DC-SCRIPT is a novel regulator of the tumor suppressor gene CDKN2B and induces cell cycle arrest in ER alpha-positive breast cancer cells

Breast cancer is one of the most common causes of cancer-related deaths in women. The estrogen receptor (ER alpha) is well known for having growth promoting effects in breast cancer. Recently, we have identified DC-SCRIPT (ZNF366) as a co-suppressor of ER alpha and as a strong and independent prognostic marker in ESR1 (ER alpha gene)-positive breast cancer patients. In this study, we further investigated the molecular mechanism on how DC-SCRIPT inhibits breast cancer cell growth. DC-SCRIPT mRNA levels from 190 primary ESR1-positive breast tumors were related to global gene expression, followed by gene ontology and pathway analysis. The effect of DC-SCRIPT on breast cancer cell growth and cell cycle arrest was investigated using novel DC-SCRIPT-inducible MCF7 breast cancer cell lines. Genome-wide expression profiling of DC-SCRIPT-expressing MCF7 cells was performed to investigate the effect of DC-SCRIPT on cell cycle-related gene expression. Findings were validated by real-time PCR in a cohort of 1,132 ESR1-positive breast cancer patients. In the primary ESR1-positive breast tumors, DC-SCRIPT expression negatively correlated with several cell cycle gene ontologies and pathways. DC-SCRIPT expression strongly reduced breast cancer cell growth in vitro, breast tumor growth in vivo, and induced cell cycle arrest. In addition, in the presence of DC-SCRIPT, multiple cell cycles related genes were differentially expressed including the tumor suppressor gene CDKN2B. Moreover, in 1,132 primary ESR1-positive breast tumors, DC-SCRIPT expression also correlated with CDKN2B expression. Collectively, these data show that DC-SCRIPT acts as a novel regulator of CDKN2B and induces cell cycle arrest in ESR1-positive breast cancer cells

Agreement between physical therapists and radiologists of stratifying patients with shoulder pain into new treatment related categories using ultrasound; an exploratory study

© 2019 Elsevier Ltd Study design: A systematic overview of the literature and an agreement study. Objectives: The aim of this study is to explore the inter-professional agreement of diagnostic musculoskeletal ultrasound (DMUS) between physical therapists (PT) and radiologists, using a new classification strategy based upon the therapeutic consequences in patients with shoulder pain. Background: DMUS is frequently used by PTs, although the agreement regarding traditional diagnostic labels between PTs and radiologists is only fair. Nevertheless, DMUS could be useful when used as a stratifying-tool. Methods: First, a systematic overview of current evidence was performed to assess which traditional diagnostic labels could be recoded into new treatment related categories (referral to secondary care, corticosteroid injections, physical therapy, watchful waiting). Next, kappa values were calculated for these categories between PTs and radiologists. Results: Only three categories were extracted, as none of the traditional diagnostic labels were classified into the ‘corticosteroid injection’ category. Overall, we found moderate agreement to stratify patients into treatment related categories and substantial agreement for the category ‘referral to secondary care’. Both categories ‘watchful waiting’ and ‘indication for physical therapy’ showed moderate agreement between the two professions. Conclusion: Our results indicate that the agreement between radiologists and PTs is moderate to substantial when labelling is based on treatment consequences. DMUS might be able to help the PT to guide treatment, especially for the category ‘referral to secondary care’ as this showed the highest agreement. However, as this is just an explorative study, more research is needed, to validate and assess the consequences of this stratification classification for clinical care

The influence of baseline risk on the relation between HbA1c and risk for new cardiovascular events and mortality in patients with type 2 diabetes and symptomatic cardiovascular disease.

Background Strict glycaemic control in patients with type 2 diabetes has proven to have microvascular benefits while the effects on CVD and mortality are less clear, especially in high risk patients. Whether strict glycaemic control would reduce the risk of future CVD or mortality in patients with type 2 diabetes and pre-existing CVD, is unknown. This study aims to evaluate whether the relation between baseline HbA1c and new cardiovascular events or mortality in patients with type 2 diabetes and pre-existing cardiovascular disease (CVD) is modified by baseline vascular risk. Methods A cohort of 1096 patients with type 2 diabetes and CVD from the Second Manifestations of ARTerial Disease (SMART) study was followed. The relation between HbA1c at baseline and future vascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality was evaluated with Cox proportional hazard analyses in a population that was stratified for baseline risk for vascular events as calculated with the SMART risk score. The mean follow-up duration was 6.9 years for all-cause mortality and 6.4 years for vascular events, in which period 243 and 223 cases were reported, respectively. Results A 1 % increase in HbA1c was associated with a higher risk for all-cause mortality (HR 1.18, 95 % CI 1.06–1.31). This association was also found in the highest SMART risk quartile (HR 1.33, 95 % CI 1.11–1.60). There was no relation between HbA1c and the occurrence of cardiovascular events during follow-up (HR 1.03, 95 % CI 0.91–1.16). The interaction term between HbA1c and SMART risk score was not significantly related to any of the outcomes. Conclusion In patients with type 2 diabetes and CVD, HbA1c is related to the risk of all-cause mortality, but not to the risk of cardiovascular events. The relation between HbA1c and all-cause mortality in patients with type 2 diabetes and vascular disease is not dependent on baseline vascular risk

320-row CT: does beat-to-beat motion of the coronary arteries affect image quality?

Vascular Biology and Interventio

Functional analysis by 64-slice CT scanning: prediction of left ventricular dysfunction together with reduction in radiation exposure?

Cardiac Dysfunction and Arrhythmia

320-row CT scanning: reduction in tube current parallels reduction in radiation exposure?

Cardiac Dysfunction and Arrhythmia

100 kV versus 120 kV: effective reduction in radiation dose?

Atherosclerosi

Rationale, design, and results of the first screening round of a comprehensive, register-based, Chlamydia screening implementation programme in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Implementing <it>Chlamydia trachomatis </it>screening in the Netherlands has been a point of debate for several years. The National Health Council advised against implementing nationwide screening until additional data collected from a pilot project in 2003 suggested that screening by risk profiles could be effective. A continuous increase in infections recorded in the national surveillance database affirmed the need for a more active approach. Here, we describe the rationale, design, and implementation of a <it>Chlamydia </it>screening demonstration programme.</p> <p>Methods</p> <p>A systematic, selective, internet-based <it>Chlamydia </it>screening programme started in April 2008. Letters are sent annually to all 16 to 29-year-old residents of Amsterdam, Rotterdam, and selected municipalities of South Limburg. The letters invite sexually active persons to login to <url>http://www.chlamydiatest.nl</url> with a personal code and to request a test kit. In the lower prevalence area of South Limburg, test kits can only be requested if the internet-based risk assessment exceeds a predefined value.</p> <p>Results</p> <p>We sent invitations to 261,025 people in the first round. One-fifth of the invitees requested a test kit, of whom 80% sent in a sample for testing. The overall positivity rate was 4.2%.</p> <p>Conclusions</p> <p>This programme advances <it>Chlamydia </it>control activities in the Netherlands. Insight into the feasibility, effectiveness, cost-effectiveness, and impact of this large-scale screening programme will determine whether the programme will be implemented nationally.</p

Disrupting the rhythm of depression using Mobile Cognitive Therapy for recurrent depression: randomized controlled trial design and protocol

Background: Major depressive disorder (MDD) is projected to rank second on a list of 15 major diseases in terms of burden in 2030. The major contribution of MDD to disability and health care costs is largely due to its highly recurrent nature. Accordingly, efforts to reduce the disabling effects of this chronic condition should shift to preventing recurrence, especially in patients at high risk of recurrence. Given its high prevalence and the fact that interventions are necessary during the remitted phase, new approaches are needed to prevent relapse in depression. Methods/design: The best established effective and available psychological intervention is cognitive therapy. However, it is costly and not available for most patients. Therefore, we will compare the effectiveness and cost-effectiveness of self-management supported by online CT accompanied by SMS based tele-monitoring of depressive symptomatology, i.e. Mobile Cognitive Therapy (M-CT) versus treatment as us usual (TAU). Remitted patients (n = 268) with at least two previous depressive episodes will be recruited and randomized over (1) M-CT in addition to TAU versus (2) TAU alone, with follow-ups at 3, 12, and 24 months. Randomization will be stratified for number of previous episodes and type of treatment as usual. Primary outcome is time until relapse/recurrence over 24 months using DSM-IV-TR criteria as assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). For the economic evaluation the balance between costs and health outcomes will be compared across strategies using a societal perspective. Discussion: Internet-based interventions might be helpful in empowering patients to become their own disease managers in this lifelong recurrent disorder. This is, as far as we are aware of, the first study that examines the (cost) effectiveness of an E-mental health program using SMS monitoring of symptoms with therapist support to prevent relapse in remitted recurrently depressed patient