Sedative properties of Mitracarpus villosus leaves in mice

The leaves of Mitracarpus villosus (Sw.) DC. (Rubiaceae) have several therapeutic applications in the West African folk medicine for the management of a plethora of stress-related diseases including headaches. This study was designed to evaluate the sedative properties of the ethylacetate extract of Mitracarpus villosus on open field (OFT), diazepam-induced sleep, staircase climbing, head-dips in the hole-board test and rota rod test in mice. Graded doses (100 – 400 mg/kg) of the extract significantly and dose-dependently prolonged the duration of diazepam-induced sleep (P<0.05), decreased the number of squares crossed in the OFT (P<0.0001), decreased number of head-dips in the hole-board test (P<0.05) and reduced steps climbing (P<0.05) in mice. The extract at the doses tested had no effect on motor coordination as observed in the rota-rod treadmill assay in mice. Our results revealed that the ethylacetate extract of Mitracarpus villosus leaves may contain psychoactive principles that are sedative in nature, thus supporting further development of the psychoactive components of this plant for management of stress-related diseases.Keywords: Mitracarpus villosus, sedation, diazepam, locomotion

Microrna profiling analysis of differences between the melanoma of young adults and older adults

<p>Abstract</p> <p>Background</p> <p>This study represents the first attempt to perform a profiling analysis of the intergenerational differences in the microRNAs (miRNAs) of primary cutaneous melanocytic neoplasms in young adult and older age groups. The data emphasize the importance of these master regulators in the transcriptional machinery of melanocytic neoplasms and suggest that differential levels of expressions of these miRs may contribute to differences in phenotypic and pathologic presentation of melanocytic neoplasms at different ages.</p> <p>Methods</p> <p>An exploratory miRNA analysis of 666 miRs by low density microRNA arrays was conducted on formalin fixed and paraffin embedded tissues (FFPE) from 10 older adults and 10 young adults including conventional melanoma and melanocytic neoplasms of uncertain biological significance. Age-matched benign melanocytic nevi were used as controls.</p> <p>Results</p> <p>Primary melanoma in patients greater than 60 years old was characterized by the increased expression of miRs regulating TLR-MyD88-NF-kappaB pathway (hsa-miR-199a), RAS/RAB22A pathway (hsa-miR-204); growth differentiation and migration (hsa-miR337), epithelial mesenchymal transition (EMT) (let-7b, hsa-miR-10b/10b*), invasion and metastasis (hsa-miR-10b/10b*), hsa-miR-30a/e*, hsa-miR-29c*; cellular matrix components (hsa-miR-29c*); invasion-cytokinesis (hsa-miR-99b*) compared to melanoma of younger patients. MiR-211 was dramatically downregulated compared to nevi controls, decreased with increasing age and was among the miRs linked to metastatic processes. Melanoma in young adult patients had increased expression of hsa-miR-449a and decreased expression of hsa-miR-146b, hsa-miR-214*. MiR-30a* in clinical stages I-II adult and pediatric melanoma could predict classification of melanoma tissue in the two extremes of age groups. Although the number of cases is small, positive lymph node status in the two age groups was characterized by the statistically significant expression of hsa-miR-30a* and hsa-miR-204 (F-test, p-value < 0.001).</p> <p>Conclusions</p> <p>Our findings, although preliminary, support the notion that the differential biology of melanoma at the extremes of age is driven, in part, by deregulation of microRNA expression and by fine tuning of miRs that are already known to regulate cell cycle, inflammation, Epithelial-Mesenchymal Transition (EMT)/stroma and more specifically genes known to be altered in melanoma. Our analysis reveals that miR expression differences create unique patterns of frequently affected biological processes that clearly distinguish old age from young age melanomas. This is a novel characterization of the miRnomes of melanocytic neoplasms at two extremes of age and identifies potential diagnostic and clinico-pathologic biomarkers that may serve as novel miR-based targeted modalities in melanoma diagnosis and treatment.</p

Structural evaluation of WIPP disposal room raised to Clay Seam G.

An error was discovered in the ALGEBBRA script used to calculate the disturbed rock zone around the disposal room and the shear failure zone in the anhydrite layers in the original version. To correct the error, a memorandum of correction was submitted according to the Waste Isolation Pilot Plant (WIPP) Quality Assurance program. The recommended course of action was to correct the error, to repeat the post-process, and to rewrite Section 7.4, 7.5, 8, and Appendix B in the original report. The sections and appendix revised by the post-process using the corrected ALGEBRA scripts are provided in this revision. The original report summarizes a series of structural calculations that examine effects of raising the WIPP repository horizon from the original design level upward 2.43 meters. Calculations were then repeated for grid changes appropriate for the new horizon raised to Clay Seam G. Results are presented in three main areas: (1) Disposal room porosity, (2) Disturbed rock zone characteristics, and (3) Anhydrite marker bed failure. No change to the porosity surface for the compliance re-certification application is necessary to account for raising the repository horizon, because the new porosity surface is essentially identical. The disturbed rock zone evolution and devolution are charted in terms of a stress invariant criterion over the regulatory period. This model shows that the propagation of the DRZ into the surrounding rock salt does not penetrate through MB 139 in the case of both the original horizon and the raised room. Damaged salt would be expected to heal in nominally 150 years. The shear failure does not occur in either the upper or lower anhydrite layers at the moment of excavation, but appears above and below the middle of the pillar one day after the excavation. The damaged anhydrite is not expected to heal as the salt in the DRZ is expected to

Safeguarding children in dentistry: 1. Child protection training, experience and practice of dental professionals with an interest in paediatric dentistry

* Few dental professionals with child protection training have experience of making referrals. * There is a wide gap in practice between recognising signs of child abuse and neglect and responding effectively. * This may indicate missed opportunities to save children from continuing abuse. * There is a need for improved child protection information, support and training for dental professionals. Abstract Following several highly publicised inquiries into the deaths of children from abuse and neglect, there has been much recent interest in the role and responsibility of all health professionals to protect children at risk of maltreatment. The findings of a postal questionnaire, sent in March 2005 to 789 dentists and dental care professionals with an interest in paediatric dentistry working in varied settings in the UK, are presented in a two-part report and discussed in the context of current multi-agency good practice in safeguarding and promoting the welfare of children. This first part explores reported child protection training, experience and practice. There was a significant gap between recognising signs of abuse and responding effectively: 67% of respondents had suspected abuse or neglect of a child patient at some time in their career but only 29% had ever made a child protection referral. The dental profession is alerted to the need to ensure necessary appropriate action to safeguard children is always taken when child abuse or neglect are suspected

Melaena with Peutz-Jeghers syndrome: a case report

Introduction: Peutz-Jeghers syndrome (PJS) is a rare familial disorder characterised by mucocutaneous pigmentation, gastrointestinal and extragastrointestinal hamartomatous polyps and an increased risk of malignancy. Peutz-Jeghers polyps in the bowel may result in intussusception. This complication usually manifests with abdominal pain and signs of intestinal obstruction. Case Presentation: We report the case of a 24-year-old Caucasian male who presented with melaena. Pigmentation of the buccal mucosa was noted but he was pain-free and examination of the abdomen was unremarkable. Upper gastrointestinal endoscopy revealed multiple polyps. An urgent abdominal computed tomography (CT) scan revealed multiple small bowel intussusceptions. Laparotomy was undertaken on our patient, reducing the intussusceptions and removing the polyps by enterotomies. Bowel resection was not needed. Conclusion: Melaena in PJS needs to be urgently investigated through a CT scan even in the absence of abdominal pain and when clinical examination of the abdomen shows normal findings. Although rare, the underlying cause could be intussusception, which if missed could result in grave consequences

Self-assembly of polymers in confined geometrics.

Athermal, tethered chains are modeled with Density Functional (DFT) theory for both the explicit solvent and continuum solvent cases. The structure of DFT is shown to reduce to Self-Consistent-Field (SCF) theory in the incompressible limit where there is symmetry between solvent and monomer, and to Single-Chain-Mean-Field (SCMF) theory in the continuum solvent limit. We show that by careful selection of the reference and ideal systems in DFT theory, self-consistent numerical solutions can be obtained, thereby avoiding the single chain Monte Carlo simulation in SCMF theory. On long length scales, excellent agreement is seen between the simplified DFT theory and Molecular Dynamics simulations of both continuum solvents and explicit-molecule solvents. In order to describe the structure of the polymer and solvent near the surface it is necessary to include compressibility effects and the nonlocality of the field

The Waiting Time for Inter-Country Spread of Pandemic Influenza

BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza

Sexual Segregation and Flexible Mating Patterns in Temperate Bats

Social structure evolves from a trade-off between the costs and benefits of group-living, which are in turn dependent upon the distribution of key resources such as food and shelter. Males and females, or juveniles and adults, may have different priorities when selecting habitat due to differences in physiological or behavioural imperatives, leading to complex patterns in group composition. We studied social structure and mating behaviour in the insectivorous bat Myotis daubentonii along an altitudinal gradient, combining field studies with molecular genetics. With increasing altitude the proportion of males in summer roosts increased and only males were present in the highest roosts. With increasing altitude environmental temperature decreased, nightly variation in temperature increased, and bat foraging activity decreased, supporting the hypothesis that the harsher, high elevation sites cannot support breeding females. We found that offspring in female-dominated lowland roosts had a very high probability of being fathered by bats caught during autumn swarming at hibernation sites, in contrast to those in intermediate roosts, which had a high probability of being fathered by males sharing the nursery roost with the females. Whilst females normally appear to exclude males from nursery colonies, for those in marginal habitats, one explanation for the presence of males is that the thermoregulatory benefits to the females may outweigh disadvantages, such as competition for food, and give some males an opportunity to increase their breeding success. We suggest that the environment, and its effects on resource distribution, thus determine social structure, which in turn determines the mating pattern that has evolved

DRSPALL :spallings model for the Waste Isolation Pilot Plant 2004 recertification.

This report presents a model to estimate the spallings releases for the Waste Isolation Pilot Plant Performance Assessment (WIPP PA). A spallings release in the context of WIPP PA refers to a portion of the solid waste transported from the subsurface repository to the ground surface due to inadvertent oil or gas drilling into the WIPP repository at some time after site closure. Some solid waste will be removed by the action of the drillbit and drilling fluid; this waste is referred to as cuttings and cavings. If the repository is pressurized above hydrostatic at the time of intrusion, solid waste material local to the borehole may be subject to mechanical failure and entrainment in high-velocity gases as the repository pressure is released to the borehole. Solid material that fails and is transported into the wellbore and thus to the surface comprise the spallings releases. The spallings mechanism is analogous to a well blowout in the modern oil and gas drilling industry. The current spallings conceptual model and associated computer code, DRSPALL, were developed for the 2004 recertification because the prior spallings model used in the 1996 WIPP Compliance Certification Application (CCA) was judged by an independent peer review panel as inadequate (DOE 1996, 9.3.1). The current conceptual model for spallings addresses processes that take place several minutes before and after a borehole intrusion of a WIPP waste room. The model couples a pipe-flow wellbore model with a porous flow repository model, allowing high-pressure gas to flow from the repository to the wellbore through a growing cavity region at the well bottom. An elastic stress model is applied to the porous solid domain that allows for mechanical failure of repository solids if local tensile stress exceeds the tensile strength of the waste. Tensile-failed solids may be entrained into the wellbore flow stream by a fluidized bed model, in which case they are ultimately transported to the land surface comprising a release. In July 2003, DOE/SNL presented the spallings conceptual model to a independent peer review panel in accordance with NUREG 1297 guidelines (NRC, 1988). The panel ultimately judged the model as adequate for implementation in WIPP PA (Yew et al., 2003). This report documents the spallings model history from 1997 to the implementation of DRSPALL in the 2004 Compliance Recertification Application (CRA) (DOE, 2004). The scope of this report includes descriptions of the conceptual model, numerical model, verification and validation techniques, model sensitivity studies, and WIPP PA spallings results as presented in the 2004 CRA