In vitro activity of fosfomycin tromethamine against extended spectrum beta-lactamase producing urinary tract bacteria.
To determine the in vitro activity of Fosfomycin tromethamine against extended spectrum beta-lactamase producing uropathogens. Experimental study. Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from October 2011 to October 2012. A total of 381 culture positive ESBL producing isolates from 2400 urine samples submitted over a period of one year were included in this study. Identification of isolates was done by standard biochemical profile of the organisms. The antimicrobial susceptibility of culture positive isolates was performed by disk diffusion method as recommended by Clinical Laboratory Standard Institute guidelines (CLSI). The antimicrobial activity of Fosfomycin to various isolates revealed that 93% of E. coli, 64% Klebsiella spp. 50% Proteus spp. 75% Enterobacter cloacae, 100% Citrobacter freundii, 100% Burkholderia spp. 100% Serratia spp. and 50% Stenotrophomonas maltophilia were susceptible to this chemical compound. Fosfomycin showed excellent effectiveness to most of the common ESBL producing bacteria such as E. coli, Klebsiella and Proteus spp.


Risk factors for cervical intraepithelial neoplasia and cervical cancer in Chinese women: large study in Jiexiu, Shanxi Province, China.
We aimed to investigate the risk factors for cervical intraepithelial neoplasia (CIN) in Jiexiu, Shanxi Province, China. Twenty thousand eligible married women (age: 18-65 years) were administered with a questionnaire on potential risk factors for CIN and underwent liquid based Pap test. All women with abnormal cytological results underwent colposcopy with biopsy. Based on the biopsy pathology results, women were then assigned to either study group (with CIN) or control group (negative for histological results and volunteered to participate in the follow up study). The women in both study group and control group underwent vaginal microflora detection and dietary survey. The potential risk factors were analyzed by using ordinal logistic regression. Among the 20,000 women ne 1,438 women (7.19%) had cytologic abnormalities and 410 (2.05%) women were diagnosed histologically with CIN lesions, including 317 (1.58%) with CIN1, 93 (0.50%) with CIN2/3and 11 (55/100,000) with squamous cell carcinoma (SCC). The average daily dietary folate intake was significantly lower in the study group (344.61±153.07μg) than in the control group (371.50±166.58μg; P<0.001). Multivariate analysis demonstrated that age of 56-65 years, farming as the husband's occupation, unwashing the vulva after sexual intercourse, and low self-reported folate intake were positively associated with CIN development and might have contribution to the increased CIN incidence in this population. These findings may provide help to develop the strategies to reduce the risk of cervical cancer in China.


Heme prevents amyloid beta peptide aggregation through hydrophobic interaction based on molecular dynamics simulation.
Heme, which is abundant in hemoglobin and many other hemoproteins, is known to play an important role in electron transfer, oxygen transport, regulation of gene expression, and many other biological functions. With the belief that the aggregation of Aβ peptides forming higher order oligomers is one of the central pathological pathways in Alzheimer's disease, the formation of the Aβ-heme complex is essential as it inhibits Aβ aggregation and protects the neurons from degradation. In our studies, conventional molecular dynamics simulations were performed on the 1 Aβ + 1 heme and 2 Aβ + 4 hemes system, respectively, with the identification of several dominant binding motifs. We found that hydrophobic residues of the Aβ peptide have a high affinity to interact with heme instead of the histidine residue. We conclude that hydrophobic interaction plays a dominant role in the Aβ-heme complex formation which indirectly serves to physically prevent Aβ aggregation.


[Analysis on Clenbuterol pollution in swine products in Beijing, 2002].
To explore the status of clenbuterol pollution in swine products in Beijing city in 2002. European Union method (EUR 15127-EN Cy2.3) was adopted to examine the samples. Samples were screened by enzyme-linked immunosorbent assay (ELISA) and confirmed by GC-MS. Detected limit of the method was 0.5 micro g/kg. Samples, including lung, liver, pork, kidney and urine of swine, were collected from slaughterhouses, refrigeratories and markets in 11 districts of Beijing. The results indicated that 185 out of 1 379 samples were positive with an annual positive rate of 13.4%. The highest was 15.7% in lung of swine, followed by urine 15.2% and pork liver 14.0%. Rates of detection had decreased from 30.0% to 2.7% during 2002.


Superaerophilic Wedge-Shaped Channels with Precovered Air Film for Efficient Subaqueous Bubbles/Jet Transportation and Continuous Oxygen Supplementation.
Pumpless and directed gas transportation in aqueous environments has promising application prospects in various domains. So far, researches on gas transportation based on superaerophilic channels are limited to the transportation of fewer bubbles with low transportation velocity. How to enhance the transportation velocity and realize the transportation of a large quantity of bubbles (especially for gas jet) for practical applications remain unclear. Here, a half-open wedge-shaped channel with subaqueous superaerophilicity is fabricated, which demonstrates excellent bubble affinity and can realize the pumpless and directed bubble transportation. It is proposed that a Laplace force is the main driving force during the transportation and the magnitude of the force is influenced by both the wedge angle of the channel and geometric parameters of the bubble whereas the direction of the force is determined by the orientation of the channel. By applying a precovered air film on the subaqueous superaerophilic wedge-shaped channel, bubbles demonstrate a higher transportation velocity. Additionally, the prepared channel shows an outstanding affinity to oxygen jet at high flux, which can be utilized to transport oxygen for continuous subaqueous oxygen supplementation.


TWEAK as a target for therapy in systemic lupus erythematosus.
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily. Through activation of the fibroblast growth factor-inducible 14 (Fn14) receptor, TWEAK regulates cell proliferation, cell death and inflammation. The available evidences have indicated that TWEAK might be a target for therapeutic intervention in renal, vascular injury and neuropathy. Since renal, vascular and neuropsychiatric complications are frequently encountered in systemic lupus erythematosus (SLE)--a systemic autoimmune disease, TWEAK-Fn14 pathway may be implicated in the pathogenesis of SLE. In this review, we will discuss the TWEAK-Fn14 pathway and the therapeutic potential of modulating this pathway in SLE.


Front explosions in three-dimensional resonantly-forced oscillatory systems.
Interface dynamics in a three-dimensional coupled map lattice with a period-3 local map is studied. The system possesses a parameter regime where one typically finds three-phase patterns consisting of spatially uniform domains which follow the period-3 cycle and oscillate among the three different phases. The interfaces where these domains meet may exhibit complex irregular dynamics. The system also has a parameter regime of "turbulent" dynamics, which is a chaotic transient with a superexponentially long lifetime. The transition from the three-phase pattern regime to the turbulent regime is studied. As a control parameter is tuned, the interfaces between domains develop turbulent structure. The thickness of the turbulent zone remains finite up to a critical parameter value after which it is infinite. We characterize this "front explosion" transition in three-dimensional systems and compare it with the analogous transition in two-dimensional systems where the critical properties are markedly different. The front explosion in the three-dimensional resonantly-forced complex Ginzburg-Landau equation is also investigated briefly and its character differs from that in the three-dimensional coupled map lattice.


Steric, hydrogen-bonding and structural heterogeneity effects on the nucleophilic substitution of N-(p-fluorophenyldiphenylmethyl)-4-picolinium chloride in ionic liquids.
The nucleophilic substitution of N-(p-fluorophenyldiphenylmethyl)-4-picolinium chloride was investigated using water and a range of alcoholic nucleophiles in ionic liquid solvents. The reactivity patterns across the nucleophiles examined could be attributed to steric factors, which mediated the relative nucleophilicities. Reducing the hydrogen-bond acidity of the ionic liquid cation was found to generally increase the rate of reaction, however, the magnitude of this rate effect could be influenced by the steric bulk of the nucleophile and the structural heterogeneity of the ionic liquid. Preferential solvation phenomena in binary mixtures of ionic liquids were examined and suggest that the mechanism behind the hydrogen-bond solvation phenomenon arises from direct cation-mediated, rather than indirect anion-mediated, effects.


Increased risk of BVDV infection of calves from pregnant dams on communal Alpine pastures in Switzerland.
Skin biopsies and blood samples from 117 calves, the offspring of dams that had been pastured on communal Alpine pastures while pregnant, were examined for bovine viral diarrhoea virus (BVDV) antigen. Immunohistochemical evaluation of skin biopsy samples revealed BVDV antigen in nine (7.7%) calves, and ELISA testing of serum samples was positive for BVDV antigen in six (5.1%). Three calves with positive skin biopsy samples and negative serum results were < 11 days old; it was assumed that maternal antibody interfered with the ELISA testing. Serum samples that were collected at a later date from two of the three calves were positive for BVDV antigen. These results were significantly different from those of a previous study in which the prevalence of persistently infected calves in an average Swiss cattle population was 0.64%. It was concluded that the risk of infection with BVDV is high in cattle sharing a communal Alpine pasture.


Perinatal exposure to 5-methoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat.
Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models, and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to, pregnant dams from gestational days 12 to 21 (1mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5mg kg s.c.), induce in the adolescent rat offspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity and rearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimming in the forced swim test. Acute administration of LY 228729 (1.5mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activity in the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposed offspring. Co-administration of WAY 100635 (0.25mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in the adolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action on presynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds.


Protamine-induced histamine release in human skin mast cells.
Rapid intravenous (iv) infusion of protamine sulfate is associated with hypotension in humans. A possible mechanism for this hypotension is the release of inflammatory mediators, including histamine, from tissue mast cells lining the blood vessels. To determine whether protamine caused nonimmunologic release of histamine, histamine released from dispersed human skin mast cells exposed to protamine sulfate was measured. Skin from seven adult patients was washed, chopped into small tissue fragments, and incubated with collagenase, hyaluronidase, and DNAase. Dispersed mast cells were harvested after 12 h of short-term tissue culture, washed, and challenged with protamine sulfate. Histamine release was measured using an automated histamine analyzer and expressed as a per cent of total released histamine measured minus the spontaneous histamine release. Spontaneous histamine release averaged 6 +/- 1%. Protamine produced dose-related histamine release. At a concentration of 3 X 10(-3) M, protamine sulfate released 14 +/- 2% (P less than 0.05), which significantly differed from spontaneous release. This study demonstrates that protamine sulfate causes nonimmunologic histamine release in dispersed human skin mast cells. However, histamine release occurred only at concentrations much greater than those used in clinical practice. Thus, these data do not support the hypothesis that nonimmunologic histamine release is a likely mechanism for protamine-induced hypotension in vivo.


Atrial septal aneurysm with rare comorbid pulmonary arteriovenous malformation as aetiology for cryptogenic stroke.
Atrial septal aneurysms have two mechanisms for cardioembolic events. One is the aneurysm itself can act as a nidus for thrombus formation in the left atrium. The aneurysm creates an area of low turbulence leading to haemostasis allowing fibrin-platelet adhesions to form. If the clot is on the left atrial wall, it may be dislodged by oscillations of the septum and travel into the systemic circulation. The second mechanism is via, an often comorbid, interatrial shunt such as a Patent Foramen Ovale or Atrial Septal Defect. We report a unique case where the associated right to left shunt leading to the cryptogenic stroke is a pulmonary arteriovenous malformation.


[Hypokalemic rhabdomyolysis and tetany as a presentation of celiac disease in an adult].
We describe the case of a 38-year-old man with an hypokalaemic rhabdomyolysis and tetany as a presentation of celiac disease. We discuss the several electrolytic disturbances found in this patient with chronic diarrhoea and malabsorption syndrome and also the treatment which conduced to complete clinical resolution. We conclude that celiac disease should be considered a cause of hypokalaemic rhabdomyolysis.


CD38 and Regulation of the Immune Response Cells in Cancer.
Cancer is a leading cause of death worldwide. Understanding the functional mechanisms associated with metabolic reprogramming, which is a typical feature of cancer cells, is key to effective therapy. CD38, primarily a NAD + glycohydrolase and ADPR cyclase, is a multifunctional transmembrane protein whose abnormal overexpression in a variety of tumor types is associated with cancer progression. It is linked to VEGFR2 mediated angiogenesis and immune suppression as it favors the recruitment of suppressive immune cells like Tregs and myeloid-derived suppressor cells, thus helping immune escape. CD38 is expressed in M1 macrophages and in neutrophil and T cell-mediated immune response and is associated with IFNγ-mediated suppressor activity of immune responses. Targeting CD38 with anti-CD38 monoclonal antibodies in hematological malignancies has shown excellent results. Bearing that in mind, targeting CD38 in other nonhematological cancer types, especially carcinomas, which are of epithelial origin with specific anti-CD38 antibodies alone or in combination with immunomodulatory drugs, is an interesting option that deserves profound consideration.


Automatic method of analysis and measurement of additional parameters of corneal deformation in the Corvis tonometer.
The method for measuring intraocular pressure using the Corvis tonometer provides a sequence of images of corneal deformation. Deformations of the cornea are recorded using the ultra-high-speed Scheimpflug camera. This paper presents a new and reproducible method of analysis of corneal deformation images that allows for automatic measurements of new features, namely new three parameters unavailable in the original software. The images subjected to processing had a resolution of 200 × 576 × 140 pixels. They were acquired from the Corvis tonometer and simulation. In total 14,000 2D images were analysed. The image analysis method proposed by the author automatically detects the edge of the cornea and sclera fragments. For this purpose, new methods of image analysis and processing proposed by the author as well as those well-known, such as Canny filter, binarization, median filtering etc., have been used. The presented algorithms were implemented in Matlab (version 22.214.171.1244-R2010b) with Image Processing toolbox (version 7.1-R2010b) using both known algorithms for image analysis and processing and those proposed by the author. Owing to the proposed algorithm it is possible to determine three parameters: (1) the degree of the corneal reaction relative to the static position; (2) the corneal length changes; (3) the ratio of amplitude changes to the corneal deformation length. The corneal reaction is smaller by about 30.40% compared to its static position. The change in the corneal length during deformation is very small, approximately 1% of its original length. Parameter (3) enables to determine the applanation points with a correlation of 92% compared to the conventional method for calculating corneal flattening areas. The proposed algorithm provides reproducible results fully automatically within a few seconds/per patient using Core i7 processor. Using the proposed algorithm, it is possible to measure new, additional parameters of corneal deformation, which are not available in the original software. The presented analysis method provides three new parameters of the corneal reaction. Detailed clinical studies based on this method will be presented in subsequent papers.


Development and efficacy of a drug-releasing soft contact lens.
The purpose of this study was to investigate the uptake and the release of antibiotics from a newly synthesized drug delivery hydrogel soft contact lens (SCL) using an ion ligand mechanism. The antibiotics used were Gatifloxacin (GFLX) and Moxifloxacin (MFLX). The uptake amount and the sustained-release kinetics of antibiotics were investigated in vitro, and were also compared with newly synthesized SCLs, etafilcon A and polymacon. The antibiotic concentrations in the cornea, aqueous humor, and crystalline lens, and the effect against bacterial proliferation were investigated in vivo using rabbit subjects. Additionally the drug release efficacy of the new SCL was compared with that of eye drop administrations. In vitro, antibiotic uptake was increased with the weight percent (wt%) of the anionic group, and the released amount of antibiotics was highest during the initial 1 hour period, which then decreased over the next 72 hours. The released antibiotics volume of the new SCLs was significantly higher throughout 72 hours than that of the other two materials, etafilcon A and polymacon (P < 0.01). Whereas in vivo, the concentrations found in the cornea and aqueous humor were higher than those for the eye drop groups (P < 0.05 or P < 0.01). Antibiotic release at those sites decreased over 72 hours. No bacterial populations were detectable in the group treated with the new SCL presoaked in antibiotics throughout the experimental periods. The new SCLs released the antibiotics over several days, and showed improved penetration into the eye, along with prevention of bacterial proliferation.


Influence of adrenaline on the dissemination of antibody-producing cells from the spleen.
Plaque-forming cells (PFC) and rosette-forming cells (RFC) were quantificated in splenic venous and splenic arterial blood and in spleen suspensions of guinea-pigs during a secondary immune response to sheep red blood cells (SRBC). The splenic veno-arterial differences in content of PFC and RFC were determined, indicating whether there had been a release of such cells from the spleen into the blood. The effect of an intracardial injection of adrenaline on the release of immune lymphocytes was investigated. In immunized control animals a splenic release of antigen-binding and antibody-forming cells was found, the release being restricted to the peak of the immune response in the spleen. However, after exogenous adrenaline a considerably increased release of both antigen-binding and antibody-forming cells occurred during a longer period of the immune response. Thus, adrenaline caused an enormous release of PFC from the spleen into the blood on day 4 of the secondary immune response, resulting in a diminished number of PFC remaining in the spleen after the treatment. A physiological significance of an adrenaline-induced dissemination of immune lymphocytes in the body during an immune response to a severe infectious disease is suggested.


Endogenous glucocorticoids promote the expansion of myeloid-derived suppressor cells in a murine model of trauma.
Stress-dose of glucocorticoid has been demonstrated to be beneficial for trauma patients in clinical studies. Recently, a heterogeneous population of myeloid cells with immunosuppressive activity named myeloid-derived suppressor cells (MDSCs) has been found to accumulate in the trauma host and can be induced by glucocorticoids in vitro. In order to explore the effect of endogenous glucocorticoids on MDSCs under trauma conditions, we blocked the glucocorticoid signal in a murine trauma model using the antagonist of the glucocorticoid receptor RU486 (mifepristone). We found for the first time that RU486 not only blunted MDSC expansion induced by trauma in the spleen, peripheral blood and bone marrow especially at 6 h after traumatic stress but also decreased the survival rate from 100 to 20% in traumatic mice within 7 days. Moreover, neither MDSCs producing arginase-1 nor the morphological characterization of trauma-induced MDSCs was affected by the blockage of the glucocorticoid receptor. Our results suggest that endogenous glucocorticoids may promote MDSCs expansion in a murine trauma model and MDSCs may be beneficial for the trauma host.


An electromyographic analysis of compartments in cat lateral gastrocnemius muscle during unrestrained locomotion.
Cat lateral gastrocnemius (LG) muscle is composed of four compartments, each of which is supplied by a primary branch of the LG muscle nerve and each of which contains a discrete population of motor units/muscle fiber types. The activation patterns of these different motor-unit populations were examined from recordings made using selective electromyographic (EMG) electrodes, which were carefully placed into the different LG compartments. Recordings were made as the cats stepped overground along a wooden walkway at a variety of different stepping speeds. Electrical activity was correlated with stepping movements using high-speed cinematography. A number of different activation patterns of the different compartments were noted during stepping. In one such pattern, more intense EMG activity was found in distal than proximal compartments at slow stepping speeds, but at moderate to fast stepping speeds the intensity of activity in proximal compartments was equal to or greater than in distal compartments. In other patterns, a less consistent relationship between compartment EMG intensity and stepping speed was observed. These results are generally consistent with an orderly pattern of activation of motor units in the LG during stepping but also indicate that more than one activation pattern exists.


Cu3 MS4 (M=V, Nb, Ta) and its Solid Solutions with Sulvanite Structure for Photocatalytic and Photoelectrochemical H2 Evolution under Visible-Light Irradiation.
Solid solutions with of Cu3 VS4 with either Cu3 NbS4 or Cu3 TaS4 (Cu3 Nb1-x Vx S4 or Cu3 Ta1-x Vx S4 ) were prepared by a solid-state reaction and adopted a sulvanite structure. Their band gaps were 1.6-1.7 eV corresponding to the absorption of a wide range of visible light. Ru cocatalyst-loaded Cu3 MS4 (M=V, Nb, Ta), Cu3 Nb1-x Vx S4 , and Cu3 Ta1-x Vx S4 showed photocatalytic activities for sacrificial H2 evolution under visible-light irradiation. Most solid solutions showed better activities than the single-component Cu3 MS4 (M=V, Nb, Ta). Cu3 MS4 (M=V, Nb), Cu3 Nb1-x Vx S4 , and Cu3 Ta1-x Vx S4 also functioned as photoelectrodes and gave cathodic photocurrents under visible-light irradiation, indicating a p-type semiconductor character. Cu3 Nb0.9 V0.1 S4 showed the best photocatalytic and photoelectrochemical performances. When Ru-loaded Cu3 Nb0.9 V0.1 S4 was used as a photocathode with a CoOx -loaded BiVO4 photoanode, photoelectrochemical water splitting proceeded under simulated sunlight irradiation without an external bias.


Analysis of metal(loid)s contamination and their continuous input in soils around a zinc smelter: Development of methodology and a case study in South Korea.
Soil contamination due to atmospheric deposition of metals originating from smelters is a global environmental problem. A common problem associated with this contamination is the discrimination between anthropic and natural contributions to soil metal concentrations: In this context, we investigated the characteristics of soil contamination in the surrounding area of a world class smelter. We attempted to combine several approaches in order to identify sources of metals in soils and to examine contamination characteristics, such as pollution level, range, and spatial distribution. Soil samples were collected at 100 sites during a field survey and total concentrations of As, Cd, Cr, Cu, Fe, Hg, Ni, Pb, and Zn were analyzed. We conducted a multivariate statistical analysis, and also examined the spatial distribution by 1) identifying the horizontal variation of metals according to particular wind directions and distance from the smelter and 2) drawing a distribution map by means of a GIS tool. As, Cd, Cu, Hg, Pb, and Zn in the soil were found to originate from smelter emissions, and As also originated from other sources such as abandoned mines and waste landfill. Among anthropogenic metals, the horizontal distribution of Cd, Hg, Pb, and Zn according to the downwind direction and distance from the smelter showed a typical feature of atmospheric deposition (regression model: y = y0 + αe-βx). Lithogenic Fe was used as an indicator, and it revealed the continuous input and accumulation of these four elements in the surrounding soils. Our approach was effective in clearly identifying the sources of metals and analyzing their contamination characteristics. We believe this study will provide useful information to future studies on soil pollution by metals around smelters.


Maladaptive Perfectionism and Depression: Testing the Mediating Role of Self-Esteem and Internalized Shame in an Australian Domestic and Asian International University Sample.
To assess whether maladaptive perfectionism (parental and intrapersonal), mediated by self-esteem and internalized shame, lead to depressive symptoms, and to identify whether this model was invariant (i.e., structurally unchanged) across groups of Australian domestic and Asian international students. A total of 624 (308 Australian domestic and 316 Asian international undergraduate university students) completed a questionnaire on the variables of interest. Australian domestic and Asian international students did not significantly differ in reported levels of study variables apart from parental maladaptive perfectionism, on which Australian domestic students scored significantly higher. The proposed path-model differed across student groups, with findings indicating that intrapersonal maladaptive perfectionism impacted indirectly on depressive symptoms through internalized shame in both groups, however, indirectly through self-esteem in only the Asian international student group. Intrapersonal maladaptive perfectionism may be a culturally independent process, capable of predisposing all university students to develop depressive symptoms, but that self-esteem may be a particularly relevant mediator of this relationship among Asian international students.


Paclitaxel as a radiosensitizer combined with fractionated stereotactic radiotherapy in the treatment of recurrent medulloblastoma.
This report describes the treatment of a 39-year-old man with recurrent medulloblastoma previously treated with extensive chemotherapy and radiation therapy. A novel treatment technique combining paclitaxel (275 mg IV bolus) and fractionated stereotactic radiotherapy (30 Gy in six fractions over 3 weeks) was given to palliate the patient's significant neurologic symptoms. The patient experienced a significant improvement both radiographically and in the quality of his life at follow-up 5 months after completion of treatment. No toxicity has been observed. The treatment of medulloblastoma with paclitaxel and fractionated stereotactic radiotherapy, either alone or in combination, merits further investigation.


GPI-anchor deficiency in myeloid cells causes impaired FcgammaR effector functions.
Signaling by transmembrane immunoglobulin G (IgG)-Fc receptors (FcgammaRs) in response to ligand involves association with membrane microdomains that contain glycosyl phosphatidylinositol (GPI)-anchored proteins. Recent in vitro studies showed enhancement of FcgammaR signaling by forced monoclonal antibody-mediated cocrosslinking with various GPI-anchored proteins. Here, the possibility that GPI-anchored proteins are involved in normal physiologic FcgammaR effector functions in response to a model ligand was studied using myeloid-specific GPI-anchor-deficient mice, generated by Cre-loxP conditional targeting. GPI-anchor-deficient primary myeloid cells exhibited normal FcgammaR expression and binding or endocytosis of IgG-immune complexes (IgG-ICs). Strikingly, after stimulation with IgG-ICs, tumor necrosis factor-alpha release, dendritic cell maturation, and antigen presentation were strongly reduced by GPI-anchor deficiency. Tyrosine phosphorylation of the FcR gamma-chain in response to IgG-IC was impaired in GPI-anchor-deficient cells. Myeloid GPI-anchor deficiency resulted in attenuated in vivo inflammatory processes during IgG-IC-mediated alveolitis. This study provides the first genetic evidence for an essential role of GPI-anchored proteins in physiologic FcgammaR effector functions in vitro and in vivo.


On top of cradle cap.
Cradle cap is often viewed as the norm in infancy. It is, however, highly amenable to treatment. While cradle cap generally causes no ill-effects to the newborn baby, new parents may experience disappointment in their attempts to resolve the problem and be distressed by others' response to their infant's appearance. Moisturisers have an important role in softening scale, yet baby oil alone is often not sufficient. Greasier emollients may not be cosmetically acceptable and parental choice can be a key factor in the successful treatment of the problem. Parents may benefit from instructions on how to apply topical treatments effectively, and the opportunity to discuss their anxieties. Good skin care (i.e. the use of emollients) will promote general skin health and reduce any dryness associated with co-existing atopic eczema.


Detaching Microparticles from a Liquid Surface.
The work required to detach microparticles from fluid interfaces depends on the shape of the liquid meniscus. However, measuring the capillary force on a single microparticle and simultaneously imaging the shape of the liquid meniscus has not yet been accomplished. To correlate force and shape, we combined a laser scanning confocal microscope with a colloidal probe setup. While moving a hydrophobic microsphere (radius 5-10 μm) in and out of a 2-5 μm thick glycerol film, we simultaneously measured the force and imaged the shape of the liquid meniscus. In this way we verified the fundamental equations [D. F. James, J. Fluid Mech. 63, 657 (1974)JFLSA70022-112010.1017/S0022112074002126; A. D. Scheludko, A. D. Nikolov, Colloid Polymer Sci. 253, 396 (1975)] that describe the adhesion of particles in flotation, deinking of paper, the stability of Pickering emulsions and particle-stabilized foams. Comparing experimental results with theory showed, however, that the receding contact angle has to be applied, which can be much lower than the static contact angle obtained right after jump in of the particle.


[Presbycusis: neural degeneration and aging on the auditory receptor of C57/BL6J mice].
Presbycusis is a progressive hearing impairment associated with aging, characterized by hearing loss and a degeneration of cochlear structures. In this paper we analyze the effects of aging on the auditory system of C57/BL6J mice, with electrophysiological and morphological studies. With this aim the auditory potentials of mice aging 1, 3, 6, 9, 12, 15, 18, 21 and 24 months were recorded, and then the morphology of the cochleal were analyzed. Auditory potentials revealed an increase in wave latencies, as well as a decrease in their amplitudes during aging. Morphological results showed a total Corti's organ degeneration, being replaced by a flat epithelial layer, and a total absence of hair cells.


The Construction of a Multidomain Risk Model of Alzheimer's Disease and Related Dementias.
Alzheimer's disease (AD) and related dementia (ADRD) risk is affected by multiple dependent risk factors; however, there is no consensus about their relative impact in the development of these disorders. To rank the effects of potentially dependent risk factors and identify an optimal parsimonious set of measures for predicting AD/ADRD risk from a larger pool of potentially correlated predictors. We used diagnosis record, survey, and genetic data from the Health and Retirement Study to assess the relative predictive strength of AD/ADRD risk factors spanning several domains: comorbidities, demographics/socioeconomics, health-related behavior, genetics, and environmental exposure. A modified stepwise-AIC-best-subset blanket algorithm was then used to select an optimal set of predictors. The final predictive model was reduced to 10 features for AD and 19 for ADRD; concordance statistics were about 0.85 for one-year and 0.70 for ten-year follow-up. Depression, arterial hypertension, traumatic brain injury, cerebrovascular diseases, and the APOE4 proxy SNP rs769449 had the strongest individual associations with AD/ADRD risk. AD/ADRD risk-related co-morbidities provide predictive power on par with key genetic vulnerabilities. Results confirm the consensus that circulatory diseases are the main comorbidities associated with AD/ADRD risk and show that clinical diagnosis records outperform comparable self-reported measures in predicting AD/ADRD risk. Model construction algorithms combined with modern data allows researchers to conserve power (especially in the study of disparities where disadvantaged groups are often grossly underrepresented) while accounting for a high proportion of AD/ADRD-risk-related population heterogeneity stemming from multiple domains.


Weinberger adjustment typology and the five factor model of personality.
Construct validity of Weinberger's Six-group Typology of Adjustment was investigated by testing the hypothesis that the six personality types have different personality profiles. The Weinberger Adjustment Inventory and the Revised NEO Personality Inventory were completed by 170 psychology undergraduates (84 men and 86 women). Results strongly supported the tested hypothesis.


Flexion contracture of the elbow due to phlebosclerosis induced by anti-cancer drug infusion.
This case report describes a patient with elbow contracture due to phlebosclerosis induced by anti-cancer drug infusion. Limitation of elbow extension was completely relieved by surgical excision of the sclerotic vein.


Behavioral correlates of the decision process in a dynamic environment: post-choice latencies reflect relative value and choice evaluation.
One characteristic of natural environments is that outcomes vary across time. Animals need to adapt to these environmental changes and adjust their choices accordingly. In this experiment, we investigated the sensitivity with which rats could detect, and adapt to, multiple changes in the environment. Rats chose between two spouts which delivered 5% sucrose rewards with distinct probabilities. Across three phases, reward probabilities changed in size (large or small) and direction (increase or decrease). A discrete trial-structure was used, which allowed the choice process to be decomposed into three distinct response latency measures (choice execution latency, spout sampling duration, and trial-initiation latency). We found that a large decrease in reward probabilities rapidly produced the greatest change in choice proportions. The time taken to execute a choice reflected the differences in reward probabilities across the two spouts in some cases, but also reflected training history. By contrast, the amount of time rats spent responding at reward spouts in anticipation of reward consistently reflected the relative likelihood of reward across the two spouts and not the absolute probability of reward. The latency to initiate the subsequent trial reflected choice evaluation. These three response latencies thus indexed key behavioral correlates of the choice process as it unfolds in time. We discuss how this paradigm can be used to assess the corresponding neural correlates of decision-making.


The Construction of Big Data Computational Intelligence System for E-Government in Cloud Computing Environment and Its Development Impact.
The traditional E-government big data system fills and classifies algorithms with low accuracy and poor work efficiency. With the development and wide application of big data, the internet of things, and other technologies, the integration of information resources has become the key to information construction. In the process of information resource integration, there are still outstanding problems such as incomplete government information resource system, different standards of government information resource management system construction, and serious threats to network and information security. In order to solve this problem, a new E-government big data system filling and classification algorithm is studied in the cloud computing environment; E-government big data filling is carried out on the basis of complete compatibility theory; and the E-government big data computing intelligence system in the cloud computing environment is constructed and its development impact, so as to parallelize the data, classify the data through decision trees, and realize incremental update decision forest parallelization processing. To verify the effectiveness of the method, comparative experiments are set, and the results demonstrate that experiment one is randomly built into the classification model, and according to the decision forest algorithm, the optimal number of decision trees is 24.


Childhood overweight, obesity and associated factors among primary school children in dire dawa, eastern Ethiopia; a cross-sectional study.
Obesity in children is increasing worldwide. Malnutrition has become a double burden challenge of public health concern in developing countries. Childhood obesity increases the risk of chronic disease in childhood as well as adulthood. However, information is very scarce about childhood obesity in developing countries specifically in Ethiopia. Therefore, we aimed to assess childhood overweight, obesity and associated factors among primary school children at Dire Dawa, Eastern Ethiopia. A school based cross-sectional study was conducted in Dire Dawa from 1st to 30th March, 2016. Study participants were selected using multistage sampling method. Pre-tested self-administered questionnaire, face to face interview technique and anthropometric measurements were used to collect data by eight well trained data collectors. Data were coded, cleaned and entered into EpiData software version 3.5.1, and exported into SPSS (version 21.0) statistical software, for data analysis. Bivariate and multivariate logistic regression were carried out to identify associated factors with childhood overweight and obesity. Statistical significance was declared using Adjusted Odds Ratio (AOR) at 95% CI and p-value less than 0.05. The prevalence of overweight and obesity were 14.7% (95% CI: 11.7, 18.0) and 5.8% (95% CI: 3.6, 8.0), respectively. Children who were from private school (AOR = 3.4, 95% CI: 1.4, 8.5), from families belonged to high socioeconomic class (AOR = 16.9, 95% CI: 6.5, 23.9), preferred sweetened foods (AOR = 2.3, 95% CI: 1.1, 5.1), had not engaged in regular physical exercise (AOR = 3.8, 95% CI: 1.5, 9.8), had experienced sedentary life style like spent their free time watching TV (AOR = 3.6, 95% CI: 1.6, 7.9), play computer game (AOR = 4.6, 95% CI:1.4,15.4), and were not having close friends (AOR = 2.9, 95% CI: 1.4, 6.2) were significantly associated with overweight/obesity risk. Overweight/obesity in children is on alarming stage in the study area. Therefore, more attention should be given to creating awareness about healthy diet and improving life style through school and public media in collaboration with concerned bodies.


Subchronic toxicity and anti-HSV-1 activity in experimental animal of dolabelladienetriol from the seaweed, Dictyota pfaffii.
This study examined in rats the subchronic toxicity and anti- HSV-1activity after oral administration of dolabelladienetriol (D1), a diterpene isolated from the seaweed Dictyota pfaffii. In subchronic toxicity (SCT) tests, female rats received D1 by gavage 15 mg/kg/day (n = 5) for 50 days, and general behavior, death, hematological, biochemical and histological changes in the liver, kidney, stomach, and duodenum were determined. For the anti-HSV-1 activity, female mice were infected and treated orally with a dose of 20 mg/kg (n = 5) twice a day with D1 and any lesions in the skin were then recorded for 18 days. Dolabelladienetriol in SCT did not significantly change behavior, body weight, hematological or biochemical profiles. The liver and kidneys, however, showed some alterations in rats treated with D1, similar to those in rats treated with ACV, while the other tissues had no significant changes. The anti-HSV-1 activity of D1 had a similar efficacy to the ACV drug control in mice. Our results showed that D1 has potential commercial development as a new HSV-1drug.


[Extragenital lichen sclerosus et atrophicus: about a case].
Lichen sclerosus et atrophicus is a chronic inflammatory dermatosis, characterized by a specific external genital mucosal tissue tropism. Isolated cutaneous manifestation is rare. We report a case of lichen sclerosus et atrophicus in a woman with purely cutaneous involvement, in order to highlight the importance of evoking this diagnosis in the absence of obvious genital involvement.


REducing Colonoscopies in patients without significant bowEl DiseasE: the RECEDE Study - protocol for a prospective diagnostic accuracy study.
Demand for colonoscopies and CT colonography (CTC) is exceeding capacity in National Health Service Trusts. In many patients colonoscopies and CTCs show no significant bowel disease (SBD). Faecal Immunochemical Testing (FIT) is being introduced to prioritise patients for colonoscopies but is insufficient to identify non-SBD patients meaning colonoscopy and CTC demand remains high. The REducing Colonoscopies in patients without significant bowEl DiseasE (RECEDE) study aims to test urine volatile organic compound (VOC) analysis alongside FIT to improve detection of SBD and to reduce the number of colonoscopies and CTCs. This is a multicentre, prospective diagnostic accuracy study evaluating whether stool FIT plus urine VOC compared with stool FIT alone improves detection of SBD in patients referred for colonoscopy or CTC due to persistent lower gastrointestinal symptoms. To ensure SBD is not missed, the dual test requires a high sensitivity, set at 97% with 95% CI width of 5%. Our assumption is that to achieve this sensitivity requires 200 participants with SBD. Further assuming 19% of all participants will have SBD and 55% of all participants will return both stool and urine samples we will recruit 1915 participants. The thresholds for FIT and VOC results diagnosing SBD have been pre-set. If either FIT or VOC exceeds the respective threshold, the participant will be classed as having suspected SBD. As an exploratory analysis we will be testing different thresholds. The reference comparator will be a complete colonoscopy or CTC. Secondary outcomes will look at optimising the FIT and VOC thresholds for SBD detection. An economic evaluation, using a denovo decision analytic model, will be carried out determine the costs, benefits and overall cost-effectiveness of FIT +VOC vs FIT followed by colonoscopy. Ethical approval was obtained by Liverpool Central Research Ethics Committee (20/NW/0346). RECEDE is registered on Clinicaltrials.gov NCT04516785 & ISRCTN14982373. This protocol was written and published before results of the trial were available.


A Simple Method for Immunohistochemical Staining of Zebrafish Brain Sections for c-fos Protein Expression.
Immediate early genes (IEGs) are transcription factors whose own transcription is initiated rapidly, for example, in the brain in response to environmental stimuli. c-fos is an IEG often used as a marker of neuronal activation. c-fos mRNA expression has started to be quantified and localized in the zebrafish brain following environmental manipulations but analysis of the expression of c-fos protein in the zebrafish brain has rarely been attempted. Here, we describe an immunofluorescence staining method for quantifying c-fos protein expression in different regions of the zebrafish brain. In addition, we expose zebrafish to caffeine, a positive control for c-fos activation in the brain. To confirm cell nucleus specific binding of the c-fos antibody, we counterstained brain sections with the nuclear fluorescent stain DAPI. Furthermore, we describe a method for reducing background autofluorescence often observed in zebrafish brain tissue. Our analysis showed that exposure to caffeine increased the number of c-fos protein-positive cells in specific zebrafish brain regions detected by the immunofluorescence method. Our results demonstrate the feasibility of immunofluorescence-based methods in the analysis of neuronal activation in the zebrafish brain, and reinforce the utility of the zebrafish in behavioral neuroscience research.


Multi-locus phylogeny of southern African Acontias aurantiacus (Peters) subspecies (Scincidae: Acontinae) confirms the presence of three genetically, geographically and morphologically discrete taxa.
Acontias aurantiacus (Peters) presently consists of five subspecies that are largely restricted to the coastal regions and offshore islands of Mozambique and northern South Africa, with subspecies being defined on the basis of morphological differences and/or parapatric distributions. In this study one nuclear (RAG1) and two mitochondrial (cyt b and 16S) genes of 30 individuals sampled from four Mozambican and five South African localities were used to assess the taxonomic relationships of three mainland A. aurantiacus subspecies. Our analyses suggest that A. aurantiacus is a species complex that is sister to A. bicolor (Hewitt), A. cregoi (Boulenger) and A. rieppeli (Sternfeld). Our molecular results support other lines of evidence (consistent morphological differences and parapatric distributions between the subspecies) in suggesting that each of these subspecies are taxonomically distinct. In light of this, and supported by the genetic distances between these subspecies which exceed those of other recognised Acontias species, we propose elevating A. fitzsimonsi (Broadley) and A. parietalis (Broadley) to specific status. Our results further suggest that the melanistic and typically-coloured forms of each taxon are nested within the same clades, supporting previous contentions that melanistic individuals are not cryptic taxa.


Clinical utility of the Structured Observation of Motor Performance in Infants within the child health services.
This study aimed to evaluate the clinical utility of the Structured Observation of Motor Performance in Infants (SOMP-I) when used by nurses in routine child healthcare by analyzing the nurses' SOMP-I assessments and the actions taken when motor problems were suspected. Infants from three child health centers in Uppsala County, Sweden, were consecutively enrolled in a longitudinal study. The 242 infants were assessed using SOMP-I by the nurse responsible for the infant as part of the regular well-child visits at as close to 2, 4, 6 and 10 months of age as possible. The nurses noted actions taken such as giving advice, scheduling an extra follow-up or referring the infant to specialized care. The infants' motor development was reassessed at 18 months of age through review of medical records or parental report. The assessments of level of motor development at 2 and 10 months showed a distribution corresponding to the percentile distribution of the SOMP-I method. Fewer infants than expected were assessed as delayed at 4 and 6 months or deficient in quality at all assessment ages. When an infant was assessed as delayed in level or deficient in quality, the likelihood of the nurse taking actions increased. This increased further if both delay and quality deficit were found at the same assessment or if one or both were found at repeated assessments. The reassessment of the motor development at 18 months did not reveal any missed infants with major motor impairments. The use of SOMP-I appears to demonstrate favorable clinical utility in routine child healthcare as tested here. Child health nurses can assess early motor performance using this standardized assessment method, and using the method appears to support them the clinical decision-making.


Computed tomography in congenital heart disease.
The CT results in defining anatomic and certain physiologic features in patients with congenital heart and great vessel anomalies were reviewed in 32 patients with a variety of congenital cardiac and aortic arch anomalies. Most of these cases (18 patients) were selected on the basis of angiocardiographic or echocardiographic studies performed prior to the CT evaluation. In 14 patients CT was performed as the initial study. All examinations were contrast enhanced and performed on a third generation CT scanner with scan time of 2 or 4 s. The CT demonstration of abnormalities of the great vessels such as positional anomalies, atresias, and hypoplasias was equivalent to angiocardiography and usually superior to two-dimensional echocardiography. The CT results in 14 patients were sufficient to obviate catheterization and angiography; most of these cases were abnormalities of the thoracic aorta. The CT evaluation of intracardiac anatomy was inconsistent. It adequately defined septal defects and configurational (Ebstein anomaly) and bulboventricular loop abnormalities of the ventricles. However, valve anomalies were not adequately demonstrated by CT. The three-dimensional representation of cardiac and mediastinal vascular anatomy provided by this relatively noninvasive technique gives unique information in some cardiovascular anomalies. When faster scanning times are introduced, more definition of the cardiac structures should be possible, further increasing the diagnostic potential of CT.


Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection.
Helicobacter pylori (H. pylori) eradication rates in northern Sardinia using standard 1-wk triple therapies (i.e., a proton pump inhibitor and two antibiotics) are typically <60%, primarily because of antibiotic resistance. The aim of this study was to test b.i.d. quadruple therapy as primary and as salvage therapy in this population. This was a prospective, single center study of consecutive dyspeptic H. pylori-infected patients. Therapy consisted of omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg, all b.i.d. with the midday and evening meals for 14 days. H. pylori status was evaluated by 13C-urea breath test and histology before and 4-6 wk after therapy. Eradication was defined as no positive test. We enrolled 118 consecutive dyspeptic patients (mean age 46 yr; 73 men, including 15 with peptic ulcer disease). Of the patients, 42 (38%) had failed prior therapy: twice in 21 cases, three times in 12, and four or more times in nine. The intention-to-treat cure rate was 95% (110 of 116) (95% CI = 90-98%) overall, and 98% per protocol, irrespective of diagnosis, age, prior treatment failure, or smoking status. Moderate or severe side effects were experienced by only 5% of patients. Bismuth subcitrate-based b.i.d. quadruple therapy was an excellent primary and salvage therapy and should be considered as first line therapy.


The role of interleukin-1 receptor antagonist in the prevention and treatment of disease.
Abstract Interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) play key proinflammatory roles in a variety of human diseases, including rheumatoid arthritis (RA). IL-1 receptor antagonist (IL-1Ra) is a naturally occurring structural variant of IL-1 that competitively inhibits receptor binding of IL-1. Four forms of IL-1Ra have been described: secretory IL-1Ra (sIL-1Ra) and three intracellular molecules (icIL-1Ra1, 2, and 3). Excess amounts of IL-1Ra are necessary to inhibit the biological effects of IL-1. The endogenous production of IL-1Ra plays an anti-inflammatory role, but the level of production of IL-1Ra in inflamed tissues may not be adequate to block IL-1 effectively. An allelic polymorphism in the IL-1Ra gene is associated with a variety of human diseases, largely of epithelial or endothelial cell origin. The disease associated allele IL1RN(*)2 may lead to a decreased production of icIL-1Ra1 by these cells, predisposing the patient to an imbalance in the IL-1 system. The therapeutic administration of IL-1Ra was found to be safe and efficacious in the treatment of RA. Intraarticular delivery of the IL-1Ra cDNA by ex vivo gene therapy in patients with RA was effective in enhancing local IL-1Ra production. This unique form of therapy is under further evaluation.


General chemistry: expanding the learning outcomes and promoting interdisciplinary connections through the use of a semester-long project.
The laboratory component of a first-semester general chemistry course for science majors is described. The laboratory involves a semester-long project undertaken in a small-group format. Students are asked to examine whether plants grown in soil contaminated with lead take up more lead than those grown in uncontaminated soil. They are also asked to examine whether the acidity of the rainwater affects the amount of lead taken up by the plants. Groups are then given considerable independence in the design and implementation of the experiment. Once the seeds are planted, which takes about 4 wk into the term, several shorter experiments are integrated in before it is time to harvest and analyze the plants. The use of a project and small working groups allows for the development of a broader range of learning outcomes than occurs in a "traditional" general chemistry laboratory. The nature of these outcomes and some of the student responses to the laboratory experience are described. This particular project also works well at demonstrating the connections among chemistry, biology, geology, and environmental studies.


Interferon-mediated transcriptional and post-transcriptional modulation of complement gene expression in human monocytes.
The addition of lymphoblastoid interferon alpha, fibroblast interferon beta and recombinant interferon gamma to in vitro monocyte cultures produced dose-dependent increases in transcription rates of the genes encoding the second component of complement (C2), factor B (B) and C1 inhibitor, and the abundance of their respective mRNA. Interferon gamma was the most effective at stimulating transcription of the C1-inhibitor gene whereas interferons alpha and beta were more effective at increasing the transcription of the C2 and B genes. Transcription of the C3 gene was reduced by interferon gamma. None of these cytokines altered the level of transcription of the actin gene. Interferon-induced changes in the levels of transcription of the C2, B and C1-inhibitor genes occurred rapidly, with significant changes occurring within 30 min of exposure to these cytokines. Within 4 h of removal of the interferons from the culture fluid, the level of transcription of the C1-inhibitor, C2, B and C3 genes returned to control values, as did abundance of C2, B and C3 mRNA. However, the abundance of C1-inhibitor mRNA remained elevated in interferon-gamma-treated monocytes. Combinations of interferons produced less than additive effects on the stimulation of the transcription of C2, B and C1-inhibitor genes, whereas measurements of C1-inhibitor mRNA and B mRNA showed that interferon gamma acted synergistically with interferon gamma to increase the abundance of the mRNA. Their effects on C2 mRNA abundance were less than additive. The half-lives of C1-inhibitor, C2, B and C3 mRNA were not altered by interferon alpha, whereas interferon gamma shortened the half-life of C2 mRNA by approximately 50%, and prolonged the half-lives of B and C1-inhibitor mRNA approximately twofold and fivefold, respectively. The half-life of C3 mRNA was unaltered by either interferon. These results show that the large increase in C1-inhibitor synthesis which occurs in interferon-gamma-treated monocytes, is due to a combination of increased transcription and increased C1-inhibitor mRNA stability. They also suggest that the synergistic effects of interferon alpha together with interferon gamma on C1-inhibitor and factor B synthesis is also dependent upon increased transcription and increased mRNA stability.


Microfluidic production of single micrometer-sized hydrogel beads utilizing droplet dissolution in a polar solvent.
In this study, a microfluidic process is proposed for preparing monodisperse micrometer-sized hydrogel beads. This process utilizes non-equilibrium aqueous droplets formed in a polar organic solvent. The water-in-oil droplets of the hydrogel precursor rapidly shrunk owing to the dissolution of water molecules into the continuous phase. The shrunken and condensed droplets were then gelled, resulting in the formation of hydrogel microbeads with sizes significantly smaller than the initial droplet size. This study employed methyl acetate as the polar organic solvent, which can dissolve water at 8%. Two types of monodisperse hydrogel beads-Ca-alginate and chitosan-with sizes of 6-10 μm (coefficient of variation < 6%) were successfully produced. In addition, we obtained hydrogel beads with non-spherical morphologies by controlling the degree of droplet shrinkage at the time of gelation and by adjusting the concentration of the gelation agent. Furthermore, the encapsulation and concentration of DNA molecules within the hydrogel beads were demonstrated. The process presented in this study has great potential to produce small and highly concentrated hydrogel beads that are difficult to obtain by using conventional microfluidic processes.


Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells.
Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis (i.e., osteoblast but not stromal fibroblast proliferation). In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation [( 3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens. Biochemical characterization supported the hypothesis that the PC3 cell growth factor was unique from other growth factors. The PC3 growth factor did not bind to heparin and was resistant to acid as well as the reducing agent, dithiothreitol. Sephadex G-75 and fast protein liquid chromatography Mono S cation-exchange chromatography revealed the PC3-derived mitogen to be an Mr 26,000-30,000 basic protein. Therefore, we conclude that PC3 cells release a mitogen which exhibits higher specificity for human osteoblasts than human fibroblasts and is unique from other growth factors tested. Production of this mitogen by human prostatic carcinoma cells could play an etiological role in the intense osteoblast-specific stimulation that occurs at sites of bone metastases.


Vectorization efforts to increase Gram-negative intracellular drug concentration: a case study on HldE-K inhibitors.
In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their gram-negative intracellular concentration. Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed. While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin. Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies.


The biochemical and histopathological effects of ursodeoxycholic acid and metronidazole on total parenteral nutrition-associated hepatic dysfunction: an experimental study.
Total parenteral nutrition causes many complications such as cholestasis. Ursodeoxycholic acid is used for the treatment of several cholestatic problems. Metronidazole was investigated before for preventing some components of total parenteral nutrition-associated hepatic dysfunction. This study was designed to investigate the effects of ursodeoxycholic acid alone and ursodeoxycholic acid + metronidazole combination on total parenteral nutrition-associated cholestasis. Eighteen rabbits were divided into three groups as follows: group A received a standard formula of total parenteral nutrition only, group B received total parenteral nutrition + ursodeoxycholic acid (3 mg/kg/day), and group C were given total parenteral nutrition + ursodeoxycholic acid + metronidazole (25 mg/kg/day) for eight days, respectively. Several parameters of liver function tests were compared among these groups. These were transaminases, alkaline phosphatase, total bilirubin, total cholesterol, triglycerides, and serum bile acids. Liver histology was detected in each group at the end of the experiment. In group A, total parenteral nutrition administration resulted in remarkably higher serum values of transaminases, alkaline phosphatase, total cholesterol, total bilirubin, triglycerides, and free bile acids whereas ursodeoxycholic acid administration showed important improvements in the serum values of these parameters in group B animals. The metronidazole group showed nearer or similar laboratory values with group B, but significant differences appeared in bilirubin values (P < 0.05) among these groups. Liver histology presented marked differences between group A and group B. Steatosis formed the main component of liver histology in 4 animals out of 6 in group A. Contrary to this, all of the specimens showed normal liver structure except one in group B. In the third group we did not see better morphology than in group B. These results suggested that oral ursodeoxycholic acid therapy during total parenteral nutrition reduces bilirubin levels and improves the other indicators of cholestasis and helps prevent disturbances of liver histology. When it is combined with metronidazole a significant decrease in bilirubin levels has been gained. With the help of ursodeoxycholic acid we can provide enterohepatic circulation of bile acids and regulate lipid metabolism. Metronidazole can be an antibiotic of choice during total parenteral nutrition when needed.


A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells.
Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and the development of drug resistance after a first platinum-based regimen. The presence of a specific population of "cancer stem cells" could be responsible of the relapse of the tumor and the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy. We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them. Interestingly, there were compounds active only on stem cells, only on differentiated cells, and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.


A "tilt" toward cinefluoroscopy.
Fluoroscopy permits rapid and straightforward assessment of mechanical valve function and allows a distinction between normal and malfunctional prostheses, acting as a complementary diagnostic step.


Neither the New Zealand genetically hypertensive strain nor Dahl salt-sensitive strain has an A1079T transversion in the alpha1 isoform of the Na(+),K(+)-ATPase gene.
A putative 1079A-->T mutation in the alpha1 isoform of the Na(+), K(+)-ATPase (Atp1a1) gene of the Dahl salt-sensitive rat inbred by John Rapp (SS/Jr) strain was projected to cause a conformation change in the membrane hydrophobic region of the protein product, possibly resulting in hypertension. The existence of the mutation was challenged, but the challenge was apparently rebutted. The New Zealand genetically hypertensive (GH) rat is known to have a blood pressure quantitative trait locus on chromosome 2 containing the gene for the ATPase. Thus, we sought to determine whether the GH rat carried the 1079A-->T transversion. We chose a method, first nucleotide change analysis, that can detect point mutations in a mixed population of polymerase chain reaction (PCR) products, even in the presence of PCR bias, and confirmed our analysis by restriction enzyme digestion of PCR products. To ensure the validity of our analyses, we used site-directed mutagenesis to create positive controls containing the mutation. Surprisingly, we found that neither the GH nor the SS/Jr strain had the A1079T transversion. Indeed, the transversion was not found in any strain tested. As an incidental observation, we have sequenced the intron preceding the exon containing the putative A1079T transversion. Within this intron, a single-base C/T polymorphism was observed at base 132. Our results definitively eliminate the putative A1079T transversion in Atp1a1 as a causative factor underlying hypertension in the GH, spontaneously hypertensive, and SS/Jr rat strains and indicate that alternative candidate genes in the region defined by the chromosome 2 hypertension quantitative trait locus should be examined.


Potential central nervous system antitumor agents. Hydantoin derivatives.
Hydantoin derivatives of varying lipophilic character were prepared as nitrogen mustard carriers for CNS antitumor evaluation. Activity was studied in the murine ependymoblastoma brain tumor system. Multiple cures were observed for three of the four analogs examined. The compounds were also active in the intraperitoneal leukemia L1210 and P388 systems as well as in B16 melanoma and Lewis lung carcinoma.


Nanopatterned Adhesive, Stretchable Hydrogel to Control Ligand Spacing and Regulate Cell Spreading and Migration.
Spatial molecular patterning enables the regulation of adhesion receptor clustering and can thus play a pivotal role in multiple biological activities such as cell adhesion, viability, proliferation, and differentiation. A wide range of nanopatterned, adhesive interfaces have been designed to decipher the essence of molecular-scale interactions between cells and the adhesive interface. Although an interligand spacing of less than 70 nm is a proven prerequisite for the formation of stable focal adhesions, there is a paucity of data concerning how cells behave on substrates featuring heterogeneous adhesiveness. In this study, a stretchable hydrogel functionalized with a quasi-hexagonally arranged nanoarray was stretched along one direction, resulting in ligands periodically arranged in a pattern resembling a centered rectangular lattice with an interligand spacing smaller than 70 nm in one direction and greater than 70 nm in the orthogonal direction. This substrate was utilized to modulate interligand spacing and investigate cell adhesion and migration. An interligand spacing larger than 70 nm-even in just one direction-prevented the establishment of stable focal adhesions. The stretched interface promoted dynamic remodeling at cell contacts, resulting in higher cellular mobility. Our nanopatterned stretchable hydrogel permits reversible control over cell adhesion and migration on nanopatterned ligand interfaces.


Estimating bradykinesia severity in Parkinson's disease by analysing gait through a waist-worn sensor.
Bradykinesia is a cardinal symptom of Parkinson's disease (PD) and describes the slowness of movement revealed in patients. Current PD therapies are based on dopamine replacement, and given that bradykinesia is the symptom that best correlates with the dopaminergic deficiency, the knowledge of its fluctuations may be useful in the diagnosis, treatment and better understanding of the disease progression. This paper evaluates a machine learning method that analyses the signals provided by a triaxial accelerometer placed on the waist of PD patients in order to automatically assess bradykinetic gait unobtrusively. This method employs Support Vector Machines to determine those parts of the signals corresponding to gait. The frequency content of strides is then used to determine bradykinetic walking bouts and to estimate bradykinesia severity based on an epsilon-Support Vector Regression model. The method is validated in 12 PD patients, which leads to two main conclusions. Firstly, the frequency content of the strides allows for the dichotomic detection of bradykinesia with an accuracy higher than 90%. This process requires the use of a patient-dependant threshold that is estimated based on a leave-one-patient-out regression model. Secondly, bradykinesia severity measured through UPDRS scores is approximated by means of a regression model with errors below 10%. Although the method has to be further validated in more patients, results obtained suggest that the presented approach can be successfully used to rate bradykinesia in the daily life of PD patients unobtrusively.


Assessing the application of an additive model to estimate toxicity of a complex effluent.
A number of industries monitor levels of chemicals in their effluent, but few have undertaken prolonged biological monitoring of this wastewater. The focus of the present study was to determine whether past chemical data for effluent from a lead smelter could be used to estimate its past toxicity. Since the interactive effects of metals in effluents are often assumed to be additive, it was hypothesized that an additive model, 100/[sigma(metal concentration in effluent/EC50 for individual metal)], could be used to generate an EC50 from chemical data (where EC50 is the concentration of test material that affects 50% of the test organisms). To test the approach, a larval development toxicity test with the marine polychaete, Galeolaria caespitosa, was used to test 26 separate samples of effluent from a lead smelter, generating empirical EC50 values. EC50 values for each individual metal in the effluent were also generated using the larval development toxicity test. The concentrations of trace metals in each effluent sample were determined and, using the additive model, EC50 values were calculated. For the majority of effluent samples tested, the additive model underestimated toxicity, suggesting the presence of additional unidentified contaminants in the effluent samples. Additionally, a nonlinear rather than linear regression curve was found to best describe the relationship between the model and empirically derived EC50 values. This relationship was then used to estimate past trends in toxicity of the smelter effluent. Forty-eight percent of the variability in measured toxicity was explained by the model, with the model underestimating toxicity in the majority of samples.


Cost containment and labor-intensive tests. The case of the leukocyte differential count.
We conducted an analysis of the use of the leukocyte differential count to determine (1) the services ordering the largest numbers of tests, (2) the proportion of differentials that were clinically justifiable and useful, and (3) the potential for real cost savings as opposed to reduction in charges if unjustified differentials could be eliminated. The sources of all laboratory requisitions during three nonconsecutive weeks were determined; criteria for test justifiability were established; an audit of a random sample of medical records was conducted on two services obtaining the most tests; and a time-motion study was undertaken in the hospital hematology laboratory. Forty-seven percent of differentials were obtained on medical and surgical inpatients and only 10% in the medical clinics. Forty-eight percent and 62% of differentials on the medical and surgical services, respectively, were unjustifiable , making up 26% of all differentials done in the hospital laboratory. Test results appear to have affected patient management in less than 3% of patients; no unjustified test altered a patient's diagnosis or therapy. Elimination of only "unjustified" medical and surgical differentials would permit a reduction of 1.8 full-time equivalent positions from the hospital laboratory. The leukocyte differential is over-used, only occasionally useful, and amenable to real cost reduction.


Safety in Japanese Advanced Breast Cancer Patients Who Received Abemaciclib in MONARCH 2 and MONARCH 3: Assessment of Treatment-Emergent Neutropenia, Diarrhea, and Increased Alanine Aminotransferase and Aspartate Aminotransferase Levels.
Our objective was to gain a better understanding of the safety of abemaciclib in Japanese patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Treatment-emergent adverse events (TEAEs) were assessed in pooled Japanese subpopulation data from two phase 3 studies assessing abemaciclib/placebo in combination with fulvestrant (MONARCH 2; M2) or non-steroidal aromatase inhibitors (MONARCH 3; M3). For common, clinically relevant TEAEs, event characteristics and management were summarized by study. In the Japanese safety subpopulation (abemaciclib: N=101; placebo: N=46), all patients experienced ≥1 TEAE (Grade ≥ 3: abemaciclib, 71.3%; placebo, 23.9%; no Grade 5). Clinically relevant TEAEs that were more frequent in abemaciclib-treated Japanese patients compared to the overall safety populations included diarrhea (any grade, 95.0%; Grade ≥ 3, 12.9%), neutropenia (any grade, 75.2%; Grade 3-4, 35.6%), increased alanine aminotransferase (ALT; any grade, 39.6%; Grade 3-4, 14.9%), and increased aspartate aminotransferase (AST; any grade, 37.6%; Grade 3-4, 8.9%). Diarrhea was Grade ≤3 and successfully managed with medications (≥87%) and dose reductions (≤25%) and/or omissions (≤23.3%). Most Grade ≥2 diarrhea occurred in the first treatment cycle, declining thereafter. Neutropenia, the most common Grade ≥3 TEAE in abemaciclib-treated Japanese patients, was generally manageable with dose omissions (M2: 42.0%; M3: 23.1%) and/or reductions (M2: 16%; M3: 15.4%). Neutrophil counts plateaued after Cycle 2, recovering to pretreatment levels after discontinuation of abemaciclib. Hepatic events were managed with medication (≤21%) and dose adjustments (≤33.3%), with most Grade ≥2 events occurring in early treatment cycles. Discontinuation of any study treatment in Japanese patients occurred more frequently due to increased ALT/AST (M2: 9.1%/10.5%; M3: 16.7%/10.5%) compared with diarrhea (M2: 0%; M3: 2.8%) or neutropenia (M2: 0%; M3: 3.8%). Abemaciclib was well tolerated in Japanese patients in MONARCH 2 and MONARCH 3, with common, clinically relevant TEAEs manageable with appropriate interventions.


Do Finite-Size Lyapunov Exponents detect coherent structures?
Ridges of the Finite-Size Lyapunov Exponent (FSLE) field have been used as indicators of hyperbolic Lagrangian Coherent Structures (LCSs). A rigorous mathematical link between the FSLE and LCSs, however, has been missing. Here, we prove that an FSLE ridge satisfying certain conditions does signal a nearby ridge of some Finite-Time Lyapunov Exponent (FTLE) field, which in turn indicates a hyperbolic LCS under further conditions. Other FSLE ridges violating our conditions, however, are seen to be false positives for LCSs. We also find further limitations of the FSLE in Lagrangian coherence detection, including ill-posedness, artificial jump-discontinuities, and sensitivity with respect to the computational time step.


The role of the gastric mucosal sulfhydryls in the ulcer-protecting effects of sulphasalazine.
The role of gastric mucosal sulfhydryls in gastric ulceration, produced by restraint at 4 degrees C (stress) for 2 h, and in the ulcer-protecting effects of sulphasalazine and its constituents (sulphapyridine and 5-aminosalicylic acid), have been studied in rats. Stress significantly raised the mucosal sulphydryl content, but sulphasalazine and sulphapyridine did not influence these changes; only 5-aminosalicylic acid decreased the mucosal sulphydryl concentration. These results indicate that depletion of mucosal sulfhydryls does not occur in stress-induced ulceration, in contrast to what has been shown in other experimental ulcer models. The antiulcer effects of sulphasalazine or of any of its constituents may, therefore, not involve the sulphydryl mechanism.


Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs.
Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p < 0.01). IAPCs produced more PTN than MK (p < 0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p < 0.05) and in MDDCs by TLRs 7/8 (p < 0.05). TLR4 induced a stronger MK production than NAS TLRs (p ≤ 0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p < 0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering.


Improving visible light OCT of the human retina with rapid spectral shaping and axial tracking.
Visible light optical coherence tomography (OCT) theoretically provides finer axial resolution than near-infrared OCT for a given wavelength bandwidth. To realize this potential in the human retina in vivo, the unique technical challenges of visible light OCT must be addressed. We introduce three advances to further the performance of visible light OCT in the human retina. First, we incorporate a grating light valve spatial light modulator (GLV-SLM) spectral shaping stage to modify the source spectrum. This enables comfortable subject alignment with a red light spectrum, and image acquisition with a broad "white light" spectrum, shaped to minimize sidelobes. Second, we develop a novel, Fourier transform-free, software axial motion tracking algorithm with fast, magnetically actuated stage to maintain near-optimal axial resolution and sensitivity in the presence of eye motion. Third, we implement spatially dependent numerical dispersion compensation for the first time in the human eye in vivo. In vivo human retinal OCT images clearly show that the inner plexiform layer consists of 3 hyper-reflective bands and 2 hypo-reflective bands, corresponding with the standard anatomical division of the IPL. Wavelength-dependent images of the outer retina suggest that, beyond merely improving the axial resolution, shorter wavelength visible light may also provide unique advantages for visualizing Bruch's membrane.


Spectrophotometric determination of isopropamide iodide and trifluoperazine hydrochloride in presence of trifluoperazine oxidative degradate.
Four sensitive, selective and precise stability indicating methods for the determination of isopropamide iodide (ISO) and trifluoperazine hydrochloride (TPZ) in their binary mixture and in presence of trifluoperazine oxidative degradate (OXD). Method A is a derivative spectrophotometric one, where ISO was determined by first derivative (D(1)) at 226.4 nm while TPZ was determined by second derivative (D(2)) at 270.2 nm. Method B is the first derivative of the ratio spectra (DD(1)) spectrophotometric method, ISO can be determined by measuring the peak amplitude at 227.4 nm using 5 microg mL(-1) of OXD as a divisor, while TPZ can be determined by measuring the peak amplitude at 249.2 and 261.4 nm using 15 microg mL(-1) of ISO as a divisor. Method C is the isoabsorptive spectrophotometric method. This method allows determination of ISO and TPZ in their binary mixture by measuring total concentration of ISO and TPZ at their isoabsorptive point at lambda(229.8) nm (Aiso1) while TPZ concentration alone can be determined at lambda(max) 311.2 nm, then ISO concentration can be determined by subtraction. On the same basis TPZ can be determined in presence of ISO and OXD, where OXD concentration alone was determined by measuring the peak amplitude at lambda(281.6) and lambda(309.4) nm while total concentration of TPZ and OXD was determined at their isoabsorptive points at (Aiso2 = 270.2 nm), (Aiso3 = 310.6 nm) and (Aiso4 = 331.8 nm) then TPZ concentration was determined by subtraction. Method D is the multivariate calibration techniques [the classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS)], using the information contained in the absorption spectra of ISO, TPZ and OXD mixtures. The selectivity of the proposed methods was checked using laboratory prepared mixtures. The proposed methods have been successfully applied to the analysis of ISO and TPZ in pharmaceutical dosage form without interference from other dosage form additives and the results were statistically compared with the reported method.


Bronchiolitis: A Practical Approach for the General Radiologist.
Radiologists consciously or unconsciously encounter bronchiolitis on images frequently. The purpose of this article is to simplify the concept of bronchiolitis to facilitate the formulation of a succinct and accurate differential diagnosis and suggest potential causes for the imaging findings. Direct and indirect signs of bronchiolitis that are seen on computed tomographic images are detailed. The most common causes of bronchiolitis are covered, including several distinct entities to be considered in specific clinical scenarios. In order of prevalence, the top two causes of bronchiolitis are infection and aspiration. Less common entities include respiratory bronchiolitis and hypersensitivity pneumonitis, which tend to manifest with ground-glass centrilobular nodules. Some types of bronchiolitis affect specific ethnic groups or are associated with a characteristic clinical history. For example, diffuse panbronchiolitis typically affects Japanese subjects. Constrictive bronchiolitis should be considered in lung transplant recipients with ongoing rejection. Given the high frequency of bronchiolitis, radiologists should develop a systematic approach to both cellular and constrictive bronchiolitis. Recognition of specific clinical or imaging characteristics may be sufficient for providing a relevant differential diagnosis. ©RSNA, 2017.


Silicosis in mice: effects of dose, time, and genetic strain.
Experimental silicosis allows study of the mechanisms of lung injury, inflammation, and fibrosis. Inbred mice are an attractive species in which to study these mechanisms because of recent progress in murine immunology, molecular biology, and genetics. We exposed mice to an aerosol of silica and examined the effects of exposure dose, the evolution of disease features over time, and the variation in responses among four inbred strains. In C3H/HeN mice incremental cumulative exposure doses of cristobalite silica caused increased initial lung dust burden 12 to 16 weeks post-exposure, progressively intense pathological responses, and increased total lung collagen (hydroxyproline). The histopathological changes and total lung collagen increased progressively over time after exposure. We compared the features of silicosis in four strains of inbred mice selected for common use or immunologic reactivity 16 weeks after aerosol inhalation exposure to crystalline cristobalite silica (70 mg/m3, 5 hours/day, 12 days). C3H/HeN mice demonstrated histopathological silicotic lesions and enlarged intrapulmonary lymphoid tissue, and increased lung wet weight, bronchoalveolar lavage (BAL) recovery of macrophages, lymphocytes, and neutrophils, and total lung collagen (hydroxyproline). BALB/c mice developed slight pulmonary lesions; MRL/MpJ mice demonstrated prominent pulmonary infiltrates with lymphocytes; New Zealand Black mice developed extensive alveolar proteinaceous deposits, inflammation, and fibrosis. Our findings demonstrate orderly dose-time-response relationships, and a substantial variation of responses among inbred strains of mice. This model should prove valuable for future experimental interventions into the mechanisms of silicosis.


Elevated birth defects in racial or ethnic minority children of women living near hazardous waste sites.
This case-control study evaluated the relationship between birth defects in racial or ethnic minority children born during 1983-1988 and the potential exposure of their mothers to contaminants at hazardous waste sites in California. Four categories of race or ethnicity were used: black/African American, Hispanic/Latino, American Indian/Alaska Native, and Asian/Pacific Islander. Case subjects were 13,938 minority infants with major structural birth defects (identified by the California Birth Defects Monitoring Program) whose mothers resided in selected counties at the time of delivery. The control group was composed of 14,463 minority infants without birth defects who were randomly selected from the same birth cohort as the case subjects. The potential for exposure was determined by whether the mother resided at the time of delivery in the same census tract as a hazardous waste site that was on the U.S. Environmental Protection Agency's National Priorities List (NPL). Racial/ethnic minority infants whose mothers had been potentially exposed to hazardous waste were at slightly increased risk for birth defects (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 0.98-1.27) than were racial/ethnic minority infants whose mothers had not been potentially exposed. The greatest association was between potential exposure and neural tube defects (OR = 1.54, 95% CI = 0.93-2.55), particularly anencephaly (OR = 1.85, 95% CI = 0.91-3.75). The strongest association between birth defects and potential exposure was among American Indians/Alaska Natives (OR = 1.19, 95% CI = 0.62-2.27). Despite the limitations of this study, the consistency of these findings with previous studies suggests an association between environmental risk factors and birth defects. This is particularly relevant to minority populations. We recommend further investigation of birth defects among minority communities, particularly among American Indians/Alaska Natives. Special attention should also be paid to those defects and contaminants that consistently are associated with exposure to hazardous waste.


Kinetic and thermodynamic analysis of triplex formation between peptide nucleic acid and double-stranded RNA.
Kinetics and thermodynamics of triplex formation between 9-mer homopyrimidine PNA (H2N-Lys-TCTCCTCCC-CONH2) and double-stranded RNA (dsRNA, 5'-AGAGGAGGG-3'/3'-UCUCCUCCC-5') at acidic pH were studied by means of a stopped-flow technique and isothermal titration calorimetry (ITC). These results revealed the following main findings: (i) the stable PNA-dsRNA triplex formation mostly originated from the large association rate constant (kon), which was dominated by both the charge neutral PNA backbone and the protonation level of the PNA cytosine. (ii) The temperature dependence of the enthalpy change (ΔH) and kon suggested that the association phase of the PNA-dsRNA triplex formation comprised a non-directional nucleation-zipping mechanism that was coupled with the conformational transition of the unbound PNA. (iii) The destabilization by a mismatch in the dsRNA sequence mainly resulted from the decreased magnitude of both kon and ΔH. (iv) There was sequence and position dependence of the mismatch on ΔH and the activation energy (Eon), which illustrated the importance of base pairing in the middle of the sequence. Our results for the first time revealed an association mechanism for the PNA-dsRNA triplex formation. A set of the kinetic and thermodynamic data we reported here will also expand the scope of understanding for nucleic acid recognition by PNA.


Shared genetic determinant of axial length, anterior chamber depth, and angle opening distance: the Guangzhou Twin Eye Study.
To estimate the extent to which common genetic and environmental effects contribute to covariances among axial length, anterior chamber depth, and angle-opening distance. The study participants were recruited from the Guangzhou Twin Registry. Anterior segment optical coherence tomography and custom software were used to quantify the angle opening distance (AOD) at the location 500 microm anterior to the scleral spur. Anterior chamber depth (ACD) and axial length (AL) were measured using laser interferometry. Cross-trait, cross-twin correlations for monozygotic (MZ) and dizygotic (DZ) twins and the Cholesky model were used to quantify shared genetic and environmental effects for AL, ACD, and AOD after adjusting for age and sex. A group of 459 pairs of twins (304 MZ and 155 DZ) aged 8 to 16 years were available for analysis. The phenotypic correlations among AL, ACD, and AOD ranged from 0.39 to 0.64. Cross-twin, cross-trait correlations for these three phenotypes for MZ twins were consistently greater than the corresponding correlations for DZ twins. The results of the Cholesky model-fitting analyses can be summarized as follows: first, of 70% of additive genetic factors for AOD, 23% and 13% were those shared with ACD and AL, respectively, whereas the remaining 34% were those unique to AOD. Second, of 89% of additive genetic factors for ACD, 25% were those shared with AL, whereas 64% were those unique to ACD. Third, random environmental influences on covariances among AL, ACD, and AOD were very small. Analyses of Chinese children twin data suggest that shared genes are responsible for the significant phenotypic correlations found for AL ACD, and AOD.


An eight-degree-of-freedom quantum dynamics study of the isotopic effect on the reaction: HD+C(2)H.
An eight-dimensional time-dependent quantum dynamics calculation is reported to study the isotopic reaction, HD+C(2)H, on a new modified potential energy surface. Initial-state-selected reaction probability, integral cross section, and rate constants are presented in this isotopic reaction study. Initial-state-selected reaction probability is obtained by summing over all the possible product's arrangements in this isotopic reaction study. This study shows that vibrational excitations of HD enhance the reactivity, whereas stretching excitations of C(2)H only have a small effect on the reactivity. Furthermore, the bending excitations of C(2)H, compared to the ground-state reaction probability, hinder the reactivity. The present results are consistent with those obtained for the H(2)+C(2)H reaction. The comparison of these two reactions also shows the isotopic effect in the initial-state-selected reaction probability, integral cross section, and rate constants. The rate constant comparison shows that the HD+C(2)H reaction has a smaller reactivity than the H(2)+C(2)H reaction.


Preparation and characterization of a collagen/chitosan/heparin matrix for an implantable bioartificial liver.
A new type of collagen/chitosan/heparin matrix, fabricated by gelation of collagen/ chitosan with heparin sodium containing ammonia, was produced to construct livers by tissue engineering and regenerative engineering. The obtained collagen/chitosan/heparin matrix was found to be highly porous, swelled rapidly in PBS solution and was stable in vitro for at least 60 days in collagenase/lysozyme containing buffered aqueous solution (PBS, pH 7.4) at 37 degrees C. The collagen/chitosan/heparin matrix resulted in a superior blood compatibility compared to the ammonia-treated collagen and collagen/chitosan matrices. The morphology and behavior of the cells on the collagen/chitosan/heparin membrane were found to be similar to those on the collagen membrane but different from those on the collagen/chitosan membrane. Hepatocytes cultured on the collagen/chitosan/heparin matrices exhibited highest urea and triglyceride secretion functions 25 days post seeding. These results suggest that this collagen/chitosan/heparin matrix is a potential candidate for liver tissue engineering.


Autophagy impacts on oxaliplatin-induced hepatocarcinoma apoptosis via the IL-17/IL-17R-JAK2/STAT3 signaling pathway.
The interleukin (IL)-17/IL-17 receptor (IL-17R) complex has been shown to be important for the regulation of inflammation; however, its role in the regulation of tumor processes has recently emerged as a research focus. The present study demonstrated that oxaliplatin was able to increase the levels of IL-17/IL-17R in hepatocellular carcinoma (HCC) patients and cells lines, and that it had important roles in reducing the susceptibility of the cells to oxaliplatin-induced apoptosis. Furthermore, the expression of autophagy-related proteins was induced by IL-17/IL-17R and autophagy was shown to induce resistance to oxaliplatin in HCC. In addition, the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway was shown to be an important pathway in the induction of autophagy in response to oxaliplatin. Autopjhagy was inhibited by 3-methyladenine and JAK2/STAT3 signaling was blocked by AG490, which induced apoptosis in SMMC7721 cells treated with oxaliplatin. The results of the present study may help to elucidate the mechanism underlying the role of IL-17/IL-17R-induced autophagy in the chemoresistance of HCC, as well as help to establish and develop measures to overcome chemoresistance in HCC.