Enhancing Cr(VI) bio-reduction by conductive materials and enrichment of functional microbes under anaerobic conditions.
A few studies reported the impact of mineral conductivity properties on contaminant-mineral-microbe interactions and microbial community structure changes in the interaction process. To fill the gap, conductive minerals (magnetite/hematite) and an insulative mineral (quartz) were introduced into Cr(VI) reduction systems to investigate the effect of mineral conductivity properties on Cr(VI) removal. Results showed that conductive minerals enhanced Cr(VI) reduction rate as compared to insulative minerals. Higher reduction percentage (>86%) was observed when both ERB (extracellular respiratory bacteria) and conductive minerals were presence than those with only minerals (<10%) or ERB (<55%), indicating a synergistic effect existed in this bio-remediation system. Moreover, surface elements detection manifested higher Fe-containing groups and Fe(III)-Cr(III) complexes covered on conductive minerals surface when ERB was present. Electrochemical data suggested that ERB facilitated the activity of electron transference on the surface of conductive minerals. Our results indicated that conductive minerals did act as an "electron shuttle" while insulative minerals increased adsorption sites to accelerate Cr(VI) reduction. 16S rRNA sequences results demonstrated that conductive minerals changed the microbial community structure and increased the diversity of the functional microbes including Pseudomonas spp. and Exiguobacterium spp. This work is of deep significance for better understanding the process of elements biogeochemical and elimination of pollutants.


Immune pathophysiology of autoimmune thrombocytopenic purpura.
Chronic autoimmune thrombocytopenic purpura (AITP) is an immune-mediated, bleeding disorder in which platelets are opsonized by autoantibodies and prematurely destroyed by phagocytic cells in the reticuloendothelial system. It is classed as an organ-specific autoimmune disease primarily mediated by immunoglobulin G (IgG) autoantibodies and its etiology appears to be similar to that observed for other organ-specific autoimmune diseases. Th1 cells are important in the process, and the costimulation of Th1 cells and B cells takes place in a cytokine milieu that is reminiscent of a proinflammatory process. Chronic AITP has classically been treated with nonspecific, immunosuppressive regimens (e.g., steroids). One of the most significant developments in the treatment of AITP in the last 20 years has been the use of intravenous immunoglobulin (IVIg) and anti-D preparations. These treatments confer benefit to patients with AITP by significantly raising platelet counts. Despite this, their exact mechanisms of action remain elusive. This review focuses on cell-mediated and cytokine abnormalities within AITP, and presents data related to the mechanism of action of anti-D.


An experimental test of the effect of acute anxious arousal and anxiety sensitivity on negative reinforcement smoking.
Although anxiety sensitivity has been reliably associated with smoking-anxiety comorbidity, there has not been a test of whether this construct moderates the effect of acute anxious arousal on actual smoking behavior. The present study utilized an experimental design to test the moderating role of anxiety sensitivity on laboratory-induced anxious arousal in terms of smoking urges and topography (puff style). Participants were adult daily smokers (n=90; Mage=43.6 SD =9.7); average 15.8 cigarettes per day). A between-subjects design was used; participants were randomly assigned to complete a biological challenge procedure consisting of either a single vital capacity inhalation of 35% carbon dioxide (CO2)-enriched air mixture or compressed room air. Smoking urges and smoking topography (puff behavior) were assessed before and after the challenge. Results revealed a significant interaction between anxiety sensitivity and experimental condition (b=-9.96, p=0.014), such that high anxiety sensitive smokers exposed to 35% CO2-enriched air reported significantly lower levels of smoking urges, relative to low anxiety sensitive smokers; the conditional effect of anxiety sensitivity was not observed for the room air condition. There were no significant interaction effects of experimental manipulation by anxiety sensitivity for any of the smoking topography outcomes. The present results suggest for smokers with higher levels of anxiety sensitivity, the acute experience of anxious arousal is related to decreased subjective smoking urges. These data invite future research to explore the reasons for dampened smoking urges, including cardiorespiratory symptom severity.


Cellular and subcellular imaging in live mice using fluorescent proteins.
Fluorescent proteins have revolutionized in vivo biology. Due to their intrinsic brightness, multiple colors, and ease of genetic manipulation, fluorescent proteins have been demonstrated to be the reporters of choice for in vivo imaging. The present report reviews applications of fluorescent proteins for imaging cancer progression, gene expression, angiogenesis, stem cells, bacterial infection, Leishmania infection, and asthma, at the cellular and subcellular level in live mice. With fluorescent-protein-expressing cells and a highly sensitive small animal imaging system, cellular and subcellular dynamics can now be observed in live mice in real time. Such imaging possibilities can provide new visual targets for novel drug therapy. Fluorescent proteins thus enable both micro as well as macro imaging technology and thereby provide the basis for the new field of in vivo cell biology.


[Analysis on nutritional component of Cervus elaphus products].
To investigate nutrient values in the Cervus elaphus, so as to provide a scientific basis for choosing products by businesses and consumers. According to the national standards required for various nutritional elements, the amount of protein, energy, fat, water, ash, amino acids, minerals, vitamin in different parts of the Cervus elaphus (venison, tail, penis cervi, sinew) were determined, carbohydrate and energy were calculated, and were compared with Cervus nippon. Nutritive characteristics of Cervus elaphus and Cervus nippon were similar. The respective portion of protion in Cervus elaphus venison, Cervus elaphus tail, Cervus elaphus penis cervi, Cervus elaphus sinew were 22.6, 70.7, 85.8 and 89.5 g/100 g; The respective Amino acid score portion in Cervus elaphus venison, Cervus elaphus tail, Cervus elaphus penis cervi, Cervus elaphus sinew were 97, 78, 45, 37. In all Cervus elaphus products, the highest contents of fat, cholesterol, calcium, potassium, iron, vitamin B2 and vitamin B12 were found in Cervus elaphus tail. The highest contents of protion and the lowest contents of potassium, iron and zinc were found in Cervus elaphus sinew. The INQ of protein, cholesterol, potassium, iron, zinc, vitamin B2 and vitamin B12 in Cervus elaphus venison were all above 2, and fat INQ was under 1. Cervus elaphus is a kind of high quality animal food which is rich in protein, potassium, iron, zinc, vitamin B2, vitamin B12 and essential amino acids, and low in fat.


Convolutional neural network models for automatic diagnosis and graduation in skin frostbite.
The study aimed to develop and validate a convolutional neural network (CNN)-based deep learning method for automatic diagnosis and graduation of skin frostbite. A dataset of 71 annotated images was used for the training, the validation, and the testing based on ResNet-50 model. The performances were evaluated with the test set. The diagnosis and graduation performance of our approach was compared with two residents from burns department. The approach correctly identified all the frostbite of IV (18/18, 100%), but with respectively 1 mistake in the diagnosis of degree I (29/30, 96.67%), II (28/29, 96.55%) and III (37/38, 97.37%). The accuracy of the approach on the whole test set was 97.39% (112/115). The accuracy of the two residents were respectively 77.39% and 73.04%. Weighted Kappa of 0.583 indicates good reliability between the two residents (P = .445). Kendall's coefficient of concordance is 0.326 (P = .548), indicating differences in accuracy between the approach and the two residents. Our approach based on CNNs demonstrated an encouraging performance for the automatic diagnosis and graduation of skin frostbite, with higher accuracy and efficiency.


Effects of indomethacin and arachidonic acid on sister chromatid exchange induction by styrene and styrene-7,8-oxide.
Styrene is converted into styrene-7,8-oxide in human lymphocyte cultures, in a reaction probably mediated by oxyhemoglobin. As a consequence, styrene induces sister-chromatid exchanges (SCEs) in whole-blood lymphocyte cultures without exogenous metabolic activation systems. Another metabolic pathway that could be involved in the metabolism of styrene is cooxidation by prostaglandin-endoperoxide synthase (PES). To study the role of PES in the metabolism of styrene, human whole-blood lymphocyte cultures were treated for the entire culture time of 72-h with styrene (0.5 and 1 mM) or styrene-7,8-oxide (50 and 100 microM), in the presence and absence of 75 or 150 microM indomethacin (an inhibitor of PES) and arachidonic acid (substrate of PES). Indomethacin potentiated SCE induction by both styrene and styrene-7,8-oxide; a slight but statistically significant enhancement (16-32%; p < 0.05-p < 0.001) was observed in all treatments with styrene and at 150 microM indomethacin in the case of styrene-7,8-oxide. At 150 microM, arachidonic acid induced a 15-20% suppression (p < 0.01) in SCE induction by both styrene (1 mM only) and styrene-7,8-oxide (100 microM only). Indomethacin or arachidonic acid did not alone influence the frequency of SCEs. The results suggest that PES acts as an inactivation route for styrene and styrene-7,8-oxide in human whole-blood lymphocyte cultures, possibly through PES-mediated binding to glutathione.


Photocurrent enhancement by surface plasmon resonance of silver nanoparticles in highly porous dye-sensitized solar cells.
Localized surface plasmon resonance (LSPR) by silver nanoparticles that are photochemically incorporated into an electrode-supported TiO(2) nanoparticulate framework enhances the extinction of a subsequently adsorbed dye (the ruthenium-containing molecule, N719). The enhancement arises from both an increase in the dye's effective absorption cross section and a modest increase in the framework surface area. Deployment of the silver-modified assembly as a photoanode in dye-sensitized solar cells leads to light-to-electrical energy conversion with an overall efficiency of 8.9%. This represents a 25% improvement over the performance of otherwise identical solar cells lacking corrosion-protected silver nanoparticles. As one would expect based on increased dye loading and electromagnetic field enhanced (LSPR-enhanced) absorption, the improvement is manifested chiefly as an increase in photocurrent density ascribable to improved light harvesting.


SARS-CoV-2 in Exhaled Aerosol Particles from COVID-19 Cases and Its Association to Household Transmission.
Coronavirus disease 2019 (COVID-19) transmission via exhaled aerosol particles has been considered an important route for the spread of infection, especially during super-spreading events involving loud talking or singing. However, no study has previously linked measurements of viral aerosol emissions to transmission rates. During February-March 2021, COVID-19 cases that were close to symptom onset were visited with a mobile laboratory for collection of exhaled aerosol particles during breathing, talking, and singing, respectively, and of nasopharyngeal and saliva samples. Aerosol samples were collected using a BioSpot-VIVAS and a NIOSH bc-251 2-stage cyclone, and all samples were analyzed by RT-qPCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection. We compared transmission rates between households with aerosol-positive and aerosol-negative index cases. SARS-CoV-2 RNA was detected in at least 1 aerosol sample from 19 of 38 (50%) included cases. The odds ratio (OR) of finding positive aerosol samples decreased with each day from symptom onset (OR 0.55, 95 confidence interval [CI] .30-1.0, P = .049). The highest number of positive aerosol samples were from singing, 16 (42%), followed by talking, 11 (30%), and the least from breathing, 3 (8%). Index cases were identified for 13 households with 31 exposed contacts. Higher transmission rates were observed in households with aerosol-positive index cases, 10/16 infected (63%), compared to households with aerosol-negative index cases, 4/15 infected (27%) (χ2 test, P = .045). COVID-19 cases were more likely to exhale SARS-CoV-2-containing aerosol particles close to symptom onset and during singing or talking as compared to breathing. This study supports that individuals with SARS-CoV-2 in exhaled aerosols are more likely to transmit COVID-19.


Anatomic localization of immature and mature dendritic cell subsets in dermatomyositis and polymyositis: Interaction with chemokines and Th1 cytokine-producing cells.
To clarify the involvement of dendritic cells (DCs), chemokines, and proinflammatory Th1 cytokines in the pathogenesis of the chronic muscle diseases dermatomyositis (DM) and polymyositis (PM). We characterized by immunohistochemistry the DC subsets and their interaction with cells producing chemokines and the Th1 cytokines interleukin-17 (IL-17) and interferon-gamma (IFNgamma). Immature and mature DCs were defined by the expression of CD1a and DC-LAMP/CD83, respectively. Immature DCs were mainly detected in lymphocytic infiltrates in DM and PM muscle tissue samples. Mature DCs were detected in perivascular infiltrates and surrounded muscle fibers. IL-17-positive and IFNgamma-positive cells were also observed in perivascular infiltrates in both cases. We then focused on the expression of the CCL20/CCR6 chemokine/receptor complex, which controls immature DC migration, and on the expression of the CCL19/CCR7 and CCL21/CCR7 chemokine/receptor complexes, which control mature DC migration. CCL20 and CCR6 colocalized in lymphocytic infiltrates in DM and PM samples. CCL21 was rarely observed in DM samples and never observed in PM samples. CCL19- and CCR7-expressing cells were absent in both tissues. The close association between CCL20/CCR6 and immature DCs suggests the contribution of CCL20 to CCR6+ immature DC homing. Detection of mature DCs in DM and PM muscle tissue samples despite the lack of CCL19 and CCR7 is evidence for a local maturation of DCs in inflammatory muscle tissue without lymphoid organ organization.


Relevance of the volume-axis intercept, V0, compared with the slope of end-systolic pressure-volume relationship in response to large variations in inotropy and afterload in rats.
The end-systolic pressure-volume relationship (ESPVR) is proposed and used as a reliable index of left ventricular (LV) contractility despite the fact that its afterload independence has been challenged. Furthermore, the physiological relevance of its volume-axis intercept, V(0), remains unclear. Systemic haemodynamics and pressure-volume loops obtained by inferior vena cava occlusion were recorded in 21 rats anaesthetized by isoflurane inhalation and instrumented with a conductance pressure-volume catheter in response to incremental I.V. doses of adrenaline, dobutamine, phenylephrine, metoprolol, papaverine and isoflurane inhalation. In conditions with large variations (± 100%) of both inotropy and afterload, infusion of negative inotropic drugs was associated with a dose-dependent rightward shift of ESPVR accompanied by a decrease in its slope (end-systolic elastance, E(es)), whereas positive inotropic agents produced an isolated decrease in V(0). With the predominant vasoactive drugs, there was a dose-dependent change in E(es) without major horizontal shifts, demonstrating that this slope mainly represents LV afterload rather than inotropy. When contractility was altered, V(0) was negatively correlated to the preload-adjusted contractility index, PAdP/dt(max), demonstrating that a reduced V(0) provides a good reflection of increased LV contractility. From these results, we computed a logarithmically adjusted E(es)/V(0) ratio, which resulted in reasonably strong concordance with PAdP/dt(max), including all the investigated drugs and dosages [n = 288; bias, 0.8 ± 16.2% (SD)]. Concordance with E(es) (bias, 7.2 ± 58.7%) or V(0) (bias, -0.6 ± 33.4%), used alone or with other commonly used contractility indices, was far less significant. In contrast to E(es), V(0) provides a relatively good LV contractility index because it is much less sensitive to afterload.


First glimpses at structure-function relationships of the nucleocapsid protein of retroviruses.
Retroviruses are a family of widespread small animal viruses about 110 nm in diameter, composed of an inner core surrounded by an outer envelope formed of a lipid bilayer of cellular origin in which are anchored viral glycoproteins. The inner core is formed by an outer shell of capsid protein molecules (CA protein) surrounding the dimeric RNA genome in close association with about 2000 molecules of nucleocapsid protein (NC protein) and molecules of reverse transcriptase (RT) and integrase (IN). Conversion of the genomic single-stranded RNA into a double-stranded proviral DNA by RT takes place in the nucleocapsid substructure and involves two DNA strand transfers to generate the long terminal repeats (LTR) required for IN-mediated integration of the proviral DNA into the cellular genome and its expression. In this review we have summarized some of the properties and functions of the nucleocapsid protein of the most intensely studied oncoretroviruses (MuLV and ASLV) and lentiviruses (HIV-1). Recent biochemical and genetic data on retroviral NC proteins have shown that this small viral protein endowed with a strong affinity for nucleic acids exhibits nucleic acid annealing and strand transfer activities and is required for the formation of infectious viral particles. These new activities of NC protein are most probably necessary at the early steps of proviral DNA synthesis. The 3-D structures of HIV-1 and MoMuLV NC proteins, deduced from NMR studies, are characterized by a central globular domain with one (MoMuLV) or two (HIV-1) zinc fingers. This should facilitate a rational approach of new anti-HIV therapies based on inhibition of NC protein functions. Due to space limitations and the very abundant literature on retroviruses, references to articles prior to the publication of the second volume of RNA Tumor Viruses in 1985 (Weiss et al., 1985) will be minimal. We also direct the reader to an excellent review which summarizes recent insights into biochemical and structural aspects of the retroviral enzymes PR, RT and IN (Katz & Skalka, 1994).


Polysaccharide Based Scaffolds for Soft Tissue Engineering Applications.
Soft tissue reconstructs require materials that form three-dimensional (3-D) structures supportive to cell proliferation and regenerative processes. Polysaccharides, due to their hydrophilicity, biocompatibility, biodegradability, abundance, and presence of derivatizable functional groups, are distinctive scaffold materials. Superior mechanical properties, physiological signaling, and tunable tissue response have been achieved through chemical modification of polysaccharides. Moreover, an appropriate formulation strategy enables spatial placement of the scaffold to a targeted site. With the advent of newer technologies, these preparations can be tailor-made for responding to alterations in temperature, pH, or other physiological stimuli. In this review, we discuss the developmental and biological aspects of scaffolds prepared from four polysaccharides, viz. alginic acid (ALG), chitosan (CHI), hyaluronic acid (HA), and dextran (DEX). Clinical studies on these scaffolds are also discussed.


Inhibitory effect of selenium on biliary secretion of methyl mercury in rats.
The inhibitory effect of sodium selenite on biliary secretion of methyl mercury was examined in rats. The biliary secretion of methyl mercury in rat treated with 1 mumol/kg of methyl mercury was significantly decreased by administration of selenite at doses of 0.05 mumol/kg or higher. In rats given 10 mumol/kg of methyl mercury, marked depression of biliary secretion of mercury was observed when selenite was injected at a dose of 0.2 mumol/kg. On the other hand, secretion of substantial amounts of selenium was observed when biliary secretion of mercury was depressed. When the concentration of selenium in the bile was higher than 5 nmol/ml, biliary secretion of mercury was markedly depressed independently of the dose of methyl mercury administered (1 mumol/kg or 10 mumol/kg). These results suggest that the degree of inhibitory effect of selenite may be determined by the selenium concentration in the liver or the bile after treatment with selenite rather than the molar ratio of the dose of methyl mercury and selenite. We concluded that the decrease in biliary secretion of methyl mercury induced by selenite may result from inhibition of pathway for secretion of methyl mercury from liver to bile rather than the direct formation of a complex between methyl mercury and selenium. Methyl mercury has been considered to be secreted from liver to bile as a complex with glutathione (GSH). However, administration of selenite did not affect biliary secretion of GSH or hepatic glutathione S-transferase activity. Moreover, gel filtration of liver cytosol demonstrated that the distribution pattern of hepatic methyl mercury between macromolecules and GSH was not significantly changed by administration of selenite. These results suggest that selenite does not affect complex formation of methyl mercury with GSH at least in the liver. Selenite might specifically inhibit the activity of the canalicular transporter(s) which transport complexes of methyl mercury and GSH from the liver to bile.


Three cases of idiopathic interstitial pneumonia with bullae seen in schoolteachers.
We encountered three patients with chronic interstitial pneumonia with many bullae in the lower lung fields whose lifetime occupation was teaching school. Pathological examination of autopsy lungs of these patients revealed interstitial pneumonia and multiple bullae throughout the lungs, including the lower lobe. Since blackboard chalk has been used as a popular writing material among teachers in Japan, the mineral contents in the lungs of two of the three cases and four control cases with idiopathic interstitial pneumonia (IIP) (whose occupations were not teaching) were analyzed. The amount of deposition of total dust, inorganic dust, non-SiO2 inorganic dust, and calcium was significantly higher in the lungs of two schoolteachers compared with those of the control lungs. The amount of free silica in case 1 and alpha-quartz in case 3 were also significantly higher than in the controls. Two thirds of the chalk produced in Japan is still made from gypsum and involves small amounts of silica and other minerals, in addition to calcium. These findings indicated the deposition of chalk in the lungs of these patients with interstitial pneumonia and multiple bullae.


Reach-to-grasp movements in Macaca fascicularis monkeys: the Isochrony Principle at work.
Humans show a spontaneous tendency to increase the velocity of their movements depending on the linear extent of their trajectory in order to keep execution time approximately constant. Termed the isochrony principle, this compensatory mechanism refers to the observation that the velocity of voluntary movements increases proportionally with their linear extension. Although there is a wealth of psychophysical data regarding isochrony in humans, there is none regarding non-human primates. The present study attempts to fill that gap by investigating reach-to-grasp movement kinematics in free-ranging macaques. Video footage of monkeys grasping objects located at different distances was analyzed frame-by-frame using digitalization techniques. The amplitude of arm peak velocity was found to be correlated with the distance to be covered, and total movement duration remained invariant although target distances varied. Like in humans, the "isochrony principle" seems to be operative as there is a gearing down/up of movement velocity that is proportional to the distance to be covered in order to allow for a relatively constant movement duration. Based on a centrally generated temporal template, this mode of motor programming could be functional in macaques given the high speed and great instability of posture and joint kinematics characterizing their actions. The data presented here take research in the field of comparative motor control a step forward as they are based on precise measurements of spontaneous grasping movements by animals living/acting in their natural environment.


RGD dendron bodies; synthetic avidity agents with defined and potentially interchangeable effector sites that can substitute for antibodies.
Poly(amidoamine) (PAMAM) dendrons were synthesized with c(RGDyK) peptide on the surface to create a scaffold for cellular targeting and multivalent binding. Binary dendron-RGD conjugates were synthesized with a single Alexa Fluor 488, biotin, methotrexate drug molecule, or additional functionalized dendron at the focal point. The targeted dendron platform was shown to specifically target αvβ3 integrin expressing human umbilical vein endothelial cells (HUVEC) and human glioblastoma cells (U87MG) in Vitro via flow cytometry. Specific targeting of the dendron-RGD platform was further confirmed by confocal microscopy. Biological activity of the targeted drug conjugate was confirmed via XTT assay. The orthogonal reaction chemistry used at the dendron focal point gives a precise 1:1 ratio of the attachment of multiple functionalities to a small-molecular-weight, chemically stable, high avidity molecule. These studies serve as a framework to selectively combine biologically relevant functions with enhanced specific binding activity to substitute for antibodies in many diagnostic and therapeutic applications.


Nucleation and aggregative growth process of platinum nanoparticles studied by in situ quick XAFS spectroscopy.
The early stage in the nucleation and subsequent aggregative particle growth of the colloidal platinum (Pt) dispersions produced by photoreduction in an aqueous ethanol solution of poly(N-vinyl-2-pyrrolidone) (PVP) was quantitatively investigated by means of in situ quick XAFS (QXAFS) measurements. The stages of the reduction-nucleation and the association process (aggregative particle growth and Ostwald ripening) of Pt atoms to produce Pt nanoparticles was successfully discriminated in course of the photoreduction time. The present QXAFS analysis indicated that Pt nuclei (i.e., (Pt(0))(m) nucleates approximately m = 4) were continuously produced in the reduction-nucleation process at the early time, followed by the aggregative particle growth with the autocatalytic reduction of Pt ionic species on the surface of Pt nuclei to produce Pt nanoparticles. Subsequently the particle growth proceeded via Ostwald ripening, resulting in the production of larger Pt nanoparticles at a later time. It was also found that the aggregative particle growth follows a sigmoidal profile well described either by the solid-state kinetic model or by the chemical-mechanism-based kinetic model, specifically the Avrami-Erofe'ev or Finke-Watzky models. The difference in terms of the formation mechanism was observed between the reduction of Pt(IV)Cl(6)(2-) and Pt(II)Cl(4)(2-) as a source material. Also presented is that the addition of the photoactivator such as benzoin, benzophenone, and acetophenone in the system is very effective to enhance the rate for the formation of Pt nanoparticles.


Communications: On artificial frequency shifts in infrared spectra obtained from centroid molecular dynamics: Quantum liquid water.
Centroid molecular dynamics (CMD) is a popular method to extract approximate quantum dynamics from path integral simulations. Very recently we have shown that CMD gas phase infrared spectra exhibit significant artificial redshifts of stretching peaks, due to the so-called "curvature problem" imprinted by the effective centroid potential. Here we provide evidence that for condensed phases, and in particular for liquid water, CMD produces pronounced artificial redshifts for high-frequency vibrations such as the OH stretching band. This peculiar behavior intrinsic to the CMD method explains part of the unexpectedly large quantum redshifts of the stretching band of liquid water compared to classical frequencies, which is improved after applying a simple and rough "harmonic curvature correction."


Can Digital Instruments Like the Macula-App Support AMD Therapy?
A long lasting and continuous anti VEGF-therapy represents a gold standard in nAMD treatment to maintain and stabilize vision in the individual patient. Disease Management represents a daily life challenge for patients and relatives and "Real-life" clinical outcomes of patients treated with IVOM therapy are often inferior to results from randomized clinical trials. After their diagnosis, AMD-patients undergo individualized long-term therapeutic approaches. An important success factor is, that this care is patient centered and provided continuously. This study aimed at evaluating, whether digital tools, such as Makula-App 1.0 developed by the AMD-Netz can support AMD patients. The results of a user survey integrated in the Makula-App 1.0 (n = 110) as well as the results of an additional survey on the topic of "Digital appointment management in IVOM therapy" by ophthalmologists (n = 54) and patients (n = 60) were analysed with respect to use and acceptance of the Makula-App. The survey revealed: 79% of Makula-App user rely on the information presented, 71% perceive the device helpful for their daily life and 80% would recommend the device. 52% of ophthalmologists and 65% of patients regard clear benefits of future digital tools for patient adherence. A digital appointment management function is rated as important by 82% of ophthalmologists. User perceived Makula-App 1.0 as well as its future development options as beneficial especially for the management of appointment arrangements but also as information tool. Ophthalmologists confirm the importance and usefulness of devices such as Makula-App 1.0 with respect to an optimized management of appointments and an improved patient adherence. These promising results support the future development of a Makula-App 2.0 platform, providing interfaces for an information exchange between patient and treating ophthalmologist.


Kinetically inhibited order in a diamond-lattice antiferromagnet.
Frustrated magnetic systems exhibit highly degenerate ground states and strong fluctuations, often leading to new physics. An intriguing example of current interest is the antiferromagnet on a diamond lattice, realized physically in A-site spinel materials. This is a prototypical system in three dimensions where frustration arises from competing interactions rather than purely geometric constraints, and theory suggests the possibility of unusual magnetic order at low temperature. Here, we present a comprehensive single-crystal neutron scattering study of CoAl(2)O(4), a highly frustrated A-site spinel. We observe strong diffuse scattering that peaks at wavevectors associated with Néel ordering. Below the temperature T(∗) = 6.5 K, there is a dramatic change in the elastic scattering lineshape accompanied by the emergence of well-defined spin-wave excitations. T(∗) had previously been associated with the onset of glassy behavior. Our new results suggest instead that T(∗) signifies a first-order phase transition, but with true long-range order inhibited by the kinetic freezing of domain walls. This scenario might be expected to occur widely in frustrated systems containing first-order phase transitions and is a natural explanation for existing reports of anomalous glassy behavior in other materials.


Sleep duration during weekdays affects hippocampal gray matter volume in healthy children.
Sleep is essential for living beings, and sleep loss has been shown to affect hippocampal structure and function in rats by inhibiting cell proliferation and neurogenesis in this region of the brain. We aimed to analyze the correlation between sleep duration and the hippocampal volume using brain magnetic resonance images of 290 healthy children aged 5-18 years. We examined the volume of gray matter, white matter, and the cerebrospinal fluid (CSF) space in the brain using a fully automated and established neuroimaging technique, voxel-based morphometry, which enabled global analysis of brain structure without bias towards any specific brain region while permitting the identification of potential differences or abnormalities in brain structures. We found that the regional gray matter volume of the bilateral hippocampal body was significantly positively correlated with sleep duration during weekdays after adjusting for age, sex, and intracranial volume. Our results indicated that sleep duration affects the hippocampal regional gray matter volume of healthy children. These findings advance our understanding of the importance of sleep habits in the daily lives of healthy children.


Electromagnetic response of Weyl semimetals.
It has been suggested recently, based on subtle field-theoretical considerations, that the electromagnetic response of Weyl semimetals and the closely related Weyl insulators can be characterized by an axion term θE·B with space and time dependent axion angle θ(r,t). Here we construct a minimal lattice model of the Weyl medium and study its electromagnetic response by a combination of analytical and numerical techniques. We confirm the existence of the anomalous Hall effect expected on the basis of the field theory treatment. We find, contrary to the latter, that chiral magnetic effect (that is, ground state charge current induced by the applied magnetic field) is absent in both the semimetal and the insulator phase. We elucidate the reasons for this discrepancy.


Tivantinib: critical review with a focus on hepatocellular carcinoma.
Sorafenib is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). Sorafenib is an oral multikinase inhibitor that blocks several receptors involved in tumor cell proliferation and angiogenesis. The hepatocyte-growth factor/mesenchymal-epithelial transition (MET) factor pathway represents another emerging target in HCC. Tivantinib (ARQ 197) is an oral, selective small MET tyrosine kinase inhibitor with antitumor activity, especially in MET-high patients. Recent clinical data exhibit promising activity in HCC. This article reviews the preclinical and clinical data of tivantinib (published and ongoing trials), focusing on development in advanced HCC. Comments regarding the failure of trials with nonspecific drugs reported in the past 2 years are also included. A randomized Phase II trial in second-line HCC showed a significant improvement in time to progression with tivantinib treatment in MET-high patients. Tivantinib remains in clinical development and has not yet been approved for any indication. A Phase III study in MET-high HCC is ongoing in a second-line setting, after sorafenib failure. In case of a survival benefit, tivantinib might become the first treatment for selected patients, based on MET status as a predictor. Therefore, there is a need for identifying HCC molecular subclasses and for developing a trial design based on molecular biomarkers.


Uncommon of the uncommon: malignant perivascular epithelioid cell tumor of the lung.
A perivascular epithelioid cell (PEC) tumor is a rare mesenchymal tumor characterized by abundant cytoplasmic Periodic acid-Schiff positive glycogen (also called sugar tumor or clear cell tumor of the lung for this characteristic) and is mostly benign. We report a case of a 63-year-old man who presented with an enlarging mass on chest radiograph. After a thorough workup, diagnosis of malignant pulmonary PEC tumor with lung to lung metastases was established. Herein, the difficulties of diagnosis and management we confronted are described.


Analysis for identification in amnesty bin samples from dance venues.
The analysis of unknown substances discarded in amnesty bins, first described by Ramsey et al, from a large central London club and 7 smaller clubs in Manchester, UK are described. The contents of the bins were collected between July 2003 and March 2004. Solid dosage formulations were identified using the TICTAC database, chemical tests, and GC-MS screening. Drugs that could not be readily identified were subjected to other analytical techniques. The goal was to document the current range of drugs available on the dance scene and compare the findings between the London club, which had been the subject of a previous survey, and Manchester clubs. More than 1000 tablets, capsules, and powder doses were discarded in the amnesty bins. Tablets containing only MDMA (ecstasy) were found to be >94% and >84% of the total in London and Manchester, respectively. Although the quantities of tablets and powders recovered were different between London and Manchester, the proportions of the drugs were remarkably similar. The most common drugs found in powders in London and Manchester respectively were cocaine (29%, 40%), amphetamine (25%, 26%), ketamine (19%, 20%), and MDMA (19%, 11%).


The many faces of ribosome translocation along the mRNA: reading frame maintenance, ribosome frameshifting and translational bypassing.
In each round of translation elongation, the ribosome translocates along the mRNA by precisely one codon. Translocation is promoted by elongation factor G (EF-G) in bacteria (eEF2 in eukaryotes) and entails a number of precisely-timed large-scale structural rearrangements. As a rule, the movements of the ribosome, tRNAs, mRNA and EF-G are orchestrated to maintain the exact codon-wise step size. However, signals in the mRNA, as well as environmental cues, can change the timing and dynamics of the key rearrangements leading to recoding of the mRNA into production of trans-frame peptides from the same mRNA. In this review, we discuss recent advances on the mechanics of translocation and reading frame maintenance. Furthermore, we describe the mechanisms and biological relevance of non-canonical translocation pathways, such as hungry and programmed frameshifting and translational bypassing, and their link to disease and infection.


Decline and rise of mortality from motor neuron disease in Spain, 1960-1989: demographic, environmental and competitive influences.
Mortality rates from motor neuron disease (MND) in Spain were analysed for the years 1960-1989, a period in which 3,530 deaths were recorded from the disease and during which the crude annual mortality rate ranged between 0.35 and 0.95 deaths per 100,000 persons. Whilst the crude mortality rate fell by 54% during the decade 1960-1969, there was a net increase of 26% over the entire period. The influence of three sets of variables-the increasing mean age of the population, changing environmental factors, and changing competition between diseases-upon mortality rates were investigated through Gompertzian analysis of crude and age-adjusted mortality rates. The increased mean age of the population contributed significantly to the overall rise in mortality from MND over the whole period, a feature that has previously been demonstrated to occur in the majority of industrialised countries. The unusual pattern of a decline and subsequent rise in mortality appears to be due to the influence of changing environmental factors on a sub-population susceptible to the disease.


Management of insulin dependent diabetes.
Modern management of patients with insulin-dependent diabetes mellitus (IDDM) is a specialised area, usually undertaken as a team effort by general practitioner, diabetes specialist, diabetes educator and dietitian. Treatment includes that of associated problems, early intervention and management of foot problems and of sick days.


Nano-graphene oxide-mediated In vivo fluorescence imaging and bimodal photodynamic and photothermal destruction of tumors.
Cancer is one of the major life-threatening diseases among human beings. Developing a simple, cost-effective and biocompatible approach to treat cancers using ultra-low doses of light is a grand challenge in clinical cancer treatments. In this study, we report for the first time that nano-sized graphene oxide (GO) exhibits single-photon excitation wavelength dependent photoluminescence in the visible and short near-infrared (NIR) region, suitable for in vivo multi-color fluorescence imaging. We also demonstrate in both in vitro and in vivo experiments to show that nano GO can sensitize the formation of singlet oxygen to exert combined nanomaterial-mediated photodynamic therapeutic (NmPDT) and photothermal therapy (NmPTT) effects on the destruction of B16F0 melanoma tumors in mice using ultra-low doses (∼0.36 W/cm(2)) of NIR (980 nm) light. The average half-life span of the mice treated by the GO-PEG-folate-mediated NmPDT effects is beyond 30 days, which is ∼1.8 times longer than the mice treated with doxorubicin (17 days). Overall, the current study points out a successful example of using GO-PEG-folate nanocomposite as a theranostic nanomedicine to exert simultaneously in vivo fluorescent imaging as well as combined NmPDT and NmPTT effects for clinical cancer treatments.


Spontaneous intracerebral hemorrhage and the challenge of surgical decision making: a review.
Decision making for patients with spontaneous intracerebral hemorrhage (ICH) poses several challenges. Outcomes in this patient population are generally poor, prognostication is often uncertain, and treatment strategies offer limited benefits. Studies demonstrate variability in the type and intensity of treatment offered, which is attributed to clinical uncertainty and habits of training. Research has focused on new techniques and more stringent evidence-based selection criteria to improve outcomes and produce consensus around treatment strategies for patients with ICH. Such focus, however, offers little description of how ICH treatment decisions are made and how such decisions reflect patient preferences regarding medical care. A growing body of literature suggests that the process of decision making in ICH is laden with bias, value assumptions, and subjective impressions. Factors such as geography, cognitive biases, patient perceptions, and physician characteristics can all shape decision making and the selection of treatment. Such factors often serve as a barrier to providing patient-centered medical care. In this article, the authors review how surgical decision making for patients with ICH is shaped by these decisional factors and suggest future research pathways to study decision making in ICH. Such research efforts are important for establishing quality guidelines and pay-for-performance measures that reflect the preferences of individual patients and the contextual nature of medical decision making.


Procyanidin B1 purified from Cinnamomi cortex suppresses hepatitis C virus replication.
A combination of pegylated interferon and ribavirin is the current standard therapy for hepatitis C virus (HCV) infection, but this combination provides relatively low efficacy, especially in some patients with HCV genotype 1 infection; therefore, the development of novel therapeutic agents is required for further improvement in the treatment of chronic HCV infection. HCV pseudotype and subgenomic replicon assays were used in this study. The interaction of compounds with HCV receptors was examined using flow cytometry. Intracellular RNA levels were determined by semi-quantitative reverse transcriptase PCR. Procyanidin B1 (PB1), a dimer of (-)-epicatechin and (+)-catechin, purified from Cinnamomi cortex, inhibits infection by vesicular stomatitis virus and HCV pseudotype virus in Huh-7 cells, with 50% effective concentrations of 29 and 15 microM, respectively. No inhibitory effects were observed in each component of PB1. We found that PB1 does not interfere with viral entry or receptor expression, but inhibits HCV RNA synthesis in a dose-dependent manner. These results indicate that PB1 suppresses HCV RNA synthesis, possibly as a HCV RNA polymerase inhibitor. Our results might contribute towards the development of more effective inhibitors for HCV infection from natural plants.


Aquaporin inhibition by gold(III) compounds: new insights.
Aquaporins (AQPs) are membrane water/glycerol channels with essential roles in biological systems, as well as being promising targets for therapy and imaging. Using a stopped-flow method, a series of gold(III), platinum(II) and copper(II) complexes bearing nitrogen donor ligands, such as 1,10-phenatroline, 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, 4,4'-diamino-2,2'-bipyridine and 2,2';6',2"-terpyridine, were evaluated in human red blood cells expressing AQP1 and AQP3, responsible for water and glycerol movement, respectively. The results showed that the gold(III) complexes selectively modulate AQP3 over AQP1. Molecular modeling and density functional theory (DFT) calculations were subsequently performed to rationalize the observations and to investigate the possible molecular mechanism through which these gold compounds act on their putative target (AQP3). In the absence of any crystallographic data, a previously reported homology model was used for this purpose. Combined, the findings of this study show that potent and selective modulation of these solute channels is possible, however further investigation is required into the selectivity of this class of agents against all AQP isoforms and their potential therapeutic uses.


[Glycoproteins of mucus of gastric and duodenal wall surface during ulcerogenesis and the impact of fenugreek].
The comparative evaluation of qualitative and quantitative composition of glycoproteins of gastric and duodenal wall surface layer of protective mucus in the normal, at the modeling of ulcers in rats and at the introduction to animals with ulcerative lesions of fenugreek extract carried out. It was shown in control (normally) the general level of glycosylation of glycoproteins gastric mucus is 1.7 times more than the duodenum. Under acute stress model ulceration in the stomach mucus decrease in hexosamine (1.4 times), galactose (2.2 times), fucose (1.3-fold) and an increase in NANA (3.6 times) observed. Under cysteamine model ulceration in duodenal mucus increase galactose (2.7 times), NANA (2.4 times), fucose (1.8-fold) but significant decrease in the amount of hexosamines 3 times compared to the control occurred. It was proved the protective effect of fenugreek extract to the wall surface mucus of the stomach and duodenum mucosa under conditions modeling ulceration in rats.


Embolization of hepatic hemangiomas in infants.
A small number of cavernous liver hemangiomas in infants cause serious symptoms, requiring active treatment. We report two newborns with giant liver hemangiomas, treated by intra-arterial embolization. The babies presented at 2 - 8 days after birth with tachypnoea and cardiac dilation. A giant liver hemangioma located in the right liver lobe in one infant and in the left liver lobe in the other was found at ultrasonography and computed tomography. Dilated liver veins indicated abnormal shunting of the blood through the hemangiomas. Because of progress of symptoms superselective embolization of the arteries feeding the hemangiomas and arising from the celiac trunk was performed with a mixture of Lipoidol and Histoacryl. A decrease of tachypnoea and of heart volume was noted after embolization. In one infant surgery was necessary due to gastrointestinal bleeding. The intra-arterial embolization is a valuable method for the treatment of newborns with symptomatic cavernous liver hemangiomas.


Prognostic Value of NRAS Gene for Survival of Colorectal Cancer Patients: A Systematic Review and Meta-Analysis
Introduction: NRAS gene is associated with malignant proliferation and metastasis of colorectal cancer (CRC). But its prognostic value on CRC is still unknown. The objective of this study is to perform a meta-analysis to obtain its prognostic value on survival of CRC patients. Methods: The systematic review and meta-analysis was designed, undertaken and reported using items from the PRISMA statement. Relevant articles were identified through PubMed (containing Medline), Embase, Web of Science databases and Google scholar search engines from their inception up to October 3, 2016. The articles about NRAS on prognosis of CRC patients were enrolled. The association between NRAS and CRC survival time (including overall survival [OS], progression-free survival [PFS], and disease-free survival [DFS]) was evaluated using hazard ratio (HR) with its corresponding 95% confidence interval (CI). Results: A total of fifteen articles were included. High-expression of NRAS was significantly associated with poor OS (HR: 1.36, 95% CI: 1.15–1.61), and poor PFS (HR: 1.75, 95% CI: 1.04–2.94). The combined HR of NRAS on DFS was 0.87 (95% CI: 0.37–2.03). Subgroup analysis showed that NRAS was significantly associated with poor OS for patients from Western countries (HR: 1.38, 95% CI: 1.09–1.73), but not for those from Asian countries. Conclusions: This meta-analysis demonstrate that NRAS gene could predict the poor prognosis for the CRC patients. More large-sample cohort studies are needed to further confirm this conclusion.


Carcinoma of the middle bile duct: is bile duct segmental resection appropriate?
To compare survival between bile duct segmental resection (BDSR) and pancreaticoduodenectomy (PD) for treating distal bile duct cancers. Retrospective analysis was conducted for 45 patients in a BDSR group and for 149 patients in a PD group. The T-stage (P < 0.001), lymph node invasion (P = 0.010) and tumor differentiation (P = 0.005) were significant prognostic factors in the BDSR group. The 3- and 5-year overall survival rates for the BDSR group and PD group were 51.7% and 36.6%, respectively and 46.0% and 38.1%, respectively (P = 0.099). The BDSR group and PD group did not show any significant difference in survival when this was adjusted for the TNM stage. The 3- and 5-year survival rates were: stage Ia [BDSR (100.0% and 100.0%) vs PD (76.9% and 68.4%) (P = 0.226)]; stage Ib [BDSR (55.8% and 32.6%) vs PD (59.3% and 59.3%) (P = 0.942)]; stage IIb [BDSR (19.2% and 19.2%) vs PD (31.9% and 14.2%) (P = 0.669)]. BDSR can be justified as an alternative radical operation for patients with middle bile duct in selected patients with no adjacent organ invasion and resection margin is negative.


Occupational therapists' use of advocacy in brain injury rehabilitation settings.
Occupational therapists working in brain injury rehabilitation are required to use the skill of advocacy to ensure that people with a brain injury have the right to engage in their chosen occupations. However, no studies were found exploring the use of advocacy by occupational therapists working in brain injury rehabilitation. To investigate how occupational therapists working in brain injury rehabilitation defined and implemented the skill of advocacy when working with clients. Interpretative phenomenological analysis was used to guide planning, data collection and analysis. Thirteen occupational therapists from six NSW metropolitan, regional and rural brain injury rehabilitation units participated in semi-structured interviews. All interviews were transcribed and member-checked prior to in-depth idiographic, inductive and interrogative analysis of each transcript. Participants identified the key elements of advocacy as the representation and education of clients and significant others. They indicated that all brain injury rehabilitation workers used advocacy when working with their clients, but were unable to identify unique ways that occupational therapists used advocacy when compared with other brain injury rehabilitation staff. However, they all felt that occupational therapists were well suited to advocate for clients in brain injury rehabilitation settings. Although participants had difficulty identifying unique ways in which occupational therapists used advocacy in brain injury rehabilitation settings, they all agreed that advocacy was an important skill for occupational therapists to develop and implement.


Growth characteristics in axenic and cell cultures, protein profiles, and zymodeme typing of three Trypanosoma cruzi isolates from Louisiana mammals.
Rates of trypomastigote adherence, interiorization, amastigote division in, and trypomastigote release from Vero cells were measured for Trypanosoma cruzi isolates from a dog (Tc-D), opossum (Tc-O), and an armadillo (Tc-A) from Louisiana. Because the Tc-O and Tc-A (wild isolates) trypomastigotes became interiorized rapidly, the media were quickly depleted of trypomastigotes thus reducing the numbers available to adhere to cells. In contrast, the Tc-D trypomastigote interiorization rate was slower. Intracellular amastigote division rate was slower for the Tc-D than the wild isolates. The Tc-D trypomastigotes were released from cells approximately 2 days later than wild isolate trypomastigotes, but twice the number were released. Growth rate for Tc-D epimastigotes in liver infusion tryptose media was faster than that of wild isolates. The doubling times for Tc-D, Tc-O, and Tc-A were 48.0, 69.0, and 67.4 hr, respectively. Soluble parasite extract was produced from epimastigotes of each isolate by freeze/thawing, sonication, and high-speed centrifugation. Proteins were separated on an SDS-PAGE slab gel and stained with Coomassie blue. Although similar bands were present in each preparation, the general pattern of staining was similar only between the Tc-O and Tc-A preparations, which showed some differences from the Tc-D preparation. Each isolate was zymodeme typed using 5 enzymes in lysates produced from epimastigotes of each isolate. Enzymes were separated electrophoretically and stained. Wild isolates showed similar patterns as zymodeme 1 reference stock, whereas the Tc-D isolate produced a pattern that did not resemble any of the reference stocks examined.


Effect of Corroded Surface Morphology on Ultra-Low Cycle Fatigue of Steel Bridge Piers.
Corrosion is a common form of durability degradation of steel bridges. Corrosion morphology affects stress distribution under cyclic loads and causes strain concentrations in pits, thus affecting the mechanical properties of steel structures, including ultra-low cycle fatigue (ULCF). To precisely simulate corrosion morphology and investigate the ULCF failure mechanism of corroded steel piers, a sculpting method was applied to mesh units using three-dimensional surface morphology data of corroded steel specimens. Moreover, the ULCF crack-initiation life was numerically predicted using the finite element model based on the cyclic void growth model (CVGM). The cumulative equivalent plastic strain, cyclic void growth index, and critical void growth index of corroded steel piers with different corroded morphologies were compared. Results reveal that, regardless of whether the pier is corroded, fatigue cracks tend to initiate at the weld toe at corners when exposed to cyclic loads under an oblique direction at the pier top. Additionally, the ULCF crack-initiation life in a corroded pier is less than that in an uncorroded pier, and it is significantly affected by a reduction in the pier wall thickness. Corrosion pits affect the position of ULCF crack initiation in a steel pier and cracks tend to initiate at the bottom of pits with large depth-to-diameter ratios. In the case of minor corrosion, the corrosion morphology affects the seismic performance of piers to a small extent.


Structural and functional alterations in untreated patients with major depressive disorder and bipolar disorder experiencing first depressive episode: A magnetic resonance imaging study combined with follow-up.
Magnetic resonance imaging (MRI) could assist in identifying objective biomarkers and follow-up study could effectively improve subjective diagnostic accuracy. By combining MRI with follow-up, this study aims to determine the shared and distinct alterations between major depressive disorder (MDD) and bipolar disorder (BD). Untreated patients with MDD experiencing the first episode were subjected to MRI and subsequent follow-up. Fifteen patients with mania or hypomania were regrouped into BD group. Twenty patients were still grouped as MDD after an average of 37.95 months follow-up. Thirty healthy controls (HCs) were recruited to match the patients. Gray matter volume (GMV) and amygdala-seed functional connectivity (FC) in the whole brain were detected and compared among the three groups. GMV analysis revealed that the MDD and BD groups presented reduced GMV predominantly in the parietal, occipital, and frontal regions in the bilateral cerebrum compared with the HCs. The BD group had reduced GMV predominantly in the parietal, temporal, insular regions and the Rolandic operculum in the right-side cerebrum compared with MDD and HC groups. FC analysis revealed that the MDD and BD patients displayed increased FC values mainly in the bilateral parietal, and left occipital regions. Only the BD group displayed increased FC values in the temporal, occipital, parietal and limbic regions in the right-side cerebrum relative to HCs. The main limitation is the relatively small sample size. Alterations in the cortical regions and cortico-limbic neural system may provide the scientific basis for differential diagnosis in affective disorders.


Has Asthma Medication Use Caught Up With the Evidence?: A 12-Year Population-Based Study of Trends.
The importance of balance between controller and reliever medications in asthma is recognized. However, to our knowledge, the extent to which real-world practice has caught up with evidence-based guidelines has not been studied. This was a retrospective cohort study of individuals 15 to 67 years of age who satisfied a validated case definition of asthma in the administrative health database of British Columbia, Canada between 2002 and 2013. Each patient-year was assessed for inappropriate and excessive prescription of short-acting beta-agonists (SABAs) and the balance between controller and reliever medications. Trends on three time axes were evaluated: calendar time, time course of asthma, and age. Poisson regression was used to test for a linear trend. Three hundred fifty-six thousand, one hundred twelve patients (56.5% female sex; mean age, 30.5 years) contributed 2.6 million patient-years. In 7.3% of the patient-years, SABAs were prescribed inappropriately. This proportion dropped by a relative rate of 5.3% per year (P < .001). In the first year of asthma, 6.3% of patients had indicators of inappropriate SABA use, which dropped within the first 3 years but increased thereafter. Excessive prescription of SABAs increased rapidly during the time course of asthma (change of 23.3% per year; P < .001) and by age (change of 5.1% per year; P < .001). Despite overwhelming evidence regarding the risks, inappropriate prescription for SABAs was prevalent. Excessive SABA use might explain high asthma mortality in older patients. Inappropriate prescriptions declined over the study period but increased over the time course of asthma. These trends might have contributed to the declining asthma hospitalization rates in British Columbia, but there remain gaps in care and potential for improvement in asthma outcomes.


The effect of genetic structure on molecular dating and tests for temporal signal.
'Dated-tip' methods of molecular dating use DNA sequences sampled at different times, to estimate the age of their most recent common ancestor. Several tests of 'temporal signal' are available to determine whether data sets are suitable for such analysis. However, it remains unclear whether these tests are reliable.We investigate the performance of several tests of temporal signal, including some recently suggested modifications. We use simulated data (where the true evolutionary history is known), and whole genomes of methicillin-resistant Staphylococcus aureus (to show how particular problems arise with real-world data sets).We show that all of the standard tests of temporal signal are seriously misleading for data where temporal and genetic structures are confounded (i.e. where closely related sequences are more likely to have been sampled at similar times). This is not an artefact of genetic structure or tree shape per se, and can arise even when sequences have measurably evolved during the sampling period. More positively, we show that a 'clustered permutation' approach introduced by Duchêne et al. (Molecular Biology and Evolution, 32, 2015, 1895) can successfully correct for this artefact in all cases and introduce techniques for implementing this method with real data sets.The confounding of temporal and genetic structures may be difficult to avoid in practice, particularly for outbreaks of infectious disease, or when using ancient DNA. Therefore, we recommend the use of 'clustered permutation' for all analyses. The failure of the standard tests may explain why different methods of dating pathogen origins have reached such wildly different conclusions.


Nucleophilic scandium carbene complexes.
Using a geminal dianion as precursor, a nucleophilic scandium carbene complex (2) has been synthesized by salt metathesis on ScCl(3)(THF)(3) in 52% isolated yield. The X-ray structure as well as an NBO analysis points to a double interaction between the carbon and the scandium atoms. Quantification of the electron density donation from the carbon to the metal center, from both σ and π symmetry orbitals, predicts a "nucleophilic carbene" behavior. Addition of benzophenone on complex 2 results in the formation of the expected alkene derivative and the trapping of a rare, μ(3)-oxo-Sc species via a "scandia-Wittig" reaction.


Protective role of nitric oxide in ocular toxoplasmosis.
To evaluate the role of nitric oxide (NO) in ocular involvement during systemic toxoplasmosis. C57B1/6 mice were infected with Toxoplasma gondii strain ME49. The synthesis of NO was inhibited by an intraperitoneal injection of aminoguanidine every 8 hours, starting on the day of infection. Control infected mice received phosphate buffered saline vehicle alone. After 14 days, the ocular lesions were evaluated by histopathological examination. The expression of NO synthase induced in the spleen by toxoplasma infection was evaluated by immunostaining. The production of NO by the spleen cells of infected mice was measured by the colorimetric assay of Griess in the supernatant of cultures stimulated with toxoplasma antigen or concanavalin A. The inhibition of NO production in T gondii infected mice resulted in a marked increase in the symptoms of ocular inflammation. We observed a strong induction of NO synthase expression in the spleen of infected animals. In culture, the spleen cells from these mice produced high levels of NO in response to T gondii antigens. This elevation of NO synthesis was suppressed in the presence of aminoguanidine. This study indicates that NO plays a crucial role in the protection against T gondii infection as reflected by the severity of the ocular involvement.


The Potential Mechanism of Cancer Patients Appearing More Vulnerable to SARS-CoV-2 and Poor Outcomes: A Pan-Cancer Bioinformatics Analysis.
To explore the potential mechanism of cancer patients appearing more vulnerable to SARS-CoV-2 infection and poor COVID-19 outcomes, we conducted an integrative bioinformatics analysis for SARS-CoV-2-required genes and host genes and variants related to SARS-CoV-2 susceptibility and COVID-19 severity. BLCA, HNSC, KIRC, KIRP, LGG, PCPG, PRAD, TGCT, and THCA patients carrying rs10774671-A (OAS1) genotype may be more likely to have poor COVID-19 outcomes relative to those who carry rs10774671-G, because individuals carrying rs10774671-A will have lower expression of OAS1, which serves as a protective factor against SARS-CoV-2 processes and poor COVID-19 outcomes. SARS-CoV-2-required genes were correlated with TME, immune infiltration, overall survival, and anti-cancer drug sensitivity. CHOL patients may have a higher risk of SARS-CoV-2 infection than healthy subjects. SARS-CoV-2-induced ACE2 and NPC1 elevation may have a negative influence on the immune responses of LUSC and CD8+T infiltration of LUAD, and negatively affect the sensitivity of anti-lung cancer drugs. LUSC and LUAD patients may have a varying degree of adverse outcomes if they are infected with SARS-CoV-2. miR-760 may target and inhibit ACE2 expression. Cancer patients appearing vulnerable to SARS-CoV-2 infection and having poor COVID-19 outcomes may be partly due to host genetic factors and dysregulation of SARS-CoV-2-required genes. OAS1, ACE2, and miR-760 could serve as the treatment and intervention targets for SARS-CoV-2.


Morphological, Chemical, and Biological Investigation of Ionic Substituted, Pulse Current Deposited Calcium Phosphate Coatings.
Ionic substituted calcium phosphate coatings (iCP) have been prepared by the electrochemical pulse current deposition technique with an alternate pulse on and off time of 5 ms onto a titanium alloy substrate. The elemental distribution and morphology of the deposited layers have been extensively studied by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and transmission electron microscopy (TEM). The crystallinity and phase structure of iCPs have been investigated by X-ray diffraction (XRD). The corrosion characteristics and biodegradability of coatings have been determined by electrochemical measurements, recording potentiodynamic curves in a physiological solution over a long-term immersion period. The cell viability tests confirmed that the iCP coating was biocompatible, while the corrosion tests proved its biodegradable characteristic. In our paper, we compare the morphological, chemical, and biological characteristics of silver and zinc substituted calcium phosphate layers deposited by the electrochemical method.


Cathepsin D (C224T) polymorphism in sporadic and genetic Creutzfeldt-Jakob disease.
Accumulation of cathepsin D immunoreactive lysosomes correlates with tissue pathology in sporadic Creutzfeldt-Jakob disease (CJD) brains. The C-to-T transition within exon 2 of the cathepsin D (CTSD) gene is associated with altered enzymatic activity. Possession of the TT genotype is a risk factor for variant CJD. To verify the association between the CTSD position 224T allele and the risk for and survival in sporadic and genetic CJD, we genotyped 540 sporadic, 101 genetic CJD, and 723 control individuals. Genotype data and duration of illness were compared using multiple logistic regression and Kruskal-Wallis test. Multivariate survival analysis was performed using Cox's regression model. The distribution of CTSD position 224 alleles was approximately the same in all groups. We observed a trend for shorter survival in sporadic CJD patients harboring the T allele at position 224 of the CTSD gene in particular in sporadic CJD patients with the prion protein gene position 129 MM genotype. We conclude that the CTSD position 224 polymorphism alone is not a significant risk or disease-modifying factor in sporadic or genetic CJD.


Both O4-methylthymine and O4-ethylthymine preferentially form alkyl T.G pairs that do not block in vitro replication in a defined sequence.
The mutagenic potential of O4-methylthymine (m4T) and O4-ethylthymine (e4T) was determined by a primer extension assay on a 25mer oligonucleotide containing a single site-specifically incorporated modified thymine. The e4T-containing oligonucleotide was prepared by using a new synthetic procedure suitable for large alkyl groups on thymine. The second-order rate constants, K(app)m and V(rel)max, permitted calculation of the frequency of formation and extension of modified base pairs compared to Watson-Crick pairing. With both m4T and e4T, the T.G type pairing was formed at least 10-fold more frequently than the nonmutagenic alkyl T.A pairing. However, there was a small but reproducible preference for m4T.G pairing. In both cases T-->C transitions would result. There was no evidence for formation of alkyl T.C or T.T. These data suggest that reported T-->A transversions by ethylation are not likely to result from O4-alkylthymine. In contrast to insertion, extension beyond alkylthymine under kinetic conditions did not occur with alkyl T.A. but only with the alkyl T.G termini. For this latter T.G type pairing, the larger ethyl group did not hinder extension compared to that of the methyl group, in the sequence studied. Under non-limiting conditions of dNTP concentration and time, complete replication could be demonstrated for both methyl- and ethyl-containing oligonucleotides. We conclude that the increase in size of the alkyl group from methyl to ethyl does not significantly affect the mutagenic potential and type of mutations of O4-alkylthymine in vitro.


Evaluation, modelling and optimization of the cleaning process of contaminated plastic food refillables.
In this study several types of bottle materials (glass, PET (polyethylene terephthalate), PC (polycarbonate), HDPE (high density polyethylene), PP (polypropylene) and PVC (polyvinyl chloride)) were evaluated in order to be used as food refillables, comparing the residual chemical contamination after classical caustic washing. Bottles were contaminated with model chemicals (chloroxylenol and d-limonene) and caustic washed with varied process parameters using a simulated laboratory-scale washing procedure. After washing, the chemical-contaminated bottles were filled with water and stored for 28 days at 37 degrees C. The concentrations of the model chemicals in the water after storage were taken as a measure of chemical contamination. The influence of the cleaning parameters (temperature, caustic and commercial additive concentration) was studied using response surface methodology. Washing temperature showed a significant influence on the removal of absorbed chemicals from surfaces compared with the effect of the caustic and especially the additive concentration. Optimization of caustic cleaning for the cleaning process in question led to better cleaning effectiveness, although none of the different washing conditions were able to remove all absorbed chemicals out of the polymeric resins. Commercially available plastic refillables (PET and PC) showed the best chemical rinsability. Glass bottles, however, had in every case the best rinsing characteristics.


Solution studies of recombinant human stromal-cell-derived factor-1.
Stromal-cell-derived factor-1 (SDF-1alpha) is an 8-kDa chemokine that is constitutively expressed in bone-marrow-derived stromal cells and has been identified as a ligand for the CXCR4 receptor. We produced the chemokine recombinantly as methionine-SDF-1alpha in Escherichia coli without the leader peptide sequence. The protein was denatured, refolded, and further purified by reversed-phase HPLC. SDF-1alpha was shown to be >95% pure as judged by SDS-PAGE. The final yield of purified and refolded SDF-1alpha was 1-2 mg per gram of wet cell paste. The refolded protein is a ligand for the CXCR4 receptor and has been used to block HIV-mediated cell fusion and downmodulates the CXCR4 receptor. Our ability to purify hundreds of milligrams of refolded protein allowed us to conduct detailed studies of the biophysical properties of the protein. We have used a combination of biophysical techniques to study the solution properties of SDF-1alpha. The average mass of SDF-1alpha, as determined by static light scattering, gave us the first indications that the chemokine may self-associate. Further investigation with sedimentation velocity ultracentrifugation confirmed the existence of two species. The measured s(20, W) values defined two masses corresponding to monomer and dimer. Finally, sedimentation equilibrium ultracentrifugation and dynamic light scattering yielded a composite value of 150 +/- 30 microM for the dimerization constant. We conclude that SDF-1alpha exists in a monomer-dimer equilibrium.


Origin and control of adhesion between emulsion drops stabilized by thermally sensitive soft colloidal particles.
We used soft microgels made of poly(N-isopropylacrylamide) (pNIPAM) of variable cross-linking degrees and the same colloidal size to stabilize oil-in-water Pickering emulsions. The extent of droplet flocculation increased and the resistance of the emulsions to mechanical stresses decreased as the cross-linking density was augmented. Large flat films were separating the droplets, and we could measure the adhesion angle at the junction with the free interfaces through several microscopy methods. The size of the flat films and the values of the angles were reflecting strong adhesive interactions between the interfaces as a result of microgel bridging. In parallel, cryo-SEM imaging of the thin films allowed a precise determination of their structure. The evolution of the adhesion angle and of the film structure as a function of microgels cross-linking density provided interesting insights into the impact of particle softness on film adhesiveness and emulsion stability. We exploited our main findings to propose a novel route for controlling the emulsions end-use properties (flocculation and stability). Owing to particle softness and thermal sensitivity, the interfacial coverage was a path function (it depended on the sample "history"). As a consequence, by adapting the emulsification conditions, the interfacial monolayer could be trapped in a very dense and rigid configuration, providing improved resistance to bridging flocculation and to flow-induced coalescence.


Disposition and metabolism of 2,3,7,8-tetrachlorodibenzofuran by rainbow trout (Oncorhynchus mykiss).
The disposition and metabolism of 2,3,7,8-tetrachlorodibenzofuran (TCDF) was investigated in rainbow trout (Oncorhynchus mykiss) in order to better understand the metabolic and physiological factors that modulate the fate of this extremely toxic compound in rainbow trout compared to other species. The fish were dosed orally with [3H]TCDF (1 microgram/kg); fish were terminated at 1-19 days for the determination of whole body half-life or at 0.3-28 days for determination of tissue distribution. Unassimilated TCDF (51.5% of the dose) was eliminated with a half-life of 0.84 days. The assimilated body burden of TCDF equivalents decreased with a half-life of 14.8 days (determined between 3 and 19 days). Trout muscle showed a relatively high capacity to accumulate and retain (unmetabolized) TCDF, accounting, at 3 days, for 32% of the body burden of TCDF equivalents (half-life in muscle, 15.2 days). Trout liver, on the other hand, showed a relatively low capacity to accumulate and metabolize TCDF. At 3 days, the concentrations of TCDF equivalents in liver and bile were, respectively, 0.37 ng/g liver (0.88% of the body burden) and 4.8 ng/ml bile. The data suggest that the relatively high affinity of lipid-rich trout muscle for TCDF limits the ability of the liver to accumulate and metabolize TCDF. The major TCDF metabolites found in trout liver and bile were, respectively, 4-OH-TCDF and TCDF-4-O-glucuronide.


Symphysis revisited: clinical and histologic evaluation of newly formed bone and reharvesting potential of previously used symphysial donor sites for onlay bone grafting.
This article reports on the reharvesting potential of newly formed bone in previously used symphysial donor sites. This study included five patients who were scheduled for sequential onlay bone augmentations prior to dental implant placement using the symphysis area as a donor site. At 5 months after bone augmentation, computed tomography scans of donor sites revealed healing from the first surgery. Because additional bone augmentation was required, the same sites were revisited for bone harvesting. Reharvesting was performed 5 months after the first harvesting. A small portion of the harvested bone from two patients was evaluated histologically. Five months postharvesting, clinical observation of the donor sites resembled newly formed bone as a conglomerate of bovine bone particles. In the five patients, bone continuity was observed between new bone at the donor defect sites and surrounding bone. Additional blocks were reharvested from the same sites and successfully grafted to recipient sites. Dental implants were inserted 5 months after the second augmentation, which healed uneventfully. Histologically, bovine bone particles were surrounded by woven bone, with areas of mature bone with well-organized osteons. Remodeling of a symphysial donor area enabled reuse of the site for additional harvesting. Intraoral bone sources could serve as a long-lasting renewable source of high-quality bone.


Fresh blood product manufacture, issue, and use: a chain of diminishing returns?
The available pool of potential blood donors continues to decrease. There are blood component losses all along the chain of production from the recruitment of the donor, attendance and bleeding of the donor, production process, storage of the inventory in the blood center, storage in the hospital or laboratory, selection, and transfusion of the recipient. There is a requirement and potential to improve product availability by better recruitment strategies, production methods, inventory management, and recipient selection. All of these areas of transfusion medicine have been investigated, and some data and options for improving donor/donation utilization are available in the literature. There are also some developing strategies that have the potential to have a positive influence on the availability of blood components. They include the use of blood components that have often been regarded as expensive. Further studies are required to determine if products such as leukoreduced red cells and platelets, unrefrigerated or fresh whole blood, and some recombinant products can conserve large numbers of other components or reduce hospital costs.


Controlling the Microstructure and Phase Behavior of Confined Soft Colloids by Active Interaction Switching.
We explore the microstructure and phase behavior of confined soft colloids which can actively switch their interactions at a predefined kinetic rate. For this, we employ a reactive dynamical density-functional theory and study the effect of a two-state switching of the size of colloids interacting with a Gaussian pair potential in the nonequilibrium steady state. The switching rate interpolates between a near-equilibrium binary mixture at low rates and a nonequilibrium monodisperse liquid for large rates, strongly affecting the one-body density profiles, adsorption, and pressure at confining walls. Importantly, we show that sufficiently fast switching impedes the phase separation of an (in equilibrium) unstable liquid, allowing the control of the degree of mixing and condensation and local microstructuring in a cellular confinement by tuning the switching rate.


Potential causes of the preoperative increase in the rectosigmoid cyclic motor pattern: A high-resolution manometry study.
Cyclic motor patterns (CMPs) are the most common motor pattern in the distal colon. This study used high-resolution (HR) colonic manometry to quantify trends in distal colonic motor activity before elective colonic surgery, determine the effect of a preoperative carbohydrate load, and compare this with a meal response in healthy controls. Fiber-optic HR colonic manometry (36 sensors, 1 cm intervals) was used to investigate distal colonic motor activity in 10 adult patients prior to elective colonic surgery, 6 of whom consumed a preoperative carbohydrate drink (200 kCal). Data were compared with nine healthy volunteers who underwent HR colonic manometry recordings while fasted and following a 700 kCal meal. The primary outcome was the percentage of recording occupied by CMPs, defined as propagating contractions at 2-4 cycles per minute (cpm). Secondary outcomes included amplitude, speed, and distance of propagating motor patterns. The occurrence of CMPs progressively increased in time periods closer to surgery (p = 0.001). Consumption of a preoperative drink resulted in significantly increased CMP occurrence (p = 0.04) and propagating distance (p = 0.04). There were no changes in amplitude or speed of propagating motor patterns during the preoperative period. The increase in activity following a preoperative drink was of similar magnitude to the colonic meal response observed in healthy controls, despite the lesser caloric nutrient load. Distal colonic CMP increased in occurrence prior to surgery, amplified by ingestion of preoperative carbohydrate drinks. We hypothesize that anxiety, which is also known to rise with proximity to surgery, could play a contributing role.


Efficacy of Regional Chemotherapy Approach in Peritoneal Metastatic Gastric Cancer.
Peritoneal spread is frequent in gastric cancer (GC) and a palliative condition. After failure to systemic chemotherapy (sCTx) remaining therapeutic options are very limited. We evaluated the feasibility and efficacy of locoregional chemotherapy (RegCTx) in peritoneal metastatic GC. In total, 38 (23 male and 15 female) patients with peritoneal metastatic GC after failure of previous sCTx and unresectable disease were enrolled in this study. Using the hypoxic abdominal stop-flow perfusion, upper abdominal perfusion and intraarterial infusion technique in total 114 cycles with Cisplatin, Adriamycin and Mitomycin C were applied. No significant procedure related toxicity was noticed- especially no Grade 3 or 4 toxicity occurred. With the RegCTx approach a median overall survival of 17.4 months was achieved. Patients who had undergone previously resection of the GC the median overall survival was even better with 23.5 months. RegCTx is a promising, safe and efficient approach in diffuse metastatic GC. The evaluation of RegCTx in the setting of multimodal treatment approach at less advanced stages is also warranted.


Exponential Fermi acceleration in general time-dependent billiards.
We show, that under very general conditions, a generic time-dependent billiard, for which a phase space of corresponding static (frozen) billiards is of the mixed type, exhibits the exponential Fermi acceleration in the adiabatic limit. The velocity dynamics in the adiabatic regime is represented as an integral over a path through the abstract space of invariant components of corresponding static billiards, where the paths are generated probabilistically in terms of transition-probability matrices. We study the statistical properties of possible paths and deduce the conditions for the exponential Fermi acceleration. The exponential Fermi acceleration and theoretical concepts presented in the paper are demonstrated numerically in four different time-dependent billiards.


Water under temperature gradients: polarization effects and microscopic mechanisms of heat transfer.
We report non-equilibrium molecular dynamics simulations (NEMD) of water under temperature gradients using a modified version of the central force model (MCFM). This model is very accurate in predicting the equation of state of water for a wide range of pressures and temperatures. We investigate the polarization response of water to thermal gradients, an effect that has been recently predicted using Non-Equilibrium Thermodynamics (NET) theory and computer simulations, as a function of the thermal gradient strength. We find that the polarization of the liquid varies linearly with the gradient strength, which indicates that the ratio of phenomenological coefficients regulating the coupling between the polarization response and the heat flux is independent of the gradient strength investigated. This notion supports the NET theoretical predictions. The coupling effect leading to the liquid polarization is fairly strong, leading to polarization fields of ~10(3-6) V m(-1) for gradients of ~10(5-8) K m(-1), hence confirming earlier estimates. Finally we employ our NEMD approach to investigate the microscopic mechanism of heat transfer in water. The image emerging from the computation and analysis of the internal energy fluxes is that the transfer of energy is dominated by intermolecular interactions. For the MCFM model, we find that the contribution from hydrogen and oxygen is different, with the hydrogen contribution being larger than that of oxygen.


GH sensitivity of GH-deficient adults is dependent on gender but not timing of onset.
Females secrete 2-3 -fold greater amounts of GH compared with males despite maintaining similar IGF-I levels. IGF-I generation tests in healthy subjects suggest this discordancy results from relative resistance to GH in females. In GHD females the presumed relative insensitivity to GH is reflected by a lower basal IGF-I and the need for higher GH maintenance doses during replacement. Adults with severe GHD of childhood-onset (CO) have lower basal IGF-I SDS and require higher GH maintenance doses compared with adult-onset (AO) patients with GHD of equal severity. We hypothesised CO-GHD adults to be less sensitive to GH than AO-GHD patients. In a single site study we analysed the incremental change in IGF-I (DeltaIGF-I) in 116 GHD adults following initiation of GH replacement. The data were corrected to provide DeltaIGF-I/mg GH because of slight variances in initial GH dose. Following GH replacement DeltaIGF-I was 230 +/- 245 and 356 +/- 278 ng/ml/mg GH in females and males, respectively (P = 0.01). In CO and AO patients DeltaIGF-I was 282 +/- 206 and 294 +/- 292 ng/ml/mg GH, respectively (P = 0.83). Further analysis after stratification by both gender and timing of onset of GHD showed DeltaIGF-I was 226 +/- 164, 324 +/- 228, 231 +/- 268, and 373 +/- 304 ng/ml/mg GH in the CO females, CO males, AO females, and AO males, respectively (AO males vs. AO females, P = 0.03; CO males vs. CO females, P = 0.17; AO males vs. CO males, P > 0.05; AO females vs. CO females, P > 0.05). Multiple linear regression with DeltaIGF-I as the dependent variable and age, gender, BMI, baseline IGF-I level, and timing of onset as independent variables showed DeltaIGF-I to be dependent on gender alone (R = 0.28, P = 0.004). Age (P = 0.44), BMI (P = 0.54), baseline IGF-I level (P = 0.63) and timing of onset (P = 0.61) had no effect on DeltaIGF-I. We have shown gender to have a significant impact on GH sensitivity in GHD adults, which, at least in part, explains differences in maintenance dosages during replacement. None of the additional variables impacted significantly on GH sensitivity. The lower basal IGF-I SDS and higher GH replacement requirement reported in CO compared with AO patients cannot be explained by differences in sensitivity to GH.


Comparison of surveillance sample demographics over two cycles of the National HIV Behavioral Surveillance Project, Houston, Texas.
We examined differences in sample demographics across cycles of the National HIV Behavioral Surveillance project, that examines HIV risk behaviors among men who have sex with men (MSM), injection drug users (IDU), and heterosexuals living in areas of high HIV prevalence (HET). MSM were recruited through venue-based sampling, and IDU and HET through respondent driven sampling (RDS). RDS data were weighted to account for sampling bias. We compared crude prevalence estimates from MSM1 (2004) to those from MSM2 (2008) for demographic factors known to influence risky sexual and drug-use behaviors. We compared crude and adjusted prevalence estimates for IDU1 (2005) and IDU2 (2009) and HET1 (2006) and HET2 (2010). In the MSM cycle, we found differences in age, and the proportions seeking medical care and reporting a recent arrest. There were no differences in the comparison of crude and weighted estimates for the RDS collected samples, nor were there differences comparing HET1 and HET2 weighted estimates. IDU2 recruited a larger proportion of males, and had a higher percent who graduated from high school and who reported recent medical care and a previous HIV test. Differences across MSM cycles may be related to differences in venues identified for each cycle. Differences in the IDU cycles may be due to an effort on our part to increase the racial/ethnic and drug-use diversity of the sample in IDU2. Our findings show the importance of formative work for both venue-based and RDS samples to increase understanding of the dimensions that affect social networks and the dynamics of populations in space and time. With familiarity of the target population, we believe that both venue-based and RDS recruitment approaches for NHBS work well and can be used to evaluate changes in risky sexual and drug use behaviors and in HIV testing behaviors.


Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics.
The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry (MS). Studies using advanced MS have resulted in new insights into cell biology and the etiology of diseases as well as its use in clinical applications. This review discusses recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It also discusses the issues around translating the research findings to the clinic and provides an outline of where the field is moving. Expert commentary: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics.


[The shortage of nurses: a reversing trend?].
With fewer people becoming nurses, projections of the past years indicated a declining in the size of nursing workforce and forecast a shortage of up to 1 million of nurses. This trend seems revolving as in the US, due to a series of public and private initiatives, the number of applicants for nursing courses more than doubled since 1985. While the number of nurses is increasing, in some European countries, hospitals are facing a severe shortage of nurses, for costs constraints due to the economic crisis and a mismatch between health and NHS priorities and policies.


Analysis of social and economic factors affecting mortality in China.
"In this study, the author compares the data from the 1982 and 1990 [Chinese] censuses...,conducts on the basis of the 1990 census a gradual regression analysis of the social and economic factors that affect mortality in various regions, including both urban and rural areas, selects the major factors, and proposes [methods of] further lowering mortality in China."


Coping with trauma: narrative and cognitive perspectives.
The immediate period following a traumatic event is a crucial time in the survivors' process of recovery. During this time, a narrative of the trauma is generated and constructed, alongside a process of cognitive processing of the traumatic events. In the first part of the article we present the outlines of the narrative and cognitive attitudes to trauma; the second part will illustrate the developmental process through which the trauma narrative is shaped, in the stories of five survivors of a terror attack. We suggest that by analyzing three main components of the trauma narrative (coherence, finding meaning and self-evaluation), together with the equivalent cognitive attitudes, it is possible to evaluate the process of recovery, identify foci of difficulties in this process and pinpoint possible therapeutic interventions in the early stages after the trauma.


Race is gendered: how covarying phenotypes and stereotypes bias sex categorization.
We argue that race and sex categories are psychologically and phenotypically confounded, affecting social categorizations and their efficiency. Sex categorization of faces was facilitated when the race category shared facial phenotypes or stereotypes with the correct sex category (e.g., Asian women and Black men) but was impaired when the race category shared incompatible phenotypes or stereotypes with the correct sex category (e.g., Asian men and Black women). These patterns were evident in the disambiguation of androgynous faces (Study 1) and the efficiency of judgments (Studies 1, 2, 4, and 5). These patterns emerged due to common facial phenotypes for the categories Black and men (Studies 3 and 5) and due to shared stereotypes among the categories Black and men and the categories Asian and women (Studies 4 and 5). These findings challenge the notion that social categories are perceived independent of one another and show, instead, that race is gendered.


Funding therapies for rare diseases: an ethical dilemma with a potential solution.
Funding rare disease therapies presents a challenge in Australia where there is a legislative requirement to consider cost-effectiveness. Currently the Life Saving Drugs Programme (LSDP) provides subsidised access to high-cost therapies for rare, life-threatening conditions. However the LSDP is currently under review by the Minsiter for Health and future access to rare disease therapies in uncertain. Internationally there is no gold standard model to evaluate and fund rare disease therapies, and considerable variation exists. However, common features of international systems include the opportunity for early stakeholder engagement, flexibility with evidence requirements, cost-effectiveness criteria and transparency in relation to the decision making framework and outcomes. Australians value equality and equal opportunity in relation to health care. To meet these expectations there is a clear need to maintain a separate fit-for-purpose framework to evaluate and fund rare disease therapies drawing on overseas best practice. This will provide certainty for industry to continue to invest in such treatments, as well as ensuring funding recommendations are reflective of Australian values balanced against the need for financial sustainability.


Lung uptake of 201Tl in myocardial stress imaging: correlation with echocardiographic and scintigraphic variables of myocardial ischaemia.
The lung uptake of thallium-201 (201Tl) in planar imaging was evaluated in 384 patients enrolled in the SIRT study (Italian Multicentre Study on Thallium Reinjection). All patients underwent treadmill exercise, and at peak exercise 74 MBq of 201TI were injected. The patients were then evaluated after reinjection of 201Tl under baseline conditions. The left ventricle was subdivided into 16 echocardiographic and 15 scintigraphic segments. The best correlates of visually scored 201Tl lung uptake, of the lung heart ratio and lung wash-out were checked. The independent variables entered in the stepwise multiple-regression analysis were: the echocardiographic wall motion index, the scintigraphic perfusion score index, and the number of segments that improved by at least 1 and 2 grades after redistribution and after reinjection. We concluded that the lung:heart ratio and, in particular, lung wash-out do not correlate more closely than the visual score with the variables taken into consideration. This suggests that visually scored lung uptake of 201Tl is still of value in nuclear cardiology practice. The scintigraphic variables associated with reinjection do not seem to offer any additional information with respect to redistribution variables. We also analysed the impact on 201Tl lung uptake of several other index variables. Student's t-test revealed that no single variable significantly alters lung uptake after stress testing.


[Multiple calcifications and ossifications of tendons].
Multiple calcifications and ossifications of tendons are, as a rule, associated with similar lesions of other articular and/or periarticular structures. The nature and multiplicity of these lesions gives them an unquestionable diagnostic and nosological value. Multiple calcifications are part of the apatite arthritis or of diffuse articular chondrocalcinosis. Multiple ossifications of tendons often suggest Forestier's disease and ankylosing spondylitis.


Topiramate-induced nephrolithiasis.
Nephrolithiasis is a less common side effect of the antiepileptic drug topiramate. We report the case of a 3-year-old boy who presented to the emergency department with abdominal pain; examinations revealed a large calcification in the left kidney. Regular ultrasound examinations are recommended in children using topiramate.