Altered development of the brain after focal herpesvirus infection of the central nervous system

Human cytomegalovirus infection of the developing central nervous system (CNS) is a major cause of neurological damage in newborn infants and children. To investigate the pathogenesis of this human infection, we developed a mouse model of infection in the developing CNS. Intraperitoneal inoculation of newborn animals with murine cytomegalovirus resulted in virus replication in the liver followed by virus spread to the brain. Virus infection of the CNS was associated with the induction of inflammatory responses, including the induction of a large number of interferon-stimulated genes and histological evidence of focal encephalitis with recruitment of mononuclear cells to foci containing virus-infected cells. The morphogenesis of the cerebellum was delayed in infected animals. The defects in cerebellar development in infected animals were generalized and, although correlated temporally with virus replication and CNS inflammation, spatially unrelated to foci of virus-infected cells. Specific defects included decreased granular neuron proliferation and migration, expression of differentiation markers, and activation of neurotrophin receptors. These findings suggested that in the developing CNS, focal virus infection and induction of inflammatory responses in resident and infiltrating mononuclear cells resulted in delayed cerebellar morphogenesis

The Late-Effect Of X-Irradiation on the Mouse Submandibular Gland

INTRODUCTION: Life-long severe xerostomia is a common complication after radiotherapy of head and neck malignancy. It is a clinical entity which causes a great deal of suffering and disability for the patient. Saliva is an important factor for denture retention. Hyposalivation causes reduced retention of full dentures. The aim of the study was to determine late consequences of irradiation in the mouse submandibular gland. MATERIAL AND METHODS : Mouse submandibular glands were locally X-irradiated by single dose irradiation with 15Gy. Day 90 post-irradiation tissues were analyzed by morphology and morphometry. RESULTS: Strong vacuolization of almost all acini was noted. Kariopyknotic nuclei were found in numerous acini and the largest amount of acini was in the lysis. The epithelial cells of the granular convoluted tubule were degenerated and desquamated in the lumen, and some granular convoluted tubules were in the lysis. In the interstitial connective tissue disseminated focal mononuclear infiltrate was found. With respect to the control group a statistically significant decrease in the number of acinar cells (p<0.001) was determined, as well as a significant increase in the number of granular convoluted tubule cells (p<0.001). Whereas the number of intercalated duct cells was not different with respect to the control (p=0.10). CONCLUSION: The results of this study suggest that hypofunction in the late stage is a consequence of morphological changes and loss of acinar cells. The patients should use a saliva substitute to alleviate their symptoms easier

Synthesis of Hybrid Computational Fluid Dynamics Results for F-16XL Aircraft Aerodynamics

A synthesis is presented of recent numerical predictions for the F-16XL aircraft flowfields and aerodynamics. The computational results were all performed with hybrid RANS/LES formulations, with an emphasis on unsteady flows and subsequent aerodynamics, and results from five computational methods are included. The work was focused on one particular low-speed, high angle-of-attack flight test condition, and comparisons against flight-test data are included. This work represents the third coordinated effort using the F-16XL aircraft, and a unique flight-test data set, to advance our knowledge of slender airframe aerodynamics as well as our capability for predicting these aerodynamics with advanced CFD formulations. The prior efforts were identified as Cranked Arrow Wing Aerodynamics Project International, with the acronyms CAWAPI and CAWAPI-2

The Child and Adolescent Psychiatry: Study of Training in Europe (CAP-STATE)

There is great cultural diversity across Europe. This is reflected in the organisation of child and adolescent mental health (CAMH) services and the training of the respective professionals in different countries in Europe. Patients and their parents will want a high quality, knowledgeable, and skillful service from child and adolescent psychiatrists (CAPs) wherever they see them in Europe. A European comparison of training programs allows all stakeholders in different European countries to assess the diversity and to initiate discussions as to the introduction of improvements within national training programs. Major issues to be addressed in comparing child and adolescent psychiatric training programs across Europe include: (1) formal organisation and content of training programs and the relationship to adult psychiatry and paediatrics; (2) flexibility of training, given different trainee interests and that many trainees will have young families; (3) quality of governance of training systems; (4) access to research; and (5) networking. The Child and Adolescent Psychiatry-Study of Training in Europe (CAP-State) is a survey of training for child and adolescent psychiatrists (CAPs) across European countries. It aims to revisit and extend the survey carried out in 2006 by Karabekiroglu and colleagues. The current article is embedded in a special issue of European Child + Adolescent Psychiatry attempting to for the first time address training in CAP at the European and global levels. Structured information was sought from each of 38 European and neighboring countries (subsequently loosely referred to as Europe) and obtained from 31. The information was provided by a senior trainee or recently qualified specialist and their information was checked and supplemented by information from a senior child and adolescent psychiatry trainer. Results showed that there is a very wide range of provision of training in child and adolescent psychiatry in different countries in Europe. There remains very substantial diversity in training across Europe and in the degree to which it is subject to national oversight and governance. Some possible reasons for this variation are discussed and some recommendations made.info:eu-repo/semantics/publishedVersio

Research on the effectiveness and tolerability of vaginal administration of probiotic Lactobacillus acidophilus in women with symptoms of colpitis

Probiotici su živi mikroorganizmi koji primijenjeni u dostatnoj količini mijenjaju sastav i metaboličku aktivnost mikroflore ili utječu na imunološki sustav što djeluje povoljno na zdravlje čovjeka. Lactobacillus acidophilus je najbolje proučena acidofilna bakterija koju prirodno nalazimo u jogurtu i acidofilnom mlijeku. Cilj ovog ispitivanja je bio istražiti djelotvornost i podnošljivost vaginalne primjene probiotika Lactobacillus acidophilus u bolesnica sa simptomima kolpitisa. U ovom prospektivnom ispitivanju djelotvornosti i podnošljivosti sedmodnevne primjene Lactobacillus acidophilus solucije za vaginalnu primjenu u žena s kolpitisom – probiotik Lactobacillus acidophilus se pokazao djelotvoran s obzirom da je 42 od ukupno 50 liječenih žena bilo klinički izliječeno. Klinički uspjeh bio je češći u žena iznad 50 godina starosti, te u žena koje su imale simptome iritacije i svrbeža. Lactobacillus acidophilus solucija za vaginalnu primjenu se pokazala izrazito podnošljiva s obzirom da niti jedna od 50 liječenih žena nije imala nuspojave liječenja.Probiotics are live microorganisms which, when administered in adequate amounts, change the structure and metabolic activity of human microflora or affect the immune system in a way beneficial for human health. Lactobacillus acidophilus is the most studied acidophilus bacteria that is naturally found in yogurt and acidophilus milk. The aim of this research was to investigate the effectiveness and tolerability of vaginal administration of probiotic Lactobacillus acidophilus in patients with symptoms of colpitis. In this prospective research on the efficacy and tolerability of Lactobacillus acidophilus vaginal solution used for 7 days in women with colpitis – probiotic Lactobacillus acidophilus has proved effective in 42 out of 50 treated women. Clinical success was more common in women over 50 years of age and in women with symptoms of irritation and pruritis. Lactobacillus acidophilus vaginal solution has proved especially tolerable since not one among 50 treated women experienced treatmant side effects

Mutation and deletion analysis of GFRα-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours

Glial cell line-derived neurotrophic factor (GDNF) plays a key role in the control of vertebrate neuron survival and differentiation in both the central and peripheral nervous systems. GDNF preferentially binds to GFRα-1 which then interacts with the receptor tyrosine kinase RET. We investigated a panel of 36 independent cases of mainly advanced sporadic brain tumours for the presence of mutations in GDNF and GFRα-1. No mutations were found in the coding region of GDNF. We identified six previously described GFRα-1 polymorphisms, two of which lead to an amino acid change. In 15 of 36 brain tumours, all polymorphic variants appeared to be homozygous. Of these 15 tumours, one also had a rare, apparently homozygous, sequence variant at codon 361. Because of the rarity of the combination of homozygous sequence variants, analysis for hemizygous deletion was pursued in the 15 samples and loss of heterozygosity was found in 11 tumours. Our data suggest that intragenic point mutations of GDNF or GFRα-1 are not a common aetiologic event in brain tumours. However, either deletion of GFRα-1 and/or nearby genes may contribute to the pathogenesis of these tumours

Changes in Glial Cell Line-derived Neurotrophic Factor Expression in the Rostral and Caudal Stumps of the Transected Adult Rat Spinal Cord

Limited information is available regarding the role of endogenous Glial cell line-derived neurotrophic factor (GDNF) in the spinal cord following transection injury. The present study investigated the possible role of GDNF in injured spinal cords following transection injury (T9–T10) in adult rats. The locomotor function recovery of animals by the BBB (Basso, Beattie, Bresnahan) scale score showed that hindlimb support and stepping function increased gradually from 7 days post operation (dpo) to 21 dpo. However, the locomotion function in the hindlimbs decreased effectively in GDNF-antibody treated rats. GDNF immunoreactivty in neurons in the ventral horn of the rostral stump was stained strongly at 3 and 7 dpo, and in the caudal stump at 14 dpo, while immunostaining in astrocytes was also seen at all time-points after transection injury. Western blot showed that the level of GDNF protein underwent a rapid decrease at 7 dpo in both stumps, and was followed by a partial recovery at a later time-point, when compared with the sham-operated group. GDNF mRNA-positive signals were detected in neurons of the ventral horn, especially in lamina IX. No regenerative fibers from corticospinal tract can be seen in the caudal segment near the injury site using BDA tracing technique. No somatosensory evoked potentials (SEP) could be recorded throughout the experimental period as well. These findings suggested that intrinsic GDNF in the spinal cord could play an essential role in neuroplasticity. The mechanism may be that GDNF is involved in the regulation of local circuitry in transected spinal cords of adult rats

Real-Space Mesh Techniques in Density Functional Theory

This review discusses progress in efficient solvers which have as their foundation a representation in real space, either through finite-difference or finite-element formulations. The relationship of real-space approaches to linear-scaling electrostatics and electronic structure methods is first discussed. Then the basic aspects of real-space representations are presented. Multigrid techniques for solving the discretized problems are covered; these numerical schemes allow for highly efficient solution of the grid-based equations. Applications to problems in electrostatics are discussed, in particular numerical solutions of Poisson and Poisson-Boltzmann equations. Next, methods for solving self-consistent eigenvalue problems in real space are presented; these techniques have been extensively applied to solutions of the Hartree-Fock and Kohn-Sham equations of electronic structure, and to eigenvalue problems arising in semiconductor and polymer physics. Finally, real-space methods have found recent application in computations of optical response and excited states in time-dependent density functional theory, and these computational developments are summarized. Multiscale solvers are competitive with the most efficient available plane-wave techniques in terms of the number of self-consistency steps required to reach the ground state, and they require less work in each self-consistency update on a uniform grid. Besides excellent efficiencies, the decided advantages of the real-space multiscale approach are 1) the near-locality of each function update, 2) the ability to handle global eigenfunction constraints and potential updates on coarse levels, and 3) the ability to incorporate adaptive local mesh refinements without loss of optimal multigrid efficiencies.Comment: 70 pages, 11 figures. To be published in Reviews of Modern Physic