Sleep effects on slow-brain-potential reflections of associative learning

Previous research has indicated that information acquired before sleep gets consolidated during sleep. This process of consolidation might be reflected after sleep in changed extent and topography of cortical activation during retrieval of information. Here, we designed an experiment to measure those changes by means of slow event-related EEG potentials (SPs). Retrieval of newly learnt verbal or spatial associations was tested both immediately after learning and two days later. In the night directly following immediate recall, participants either slept or stayed awake. In line with previous studies, SPs measured during retrieval from memory had parietal or left-frontal foci depending on whether the retrieved associations were spatial or verbal. However, contrary to our expectations, sleep-related consolidation did not further accentuate these content-specific topographic profiles. Rather, sleep modified SPs independently of the spatial or verbal type of learned association: SPs were reduced more after sleep than after waking specifically for those stimulus configurations that had been presented in the same combination at retrieval before sleep. The association-independent stimulus-specific effect might generally form a major component of sleep-related effects on memory.     

A neurophysiological deficit in early visual processing in schizophrenia patients with auditory hallucinations

Existing 67‐channel event‐related potentials, obtained during recognition and working memory paradigms with words or faces, were used to examine early visual processing in schizophrenia patients prone to auditory hallucinations (AH, n = 26) or not (NH, n = 49) and healthy controls (HC, n = 46). Current source density (CSD) transforms revealed distinct, strongly left‐ (words) or right‐lateralized (faces; N170) inferior‐temporal N1 sinks (150 ms) in each group. N1 was quantified by temporal PCA of peak‐adjusted CSDs. For words and faces in both paradigms, N1 was substantially reduced in AH compared with NH and HC, who did not differ from each other. The difference in N1 between AH and NH was not due to overall symptom severity or performance accuracy, with both groups showing comparable memory deficits. Our findings extend prior reports of reduced auditory N1 in AH, suggesting a broader early perceptual integration deficit that is not limited to the auditory modality.     

Successful prediction of a model pharmaceutical in the fifth blind test of crystal structure prediction

The range of target structures in the fifth international blind test of crystal structure prediction was extended to include a highly flexible molecule, (benzyl-(4-(4-methyl-5-(p-tolylsulfonyl)-1,3-thiazol-2-yl)phenyl)carbamate, as a challenge representative of modern pharmaceuticals. Two of the groups participating in the blind test independently predicted the correct structure. The methods they used are described and contrasted, and the implications of the capability to tackle molecules of this complexity are discussed.     

Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications

The poor oral bioavailability arising from poor aqueous solubility should make drug research and development more difficult. Various approaches have been developed with a focus on enhancement of the solubility, dissolution rate, and oral bioavailability of poorly water-soluble drugs. To complete development works within a limited amount of time, the establishment of a suitable formulation strategy should be a key consideration for the pharmaceutical development of poorly water-soluble drugs. In this article, viable formulation options are reviewed on the basis of the biopharmaceutics classification system of drug substances. The article describes the basic approaches for poorly water-soluble drugs, such as crystal modification, micronization, amorphization, self-emulsification, cyclodextrin complexation, and pH modification. Literature-based examples of the formulation options for poorly water-soluble compounds and their practical application to marketed products are also provided. Classification of drug candidates based on their biopharmaceutical properties can provide an indication of the difficulty of drug development works. A better understanding of the physicochemical and biopharmaceutical properties of drug substances and the limitations of each delivery option should lead to efficient formulation development for poorly water-soluble drugs.     

Migraine and Its Association with Hyperactivity of Cell Membranes in the Course of Latent Magnesium Deficiency—Preliminary Study of the Importance of the Latent Tetany Presence in the Migraine Pathogenesis

So far, there is no consistent and convincing theory explaining the pathogenesis of migraines. Vascular disorders, the effect of oxidative stress on neurons, and the contribution of magnesium-calcium deficiencies in triggering cortical depression and abnormal glutaminergic neurotransmission are taken into account. However, there are no reliable publications confirming the role of dietary deficits of magnesium and latent tetany as factors triggering migraine attacks. The aim of the study was to evaluate the influence of latent magnesium deficiency assessed with the electrophysiological tetany test on the course of migraine. The study included: a group of 35 patients (29 women and six men; in mean age 41 years) with migraine and a control group of 24 (17 women and seven men; in mean age 39 years) healthy volunteers. Migraine diagnosis was based on the International Headache Society criteria, 3rd edition. All patients and controls after full general and neurological examination were subjected to a standard electrophysiological ischemic tetany test. Moreover, the level of magnesium in blood serum was tested and was in the normal range in all patients. Then, the incidence of a positive tetany EMG test results in the migraine group and the results in the subgroups with and without aura were compared to the results in the control group. Moreover, the relationship between clinical markers of spasmophilia and the results of the tetany test was investigated in the migraine group. As well as the relationship between migraine frequency and tetany test results. There was no statistically significant difference in the occurrence of the electrophysiological exponent of spasmophilia between the migraine and control group. Neither correlation between the occurrence of clinical symptoms nor the frequency of migraine attacks and the results of the tetany test was stated (p > 0.05). However, there was an apparent statistical difference between the subgroup of migraine patients with aura in relation to the control group (p < 0.05). The result raises hope to find a trigger for migraine attacks of this clinical form, the more that this factor may turn out to be easy to supplement with dietary supplementation.     

Analysis of residue conformations in peptides in Cambridge structural database and protein‐peptide structural complexes

A comprehensive statistical analysis of the geometric parameters of peptide chains in a reduced dataset of protein‐peptide complexes in Protein Data Bank (PDB) is presented. The angular variables describing the backbone conformations of amino acid residues in peptide chains shed insights into the conformational preferences of peptide residues interacting with protein partners. Nonparametric statistical approaches are employed to evaluate the interrelationships and associations in structural variables. Grouping of residues based on their structure into chemical classes reveals characteristic trends in parameter relationships. A comparison of canonical amino acid residues in free peptide structures in Cambridge structural database (CSD) with identical residues in PDB complexes, suggests that the information can be integrated from both the structural repositories enabling efficient and accurate modeling of biologically active peptides.     

北京地区70万人群冠心病猝死流行病学调查

本文报告1984－1985年北京地区70万自然人群中25－74岁年龄组冠心病猝死率及其流行病学特点。结果显示：冠心病死亡中约一半为猝死。男性猝死率高于女性。猝死者大部分有心血管病史，约一半有前驱症状，但特异性较差。本文就冠心病猝死诊断标准及院外心肺复苏等问题进行了讨论。     

Neuronal generator patterns of olfactory event‐related brain potentials in schizophrenia

To better characterize neurophysiologic processes underlying olfactory dysfunction in schizophrenia, nose–referenced 30–channel electroencephalogram was recorded from 32 patients and 35 healthy adults (18 and 18 male) during detection of hydrogen sulfide (constant‐flow olfactometer, 200 ms unirhinal exposure). Event‐related potentials (ERPs) were transformed to reference–free current source density (CSD) waveforms and analyzed by unrestricted Varimax–PCA. Participants indicated when they perceived a high (10 ppm) or low (50% dilution) odor concentration. Patients and controls did not differ in detection of high (23% misses) and low (43%) intensities and also had similar olfactory ERP waveforms. CSDs showed a greater bilateral frontotemporal N1 sink (305 ms) and mid‐parietal P2 source (630 ms) for high than low intensities. N1 sink and P2 source were markedly reduced in patients for high intensity stimuli, providing further neurophysiological evidence of olfactory dysfunction in schizophrenia.