Can Gait Features Help in Differentiating Parkinson's Disease Medication States and Severity Levels? A Machine Learning Approach.
Parkinson's disease (PD) is one of the most prevalent neurological diseases, described by complex clinical phenotypes. The manifestations of PD include both motor and non-motor symptoms. We constituted an experimental protocol for the assessment of PD motor signs of lower extremities. Using a pair of sensor insoles, data were recorded from PD patients, Elderly and Adult groups. Assessment of PD patients has been performed by neurologists specialized in movement disorders using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-Part III: Motor Examination, on both ON and OFF medication states. Using as a reference point the quantified metrics of MDS-UPDRS-Part III, severity levels were explored by classifying normal, mild, moderate, and severe levels of PD. Elaborating the recorded gait data, 18 temporal and spatial characteristics have been extracted. Subsequently, feature selection techniques were applied to reveal the dominant features to be used for four classification tasks. Specifically, for identifying relations between the spatial and temporal gait features on: PD and non-PD groups; PD, Elderly and Adults groups; PD and ON/OFF medication states; MDS-UPDRS: Part III and PD severity levels. AdaBoost, Extra Trees, and Random Forest classifiers, were trained and tested. Results showed a recognition accuracy of 88%, 73% and 81% for, the PD and non-PD groups, PD-related medication states, and PD severity levels relevant to MDS-UPDRS: Part III ratings, respectively.


Revisiting the substrate specificity of mammalian α1,6-fucosyltransferase reveals that it catalyzes core fucosylation of N-glycans lacking α1,3-arm GlcNAc.
The mammalian α1,6-fucosyltransferase (FUT8) catalyzes the core fucosylation of N-glycans in the biosynthesis of glycoproteins. Previously, intensive in vitro studies with crude extract or purified enzyme concluded that the attachment of a GlcNAc on the α1,3 mannose arm of N-glycan is essential for FUT8-catalyzed core fucosylation. In contrast, we have recently shown that expression of erythropoietin in a GnTI knock-out, FUT8-overexpressing cell line results in the production of fully core-fucosylated glycoforms of the oligomannose substrate Man5GlcNAc2, suggesting that FUT8 can catalyze core fucosylation of N-glycans lacking an α1,3-arm GlcNAc in cells. Here, we revisited the substrate specificity of FUT8 by examining its in vitro activity toward an array of selected N-glycans, glycopeptides, and glycoproteins. Consistent with previous studies, we found that free N-glycans lacking an unmasked α1,3-arm GlcNAc moiety are not FUT8 substrates. However, Man5GlcNAc2 glycan could be efficiently core-fucosylated by FUT8 in an appropriate protein/peptide context, such as with the erythropoietin protein, a V3 polypeptide derived from HIV-1 gp120, or a simple 9-fluorenylmethyl chloroformate-protected Asn moiety. Interestingly, when placed in the V3 polypeptide context, a mature bi-antennary complex-type N-glycan also could be core-fucosylated by FUT8, albeit at much lower efficiency than the Man5GlcNAc2 peptide. This study represents the first report of in vitro FUT8-catalyzed core fucosylation of N-glycans lacking the α1,3-arm GlcNAc moiety. Our results suggest that an appropriate polypeptide context or other adequate structural elements in the acceptor substrate could facilitate the core fucosylation by FUT8.


[Study of rat pulmonary macrophages as affected by hydrocortisone administration and adrenalectomy].
The blood clearance rate of inert colloidal particles and the number of rat lung interstitial phagocytic cells decrease considerably on the 7th day after daily subcutaneous hydrocortisone acetate (HC) injection at a dose of 125 mg/kg. The number of cells in the bronchoalveolar lavage (BAL) increases more than 5-fold, and the absolute quantity of neutrophils is 66 times higher than in the control. Phagocytic and microbicidal activity of HC-treated animal alveolar macrophages (AM) decreases. Stimulation with zymosan led only to the recovery of the normal parameters of mononuclear phagocytosis system (MPC) and its pulmonary compartment activity. The parameters of MPS and AM studied increase on the 7th day after bilateral adrenalectomy (AE). The number of BAL cell increases 1.4-fold due to the animals' death immediately after intravenous zymosan injection because of total hemorrhage. The data obtained testify to the influence of glucocorticoids on the composition and activity of bronchoalveolar space cells, which in turn determine the resistance of the lung tissue.


Evaluation of Cobas Integra 800 under simulated routine conditions in six laboratories.
The new selective access analyser Cobas Integra 800 from Roche Diagnostics was evaluated in an international multicentre study at six sites. Routine simulation experiments showed good performance and full functionality of the instrument and provocation of anomalous situations generated no problems. The new features on Cobas Integra 800, namely clot detection and dispensing control, worked according to specifications. The imprecision of Cobas Integra 800 fulfilled the proposed quality specifications regarding imprecision of analytical systems for clinical chemistry with few exceptions. Claims for linearity, drift, and carry-over were all within the defined specifications, except urea linearity. Interference exists in some cases, as could be expected due to the chemistries applied. Accuracy met the proposed quality specifications, except in some special cases. Method comparisons with Cobas Integra 700 showed good agreement; comparisons with other analysis systems yielded in several cases explicable deviations. Practicability of Cobas Integra 800 met or exceeded the requirements for more than 95% of all attributes rated. The strong points of the new analysis system were reagent handling, long stability of calibration curves, high number of tests on board, compatibility of the sample carrier to other Roche systems, and the sample integrity check for more reliable analytical results. The improvement of the workflow offered by the 5-position rack and STAT handling like on Cobas Integra 800 makes the instrument attractive for further consolidation in the medium-sized laboratory, for dedicated use of special analytes, and/or as back-up in the large routine laboratory.


Circulating interferon in rabbits and monkeys after administration of human gamma interferon by different routes.
Rabbits and rhesus monkeys were injected with 3 X 10(5) units of human gamma interferon (IFN) prepared in human leukocyte suspensions. Circulating IFN was detected up to 4 h after intravenous administration. Intramuscular injection maintained a relatively stable serum IFN level of about 50 units/ml for 7 to 9 h. The results in both species were similar. Little or no circulating IFN was detected after subcutaneous injection of 3 X 10(5) units, but 1.5 X 10(6) units maintained about 50 units per ml of serum for 30 h. Pharmacokinetically, human gamma IFN resembled human alpha interferons rather than human beta IFN.


An x-ray diffraction study of ribosome structure.
Dense gels of E. coli 70 S ribosomes, their 50 S subunits, CM-like particles, RNP strands and their fragments, 38 S particles obtained from RNP strand folding upon addition of Mg2+ ions, and of unoriented salt-free and free rRNA sodium and magnesium salts were studied by X-ray diffraction. It was shown that under dense gel conditions RNA molecules contained in ribosomes unfolded by desalting, like all other particles considered here, have helical regions. Under these conditions free desalted RNA has no helical regions. Experimental data on X-ray scattering at medium angles were compared with the diffraction curves calculated for homogeneous prolate and oblate ellipsoids, for various ellipsoids containing a dense region or an internal cavity, and for ellipsoids containing internal periodic regions. The results indicate that the internal structure of the 50 S ribosome is periodic, i. e., its components form a periodic lattice. The lattice spacings are approximately 42 and 28 A with a 0.8g/g dry weight sample water content. When the 50 S particle water content drops below 0.2 g/g dry weight the periodic structure is disrupted. This disruption is reversible. It was shown that CM-like particles at high ionic strenght (2 M LiCl) have approximately the same internal periodicity as the 50 S particles, but in contrast they lose this periodicity at low ionic strength (10-2M tris-HCl and 5-10-3 M MgCl2).


Trial-to-trial variability of single cells in motor cortices is dynamically modified during visuomotor adaptation.
Neurons in all brain areas exhibit variability in their spiking activity. Although part of this variability can be considered as noise that is detrimental to information processing, recent findings indicate that variability can also be beneficial. In particular, it was suggested that variability in the motor system allows for exploration of possible motor states and therefore can facilitate learning and adaptation to new environments. Here, we provide evidence to support this idea by analyzing the variability of neurons in the primary motor cortex (M1) and in the supplementary motor area (SMA-proper) of monkeys adapting to new rotational visuomotor tasks. We found that trial-to-trial variability increased during learning and exhibited four main characteristics: (1) modulation occurred preferentially during a delay period when the target of movement was already known, but before movement onset; (2) variability returned to its initial levels toward the end of learning; (3) the increase in variability was more apparent in cells with preferred movement directions close to those experienced during learning; and (4) the increase in variability emerged at early phases of learning in the SMA, whereas in M1 behavior reached plateau levels of performance. These results are highly consistent with previous findings that showed similar trends in variability across a population of neurons. Together, the results strengthen the idea that single-cell variability can be much more than mere noise and may be an integral part of the underlying mechanism of sensorimotor learning.


Characteristics of Official Wheelchair Basketball Games in Hot and Temperate Conditions.
This study compared performance parameters of two wheelchair basketball games under hot (30.3 °C, 52% relative humidity) and temperate (21.6 °C, 30% relative humidity) environmental conditions and described the characteristics of wheelchair basketball. Eight wheelchair basketball players from two teams were monitored during two games using an indoor position tracking system. Total distance, mean- and peak-speed, playing-time, number of sprints, sprints per minute, heart rate and rate of perceived exertion were recorded. Additionally, athletes with a lesion level above and below T6 were compared. No measured parameter differed between the games. Across quarters (Q) mean velocity (m/s) (Q1: 1.01; Q2: 1.10; Q3: 1.18; Q4: 1.06; p < 0.001) and sprints per minute (Q1: 16; Q2: 14; Q3: 23; Q4: 14; p = 0.033) differed significantly, independent of the conditions. Descriptive statistics did not reveal differences between the groups with a lesion level below or above T6. In the present study, hot environmental conditions seemed not to have an impact on activity parameters of wheelchair basketball players. It was speculated that the game intensity and therefore metabolic heat production was too low; consequently, the athletes had a sufficient heat loss to prevent a decrease in performance during the play in hot conditions.


Enrichment of prostate cancer cells from blood cells with a hybrid dielectrophoresis and immunocapture microfluidic system.
The isolation of circulating tumor cells (CTCs) from cancer patient blood is a technical challenge that is often addressed by microfluidic approaches. Two of the most prominent techniques for rare cancer cell separation, immunocapture and dielectrophoresis (DEP), are currently limited by a performance tradeoff between high efficiency and high purity. The development of a platform capable of these two performance criteria can potentially be facilitated by incorporating both DEP and immunocapture. We present a hybrid DEP-immunocapture system to characterize how DEP controls the shear-dependent capture of a prostate cancer cell line, LNCaP, and the nonspecific adhesion of peripheral blood mononuclear cells (PBMCs). Characterization of cell adhesion with and without DEP effects was performed in a Hele-Shaw flow cell that was functionalized with the prostate-specific monoclonal antibody, J591. In this model system designed to make nonspecific PBMC adhesion readily apparent, we demonstrate LNCaP enrichment from PBMCs by precisely tuning the applied AC electric field frequency to enhance immunocapture of LNCaPs and reduce nonspecific adhesion of PBMCs with positive and negative DEP, respectively. Our work shows that DEP and immunocapture techniques can work synergistically to improve cancer cell capture performance, and it informs the design of future hybrid DEP-immunocapture systems with improved CTC capture performance to facilitate research on cancer metastasis and drug therapies.


Amino-terminal region of the human immunodeficiency virus type 1 nucleocapsid is required for human APOBEC3G packaging.
APOBEC3G exerts its antiviral activity by targeting to retroviral particles and inducing viral DNA hypermutations in the absence of Vif. However, the mechanism by which APOBEC3G is packaged into virions remains unclear. We now report that viral genomic RNA enhances but is not essential for human APOBEC3G packaging into human immunodeficiency virus type 1 (HIV-1) virions. Packaging of APOBEC3G was also detected in HIV-1 Gag virus-like particles (VLP) that lacked all the viral genomic RNA packaging signals. Human APOBEC3G could be packaged efficiently into a divergent subtype HIV-1, as well as simian immunodeficiency virus, strain mac, and murine leukemia virus Gag VLP. Cosedimentation of human APOBEC3G and intracellular Gag complexes was detected by equilibrium density and velocity sucrose gradient analysis. Interaction between human APOBEC3G and HIV-1 Gag was also detected by coimmunoprecipitation experiments. This interaction did not require p6, p1, or the C-terminal region of NCp7. However, the N-terminal region, especially the first 11 amino acids, of HIV-1 NCp7 was critical for HIV-1 Gag and APOBEC3G interaction and virion packaging. The linker region flanked by the two active sites of human APOBEC3G was also important for efficient packaging into HIV-1 Gag VLP. Association of human APOBEC3G with RNA-containing intracellular complexes was observed. These results suggest that the N-terminal region of HIV-1 NC, which is critical for binding to RNA and mediating Gag-Gag oligomerization, plays an important role in APOBEC3G binding and virion packaging.


Cell-wall lipopolysaccharide of Escherichia coli 0114:H2. Structure of the polysaccharide chain.
The O-specific polysaccharide of the 0114 antigen (lipopolysaccharide) of Escherichia coli 0114 and oligosaccharides obtained from it by Smith degradation and hydrogen fluoride solvolysis were analyzed, using proton and 13C nuclear magnetic resonance spectroscopy and methylation. The results indicated that the 0114 polysaccharide has the tetrasaccharide repeating unit alpha-N-acetylglucosamine(1 leads to 4) beta-3,6-dideoxy-3-(N-acetyl-L-seryl)aminoglucose(1 leads to 3) beta-ribofuranose(1 leads to 4)galactose. In the polysaccharide the repeating units are joined through beta 1 leads to 3-galactosyl linkages. This structure is compared with that of the serologically cross-reacting Shigella boydii 08 antigen and the serological similarity is discussed.


Diagram-based Analysis of Causal Systems (DACS): elucidating inter-relationships between determinants of acute lower respiratory infections among children in sub-Saharan Africa.
Effective interventions require evidence on how individual causal pathways jointly determine disease. Based on the concept of systems epidemiology, this paper develops Diagram-based Analysis of Causal Systems (DACS) as an approach to analyze complex systems, and applies it by examining the contributions of proximal and distal determinants of childhood acute lower respiratory infections (ALRI) in sub-Saharan Africa. Diagram-based Analysis of Causal Systems combines the use of causal diagrams with multiple routinely available data sources, using a variety of statistical techniques. In a step-by-step process, the causal diagram evolves from conceptual based on a priori knowledge and assumptions, through operational informed by data availability which then undergoes empirical testing, to integrated which synthesizes information from multiple datasets. In our application, we apply different regression techniques to Demographic and Health Survey (DHS) datasets for Benin, Ethiopia, Kenya and Namibia and a pooled World Health Survey (WHS) dataset for sixteen African countries. Explicit strategies are employed to make decisions transparent about the inclusion/omission of arrows, the sign and strength of the relationships and homogeneity/heterogeneity across settings.Findings about the current state of evidence on the complex web of socio-economic, environmental, behavioral and healthcare factors influencing childhood ALRI, based on DHS and WHS data, are summarized in an integrated causal diagram. Notably, solid fuel use is structured by socio-economic factors and increases the risk of childhood ALRI mortality. Diagram-based Analysis of Causal Systems is a means of organizing the current state of knowledge about a specific area of research, and a framework for integrating statistical analyses across a whole system. This partly a priori approach is explicit about causal assumptions guiding the analysis and about researcher judgment, and wrong assumptions can be reversed following empirical testing. This approach is well-suited to dealing with complex systems, in particular where data are scarce.


Visual event-related potentials index focused attention within bilateral stimulus arrays. II. Functional dissociation of P1 and N1 components.
Event-related potentials (ERPs) were recorded from 12 subjects as they attended to the left or right hemifield of a visual display while fixating a central point. Stimuli were presented to the left or right visual fields on separate trials (unilateral stimuli) or to both fields simultaneously (bilateral stimuli). In different conditions, the stimulus sequences contained only bilateral stimuli, only unilateral stimuli, or a mixture of unilateral and bilateral stimuli. Bilateral stimuli elicited an enhanced positivity lasting from about 75 to 250 msec that was largest at posterior electrode sites contralateral to the attended hemifield. The early phase of this attention-related positivity appeared to be an enhancement of the exogenous P1 component. In contrast, both the posterior P1 and N1 components were enhanced in response to attended unilateral stimuli. Moreover, the N1 attention effect was reduced when the preceding stimulus contained elements in the attended field. It was concluded that modulations of the N1 and P1 components in these experiments represent different aspects of visual spatial attention: N1 may represent the orienting of attention to a task-relevant stimulus, whereas P1 may represent a facilitation of early sensory processing for items presented to a location where attention is already focused.


[Severe multiorgan failure caused by aspiration with laryngeal mask airway].
We report a case of a 77-year-old woman who developed severe multiple organ failure after aspiration with the LMA during ureteral splinting. Two hours after induction of anaesthesia the urologists decided for nephrostomy in prone position. Therefore the patient was intubated. During removal of the LMA bilious secretion was recognized inside the LMA and in the pharynx. Endotracheal suction and immediate bronchoscopy showed severe aspiration. After the operation the patient was submitted to the ICU. She developed a severe multiple organ failure within 12 hours. Recovery took 54 days. The discussion is focussed on risk factors for the use of the LMA, adequate intraoperative monitoring, possible disadvantages of the applied anaesthetic technique and initial treatment after aspiration.


The use of low-molecular-weight heparin in acute coronary syndromes.
The initiating event in unstable angina (USA) and non-Q-wave myocardial infarction (NQMI) is the rupture of an atherosclerotic plaque resulting in local thrombosis. The current standard treatment is the administration of aspirin and heparin. The introduction of low-molecular-weight heparin (LMWH) offers a potential alternative therapy. Clinical trials have begun to examine the efficacy and safety of using LMWH in the management of acute coronary syndromes. Two pivotal studies have evaluated the effects of LMWH preparations on patients with USA or NQMI: The ESSENCE and the TIMI 11B trials. These studies suggest that LMWH plus aspirin is more effective and safer than unfractionated heparin in preventing myocardial infarction, recurrent angina, or death. Because of these differences, the American College of Cardiology and the American Heart Association have updated their guidelines for the treatment of USA and NQMI.


Metformin inhibits IgE- and aryl hydrocarbon receptor-mediated mast cell activation in vitro and in vivo.
Metformin, an anti-diabetic drug, possesses anti-inflammatory property beyond its glucose-lowering activity, but its regulatory effect on mast cells and allergic responses remains unknown, wherein the aryl hydrocarbon receptor (AhR)-ligand axis is critical in controlling mast cell activation. Herein, we provide evidence supporting the role of metformin in modulating mast cell activation by FcεR1-, AhR-mediated signaling or their combination. Metformin at relatively low doses was shown to suppress FcεR1-mediated degranulation, IL-13, TNF-α and sphingosine-1-phosphate (S1P) secretion in murine bone marrow-derived mast cells (BMMCs). In contrast, metformin at the same doses potently inhibited all parameters in mast cells stimulated with an AhR ligand, 5,11-dihydroindolo[3,2-b]carbazole-6-carbaldehyde (FICZ). Further, metformin was shown to inhibit FcεR1- and AhR-mediated passive cutaneous anaphylaxis (PCA) in vivo, reversible by a S1P receptor 2 antagonist, JTE-013. Using AhR reporter cells, Huh7-DRE-Luc cells, a human mast cell line, HMC-1, and BMMCs, metformin's inhibitory effect was mediated through the suppression of FICZ-induced AhR activity, calcium mobilization and ROS generation. Notably, FICZ-mediated oxidation of S1P lyase (S1PL) and its reduced activity were reversed by metformin, resulting in decreased levels of S1P. Collectively, these results suggested the potential utility of metformin in treating allergic diseases, particularly in cases with comorbid type II diabetes mellitus.


Development of formulations of biological agents for management of root rot of lettuce and cucumber.
The effect of various carrier formulations of Bacillus subtilis and Pseudomonas putida were tested on germination, growth, and yield of lettuce and cucumber crops in the presence of Pythium aphanidermatum and Fusarium oxysporum f.sp. cucurbitacearum, respectively. Survival of B. subtilis and P. putida in various carriers under refrigeration (about 0 degree C) and at room temperature (about 22 degrees C) was also studied. In all carrier formulations, B. subtilis strain BACT-0 survived up to 45 days. After 45 days of storage at room temperature (about 22 degrees C), populations B. subtilis strain BACT-0 were significantly higher in vermiculite, kaolin, and bacterial broth carriers compared with other carriers. Populations of P. putida were significantly higher in vermiculite, peat moss, wheat bran, and bacterial broth than in other carriers when stored either under refrigeration (about 0 degree C) or at room temperature (about 22 degrees C) for 15 or 45 days. Germination of lettuce seed was not affected in vermiculite, talc, kaolin, and peat moss carriers, but germination was significantly reduced in alginate and bacterial broth carriers of B. subtilis compared to the non-treated control. Germination of cucumber seed was not affected by any of the carriers. Significantly higher fresh lettuce and root weights were observed in vermiculite and kaolin carriers of B. subtilis compared with P. aphanidermatum-inoculated control plants. Lettuce treated with vermiculite, and kaolin carriers of B. subtilis, or non-inoculated control lettuce plants had significantly lower root rot ratings than talc, peat moss, bacterial broth, and P. aphanidermatum-inoculated control plants. Growth and yield of cucumber plants were significantly higher in vermiculite-based carrier of P. putida than the other carriers and Fusarium oxysporum f.sp. cucurbitacearum-inoculated plants.


Introducing a Real-Time Method for Identifying the Predictors of Noncompliance with Event-Based Reporting of Tobacco Use in Ecological Momentary Assessment.
Little is known about the factors that bias event-based (i.e., self-initiated) reporting of health behaviors in ecological momentary assessment (EMA) due to the difficulty inherent to tracking failures to self-initiate reports. To introduce a real-time method for identifying the predictors of noncompliance with event-based reporting. N = 410 adults who used both cigarettes and e-cigarettes completed a 1-week EMA protocol that combined random reporting of current contexts with event-based reporting of tobacco use. Each random assessment first asked if participants were currently using tobacco and, if so, the assessment converted into a "randomly captured" event report-indicating failure to self-initiate that report. Multilevel modeling tested predictors of failing to complete random reports and failing to self-initiate event reports. On the person level, male sex, higher average cigarette rate, and higher average cigarette urge each predicted missing random reports. The person-level predictors of failing to self-initiate event reports were older age, higher average cigarette and e-cigarette rates, higher average cigarette urge, and being alone more on average; the moment-level predictors were lower cigarette urge, lower positive affect, alcohol use, and cannabis use. Strikingly, the randomly captured events comprised more of the total EMA reports (28%) than did the self-initiated event reports (24%). These report types were similar across most variables, with some exceptions, such as momentary cannabis use predicting the random capture of tobacco events. This study demonstrated a method of identifying predictors of noncompliance with event-based reporting of tobacco use and enhancing the real-time capture of events.


Differential roles of STIM1, STIM2 and Orai1 in the control of cell proliferation and SOCE amplitude in HEK293 cells.
Orai1, together with STIM1 and STIM2, constitutes the molecular basis for store-operated calcium entry (SOCE) and we have investigated their role in cell proliferation and cell cycle progression in HEK293 cells. 48-h serum deprival, and a 24-h treatment with 1 mM hydroxyurea or with 10 microM RO-3306--a cyclin-dependent kinase 1 inhibitor--induced cell cycle block in G1, S and G2/M, respectively. SOCE amplitude, monitored in whole-cell voltage clamped cells, was markedly reduced (60-70%) in all conditions, with full reversibility within 4h. Silencing of Orai and STIM1 using siRNA resulted in a large inhibition of SOCE (70-80%) whereas siSTIM2 had a smaller but significant effect (30%). However, the cell population doubling time was not affected in siSTIM1 cells (18 h, the same as in control cells) but was increased in both siOrai1 cells (29 h) and in siSTIM2 (23 h) even when combined with siSTIM1. This suggests that STIM1 plays no role in cell proliferation in HEK293 cells while STIM2 is involved in both SOCE and cell proliferation in these cells. Finally, the cell cycle block induced SOCE inhibition was associated with reduced Orai1 expression with full recovery within 4h, whereas the expression of STIM1 and STIM2 remained unaltered. These observations reveal a tight relation between cell proliferation, calcium entry and Orai1 expression in HEK293 cells.


Hesperidin Alleviates Methotrexate-Induced Memory Deficits via Hippocampal Neurogenesis in Adult Rats.
Methotrexate (MTX), a folic acid antagonist, is widely used in cancer treatment. However, treatment with MTX reduces hippocampal neurogenesis, leading to memory deficits. Hesperidin (Hsd) is a flavonoid glycoside that promotes anti-inflammation, acts as an antioxidant, and has neuroprotective properties. Consumption of Hsd enhances learning and memory. In the present study, we investigated the protective effects of Hsd against MTX-induced impairments of memory and neurogenesis; male Sprague Dawley rats were administered with a single dose of MTX (75 mg/kg) by intravenous (i.v.) injection on days 8 and 15 or Hsd (100 mg/kg) by oral gavage for 21 days. Memory was tested using novel object location (NOL) and novel object recognition (NOR) tasks. Immunofluorescence staining of Ki-67, bromodeoxyuridine (BrdU), and doublecortin (DCX) was performed to assess cell proliferation, survival, and immature neurons. The data showed that Hsd and MTX did not disable locomotor ability. The MTX animals exhibited memory deficits in both memory tests. There were significant decreases in the numbers of cell proliferation, survival, and immature neurons in the MTX animals. However, co-administration with MTX and Hsd alleviated memory loss and neurogenesis decline. These results revealed that Hsd could protect against MTX side effects in the animals in this study.


Female Athletes With Varying Levels of Vertical Stiffness Display Kinematic and Kinetic Differences During Single-Leg Hopping.
Vertical stiffness may contribute to lower-extremity injury risk; however, it is unknown whether athletes with different stiffness levels display differences in biomechanics. This study compared differences in biomechanics between female athletes (n = 99) with varying stiffness levels during a repetitive, single-leg, vertical hopping task. Vertical stiffness was calculated as the ratio of peak vertical ground-reaction force to maximum center-of-mass displacement. Tertiles were established using stiffness values, and separate 1-way ANOVAs were used to evaluate between-group differences. Stance times decreased, and flight times, ground-reaction force, and stiffness increased, from the low- to high-stiffness group (P < .050). The high-stiffness group displayed: (1) greater lateral trunk flexion (P = .009) and lesser hip adduction (P = .022) at initial ground contact compared to the low- and moderate-stiffness groups, respectively; (2) lesser peak hip adduction compared to the low-stiffness group (P = .040); (3) lesser lateral trunk-flexion (P = .046) and knee-flexion (P = .010) excursion compared to the moderate- and low-stiffness groups, respectively; and (4) greater peak hip-flexion (P = .001), ankle-dorsiflexion (P = .002), and ankle-eversion (P = .038) moments compared to the low-stiffness group. A wide range of variability in stiffness exists within a relatively homogenous population. Athletes with varying stiffness levels display biomechanical differences that may help identify the potential mechanism(s) by which stiffness contributes to injury risk.


Chiral polychlorinated biphenyl transport, metabolism, and distribution: a review.
Chirality can be exploited to gain insight into enantioselective fate processes that may otherwise remain undetected because only biological, but not physical and chemical transport and transformation processes in an achiral environment will change enantiomer compositions. This review provides an in-depth overview of the application of chirality to the study of chiral polychlorinated biphenyls (PCBs), an important group of legacy pollutants. Like other chiral compounds, individual PCB enantiomers may interact enantioselectively (or enantiospecifically) with chiral macromolecules, such as cytochrome P-450 enzymes or ryanodine receptors, leading to differences in their toxicological effects and the enantioselective formation of chiral biotransformation products. Species and congener-specific enantiomer enrichment has been demonstrated in environmental compartments, wildlife, and mammals, including humans, typically due to a complex combination of biotransformation processes and uptake via the diet by passive diffusion. Changes in the enantiomer composition of chiral PCBs in the environment have been used to understand complex aerobic and anaerobic microbial transformation pathways, to delineate and quantify PCB sources and transport in the environment, to gain insight into the biotransformation of PCBs in aquatic food webs, and to investigate the enantioselective disposition of PCBs and their methylsulfonyl PCBs metabolites in rodents. Overall, changes in chiral signatures are powerful, but currently underutilized tools for studies of environmental and biological processes of PCBs.


Integrated ecological and chemical food web accumulation modeling explains PAH temporal trends during regime shifts in a shallow lake.
Shallow lakes can switch suddenly from a turbid situation with high concentrations of phytoplankton and other suspended solids to a vegetated state with clear water, and vice versa. These alternative stable states may have a substantial impact on the fate of hydrophobic organic compounds (HOCs). Models that are fit to simulate impacts from these complex interactions are scarce. We developed a contaminant fate model which is linked to an ecosystem model (PCLake) for shallow lakes. This integrated model was successful in simulating long-term dynamics (1953-2012) of representative polycyclic aromatic hydrocarbons (PAHs) in the main biotic and abiotic components in a large shallow lake (Chaohu in China), which has undergone regime shifts in this period. Historical records from sediment cores were used to evaluate the model. The model revealed that regime shifts in shallow lakes had a strong impact on the fate of less hydrophobic compounds due to the large storage capacity of macrophytes, which accumulated up to 55.6% of phenanthrene in the clear state. The abrupt disappearance of macrophytes after the regime shift resulted in a sudden change in phenanthrene distribution, as the sediment became the major sink. For more hydrophobic compounds such as benzo(a)pyrene, the modeled impact of the regime shift was negligible for the whole environment, yet large for biotic compartments. This study is the first to provide a full mechanistic analysis of the impact of regime shifts on the fate of PAHs in a real lake ecosystem.


'I've used the word cancer but it's actually good news': discursive performativity of cancer and the identity of urological cancer services.
Drawing on the ethnographic study of urological cancer services, this article explores how a set of particular discourses embedded in the everyday clinical work in a large teaching hospital in the UK helps materialise particular configurations of cancer and related professional identities. Emerging on the intersection of specific socio-material arrangements (cancer survival rates, treatment regimens, cancer staging classifications, metaphors, clinical specialities) and operating across a number of differential relations (curable/incurable, treatable/untreatable, aggressive/nonaggressive), these configurations help constitute the categories of 'good' and 'bad' cancers as separate and contrasting entities. These categories help materialise particular distributions of power and are thus implicated in the making of specific claims about the identity of urological cancer services as unique and privileged. Exploring these issues in view of feminist and material-semiotic approaches to studying science, technology and medicine, this article seeks to move away from the understanding of cancer discourses as primarily linguistic performances, proposing to see them instead as arrangements of practices and relations simultaneously material and semiotic through which particular categories, entities and phenomena acquire their determinate nature. In doing so, it seeks to contribute to sociology's broader concern with discursive performativity of cancer.


Predicting concentrations of the cytostatic drugs cyclophosphamide, carboplatin, 5-fluorouracil, and capecitabine throughout the sewage effluents and surface waters of Europe.
The present study evaluated the potential environmental concentrations of 4 cytostatic (also known as cytotoxic) drugs in rivers. The antimetabolite 5-fluorouracil (5FU) and its pro-drug capecitabine were examined based on their very high use rates, cyclophosphamide (CP) for its persistence, and carboplatin for its association with the metal element platinum. The study combined drug consumption information across European countries, excretion, national water use, and sewage removal rates to derive sewage effluent values across the continent. Results showed considerable variation in the popularity of individual cytostatic drugs across Europe, including a 28-fold difference in 5FU use and 15-fold difference in CP use. Such variations could have a major effect on the detection of these compounds in effluent or river water. Overall, capecitabine and CP had higher predicted levels in effluent than 5FU or carboplatin. Predicted effluent values were compared with measurements in the literature, and many non-detects could be explained by insufficient limits of detection. Linking the geographic based water resources model GWAVA with this information allowed water concentrations throughout 1.2 million km of European rivers to be predicted. The 90th percentile (worst case) prediction indicated that, with the exception of capecitabine, more than 99% of Europe's rivers (by length) would have concentrations below 1 ng/L for these cytostatic drugs. For capecitabine, 2.2% of river length could exceed 1 ng/L.


Benthic meiofaunal community response to the cascading effects of herbivory within an algal halo system of the Great Barrier Reef.
Benthic fauna play a crucial role in organic matter decomposition and nutrient cycling at the sediment-water boundary in aquatic ecosystems. In terrestrial systems, grazing herbivores have been shown to influence below-ground communities through alterations to plant distribution and composition, however whether similar cascading effects occur in aquatic systems is unknown. Here, we assess the relationship between benthic invertebrates and above-ground fish grazing across the 'grazing halos' of Heron Island lagoon, Australia. Grazing halos, which occur around patch reefs globally, are caused by removal of seagrass or benthic macroalgae by herbivorous fish that results in distinct bands of unvegetated sediments surrounding patch reefs. We found that benthic algal canopy height significantly increased with distance from patch reef, and that algal canopy height was positively correlated with the abundances of only one invertebrate taxon (Nematoda). Both sediment carbon to nitrogen ratios (C:N) and mean sediment particle size (μm) demonstrated a positive correlation with Nematoda and Arthropoda (predominantly copepod) abundances, respectively. These positive correlations indicate that environmental conditions are a major contributor to benthic invertebrate community distribution, acting on benthic communities in conjunction with the cascading effects of above-ground algal grazing. These results suggest that benthic communities, and the ecosystem functions they perform in this system, may be less responsive to changes in above-ground herbivorous processes than those previously studied in terrestrial systems. Understanding how above-ground organisms, and processes, affect their benthic invertebrate counterparts can shed light on how changes in aquatic communities may affect ecosystem function in previously unknown ways.


[DNA arrays: technological aspects and applications].
The Human Genome Project has allowed considerable progress in the construction of physical and genetic maps and the identification of genes involved in human sicknesses. The accelerated accumulation of biological information and knowledge is due in large part to the sequencing projects of other organisms, which in fact paved the way for the Human Genome Project. In parallel, recently developed techniques which take advantage of genomic sequences allow large scale molecular analyses resulting in the functional annotation of many of the proteins represented by these genes. This is the goal of functional genomics. These progresses are at the origin of the present revolution in biomedical research. DNA microarrays are playing a dominant role compared to the other developing technologies since they are relatively easy to make and use and are applicable to numerous scientific inquiries. They allow the simultaneous analysis of several thousands of genes in biological samples from sick or healthy tissues, at the genome or transcriptome level. The data obtained is expected to result in major advances in the health sciences. In addition to an improved understanding of the complex molecular interaction networks of healthy cells and tissues, a more precise genetic characterization of the molecular mechanisms involved in pathology should result in the identification of new therapeutic targets and the development of new medicines. The genetic profiles thus obtained should also permit the definition of new pathologic subclasses not recognizable by traditional clinical factors, as well as new markers for susceptibility to certain illnesses, and new prognostic markers or methods of predicting responses to treatment. In this article, we present the different approaches and potential applications of DNA microarray technology, in particular as applied to cancer research.


How I treat cobalamin (vitamin B12) deficiency.
The challenges in medical management of cobalamin deficiency lie in attention to the unique pathophysiology that underlies cobalamin deficiency, more than in the mechanics of therapy. The central physiologic principles are that clinically important deficiency is more likely to occur (and progress) when intrinsic factor-driven absorption fails than when diet is poor and that most causes take years to produce clinically obvious deficiency. Transient defects have little clinical impact. The key management principle is the importance of follow-up, which also requires knowing how the deficiency arose. The virtues of these principles are not always fully appreciated. Recent developments have made diagnosis and management more difficult by diminishing the ability to determine cobalamin absorption status. Clinicians must also grapple with premature medicalization of isolated, mild biochemical changes that added many asymptomatic cases of still undetermined medical relevance to their caseload, often expanded by inflated cobalamin level criteria. The potential for misattribution of cobalamin-unrelated presentations to nongermane cobalamin and metabolite abnormalities has grown. Pathophysiologically based management requires systematic attention to each of its individual components: correctly diagnosing cobalamin deficiency, reversing it, defining its underlying cause, preventing relapse, managing the underlying disorder and its complications, and educating the patient.


[Intraoperative anaphylactic/anaphylactoid reaction to infusion of a modified liquid gelatin].
A clinical observation of an extremely rare but highly severe complication, i.e. anaphylatic/anaphylactoid reaction to the infusion of a synthetic colloid plasma-expander (Gelofusion) is described in the paper. Dropping arterial pressure concurrent with tachycardia and a negative dynamics of ST segment in ECGS were the main reaction signs. Besides, mechanisms of allergic reactions developing during the anesthesia implementation as well as the related measures of prevention and therapy are also elucidated.


Extended optical waveguide theory with magneto-optical effect and magnetoelectric effect.
Optical waveguide theory is essential to the development of various optical devices. Although there are reports on the theory of optical waveguides with magneto-optical (MO) and magnetoelectric (ME) effects, a comprehensive theoretical analysis of waveguides considering these two effects has not yet been published. In this study, the conventional waveguide theory is extended by considering constitutive relations that account for both MO and ME effects. Using the extended waveguide theory, the propagation properties are also analyzed in a medium where metamaterials and magnetic materials are arranged such that MO and ME effects can be controlled independently. It has been confirmed that the interaction between MO and ME effects occurs depending on the arrangement of certain metamaterials and the direction of magnetization. This suggests a nonreciprocal polarization control that rotates the polarization in only one direction when propagating in plane wave propagation and enhances the nonreciprocal nature of the propagating waves in waveguide propagation.


Life span effects of Hypericum perforatum extracts on Caenorhabditis elegans under heat stress.
The beneficial effects of antioxidants in plants are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary antioxidants are beneficial in whole animals' life span or not. To address this question, under heat stress (35°C), Hypericum perforatum was extracted with petroleum ether and the nematodes Caenorhabditis elegans exposed to three different extract concentrations (1mg/mL, 0.1mg/mL, 0.01mg/mL) of H. perforatum. We report that Hypericum perforatum extracts did not increase life span and slow aging related increase in C. elegans. Moreover, one fraction (1mg/mL) increased declines of C. elegans life span and thermotolerance. Given this mounting evidence for life span role of H. perforatum in the presence of heat stress in vivo, the question whether H. perforatum acts as a prooxidant or an antioxidant in vivo under heat stress arises.


Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1.
To examine the prevalence of mild cognitive impairment (MCI) and its diagnostic classification in the Cardiovascular Health Study (CHS) Cognition Study. The CHS Cognition Study is an ancillary study of the CHS that was conducted to determine the presence of MCI and dementia in the CHS cohort. Multicenter population study. We examined 3608 participants in the CHS who had undergone detailed neurological, neuropsychological, neuroradiological, and psychiatric testing to identify dementia and MCI. The prevalence of MCI was determined for the whole cohort, and specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa, center (n = 927). Mild cognitive impairment was classified as either MCI amnestic-type or MCI multiple cognitive deficits-type. The overall prevalence of MCI was 19% (465 of 2470 participants); prevalence increased with age from 19% in participants younger than 75 years to 29% in those older than 85 years. The overall prevalence of MCI at the Pittsburgh center was 22% (130 of 599 participants); prevalence of the MCI amnesic-type was 6% and of the MCI multiple cognitive deficits-type was 16%. Twenty-two percent of the participants aged 75 years or older had MCI. Mild cognitive impairment is a heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI multiple cognitive deficits-type. Most of the participants with MCI had comorbid conditions that may affect their cognitive functions.


Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants.
Candida albicans is a major life-threatening human fungal pathogen. Host defence against systemic Candida infection relies mainly on phagocytosis of fungal cells by cells of the innate immune system. In this study, we have employed video microscopy, coupled with sophisticated image analysis tools, to assess the contribution of distinct C. albicans cell wall components and yeast-hypha morphogenesis to specific stages of phagocytosis by macrophages. We show that macrophage migration towards C. albicans was dependent on the glycosylation status of the fungal cell wall, but not cell viability or morphogenic switching from yeast to hyphal forms. This was not a consequence of differences in maximal macrophage track velocity, but stems from a greater percentage of macrophages pursuing glycosylation deficient C. albicans during the first hour of the phagocytosis assay. The rate of engulfment of C. albicans attached to the macrophage surface was significantly delayed for glycosylation and yeast-locked morphogenetic mutant strains, but enhanced for non-viable cells. Hyphal cells were engulfed at a slower rate than yeast cells, especially those with hyphae in excess of 20 µm, but there was no correlation between hyphal length and the rate of engulfment below this threshold. We show that spatial orientation of the hypha and whether hyphal C. albicans attached to the macrophage via the yeast or hyphal end were also important determinants of the rate of engulfment. Breaking down the overall phagocytic process into its individual components revealed novel insights into what determines the speed and effectiveness of C. albicans phagocytosis by macrophages.


Lipid-lowering agents and their meaning in the treatment of the fat metabolism-atherosclerosis functional circle.
The clinical pharmacology of lipid-lowering agents and their meaning in the treatment of the fat metabolism-atherosclerosis functional circle are described. All the aspects associated with these important problems are carefully analyzed and the possible consequences for their rational use are interpreted. The current view of the actual situation in this field is presented and the trends in the development of prophylactic and therapeutic treatment with lipid-lowering agents in the fat metabolism-atherosclerosis functional circle are shown. Epidemiologic considerations complement these reflections.


Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin.
Heterochromatin regulation is critical for genomic stability. Different H3K9 methylation states have been discovered, with distinct roles in heterochromatin formation and silencing. However, how the transition from H3K9me2 to H3K9me3 is controlled is still unclear. Here, we investigate the role of the conserved bromodomain AAA-ATPase, Abo1, involved in maintaining global nucleosome organisation in fission yeast. We identified several key factors involved in heterochromatin silencing that interact genetically with Abo1: histone deacetylase Clr3, H3K9 methyltransferase Clr4, and HP1 homolog Swi6. Cells lacking Abo1 cultivated at 30 °C exhibit an imbalance of H3K9me2 and H3K9me3 in heterochromatin. In abo1∆ cells, the centromeric constitutive heterochromatin has increased H3K9me2 but decreased H3K9me3 levels compared to wild-type. In contrast, facultative heterochromatin regions exhibit reduced H3K9me2 and H3K9me3 levels in abo1∆. Genome-wide analysis showed that abo1∆ cells have silencing defects in both the centromeres and subtelomeres, but not in a subset of heterochromatin islands in our condition. Thus, our work uncovers a role of Abo1 in stabilising directly or indirectly Clr4 recruitment to allow the H3K9me2 to H3K9me3 transition in heterochromatin.


Effect of finasteride on serum androstenedione and risk of prostate cancer within the prostate cancer prevention trial: differential effect on high- and low-grade disease.
To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial. We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme. We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score <7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and the risk of high-grade disease. The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT) and of androstenedione to 5α-androstanedione-3,17-dione, which also leads to the reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression.


Low Alanine Aminotransferase Cut-Off for Predicting Liver Outcomes; A Nationwide Population-Based Longitudinal Cohort Study.
Recent practice guidelines suggest healthy normal alanine aminotransferase (ALT) levels should be less than 30 U/L for males and 19 U/L for females. We tried to validate the prediction power of the "low cut off" for liver related outcomes in the general population. A total of 426,013 subjects were followed up for 10 years using the National Health Screening Cohort database. Prediction ability of long term mortality and liver related outcomes between conventional (<40 U/L in men and women) and low (<30 U/L in men and <19 U/L in women) ALT cut-off values were compared. Both conventional and low ALT cut-offs predicted liver related unfavorable outcomes in Kaplan-Meier analysis. Following adjustment for age, body mass index, smoking, exercise, alcohol consumption, fasting blood glucose, and cholesterol via multivariate Cox regression, abnormal ALT using new 'low ALT cut off' was a significant independent predictor for liver-related mortality, HCC, and decompensated liver events. When the low cut-off criteria were added to the prediction model, the ability to predetect liver-related hard outcomes significantly increased in both men and women (p-values < 0.0001). The C-index values for predicting liver-related adverse events were the same in both ALT cut-offs, after adjusting confounding factors (C index value: 0.73~0.88). New low ALT cut-off showed good prediction power for liver related unfavorable outcomes.


[Significance of birds in the dissemination of Trichinella spp. larvae in coastal and aquatic biocenoses].
The real possibilities of mechanical transmission of trichinae through avian feces to terrestrial and aquatic mammals with the participation of a number of invertebrates (ostraceans, crustaceans, and dipteran larvae) and fishes were studied. Laboratory models have proven that the mammals can be biologically infected with trichinosis from the above species of vertebrates and invertebrates, the mechanical vectors of this infestation.


Planning comparison between standard and conformal 3D techniques in post-operative radiotherapy of gastric cancer: a systematic review.
The objective of this study was to establish the impact of three-dimensional conformal radiotherapy (3D-CRT) technique in post-operative radiotherapy of gastric cancer. A bibliographical research was performed using the PubMed. On the database, Search was carried out using Medical Subject Heading (MeSH) database; the algorithm for search was ''Radiotherapy" (MeSH) AND ''Stomach Neoplasms" (MeSH). Only planning comparative studies on conformal techniques vs standard techniques in post-operative radiotherapy of gastric cancer were included in the review process. We identified 185 papers, five of them fulfilling the inclusion criteria. A great inhomogeneity was observed regarding the analysed dosimetric end points. Three of the five studies reported a benefit in favour of 3D-CRT for target irradiation despite a minimal advantage in most cases. The liver was better spared from irradiation by the traditional technique in all studies. No univocal result was obtained for the right kidney: the traditional technique performed better in two studies, 3D-CRT yielded better results in two others, whereas in the fifth study, each technique was either better or worse according to the different considered end point. 3D-CRT, however, allowed for better sparing of the left kidney in four studies. There is no absolute reason to prefer 3D-CRT with multiple beams in every patient. It may be preferable to choose the technique based on individual patient characteristics. Because there is no proof of superiority for 3D-CRT, there is no absolute reason to exclude patients who are treated in centres equipped with only the two-dimensional technique from the potential benefit of post-operative chemoradiation.


Photochemical studies on bis-sulfide and -sulfone tethered polyenic derivatives.
This study focusses on the [2 + 2]-photocycloaddition of a symmetric polyenic system tethered by an aryl bis-sulfide or sulfone platform. Using direct irradiation or photosensitization, no expected ladderane product was isolated. In most cases, only tricyclic products including a single cyclobutane moiety were formed. Irradiation of bis-acrylic precursors in water with encapsulation by a host (cyclodextrin or cucurbituril) provided a stereoselective access to valuable cyclobutyl adducts.


Split luciferase-based biosensors for characterizing EED binders.
The EED (embryonic ectoderm development) subunit of the Polycomb repressive complex 2 (PRC2) plays an important role in the feed forward regulation of the PRC2 enzymatic activity. We recently identified a new class of allosteric PRC2 inhibitors that bind to the H3K27me3 pocket of EED. Multiple assays were developed and used to identify and characterize this type of PRC2 inhibitors. One of them is a genetically encoded EED biosensor based on the EED[G255D] mutant and the split firefly luciferase. This EED biosensor can detect the compound binding in the transfected cells and in the in vitro biochemical assays. Compared to other commonly used cellular assays, the EED biosensor assay has the advantage of shorter compound incubation with cells. The in vitro EED biosensor is much more sensitive than other label-free biophysical assays (e.g. DSF, ITC). Based on the crystal structure, the DSF data as well as the biosensor assay data, it's most likely that compound-induced increase in the luciferase activity of the EED[G255D] biosensor results from the decreased non-productive interactions between the EED subdomain and other subdomains within the biosensor construct. This new insight of the mechanism might help to broaden the use of the split luciferase based biosensors.


Molecular imaging of pancreatic cancer in an animal model using targeted multifunctional nanoparticles.
Identification of a ligand/receptor system that enables functionalized nanoparticles to efficiently target pancreatic cancer holds great promise for the development of novel approaches for the detection and treatment of pancreatic cancer. Urokinase plasminogen activator receptor (uPAR), a cellular receptor that is highly expressed in pancreatic cancer and tumor stromal cells, is an excellent surface molecule for receptor-targeted imaging of pancreatic cancer using multifunctional nanoparticles. The uPAR-targeted dual-modality molecular imaging nanoparticle probe is designed and prepared by conjugating a near-infrared dye-labeled amino-terminal fragment of the receptor binding domain of urokinase plasminogen activator to the surface of functionalized magnetic iron oxide nanoparticles. We have shown that the systemic delivery of uPAR-targeted nanoparticles leads to their selective accumulation within tumors of orthotopically xenografted human pancreatic cancer in nude mice. The uPAR-targeted nanoparticle probe binds to and is subsequently internalized by uPAR-expressing tumor cells and tumor-associated stromal cells, which facilitates the intratumoral distribution of the nanoparticles and increases the amount and retention of the nanoparticles in a tumor mass. Imaging properties of the nanoparticles enable in vivo optical and magnetic resonance imaging of uPAR-elevated pancreatic cancer lesions. Targeting uPAR using biodegradable multifunctional nanoparticles allows for the selective delivery of the nanoparticles into primary and metastatic pancreatic cancer lesions. This novel receptor-targeted nanoparticle is a potential molecular imaging agent for the detection of pancreatic cancer.


Effects of scald injury on hepatic PO2, blood flow, and ultrastructure in the rat.
Stagnant hypoxia has been suggested as a significant factor underlying acute liver disease following thermal injury. To examine this possibility in circumstances of moderate scald injury, rats were dipped (15% body surface area) in 90-95 degrees C water for 25 sec, fluid resuscitated, and studied at 1, 6, and 24 h. Hepatic PO2, obtained by multicathode surface measurement, was reduced significantly at 1 h (10.8 vs. 20.8 mm Hg in controls), although clearance times for low dose indocyanine green (ICG) suggested normal liver blood flow. The reduction of PO2 was transient; at 6 h levels were only slightly lower than in controls. At 24 h, however, liver PO2 was again reduced significantly, albeit less deeply (14.9 mm Hg). Increased clearance times for low and high dose ICG at 24 h suggested impairment of both blood flow and hepatocyte function. Hepatic ultrastructure showed foci of cells with anomalous and degenerate mitochondria, atypical of those associated with hypoxia. Sinusoids were often occluded by aggregates of vesicles of hepatocyte origin. It is not clear that acute restriction of oxygen availability during the first hour postburn was of sufficient intensity to cause the liver pathology evident at 24 h.


[Local government and public dental health services: an analysis of inequality in use].
The aim of this study was to identify factors associated with the use of primary and specialized public dental health services and private services. A population-based household survey was conducted in two cities of Bahia State, Brazil. Key informants provided data on socioeconomic variables and use of dental health services. Organization of the local public dental health service was ranked as worse versus better. Univariate and multivariate polytomous logistic regression was performed. Of the total of 1,290 individuals, 38.76% used private services, 33.80% used public primary care, and 17.29% used both primary care and the Center for Dental Specialties. Less use of both primary care and specialized public services was associated with lower education (OR = 1.47; 95%CI: 1.03-2.10) and worse organization of services (OR = 1.74; 95%CI: 1.22-2.48), when compared to the exclusive use of primary care. The study showed inequality in the use of dental services, even when comparing more homogeneous groups, namely users of public services.


The diversification of Heliconius butterflies: what have we learned in 150 years?
Research into Heliconius butterflies has made a significant contribution to evolutionary biology. Here, we review our understanding of the diversification of these butterflies, covering recent advances and a vast foundation of earlier work. Whereas no single group of organisms can be sufficient for understanding life's diversity, after years of intensive study, research into Heliconius has addressed a wide variety of evolutionary questions. We first discuss evidence for widespread gene flow between Heliconius species and what this reveals about the nature of species. We then address the evolution and diversity of warning patterns, both as the target of selection and with respect to their underlying genetic basis. The identification of major genes involved in mimetic shifts, and homology at these loci between distantly related taxa, has revealed a surprising predictability in the genetic basis of evolution. In the final sections, we consider the evolution of warning patterns, and Heliconius diversity more generally, within a broader context of ecological and sexual selection. We consider how different traits and modes of selection can interact and influence the evolution of reproductive isolation.


Readmission With Major Abdominal Complications After Penetrating Abdominal Trauma.
Despite improvements in operative techniques, major abdominal complications (MACs) continue to occur after penetrating abdominal trauma (PAT). This study aimed to evaluate the burden of MAC after PAT. The (2012-2015) National Readmission Database was queried for all adult (age ≥18 y) trauma patients with penetrating injuries who underwent exploratory laparotomy and were readmitted within 6 mo of index hospitalization discharge. Patients were stratified by firearm injuries (FIs) and stab injuries (SIs). Primary outcomes were rates of MAC: intra-abdominal abscesses (IAAs), superficial surgical site infection (SSI), and fascial dehiscence within 6 mo after discharge. Secondary outcomes were both nonabdominal complications and mortality, postdischarge, and 6-mo readmission. Regression analysis was performed. A total of 4473 patients (FI, 2326; SI, 2147) were included in the study; the mean age was 32 ± 14 y, the Injury Severity Score was 19 (15-25), and 23% underwent damage control laparotomy (DCL). The rate of MAC within 6 mo was 22% (IAA 19%, SSI 7%, and fascial dehiscence 4%). Patients with FIs had a higher rate of IAA (27% versus 10%; P < 0.01), SSI (11% versus 3%; P < 0.01), fascial dehiscence (5% versus 3%; P = 0.03), nonabdominal complications (54% versus 24%; P < 0.01), and postdischarge mortality (8% versus 6%; P < 0.01) compared with patients with SIs . On regression analysis, DCL (P < 0.01), large bowel perforation (P < 0.01), biliary-pancreatic injury (P < 0.01), hepatic injury (P < 0.01), and blood transfusion (P = 0.02) were predictors of MAC. MAC developed in one in five patients after PAT. FIs have a higher potential for hollow viscus injury and peritoneal contamination, and are more predictive of MAC and nonabdominal complications, especially after DCL. Level III Prognostic.


Is diacerein an alternative for the treatment of osteoarthritis?
Among the possibilities for the management of osteoarthritis, different pharmacological alternatives have been proposed, being diacerein one of them due to its anti-inflammatory effect. However, diacerein clinical utility is not clear. To answer this question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded diacerein may lead to a slight reduction in pain and probably not improve functionality among patients with knee osteoarthritis and can frequently present diarrhea as an adverse effect. [corrected].


Expression study of cadherin7 and cadherin20 in the embryonic and adult rat central nervous system.
Vertebrate classic cadherins are divided into type I and type II subtypes, which are individually expressed in brain subdivisions (e.g., prosomeres, rhombomeres, and progenitor domains) and in specific neuronal circuits in region-specific manners. We reported previously the expression of cadherin19 (cad19) in Schwann cell precursors. Cad19 is a type II classic cadherin closely clustered on a chromosome with cad7 and cad20. The expression patterns of cad7 and cad20 have been reported previously in chick embryo but not in the developing and adult central nervous system of mammals. In this study, we identified rat cad7 and cad20 and analyzed their expression patterns in embryonic and adult rat brains. Rat cad7 protein showed 92% similarity to chick cad7, while rat cad20 protein had 76% similarity to Xenopus F-cadherin. Rat cad7 mRNA was initially expressed in the anterior neural plate including presumptive forebrain and midbrain regions, and then accumulated in cells of the dorsal neural tube and in rhombomere boundary cells of the hindbrain. Expression of rat cad20 mRNA was specifically localized in the anterior neural region and rhombomere 2 in the early neural plate, and later in longitudinally defined ventral cells of the hindbrain. The expression boundaries of cad7 and cad20 corresponded to those of region-specific transcription factors such as Six3, Irx3 and Otx2 in the neural plate, and Dbx2 and Gsh1 in the hindbrain. At later stages, the expression of cad7 and cad20 disappeared from neuroepithelial cells in the hindbrain, and was almost restricted to postmitotic cells, e.g. somatic motor neurons and precerebellar neurons. These results emphasized the diversity of cad7 and cad20 expression patterns in different vertebrate species, i.e. birds and rodents. Taken together, our findings suggest that the expression of cad7 and cad20 demarcates the compartments, boundaries, progenitor domains, specific nuclei and specific neural circuits during mammalian brain development.


A Review of Key Properties of Thermoelectric Composites of Polymers and Inorganic Materials.
This review focusses on the development of thermoelectric composites made of oxide or conventional inorganic materials, and polymers, with specific emphasis on those containing oxides. Discussion of the current state-of-the-art thermoelectric materials, including the individual constituent materials, i.e., conventional materials, oxides and polymers, is firstly presented to provide the reader with a comparison of the top-performing thermoelectric materials. Then, individual materials used in the inorganic/polymer composites are discussed to provide a comparison of the performance of the composites themselves. Finally, the addition of carbon-based compounds is discussed as a route to improving the thermoelectric performance. For each topic discussed, key thermoelectric properties are tabulated and comparative figures are presented for a wide array of materials.


Solution conformation of nociceptin.
Nociceptin, a novel heptadecapeptide, interacts with ORL1 a G protein-coupled receptor whose sequence is closely related to that of the kappa opioid receptor but has no opioid activity. We have investigated the conformational preferences of Nociceptin also in comparison to Dynorphin A. The N-terminal part of Nociceptin has the same conformational preferences of the message of endogenous opioids but the C-terminal part of the sequence is more flexible than the corresponding address of Dynorphin A. [Tyr1]-Nociceptin, while retaining nociceptive activity, has also an opioid activity comparable to that of enkephalins.


Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase.
Gab1 has structural similarities with Drosophila DOS (daughter of sevenless), which is a substrate of the protein tyrosine phosphatase Corkscrew. Both Gab1 and DOS have a pleckstrin homology domain and tyrosine residues, potential binding sites for various SH2 domain-containing adapter molecules when they are phosphorylated. We found that Gab1 was tyrosine phosphorylated in response to various cytokines, such as interleukin-6 (IL-6), IL-3, alpha interferon (IFN-alpha), and IFN-gamma. Upon the stimulation of IL-6 or IL-3, Gab1 was found to form a complex with phosphatidylinositol (PI)-3 kinase and SHP-2, a homolog of Corkscrew. Mutational analysis of gp130, the common subunit of IL-6 family cytokine receptors, revealed that neither tyrosine residues of gp130 nor its carboxy terminus was required for tyrosine phosphorylation of Gab1. Expression of Gab1 enhanced gp130-dependent mitogen-activated protein (MAP) kinase ERK2 activation. A mutation of tyrosine 759, the SHP-2 binding site of gp130, abrogated the interactions of Gab1 with SHP-2 and PI-3 kinase as well as ERK2 activation. Furthermore, ERK2 activation was inhibited by a dominant negative p85 PI-3 kinase, wortmannin, or a dominant negative Ras. These observations suggest that Gab1 acts as an adapter molecule in transmitting signals to ERK MAP kinase for the cytokine receptor gp130 and that SHP-2, PI-3 kinase, and Ras are involved in Gab1-mediated ERK activation.


Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes.
Gap junctions are composed of a family of structural proteins called connexins, which oligomerize into intercellular channels and function to exchange low molecular weight metabolites and ions between adjacent cells. We have cloned a new member of the connexin family from lens cDNA, with a predicted molecular mass of 46 kD, called rat connexin46 (Cx46). Since a full-length cDNA corresponding to the 2.8-kb mRNA was not obtained, the stop codon and surrounding sequences were confirmed from rat genomic DNA. The RNA coding for this protein is abundant in lens fibers and detectable in both myocardium and kidney. Western analysis of both rat and bovine lens membrane proteins, using the anti-MP70 monoclonal antibody 6-4-B2-C6 and three anti-peptide antibodies against Cx46 demonstrates that Cx46 and MP70 are different proteins. Immunocytochemistry demonstrates that both proteins are localized in the same lens fiber junctional maculae. Synthesis of Cx46 in either reticulocyte lysate or Xenopus oocytes yields a 46-kD polypeptide; all anti-Cx46 antisera recognize a protein in rat lens membranes 5-10 kD larger, suggesting substantive lenticular posttranslational processing of the native translation product. Oocytes that have synthesized Cx46 depolarize and lyse within 24 h, a phenomenon never observed after expression of rat connexins 32 or 43 (Cx32 and Cx43). Lysis is prevented by osmotically buffering the oocytes with 5% Ficoll. Ficoll-buffered oocytes expressing Cx46 are permeable to Lucifer Yellow but not FITC-labeled BSA, indicating the presence of selective membrane permeabilities. Cx43-expressing oocytes are impermeable to Lucifer Yellow. Voltage-gated whole cell currents are measured in oocytes injected with dilute concentrations of Cx46 but not Cx43 mRNA. These currents are activated at potentials positive to -10 mV. Unlike other connexins expressed in Xenopus oocytes, these results suggest that unprocessed Cx46 induces nonselective channels in the oolemma that are voltage dependent and opened by large depolarizations.


Genome-wide comparative analyses of domain organisation of repertoires of protein kinases of Arabidopsis thaliana and Oryza sativa.
A comparative analysis on protein kinases encoded in the completely sequenced genomes of two plant species, namely Arabidopsis thaliana and Oryza sativa spp japonica cv. Nipponbare is reported in the current study. We have analysed 836 and 1386 kinases identified from A. thaliana and the O. sativa genomes respectively. Their classification into known subfamilies reveals selective expansions of the plant receptor kinase subfamily comprising of Ser/Thr receptor kinases. The presence of calcium dependent kinases, and potential absence of cyclic nucleotide-dependent protein kinase of the type found in other (non-plant) eukaryotes, are other notable features of the two plant kinomes described here. An analysis on domain organisation of each of the protein kinases encoded in the plant genome has been carried out. Uncommon composition of functional domains like nuclear translocation factor domain, redox sensor domain (PAS), ACT and lectin domains are observed in few protein kinases shared between the two plant species. Biochemical functions characteristic of the domains recruited in these protein kinase gene products suggest their mode of regulation by alternate cellular localisation, oxidation potential, amino acid flux and binding of carbohydrates. Occurrence of multi-functional kinases with diverse enzymatic modules, such as Transposases and peptidases, tethered to the kinase catalytic domain is another interesting feature of the protein kinase complement of the O. sativa genome. Co-occurrence of diverse nucleotide and carbohydrate binding domains with catalytic kinase domain containing gene products has also been observed. Putative homologues of protein kinases of A. thaliana that regulate plant-specific physiological processes like ethylene hormone response, somatic embryogenesis and pathogen defence have been identified in O. sativa genome as well.


Combined Therapy with Rheum tanguticum Polysaccharide and Low-dose 5-ASA Ameliorates TNBS-Induced Colitis in Rats by Suppression of NF-κB.
The most common conventional therapy for inflammatory bowel disease in clinical practice involves the use of nonsteroidal anti-inflammatory drugs, such as 5-amino salicylic acid. However, a high dose of 5-amino salicylic acid may bring about severe side effects. Chinese people have used Rheum tanguticum as a folk remedy for gastrointestinal disease for two thousand years. Our group has isolated R. tanguticum polysaccharide 1 from R. tanguticum and verified that it can attenuate 2,4,6-trinitrobenzene sulfonic acid-induced colitis in murines/rats. The present study aims to evaluate whether the addition of R. tanguticum polysaccharide 1 can improve efficacy and limit subsequent side effects of conventional treatment (5-amino salicylic acid) in rats with 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Sixty Sprague-Dawley male rats were randomized into five groups and treated with (1) saline (saline, 0.2 mL/day × 5, p. o.), (2) 2,4,6-trinitrobenzene sulfonic acid alone (saline, 0.2 mL/day × 5, p. o.), (3) 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid (5-amino salicylic acid, 75 mg/kg/day × 5, p.o), (4) 2,4,6-trinitrobenzene sulfonic acid + R. tanguticum polysaccharide 1 (R. tanguticum polysaccharide 1, 200 mg/kg/day × 5, p. o.), and (5) 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid + R. tanguticum polysaccharide 1 (5-amino salicylic acid, 25 mg/kg/day × 5, p.o; R. tanguticum polysaccharide 1, 200 mg/kg/day × 5, p. o.). All the rats were sacrificed on the 6th day after treatment using an overdose of anesthesia. A histological assessment was performed using semiquantitative scores; nuclear factor-kappa B and tumor necrosis factor-α were measured with Western blot, cyclooxygenase 1 and cyclooxygenase 2 protein expressions were investigated by RT-polymerase chain reaction, and prostoglandin E2 and inducible nitric oxide synthase productions were investigated by ELISA. The extent and severity of histological signs were attenuated significantly in the 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid + R. tanguticum polysaccharide 1 group. Treatment with R. tanguticum polysaccharide 1 plus 5-amino salicylic acid markedly decreased nuclear factor-kappa Bp65 and tumor necrosis factor-α protein expressions. R. tanguticum polysaccharide 1 and 5-amino salicylic acid had no effect on cyclooxygenase 1 protein expression, but inhibited the overexpression of the cyclooxygenase 2 protein. After treatment with 5-amino salicylic acid and R. tanguticum polysaccharide 1, the prostoglandin E2 level increased significantly and the inducible nitric oxide synthase level decreased considerably in the 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid + R. tanguticum polysaccharide 1 group compared with the 2,4,6-trinitrobenzene sulfonic acid alone group. These results demonstrate that combined therapy with R. tanguticum polysaccharide 1 and low-dose 5-amino salicylic acid had more favorable effects on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats, and its effects may be associated with inhibiting nuclear factor-kappa Bp65 protein expression and tumor necrosis factor-α production, resulting in a decrease of cyclooxygenase 2 and inducible nitric oxide synthase protein expressions.


Obesity, metabolic syndrome, and type 2 diabetes: inflammatory basis of glucose metabolic disorders.
The latter half of the 20th century has witnessed rapid advances in medicine. Concurrently, secular trends in lifestyle practices in our increasingly sedentary society have led to burgeoning rates of obesity, metabolic syndrome, and type 2 diabetes. The number of Americans with type 2 diabetes more than doubled between 1980 and 2004 and the prevalence increases with age. Potential causes of this growing epidemic include changes in dietary patterns, physical inactivity, and obesity but may also include as yet unidentified genetic and environmental determinants. In this regard, experimental data provide evidence for a direct link between obesity and subclinical inflammation and support the concept that the metabolic syndrome and type 2 diabetes are, at least in part, inflammatory conditions. Furthermore, elevated levels of inflammatory biomarkers are not only associated with the development of future diabetes but cardiovascular disease as well. These findings suggest that subclinical inflammation may be a contributing factor not only to the etiology of these metabolic disorders but also their cardiovascular complications.


Uncrossed and crossed inhibition in the inferior colliculus of the cat: a combined 2-deoxyglucose and electrophysiological study.
The cat inferior colliculus (IC) was studied with 2-deoxyglucose (2-DG). By presenting high-frequency tone bursts to one ear and white noise bursts simultaneously to the other, a band of reduced or inhibitory labeling was revealed in the central nucleus (ICC) of the IC ipsilateral to the ear receiving the tone bursts. It was concluded that this ipsilateral inhibition might be related to the organization of excitatory/inhibitory units in ICC. In the opposite ICC, narrow bands of increased labeling were seen. In some animals, the positions of single units were marked, and tone frequencies were presented under 2-DG, which were the same as these units' characteristic frequencies (CFs). The positions of the units coincided with the position of the inhibitory bands, indicating that they were functional isofrequency-inhibitory contours. Unlike higher auditory centers, the binaural inhibitory areas were in register with and not orthogonal to the excitatory isofrequency contours. The inhibitory contours were generally larger than the excitatory contours and became even larger in more caudal sections. Both the inhibitory and excitatory contours extended into dorsal cortex areas of IC. In two other cats, high-frequency tone bursts and white noise bursts were presented to the same ear, and both a band of increased and a band of reduced labelling were found in the IC contralateral to this ear. The inhibitory band was always lateral to the excitatory band and was often smaller. They did not become larger in more caudal sections. The position of a unit in one cat was marked by pontamine sky blue, and the position of the unit coincided with the position of the excitatory band. It was concluded that this lateral inhibitory band represents high-frequency inhibitory sidebands of cells with CFs lower than the stimulating tone. It is concluded that the 2-DG method might reveal hitherto unknown inhibitory systems if stimuli could be combined with diffuse stimuli that raised the general background activity of sensory systems.


Glucocorticoid-regulated compartmentalization of cell surface-associated glycoproteins in rat hepatoma cells: evidence for an independent response that requires receptor function and de novo RNA synthesis.
The role of glucocorticoid hormones in the compartmentalization of cell surface-associated mouse mammary tumor virus (MMTV) glycoproteins was examined in M1.54, a cloned line of MMTV-infected rat hepatoma tissue culture cells. The expression of cellular [2-3H]mannose-labeled and cell surface 125I-labeled MMTV glycoproteins was examined throughout a time course of exposure to dexamethasone, a synthetic glucocorticoid. Posttranslational localization of cell surface MMTV glycoproteins required 6 h of exposure to hormone and occurred approximately 4 h after their initial production in an intracellular fraction. This regulated localization to the cell surface correlated with glucocorticoid receptor occupancy and was inhibited by exposure to RU 38486, a powerful antagonist of glucocorticoid-mediated responses. Cell surface immunoprecipitation demonstrated that actinomycin D, an inhibitor of de novo RNA synthesis, prevented regulated expression of cell surface viral glycoproteins, suggesting that newly synthesized cellular components mediate this process. The localization of cell surface MMTV glycoproteins appeared normal in a transcriptional variant (CR1) that produces basal levels of MMTV RNA and glycoprotein precursors in the presence of dexamethasone. Thus, regulated compartmentalization of viral glycoproteins is not an obligate consequence of a critical precursor concentration. Taken together, our results suggest that posttranslational trafficking of cell surface-destined MMTV glycoproteins resulted from an independent glucocorticoid hormone response that required receptor function and de novo RNA synthesis.


Falsified antimalarials: a minireview.
Malaria is a curable disease, provided timely access to efficacious drugs is sought. Poor quality and, in particular, falsified antimalarial drugs harm the population of malaria endemic areas; they put lives in peril, cause economic losses to patients, families, industry, and generally undermine the trust in health systems. The extent of the problem is not easily assessed, and although a prevalence of up to 35% of poor-quality antimalarials has been reported, this number should be interpreted with caution given the heterogeneity of methods used to measure it. The trade in falsified antimalarials can be curtailed by putting in place drug quality surveillance, better legislation and improving the access and affordability of these essential drugs.


Flow injection spectroscopic analysis of model drugs using on-line UV-diode array, FT-infrared and 1H-nuclear magnetic resonance spectroscopy and time-of-flight mass spectrometry.
A prototype flow injection analysis (FIA) system for the characterisation of compounds via a combination of diode array UV, 1H NMR, FT-IR spectroscopy and time-of-flight (TOF) mass spectrometry has been investigated using a number of pharmaceuticals and related compounds as model compounds. This combination of spectrometers allowed the on-flow collection of UV, 1H NMR, IR and mass spectra together with atomic composition data, enabling almost complete structural characterisation to be performed. Practical detection limits with the current system were in the region of 50 micrograms, however, the use of state of the art spectrometers would result in a significant reduction in the amount of material required.


[Chromosome aberrations in the somatic cells of mammals evoked by chromium compounds].
It is established that potassium bichromate (K2Cr2O7) in chronic and acute poisoning evokes a significant increase in frequency of cells with chromosome aberrations in bone marrow of rats. Mutagenic effect of chromium compounds is not always in correlation with their toxic action. It is supposed that chromium compounds possess the properties of chemical mutagenes of delayed action.


[Gaseous content regeneration system].
The article presents a possible design of an atmosphere revitalization system (ARS) as a component part of a new generation life support system (LSS). The main goal of the test investigation was to block formation of solid hard-to-remove carbon as a by-product of carbon dioxide and hydrogen processing. The Bosch reaction stage of CO2 conversion into CO and water was chosen as the core one. Beside the C02 and hydrogen conversion unit, other ARS constituents are a palladium membrane to generate ultrapure hydrogen, a water electrolysis unit, a hydrogen accumulator and a hydrogen absorber. To reach the materials balance, ARS was complemented with a system for trace contaminants and CO2 removal, and a Co2 concentrator. Zeolites in the CO2 removal system and concentrator ensure microwave energy absorption. Hydrogen is accumulated and absorbed by a LaNi5-based intermetallide. The palladium membrane serves to separate hydrogen from the CO-CO2 mixture.


Ovarian torsion in adolescent with chronic immune thrombocytopenia.
Ovarian torsions in adolescence are rarity, particularly bilateral, with mostly unknown etiology. Enlargement of the ovary contributes to torsion. Young girl presenting with abdominal pains, nausea and vomiting was for two days suspected and observed as gastroenteritis. By exclusion of gastroenteritis she was admitted for gynecological work-up. Ultrasound showed significantly enlarged right ovary, with tumor-like appearance. At the laparotomy, gynecologist found torsioned, necrotic ovary and ovariectomy was performed. Histology showed massive stromal bleeding (haemorrhage). Asymptomatic enlargement of remaining ovary occurred nine months after the ovariectomy. This enlargement was accompanied with platelets' fall and the possibility of repeated torsion impended. Thrombocytopenia was suspected from the first moment, but diagnosed after the surgery. Thrombocytopenia in adolescence requires additional attention as possible cause of intra-ovarian bleeding with consecutive enlargement and may lead to torsion. Oral contraceptives regulate dysfunctional bleeding, decrease ovarian volume and by so, may minimize risk of torsion. This strategy proved effective in the case we present.


The mechanism of agrin-induced acetylcholine receptor aggregation.
Agrin, a protein isolated from the synapse-rich electric organ of Torpedo californica, induces the formation of specializations on myotubes in culture which resemble the post-synaptic apparatus at the vertebrate skeletal neuromuscular junction. For example, the specializations contain aggregates of acetylcholine receptors and acetylcholinesterase. This report summarizes the evidence that the formation of the post-synaptic apparatus at developing and regenerating neuromuscular junctions is triggered by the release of agrin from motor axon terminals and describes results of recent experiments which suggest that agrin-induced tyrosine phosphorylation of the beta subunit of the acetylcholine receptor may play a role in receptor aggregation.


[Questionnaire survey of the actual working conditions of care-managers].
In order to clarify the present status of care-managers, a questionnaire was sent to 1,714 care-managers working in Kanagawa Prefecture in June 2002. The aspects investigated included their background, amount of care-management and degree of achievement, conditions of employment, opinion poll and training system. The response rate was 45.6% (782 out of 1,714). Concerning the total number of users in care at present, 37% of care-managers had less than 30 people, 24% from 31 to 50 and, surprisingly, 39% had more than 51 people. However, 42% answered that less than 30 was an appropriate number of users, 52% said 31 to 50 and only 6% answered that more than 51 people was an appropriate number. The conferences of users service representative were held only 8%. Concerning the burden of care-management, 87% of them answered the evaluation of every month and 86% did the conferences of users service representative. The cases requiring much time for the support, had problems not only the users but also in the household, who lacked the understanding and judgment for long-term care insurance. Most care-managers needed information on the available services and newly open care-service institutions. 27% of care-managers satisfied their care-management, 25% dissatisfied and the remainder were neither off nor on. The satisfaction to the care-management correlated well with the intelligibility of the management leader, motivation regarding care management and the degree of satisfaction with their income. It is concluded that the number of users per care-manager is too large, and that unfortunately it might further increase in the future. The conferences of users service representative were extremely held too low. It is also showed that information of the other service office and informal service with the exception of long-term care insurance are required.


Caspase-7 gene disruption reveals an involvement of the enzyme during the early stages of apoptosis.
Caspases play a key role during apoptotic execution. In an attempt to elucidate the specific role of caspase-7 we generated a chicken DT40 cell line in which both alleles of the gene were disrupted. Viability assays showed that caspase-7-/- clones are more resistant to the common apoptosis-inducing drugs etoposide and staurosporine. Caspase-7-/- cells show a delay in phosphatidylserine externalization and DNA fragmentation as well as cleavage of the caspase substrates poly(ADP-ribose) polymerase 1 and lamins B1 and B2. Caspase affinity labeling and activity assays indicated that deficient cells exhibit a delay in caspase activation compared with wild type DT40 cells, providing an explanation for the differences in apoptotic execution between caspase-7 null and wild type DT40 cells. These results strongly suggest that caspase-7 is involved earlier than other effector caspases in the apoptotic execution process in DT40 B lymphocytes.


E-Cigarettes and Cancer Risk.
From the time of their introduction, the popularity of e-cigarettes (electronic nicotine-delivery systems) has been rising. This trend may reflect the general belief that e-cigarettes are a less hazardous alternative to combustible cigarettes. However, the potential cancer-related effects of increased activation of the sympathoadrenal system induced by the inhalation of nicotine, the primary component of the e-cigarettes, are completely overlooked. Therefore, the aim of this review is to describe mechanisms that may connect the use of e-cigarettes and an increased risk for cancer development, as well as their stimulatory effect on cancer progression. Available preclinical data indicate that activation of the sympathetic nervous system by nicotine inhaled from e-cigarettes may stimulate cancer development and growth by several mechanisms. This issue might be especially important for oncological patients as they may have the misconception that compared with combustible cigarettes, e-cigarettes represent a risk-free alternative.


[Methodological problems of controlled clinical trials in surgical subspecialties].
Surgical subspecialties are handicapped in classical drug development considering professional and ethical solutions to questions in relation to introduction of new methods. The experts of invasive procedures are challenged significantly to comply with evidence based medicine and answer questions of the national health fund and/or health insurance companies, which are responsible for resource allocation. Sham operation is one of the ways to carry out controlled clinical trials. It had been pursued less frequently in the past, but we can see it as an important tool of invasive clinical trials nowadays. The contemplation about the applicability of sham operation contributes to understand other important issues in the development of invasive procedures.


AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses.
Silent synapses form between some primary sensory afferents and dorsal horn neurons in the spinal cord. Molecular mechanisms for activation or conversion of silent synapses to conducting synapses are unknown. Serotonin can trigger activation of silent synapses in dorsal horn neurons by recruiting AMPA receptors. AMPA-receptor subunits GluR2 and GluR3 interact via their cytoplasmic C termini with PDZ-domain-containing proteins such as GRIP (glutamate receptor interacting protein), but the functional significance of these interactions is unclear. Here we demonstrate that protein interactions involving the GluR2/3 C terminus are important for serotonin-induced activation of silent synapses in the spinal cord. Furthermore, PKC is a necessary and sufficient trigger for this activation. These results implicate AMPA receptor-PDZ interactions in mechanisms underlying sensory synaptic potentiation and provide insights into the pathogenesis of chronic pain.