Novel Therapeutic Effects in Rat Spinal Cord Injuries: Recovery of the Definitive and Early Spinal Cord Injury by the Administration of Pentadecapeptide BPC 157 Therapy

Recently, marked therapeutic effects pertaining to the recovery of injured rat spinal cords (1 min compression injury of the sacrocaudal spinal cord (S2-Co1) resulting in tail paralysis) appeared after a single intraperitoneal administration of the stable gastric pentadecapeptide BPC 157 at 10 min post-injury. Besides the demonstrated rapid and sustained recovery (1 year), we showed the particular points of the immediate effect of the BPC 157 therapy that began rapidly after its administration, (i) soon after injury (10 min), or (ii) later (4 days), in the rats with a definitive spinal cord injury. Specifically, in counteracting spinal cord hematoma and swelling, (i) in rats that had undergone acute spinal cord injury, followed by intraperitoneal BPC 157 application at 10 min, we focused on the first 10–30 min post-injury period (assessment of gross, microscopic, and gene expression changes). Taking day 4 post-injury as the definitive injury, (ii) we focused on the immediate effects after the BPC 157 intragastric application over 20 min of the post-therapy period. Comparable long-time recovery was noted in treated rats which had definitive tail paralysis: (iii) the therapy was continuously given per orally in drinking water, beginning at day 4 after injury and lasting one month after injury. BPC 157 rats presented only discrete edema and minimal hemorrhage and increased Nos1, Nos2, and Nos3 values (30 min post-injury, (i)) or only mild hemorrhage, and only discrete vacuolation of tissue (day 4, (ii)). In the day 4–30 post-injury study (iii), BPC 157 rats rapidly presented tail function recovery, and no demyelination process (Luxol fast blue staining).     

Measuring Large-Scale Social Networks with High Resolution

This paper describes the deployment of a large-scale study designed to measure human interactions across a variety of communication channels, with high temporal resolution and spanning multiple years—the Copenhagen Networks Study. Specifically, we collect data on face-to-face interactions, telecommunication, social networks, location, and background information (personality, demographics, health, politics) for a densely connected population of 1 000 individuals, using state-of-the-art smartphones as social sensors. Here we provide an overview of the related work and describe the motivation and research agenda driving the study. Additionally, the paper details the data-types measured, and the technical infrastructure in terms of both backend and phone software, as well as an outline of the deployment procedures. We document the participant privacy procedures and their underlying principles. The paper is concluded with early results from data analysis, illustrating the importance of multi-channel high-resolution approach to data collection.     

Vaginal delivery and continuous epidural analgesia: should we change our clinical approach?

The aim of the study was to investigate the effects of continuous epidural analgesia (EA) on the course of vaginal delivery with an emphasis on duration of labor and instrumental interventions. In a prospective 2-year trial, the study group included singleton vaginal births between 35 and 41 gestational weeks with a vertex fetus, in which continuous EA with bupivacaine or chirocaine in concentration of 0.125% combined with 2-4 microg of fentanyl or 0.5 microg of sufenta was used. The control group was created randomly from laboring patients with singleton pregnancies but without EA. The groups were adjusted for epidemiological characteristics and compared regarding the obstetric data and perinatal outcome. Student t-test and Mann-Whitney U-test were performed for normally and non-normally distributed results, respectively. Out of 1284 patients, 551 pregnant women were included in the study group and 733 in the control group. The statistically significant differences between the groups related to duration of the first and second stage of labor, frequency of premature rupture of membranes, intrapartal complications, and incidence of operative deliveries were found. Both stages of labor were significantly protracted and the incidence of operative deliveries was higher in the study group of patients compared with controls. There is a need for an active obstetric approach and management of vaginal deliveries of women who receive continuous EA, particularly if it is medically indicated.     

Non-functional Fas ligand increases the formation of cartilage early in the endochondral bone induction by rhBMP-2

It has previously been shown that mice with a defect in Fas ligand-mediated apoptosis have an enhancement of ectopic bone formation. We investigated the expression of bone-related markers--alkaline phosphatase, collagen, bone sialoprotein, osteocalcin, osteopontin, and bone morphogenetic proteins (BMP) -2, -4, and -7; and cytokines interleukin-1alpha (IL-1), IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) in ectopic new bone induced by recombinant human (rh) BMP-2 in mice without functional Fas-ligand (gld mice). At day 6 after rhBMP-2 implantation, gld mice formed more cartilage and mesenchyme compared with their wild type littermates. At later stages, gld mice did not differ from the control mice in the volume of newly formed tissue, expressing higher level of BMP genes and lower levels of genes involved in osteoblast maturation--bone sialoprotein and osteopontin. Differences in the levels of expression of IL-1alpha and TNF-alpha were observed only at day 12 after rhBMP-2 implantation. These results suggest that gld mice have an increased recruitment of cells of mesenchymal origin and an abnormal pattern of differentiation and maturation of the newly formed mesenchymal tissues.     

Assessing psychosocial factors in depressed patients--accordance of patient's and physician's assessment

Aim of this study was to investigate the differences in the assessment of psychosocial factors by depressed and non depressed patients, and their congruence with physicians' assessment for both groups. The cross-sectional study was conducted in three family physicians' practices in Zagreb, Croatia, during 2007. Sample of depressed patients included 76 patients out of 85, and randomized comparison group of 189 out of 235. Questionnaire recommended by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice was used for the assessment of psychosocial factors. Depressed patients significantly more frequently reported about social isolation (p(alone) = 0.013; p(close confident) = 0.005; p(help) = 0.001), family stress (p < 0.001), work stress (p(appropriate reward) = 0.029) and lower life satisfaction (p < 0.001) than non depressed. Their worse psychosocial functioning was noticed by family physicians who assessed social isolation (p(alone) = 0.013; p(close confident) = 0.032), family stress (p < 0.001) and life satisfaction (p < 0.001) significantly lower for depressed patients than for the random sample. Incongruence between family physicians and depressed patients assessment was valued by physicians to be of higher economic status (p < 0.001), and more intense family stress (p < 0.001). Assessment of psychosocial factors varied within the group of depressed patients and the random sample assessed either by themselves or by physicians. Congruence between family physicians and non depressed patients in the assessment of observed psychosocial factors was better than between physicians and depressed patients.     

Serum cholesterol concentration and structured individual psychoanalytic psychotherapy in suicidal and non-suicidal male patients suffering from borderline personality disorder

Findings from numerous studies suggest an association between low cholesterol levels and suicidal behavior in patients with different psychiatric diagnoses. The aims of this case-control study were to test whether cholesterol levels in male suicidal patients (N=20) with borderline personality disorder (BPD) are lower than in male non-suicidal patients (N=20) with BPD and male healthy control group (N=20), and to evaluate the influence of structured individual psychoanalytic psychotherapy on suicidal behavior. The groups were matched for age and body mass index (BMI). Results showed that serum cholesterol levels did not differ significantly between suicidal and non-suicidal BPD patients and healthy controls. The level of psychopathology (measured by Brief Psychiatric Rating Scale and Hamilton Depression Rating Scale) was significantly higher in the group of suicidal patients, which indicates the importance of evaluating particular clinical symptoms in BPD, in order to prevent suicidal behavior. Non-suicidal male patients suffering from BPD received more frequently structured individual psychoanalytic psychotherapy prior to the hospitalization than suicidal group. These results emphasized the role of this type of psychotherapy in preventing suicidal behavior in BPD patients.     

T cells recognizing a peptide contaminant undetectable by mass spectrometry

Synthetic peptides are widely used in immunological research as epitopes to stimulate their cognate T cells. These preparations are never completely pure, but trace contaminants are commonly revealed by mass spectrometry quality controls. In an effort to characterize novel major histocompatibility complex (MHC) Class I-restricted β-cell epitopes in non-obese diabetic (NOD) mice, we identified islet-infiltrating CD8+ T cells recognizing a contaminating peptide. The amount of this contaminant was so small to be undetectable by direct mass spectrometry. Only after concentration by liquid chromatography, we observed a mass peak corresponding to an immunodominant islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214) epitope described in the literature. Generation of CD8+ T-cell clones recognizing IGRP(206-214) using a novel method confirmed the identity of the contaminant, further underlining the immunodominance of IGRP(206-214). If left undetected, minute impurities in synthetic peptide preparations may thus give spurious results.     

Variation in the Form of Pavlovian Conditioned Approach Behavior among Outbred Male Sprague-Dawley Rats from Different Vendors and Colonies: Sign-Tracking vs. Goal-Tracking

Even when trained under exactly the same conditions outbred male Sprague-Dawley (SD) rats vary in the form of the Pavlovian conditioned approach response (CR) they acquire. The form of the CR (i.e. sign-tracking vs. goal-tracking) predicts to what degree individuals attribute incentive salience to cues associated with food or drugs. However, we have noticed variation in the incidence of these two phenotypes in rats obtained from different vendors. In this study, we quantified sign- and goal-tracking behavior in a reasonably large sample of SD rats obtained from two vendors (Harlan or Charles River), as well as from individual colonies operated by both vendors. Our sample of rats acquired from Harlan had, on average, more sign-trackers than goal-trackers, and vice versa for our sample of rats acquired from Charles River. Furthermore, there were significant differences among colonies of the same vendor. Although it is impossible to rule out environmental variables, SD rats at different vendors and barriers may have reduced phenotypic heterogeneity as a result of genetic variables, such as random genetic drift or population bottlenecks. Consistent with this hypothesis, we identified marked population structure among colonies from Harlan. Therefore, despite sharing the same name, investigators should be aware that important genetic and phenotypic differences exist among SD rats from different vendors or even from different colonies of the same vendor. If used judiciously this can be an asset to experimental design, but it can also be a pitfall for those unaware of the issue.     

Genome sequence of the bacteriocin-producing oral probiotic Streptococcus salivarius strain M18

Streptococcus salivarius is a Gram-positive bacterial commensal and pioneer colonizer of the human oral cavity. Many strains produce ribosomally synthesized proteinaceous antibiotics (bacteriocins), and some strains have been developed for use as oral probiotics. Here, we present the draft genome sequence of the bacteriocin-producing oral probiotic S. salivarius strain M18.     

Exploring the robustness of macrophyte-based classification methods to assess the ecological status of coastal and transitional ecosystems under the Water Framework Directive

Identifying and quantifying the factors that contribute to the potential misclassification of the ecological status of water bodies is a major challenge of the Water Framework Directive (WFD). The present study compiles extensive biomonitoring data from a range of macrophyte-based classification methods developed by several European countries. The data reflect spatial and temporal variation as well as inter-observer variation. Uncertainty analysis identified that factors related to the spatial scale of sampling generally contributed most to the uncertainty in classifying water bodies to their ecological status, reflecting the high horizontal and depth-related heterogeneity displayed by macrophyte communities. In contrast, the uncertainty associated with temporal variation was low. In addition, inter-observer variation, where assessed, did not contribute much to overall uncertainty, indicating that these methods are easily transferable and insensitive to observer error. The study, therefore, suggests that macrophyte-based sampling schemes should prioritize large spatial replication over temporal replication to maximize the effectiveness and reliability of water body classification within the WFD. We encourage conducting similar uncertainty analyses for new/additional ecological indicators to optimize sampling schemes and improve the reliability of classification of ecological status.