eIF4EBP3 was downregulated by methylation and acted as a tumor suppressor by targeting eIF4E/β-catenin in gastric cancer

Gastric Cancer - Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Through a methylome...     

Factors associated with the quality of laboratory performance in the United Kingdom external quality assessment scheme for serum growth hormone

A search was made for associations between poor performance in the UK External Quality Assessment Scheme (EQAS) for serum growth hormone (GH), and a range of factors including assay method, laboratory workload and staffing, and Internal Quality Control (IQC) procedures. On the basis of the factors identified as being associated with poor performance we recommend the following. 1. Laboratories using RIA for GH should routinely analyse samples at two dilutions and report a mean result. 2. The use of 125I-GH which is 5 or more weeks old should be avoided. Tracer should also be chromatographed to remove aggregate before use. 3. Laboratories using RIA should avoid using a standard curve which covers too wide a range concentration; a curve midpoint (ie GH concentration to reduce the zero standard binding by 50%) of about 8 mU/l or less is probably acceptable. 4. It should be noted that high workloads present a risk of some loss in quality of responsible for checking IQC data. 6. Laboratories which do not have the resources to maintain fully their own RIA as outlined above should carefully consider use of an unbiased, precise IRMA. The UK EQAS has identified two assays (Boots-Celltech Sucrosep, NETRIA) that appear to meet these criteria [2]. The above observations may also be relevant to immunoassays for other peptide hormones.     

Effectiveness and nutritional consequences of amino acid-based vs glucose-based dialysis solutions in infants and children receiving CAPD

Excessive glucose absorption and dialysate amino acid and protein losses contribute to malnutrition in children on glucose-based continuous ambulatory peritoneal dialysis (CAPD). We used 2.5 and 4.25% glucose and 1.1 and 2.0% amino acid dialysates to assess short-term effectiveness and nutritional consequences of amino acid-based dialysis solutions. Plasma and effluent urea and creatinine concentrations were similar with amino acid and glucose dialysis although 16% less fluid was removed with amino acid dialysates. Absorption of 77.3 +/- 5.3% of dialysate amino acids exceeded losses of amino acids and protein in glucose effluent. With amino acid dialysates, fasting plasma glucose concentrations were maintained while plasma amino acid levels rose, peaked at 1 h, and, excepting methionine, isoleucine, and phenylalanine with the 2.0% solution, returned to initial levels after 5 h. Compared with glucose, amino acid dialysates provide reduced but satisfactory fluid and waste removal, maintain normoglycemia, and more than compensate for effluent losses of amino acids and protein.     

Energy recommendations for normal weight,overweight and obese children and adolescents: are different equations necessary?

In 2002/2005, separate energy requirement equations were generated by the Institute of Medicine's (IOM) Dietary Reference Intake process for normal weight and overweight/obese children and adolescents. The current paper questions the theoretical rationale of having two sets of equations (based solely on body-weight classification): when body weight is considered, overweight and obese children and adolescents do not seem to differ from their normal weight counterparts in energy expended for basal metabolism or physical activity tasks. However, energy needs for weight maintenance among overweight/obese girls were consistently higher when predicted using the equations for overweight/obese individuals compared with those developed for normal weight individuals. In contrast, among overweight/obese boys, they were consistently lower . Although the differences are within the variability of the estimates, even theoretical support for a higher energy intake (as occurs in girls) seems unwise because of the potential contribution to a higher body mass in children who are already at risk. It is the opinion of the authors that the IOM revisit the use of two separate equations and generate one set that is appropriate for all children and adolescents.     

Postoperative Cognitive Dysfunction in Middle-aged Patients

Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent.

Methods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living.

Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months.     

Sub-angiographic peripheral emboli in high resolution DWI after endovascular recanalization

Journal of Neurology - To analyze the incidence of peripheral emboli after successful mechanical thrombectomy (MT) of intracranial large vessel occlusions (LVO). We performed a prospective analysis...     

Ischemic lesion water homeostasis after thrombectomy for large vessel occlusion stroke within the anterior circulation: The impact of age

The effect of age on lesion pathophysiology in the context of thrombectomy has been poorly investigated. We aimed to investigate the impact of age on ischemic lesion water homeostasis measured with net water uptake (NWU) within a multicenter cohort of patients receiving thrombectomy for anterior circulation large vessel occlusion (LVO) stroke. Lesion-NWU was quantified in multimodal CT on admission and 24 h for calculating Δ-NWU as their difference. The impact of age and procedural parameters on Δ-NWU was analyzed. Multivariable regression analysis was performed to identify significant predictors for Δ-NWU. Two hundred and four patients with anterior circulation stroke were included in the retrospective analysis. Comparison of younger and elderly patients showed no significant differences in NWU on admission but significantly higher Δ-NWU (p = 0.005) on follow-up CT in younger patients. In multivariable regression analysis, higher age was independently associated with lowered Δ-NWU (95% confidence interval: −0.59 to −0.16, p < 0.001). Although successful recanalization (TICI ≥ 2b) significantly reduced Δ-NWU progression by 6.4% (p < 0.001), younger age was still independently associated with higher Δ-NWU (p < 0.001). Younger age is significantly associated with increased brain edema formation after thrombectomy for LVO stroke. Younger patients might be particularly receptive targets for future adjuvant neuroprotective drugs that influence ischemic edema formation.     

Free insulin levels and metabolic effects of meal-time bolus and square-wave intraperitoneal insulin infusion in insulin-dependent diabetic patients

Summary The intraperitoneal route may offer more physiological insulin delivery through absorption of a proportion of the dose into the portal circulation. We have compared 1-h square-wave and bolus supplemental infusions of a fixed dose of 10 U of intraperitoneal insulin in 6 C-peptide negative insulin-dependent diabetic patients eating a standard breakfast and compared the insulin, glucose and metabolite responses with those of non-diabetic control subjects. Blood glucose profiles were similar on the two experimental days and although the peak glucose levels were not different from normal they were delayed by 30 min (p<0.05). Basal free insulin levels were elevated in diabetic patients (square-wave 19.6±2.3, bolus 18.7±1.9mU/l) compared to controls (7.3±1.0mU/l, p< 0.02) and rose more rapidly after bolus injection than infusion. Peak insulin concentration was achieved at 33±4 min after bolus, 90±13 min after infusion (p<0.02) and 39±5 min in normal control subjects. The shape of the profile of free insulin concentration was similar after bolus injection and in the controls, but after square-wave infusion the return to baseline was delayed (p< 0.05). Fasting intermediary metabolite concentrations were normal on both study days in the patients, but serum cortisol levels were significantly elevated and glucagon concentrations low. Metabolite responses to the meal were not significantly different from normal after bolus injection but increases in lactate and glycerol were seen at some time points between 60 and 180 min after infusion. Glucagon levels remained low after square-wave infusion. We conclude that bolus injection of the breakfast insulin supplement gives a more optimal profile of insulin delivery for patients on intraperitoneal insulin.