The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver.
Organic anion transporting polypeptides (rodent Oatp; human OATP) mediate cellular uptake of numerous organic compounds including xenobiotic toxins into mammalian hepatocytes. In the little skate Leucoraja erinacea a liver-specific Oatp (Oatp1d1, also called sOatp) has been identified and suggested to represent an evolutionarily ancient precursor of the mammalian liver OATP1B1 (human), Oatp1b2 (rat), and OATP1B3 (human). The present study tested whether Oatp1d1 shares functional transport activity of the xenobiotic oligopeptide toxins phalloidin and microcystin with the mammalian liver Oatps/OATPs. The phalloidin analogue [(3)H]-demethylphalloin was taken up into skate hepatocytes with high affinity (Km approximately 0.4 microM), and uptake could be inhibited by phalloidin and a variety of typical Oatp/OATP substrates such as bromosulfophthalein, bile salts, estrone-3-sulfate, cyclosporine A and high concentrations of microcystin-LR (Ki approximately 150 microM). When expressed in Xenopus laevis oocytes Oatp1d1 increased uptake of demethylphalloin (Km approximately 2.2 microM) and microcystin-LR (Km approximately 27 microM) 2- to 3-fold over water-injected oocytes, whereas the alternative skate liver organic anion transporter, the dimeric Ostalpha/beta, exhibited no phalloidin and only minor microcystin-LR transport. Also, the closest mammalian Oatp1d1 orthologue, the human brain and testis OATP1C1, did not show any phalloidin transport activity. These results demonstrate that the evolutionarily ancient Oatp1d1 is able to mediate uptake of cyclic oligopeptide toxins into skate liver. The findings support the notion that Oatp1d1 is a precursor of the liver-specific mammalian Oatps/OATPs and that its transport properties are closely associated with certain forms of toxic liver injury such as for example protein phosphatase inhibition by the water-borne toxin microcystin.


Comparison of Schirmer's test and tear film breakup time test to detect tear film abnormalities in patients with pterygium.
To compare tear film breakup time test with Schirmer's test in patients with pterygium. The case-control study, involving 86 patients with unilateral primary pterygium aged between 30 and 70 years, was conducted at the Department of Ophthalmology, Karachi Medical and Dental College, Abbasi Shaheed Hospital, from May 2009 to December 2010. The eye with pterygium was taken as the case, and was compared with the other eye without pterygium which was taken as the control in these patients. All patients underwent routine ophthalmic examination. Tear film tests such as Schirmer's test and tear film breakup time test were performed on all these eyes. Results of tear function test between the eyes with pterygium (cases) and the eye without pterygium (control) were compared. SPSS 17 was used for statistical analysis. Chi square test was used for comparing the results of the cases and the controls. Of the 86 patients, 63 (73.3%) were men, while 23 (26.7%) were women. The median age was 41 years. There were 62 (72.1%) patients with pterygium in the right eye, while 24 (27.9%) had it in the left. Among the involved eyes, decreased tear breakup time (<10 seconds) was observed in 65 (75.6%) eyes, while 21 (24.4%) eyes did not show decreased tear breakup time i.e.>10 seconds. On the other hand, 8 (9.3 %) eyes with pterygium had Schirmer's test positive and 78 (90.7 %) eyes had it negative. Tear film breakup time test has better diagnostic value compared to Schirmer's test in detecting tear film abnormality in patients with pterygium.


[Plastid stromules as specific elements of the multipurpose endoplasmic reticulum].
It is supposed, that the compromise between all groups of researchers of stromules can be reached if to accept, that an external membrane of stromules together with an external membrane of initial plastid are the specific domain of endoplasmic reticulum. Such domain co-operates with other membranes of a cell by means of membrane contact sites with free permeability for small molecules (presumably to 1.5 KDa).


Metabolomics Analysis of the Prefrontal Cortex in a Rat Chronic Unpredictable Mild Stress Model of Depression.
Depressive disorder is the leading cause of disability and suicidality worldwide. Metabolites are considered indicators and regulators of depression. However, the pathophysiology of the prefrontal cortex (PFC) in depression remains unclear. A chronic unpredictable mild stress (CUMS) model and a maturation rodent model of depression was used to investigate metabolic changes in the PFC. Eighteen male Sprague-Dawley rats were randomly divided into CUMS and control groups. The sucrose preference test (SPT) and forced swimming test (FST) were employed to evaluate and record depression-associated behaviors and changes in body weight (BW). High-performance liquid chromatography-tandem mass spectrometry was applied to test metabolites in rat PFC. Furthermore, principal component analysis and orthogonal partial least-squares discriminant analysis were employed to identify differentially abundant metabolites. Metabolic pathways were analyzed using MetaboAnalyst. Finally, a metabolite-protein interaction network was established to illustrate the function of differential metabolites. SPT and FST results confirmed successful establishment of the CUMS-induced depression-like behavior model in rats. Five metabolites, including 1-methylnicotinamide, 3-methylhistidine, acetylcholine, glycerophospho-N-palmitoyl ethanolamine, α-D-mannose 1-phosphate, were identified as potential biomarkers of depression. Four pathways changed in the CUMS group. Metabolite-protein interaction analysis revealed that 10 pathways play roles in the metabolism of depression. Five potential biomarkers were identified in the PFC and metabolite-protein interactions associated with metabolic pathophysiological processes were explored using the CUMS model. The results of this study will assist physicians and scientists in discovering potential diagnostic markers and novel therapeutic targets for depression.


Wavelet PCA for automatic identification of walking with and without an exoskeleton on a treadmill using pressure and accelerometer sensors.
Nowadays portable devices with more number of sensors are used for gait assessment and monitoring for elderly and disabled. However, the problem with using multiple sensors is that if they are placed on the same platform or base, there could be cross talk between them, which could change the signal amplitude or add noise to the signal. Hence, this study uses wavelet PCA as a signal processing technique to separate the original sensor signal from the signal obtained from the sensors through the integrated unit to compare the two types of walking (with and without an exoskeleton). This comparison using wavelet PCA will enable the researchers to obtain accurate sensor data and compare and analyze the data in order to further improve the design of compact portable devices used to monitor and assess the gait in stroke or paralyzed subjects. The advantage of designing such systems is that they can also be used to assess and monitor the gait of the stroke subjects at home, which will save them time and efforts to visit the laboratory or clinic.


[Amplification of oncogene N-myc in human neuroblastomas].
The basic mechanisms of oncogene activation are gene amplification, increased expression of a single copy gene and somatic mutation, resulting in a genetic product with increased oncogenic potential. Gene amplification appears to be a more common mechanism of oncogene overexpression and its clinical significance is beginning to be appreciated. In human neuroblastomas, N-myc amplification is highly correlated with advanced stages of disease and rapid disease progression, suggesting that the N-myc gene plays a crucial part in determining the degree of malignancy of neuroblastomas. Chromosome aberrations such as double minutes and homogeneously staining region which observed frequently in neuroblastomas are the cytological manifestation of N-myc amplification and its surrounding DNA fragments.


Deciduous and evergreen trees differ in juvenile biomass allometries because of differences in allocation to root storage.
Biomass partitioning for resource conservation might affect plant allometry, accounting for a substantial amount of unexplained variation in existing plant allometry models. One means of resource conservation is through direct allocation to storage in particular organs. In this study, storage allocation and biomass allometry of deciduous and evergreen tree species from seasonal environments were considered. It was expected that deciduous species would have greater allocation to storage in roots to support leaf regrowth in subsequent growing seasons, and consequently have lower scaling exponents for leaf to root and stem to root partitioning, than evergreen species. It was further expected that changes to root carbohydrate storage and biomass allometry under different soil nutrient supply conditions would be greater for deciduous species than for evergreen species. Root carbohydrate storage and organ biomass allometries were compared for juveniles of 20 savanna tree species of different leaf habit (nine evergreen, 11 deciduous) grown in two nutrient treatments for periods of 5 and 20 weeks (total dry mass of individual plants ranged from 0·003 to 258·724 g). Deciduous species had greater root non-structural carbohydrate than evergreen species, and lower scaling exponents for leaf to root and stem to root partitioning than evergreen species. Across species, leaf to stem scaling was positively related, and stem to root scaling was negatively related to root carbohydrate concentration. Under lower nutrient supply, trees displayed increased partitioning to non-structural carbohydrate, and to roots and leaves over stems with increasing plant size, but this change did not differ between leaf habits. Substantial unexplained variation in biomass allometry of woody species may be related to selection for resource conservation against environmental stresses, such as resource seasonality. Further differences in plant allometry could arise due to selection for different types of biomass allocation in response to different environmental stressors (e.g. fire vs. herbivory).


A Study of Differential Gene Expression and Core Canonical Pathways Involved in Rhenium Ligand Treated Epithelial Mesenchymal Transition (EMT) Induced A549 Lung Cancer Cell Lines by INGENUITY Software System.
Rhenium compounds have shown anti-cancer properties against many different types of cancer cell lines; however, the cellular signaling mechanisms involved in the cytotoxic properties of rhenium-based compounds were never deciphered or reported. In this manuscript, we report the results of an investigation done by RNA sequencing of rhenium treated A549 lung cancer cell lines along with an untreated vehicular control, analyzed by the Ingenuity Pathway Analysis (IPA) software system to decipher the core canonical pathways involved in rhenium induced cancer cell death. A549 EMT lung cancer cell lines were treated with rhenium ligand (Tricarbonylperrhenato(bathocuproine)rhenium(I), PR7) for seven days along with vehicular control. RNA was isolated from the treated and control cells and sequenced by a commercial company (PrimBio Corporation). The RNA sequencing data was analyzed by the INGNUITY software system and the core canonical pathways involved with differential gene expression were identified. Our report is showing that there are several cellular pathways involved in inducing cell death by rhenium-based compound PR7.


Green vegetable juice increases polyunsaturated fatty acid of erythrocyte membrane phospholipid in hypercholesterolaemic patients.
Treatment with green vegetable juice rich in dark-green leafy and cruciferous vegetables, such as cabbage, was tested in 31 hypercholesterolaemic patients for three weeks. Green vegetable juice supplementation significantly increased the content of polyunsaturated fatty acids (PUFA; P); 18:2n-6, 20:3n-6, 20:4n-6, 20:5n-3, 22:4n-6, 22:5n-3 and 22:6n-3 of erythrocyte membrane phospholipid and decreased saturated fatty acids (SFA; S): 14:0 and 18:0, and therefore increased the polyunsaturated fatty acids/saturated fatty acids (P/S) ratio markedly from 0.26 ± 0.01 to 0.49 ± 0.01 (p<0.001). Green vegetable juice supplementation increased both n-6 and n-3 PUFA, but the increase of n-3 PUFA was greater than that of n-6 PUFA. Therefore, the n-6/n-3 ratio decreased significantly from 4.29 ± 0.42 to 3.00 ± 0.16 (p<0.05). Plasma thiobarbituric acid reactive substance production decreased, following the green vegetable juice supplementation. These results suggest that green vegetable juice may protect the erythrocyte membrane from oxidative stress, and the decrease in n-6/n-3 and increase in P/S ratio in the erythrocyte membrane phospholipid may be accompanied by rheological and functional changes in erythrocytes in hypercholesterolaemic patients.


A Novel Calibration Method of Line Structured Light Plane Using Spatial Geometry.
The line structured light plane calibration method using a plane target cannot produce satisfactory calibration results due to inaccurate positioning of the calibrated points. Field of view noise and sensor noise affect the target light stripe extraction and camera parameter calculation during the calibration process. These factors will cause the calculation of the coordinates of the calibrated point to deviate, and thus affect the light plane calibration. To solve this problem, we propose a new method to calculate the calibrated point based on spatial geometry. Firstly, for the projection line corresponding to the feature point on the light stripe and the corresponding line on the target, a common perpendicular of these two lines above is established, and since the sum of the squares of the distances from the midpoint to the two straight lines is the smallest, the midpoint of the common perpendicular is taken as the calibrated point. Secondly, the target is moved to different positions, and the non-collinear calibrated points are calculated. Finally, the parameters of the light plane are obtained by fitting these calibrated points. This method requires only a checkerboard target, and has a simple calibration process. The experimental results show that the average error of the calibration method proposed in this paper is 0.011 mm, which is less than the 0.031 mm of the calibration method based on the plane target with cross-ratio invariant.


Intervertebral Disc-Derived Stem/Progenitor Cells as a Promising Cell Source for Intervertebral Disc Regeneration.
Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain. Despite remarkable improvements in both pharmacological and surgical management of IVD degeneration (IVDD), therapeutic effects are still unsatisfactory. It is because of the fact that these therapies are mainly focused on alleviating the symptoms rather than treating the underlying cause or restoring the structure and biomechanical function of the IVD. Accumulating evidence has revealed that the endogenous stem/progenitor cells exist in the IVD, and these cells might be a promising cell source in the regeneration of degenerated IVD. However, the biological characteristics and potential application of IVD-derived stem/progenitor cells (IVDSCs) have yet to be investigated in detail. In this review, the authors aim to perform a review to systematically discuss (1) the isolation, surface markers, classification, and biological characteristics of IVDSCs; (2) the aging- and degeneration-related changes of IVDSCs and the influences of IVD microenvironment on IVDSCs; and (3) the potential for IVDSCs to promote regeneration of degenerated IVD. The authors believe that this review exclusively address the current understanding of IVDSCs and provide a novel approach for the IVD regeneration.


Regulation of Cdx2 expression by promoter methylation, and effects of Cdx2 transfection on morphology and gene expression of human esophageal epithelial cells.
Caudal-related homeobox 2 (Cdx2) has been suggested as an early marker of Barrett's esophagus (BE), which is the premalignant lesion of esophageal adenocarcinoma (EAC). However, the mechanism of ectopic Cdx2 expression in the esophageal epithelial cells and its role in the development of BE remained unclear. RT-PCR, pyrosequencing and methylation-specific PCR were used to determine expression and promoter methylation of Cdx2 in human esophageal epithelial cells (HET1A and SEG1) after treatment with 5-aza-2'-deoxycytidine (DAC), acid, bile acids and their combination. HET1A cells with stable transfection of Cdx2 were characterized for morphology and gene expression profiles with Affymetrix array. We found Cdx2 was expressed in most human EAC cell lines, but not in squamous epithelial cell lines. DAC-induced demethylation and expression of Cdx2 in HET1A and SEG1 cells, and treatment with a DNA methylating agent counteracted the effect of DAC. Treatment of HET1A and SEG1 cells with acid, bile acids or both also resulted in promoter demethylation and expression of Cdx2. HET1A cells with stable transfection of human Cdx2 formed crypt-like structures in vitro. Microarray analysis and quantitative real-time PCR showed that stable transfection of Cdx2 up-regulated differentiation markers of intestinal columnar epithelial cells and goblet cells in HET1A cells. This may be partially due to modulation of Notch signaling pathway, as western blotting confirmed down-regulation of Hes1 and up-regulation of Atoh1 and Muc2. Our data suggest that exposure to acid and/or bile acids may activate Cdx2 expression in human esophageal epithelial cells through promoter demethylation, and ectopic Cdx2 expression in esophageal squamous epithelial cells may contribute to intestinal metaplasia of the esophagus.


The relations of quality of life in patients with lupus erythematosus: Regression models versus qualitative comparative analysis.
Lupus erythematosus (LE) is an autoimmune disease that can have negative repercussions on the quality of life (QL) of those who suffer from it. The QL can be influenced by socio-demographic factors are related to the disease itself. To analyse the associative power of socio-demographic (age and sex) and medical variables (type of lupus, diagnostic time and symptomatically associated with lupus) on the QL in patients with lupus by comparing linear relations models and models based on comparative qualitative fuzzy analysis. This is a retrospective cross-sectional design. The sample consisted of 161 patients (88.4% female) diagnosed with LE between the ages of 18-66 years. Data were collected between 2015 - 2017 using the Lupus Erythematosus Quality of Life Questionnaire. Two different statistical methodologies were used: traditional regression models and qualitative comparative analysis models of fuzzy sets. The results of the regression model suggest that none of the variables considered could explain the QL of these patients. On the other hand, the results of the fuzzy models suggest that being female, young and a shorter time to diagnosis explain higher levels of QL in these types of patients. Since nurses are the people who interact most with patients, detecting risk groups of patients with lupus respect to their QL. This can help develop intervention programs from a nursing perspective.


Phylogenetic comparison of the photoaffinity-labeled benzodiazepine receptor subunits.
The late evolutionary appearance of the benzodiazepine receptor (BZR) allows an experimental approach for evaluation of the qualitative development of its subunits. Photoaffinity labeling of brain membranes with [3H]flunitrazepam followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography offers a suitable method for tracing the qualitative evolution of the BZR. A systematic comparison of the subunit patterns in fishes, amphibians, reptiles, birds, and mammals revealed that the subunit of 53K is phylogenetically the oldest photoaffinity labeled subunit; whereas it is the only band present in the lungfish and most amphibians, additional bands are apparent in higher tetrapods. In fishes, the evolution of the BZR subunits leads to the loss of the 53K subunit. KD values are discussed in relation to specific subunit patterns. Possible explanations for the observed variation of the subunits are discussed, with special emphasis placed on the possible evolution by gene duplication and subsequent divergence.


Using qualitative data to inform the adaptation of a stroke preparedness health intervention.
Qualitative research methods are often used to develop health interventions, but few researchers report how their qualitative data informed intervention development. Improved completeness of reporting may facilitate the development of effective behavior change interventions. Our objective was to describe how we used qualitative data to develop our stroke education intervention consisting of a pamphlet and video. First, we created a questionnaire grounded in the theory of planned behavior to determine reasons people delay in activating emergency medical services and presenting to the hospital after stroke symptom onset. From our questionnaire data, we identified theoretical constructs that affect behavior which informed the active components of our intervention. We then conducted cognitive interviews to determine emergency department patients' understanding of the intervention pamphlet and video. Our cognitive interview data provided insight into how our intervention might produce behavior change. Our hope is that other researchers will similarly reflect upon and report on how they used their qualitative data to develop health interventions.


Measurement and Modeling of Microbial Growth Using Timelapse Video.
The development of timelapse videos for the investigation of growing microbial colonies has gained increasing interest due to its low cost and complexity implementation. In the present study, a simple experimental setup is proposed for periodic snapshot acquisition of a petri dish cultivating a fungus of the genus Candida SPP, thus creating a timelapse video. A computational algorithm, based on image processing techniques is proposed for estimating the microbial population and for extracting the experimental population curves, showing the time evolution of the population of microbes at any region of the dish. Likewise, a novel mathematical population evolution modeling approach is reported, which is based on the logistic function (LF). Parameter estimation of the aforementioned model is described and visually assessed, in comparison with the conventional and widely-used LF method. The effect of the image analysis parameterization is also highlighted. Our experiments take into account different area sizes, i.e., the number of pixels in the neighborhood, to generate population curves and calculate the model parameters. Our results reveal that, as the size of the area increases, the curve becomes smoother, the signal-to-noise-ratio increases and the estimation of model parameters becomes more accurate.


Adaptation problems with nursing home application for elderly persons: an application of the Roy adaptation nursing model.
This study sought to identify adaptation problems on the part of elderly persons and significant others that were associated with nursing home applications for elderly persons. Within the framework of the Roy Adaptation Nursing Model, an ex post facto research design was utilized to identify these adaptation problems. The four adaptive modes in this model are: physiological, self-concept, role function, and interdependence. The study group (n = 22) and a control group of elderly persons living in Calgary, as well as their significant others, were administered a structured questionnaire. Five hypotheses relating to overall adaptation problems, powerlessness, role reversal, guilt, and knowledge and utilization of services were formulated and tested. Only the hypothesis indicating role reversal on the part of the significant others was accepted. Adaptation problems encountered by the elderly which were associated with nursing home applications occurred in the self-concept and interdependence adaptive modes. The adaptation problems perceived by the significant others, which were associated with nursing home applications for their elderly, occurred in the self-concept, role function, and interdependence modes. Adaptation problems from the significant others' perception rather than from the elderly persons' perception appear to be more significantly associated with nursing home applications.


Isolation and culture of rat embryonic neural cells: a quick protocol.
We are describing a quick method to dissociate and culture hippocampal or cortical neurons from E15-17 rat embryos. The procedure can be applied successfully to the isolation of mouse and human primary neurons and neural progenitors. Dissociated neurons are maintained in serum-free medium up to several weeks. These cultures can be used for nucleofection, immunocytochemistry, nucleic acids preparation, as well as electrophysiology. Older neuronal cultures can also be transfected with a good efficiency rate by lentiviral transduction and, less efficiently, with calcium phosphate or lipid-based methods such as lipofectamine.


Transcranial magnetic stimulation over posterior parietal cortex disrupts transsaccadic memory of multiple objects.
The posterior parietal cortex (PPC) plays a role in spatial updating of goals for eye and arm movements across saccades, but less is known about its role in updating perceptual memory. We reported previously that transsaccadic memory has a capacity for storing the orientations of three to four Gabor patches either within a single fixation (fixation task) or between separate fixations (saccade task). Here, we tested the role of the PPC in transsaccadic memory in eight subjects by simultaneously applying single-pulse transcranial magnetic stimulation (TMS) over the right and left PPC, over several control sites, and comparing these to behavioral controls with no TMS. In TMS trials, we randomly delivered pulses at one of three different time intervals around the time of the saccade, or at an equivalent time in the fixation task. Controls confirmed that subjects could normally retain at least three visual features. TMS over the left PPC and a control site had no significant effect on this performance. However, TMS over the right PPC disrupted memory performance in both tasks. This TMS-induced effect was most disruptive in the saccade task, in particular when stimulation coincided more closely with saccade timing. Here, the capacity to compare presaccadic and postsaccadic features was reduced to one object, as expected if the spatial aspect of memory was disrupted. This finding suggests that right PPC plays a role in the spatial processing involved in transsaccadic memory of visual features. We propose that this process uses saccade-related feedback signals similar to those observed in spatial updating.


Coupled topological flat and wide bands: Quasiparticle formation and destruction.
Flat bands amplify correlation effects and are of extensive current interest. They provide a platform to explore both topology in correlated settings and correlation physics enriched by topology. Recent experiments in correlated kagome metals have found evidence for strange-metal behavior. A major theoretical challenge is to study the effect of local Coulomb repulsion when the band topology obstructs a real-space description. In a variant to the kagome lattice, we identify an orbital-selective Mott transition in any system of coupled topological flat and wide bands. This was made possible by the construction of exponentially localized and Kramers-doublet Wannier functions, which, in turn, leads to an effective Kondo-lattice description. Our findings show how quasiparticles are formed in such coupled topological flat-wide band systems and, equally important, how they are destroyed. Our work provides a conceptual framework for the understanding of the existing and emerging strange-metal properties in kagome metals and beyond.


Corneal ulcer due to Achromobacter xylosoxidans.
We report a case of corneal ulcer caused by the opportunistic organism Achromobacter xylosoxidans which developed during chronic topical steroid treatment of an eye with neovascular glaucoma. A. xylosoxidans has probably been underreported as a cause of ocular infection because of confusion between this organism and other Gram-negative organisms, particularly pseudomonas. A. xylosoxidans is resistant to aminoglycosides and some cephalosporins but not carbenicillin. This difference in antibiotic sensitivity patterns between A. xylosoxidans and pseudomonas makes an accurate differentiation between the 2 organisms important. This case was successfully treated after substituting topical carbenicillin for topical gentamicin and amikacin.


Sensitive skin is a neuropathic disorder.
Sensitive skin is defined by the occurrence of unpleasant sensations such as tingling, burning, tautness, itching or pain. Mechanisms explaining sensitive skin are controversial, and many hypotheses have been proposed. Because sensitive skin is primarily characterized by a wide variety of neuropathic-like symptoms, it is highly likely that neurosensory dysfunction in the skin represents one of the pathological mechanisms of sensitive skin. This hypothesis does not exclude other explanations like role of keratinocyte, transient receptor potential channels, vasculature or environmental factors. Nevertheless, the role of the nervous system in the development of sensitive skin is crucial, and growing evidence supports this hypothesis. Pain and pruritus described by patients with sensitive skin correspond to neuropathic component, and its assessment shows an increase in neuropathic measures (DN-4, Douleur Neuropathique 4) compared with control. These sensations are similar to the sensations observed in small-fibre neuropathy (SFN), which is a group of disorders that affect thin nerve fibres. One study on the pathophysiology of sensitive skin demonstrated that intra-epidermal nerve fibre density, especially of peptidergic C-fibres, was lower in the sensitive skin group. A recent study showed a modification in heat-pain detection threshold in patients with sensitive skin. All these results indicate that C-fibre damage can help explain sensitive skin. Consequently, the role of the nervous system is increasingly obvious. Nevertheless, keratinocytes and other epidermal cells closely participate in sensory transduction. Therefore, the results of neurophysiological studies should be interpreted in the light of this information that the whole epidermis represents a huge polymodal nociceptor.


A novel voice coil motor-driven compliant micropositioning stage based on flexure mechanism.
This paper presents a 2-degrees of freedom flexure-based micropositioning stage with a flexible decoupling mechanism. The stage is composed of an upper planar stage and four vertical support links to improve the out-of-plane stiffness. The moving platform is driven by two voice coil motors, and thus it has the capability of large working stroke. The upper stage is connected with the base through six double parallel four-bar linkages mechanisms, which are orthogonally arranged to implement the motion decoupling in the x and y directions. The vertical support links with serially connected hook joints are utilized to guarantee good planar motion with heavy-loads. The static stiffness and the dynamic resonant frequencies are obtained based on the theoretical analyses. Finite element analysis is used to investigate the characteristics of the developed stage. Experiments are carried out to validate the established models and the performance of the developed stage. It is noted that the developed stage has the capability of translational motion stroke of 1.8 mm and 1.78 mm in working axes. The maximum coupling errors in the x and y directions are 0.65% and 0.82%, respectively, and the motion resolution is less than 200 nm. The experimental results show that the developed stage has good capability for trajectory tracking.


Reduction of GVHD and enhanced antitumor effects after adoptive infusion of alloreactive Ly49-mismatched NK cells from MHC-matched donors.
We investigated if an infusion of alloreactive natural killer (NK) cells would reduce GVHD and mediate antitumor effects in mice undergoing MHC-matched allogeneic stem cell transplantation (SCT). Balb/c mice bearing RENCA tumors underwent an allogeneic SCT from MHC-matched B10.d2 donors and were given a single infusion of either Ly49 ligand-matched, ligand-mismatched, or no donor NK cells. Recipients of Ly49 ligand-mismatched NK cells had a reduced incidence of graft-versus-host disease (GVHD; 39% vs 100%; P < .01), and prolonged survival (median 84 days vs 39 days; P < .01) compared with SCT recipients not receiving NK cells. Recipients of Ly49 ligand-matched NK cells had the same incidence of GVHD and similar survival compared with controls not receiving NK cells. Pulmonary tumor burden was significantly (P < .01) lower in recipients that received Ly49-mismatched or Ly49-matched NK cells compared with recipients not receiving NK cells. These data provide in vivo evidence that a single infusion of alloreactive donor NK cells reduces GVHD and mediates antitumor effects following MHC-matched allogeneic transplantation.


[Mounting device for constancy tests of linear accelerators according to DIN 6847-5].
According to the German Industrial Norm DIN 6847-5 for constancy tests of linear accelerators, the measurements of the dose-monitor calibration and of the flatness of electron and photon beams for four different gantry angles are mandatory. The mounting devices developed in the Clinic for Radiation Therapy in Augsburg offer the possibility to perform all necessary constancy tests.


Effects of intermittent hypoxic training on amino and fatty acid oxidative combustion in human permeabilized muscle fibers.
The effects of concurrent hypoxic/endurance training on mitochondrial respiration in permeabilized fibers in trained athletes were investigated. Eighteen endurance athletes were divided into two training groups: normoxic (Nor, n = 8) and hypoxic (H, n = 10). Three weeks (W1-W3) of endurance training (5 sessions of 1 h to 1 h and 30 min per week) were completed. All training sessions were performed under normoxic [160 Torr inspired Po(2) (Pi(O(2)))] or hypoxic conditions ( approximately 100 Torr Pi(O(2)), approximately 3,000 m) for Nor and H group, respectively, at the same relative intensity. Before and after the training period, an incremental test to exhaustion in normoxia was performed, muscle biopsy samples were taken from the vastus lateralis, and mitochondrial respiration in permeabilized fibers was measured. Peak power output (PPO) increased by 7.2% and 6.6% (P < 0.05) for Nor and H, respectively, whereas maximal O(2) uptake (Vo(2 max)) remained unchanged: 58.1 +/- 0.8 vs. 61.0 +/- 1.2 ml.kg(-1).min(-1) and 58.5 +/- 0.7 vs. 58.3 +/- 0.6 ml.kg(-1).min(-1) for Nor and H, respectively, between pretraining (W0) and posttraining (W4). Maximal ADP-stimulated mitochondrial respiration significantly increased for glutamate + malate (6.27 +/- 0.37 vs. 8.51 +/- 0.33 mumol O(2).min(-1).g dry weight(-1)) and significantly decreased for palmitate + malate (3.88 +/- 0.23 vs. 2.77 +/- 0.08 mumol O(2).min(-1).g dry weight(-1)) in the H group. In contrast, no significant differences were found for the Nor group. The findings demonstrate that 1) a 3-wk training period increased the PPO at sea level without any changes in Vo(2 max), and 2) a 3-wk hypoxic exercise training seems to alter the intrinsic properties of mitochondrial function, i.e., substrate preference.


Exploring additivity effects of double mutations on the binding affinity of protein-protein complexes.
Additivity in binding affinity of protein-protein complexes refers to the change in free energy of binding (ΔΔGbind ) for double (or multiple) mutations which is approximately equal to the sum of their corresponding single mutation ΔΔGbind values. In this study, we have explored the additivity effect of double mutants, which shows a linear relationship between the binding affinity of double and sum of single mutants with a correlation of 0.90. However, the comparison of ΔΔGbind values showed a mean absolute deviation of 0.86 kcal/mol, and 25.6% of the double mutants show a deviation of more than 1 kcal/mol, which are identified as non-additive. The additivity effects have been analyzed based on the influence of structural features such as accessible surface area, long range order, binding propensity change, surrounding hydrophobicity, flexibility, atomic contacts between the mutations and distance between the 2 mutations. We found that non-additive mutations tend to be closer to each other and have more contacts. We have also used machine learning methods to discriminate additive and non-additive mutations using structure-based features, which showed the accuracies in the range of 0.77-0.92 for protein-protein complexes belonging to different functions. Further, we have compared the additivity effects of protein stability along with binding affinity and explored the similarities and differences between them. The results obtained in this study provide insights into the effects of various structural features on binding affinity of double mutants, and will aid the development of accurate methods to predict the binding affinity of double mutants.


Effect of tannin-containing hays on enteric methane emissions and nitrogen partitioning in beef cattle1.
The objective of this study was to determine whether feeding tannin-containing hays to heifers and mature beef cows influences enteric methane (CH4) emissions and nitrogen (N) excretion relative to feeding traditional legume and grass hays. Fifteen mature beef cows (Exp. 1) and 9 yearling heifers (Exp. 2) were each randomly assigned to treatment groups in an incomplete bock design with 2 periods and 6 types of hays with 3 hays fed each period (n = 5 cows and 3 heifers per treatment). Groups were fed tannin-containing [birdsfoot trefoil (BFT), sainfoin (SAN), small burnet (SML)] or non-tannin-containing [alfalfa (ALF), cicer milkvetch (CMV), meadow bromegrass (MB)] hays. Each period consisted of 14 d of adjustment followed by 5 d of sample collection. Nine cows and 9 heifers were selected for the measurement of enteric CH4 emissions (sulfur hexafluoride tracer gas technique), and excretion of feces and urine, while dry matter intake (DMI) was measured for all animals. The concentration of condensed tannins in SAN and BFT was 2.5 ± 0.50% and 0.6 ± 0.09% of dry matter (DM), respectively, while SML contained hydrolyzable tannins (4.5 ± 0.55% of DM). Cows and heifers fed tannin-containing hays excreted less urinary urea N (g/d; P < 0.001) and showed lower concentrations of blood urea N (mg/dL; P < 0.001) than animals fed ALF or CMV, indicating that tannins led to a shift in route of N excretion from urine to feces. Additionally, cows fed either BFT or CMV showed the greatest percentage of retained N (P < 0.001). Enteric CH4 yield (g/kg of DMI) from heifers (P = 0.089) was greatest for MB, while daily CH4 production (g/d) from heifers (P = 0.054) was least for SML. However, digestibility of crude protein was reduced for cows (P < 0.001) and heifers (P < 0.001) consuming SML. The results suggest that tannin-containing hays have the potential to reduce urinary urea N excretion, increase N retention, and reduce enteric CH4 emissions from beef cattle. The non-bloating tannin-free legume CMV may also reduce environmental impacts relative to ALF and MB hays by reducing N excretion in urine and increasing N retention.


Effect of human recombinant interleukin 4 on in vitro granulopoiesis of human bone marrow cells.
Utilizing in vitro colony assay, we investigated the effect of human recombinant interleukin 4 (hIL-4) on granulopoiesis of normal human bone marrow cells. Though hIL-4 itself did not possess any colony-stimulating activity, the number of neutrophil (N) colonies, particularly the number of small colonies, supported by human recombinant G-CSF (hG-CSF) was significantly increased when hIL-4 was used as a costimulant. In contrast, the number of eosinophil (Eo) colonies supported by hIL-5 was decreased when hIL-4 was used as a costimulant. Also, the numbers of N and Eo colonies supported by hIL-3 or hGM-CSF were both significantly decreased when hIL-4 was added. These data suggest that hIL-4 has diverse positive and negative regulatory effects on human neutro- and eosinophilopoiesis as a cofactor of various CSFs.


Identification of microsatellite instability and immune-related prognostic biomarkers in colon adenocarcinoma.
Colon adenocarcinoma (COAD) is a prevalent malignancy that causes significant mortality. Microsatellite instability plays a pivotal function in COAD development and immunotherapy resistance. However, the detailed underlying mechanism requires further investigation. Consequently, identifying molecular biomarkers with prognostic significance and revealing the role of MSI in COAD is important for addressing key obstacles in the available treatments. CIBERSORT and ESTIMATE analyses were performed to evaluate immune infiltration in COAD samples, followed by correlation analysis for MSI and immune infiltration. Then, differentially expressed genes (DEGs) in MSI and microsatellite stability (MSS) samples were identified and subjected to weighted gene co-expression network analysis (WGCNA). A prognostic model was established with univariate cox regression and LASSO analyses, then evaluated with Kaplan-Meier analysis. The correlation between the prognostic model and immune checkpoint inhibitor (ICI) response was also analyzed. In total, 701 significant DEGs related to MSI status were identified, and WGCNA revealed two modules associated with the immune score. Then, a seven-gene prognostic model was constructed using LASSO and univariate cox regression analyses to predict survival and ICI response. The high-risk score patients in TCGA and GEO cohorts presented a poor prognosis, as well as a high immune checkpoint expression, so they are more likely to benefit from ICI treatment. The seven-gene prognostic model constructed could predict the survival of COAD and ICI response and serve as a reference for immunotherapy decisions.


[Genetic etiology of newborn deaths].
Objective: To explore the genetic etiologies of newborn deaths. Methods: A total of 98 newborns who were recruited to the Neonatal Genome Project of the Children's Hospital of Fudan University and died in the hospital from January 2018 to August 2020 were enrolled in this study. The genetic information and the interventions based on the genetic findings were retrospectively analyzed. T-test, Mann-Whitney U test, Chi square test and Fisher's exact probability test were used to compare the demographic features and clinical characteristics between the patients with or without a genetic finding. Results: Among 98 newborns (55 males and 43 females), there were 63 preterm and 35 term infants, with a gestational age of (33±5) weeks, a birth weight of (2 107±975) g and the age at death of 12 (2,34) days. Sixteen (16%)patients were identified with genetic variants, including 11 with single nucleotide variants, 4 with copy number variants and 1 with both single nucleotide variant and copy number variant. The detected single nucleotide variants were spanning 12 genes, among which 3 were multiple disorders-related, 2 metabolic disorder-related, 2 hematological disorder-related, 2 respiratory disorder-related, 2 cardiovascular disorder-related and 1 skeletal disorder-related. The patients with a positive genetic finding had significant differences in the birth weight ((2 605±940) vs. (2 009±957) g, t=2.283, P=0.025), the gestational age ((36±5) vs. (33±5) weeks, t=2.131, P=0.036), the age at death ((37 (5, 69) vs. 11 (2, 29) days, Ζ=-2.245, P=0.025) and the history of asphyxia at birth (1/16 vs. 46% (38/82), P=0.002)when compared to those without a genetic finding. In addition, the genetic etiology rates of patients who were born term or with a birth weight ≥ 2 000 g were significantly higher than those who were born preterm (29% (10/35) vs. 10% (6/63), P=0.022) or with a birth weight<2 000 g (25% (13/51) vs. 7% (3/46), χ2=5.016,P=0.025), respectively. Six cases were medically actionable based on the genetic findings and the treatments included special diet, applying specific medicine, hematopoietic stem cell transplantation and lung transplantation. Conclusions: Genetic etiologies are not rare in newborn deaths and mainly associated with metabolic disorder, multi-system disorders, hematological disorder, respiratory disorder, cardiovascular disorder and skeletal disorder. Some findings are medically actionable, based on which the specific treatments could be scheduled timely. A genetic etiology should be investigated in newborn deaths especially in those who are term birth or with a birth weight ≥2 000 g or without a history of asphyxia at birth.


Prevalence of hypertension by duration and age at exposure to the stroke belt.
Geographic variation in hypertension is hypothesized as contributing to the stroke belt, an area in the southeastern United States with high stroke mortality. No study has examined hypertension by lifetime exposure to the stroke belt. This association was studied in 19,385 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national population-based cohort. Prevalent hypertension was defined as systolic blood pressure >/=140, diastolic blood pressure >/=90, or use of antihypertensive medications. Stroke belt exposure was assessed by residence at birth, currently, early childhood, adolescence, early adulthood, mid-adulthood, and recently. After adjustment for age, race, sex, physical activity level, body mass index, smoking, alcohol, education, and income, the prevalence of hypertension was significantly more strongly related (P < .0001) with lifetime exposure, adolescence, or early adulthood exposure than exposures at other times. Birthplace and current residence were independently associated with hypertension; however, lifetime, adolescence, or early adulthood exposures were more predictive than joint model with both birthplace and current residence. That adolescence and early adulthood periods are more predictive than residence in the stroke belt for most recent 20-year period suggests community and environmental strategies to prevent hypertension need to start earlier in life.


Health system foundations for Sláintecare implementation in 2020 and beyond - co-producing a Sláintecare Living Implementation Framework with Evaluation: Learning from the Irish health system's response to COVID-19. A mixed-methods study protocol.
All over the world, health systems are responding to the major shock of the COVID-19 pandemic. The virus is causing urgent and fast-paced change in the delivery of health and social care as well as highlighting pre-existing deficiencies and inequalities in the health system and broader society. In Ireland, COVID-19 is occurring during the second full year of Sláintecare's implementation - Ireland's 10-year plan for health reform to deliver universal access to timely, integrated care. This research will coproduce a Living Implementation Framework with Evaluation (LIFE) linking evidence, policy and practice that feeds into real-world Sláintecare implementation. In partnership with senior leadership in the Sláintecare Programme Implementation Office, the Department of Health and the HSE, the researchers will scope, document, measure and analyse the Sláintecare relevant COVID-19 responses using qualitative and quantitative methods. The LIFE will initially take the form of a live spreadsheet which contains the COVID-19 responses most relevant to Sláintecare. For each response, 3-4 indicators will be collected which enables monitoring overtime. The spreadsheet will be accompanied by a series of rapid reviews, narrative descriptions of multiple case studies, research papers, stakeholder engagement and formative feedback. These collectively make up the 'LIFE', informing dialogue with the project partners, which is happening in real time (living), influencing health policy and system decision-making and implementation as the project progresses. The LIFE will inform health system reform in Ireland in the months and years after the emergence of COVID-19 as well as contributing to international health systems and policy research.


Granulocytic sarcoma after stem cell transplantation in a child with biphenotypic leukemia.
Granulocytic sarcoma is an extramedullary tumor composed of leukemic blasts. Isolated granulocytic sarcoma has rarely been reported in children with leukemia undergoing allogeneic stem cell transplantation. We report a case of isolated granulocytic sarcoma arising from the pleura in an 11-year-old girl who was previously treated for biphenotypic leukemia with allogeneic stem cell transplantation. Complete resolution of the tumor was achieved after two inductions with MRC 12 protocol; however, she died of sepsis during the neutropenic period. The unusual presentation, immunophenotypic differences at diagnosis and relapse, and the management options are discussed.


A discharge planning program in orthopaedics: experiences in implementation and evaluation.
The acute care orthopaedic registered nurse plays a key role in assessing and communicating the continuing care needs of patient's and their families, coordinating community resources, and formulating a timely discharge plan to maximize rehabilitation and recovery. Developing and maintaining a staff nurse's discharge planning knowledge and skills can be a challenging endeavor. Discharge Planning Coordinators at a tertiary medical center developed and implemented a Discharge Planning Mentorship Program, an educational pilot program designed to enhance the knowledge and skill level of select nurses in the orthopaedic specialty practice, thus maximizing expert resources at the bedside. Program implementation and evaluation of role preparation, practice changes, and actualization challenges are discussed in this article. Overall, participants demonstrated increased skill in articulating and problem solving a patient's postdischarge needs, devised creative strategies to enhance communication between multiple levels of care, and developed a greater knowledge of community resources and reimbursement mechanisms for continuing care.


Fine particulate air pollution and hospital admissions for congestive heart failure: a case-crossover study in Taipei.
This study was undertaken to determine whether there was an association between fine particles (PM₂.₅) levels and hospital admissions for congestive heart failure (CHF) in Taipei, Taiwan. Hospital admissions for CHF and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality and long-term time trends. For the single pollutant model (without adjustment for other pollutants), increased CHF admissions were significantly associated with PM₂.₅ both on warm days (>23 °C) and cool days (<23 °C), with an interquartile range increase associated with a 13% (95% CI = 9-17%) and 3% (95% CI = 0-7%) increase in CHF admissions, respectively. In the two-pollutant models, PM₂.₅ remained significant after the inclusion of SO₂ or O₃ both on warm and cool days. This study provides evidence that higher levels of PM₂.₅ increase the risk of hospital admissions for CHF.


Reference values of one-point carotid stiffness parameters determined by carotid echo-tracking and brachial pulse pressure in a large population of healthy subjects.
Arterial stiffness can predict cardiovascular events, and the aim of this study was to produce age- and sex-specific reference values for echo-tracking carotid stiffness in healthy subjects. A total of 900 subjects (500 males, mean age 45.8±19 years) were enrolled. Common carotid artery stiffness and compliance, using a high-definition echo-tracking ultrasound system, were evaluated. To compare stiffness parameters across the different age groups, individual scores were transformed into T-scores, indicating how many standard deviation (s.d.) units an individual's score was above or below the mean that was observed in the group including same-sex individuals aged 36 to 44 years. Carotid stiffness was similar among genders, except compliance, which was lower in women (P<0.0001). These characteristics were also maintained when the studied population was divided into seven age groups. Stiffness parameters increased significantly with age, but the opposite occurred for compliance. The T-score was found to increase significantly across all age groups, with a steeper increase in stiffness around the age of 60 years in women. For each T-score s.d., the corresponding carotid absolute values for arterial stiffness and compliance were obtained. In a multivariate model, carotid stiffness parameters were constantly and independently associated with age, mean arterial pressure, pulse pressure, heart rate and body mass index. Our study provides a normogram of carotid arterial stiffness and compliance indices obtained with the echo-tracking method in a large population of healthy subjects stratified by gender and age that can be used in clinical practice.


The brain-gut axis in gastrointestinal cancers.
Recent developments have given more credence into the brain-gut-microbiota axis and its role in the development of tumor genesis. The microbiota have multiple functions including maintenance of the epithelial barrier, immune response, digestion, cortisol regulation, and control of neurotransmitters and their metabolism [e.g., serotonin, dopamine, noradrenaline and gamma-Aminobutyric Acid (GABA)]. Changes in gut microbiota can interfere with homeostasis leading to dysbiosis microbiota, which is linked to colorectal cancer. Microbiota composition can cause pronounced effect on medical interventions including medications, chemotherapy, and radiation. Altered primary immune system is associated with microbiota disassociation and development of colorectal cancer. This article reviews the current research in brain-gut axis with focus on microbiota and its role in the development of gastrointestinal cancers. We conducted a literature review on PubMed, Cochrane, and Science direct using English language. We begin by reviewing the brain-gut axis and its function and then discuss its effect on the development of gastrointestinal cancers. We reviewed 70 manuscripts and found association between microbiota dysfunction and development of colorectal cancers predisposing to psychiatric manifestations. Lasting disturbances in the microbiota can lead to systemic inflammation with implications on disease development or treatment modifications. These disruptions of the intestinal flora can play an important role in the pathogenesis of cancers. Most psychological reactions to cancer are similar across cancer types but each cancer when examined individually has its own unique features associated with it. Correlation between fear of recurrence and the level of pathological distress is viewed as an indicator of overall adjustment to cancer survival.


Shape encoding consistency across colors in primate V4.
Neurons in primate cortical area V4 are sensitive to the form and color of visual stimuli. To determine whether form selectivity remains consistent across colors, we studied the responses of single V4 neurons in awake monkeys to a set of two-dimensional shapes presented in two different colors. For each neuron, we chose two colors that were visually distinct and that evoked reliable and different responses. Across neurons, the correlation coefficient between responses in the two colors ranged from -0.03 to 0.93 (median 0.54). Neurons with highly consistent shape responses, i.e., high correlation coefficients, showed greater dispersion in their responses to the different shapes, i.e., greater shape selectivity, and also tended to have less eccentric receptive field locations; among shape-selective neurons, shape consistency ranged from 0.16 to 0.93 (median 0.63). Consistency of shape responses was independent of the physical difference between the stimulus colors used and the strength of neuronal color tuning. Finally, we found that our measurement of shape response consistency was strongly influenced by the number of stimulus repeats: consistency estimates based on fewer than 10 repeats were substantially underestimated. In conclusion, our results suggest that neurons that are likely to contribute to shape perception and discrimination exhibit shape responses that are largely consistent across colors, facilitating the use of simpler algorithms for decoding shape information from V4 neuronal populations.


Risk factors for spontaneous abortion: a preliminary study on Saudi women.
A preliminary case-control study was conducted on Saudi women to detect possible risk factors for spontaneous abortion (SA). Two hundred and twenty six consecutive women hospitalised for SA and 226 women admitted for normal delivery and used as controls, were studied. Women with SA were significantly older at menarche (Relative Risk (RR) = 3.2), more frequently married to blood-related husbands (RR = 2.1) and husbands older than 50 years (RR = 2.4). Number of previous abortions related linearly to the risk of aborting spontaneously in the next pregnancy. Compared to primigravidas, the RR was 3.2 if the outcome of the most recent pregnancy was SA, and 0.8 if it was a livebirth. A family history of SA was more common among cases (RR = 4.6). Spontaneous abortion was also associated with daily consumption of more than 150 mg of caffeine, abdominal trauma, infection and fever during pregnancy. No significant association, however, emerged with maternal age, social class, education, exposure to video display terminals, parity, use of contraception, diabetes or obesity. The application of these data in clinical practice and future research needs are discussed.


Periostin promotes migration, proliferation, and differentiation of human periodontal ligament mesenchymal stem cells.
Periostin (POSTN) is critical to bone and dental tissue morphogenesis, postnatal development, and maintenance; however, its roles in tissue repair and regeneration mediated by human periodontal ligament mesenchymal stem cells (PDLSCs) remain unclear. The present study was designed to evaluate the effects of POSTN on hPDLSCs in vitro. hPDLSCs were isolated and characterized by their expression of the cell surface markers CD44, CD90, CD105, CD34, and CD45. Next, 100 ng/mL recombinant human POSTN protein (rhPOSTN) was used to stimulate the hPDLSCs. Lentiviral POSTN shRNA was used to knockdown POSTN. The cell counting kit-8 (CCK8) and scratch assay were used to analyze cell proliferation and migration, respectively. Osteogenic differentiation was investigated using an alkaline phosphatase (ALP) activity assay, alizarin staining, and quantitative calcium analysis and related genes/protein expression assays. Isolated hPDLSCs were positive for CD44, CD90, and CD105 and negative for CD34 and CD45. In addition, 100 ng/mL rhPOSTN significantly accelerated scratch closure, and POSTN-knockdown cells presented slower closure at 24 h and 48 h. Furthermore, the integrin inhibitor Cilengitide depressed the scratch closure that was enhanced by POSTN at 24 h. The CCK8 assay showed that 100 ng/mL rhPOSTN promoted hPDLSC proliferation. Moreover, 100 ng/mL rhPOSTN increased the expression of RUNX2, OSX, OPN, OCN, and VEGF and enhanced ALP activity and mineralization. POSTN silencing decreased the expression of RUNX2, OSX, OPN, OCN, and VEGF and inhibited ALP activity and mineralization. POSTN accelerated the migration, proliferation, and osteogenic differentiation of hPDLSCs.


Spin-splitting and switchable half-metallicity in a van der Waals multiferroic CuBiP2Se6/GdClBr heterojunction.
Multiferroic van der Waals (vdW) heterojunctions have a strong and nonvolatile magnetoelectric coupling effect, which is of great significance in spintronic devices. The electronic structure and magnetic properties of a GdClBr/CuBiP2Se6 vdW multiferroic heterojunction have been calculated using first-principles methods. Due to the spin-up charge transfer and Zeeman field, the ferroelectric CuBiP2Se6 exhibits spin splitting at the gamma point. It is found that the electronic structure and magnetic properties of the GdClBr/CuBiP2Se6 vdW multiferroic heterojunction have been significantly modulated by the electric polarization of CuBiP2Se6. During the reversal of the ferroelectric polarization of CuBiP2Se6, the ferromagnetic GdClBr monolayer transforms from a semiconductor to a half-metal. Meanwhile, in both upward and downward ferroelectric polarization, the GdClBr/CuBiP2Se6 heterojunction exhibits perpendicular magnetic anisotropy with a Curie temperature of 239 K. As the strain changes from -6% to 6%, the band structure of GdClBr shifts upward, and the band structure of CuBiP2Se6 shifts downward. Compressive strain can increase the Curie temperature of the GdClBr/CuBiP2Se6 heterojunction. The magnetic anisotropy of heterojunctions highly depends on biaxial strain, where the perpendicular (in-plane) magnetic anisotropy increases with the increased compressive (tensile) strain. The vdW multiferroic GdClBr/CuBiP2Se6 heterojunction has potential applications in spintronic devices.


Adjuvant use of abciximab for balloon angioplasty of symptomatic middle cerebral artery stenosis.
To evaluate the safety of adjuvant intravenous use of abciximab in balloon angioplasty for symptomatic middle cerebral artery stenosis. Seven patients with symptomatic stenosis at the main trunk (n=5), or proximal post-trifurcation portion (n=2) of the middle cerebral artery, were enrolled in the study. A bolus dose of abciximab (0.15 mg/kg) was given intravenously immediately before the procedure. The immediate morphologic results as well as the presence of hyperacute thrombosis or hemorrhage after angioplasty were evaluated. Clinical evaluation was performed 1 day and 1 month following angioplasty. Oral antiplatelets were administered during the follow-up period. Follow-up angiography was performed after 7 to 14 (mean 10.4) months. Stenosis of a vessel greater than 50% was considered as restenosis. The procedure was technically successful in all patients. Immediate residual stenosis was insignificant in 4 and mild (less than 50%) in 3 patients. There was no evidence of intimal dissection. Mild gum bleeding was noted in two patients. All study patients were clinically stable at follow-up without newly developed neurological abnormality even though there was one case of occlusion and one case of restenosis on follow-up angiography. Angiographic patency rate was 71%. In performing proximal middle cerebral artery balloon angioplasty, abciximab may be safely used to prevent acute thrombosis. The mid-term patency of the vessels was also acceptable.


High allergic reactivity in a tropical environment.
The prevalence of atopic disease in tropical populations is often considered to be low, and this has been attributed to an immunological modulating effect of intestinal helminthiasis. We, however, report that the frequency of positive allergic history and skin-test reactivity to groups of major environmental allergens is extremely high (43 and 63% respectively) in children in Caracas, Venezuela (Lat. 10 degrees N). These values were statistically significantly greater than in a group of children with a similar age and sex distribution studied in parallel, but having limited or no contact with a tropical environment (29 and 37% respectively). The two groups differed with respect to the sporadic and light intestinal helminthic infections (such as ascariasis) experienced by the Venezuelans, compared to rare contact in the 'non-tropical' group. This was probably the cause of the increased total serum IgE levels of the former children (369 vs 68 iu/ml), and possibly, therefore, their higher allergic reactivity.


Antimicrobial peptide 99mTc-ubiquicidin 29-41 as human infection-imaging agent: clinical trial.
Ubiquicidin (UBI) 29-41 is a cationic, synthetic antimicrobial peptide fragment that binds preferentially with the anionic microbial cell membrane at the site of infection. The current study was conducted to evaluate its potential as an infection-imaging agent in humans. Eighteen patients, 9 female and 9 male (mean age, 31.7 y; range, 5-75 y), with suspected bone, soft-tissue, or prosthesis infections were included in the study. (99m)Tc-UBI 29-41 in a dose of 400 microg/370-400 MBq was injected intravenously in adults. A dynamic study was followed by spot views of the suspected region of infection (target) and a corresponding normal area (nontarget) at 30, 60, 120, and 240 min. The target-to-nontarget ratios were used to find the optimum time for imaging. Whole-body anterior and posterior images were also acquired at 30, 120, and 240 min to study biodistribution. Activity in each organ was expressed as percentage retained dose. Visual score (0-3) was used to categorize studies as positive or negative, with scores of 0 (minimal or no uptake; equivalent to soft tissue) and 1 (mild; less uptake than in liver) being considered negative and scores of 2 (moderate; uptake greater than or equal to that in liver) and 3 (intense; uptake greater than or equal to that in kidneys) being considered positive. Scans were interpreted as true- or false-positive and true- or false-negative on the basis of bacterial culture as the major criterion and the results of clinical tests, radiography, and 3-phase bone scanning as minor criteria. The biodistribution study showed a gradual decline in renal activity as percentage of administered dose from 6.53% +/- 0.58% at 30 min to 4.54% +/- 0.57% at 120 min and 3.38% +/- 0.55% at 240 min. The liver showed a similar trend, with values of 5.43% +/- 0.76%, 3.17% +/- 0.25%, and 2.02% +/- 0.30% at 30, 120, and 240 min, respectively. Radioactivity accumulated gradually in the urinary bladder, with values of 4.60% +/- 0.92% at 30 min, 23.00% +/- 2.32% at 120 min, and 38.85% +/- 4.01% at 240 min. Of 18 studies performed with 99mTc-UBI 29-41, 14 showed positive findings and 4 showed negative findings. Negative findings were subsequently confirmed to be true negative. The positive findings for 1 scan were interpreted as false positive, as no growth was obtained on bacterial culture and no evidence of infection was found on minor criteria. In 10 cases, the major criterion was used, whereas in 4 cases minor criteria had to be used for interpretation. Quantitative analysis revealed a maximum mean target-to-nontarget ratio of 2.75 +/- 1.69 at 30 min, which decreased to 2.04 +/- 1.01 at 120 min. The overall sensitivity, specificity, and accuracy were 100%, 80%, and 94.4%, respectively. No adverse reactions were observed during image acquisition and within 5 d after the study. 99mTc-UBI 29-41 showed promise in localizing foci of infection, with optimal visualization at 30 min.


68Ga-PSMA-11 PET/CT: the rising star of nuclear medicine in prostate cancer imaging?
Ever since the introduction of 68Ga-prostate-specific membrane antigen 11 positron-emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) a few years ago, it has rapidly achieved great success in the field of prostate cancer imaging. A large number of studies have been published to date, indicating a high potential of 68Ga-PSMA-11 PET/CT in the work-up of prostate cancer patients, including primary diagnosis, staging and biochemical recurrence. The aim of this review is to present the most important data on this novel, highly promising imaging technique, and to formulate recommendations for possible applications of 68Ga-PSMA-11 PET/CT in clinical routine.


Assessing adaptive immune response phenotypes in Australian Holstein-Friesian heifers in a pasture-based production system.
The objective of this study was to determine the repeatability of ranking Holstein-Friesian heifers reared in an Australian pasture-based production system for immune responses (IR) when ranking was based on secondary versus tertiary IR. Further objectives were to investigate associations between IR and stress responsiveness, ADG and resistance to internal parasites. A total of 100 heifers were IR phenotyped at 5 to 6 mo of age and again at 12 to 13 mo of age using commercial vaccine antigens to induce measurable IR. Antibody production to tetanus toxoid (TT) was used to assess antibody-mediated IR (AMIR), and delayed-type hypersensitivity reactions to vaccine antigens were used to assess cell-mediated IR (CMIR). Changes in serum cortisol and haptoglobin were used to assess stress responsiveness and fecal egg counts used as a measure of resistance to internal parasites. Based on testing, animals were categorized as either average to above-average (High) or low responders for IR. Secondary and tertiary AMIR were well correlated (r = 0.651, adjusted R(2) = 0.418, P < 0.0001), whereas correlations between secondary and tertiary CMIR were poor (r = 0.078, R(2) = –0.004, P = 0.450). A Cohen kappa (κ) test of agreement was used to test the consistency of ranking of individual animal for IR and, therefore, the ability to consistently identify low immune responder animals within the herd across test periods. The consistency of ranking (High versus low) was moderately high for AMIR (κ = 0.445), poor for CMIR (κ = –0.055), and fair to moderate for combined IR (κ = 0.395). High AMIR phenotype animals had significantly higher serum cortisol concentrations than their low immune responder counterparts (P = 0.045). A similar relationship was observed in heifers categorized for CMIR, with High CMIR responders having higher serum cortisol concentrations than their low responder counterparts (P = 0.008). High AMIR calves had a higher ADG compared with low AMIR calves (0.72 ± 0.02 versus 0.66 ± 0.06 kg/d; P = 0.009). Serum haptoglobin concentrations and worm egg counts were very low and could not be used to investigate associations with immune responsiveness. It is concluded that secondary and tertiary antibody responses to TT were well correlated in the Holstein-Friesian heifers in this study and that by using the testing procedure described here, low antibody responders were able to be consistently identified in the herd.


Co-stimulation blockade targeting CD154 and CD28/B7 modulates the induced antibody response after a pig-to-baboon cardiac xenograft.
The induced antibodies against Galalpha1,3Gal (Gal) and non-Gal epitopes may contribute to delayed xenograft rejection (DXR). We asked whether blockade of the CD40/CD154 and CD28/B7 co-stimulatory pathways modulates the baboon elicited antibody response to pig Gal and non-Gal antigens. Eighteen baboons received heterotopic heart transplants from pigs transgenic for human decay-accelerating factor (n = 13) or membrane cofactor protein (n = 5). Ten reference ''conventional therapy'' animals received cyclosporin A, cyclophosphamide and mycophenolate mofetil, with (n = 4) or without (n = 6) anti-CD20. Eight ''co-stimulation blockade'' animals received anti-CD154 mAb (IDEC-131) and anti-thymocyte globulin, with (n = 4) or without (n = 4) anti-CD20; two of these animals also received CTLA4-Fc. Anti-alphaGal IgG and IgM, anti-non-Gal antibodies and graft histology were assessed serially. Excluding two early graft failures, median graft survival with conventional therapy was 15 days (range 6 to 36 days, n = 8). Anti-Gal IgG antibody remained low through day 6 to 10, only one graft failure was accompanied by significant rise in anti-Gal IgG, and the anti-non-Gal response was weak (n = 2) or absent (n = 7). However many recipients succumbed with infection (n = 4) or coagulopathy (n = 2); DXR and ICOS+ T cells were prevalent in long-surviving grafts. With co-stimulation blockade, excluding three early graft failures, median graft survival was 7 days (range 6 to 11 days, n = 5). This regimen was very well tolerated, but increased anti-Gal antibody titer within 14 days was associated with graft failure in four of six animals. Although an anti-non-Gal response was present in three of six animals during IDEC-131 monotherapy (one strong, two weak), it was absent in both cases with additional CTLA4-Fc treatment. As used here, CD154 blockade alone does not completely prevent induction of Gal and non-Gal anti-pig antibodies. Our preliminary data suggest that other co-stimulation pathways, including CD28/B7 and ICOS, are sufficient to mediate high-titer anti-non-Gal antibody to porcine antigens in baboons, and contribute significantly to the pathogenesis of DXR.


Effects of systemic chlorogenic acid on random-pattern dorsal skin flap survival in diabetic rats.
There has been considerable interest in understanding the effects of antioxidants in flap survival during diabetes. Previous studies showed that chlorogenic acid (CGA) exhibits potent antioxidant effects. We aimed to determine the effects of systemic CGA treatment on skin flap survival in an experimental random-pattern dorsal skin flap model in diabetic rats. Twenty-eight male Wistar rats were divided into four groups: phosphate buffered saline (PBS)-treated or CGA-treated nondiabetic rats, PBS-treated or CGA-treated diabetic rats. Diabetes was induced by streptozotocin (45 mg/kg). Caudally based bipedicled dorsal skin flaps were elevated. CGA (100 mg/kg) or PBS (mL/kg; as vehicle) was administered intraperitoneally once daily. On postoperative day 7, flap survival, regional blood perfusion and microangiography were evaluated. The malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and nitric oxide (NO) levels were evaluated from the flap tissue. Capillary density and vascular endothelial growth factor (VEGF) expression were assessed. Harmful effects of diabetes on flap survival were observed. CGA attenuated these effects and allowed greater survival and blood perfusion. CGA decreased MDA and NO levels and increased GSH and SOD levels. CGA elevated capillary density and VEGF expression. This study showed that peripherally administered CGA significantly improved flap survival in diabetic and nondiabetic rats.


Transoval trigeminal cisternography and glycerol injection in trigeminal neuralgia.
In a series of 25 consecutive patients suffering from essential trigeminal neuralgia, transoval glycerol injection following Håkanson was performed in order to alleviate the pain attacks. This treatment proved to be successful in 76% of the patients. No major side-effects were reported. Authors stress the importance of a precise cisternography of Meckel's cave to ascertain the correct position of the needle, before injecting the glycerol. They discuss their mode of conducting the examination in using a conventional radiologic set-up. Transoval glycerol injection is a valuable interventional radiologic procedure and has to be taken into account as an alternative treatment of essential trigeminal neuralgia, especially when current therapeutic measures have failed.


Differential Energy Criterion for Brittle Fracture: Conceptualization and Application to the Analysis of Axial and Lateral Deformation in Uniaxial Compression of Rocks.
This paper discusses modeling the behavior and prediction of fracture of brittle materials. Numerous publications show that progress in this area is characterized by the emergence of a number of new models that meet the requirements of the mining industry, construction and other engineering practices. The authors focus only on one class of models, paying special attention to the compromise between simplicity of solution and versatility of the model. A new version of the model is proposed, taking into account the advantages of previous models. We present a differential energy criterion for brittle fracture substantiated, according to which, fracture occurs at a certain ratio of dissipated and stored (elastic) energy. Fracture is considered as the end of the deformation process with a virtual transformation of the initial material almost without cracks into a real material with cracks. The highest and lowest elastic moduli are analytically determined, respectively, on the ascending and descending branches of the stress-strain curve. A graphical version of the algorithm for determining the brittle fracture point on the post-peak branch of the stress-strain curve is proposed. The modeling results are consistent with the experimental data known from the literature.


Familial Atrial Myxoma: Three Related Cases at an Australian Tertiary Institution.
Carney complex accounts for up to two-thirds of familial cardiac myxoma. It is a rare autosomal dominant syndrome, which is also characterized by multiple mucocutaneous lesions and endocrine tumors. We report on three first-degree relatives who underwent surgical resection at the same Australian tertiary institution. One patient re-presented with a recurrent tumor at an interval of 6 years. In this context, the role of interval surveillance, family screening, and genetic testing is explored. We recommend interval echocardiographic surveillance for affected individuals and first-degree relatives given the high risk of recurrence and the morbidity and mortality associated with cardiac tumors in any location.


Achieving directional propagation of elastic waves via topology optimization.
This paper presents a study on topology optimization of novel material microstructural configurations to achieve directional elastic wave propagation through maximization of partial band gaps. A waveguide incorporating a periodic-microstructure material may exhibit different propagation properties for the plane elastic waves incident from different inlets. A topology optimization problem is formulated to enhance such a property with a gradient-based mathematical programming algorithm. For alleviating the issue of local optimum traps, the random morphology description functions (RMDFs) are introduced to generate random initial designs for the optimization process. The optimized designs finally converge to the orderly material distribution and numerical validation shows improved directional propagation property as expected. The utilization of linear two-dimension phononic crystal with efficient partial band gap is suitable for directional propagation with a broad frequency range.


Fluvoxamine impairs single-dose caffeine clearance without altering caffeine pharmacodynamics.
Coadministration of fluvoxamine impairs the clearance of caffeine and prolongs its elimination half-life, which is attributable to inhibition of CYP1A2 by fluvoxamine. The clinical importance of this interaction is not established. To evaluate the effects of fluvoxamine on the kinetics and dynamics of single doses of caffeine. Seven healthy subjects received single 250 mg doses of caffeine (or matching placebo) together with fluvoxamine (four doses of 100 mg over 2 days) or with matching placebo in a double-blind, four-way crossover study. For 24 h after caffeine or placebo administration, plasma caffeine and fluvoxamine concentrations were determined. Psychomotor performance, sedation, and electroencephalographic (EEG) "beta" frequency activity were also assessed. Fluvoxamine significantly reduced apparent oral clearance of caffeine (105 vs. 9.1 mL min(-1), P < 0.01; mean difference: 95.7 mL min(-1), 95% CI: 54.9-135.6), and prolonged its elimination half-life (4.9 vs. 56 h, P < 0.01; mean difference: 51 h, 95% CI: 26-76). Caffeine produced CNS-stimulating effects compared with placebo. However, psychomotor performance, alertness, or EEG effects attributable to caffeine were not augmented by coadministration of fluvoxamine. Fluvoxamine greatly impaired caffeine clearance, but without detectable changes in caffeine pharmacodynamics. However, this study does not rule out possible adverse effects due to extensive accumulation of caffeine with daily ingestion in fluvoxamine-treated individuals.


Separation and characterization of three insulin receptor species that differ in subunit composition.
Partially purified human placental insulin receptor preparations give rise to three distinct insulin-binding peaks when eluted from a Mono Q high-performance liquid chromatography anion-exchange column. We analyzed the basis for this phenomenon by affinity cross-linking of insulin to each peak, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We find that the three insulin-binding peaks represent different molecular weight complexes with the following subunit composition: (alpha beta)2, (alpha beta)(alpha beta'), and (alpha beta')2, where beta' represents a proteolytically derived fragment of the beta subunit. This analysis of subunit composition was confirmed by silver staining of affinity-purified insulin receptor following resolution of the forms on a Mono Q column as described previously. We have characterized the three isolated insulin receptor forms with regard to ligand binding by LIGAND and Scatchard analysis. We also measured insulin-stimulatable autophosphorylation and exogenous kinase activity directed toward poly(Glu/Tyr) (4:1). The three forms of the insulin receptor exhibit similar KD's for insulin binding to the high- and low-affinity sites. The (alpha beta)2 and (alpha beta)(alpha beta') forms of the insulin receptor display superimposable curvilinear Scatchard plots. In contrast, only the intact holoreceptor (alpha beta)2 form demonstrates insulin-stimulatable autophosphorylation and exogenous kinase activity. The (alpha beta)(alpha beta') form has reduced basal kinase activity which was not increased by prior incubation with insulin. The (alpha beta')2 form lacks a kinase domain and consequently demonstrated no kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Platelet Functions in Patients with Allergic Asthma.
To investigate platelet functions in patients suffering from allergic diseases including asthma, blood was collected from ten asthmatic patients (five females, five males) and ten healthy controls (five females, five males) and by using whole-blood electrical impedance system; platelet count and platelet aggregation studies (maximum aggregation extent, maximum aggregation rate) were performed. Allergy screening was performed with skin test reactions and with high total and specific immunoglobulin E levels (CAP-Phadiatop system). Platelet count (333.1 ± 41.1 x 109/L), collagen induced the response of platelet aggregation (12.95 ± 4.19) and maximum rate of aggregation (8.00 ± 5.22) in allergic patients were found significantly higher than those of controls (252.1 ± 49.1 x 109/L; 8.33 ± 1.19; 4.28 ± 1.31) (p< 0.05). Also ADP induced response of platelet aggregation (18.21 ± 3.56) and maximum rate of aggregation (10.64 ± 2.12) in asthmatic patients were higher than controls (12.37 ± 2.63; 7.80 ± 1.64) with statistical significance (p< 0.01). Secretion products of activated platelets such as histamine, serotonin, PGF2α and PAF may play role in bronchial responsiveness in allergic asthma. The results of this study showed that platelet function tests were effected in asthmatic patients. The changes in platelet functions are thought to be related with increased IgE levels and stimulation of platelets by these antibodies.


Hierarchical K-means clustering method for accelerated Lorentzian estimation (KALE) in chemical exchange saturation transfer-magnetic resonance imaging quantification.
Quantification of in vivo chemical exchange saturation transfer (CEST) magnetic resonance signals is challenging due to contamination from coexisting effects, including the direct water effect and asymmetric magnetization transfer. Fitting-based analysis allows the calculation of multiple types of signals from the line shape of Z-spectra. However, the conventional voxelwise method has several drawbacks, including its long computation time and its susceptibility to image noise and Z-spectra oscillations, and it is difficult to determine the initial fitting parameters. Herein, we propose a K-means clustering method for accelerated Lorentzian estimation (KALE) in CEST quantification. Briefly, voxels in CEST images are clustered into K groups according to their Z-spectra characteristics. A 'groupwise' fitting process is then performed with preset initial values, yielding a set of fitted spectra and fitted parameters for each group. With the updated initial values, each group is further clustered into subgroups, and groupwise fitting is performed again. This hierarchical K-means clustering and parameter updating process continues until the pixel number or intensity error meets the termination criteria. Voxelwise fitting could be further conducted to improve the quantification images (termed voxel-K) by utilizing the previous groupwise KALE results as the initial values (termed group-K). Incorporated with Lorentzian difference (LD) quantification, KALE was first optimized and evaluated on 5 healthy human brain datasets at 3 Tesla. Compared with traditional voxel-by-voxel LD quantification, the computation times of group-K and voxel-K were significantly reduced by ~85% and ~70%, respectively (P<0.001). Furthermore, the group-K images exhibited better denoising performance than traditional LD and voxel-K. KALE was further validated on six ischemic rat brains acquired at 7 Tesla, with both LD_group-K and LD_voxel-K displaying almost identical contrast maps with traditional voxelwise maps. When incorporated with the five-pool Lorentzian fitting (LF), KALE exhibited an improved contrast-to-noise ratio (CNR) for amplitude maps of each pool [P=0.003, 0.015, 0.047, and 0.047 for amide, nuclear Overhauser effect (NOE), magnetic transfer (MT) and guanidine amine, respectively] and improved fitting goodness (P=0.033). KALE quantification provides comparable or even superior contrast maps to traditional voxelwise fitting, with significantly reduced computation time. The 'smart' and hierarchical voxel-clustering and parameter updating process of KALE may facilitate more preclinical and clinical CEST applications.


Glandular odontogenic cyst of the maxilla: a case report and literature review.
Glandular Odontogenic Cyst is a relatively rare cyst of odontogenic origin, which shows glandular or salivary features that are thought to indicate the pluripotentiality of odontogenic epithelium. It is seen in middle-aged adults, and commonly involves the anterior region of the jaws, especially the mandible. It shows non-specific clinico-radiographic findings which may resemble other lesions, but has characteristic histopathologic features which help in its diagnosis. This paper reports an unusual presentation of a glandular odontogenic cyst which was diagnosed in a 64-year old female in the posterior maxilla, along with a literature review of this cyst, especially the cases reported in India in the past.


Serum 25(OH)-vitamin D levels and bone metabolism in patients on maintenance hemodialysis.
An increasing amount of evidence suggests that 25-hydroxy vitamin D3 (25(OH)D3) may contribute to the bone health of patients with chronic kidney disease (CKD). The underlying vitamin D status of these patients, however, has often been neglected. In a cross-sectional study we assessed the association between vitamin D status and parathyroid function, bone turnover, bone mass and structure in patients on maintenance hemodialysis. 69 patients on maintenance hemodialysis were assessed by bone densitometry (DEXA) and quantitative bone ultrasound (QUS). Serum 25-hydroxy vitamin D3 levels, serum markers of bone turnover and clinical data were tabulated. A high prevalence of potentially significant vitamin D3 deficiency was found in this patient group: 59% of the patients had a 25(OH)D3 level below 20 nmol/l. There was a significant negative correlation between serum 25(OH)D3 levels and serum intact parathyroid hormone (iPTH) (r = -0.231, p < 0.05), and this association remained significant after controlling for potential covariables. Furthermore, we show here that serum 25(OH)D3 concentration is positively correlated with bone mineral density (BMD) measured at the radius (r = 0.424, p < 0.01). Finally, we show for the first time that 25(OH)D3 levels are significantly and independently correlated with broadband ultrasound attenuation (beta = 0.262, p < 0.05) measured with calcaneal quantitative bone ultrasound (QUS) in patients with chronic renal failure. Vitamin D3 deficiency may contribute to the impaired bone health of patients on maintenance dialysis.


Molecular description of meningeal solitary fibrous tumors/hemangiopericytomas compared to meningiomas: two completely separate entities.
Meningeal solitary fibrous tumors (SFT), like all SFT, are defined by NAB2-STAT6 fusion and share clinicopathologic similarities with meningiomas, the most frequent meningeal tumors. Our aim is to establish the molecular identity of meningeal SFT and seek molecular prognostic factors. RNA sequencing and whole exome sequencing were performed in STAT6-positive SFT and grade 2-3 meningiomas, and data concerning other soft tissues tumors was obtained from the local database. Uniform manifold approximation and projection, individual gene expression and Gene Set Enrichment Analysis were performed. RNA clustering shows that SFT share a common molecular signature, different from any other type of tumoral tissue. Meningeal SFT aggregate with other SFT, with no clinical or histological subgroup. Comparison of genes expressions suggests significant over-expressions of ZIC2, ZIC3, ZIC5, GABBR2, TP53 in CNS-SFT. The pathogenic TP53 c.743G>T variant, previously undescribed in SFT, was found in one sample of meningeal SFT during malignant progression. Meningeal SFT are molecular counterparts of extra-meningeal SFT, completely separate from meningiomas. They might develop from the same tissues and benefit from the same treatments as SFT.


Infrared pseudo matrix isolation spectroscopy: analysis of gas mixtures.
A new low-temperature technique provides a practical and sensitive method of infrared quantitative analysis of all infrared-absorbing gases and volatile liquids. Because pseudo matrix isolation is suitable for qualitative identifications also, it provides a tool for analysis of complex gas mixtures.


Transcriptional profiling of the pea shoot apical meristem reveals processes underlying its function and maintenance.
Despite the importance of the shoot apical meristem (SAM) in plant development and organ formation, our understanding of the molecular mechanisms controlling its function is limited. Genomic tools have the potential to unravel the molecular mysteries of the SAM, and legume systems are increasingly being used in plant-development studies owing to their unique characteristics such as nitrogen fixation, secondary metabolism, and pod development. Garden pea (Pisum sativum) is a well-established classic model species for genetics studies that has been used since the Mendel era. In addition, the availability of a plethora of developmental mutants makes pea an ideal crop legume for genomics studies. This study aims to utilise genomics tools in isolating genes that play potential roles in the regulation of SAM activity. In order to identify genes that are differentially expressed in the SAM, we generated 2735 ESTs from three cDNA libraries derived from freshly micro-dissected SAMs from 10-day-old garden peas (Pisum sativum cv Torsdag). Custom-designed oligonucleotide arrays were used to compare the transcriptional profiles of pea SAMs and non-meristematic tissues. A total of 184 and 175 transcripts were significantly up- or down-regulated in the pea SAM, respectively. As expected, close to 61% of the transcripts down-regulated in the SAM were found in the public database, whereas sequences from the same source only comprised 12% of the genes that were expressed at higher levels in the SAM. This highlights the under-representation of transcripts from the meristematic tissues in the current public pea protein database, and demonstrates the utility of our SAM EST collection as an essential genetic resource for revealing further information on the regulation of this developmental process. In addition to unknowns, many of the up-regulated transcripts are known to encode products associated with cell division and proliferation, epigenetic regulation, auxin-mediated responses and microRNA regulation. The presented data provide a picture of the transcriptional profile of the pea SAM, and reveal possible roles of differentially expressed transcripts in meristem function and maintenance.


Forest edge effects on moss growth are amplified by drought.
Forest fragmentation increases the amount of edges in the landscape. Differences in wind, radiation, and vegetation structure create edge-to-interior gradients in forest microclimate, and these gradients are likely to be more pronounced during droughts and heatwaves. Although the effects of climate extremes on edge influences have potentially strong and long-lasting impacts on forest understory biodiversity, they are not well understood and are not often considered in management and landscape planning. Here we used a novel method of retrospectively quantifying growth to assess biologically relevant edge influences likely caused by microclimate using Hylocomium splendens, a moss with annual segments. We examined how spatio-temporal variation in drought across 3 years and 46 sites in central Sweden, affected the depth and magnitude of edge influences. We also investigated whether edge effects during drought were influenced by differences in forest structure. Edge effects were almost twice as strong in the drought year compared to the non-drought years, but we did not find clear evidence that they penetrated deeper into the forest in the drought year. Edge influences were also greater in areas that had fewer days with rain during the drought year. Higher levels of forest canopy cover and tree height buffered the magnitude of edge influence in times of drought. Our results demonstrate that edge effects are amplified by drought, suggesting that fragmentation effects are aggravated when droughts become more frequent and severe. Our results suggest that dense edges and buffer zones with high canopy cover can be important ways to mitigate negative drought impacts in forest edges.


Hospital-acquired respiratory tract infections: clinical experience with beta-lactam/beta-lactamase inhibitors.
The treatment of nosocomial pneumonia presents a major treatment challenge and one complicated by the rising prevalence of multidrug resistance among nosocomial pathogens. Contemporary treatment strategies for nosocomial pneumonia, which is most often attributable to Gram-negative bacilli or Staphylococcus aureus, mandate early empiric therapy with broad-spectrum antibacterial agents. The choice of agents for empiric therapy is fundamental to outcome, and the selection of inappropriate agents, to which pathogens are resistant, contributes significantly to morbidity and mortality. The adoption of practice guidelines, such as those proposed by the American Thoracic Society, can help to guide antibiotic selection, especially when combined with knowledge of local patterns of infection and antimicrobial susceptibility. Beta-Lactam/beta-lactamase inhibitor combinations, particularly those with activity against Pseudomonas aeruginosa, are among the core antibiotic agents considered suitable for empiric therapy of nosocomial pneumonia. They are particularly suited to use in hospitals with high rates of beta-lactamase-mediated resistance, especially resistance due to extended-spectrum beta-lactamases, infections with Acinetobacter spp. and those of mixed aetiology.


Is accurate rate response programming necessary?
Exercise capacity and general well-being are improved by appropriately programmed rate responsive pacemakers when compared to fixed rate units. Ten patients had activity sensing DDDR units implanted for combined AV block and sinus node incompetence. Ten patients had Sensolog activity sensing VVIR units implanted for complete heart block. The effects of over and under programming of rate response in both dual and single chamber activity sensor rate adaptive pacemakers has been assessed subjectively by visual analog scales and specific activity questionnaires and objectively by graded treadmill testing and the performance of standardized daily activities. Patients were randomly programmed to absent rate response (VVI in the Sensolog group), hyporesponsive (DDD in the dual chamber group), appropriate response (VVIR, DDDR according to Manufacturer's instructions) and over responsive (VVIR+, DDDR+) in a double-blind crossover design. Thirty percent of patients demanded early crossover from VVI, 30% from DDDR+ and 50% from VVIR+. Perception of Exercise Capability was similar to objective exercise treadmill times which were shorter in VVI than in VVIR or VVIR+ (P less than 0.05) or control subjects (P less than 0.001). There was no difference between any dual chamber mode or control subjects. General well-being was poorest in DDDR+ and VVIR+ modes despite objective improvement in exercise capacity. Symptoms were least in VVIR and DDDR and all but one patient chose appropriate programming as their overall preferred mode. Thus, even inaccurate rate response programming results in similar and improved exercise capacity compared to absent rate response but overprogramming is unacceptable to most patients, confirming that appropriate programming and sensor specificity is critical in rate responsive pacing.