Incidence and predictors of de novo late-onset persistent atrial fibrillation in postoperative rheumatic heart disease patients (LOAF-RHD study)

Journal of Interventional Cardiac Electrophysiology - Late-onset atrial fibrillation (LOAF) after valve surgery for degenerative mitral valve disease often with underlying mitral valve prolapse is...     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Effect of loading conditions on Doppler-derived transmitral flow indices in normal subjects and patients with coronary artery disease

The influence of alterations in preload and afterload on left ventricular diastolic filling using echocardiography was examined in nine normal volunteers (NLS) and nine patients (PTS) with coronary artery disease. The sequential interventions used were handgrip to increase afterload, nitroglycerin to decrease preload, and nifedipine to decrease afterload. Transmitral flow was measured using pulsed-Doppler echocardiography. Measurements were made pre- and post interventions. With increase in afterload using handgrip, the A and E wave velocities and the A/E ratio increased in both groups: 0.62 +/- 0.14 versus 0.86 +/- 0.17 in NLS; 0.75 +/- 0.45 versus 0.84 +/- 0.50 in PTS (P less than 0.05). Following administration of nitroglycerin to reduce preload, the A wave velocities increased, the E wave velocity decreased in both groups, and the A/E ratio increased 0.57 +/- 0.11 versus 0.67 +/- 0.13 in NLS; 0.78 +/- 0.40 versus 0.91 +/- 0.44 in PTS (P less than 0.05). Following use of nifedipine, the A and E wave velocities decreased in both groups with an increase in the A/E ratio in the patient group 0.83 +/- 0.13 versus 0.89 +/- 0.11 (P = NS). Thus, both normal subjects and patients with coronary artery disease had similar changes in Doppler-derived indices of left ventricular filling following interventions that changed left ventricular preload and afterload.     

Ultra‐deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The Association Between Autistic Traits and Disordered Eating is Moderated by Sex/Gender and Independent of Anxiety and Depression

Journal of Autism and Developmental Disorders - Previous studies have reported positive correlations between autistic traits and disordered eating, though it is unclear whether the association is...     

Modified graphene supported Ag–Cu NPs with enhanced bimetallic synergistic effect in oxidation and Chan–Lam coupling reactions

Herein, well dispersed Ag–Cu NPs supported on modified graphene have been synthesized via a facile and rapid approach using sodium borohydride as a reducing agent under ambient conditions. Dicyandiamide is selected as an effective nitrogen source with TiO₂ as an inorganic material to form two kinds of supports, labelled as TiO₂–NGO and NTiO₂–GO. Initially, the surface area analysis of these two support materials was carried out which indicated that N-doping of GO followed by anchoring with TiO₂ has produced support material of larger surface area. Using both types of supports, ten nano-metal catalysts based on Ag and Cu were synthesized. Benefiting from the bimetallic synergistic effect and larger specific surface area of TiO₂–NGO, Cu@Ag–TiO₂–NGO is found to be a highly active and reusable catalyst out of other synthesized catalysts. It exhibits excellent catalytic activity for oxidation of alcohols and hydrocarbons as well as Chan–Lam coupling reactions. The nanocatalyst is intensively characterized by BET, SEM, HR-TEM, ICP-AES, EDX, CHN, FT-IR, TGA, XRD and XPS.

Cu@Ag–TiO₂–NGO prepared from modified graphene by simple methodology exhibits enhanced catalytic activity towards oxidation and Chan–Lam coupling due to the synergistic effect between Ag and Cu NPs.     

The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes

Aims/hypothesis

Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes increases the risk of severe hypoglycaemia sixfold and can be resistant to intervention. We explored the impact of IAH on central responses to hypoglycaemia to investigate the mechanisms underlying barriers to therapeutic intervention.

Methods

We conducted [¹⁵O]water positron emission tomography studies of regional brain perfusion during euglycaemia (target 5 mmol/l), hypoglycaemia (achieved level, 2.4 mmol/l) and recovery (target 5 mmol/l) in 17 men with type 1 diabetes: eight with IAH, and nine with intact hypoglycaemia awareness (HA).

Results

Hypoglycaemia with HA was associated with increased activation in brain regions including the thalamus, insula, globus pallidus (GP), anterior cingulate cortex (ACC), orbital cortex, dorsolateral frontal (DLF) cortex, angular gyrus and amygdala; deactivation occurred in the temporal and parahippocampal regions. IAH was associated with reduced catecholamine and symptom responses to hypoglycaemia vs HA (incremental AUC: autonomic scores, 26.2?±?35.5 vs 422.7?±?237.1; neuroglycopenic scores, 34.8?±?88.8 vs 478.9?±?311.1; both p?<?0.002). There were subtle differences (p?<?0.005, k?≥?50 voxels) in brain activation at hypoglycaemia, including early differences in the right central operculum, bilateral medial orbital (MO) cortex, and left posterior DLF cortex, with additional differences in the ACC, right GP and post- and pre-central gyri in established hypoglycaemia, and lack of deactivation in temporal regions in established hypoglycaemia.

Conclusions/interpretation

Differences in activation in the post- and pre-central gyri may be expected in people with reduced subjective responses to hypoglycaemia. Alterations in the activity of regions involved in the drive to eat (operculum), emotional salience (MO cortex), aversion (GP) and recall (temporal) suggest differences in the perceived importance and urgency of responses to hypoglycaemia in IAH compared with HA, which may be key to the persistence of the condition.