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Chronic insomnia is highly prevalent in the general population, provoking personal distress and increased risk for psychiatric and medical disorders. Autonomic hyper-arousal could be a pathogenic mechanism of chronic primary insomnia. The aim of this study was to investigate autonomic activity in patients with chronic primary insomnia by means of heart rate variability (HRV) analysis. Eighty-five consecutive patients affected by chronic primary insomnia were enrolled (38 men and 47 women; mean age: 53.2 ± 13.6). Patients were compared with a control group composed of 55 healthy participants matched for age and gender (23 men and 32 women; mean age: 54.2 ± 13.9). Patients underwent an insomnia study protocol that included subjective sleep evaluation, psychometric measures, and home-based polysomnography with evaluation of HRV in wake before sleep, in all sleep stages, and in wake after final awakening. Patients showed modifications of heart rate and HRV parameters, consistent with increased sympathetic activity, while awake before sleep and during Stage-2 non-REM sleep. No significant differences between insomniacs and controls could be detected during slow-wave sleep, REM sleep, and post-sleep wake. These results are consistent with the hypothesis that autonomic hyper-arousal is a major pathogenic mechanism in primary insomnia, and confirm that this condition is associated with an increased cardiovascular risk.

We previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al., Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various autoimmune diseases and conditions., (Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

The n-back task is widely used to investigate the neural basis of Working Memory (WM) processes. The principal aim of this study was to explore and compare the EEG power spectra during two n-back tests with different levels of difficulty (1-back vs. 3-back). Fourteen healthy subjects were enrolled (seven men and seven women, mean age 31.21 ± 7.05 years, range: 23-48). EEG was recorded while performing the N-back test, by means of 19 surface electrodes referred to joint mastoids. EEG analysis were conducted by means of the standardized Low Resolution brain Electric Tomography (sLORETA) software. The statistical comparison between EEG power spectra in the two conditions was performed using paired t-statistics on the coherence values after Fisher's z transformation available in the LORETA program package. The frequency bands considered were: delta (0.5-4 Hz); theta (4.5-7.5 Hz); alpha (8-12.5 Hz); beta (13-30 Hz); gamma (30.5-100 Hz). Significant changes occurred in the delta band: in the 3-back condition an increased delta power was localized in a brain region corresponding to the Brodmann Area (BA) 28 in the left posterior entorhinal cortex (T = 3.112; p < 0.05) and in the BA 35 in the left perirhinal cortex in the parahippocampal gyrus (T = 2.876; p < 0.05). No significant differences were observed in the right hemisphere and in the alpha, theta, beta, and gamma frequency bands. Our results indicate that the most prominent modification induced by the increased complexity of the task occur in the mesial left temporal lobe structures.

Music performance is characterized by complex cross-modal interactions, offering a remarkable window into training-induced long-term plasticity and multimodal integration processes. Previous research with pianists has shown that playing a musical score is affected by the concurrent presentation of musical tones. We investigated the nature of this audio-motor coupling by evaluating how congruent and incongruent cross-modal auditory cues affect motor performance at different time intervals. We found facilitation if a congruent sound preceded motor planning with a large Stimulus Onset Asynchrony (SOA -300 and -200 ms), whereas we observed interference when an incongruent sound was presented with shorter SOAs (-200, -100 and 0 ms). Interference and facilitation, instead of developing through time as opposite effects of the same mechanism, showed dissociable time-courses suggesting their derivation from distinct processes. It seems that the motor preparation induced by the auditory cue has different consequences on motor performance according to the congruency with the future motor state the system is planning and the degree of asynchrony between the motor act and the sound presentation. The temporal dissociation we found contributes to the understanding of how perception meets action in the context of audio-motor integration.

The calculation of free-energy landscapes in proteins is a challenge for modern numerical simulations. As to the case of potassium ion channels is concerned, it is particularly interesting because of the nanometric dimensions of the selectivity filter, where the complex electrostatics is highly relevant. The present study aims at comparing three different techniques used to bias molecular dynamics simulations, namely Umbrella Sampling, Steered Molecular Dynamics, and Metadynamics, never applied all together in the past to the same channel protein. Our test case is represented by potassium ions permeating the selectivity filter of the KcsA channel.

This paper presents a computational analysis of the noise associated with the ion current in single open ion channels. The study is performed by means of a coupled molecular dynamics/Monte Carlo approach able to simulate the conduction process on the basis of all microscopic information today available from protein structural data and atomistic simulations. The case of potassium ions permeating the KcsA channel is considered in the numerical calculations. The results show a noise spectrum different from what is theoretically predicted for Poisson noise, confirmed by the existence of a correlation in ion-exit events.

We report the results of a search for a W' boson produced in pp collisions at a center-of-mass energy of 1.8 TeV using a 107 pb-1 data sample recorded by the Collider Detector at Fermilab. We consider the decay channel W'-->&munumu and search for anomalous production of high transverse mass munumu lepton pairs. We observe no excess of events above background and set limits on the rate of W' boson production and decay relative to standard model W boson production and decay using a fit of the transverse mass distribution observed. If we assume standard model strength couplings of the W' boson to quark and lepton pairs, we exclude a W' boson with invariant mass less than 660 GeV/c2 at 95% confidence level.

Since the oral glucose tolerance test is not applicable in large surveys for diabetes mellitus, economic tests or clinical criteria are required to select subjects needing a complete glycometabolic assessment. This study evaluated, in a selected high risk population (110 subjects; 71 males; median age: 53 years, range 30-70), the utility of glycosuria after a meal rich in carbohydrates in the detecting of diabetes, compared to other tests for glycosuria (fasting glycosuria, glycosuria after a glucose load) and clinical criteria (diabetic family history, overweight and their combination). For each test and, retrospectively, for clinical criteria, sensitivity, sensibility, predictive value positive (PVP) and predictive value negative (PVN) were calculated. Postprandial glycosuria resulted to be an effective approach (sensitivity: 100%; specificity: 44%; PVP: 23%, PVN: 100%) in people over 50 years old, in which both clinical criteria (sensitivity: 22-78%; PVN: 81-90%) and fasting glycosuria (sensitivity 11%; PVN: 86%) proved defective. In younger subjects both the presence of fasting glycosuria (sensitivity: 100%; specificity: 96%; PVP: 33%; PVN: 100%) and of relevant diabetic family history (sensitivity: 100%; specificity: 85%; PVN: 100%) proved more adequate as screening procedures.

The frequencies of micronuclei (MNi) in the gill cells of the mussel Mytilus galloprovincialis were determined over a long period (up to 28 days) following a 48-h treatment with colchicine. The frequency of MNi at the end of treatment was significantly higher than in controls and 24 h later it had increased even more. After this period, the frequency of MNi rapidly declined until a plateau level was reached on day 2-3, which was significantly higher than the control baseline level, and persisted until the end of the experiment (28th day). In the same cell system we previously reported a persistence of an increased frequency of MNi after treatment with mitomycin C (MMC) (Majone et al., 1987). In order to establish the origin of MNi, the difference between their size distribution in MMC- and colchicine-treated animals was determined at the end of treatment as well as during the plateau phase. The difference was statistically significant (P less than 0.001) at the end of treatment, the MNi induced by MMC being smaller than those induced by colchicine. However, the difference during the plateau phase was not statistically significant. Human CREST antikinetochore fluorescent antibodies reacted with chromosome centromeres of Mytilus and were applied to gill cells at the end of a 48-h treatment with MMC or colchicine. About 60% of the MNi induced by colchicine but only 30% of those produced by MMC reacted positively with the fluorescent antibodies. This result indicates that the majority of MNi observed at the end of a 48-h treatment with MMC or colchicine originate, respectively, from acentric chromosome fragments and from whole lagging chromosomes.

The frequency of micronuclei induced by mitomycin C (MMC) in cells of the gill tissue of the marine mussel, Mytilus galloprovincialis Lmk., was determined over a long period (up to 40-52 days) following treatment. Two doses of MMC (0.5 X 10(-7) and 10(-7) M) were tested at 13 degrees C and 23 degrees C, temperatures representative of the winter and summer thermic conditions of the Mediterranean Sea. In all cases, the frequency of micronuclei was significantly increased by MMC and declined after treatment until it reached a plateau level, significantly higher than the control value. This persisted for a very long time. The frequency of micronuclei induced by a second treatment with MMC performed on the 28th day, did not differ significantly from that produced by the first treatment at the same dose. Temperature did not influence the pattern of the described phenomena to a significant extent. The reason for the persistence of an increased frequency of micronuclei is discussed, and a system is proposed for evaluating the genotoxicity of water pollutants present long before sampling.

Sex gland extracts ofOstrinia nubilalis females collected in the wild or laboratory-reared from Switzerland, Italy, and Hungary were analyzed. Individuals collected in the north of Switzerland contained (Z)- and (E)-11-tetradecenyl acetate at the approximate ratio of 97∶3 (Z type), in accordance with field responses of males and previous findings. On the other hand, females from a laboratory culture derived from field collections made in the same area and reared for four to five generations contained theZ andE isomers at ratios of ca. 3∶97 and 35∶65, respectively. In the south, one of the eight wild females analyzed was of theZ type and the rest intermediate, whereas males were predominantly trapped with blends of the two isomers containing 60 to 97E. In a laboratory culture reared for one to two generations from corn borers collected in Hungary, three of nine females were of the intermediate type and the restZ. Small amounts of (Z)-11-hexadecenyl acetate were detected in female glands of theE strain; however, no effect of this compound could be observed in the field.

The case is described of a 39 year old man referred for clinical treatment of widespread oedema in the lower half of the body, especially the lower extremities. He was suffering from a gastroenteric protein malabsorption syndrome caused by syphilitic hypertrophic gastritis (tertiary syphilis). The syphilitic origin of the gastropathy was confirmed ex iuvantibus by penicillin treatment which cured the condition completely. The various forms of gastric lues, gastrointestinal malabsorption syndromes and ex iuvantibus criteria are discussed.

The frequencies of micronuclei induced by ZnCl2 and detected on the gill tissue of the marine mussel Mytilus galloprovincialis with different staining techniques (acridine orange, gallocyanin chromallum, Feulgen, Giemsa) were compared. At least in the used system, the Feulgen and gallocyanin chromallum methods gave a frequency of micronuclei significantly lower than that obtained with the acridine orange and Giemsa techniques. No significant difference between the frequencies obtained with acridine orange and Giemsa was shown. So, though the acridine orange is surely the method which provides the more reliable data, in environmental screening works the Giemsa technique may be more suitable for its simplicity.

The three California state hospitals for mentally retarded persons have been having a severe problem with amebic and bacillary dysentery and with other infectious diseases of the gastrointestinal tract. At Sonoma, the oldest of these hospitals, this problem is known to have existed for many years. Improved medical and nursing staffing and the use of antibiotics and other effective drugs developed in recent years have greatly lowered morbidity and mortality rates in these institutions. However, in themselves these measures have not been effective in lowering the incidence of infection. Studies have demonstrated that mass treatment of cottage groups known to have a high incidence of amebic infection has resulted in control of this disease where such mass treatment was followed by adequate laboratory follow-up, with isolation and retreatment of treatment failures. Where mass treatment of such groups has been carried out without such laboratory followup, there was a rapid return to the previous high incidence of infection. Statistics show that these diseases are a serious threat to employees working in these institutions. Increasing attention is being paid to the potential threat to the surrounding communities and the state as a whole from the focus of infection present in these hospitals.

Typhoid fever in California is no longer a major public health problem. The previously high incidence of water- and milk-borne infections has been greatly reduced. Human carriers now are the source of most infections. Chloramphenicol has proven to be a valuable aid in the therapy of the acutely ill patient, but it has not as yet solved the therapeutic or public health problems of typhoid fever. It continues to be vital for the protection of the public that every suspected case of typhoid fever be definitely established by appropriate public health laboratory procedures, that thorough investigation be carried out to determine the source of infection, and that careful follow-up examinations be done so that if a carrier state develops, proper measures can be taken.