A 1063G-->A mutation in exon 12 of glycoprotein (GP)IIb associated with a thrombasthenic phenotype: mutation analysis of [324E]GPIIb

We report the molecular, genetic and functional analysis of a case of thrombasthenic phenotype. The proband showed absence of platelet glycoprotein (GP)IIb and very low content of GPIIIa, and both his parents showed a marked reduction in the levels of platelet GPIIb-IIIa. Single-stranded conformational polymorphism-polymerase chain reaction (SSCP-PCR) analysis and direct sequencing of PCR-amplified GPIIb exon-12 revealed the presence of a G-->A transition at position 1063 with the expected substitution of glutamate 324 with lysine (K). This mutation did not alter the level of GPIIb mRNA. Co-expression of normal or mutant [324K] GPIIb with normal human GPIIIa in Chinese hamster ovary (CHO) cells failed to show surface exposure of [324K]GPIIb-IIIa complexes. Pulse-chase and immunoprecipitation analysis demonstrated that [324K]GPIIb cDNA was translated into proGPIIb, but neither mutant GPIIb heavy chain (GPIIbH) nor [324K]GPIIb-GPIIIa complexes were detected, suggesting that this mutation is the underlying molecular basis for the thrombasthenic phenotype. Mutation analysis demonstrated that 324E of GPIIb could be replaced by other negatively charged or polar amino acids (AAs) without impairing the surface expression of GPIIb-IIIa. However, substitution of 324E of GPIIb for a positively charged AA other than K prevented the expression of GPIIb-IIIa complexes. These observations suggest that a domain encompassing 324E of GPIIb is essential for heterodimerization with GPIIIa and its substitution for a positively charged residue precludes normal subunit association.     

Evidence for the early clinical relevance of hallucinatory‐delusional states in the general population

Nuevo R, Van Os J, Arango C, Chatterji S, Ayuso‐Mateos JL. Evidence for the early clinical relevance of hallucinatory‐delusional states in the general population. Objective: To analyze, in a general population sample, clustering of delusional and hallucinatory experiences in relation to environmental exposures and clinical parameters. Method: General population‐based household surveys of randomly selected adults between 18 and 65 years of age were carried out. Setting: 52 countries participating in the World Health Organization’s World Health Survey were included. Participants: 225 842 subjects (55.6% women), from nationally representative samples, with an individual response rate of 98.5% within households participated. Results: Compared with isolated delusions and hallucinations, co‐occurrence of the two phenomena was associated with poorer outcome including worse general health and functioning status (OR = 0.93; 95% CI: 0.92–0.93), greater severity of symptoms (OR = 2.5 95% CI: 2.0–3.0), higher probability of lifetime diagnosis of psychotic disorder (OR = 12.9; 95% CI: 11.5–14.4), lifetime treatment for psychotic disorder (OR = 19.7; 95% CI: 17.3–22.5), and depression during the last 12 months (OR = 11.6; 95% CI: 10.9–12.4). Co‐occurrence was also associated with adversity and hearing problems (OR = 2.0; 95% CI: 1.8–2.3). Conclusion: The results suggest that the co‐occurrence of hallucinations and delusions in populations is not random but instead can be seen, compared with either phenomenon in isolation, as the result of more etiologic loading leading to a more severe clinical state.     

The translational repressor eIF4E-binding protein 2 (4E-BP2) correlates with selective delayed neuronal death after ischemia

Transient brain ischemia induces an inhibition of translational rates and causes delayed neuronal death in selective regions and cognitive deficits, whereas these effects do not occur in resistant areas. The translational repressor eukaryotic initiation factor (eIF) 4E-binding protein-2 (4E-BP2) specifically binds to eIF4E and is critical in the control of protein synthesis. To link neuronal death to translation inhibition, we study the eIF4E association with 4E-BP2 under ischemia reperfusion in a rat model of transient forebrain ischemia. Upon reperfusion, a selective neuronal apoptosis in the hippocampal cornu ammonis 1 (CA1) region was induced, while it did not occur in the cerebral cortex. Confocal microscopy analysis showed a decrease in 4E-BP2/eIF4E colocalization in resistant cortical neurons after reperfusion. In contrast, in vulnerable CA1 neurons, 4E-BP2 remains associated to eIF4E with a higher degree of 4E-BP2/eIF4E colocalization and translation inhibition. Furthermore, the binding of a 4E-BP2 peptide to eIF4E induced neuronal apoptosis in the CA1 region. Finally, pharmacological-induced protection of CA1 neurons inhibited neuronal apoptosis, decreased 4E-BP2/eIF4E association, and recovered translation. These findings documented specific changes in 4E-BP2/eIF4E association during ischemic reperfusion, linking the translation inhibition to selective neuronal death, and identifying 4E-BP2 as a novel target for protection of vulnerable neurons in ischemic injury.     

Impact of preoperative immunonutrition on morbidity following cystectomy for bladder cancer: a case–control pilot study

Purpose

To compare postoperative complications in patients with or without preoperative immunonutrition before cystectomy.

Methods

A prospective, multicenter, pilot, case–control study was conducted during 6 months. Patients with 7-day preoperative immunonutrition were prospectively included and compared with a retrospective, matched control group without immunonutrition. Early complication rates and the length of hospital stay were analyzed. The bilateral type I error was <0.05; the power was 90 %. Thirty patients in each group were required.

Results

Thirty patients were included in each group, on a comparable basis. In the immunonutrition group, fewer postoperative complications (40 vs. 76.7 %; p = 0.008), less paralytic ileus at D7 (6.6 vs. 33.3 %; p = 0.02), fewer infections (23.3 vs. 60 %; p = 0.008), and in particular less pyelonephritis (16.7 vs. 46.7 %; p = 0.03) occurred. Clavien’s grades for complications were higher in the control group (p = 0.04). Mortality, pulmonary embolism, anastomotic fistulae, and wound dehiscence were similar between two groups. The length of stay was reduced by 3 days in the immunonutrition group.

Conclusions

In this pilot case–control study, immunonutrition is associated with a decrease in postoperative complications, urinary tract infections, Clavien’s grade for complications, and paralytic ileus in patients undergoing cystectomy for bladder cancer. Prospective randomized placebo control studies are needed to confirm these promising results.     

Decreased spectral entropy modulation in patients with schizophrenia during a P300 task

Spectral entropy (SE), also known as Shannon entropy, is a useful parameter for quantifying the global regularity of the electroencephalographic (EEG) signal. Hence, it is of interest in the assessment of the electrophysiological correlates of cognitive processing in schizophrenia. However, to date, SE has been barely used in studies comparing resting EEG recordings between patients and controls. In this work, we compared SE between resting baseline [?250 0] ms and active task [150 550] ms windows of a P300 task in 31 patients with schizophrenia and 38 controls. Moreover, we also calculated the median frequency (MF) and relative power in each frequency band for these windows to assess the correlates of the possible SE differences. Controls showed a significant (p < 0.0029) SE decrease (i.e., meaning higher signal regularity) from baseline to the active task window at parietal and central electrode sites. This SE decrease from baseline to active conditions was significantly lower in patients. In controls, this SE decrease was accompanied by a statistically significant decrease in MF (i.e., a significant slowing of the EEG activity), not observed in patients. In this latter group, the difference in SE between resting baseline and active task windows was inversely correlated to positive and total symptoms scores, as measured with the positive and negative symptoms scale. Our data support the relevance of SE in the study of cerebral processing in schizophrenia.     

Prevalence and risk factors of silent brain infarcts in patients with AF detected by 3T-MRI

Journal of Neurology - Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause...