Impact of Chronic Sleep Disturbance for People Living With T1 Diabetes.

AIM: The aim was to explore personal experiences and to determine the impact of impaired sleep on well-being and diabetes-related activities/decision making among a cohort of people living with T1D. METHOD: Adults with T1D over the age of 18 and parents/carers of children with T1D were invited to complete an online questionnaire about their quality and quantity of sleep. Questions included impact of sleep on diabetes-related decision making, effective calculation of bolus doses, important aspects of psychosocial functioning, and frequency of waking. Diasend download data were used to objectively determine frequency of nocturnal blood glucose testing in children. RESULTS: A total of 258 parent/carer participants (n = 221 female, 85.6%) and 192 adults with T1D (n = 145, 75.5% female, age range 19 to 89 years) took part. In all, 239 parents/carers and 160 adults believed waking in the night has an impact on their usual daily functioning. Of these, 236 parents/carers and 151 (64%) adults reported the impact as negative. Chronic sleep interruption was associated with detrimental impact on mood, work, family relationships, ability to exercise regularly, ability to eat healthily, and happiness. CONCLUSION: Chronic sleep interruption is highly prevalent in adults with T1D and parents/carers of children with T1D with negative effects on daily functioning and well-being. Appropriate interventions are required to alleviate this burden of T1D, address modifiable risk factors for nocturnal hypoglycemia, and reduce the (perceived) need for nocturnal waking

p53 mutations in urinary bladder cancer

We have screened for mutations in exons 5–8 of the p53 gene in a series consisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1–G2a) and 106 (56%) were highly malignant (G2b–G4 or ≥T1). Only one mutation was in a lowly malignant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) of the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT)n repeat markers. 31 samples (21%) showed LOH but were not mutated, suggesting other mechanisms inactivating p53 than mutations. 4 mutations were found at codon 280 and 2 mutations were found at codon 285, 2 previously reported hot spots for urinary bladder cancer. The study indicate a boundary between G2a and G2b tumours concerning the occurrence of genetic events affecting p53 function; moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that they should not be grouped together but instead, for example, be categorized as either lowly or highly malignant. © 2001 Cancer Research Campaign http://www.bjcancer.co

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia : further evidence and meta-analysis

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PostprintPeer reviewe

Measurement of D-0, D+, D+* and D-s(+) production in pp collisions at root s=5.02 TeV with ALICE

The measurements of the production of prompt D0, D+, D+, and Ds+ mesons in proton-proton (pp) collisions at TeV with the ALICE detector at the Large Hadron Collider (LHC) are reported. D mesons were reconstructed at mid-rapidity (|y|<0.5) via their hadronic decay channels D0K-+, D+K-++, D+D0+K-++, Ds+phi+K+K-+, and their charge conjugates. The production cross sections were measured in the transverse momentum interval 0<36 for D0, 1<36 for D+ and D+, and in 2<24 for Ds+ mesons. Thanks to the higher integrated luminosity, an analysis in finer pT bins with respect to the previous measurements at sTeV was performed, allowing for a more detailed description of the cross-section pT shape. The measured pT-differential production cross sections are compared to the results at s=7TeV and to four different perturbative QCD calculations. Its rapidity dependence is also tested combining the ALICE and LHCb measurements in pp collisions at s=5.02 TeV. This measurement will allow for a more accurate determination of the nuclear modification factor in p-Pb and Pb-Pb collisions performed at the same nucleon-nucleon centre-of-mass energy

Scandinavian Olecranon Research in the Elderly (SCORE) : protocol for a non- inferiority, randomised, controlled, multicentre trial comparing operative and conservative treatment of olecranon fractures in the elderly

Introduction The incidence of olecranon fractures is growing in the elderly population. The traditional operative approach is giving way among the elderly to conservative treatment, which seems to provide a comparable functional outcome with a lower complication burden. However, there is still a lack of reliable evidence to support this shift. The objective of this trial is to investigate whether conservative treatment of displaced olecranon fractures in patients aged 75 or older yields comparable results to those of operative treatment in terms of pain and daily function. Methods and analysis Scandinavian Olecranon Research in the Elderly (SCORE) is a randomised, controlled, multicentre, non-inferiority trial. Eligible patients will be randomised to either conservative or operative treatment. The sample size will be 68 patients and allocation done at a 1:1 ratio (34 patients per group). The randomisation is stratified according to the participating hospital and patient's sex. Both groups will receive the same postoperative physiotherapy and pain management. The primary outcome is Disabilities of the Arm, Shoulder and Hand at 1-year follow-up. Secondary outcomes are pain and satisfaction measured on visual analogue scales, Patient Reported Elbow Evaluation, range of motion of the elbow and extension strength of the elbow compared with the unaffected arm. Radiographs will be taken at each follow-up. Primary analysis of the results will be conducted on an intention-to-treat basis. Ethics and dissemination The study protocol for this clinical trial has been approved by the Ethics Committee of the Hospital District of Southwest Finland and will be submitted for approval to the Regional Ethics Committees in Linkoping, Sweden and Copenhagen, Denmark. Every recruiting centre will apply local research approvals. The results of this study will be submitted for publication in peer-reviewed journals.Peer reviewe