Influence of process temperature and residence time on the manufacturing of amorphous solid dispersions in hot melt extrusion.
The manufacturing of amorphous solid dispersions via hot melt extrusion is a topic of high interest in pharmaceutical development. By this technique, the drug is dissolved in the molten polymer above solubility temperature within the process time. In this study, an experimental framework is proposed determining the minimum required process temperature and the residence time using particularly low quantities of material. Drug/polymer mixtures in different ratios were processed in a micro-scale extruder while the process temperature and residence time were varied systematically. The phase situation was assessed by the turbidity of the final extrudate. Four different drug/polymer mixtures were investigated in three drug/polymer ratios. The minimum required process temperature was close to solubility temperature for each specific formulation. Moreover, an influence of residence time on the phase situation was found. About three minutes were required in order to dissolve the drug in the polymer at these process conditions.


Anesthetic management of thoracoscopic pulmonary wedge resection with a giant tracheal diverticulum in the carina: a case report and review of the literature.
A tracheal diverticulum (TD) is a rare disease that is usually diagnosed as an incidental finding on thoracic computed tomography or bronchoscopy. TDs can be classified as congenital or acquired. In patients undergoing surgery, TDs can result in difficult intubation, difficult ventilation, pneumothorax, and other complications. We herein report a case of anesthetic management of thoracoscopic pulmonary wedge resection in a patient with a giant TD in the carina. Intraoperative double-lumen intubation and single-lung ventilation were challenging to perform. Fiberoptic-guided intubation was helpful, and intraoperative management was tailored to avoid diverticulum rupture. In this report, we also review complications related to TD in surgical patients undergoing mechanical ventilation. Ventilation is one of the most prominent anesthetic challenges. The close collaboration of the entire medical team was a key factor in the successful management of this rare case.


A new bis(imidazolyl)(alkylthiolate) tripodal ligand and the spontaneous formation of a disulfide-linked, hydroxo-bridged dinuclear zinc complex.
The new sterically encumbered, tripodal N2S(alkylthiolate) ligand, LIm2SH, has been synthesized and used to prepare [(LIm2S)ZnCH3], which upon protonolysis under acidic conditions leads to the synthesis of a novel dinucleating ligand and a zinc dimer with an unusual structure.


Benefits of a factorial design focusing on inclusion of female and male animals in one experiment.
Disease occurrence, clinical manifestations, and outcomes differ between men and women. Yet, women and men are most of the time treated similarly, which is often based on experimental data over-representing one sex. Accounting for persisting sex bias in biomedical research is the misconception that the analysis of sex-specific effects would double sample size and costs. We designed an analysis to test the potential benefits of a factorial study design in the context of a study including male and female animals. We chose a 2 × 2 factorial design approach to study the effect of treatment, sex, and an interaction term of treatment and sex in a hypothetical situation. We calculated the sample sizes required to detect an effect of a given magnitude with sufficient power and under different experimental setups. We demonstrated that the inclusion of both sexes in experimental setups, without testing for sex effects, requires no or few additional animals in our scenarios. These experimental designs still allow for the exploration of sex effects at low cost. In a confirmatory instead of an exploratory design, we observed an increase in total sample sizes by 33%, at most. Since the complexities associated with this mathematical model require statistical expertise, we generated and provide a sample size calculator for planning factorial design experiments. For the inclusion of sex, a factorial design is advisable, and a sex-specific analysis can be performed without excessive additional effort. Our easy-to-use calculation tool provides help in designing studies with both sexes and addresses the current sex bias in preclinical studies. KEY MESSAGES: • Both sexes should be included into animal studies. • Exploratory study of sex effects can be conducted with no or small increase in animal number. • Confirmatory analysis of sex effects requires maximum 33% more animals per study. • Our calculation tool supports the design of studies with both sexes.


Genetics of Hereditary Angioedema Revisited.
Contemporary genetic research has provided evidences that angioedema represents a diverse family of disorders related to kinin metabolism, with a much greater genetic complexity than was initially considered. Convincing data have also recently been published indicating that the clinical heterogeneity of hereditary angioedema due to C1 inhibitor deficiency (classified as C1-INH-HAE) could be attributed at least in part, either to the type of SERPING1 mutations or to mutations in genes encoding for enzymes involved in the metabolism and function of bradykinin. Alterations detected in at least one more gene (F12) are nowadays considered responsible for 25 % of cases of hereditary angioedema with normal C1-INH (type III hereditary angioedema (HAE), nlC1-INH-HAE). Interesting data derived from genetic approaches of non-hereditary angioedemas indicate that other immune pathways might be implicated in the pathogenesis of HAE. More than 125 years after the recognition of the hereditary nature of HAE by Osler, the heterogeneity of clinical expressions, the genetics of this disorder, and the genotype-phenotype relationships, still presents a challenge that will be discussed in this review. Large scale, in-depth genetic studies are expected not only to answer these emerging questions but also to further elucidate many of the unmet aspects of angioedema pathogenesis. Uncovering genetic biomarkers affecting the severity of the disease and/or the effectiveness of the various treatment modalities might lead to the prevention of attacks and the optimization of C1-INH-HAE management that is expected to provide a valuable benefit to the sufferers of angioedema.


Strength and elasticity of SiO2 across the stishovite-CaCl2-type structural phase boundary.
Radial x-ray diffraction experiments were conducted under nonhydrostatic compression on SiO2 to 60 GPa in a diamond anvil cell. This ratio of differential stress to shear modulus t/G is 0.019(3)-0.037(5) at P=15-60 GPa. The ratio for octahedrally coordinated stishovite is lower by a factor of about 2 than observed in four-coordinated silicates. Using a theoretical model for the shear modulus, the differential stress of stishovite is found to be 4.5(1.5) GPa below 40 GPa and to decrease sharply as the stishovite-CaCl2-type phase transition boundary is approached. Inversion of measured lattice strains provides direct experimental evidence for softening of C11-C12.


Differential Lipid Composition and Gene Expression in the Semi-Russeted "Cox Orange Pippin" Apple Variety.
Russeting is characterized by a particular rough and brown phenotype, which is mainly due to the accumulation of suberin in the inner part of the epidermal cell walls. In our previous bulk transcriptomic analysis, comparing fully russeted, and waxy apple varieties, showed, in apple fruit skin, a massive decreased expression of cutin, wax and some pentacyclic triterpene biosynthesis genes in the russeted varieties, with an expected concomitant enhanced expression of the suberin biosynthetic genes. In the present work, we performed a deep investigation of the aliphatic composition of the cutin, suberin, waxes, and triterpenes in the waxy and russeted patches of the semi-russeted apple variety "Cox Orange Pippin." A targeted gene expression profiling was performed to validate candidate genes which were identified in our previous work and might be involved in the respective metabolic pathways. Our results showed that a decrease of cuticular waxes, ursolic acid and oleanolic acid, accompanied by an accumulation of alkyl-hydroxycinamates and betulinic acid, occurs in the russeted patches. The suberin monomer composition is characterized by specific occurrence of 20, 22, and 24 carbon aliphatic chains, whereas cutin is mainly represented by common C16 and C18 aliphatic chains. This work depicts, for the first time in apple, the complex composition of suberin, cutin, waxes and triterpenes, and confirms the strong interplay between these epidermal polymers in apple fruit skin.


Neural correlates of alexithymia: a meta-analysis of emotion processing studies.
Alexithymia is a personality trait characterized by difficulties in the experience and cognitive processing of emotions. It is considered a risk factor for a range of psychiatric and neurological disorders. Functional neuroimaging studies investigating the neural correlates of alexithymia have reported inconsistent results. To integrate previous findings, we conducted a parametric coordinate-based meta-analysis including fifteen neuroimaging studies on emotion processing in alexithymia. During the processing of negative emotional stimuli, alexithymia was associated with a diminished response of the amygdala, suggesting decreased attention to such stimuli. Negative stimuli additionally elicited decreased activation in supplementary motor and premotor brain areas and in the dorsomedial prefrontal cortex, possibly underlying poor empathic abilities and difficulties in emotion regulation associated with alexithymia. Positive stimuli elicited decreased activation in the right insula and precuneus, suggesting reduced emotional awareness in alexithymia regarding positive affect. Independent of valence, higher (presumably compensatory) activation was found in the dorsal anterior cingulate possibly indicating increased cognitive demand. These results suggest valence-specific as well as valence-independent effects of alexithymia on the neural processing of emotions.


A Modular System for the Design of Stimuli-Responsive Multifunctional Nanoparticle Aggregates by Use of Host-Guest Chemistry.
A self-assembly approach for the design of multifunctional nanomaterials consisting of different nanoparticles (gold, iron oxide, and lanthanide-doped LiYF4 ) is developed. This modular system takes advantage of the light-responsive supramolecular host-guest chemistry of β-cyclodextrin and arylazopyrazole, which enables the dynamic and reversible self-assembly of particles to spherical nanoparticle aggregates in aqueous solution. Due to the magnetic iron oxide nanoparticles, the aggregates can be manipulated by an external magnetic field leading to the formation of linear structures. As a result of the integration of upconversion nanoparticles, the aggregates are additionally responsive to near-infrared light and can be redispersed by use of the upconversion effect. By varying the nanoparticle and linker concentrations the composition, size, shape, and properties of the multifunctional nanoparticle aggregates can be fine-tuned.


Excel Methods to Design and Validate in Microelectronics (Complementary Metal-Oxide-Semiconductor, CMOS) for Biomedical Instrumentation Application.
CMOS microelectronics design has evolved tremendously during the last two decades. The evolution of CMOS devices to short channel designs where the feature size is below 1000 nm brings a great deal of uncertainty in the way the microelectronics design cycle is completed. After the conceptual idea, developing a thinking model to understand the operation of the device requires a good "ballpark" evaluation of transistor sizes, decision making, and assumptions to fulfill the specifications. This design process has iterations to meet specifications that exceed in number of the available degrees of freedom to maneuver the design. Once the thinking model is developed, the simulation validation follows to test if the design has a good possibility of delivering a successful prototype. If the simulation provides a good match between specifications and results, then the layout is developed. This paper shows a useful open science strategy, using the Excel software, to develop CMOS microelectronics hand calculations to verify a design, before performing the computer simulation and layout of CMOS analog integrated circuits. The full methodology is described to develop designs of passive components, as well as CMOS amplifiers. The methods are used in teaching CMOS microelectronics to students of electronic engineering with industrial partner participation. This paper describes an exhaustive example of a low-voltage operational transconductance amplifier (OTA) design which is used to design an instrumentation amplifier. Finally, a test is performed using this instrumentation amplifier to implement a front-end signal conditioning device for CMOS-MEMS biomedical applications.


The management of cervical intra-epithelial neoplasia (CIN): extensiveness and costs in The Netherlands.
In order to provide greater insight into both the extensiveness and the medical costs of the diagnosis and treatment of screen-detected cervical intra-epithelial neoplasia (CIN) in general medical practice in The Netherlands, data from national registries and gynaecology departments were retrieved, and experts were interviewed. Of the 5060 women diagnosed with CIN in 1988, more than 50% were treated in hospital with conisation or hysterectomy, which on average took 5.5 days stay per admission. The assessed average duration of the total pre- and post-treatment period is 4.6 years. The average total medical costs in women with detected CIN III are Dfl 3700 per woman. The diagnosis of CIN I and II involves more medical procedures and time than CIN III, but fewer women have conisation or hysterectomy, resulting in lower total medical costs (Dfl 2572). The overall extent and costs of the management of CIN should be accounted for when balancing the benefits, unfavourable effects and costs of cervical cancer screening.


Midkine Is a Potential Therapeutic Target of Tumorigenesis, Angiogenesis, and Metastasis in Non-Small Cell Lung Cancer.
Hypoxia-inducible factors (HIFs) induced by reduced O2 availability activate the transcription of target genes encoding proteins that play important roles in communication between cancer and stromal cells. Cancer cells were incubated under hypoxic conditions: H1299, A549 (NSCLC); Hep3B, HepG2 (HCC); HCT116, CT26 (Colon cancer); MCF-7, MDAMB231 (Breast cancer); MKN1, MKN5 (Gastric cancer); U87MG, SHSY5Y (Brain cancer); and SKOV3, SNU840 (Ovary cancer). All cells expressed HIF-1α and HIF-2α mRNA and proteins. However, cell proliferation of NSCLC, breast, gastric, and brain cancer cells under hypoxia was more dependent on HIF-1α except for HCC cells where it was more dependent on HIF-2α. Among HIF-1α dependent cells H1299 was the most affected in terms of cell proliferation by HIF-1α knockdown. To examine which cytokines are secreted in NSCLC cells by HIF-1α to communicate with stromal cells, we performed a cytokine-profiling array with H1299. We screened the top 14 cytokines which were dependent on the HIF-1α expression pattern. Among them, midkine (MDK) expression was affected the most in response to HIF-1α. MDK is a heparin-binding growth factor that promotes angiogenesis and carcinogenesis. Indeed, MDK significantly increased HUVEV endothelial cell migration and neo- vascularization in chick chorioallantoic membrane assay (CAM) assay via paracrine signaling. In addition, MDK secreted from NSCLC cells interacted with Notch2 which activated the Notch signaling pathway and induced EMT, upregulated NF-κB, and increased cancer promotion. However, in response to MDK knock down, siRNA or the MDK inhibitor, iMDK treatment not only decreased MDK-induced migration and angiogenesis of endothelial cells but also abrogated the progression and metastasis of NSCLC cells in in vitro and in vivo orthotopic and spontaneous lung metastasis models. Consequently, iMDK treatment significantly increased mice survival rates compared with the control or MDK expression group. MDK plays a very important role in the progression and metastasis of NSCLC cells. Moreover, the MDK targeting strategy provides a potential therapeutic target for the treatment of MDK-expressing lung cancers.


Applicability of experience from laboratory reactors with biological phosphorus removal in full-scale plants.
Enhanced biological phosphorus removal (EBPR) has been used at many wastewater treatment plants all over the world for many years. In this study a full-scale sludge with good EBPR was tested with P-release batch tests and combined FISH/MAR (fluorescence in situ hybridisation and microautoradiography). Proposed models of PAOs and GAOs (polyphosphate- and glycogen-accumulating organisms) and microbial methods suggested from studies of laboratory reactors were found to be applicable also on sludge from full-scale plants. Dependency of pH and the uptake of both acetate and propionate were studied and used for calculations for verifying the models and results from microbial methods. All rates found from the batch tests with acetate were higher than in the batch tests with propionate, which was explained by the finding that only those parts of the bacterial community that were able to take up acetate anaerobically were able to take up propionate anaerobically.


Chromatography approaches for early screening of the phospholipidosis-inducing potential of pharmaceuticals.
Drug-induced phospholipidosis (PLD) is an excessive accumulation of polar phospholipids within cells as a result of medical treatment. Even though a direct link between in vitro drug-induced PLD and toxicity in humans has not yet been firmly established, the development of PLD during preclinical testing in animals is a recognized problem in the pharmaceutical industry and can delay or abort the development process. Therefore, it is of interest to investigate the potential PLD risk of candidates at an early stage of the drug discovery process. In this work, a high throughput physicochemical approach, which is based on measuring the retention factors of the test compound within several different separation systems, was developed for screening phospholipidosis-inducing potential (PLIP) of pharmaceuticals. The measured retention factors of 36 drugs were compared with literature data on PLIP risk from three different sources. It is clearly shown that there is a statistical correlation between the chromatographic retention parameters of tested drugs and their PLIP risk. In conclusion, the retention factor (logk(AOT)) observed on a docusate sodium salt (AOT) surfactant vesicle electrokinetic chromatography (EKC) system and the logarithm of the volume of distribution (logV(d)) calculated from immobilized artificial membrane chromatography at pH 7.4 (CHI IAM(7.4)) and HSA binding value (% HSA) can provide primary profile prediction for a large number of drug candidates early in the drug discovery process with minimal resources. The observations are that the higher the value of both logk(AOT) and logV(d), the higher the PLIP risk, and we would recommend this dual approach.


Regulation of ribulose diphosphate formation in vivo by light.
Light-dependent formation of ribulose-1,5 diphosphate is completely inhibited by low concentrations of 3-(3,4-dichlorophenyl)-1,1-dimethylurea which do not severely affect cyclic photophosphorylation. Also in Scenedesmus mutant number 11, capable of cyclic photophosphorylation, cellular ribulose-1,5 diphosphate-levels do not increase upon illumination. When mutant cells are H(2) adapted, however, a light-dependent formation of ribulose-1,5 diphosphate is observed in the presence of H(2). From these results it has been concluded that at least part of the Calvin cycle does not operate in the dark, since a reductant is lacking which is generated in the light.


Induction of monocyte chemoattractant protein-1 (MCP-1) production by Pseudomonas nitrite reductase in human pulmonary type II epithelial-like cells.
Monocyte chemoattractant protein-1 (MCP-1), a chemoattractant for monocytes, is presumed to play a pivotal role in the recruitment and accumulation of monocytes in various diseases including pulmonary infections. We examined here whether or not Pseudomonas nitrite reductase (PNR), a recently identified IL-8 inducer in various respiratory cells, could stimulate human pulmonary type II epithelial-like cells (A549) to induce MCP-1 production. A time- and dose-dependent induction of MCP-1 protein synthesis associated with an increase of MCP-1 mRNA expression by A549 cells was observed in response to PNR. New protein translation was not required for PNR-mediated MCP-1 mRNA expression in the same cells. When anti-human MCP-1 monoclonal antibody was used for neutralizing of monocyte chemotactic factor (MCF) activities in the culture supernatants of these cells stimulated with PNR, significant reductions of MCF activities (the mean reduction rate; 49-59%, P<0. 05) were observed. These data suggest that PNR may contribute to monocyte migration, through inducing pulmonary epithelial cell-derived MCP-1 production in the airway of patients with pneumonia due to P. aeruginosa.


HeLa cell and buccal epithelial cell adhesion assays for detecting intestinal Escherichia coli with adhesive properties in ulcerative colitis.
The two methods used to detect intestinal Escherichia coli in patients with ulcerative colitis, HeLa cell and buccal epithelial cell (BEC) adhesion assays, were compared. Both methods showed a significant difference between the adhesive property of colitic and control E coli: p less than 0.0002 and p less than 0.01 for the buccal epithelial cell and HeLa cell methods, respectively. HeLa cells did not detect all BEC positive isolates which were quantitatively more adhesive than any control isolate. All BEC negative isolates were HeLa cell negative. The BEC technique seems to be more sensitive for detecting adhesive E coli in ulcerative colitis because the true incidence of adhesive E coli in ulcerative colitis was higher than that determined by the HeLa cell method.


Endogenous Gibberellins in Elongating Shoots of Clones of Salix dasyclados and Salix viminalis.
Elongating shoots of rapidly growing clones of Salix viminalis L. (clone 683-4) and Salix dasyclados Wimm. (clone 908) harvested in early August were analyzed for endogenous gibberellins (GA). Distribution of GA-like activity, determined by Tan-ginbozu dwarf rice microdrop bioassay after reverse phase C(18) high performance chromatography, was similar for both species. For S. dasyclados, combined gas chromatography-selected ion monotoring (GC-SIM) yielded identifications of GA(1), GA(8), GA(19), GA(20), and GA(29). Identifications of GA(4) and GA(9) were also made using co-injections of known amounts of [17, 17-(2)H(2)]GAs. By bioassay, the main activity was GA(19)-like in both species. Gibberellin A(1), GA(19), and GA(20) concentrations were approximated by GC-SIM using co-injections of known amounts of [17,17-(2)H(2)]GAs. Both bioassay and GC-SIM results indicated very high concentrations of GA(19) and GA(20) (about 6000 nanograms per kilogram fresh weight shoot tissue using GC-SIM: 800 ng using bioassay), compared to the concentration of GA(1) (about 130 nanograms per kilogram fresh weight using either GC-SIM or bioassay).


Master curves and radial distribution functions for shear dilatancy of liquid n-hexadecane via nonequilibrium molecular dynamics simulations.
Shear dilatancy, a significant nonlinear behavior of nonequilibrium thermodynamics states, has been observed in nonequilibrium molecular dynamics (NEMD) simulations for liquid n-hexadecane fluid under extreme shear conditions. The existence of shear dilatancy is relevant to the relationship between the imposed shear rate gamma and the critical shear rate gamma(c). Consequently, as gamma<gamma(c), the intermolecular equilibrium distance of the fluid remains unchanged, while the nonequilibrium state of the fluid approaches equilibrium. In contrast to gamma>gamma(c), the intermolecular distance is lengthened substantially by strong shear deformation breaking the equilibrium thermodynamic state so that shear dilatancy takes place. Notably, a characteristic shear rate gamma(m), which depends on the root mean square molecular velocity and the average free molecular distance, is found in nonequilibrium thermodynamics state curves. Studies of the variations in the intermolecular radial distribution function (RDF) with respect to the shear rate provide a direct measure of the variation in the degree of intermolecular separation. Additionally, the variations of the RDF curve in the microscopic regime are consistent with those of the nonequilibrium thermodynamic state in the macroscopic world. By inspecting the overall shape of the RDF curve, it can be readily corroborated that the fluid of interest exists in the liquid state. More importantly, both primary characteristic values, the equilibrium thermodynamic state variable and a particular shear rate of gamma(p), are determined cautiously, with gamma(p) depending on the gamma(m) value and the square root of pressure. Thereby, the nonequilibrium thermodynamic state curves can be normalized as temperature-, pressure-, and density-invariant master curves, formulated by applying the Cross constitutive equation. Clearly, gamma(c) occurs at which a reduced shear rate gamma/gamma(p) approaches 0.1. Furthermore, the trends in the rates of shear dilatancy in both the constant-pressure and constant-volume NEMD systems under isothermal conditions conform to the cyclic rule of pressure, as a function of density and shear rate.


Follow Up imaging After Left Atrial Appendage Occlusion-Something or Nothing and for How Long?
Routine postprocedural imaging with transesophageal echocardiography or cardiac computed tomography angiography is the most commonly used imaging modality for follow-up surveillance usually performed 1 to 6 months after the procedure. Imaging enables recognition of well-suited and sealed devices in the left atrial appendage as well as of potential harmful complications such as peri-device leaks, device-related thrombus, and device embolization, which may lead to further surveillance observation with recurrent imaging, reinitiation of oral anticoagulants, or additional interventional procedures.


Lipid signatures reflect the function of the murine primary placentation†.
The placenta regulates maternal-fetal communication, and its defect leads to significant pregnancy complications. The maternal and embryonic circulations are primitively connected in early placentation, but the function of the placenta during this developmentally essential period is relatively unknown. We thus performed a comparative proteomic analysis of the placenta before and after primary placentation and found that the metabolism and transport of lipids were characteristically activated in this period. The placental fatty acid (FA) carriers in specific placental compartments were upregulated according to gestational age, and metabolomic analysis also showed that the placental transport of FAs increased in a time-dependent manner. Further analysis of two mutant mice models with embryonic lethality revealed that lipid-related signatures could reflect the functional state of the placenta. Our findings highlight the importance of the nutrient transport function of the primary placenta in the early gestational period and the role of lipids in embryonic development. The placenta is activated characteristically in terms of lipid transport during primary placentation, and the lipid-related signatures closely reflect the functional state of the placenta.


Crystal structure of a four-copper laccase complexed with an arylamine: insights into substrate recognition and correlation with kinetics.
Laccases are multicopper oxidases that catalyze the oxidation of a wide range of phenols or arylamines, and their use in industrial oxidative processes is increasing. We purified from the white rot fungus Trametes versicolor a laccase that exists as five different isozymes, depending on glycosylation. The 2.4 A resolution structure of the most abundant isozyme of the glycosylated enzyme was solved. The four copper atoms are present, and it is the first crystal structure of a laccase in its active form. The crystallized enzyme binds 2,5-xylidine, which was used as a laccase inducer in the fungus culture. This arylamine is a very weak reducing substrate of the enzyme. The cavity enclosing 2,5-xylidine is rather wide, allowing the accommodation of substrates of various sizes. Several amino acid residues make hydrophobic interactions with the aromatic ring of the ligand. In addition, two charged or polar residues interact with its amino group. The first one is an histidine that also coordinates the copper that functions as the primary electron acceptor. The second is an aspartate conserved among fungal laccases. The purified enzyme can oxidize various hydroxylated compounds of the phenylurea family of herbicides that we synthesized. These phenolic substrates have better affinities at pH 5 than at pH 3, which could be related to the 2,5-xylidine binding by the aspartate. This is the first high-resolution structure of a multicopper oxidase complexed to a reducing substrate. It provides a model for engineering laccases that are either more efficient or with a wider substrate specificity.


Control of nanopore wetting by a photochromic spiropyran: a light-controlled valve and electrical switch.
By modifying the surface of nanoporous alumina membranes using mixtures of a photochromic spiropyran and hydrophobic molecules, it is possible to control the admission of water into the membrane using light. When the spiropyran is in the thermally stable, relatively hydrophobic closed form, the membrane is not wet by an aqueous solution. Upon exposure to UV light, the spiropyran photoisomerizes to the more polar merocyanine form, allowing water to enter the pores and cross the membrane. Thus, the photosensitive membrane acts as a burst valve, allowing the transport of water and ions across the membrane. If the aqueous solution contains ions, then the membrane acts as an electrical switch; photoisomerization leads to a two-order-of-magnitude increase in ionic conductance, allowing a current to flow across the membrane. Exposure to visible light causes photoisomerization of the merocyanine back to the closed, spiro form, but dewetting of the membrane does not occur spontaneously, due to a high activation barrier.


Effective visible-excited charge separation in silicate-bridged ZnO/BiVO4 nanocomposite and its contribution to enhanced photocatalytic activity.
It is highly desired to enhance the visible-excited charge separation of nanosized BiVO4 for utilization in photocatalysis. Here ZnO/BiVO4 nanocomposites in different molar-ratios are fabricated by simple wet-chemical processes, after synthesis of nanosized BiVO4 and ZnO by hydrothermal methods. It is shown by means of atmosphere-controlled steady-state surface photovoltage spectra and transient-state surface photovoltage responses that the photogenerated charges of resulting nanocomposite shows longer lifetime and higher separation than that of BiVO4 alone. This leads to its superior photoactivities for water oxidation to produce O2 and for colorless pollutant degradation under visible irradiation, with about three times enhancement. Interestingly, it is suggested that the prolonged lifetime and enhanced separation of photogenerated charges in the nanocomposite is attributed to the unusual spatial transfer of visible-excited high-energy electrons, by visible radiation from BiVO4 to ZnO on the basis of the ultralow-temperature electron paramagnetic resonance measurements and the photocurrent action spectra. Moreover, it is clearly demonstrated that the photogenerated charge separation of resulting ZnO/BiVO4 nanocomposite could be further enhanced after introducing the silicate bridges so as to improve the visible photocatalytic activity greatly, attributed to the built bridge favorable to charge transfer. This work would provide a feasible way to enhance the solar energy utilization of visible-response semiconductor photocatalysts.


[Vascular endothelial growth factor].
VEGF, vascular endothelial growth factor, is a substance firstly described in 1983 as a tumor-secreted protein which causes the development of ascitic fluid in case of abdominal tumors. Its influence on angiogenesis was ascertained by many studies. The strongest stimulus for its production is hypoxia, which leads to higher secretion of VEGF and new angiogenesis of so affected tissue. The neurogenic effect was firstly mentioned in 1999. Its protective and proliferative influence both on CNS and peripheral nerves is now widely accepted. It was demonstrated that VEGF has more wide ranging effect than previously thought.


The Swedish Fracture Register - ten years of experience and 600,000 fractures collected in a National Quality Register.
Before the creation of the Swedish Fracture Register (SFR), there was no national quality register that prospectively collects data regarding all types of fractures regardless of treatment in an emergency setting. Observational data on fractures registered in a sustainable way may provide invaluable tools for quality improvements in health care and research. Ten years after its implementation, the Swedish Fracture Register has 100% coverage among orthopaedic and trauma departments in Sweden. The completeness of registrations reached in 2020 69-96% for hip fractures at the different departments, with the majority reporting a completeness above 85%. The Swedish Fracture Register is a fully web-based national quality register created and run by orthopaedic professionals, with financial support from public healthcare providers and the government. All users have full access to both the registration platform and all aggregated statistics in real time. The web-based platform was created for use in health quality registers and it has easily gained acceptance among users. The register has gradually developed by the addition of more fracture types and skeletal parts. Research activity is high and 31 scientific publications have been published since 2016. The strategy from the start was to publish validation data and basic epidemiological data. However, over the past few years, publications on outcomes, such as re-operations and mortality, have been published and four register-based, randomised, controlled trials are ongoing. It is possible to create a fracture register, to gain professional acceptance and to collect fracture data in a sustainable way on a national level if the platform is easy to use. Such a platform can also be used as a randomisation platform for prospective studies.


Effectiveness of the "Baby Think It Over" teen pregnancy prevention program.
In an effort to reduce teen pregnancy, schools are purchasing a program called "Baby Think It Over," a computerized infant simulator intended to provide a realistic infant care experience. However, little empirical, especially experimental, program effectiveness data exist. This study determined if the program changed participants' attitudes toward parenting, as well as sexual and contraceptive behaviors linked to avoidance of teen pregnancy. Development of measurement tools was a part of the purpose. The study also asked teen-agers, through narrative questions, about their conscious perceptions of the baby's utility and impact. Participants included experimental (n = 151) and control (n = 62) groups of primarily White, middle class, suburban high school' students (mean age = 16.2). The quasi-experimental portion of the study failed to reveal a statistically significant effect. Narrative data revealed several positive and notable program effects.


Brain-derived neurotrophic factor mRNA levels are up-regulated in hindlimb skeletal muscle of diabetic rats: effect of denervation.
In a previous study the levels of brain-derived neurotrophic factor (BDNF) mRNA were shown to be elevated in skeletal muscle of the diabetic rat compared with age-matched control animals. It was proposed that diabetes-induced changes in nerve function may initiate changes in nerve/muscle contact akin to those following denervation of target skeletal muscle. In this study hindlimb skeletal muscles were denervated by sciatic nerve crush or transection and the effect on BDNF mRNA levels in control and diabetic rats was observed using Northern blotting. Contralateral to the side of nerve injury, the levels of BDNF mRNA in soleus muscle of diabetic rats were higher than in controls (three- to sevenfold), as has been seen previously in diabetic rats without any axotomy. Sciatic nerve crush or transection, of 1 week or of 3 weeks duration, lowered the levels of BDNF mRNA by 50% in ipsilateral soleus muscle of diabetic rats. BDNF mRNA levels in contralateral gastrocnemius muscle were not similarly raised in diabetic rats compared with controls and nerve injury had no effect. In control animals, ipsilaterally, the BDNF mRNA levels of soleus muscle were raised approximately twofold at 1 week and were lowered by approximately 50% at 3 weeks following nerve injury. Neurotrophin-3 mRNA levels were reduced approximately 50% in soleus muscle of diabetic rats compared with control rats, and nerve injury had no significant effect. The specific up-regulation of BDNF mRNA in soleus muscle of diabetic rats is discussed in terms of a proposed diabetes-induced ischemia within hindlimb skeletal muscle, with a protective role for BDNF in muscle and/or nerve being introduced.


Comparative activity of pulsed or continuous estradiol exposure on gene expression and proliferation of normal and tumoral human breast cells.
Intranasal administration of hormone replacement therapy presents an original plasma kinetic profile with transient estrogen levels giving rise to the concept of pulsed therapy. To further understand the molecular effects of this new therapy, we have compared the effects of pulsed and continuous estradiol treatments on two critical aspects of estradiol action: gene expression and cell proliferation. Cells were stimulated with estradiol as 1-h pulsed or 24-h continuous treatments at concentrations such that the 24-h exposure (concentration x time) was identical in both conditions. In MCF7 cells, the transcriptional activity of estrogen receptors (ER) on a transiently transfected responsive estrogen response element-luciferase reporter construct was shown to be drastically (approximately 10-fold) and similarly stimulated after both treatments. Moreover, the increased mRNA expression of three representative estradiol-sensitive genes (pS2, cathepsin D, progesterone receptor), evaluated by Northern blot, was identical after 1-h pulse with 7 nM estradiol or continuous treatment with 0.29 nM estradiol with the same kinetic profile over 48 h. Proliferation was quantified by a histomorphometric method on primary cultures of human normal breast cells from reduction mammoplasties and using a fluorescence DNA assay in six human breast cancer cell lines which were ER positive or negative. After a 7-day treatment period, estradiol had no effect on the proliferation of the three ER negative cell lines (BT20, MDA MB231, SK BR3) but significantly stimulated the proliferation of the normal cells and of the three tumoral hormone-sensitive cell lines (MCF7, T47D, ZR 75-1); both hormone treatments producing the same increases in cell growth. In conclusion, we have shown that the genomic or proliferative effects of estradiol were identical with pulsed or continuous treatments, thus indicating that estrogenic effects are not strictly related to concentrations but rather to total hormone exposure.


DNA fragmentation during apoptosis is caused by frequent single-strand cuts.
One of the hallmarks of apoptosis is the digestion of genomic DNA by an endonuclease, generating a ladder of small fragments of double-stranded DNA. We have examined the nature of the DNA breaks produced in mouse thymocytes triggered to undergo apoptosis by steroids or by stimulation of the T cell receptor. Whereas the typical ladder pattern of oligonucleosomal fragments was observed after agarose gel electrophoresis, numerous single-strand cuts were detected after electrophoresis under denaturing conditions. Single-strand nicks were found to be very frequent in the internucleosomal regions, but also to occur in the core particle-associated DNA. An identical pattern of single-strand nicks was obtained when chromatin DNA was exposed to the single-strand cleaving deoxyribonuclease I. The nicked DNA fragments, extracted from apoptotic thymocytes, were sensitive to the action of S1-nuclease. We propose that DNA fragmentation induced during apoptosis is not due to a double-strand cutting enzyme as previously postulated, but rather is the result of single-strand breaks. This ensures the dissociation of the DNA molecule at sites where cuts are found within close proximity.


Concept and modeling analysis of a high fidelity multimode deformable mirror.
Conventional deformable mirrors (DM) cannot meet the requirement of aberration controlling for advanced lithography tools. This paper illustrates an approach using the property that deformation of a thin plate is similar to optical modes to realize a high fidelity multimode deformable mirror whose deformation has characteristics of optical aberration modes. The way to arrange actuators is also examined. In this paper, a 36-actuator deformable mirror is taken as an example to generate low-order Zernike modes. The result shows that this DM generates the fourth fringe Zernike mode (Z4) defocus, and primary aberration Z5-Z8 with an error less than 0.5%, generates the fifth-order aberration Z10-Z14, and generates the seventh-order aberration Z17-Z20 with an error less than 1.1%. The high fidelity replication of the Zernike mode indicates that the DM satisfies the demand of controlling aberrations corresponding to the first 20 Zernike modes in an advanced lithography tool.


Evaluation of two single-factor models of metabolic syndrome: a confirmatory factor analysis for an adult population in Beijing.
Prevalence of metabolic syndrome is high and increasing in China. The causation of this disorder is, yet, to be fully understood. Several studies with confirmatory factor analysis have been performed to investigate the core of the disease in some races other than Chinese, and amongst the other studies, they have yielded a sound model fit. This study was to evaluate and compare two single-factor models of the underlying factor structure of metabolic syndrome in a Chinese population using confirmatory factor analysis. Findings showed that in a Chinese sample of 7,472 individuals, Model 1 (with waist circumference, triglycerides/HDL-C ratio, fasting plasma glucose and mean artery pressure) yielded good level of fitness (SRMR < 0.08, CFI > 0.96 and RMSEA < 0.10) in men and women of all age groups; and Model 2 (with waist circumference, triglycerides, fasting plasma glucose and systolic blood pressure) fitted well in men aged 18-34 and over 60 and in all women, except in men of 35-59 (RMSEA = 0.142). In comparison, Model 2 were shown to be better fit (with relative larger GFI and smaller AIC, BIC, CAIC, and EVIC) in women of all age groups and in men of 18-34 and over 60 years old; Model 1 had a better fit in men between 35 and 59. This study suggests that the single-factor model of metabolic syndrome with waist circumference, triglycerides, fasting plasma glucose and systolic blood pressure are plausible in women of all age groups and young and senior men in Beijing. The model with waist circumference, triglycerides/HDL-C ratio, fasting plasma glucose and mean artery pressure fits middle-aged men.


GEOlimma: differential expression analysis and feature selection using pre-existing microarray data.
Differential expression and feature selection analyses are essential steps for the development of accurate diagnostic/prognostic classifiers of complicated human diseases using transcriptomics data. These steps are particularly challenging due to the curse of dimensionality and the presence of technical and biological noise. A promising strategy for overcoming these challenges is the incorporation of pre-existing transcriptomics data in the identification of differentially expressed (DE) genes. This approach has the potential to improve the quality of selected genes, increase classification performance, and enhance biological interpretability. While a number of methods have been developed that use pre-existing data for differential expression analysis, existing methods do not leverage the identities of experimental conditions to create a robust metric for identifying DE genes. In this study, we propose a novel differential expression and feature selection method-GEOlimma-which combines pre-existing microarray data from the Gene Expression Omnibus (GEO) with the widely-applied Limma method for differential expression analysis. We first quantify differential gene expression across 2481 pairwise comparisons from 602 curated GEO Datasets, and we convert differential expression frequencies to DE prior probabilities. Genes with high DE prior probabilities show enrichment in cell growth and death, signal transduction, and cancer-related biological pathways, while genes with low prior probabilities were enriched in sensory system pathways. We then applied GEOlimma to four differential expression comparisons within two human disease datasets and performed differential expression, feature selection, and supervised classification analyses. Our results suggest that use of GEOlimma provides greater experimental power to detect DE genes compared to Limma, due to its increased effective sample size. Furthermore, in a supervised classification analysis using GEOlimma as a feature selection method, we observed similar or better classification performance than Limma given small, noisy subsets of an asthma dataset. Our results demonstrate that GEOlimma is a more effective method for differential gene expression and feature selection analyses compared to the standard Limma method. Due to its focus on gene-level differential expression, GEOlimma also has the potential to be applied to other high-throughput biological datasets.


The effect of myocardial injury on the clinical course of snake envenomation in South Korea.
This study investigated the incidence, progression and clinical course of myocardial injury-related snake envenomation in South Korea. In addition, this study evaluated whether antivenom guidelines are appropriate to control envenomation in patients with myocardial injury. The study included 198 patients who received antivenom after a snakebite, and they were divided into two groups according to evidence of myocardial injury (defined as elevated troponin I or ischemic change on electrocardiogram) at presentation. Data including serial troponin I, echocardiogram/coronary angiogram findings, the clinical course, and treatment were collected and analyzed. The incidence of myocardial injury at presentation was 15.2%. The troponin I level was 0.11 (0.07-0.56) ng/ml at presentation and tended to decrease over 24 h. Echocardiograms revealed neither regional wall motion abnormalities nor left ventricular dysfunction in 15 of 17 patients, while two patients showed signs of coronary artery stenosis on echocardiograms and coronary angiograms. However, compared with patients without myocardial injury, patients with myocardial injury had a higher frequency of systemic envenomation complications, including bleeding, respiratory failure, hypotension, acute kidney injury, thrombocytopenia and venom-induced consumption coagulopathy (VICC). The patients with myocardial injury at presentation needed significantly more frequent and larger doses of antivenom than indicated by the initial severity of envenomation. Multivariate analysis showed that myocardial injury was associated with the need for additional antivenom administration after initial administration. Myocardial injury is not uncommon after snake envenomation in Korea. Although myocardial injury itself seems to be benign, the clinical course of patients with myocardial injury is complicated, and myocardial injury is associated with the need for additional antivenom administration. The optimal use of antivenom to control envenomation in patents with myocardial injury after snake envenomation in South Korea should be established.


Comparison between iloprost and alprostadil in the treatment of Raynaud's phenomenon.
The prostanoids iloprost and alprostadil are widely used to treat ischaemic changes in patients with Raynaud's phenomenon (RP), but the optimal regimen is poorly defined. We evaluated whether there are differences between iloprost and alprostadil, in terms of either clinical efficacy or of laboratory data, with the aim of assisting in the treatment of connective tissue disease (CTD)-associated RP. Twenty-one women with CTD-associated RP were given intravenous iloprost (11 patients) or alprostadil (10 patients) cyclically (5 consecutive days, followed by 1 day every 30 days). Clinical efficacy (RP symptoms, skin score, digital ulcers) and circulating levels of von Willebrand factor (VWf), tissue plasminogen activator (tPA), thrombomodulin (TM) and Type III procollagen N-terminal propeptide (PIIINP) were evaluated by enzyme-linked immunoassay at different intervals. The overall benefits of iloprost and alprostadil were similar. RP improved in 45% versus 90% of patients; ulcers in 60% versus 40% of patients (iloprost versus alprostadil). Skin score did not significantly change with either drug. Circulating VWf decreased with either drug (iloprost -6.2%, alprostadil -9.4%), while tPA, TM, and PIIINP remained unchanged. Side effects were only minor and less frequent with alprostadil. Iloprost and alprostadil were both of benefit in CTD-associated RP, without significant differences in either clinical efficacy or circulating markers. However, ease of handling and the lower price favours alprostadil.


Cardiac remodelling and RAS inhibition.
Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS.


Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium.
We measured changes in basal release of nitric oxide and its effect on polymorphonuclear leukocyte (PMN) adherence to endothelial cells (ECs) in a feline model of myocardial ischemia (90 minutes) and reperfusion. Basal release of nitric oxide from the left anterior descending coronary artery (LAD) after myocardial ischemia/reperfusion and from the control left circumflex coronary artery (LCX) was assessed by NG-nitro L-arginine methyl ester (L-NAME)-induced vasocontraction. L-NAME induced a significant EC-dependent vasocontraction in control LCX rings (0.28 +/- 0.04 g), which was fully reversed by L-arginine but not D-arginine. L-NAME-induced vasocontraction of LAD rings was not significantly changed after 90 minutes of myocardial ischemia without reperfusion. However, 10 minutes of reperfusion reduced the L-NAME-induced vasocontraction to 0.13 +/- 0.04 g (p < 0.05), and this was restored by addition of 3 mM L-arginine but not D-arginine. Longer periods of reperfusion progressively decreased L-NAME-induced vasocontraction. After 270 minutes of reperfusion, L-NAME-induced vasocontraction was virtually abolished. Myocardial ischemia without reperfusion did not increase PMN adherence to ECs. However, PMN adherence to LAD ECs was significantly increased after 20 minutes of reperfusion (39 +/- 6 to 105 +/- 9 PMNs/mm2, p < 0.01), and incubation of LAD segments with L-arginine significantly attenuated this increase in PMN adherence. After 270 minutes of reperfusion, PMN adherence to LAD ECs was further increased to 224 +/- 10 PMNs/mm2 (p < 0.001). This increase in PMN adherence was almost completely blocked by MAb R15.7, a monoclonal antibody against CD18 of PMNs, and was significantly attenuated by MAb RR1/1, a monoclonal antibody against intercellular adhesion molecule-1 of ECs (p < 0.01). These results indicate that decreased basal release of endothelium-derived relaxing factor after myocardial ischemia/reperfusion precedes enhanced PMN adherence to the coronary endothelium, which may lead to PMN-induced myocardial injury.


Steerable catheters for minimally invasive surgery: a review and future directions.
The steerable catheter refers to the catheter that is manipulated by a mechanism which may be driven by operators or by actuators. The steerable catheter for minimally invasive surgery has rapidly become a rich and diverse area of research. Many important achievements in design, application and analysis of the steerable catheter have been made in the past decade. This paper aims to provide an overview of the state of arts of steerable catheters. Steerable catheters are classified into four main groups based on the actuation principle: (1) tendon driven catheters, (2) magnetic navigation catheters, (3) soft material driven catheters (shape memory effect catheters, steerable needles, concentric tubes, conducting polymer driven catheters and hydraulic pressure driven catheters), and (4) hybrid actuation catheters. The advantages and limitations of each of them are commented and discussed in this paper. The future directions of research are summarized.


Influence of higher-order modes on ferroconvection.
Using Fourier representations, an elaborate study of regular cellular-convective and chaotic motions in a ferrofluid is made. Investigation is made on the adequacy or otherwise of the minimal mode in studying such motions. Higher-order modes are also considered by adding modes (vertical/horizontal/combined extension). For higher modes, the extensions yield a dynamical system of order greater than three. The characteristic features of extended ferromagnetic-Lorenz models are analyzed using the largest Lyapunov exponent(LE), second largest LE, bifurcation diagram, and phase-space plots. The effect of additional modes on critical modal-Rayleigh (infinitesimal and finite-amplitude ones) numbers and the Rayleigh number at which transition to chaos occurs are examined to report features of ferroconvection hitherto unseen in previous studies. As both horizontal and vertical modes are increased, our findings infer that the dynamical system displays advanced onset of regular convection and delayed chaotic motion. Vigorous-chaotic motion is seen on adding vertical modes, whereas on adding horizontal modes, intense chaos appears with decreased intensity for large values of the scaled Rayleigh number. Most important finding from the study is that as modes are increased (vertical/horizontal), the transition from regular to chaotic motion is greatly modified and leads the system to a hyper-chaotic state. Conventionally, the chaotic or hyper-chaotic state is intermittent with a periodic/quasi-periodic state but it can be retained in the chaotic or hyper-chaotic state by considering moderate values of the Prandtl number and/or by bringing in the ferromagnetic effect.


Intraoperative myocardial infarction and refractory cardiogenic shock during major hepatectomy: a case report.
Myocardial infarction (MI) complicated by cardiogenic shock during non-cardiac surgery is a rare but fatal complication. The management of intraoperative MI is challenging. A 77-year-old hypertensive man with good functional capacity was scheduled for hepatectomy. After the start of liver resection, the electrocardiogram monitor showed ST depression, and the patient developed refractory cardiogenic shock. Transesophageal echocardiography revealed severe hypokinesis of the anteroseptal wall. The surgery was suspended, and an intra-aortic balloon pump was placed following immediate abdominal closure. Coronary angiography revealed severe stenosis of the left main coronary trunk, and percutaneous coronary intervention (PCI) was performed. Myocardial wall motion improved, and blood pressure stabilized. Two days after PCI, hepatectomy, which had been suspended, was successfully completed. Once intraoperative MI has occurred, early diagnosis and multidisciplinary approaches are important to manage the difficult clinical situation.


Terminating polyelectrolyte in multilayer films influences growth and morphology of adhering cells.
Polyelectrolyte films of anionic poly(sodium 4-styrenesulphonate) (PSS) and cationic poly (allylamine hydrochloride) (PAH) were constructed using layer-by-layer assembly. The authors examined the cytocompatibility of these films for future use in nanobiotechnology applications. Cell lines HEK-293 and 3T3-L1 were cultured on these films and the initial attachment, adhesion, proliferation and cytotoxicity of the cells were measured using a propidium iodide assay. The morphology and spread of the cells were measured by phase-contrast microscopy. The actin cytoskeleton was observed using fluorescent microscopy. Neither the PAH-terminated nor the PSS-terminated polyelectrolyte films were cytotoxic. The PAH-terminated polyelectrolyte films improved the initial attachment and subsequent adhesion of the cells, in addition to enhancing the production of extracellular matrix and the modelling of the actin filaments. The PSS-terminated film enhanced the proliferation of the cells compared to the PAH-terminated film. That was despite the cell cycle, the spreading or the cytotoxicity of both cell types being similar for either the PSS-terminated surfaces or the PAH-terminated surfaces. Cell behaviour can be modulated by the final surface charge of the polyelectrolyte film and the results are useful in guiding the choice of substrates and/or coatings for potential biomedical applications (e.g. implants) as well as cell biology research.


Recurrent headache in adolescents: nonreferred versus clinic population.
To compare headache activity, psychosocial measures, and cold pressor response between referred and nonreferred adolescents with frequent headache. Thirteen boys and 19 girls with a mean age of 13.4 +/- 0.9 years who had been referred to a hospital-based behavioral treatment program for recurrent headache were compared with an age- and sex-matched school-based population of nonreferred students consisting of 31 adolescents with frequent headaches and 32 adolescents with infrequent or no headaches. All subjects completed the Spielberger State-Trait Anxiety Inventory/Trait form, the Children's Depression Inventory, the Childhood Somatization Inventory, and measures of headache activity and related functional disability. Additionally, all subjects reported interval discomfort scores on a 40-second cold pressor test with arm immersion in a 10 degrees +/- 1 degree C cold water bath. Subjects from both headache groups reported significantly more anxiety than those with infrequent or no headaches. The school-based nonreferred adolescents reported more depressive symptoms than the clinic-based referred subjects. In addition, the latter group reported headaches of longer duration and more school days missed due to headaches than both other groups. Whereas school-based subjects and those with infrequent or no headaches reported relatively low initial cold pressor test scores and gradually reported increasing scores with time, clinic-based subjects rated their discomfort as high at the initial interval report and maintained high levels throughout the test. No differences in somatization were found among groups. Although adolescents who seek behavioral treatment for recurrent headache do not report more psychological symptoms than nonreferred adolescents with frequent headaches, they report headaches of longer duration, miss more school days due to headache, and report higher initial sustained discomfort scores to a standardized noxious stimulus.


Biocompatible Materials in Otorhinolaryngology and Their Antibacterial Properties.
For decades, biomaterials have been commonly used in medicine for the replacement of human body tissue, precise drug-delivery systems, or as parts of medical devices that are essential for some treatment methods. Due to rapid progress in the field of new materials, updates on the state of knowledge about biomaterials are frequently needed. This article describes the clinical application of different types of biomaterials in the field of otorhinolaryngology, i.e., head and neck surgery, focusing on their antimicrobial properties. The variety of their applications includes cochlear implants, middle ear prostheses, voice prostheses, materials for osteosynthesis, and nasal packing after nasal/paranasal sinuses surgery. Ceramics, such as as hydroxyapatite, zirconia, or metals and metal alloys, still have applications in the head and neck region. Tissue engineering scaffolds and drug-eluting materials, such as polymers and polymer-based composites, are becoming more common. The restoration of life tissue and the ability to prevent microbial colonization should be taken into consideration when designing the materials to be used for implant production. The authors of this paper have reviewed publications available in PubMed from the last five years about the recent progress in this topic but also establish the state of knowledge of the most common application of biomaterials over the last few decades.


Fluorination reactions in microreactors.
The DAST-mediated conversion of a range of alcohols to the corresponding fluorides in a microstructured device is described. This safe, practical fluorination method will facilitate reactions currently challenging on large scale.


Oncological Outcomes following Rectal Cancer Surgery with High or Low Ligation of the Inferior Mesenteric Artery.
The level of inferior mesenteric artery (IMA) ligation for anterior resection of rectal cancer has several considerations concerning oncological outcomes. The primary endpoint of this randomized controlled trial (RCT) was to assess bowel function between high and low ligation. This study was intended to clarify oncological outcome as the secondary endpoint. The aim of this study was to assess in a prospective RCT whether the ligation level of the IMA in rectal cancer influences oncological outcomes. Between February 2008 and December 2011, 100 patients who underwent anterior resection for rectal cancer were randomized to perform either high or low ligation of the IMA. Oncological outcomes was the secondary endpoint of this RCT, whereas assessing bowel function was the primary endpoint. This RCT was registered at clinicaltrials.gov (NCT00701012). There were no differences between the groups in terms of clinical data except for tumor stage. There were more advanced-stage patients in the high ligation group (p = 0.046). There were no lymph node (LN) metastases in the root of the IMA in the high ligation group. The average number of harvested LNs for the high and low ligation groups was 16.7 and 14.9, respectively. There was no difference in disease-free survival (DFS), site of first recurrence, and overall survival (OS). When patients were in stage III, there was also no difference in DFS and OS. The ligation level of the IMA in rectal cancer may not influence oncological outcomes. However, further large-scale RCTs are needed to conclude this issue.


Comparison between Biosynthesis of ent-Kaurene in Germinating Tomato Seeds and Cell Suspension Cultures of Tomato and Tobacco.
Biosynthesis of ent-kaurene was investigated in extracts of cell suspension cultures derived from tobacco callus (Nicotiana tabacum L.), tomato callus (Solanum lycopersicum L.), and in germinating tomato seeds. Incubation of extracts derived from the two cell cultures with either isopentenyl pyrophosphate-(14)C or with (14)C-labeled mevalonate, followed by alkaline phosphatase hydrolysis, resulted in the formation of trans-geranylgeraniol-(14)C and trans-farnesol-(14)C. The corresponding pyrophosphates of trans-geranyl-geraniol-(14)C and trans-farnesol-(14)C were also detected. No detectable amount of ent-kaurene-(14)C was produced by these enzymatic preparations when trans-geranylgeranyl-(14)C pyrophosphate served as substrate. However, copalyl-(14)C pyrophosphate served as a substrate for the production of ent-kaurene. Cell-free extracts derived from germinating tomato seeds catalyzed the formation of ent-kaurene-(14)C from mevalonate-(14)C, isopentenyl-(14)C pyrophosphate, trans-geranylgeranyl-(14)C pyrophosphate, and copalyl-(14)C pyrophosphate.


Risk of potential drug-drug interactions among Brazilian elderly: a population-based, cross-sectional study.
Drug-drug interactions (DDIs) are one of the main causes of adverse reactions related to medications, being responsible for up to 23% of hospital admissions. However, only a few studies have evaluated this problem in elderly Brazilians. To determine the prevalence of potential DDIs (PDDIs) in community-dwelling elderly people in Brazil, analyse these interactions with regard to severity and clinical implications, and identify associated factors. A population-based cross-sectional study was carried out involving 2143 elderly (aged >or=60 years) residents of the metropolitan area of Sao Paulo, Brazil. Data were obtained from the SABE (Saúde, Bem estar e Envelhecimento [Health, Well-Being, and Aging]) survey, which is a multicentre study carried out in seven countries of Latin America and the Caribbean, coordinated by the Pan-American Health Organization. PDDIs were analysed using a computerized program and categorized according to level of severity, onset, mechanism and documentation in the literature. The STATA software statistical package was used for data analysis, and logistic regression was conducted to determine whether variables were associated with PDDIs. Analysis revealed that 568 (26.5%) of the elderly population included in the study were taking medications that could lead to a DDI. Almost two-thirds (64.4%) of the elderly population exposed to PDDIs were women, 50.7% were aged >or=75 years, 71.7% reported having fair or poor health and 65.8% took 2-5 medications. A total of 125 different PDDIs were identified; the treatment combination of an ACE inhibitor with a thiazide or loop diuretic (associated with hypotension) was the most frequent cause of PDDIs (n = 322 patients; 56.7% of individuals with PDDIs). Analysis of the PDDIs revealed that 70.4% were of moderate severity, 64.8% were supported by good quality evidence and 56.8% were considered of delayed onset. The multivariate analysis showed that the risk of a PDDI was significantly increased among elderly individuals using six or more medications (odds ratio [OR] 3.37) and in patients with hypertension (OR 2.56), diabetes mellitus (OR 1.73) or heart problems (OR 3.36). Approximately one-quarter of the elderly population living in Sao Paulo could be taking two or more potentially interacting medicines. Polypharmacy predisposes elderly individuals to PDDIs. More than half of these drug combinations (57.6%, n = 72) were part of commonly employed treatment regimens and may be responsible for adverse reactions that compromise the safety of elderly individuals, especially at home. Educational initiatives are needed to avoid unnecessary risks.


Acute effects of antagonist of S2-receptors.
Intravenous administration of ketanserin--a selective antagonist of serotonin receptors--to hypertensive patients resulted in an immediate marked drop of blood pressure accompanied by a decreased excretion of vanilmandelic acid and 5-hydroxy-3-indolylacetic acid. The drug was well tolerated by all patients without any serious complaints.


Depth-based shape-analysis.
In this paper we propose a new method for shape analysis based on the depth-ordering of shapes. We use this depth-ordering to non-parametrically define depth with respect to a normal control population. This allows us to quantify differences with respect to "normality". We combine this approach with a permutation test allowing it to test for localized shape differences. The method is evaluated on a synthetically generated striatum dataset as well as on a real caudate dataset.


[Effect of Ultra-fast-track Extubation in Cardiovascular Surgery].
Fast-track surgery has been widely implemented and allows such immediate extubation as in the operating room(OR). We retrospectively investigated the effect of routine ultra-fast-track(UFT) surgery extubating in the OR in patients undergoing cardiovascular operations. Among 333 consecutive patients, 224 (67.3%)were extubated in the OR. Five patients were re-intubated, but none were because of heart or respiratory failure. Independent predictors for failure of OR extubation were preoperative renal failure, pre-existent cerebrovascular disease, emergency surgery, and prolonged operation and/or cardiopulmonary bypass times. In patients extubated in the OR, postoperative pneumonia and delirium were less frequent, oral intake was facilitated, and lengths of stay in the intensive care unit as well as hospital were shortened. UFT in cardiovascular surgery can be safely and effectively performed in a majority of patients.


Low grade glioma growth modeling considering chemotherapy and radiotherapy effects from magnetic resonance images.
Studying tumor growth using mathematical models from magnetic resonance (MR) images is an important application that is believed to play a major role in cancer treatment by predicting tumor evolution, quantifying the response to therapy, and treatment planning. Reaction diffusion is the most popular model because of its simplicity and consistency with the biological growth process. However, most of the current growth models focus on presurgical images and likely without treatment. In this paper, we propose a new reaction diffusion model to consider the chemotherapy and radiotherapy effects on the tumor growth modelling for patients with low grade glioma. The proposed model does not consider the tensor information from diffusion tensor imaging. Instead it uses a weighted parameter to promote higher diffusivity in white matter. The radiotherapy and chemotherapy effects are considered as a loss terms in the proposed model. The preliminary results of the proposed model on synthetic and 2 real MR images show that, our model can effectively simulate tumor growth with high accuracies when treatments are administrated to low grade glioma patients.


A flavanone and antimicrobial activities of the constituents of extracts from Mundulea sericea.
In this study, 12 compounds, which include a new flavanone 5-methoxy mundulin, were isolated from the leaves, stem bark and twigs of Mundulea sericea (Willd.) A. Chev. (Fabaceae; Papilionoideae). The structures of the compounds were identified based on spectral data analyses. The constituents of M. sericea also showed antimicrobial activities (MIQ = 0.01-100 µg) against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans.


Long non-coding RNA long intergenic non-coding 00641 mediates cell progression with stimulating cisplatin-resistance in osteosarcoma cells via microRNA-320d/myeloid cell leukemia-1 axis.
As a staple chemotherapy medicine, cisplatin (DDP) is extensively applied in cancer patients, but its drug resistance is limited. Numerous studies have elucidated that long non-coding RNA (lncRNA) performs as a pivotal agent in osteosarcoma (OS). Nevertheless, lncRNA long intergenic non-coding 00641 (LINC00641)'s functions in DDP resistance for OS remain obscure. The purpose of this study was to investigate the effect and mechanism of LINC00641 on drug resistance of OS. The tissues of both clinical cancer patients and the normal control were gathered. Detection of LINC00641, microRNA-320d (miR-320d) and myeloid cell leukemia-1 (MCL1) was conducted. After the selection of OS cell lines, the detection of cell advancement was applied. Series of experiments were conducted to verify the interaction of LINC00641, miR-320d and MCL1. Xenografted tumor model in vivo was utilized to determine the function of LINC00641. The data displayed, LINC00641 was prominently elevated in OS tissues and cells, especially in DDP-resistant tumors and cell lines. Knock-down LINC00641 was able to attenuate progression of DDP-resistant OS cells thus dampening their drug resistance toward DDP. Moreover, knock-downing LINC00641 gene was also able to manifest antagonism toward DDP-resistance in vivo. On the grounds of bioinformatics prediction, a direct binding of LINC00641 with miR-320d existed, whose target was MCL1. Meanwhile, LINC00641 modulated MCL1 via targeting miR-320d. Additionally, repressive LINC00641 blocked MCL1 via emulative interaction with miR-320d, thus expediting DDP-sensitivity of OS cells. All in all, it is found that LINC00641 is available to escalate drug resistance of DDP-resistant OS cells via mediation of miR-320d/MCL1 axis.


Can a cysteine challenge assay predict the in vivo behavior of 99mTc-labeled antibodies?
Recent investigations have shown that transchelation to cysteine in a principal mode of in vivo instability of 99mTc-labeled antibodies. In this investigation, a cysteine challenge assay was used to measure the in vitro instability of 99mTc directly labeled to two IgG antibodies (B72.3 and C110) via two established direct labeling methods employing mercaptoethanol and stannous ion for antibody reduction and by a novel method using glutathione for this purpose. For both antibodies, the greatest instability to cysteine occurred with stannous ion reduction. The stability of glutathione-reduced B72.3 was indistinguishable from mercaptoethanol-reduced B72.3 whereas glutathione-reduced C110 showed stability roughly intermediate between that of the other reducing agents for this antibody. Results obtained in normal mice were in the direction predicted by the assay: for both antibodies, urinary clearance of 99mTc was fastest in mice receiving antibodies labeled via stannous ion reduction, presumably because of the increased transchelation of label to cysteine in vivo. Urinary clearance was slower and identical in mice receiving B72.3 labeled via glutathione or mercaptoethanol whereas clearance in the case of glutathione-reduced C110 was intermediate between that of the other two reducing agents. At both time points, higher radioactivity levels were observed in kidneys and lower levels in blood and most other tissues for both antibodies in the case of stannous ion reduction as expected for the label of greatest instability. In the B72.3 case, with only one exception, tissue and blood levels following administration of glutathione-reduced antibody were indistinguishable from that following administration of mercaptoethanol-reduced antibody. In the C110 case, significant differences in activity levels were observed in several tissues between glutathione- and mercaptoethanol-reduced antibodies. In conclusion, the relative in vivo behaviour of 99mTc when administered to mice while labeled to two IgG antibodies were successfully predicted based on the results of an in vitro cysteine challenge assay.


Effect of processing by hydrostatic high pressure of two ready to heat vegetable meals and stability after refrigerated storage.
The effect of high pressure processing (HPP) (400 and 600 MPa for 1 and 5 min) and the stability during storage were studied in two ready to heat vegetable meals: meal A, mainly composed by pumpkin and broccoli, and meal B, mainly composed by eggplant, zucchini, chard and spinach. The treatment at 600 MPa/5 min was the most effective to reduce the initial microbial loads of the meals and maintained better the microbial safety during storage. HPP had no effect on the physico-chemical and sensory properties. HPP at 600 MPa increased the antioxidant activity of the meal A. In contrast HPP reduced the antioxidant activity of the meal B, although in general high levels of antioxidants were maintained after processing and during storage. In conclusion, treatments at 600 MPa for 5 min were the most suitable to increase the shelf-life of the meals without affecting their physico-chemical, antioxidant and sensory properties.


The homologous series of 1,1'-ferrocenylenebisdihalophosphanes (C5H4PX2)2Fe (X = F, Cl, Br, I): precursors for the first metallocene bridged bisphosphaalkene.
A facile synthetic access to the homologous series of 1,1'-ferrocenylene bisdihalophosphanes Fc'(PX2)2 (X = F, Cl, Br, I; Fc' = 1,1'-ferrocenediyl = ferrocenylene = -C5H4FeC5H4-) is reported. The 31P NMR spectroscopic data of this series suggest a similar electronic interaction of the -PX(2) unit with the ferrocene system as in monofunctional ferrocenyldihalophosphanes. Crystal structures for Fc'(PCl2)2 and Fc'(PBr2)2 reveal that the nature of the halogen atom within the phosphane unit strongly influences the twist angle of the ferrocene system, while leaving the other structural parameters mostly unaffected. Based on these bisdihalophosphanes, a synthetic access to the first metallocene bridged bisphosphaalkene ((C5H4P=C(t-Bu)OTMS)2Fe) is reported in which the tert-butyl substituents provide sufficient steric pressure to control the E/Z isomeric ratio which leads to the almost exclusive formation of the most stable Z,Z isomer out of the three possible isomers.


Structural phase transitions in the process of an A(60) cluster formation.
The explanation of the existence of the two critical parameters corresponding to the formation of an A(60) fullerene cluster in the lattice gas model is given. The presented treatment suggests the possibility of the existence of the two phases of the same symmetry type -- high-density phase and low-density phase. These theoretical results can be applied to the carbon fullerene or nanotube research.


18F-FDG uptake in accessory respiratory muscles shows the respiratory effort of patients with pleuroparenchymal fibroelastosis.
Patients with pleuroparenchymal fibroelastosis (PPFE) have severe breathlessness even with mild hypoxaemia. In patients with PPFE, accessory respiratory muscles, such as the sternocleidomastoid muscles, are used to maintain ventilation. An intense 18F-fluorodeoxyglucose uptake in accessory respiratory muscles using positron emission tomography/computed tomography reflects the strong respiratory effort of patients with PPFE.


Screen Failure Rates in Contemporary Randomized Clinical Phase II/III Therapeutic Trials in Genitourinary Malignancies.
Screen failures, defined as individuals who undergo screening but are not enrolled in a clinical trial, incur significant costs without contributing valuable data to the study. Despite these costs, there are few published data about the rate or reasons for screen failures in advanced genitourinary cancer clinical trials. We reviewed 50 phase II and III trials in advanced genitourinary cancers conducted between 1999 and 2016. Of the 50 trials, only 48% (24 of 50) published screen failure rates: 68% (13 of 19) of those in prostate cancer, 33% (6 of 18) in kidney cancer, and 58% (5 of 13) in bladder cancer. Among the phase III trials in prostate cancer, the mean screen failure rate was 26% (range, 12%-45%). The main reason for screen failure was reported as ineligibility. Among the phase III trials in kidney cancer, the mean screen failure rate was 25% (range, 21%-29%), with the most frequent reasons being ineligibility and patient refusal. Among the phase II/III trials in bladder cancer, the mean screen failure rate was 19% (range, 4%-28%), with the main reasons being ineligibility and patient refusal. Contemporary trials in genitourinary cancer reported screen failure rates of approximately 20% to 30%. Many trials did not report on the numbers of, and reasons for, screen failures. Greater standardization of definitions, methods, and reporting are needed to better understand and decrease screen failure rates in genitourinary cancer clinical trials.


Heritability of type-D personality.
To quantify the influence of genes and environment on individual differences in type-D status, and the type-D subcomponents negative affectivity and social inhibition. Type-D personality independently predicts poor prognosis in patients with cardiovascular disease. However, no previous study has determined the heritability of type-D personality. This study determined type-D personality by applying the "combination of scales" method to survey data collected by the Netherlands Twin Register in 3331 healthy, young adult twins. Using structural equation modeling (SEM), the relative contributions of additive genetic, nonadditive genetic, and nonshared environmental factors to the variance in type-D and its subcomponents were determined. SEM indicated that type-D personality was substantially heritable (52%). The subcomponents negative affectivity and social inhibition were equally heritable, with broad heritability estimates of 46% and 50%. Although negative affectivity was determined by additive genetic effects and nonshared environment, individual differences in social inhibition were predominantly determined by nonadditive genetic effects and nonshared environment. This study provides strong evidence that genes are important in determining individual differences in type-D personality and the type-D subcomponents negative affectivity and social inhibition.


A comparison of rural and urban older adults in Iowa on specific markers of successful aging.
This study examines the differences between rural and urban older adults on level of life satisfaction and depressive symptoms, focusing on the effect of social support. Data were collected through structured interviews at senior centers and senior meal sites in eastern and southeastern Iowa. The Duke Social Support Index (DSSI), the Life Satisfaction Index-Z (LSI-Z), and the Geriatric Depression Scale 15 (GDS15) were used. Correlations (Pearson's r), independent sample t-tests, and multiple regression were computed. Findings indicated that urban residents reported more depressive symptoms, as compared to rural residents. Subjective level of social support was a stronger predictor of life satisfaction and was more negatively related to depressive symptoms among rural than among urban older adults. Results suggest that social workers who work with aging people need to be aware of rural-urban differences in mental health. Furthermore, social workers need to have knowledge of older adults' social networks and work to ensure greater opportunity for social interaction.


Obstructive sleep apnea syndrome: its relationship with hypertension.
Respiratory disturbance during sleep, in its most common form, obstructive sleep apnea, is a prevalent condition in the general population. During the past several years, researchers have investigated a possible link between obstructive sleep apnea and hypertension. This article discusses the available epidemiologic and clinical evidence supporting this link. The possible mechanisms leading to the development of hypertension in patients with obstructive sleep apnea will also be discussed, as well as the effects of therapeutic interventions on arterial blood pressure. Last, the clinical importance of such interaction, which may lead to excessive cardiovascular morbidity and mortality, will be addressed.


Effect of salinity on root-nodule conductance to the oxygen diffusion in the Cicer arietinum-Mesorhizobium ciceri symbiosis.
Nodule conductance to O2 diffusion has been involved as a major factor of the inhibition of N2 fixation by soil salinity that severely reduces the production of grain legumes. In order to determine the effect of this constraint on the nodule conductance, oxygen uptake by the nodulated roots of Cicer arietinum was measured by recording the concentration of O2 as a function of pO2 in a gas-tight incubator. After germination and inoculation with the strain Mesorhizobium ciceri UPMCa7, the varieties Amdoun 1 and INRAT 93-1 were hydroponically grown in a glasshouse on 1L glass bottles filled with nutrient solution containing 25 mM NaCl. Salinity induced a marked decrease in shoot (30% versus 14%), root (43% versus 20%), and nodule biomass (100% versus 43%) for Amdoun 1 relative to INRAT 93-1. Although salinity completely prevented nodule formation in the sensitive variety Amdoun 1, nodule number and biomass were higher in the first than in the second variety in the absence of salt. This effect was associated with a significantly higher O2 uptake by nodulated root (510 versus 255 micromol O2 plant(-1)h(-1)) and nodule conductance (20 versus 5 microm s(-1)) in Amdoun 1 than in INRAT 93-1. Salinity did not significantly change the nodule conductance and nodule permeability for INRAT 93-1. Thus, the salt tolerance of this variety appears to be associated with stability in nodule conductance and the capacity to form nodules under salt constraint.


LINC01063 functions as an oncogene in melanoma through regulation of miR-5194-mediated SOX12 expression.
Melanoma is one of the most aggressive skin cancers and a major cause of cancer-linked deaths worldwide. As the morbidity and mortality of melanoma are increasing, it is necessary to elucidate the potential mechanism influencing melanoma progression. Tumor tissues and adjacent normal tissues (5 cm away from tumors) from 22 melanoma patients at the I-II stage and 39 patients at the III-VI stage were acquired. The expression of LINC01063 in melanoma was estimated by quantitative PCR. Functional assays were employed to investigate the function of LINC01063 in melanoma. Mechanism assays were adopted to explore the mechanism of LINC01063. LINC01063 knockdown impeded melanoma cell proliferation, migration, invasion, and epithelial-mesenchymal transition as well as melanoma tumor growth. Mechanistically, LINC01063 acted as an miR-5194 sponge to upregulate SOX12 expression. Finally, LINC01063 was tested to facilitate the malignant behaviors of melanoma cells via targeting miR-5194/SOX12. LINC01063 was significantly upregulated in melanoma. Specifically, LINC01063 displayed a higher level in patients at an advanced stage or with metastasis than those at an early stage or without metastasis. Our study revealed the oncogenic effects of LINC01063 on melanoma cell/tumor growth and its molecular mechanism involving miR-5194/SOX12, which might support LINC01063 to be the potential prognostic or therapeutic biomarker against melanoma.


[Early and late complications after surgical gastric resection for peptic ulcer].
For evaluating early and late complications after partial gastrectomy in gastric and duodenal ulcer, performed in 1976-92 years, was investigated 585 patients. The surgery was carry out mutables Rydygier and Billroth-2 methods. The smallest complications early and late found after the operations Finney-Haberer and Billroth-2 with Braun anastomosis and vagotomy.


Association of the beta2-adrenergic receptor gene with essential hypertension in the non-Han Chinese Yi minority human population.
The human beta2-adrenergic receptor (ADRB2) gene is a candidate for contributing to the pathophysiology of essential hypertension. The aims of the present study were to investigate the associations of differing single nucleotide polymorphisms (SNPs) and haplotypes of the ADRB2 gene promoter and coding regions with essential hypertension in genetically homogeneous Hani and Yi minority groups that are non-Han Chinese. Four SNPs in the regulatory and seven SNPs in the coding region were genotyped in 271 essential hypertension individuals and 267 controls, and eight haplotypes in the regulatory and five haplotypes in the coding region were determined and tested for association using the likelihood test statistic. There were significant associations of essential hypertension with separate SNPs located in both the regulatory and coding regions in the Yi minority group. In contrast, no associations of essential hypertension were detected with any of single SNPs in the Hani minority group. There is a significant difference in haplotype frequency distributions between the hypertensive participants and the controls in two groups (P < 10). The results indicate that variants at the ADRB2 locus may play a role in the pathophysiology of hypertension specifically in the Yi minority group.


Relationship Between Heat Shock Protein Expression and Obesity With and Without Metabolic Syndrome.
Background: Obesity is considered a chronic inflammatory disease in which the physiological mechanism responsible for reducing inflammation is weakened, prompting low-grade inflammation throughout the body. One of the key stress response systems that is dysregulated in obesity is the heat shock response, which is a critical defense mechanism that is activated in stressful conditions. Obesity is primary to metabolic syndrome (MetS) as it appears to lead to the increase in other MetS risk factors. Aim of the Study: We aimed to investigate the different expression levels of intracellular heat shock protein (iHSP) 70 and iHSP27 in obese patients with and without MetS and compare these levels to those of a lean control group. Patients and Methods: One hundred ten lean subjects were compared with 44 obese subjects without MetS and 56 obese subjects with MetS. HSP70 and HSP27 mRNA expression levels were measured by quantitative real-time polymerase chain reaction. Results: iHSP70 mRNA expression was significantly higher in obese subjects without MetS than in lean subjects (p = 0.04), whereas iHSP70 mRNA expression was significantly lower in obese subjects with MetS than in those without MetS (p = 0.02) as well as in those in the lean group (p = 0.03). iHSP27 mRNA expression was significantly lower in obese subjects with MetS than in those without MetS and in lean subjects (p = 0.037 and 0.031, respectively). Conclusion: We conclude that the intracellular expression levels of HSP70 and HSP27 may play an important role in the pathogenesis of MetS.


Rapid Assessment of Insect Steroid Hormone Entry Into Cultured Cells.
Steroid hormones control development and homeostasis in a wide variety of animals by interacting with intracellular nuclear receptors. Recent discoveries in the fruit fly Drosophila melanogaster revealed that insect steroid hormones or ecdysteroids are incorporated into cells through a membrane transporter named Ecdysone Importer (EcI), which may become a novel target for manipulating steroid hormone signaling in insects. In this study, we established an assay system that can rapidly assess EcI-mediated ecdysteroid entry into cultured cells. Using NanoLuc Binary Technology (NanoBiT), we first developed an assay to detect ligand-dependent heterodimerization of the ecdysone receptor (EcR) and retinoid X receptor (RXR) in human embryonic kidney (HEK) 293T cells. We also developed HEK293 cells that stably express EcI. By combining these tools, we can monitor ecdysteroid entry into the cells in real time, making it a reliable system to assess EcI-mediated steroid hormone incorporation into animal cells.


Rosidal K: a short-stretch compression bandage system.
Management of venous leg ulcers account for a large proportion of the work of healthcare professionals, especially for those who are community based. Multilayer and long-stretch bandage systems have been used successfully for many years in venous leg ulcer management. Rosidal K, a short-stretch bandage, is now also becoming more widely accepted in this country as an effective and cost-effective bandage system. This product focus looks at bandage systems and examines the research supporting the use of short-stretch bandages and Rosidal K.


Use of single-stranded DNA oligonucleotides in programming ribosomes for translation.
Single-stranded DNA (ssDNA) oligomers were compared to synthetic RNA oligomers in their ability to program E. coli ribosomes in vitro. AUG and dATG-containing oligomers promoted the non-enzymatic binding of fmet-tRNA to ribosomes, with similar dependence on time and magnesium concentration; only at 10 mM Mg++ or at low oligomer concentration was RNA slightly preferred in complex formation. These initiation complexes were biologically active in that fmet-tRNA, bound in response to ssDNA or RNA, was fully reactive with puromycin. While dAUG could not function as an initiation codon, p-dAUG functioned as well as AUG or dATG. However, dUAA and p-dUAA could not replace UAA in directing release-factor (RF) activity, and dTAA functioned only to a slight extent. Release factors had specificity for termination complexes containing dATGTAA, dATGTAG, or dATGTGA. At Mg++ concentrations of 15 mM or higher, these hexamers directed peptidyl transferase-dependent fmet-tRNA hydrolysis in the absence of RF. We suggest this RF-independent activation of peptidyl transferase as a unique system for studying the mechanism of termination. Overall, these results indicate that ssDNA can be used in place of RNA for certain studies of protein synthesis.


Isolation of a new type of human papillomavirus (HPV52b) with a transforming activity from cervical cancer tissue.
Substantial evidence has implicated human papillomaviruses (HPVs) as etiological agents of human cervical cancer. We detected and cloned an unidentified HPV genome in cellular DNA extracted from a surgical specimen of a Japanese patient with cervical cancer. Hybridization studies suggested that this HPV was the most homologous to HPV33 among more than 51 types of HPV ever identified. A recently identified new HPV, isolated by W. Lancaster and designated HPV52, is also most homologous to HPV33 (W. Lancaster et al., unpublished data). Our HPV was found to be homologous but not identical to HPV52 and hence was designated HPV52b. By introducing it into NIH3T3 cells, we found that HPV52b DNA had growth-stimulating activity as HPV16 DNA. This newly identified HPV52b DNA was present as episomes in cervical cancer cells of two out of two specimens so far examined and the integrated copies were not detected. HPV52b was present in three out of 15 (20%) specimens in Japan. In addition, the presence of three additional unidentified HPV sequences homologous to HPV52b was detected in three other specimens. The results suggest that this group of HPV may be prevalent and involved in carcinogenesis of cervical cancer in Japan.


Fully Automated Creation of Virtual Chemical Fragment Spaces Using the Open-Source Library OpenChemLib.
Synthetically accessible chemical spaces provide a valuable source to search for small-molecule analogues or new starting points in drug discovery projects. Having a toolbox at hand that can automatically create searchable representations of such spaces using reaction definitions and building blocks as inputs is a prerequisite to put this approach into practice. Herein, we present a tool kit to create such virtual chemical spaces. It is part of the OpenChemLib, an open-source Cheminformatics tool kit. Furthermore, we demonstrate the creation of a several billion molecules large chemical space from commercial building blocks and a list of common organic chemistry reactions.


The neural basis of the central executive system of working memory.
Working memory refers to a system for temporary storage and manipulation of information in the brain, a function critical for a wide range of cognitive operations. It has been proposed that working memory includes a central executive system (CES) to control attention and information flow to and from verbal and spatial short-term memory buffers. Although the prefrontal cortex is activated during both verbal and spatial passive working memory tasks, the brain regions involved in the CES component of working memory have not been identified. We have used functional magnetic resonance imaging (fMRI) to examine brain activation during the concurrent performance of two tasks, which is expected to engage the CES. Activation of the prefrontal cortex was observed when both tasks are performed together, but not when they are performed separately. These results support the view that the prefrontal cortex is involved in human working memory.