NEAT1 and paraspeckles in neurodegenerative diseases: A missing lnc found?

Neurodegenerative diseases are among the most common causes of disability worldwide. Although neurodegenerative diseases are heterogeneous in both their clinical features and the underlying physiology, they are all characterised by progressive loss of specific neuronal populations. Recent experimental evidence suggests that long non-coding RNAs (lncRNAs) play important roles in the CNS in health and disease. Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is an abundant, ubiquitously expressed lncRNA, which forms a scaffold for a specific RNA granule in the nucleus, or nuclear body, the paraspeckle. Paraspeckles act as molecular hubs for cellular processes commonly affected by neurodegeneration. Transcriptomic analyses of the diseased human tissue have revealed altered NEAT1 levels in the CNS in major neurodegenerative disorders as well as in some disease models. Although it is clear that changes in NEAT1 expression (and in some cases, paraspeckle assembly) accompany neuronal damage, our understanding of NEAT1 contribution to the disease pathogenesis is still rudimentary. In this review, we have summarised the available knowledge on NEAT1 involvement in the molecular processes linked to neurodegeneration and on NEAT1 dysregulation in this type of disease, with a special focus on amyotrophic lateral sclerosis. The goal of this review is to attract the attention of researchers in the field of neurodegeneration to NEAT1 and paraspeckles

Risk factors for childhood obesity at age 5: Analysis of the Millennium Cohort Study

<p>Abstract</p> <p>Background</p> <p>Weight at age 5 is a predictor for future health of the individual. This study examines risk factors for childhood obesity with a focus on ethnicity.</p> <p>Methods</p> <p>Data from the Millennium Cohort study were used. 17,561 singleton children of White/European (n = 15,062), Asian (n = 1,845) or African (n = 654) background were selected. Logistic regression and likelihood ratio tests were used to examine factors associated with obesity at age 5. All participants were interviewed in their own homes. The main exposures examined included; Birth weight, sedentary lifestyle, family health behaviours, ethnicity, education and income.</p> <p>Results</p> <p>Children with a sedentary lifestyle, large at birth, with high risk family health behaviours (overweight mothers, smoking near the child, missing breakfast) and from a family with low income or low educational attainment, were more likely to be obese regardless of ethnicity. Feeding solid food before 3 months was associated with obesity in higher income White/European families. Even when controlling for socioeconomic status, ethnic background is an important independent risk factor for childhood obesity [Odds ratio of obesity; was 1.7 (95%CI: 1.2-2.3) for Asian and 2.7 (95%CI: 1.9-3.9) for African children, compared to White/European]. The final adjusted model suggests that increasing income does not have a great impact on lowering obesity levels, but that higher academic qualifications are associated with lower obesity levels [Odds of obesity: 0.63 (95%CI: 0.52-0.77) if primary carer leaves school after age 16 compared at age 16].</p> <p>Conclusions</p> <p>Education of the primary carer is an important modifiable factor which can be targeted to address rising obesity levels in children. Interventions should be family centred supporting and showing people how they can implement lifestyle changes in their family.</p

Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer.

Contains fulltext : 52756tjan-heijnen.pdf (publisher's version ) (Closed access)BACKGROUND: Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy. METHODS: Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. Responding patients were subsequently randomly assigned to surgical resection or radiotherapy. Survival curves were estimated using Kaplan-Meier analyses from time of randomization. RESULTS: Induction chemotherapy resulted in a response rate of 61% (95% confidence interval [CI] = 57% to 65%) among the 579 eligible patients. A total of 167 patients were allocated to resection and 165 to radiotherapy. Of the 154 (92%) patients who underwent surgery, 14% had an exploratory thoracotomy, 50% a radical resection, 42% a pathologic downstaging, and 5% a pathologic complete response; 4% died after surgery. Postoperative radiotherapy was administered to 62 (40%) of patients in the surgery arm. Among the 154 (93%) irradiated patients, overall compliance to the radiotherapy prescription was 55%, and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7%; one patient died of radiation pneumonitis. Median and 5-year overall survival for patients randomly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (hazard ratio = 1.06, 95% CI = 0.84 to 1.35). Rates of progression-free survival were also similar in both groups. CONCLUSION: In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy, surgical resection did not improve overall or progression-free survival compared with radiotherapy. In view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these patients

Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents

Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, large-scale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Munster Study Group. The study identified 213 patients with non-Hodgkin lymphoma and a pre-existing condition. Four subcategories were established: a) cancer predisposition syndromes (n=124, 58%); b) primary immunodeficiencies not further specified (n=27, 13%); c) genetic diseases with no increased cancer risk (n=40, 19%); and d) non-classifiable conditions (n=22, 10%). Seventy-nine of 124 (64%) cancer predispositions were reported in groups with more than 20 patients: ataxia telangiectasia (n=32), Nijmegen breakage syndrome (n=26), constitutional mismatch repair deficiency (n=21). For the 151 patients with a known cancer risk, 5-year event-free survival and overall survival rates were 40%+/-4% and 51%+/-4%, respectively. Five-year cumulative incidences of progression/relapse and treatment-related death as a first event were 22%+/-4% and 24%+/-4%, respectively. Ten-year incidence of second malignancy was 24%+/-5% and 7-year overall survival of the 21 patients with a second malignancy was 41%+/-11%. Patients with non-Hodgkin lymphoma and pre-existing conditions have an inferior survival rate with a large proportion of therapy-related deaths compared to patients with non-Hodgkin lymphoma and no pre-existing conditions. They may require special vigilance when receiving standard or modified/reduced-intensity chemotherapy or when undergoing allogeneic stem cell transplantation

Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study

Contains fulltext : 110658.pdf (publisher's version ) (Closed access