Age-related skeletal muscle atrophy in humans: an immunohistochemical and morphometric study.
The aim of this study was to determine age-related changes in three human muscles with different function and location in the body. The cross sectional area and the percentage of fibers type I, type IIA and type IIX were studied in vastus lateralis, deltoideus and external intercostal muscle. Muscle samples were obtained from 30 male subjects, aged 20-80 years. Fiber types were defined immunohistochemically, using monoclonal antibodies specific for type I, type IIA and type IIX fibers. Cross sectional area of muscle fibers was analyzed morphometrically by computerized image analysis. All muscle fiber types (I, IIA, IIX) showed the reduction in the fiber size in all three examined muscles. In all muscles the proportion of type I and type IIA was changed, but not in type IIX. With increasing age results showed the increase in proportion of type I, while proportion of type IIA fibers decreased, with vastus lateralis muscle being the most affected. These results suggest that age-related muscle atrophy is not a general phenomenon, and does not affect all muscles equally.


Evaluation of genotoxicity of nitrile fragrance ingredients using in vitro and in vivo assays.
Genotoxicity studies were conducted on a group of 8 fragrance ingredients that belong to the nitrile family. These nitriles are widely used in consumer products however there is very limited data in the literature regarding the genotoxicity of these nitriles. The 8 nitriles were assessed for genotoxicity using an Ames test, in vitro chromosome aberration test or in vitro micronucleus test. The positive results observed in the in vitro tests were further investigated using an in vivo micronucleus test. The results from these different tests were compared and these 8 nitriles are not considered to be genotoxic. Dodecanitrile and 2,2,3-trimethylcyclopent-3-enylacetonitrile were negative in the in vitro chromosome aberration test and in vitro micronucleus test, respectively. While citronellyl nitrile, 3-methyl-5-phenylpentanenitrile, cinnamyl nitrile, and 3-methyl-5-phenylpent-2-enenitrile revealed positive results in the in vitro tests, but confirmatory in vivo tests determined these nitriles to be negative in the in vivo micronucleus assay. The remaining two nitriles (benzonitrile and α-cyclohexylidene benzeneacetonitrile) were negative in the in vivo micronucleus test. This study aims to evaluate the genotoxicity potential of these nitriles as well as enrich the literature with genotoxicity data on fragrance ingredients.


Understanding chemical reaction mechanisms in ionic liquids: successes and challenges.
The focus of this article is an examination of chemical reaction mechanisms in ionic liquids. These mechanisms are compared with those pertaining to the same reactions carried out in conventional solvents. In cases where the mechanisms differ, attempts to provide an explanation in terms of the chemical and physicochemical properties of the reactants and of the components of the ionic liquids are described. A wide range of reactions from different branches of chemistry has been selected for this purpose. A sufficient background for student readers has been included. This tutorial review should also be of interest to kineticists, and to both new and experienced investigators in the ionic liquids field.


Bonding in Sulfur-Oxygen Compounds-HSO/SOH and SOO/OSO: An Example of Recoupled Pair π Bonding.
The ground states (X(2)A″) of HSO and SOH are extremely close in energy, yet their molecular structures differ dramatically, e.g., re(SO) is 1.485 Å in HSO and 1.632 Å in SOH. The SO bond is also much stronger in HSO than in SOH: 100.3 kcal/mol versus 78.8 kcal/mol [RCCSD(T)-F12/AVTZ]. Similar differences are found in the SO2 isomers, SOO and OSO, depending on whether the second oxygen atom binds to oxygen or sulfur. We report generalized valence bond and RCCSD(T)-F12 calculations on HSO/SOH and OSO/SOO and analyze the bonding in all four species. We find that HSO has a shorter and stronger SO bond than SOH due to the presence of a recoupled pair bond in the π(a″) system of HSO. Similarly, the bonding in SOO and OSO differs greatly. SOO is like ozone and has substantial diradical character, while OSO has two recoupled pair π bonds and negligible diradical character. The ability of the sulfur atom to form recoupled pair bonds provides a natural explanation for the dramatic variation in the bonding in these and many other sulfur-oxygen compounds.


Cardiac excitation mechanisms, wavefront dynamics and strength-interval curves predicted by 3D orthotropic bidomain simulations.
The assessment and understanding of cardiac excitation mechanisms is very important for the development and improvement of implantable cardiac devices, pacing protocols, and arrhythmia treatments. Previous bidomain simulation studies have investigated cathodal and anodal make/break mechanisms of cardiac excitation and strength-interval (S-I) curves in two-dimensional sheets or cylindrical domains, that by symmetry reduce to the two-dimensional case. In this work, cathodal and anodal S-I curves are studied by means of detailed bidomain simulations which include: (i) three-dimensional cardiac slabs; (ii) transmural fiber rotation; (iii) unequal orthotropic anisotropy of the conducting media; (iv) incorporation of funny and electroporation currents in the ventricular membrane model. The predicted shape of cathodal and anodal S-I curves exhibit the same features of the S-I curves observed experimentally and the break/make transition coincides with the final descending phase of the S-I curves. Away from the break/make transition, only the break or make excitation mechanism is observed independently of the stimulus strength, whereas within an interval at the break/make transition, new paradoxical excitation behaviors are observed that depend on the stimulus strength.


3D Mechanical properties of the layered esophagus: experiment and constitutive model.
The identification of a three dimensional constitutive model is useful for describing the complex mechanical behavior of a nonlinear and anisotropic biological tissue such as the esophagus. The inflation tests at the fixed axial extension of 1, 1.125, and 1.25 were conducted on the muscle and mucosa layer of a porcine esophagus separately and the pressure-radius-axial force was recorded. The experimental data were fitted with the constitutive model to obtain the structure-related parameters, including the collagen amount and fiber orientation. Results showed that a bilinear strain energy function (SEF) with four parameters could fit the inflation data at an individual extension very well while a six-parameter model had to be used to capture the inflation behaviors at all three extensions simultaneously. It was found that the collagen distribution was axial preferred in both layers and the mucosa contained more collagen, which were in agreement with the findings through a pair of uniaxial tensile test in our previous study. The model was expected to be used for the prediction of stress distribution within the esophageal wall under the physiological state and provide some useful information in the clinical studies of the esophageal diseases.


Induction of human matrix metalloproteinase-12 gene transcriptional activity by GM-CSF requires the AP-1 binding site in human U937 monocytic cells.
Matrix metalloproteinase-12 (MMP-12) is critical for the migration of monocytes/macrophages into inflammatory sites through the basement membranes. We previously reported that MMP-12 expression was initially induced by granulocyte macrophage colony-stimulating factor (GM-CSF) in human peripheral blood monocytes and U937 monocytic cells. To further elucidate the molecular mechanism for the regulation of MMP-12 expression by GM-CSF in monocytes, we determined the sequence requirements for the MMP-12 gene transcriptional response of U937 monocytic cells to GM-CSF by using luciferase reporter and electrophoretic mobility shift assays. A series of 5'-deletion and site-directed mutation of the human MMP-12 promoter demonstrated that an AP-1 site spanning the -81 to -75-bp region is critical for the induction of MMP-12 promoter activity by GM-CSF. The electrophoretic mobility shift assay revealed that AP-1 binding activity was increased by GM-CSF treatment and that the AP-1 complex induced by GM-CSF consisted of multiple Jun and Fos isoforms. These results indicate that MMP-12 expression in U937 monocytes was initially induced by GM-CSF through the AP-1 binding activity.


A targeted reweighting method for accelerating the exploration of high-dimensional configuration space.
Time scales available to biomolecular simulations are limited by barriers among states in a high-dimensional configuration space. If equilibrium averages are to be computed, methods that accelerate barrier passage can be carried out by non-Boltzmann sampling. Barriers can be reduced by modifying the potential-energy function and running dynamics on the modified surface. The Boltzmann average can be restored by reweighting each point along the trajectory. We introduce a targeted reweighting scheme where some barriers are reduced, while others are not modified. If only equilibrium properties are desired, trajectories in configuration space can be generated by Langevin dynamics. Once past a transient time, these trajectories guarantee equilibrium sampling when reweighted. A relatively high-order stochastic integration method can be used to generate trajectories. The targeted reweighting scheme is illustrated by a series of double-well models with varying degrees of freedom and shown to be a very efficient method to provide the correct equilibrium distributions, in comparison with analytic results. The scheme is applied to a protein model consisting of a chain of connected beads characterized by dihedral angles and the van der Waals interactions among the beads. We investigate the sampling of configuration space for a model of a helix-turn-helix motif. The targeted reweighting is found to be essential to permit the original all-helical conformation to bend and generate turn structures while still maintaining the alpha-helical segments.


Augmentation of suppression in cyclophosphamide-treated rats bearing allogeneic skin implants in the anterior chamber of the eye.
This study shows that alloantigen presentation via the anterior chamber (AC) of the eye coupled with a single high dose cyclophosphamide (CP) (100 mg/kg) treatment effectively suppresses the skin graft rejection reaction of the recipient. Lewis (Le) rats bearing allogeneic Brown Norway (BN) skin implants in the AC of the eye demonstrate a modest increase in the survival time of orthotopic BN skin grafts. A slight prolongation of the survival of orthotopic BN skin grafts was also demonstrated in nonimplant or syngeneic implant-bearing Le recipients which received a single injection of a large dose of CP. Augmentation of suppression was evident in rats which were treated with a single dose of 75 mg/kg CP but not 25 mg/kg. The augmentation of suppression was evident when CP treatment and skin grafting of the recipient occurred on either 0, 7, or 14 days postimplantation. Recipient splenectomy did not interfere with the augmentation of suppression.


Flavonoid compounds from Pyrus communis L. flowers.
Five flavonoid glycosides: kaempferol 3-O-beta-D-glucopyranoside (IV), isorhamnetin 3-O-beta-D-glucopyranoside (V), isorhamnetin 3-O-beta-D-(6''-O-alpha-L-rhamnopyranosyl)-glucopyranoside (VIII), 8-methoxykaempferol 3-O-beta-D-(2''-O-alpha-D-glucopyranosyl)-glucopyranoside (VI), 8-methoxykaempferol 3-O-beta-D-(2''-O-alpha-L-rhamnopyranosyl)-glucopyranoside (VII) and chlorogenic acid (IX) were isolated from the flowers naturally growing Pyrus communis L. They were identified by chemical and spectroscopic methods.


Real time 3D visualization of ultrasonic data using a standard PC.
This paper describes a flexible, software-based scan converter capable of rendering 3D volumetric data in real time on a standard PC. The display system is used in the remotely accessible and software-configurable multichannel ultrasound sampling system (RASMUS system) developed at the Center for Fast Ultrasound Imaging. The display system is split into two modules: data transfer and display. These two modules are independent and communicate using shared memory and a predefined set of functions. It is, thus, possible to use the display program with a different data-transfer module which is tailored to another source of data (scanner, database, etc.). The data-transfer module of the RASMUS system is based on a digital signal processor from Analog Devices--ADSP 21060. The beamformer is connected to a PC via the link channels of the ADSP. A direct memory access channel transfers the data from the ADSP to a memory buffer. The display module, which is based on OpenGL, uses this memory buffer as a texture map that is passed to the graphics board. The scan conversion, image interpolation, and logarithmic compression are performed by the graphics board, thus reducing the load on the main processor to a minimum. The scan conversion is done by mapping the ultrasonic data to polygons. The format of the image is determined only by the coordinates of the polygons allowing for any kind of geometry to be displayed on the screen. Data from color flow mapping is added by alpha-blending. The 3D data are displayed either as cross-sectional planes, or as a fully rendered 3D volume displayed as a pyramid. All sides of the pyramid can be changed to reveal B-mode or C-mode scans, and the pyramid can be rotated in all directions in real time.


A 15-Plex/xMAP Method to Detect 15 Animal Ingredients by Suspension Array System Coupled with Multifluorescent Magnetic Beads.
A 15-plex/xMAP method was established to simultaneously detect 15 animal ingredients. The method, based on multiplex PCR and the Luminex multifluorescent bead detection system, was able to sensitively differentiate mammal and ruminant species, and in particular, to detect 11 mammal and two poultry species. The estimated sensitivity of a mixed-meat sample was 0.1% (weight percentage). In a survey of commercially processed meat products, nine of 16 samples were found to contain adulterated ingredients. The assay of the 16 samples took only 3 h for the identification of the 15 animal ingredients.


The development and implementation of a standardized policy for the management of dysphagia in motor neurone disease.
Following an audit to determine the standards of the assessment and management of dysphagia within the Wisdom Hospice, a standardized, multidisciplinary dysphagia policy was established, incorporating a dysphagia trained nurse (DTN) scheme. The standards of care of dysphagic patients were audited after its introduction and the results indicate that the resourcing and quality of care difficulties identified have been improved by the implementation of the policy. The service development implications for the management of dysphagia in palliative care settings are discussed.


Implication of liver cardiolipins in mitochondrial energy metabolism disorder in cancer cachexia.
Mitochondrial membranes are essential for the good functioning of the organelle. For instance, the inner mitochondrial membrane contains the oxidative phosphorylation system that permits ATP synthesis. Phospholipids environment and especially cardiolipin are crucial for the mitochondrial energy metabolism. Indeed, cardiolipin is known to provide essential structural and functional support to several proteins involved in oxidative phosphorylation. Alterations in cardiolipin structure, content and fatty acids composition have been associated with mitochondrial dysfunction in several physiopathological conditions and diseases. Cancer cachexia is a complex and dynamic process characterized by a negative energy balance induced by anorexia and hypermetabolism which leads to a drastic loss in body weight that aggravate prognosis of cancer patients. The underlying mechanisms of hypermetabolism are not fully understood. Whether the mitochondrial energy metabolism is altered during this disease and may participate to hypermetabolism is not clear. This mini-review focuses on cardiolipin especially its biosynthesis and remodeling pathways, its relation with mitochondrial energy metabolism and its possible implication in the cancer cachexia syndrome.


Pathogenic implications of human mitochondrial aminoacyl-tRNA synthetases.
Mitochondria are considered as the powerhouse of eukaryotic cells. They host several central metabolic processes fueling the oxidative phosphorylation pathway (OXPHOS) that produces ATP from its precursors ADP and inorganic phosphate Pi (PPi). The respiratory chain complexes responsible for the OXPHOS pathway are formed from complementary sets of protein subunits encoded by the nuclear genome and the mitochondrial genome, respectively. The expression of the mitochondrial genome requires a specific and fully active translation machinery from which aminoacyl-tRNA synthetases (aaRSs) are key actors. Whilst the macromolecules involved in mammalian mitochondrial translation have been under investigation for many years, there has been an explosion of interest in human mitochondrial aaRSs (mt-aaRSs) since the discovery of a large (and growing) number of mutations in these genes that are linked to a variety of neurodegenerative disorders. Herein we will review the present knowledge on mt-aaRSs in terms of their biogenesis, their connection to mitochondrial respiration, i.e., the respiratory chain (RC) complexes, and to the mitochondrial translation machinery. The pathology-related mutations detected so far are described, with special attention given to their impact on mt-aaRSs biogenesis, functioning, and/or subsequent activities. The collected data to date shed light on the diverse routes that are linking primary molecular possible impact of a mutation to its phenotypic expression. It is envisioned that a variety of mechanisms, inside and outside the translation machinery, would play a role on the heterogeneous manifestations of mitochondrial disorders.


Properties of volume-sensitive Cl- channels in a human epithelial cell line.
A regulatory volume decrease is accomplished by parallel activation of Ca(2+)-dependent K+ channels and Ca(2+)-independent Cl- channels in cultured human intestinal epithelial cells (Intestine 407). The anion selectivity of whole-cell currents recorded in osmotically swollen cells falls into the Eisenman type I sequence corresponding to a low-field anion channel. The volume-sensitive Cl- channel has an intermediate unitary conductance. Both the whole-cell and single-channel Cl- currents exhibit unique voltage-dependency. The Cl- current can be maintained in the activated state in the physiological voltage range. However, at very large depolarizations (over +50 mV), the current is quickly inactivated. The Cl- current shows moderate outward rectification. The whole-cell Cl- current is sensitive to Cl- channel blockers such as SITS and NPPB as well as to cis unsaturated fatty acids such as arachidonic acid and oleic acid. The whole-cell current is totally independent of Ca2+ and cyclic AMP, but inhibited by increases in cytosolic free Mg2+ ions. Removal of intracellular ATP, but not Mg2+, abolishes the Cl- current. The ATP role can be substituted for non-hydrolyzable ATP analogs. Therefore, it is likely that intracellular ATP maintains the channel activity through non-hydrolytic binding.


Trimethyltin-induced changes in gross morphology of the hippocampus.
Acute exposure to trimethyltin (TMT) produces alterations in hippocampal morphology. The purpose of this study was to arrive at a simple method for quantitative assessment of the gross changes in morphology which could then be used as a correlate in studies of TMT toxicity. Adult Long-Evans male hooded rats were treated with a single dose of TMT chloride and sacrificed either (a) within 11 days; (b) following 30 days; or (c) 105 days following treatment. Among a variety of morphological measures explored, the easiest and most clearly dosage-related was length of the line of pyramidal cells, from CA1 through CA3c. TMT shortened this line in a dosage- and time-dependent manner. Loss of cells appeared to begin in CA3c and progress through CA3b and CA3a as a dosage and time since treatment increased. It was concluded that this measurement may provide a useful morphological correlate for physiological and behavioral studies of TMT toxicity.


Relationship between semen quality and tobacco chewing in men undergoing infertility evaluation.
Male fertility is affected by a variety of lifestyle habits that include tobacco use. A large population of Indian men is addicted to tobacco chewing. The objective of our study was to assess the relationship between tobacco chewing in these Indian men--who were part of an infertile couple--and their sperm characteristics. Retrospective study. Private infertility clinic. Six hundred thirty-eight male patients undergoing infertility evaluations were grouped according to the frequency of their tobacco chewing habit: mild (< 3 times/day, n = 177), moderate (3-6 times/day, n = 264), and severe (> 6 times/day, n = 197). None. Sperm characteristics (concentration, motility, morphology, and viability). Sperm concentration, percentage motility, morphology, and percentage viability were significantly higher in the mild group vs. the moderate group and in the moderate group vs. the severe group. The percentage of men with azoospermia rose with the level of addiction (1%, 3%, and 14%) as did the percentage of men with oligoasthenoteratozoospermia (2%, 8%, and 29%), although the differences were not statistically significant. In our study, use of chewing tobacco by a group of Indian men who were undergoing infertility evaluation was strongly associated with a decrease in sperm quality and to a lesser extent with oligoasthenozoospermia or azoospermia. Infertile men should be counseled about the adverse effects of tobacco chewing on sperm quality.


Propensity rule for novel selective double photoexcitation of helium atoms in strong static electric fields.
We studied the double photoexcitation spectra of helium in a strong dc electric field and compared the results with the recent experimental data of Harries et al. [Phys. Rev. Lett. 90, 133002 (2003)]]. We derived the propensity rules based on the crossing or noncrossing of energies in the Stark map to predict the selective subset of doubly excited states that are preferentially populated in such experiments. It is shown that the propensity rule is a consequence of the ubiquitous correlation properties of doubly excited states in general.


Autoradiography and density gradient separation of technetium-99m-exametazime (HMPAO) labelled leucocytes reveals selectivity for eosinophils.
Technetium-99m-Exametazime (HMPAO) is widely used for radiolabelling leucocytes for localization of infection. The subcellular distribution of radionuclide in the labelled cells and the distribution of radioactivity among the leukocyte population are incompletely understood. Frozen section autoradiography was used to determine quantitatively the distribution of 99mTc in leucocytes labelled with 99mTc-Exametazime. Sections of rapidly frozen suspensions of labelled leucocytes in plasma were autoradiographed on Ilford K2 emulsion and stained with haematoxylin and eosin. Neutrophils, eosinophils and mononuclear cells were separated by Percoll density gradient centrifugation. Cell nuclei were isolated by a rapid cell-breakage and fractionation method. In a typical experiment mean grain densities [grains/100 microns2 (ESD)] over cells were: eosinophils 31.2 (18.4), neutrophils 3.5 (3.5), mononuclear cells 4.2 (5.1). Mean grain numbers per cell (ESD) were: eosinophils 13 (6.8), neutrophils 1.3 (1.3), mononuclear cells 1.1 (1.3). These findings were confirmed by separation of labelled leucocytes on discontinuous density gradients. In four separation experiments, the mean activity-per-cell ratio for eosinophils to neutrophils was 10.1 (4.8):1, and for eosinophils to mononuclear cells, 14.1 (6.7):1. The subcellular distribution of the label was investigated using image analysis of autoradiographs and cell fractionation. This revealed no selectivity for nuclear or extranuclear compartments. It may be concluded that 99mTc-Exametazime has strong selectivity for eosinophils over other leukocytes but no selectivity for nuclear/cytoplasmic compartments.


Detection of nanoscale magnetic activity using a single carbon nanotube.
The ultimate conductometric sensor for ferromagnetic activity of nanoscale magnetic materials could be a single carbon nanotube. We show that the electrical conductance of an individual carbon nanotube is sensitive to magnetic transitions of nanoscale magnets embedded inside it. To establish this, multiwall carbon nanotubes were impregnated with cobalt nanoclusters. Temperature dependence of conductance (5 K < T <300 K) of these nanotubes shows the usual Lüttinger-liquid power law behavior at higher temperatures and an onset of Coulomb blockade at lower temperatures. At the lowest temperature (T approximately 6 K), the differential conductance (dI/dV versus V) develops aperiodic fluctuations under an external magnetic field B, the rms amplitude of which grows with the magnitude of the field itself. Low-temperature magnetoconductance, studied as function of temperature and bias, can be interpreted in terms of weak antilocalization effects due to the presence of the magnetized clusters. The temperature dependence of magnetoconductance further presents a "peak"-like feature and slow dynamics around T =55 K, which depend on the magnitude and history of the applied B field. These observations indicate a sensitivity of electronic transport in the multiwall nanotubes to the dynamics of nanoscale magnets at low temperature.


The Child and Adolescent Psychiatric Assessment (CAPA).
To describe the Child and Adolescent Psychiatric Assessment (CAPA). The base interview covers the age range from 9 to 17 years. The interview glossary that provides detailed operational definitions of symptoms and severity ratings is described, and psychometric data and further developments of the interview are presented. Across 5,962 parent-child interviews, the core sections of the CAPA (psychiatric symptoms, functional impairment, demographics, family structure and functioning) took on average 59 minutes for children and 66 minutes for parents. Test-retest reliability for diagnoses ranged from kappa = 0.55 for conduct disorder (CD) to kappa = 1.0 for substance abuse/dependence. Validity as judged by 10 different criteria was good. Developments of the CAPA include a shorter "gateway" version using core symptoms as screen items, a Spanish version, and versions for twin studies, use with young adults (YAPA), and preschool-age children (PAPA). There is a place in both research and clinical settings for a rigorously operationalized interview (such as the CAPA) that focuses on ensuring that respondents understand what is being asked and on clearly defining levels of symptom severity and functional impairment.


Usefulness of dura mater in providing DNA samples for identifying cadavers.
We examined the usefulness of the dura mater in identifying human remains. Dura mater was collected from 50 cadavers, including drowned, charred, and mummified remains. The STR genotype using the AmpFlSTR Identifiler Kit could be typed at 15 STR and amelogenin loci in 30 samples of 33 cases. Furthermore, the ABO genotype and amelogenin using gel-based methods could be typed in 44 samples of 50 cases. In cases with successful typing of STR, ABO-DNA, and amelogenin, the longest time after death was from 12 to 26 days in a drowned body. The minimum quantity of dura mater required for DNA extraction was about 2.5 mg, dried and fixed by ethanol, in a cadaver 15 h after death. The state of the DNA from the dura mater from the calvaria may be better than that from the basis cranii interna. We found that DNA from dura mater is one of the most useful samples for forensic identification.


Fused kidneys: morphologic study and theory of embryogenesis.
A study was made of 50 fused kidneys; 41 postmortem specimens and 9 living patients' records were reviewed. Three patterns of renal fusion were identified--midline fused horseshoe kidney [15], laterally fused horseshoe kidney [21], and crossed renal ectopia [14]. These morphologic renal patterns were correlated with coexisting abnormalities of the urinary tract and other organ systems. A high incidence of hydronephrosis of varied etiology, vertebral, and anorectal defects was found in the laterally fused horseshoe and crossed renal ectopic groups. A theory of embryogenesis was developed to explain the asymmetric patterns of renal fusion exemplified by laterally fused and crossed fused kidneys. It was based on the effects that the lateral flexion and rotation of the hind end in the 4- to 5-mm embryo exert on the relative positions of the nephrogenic cords and wolffian ducts.


Enhancement along the normal facial nerve in the facial canal: MR imaging and anatomic correlation.
Normal facial nerves are reported to show no enhancement at magnetic resonance (MR) imaging, in contradiction to the authors' clinical experience. To investigate this inconsistency, the authors searched MR imaging files and clinical records to find patients who underwent MR imaging of the temporal bone (at 1.5 T) before and after intravenous administration of gadopentetate dimeglumine and who had bilateral clinically normal facial nerves. When the MR images of 93 patients (186 facial nerves) were analyzed subjectively, 142 nerves (76%) were visibly enhanced along at least one segment of the facial nerve within the facial canal; the nerves of 64 of the 93 patients (69%) showed right-left asymmetry in enhancement, which was inhomogeneously distributed along each nerve. The facial nerve in the cerebellopontine angle cistern and in the internal auditory canal, as well as in the visualized proximal portion of the extracranial facial nerve, showed no enhancement. Comparison with reference anatomic sections showed that this enhancement pattern corresponded exactly to the topography of the circumneural facial arteriovenous plexus and should not necessarily be considered a sign of anatomic abnormality.


Screening of Potential Inhibitor against Coat Protein of Apple Chlorotic Leaf Spot Virus.
In this study, we analyzed Coat protein (CP) of Apple chlorotic leaf spot virus (ACLSV), an important latent virus on Apple. Incidence of the virus is upto 60% in various apple cultivars, affecting yield losses of the order of 10-40% (depending upon the cultivar). CP plays an important role as the sole building block of the viral capsid. Homology approach was used to model 193 amino acid sequence of the coat protein. We used various servers such as ConSurf, TargetS, OSML, COACH, COFACTOR for the prediction of active site residues in coat protein. Virtual screening strategy was employed to search potential inhibitors for CP. Top twenty screened molecules considered for drugability, and toxicity analysis and one potential molecule was further analyzed by docking analysis. Here, we reported a potent molecule which could inhibit the formation of viron assembly by targeting the CP protein of virus.


Sorafenib down-regulates c-IAP expression post-transcriptionally in hepatic carcinoma cells to suppress apoptosis.
Hepatocellular carcinoma (HCC) is one of leading causes of cancer-related death with a heterogeneous patient demographic and divergent pathogenic pathways. Sorafenib is the first effective drug approved for the treatment of HCC. Although it is known that sorafenib promotes apoptosis of HCC cells, the underlying mechanism remains largely obscure. Here we report that sorafenib down-regulates protein expression of the anti-apoptotic protein c-IAP1 in a time- and dose-dependent manner in HCC cells in vitro and in vivo. Furthermore, we demonstrate that sorafenib represses c-IAP1 levels without altering its transcription or protein stability. Instead, sorafenib attenuates c-IAP1 translation by targeting the internal ribosome entry site (IRES) within the c-IAP1 mRNA. Finally, ectopic expression of c-IAP1 alleviates sorafenib induced cancer cell apoptosis. In conclusion, our data highlight a previously unidentified pathway that contributes to sorafenib mediated HCC cell apoptosis and as such provide novel mechanistic insight into the rational use of sorafenib in treating HCC.


Eutopic endometrium and peritoneal, ovarian and bowel endometriotic tissues express a different profile of matrix metalloproteinases-2, -3 and -11, and of tissue inhibitor metalloproteinases-1 and -2.
Endometriosis is subsequent to the ability of endometrial glands to invade normal tissues. Matrix metalloproteinases (MMPs)--enzymes that mediate normal tissue turnover, including endometrial breakdown during menstruation-appear to be involved in this invasive process. Here, we examined the immunohistochemical expression of MMP-2, MMP-3, MMP-11, tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2 in endometrium from women with (n=9) or without endometriosis (n=18) in comparison with peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20). Women with endometriosis showed decreased endometrial MMP-2 expression compared with women without endometriosis (mean+/-SD positive cells: 24.3+/-28.3% and 69.3+/-12.1%), together with loss of MMP-3 expression (0 versus 17.5%+/-20.2). MMP-11, TIMP-1 and TIMP-2 expression was similar in the two groups. Endometrial MMP-2, -3 and -11 expression and TIMP-1 and -2 expression were similar in women with endometriosis and in those with peritoneal endometriosis. MMP-2, -3 and -11 expression was higher in colorectal endometriosis than in ovarian and peritoneal endometriosis. TIMP-2 expression was lower in colorectal endometriosis (P=0.0002) and ovarian endometriotic cysts (P=0.003) than in peritoneal endometriosis. TIMP-1 expression did not vary according to the location of endometriotic lesions. These results suggest that MMP-2 and -3 and TIMP-2 may be involved in the pathogenesis of endometriosis. Interestingly, MMP-2 and -3 overexpression was related to the infiltrative nature of endometriotic lesions, with possible sequential expression from peritoneal to colorectal endometriosis.


Treatment-resistant medication overuse headache can be cured.
To evaluate the long-term efficacy of a structured, multidisciplinary treatment program in patients who had been treated unsuccessfully for medication overuse headache by specialists in an open-label design. Medication overuse headache is a common and disabling disease. Management is complicated by substantial treatment failure and relapse, and those who relapse and nonresponders to treatment are often excluded from studies on medication overuse headache. Patients with medication overuse headache who had previously been unsuccessfully treated by specialists and referred to a specialized, tertiary headache centre were recruited. They underwent a structured 2-month detoxification program and were subsequently closely followed up for 10 months by a multidisciplinary team of physicians, nurses, physiotherapists, and psychologists. Eighty-six of 98 patients completed the study. At 12-month follow-up, headache frequency was reduced by 39.3% (P < .001), 71 patients (82.6%) remained cured of medication overuse, reduction in headache frequency of more than 50% occurred in 42 patients (48.8%), and 52 (60.5%) reverted to episodic headache. Both of these figures had increased significantly from month 2 to month 12 (P < .001). Medication use was reduced by 62.8% (P < .001). Patients with medication overuse headache previously regarded treatment-resistant benefit considerably from multidisciplinary treatment in a structured detoxification program with close follow-up.


Fat-specific protein 27, a novel lipid droplet protein that enhances triglyceride storage.
Fat-specific protein (FSP)27/Cidec is most highly expressed in white and brown adipose tissues and increases in abundance by over 50-fold during adipogenesis. However, its function in adipocytes has remained elusive since its discovery over 15 years ago. Here we demonstrate that FSP27/Cidec localizes to lipid droplets in cultured adipocytes and functions to promote lipid accumulation. Ectopically expressed FSP27-GFP surrounds lipid droplets in 3T3-L1 adipocytes and colocalizes with the known lipid droplet protein perilipin. Immunostaining of endogenous FSP27 in 3T3-L1 adipocytes also confirmed its presence on lipid droplets. FSP27-GFP expression also markedly increases lipid droplet size and enhances accumulation of total neutral lipids in 3T3-L1 preadipocytes as well as other cell types such as COS cells. Conversely, RNA interference-based FSP27/Cidec depletion in mature adipocytes significantly stimulates lipolysis and reduces the size of lipid droplets. These data reveal FSP27/Cidec as a novel adipocyte lipid droplet protein that negatively regulates lipolysis and promotes triglyceride accumulation.


Retinoic acid-induced Smad3 expression is required for the induction of osteoblastogenesis of mesenchymal stem cells.
Mesenchymal stem cells are pluripotent precursor cells that can differentiate into osteoblasts, adipocytes, chondrocytes and myocytes. Despite their important therapeutic potential little is known about the transcriptional cascades that govern lineage decisions in these cells. Treatment of C3H10T1/2 mouse mesenchymal stem cells with retinoic acid (RA) inhibits adipogenesis and enhances osteoblastogenesis. In particular, RA treatment stimulates the expression of the osteoblast master regulator, runt-related transcription factor 2 (Runx2), whose expression is necessary for the formation of bone. We have shown previously in mesenchymal stem cells that RA acts to stimulate osteoblastogenesis by interfering with the actions of the bzip transcription factor CCAAT/Enhancer Binding Protein beta (C/EBPβ), where it binds to a negative regulatory element within the Runx2 promoter and inhibits its expression. Herein we show that Smad3, whose expression is stimulated by RA, relays the effects of RA on differentiation by initiating the displacement of C/EBPβ from the Runx2 promoter. In addition to stimulating Smad3 expression, RA also stimulated the nuclear localization of this factor, such that in the absence of RA, ectopic Smad3 was unable to drive osteoblastogenesis. While not sufficient to promote osteoblastogenesis, knockdown of Smad3 using a specific shRNA prevented the RA-mediated stimulation of differentiation and displacement of C/EBPβ from the Runx2 P1 promoter. Taken together, these data indicate that Smad3 is an important mediator of RA activity during mesenchymal stem cell differentiation and is necessary for the stimulation of osteoblastogenesis.


Getting the most out of Student Selected Components: 12 tips for participating students.
Student Selected Components (SSCs) are an established feature of UK undergraduate medical curricula that offer students choice. They represent a large investment in time and resources. Although programmes vary between Schools, the major learning objectives remain broadly similar. Providing students engage fully with the activity, the final learning outcomes should also be comparable. However, engaging effectively and purposefully with such programmes may not be a clear and straightforward process for students. To present the challenges and solutions to inform students how to derive the greatest benefit from the learning activities in their SSC programmes. Synthesis of the accumulated experience over more than 10 years of developing, running and evaluating SSCs by the Directors of SSCs in five Scottish Medical Schools, combined with analysis of course evaluation and student feedback. Consensus defined 12 tips aimed at improving the approach taken by students to their SSCs, and to provide a structure to maximise their final learning outcomes. SSC programmes provide diverse opportunities for students to develop and expand their learning. With increasing emphasis being placed upon student assessment to judge a wide range of professional skills and standards into foundation and specialist training, much greater importance is now being given to SSCs as an opportunity for personal, professional and academic developments. However, it is important that this is performed in a purposeful manner to maximise this opportunity. These 12 tips provide guidance to students on how they can maximise the opportunity presented to them by SSCs.


[Anomaloscopic results in extrem-anomalous trichromats (author's transl)].
The results in 55 extreme deuteran and 34 extreme protan trichromats examined with the anomaloscope are reported, which make together about 9% of all red-green vision disturbances in a group of Federal Army relatives. Not only the deuteran but also the protan group make fewer mistakes with red colours as with green.


Studies on viral leukoencephalomyelitis and swayback in goats.
Six kid goats with CNS disease were studied by a variety of techniques. All had morphological evidence of Viral Leukoencephalomyelitis of Goats. (VLG) characterized by demyelinating encephalomyelitis and pneumonitis. Attempts were made to isolate a virus from 5 of these goats by direct culture of CNS and visceral tissues. Syncytial formation was found in some lung, spleen and bone marrow cultures but syncytia were found to be free of complete virus by electron microscopy. When newborn goats were inoculated with syncytia forming cells, a visna-like virus was found in bone marrow cultures of 1 goat 8 days post inoculation. Bone marrow cells from a twin goat 3 months after inoculation produced syncytia without complete virus. it is suggested that complete virus might be present in goats shortly after infection, while persisting in an incomplete form. Three of the 6 goats studied also had lesions of swayback with diffuse encephalomyelopathy and low liver copper levels. Control copper levels in kids with non-neurological disease were variable, occasionally being as low as swayback animals. The experience of others that swayback in the goat and low copper status are poorly correlated is confirmed. Discrepancies inherent in assaying formalin preserved tissues for copper are described.


Morphine in postmortem blood: its importance for the diagnosis of deaths associated with opiate addiction.
This article describes an analytical method for the determination of morphine, the active metabolite of heroin, in post-mortem blood by HPLC with electrochemical detection. An extraction technique allowing the determination of free and total morphine (free morphine + morphine glucuronide) was used. Blood morphine levels in postmortem cases are reported and the ratio of free to total morphine was measured in 52 cases obtained at autopsy. The importance of this ratio is discussed in relation to the circumstances of the death.


Reciprocal focus profile.
A focus profile having a steeper peak is more resistant to image noise in the autofocus (AF) process of a digital camera. However, a focus profile of such shape normally has a flatter out-of-focus region on either side of the profile, resulting in a slow AF process due to the lack of clue about where the lens should move when the lens is in such regions. To address the problem, we provide a statistical analysis of the focus profile and show that a strictly monotonic transformation of the focus profile preserves the accuracy of the AF. On the basis of this analysis, we propose a new focus profile representation that transforms the focus profile to the reciprocal domain in which the reciprocal focus profile is modeled by a polynomial function. This transformation makes the AF mathematically tractable and boosts the search speed. Experimental results are shown to demonstrate the advantage of the proposed representation.


Inhibitory effect of regucalcin on Ca2+/calmodulin-dependent cyclic AMP phosphodiesterase activity in rat kidney cytosol.
The effect of regucalcin, a novel Ca2+-binding protein, on Ca2+/calmodulin-dependent cyclic adenosine monophosphate (AMP) phosphodiesterase activity in the cytosol of rat renal cortex was investigated. Regucalcin with physiologic concentration (10[-7] M) in rat kidney had no effect on cyclic AMP phosphodiesterase activity in the absence of CaCl2 and calmodulin. However, the activatory effect of both CaCl2 (10 microM) and calmodulin (20 U/ml) on cyclic AMP phosphodiesterase was markedly inhibited by the addition of regucalcin (10[-8] to 10[-6] M) in the enzyme reaction mixture. The inhibitory effect of regucalcin on the enzyme activity was also seen in the presence of CaCl2 (5-50 microM) or calmodulin (5-50 U/ml) with increasing concentrations. The presence of trifluoperazine (10 microM), an antagonist of calmodulin, caused a partial inhibition of Ca2+/calmodulin-dependent cyclic AMP phosphodiesterase activity. This inhibition was further enhanced by the addition of regucalcin (10[-7] M). The inhibitory effect of regucalcin (10[-7] M) was not seen in the presence of 20 microM trifluoperazine. Moreover, the activatory effect of calmodulin (20 U/ml) on cyclic AMP phosphodiesterase was not entirely seen, when calmodulin was added 10 min after incubation in the presence of CaCl2 (10 microM) and regucalcin (10[-7] M). The present results demonstrates that regucalcin has an inhibitory effect on Ca2+/calmodulin-dependent cyclic AMP phosphodiesterase activation in the cytosol of rat renal cortex.


Hospital safety and infection control: an update on new dangers and liability trends.
Patient and employee safety remains high on the list of hospital problems, with a number of new challenges facing safety officials. Lawsuits for negligent safety, the leading source of litigation against health care facilities, continue to produce costly judgments. In this update, we'll present a number of problems to watch out for and review some recent slip and fall and injury cases.


Storage of vaccines in different health centers and pharmacies at Karachi, Pakistan: The handling errors.
The fundamental human desire is prevention from the infectious disease. Vaccine is the basic element to fulfill this human craving. The proper handling of vaccine can minimize the degradation. The main aim of this study is to find out the knowledge of respondents and storage condition and handling of marketed vaccines in different private clinics, hospitals and community pharmacies in Karachi, Pakistan. The present study revealed that ~77% have been allowed to visit their vaccine storage compartment. The cumulative knowledge of respondents regarding recommended temperature, shake test, thermal, freezing and photo degradation were 49.34%, 24.01%, 95.78%, 54.35% and 47.23% respectively. The major mishandling like the medicines, food and drinks and even laboratory specimen have been noticed 76.3%, 61.62% and 5.35% respectively. Moreover, water filled bottles on upper, lower and door shelves and ice packs or ice trays 3.43% and 14.18%, respectively, have been found in refrigerators and freezers, respectively. No expired vaccines have been found. The major consequence, in the study has been found to be mishandling by the absence of non-professional personnel. Either doctors or pharmacist (health associated professionals) as respondents were nearly all aware about the consequences of the mishandling of vaccines and have the knowledge about the recommended temperature, thermal, photo degradation, and freezing hazards of vaccines. The world-renowned immunization authorities have strongly recommended national/local immunization programs. On the basis of the present study, it is recommended to train the staff and prepare a national guideline for the storage and handling of vaccines, and forcefully implements the law to adopt the particular guideline.


An association of upper respiratory cancer with exposure to diethyl sulfate.
A morbidity and mortality study of workers at an alcohol manufacturing plant which included several weak acid isopropyl alcohol units and a strong acid ethanol unit is described. An excess mortality of upper respiratory cancer was found and associated with work on the strong acid ethanol unit. The strong acid ethanol process used resulted in high concentrations of diethyl sulfate, which has been shown to be carcinogenic in animals, and the unit, which closed on 1975, had significant opportunities for worker exposure to diethyl sulfate. These facts, plus previous reports of excess upper respiratory cancer on strong acid isopropyl alcohol units with similarly high concentrations of the animal carcinogen diisopropyl sulfate, lead to the tentative conclusion that diethyl sulfate was primarily responsible for the ethanol unit cancer cases. In the modern weak acid isopropyl alcohol plants, where only trace amounts of diisopropyl sulfate are present and exposures are much lower, the problems found on the old strong acid units do not exist.


Maintenance of open gay relationships: some strategies for protection against HIV.
The role of sexual exclusivity (monogamy) in relation to HIV, and the use of rule making in non-exclusive (open) relationships, are discussed. Data from interviews with 387 homosexually active men are presented. The most common sexual/relational configuration amongst these men is that of open relationships. Sexual non-exclusivity was found to be associated with longer relationships, and a greater age difference between partners. The strategies some of these men are using to maintain sexually non-exclusive relationships are outlined. These rules pertain both to interpersonal dynamics and HIV prevention. Differing epidemiological significance of the rules and some implications for health education are discussed.


A SARS-CoV protein, ORF-6, induces caspase-3 mediated, ER stress and JNK-dependent apoptosis.
Severe acute respiratory syndrome (SARS) coronavirus (CoV) spread from China to more than 30 countries, causing severe outbreaks of atypical pneumonia and over 800 deaths worldwide. CoV primarily infects the upper respiratory and gastrointestinal tract; however, SARS-CoV has a unique pathogenesis because it infects both the upper and lower respiratory tracts and leads to human respiratory diseases. SARS-CoV genome has shown containing 14 open reading frames (ORFs) and 8 of them encode novel proteins. Previous reports show that overexpression of ORF-3a, ORF-3b and ORF-7a induce apoptosis. In this report, we demonstrate that overexpression of ORF-6 also induces apoptosis and that Caspase-3 inhibitor and JNK inhibitor block ORF-6 induced apoptosis. Importantly, the protein level of ER chaperon protein, GRP94, was up-regulated when ORF-6 was overexpressed. All these data suggest that ORF-6 induces apoptosis via Caspase-3 mediated, ER stress and JNK-dependent pathways.


The effect of charcoal hemoperfusion on the catecholamine levels in severely intoxicated patients.
The plasma adrenaline and noradrenaline levels in patients with shock due to severe drug intoxication are elevated. Important extration of the catecholamines by the charcoal during combined hemoperfusion-hemodialysis treatment does not result in depletion.


Determination of 19 drugs of abuse and metabolites in whole blood by high-performance liquid chromatography-tandem mass spectrometry.
A high-performance liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method has been developed and validated for the determination of 19 drugs of abuse and metabolites and used in whole blood. The following compounds were included: amphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylenedioxymethamphetamine, methamphetamine, cocaine, benzoylecgonine, morphine, 6-acetylmorphine, codeine, methadone, buprenorphine, norbuprenorphine, ketobemidone, tramadol, O-desmethyltramadol, zaleplone, zolpidem, and zopiclone. The sample pretreatment consisted of solid-phase extraction using mixed-mode columns (Isolute Confirm HCX). Deuterated analogues were used as internal standards for all analytes, except for ketobemidone and O-desmethyltramadol. The analytes were separated by a methanol/ammonium formate gradient using high-performance LC (Agilent HPLC 1100) with a 3 mm x 100 mm Varian Pursuit 3 C(18) column, 3-microm particle size, and were quantified by MS/MS (Waters Quattro micro tandem quadrupole mass spectrometer) using multiple reaction monitoring in positive mode. Two transitions were used for all analytes, except for tramadol and O-desmethyltramadol. The run time of the method was 35 min including the equilibration time. For all analytes, responses were linear over the range investigated, with R(2) > 0.99. One-point calibration was found to be adequate by validation, thereby saving analysis of multiple calibrators. The limits of quantification (LOQs) for the analytes ranged from 0.0005 to 0.01 mg/kg. Absolute recoveries of the analytes were from 34 to 97%, except for zaleplone (6%). Both the interday precision and the intraday precision were less than 15% (20% at the LOQ) for all analytes, except buprenorphine, norburprenorphine, and zaleplone (less than 18%). Accuracy (bias) was within +/-15% (+/-20% at the LOQ) for all analytes, except MDMA and O-desmethyltramadol (within +/-19%). No ion suppression or enhancement was seen nor was suppression from coeluted analytes seen. Matrix effects were found to be less than 23% for all analytes, except zopiclone (64%). High-concentration and low-concentration quality control samples gave acceptable values, and the method has been tried in international proficiency test schemes with good results. The present LC-MS/MS method provides a simple, specific, and sensitive solution for the quantification of some of the most frequent drugs of abuse and their metabolites in whole blood. The quantification by LC-MS/MS was successfully applied to 412 forensic cases from October 2008 to mid February 2009, where 267 cases were related to zero-tolerance traffic legislation.


[Problems in the genetics of peptic ulcer. I. The nature of the inheritance and an analysis of different forms of the disease].
The analysis of literary data on the genetic investigation of duodenal ulcer is given. The investigation proper represents the analysis of 537 pedigree probands with various forms of duodenal ulcer and of 600 families of the control group. Basing on the analysis of distribution of frequency of forms of the disease, segregation analysis, as well as the distribution of forms of duodenal ulcer depending on the sex and age of the manifestation, the discrepancy is demonstrated of the opinion that duodenal ulcer is a monogenic disease, and a conclusion is drawn about the polygen conditionality of genetic component of various forms. The data have been obtained testifying in favour of a considerable heterogeneity of the duodenal ulcer and also the importance of the contribution to the genetic factors in the realization of different forms of the disease, which are approximately 60%. Some difficulties are illustrated, arising during the analysis of multifactorial disease, and the necessity is demonstrated of accounting its certain features (e.g. sex, the age of manifestation) during the interpretation of the results obtained.


Two new species of Plutomurus Yosii (Collembola, Tomoceridae) from the Caucasus.
Two new species of Plutomurus, P. pichkhaiai sp. nov. from Garakha and Letsurtsume caves and P. shurubumuensis sp. nov. from Shurubumu Cave (Chkhorotsku district, Western Georgia) are described, and illustrated. The new species are very similar to P. kelasuricus from the Tsebelda karst massif formation in Apkhazeti, Georgia, but differ in having two inner spine-like chaetae on the inner edge of the hind tibiotarsus (only one in P. kelasuricus) and in occupying different, isolated cave formations separated by a geographic distance of nearly a 100 km. A key to the species of Plutomurus with 6 prelabral chaetae is provided.


Mechanisms of impaired glucose tolerance and insulin secretion during isoflurane anesthesia.
Volatile anesthetics impair insulin secretion and glucose utilization; however, the precise mechanism of action that underlies these effects is unknown. The authors hypothesized that isoflurane inhibits glucose-induced inhibition of adenosine triphosphate-sensitive potassium channel activity in pancreatic beta cells, which could result in impaired insulin secretion and glucose tolerance. Intravenous glucose tolerance tests were performed on 28 male Japanese White rabbits anesthetized with sodium pentobarbital. Glibenclamide (50 microg/kg + 33.5 microg x kg x h) or vehicle was administered 75 min before intravenous administration of 0.6 g/kg glucose. Half of the animals (n = 7) in the vehicle and glibenclamide groups received isoflurane at 1.0 minimum alveolar concentration 30 min before administration of glucose, and the other half received a vehicle control. Hemodynamics, blood glucose, and plasma insulin were measured. A cell-attached patch clamp configuration was used to record single channel currents in the pancreas from male Swiss-Webster mice. Isoflurane alone or a combination of isoflurane and glibenclamide inhibited the insulinogenic index to a greater extent than in the vehicle and glibenclamide groups. In the patch clamp experiments, channel activity was significantly decreased as the glucose concentration was increased from 0 to 10 mm. The subsequent application of 0.5 mm isoflurane reversed the effects of glucose on channel activity. These results show that isoflurane impairs insulin secretion and glucose utilization. The mechanism of action responsible for these effects may involve a decrease in glucose-induced inhibition of adenosine triphosphate-sensitive potassium channel activity in pancreatic beta cells.


Olivocerebellar fiber maturation in normal and lurcher mutant mice: defective development in lurcher.
Olivocerebellar fiber maturation was examined in normal and lurcher mutant mice between postnatal day 5 (P5) and P15, using the anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) from the inferior olive. Immunocytochemistry for the Purkinje cell marker PEP-19 was used to demonstrate Purkinje cell development in the same material. In mutant and normal animals, a regional developmental variation is observed such that, when compared at a given age, cortex lining the vermal fissures appears developmentally advanced over cortex in the cerebellar hemispheres. In the primary fissure of the normal animals, the first recognizable Purkinje cell dendrites appear on P6, and the olivocerebellar fibers first enter the climbing stage of their development on P9. In lurcher animals Purkinje cell development proceeds on this schedule, but olivocerebellar fibers are never observed to enter the molecular layer. These afferents maintain dense perisomatic nests around Purkinje cells, even in P13-15 lurchers. Examination of P14 lurchers by transmission electron microscopy indicates that the olivocerebellar fibers form synapses on Purkinje cell somatic spines and that the basket cell axons fail to form their typical perisomal nests around Purkinje cells. In addition, parallel fibers can be observed to synapse on dendritic spines on the Purkinje cell primary dendrites. We interpret these results as indicating a recognition defect between olivocerebellar fibers and Purkinje cell dendrites. An analysis of this defect in lurcher may reveal how the normal transformation of olivocerebellar fibers, from perisomal to dendritic terminals, is achieved.


Propranolol and prednisolone combination for the treatment of segmental haemangioma in PHACES syndrome.
Posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe syndrome (also known as PHACES syndrome) is a rare neurocutaneous disorder. Children presenting with these manifestations need careful ophthalmological, cardiac and neurological assessment. They may have one or more of these extracutaneous manifestations, the most common being cerebral and cardiovascular anomalies. There is controversy about treating these children with propranolol especially if they have cerebrovascular involvement with narrow, dysplastic or absent blood vessels. The concern with propranolol is that hypotension may lead to reduced cerebral blood flow and neurological consequences. Prior to propranolol the systemic treatment for haemangiomas was prednisolone and then the concern was the opposite, namely hypertension. Our proposal was whether a combination of these two drugs would provide a safer and faster recovery. We report three retrospective cases of PHACES syndrome, each of whom received treatment with a combination of propranolol and prednisolone: two children were started on prednisolone and propranolol was added because the haemangiomas failed to respond adequately; the third child was started on propranolol and developed peripheral ischaemia and ulceration necessitating a reduction in dose addition of a low dose of prednisolone. All three patients, who failed on the one treatment, responded well to combination therapy without any significant complications. These outcomes suggest that for some patients with PHACES syndrome the use of combination treatment with propranolol and prednisolone could be advantageous, potentially allowing for the introduction of low doses of each with an enhanced combined effect. The doses can be increased gradually depending on the magnetic resonance imaging findings.


First observation of African tigerfish Hydrocynus vittatus predating on barn swallows Hirundo rustica in flight.
A population of African tigerfish Hydrocynus vittatus from the Schroda Dam, actively prey on barn swallows Hirundo rustica in flight. This behaviour was discovered during a radio telemetry study and documented using a motion picture video camera. These results show that an avivorous diet is a part of the feeding biology of H. vittatus, and may occur in other populations.


Color Doppler tissue imaging in assessing the elastic properties of the aorta and in predicting coronary artery disease.
We hypothesized that the change in aortic elastic properties could directly be shown with color Doppler tissue imaging (CDTI), that these findings could be related to aortic stiffness and distensibility and that, through these, coronary artery disease (CAD) could be predicted. One hundred and twenty six patients (group I: 83 with CAD, mean age 54+/-10 years, 18 female, 65 male; group II: 43 without CAD, mean age 53+/-10 years, 27 female, 16 male) having been evaluated for coronary artery disease by angiography were examined by echocardiography. Arterial pressure was measured immediately before echocardiographic evaluation. Internal aortic systolic and diastolic diameters by M-mode echocardiography and aortic upper wall tissue velocities (Aortic S, E, A, m/sec) by CDTI were measured 3 cm above the aortic valve. Lateral mitral annulus tissue velocities (Annulus S, E, A, m/sec) were also recorded. Aortic distensibility (cm2 x dynes(-1)) and aortic stiffness index were calculated using formulas. In the statistical analyses, CAD risk factors and left ventricular ejection fraction were used for adjustment. Aortic stiffness (2.79+/-3.49 vs 1.62+/-1.31, P=0.03), distensibility (1.55+/-1.46 vs 2.37+/-3.08, P=0.04), and aortic S velocity (0.057+/-0.016 vs 0.064+/-0.015, P=0.02) differed significantly between groups I and II. After adjustment, while aortic stiffness and S velocity were still statistically different (P=0.04; P=0.03 respectively), the significance of the difference in aortic distensibility disappeared (P=0.051). Aortic stiffness and aortic S velocity (0.06 m/sec<) were important CAD determinants (Odds ratio=1.4 P=0.03; Odds ratio=3.6 P=0.01, respectively), but aortic distensibility was not. Aortic stiffness was correlated only with aortic S velocity (r=-0.28, P=0.01), and aortic distensibility had a significantly positive correlation with aortic S velocity (r=0.20, P=0.02). The interobserver and intraobserver correlation coefficients for aortic S velocities were 0.65 and 0.71, respectively (P<0.05). Elastic properties of the aorta can directly be assessed by reproducibly measuring the movements in the upper wall of the aorta by CDTI. Reduced aortic S velocity is associated with increased aortic stiffness. Increased aortic stiffness and reduced aortic S velocity are important predictors of CAD.


Application of a random effects negative binomial model to examine tram-involved crash frequency on route sections in Melbourne, Australia.
Safety is a key concern in the design, operation and development of light rail systems including trams or streetcars as they impose crash risks on road users in terms of crash frequency and severity. The aim of this study is to identify key traffic, transit and route factors that influence tram-involved crash frequencies along tram route sections in Melbourne. A random effects negative binomial (RENB) regression model was developed to analyze crash frequency data obtained from Yarra Trams, the tram operator in Melbourne. The RENB modelling approach can account for spatial and temporal variations within observation groups in panel count data structures by assuming that group specific effects are randomly distributed across locations. The results identify many significant factors effecting tram-involved crash frequency including tram service frequency (2.71), tram stop spacing (-0.42), tram route section length (0.31), tram signal priority (-0.25), general traffic volume (0.18), tram lane priority (-0.15) and ratio of platform tram stops (-0.09). Findings provide useful insights on route section level tram-involved crashes in an urban tram or streetcar operating environment. The method described represents a useful planning tool for transit agencies hoping to improve safety performance.


[Application of rat tail collagen in the primary culture of rats marginal cells of stria vascularis].
To study the feasibility of application of rat-tail collagen in the primary culture of rats marginal cells of stria vascularis. The effect of self-made rat-tail collagen on the primary culture of rats marginal cells of stria vascularis was observed and estimated. When cochlear stria vascularis fragment was isolated and cultured for 24 h, a few culture cells appeared around the fragments. About 48 to approximately 72 h later, clusters of culture cells could be seen,these cells showed the cobblestone shape under the microscope. The immunohistochemistry and the transmission electron microscopy showed the epithelial origination of these cells. It is feasible to the primarily culture the rats marginal cells of stria vascularis with self-made rat-tail collagen.


The unique N-terminal region of SRMS regulates enzymatic activity and phosphorylation of its novel substrate docking protein 1.
SRMS (Src-related tyrosine kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites) belongs to a family of nonreceptor tyrosine kinases, which also includes breast tumour kinase and Fyn-related kinase. SRMS, similar to breast tumour kinase and Fyn-related kinase, harbours a Src homology 3 and Src homology 2, as well as a protein kinase domain. However, unlike breast tumour kinase and Fyn-related kinase, SRMS lacks a C-terminal regulatory tail but distinctively possesses an extended N-terminal region. Both breast tumour kinase and Fyn-related kinase play opposing roles in cell proliferation and signalling. SRMS, however, is an understudied member of this family. Although cloned in 1994, information on the biochemical, cellular and physiological roles of SRMS remains unreported. The present study is the first to explore the expression pattern of SRMS in breast cancers, its enzymatic activity and autoregulatory elements, and the characterization of docking protein 1 as its first bonafide substrate. We found that, similar to breast tumour kinase, SRMS is highly expressed in most breast cancers compared to normal mammary cell lines and tissues. We generated a series of SRMS point and deletion mutants and assessed enzymatic activity, subcellular localization and substrate recognition. We report for the first time that ectopically-expressed SRMS is constitutively active and that its N-terminal region regulates the enzymatic activity of the protein. Finally, we present evidence indicating that docking protein 1 is a direct substrate of SRMS. Our data demonstrate that, unlike members of the Src family, the enzymatic activity of SRMS is regulated by the intramolecular interactions involving the N-terminus of the enzyme and that docking protein 1 is a bona fide substrate of SRMS.


Gene expression of EXT1 and EXT2 during mouse brain development.
Heparan sulfate (HS) and heparan sulfate proteoglycans (HSPGs) play significant roles in various biological processes. There is a wealth of circumstantial and experimental evidence suggesting the roles of HS in mammalian neural development. HS synthesis is governed by a series of enzymes. Among them, two enzymes, EXT1 and EXT2, catalyze polymerization of glucuronic acid and N-acetylglucosamine, the crucial step of HS synthesis. To obtain insight into the roles of HS in neural development, we examined the spatiotemporal expression patterns of EXT1 and EXT2 during mice brain development. RT-PCR analyses showed that expression of EXT1 and EXT2 peaks during early postnatal period in the cerebrum and around birth in the cerebellum. In situ hybridization revealed that in the embryonic brain, EXT1 and EXT2 were localized primarily in the neuroepithelial cells surrounding the lateral ventricles, the mesencephalic vesicle, and the fourth ventricle. In the early postnatal stage, intense expression of EXT1 and EXT2 was observed in the cerebral cortex and the hippocampus formation. In the postnatal cerebellum, expression of EXT1 and EXT2 was mainly observed in external and internal granular layers. Our results demonstrate that EXT1 and EXT2 are highly expressed in the developing brain, and that their expression is developmentally regulated, suggesting that HS is involved in various neurodevelopmental processes.


[Concentration levels of thyroxine binding globulin and thyroxine in the blood of euthyroid children. Reliability and diagnostic value of the T4/TBG quotiens--establishing reference values].
The most important transportprotein for thyroxine (T4) is the thyroxine-binding globulin (TBG). This protein and T4 were determined using the radioimmunoassay method in bloodserum of 443 euthyreotic children. The age-specific analysis showed high TBG and T4 concentrations in the postnatal phase, nearly constancy between 1. and 9. years with concentrations in the upper physiological range of adults, elevation of the values in the age of 10/11. years and definite attainment of the normal range for adults at 12/13. years. The importance of the T4/TBG quotient for thyroid gland diagnostics was discussed.


The impact of extended lymph node dissection versus neoadjuvant therapy with limited lymph node dissection on biochemical recurrence in high-risk prostate cancer patients treated with radical prostatectomy: a multi-institutional analysis.
The optimal treatment for high-risk prostate cancer (Pca) remains to be established. The current guidelines recommend extended pelvic lymph node dissection (e-PLND) for selected intermediate- and high-risk patients treated with RP. However, the indications, optimal extent, and therapeutic benefits of e-PLND remain unclear. The aim of this study was to assess whether e-PLND confers an oncological benefit for high-risk Pca compared to neoadjuvant luteinizing hormone-releasing hormone and estramustine (LHRH + EMP). The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at four institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The outcome measure was BRFS. The 5-year biochemical recurrence-free survival rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9 and 54.7%, respectively (P < 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Although the present study was not randomized, neoadjuvant LHRH + EMP therapy followed by RP might reduce the risk of biochemical recurrence.


Plasmonic Circuit Theory for Multiresonant Light Funneling to a Single Spatial Hot Spot.
We present a theoretical framework, based on plasmonic circuit models, for generating a multiresonant field intensity enhancement spectrum at a single "hot spot" in a plasmonic device. We introduce a circuit model, consisting of an array of coupled LC resonators, that directs current asymmetrically in the array, and we show that this circuit can funnel energy efficiently from each resonance to a single element. We implement the circuit model in a plasmonic nanostructure consisting of a series of metal bars of differing length, with nearest neighbor metal bars strongly coupled electromagnetically through air gaps. The resulting nanostructure resonantly traps different wavelengths of incident light in separate gap regions, yet it funnels the energy of different resonances to a common location, which is consistent with our circuit model. Our work is important for a number of applications of plasmonic nanoantennas in spectroscopy, such as in single-molecule fluorescence spectroscopy or Raman spectroscopy.


Cellular immune responses of cattle to Cowdria ruminantium.
Peripheral blood mononuclear cells (PBM) from cattle immunised against Cowdria ruminantium infection (Heartwater), proliferated in vitro in the presence of either infected autologous endothelial cells pre-treated with T cell growth factors to induce MHC class II expression, or infected autologous monocytes. Proliferation was not observed in PBM cultured with a soluble extract of the agent, but PBM responded to two recombinant antigens of C. ruminantium, namely a 32 kDa (MAP1) and a 21 kDa antigen (MAP2). We hypothesize that infected endothelial cells and monocytes present Cowdria antigens to specific lymphocytes during infection and thereby play a role in the pathogenesis/immune response to the pathogen.


Changes in the traditional Korean medical sector as a result of health related legislation.
The objective of this study is to determine the effect of changes in the legal systems related to traditional Korean medicine (TKM) and their effect on health care in Korea. To cope with the many changes and challenges in the Korean health care system, health law has been used as an instrument to implement national health policies and support the developments of health systems. In particular, the Medical Service Act, amended in 1951, was the key factor for the coexistence of TKM and Western medicine in Korea. For systematizing the TKM, the roles of the National Health Insurance Act and the Medical Service Act were crucial. Considering Korea's experiences, health laws related to TKM were designed to regulate the health care system and have contributed to improve the quality and safety of TKM.


[SERS spectra of L-carnosine under the interaction of coordination with adsorbed SnCl2].
The authors have found that by virtue of utilizing the interaction of strongly chemically adsorbed SnCl2 with the analytes of organic/biologic molecules, the authors can not only effectively eliminate the laser carbonization and oxidation of probe molecules (e. g. pyridine), but also obtain specially enhanced Raman signals (e. g. vitamin B6). This method is applicable to the SERS spectroscopic analysis of highly reactive organic/biologic molecules. In the present paper, the authors report the investigation results on the electrochemical SERS spectra of L-carnosine (LCar) for the first time, mainly concentrating on the influence of adsorbed SnCl2 and applied potential on the SERS spectra of LCar. The SERS spectra of LCar were badly interfered by laser carbonization in the absence of SnCl2. However, in the presence of SnCl2 high quality SERS spectra of LCar could be obtained free of carbonization. It is demonstrated that LCar can be immobilized on the gold substrate indirectly via surface coordination with the pre-adsorbed SnCl2 under potential control. Apparently, such a sandwich-like adsorption configuration as Au-Sn(II)-LCar is beneficial both to sensing the strong electromagnetic field at the nanostructured gold surface and to preventing the LCar from damage by the laser.


A biomimetic receptor for glucose.
Specific molecular recognition is routine for biology, but has proved difficult to achieve in synthetic systems. Carbohydrate substrates are especially challenging, because of their diversity and similarity to water, the biological solvent. Here we report a synthetic receptor for glucose, which is biomimetic in both design and capabilities. The core structure is simple and symmetrical, yet provides a cavity which almost perfectly complements the all-equatorial β-pyranoside substrate. The receptor's affinity for glucose, at Ka ~ 18,000 M-1, compares well with natural receptor systems. Selectivities also reach biological levels. Most other saccharides are bound approximately 100 times more weakly, while non-carbohydrate substrates are ignored. Glucose-binding molecules are required for initiatives in diabetes treatment, such as continuous glucose monitoring and glucose-responsive insulin. The performance and tunability of this system augur well for such applications.


Dental infection control at the year 2000: accomplishment recognized.
Health care providers have strived to address the many elements necessary to achieve effective infection control. Historical progress in microbiology and hospital asepsis provided the foundation for advances in dental preventive practices. Evidence supporting the application of current practices includes a long history of scientific and clinical investigations, technological advances in equipment and materials, and periodic publication of updated recommendations by professional health care organizations. The routine application of precautions such as multiple aseptic procedures, latex gloves, masks, protective eyewear, clinic coats, automated instrument decontamination devices, time-efficient heat sterilization modalities, chemical disinfectants, waste management procedures and single-use disposable items have created a safer environment for dental personnel and patients alike.


Association of interleukin-10 gene single nucleotide polymorphisms with rheumatoid arthritis in a Chinese population.
Increasing numbers of studies show that interleukin (IL)-10 plays a key role in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and acts as an immunomodulatory cytokine. The purpose of the present study was to analyse the relationship between gene single nucleotide polymorphisms (SNPs) in the IL-10 gene and RA susceptibility. We genotyped three SNPs (rs1800890, rs3024495, rs3024505) of the IL-10 gene in a Chinese population of 354 RA patients and 367 controls. Genotyping was conducted using TaqMan SNP genotyping assays. Plasma IL-10 levels were measured by ELISA. The A allele of the rs1800890 variant was significantly related to decreased risk for RA compared with the T allele (A vs T: OR 0.580, 95% CI 0.345 to 0.975, P=0.038). No significant association between the genotype distribution of these SNPs and RA susceptibility was detected. The genotype effect of the dominant model was also evaluated, but no statistical difference was found. Further analysis in RA patients demonstrated that none of these SNPs were associated with rheumatoid factor (RF) or anti-citrullinated protein antibody (anti-CCP). In addition, no significant differences in plasma IL-10 levels were observed among RA patients with different genotypes. The IL-10 rs1800890 variant might contribute to RA susceptibility in the Chinese population. Replication studies in different ethnic groups are required to further examine the critical role of IL-10 gene variation in the pathogenesis of RA.


Simultaneous arterial switch and totally anomalous pulmonary venous connection repair in a 5-hour-old child, complicated by pulmonary venous stenosis.
A 5-hour-old boy underwent arterial switch operation and totally anomalous pulmonary venous connection repair. Subsequently developed severe pulmonary venous stenosis was successfully treated with hybrid balloon angioplasty.


Addressing central nervous system (CNS) penetration in drug discovery: basics and implications of the evolving new concept.
Despite enormous efforts, achieving a safe and efficacious concentration profile in the brain remains one of the big challenges in central nervous system (CNS) drug discovery and development. Although there are multiple reasons, many failures are due to underestimating the complexity of the brain, also in terms of pharmacokinetics (PK). To this day, PK support of CNS drug discovery heavily relies on improving the blood-brain barrier (BBB) permeability in vitro and/or the brain/plasma ratio (Kp) in vivo, even though neither parameter can be reliably linked to pharmacodynamic (PD) and efficacy readouts. While increasing BBB permeability may shorten the onset of drug action, an increase in the total amount in brain may not necessarily increase the relevant drug concentration at the pharmacological target. Since the traditional Kp ratio is based on a crude homogenization of brain tissue, it ignores the compartmentalization of the brain and an increase favors non-specific binding to brain lipids rather than free drug levels. To better link exposure/PK to efficacy/PD and to delineate key parameters, an integrated approach to CNS drug discovery is emerging which distinguishes total from unbound brain concentrations. As the complex nature of the brain requires different compartments to be considered when trying to understand and improve new compounds, several complementary parameters need to be measured in vitro and in vivo, and integrated into a coherent model of brain penetration and distribution. The new paradigm thus concentrates on finding drug candidates with the right balance between free fraction in plasma and brain, and between rate and extent of CNS penetration. Integrating this data into a coherent model of CNS distribution which can be linked to efficacy will allow it to design compounds with an optimal mix in physicochemical, pharmacologic, and pharmacokinetic properties, ultimately mitigating the risk for failures in the clinic.


Persistent halogenated organic contaminants and mercury in northern fulmars (Fulmarus glacialis) from the Canadian Arctic.
Northern fulmars from two breeding colonies in the Canadian Arctic, Cape Vera and Prince Leopold Island, were analyzed for organochlorine pesticides, PCBs, perfluorinated compounds (PFCs) and total mercury (Hg). Hepatic concentrations of organochlorines and Hg were highest in the male fulmars from Cape Vera. Perfluorooctane sulfonate (PFOS) concentrations did not vary significantly between sexes or colonies. However, concentrations of the perfluorinated carboxylates (PFCAs) were higher in fulmars from Cape Vera than Prince Leopold Island. The C(11)-C(15) PFCAs averaged 90% of the PFCA profile at both colonies. Polychorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and non-ortho PCBs (NO-PCBs) were measured only in birds from Prince Leopold Island. Concentrations of PCDDs, PCDFs, NO-PCBs and Toxic Equivalents (TEQs) did not differ significantly between sexes. ΣTEQ was comprised mainly of ΣTEQ(PCDF). Concentrations of Hg and the persistent halogenated compounds reported in this study were below published toxicological threshold values for wild birds.


Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on biogenic amines and their acidic metabolites in brain and cerebrospinal fluid of rats.
Effects of single subcutaneous doses of sodium 2,4-dichlorophenoxyacetate (2,4-D-Na) on biogenic amines and their acidic metabolites in rat brain and cerebrospinal fluid (CSF) were analyzed by high pressure liquid chromatography. After 200 mg/kg 2,4-D-Na, the cerebral concentration of 5-hydroxytryptamine (5-HT) was increased slightly and that of 5-hydroxyindoleacetic acid (5-HIAA) roughly 3-fold between 1 and 8 h after the administration. There was also a tendency towards slightly lowered dopamine (DA) levels. No statistically significant changes in brain concentrations of noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) or tryptophan (TRY) were found. At the same time, however, the maximal increase in DOPAC, HVA and 5-HIAA concentrations in the CSF was 2.3-5.8-fold. The dependency of biogenic amines and metabolites on 2,4-D-Na dose was studied by injecting s.c. 0, 10, 30 and 100 mg/kg and sacrificing the rats at 2 h. In the brain, there was a dose-dependent increase in concentrations of 5-HIAA (at the two highest doses) and HVA (at the highest dose) while in the CSF those of all three acidic metabolites increased at the two highest doses. The 10 mg/kg dose had no effect. The results agree with the hypothesis that 2,4-D inhibits the organic acid transport out of the brain, which should then result in increased cerebral levels of acidic metabolites of biogenic amines, but it may also have effects on the activity of serotoninergic and dopaminergic neurones.


Dual-stressor selection alters eco-evolutionary dynamics in experimental communities.
Recognizing when and how rapid evolution drives ecological change is fundamental for our understanding of almost all ecological and evolutionary processes such as community assembly, genetic diversification and the stability of communities and ecosystems. Generally, rapid evolutionary change is driven through selection on genetic variation and is affected by evolutionary constraints, such as tradeoffs and pleiotropic effects, all contributing to the overall rate of evolutionary change. Each of these processes can be influenced by the presence of multiple environmental stressors reducing a population's reproductive output. Potential consequences of multistressor selection for the occurrence and strength of the link from rapid evolution to ecological change are unclear. However, understanding these is necessary for predicting when rapid evolution might drive ecological change. Here we investigate how the presence of two stressors affects this link using experimental evolution with the bacterium Pseudomonas fluorescens and its predator Tetrahymena thermophila. We show that the combination of predation and sublethal antibiotic concentrations delays the evolution of anti-predator defence and antibiotic resistance compared with the presence of only one of the two stressors. Rapid defence evolution drives stabilization of the predator-prey dynamics but this link between evolution and ecology is weaker in the two-stressor environment, where defence evolution is slower, leading to less stable population dynamics. Tracking the molecular evolution of whole populations over time shows further that mutations in different genes are favoured under multistressor selection. Overall, we show that selection by multiple stressors can significantly alter eco-evolutionary dynamics and their predictability.


Dispositional mindfulness and reward motivated eating: The role of emotion regulation and mental habit.
Evidence regarding the effectiveness of mindfulness based interventions (MBIs) for eating disorders, weight management and food craving is emerging and further studies are required to understand the underlying mechanisms of MBIs in these domains. The current study was designed to establish the role of specific mechanisms underlying the putative relationship between mindfulness and reward motivated eating. We predicted that mindfulness would be negatively related to features of reward motivated eating and that this association would be mediated by emotion regulation and habitual negative self-thinking. A cross-sectional survey measuring uncontrolled and emotional eating, mindfulness, emotion regulation and habitual negative self-thinking was completed by female and male meditators and non-meditators (N = 632). Lower levels of dispositional mindfulness were associated with difficulties in emotion regulation, habitual negative self-thinking and both emotional and uncontrolled eating. Difficulties in emotion regulation significantly mediated the mindfulness-uncontrolled eating relationship. Habitual negative self-thinking significantly mediated the mindfulness-emotional eating relationship. Participants with meditation experience reported greater levels of dispositional mindfulness, fewer difficulties with emotion regulation and habitual negative self-thinking and reduced uncontrolled eating tendencies, compared to non-meditators. The findings suggest that MBIs designed to change reward motivated eating and weight control should focus on emotion regulation and mental habits as underlying mechanisms.


Gene expression profile of inflammatory neutrophils: alterations in the inhibitors of apoptosis proteins during spontaneous and delayed apoptosis.
Inflammatory mediators delay neutrophil apoptosis, which contributes to the persistence of inflammation. The mechanisms responsible for this delay and resistance to Fas antibody-induced apoptosis are unknown but are dependent on protein synthesis. These proteins have been shown to inhibit caspase activity central to the induction of apoptosis. The inhibitors of apoptosis proteins have been shown to inhibit caspase activity and prevent apoptosis in a number of cellular systems. We hypothesize that the regulation of neutrophil apoptosis is dependent on the expression of the IAPs. c-IAP-1, c-IAP-2, and XIAP are expressed in the neutrophil at both the mRNA and protein level, but their relative protein expression is low compared with other cell types. The in vitro aging of human neutrophils results in their induction of apoptosis, which is associated with the loss of c-IAP-1 expression. The pancaspase inhibitor (zVAD-FMK) and LPS, which delay spontaneous apoptosis, also prevented this loss of c-IAP-1. Gene chip microarrays have shown that LPS increases c-IAP-1 and c-IAP-2 mRNA expression in neutrophils. However, this does not correspond to an increase in protein. Neutrophils from septic patients with delayed apoptosis show an increase in XIAP, with no change in cIAP-1 or cIAP-2 mRNA, demonstrating that different mechanisms contribute to the delay in neutrophil apoptosis. This study demonstrates that the loss of IAP expression may facilitate the induction of neutrophil apoptosis, and preventing this loss of IAP expression may represent a more significant contribution to delayed apoptosis rather than an increase in their expression.


Formation of nanogaps in InAs nanowires by selectively etching embedded InP segments.
We present a method to fabricate nanometer scale gaps within InAs nanowires by selectively etching InAs/InP heterostructure nanowires. We used vapor-liquid-solid grown InAs nanowires with embedded InP segments of 10-60 nm length and developed an etching recipe to selectively remove the InP segment. A photo-assisted wet etching process in a mixture of acetic acid and hydrobromic acid gave high selectivity, with accurate removal of InP segments down to 20 nm, leaving the InAs wire largely unattacked, as verified using scanning electron and transmission electron microscopy. The obtained nanogaps in InAs wires have potential as semiconducting electrodes to investigate electronic transport in nanoscale objects. We demonstrate this functionality by dielectrophoretically trapping 30 nm diameter gold nanoparticles into the gap.


Isolation of a cDNA for the human homolog of MAT-1 oncogene and its expression in human breast cancer cells.
Overexpression of mouse MAT-1 oncogene is associated with carcinogensis of mouse mammary epithelial cells. A human cDNA (hMAT) homologous to MAT-1 was isolated from normal human breast tissue. The hMAT cDNA is 1312 bp long and produces a 8.5 kDa peptide in vitro. The hMAT probe hybridized with 2.5 kb RNA in normal human breast epithelial cells from reduction mammoplasty specimens and in human breast cancer cell lines. The extent of hMAT gene expression in human breast cancer cell line was variable, with BT-20, T47-D, and MDA-MB-231 showing about a 10-fold overexpression compared to primary normal human breast epithelial cells, MCF-7, and ZR-75-1.


Rabbit rubeosis iridis induced by intravitreal latex-derived angiogenic fraction.
To describe the presence of iris neovascularization in a rabbit-model of retinal neovascularization induced by the intravitreal injection of latex-derived angiogenic fraction microspheres (LAF). Eight New Zealand rabbits received one intravitreal injection of PLGA (L-lactide-co-glycolide) microspheres with 50 ug of LAF in the right eye (Group A). Microspheres without the LAF (0.1 ml) were injected in controls (Group B; n = 8). Follow-up with clinical evaluation and iris fluorescein angiography was performed after 4 weeks when eyes were processed for light microscopy. All eyes from Group A showed significant vascular dilation, conjunctival hyperemia and neovascularization on the iris surface, after LAF injection. No vascular changes were observed in Group B. The intravitreal injection of microspheres containing the LAF can induce rubeosis iridis in rabbits and could be used as a simple experimental model for iris neovascularization.


Isotachophoretic separation of middle molecule peptides in uremic body fluids.
By applying analytical isotachophoresis six solutes in the middle molecule range were isolated as a further separation of a middle molecule fraction isolated from uremic body fluids using an earlier described technique of combined high speed gel filtration--gradient elution chromatography. The solutes separated with isotachophoresis could be identified by determining the net mobilities and the corresponding UV levels. Identical net solute mobilities were found in different biological fluids from different uremic patients. By measuring the zone length it was possible to estimate the amounts of material present in uremic biological fluids. During these investigations the reproducibility was better than +/-2% for the six solutes measured.


Current progress in host innate and adaptive immunity against hepatitis C virus infection.
Hepatitis C virus (HCV) infects more than 170 million people worldwide and is the main cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Although the newly developed direct-acting antivirals (DAAs) have transformed the treatment of HCV infection, controlling HCV infection on a global scale remains a challenge because of the high cost, low resistance barrier of DAAs and lack of HCV vaccine. The host immune responses associated with HCV infection, especially HCV-specific T cellular immunity, determine the outcome of HCV infection: either acute or chronic infection. It is important to fully interpret the immunopathogenesis of HCV infection and consequently to exploit effective strategies to eliminate HCV. Here, we review the current progress in HCV immunology, which will deepen our understanding of the spectrum of HCV infection and immunity in humans.


PTSD in ambulant RTA victims: a randomized controlled trial of debriefing.
This report examines initial distress levels, course of symptoms, incidence of posttraumatic stress disorder (PTSD), predictors of short-term outcome, and value of prophylactic counseling in a consecutive series of 40 ambulant trauma clinic attenders with minor road traffic accident (RTA) injuries. Subjects were randomly allocated to intervention and monitoring groups following assessment at a mean of 7 days posttrauma and reassessed at 3 months using a variety of standard rating scales. Seventy-five percent reported significant levels of distress at 1 week posttrauma. By 3 months this had decreased sharply to 35%, and 22% were significantly impaired by clinical assessment. Incidence of PTSD over 3 months was estimated at 19% and point prevalence at 3 months posttrauma was 9%. High initial distress, increasing age, and high levels of perceived threat were significant independent predictors of morbidity, and no significant differences in outcome were found between intervention and monitoring groups at 3 months.


Heart rate variability in middle-aged sprint and endurance athletes.
Aging is associated with decreased autonomic balance which could be assessed by Heart Rate Variability (HRV). Exercise training improves autonomic balance, but there is a lack in the literature regarding the heart rate variability (HRV) of master sprinters and endurance athletes. The effects of lifelong endurance and sprint training on cardiac autonomic balance were assessed in master athletes and compared with age-matched controls and young untrained controls. Participants (n = 81) were 8 master sprinters (MS; 51.8 ± 11.1 yrs), 8 master endurance athletes (EN, n = 8, 53.6 ± 8.6 yrs), 17 age-matched untrained (CON, 47.47 ± 6.00 yrs) and 48 young controls (YC, 25.40 ± 3.87 yrs). For the acquisition of RR intervals (iRR) (Polar RS800X Heart Rate Monitor®) the participants remained seated for 15-min with the final 10-min being considered for analysis. HRV was measured using Kubios software. A one-way ANOVA with repeated measures was applied. All studied parameters did not differ between MS and EN {Time Domain [HR (bpm) 59.00 ± 6.13 vs. 58.94 ± 12.75], [R-R (ms) 1030.45 ± 107.45 vs. 1068.77 ± 206.17], [SDNN (ms) 57.35 ± 20.07 vs. 80.66 ± 71.07], [RMSSD (ms) 40.88 ± 20.07 vs. 38.93 ± 20.44]; Non-linear domain [SD1 (ms) 28.93 ± 14.20 vs. 27.56 ± 14.46]}, whose demonstrated a reduced HR and elevated mean R-R intervals in comparison to both YC {[HR (bpm) 69.64 ± 9.81]; [R-R (ms) 883.93 ± 124.11]} and age-matched controls {[HR (bpm) 70.06 ± 6.63]; [R-R (ms) 865.11 ± 78.39]}. It was observed a lower HRV for middle-aged CON {[RMSSD (ms) 20.23 ± 5.87], [SDNN (ms) 37.79 ± 10.15] and [SD1 (ms) 14.31 ± 4.15]} compared to YC {[RMSSD (ms) 43.33 ± 26.41], [SDNN (ms) 67.07 ± 28.77] and [SD1 (ms) 30.66 ± 18.69; p < .05]}. These last age-related differences were not observed for MS and EN. For master athletes, regardless of whether they are trained in endurance or sprinters, both training modes revealed to be equally beneficial in attenuating the effects of aging on the autonomic balance.