Response to an applied electric field in an antiferroelectric 1/2 subphase: The role of thermal fluctuations.
The response to an applied electric field in the q_{T}=1/2 subphase of the MC881-MC452 binary mixture system is studied by using thick homeotropically aligned cells. In the ordinary antiferroelectric SmC_{A}^{*} and 1/2 (sub)phases, some nonplanar asymmetric distortions in the antiferroelectric unit cell structure produce induced polarization in the applied field direction, starts to unwind the helix from the beginning, and tends to align the averaged tilt plane direction parallel to the applied field. In the 1/2 subphase under consideration, however, the helix resists being deformed at the beginning and then the thresholdlike steep increase of birefringence Δn occurs in the transition from 1/2 to unwound SmC^{*} at a field of less than 0.5 V/µm; we conclude that the thermal fluctuations play an important role in promoting the director flip-flopping in a single layer under the applied field and bring about additional induced polarization, which counteracts the aforementioned ordinary induced one and prevents the helix from unwinding. This suggests that the Langevin-like director reorientation is the mechanism of the V-shaped switching which was actually observed in the thin films of Mitsui mixture [Phys. Rev. Lett. 87, 015701 (2001)0031-900710.1103/PhysRevLett.87.015701] and must have been used in prototyped thresholdless antiferroelectric liquid-crystal displays.


Differential regulation of gap junctions by proinflammatory mediators in vitro.
The development of inflammation is an important component of host defense against infection. The cellular and molecular processes underlying inflammation are well-studied, and it is known that cells of the blood vessel wall, such as endothelial cells and smooth muscle cells, play pivotal roles. Additionally, a wide variety of proinflammatory mediators have been defined, which coordinate the multicellular processes of inflammation. Knowledge of the potential role of blood vessel gap junctional intercellular communication (GJIC) in coordinating the inflammation process, however, is limited. In this study, we report that bacterial lipopolysaccharide (LPS), as well as the proinflammatory cytokines TNF-alpha and IL-1beta, selectively inhibit human myoendothelial GJIC in vitro without affecting GJIC between the respective homologous cell populations. This finding may represent a physiologically relevant component of the inflammatory response to infection. The work also provides some of the first clear evidence suggesting that a single eukaryotic cell can differentially regulate its GJIC between homologous and heterologous cell types in a simultaneous manner.


Free-standing ultrathin CoMn2O4 nanosheets anchored on reduced graphene oxide for high-performance supercapacitors.
Ultrathin CoMn2O4 nanosheets supported on reduced graphene oxide (rGO) are successfully synthesized through a simple co-precipitation method with a post-annealing treatment. With the assistance of citrate, the free-standing CoMn2O4 ultrathin nanosheets can form porous overlays on both sides of the rGO sheets. Such a novel hybrid nanostructure can effectively promote charge transport and accommodate volume variation upon prolonged charge/discharge cycling. When evaluated as a promising electrode for supercapacitors in a 6 M KOH solution electrolyte, the hybrid nanocomposites demonstrate highly enhanced capacitance and excellent cycling stability.


Inferring hidden symmetries of exotic magnets from detecting explicit order parameters.
An unconventional magnet may be mapped onto a simple ferromagnet by the existence of a high-symmetry point. Knowledge of conventional ferromagnetic systems may then be carried over to provide insight into more complex orders. Here we demonstrate how an unsupervised and interpretable machine-learning approach can be used to search for potential high-symmetry points in unconventional magnets without any prior knowledge of the system. The method is applied to the classical Heisenberg-Kitaev model on a honeycomb lattice, where our machine learns the transformations that manifest its hidden O(3) symmetry, without using data of these high-symmetry points. Moreover, we clarify that, in contrast to the stripy and zigzag orders, a set of D_{2} and D_{2h} ordering matrices provides a more complete description of the magnetization in the Heisenberg-Kitaev model. In addition, our machine also learns the local constraints at the phase boundaries, which manifest a subdimensional symmetry. This paper highlights the importance of explicit order parameters to many-body spin systems and the property of interpretability for the physical application of machine-learning techniques.


Monte Carlo simulations of bosonic reaction-diffusion systems.
An efficient Monte Carlo simulation method for bosonic reaction-diffusion systems which are mainly used in the renormalization group (RG) study is proposed. Using this method, one-dimensional bosonic single species annihilation model is studied and, in turn, the results are compared with RG calculations. The numerical data are consistent with RG predictions. As a second application, a bosonic variant of the pair contact process with diffusion (PCPD) is simulated and shown to share the critical behavior with the PCPD. The invariance under the Galilean transformation of this boson model is also checked and discussion about the invariance in conjunction with other models are in order.


NATURAL SELECTION ON BILL CHARACTERS IN THE TWO BILL MORPHS OF THE AFRICAN FINCH PYRENESTES OSTRINUS.
Evidence for natural selection on seven bill and body characters is examined in the two bill morphs of the African estrildid finch Pyrenestes ostrinus. Two regression methods are used in examining natural selection in association with survivorship: a parametric (Lande and Arnold, 1983) and a non-parametric (Schluter, 1988) method. Selection was estimated in adult males, females and juveniles over a four-year period in a population in south-central Cameroon. Selection was common among groups but patterns differed and depended on the method used in detecting selection. The non-parametric method revealed evidence for disruptive selection occurring on bill width and is explained within the context of known feeding efficiencies and the hardness of important seeds in finch diets. Directional selection was common on bill characters in all groups, but infrequent on other characters. There was no evidence of selection on generalized size or shape characters. Selection on bill characters was common across groups despite low annual variation in rainfall. This contrasts with studies of Galápagos finches in which selection is frequently associated with dramatic changes in food supply caused by high variance in annual rainfall. Patterns of selection on bill traits in P. ostrinus also differ from those in song sparrows and Galápagos finches by exhibiting evidence for natural selection on all bill dimensions.


Lichen spinulosus with immunofluorescent studies.
A typical case of lichen spinulosus in a 15-year-old boy is described. Keratotic papules and plaques occurred on the knees, elbows, and lower legs. A biopsy showed follicular hyperkeratosis consistent with lichen spinulosus. Studies for immunofluorescence demonstrated linear IgM at the basement membrane zone without colloid bodies. The relationship of lichen spinulosus and lichen planus is discussed. The patient responded to treatment with a salicylic acid gel.


Factors associated with dropout from physical function assessment programs among participants receiving maintenance hemodialysis: A retrospective observational cohort study.
We aimed to investigate the factors associated with dropout from a physical function assessment program among participants receiving outpatient hemodialysis (HD). The participants were divided into continuation and dropout groups and followed up for 3 years after the initial physical function assessment. Multivariate logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the dropout group to determine the factors associated with dropout from the physical function assessment program. The continuation and dropout groups included 43 and 58 participants, respectively. The continuation group had a significantly higher self-efficacy (SE) and age than the dropout group (p = 0.001, p = 0.047). Multivariate logistic regression analysis indicated that only SE (OR: 1.202, 95% CI: 1.082-1.334) remained a significant predictor after adjustment (p < 0.05). There is a need to evaluate SE to prevent dropout from physical functioning assessment programs.


Successful treatment of burn and visceral injury combined with full-thickness loss of the abdominal wall after blast injury.
A 29-year-old man was admitted to our institution 10 days after he had undergone an urgent exploratory laparotomy at a local army hospital after a terrorist bombing attack. On admission, deep second-degree and third-degree burns involving 25% of the upper and lower extremities were present, together with a 25 x 10-cm abdominal full-thickness blast injury defect on the left side, an infected eviscerated midline incision, and a colostomy on the right side of the abdomen. The patient underwent a second laparotomy, at which time the intraabdominal abscess was drained, and the abdominal cavity was irrigated with saline. A jejunal perforation was found and sutured. The abdominal cavity was left open and covered with a Bogota bag for temporary closure. On postburn day 18, the patient underwent débridment and grafting of the third-degree burns to the left and right arm and right lower extremities. After several débridment sessions (postburn days 16, 18, 20, 22, and 24), an abdominal skin release and reapproximation were performed (postburn day 26). On postburn day 36, split-thickness skin grafts were placed directly on the granulated tissue of the intestines and on a defect in the left flank and iliac regions. Postoperatively, the patient did well. He was discharged on postburn day 78 with all wounds well healed. In our opinion, temporary closure followed by direct application of meshed split-thickness skin grafts to exposed abdominal viscera represents a simple method of reconstruction that can be safely performed, with minimal risk, on critically ill patients.


CO2-sensitive preinspiratory neurons of the parafacial respiratory group express Phox2b in the neonatal rat.
Phox2b protein is a specific marker for neurons in the parafacial region of the ventral medulla, which are proposed to play a role in central chemoreception and postnatal survival. Mutations of PHOX2B cause congenital central hypoventilation syndrome. However, there have been no reports concerning electrophysiological characteristics of these Phox2b-expressing neurons in the parafacial region of the neonate immediately after birth. This region overlaps with the parafacial respiratory group (pFRG) composed predominantly of preinspiratory (Pre-I) neurons that are involved in respiratory rhythm generation. We studied (1) whether pFRG neurons are Phox2b immunoreactive or not and (2) whether they show intrinsic CO(2) chemosensitivity. We found that most pFRG/Pre-I neurons were Phox2b immunoreactive and depolarized upon increase in CO(2) concentration under condition of action potential-dependent synaptic transmission blockade by tetrodotoxin. We also confirmed that these pFRG neurons expressed neurokinin-1 receptor. They were tyrosine hydroxylase negative and presumed to be glutamatergic. Our findings suggest that Phox2b-expressing parafacial neurons play a role in respiratory rhythm generation as well as central chemoreception and thus are essential for postnatal survival.


Identification and control of plasma vertical position using neural network in Damavand tokamak.
In this work, a nonlinear model is introduced to determine the vertical position of the plasma column in Damavand tokamak. Using this model as a simulator, a nonlinear neural network controller has been designed. In the first stage, the electronic drive and sensory circuits of Damavand tokamak are modified. These circuits can control the vertical position of the plasma column inside the vacuum vessel. Since the vertical position of plasma is an unstable parameter, a direct closed loop system identification algorithm is performed. In the second stage, a nonlinear model is identified for plasma vertical position, based on the multilayer perceptron (MLP) neural network (NN) structure. Estimation of simulator parameters has been performed by back-propagation error algorithm using Levenberg-Marquardt gradient descent optimization technique. The model is verified through simulation of the whole closed loop system using both simulator and actual plant in similar conditions. As the final stage, a MLP neural network controller is designed for simulator model. In the last step, online training is performed to tune the controller parameters. Simulation results justify using of the NN controller for the actual plant.


Inhibition of mitogenesis induced by phytohemagglutinin and Lens culinaris lectin in adherent-cell supernatants treated with protein extract of Mycobacterium tuberculosis.
Specific stimulation of T cells by phytohemagglutinin and Lens culinaris lectin was inhibited by a soluble factor(s) secreted by normal adherent cells stimulated with culture filtrate protein extract (CFPE) derived from bacterial cultures of Mycobacterium tuberculosis H37Ra (avirulent) and H37Rv (virulent). The induction of the inhibitory factor was blocked by the presence of hyperimmune antisera to H37Rv or H37Ra CFPE. The inhibitory factor did not seem to be a CFPE reprocessed by the adherent cells. Inhibitory activity was maximal in supernatants of adherent-cell cultures incubated for 48 h; the inhibitory factor was heat labile, and its production was dependent on the concentration of M. tuberculosis CFPE. A mouse monocyte-macrophage cell line, ATCC J774A.1, produced an identical inhibitory factor, thus excluding a non-macrophage-contaminating adherent cell as the source of the factor. This inhibitory factor also interfered with the recognition of phytohemagglutinin and Lens culinaris lectin by T cells.


An unusual combination of sciatic and popliteal artery aneurysms.
A 68-year-old male presented with an asymptomatic pulsatile swelling on the back of his left thigh. Angiography revealed this to be aneurysmal degeneration of a persistent sciatic artery (PSA), an embryological variant whereby the primitive vascular tree persists as the main blood supply to the lower limb. Initial treatment was with an inlay graft to exclude the aneurysm from the circulation. The patient was re-referred 12 years later with a pulsatile swelling distal to the old scar. Angiography showed a popliteal artery aneurysm separate to both the sciatic artery and the anastomosis. The second procedure fashioned an inlay graft from the original graft down to the distal popliteal artery. The patient remains under follow-up. Patients with a PSA are prone to aneurysmal degeneration, which may also occur in adjacent vessels. For this reason, the authors recommend these individuals are kept under lifelong follow-up.


In vitro construction of different oligomeric forms of lambdadv DNA and studies of their transforming activities.
Plasmid lambdadv1, which is in a dimeric form, was converted to a linear monomer duplex by the action of EcoRI restriction endonuclease that incises at a unique site in this plasmid genome. The resulting products were then joined by Escherichia coli DNA ligase to produce molecules with various oligomeric forms, and from these monomeric, dimeric, or trimeric circular molecules were purified. By transformation of cells with these DNAs, clones were obtained that carried lambdadv1 in a monomeric or dimeric form. The former type of clones have not been generated in vivo, except for one in a different host strain, and carriers of timeric or tetrameric lambdadv1's have not been obtained so far. It was observed that a considerable fraction of these oligomeric circular DNAs were converted to lower oligomers (e.g., from trimer to dimer) during transformation. The characteristics of the monomeric lambdadv1 carriers obtained were compared with those of dimeric lambdadv1 carriers. The stabilities of the plasmids of the two forms were the same. However, the monomeric plasmid carriers were less tolerant to lambdavir phage infection and perpetuated about 30% less plasmid genomes in monomer units. Furthermore, dimeric plasmid carriers appeared spontaneously and accumulated in cultures of the monomeric lambdadv1 carriers.


Cost-effectiveness of linezolid versus vancomycin in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant staphylococcus aureus.
Linezolid, an oxazolidinone-class antimicrobial agent, is a new drug; its use has frequently been questioned due to its high price. However, recent trials have demonstrated that the use of linezolid in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (VAP-MRSA) may be justified due to its improved efficacy compared to vancomycin. Price and cost have different magnitudes, and clinical efficacy should always be considered in the decision-making process. Our objective was to determine whether linezolid treatment was more cost-effective than vancomycin for treating VAP-MRSA. Elaboration of an economic model from a metanalysis of previous clinical trials comparing both drugs, through a cost-effectiveness analysis. Costs of the treatments were calculated using Brazilian parameters and were compared to the results obtained in the metanalysis. In order to compare the results with real life conditions, costs were calculated for both name brand and for generic vancomycin. The cost (May/2004) per unit (vial, ampoule or bag) was R$ 47.73 for the name-brand vancomycin, R$ 14.45 for generic vancomycin and R$ 214.04 for linezolid. Linezolid's efficacy in VAP-MRSA according to the metanalysis was 62.2% and vancomycin's efficacy was 21.2%. The total cost per cured patient was R$ 13,231.65 for the name-brand vancomycin, R$ 11,277.59 for generic vancomycin and R$ 7,764.72 for linezolid. Despite the higher price per unit, linezolid was more cost-effective than vancomycin.


A null mutation for the alpha3 nicotinic acetylcholine (ACh) receptor gene abolishes fast synaptic activity in sympathetic ganglia and reveals that ACh output from developing preganglionic terminals is regulated in an activity-dependent retrograde manner.
In vertebrates, synaptic activity exerts an important influence on the formation of neural circuits, yet our understanding of its role in directing presynaptic and postsynaptic differentiation during synaptogenesis is incomplete. This study investigates how activity influences synaptic differentiation as synapses mature during early postnatal life. Specifically, we ask what happens to presynaptic terminals when synapses develop without functional postsynaptic receptors and without fast synaptic transmission. To address this issue, we investigated cholinergic nicotinic synapses in sympathetic ganglia of mice with a null mutation for the alpha3 nicotinic ACh receptor gene. Disrupting the alpha3 gene completely eliminates fast excitatory synaptic potentials on postganglionic sympathetic neurons, establishing a crucial role for alpha3-containing postsynaptic receptors in synaptic transmission. Interestingly, the preganglionic nerve terminals form morphologically normal synapses with sympathetic neurons, and these synapses persist without activity in postnatal animals. Surprisingly, when stimulating the preganglionic nerve at physiological rates, we discovered a significant decrease in ACh output from the presynaptic terminals in these alpha3(-/-) sympathetic ganglia. We show that this decrease in ACh output from the presynaptic terminals results, in part, from a lack of functional high-affinity choline transporters. We conclude the following: (1) fast synaptic transmission in mammalian SCG requires alpha3 expression; (2) in the absence of activity, the preganglionic nerve forms synapses that appear morphologically normal and persist for several weeks; and (3) to sustain transmitter release, developing presynaptic terminals require an activity-dependent retrograde signal.


Real-time estimation of respiratory rate from a photoplethysmogram using an adaptive lattice notch filter.
Many researchers have attempted to acquire respiratory rate (RR) information from a photoplethysmogram (PPG) because respiration affects the waveform of the PPG. However, most of these methods were difficult to operate in real-time because of their complexity or computational requirements. From these needs, we attempted to develop a method to estimate RR from a PPG with a light computational burden. To obtain RR information, we adopt a sequential filtering structure and frequency estimation technique, which extracts a dominant frequency from a given signal. In particular, we used an adaptive lattice notch filter (ALNF) to estimate RR from a PPG along with an additional heart rate that is utilized as an adaptation parameter of our method. Furthermore, we designed a sequential infinite impulse response (IIR) notch filtering system (i.e., harmonic IIR notch filter) to eliminate the cardiac component and its harmonics from the PPG. We compared the proposed method with Burg's AR modeling method, which is widely used to estimate RR from a PPG, using open-source data and measured data. By using a statistical test, it was determined that our adaptive lattice-type respiratory rate estimator (ALRE) was significantly more accurate than Burg's AR model method (p <0.0001). Furthermore, the ALRE's tracking performance was better than that of Burg's method, and the variances of its estimates were smaller than those of Burg's method. In short, our method showed a better performance than Burg's AR modeling method for real-time applications.


The Impact of Hyaluronan on Tumor Progression in Cutaneous Melanoma.
The incidence of cutaneous melanoma is rapidly increasing worldwide. Cutaneous melanoma is an aggressive type of skin cancer, which originates from malignant transformation of pigment producing melanocytes. The main risk factor for melanoma is ultraviolet (UV) radiation, and thus it often arises from highly sun-exposed skin areas and is characterized by a high mutational burden. In addition to melanoma-associated mutations such as BRAF, NRAS, PTEN and cell cycle regulators, the expansion of melanoma is affected by the extracellular matrix surrounding the tumor together with immune cells. In the early phases of the disease, hyaluronan is the major matrix component in cutaneous melanoma microenvironment. It is a high-molecular weight polysaccharide involved in several physiological and pathological processes. Hyaluronan is involved in the inflammatory reactions associated with UV radiation but its role in melanomagenesis is still unclear. Although abundant hyaluronan surrounds epidermal and dermal cells in normal skin and benign nevi, its content is further elevated in dysplastic lesions and local tumors. At this stage hyaluronan matrix may act as a protective barrier against melanoma progression, or alternatively against immune cell attack. While in advanced melanoma, the content of hyaluronan decreases due to altered synthesis and degradation, and this correlates with poor prognosis. This review focuses on hyaluronan matrix in cutaneous melanoma and how the changes in hyaluronan metabolism affect the progression of melanoma.


Comparison of antigen-induced leukotriene and histamine release from nasal scrapings in allergic rhinitis.
In the early phase response of allergic rhinitis, the nasal mucosa produces important mediators including histamine and leukotrienes. To investigate the relationship between antigen-induced leukotriene release and histamine secretion in nasal scrapings. Using nasal mucosal scrapings from patients sensitized to only house dust mite, we studied the time course of antigen-induced leukotriene release and its relationship to histamine release. Cumulative peptydyl leukotriene (LT) production from nasal scrapings increased from 10 min to approximately 90 min following exposure to mite antigen. The rate of LT release was small (<5 pg/10 min) until 10 min following antigen exposure, increased to approximately 250 to 350 pg LT/10 min from 10 to 45 min post exposure, was reduced to <100 pg/10 min by 60 to 150 min, and by 180 min LT production was negligible. By contrast, histamine secretion began 30 sec after antigen exposure and was complete within approximately 10 min. Net antigen-induced LT secretion strongly correlated (R=0.72) with net antigen induced histamine secretion with a ratio of 1:8.7. In addition, net LT/ng histamine and total LT secretion correlated well with antigen-specific IgE in serum, and with the patients' symptoms. There is a close relationship between amounts of histamine and LT secretion from antigen challenged nasal mucosa, although the time course of LT release is delayed. In the early phase response, LT are likely to be generated from mucosal mast cells, and thus, mast cell activation will provide an important therapeutic target.


And Yet One More Adds To The Sorrow.
Chikungunya is one of the vector borne diseases. It is caused by Chikungunya virus, an alpha virus, spread by the bite of female Aedes mosquito. Chikungunya is a non-fatal, self-limiting Dengue like illness which is characterized by high grade fever, headache, skin rash, and prolong debilitating arthralgia mostly affecting peripheral small joints. Treatment is usually supportive for the symptoms which includes antipyretic, analgesics and anti-inflammatory drugs. Current outbreak in Karachi is the first declared outbreak in Pakistan. To control the current outbreak, integrated vector management approach must be used to control Aedes not only to combat the current outbreak but also to reduce the endemicity and to prevent introduction of other Aedes borne diseases.


Lysis of antigenically unrelated tumor cells mediated by Lyt 2+ splenic T-cells from melphalan-cured MOPC-315 tumor bearers.
We have previously shown that mice cured of a large MOPC-315 tumor following low-dose melphalan (L-phenylalanine mustard, L-PAM) therapy can exert, upon challenge with MOPC-315 tumor cells, an antitumor effect against innocent bystander tumor cells present within the same tumor site (Barker, E., and Mokyr, M.B. Cancer Immunol. Immunother., 25: 215-224, 1987). Here we show that T-cells are important for the MOPC-315-induced rejection of MOPC-104E tumor cells present within the same site. To further characterize the innocent bystander killing activity exerted by L-PAM-cured MOPC-315 tumor bearers upon stimulation with MOPC-315 tumor cells, we established the in vitro conditions under which lymphoid cells from L-PAM-cured MOPC-315 tumor bearers can exert an antitumor effect against innocent bystanders. Specifically, we established that spleen cells from mice that just completed the rejection of a large MOPC-315 tumor following low-dose L-PAM therapy can, upon stimulation with MOPC-315 tumor cells, bring about the killing of antigenically unrelated tumor cells in a 12-h 51Cr release assay. The magnitude of lysis of EL4 and WEHI 22.1 tumor cells by MOPC-315 in vitro-immunized (IVI) spleen cells from L-PAM-cured MOPC-315 tumor bearers can be substantially enhanced upon reexposure of the spleen cells to MOPC-315-associated antigens during the 12-h 51Cr release assay. The lysis of innocent bystander tumor cells by these MOPC-315-IVI spleen cells was found to be mediated by T-cells of the Lyt 2 and not the L3T4 phenotype. These Lyt 2+ T-cells did not appear to mediate their lytic activity for innocent bystander tumor cells via effector macrophages, since a drastic reduction in macrophage frequency among the MOPC-315-IVI spleen cells just prior to assessing the lytic activity of the spleen cells did not reduce, but actually enhanced, the magnitude of EL4 lysis. In addition, a Lyt 2+ T-cell clone derived from mice cured of a large MOPC-315 tumor by a low dose of drug was capable, upon stimulation with MOPC-315 tumor cells, of exerting a potent lytic effect against EL4 and WEHI 22.1 tumor cells in the 12-h 51Cr release assay. Thus, Lyt 2+ T-cells independent of effector macrophages are responsible for lysis of innocent bystander tumor cells by MOPC-315-IVI spleen cells from L-PAM-cured MOPC-315 tumor bearers.


Modulation of macrophage functions by compounds isolated from Zingiber officinale.
Bioactivity-guided fractionation of Zingiber Officinale (zingiberaceae) led us to isolate 14 compounds, -gingerol ( 1), -gingerol ( 2), -gingerol ( 3), -gingerol ( 4), -paradol ( 5), -shogaol ( 6), -shogaol ( 7), 1-dehydro- -gingerdione ( 8), -gingerdione ( 9), hexahydrocurcumin ( 10), tetrahydrocurcumin ( 11), gingerenone A ( 12), 1,7-bis-(4' hydroxyl-3' methoxyphenyl)-5-methoxyhepthan-3-one ( 13), and methoxy- -gingerol ( 14). Using the RAW 264.7 cell line, the inhibitory effects on nitric oxide production induced by lipopolysaccharide and the stimulatory effects on phagocytosis of these compounds were evaluated. Compounds 7, 8, and 9 significantly decreased lipopolysaccharide-induced nitric oxide production, and compounds 7 and 8 significantly reduced inducible nitric oxide synthase expression. Among them, compound 8 also showed significant stimulatory effects on phagocytosis.


Differences in Signal Activation by LH and hCG are Mediated by the LH/CG Receptor's Extracellular Hinge Region.
The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) - secreted by the placenta, and lutropin (LH) - produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor's leucine-rich-repeat domain (LRRD), as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting) mutations. These helix preserving modifications showed no effect on hormone-induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10-deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the hinge region of the receptor.


Pulsed electron paramagnetic resonance spectroscopy of (33)S-labeled molybdenum cofactor in catalytically active bioengineered sulfite oxidase.
Molybdenum enzymes contain at least one pyranopterin dithiolate (molybdopterin, MPT) moiety that coordinates Mo through two dithiolate (dithiolene) sulfur atoms. For sulfite oxidase (SO), hyperfine interactions (hfi) and nuclear quadrupole interactions (nqi) of magnetic nuclei (I ≠ 0) near the Mo(V) (d(1)) center have been measured using high-resolution pulsed electron paramagnetic resonance (EPR) methods and interpreted with the help of density functional theory (DFT) calculations. These have provided important insights about the active site structure and the reaction mechanism of the enzyme. However, it has not been possible to use EPR to probe the dithiolene sulfurs directly since naturally abundant (32)S has no nuclear spin (I = 0). Here we describe direct incorporation of (33)S (I = 3/2), the only stable magnetic sulfur isotope, into MPT using controlled in vitro synthesis with purified proteins. The electron spin echo envelope modulation (ESEEM) spectra from (33)S-labeled MPT in this catalytically active SO variant are dominated by the "interdoublet" transition arising from the strong nuclear quadrupole interaction, as also occurs for the (33)S-labeled exchangeable equatorial sulfite ligand [ Klein, E. L., et al. Inorg. Chem. 2012 , 51 , 1408 - 1418 ]. The estimated experimental hfi and nqi parameters for (33)S (aiso = 3 MHz and e(2)Qq/h = 25 MHz) are in good agreement with those predicted by DFT. In addition, the DFT calculations show that the two (33)S atoms are indistinguishable by EPR and reveal a strong intermixing between their out-of-plane pz orbitals and the dxy orbital of Mo(V).


Anemia in diabetes: marker or mediator of microvascular disease?
Anemia is a common finding in patients with diabetes due to the high burden of chronic kidney disease in this population. Anemia is more prevalent and is found earlier in patients with diabetes than in those with kidney disease from other causes. The increased risk of anemia in diabetes probably reflects changes in the renal tubulointerstitium associated with diabetic kidney disease, which disrupt the delicate interaction between interstitial fibroblasts, capillaries and tubular cells required for normal hemopoietic function. In particular, the uncoupling of the hemoglobin concentration from renal erythropoietin synthesis seems to be the key factor underlying the development of anemia. Systemic inflammation, functional hematinic deficiencies, erythropoietin resistance and reduced red cell survival also drive anemia in the setting of impaired renal compensation. Although anemia can be considered a marker of kidney damage, reduced hemoglobin levels independently identify diabetic patients with an increased risk of microvascular complications, cardiovascular disease and mortality. Nevertheless, a direct role in the development or progression of diabetic complications remains to be clearly established and the clinical utility of correcting anemia in diabetic patients has yet to be demonstrated in randomized controlled trials. Correction of anemia certainly improves performance and quality of life in diabetic patients. In the absence of additional data, treatment should be considered palliative, and any functional benefits must be matched against costs to the patient and the health system.


Arginase and kallikrein activities as biochemical indices of occupational exposure to lead.
In a group of 60 workers occupationally exposed to lead the blood and urine lead concentrations, haematocrit, ALA-D and arginase activities, and urinary 5-aminolaevulinic acid (ALA) and coproporphyrin concentrations, and kallikrein activity were determined. Correlation coefficients of -0.78 and 0.77 for Pb-B/ALA and Pb-B/arginase were found respectively for lead concentrations above 40 microgram/dl blood, and 0.83, 0.76, 0.74, and -0.64 for Pb-U/ALA, Pb-U/Cp-U, Pb-U/kallikrein, and Pb.U/kallikrein, respectively. It seems that the increase in serum arginase activity may be indicative of liver damage while the decrease in kallikrein activity may indicate kidney damage in workers exposed to lead.


Safety and effectiveness of propranolol in severely burned patients: systematic review and meta-analysis.
The objective of this systematic review was to determine the effectiveness and safety of propranolol compared to placebo or usual care for improving clinical relevant outcomes in severely burned patients (TBSA >20%). Relevant articles from randomized controlled trials were identified by a literature search in MEDLINE, EMBASE, and CENTRAL. We included trials involving patients with a severe burn (>20% of total body surface area affected). Trials were eligible if they evaluated propranolol and compared to usual care or placebo. Two investigators independently assessed articles for inclusion and exclusion criteria and selected studies for the final analysis. We conducted a meta-analysis using a random-effects model. We included ten studies in our systematic review. These studies randomized a total of 1236 participants. There were no significant differences between propranolol and placebo with respect to mortality (RD -0.02 [95% CI -0.06 to 0.02]), sepsis (RD -0.03 [95% CI -0.09 to 0.04]), and the overall hospital stay (MD -0.37 [-4.52 to 3.78]). Propranolol-treated adults had a decrease in requirements of blood transfusions (MD -185.64 [95% CI -331.06 to -40.43]) and a decreased heart rate (MD -26.85 [95% CI -39.95 to -13.75]). Our analysis indicates that there were no differences in mortality or sepsis in severely burned patients treated with propranolol compared with those who had usual care or placebo. However, the use of propranolol in these patients resulted in lower requirements of blood transfusion and lower values of heart rate. The evidence synthesized in this systematic review is limited to conclude that propranolol reduces the length of hospital stay among severely burned patients. Future trials should assess the impact of propranolol on clinically relevant outcomes such as mortality and adverse events.


An Assessment of Fetal Cerebral and Hepatic Perfusion in Normal Pregnancy and Pre-Eclampsia Using Three-Dimensional Ultrasound.
Pre-eclampsia and placental causes of intrauterine growth restriction (IUGR) are part of the same spectrum of disorders. In IUGR, there is preferential shunting of blood to the fetal brain at the expense of other organs. We wanted to demonstrate that this also occurs in pre-eclampsia using three dimensional (3D) ultrasound. The 3D indices of perfusion are: flow index (FI), vascular index (VI) and vascularisation flow index (VFI) which reflect tissue vascularity and flow intensity. Fourteen normal pregnant women and 14 with diagnosed pre-eclampsia were recruited. Scanning was conducted by 2 observers using a Voluson E8 machine. Perfusion was measured at a pre-defined position within the fetal brain and fetal liver. The power Doppler signals were quantified using the 'histogram facility' to generate 3 indices of vascularity: FI, VI and VFI. The unpaired t-test was used to compare differences between groups. The hypothesis was that fetal brain FI, VI and VFI would be similar between women with normal pregnancy and women with pre-eclampsia, but measurements would be reduced in the fetal liver in women with pre-eclampsia. Maternal characteristics of age, body mass index and gestation were not different between groups. The depth of insonnation did not differ between groups. Fetal cerebral perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 22.4 (5.7) vs. 21.1 (4.3) respectively (p=0.49). For VI, the mean (SD) was as 64.7 (40.4) vs. 79.1 (27.4) respectively (p=0.28). For VFI, the mean (SD) was 14.8 (10.3) vs. 16.1 (5.5) respectively (p = 0.66). Fetal hepatic perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 34.4 (19.9) vs. 27.8 (11.0) respectively (p = 0.28). For VI, mean (SD) was 67.6 (36.0) vs. 87.3 (25.8) respectively (p=0.11). For VFI, the mean (SD) was 19.6 (11.6) vs. 23.1 (10.6) respectively (p=0.42). Using 3D ultrasound, we were not able to demonstrate preferential shunting of blood to the fetal brain at the expense of the fetal liver. Due to the high variability of our data, no definite conclusions can be derived from this work. A larger study may be required.


Role of G protein-coupled receptors (GPCR), matrix metalloproteinases 2 and 9 (MMP2 and MMP9), heparin-binding epidermal growth factor-like growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) in trenbolone acetate-stimulated bovine satellite cell proliferation.
Implanting cattle with steroids significantly enhances feed efficiency, rate of gain, and muscle growth. However, the mechanisms responsible for these improvements in muscle growth have not been fully elucidated. Trenbolone acetate (TBA), a testosterone analog, has been shown to increase proliferation rate in bovine satellite cell (BSC) cultures. The classical genomic actions of testosterone have been well characterized; however, our results indicate that TBA may also initiate a quicker, nongenomic response that involves activation of G protein-coupled receptors (GPCR) resulting in activation of matrix metalloproteinases 2 and 9 (MMP2 and MMP9) that release membrane-bound heparin-binding epidermal growth factor-like growth factor (hbEGF), which then binds to and activates the epidermal growth factor receptor (EGFR) and/or erbB2. Furthermore, the EGFR has been shown to regulate expression of the IGF-1 receptor (IGF-1R), which is well known for its role in modulating muscle growth. To determine whether this nongenomic pathway is potentially involved in TBA-stimulated BSC proliferation, we analyzed the effects of treating BSC with guanosine 5'-O-2-thiodiphosphate (GDPβS), an inhibitor of all GPCR; a MMP2 and MMP9 inhibitor (MMPI); CRM19, a specific inhibitor of hbEGF; AG1478, a specific EGFR tyrosine kinase inhibitor; AG879, a specific erbB2 kinase inhibitor; and AG1024, an IGF-1R tyrosine kinase inhibitor on TBA-stimulated proliferation rate (H-thymidine incorporation). Assays were replicated at least 9 times for each inhibitor experiment using BSC cultures obtained from at least 3 different animals. Bovine satellite cell cultures were obtained from yearling steers that had no previous exposure to androgenic or estrogenic compounds. As expected, BSC cultures treated with 10 n TBA showed ( < 0.05) increased proliferation rate when compared with control cultures. Additionally, treatment with 5 ng hbEGF/mL stimulated proliferation in BSC cultures ( < 0.05). Treatment with GDPβS, MMPI, CRM197, AG1024, AG1478, and/or AG879 all suppressed ( < 0.05) TBA-induced increases in proliferation. These data indicate that TBA likely initiates a nongenomic response involving GPCR, MMP2 and MMP9, hbEGF, EGFR, erbB2, and IGF-1R, which may play a role in TBA-mediated increases in BSC proliferation.


Change in food ingestion induces rapid shifts in the diversity of microbiota associated with cutaneous mucus of Atlantic salmon Salmo salar.
To test the hypothesis that a switch in diet might cause changes in the abundance and composition of mucous-dwelling microorganisms, a short-term experiment was conducted with Atlantic salmon Salmo salar. Fish were fed on three different diets: pelleted S. salar feed, macroinvertebrates or pellets supplemented with an antibiotic. A fourth group of fish was deprived of food throughout the trial. Seven days after manipulating diets, significant differences were found in microbial density and community composition (quantified by different morphologically distinct colonies), particularly between fed and unfed animals. Moreover, food deprivation caused a rapid decrease in the number of epidermal mucous cells of the lateral skin, which may indicate a decrease in mucous secretion and explain differences in the diversity of mucous-dwelling microbiota observed in the fish. This is the first report of an effect of feeding regime on the abundance of microbial communities associated with cutaneous mucus of fishes.


Recent Advances in Functional Nanomaterials for Diagnostic and Sensing Using Self-Assembled Monolayers.
Functional nanomaterials have attracted attention by producing different structures in any field. These materials have several potential applications, including medicine, electronics, and energy, which provide many unique properties. These nanostructures can be synthesized using various methods, including self-assembly, which can be used for the same applications. This unique nanomaterial is increasingly being used for biological detection due to its unique optical, electrical, and mechanical properties, which provide sensitive and specific sensors for detecting biomolecules such as DNA, RNA, and proteins. This review highlights recent advances in the field and discusses the fabrication and characterization of the corresponding materials, which can be further applied in optical, magnetic, electronic, and sensor fields.


Written simulation of patient-doctor encounters. 3. Comparison of the performance in the simulation with prescription and referral data in reality.
The performance of 19 general practitioners in a written simulation of patient-doctor encounters was compared with real data on prescription and referral from 'sick-fund' patients. Two issues were studied: the amounts of certain drugs prescribed (analgesics and antirheumatics; hypnotics/sedatives and tranquillizers; neuroleptics and antidepressants) and the number of referrals to specialists. In the simulation, experts assessed the 'risk of unnecessary harm to the patient' induced by the therapeutic procedures of these general practitioners, as described previously. A close correlation was found between the ratings of the risk of unnecessary harm in the simulation and the prescription and referral data in reality for general practitioners who were consistently generous or frugal in prescribing the above drugs and referring the patients to specialists. The tentative conclusion is that the written simulation with its rating procedure discriminates reliably between general practitioners who induce less risk of unnecessary harm from those who are likely to cause harm to the patient.


Food proteins and gut mucosal barrier I. Binding and uptake of cow's milk proteins by adult rat jejunum in vitro.
To study small intestinal binding, breakdown, and uptake of bovine serum albumin (BSA) and beta-lactoglobulin ( BLG ), radiolabeled with 125I or 14C, the rat everted gut sac technique was used as a model of intestinal protein handling. Binding and uptake were found to be nonspecific and nonsaturable. There was a close correlation between both processes (r = 0.8). A consistent difference between BSA and BLG was shown in that more BLG was bound and taken up between 1 and 30 min than was BSA (P less than 0.001). As shown by trichloroacetic acid precipitation and gel filtration on Sephadex G-100 and Bio-Gel P-2, this difference was due to differential protein breakdown that takes place during protein attachment and transport across the intestinal mucosa. High-molecular-weight fragments were generated from BSA, whereas the molecular weight of most fragments generated from BLG was very low (mol wt less than 500). Size and structure of these food protein fragments might not only influence their intestinal binding and uptake characteristics but might also play a role in the physiological induction of tolerance and their relative antigenic potential.


Prospective study of children with Guillain-Barre syndrome.
To see the pattern, and outcome of Guillain Barre syndrome in this country. All the children under fifteen years with final diagnosis of Guillain-Barre syndrome formed the subjects of the study. All children with acute flaccid paralysis were investigated for the underlying cause. The diagnosis of Gullain-Barre syndrome was made on clinical criteria, cerebrospinal findings and the nerve conduction studies. Intravenous immunoglobulins were given to all and only two children needed plasmapharesis. Fifty-two children were seen and constituted 20% of total acute flaccid paralysis cases. Cranial nerves were involved in fifty percent children. Albuminocytological dissociation in cerebrospinal fluid was seen in 97.5 percent cases. Acute relapse was seen in 11.5%. Seventeen percent required ventilation. The complete recovery was seen in 45 to 282 days (mean 68 days). Three children (5.8%) were left with minimal residual defecit. There was no mortality. The Guillain-Barre syndrome, though is a serious disease, recovery is the rule in children. Very low mortality and morbidity is seen. Immunoglobulins have reduced the length of hospital stay and also reduced the total time for recovery.


Assessment of novel foods in animal nutrition.
Composition of feeds from GMO crops were determined as well as digestion and feeding experiments were carried out with broilers (Bt-corn), layers (Bt-Corn, Pat-corn), pigs (Bt-corn, Pat-sugar beet, soybeans), sheep (Bt-corn silage, Pat-corn silage), growing bulls (Bt-corn silage) and fistulated cows (Bt-corn silage). Up to now, no significant differences in nutritional value between feeds from isogenic and transgenic plants of the first generation were observed. The so-called substantial equivalence, but also the nutritional equivalence of transgenic hybrids could be demonstrated. Recombinant plant DNA constructs were not detected in animal tissues samples. In the future, long term feeding experiments for nutritional assessment of novel feeds should be combined with risk assessment studies. Proposal for discussion has been submitted.


Care of the patient receiving radiation therapy.
External radiation therapy, or teletherapy, is the use of ionizing radiation to destroy cancer cells. Clinical use of ionizing radiation as treatment for cancer began with the discovery of x-rays in 1895, the identification of natural radioactivity (radium) in 1896, and the first reported cure of cancer, a basal cell epithelioma, induced by radiation in 1899. Initially, radiation was administered as a single large dose and produced severe, life-threatening side effects. The basis for the use of ionizing radiation in daily increments for a period of weeks was provided by Regaud in 1922; ten years later, Coutard clinically developed the method of dose fractionation, which remains in use today. Although the use of ionizing radiation as a treatment is over eighty years old, only in recent years have advancements in its clinical application been based on research related to the biologic effect of radiation on human cells. To effectively care for the patient prior to, during, and at the completion of external radiation therapy, the nurse must know the physical and biologic basis of external radiation therapy and its clinical application.


Design of Potassium-Selective Mixed Ion/Electron Conducting Polymers.
An approach providing cation-selective poly-(3,4-ethylenedioxythiophene)(PEDOT):polyelectrolyte-mixed conductors is presented in this communication based on the structural modification of this ambivalent (ionic and electronic conductive) polymer complex. First, an 18-crown-6 moiety is integrated into the styrene sulfonate monomer structure as a specific metal cation scavenger particularly targeting K+ versus Na+ detection. This newly functionalized monomer is characterized by 1 H NMR titration to evaluate the ion selectivity. Aqueous PEDOT dispersion inks containing the polymeric ion-selective moieties are designed and their electrical and electrochemical properties analyzed. These biocompatible inks are the first proof-of-concept step towards ion selectivity in view of their interfacing with biological cells and microorgans of interest in the field of biosensors and physiology.


Dissociated conditional-associative learning in anorexia nervosa.
This study assessed the acquisition of conditional-associations using neutral and individually threatening nouns in 16 females with anorexia nervosa (AN), 16 females with bulimia nervosa (BN) and 16 normal controls (NC). Groups did not differ in terms of age, sex, handedness, depression, intelligence, verbal memory and verbal fluency measures. Furthermore, patients and controls were widely comparable on any test assessing neuropsychological functioning. In the conditional-associative learning (CAL) task, anorexic patients displayed an impaired performance with neutral material but not with individually threatening material. Such a deficit was not evident in bulimics or in normal controls. Only anorexics showed a dissociation in the CAL of material with different emotional valence. These findings support the assumptions from functional neuroimaging investigations in AN and justify the assignment of this disorder to the obsessive-compulsive spectrum disorders.


Identification of a novel uncultured Rickettsia species strain (Rickettsia species strain Tselenti) in Cyprus.
In a previous study conducted in Cyprus, various spotted fever group Rickettsia species were detected and identified in ticks by molecular analysis. Among them, a partially characterized Rickettsia species was detected in Hyalomma anatolicum excavatum and Rhipicephalus turanicus ticks. We report characterization of this rickettsial strain by using polymerase chain reaction sequencing analysis of partial citrate synthase A, outer membrane protein A, outer membrane protein B, and 17-kD protein genes. We propose a provisional name Rickettsia sp. strain Tselenti for this strain until it is isolated and further characterized.


Ethnopharmacology, phytochemistry, pharmacology, clinical applications and toxicology of the genus Stellera Linn.: A review.
The genus Stellera Linn. consists of species of perennial herbs and shrubs, and is mainly distributed in the temperate regions of east Asia to west Asia. There are 10∼12 species in the world, two species in China: Stellera chamaejasme Linn. and Stellera formosana Hayata ex Li. As recorded, the roots of Stellera species are used to dissipate phlegm and relieve pain. The roots and the barks can be used for papermaking. This review aims to summarize the ethnopharmacological uses, chemical constituents, pharmacological activities, clinical applications and toxicology of the genus Stellera to better understand their therapeutic potential in the future. The relevant information of the genus Stellera was collected from scientific databases (Pubmed, ACS website, SciFinder Scholar, Elsevier, Google Scholar, Web of Science and CNKI). Information was also gathered from 'Flora Republicae Popularis Sinicae (〈〈〉〉)', folk records, conference papers on ethnopharmacology, Ph.D. and Masters' Dissertation. Stellera plants have been studied as traditional folk medicines all around the world. The chemical constituents of Stellera species mainly comprise terpenoids, flavonoids, coumarins, lignans, and so on. Extracts and compounds of Stellera species exhibit extensive pharmacological activities, such as anti-tumor, anti-viral, anti-convulsive, anti-epileptic, anti-bacterial and anti-insect activities, etc. Clinical applications have suggested that the genus Stellera has the effects in treating several skin diseases and cancers, however, the results should be further verification. The genus Stellera plants are toxic and should be used reasonable. This paper reviewed the ethnopharmacological uses, chemical constituents, pharmacology, clinical applications and toxicology of the genus Stellera. The genus Stellera has broad application prospects. However, further in-depth studies are needed to determine the medical uses of the genus and its chemical constituents, pharmacological activities, clinical applications and toxicology.


Evaluation of the human interferon system in viral disease.
The interferon (IFN) system in man regulates viral replication, cell multiplication and immune functions. Its action against viruses takes place in two stages. The first is the production of IFN by cells following stimulation by a variety of IFN inducers including viruses, and the second is the action of this IFN on other cells inducing in them an antiviral state which prevents replication of infecting viruses. A series of assays is described which evaluates these different parameters of the antiviral IFN system. An attempt was made to correlate between IFN production and cell response to IFN on the one hand, and clinical status on the other. Results show that healthy persons have little or no IFN in the blood (mean less than 4 units/ml), and that in 94% their PBMC are not in an antiviral state. On the other hand, patients with acute viral diseases have significantly increased levels of IFN in their blood (mean 150 +/- 284 units/ml), and in 70% their cells are in an antiviral state. In some seriously ill patients with viral disease, the IFN system was found to be functionally deficient and treatment with human leucocyte IFN rapidly changed this. It is concluded that the examination of several biological parameters of the IFN system including the intracellular antiviral state induced by IFN is necessary in order to better evaluate this antiviral system. This will enable the clinician to obtain optimal pharmacokinetic information for determining which cases are most likely to respond to IFN therapy, and help to monitor the efficacy of this treatment.


Overexpression of enhancer of zeste human homolog 2 (EZH2) gene in human cytomegalovirus positive glioblastoma multiforme tissues.
Glioblastoma multiforme (GBM) is considered to be one of the most invasive human cancers, characterized by a high mortality rate and an average survival is <1 year. These tumors are highly aggressive and insensitive to conventional radio and chemotherapy. An interesting aspect of glioblastoma is the association of active human cytomegalovirus (HCMV) infection, which is evident by the presence of viral DNA, mRNA and protein level in most glioblastoma tissues. Although the presence of the HCMV infection in glioblastoma is well established, but the oncomodulatory role of HCMV is not defined yet. Enhancer of zeste human homolog 2 (EZH2) is a key protein of the polycomb repressive complex 2, epigenetic gene silencers. There have been several reports that EZH2 activity is essential in GBM pathogenesis. In our previous research, we have found a high rate of HCMV infection in a cohort of Iranian glioblastoma patients. In this study, we investigated the expression of EZH2 in HCMV-negative versus HCMV-positive GBM tissues in comparison to non-tumor tissues. The level of expression was determined by real time PCR and the differences were calculated using the Livac or 2(-ΔΔCt) and analysis of variance (ANOVA). Relative expression of EZH2 in HCMV-negative glioblastoma tissues were increased 6.053-fold compared to non-neoplastic brain tissues, while EZH2 gene expression was increased 41.098-fold in HCMV-positive glioblastoma tissues. ANOVA test showed that there is a significant difference in EZH2 expression between normal brain tissue, HCMV-negative and HCMV-positive glioblastoma tumors (p value = 0.0001). Our data indicate that EZH2 expression can be considered a risk factor in glioblastoma and EZH2 inhibitors may serve as potential new treatment in glioblastoma. This would be an interesting new field to investigate in more detail.


Effects of epinephrine, glucagon and insulin on the activity and degree of phosphorylation of fructose-1,6-bisphosphatase in cultured hepatocytes.
The effects of epinephrine, glucagon and insulin on the activity and degree of phosphorylation of fructose-1,6-bisphosphatase in isolated hepatocytes maintained in cell culture for 24 h were investigated. Epinephrine caused a rapid decrease in the apparent Km monitored as the activity ratio between the activity at 12.5 and 83 microM fructose-1,6-bisphosphate, reaching a maximum after 5 min. Glucagon caused a slower and less pronounced activation, and insulin caused an equally slow increase in Km. The effect of epinephrine and glucagon was completely reciprocated by insulin and the action of insulin was totally erased by the other two. Glucagon stimulated the incorporation of [32P]phosphate into fructose-1,6-bisphosphatase from about 2.5 to 4.2 mol/mol enzyme and epinephrine to 3.5 mol/mol. The effect of the two hormones acting together was cumulative. Insulin brought about a decrease in the degree of phosphorylation to 2.0 mol/mol. The effect of epinephrine was shown to be caused by the beta-receptors, since it was completely blocked by propanolol (a beta-antagonist) and remained unaffected by the presence of phentolamine (an alpha-antagonist).


Liver fluke-infested graft used for living-donor liver transplantation: case report and review of the literature.
Clonorchiasis is a cholangiopathy caused by foodborne trematode parasites, also known as liver flukes. Clonorchiasis is endemic in a wide geographical area extending from Eastern Europe to Southeast Asia. Infested hosts may remain asymptomatic for decades and consequently their liver can become available as a graft. To date, 20 liver transplantations with liver fluke-infested grafts have been reported in the literature. All of them occurred in Asian countries. We, here, report the first case to our knowledge in the Western world of living-donor liver transplantation (LDLT) with an Opisthorchis felineus-infested graft, and present a review of the literature. A 6-month-old girl with decompensated secondary biliary cirrhosis underwent an LDLT with a left lateral graft infested with O. felineus. After prompt diagnosis and adequate therapy, both donor and recipient had an uneventful postoperative course and long-term follow-up. Liver grafts infested with liver flukes do not pose a contraindication to liver donation from deceased or living donors, provided that a correct diagnosis and treatment are performed in a timely fashion.


Sirtuin 7 promotes glioma proliferation and invasion through activation of the ERK/STAT3 signaling pathway.
Sirtuin7 (Sirt7) is a member of the Sir2 histone deacetylase family that functions in a number of physiological processes, including cellular metabolism, ageing and apoptosis. Several studies have indicated that Sirt7 may serve a vital role in promoting the development of cancer. However, to the best of our knowledge, its function in glioma progression has not been demonstrated. The present study revealed that Sirt7 expression was upregulated in human glioma tissues and that the high expression level of Sirt7 was positively associated with glioma malignancy. Further results indicated that the suppression of Sirt7 expression could inhibit the activation of phosphorylated extracellular signal-regulated kinase (p-ERK) concomitantly with decreased expression of cyclin-dependent kinase 2 in glioma cells. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) inhibited when Sirt7 was downregulated by siRNA interference in glioma cell lines. The findings of the present study indicated that Sirt7 affects the malignancy of glioma cells mainly in promoting glioma proliferation and invasion through ERK and STAT3 signaling. Thus, Sirt7 may function as a valuable target for the treatment of human glioma.


Reinforced thermoplastic polyimide with dispersed functionalized single wall carbon nanotubes.
Molecular pi-complexes were formed from pristine HiPCO single- wall carbon nanotubes (SWCNTs) and 1-pyrene- N-(4-N'-(5-norbornene-2,3-dicarboxyimido)phenyl butanamide, 1. Polyimide films were prepared with these complexes as well as uncomplexed SWCNTs and the effects of nanoadditive addition on mechanical, thermal, and electrical properties of these films were evaluated. Although these properties were enhanced by both nanoadditives, larger increases in tensile strength and thermal and electrical conductivities were obtained when the SWCNT/1 complexes were used. At a loading level of 5.5 wt %, the T(g) of the polyimide increased from 169 to 197 degrees C and the storage modulus increased 20-fold (from 142 to 3045 MPa). The addition of 3.5 wt % SWCNT/1 complexes increased the tensile strength of the polyimide from 61.4 to 129 MPa; higher loading levels led to embrittlement and lower tensile strengths. The electrical conductivities (DC surface) of the polyimides increased to 1 x 10(-4) Scm(-1) (SWCNT/1 complexes loading level of 9 wt %). Details of the preparation of these complexes and their effects on polyimide film properties are discussed.


[Acute reversible kidney insufficiency due to enalapril during diuretic-treated heart insufficiency].
Acute reversible renal failure with hyperkalemia developed in a 42-year-old woman during treatment of heart failure and hypertension with high doses of enalapril and diuretics. Creatinine clearance fell as low as 9 ml/min. Renal-artery stenosis and prerenal renal failure were excluded. Reduction in blood pressure in conjunction with reduced renal perfusion in heart failure can make glomerular filtration angiotensin dependent. Interruption of angiotensin II formation in this situation triggers off functional renal insufficiency.


Triosephosphate isomerase deficiency: a neurodegenerative misfolding disease.
A number of neurodegenerative diseases are mediated by mutation-induced protein misfolding. The resulting genetic defects, however, are expressed in varying phenotypes. Of the several well-established glycolytic enzyme deficiencies, triosephosphate isomerase (TPI) deficiency is the only one in which haemolytic anaemia is coupled with progressive, severe neurological disorder. In a Hungarian family with severe decrease in TPI activity, two germ line-identical but phenotypically differing compound heterozygote brothers inherited two independent (Phe(240)-->Leu and Glu(145)-->stop codon) mutations. We have demonstrated recently [Orosz, Oláh, Alvarez, Keserü, Szabó, Wágner, Kovári, Horányi, Baróti, Martial, Hollán and Ovádi (2001) Blood 98, 3106-3112] that the mutations of TPI explain in themselves neither the severe decrease in the enzyme activity characteristic of TPI deficiency nor the enhanced ability of the mutant enzyme from haemolysate of the propositus to associate with subcellular particles. Here we present kinetic (flux analysis), thermodynamic (microcalorimetry and fluores cence spectroscopy), structural (in silico) and ultrastructural (immunoelectron microscopy) data for characterization of mutant isomerase structures and for the TPI-related metabolic processes in normal and deficient cells. The relationships between mutation-induced TPI misfolding and formation of aberrant protein aggregates are discussed.


Complete Genome Sequence of Nervous Necrosis Virus Isolated from Sevenband Grouper (Epinephelus septemfasciatus) in South Korea.
The draft genome sequence of the nervous necrosis virus (NNV) SGYeosu08, isolated from sevenband grouper (Epinephelus septemfasciatus) in Yeosu, South Korea, was cloned and analyzed. The full-length RNA1 was a 3,103-nucleotide-encoding region of RNA-dependent RNA polymerase, and the RNA2 encoding a coat protein was 1,433 nucleotides in length. This genome sequence might be useful in the development of an accurate diagnostic tool.


Gender difference in subjective symptoms related to paroxysmal atrial fibrillation is also detected in postmenopausal women.
Atrial fibrillation (AF) is well known to be male-dominant. Female sex hormones may be involved, since very few premenopausal women experience AF. However, a possible gender difference in older subjects has not been fully elucidated yet. We retrospectively reviewed the symptoms of 133 patients (111 males and 22 females) with paroxysmal AF (PAF) from the medical records at our hospital from 1995 to 2000, and classified the patients according to the time of the attacks as day type, night type, or unspecific type. In females, the age at the first diagnosis of PAF was significantly higher (males: 57 +/- 1 year old, females: 65 +/- 2 years old; P = 0.006) and the proportion of cases younger than 61 years old was significantly smaller (63%, 32%; P = 0.007). As in previous reports, the female group had more cases with unspecific type (26.5%, 47.6%) or with long duration (> 24 hours) (16.9%, 37.5%). In contrast to these published results, fewer women (10.5%) had frequent attacks (more than twice a week) than men (39.8%). The incidence of regular alcohol consumption, one of the most important PAF triggers, was significantly higher in men than women (84.7%, 13.6%; P < 0.0001). Even when we focused on cases older than 60 years old, the female group still had more cases with unspecific type (53.3% versus 23.1%) or with long duration (27.3% versus 14.7%) than men, and fewer with frequent attacks (0% versus 51.7%) or regular alcohol consumption (6.7% versus 82.9%; P < 0.0001) than men. The gender difference in symptoms related to PAF may depend not only on sex hormones, but also on intrinsic or social gender differences.


The telotrophic ovary known from Neuropterida exists also in the myxophagan beetle Hydroscapha natans.
The ovary structure of the myxophagan beetle, Hycdoscapha natans, was investigated by means of light and electron microscopy for the first time. Each of the two ovaries consists of three ovarioles, the functional units of insect oogenesis. The ovary type is telotrophic meroistic but differs strongly from the telotrophic ovary found among all polyphagous beetles investigated so far. All characters found here are typical of telotrophic ovaries of Sialidae and Raphidioptera. Both taxa belong to the Neuropterida. As in all telotrophic ovaries, all nurse cells are combined in an anterior chamber, the tropharium. The tropharium houses two subsets of germ cells: numerous nurse cell nuclei are combined in a central syncytium without any cell membranes in between, surrounded by a monolayer of single-germ cells, the tapetum cells. Each tapetum cell is connected to the central syncytium via an intercellular bridge. Tapetum cells of the posterior zone, which sufficiently contact prefollicular cells, are able to grow into the vitellarium and develop as oocytes. During previtellogenic and early vitellogenic growth, oocytes remain connected with the central syncytium of the tropharium via their anterior elongations, the nutritive cords. The morphological data are discussed in the light of those derived from ovaries of other Coleoptera and from the proposed sister group, the Neuropterida. The data strongly support a sister group relationship between Coleoptera and Neuropterida. Furthermore, several switches between polytrophic and telotrophic ovaries must have occurred during the radiation of ancient insect taxa.


[Fournier's gangrene: report of 4 cases].
Fournier's gangrene is an infective necrotizing fasciitis of the perineal, genital or perianal region. We treated four cases of Fournier's gangrene from July 2002 to April 2003. All patients were male, ranging in age from 73-92 years old (80.5 +/- 6.5). They were admitted to our hospital complaining of perineal pain, scrotal swelling and high fever. Immediately, we started systemic chemotherapy with broad-spectrum antibiotics, and performed surgical debridements for all patients. Three patients made a full recovery, but one patient died of sepsis. These cases are presented with some notes on the relevant literature.


Immune Cells and Molecular Networks in Experimentally Induced Pulpitis.
Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-β, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria.


Gene delivery to the lungs: pulmonary gene therapy for cystic fibrosis.
Cystic fibrosis (CF) is a monogenic autosomal recessive disorder where the defective gene, the cystic fibrosis transmembrane conductance regulator (CFTR), is well identified. Moreover, the respiratory tract can be targeted through noninvasive aerosolized formulations for inhalation. Therefore, gene therapy is considered a plausible strategy to address this disease. Conventional gene therapy strategies rely on the addition of a correct copy of the CFTR gene into affected cells in order to restore the channel activity. In recent years, genome correction strategies have emerged, such as zinc-finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats associated to Cas9 nucleases. These gene editing tools aim to repair the mutated gene at its original genomic locus with high specificity. Besides, the success of gene therapy critically depends on the nucleic acids carriers. To date, several clinical studies have been carried out to add corrected copies of the CFTR gene into target cells using viral and non-viral vectors, some of them with encouraging results. Regarding genome editing systems, preliminary in vitro studies have been performed in order to repair the CFTR gene. In this review, after briefly introducing the basis of CF, we discuss the up-to-date gene therapy strategies to address the disease. The review focuses on the main factors to take into consideration when developing gene delivery strategies, such as the design of vectors and plasmid DNA, in vitro/in vivo tests, translation to human use, administration methods, manufacturing conditions and regulatory issues.


Affect-modulated startle in adults with childhood-onset depression: relations to bipolar course and number of lifetime depressive episodes.
To study affect regulation in adults with unipolar (n=38) and bipolar (n=38) forms of childhood-onset depression (COD), as compared with adults with no history of psychiatric illness (n=60), we examined affective modulation of the startle eyeblink reflex. Participants were subjected to binaural bursts of white noise while viewing pictures designed to elicit pleasant, neutral, or unpleasant affective states. The blink response was recorded from surface electrodes over the orbicularis oculi muscle during and following pictures. Participants rated the valence and arousal of their responses. Unlike control or bipolar groups, the unipolar group displayed a greater startle during the neutral condition than during the pleasant condition, and failed to display an increase in startle during the unpleasant condition. The bipolar group, unlike the unipolar and control groups, displayed a similar startle response after pleasant and unpleasant pictures. Participants with a high number of lifetime depressive episodes displayed a blunted startle response across affective conditions. Groups reported similar subjective responses to affective stimuli. Current affective symptoms and comorbid diagnoses did not influence startle modulation. In unipolar and bipolar forms of COD, unusual affective modulation or maintenance of the startle response, respectively, may reflect underlying deficits in affect regulation.


Enzymatic amplification of translation inhibition of rabbit beta-globin mRNA mediated by anti-messenger oligodeoxynucleotides covalently linked to intercalating agents.
The effects of anti-messenger oligodeoxynucleotides, covalently linked to an intercalating agent, on translation of rabbit beta-globin mRNA, were investigated both in wheat germ extract and in microinjected Xenopus oocytes. A specific inhibition of beta-globin synthesis was observed in both expression systems with a modified 11-mer covalently linked to an acridine derivative. In injected oocytes a more efficient block was observed with this modified oligonucleotide than with its unsubstituted homolog. This was ascribed to stacking interactions of the intercalating agent with base pairs which provide an additional stabilization of the [mRNA/DNA] hybrid. We demonstrated that in wheat germ extract, the modified and unmodified oligonucleotides behaved similarly due to the presence of a high RNaseH activity. RNaseH was also present, although to a lesser extent, in the oocyte cytoplasm. This anti-messenger DNA-induced degradation of target mRNA resulted in amplified efficiency of hybrid-arrested translation. This additional mechanism might provide anti-sense DNAs with an advantage over anti-sense RNAs.


Photochemical proteolysis of an unstructured linker of the GABAAR extracellular domain prevents GABA but not pentobarbital activation.
The GABA type A receptor (GABA(A)R) is the major inhibitory receptor in the mammalian central nervous system and the target of numerous pharmaceuticals. The alpha-subunit of these pentameric Cys-loop neurotransmitter-gated ion channels contributes to the binding of both GABA and allosteric modulators such as the benzodiazepines, suggesting a role for this subunit in the conformational changes associated with activation of the receptor. Herein we use the nonsense suppression methodology to incorporate a photoactivatable unnatural amino acid and photochemically cleave the backbone of the alpha subunit of the alpha(1)beta(2) GABA(A)R in a linker region that is believed to span the subunit. Proteolytic cleavage impairs GABA but not pentobarbital activation, strongly suggesting that conformational changes involving this linker region are critical to the GABA activation pathway.


[The phonetic development of normal-hearing pre-school children].
To collect the daily speech materials and to discuss the speech development of normal-hearing pre-school children. Based on the database of daily speech materials of children who are 3 to 5 years old, from separate monosyllabic word to syllable,analysis the frequency of words and compare them with adults. In the spoken words of children who are 3 to 5 years old, we can find all Mandarin phonemes. With independent sample t test, it was shown that there is no significant difference in the distributing of phonemes between children and adults. Children who are 3 years old have developed the phonetic system of the language basically.


External fixation of lower limb fractures in children.
26 children with 29 lower limb fractures, between the age of 2 and 15 years, were treated with an external fixator. The average time to union and removal of the fixator was 71 days for femoral and 73 days for tibial fractures. Complications included pin problems in nine cases, two devices had to be replaced with a cast and one refracture. Leg length discrepancies were noted in five children and radiological malalignment in three. We recommend external fixation for all femoral shaft fractures and all open or dislocated tibial and tibia and fibula fractures beginning at the age of three to adolescence.


Local oxidation and reduction of graphene.
Micrometer sized oxidation patterns were created in chemical vapor deposition grown graphene through scanning probe lithography (SPL) and then subsequently reduced by irradiation using a focused x-ray beam. Throughout the process, the films were characterized by lateral force microscopy, micro-Raman and micro-x-ray photoelectron spectroscopy. Firstly, the density of grain boundaries was found to be crucial in determining the maximum possible oxygen coverage with SPL. Secondly, the dominant factor in SPL oxidation was found to be the bias voltage. At low voltages, only structural defects are formed on grain boundaries. Above a distinct threshold voltage, oxygen coverage increased rapidly, with the duration of applied voltage affecting the final oxygen coverage. Finally, we found that, independent of initial conditions, types of defects or the amount of SPL oxidation, the same set of coupled rate equations describes the reduction dynamics with the limiting reduction step being C-C → C=C.


Body growth response to selection and crossbreeding in dwarf and normal broiler-type chickens.
A normal-bodied broiler population and one dwarfed by the dw sex-linked gene were each sub-divided into two lines. AGB (normal) and D2B (dwarf) were selected only for superior body weight at eight weeks of age. AGE (normal) and D2E (dwarf) were sublines in which prospective dams were selected for large egg weight while prospective sires were selected for eight-week body weight. Selection for large eight-week weight of both sexes in both dwarf and normal populations during each of three generations resulted in superior growth rate to that observed when the dams were selected for egg weight. When the selected dams were tested each generation for their ability to produce superior broiler crossbreds using a commercial broiler sire strain, AGE proved superior to AGB in the second and third generations while D2B and D2E dams produced crossbreds with similar broiler weights. Normal-bodied dams which produced crossbreds having superior growth to that of the dwarf dams in the first generation lost most of this superiority by the third generation in sons and the second generation in daughters. Reproductive fitness was superior within the dwarf lines as well as in their ability to produce more crossbred progeny.


Inhibition of the transcription factor Sp1 suppresses colon cancer stem cell growth and induces apoptosis in vitro and in nude mouse xenografts.
The transcription factor specificity protein 1 (Sp1) plays a role in the development and progression of various types of human cancers, while cancer stem cells (CSCs) are important in cancer cell self-renewal, resistance to chemotherapy and metastatic potential. This study investigated the role of Sp1 in colon CSC growth and apoptosis. Colon CSCs were successfully enriched using special culture medium and identified by typical CSC gene expression. In a quiescent state, these CSCs formed spheres with slow proliferation; overexpressed Sp1, CD44, CD166 and CD133 proteins; upregulated mesenchymal markers; and a downregulated epithelial marker were noted. In ex vivo experiments, the Sp1 protein was expressed in 74.8% of colon cancer tissues, whereas it was expressed only in 42.2% of the distant normal colon mucosae. Furthermore, inhibition of SP1 expression using Sp1 siRNA or mithramycin A (MIT) led to marked suppression of CSC growth and induced apoptosis. In addition, the percentage of CD44+/CD166+ cells was significantly downregulated both in vivo and in vitro following Sp1 inhibition. In conclusion, Sp1 suppression attenuated the characteristics of colon CSCs. Thus, Sp1 inhibition may be potentially useful for the future development of a novel therapeutic strategy to control colon cancer.


Amaurosis fugax: prognosis and the role of acetylsalicylic acid.
Amaurosis fugax has been grouped together with other forms of transient ischemic attacks (TIAs) in the neurologic literature in analyses of prognosis. Although episodes of transient visual loss (TVL) are presumed to be due to ischemia, the prognosis with respect to subsequent stroke and myocardial infarct (MI) appears to differ from cerebral TIAs. We reviewed the clinical course of 73 patients above the age of 45 years who presented to our clinics with a distinct history of TVL. With an average follow-up period of 38 months, the incidence rates of cerebrovascular accident, cerebral TIA and MI following presentation with TVL were 1%, 4% and 7% respectively. Although there was a trend toward fewer episodes of amaurosis with use of acetylsalicylic acid (ASA), the difference was not statistically significant. In addition, ASA did not appear to offer a benefit with respect to future ischemic events. Patients with monocular TVL appeared more likely to experience a TIA, whereas those with binocular TVL appeared more likely to experience an MI.


Development and Optimization of a Novel Soft Sensor Modeling Method for Fermentation Process of Pichia pastoris.
This paper introduces a novel soft sensor modeling method based on BDA-IPSO-LSSVM designed to address the issue of model failure caused by varying fermentation data distributions resulting from different operating conditions during the fermentation of different batches of Pichia pastoris. First, the problem of significant differences in data distribution among different batches of the fermentation process is addressed by adopting the balanced distribution adaptation (BDA) method from transfer learning. This method reduces the data distribution differences among batches of the fermentation process, while the fuzzy set concept is employed to improve the BDA method by transforming the classification problem into a regression prediction problem for the fermentation process. Second, the soft sensor model for the fermentation process is developed using the least squares support vector machine (LSSVM). The model parameters are optimized by an improved particle swarm optimization (IPSO) algorithm based on individual differences. Finally, the data obtained from the Pichia pastoris fermentation experiment are used for simulation, and the developed soft sensor model is applied to predict the cell concentration and product concentration during the fermentation process of Pichia pastoris. Simulation results demonstrate that the IPSO algorithm has good convergence performance and optimization performance compared with other algorithms. The improved BDA algorithm can make the soft sensor model adapt to different operating conditions, and the proposed soft sensor method outperforms existing methods, exhibiting higher prediction accuracy and the ability to accurately predict the fermentation process of Pichia pastoris under different operating conditions.


Thrombophlebitis migrans following co-trimoxazole therapy.
We report an unusual and severe vasculitic disorder following co-trimoxazole, given orally for a urinary tract infection. The vasculitis was manifest solely as thrombophlebitis migrans and involving only veins without evidence of polyarteritis nodosa, or underlying malignancy.


Study on the role of SLC14A1 gene in biochemical recurrence of prostate cancer.
Prostate cancer (PCa) is a common malignant disease among men and biochemical recurrence (BCR) is considered to be a decisive risk factor for clinical recurrence and PCa metastasis. Clarifying the genes related to BCR and its possible pathways is vital for providing diagnosis and treatment methods to delay the progress of BCR. An analysis of data concerning PCa from previous datasets of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) was performed. Immunohistochemical (IHC) staining were used to evaluate the expression of SLC14A1 in prostate tissues. Kaplan-Meier analysis, Pearson correlation, and single sample Gene Set Enrichment Analysis (ssGSEA) were used to identify the potential pathway and molecular mechanism of the function of SLC14A1 in BCR of PCa. The expression of SLC14A1 is significantly reduced in prostate cancer cells and tissue comparing to normal prostate epithelial cell and para-cancerous tissue. As indicated by Kaplan-Meier analysis, High expression of SLC14A1 could increase the BCR-free survival time of PCa patients. This effect might be related to the interaction with miRNAs (has-miR-508, has-mir-514a2, and has-mir-449a) and the infiltration of B cells. SLC14A1 is a novel important gene associated with BCR of PCa, and further studies of its molecular mechanism may delay the progress of BCR.


Isogenic mutants of the cag pathogenicity island of Helicobacter pylori in the mouse model of infection: effects on colonization efficiency.
Strains of Helicobacter pylori that contain the cag pathogenicity island (cag PAI) are associated with increased virulence and severe clinical outcomes. To evaluate the role of the cag island in infection, isogenic null mutations were generated in two clinical isolates (SS1 and Iris1) with distinct genetic backgrounds. When tested for their ability to establish infection in the stomach of CD1/SPF mice, at the early phase of infection, strains in which cagE, ORF528, ORF527 or ORF525 were inactivated showed a reduced capacity to initiate colonization compared to the wild-type strain. Strains with a mutation in the ORF524 gene were more efficient than the other mutants, but still less efficient than the wild-type strain. Mutation in the effector protein, CagA, which is injected into host cells and tyrosine-phosphorylated, did not change the colonization efficiency. In conclusion, all cag genes analysed, with the exception of the effector protein, CagA, influenced the early phase of colonization in the mouse model of infection. These results suggest that the structure of the H. pylori secretion apparatus itself is involved in this process.


[KIF1A gene-associated neurological disease: the correlation between genotype and phenotype].
KIF1A-associated-neurological-disorder (KAND) encephalopathy is a group of progressive neurodegenerative pathologies of varying severity caused by mutations in the KIF1A gene (Kinesin family member 1A) located on chromosome 2q37.3. This gene encodes a protein of the kinesin-3 family that participates in the ATP-dependent anterograde transport of presynaptic vesicles through neuronal microtubules. Four patients are described, aged 1-13 years, with a median onset of symptoms of 5 months (IQR 0-11 months), which represents an approximate prevalence of 1 per 64,000 children under 14 years of age for our pediatric population. Clinically, intellectual disability (ID), axial hypotonia and spastic paraparesis stood out in 4/4 and cerebellar symptoms in 2/4. Other manifestations were urinary incontinence, sensory-motor polyneuropathy, and behavioral alteration. In case 2, the alteration in the video-EEG stands out, which showed focal epilepsy with secondary generalization and right posterior occipito-parietal paroxysmal focality with contralateral transmission. She also showed instantaneous pluricotidian supraversion oculogyric seizures without EEG correlates. In our series, KAND encephalopathy had a predominant neurodegenerative disorder phenotype with global developmental delay, gait delay, and progressive spasticity of the lower limbs, cerebellar atrophy, and/or involvement of the visual cortex, which in one case was associated with sensory-motor polyneuropathy. The de novo missense mutation was more frequent and in three cases it is the first known description. One case showed focal epilepsy and nonepileptic oculogyric seizures.


Lability of metal complexes at spherical sensors. Dynamic voltammetric measurements.
The diffusive-kinetic steady-state (dkss) approximation is applied to the case of a metal ion reaching a transforming/consuming spherical surface (sensor) when the ion is involved in a complexation reaction in solution. Simple time-dependent expressions for the surface metal flux, the lability degree and the half-wave potential are presented, valid for any value of the ratio of concentrations at the surface and the sensor radius. The solution presented is compared with other theoretical approaches, such as the kinetic steady state (kss) and the total steady state (tss), pointing out that the easy dkss approach is much more accurate than the tss one to study the metal flux and the lability degree for any value of the radius, from ultramicro to planar sensors.


The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychotic patients.
In this open, 30-day trial, the pharmacokinetics, safety and tolerability of a combination therapy of risperidone (4 or 6 mg/day)and fluoxetine (20mg/day from day 6) were evaluated in 11 psychotic inpatients. CYP2D6 genotyping revealed that 3 and 8 patients were poor metabolizers (PMs) and extensive metabolizers (EMs) of debrisoquine, respectively. The mean (+/- SD) AUC of risperidone increased from 83.1 +/- 46.8 ng.h/ml and 398.3 +/- 33.2 ng.h/ml (monotherapy) to 345.1 +/- 158.0 ng.h/ml (p < 0.05) and 514.0 +/- 144.2 ng.h/ml (p < 0.001) when coadministered with fluoxetine in EMs and PMs, respectively. The AUC of the active moiety (risperidone plus 9-hydroxy-risperidone) increased from 470.0 +/- 170.0 ng.h/ml to 663.0 +/- 243.3 ng.h/ml (p < 0.05)and from 576.3 +/- 19.6 ng.h/ml to 788.0 +/- 89.1 ng.h/ml (ns) in EMs and PMs, respectively. In EMs, the AUC of 9-hydroxy-risperidone remained similar (monotherapy vs. combination therapy: 386.8 +/- 153.0 ng.h/ml vs. 317.7 +/- 125.2 ng.h/ml, ns),whereas it increased in PMs (178.3 +/- 23.5 ng.h/ml vs. 274.0 +/- 55.1 ng.h/ml (p < 0.05)). Ten of the 11 patients showed a clinical improvement (reduction of 20% or more in total PANSS score and 70% on the mean MADRS score compared to baseline). The severity and incidence of extrapyramidal symptoms and adverse events did not significantly increase when fluoxetine was added.


Banxia Xiexin Decoction Ameliorates t-BHP-Induced Apoptosis in Pancreatic Beta Cells by Activating the PI3K/AKT/FOXO1 Signaling Pathway.
Banxia Xiexin Decoction (BXXD) reportedly regulates glycolipid metabolism and inhibits pancreatic β-cell apoptosis. This study is aimed at investigating the protective effect of BXXD on tert-butyl hydroperoxide- (t-BHP-) induced apoptosis in MIN6 cells and the underlying mechanisms. MIN6 cells were preincubated with BXXD or liraglutide (Li) with or without PI3K inhibitor LY294002 (LY) for 12 h, following which t-BHP was added to induce MIN6 cell apoptosis. The protective effects of BXXD on MIN6 cells were evaluated by detecting cell viability and proliferation and glucose-stimulated insulin secretion (GSIS). The antiapoptotic effects were evaluated by Hoechst 33342 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL). Malondialdehyde and glutathione peroxidase content and superoxide dismutase activity were measured using commercial kits. The expression of PI3K/AKT/FOXO1 signaling pathway-related signal molecules, and that of apoptotic indicators Bax, P27, and Caspase-3, was quantified using western blotting. Preincubation with BXXD significantly improved t-BHP-induced proliferation inhibition and apoptosis and enhanced GSIS. t-BHP induced the generation of reactive oxygen species and inhibited the activities of antioxidant enzymes, which could be neutralized by pretreatment with BXXD. BXXD promoted the phosphorylation of AKT and FOXO1 in t-BHP-induced MIN6 cells. Moreover, BXXD attenuated the expression of related apoptotic indicators Bax, P27, and Caspase-3. LY abolished these effects of BXXD. BXXD protected MIN6 cells against t-BHP-induced apoptosis and improved insulin secretory function through modulation of the PI3K/AKT pathway and the downstream FOXO1, thus suggesting a novel therapeutic approach for type 2 diabetes mellitus (T2DM).


Meckel-Gruber Syndrome: A Case Who Lived for 5 Months.
The Meckel-Gruber syndrome is a rare, congenital, and lethal malformation characterized by typical manifestations such as encephalocele, polycystic kidneys, and polydactyly. Herein, we present a case of a patient with the typical triad as well as facial, ocular, liver, and genital abnormalities who lived for almost 5 months.


[Problems and outlook for plant production].
Environmental damages due to very intensive cropping systems do exist. A lot of people think it is necessary to prohibit the use of chemical fertilizers and pesticides, as well as in developed and developing countries. If so, global production would dramatically decrease while human population is increasing. The objective of feeding population of the world could not be met, particularly in Africa. On the other hand, crop modelling shows that theoretical potential plant production in the world is sufficient, if environmental damages are avoided. Future challenge is double: increasing food production and protecting the environment. Different ways to achieve this goal are analyzed. Increasing food production only in developed countries is environmentally and economically not practicable because of high cost and social damages in developing countries. Each country has to increase its own production, particularly in the South. But adopting the very intensive cropping systems existing in the North is not possible. The challenge is to be able to increase crop production in each place, taking into account biophysical, sociological, economical and political peculiarities. In some places, existing extensive cropping systems cause damages to the environment, because population pressure lead to increase cultivated areas, consequently reducing follow and pasture of forest areas: these systems are not sustainable if not intensified. In other places, even in the South, water pollution results from excessive use of fertilizers and pesticides. A new paradigm is proposed to take into account this great diversity of situations: the "Doubly Green Revolution" will allow to define adapted and sustainable cropping systems. Scientific results obtained along last century and including recent results in biotechnology, will be at the basis of these new systems.