life years (QALYs), and cumulative costs will be estimated for each arm of the trial (CBT, TAU and SH). To determine cost-effectiveness of the CBT, differences in costs and effects between the CBT group and TAU/SH group will be calculated.</p> <p>Discussion</p> <p>CBT is a potentially effective treatment option to improve quality of life and to avoid the onset of a moderate/severe major depression in elderly patients with type 2 diabetes and minor or mild-major depression. This hypothesis will be evaluated in the MIND-DIA trial. Based on these results the associated economic evaluation will provide additional evidence on the cost-effectiveness of CBT in this target population. Methodological strengths and weaknesses of the planned economic evaluation are discussed.</p> <p>Trial registration</p> <p>The MIND-DIA study has been registered at the Current Controlled Trials Register (ISRCTN58007098).</p

Irish general practitioner attitudes toward decriminalisation and medical use of cannabis: results from a national survey.

BACKGROUND: Governmental debate in Ireland on the de facto decriminalisation of cannabis and legalisation for medical use is ongoing. A cannabis-based medicinal product (Sativex®) has recently been granted market authorisation in Ireland. This unique study aimed to investigate Irish general practitioner (GP) attitudes toward decriminalisation of cannabis and assess levels of support for use of cannabis for therapeutic purposes (CTP). METHODS: General practitioners in the Irish College of General Practitioner (ICGP) database were invited to complete an online survey. Anonymous data yielded descriptive statistics (frequencies, percentages) to summarise participant demographic information and agreement with attitudinal statements. Chi-square tests and multi-nominal logistic regression were included. RESULTS: The response rate was 15% (n = 565) which is similar to other Irish national GP attitudinal surveys. Over half of Irish GPs did not support the decriminalisation of cannabis (56.8%). In terms of gender, a significantly higher proportion of males compared with females (40.6 vs. 15%; p < 0.0001) agreed or strongly agreed with this drug policy approach. A higher percentage of GPs with advanced addiction specialist training (level 2) agreed/strongly agreed that cannabis should be decriminalised (54.1 vs. 31.5%; p = 0.021). Over 80% of both genders supported the view that cannabis use has a significant effect on patients' mental health and increases the risk of schizophrenia (77.3%). Over half of Irish GPs supported the legalisation of cannabis for medical use (58.6%). A higher percentage of those who were level 1-trained (trained in addiction treatment but not to an advanced level) agreed/strongly agreed cannabis should be legalised for medical use (p = 0.003). Over 60% agreed that cannabis can have a role in palliative care, pain management and treatment of multiple sclerosis (MS). In the regression response predicator analysis, females were 66.2% less likely to agree that cannabis should be decriminalised, 42.5% less likely to agree that cannabis should be legalised for medical use and 59.8 and 37.6% less likely to agree that cannabis has a role in palliative care and in the treatment of multiple sclerosis (respectively) than males. CONCLUSIONS: The majority of Irish GPs do not support the present Irish governmental drug policy of decriminalisation of cannabis but do support the legalisation of cannabis for therapeutic purposes. Male GPs and those with higher levels of addiction training are more likely to support a more liberal drug policy approach to cannabis for personal use. A clear majority of GPs expressed significant concerns regarding both the mental and physical health risks of cannabis use. Ongoing research into the health and other effects of drug policy changes on cannabis use is required

Pompe disease diagnosis and management guideline

ACMG standards and guidelines are designed primarily as an educational resource for physicians and other health care providers to help them provide quality medical genetic services. Adherence to these standards and guidelines does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. in determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from these standards and guidelines.Duke Univ, Med Ctr, Durham, NC 27706 USAOregon Hlth Sci Univ, Portland, OR 97201 USANYU, Sch Med, New York, NY USAUniv Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32611 USAIndiana Univ, Bloomington, in 47405 USAUniv Miami, Miller Sch Med, Coral Gables, FL 33124 USAHarvard Univ, Childrens Hosp, Sch Med, Cambridge, MA 02138 USAUniversidade Federal de São Paulo, São Paulo, BrazilColumbia Univ, New York, NY 10027 USANYU, Bellevue Hosp, Sch Med, New York, NY USAColumbia Univ, Med Ctr, New York, NY 10027 USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Personality and Temperament Correlates of Pain Catastrophizing in Young Adolescents

Pain catastrophizing is generally viewed as an important cognitive factor underlying chronic pain. The present study examined personality and temperament correlates of pain catastrophizing in a sample of young adolescents (N = 132). Participants completed the Pain Catastrophizing Scale for Children, as well as scales for measuring sensitivity of the behavioral inhibition and behavioral activation systems (BIS-BAS), and various reactive and regulative temperament traits. Results demonstrated that BIS, reactive temperament traits (fear and anger-frustration), and perceptual sensitivity were positively related to pain catastrophizing, whereas regulative traits (attention control, inhibitory control) were negatively associated with this cognitive factor. Further, regression analyses demonstrated that only BIS and the temperamental traits of fear and perceptual sensitivity accounted for a unique proportion of the variance in adolescents’ pain catastrophizing scores

Comprehensive geriatric assessment, multifactorial interventions and nurse-led care coordination to prevent functional decline in community-dwelling older persons: protocol of a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>Functional decline in community-dwelling older persons is associated with the loss of independence, the need for hospital and nursing-home care and premature death. The effectiveness of multifactorial interventions in preventing functional decline remains controversial. The aim of this study is to investigate whether functional decline in community-dwelling older persons can be delayed or prevented by a comprehensive geriatric assessment, multifactorial interventions and nurse-led care coordination.</p> <p>Methods/Design</p> <p>In a cluster randomized controlled trial, with the general practice as the unit of randomization, 1281 participants from 25 general practices will be enrolled in each condition to compare the intervention with usual care. The intervention will focus on older persons who are at increased risk for functional decline, identified by an Identification of Seniors at Risk Primary Care (ISAR-PC) score (≥ 2). These older persons will receive a comprehensive geriatric assessment, an individually tailored care and treatment plan, consisting of multifactorial, evidence-based interventions and subsequent nurse-led care coordination. The control group will receive 'care as usual' by the general practitioner (GP). The main outcome after 12 months is the level of physical functioning on the modified Katz-15 index score. The secondary outcomes are health-related quality of life, psychological and social functioning, healthcare utilization and institutionalization. Furthermore, a process evaluation and cost-effectiveness analysis will be performed.</p> <p>Discussion</p> <p>This study will provide new knowledge regarding the effectiveness and feasibility of a comprehensive geriatric assessment, multifactorial interventions and nurse-led elderly care in general practice.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2653">NTR2653</a></p> <p>Grant</p> <p>Unrestricted grant 'The Netherlands Organisation for Health Research and development' no 313020201</p

Active rehabilitation for chronic low back pain: Cognitive-behavioral, physical, or both? First direct post-treatment results from a randomized controlled trial [ISRCTN22714229]

BACKGROUND: The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations: the deconditioning model, the cognitive behavioral model and the biopsychosocial model. There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment, but information is lacking about the differential effectiveness of different kinds of rehabilitation. A direct comparison of a physical, a cognitive-behavioral treatment and a combination of both has never been carried out so far. METHODS: The effectiveness of active physical, cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a randomized controlled trial in three rehabilitation centers. Two hundred and twenty three patients were randomized, using concealed block randomization to one of the following treatments, which they attended three times a week for 10 weeks: Active Physical Treatment (APT), Cognitive-Behavioral Treatment (CBT), Combined Treatment of APT and CBT (CT), or Waiting List (WL). The outcome variables were self-reported functional limitations, patient's main complaints, pain, mood, self-rated treatment effectiveness, treatment satisfaction and physical performance including walking, standing up, reaching forward, stair climbing and lifting. Assessments were carried out by blinded research assistants at baseline and immediately post-treatment. The data were analyzed using the intention-to-treat principle. RESULTS: For 212 patients, data were available for analysis. After treatment, significant reductions were observed in functional limitations, patient's main complaints and pain intensity for all three active treatments compared to the WL. Also, the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments. Several physical performance tasks improved in APT and CT but not in CBT. No clinically relevant differences were found between the CT and APT, or between CT and CBT. CONCLUSION: All three active treatments were effective in comparison to no treatment, but no clinically relevant differences between the combined and the single component treatments were found