Renal sympathetic denervation for treatment of patients with heart failure: summary of the available evidence.
Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF. This provided the rationale for trials that demonstrated survival benefit associated with the use of beta adrenergic blockers in heart failure with reduced ejection fraction. Nevertheless, the MOXCON trial demonstrated that rapid uptitration of moxonidine (inhibitor of central sympathetic outflow) in patients with heart failure was associated with excess mortality and morbidity, despite reduction of plasma norepinephrine. Interestingly, renal norepinephrine spillover was the only independent predictor of adverse outcome in patients with heart failure, in multivariable analysis. Recently, renal sympathetic denervation has emerged as a novel approach for control of blood pressure in patients with treatment-resistant hypertension. This article summarizes the available evidence for the effect of renal sympathetic denervation in the setting of heart failure. Key messages Experimental studies supported a beneficial effect of renal sympathetic denervation in heart failure with reduced ejection fraction. Clinical studies demonstrated improvement of symptoms, and left ventricular function. In heart failure and preserved ejection fraction, renal sympathetic denervation is associated with improvement of surrogate endpoints.


Recent Advances in Magnetic Microfluidic Biosensors.
The development of portable biosening devices for the detection of biological entities such as biomolecules, pathogens, and cells has become extremely significant over the past years. Scientific research, driven by the promise for miniaturization and integration of complex laboratory equipment on inexpensive, reliable, and accurate devices, has successfully shifted several analytical and diagnostic methods to the submillimeter scale. The miniaturization process was made possible with the birth of microfluidics, a technology that could confine, manipulate, and mix very small volumes of liquids on devices integrated on standard silicon technology chips. Such devices are then directly translating the presence of these entities into an electronic signal that can be read out with a portable instrumentation. For the aforementioned tasks, the use of magnetic markers (magnetic particles-MPs-functionalized with ligands) in combination with the application of magnetic fields is being strongly investigated by research groups worldwide. The greatest merits of using magnetic fields are that they can be applied either externally or from integrated microconductors and they can be well-tuned by adjusting the applied current on the microconductors. Moreover, the magnetic markers can be manipulated inside microfluidic channels by high gradient magnetic fields that can in turn be detected by magnetic sensors. All the above make this technology an ideal candidate for the development of such microfluidic biosensors. In this review, focus is given only to very recent advances in biosensors that use microfluidics in combination with magnetic sensors and magnetic markers/nanoparticles.


The effect of modulating the glycogen-associated regulatory subunit of protein phosphatase-1 on insulin action in rat skeletal muscle cells.
Recent studies from this laboratory have shown that insulin rapidly stimulates a membranous protein phosphatase-1 (PP-1) in cultured rat skeletal muscle cells and isolated rat adipocytes. Stimulation of PP-1 is accompanied by the phosphorylation of a 160-kDa regulatory subunit of PP-1 (PP-1G). To further evaluate the exact role of this subunit in insulin action, L6 rat skeletal muscle cells were stably transfected with a vector containing the gene for PP-1G in the sense and antisense orientations. Transfection with the vector containing the PP-1G gene in the sense orientation yielded three stable clones with a 4- to 6-fold increase in PP-1G protein expression compared to those of wild-type L6 cells and neo control cells harboring an empty expression vector. Compared to the neo control, overexpression of PP-1G resulted in a 3-fold increase in insulin-stimulated PP-1 catalytic activity bound to PP-1G immunoprecipitates. These cell lines were examined for insulin's effect on glucose uptake, glycogen synthase activity, and glycogen synthesis. Insulin treatment resulted in an approximately 2-fold increase in 2-deoxyglucose uptake in recombinant cells compared to control cells (P < 0.05). This increase in 2-deoxyglucose transport was accompanied by an approximately 2-fold increase in insulin-stimulated glycogen synthase fractional activity (P < 0.05) and a 2- to 4-fold increase in insulin-stimulated glycogen synthesis compared to control cells. In conjunction with these observations, we found that an 85% depletion of endogenous PP-1G, using antisense constructs, resulted in a complete lack of PP-1 activation and an inhibition of basal and insulin-stimulated glucose transport. We conclude that the PP-1G holoenzyme is the major phosphatase regulated by insulin in vivo and plays an important role in insulin-stimulated glycogen synthesis by regulating the catalytic activity of bound PP-1.


Special problems of the asthmatic patient.
Environmental factors and physical activity present special problems for the asthmatic patient. Bronchoconstriction due to workplace exposure is one of the most common forms of occupational lung disease and has similar pathogenic mechanisms to nonoccupational asthma. Diagnosing occupational asthma may be difficult because the association between symptoms during or after work and a causative agent may be obscure. Nevertheless, it is important to recognize occupational asthma because even trace amounts of the causative agent may trigger bronchoconstriction, and the affected employee must almost always avoid exposure. Bronchoconstriction induced by exercise has affected the lifestyles of many asthmatic patients and has created special problems for numerous accomplished athletes. Although exercise-induced asthma (EIA) characteristically occurs immediately after cessation of exertion, a recent study suggests that it may sometimes begin during sustained exertion. Asthmatic patients who participate in winter sports are particularly susceptible to EIA. Vocal cord dysfunction in athletes who participate in intense competition can mimic EIA. In addition to beta-agonists used immediately before exercise, newer drugs that show promise in the treatment of EIA include the leukotriene inhibitors and furosemide. Asthmatic patients are susceptible to extremes in atmospheric pressure and have increased risk of barotrauma and arterial gas embolism during scuba diving. During longer stays at high altitude, however, asthmatic patients appear to have attenuated bronchial responsiveness.


Butyrate Reduces HFD-Induced Adipocyte Hypertrophy and Metabolic Risk Factors in Obese LDLr-/-.Leiden Mice.
Adipose tissue (AT) has a modulating role in obesity-induced metabolic complications like type 2 diabetes mellitus (T2DM) via the production of so-called adipokines such as leptin, adiponectin, and resistin. The adipokines are believed to influence other tissues and to affect insulin resistance, liver function, and to increase the risk of T2DM. In this study, we examined the impact of intervention with the short-chain fatty acid butyrate following a high-fat diet (HFD) on AT function and other metabolic risk factors associated with obesity and T2DM in mice during mid- and late life. In both mid- and late adulthood, butyrate reduced HFD-induced adipocyte hypertrophy and elevations in leptin levels, which were associated with body weight, and cholesterol and triglyceride levels. HFD feeding stimulated macrophage accumulation primarily in epididymal AT in both mid- and late life adult mice, which correlated with liver inflammation in late adulthood. In late-adult mice, butyrate diminished increased insulin levels, which were related to adipocyte size and macrophage content in epididymal AT. These results suggest that dietary butyrate supplementation is able to counteract HFD-induced detrimental changes in AT function and metabolic outcomes in late life. These changes underlie the obesity-induced elevated risk of T2DM, and therefore it is suggested that butyrate has potential to attenuate risk factors associated with obesity and T2DM.


Effect of NRG-1/ErbB signaling intervention on the differentiation of bone marrow stromal cells into sinus node-like cells.
The neuregulin-1 (NRG-1)/ErbB signaling pathway is a crucial regulator of cardiac development and plays an important role in the formation of the cardiac special conduction system. To establish a rat bone marrow stromal cell (BMSC) cardiomyocyte (CM)-like differentiation model, BMSCs were treated with 5-azacytidine and fibroblast growth factor basic (FGF-basic) for 24 hours and then cocultured with neonatal rat CMs in a Transwell culture system. The feasibility of regulating the differentiation of BMSCs into sinoatrial node cells by manipulating the NRG-1/ErbB pathway was investigated. Three weeks after induction, reverse transcription-polymerase chain reaction analysis revealed that inhibition of NRG-1/ErbB signaling (using AG1478) greatly enhanced the expression of HCN4, Tbx3, and Tbx2. Additionally, Tbx3 protein levels were higher than in the control group and even produced distinct nodal-type action potentials. The expression of Nkx2.5 in the NRG-1 group (treated with exogenous NRG-1) was higher than the other 2 groups. The expression of phospho-Akt was also increased in the NRG-1 group but decreased in the AG1478 group. Together, these data demonstrate that inhibiting the endogenous NRG-1/ErbB signaling pathway when rat BMSCs differentiate into CMs can greatly enhance the pacemaker phenotype. Akt signaling may be one of the underlying molecular mechanisms responsible for these results.


[Selection of Diuretic Therapy in Cardiology Practice].
Diuretic drugs - one of the most frequently prescribed groups of drugs in cardiology practice, primarily in patients with arterial hypertension (AH) and chronic heart failure (CHF). The article discusses the features of thiazide and loop diuretics, questions the selection of individual representatives of this class of drugs. Particular attention is paid to the loop diuretic torasemide, possessing, in addition to antihypertensive and diuretic effects, additional features such as the ability to reduce the activity of the renin-angiotensin-aldosterone system, reduce the severity of myocardial fibrosis, no negative influence on lipid and carbohydrate exchange, uric acid levels and blood electrolytes.


Association between infertility treatment and intrauterine growth: a multilevel analysis in a retrospective cohort study.
This study aimed to identify intrauterine growth differences according to infertility treatment compared with spontaneous conception and to describe intrauterine growth trajectories. Retrospective cohort study. A single primary and tertiary medical centre in Japan. This study included singleton pregnant women with prenatal check-ups and delivery at the University of Yamanashi Hospital between 1 July 2012 and 30 September 2017. Patients were divided into four groups: spontaneous conception, infertility treatment without assisted reproductive technology (ART), fresh-embryo transfer and frozen embryo transfer (FET). Differences in intrauterine growth according to the infertility treatment, including ART, and birth weight were evaluated. Multilevel analysis was employed to evaluate intrauterine growth trajectories stratified by the sex of the offspring. Estimated fetal weight (EFW) assessed by ultrasound examination. We assessed data from 37 239 prenatal examination results from 2377 pregnant women (spontaneous conception, n=1764; infertility treatment without ART, n=171; fresh-embryo transfer, n=112; and FET, n=330) in the final analysis. Multilevel analysis was adjusted for gestation duration, gestation period, parity, hypertensive disorders of pregnancy, type of infertility treatment, maternal age, smoking status, placenta previa, thyroid disease, gestational diabetes mellitus and the interaction between each potential confounding factor and gestation duration. In male fetuses, the interaction between FET and gestational duration (estimate: 0.36; 95% CI: 0.06 to 0.67) significantly affected the EFW. Similarly, in female fetuses, FET (estimate: -69.85; 95% CI: -112.09 to -27.61) and the interaction between FET and gestation duration (estimate: 0.57; 95% CI: 0.28 to 0.87) significantly affected the EFW. This study shows that FET affects intrauterine growth trajectory from the second trimester to term, particularly in female fetuses. Our findings require further prospective research to examine the effect of infertility treatment on fetal growth.


Electrophoretic separation of gold nanoparticles according to bifunctional molecules-induced charge and size.
Gold nanospheres modified with bifunctional molecules have been separated and characterized by using agarose gel electrophoresis as well as optical spectroscopy and electron microscopy. The electrophoretic mobility of a gold nanosphere capped with 11-mercaptoundecanoic acid (MUA) has been found to depend on the number of MUA molecules per gold nanosphere, indicating that it increases with the surface charge of the nanoparticle. The extinction spectrum of gold nanospheres capped with MUA at an MUA molecules per gold nanosphere value of 1000 and connected via 1,6-hexanedithiol (HDT) decreases by 33% in magnitude and shifts to the red as largely as 22 nm with the increase of the molar ratio of HDT to MUA (R(HM)). Gold nanospheres capped with MUA and connected via HDT have been separated successfully using gel electrophoresis and characterized by measuring reflectance spectra of discrete electrophoretic bands directly in the gel and by monitoring transmission electron microscope images of gold nanoparticles collected from the discrete bands. Electrophoretic mobility has been found to decrease substantially with the increment of HDT to MUA, indicating that the size of aggregated gold nanoparticles increases with the concentration of HDT.


Synchrotron radiation based aerosol time-of-flight mass spectrometry for organic constituents.
A synchrotron radiation based aerosol time-of-flight mass spectrometer using tunable vacuum-ultraviolet (VUV) light is described for real-time analysis of organic compounds in ultrafine and large aerosol particles. Particles are sampled from atmospheric pressure and are focused through an aerodynamic lens assembly into the mass spectrometer. As the particles enter the source region, they impinge on a cartridge heater and are vaporized. The particle vapor expands back into the source region and is softly ionized with tunable, quasicontinuous VUV light generated with synchrotron radiation. The radiation can be tuned to an energy close to the ionization energy of the sample molecules, thus minimizing the complications resulting from ion fragmentation. Photoionization efficiency scans (photon scans) can be readily collected, which permit measurement of the molecule's ionization energy and fragmentation onsets. Four high molecular weight, low vapor pressure organic compounds of importance in atmospheric aerosols are analyzed and their ionization energies measured with uncertainties of +/-60 meV. These are oleic acid (8.68 eV), linoleic acid (8.52 eV), linolenic acid (8.49 eV), and cholesterol (8.69 eV).


Lipase reaction in AOT-isooctane reversed micelles: effect of water on equilibria.
The effect of water on equilibria for hydrolytic reaction in reversed micelles has been investigated using lipase as a model enzyme. The effect of water on equilibria has been ignored for hydrolase reactions in an aqueous phase. In a reversed micellar system, however, the equilibrium of the lipase reaction was changed when water was added during the hydrolytic reaction. Furthermore, equilibrium fractional conversion is affected by the initial water concentration, being shifted to higher values with higher water concentrations, with other reaction conditions being held constant, indicating that the reaction should be regarded as a two-substrate process. Equations corresponding to a two-substrate, second-order reversible model are derived and used for further analysis. The progress curves predicted from the rate equations agree very well with the experimental results under various reaction conditions. The values of the molar ratio of water to surfactant (R) which maximize the initial reaction rate and maximum fractional conversion is predictable from the derived rate equations and the resulting relationship between R and the kinetic constants.


Polymerization of guaiacol and a phenolic beta-O-4-substructure by Trametes hirsuta laccase in the presence of ABTS.
The reaction of the monomeric lignin model compound guaiacol and the beta-O-4-type dimer erol (1-(4-hydroxy-3-methoxyphenyl)-2(2-methoxyphenoxy)-propane-1,3-diol with laccase from Trametes hirsuta was studied in the presence of the mediator ABTS (2,2'-azino-di[3ethylbenzothiazoline-6-sulfonic acid]). The product mixtures were analyzed by means of aqueous-phase size exclusion chromatography (SEC) with 50 mM NaOH as eluent. Interestingly, in the laccase-catalyzed reaction with both substrates, the mediator not only functioned as an electron carrier but underwent coupling reactions with the substrate to give polymeric coupling products. The molecular weight of these copolymeric products was significantly higher than the molecular weight of products obtained without ABTS. After ultrafiltration, 33% and 21% of the initially applied ABTS could be found in the polymeric product fraction for the substrates guaiacol and erol, respectively, on the basis of nitrogen analysis. When ABTS was added to substrates after full laccase-catalyzed polymerization, the reaction proceeded toward higher molecular weights.


Hyperglycemia Promotes Liver Metastasis of Colorectal Cancer via Upregulation of Integrin αvβ6.
BACKGROUND Diabetes is related to higher risk of multiple cancers. This study aimed to explore the effect and mechanism of diabetes on liver metastasis of CRC. MATERIAL AND METHODS Overall and liver metastasis-free survival in diabetic and non-diabetic CRC patients were compared by Kaplan-Meier analysis. Expression of alphavß6 was detected by immunohistochemistry in clinical specimens. Effects of hyperglycemia on alphavß6 expression in colon cancer cells were assessed by western blot, real-time PCR, and flowcytometry. Effects of hyperglycemia on migration and invasion were demonstrated by Transwell assay. Expression and activity of MMP-9 and MMP-2 were determined by real-time PCR and gelatin zymography. Liver metastatic nodules were counted and b6 expression was detected by western blot in a liver metastasis mouse model. RESULTS CRC patients with diabetes had poorer overall and liver metastasis-free survival, and diabetes was associated with higher alphavß6 expression in CRC specimens. Hyperglycemia promoted the invasion and migration of colon cancer cells, and upregulated the expression and activity of MMP-9, which were attenuated by inhibition of alphavß6. Hyperglycemia upregulated the expression of ß6 and cell surface expression of avb6, which was reduced by ERK inhibitor. The in vitro results were confirmed in vivo in the mouse model. CONCLUSIONS Our study demonstrated the enhancing effect of hyperglycemia on liver metastasis of CRC, and showed that alphavß6 was involved in this process, suggesting that control of glucose levels and inhibition of alphavß6 can reduce the risk of liver metastasis in diabetic CRC patients.


[Clinico-morphological characteristics of bone chondrosarcomas].
One hundred and sixty-two cases of bone chondrosarcoma (86 males and 76 females) were studied. Course development of secondary neoplasms was more favorable than that of primary ones. Tumor size was found to be in correlation with 3-year survival only. No significant correlation was established between tumor size, on the one hand, and 5- and 10-year survival rates, on the other. Histologic type of chondrosarcoma proved to be of the highest prognostic value. The tumor followed 5 patterns: chondrosarcoma with mild (I), moderate (II), and severe (III) anaplasia, mesenchymal chondrosarcoma and the so-called "dedifferentiated" chondrosarcoma.


Growth of wrinkle-free graphene on texture-controlled platinum films and thermal-assisted transfer of large-scale patterned graphene.
Growth of large-scale patterned, wrinkle-free graphene and the gentle transfer technique without further damage are most important requirements for the practical use of graphene. Here we report the growth of wrinkle-free, strictly uniform monolayer graphene films by chemical vapor deposition on a platinum (Pt) substrate with texture-controlled giant grains and the thermal-assisted transfer of large-scale patterned graphene onto arbitrary substrates. The designed Pt surfaces with limited numbers of grain boundaries and improved surface perfectness as well as small thermal expansion coefficient difference to graphene provide a venue for uniform growth of monolayer graphene with wrinkle-free characteristic. The thermal-assisted transfer technique allows the complete transfer of large-scale patterned graphene films onto arbitrary substrates without any ripples, tears, or folds. The transferred graphene shows high crystalline quality with an average carrier mobility of ∼ 5500 cm(2) V(-1) s(-1) at room temperature. Furthermore, this transfer technique shows a high tolerance to variations in types and morphologies of underlying substrates.


Diving Accident Guidelines of the German Society for Diving and Hyperbaric Medicine: Summary version.
The following is a synopsis of the German Diving Accident Guidelines, which may be found on www.gtuem.org in German and English. It is the second revision of a guideline initially published in 2002. The first version was reviewed in 2005 and then revised and updated in 2008. It is valid until October 2011 when the next revision is scheduled. Each version was developed by a group of experts and was then presented to a consensus conference organised by the GTÜM. An independent international steering committee (jury) at the conference created the final document. This is the first version published in both English and German. The extensive reference list used in preparing this document is available on the GTÜM website.


Advances on Microsupercapacitors: Real Fast Miniaturized Devices toward Technological Dreams for Powering Embedded Electronics?
Microsupercapacitors (MSCs) have emerged as the next generation of electrochemical energy storage sources for powering miniaturized embedded electronic and Internet of Things devices. Despite many advantages such as high-power density, long cycle life, fast charge/discharge rate, and moderate energy density, MSCs are not at the industrial level in 2022, while the first MSC was published more than 20 years ago. MSC performance is strongly correlated to electrode material, device configuration, and the used electrolyte. There are therefore many questions and scientific/technological locks to be overcome in order to raise the technological readiness level of this technology to an industrial stage: the type of electrode material, device topology/configuration, and use of a solid electrolyte with high ionic conductivity and photopatternable capabilities are key parameters that we have to optimize in order to fulfill the requirements. Carbon-based, pseudocapacitive materials such as transition metal oxide, transition metal nitride, and MXene used in symmetric or asymmetric configurations are extensively investigated. In this Review, the current progress toward the fabrication of MSCs is summarized. Challenges and prospectives to improve the performance of MSCs are discussed.


Chemiluminescent reporter gene assays: sensitive detection of the GUS and SEAP gene products.
Chemiluminescent assays are described for the secreted alkaline phosphatase (SEAP) and beta-glucuronidase (GUS) reporter gene products. These assays provide simple, sensitive, non-isotopic alternatives to existing detection methods and are performed in microplate or tube luminometers or in a scintillation counter. The SEAP reporter gene product is secreted from mammalian cells and is thus easily detected in a sample of culture medium. Sensitive detection of secreted placental alkaline phosphatase is performed with CSPD chemiluminescent alkaline phosphatase substrate, and approximately 3 fg of enzyme can be detected. GUS has become the major reporter gene used for the analysis of plant gene expression. Sensitive chemiluminescent detection of GUS activity can be performed with an assay system we have developed using Glucuron, a beta-glucuronidase substrate. This chemiluminescent assay detects 60 fg of GUS and is linear over six orders of magnitude of enzyme concentration. CSPD and Glucuron substrates have been incorporated into two new chemiluminescent reporter gene assay kits for SEAP and GUS.


Disease stigma and its mediating effect on the relationship between symptom severity and quality of life among community-dwelling women with stress urinary incontinence: a study from a Chinese city.
To examine the association between disease stigma and quality of life and whether disease stigma mediates the relationship between symptom severity and quality of life among community-dwelling women with stress urinary incontinence in China. Urinary incontinent patients perceived great stigma, which inhibited from seeking medical help. There is evidence that stigma associated with some other diseases had a complex relationship with illness severity and quality of life. However, little empirical research has examined the role that stigma plays among urinary incontinent population. A cross-sectional, descriptive design was used. A purposive sample of 333 women with stress urinary incontinence from a Chinese city was enrolled. Data were collected on symptom severity, disease stigma and quality of life using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, Social Impact Scale and Incontinence Quality-of-Life Measure, respectively. The mediate effect of disease stigma was analysed using a series of hierarchical regression models. Disease stigma negatively correlated with quality of life among stress urinary incontinent women. Social isolation and internalised shame, but not social rejection, the domains of disease stigma, partially mediated the effect of symptom severity on quality of life, attenuating the effect by 34·3% together. Disease stigma impairs quality of life of women with stress urinary incontinence and mediates the association between symptom severity and quality of life. Health workers may improve their quality of life by addressing perceived stigma. Our findings suggest that in clinical practice, stigma reduction may have the potential to not only improve quality of life, but also mitigate the impact of the severity on quality of life among urinary incontinent women. Social isolation and internalised shame should be more concerned in targeted interventions.


[Isoniazid intoxication].
A 55-year-old woman presented with sustained convulsions after the ingestion of an at first unknown amount of isoniazid, rifampin, ethambutol and alcohol. At admission the patient had a severe metabolic acidosis. Blood tests showed changes caused by the hepatotoxicity of isoniazid. Because diazepam was not efficacious in controlling the convulsions the patient was intubated. In response to the therapautic measures the convulsions stopped and metabolic acidosis was quickly compensated. Pyridoxine was given intravenously as an antidote. The rare intoxication with isoniazid demands immediate administration of pyridoxine and aggressive treatment of the convulsions.


Nausea after Repeated Sprints: Is Lactic Acidosis Really the Culprit?
Nausea caused by exhaustive sprinting is associated with high lactate ([La-]) and hydrogen ion concentrations ([H+]) and fall in blood pCO2, thus raising the issue of whether there is a causal link between nausea and these variables. For this reason, this study aimed to determine whether interspersing repeated sprints (RS) with periods of active, compared with passive, recovery results in lower levels of both nausea and changes in [La-], [H+], and pCO2. Twelve male participants completed two separate sessions comprising four 30-s sprints separated by 20 min of either active (AR; cycling at 40% V˙O2peak) or passive recovery (PR). At 6 and 18 min of each recovery period, nausea was assessed via a visual analog scale (VAS), and blood samples were collected to measure [La-], [H+], and pCO2. RS significantly increased VAS score in both AR (P < 0.001) and PR (P < 0.01). After the first sprint, VAS was higher than preexercise in only AR (P < 0.01). AR was associated with lower VAS, [La-], [H+], and higher pCO2 (all P = 0.001) compared with PR after sprints 2-4. Linear mixed modeling indicated that each of the variables significantly predicts VAS scores (P < 0.0001). Repeated-measures correlation (rrm2) indicated that [La-] had the closest association with VAS (rrm2 = 0.22, P < 0.0001). The lower levels of both nausea and changes in [La-], [H+], and pCO2 in response to AR suggest that nausea associated with RS may be causally related with these variables. However, the absence of a close relationship between these variables after the first sprint and the findings that [La-], [H+], and pCO2 only account for 13%-22% of the variation in VAS indicate that other mechanisms may also mediate nausea.


Using high hydrostatic pressures to retain the antioxidant compounds and to reduce the enzymatic activity of a pitaya-pineapple (Stenocereus sp.-Fragaria ananassa) beverage.
Pitaya (Stenocereus sp.) is a fruit native to arid and semiarid areas of Mexico. It has high antioxidant activity mainly due to its contents of betalains and phenolics, but its consumption is limited due to very short shelf-life and not very recognized flavor. A beverage of pitaya and pineapple was formulated to improve sensory properties. A high hydrostatic pressure (HHP) study at 400-600 MPa and 25 °C for 2-10 min was applied in the beverage and the effect on the contents of vitamin C, total phenolics and betalains, and the pectin methylesterase (PME) activity of pitaya-pineapple beverages, was evaluated. The effect of the come up time (CUT) was also studied. Vitamin C contents increased from 5% at 600 MPa-CUT to 64% at 400 MPa/CUT. Total phenolic concentrations decreased (20-48%) at all processing conditions tested at 400 MPa/CUT, total betacyanins were retained. At 500 MPa/10 min losses of betaxanthins of up to 6% occurred. The maximum PME activity decrease was 23% at 600 MPa 5 min, but an increase of PME activity 7% was observed at 400 MPa/10 min. HHP seem to be a good option to retain most of the antioxidant compounds in pitaya-pineapple beverage, but more studies are necessary to inactivate PME.


Glassy properties and viscous slowing down: An analysis of the correlation between nonergodicity factor and fragility.
We present an extensive analysis of the proposed relationship [T. Scopigno et al., Science 302, 849 (2003)] between the fragility of glass-forming liquids and the nonergodicity factor as measured by inelastic x-ray scattering. We test the robustness of the correlation through the investigation of the relative change under pressure of the speed of sound, nonergodicity factor, and broadening of the acoustic exitations of a molecular glass former, cumene, and of a polymer, polyisobutylene. For polyisobutylene, we also perform a similar study by varying its molecular weight. Moreover, we have included new results on liquids presenting an exceptionally high fragility index m under ambient conditions. We show that the linear relation, proposed by Scopigno et al. [Science 302, 849 (2003)] between fragility, measured in the liquid state, and the slope alpha of the inverse nonergodicity factor as a function of T/T(g), measured in the glassy state, is not verified when increasing the data base. In particular, while there is still a trend in the suggested direction at atmospheric pressure, its consistency is not maintained by introducing pressure as an extra control parameter modifying the fragility: whatever is the variation in the isobaric fragility, the inverse nonergodicity factor increases or remains constant within the error bars, and one observes a systematic increase in the slope alpha when the temperature is scaled by T(g)(P). To avoid any particular aspects that might cause the relation to fail, we have replaced the fragility by other related properties often evoked, e.g., thermodynamic fragility, for the understanding of its concept. Moreover, we find, as previously proposed by two of us [K. Niss and C. Alba-Simionesco, Phys. Rev. B 74, 024205 (2006)], that the nonergodicity factor evaluated at the glass transition qualitatively reflects the effect of density on the relaxation time even though in this case no clear quantitative correlations appear.


Patient-Induced Reaction Forces and Moments Are Influenced by Variations in Spinal Manipulative Technique.
An in vivo biomechanical study. The aim of the present study was to quantify and compare the reaction loads for two spinal manipulation therapy (SMT) procedures commonly used for low back pain using a biomechanical computer model. Contemporary computer-driven rigid linked-segment models (LSMs) have made it feasible to analyze low back kinetics and kinematics during various activities including SMT procedures. Currently, a comprehensive biomechanical model analyzing actual differences in loading effects between different SMT procedures is lacking. Twenty-four healthy/asymptomatic participants received a total of six SMT applications, representing all combinations of two similar SMT procedures within three patient hip flexion angles. All contact forces, patient torso kinematics, and inertial properties were entered into a dynamic three-dimensional LSM to calculate lumbar reaction forces and moments. Peak net applied force along with the maximums, minimums, and ranges for each component of the three-dimensional reaction force and moment vectors during each SMT procedure was analyzed. One specific SMT technique (lumbar spinous pull) produced greater maximum anterior-posterior reaction force and both lateral bending and axial twisting reaction moments compared to the other technique (lumbar push procedure [all P ≤ 0.034]). SMT trials without hip flexion had lower maximum medial-lateral reaction force and range compared to those with 45 and 90 degrees of hip flexion (all P ≤ 0.041). There were no interactions between procedure and hip angle for any of the dependent measurements. The technique used to apply SMT and the participant's initial hip orientation induced significantly different actions on the low back. These findings and future research can improve patient outcomes and safety by informing clinicians on how to best use SMT given specific types of low back pain. 2.


American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange: From Inception to First Data Release and Beyond-Lessons Learned and Member Institutions' Perspectives.
The American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) is an international data-sharing consortium focused on enabling advances in precision oncology through the gathering and sharing of tumor genetic sequencing data linked with clinical data. The project's history, operational structure, lessons learned, and institutional perspectives on participation in the data-sharing consortium are reviewed. Individuals involved with the inception and execution of AACR Project GENIE from each member institution described their experiences and lessons learned. The consortium was conceived in January 2014 and publicly released its first data set in January 2017, which consisted of 18,804 samples from 18,324 patients contributed by the eight founding institutions. Commitment and contributions from many individuals at AACR and the member institutions were crucial to the consortium's success. These individuals filled leadership, project management, informatics, data curation, contracts, ethics, and security roles. Many lessons were learned during the first 3 years of the consortium, including on how to gather, harmonize, and share data; how to make decisions and foster collaboration; and how to set the stage for continued participation and expansion of the consortium. We hope that the lessons shared here will assist new GENIE members as well as others who embark on the journey of forming a genomic data-sharing consortium.


Chondrosarcoma of bone: a statistical analysis of prognostic factors.
From 1980 to 1988, 30 cases of chondrosarcoma of the bone were treated surgically. Twenty-seven cases were followed from 6 months to 8.7 years (mean, 3.2 years). In all cases, a clinicopathological review was performed and the significance of prognostic factors were analyzed. The five-year survival of total patients was 88%. The survival was related to adequacy of treatment and histologic grade of the tumor. The five-year survival of adequately treated patients was 100%, but in inadequately treated patients it was 68%. At 8.7 years, 100% of the patients with grade-1 or grade-2 tumors survived, compared to 50% of the six-month survival rate in patients with the grade-3 tumors. None of the grade-1 or grade-2 chondrosarcomas metastasized, while 75% of grade-3 chondrosarcomas metastasized. The incidence of local recurrence was influenced by adequacy of treatment. At the final follow-up, the recurrence rate in the adequately treated group was 7%, while in the inadequately treated group it was 57%.


Implicit variations of temporal predictability: Shaping the neural oscillatory and behavioural response.
Being able to predict when an event will occur (temporal predictability) can help us prepare and time our responses. We here sought to delineate the neural and behavioural corollaries of highly implicit, probabilistic temporal predictability in an auditory foreperiod paradigm. To this end, we measured electroencephalography (EEG) and response times in two independent experiments (total N =46). Unbeknownst to participants, we induced a probabilistic variation of cue-target delays (i.e., foreperiods) in a pitch-discrimination task on a noise-embedded tone: The smaller the standard deviation of the underlying foreperiod distribution, the more predictable the time of target occurrence should be. Both experiments showed that more predictive foreperiods sped up listeners' responses. Crucially, neural signatures of temporal predictability emerged when comparing EEG activity between conditions of varying temporal predictability. First, cue-related P2 evoked responses were less pronounced for cues that implicitly signalled temporal predictability of target occurrence. Second, in both experiments, fronto-central delta (1-4Hz) phase coherence was found relatively reduced during predictive foreperiods. Concomitantly, in Experiment II, the most predictive condition yielded a central alpha (7-12Hz) power increase just before the most likely time point of tone onset, likely reflecting improved temporal orienting of attention. In sum, neural oscillations in anticipation of, and response times to a target show that humans are susceptible to even strictly implicit, probabilistic temporal regularities.


Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation.
Periodontitis is a complex pathology characterized by the loss of alveolar bone. The causes and the mechanisms that promote this bone resorption still remain unknown. The knowledge of the critical regulators involved in the alteration of alveolar bone homeostasis is of great importance for developing molecular therapies. Procaine is an anesthetic drug with demethylant properties, mainly used by dentists in oral surgeries. The inhibitor role of Wnt signaling of procaine was described in vitro in colon cancer cells. In this work we evaluated the role of procaine (1 uM) in osteo/odontogenesis of rat bone marrow mesenchymal stem cells. Similarly, the mechanisms whereby procaine achieves these effects were also studied. Procaine administration led to a drastic decrease of calcium content, alkaline phosphatase activity, alizarin red staining and an increase in the expression of Matrix Gla Protein. With respect to osteo/odontogenic markers, procaine decreased early and mature osteo/odontogenic markers. In parallel, procaine inhibited canonical Wnt/β-catenin pathway, observing a loss of nuclear β-catenin, a decrease in Lrp5 and Frizzled 3, a significant increase of sclerostin and Gsk3β and an increase of phosphorylated β-catenin. The combination of osteo/odontogenic stimuli and Lithium Chloride decreased mRNA expression of Gsk3β, recovered by Procaine. Furthermore it was proved that Procaine alone dose dependently increases the expression of Gsk3β and β-catenin phosphorylation. These effects of procaine were also observed on mature osteoblast. Interestingly, at this concentration of procaine no demethylant effects were observed. Our results demonstrated that procaine administration drastically reduced the mineralization and osteo/odontogenesis of bone marrow mesenchymal stem cells inhibiting Wnt/β-catenin pathway through the increase of Gsk3β expression and β-catenin phosphorylation.


THE RISK OF HYPERCOAGULABILITY IN OVARIAN HYPERSTIMULATION SYNDROME.
Ovarian hyperstimulation syndrome (OHSS) is a rare and potentially life-threatening complication of infertility treatment occurring during either the luteal phase or early pregnancy. An increasing number of thromboembolic complications associated with the increased use of assisted reproductive techniques have been reported in the literature. Identification of the risk factors is crucial for prevention of thromboembolic events in OHSS patients. Alterations in the hemostatic system cause hypercoagulability in women affected by severe OHSS. Coexistence of inherited hypercoagulable conditions increases the risk of thromboembolism. The role of clinical parameters that can help predict development of thrombosis is controversial. Patients with a personal or family history of thrombosis undergoing infertility treatment should be considered for thrombophilia screening, while routine examination of inherited thrombophilic mutations is not indicated in infertile patients. Antithrombotic primary prevention is not indicated in healthy women undergoing assisted reproductive procedures or in women with thrombophilia. Anticoagulant therapy is indicted if there is clinical evidence of thrombosis or laboratory evidence of hypercoagulability. In this review, the risks of hypercoagulability in the OHSS are discussed.


Dynamic Multiscale Regulation of Perfusion Recovery in Experimental Peripheral Arterial Disease: A Mechanistic Computational Model.
In peripheral arterial disease (PAD), the degree of endogenous capacity to modulate revascularization of limb muscle is central to the management of leg ischemia. To characterize the multiscale and multicellular nature of revascularization in PAD, we have developed the first computational systems biology model that mechanistically incorporates intracellular, cellular, and tissue-level features critical for the dynamic reconstitution of perfusion after occlusion-induced ischemia. The computational model was specifically formulated for a preclinical animal model of PAD (mouse hindlimb ischemia [HLI]), and it has gone through multilevel model calibration and validation against a comprehensive set of experimental data so that it accurately captures the complex cellular signaling, cell-cell communication, and function during post-HLI perfusion recovery. As an example, our model simulations generated a highly detailed description of the time-dependent spectrum-like macrophage phenotypes in HLI, and through model sensitivity analysis we identified key cellular processes with potential therapeutic significance in the pathophysiology of PAD. Furthermore, we computationally evaluated the in vivo effects of different targeted interventions on post-HLI tissue perfusion recovery in a model-based, data-driven, virtual mouse population and experimentally confirmed the therapeutic effect of a novel model-predicted intervention in real HLI mice. This novel multiscale model opens up a new avenue to use integrative systems biology modeling to facilitate translational research in PAD.


Quantitative investigation of hepatic genomic response to hormonal and pathophysiological stimuli by multivariate analysis of two-dimensional mRNA activity profiles.
We have applied techniques of multivariate analysis to the characterization and comparison of the effects of various pathophysiological and hormonal stimuli on the expression of the rat hepatic genome at a pretranslational level. In vitro translated products were resolved by two-dimensional gel electrophoresis. We analyzed 10 pathophysiological states brought about by variation in thyroidal status, starvation, administration of high carbohydrate diet, and the production of experimentally induced diabetes mellitus. Each state differed significantly from every other state in the two-dimensional electrophoretic profiles. The set consisting of the minimal number of products necessary for maintaining the distinctive patterns was identified. The analysis also defined those clusters of products that behaved in a coordinate fashion in response to the various stimuli. Lastly, the similarity and dissimilarity of hepatic mRNA activity profiles to each other could be geometrically represented in three-dimensional space. Our finding that the hepatic mRNA activity profile could distinguish reliably between closely related hormonal and pathophysiological stimuli indicates the specificity of hepatic genomic expression. A systematic analysis of such profiles may be useful as an overall index of the biologic response at the hepatocellular level.


Salusin-β Is Involved in Diabetes Mellitus-Induced Endothelial Dysfunction via Degradation of Peroxisome Proliferator-Activated Receptor Gamma.
The pathophysiological mechanisms for vascular lesions in diabetes mellitus (DM) are complex, among which endothelial dysfunction plays a vital role. Therapeutic target against endothelial injury may provide critical venues for treatment of diabetic vascular diseases. We recently identified that salusin-β contributed to high glucose-induced endothelial cell apoptosis. However, the roles of salusin-β in DM-induced endothelial dysfunction remain largely elusive. Male C57BL/6J mice were used to induce type 2 diabetes mellitus (T2DM) model. Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose/high fat (HG/HF) medium. We demonstrated increased expression of salusin-β in diabetic aortic tissues and high-glucose/high-fat- (HG/HF-) incubated HUVECs. Disruption of salusin-β by shRNA abrogated the reactive oxygen species (ROS) production, inflammation, and nitrotyrosine content of HUVECs cultured in HG/HF medium. The HG/HF-mediated decrease in peroxisome proliferator-activated receptor γ (PPARγ) expression was restored by salusin-β shRNA, and PPARγ inhibitor T0070907 abolished the protective actions of salusin-β shRNA on endothelial injury in HG/HF-treated HUVECs. Salusin-β silencing obviously improved endothelium-dependent vasorelaxation, oxidative stress, inflammatory response, and nitrative stress in diabetic aorta. Taken together, our results highlighted the essential role of salusin-β in pathological endothelial dysfunction, and salusin-β may be a promising target in treatment of vascular complications of DM.


Professional, ethical, and legal implications for spiritual care in nursing.
To highlight nurses' professional and ethical responsibility to consistently provide spiritual care. The legal issue of nurse-client privilege in relation to spiritual care is also discussed. Spiritual care is consistent with the model of holistic care. Yet spiritual care often remains a neglected focus of current nursing practice. Spirituality, as an important aspect of wellness, is indispensable in nursing care. Nurses are obligated to take an active role in meeting the spiritual needs of patients.


Effect of bladder outflow obstruction on the innervation of the rabbit urinary bladder.
The effects of bladder outflow obstruction on the innervation of the bladder were studied using a rabbit animal model. Partial occlusion of the bladder neck was obtained by the placement of a silk ligature at that level; control animals underwent a sham procedure. After a 3-month period, the presence of outflow tract obstruction was confirmed using urodynamic studies. The animals were then killed and pharmacological assessments of the bladder innervation undertaken. Detrusor muscle strip studies provided evidence of damage to the cholinergic innervation of the detrusor. Also, muscle strips from obstructed animals showed reduced inhibitory responses to beta-adrenergic stimulation with isoprenaline. In addition to these muscle strip studies, the bladder content of the neuropeptide substance P was assayed, but no significant change was observed in response to obstruction. This finding suggests that substance P-containing sensory nerves may be spared from the denervating effect of bladder outflow obstruction.


Herbal Medicines for Asthmatic Inflammation: From Basic Researches to Clinical Applications.
Asthma is one of the most common chronic inflammatory disorders, associated with reversible airflow obstruction, airway hyperresponsiveness, and airway remodeling. This disease has a significant impact on individuals, their families, and society. Standardized therapeutics such as inhaled corticosteroid in combination with long acting β2 agonist have been applied for asthma control; however, complementary and alternative medicines, especially herbal medicines, are still widely used all over the world. A growing body of literature suggests that various herbals or related products might be effective in inhibiting asthmatic inflammation. In this review, we summarize recent advances about the mechanistic studies of herbal medicines on allergic airway inflammation in animal models and their potential application into clinic for asthma control.


Effect of Humic Acid on the Removal of Chromium(VI) and the Production of Solids in Iron Electrocoagulation.
Iron-based electrocoagulation can be highly effective for Cr(VI) removal from water supplies. However, the presence of humic acid (HA) inhibited the rate of Cr(VI) removal in electrocoagulation, with the greatest decreases in Cr(VI) removal rate at higher pH. This inhibition was probably due to the formation of Fe(II) complexes with HA that are more rapidly oxidized than uncomplexed Fe(II) by dissolved oxygen, making less Fe(II) available for reduction of Cr(VI). Close association of Fe(III), Cr(III), and HA in the solid products formed during electrocoagulation influenced the fate of both Cr(III) and HA. At pH 8, the solid products were colloids (1-200 nm) with Cr(III) and HA concentrations in the filtered fraction being quite high, while at pH 6 these concentrations were low due to aggregation of small particles. X-ray diffraction and X-ray absorption fine structure spectroscopy indicated that the iron oxides produced were a mixture of lepidocrocite and ferrihydrite, with the proportion of ferrihydrite increasing in the presence of HA. Cr(VI) was completely reduced to Cr(III) in electrocoagulation, and the coordination environment of the Cr(III) in the solids was similar regardless of the humic acid loading, pH, and dissolved oxygen level.


Impact of expected changes in national papanicolaou test volume on the cytotechnology labor market: an impending crisis.
With the new screening and treatment guidelines and the prospect of human papillomavirus vaccination for adolescents, the current total volume of Papanicolaou (Pap) tests will be significantly reduced. We used available data to assess the current supply and demand in the cytotechnology labor market and how an expected change in Pap test volume impacts this market. Cytotechnologists' data were obtained from the American Society for Clinical Pathology (ASCP) Board of Registry and the Center for Medicare and Medicaid Services. Data for wages and vacancies were obtained from American Society for Cytotechnologists and ASCP Surveys. Cytotechnology training program data were obtained from annual reports of the Cytotechnology Programs Review Committee of American Society for Cytopathology. In the current market, the demand for cytotechnologists increases by 3.6% and the supply by 4.0% each year. At any given time, there is a vacancy rate of 3%. In the coming years, the demand will decrease remarkably with a projected total demand for cytotechnologists of 5,623 instead of 8,033 by the year 2010 and of 8,538 instead of 14,146 by the year 2026. The cytotechnology market faces an impending crisis. There is a high need for prospectively collected accurate data on demand for and supply of cytotechnologists.


Tradeoffs in Implant Selection for Reconstructive Surgery and Adjuncts Utilized to Maximize Aesthetic Outcomes.
With many US Food and Drug Administration-approved cohesive gel implant styles currently available in the United States, surgeons and patients may feel overwhelmed by the implant-selection process. We discuss the relative merits of the most commonly used silicone cohesive gel implants and associated adjuncts, particularly in the reconstructive setting. A literature review was conducted in PubMed to identify articles that assessed the clinical impact of differing cohesive silicone gel implants and associated adjuncts on aesthetic outcomes and complications profile. First, we review how the shape, cohesivity, and texture of cohesive gel implants impact breast aesthetics and complications after implant-based breast reconstruction (IBBR). Second, we review common adjuncts used in IBBR, including fat grafting and acellular dermal matrix (ADM), and we explore their roles in prepectoral IBBR. Finally, we review future directions in IBBR, including nanoscale implant surface modifications. In the absence of data showing that shaped implants are aesthetically preferable over round implants, we turn to a risk-benefit analysis of the complication profile of each type of implant. In selecting a smooth, round cohesive silicone implant that offers a variety of cohesivity levels, the patient can enjoy the benefits of smooth shells and avoid the drawbacks of textured shells, all without sacrificing clinically significant visual aesthetics. In the era of the bioengineered breast, this remains even more true.


Thermodynamic and biodistribution studies of Zn(II), Ca(II), Gd(III) and Cu(II) complexes of 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime.
The thermodynamic equilibria of copper(II), zinc(II), calcium(II) and gadolinium(III) with 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (L1) have been studied at 25 degrees C and an ionic strength of 0.15 mol dm(-3). Copper and gadolinium form stable complexes with the ligand while the corresponding zinc species are more than 9 log units less stable. No complexes between calcium and the ligand were detected. The low binding strength of L1 towards zinc is attributed to the square-planar coordination geometry forced on the metal ion by the ligand as revealed by molecular mechanics calculations and molecular dynamics simulations. Speciation calculations, using a computer model of blood plasma, indicate that, despite the high concentration of zinc(II) and calcium(II) in vivo, L1 is able to increase the low-molecular-mass fraction of copper in plasma. Octanol/water partition coefficient of [CuL1H(-1)] indicates that although this species is largely hydrophilic, approximately 6% of the complex goes into the octanol phase and hence may promote dermal absorption of copper by the same amount. The dermal penetration rate is calculated to be 4.0 x 10(-4) mm h(-1). The [CuL1H(-1)] complex, which predominates at pH 7.4, is a poor mimic of native copper-zinc superoxide dismutase. Biodistribution experiments using the 64Cu-labelled [CuL1H(-1)] complex indicate an initial high uptake of this species in the liver followed by redistribution into muscle. Only a small amount is excreted through the urine.


Ice Surfaces.
Ice is a fundamental solid with important environmental, biological, geological, and extraterrestrial impact. The stable form of ice at atmospheric pressure is hexagonal ice, Ih. Despite its prevalence, Ih remains an enigmatic solid, in part due to challenges in preparing samples for fundamental studies. Surfaces of ice present even greater challenges. Recently developed methods for preparation of large single-crystal samples make it possible to reproducibly prepare any chosen face to address numerous fundamental questions. This review describes preparation methods along with results that firmly establish the connection between the macroscopic structure (observed in snowflakes, microcrystallites, or etch pits) and the molecular-level configuration (detected with X-ray or electron scattering techniques). Selected results of probing interactions at the ice surface, including growth from the melt, surface vibrations, and characterization of the quasi-liquid layer, are discussed.


ATPase activity of p97/valosin-containing protein is regulated by oxidative modification of the evolutionally conserved cysteine 522 residue in Walker A motif.
Valosin-containing protein (p97/VCP) has been proposed as playing crucial roles in a variety of physiological and pathological processes such as cancer and neurodegeneration. We previously showed that VCP(K524A), an ATPase activity-negative VCP mutant, induced vacuolization, accumulation of ubiquitinated proteins, and cell death, phenotypes commonly observed in neurodegenerative disorders. However, any regulatory mechanism of its ATPase activity has not yet been clarified. Here, we show that oxidative stress readily inactivates VCP ATPase activity. With liquid chromatography/tandem mass spectrometry, we found that at least three cysteine residues were modified by oxidative stress. Of them, the 522nd cysteine (Cys-522) was identified as the site responsible for the oxidative inactivation of VCP. VCP(C522T), a single-amino acid substitution mutant from cysteine to threonine, conferred almost complete resistance to the oxidative inactivation. In response to oxidative stress, VCP strengthened the interaction with Npl4 and Ufd1, both of which are essential in endoplasmic reticulum-associated protein degradation. Cys-522 is located in the second ATP binding motif and is highly conserved in multicellular but not unicellular organisms. Cdc48p (yeast VCP) has threonine in the corresponding amino acid, and it showed resistance to the oxidative inactivation in vitro. Furthermore, a yeast mutant (delta cdc48 + cdc48[T532C]) was shown to be susceptible to oxidants-induced growth inhibition and cell death. These results clearly demonstrate that VCP ATPase activity is regulated by the oxidative modification of the Cys-522 residue. This regulatory mechanism may play a key role in the conversion of oxidative stress to endoplasmic reticulum stress response in multicellular organisms and also in the pathological process of various neurodegenerative disorders.


Biomimetic and bioinspired nanoparticles for targeted drug delivery.
In drug targeting, the urgent need for more effective and less iatrogenic therapies is pushing toward a complete revision of carrier setup. After the era of 'articles used as homing systems', novel prototypes are now emerging. Newly conceived carriers are endowed with better biocompatibility, biodistribution and targeting properties. The biomimetic approach bestows such improved functional properties. Exploiting biological molecules, organisms and cells, or taking inspiration from them, drug vector performances are now rapidly progressing toward the perfect carrier. Following this direction, researchers have refined carrier properties, achieving significant results. The present review summarizes recent advances in biomimetic and bioinspired drug vectors, derived from biologicals or obtained by processing synthetic materials with a biomimetic approach.


Colorectal cancer screening among a sample of community health center attendees.
To determine the rate of colorectal cancer screening in patients attending a sample of community health centers, medical records of 1,176 patients from eight community health centers were abstracted. Among the patients studied, 43.8% of patients had undergone at least one of the three colorectal screening tests (fecal occult blood test, colonoscopy, or flexible sigmoidoscopy) in the recommended interval. Colorectal screening in this community health center population was predicted by male gender, being African American, older age, having a greater number of chronic illnesses, a family history of colorectal cancer, and by having engaged in other preventive cancer screenings in the previous year. Although screening rates certainly were not optimal, they compare favorably to rates reported in national surveys for the general population. Our results add to a growing body of evidence that community health centers, despite serving disadvantaged populations, are able to deliver preventive care at rates comparable to health facilities used by the general population.


Comprehensive community interventions to promote health: implications for college-age drinking problems.
This article reviews comprehensive community interventions that sought to reduce (1) cardiovascular disease risks; (2) smoking; (3) alcohol use disorders, alcohol-related injury and illicit drug use; or (4) sexual risk taking that could lead to HIV infection, sexually transmitted disease and pregnancy. Comprehensive community programs typically involve multiple city government agencies as well as private citizens and organizations and use multiple intervention strategies such as school-based and public education programs, media advocacy, community organizing, environmental policy changes and heightened enforcement of existing policies. This review focused on English-language papers published over the past several decades. Some programs in each of the four problem areas achieved their behavioral and health goals. The most consistent benefits were found in programs targeting behaviors with immediate health consequences such as alcohol misuse or sexual risk taking. Results were less consistent when consequences of targeted behaviors were more distant in time such as cardiovascular risks and smoking. Also, programs that targeted youth to prevent them from starting new health-compromising behaviors tended to be more successful than programs aimed at modifying preexisting habits among adults. Programs that combined environmental and institutional policy change with theory-based education programs were the most likely to be successful. Finally, programs tailored to local conditions by the communities themselves tended to achieve more behavior change than programs imported from the outside. Comprehensive community intervention approaches may have considerable potential to reduce college-age drinking problems, especially given the success of these programs in reducing alcohol-related problems and in preventing health-compromising behaviors among youth.


[Effects of chronic HBV infection on human hepatic cytochrome P450 3A4].
To study the effect of HBV on human hepatic cytochrome P450 3A4 (CYP3A4) in patients with chronic HBV infection. Liver tissue samples were obtained from 21 patients undergoing hepatic surgery with (n = 10) or without (n = 11) chronic HBV infection and were homogenized, then hepatic microsomes were separated from the homogenate using a differential centrifugation method. The activity of CYP3A4 was determined by HPLC, and the expression of CYP3A4 protein was determined by Western-blotting. The V(max) of CYP3A4 in patients with chronic HBV infection was 493 +/- 297 pmol/min/mg, significantly reduced (P = 0.03) comparing to the normal control group: 741 +/- 189 pmol/min/mg. Western-blotting showed the the CYP3A4 protein expression in patients with chronic HBV infection was 3.04 +/- 1.63, which was significantly lower than that of the normal control group: 5.67 +/- 1.52 (P = 0.003). In contrast, no significant alteration of the K(m) of CYP3A4 was observed between two groups: 0.142 +/- 0.057 micromol/L; 0.121 +/- 0.024 micromol/L (P = 0.103). The enzymatic activity and protein expression of each liver sample had a high correlation. Correlation index was 0.7683 (P < 0.001). Chronic HBV infection tends to down-regulate the expression of hepatic CYP3A4 and reduce its activity, but does not affect its structure. When patients with chronic HBV infection are given drugs metabolized by CYP3A4, the drugs' side-effects brought by the variation of their metabolism should be taken into account.


Computed tomography in recurrent or metastatic colon cancer: relation to rising serum carcinoembryonic antigen.
Twenty patients with Stage Duke B or C adenocarcinoma of the colon or rectum who have undergone radical surgical resection and demonstrated rising serum carcinoembryonic antigen (CEA) during follow-up are the subject of this study. In all cases, while there was a continuous and progressive elevation of serum CEA, CT examination of the abdomen and pelvis was performed. Abnormal CT findings were demonstrated in 19 patients and included pelvic mass, liver metastases, and periaortic or mesenteric lymphadenopathy. There was one normal CT scan in a patient who subsequently developed metastases in the sacrum. Based on the observations in these patients, it is concluded that in routine follow-up after colorectal surgery, rising serum CEA should be considered a warning sign and warrants additional investigation by CT.


The autinglobulin test in autoimmune hemolytic anemia.
The foregoing summarizes what can be learned from a carefully performed antiglobulin test using specific antisera. Clinical syndromes can be more easily considered, and mechanisms of destruction can be more certainly discerned.


Aminopyrazole Carboxamide Bruton's Tyrosine Kinase Inhibitors. Irreversible to Reversible Covalent Reactive Group Tuning.
Potent covalent inhibitors of Bruton's tyrosine kinase (BTK) based on an aminopyrazole carboxamide scaffold have been identified. Compared to acrylamide-based covalent reactive groups leading to irreversible protein adducts, cyanamide-based reversible-covalent inhibitors provided the highest combined BTK potency and EGFR selectivity. The cyanamide covalent mechanism with BTK was confirmed through enzyme kinetic, NMR, MS, and X-ray crystallographic studies. The lead cyanamide-based inhibitors demonstrated excellent kinome selectivity and rat pharmacokinetic properties.


Duloxetine: a summary of published clinical experience.
Effective oral therapy for genuine stress urinary incontinence (SUI) in women has, to date, been an unattainable goal. Although oral pharmacologic agents have been used for this condition, none has ultimately been successful, because of side effects, lack of efficacy, or problematic compliance with drug ingestion. The availability of an effective oral agent for SUI would increase the range of therapeutic options for symptom management and possibly make treatment accessible to more women who otherwise feel that surgical therapy is not an option because of social, personal, or medical reasons. Duloxetine is a selective serotonin (5-HT) and norepinephrine reuptake inhibitor that has been shown to increase rhabdosphincter activity. Rhabdosphincter contractility changes are thought to occur as the result of increased stimulation of alpha(1)-adrenergic and 5-HT(2) receptors in the sacral spinal cord, resulting in increased efferent pudendal nerve activity, producing increased pelvic floor tonus. Two large-scale studies have been completed employing subjective and objective outcomes to assess the therapeutic index of duloxetine as a therapy for SUI.


Desensitization of diliganded mouse muscle nicotinic acetylcholine receptor channels.
Nicotinic ACh receptor channels (AChRs) exposed to high concentrations of ACh adopt 'desensitized' conformations that have a high affinity for the transmitter and no measurable ion conductance. Single-channel currents elicited by 0.1 or 1 mM ACh were recorded from human embryonic kidney (HEK) cells that had been transiently transfected with mouse alpha, beta, delta, and epsilon subunits. On the time scale of approximately 0.1 ms to approximately 1 h, apparent open intervals are described by a single exponential component, and shut intervals associated with desensitization are described by the sum of four or five exponential components. The kinetic behaviour appeared to be stationary and homogeneous. Desensitization rate constants were estimated by kinetic modelling of currents from cell-attached and outside-out patches (where the number of channels in the patch was measured). A single AChR recovered from the longest-lived desensitized state only after approximately 5 min. The occupancy of an AChR for each of the desensitized states was calculated as a function of time after the continuous application of a pulse of saturating ACh. The longest-lived desensitized state accounted for 90 % of the total only after several seconds. The fractional recovery from desensitization (during a 200 ms wash period) decreased as the duration of the desensitizing pulse increased, suggesting that recovery is slower from the longer-lived desensitized states. The free energy landscape for the AChR desensitization reaction in cell-attached patches exhibited an initial destabilization, followed by a plateau region of gradually increasing stability, followed by a deep well.


Clinical significance of FLT3 in leukemia.
FLT3 is a class III receptor tyrosine kinase together with KIT, FMS and PDGFR. FLT3 mutations were first reported as internal tandem duplication (FLT3/ITD) of the juxtamembrane domain-coding sequence, and subsequently as a missense mutation of D835 (FLT3/KDM) within a kinase domain. Furthermore, point mutations, deletions, and insertions in the codons surrounding D835 have also been found. FLT3/ITD and FLT3/KDM occur in 15% to 35% and 5% to 10%, respectively, of patients with AML. FLT3 mutations are, therefore, the most frequent genetic alterations so far reported in AML. Several large-scale studies have confirmed that FLT3/ITD is strongly associated with leukocytosis and a poor prognosis. Although the clinical significance of FLT3/KDM is controversial, the meta-analysis suggests its adverse effect on the outcome. FLT3/ITD is far less common in patients with ALL, whereas FLT3/KDM is recurrently found in patients with ALL, especially in those harboring an MLL gene rearrangement or hyperdiploidy. The overexpression of FLT3 transcripts has been demonstrated in a pro-portion of the AML patients without FLT3 mutations, which are associated with a poor prognosis for overall survival. Routine screening of FLT3 mutations is recommended to stratify the patients into distinct risk groups, while the optimal treatment strategy for patients with FLT3 mutations should be further evaluated.


Mechanisms of platelet and leukocyte recruitment in experimental colitis.
Both leukocytes and platelets accumulate in the colonic microvasculature during experimental colitis, leading to microvascular dysfunction and tissue injury. The objective of this study was to determine whether the recruitment of leukocytes and platelets in inflamed colonic venules are codependent processes. The rolling and adherence of leukocytes and platelets in colonic venules of mice with dextran sodium sulfate (DSS)-induced colitis were monitored by intravital videomicroscopy. DSS elicited an increased recruitment of both rolling and adherent leukocytes and platelets. DSS-colitic mice rendered thrombocytopenic with anti-platelet serum exhibited profound reductions in leukocyte adhesion. Neutropenia, induced with anti-neutrophil serum, significantly reduced the adhesion of leukocytes and the accumulation of platelet-leukocyte aggregates while greatly enhancing the number of platelets that roll and adhere directly to venular endothelial cells. The enhanced platelet adhesion associated with neutropenia was mediated by platelet P-selectin interactions with endothelial cell P-selectin glycoprotein ligand (PSGL-1). DSS colitis was also associated with an increased expression of PSGL-1 in the colonic vasculature. These findings indicate that the recruitment of leukocytes and platelets in inflamed colonic venules are co-dependent processes.


[Psychosomatic aspects of focal dystonia: two case reports].
Dystonic movements and other dyskinesias often cause diagnostic difficulties due to their complex symptomatology. Namely focal dystonias are frequently misdiagnosed as conversion reactions. Idiopathic dystonias are generally considered a nonstructural (neurobiochemical) disorder of the basal ganglia. Many case reports, however, have dealt with patients presenting with "atypical" dystonia whose symptoms were relieved by psychotherapy or hypnosis. We present the histories of two young women exhibiting focal dystonia emerging for the first time under circumstances of profound emotional trouble. We discuss the general difficulties in the diagnosis of dystonic movement disorders and review the criteria for the diagnosis of "psychogenic dystonia". The basal ganglia integrate limbic, proprioceptive and sensorimotor inputs to create emotionally and functionally appropriate voluntary movements. Therefore, the traditional dichotomy "psychogenic-somatogenic" appears to be inappropriate when applied to extrapyramidal movement disorders. In a psychosomatic understanding, the assumption of a psychogenic "trigger" for a somatic movement disorder does not mean a contradiction.


[Principal component analysis and correlation analysis of elements in flos Chrysanthemi indici from different regions].
To explore the character of inorganic elements in Flos Chrysanthemi indici and look for relationship between the element concentration and regions. The contents of elements, including borum (B), sodium (Na), magnesium (Mg), phosphorus (P), potassium (K), calcium(Ca), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), strontium (Sr), cesium (Se), barium(Ba) and lead(Pb) in Chinese traditional herb Flos Chrysanthemi indici from different regions were determined by ICP-AES. The element distrubution diagram were plotted. The principal component analysis and correlation analysis of SPSS were applied for the study of characteristic elements. Similar curves of element concentration have been acquired. It is observed that the content of elements in the samples shows regional diversity. There are 15 correlative element pairs in correlation analysis. Four principal components which accounted for over 84.437% of the total variance were extracted from the original data. The first and second factors accounted for 60.090% of the total variance, which means that P, K, Ca, Mn, Fe, Cu, Sr, B, Na and Se may be the characteristic elements. The showed that element content in Flos Chrysanthemi Indici display special distributing diagram. Remarkable correlation is presented in some element pairs. The elements contents of Flos Chrysanthemi indici gained from Yunan, Hunan are higher than those from other regions.


Assessment of quality improvement of simulation-based learning using an evidence-based framework in dental education.
Simulation-based education is of paramount importance in a dental pre-clinical setting. Hence, continuous quality improvement is crucial to optimize students' knowledge and clinical skills. This study aimed to evaluate the impact of evidence-based simulation learning (EBSL) compared with traditional-based simulation learning (TBSL) using Plan-Do-Study-Act (PDSA) model. This quality improvement project was undertaken at a private university. Guided by the PDSA model, rubber dam application tasks were conducted in the simulation lab in 2 phases. Phase 1 included TBSL and phase 2 included EBSL comprising of 2 PDSA cycles. 'Plan' stage involved obtaining feedback from students and the concerned staff. 'Do' stage included implementation of EBSL in eight steps adopted from Higgins's framework. 'Study' stage evaluated the outcomes and in 'Act' stage amendments were made to the first EBSL cycle. In the second PDSA cycle re-implementation and evaluation of the rubber dam application exercises were carried out. Descriptive data were presented as percentages and mean scores were compared using paired t-test. Thirty-seven year 2 students participated in this study. A significant improvement in the mean scores was observed between TBSL and EBSL (3.02 + 0.16 and 3.91 + 0.27, respectively, p < .001) using PDSA model with the highest mean score for rubber dam application in the second PDSA cycle for EBSL (4.00 + 0.01). Ninety-five per cent of the students provided positive feedback pertaining to EBSL. EBSL was effective in achieving high student satisfaction, desired knowledge, and skills required during simulation-based exercises. The PDSA cycle can be considered to optimize pre-clinical skills learning.


Bose-Einstein condensation in a circular waveguide.
We have produced Bose-Einstein condensates in a ring-shaped magnetic waveguide. The few-millimeter diameter, nonzero-bias ring is formed from a time-averaged quadrupole ring. Condensates that propagate around the ring make several revolutions within the time it takes for them to expand to fill the ring. The ring shape is ideally suited for studies of vorticity in a multiply connected geometry and is promising as a rotation sensor.


Moderate daily intake of red wine inhibits mural thrombosis and monocyte tissue factor expression in an experimental porcine model.
Moderate consumption of red wine has been epidemiologically associated with a reduction in cardiovascular disease, but its mechanism of action is not fully understood. The objective was to study whether the protective effects of a daily intake of red wine (Tempranillo, 12.8% alcohol vol/vol) could be related to inhibition of thrombosis in an experimental model of diet-induced hyperlipemia. For 100 days, animals were fed a western-type proatherogenic diet containing 2% cholesterol and 20% saturated fat. Three doses of red wine were studied (20, 30, and 40 g wine-ethanol/d) and compared with placebo-control animals not taking any wine. Thrombosis under flow conditions was evaluated by radioisotopic quantification of deposited platelets on damaged arteries. Changes in RhoA translocation in platelets and monocyte tissue factor expression were also analyzed. Mural platelet deposition was significantly reduced in animals ingesting red wine with their food. Expression of RhoA in the platelet cytoplasm (inactive form) was increased in wine-fed animals. Tissue factor mRNA expression in lipopolysaccharide-stimulated monocytes was reduced in wine-fed animals. Total cholesterol levels were not significantly different among groups. Moderate red wine intake significantly reduces platelet deposition triggered by damaged vessel wall, partially explained by inhibition of RhoA translocation to the platelet membrane. Hence, a daily moderate intake of wine seems to inhibit different pathways that converge in a reduced thrombotic risk on vessel wall injury.


Additive antitumor effects of celecoxib and simvastatin on head and neck squamous cell carcinoma in vitro.
Lipid-lowering statins as well as non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to possess cancer-protective effects in many epidemiologic cohort studies. However, the underlying mechanisms of these findings are mostly unknown. To evaluate possible additive antitumor effects of statins and NSAIDs in vitro, PJ-41 and HLaC78 head and neck squamous cell carcinoma cells (HNSCC) were treated with 40 µM celecoxib, 50 µM simvastatin or a combination of both. Analysis of tumor viability, proliferation, apoptosis, cell cycle changes and secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) was conducted via MTT assay, Annexin V-propidium iodide test, cell cycle analysis, colony assay and enzyme-linked immunosorbent assay (ELISA). Celecoxib and simvastatin alone as well as a combined treatment showed a significant reduction in tumor cell viability, proliferation and secretion of IL-6 and IL-8 compared to the control group. The combined treatment even proved to have significantly greater effects. We postulate that simvastatin and celecoxib have additive antitumor effects on HNSCC in vitro, which warrants further investigation.


Clinical and electrophysiological recovery in Leber hereditary optic neuropathy with G3460A mutation.
To report a case of clinical and electrophysiological recovery in Leber hereditary optic neuropathy (LHON) with G3460A Mutation. A 10-year-old boy with a three-month history of painless bilateral sequential visual loss upon presentation underwent visual acuity (diminished), anterior and posterior segment examination (normal), fluorescein angiography (normal), Goldman kinetic perimetry (bilateral central scotomata), genetic (a point G3460A mutation) and electrophysiological investigation (undetectable pattern visual evoked potentials (VEP); low amplitude, broadened and reduced flash VEPs and loss of the N95 component in the pattern electroretinograms). Diagnosis of LHON was made. Eighteen months later vision and electrophysiological tests results began spontaneously improving. Kinetic perimetry revealed reduced density and size of scotomata. Two years later, there had been further electrophysiological improvement. This report describes both clinical and electrophysiological improvement in LHON with G3460A mutation.


Vanadia as an electron-hole recombination inhibitor on fibrous silica-titania for selective hole oxidation of ciprofloxacin and Congo red photodegradation.
Vanadia (V2O5)-incorporated fibrous silica-titania (V/FST) catalysts, which were successfully synthesized using a hydrothermal method followed by the impregnation of V2O5. The catalysts were then characterized using numerous techniques, including X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, nitrogen adsorption-desorption analyses, ultraviolet-visible diffuse reflectance spectroscopy, Fourier-transform infrared, X-ray photoelectron spectroscopy, and photoluminescence (PL) analyses. The study found that varying the amount of V2O5 (1-10 wt%) had a significant impact on the physicochemical properties of the FST, which in turn improved the photodegradation efficiency of two organic compounds, ciprofloxacin (CIP) and congo red (CR). 5V/FST demonstrated the best performance in degrading 10 mg L-1 of CIP (83%) and CR (100%) at pH 3 using 0.375 g L-1 catalyst under visible light irradiation within 180 min. The highest photoactivity of 5V/FST is mainly due to higher crystallinity and the highest number of V2O5-FST interactions. Furthermore, as demonstrated by PL analysis, the 5V/FST catalyst has the most significant impact on interfacial charge transfer and reduces electron-hole recombination. The photodegradation of both contaminants follows the Langmuir-Hinshelwood pseudo-first-order model, according to the kinetic study. The scavenger investigation demonstrated that hydroxyl radicals and holes dominated species in the system, indicating that the catalyst effectively generated reactive species for pollutant degradation. A possible mechanism was also identified for FST and 5V/FST. Interestingly, V2O5 acts as an electron-hole recombination inhibitor on FST for selective hole oxidation of ciprofloxacin and congo red photodegradation. Finally, the degradation efficiency of the catalyst remained relatively stable even after five cyclic experiments, indicating its potential for long-term use in environmental remediation.


Habituation is altered in neuropsychiatric disorders-A comprehensive review with recommendations for experimental design and analysis.
Abnormalities in the simplest form of learning, habituation, have been reported in a variety of neuropsychiatric disorders as etiologically diverse as Autism Spectrum Disorder, Fragile X syndrome, Schizophrenia, Parkinson's Disease, Huntington's Disease, Attention Deficit Hyperactivity Disorder, Tourette's Syndrome, and Migraine. Here we provide the first comprehensive review of what is known about alterations in this form of non-associative learning in each disorder. Across several disorders, abnormal habituation is predictive of symptom severity, highlighting the clinical significance of habituation and its importance to normal cognitive function. Abnormal habituation is discussed within the greater framework of learning theory and how it may relate to disease phenotype either as a cause, symptom, or therapy. Important considerations for the design and interpretation of habituation experiments are outlined with the hope that these will aid both clinicians and basic researchers investigating how this simple form of learning is altered in disease.


Superparamagnetic Nanoparticles for Atherosclerosis Imaging.
The production of magnetic nanoparticles of utmost quality for biomedical imaging requires several steps, from the synthesis of highly crystalline magnetic cores to the attachment of the different molecules on the surface. This last step probably plays the key role in the production of clinically useful nanomaterials. The attachment of the different biomolecules should be performed in a defined and controlled fashion, avoiding the random adsorption of the components that could lead to undesirable byproducts and ill-characterized surface composition. In this work, we review the process of creating new magnetic nanomaterials for imaging, particularly for the detection of atherosclerotic plaque, in vivo. Our focus will be in the different biofunctionalization techniques that we and several other groups have recently developed. Magnetic nanomaterial functionalization should be performed by chemoselective techniques. This approach will facilitate the application of these nanomaterials in the clinic, not as an exception, but as any other pharmacological compound.


Artificial living crystals in confined environment.
Similar to the spontaneous formation of colonies of bacteria, flocks of birds, or schools of fish, "living crystals" can be formed by artificial self-propelled particles such as Janus colloids. Unlike usual solids, these "crystals" are far from thermodynamic equilibrium. They fluctuate in time forming a crystalline structure, breaking apart and re-forming again. We propose a method to stabilize living crystals by applying a weak confinement potential that does not suppress the ability of the particles to perform self-propelled motion, but it stabilizes the structure and shape of the dynamical clusters. This gives rise to such configurations of living crystals as "living shells" formed by Janus colloids. Moreover, the shape of the stable living clusters can be controlled by tuning the potential strength. Our proposal can be verified experimentally with either artificial microswimmers such as Janus colloids, or with living active matter.


Trauma and recent life events in individuals at ultra high risk for psychosis: review and meta-analysis.
Childhood trauma and recent life-events have been related to psychotic disorders. The aim of the present study was to examine whether childhood trauma and recent life-events are significantly more prevalent in patients at Ultra High Risk (UHR) of developing a psychotic disorder compared to healthy controls. A search of PsychInfo and Embase was conducted, relevant papers were reviewed, and three random-effects meta-analyses were performed. One meta-analysis assessed the prevalence rate of childhood trauma in UHR subjects and two meta-analyses were conducted to compare UHR subjects and healthy control subjects on the experience of childhood trauma and recent life-events. We found 12 studies on the prevalence of (childhood) trauma in UHR populations and 4 studies on recent life-events in UHR populations. We performed a meta-analysis on 6 studies (of which trauma prevalence rates were available) on childhood trauma in UHR populations, yielding a mean prevalence rate of 86.8% (95% CI 77%-93%). Childhood trauma was significantly more prevalent in UHR subjects compared to healthy control groups (Random effects Hedges' g=1.09; Z=4.60, p<.001). In contrast to our hypothesis, life-event rates were significantly lower in UHR subjects compared to healthy controls (Random effects Hedges' g=-0.53; Z=-2.36, p<.02). Our meta-analytic results illustrate that childhood trauma is highly prevalent among UHR subjects and that childhood trauma is related to UHR status. These results are in line with studies on childhood trauma in psychotic populations. In contrast to studies on recent life-events in psychotic populations, our results show that recent life-events are not associated with UHR status.


Bioaugmentation of the anaerobic digestion of food waste by dungs of herbivore, carnivore, and omnivore zoo animals.
The potential improvement of biomethanation of food waste (FW) by adding dung of herbivore (giraffe, llama, koala), carnivore (tiger), and omnivore (sloth bear) animals to anaerobic sludge (AnS) was investigated. Adding 30% giraffe, sloth bear or koala dung to the AnS inoculum yielded, respectively, a 11.17 (±4.51), 10.10 (±1.23), and 1.41 (±0.56)% higher biomethane production, as compared to the control (FW with solely AnS). The highest biomethane production of 564.00 (±3.88) ml CH4/gVSadded obtained with 30% giraffe dung and 70% AnS was attributed to a higher solubilization of proteins (6.96 ± 2.76%) and recalcitrant carbohydrates (344.85 ± 54.31 mg/L as compared to zero). The biomethanation process could have been stimulated by the microorganisms or enzymes newly introduced, and/or the trace elements (Ni, Zn, and Co) present in the giraffe dung. These results indicate that bioaugmentation with zoo animals dung is worthy of further investigation as a strategy for improving the biomethane recovery from organic wastes.


Ethnicity and sampling bias in binge eating disorder: Black women who seek treatment have different characteristics than those who do not.
The current study investigated sampling bias as it affects recruited clinic samples of Black and White women with binge eating disorder (BED). Clinical characteristics of a recruited clinic sample (35 Black and 302 White consecutively evaluated women) with BED were compared with a community sample of Black and White women with BED drawn from the New England Women's Health Project. The clinic and community groups met the same definition of BED and were assessed with identical methods. Among White women, the clinic and community samples differed on some features (higher body mass index [BMI], and greater eating concerns and shape concerns in the clinic sample) but these differences reflected small to moderate effects sizes. In contrast, among Black women, the clinic sample had substantially higher levels (large effect sizes) of several features of eating disorders (eating concerns, dietary restraint, and shape concern), higher (moderate effect size) BMI, but lower frequency of binge eating (moderate effect size) than the community sample. A comparison of Black and White women within the clinic sample revealed little difference in clinical presentation, except for the significantly higher BMI among Black women. A sampling bias appears to exist between both White and Black recruited clinic samples of women with BED, although the bias appears to be substantially greater for Black women. Black women with BED who seek treatment have significantly different characteristics than those who do not.


Influence of conceptus number and weight on the amount of foetal fluid in the mouse.
The relation of extra-embryonic fluid weight to litter number and foetal and placental weight was studied in mice on the 18th day of pregnancy, in litters both of experimentally reduced and of normal number. Partial regression analysis showed that litter number and foetal weight both exerted a negative effect on fluid weight; placental weight had no significant effect. Increased foetal weight reduced weight locally; on the other hand the effect of litter number was exerted systemically, throughout both horns of the uterus.


Non-healing ischaemic digital ulcer in a systemic sclerosis patient: a challenging clinical case.
Ischaemic digital ulcers (DUs) are an indicator of the severity of the microangiopathy in patients with systemic sclerosis (SSc). DUs are a frequent complication, affecting about 50% of patients with SSc, and are often recurrent. In cross-sectional studies involving patients with SSc, the frequency of ischaemic DUs was 12-16% with a major impact on hand function and quality of life. Effective therapy for DUs remains elusive. Intravenous iloprost has been demonstrated to have a positive effect on healing of active DUs. Bosentan, an oral endothelin receptor antagonist, only showed a benefit in preventing the occurrence of new DUs. Despite limited evidence, recent guidelines have recommended phosphodiesterase type 5 inhibitors as an option. Injection of botulinum toxin and digital sympathectomy have been increasingly used for ischaemic DUs. Here we present the complex case of a SSc patient already treated with sildenafil and bosentan in whom an active DU was successfully treated with botulinum toxin A. Despite the lack of a randomised controlled trial, results are encouraging for the use of botulinum toxin in the treatment of DUs and could perhaps help to avoid some amputations, as in the present case.


Synthesis and bio-functionalization of multifunctional magnetic Fe(3)O(4)@Y(2)O(3):Eu nanocomposites.
A facile homogenous precipitation method has been developed for the synthesis of multifunctional, magnetic, luminescent nanocomposites with Fe(3)O(4) nanoparticles as the core and europium-doped yttrium oxide (Y(2)O(3):Eu) as the shell. The nanocomposites showed both super-paramagnetic behavior and unique europium fluorescence properties with high emission intensity. Their surface has been modified with a bifunctional ligand, p-aminobenzoic acid (PABA), and further biofunctionalized with biotin; the nanocomposites showed specific targeting for avidin-coupled polystyrene beads.


Flexibility and Stability Trade-Off in Active Site of Cold-Adapted Pseudomonas mandelii Esterase EstK.
Cold-adapted enzymes exhibit enhanced conformational flexibility, especially in their active sites, as compared with their warmer-temperature counterparts. However, the mechanism by which cold-adapted enzymes maintain their active site stability is largely unknown. In this study, we investigated the role of conserved D308-Y309 residues located in the same loop as the catalytic H307 residue in the cold-adapted esterase EstK from Pseudomonas mandelii. Mutation of D308 and/or Y309 to Ala or deletion resulted in increased conformational flexibility. Particularly, the D308A or Y309A mutant showed enhanced substrate affinity and catalytic rate, as compared with wild-type EstK, via enlargement of the active site. However, all mutant EstK enzymes exhibited reduced thermal stability. The effect of mutation was greater for D308 than Y309. These results indicate that D308 is not preferable for substrate selection and catalytic activity, whereas hydrogen bond formation involving D308 is critical for active site stabilization. Taken together, conformation of the EstK active site is constrained via flexibility-stability trade-off for enzyme catalysis and thermal stability. Our study provides further insights into active site stabilization of cold-adapted enzymes.


Global spatial distributions of nitrogen and carbon stable isotope ratios of modern human hair.
Natural stable carbon (δ(13)C) and nitrogen isotope ratios (δ(15)N) of humans are related to individual dietary habits and environmental and physiological factors. In forensic science the stable isotope ratios of human remains such as hair and nail are used for geographical allocation. Thus, knowledge of the global spatial distribution of human δ(13)C and δ(15)N values is an essential component in the interpretation of stable isotope analytical results. No substantial global datasets of human stable isotope ratios are currently available, although the amount of available (published) data has increased within recent years. We have herein summarised the published data on human global δ(13)C andδ(15)N values (around 3600 samples) and added experimental values of more than 400 additional worldwide human hair and nail samples. In order to summarise isotope ratios for hair and nail samples correction factors were determined. The current available dataset of human stable isotope ratios is biased towards Europe and North America with only limited data for countries in Africa, Central and South America and Southeast Asia. The global spatial distribution of carbon isotopes is related to latitude and supports the fact that human δ(13)C values are dominated by the amount of C4 plants in the diet, either due to direct ingestion as plant food, or by its use as animal feed. In contrast, the global spatial distribution of human δ(15)N values is apparently not exclusively related to the amount of fish or meat ingested, but also to environmental factors that influence agricultural production. There are still a large proportion of countries, especially in Africa, where there are no available data for human carbon and nitrogen isotope ratios. Although the interpretation of modern human carbon isotope ratios at the global scale is quite possible, and correlates with the latitude, the potential influences of extrinsic and/or intrinsic factors on human nitrogen isotope ratios have to be taken into consideration.