Original Research: Patient Perception of Fall Risk in the Acute Care Setting.
Hospitals are implementing a variety of fall prevention programs to reduce the fall rates of hospitalized patients. But if patients don't perceive themselves to be at risk for falling and don't adhere to fall prevention strategies, such programs are likely to be less effective. The purpose of this study was to describe the perceptions of fall risk among hospitalized patients across four acute care specialty services. One hundred patients who had been admitted to the study hospital and who had a Morse Fall Scale score over 45 were asked to complete the Patient Perception Questionnaire, a tool designed to explore a patient's confidence regarding their fall risk, fear of falling, and intention to engage in fall prevention activities. Morse Fall Scale scores were collected via retrospective chart review. Data were analyzed using descriptive statistics, Pearson correlation coefficients, and independent sample t tests. Participants' mean age was 65 years; 52% were male, 48% female. Although all 100 participants were deemed at risk for falls per their Morse Fall Scale scores, only 55% considered themselves to be at such risk. As patients' confidence in their ability to perform mobility tasks increased, their intention to ask for help and fear of falling significantly decreased. Patients who had been admitted as the result of a fall demonstrated significantly lower confidence scores and higher fear scores. Patients who score high on fall risk assessments often don't perceive themselves to be at high risk for falling, and thus might not engage in fall prevention activities. Developing a fall risk assessment method that incorporates both a patient's physiological condition and their perception of their fall risk could help reduce fall rates in the acute care setting.


Fabrication of biporous low-crystalline apatite based on mannitol dissolution from apatite cement.
Biporous (macro- and microporous) calcium phosphate gains much attention as a bone substitute material because of its large surface area and that it improves cell penetration. In the present study, we evaluated the feasibility of biporous, low-crystalline apatite based on dissolution of mannitol from self-setting apatite cement (Biopex). Mannitol--known as a biocompatible, easily dissolved monosaccharide alcohol--was recrystallized to obtain larger crystals. It was crushed with pestle and mortar, sieved to obtain crystals which passed through a 500-microm mesh but which remained against a 300-microm mesh, and then used as porogen. Although Biopex containing 60 wt% mannitol was not able to be taken out of the mold, addition of mannitol caused no initial setting inhibition to Biopex if the amount was 40 wt% or less. Similarly, transformation to apatitic product was confirmed when the apatite cement was immersed in 0.9% saline kept at 37 degrees C for seven days. The set mass became low-crystalline, biporous apatite with approximately 60% porosity.


A critical review on recent advancements of the removal of reactive dyes from dyehouse effluent by ion-exchange adsorbents.
The effluent discharged by the textile dyehouses has a seriously detrimental effect on the aquatic environment. Some dyestuffs produce toxic decomposition products and the metal complex dyes release toxic heavy metals to watercourses. Of the dyes used in the textile industry, effluents containing reactive dyes are the most difficult to treat because of their high water-solubility and poor absorption into the fibers. A range of treatments has been investigated for the decolorization of textile effluent and the adsorption seems to be one of the cheapest, effective and convenient treatments. In this review, the adsorbents investigated in the last decade for the treatment of textile effluent containing reactive dyes including modified clays, biomasses, chitin and its derivatives, and magnetic ion-exchanging particles have been critically reviewed and their reactive dye binding capacities have been compiled and compared. Moreover, the dye binding mechanism, dye sorption isotherm models and also the merits/demerits of various adsorbents are discussed. This review also includes the current challenges and the future directions for the development of adsorbents that meet these challenges. The adsorption capacities of adsorbents depend on various factors, such as the chemical structures of dyes, the ionic property, surface area, porosity of the adsorbents, and the operating conditions. It is evident from the literature survey that decolorization by the adsorption shows a great promise for the removal of color from dyehouse effluent. If biomasses want to compete with the established ion-exchange resins and activated carbon, their dye binding capacity will need to be substantially improved.


Femtosecond-assisted descemet stripping automated endothelial keratoplasty with fibrin glue-assisted sutureless posterior chamber lens implantation.
We report a surgical technique for managing postsurgical aphakia with endothelial decompensation. The technique comprises femtosecond laser-assisted Descemet stripping automated endothelial keratoplasty (DSAEK) with fibrin glue-assisted sutureless posterior chamber intraocular lens (IOL) implantation-"glued IOL". Three eyes (of 3 patients) underwent the technique. The donor lenticules were created on a 60-kHz femtosecond laser platform (Intralase; Abott Medical Optics, Santa Ana, CA). Two partial-thickness scleral flaps and sclerotomies were made in host. After this, the Descemet was scored and stripped. A 3-piece 6.5-mm posterior chamber IOL was inserted, and its haptics were externalized through the sclerotomies. The haptics were then tucked into intrascleral pockets. The donor lenticule was inserted into the anterior chamber and unfolded. Air tamponade and pull suture manipulations were used to stabilize and center it. The partial-thickness scleral flaps were apposed with fibrin glue. The uncorrected and best-corrected visual acuities improved in all cases. There were no donor dislocations. The average donor endothelial cell loss was 27.7% at 6 months. Our series suggests that there is a benefit of glued IOL with DSAEK in such scenarios. It also has potential benefits as a combined procedure with DSAEK in comparison to anterior chamber IOL because it does not reduce the anterior chamber volume, does not require intact iris tissue, and unlike suture-fixated IOL, does not have knot slippage or pseudophakodonesis.


[Injury of Medial Structures in Ankle Fractures - Epidemiological Aspects and Outcomes of Treatment].
PURPOSE OF THE STUDY Ankle fractures are characterised by a high variability of damage to bone and ligament structures which leads to diverse clinical conditions. This study aims to analyse a group of patients with surgically treated ankle fractures, with a focus on evaluating the outcomes of treatment of ankle joint medial structure injuries (medial malleolar fracture, ligament lesions). MATERIAL AND METHODS The analysed group included 186 patients (102 men and 84 women), in whom an ankle fracture surgery was performed in 2015 and 2016. The outcomes of the treatment were evaluated in 111 patients with type B and type C fractures, who underwent a follow-up examination at one year after the surgery consisting in subjective and objective assessment of the condition and an ankle radiograph. The obtained outcomes were processed using the techniques of descriptive statistics and subsequently evaluated through the Pearson´s chi-square test at 5% significance level, or the Fisher´s exact test for low frequencies. RESULTS The mean age of patients in the group was 48.6 years, while it was lower in men than in women (42.8 years compared to 53.9 years). According to Weber classification, 1 % of fractures were classified as a type A fracture, 68 % as a type B, 27 % as a type C. The group of isolated medial malleolar fractures represented 4 % of cases. The medial side of the ankle joint more frequently suffered a ligament lesion (56 %) than a medial malleolar fracture (44 %). The mean age of the patients with a medial malleolar fracture was 51.9 years, whereas the mean age of the patients with a ligament lesion on the medial side of the ankle was 44.2 years. When evaluating the outcomes using the OMA score at one year postoperatively, a statistically significant difference was found (p = 0.002) between the patients with a medial malleolar fracture (OMA 79.9) and the patients with a ligament lesion at the medial side of the ankle joint (OMA 91.2). DISCUSSION The aim of the study was to add more information on medial structures of ankle joint that are of major importance for ensuring stability of ankle fractures. In agreement with the literature, when managing the ankle fractures with an injury suffered on the medial side there is obviously a more uniform approach in cases with medial malleolar fractures. The situation is different in case of the deltoid ligament lesion, when historically there is a certain level of non-uniformity in indications for revision surgeries and treatment of the injured ligament structures. In our group, in the case of ligament lesion on the medial side of the ankle joint an emphasis is put on the fluoroscopy control of the symmetry of tibiotalar joint space before the beginning of the surgery and also after the fibular fracture stabilisation. The revision surgery was indicated in cases where asymmetry of ankle fork was found. The patients considered the treatment outcome better in cases with a ligament lesion than in cases with a medial malleolar fracture. CONCLUSIONS Proper treatment of medial structures of the ankle joint is important for ensuring the stability of ankle fractures. The patients with type B fractures reported better results at one year postoperatively compared to the patients with type C fracture according to the Weber classification. A statistically significantly better results after the ankle fracture surgery were achieved in patients with the presence of a medial ligament lesion compared to the patients with a medial malleolar fracture. Key words:ankle fracture, injury of medial structures, epidemiology, outcomes of treatment.


Nuss bar removal without straightening is a safe technique: a single center experience.
A Nuss bar often placed to correct pectus excavatum is usually removed after a period of 2 to 3 years. Bar removal can result in potentially life-threatening complications. To minimize this risk, a recent systematic review recommends in-situ straightening of the bar before removal. Alternatively, the bar can be removed without straightening by extraction along the thoracic curvature. This study reports our single-center experience with this latter technique for bar removal, with focus on perioperative complications. A single-center retrospective observational cohort study was conducted. Consecutive patients undergoing Nuss bar removal between 2011 and 2020 were eligible for inclusion. The primary outcome was the incidence of perioperative complications. Secondary outcomes included duration of operation, blood loss, and length of postoperative hospital stay. A total of 331 patients were included. Of these, 288 (87%) were male with a median age of 20 years [interquartile range (IQR), 19-26 years]. Perioperative complications occurred in a total of 4 patients (1%) following Nuss bar removal. Two patients (0.6%) experienced major complications (deep incisional surgical site infection and hemothorax respectively); there was no mortality. The median duration of surgery was 30 minutes (IQR, 20-40 minutes). Patients were discharged after a median postoperative stay of 1 day (IQR, 1-1 day). Nuss bar removal without prior in-situ bar straightening appears to be a safe and effective technique. It is associated with a low complication rate of 1%.


Unique Glutelin Expression Patterns and Seed Endosperm Structure Facilitate Glutelin Accumulation in Polyploid Rice Seed.
Rice is not only an essential food but also a source of high quality protein. Polyploidy is an evolutionary trajectory in plants, and enhancing glutelin by polyploidization is an attractive strategy for improving the nutritional value of rice seeds and presents a great potential for enhancing the commercial value of rice. Elucidating the mechanisms underlying glutelin synthesis and accumulation in tetraploid rice is of great significance. To enhance the nutritional value of rice, we developed tetraploid rice and evaluated the contents of various nutrient elements in mature seeds. The results revealed a significant increase in protein contents, including the total seed storage proteins, glutelins, and amino acids in tetraploid rice when compared with those in diploid rice. Tandem mass tag-based quantitative proteomic analyses of seeds revealed that glutelins regulated by several glutelin genes in 9311-4x were significantly up-regulated (≥1.5-fold), which was further verified by immunoblot analyses. In addition, temporal expression patterns of various glutelin subunits in different rice lines were investigated. The results revealed significant differences in the expression patterns between diploid and tetraploid rice seeds. Cytohistological analyses results revealed that the thickness of aleurone cell layers increased significantly by 32% in tetraploid rice, the structures of protein storage vacuoles (PSVs) in sub-aleurone cells were more diverse and abundant than those of diploid rice. Temporal expression and proteomic analyses results revealed that protein disulfide isomerase-like 1-1 expression levels were higher in tetraploid rice than in diploid rice, and that the gene responded to oxidative folding with increased levels of proglutelin and appropriate distribution of seed glutelins in tetraploid rice. The results of the present study revealed that polyploidization increased glutelin content by influencing glutelin biosynthesis, transport, and deposition, while variations in glutelin accumulation between tetraploid and diploid rice were largely manifested in the initial time, duration, and relative levels of various glutelin gene expressions during seed filling stages. These findings provide novel insights into improving the protein quality and nutritional value of rice seeds by polyploid breeding.


The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview.
The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine -- MDMA) is neurotoxic upon central serotonergic neurons in laboratory animals and possibly also in humans. In recent years, several studies reported alterations of serotonergic transmission and neuropsychiatric abnormalities in ecstasy users which might be related to MDMA-induced neurotoxic brain damage. To date, the most consistent findings associate subtle cognitive, particularly memory, deficits with heavy ecstasy use. However, most studies have important inherent methodological problems. One of the most serious confounds is the widespread pattern of polydrug use which makes it dif.cult to relate the findings in user populations to one specific drug. The present paper represents a brief overview on this issue. The most commonly co-used substances are alcohol, cannabis and stimulants (amphetamines and cocaine). Stimulants are also neurotoxic upon both serotonergic and dopaminergic neurons. Hence, they may act synergistically with MDMA and enhance its long-term adverse effects. The interactions between MDMA and cannabis use may be more complex: cannabis use is a well-recognized risk factor for neuropsychiatric disorders and it was shown to contribute to psychological problems and cognitive failures in ecstasy users. However, at the cellular level, cannabinoids have neuroprotective actions and they were shown to (partially) block MDMA-induced neurotoxicity in laboratory animals. In future, longitudinal and prospective research designs should hopefully lead to a better understanding of the relation between drug use and subclinical psychological symptoms or neurocognitive failures and, also, of questions around interactions between the various substances of abuse.


Primary intrasellar microgerminoma detected by magnetic resonance imaging: case report.
A case of primary intrasellar germinoma in a 24-year-old woman is presented. Her initial symptoms were diabetes insipidus and headaches. The neurological examination found no abnormalities, but the endocrinological examination disclosed a deficiency in growth hormone secretion. Her skull x-ray revealed a normal sella turcica, and a computed tomographic scan revealed no abnormal mass in the pituitary fossa, but a slightly enlarged stalk. Magnetic resonance imaging revealed a small tumor in the posterior lobe. Transsphenoidal exploration revealed a germinoma in the posterior pituitary lobe. Six cases of primary intrasellar germinoma, including our case, were reviewed. Our case is considered to be the smallest intrasellar germinoma yet reported.


Crystal structures of the yeast prion Ure2p functional region in complex with glutathione and related compounds.
The [URE3] phenotype in yeast Saccharomyces cerevisiae is due to an altered prion form of Ure2p, a protein involved in nitrogen catabolism. To understand possible conformational changes at the origin of prion propagation, we previously solved the crystal structure of the Ure2p functional region [Bousset et al. (2001) Structure 9, 39-46]. We showed the protein to have a fold similar to that of the beta class of glutathione S-transferases (GSTs). Here we report crystal structures of the Ure2p functional region (extending from residues 95-354) in complex with glutathione (GSH), the substrate of all GSTs, and two widely used GST inhibitors, namely, S-hexylglutathione and S-p-nitrobenzylglutathione. In a manner similar to what is observed in many GSTs, ligand binding is not accompanied by a significant change in the conformation of the protein. We identify one GSH and one hydrophobic electrophile binding site per monomer as observed in all other GSTs. The sulfur group of GSH, that conjugates electrophiles, is located near the amide group of Asn124, allowing a hydrogen bond to be formed. Biochemical data indicate that GSH binds to Ure2p with high affinity. Its binding affects Ure2p oligomerization but has no effect on the assembly of the protein into amyloid fibrils. Despite results indicating that Ure2p lacks GST activity, we propose that Ure2p is a member of the GST superfamily that may describe a novel GST class. Our data bring new insights into the function of the Ure2p active region.


Role of morning melatonin administration and attenuation of sunlight exposure in improving adaptation of night-shift workers.
The authors studied whether melatonin administration improves adaptation of workers to nightshift and if its beneficial effect is enhanced by attenuation of morning sunlight exposure. Twelve nightshift nurses received three treatments: Placebo (Pla), Melatonin (Mel), and Melatonin with Sunglasses (Mel-S). Each treatment procedure was administered for 2d of different 4d nightshifts in a repeated measures crossover design. In Pla, nurses were treated with placebo before daytime sleep and allowed exposure to morning sunlight. In Mel, 6mg of melatonin was similarly administered before daytime sleep with morning sunlight permitted. In Mel-S, 6 mg of melatonin was given as in Mel, with sunglasses worn in the morning to attenuate sunlight exposure. Placebo or melatonin was administered during days 2 and 3 when the first and second daytime sleep occurred. Nocturnal alertness and performance plus daytime sleep and mood states were assessed during all three treatments. The sleep period and total sleep times were significantly increased by melatonin treatments; yet, nocturnal alertness was only marginally improved. There were no differences between Mel and Mel-S. Performance tests revealed no difference between Pla and melatonin treatments. Melatonin exerted modest benefit in improving the adaptation of workers to nightshift, and its effect was not enhanced by attenuation of morning sunlight exposure.


Native State Organization of Outer Membrane Porins Unraveled by HDx-MS.
Hydrogen-deuterium exchange (HDx) associated with mass spectrometry (MS) is emerging as a powerful tool to provide conformational information about membrane proteins. Unfortunately, as for X-ray diffraction and NMR, HDx performed on reconstituted in vitro systems might not always reflect the in vivo environment. Outer-membrane vesicles naturally released by Escherichia coli were used to carry out analysis of native OmpF through HDx-MS. A new protocol compatible with HDx analysis that avoids hindrance from the lipid contents was setup. The extent of deuterium incorporation was in good agreement with the X-ray diffraction data of OmpF as the buried β-barrels incorporated a low amount of deuterium, whereas the internal loop L3 and the external loops incorporated a higher amount of deuterium. Moreover, the kinetics of incorporation clearly highlights that peptides segregate well in two distinct groups based exclusively on a trimeric organization of OmpF in the membrane: peptides presenting fast kinetics of labeling are facing the complex surrounding environment, whereas those presenting slow kinetics are located in the buried core of the trimer. The data show that HDx-MS applied to a complex biological system is able to reveal solvent accessibility and spatial arrangement of an integral outer-membrane protein complex.


A new species of Fannia (Diptera, Fanniidae) from Yunnan, China.
A new species of the genus Fannia (Diptera, Fanniidae) is described from Yunnan, China, namely Fanniabaihualingensis sp. nov. The male habitus as well as terminalia are documented with focus-stacked photographs. A detailed comparison of new species with related species is provided.


Pulmonary infection caused by an unusual, slowly growing nontuberculous Mycobacterium.
Mycobacterium triplex, a recently described slowly growing nontuberculous mycobacterium, was isolated from a Finnish patient with pulmonary mycobacteriosis. The disease was successfully treated with antimycobacterial drugs. The strain isolated, which was similar to the type strain but differed slightly from the species description, was regarded as a variant of M. triplex sensu stricto. According to present knowledge this variant of the species has never been isolated before.


seq-ImmuCC: Cell-Centric View of Tissue Transcriptome Measuring Cellular Compositions of Immune Microenvironment From Mouse RNA-Seq Data.
The RNA sequencing approach has been broadly used to provide gene-, pathway-, and network-centric analyses for various cell and tissue samples. However, thus far, rich cellular information carried in tissue samples has not been thoroughly characterized from RNA-Seq data. Therefore, it would expand our horizons to better understand the biological processes of the body by incorporating a cell-centric view of tissue transcriptome. Here, a computational model named seq-ImmuCC was developed to infer the relative proportions of 10 major immune cells in mouse tissues from RNA-Seq data. The performance of seq-ImmuCC was evaluated among multiple computational algorithms, transcriptional platforms, and simulated and experimental datasets. The test results showed its stable performance and superb consistency with experimental observations under different conditions. With seq-ImmuCC, we generated the comprehensive landscape of immune cell compositions in 27 normal mouse tissues and extracted the distinct signatures of immune cell proportion among various tissue types. Furthermore, we quantitatively characterized and compared 18 different types of mouse tumor tissues of distinct cell origins with their immune cell compositions, which provided a comprehensive and informative measurement for the immune microenvironment inside tumor tissues. The online server of seq-ImmuCC are freely available at http://wap-lab.org:3200/immune/.


Biomolecular Chemistry in Liquid Phase Separated Compartments.
Biochemical processes inside the cell take place in a complex environment that is highly crowded, heterogeneous, and replete with interfaces. The recently recognized importance of biomolecular condensates in cellular organization has added new elements of complexity to our understanding of chemistry in the cell. Many of these condensates are formed by liquid-liquid phase separation (LLPS) and behave like liquid droplets. Such droplet organelles can be reproduced and studied in vitro by using coacervates and have some remarkable features, including regulated assembly, differential partitioning of macromolecules, permeability to small molecules, and a uniquely crowded environment. Here, we review the main principles of biochemical organization in model membraneless compartments. We focus on some promising in vitro coacervate model systems that aptly mimic part of the compartmentalized cellular environment. We address the physicochemical characteristics of these liquid phase separated compartments, and their impact on biomolecular chemistry and assembly. These model systems enable a systematic investigation of the role of spatiotemporal organization of biomolecules in controlling biochemical processes in the cell, and they provide crucial insights for the development of functional artificial organelles and cells.


[Redox regulation in cancer stem cells].
CD44 was identified as a cell surface marker for cancer stem cells (CSCs) in various epithelial tumor. However, function-based evidence to support the role of CD44 in CSCs was not known. We found that expression of CD44, in particular variant forms of CD44 (CD44v), suppresses reactive oxygen species (ROS) levels by promoting the synthesis of reduced glutathione(GSH), a primary intracellular antioxidant. CD44v stabilizes xCT, a subunit of a glutamate-cystine transporter, and thereby promotes the uptake of cystine for GSH synthesis. Our findings reveal a novel function for CD44v in protection of CSCs from high levels of ROS in the tumor microenvironment.


Organic anion transporting polypeptide 1B1 activity classified by SLCO1B1 genotype influences atrasentan pharmacokinetics.
Our objective was to learn whether genetic polymorphisms of metabolic enzymes or transport proteins provide a mechanistic understanding of the in vivo disposition of atrasentan, a selective endothelin A receptor antagonist. Atrasentan uptake was measured in HeLa cells transfected to express major alleles of organic anion transporting polypeptide 1B1 (OATP1B1). The results were used to classify individuals as extensive, intermediate, or poor OATP1B1 transporters according to their SLCO1B1 genotypes. Analysis of covariance including genotype, study, age, weight, sex, and ethnicity was used to identify factors influencing atrasentan single-dose (n = 44) and steady-state (n = 38) pharmacokinetic parameters. Genotypes for cytochrome P450 3A5, uridine diphosphate-glucuronosyltransferase (UGT) 1A1, UGT2B4, UGT2B15, adenosine triphosphate-binding cassette subfamily B (ABCB) 1, solute carrier organic anion transporter (SLCO) 1B1, and solute carrier family 22 (SLC22) A2 were each assessed. Single-dose atrasentan exposure (P = .0244), steady-state atrasentan exposure (P = .0108), and maximum postdose plasma concentration (P = .0002) were associated with OATP1B1 activity classified by SLCO1B1 genotype. No other tested genotypes were observed to be associated with both single-dose and steady-state atrasentan pharmacokinetics. OATP1B1 is a meaningful factor for atrasentan disposition. Individuals may be classified as having extensive, intermediate, or poor OATP1B1 transport phenotypes according to SLCO1B1 genotypes. Increased exposures of OATP1B1 substrates might be expected in individuals who have the poor transporter phenotype or are treated with an OATP1B1 inhibitor.


Y chromosome diversity in Brazilians: switching perspectives from slow to fast evolving markers.
We have previously shown that the Y chromosomes of 'white' Brazilians have their immediate geographical origin in Europe, with low frequency of sub-Saharan African chromosomes and virtual absence of Amerindian contribution. The typing of slow evolving polymorphisms on the Y chromosome also revealed no differences between Brazilians and Portuguese, the bulk of European immigrants to Brazil, and even among Brazilians from distinct regions of Brazil, the latter being in sharp contrast with mtDNA data. In order to test if the lack of differentiation is a sex-biased and not a marker-biased phenomenon, we decided to study faster evolving Y chromosome markers in samples from Brazil and Portugal previously studied. The population structure revealed by this work confirmed that there were indeed no significant differences between Brazil and Portugal and no population differentiation within the four geographical regions of Brazil, suggesting that this phenomenon is unrelated to the nature of the markers typed. Nevertheless the fast evolving markers did uncover a higher within population diversity in Brazil than Portugal, which could be explained by the input of diverse European Y chromosomes carried by several migration waves to Brazil. Our present data highlight the significance of typing and combining Y markers that evolve according to distinct mutational paces to usefully assess the levels of diversity in a given population, and can be applied in the study of populations derived from distinct geographical origins such as the Brazilians.


Calculation of dose components in head phantom for boron neutron capture therapy.
Application of neutrons to cancer treatment has been a subject of considerable clinical and research interest since the discovery of the neutron by Chadwick in 1932 (3). Boron neutron capture therapy (BNCT) is a technique of radiation oncology which is used in treating brain cancer (glioblastoma multiform) or melanoma and that consists of preferentially loading a compound containing 10B into the tumor location, followed by the irradiation of the patient with a beam of neutron. Dose distribution for BNCT is mainly based on Monte Carlo simulations. In this work, the absorbed dose spatial distribution resultant from an idealized neutron beam incident upon ahead phantom is investigated using the Monte Carlo N-particles code, MCNP 4B. The phantom model used is based on the geometry of a circular cylinder on which sits an elliptical cylinder capped by half an ellipsoid representing the neck and head, both filled with tissue-equivalent material. The neutron flux and the contribution of individual absorbed dose components, as a function of depths and of radial distance from the beam axis (dose profiles) in phantom model, is presented and discussed. For the studied beam the maximum thermal neutron flux is at a depth of 2 cm and the maximum gamma dose at a depth of 4 cm.


The influence of core service quality associated with Korean women's volleyball on national image and consumption engagement of Korean products: Perspective of Korean Wave in Thailand.
Building on the stimulus-organism-response (SOR) framework, we proposed and tested a hypothesized model examining the effect of core service quality on national image and related behavioral intentions (i.e., intention to visit Korea and intention to purchase Korean products). Using 286 samples collected from Nakhon Ratchasima, Thailand, during the Korea-Thai Super Match, we conducted confirmatory factor analysis (CFA) and structural equation modeling (SEM) to examine the measurement model and the hypotheses, respectively. The results revealed that player attractiveness and emotional experience positively affected national image and behavioral intentions (i.e., intention to visit Korea and purchase Korean products). The findings stress that foreign spectators' attitudes toward Korean women's volleyball could translate into consumption behaviors (i.e., visits and Korean products) through the national image.


A small RNA mediated regulation of a stress-activated retrotransposon and the tissue specific transposition during the reproductive period in Arabidopsis.
Transposable elements (TEs) are key elements that facilitate genome evolution of the host organism. A number of studies have assessed the functions of TEs, which change gene expression in the host genome. Activation of TEs is controlled by epigenetic modifications such as DNA methylation and histone modifications. Several recent studies have reported that TEs can also be activated by biotic or abiotic stress in some plants. We focused on a Ty1/copia retrotransposon, ONSEN, that is activated by heat stress (HS) in Arabidopsis. We found that transcriptional activation of ONSEN was regulated by a small interfering RNA (siRNA)-related pathway, and the activation could also be induced by oxidative stress. Mutants deficient in siRNA biogenesis that were exposed to HS at the initial stages of vegetative growth showed transgenerational transposition. The transposition was also detected in the progeny, which originated from tissue that had differentiated after exposure to the HS. The results indicated that in some undifferentiated cells, transpositional activity could be maintained quite long after exposure to the HS.


Thrombospondin1 deficiency reduces obesity-associated inflammation and improves insulin sensitivity in a diet-induced obese mouse model.
Obesity is prevalent worldwide and is associated with insulin resistance. Advanced studies suggest that obesity-associated low-grade chronic inflammation contributes to the development of insulin resistance and other metabolic complications. Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix protein that is up-regulated in inflamed adipose tissue. A recent study suggests a positive correlation of TSP1 with obesity, adipose inflammation, and insulin resistance. However, the direct effect of TSP1 on obesity and insulin resistance is not known. Therefore, we investigated the role of TSP1 in mediating obesity-associated inflammation and insulin resistance by using TSP1 knockout mice. Male TSP1-/- mice and wild type littermate controls were fed a low-fat (LF) or a high-fat (HF) diet for 16 weeks. Throughout the study, body weight and fat mass increased similarly between the TSP1-/- mice and WT mice under HF feeding conditions, suggesting that TSP1 deficiency does not affect the development of obesity. However, obese TSP1-/- mice had improved glucose tolerance and increased insulin sensitivity compared to the obese wild type mice. Macrophage accumulation and inflammatory cytokine expression in adipose tissue were reduced in obese TSP1-/- mice. Consistent with the local decrease in pro-inflammatory cytokine levels, systemic inflammation was also decreased in the obese TSP1-/- mice. Furthermore, in vitro data demonstrated that TSP1 deficient macrophages had decreased mobility and a reduced inflammatory phenotype. TSP1 deficiency did not affect the development of high-fat diet induced obesity. However, TSP1 deficiency reduced macrophage accumulation in adipose tissue and protected against obesity related inflammation and insulin resistance. Our data demonstrate that TSP1 may play an important role in regulating macrophage function and mediating obesity-induced inflammation and insulin resistance. These data suggest that TSP1 may serve as a potential therapeutic target to improve the inflammatory and metabolic complications of obesity.


Dutch national identity in a majority-minority context: when the dominant group becomes a local minority.
With increasing ethnic diversity in Western European cities, more and more inhabitants without a migration background find themselves a local minority in majority-minority neighbourhoods, where less than half of the inhabitants have no migration background. We investigate whether this affects how they define national identity. We compare Dutch inhabitants without a migration background in majority-minority neighbourhoods in Amsterdam and Rotterdam to a representative sample of the overall Dutch population without a migration background and investigate how people describe what they see as truly Dutch. We find that national identity content is seen in the same way by both groups. The majority views Dutch identity as mostly achievable but does attach some importance to ascriptive characteristics. A smaller class of people is more restrictive and attaches quite some importance to both ascriptive and achievable characteristics. The smallest class considers Dutch identity achievable and not ascriptive at all. All three national identity content classes involve drawing boundaries around the nation-state, but with different degrees of permeability. Our finding that these patterns are almost identical, both in majority-minority neighbourhoods as in the overall population, suggests an important role of national public discourse on national identity formation.


Recovery and evaluation of trace material from wound edges in traumatic injury site.
A small wound found on the ear of a homicide victim was inflicted by either a knife or a sharp fragment of ceramic. To test the potential usefulness of cytologic examination of wound edges for fragments of inert material from the assault weapon, the wound was rinsed and cytologic filters were prepared from the retained rinsing material. The particulate matter present on filters included microscopic fragments of crockery admixed with blood and other tissue components. This observation supported other physical evidence that the wound was caused by the sharp edge of a ceramic crock rather than by the knife. This case demonstrates the potential usefulness of cytologic examination of wound edges.


Trajectories of Psychopathic Traits, Anxiety, and Violence Exposure Differentially Predict Antisociality in Legal System-Involved Youth.
Psychopathic traits are associated with several forms of antisociality, including criminal offending, legal system involvement, and substance use. Some research suggests that primary (high psychopathic traits, low negative emotions) versus secondary (high psychopathic traits, high negative emotions and/or negative experiences and environments) variants confer different levels of risk for antisociality. However, research has not examined trajectories of co-occurring fluctuations in psychopathic traits, negative emotions, and negative experiences and environments or how trajectory membership relates to antisociality. We implemented group-based multi-trajectory modeling in a sample of 809 justice-involved male (n = 681) and female (n = 128) youth from the Pathways to Desistance Study to address these gaps. We identified four trajectories of co-occurring change in psychopathic traits, anxiety, and violence exposure spanning three years: Low (low levels of each factor); Moderate Psychopathic Traits, High Negative Emotions and Experiences (moderate-decreasing psychopathic traits and high-decreasing anxiety/violence exposure); Potential Primary Psychopathic Traits (elevated-decreasing psychopathic traits, moderate-decreasing anxiety, moderate-stable violence exposure); and High/Secondary Psychopathic Traits (high-stable psychopathic traits, elevated-stable anxiety, high-decreasing violence exposure). Compared to the Low trajectory, all trajectories predicted greater violent crime and substance use three and four years later. Additionally, compared to the Low trajectory, the Potential Primary Psychopathic Traits trajectory predicted more nonviolent offending three years later. Finally, the High/Secondary Psychopathic Traits trajectory showed the most persistent antisociality, predicting more nonviolent crime, higher substance dependence symptoms, and higher likelihood of arrest three and four years later. Youth with co-occurring high psychopathic traits, anxiety, and violence exposure appear most at risk for severe antisociality.


A field study on residues of four insecticides used in strawberry protection.
In 1986 strawberry plots were treated with dimethoate, malathion, permethrin and cypermethrin at 80% bloom of primary flowers. In 1987 the plots were sprayed with dimethoate, malathion and permethrin at 30% bloom. Residue analysis of these insecticides on the flowers were analyzed using solvent extraction and gas liquid chromatography. Residue analysis at 0 to 18 days on flowers and fruit showed an exponential decrease. Organophosphates tended to degrade more quickly than synthetic pyrethroids. The results are discussed in the context of an integrated pest management program.


Activation of clones producing self-reactive antibodies by foreign antigen and antiidiotype antibody carrying the internal image of the antigen.
Because we found in previous work that a high fraction of antibodies exhibiting various specificities bound to glutamic acid 50-tyrosine50 homopolymer (GT) and expressed pGAT cross-reactive idiotype (IdX), we studied the activation of clones producing multireactive antibodies in 1-mo-old MRL/lpr and C3H/HeJ mice bearing VHJ haplotype. The activation of such clones was studied after mice were immunized with GT in CFA, HP20 (an anti-Id MAb carrying the internal image of GT in the D region), and a synthetic peptide corresponding to the D segment of HP20. Our results indicate that immunized mice produced both GT- and self-reactive antibodies. Study of the immunochemical properties of MAb showed that they exhibit multispecific properties and bind with similar-affinity constants to GT or self-antigens such as DNA, Smith antigen (Sm), and IgG2a. An important fraction of antibodies obtained from MRL/lpr mice immunized with HP20 expressed pGAT IdX and some of these antibodies share IdX expressed on anti-DNA, Sm, and rheumatoid factor (RFs) antibodies. The hybridomas producing multispecific autoantibodies use heavy-chain- (VH) and light-chain-variable region (VK) genes from various V gene families, suggesting that they do not derive from the pool of GAT precursors. Sequencing of VH and VK genes of two antibodies show that they can use closely related VHJ558, unmutated VK1, or different VK genes than those used by anti-GT antibodies. Our data demonstrate that clones producing antibodies binding to GT and self-antigens with similar-affinity constants can be activated by foreign or anti-Id antibodies carrying the internal image of the antigen or even by a synthetic peptide corresponding to the D segment of anti-Id antibodies.


NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family.
Erythropoietin-producing hepatocellular (EPH) receptors are transmembrane receptor tyrosine kinases. Their extracellular domains bind specifically to ephrin A/B ligands, and this binding modulates intracellular kinase activity. EPHs are key players in bidirectional intercellular signaling, controlling cell morphology, adhesion, and migration. They are increasingly recognized as cancer drug targets. We analyzed the binding of NVP-BHG712 (NVP) to EPHA2 and EPHB4. Unexpectedly, all tested commercially available NVP samples turned out to be a regioisomer (NVPiso) of the inhibitor, initially described in a Novartis patent application. They only differ by the localization of a single methyl group on either one of two adjacent nitrogen atoms. The two compounds of identical mass revealed different binding modes. Furthermore, both in vitro and in vivo experiments showed that the isomers differ in their kinase affinity and selectivity.


Prenatal diagnosis of congenital mesoblastic nephroma in mid-second trimester by sonography and magnetic resonance imaging.
Although congenital mesoblastic nephroma (CMN) is a rare benign congenital renal tumor, it is the most common solid renal tumor in the newborn period. The most common presentation of congenital mesoblastic nephroma is polyhydramnios, and only one case with prenatal fetal hydrops has been previously reported. Prenatal diagnosis of CMN has previously been made on the basis of the findings of sonography in the third trimester, and magnetic resonance imaging (MRI)-based diagnosis has been reported recently. Here we report a case of prenatally diagnosed classical type CMN diagnosed at 22 + 3 weeks of gestation based on the findings of sonography and magnetic resonance imaging. The characteristic imaging findings in this case were fetal hydrops and polyhydramnios. To our knowledge, this is the youngest reported gestational age for prenatal diagnosis of CMN and it is the second case of CMN associated with fetal hydrops detected prenatally.


Polymerization State of Vanadyl Species Affects the Catalytic Activity and Arsenic Resistance of the V2O5-WO3/TiO2 Catalyst in Multipollutant Control of NOx and Chlorinated Aromatics.
The conventional V2O5-WO3/TiO2 catalyst suffers severely from arsenic poisoning, leading to a significant loss of catalytic activity. The doping of Al or Mo plays an important role in promoting the arsenic resistance on NH3 selective catalytic reduction (NH3-SCR), but their promotion mechanism remains in debate and has yet to be explored in multipollutant control (MPC) of NOx and chlorinated organics. Herein, our experimental characterizations and density functional theory (DFT) calculations confirmed that arsenic species preferentially adsorb on both Al and Mo to form arsenate, thereby avoiding bonding to the catalytically active V sites. More importantly, Al doping partially converted the polymeric vanadyl species into monomeric ones, thereby inhibiting the near-surface and bulk lattice oxygen mobility of the V2O5-WO3/TiO2 catalyst, while Mo doping resulted in vanadyl polymerization with an enriched V5+ chemical state and exhibited superior MPC activity and COx selectivity. Our work shows that antipoisoning catalysts can be designed with the combination of site protection and occurrence state modification of the active species.


Congential lumbar hernia with malrotation of left kidney and hydronephrosis in an infant: a rare presentation.
Congenital Lumbar hernia was previously known as Lumbocostovertebral syndrome. This syndrome consists of the presence of hemivertebrae, rib defects, abdominal wall anomalies and hypoplasia of the abdominal musculature. This case report describes a 40-hour-old infant with malrotation of left kidney and hydronephrosis in association with congenital lumbar hernia. Various congenital renal anomalies like renal pyelectasis, bilateral renal agenesis and pelviureteric junction obstruction, malascended kidneys, hypospadiasis have been reported in association with this disease. Malrotation has only been reported in adults so far. However ours is the first ever case in literature to report malrotation of kidney in association with this syndrome in neonatal age group. Treatment of this condition is done usually by mesh hernioplasty. Presence of this condition must prompt the surgeon to carry out all possible investigations to rule out various other congenital orthopedic, neurological, and urological anomalies.


Site selection of Acanthochondria cornuta (Copepoda: Chondracanthidae) in Platichthys flesus (Teleostei: Pleuronectidae).
Acanthochondria cornuta (Copepoda: Chondracanthidae) (N=4841; prevalence: 80·0%; mean±s.d. [range] intensity: 28·8±24·0 [1-110] parasites) infected the branchial chambers of the European flounder, Platichthys flesus (L.), (N=210) according to an established spatial pattern. This was independent of host size. Higher intensities resulted, most frequently, in higher numbers of infection sites, probably due to increased intraspecific competition. Preferential infection of the ocular side was supported by the recorded abundance data and reflected, probably, the fish's bottom-dwelling behaviour. As the parasite develops from one stage into another, it seems to migrate towards different sites: the copepodites and pre-adult females occurred, mainly, in the holobranchs; the adults preferred the internal wall (non-gravid/post-gravid females; adult males) or the pseudobranchs (gravid females). The ventilating water current along with the blood supply are suggested as 2 major factors in determining parasite spatial distribution within the chamber. Parasite crowding in a restricted and narrow space of the posterior region of the internal wall was recorded frequently and resembled that previously reported for the plaice. Differences to other host-parasite systems previously studied should relate with the anatomy of the respiratory apparatus. Bigamous females are reported for the first time.


Blood coagulation and metabolic profiles in middle-aged male and female ob/ob mice.
Obese and diabetic states in humans are associated with an increased incidence of thrombotic diseases caused by various coagulation abnormalities. Genetically obese ob/ob mice produce metabolic abnormalities similar to those associated with type 2 diabetes. However, little is known about their coagulation features or sex differences. The present study aimed to determine the effects of obese and diabetic complications on blood coagulation and vascular diseases by exploring correlations between blood coagulation and metabolic profiles in middle-aged male and female ob/ob mice. Plasma levels of plasminogen activator inhibitor 1 (PAI-1) were significantly increased, whereas those that of platelet factor-4 (PF-4) was slightly, but significantly increased in male and female ob/ob mice compared with lean counterparts. Prothrombin time (PT) was significantly shortened in female ob/ob mice and activated partial thrombin time (APTT) significantly differed between male and female ob/ob mice. Plasma levels of antithrombin (AT) were significantly increased in male and female ob/ob mice. None of the other coagulation and fibrinolytic factors examined significantly differed between ob/ob mice and lean counterparts. On the contrary, factors such as body weight and cholesterol levels significantly differed between ob/ob and lean mice, whereas glucose, fructosamine and insulin levels significantly differed only in one sex of each strain. These results provided fundamental information about blood coagulation and metabolic features for exploring the function of altered blood coagulation states in ob/ob mice.


[The value of breath-hold diffusion-weighted imaging in small hepatocellular carcinoma lesion (<or=3 cm) detection].
To evaluate the added value of single breath-hold diffusion-weighted imaging (DWI) in detection of small HCC lesions (<or=3 cm) in patients with chronic liver disease, by comparing the detection sensitivity of DWI/conventional dynamic contrast enhancement (DCE) MRI and that of conventional DCE MRI alone. A total of 54 patients with chronic liver diseases underwent abdominal MRI at 1.5 T, including T1-weighted (T1WI), T2-weighted (T2WI), and 2D conventional DCE. For each patient study, axial DWI was performed with a single-shot echo-planar imaging (EPI) sequence using modified sensitivity encoding (mSENSE) with b-value of 500 seconds/mm2. A total of 20-24 slices were obtained during a 15-17-second breath-hold. Two observers independently interpreted the combined DWI/conventional DCE MRI images and the conventional DCE MRI images in random order. For all small HCC lesions and micro-hepatocellular carcinoma (smaller than 10 mm MHCC), the diagnostic performance using each imaging techniques were evaluated by ROC analysis. Sensitivity and positive predictive values were also calculated. The mean areas under the ROC curve (Az) of combined DWI/conventional DCE MRI images (0.945, 0.86) were statistically higher than those of conventional DCE MRI alone (0.86, 0.64) for all small HCC lesions and MHCC (micro hepatocellular carcinoma) lesions (P<0.01). The lesion detection sensitivities using the combined technique of both observers were significantly higher than those using the conventional DCE MRI alone for all small lesions and for MHCC (P<0.01). For MHCC, the sensitivities using the combined technique and the conventional DCE MRI alone were 95.8%-96.0% and 62.5%-68.0%, respectively. The positive predictive values for MHCC using the combined imaging technique (95.8%-96.0%) were higher than those using the conventional DCE MRI alone (94.1%-94.4%) (P<0.05). For all small HCC lesions, the positive predictive values using the combined imaging technique and the conventional DCE MRI alone were 98.6%-98.7% and 95.5%-95.7%, respectively and there was no statistical difference. Combined use of Breath-hold DWI with conventional DCE MRI helped to provide higher sensitivities than conventional DCE MRI alone in the detection of small HCC lesions in patients with chronic liver disease. Furthermore, DWI could provide additional valuable information that benefits the differential diagnosis.


Monoclonal antibodies as structural probes for oligomeric human interferon-gamma.
Monoclonal antibodies (MAb) B1 and B3, specific for human interferon-gamma (IFN-gamma) failed to immunoprecipitate heat-inactivated human IFN-gamma in solution. However, both MAb retained some reactivity with denatured IFN-gamma immobilized on vinyl plates. The two MAb have been employed in a sensitive immunoradiometric assay (IRMA). In this IRMA one MAb was bound to polystyrene beads and used as immunoadsorbent. The second MAb, labeled with 125I, was used as the tracer to quantitate the amount of IFN-gamma bound to the immobilized MAb. Addition of unlabeled MAb B1 did not inhibit the binding of 125I-labeled MAb B3 (and vice versa), indicating that the two MAb react with two different and nonoverlapping epitopes. Yet, when the same MAb was used in IRMA as both immunoadsorbent and tracer, the amount of labeled MAb bound to a given concentration of natural or E. coli-derived recombinant human IFN-gamma was very similar as with two different MAb, indicating that a single IFN-gamma molecule must have two or more identical binding sites for each of the two MAb. These findings show that biologically active natural and recombinant human IFN-gamma exist in oligomeric form.


[Association between human papillomavirus (HPV) type 16 infection and E6/E7 gene variant and the cervical lesions in Beijing].
To investigate the association between HPV16 infection, E6/E7 variations and the cervical lesions. HPV subtypes were detected by using flow-through hybridization technique, E6/E7 gene was extracted from cervical lesions in 80 patients with HPV16 infection, PCR amplified, cloned into plasmid pMD18-T and sequenced. HPV 16 was the most common type which accounted for 33.3% (154/463), the HPV16 infection rates increased with the severity of cervical lesions (P < 0.05). Totally in 72 cases the complete E6 and E7 regions were successfully sequenced, the DNA mutation rate of E6/E7 was 88.9% (64/72). A mutation, E6-D32E (T96G) coincided with a specific type of E7 mutation, N29S (A86G). D32E/N29S mutation rate was 38.9% (28/72), the detection rate increased with the severity of cervical lesions (P < 0.05). HPV 16 was the most common type in women with cervical lesions in Beijing, D32E/N29S variant associated with the cervical lesions.


Sensing Protein Surfaces with Targeted Fluorescent Receptors.
A methodology for creating fluorescent molecular sensors that respond to changes that occur on the surfaces of specific proteins is presented. This approach, which relies on binding cooperatively between a specific His-tag binder and a nonspecific protein-surface receptor, enabled the development of a sensor that can track changes on the surface of a His-tag-labeled calmodulin (His-CaM) upon interacting with metal ions, small molecules, and protein binding partners. The way this approach was used to detect dephosphorylation of an unlabeled calmodulin-dependent protein kinase II (CaMKII), and the binding of Bax BH3 to His-tagged B-cell lymphoma 2 (Bcl-2) protein is also presented.


Passive Directivity Detection Using Individual Biaxial Ultrasound Transducers.
Biaxial transducers are an emerging technology that can steer generated ultrasound waves using a single piezoceramic component. Simulations have also shown that biaxial transducers can passively estimate the direction of arrival (DOA) of sound waves when operating in the receive mode. This research seeks to experimentally verify biaxial directivity estimates and establish directivity as an independent parameter detected by biaxial transducers. Three cuboid ( 3.84×3.84×5.92 mm) biaxial piezoceramics with two pairs of orthogonal electrodes (one pair applied laterally and one pair applied in the polling direction) were manufactured and characterized. Each transducer was placed in a water tank where an independent hemispherical source was attached to a moveable arm and operated at 250 kHz. Terminal voltages were recorded for 81 source positions in a plane parallel to the transducer's front face and at a depth of approximately 9 cm. Collection was repeated three times per transducer to ensure reproducibility. In silico results were compared with the experimental results. Two derived metrics were then calculated using both the forward and lateral terminal voltages: the phase difference and amplitude ratio. Biaxial transducers demonstrate an ability to estimate the DOA of incident sound waves, independently of any time-of-flight (TOF) information. The phase difference and amplitude ratio complement each other to provide statistically significant and repeatable estimates over a range of 48° (from -24° to +24°). These results can be used to augment a variety of medical, geophysical, and industrial passive ultrasound imaging techniques.


Variability in the properties of silicone gel breast implants.
Several generations of silicone gel breast implants have been produced by implant manufacturers. The primary material usually viewed as the base material in the manufacture of implants is polydimethylsiloxane. Polymeric reactions are notorious for their variability and nonuniformity. The elastomer used in different types of implants can have vastly different properties. Furthermore, the material properties associated with a particular type of implant can vary considerably from one lot to the next. Considering the various designs, styles, and manufacturing techniques associated with silicone gel implants, knowledge of the original properties of the implants before implantation is important in determining the effects of aging in vivo. This study was conducted to investigate differences in key mechanical and chemical properties of silicone gel breast implant materials. The two types of implants chosen for analysis were Silastic I and Silastic II control implants. Material property data were determined for both types of controls and significant differences were found in their values. Lot-to-lot variability was also investigated and found to be significant.


The Bluetongue Disabled Infectious Single Animal (DISA) Vaccine Platform Based on Deletion NS3/NS3a Protein Is Safe and Protective in Cattle and Enables DIVA.
The bluetongue virus (BTV) is transmitted by Culicoides biting midges and causes bluetongue (BT), an OIE-notifiable disease of ruminants. At least 29 BTV serotypes are described as determined by the outer shell proteins VP2 and VP5. Vaccination is the most effective control measure. Inactivated and live-attenuated vaccines (LAVs) are currently available. These vaccines have their specific pros and cons, and both are not DIVA vaccines. The BT Disabled Infectious Single Animal (DISA) vaccine platform is based on LAV without nonessential NS3/NS3a expression and is applicable for many serotypes by the exchange of outer shell proteins. The DISA vaccine is effective and completely safe. Further, transmission of the DISA vaccine by midges is blocked (DISA principle). Finally, the DISA vaccine enables DIVA because of a lack of antibodies against the immunogenic NS3/NS3a protein (DIVA principle). The deletion of 72 amino acids (72aa) in NS3/NS3a is sufficient to block virus propagation in midges. Here, we show that a prototype DISA vaccine based on LAV with the 72aa deletion enables DIVA, is completely safe and induces a long-lasting serotype-specific protection in cattle. In conclusion, the in-frame deletion of 72-aa codons in the BT DISA/DIVA vaccine platform is sufficient to fulfil all the criteria for modern veterinary vaccines.


Dynamic changes of the phosphoproteome in postmortem mouse brains.
Protein phosphorylation is deeply involved in the pathological mechanism of various neurodegenerative disorders. However, in human pathological samples, phosphorylation can be modified during preservation by postmortem factors such as time and temperature. Postmortem changes may also differ among proteins. Unfortunately, there is no comprehensive database that could support the analysis of protein phosphorylation in human brain samples from the standpoint of postmortem changes. As a first step toward addressing the issue, we performed phosphoproteome analysis with brain tissue dissected from mouse bodies preserved under different conditions. Quantitative whole proteome mass analysis showed surprisingly diverse postmortem changes in phosphoproteins that were dependent on temperature, time and protein species. Twelve hrs postmortem was a critical time point for preservation at room temperature. At 4°C, after the body was cooled down, most phosphoproteins were stable for 72 hrs. At either temperature, increase greater than 2-fold was exceptional during this interval. We found several standard proteins by which we can calculate the postmortem time at room temperature. The information obtained in this study will be indispensable for evaluating experimental data with human as well as mouse brain samples.


ICG-001, an Inhibitor of the β-Catenin and cAMP Response Element-Binding Protein Dependent Gene Transcription, Decreases Proliferation but Enhances Migration of Osteosarcoma Cells.
High-grade osteosarcomas are the most frequent malignant bone tumors in the pediatric population, with 150 patients diagnosed every year in France. Osteosarcomas are associated with low survival rates for high risk patients (metastatic and relapsed diseases). Knowing that the canonical Wnt signaling pathway (Wnt/β-catenin) plays a complex but a key role in primary and metastatic development of osteosarcoma, the aim of this work was to analyze the effects of ICG-001, a CBP/β-catenin inhibitor blocking the β-catenin dependent gene transcription, in three human osteosarcoma cell lines (KHOS, MG63 and 143B). The cell proliferation and migration were first evaluated in vitro after ICG-001 treatment. Secondly, a mouse model of osteosarcoma was used to establish the in vivo biological effect of ICG-001 on osteosarcoma growth and metastatic dissemination. In vitro, ICG-001 treatment strongly inhibits osteosarcoma cell proliferation through a cell cycle blockade in the G0/G1 phase, but surprisingly, increases cell migration of the three cell lines. Moreover, ICG-001 does not modulate tumor growth in the osteosarcoma mouse model but, rather significantly increases the metastatic dissemination to lungs. Taken together, these results highlight, despite an anti-proliferative effect, a deleterious pro-migratory role of ICG-001 in osteosarcoma.


Mechanochemical Synthesis of PEDOT:PSS Hydrogels for Aqueous Formulation of Li-Ion Battery Electrodes.
Water-soluble binders can enable greener and cost-effective Li-ion battery manufacturing by eliminating the standard fluorine-based formulations and associated organic solvents. The issue with water-based dispersions, however, remains the difficulty in stabilizing them, requiring additional processing complexity. Herein, we show that mechanochemical conversion of a regular poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) water-based dispersion produces a hydrogel that meets all the requirements as binder for lithium-ion battery electrode manufacture. We particularly highlight the suitable slurry rheology, improved adhesion, intrinsic electrical conductivity, large potential stability window and limited corrosion of metal current collectors and active electrode materials, compared to standard binder or regular PEDOT:PSS solution-based processing. When incorporating the active materials, conductive carbon and additives with PEDOT:PSS, the mechanochemical processing induces simultaneous binder gelation and fine mixing of the components. The formed slurries are stable, show no phase segregation when stored for months, and produce highly uniform thin (25 μm) to very thick (500 μm) films in a single coating step, with no material segregation even upon slow drying. In conjunction with PEDOT:PSS hydrogels, technologically relevant materials including silicon, tin, and graphite negative electrodes as well as LiCoO2, LiMn2O4, LiFePO4, and carbon-sulfur positive electrodes show superior cycling stability and power-rate performances compared to standard binder formulation, while significantly simplifying the aqueous-based electrode assembly.


A large, naturalistic, community-based study of rivastigmine in mild-to-moderate AD: the EXTEND Study.
Previous studies in Alzheimer's Disease (AD) suggest a benefit from switching from one cholinesterase (ChE) inhibitor to another in the event of treatment failure on the index agent. This observational, open-label study sought to evaluate the efficacy of the ChE inhibitor rivastigmine on cognition, functional autonomy and behavior in patients with mild-to-moderate AD previously treated with other ChE inhibitors (switched patients) as well as in those previously ChE-inhibitor-naive (de novo users). Patients were eligible for a switch if they experienced a lack or loss of efficacy or had experienced intolerance to prior ChE inhibitor therapy. Rivastigmine was initiated at a dose of 1.5 mg b.i.d. and titration was done as per standard medical practice. Efficacy was assessed using the mini-mental state examination (MMSE) and an abbreviated version of the Clinician's Global Impression of Change (CGI-C) at Month 3 and Month 6. Caregiver burden was also assessed at Month 6 using a self-rated scale. Overall, 2633 subjects were enrolled in this study. The mean MMSE improved from 20.6 at baseline to 21.5 at Month 6. More patients improved than deteriorated on every domain of the CGI-C. Caregivers felt less burdened after the 6 month evaluation period. Efficacy parameters demonstrated favorable results for both de novo and switched patients, but more so in the first group. Open-label studies have an inherent potential for bias by both the caregiver and the physician. In this study, there was also a large percentage of missing patient records for each of the follow-up visits (Months 3 and 6). Patients with mild-to-moderate AD switched from previous ChE inhibitor therapy to rivastigmine can obtain measurable benefits, although the treatment effect may be less than in de novo patients. Further research into switching cholinesterase inhibitors is warranted.


DNA damage-binding proteins and heterogeneous nuclear ribonucleoprotein A1 function as constitutive KCS element components of the interferon-inducible RNA-dependent protein kinase promoter.
Protein kinase regulated by RNA (PKR) plays important roles in many cellular processes including virus multiplication and cell growth, differentiation, and apoptosis. The promoter of the PKR gene possesses a novel 15-bp element designated KCS, positioned upstream of a consensus interferon (IFN)-stimulated response element, that is required for both basal and interferon-inducible transcription. Protein binding to the KCS element is not dependent upon IFN treatment and correlates with transcriptional activity of the PKR promoter. The identity of KCS-binding proteins (KBP) that selectively bind at the KCS element is largely unknown, except for the transcription factor Sp1. We now have purified KBP from HeLa cell nuclear extracts by ion-exchange and DNA-affinity chromatography steps and then identified four constituent proteins of the KBP complex by mass spectrometry and immunochemistry: KBP120 and KBP45 are the damaged DNA-binding protein subunits, p127 DDB1 and p48 DDB2, respectively; KBP100 is the transcription factor Sp1; and KBP35 is the heterogeneous nuclear ribonucleoprotein A1. The steady-state levels of these four KCS-binding proteins in human cells are not altered by IFN treatment. Components of the KBP complex bind selectively and constitutively to the KCS element in the absence of IFN treatment, both in vitro as measured by competition electrophoretic mobility shift assay (EMSA) and DNA pull-down assays and in vivo as measured by chromatin immunoprecipitation assays. Depletion of DDB2 by antisense strategy reduces KBP complex formation by EMSA. These results provide new insight into the biochemical identity and activity of proteins involved in PKR promoter function.


Aberrant expression of long noncoding RNAs in autistic brain.
The autism spectrum disorders (ASD) have a significant hereditary component, but the implicated genetic loci are heterogeneous and complex. Consequently, there is a gap in understanding how diverse genomic aberrations all result in one clinical ASD phenotype. Gene expression studies from autism brain tissue have demonstrated that aberrantly expressed protein-coding genes may converge onto common molecular pathways, potentially reconciling the strong heritability and shared clinical phenotypes with the genomic heterogeneity of the disorder. However, the regulation of gene expression is extremely complex and governed by many mechanisms, including noncoding RNAs. Yet no study in ASD brain tissue has assessed for changes in regulatory long noncoding RNAs (lncRNAs), which represent a large proportion of the human transcriptome, and actively modulate mRNA expression. To assess if aberrant expression of lncRNAs may play a role in the molecular pathogenesis of ASD, we profiled over 33,000 annotated lncRNAs and 30,000 mRNA transcripts from postmortem brain tissue of autistic and control prefrontal cortex and cerebellum by microarray. We detected over 200 differentially expressed lncRNAs in ASD, which were enriched for genomic regions containing genes related to neurodevelopment and psychiatric disease. Additionally, comparison of differences in expression of mRNAs between prefrontal cortex and cerebellum within individual donors showed ASD brains had more transcriptional homogeneity. Moreover, this was also true of the lncRNA transcriptome. Our results suggest that further investigation of lncRNA expression in autistic brain may further elucidate the molecular pathogenesis of this disorder.


Effect of cation content of agar on the activity of gentamicin, tobramycin, and amikacin against Pseudomonas aeruginosa.
Fifty-five strains of Pseudomonas aeruginosa were tested against arithmetic increments in concentrations of gentamicin, tobramycin, and amikacin in 14 different lots of Mueller-Hinton agar. The divalent cation content of each lot was determined by atomic absorption spectrometry. The relation between mean minimal inhibitory concentration (MIC) for strains within each lot and cation content was studied by stepwise regression. Among the cations, the content of Zn++ most highly correlated with the MIC of each aminoglycoside; however, Zn++ accounted for only 23%, 60%, and 47% of the variability in the mean MIC of gentamicin, tobramycin, and amikacin, respectively, against all strains. In two-cation models Zn++ with Ca++ or Cu++ was most highly correlated with the mean MICs of the three aminoglycosides against all strains. No divalent cation, either singly or in combination with one or two other cations, gave a good prediction of the MICs of the aminoglycosides in agar. Furthermore, there was variability in the cations that most highly correlated with the MICs for some strains. These observations support the concept that ionic strength, cations, and a variety of other as yet poorly defined components of media influence the activity of aminoglycosides against P. aeruginosa.


Cutaneous metastatic carcinoma: diagnostic and therapeutic values.
This study was to highlight the diagnostic and therapeutic values of cutaneous metastatic carcinoma. Presented are patients with histologic diagnosis of cutaneous metastatic carcinoma seen in the University of Calabar Teaching Hospital, Calabar, Nigeria from 2000 to 2006. Six patients (2 men and 4 women) with cutaneous metastatic carcinoma whose ages ranged from 37 to 55 years presented during the study period and accounted for 6.5% of total cutaneous cancer and 0.6% of total malignancy. Cutaneous metastatic carcinoma exhibited a pattern of clinical significance. Clinicians are urged to renew interest in cutaneous nodules, chronic discharging sinuses, and ulcers.


Field performance evaluation and genetic integrity assessment of cryopreserved papaya clones.
This paper is the first report of field performance and evaluation of morphological traits following cryopreservation in four genotypes of Carica papaya (Z6, 97, TS2 and 35). It also describes the successful establishment of in vitro plantlets following vitrification-based cryopreservation of shoot tips and their acclimatisation through to field establishment. Cloned plants resulting from untreated controls, as well as controls taken at three other stages of the cryopreservation process (dissection, pre-treatment, plant vitrification solution 2 (PVS2) treatment) and cryopreserved plants were established to ensure a rigorous appraisal of any variation. Results indicate no differences between any of the control plants or cryopreserved plants for either growth performance or morphology. In addition, both randomly amplified DNA fingerprinting and amplified DNA methylation polymorphism markers were used to assess any genomic or methylation changes in genotype 97 at four different developmental stages post cryopreservation (in vitro, acclimatisation and field). Only small genomic DNA modifications (0-8.3%) were detected in field stage plants and methylation modifications (0-4.3%) were detected at both the in vitro and field stages for samples treated with PVS2 or cryopreservation.


Bovine Bacillus anthracis in Cameroon.
Bovine Bacillus anthracis isolates from Cameroon were genetically characterized. They showed a strong homogeneity, and they belong, together with strains from Chad, to cluster Aβ, which appears to be predominant in western Africa. However, one strain that belongs to a newly defined clade (D) and cluster (D1) is penicillin resistant and shows certain phenotypes typical of Bacillus cereus.


Observing finger movement influences the stimulus-response process of the subsequent non-aiming finger movement.
Aim: The present study investigated whether observing the finger movement influences the stimulus-response process of the subsequent non-aiming finger movement.Methods: Participants directed their eyes to the finger. Three auditory cues with 3 s intervals were provided in each trial. The participants abducted and adducted the index finger in response to the second and third cues; the first response was considered to be the previous response and the second response was considered to be the subsequent response. The time taken for the stimulus-response process was measured via reaction time. Vision was allowed from 0 to 1 s after the start cue of the previous response, after the cue of the subsequent response, or after the cues of the previous and subsequent responses.Results: Online visual information of the stationary finger accelerated the stimulus-response process of the non-aiming finger movement. The acceleration of the stimulus-response process induced by online visual information of the stationary finger was cancelled out by the previous response information, but this cancellation is itself then eliminated by the visual information from the previous response. The visual information from the previous response decelerated the stimulus-response process of the subsequent non-aiming movement, but this deceleration was then itself cancelled out by visual information of the stationary finger immediately before the subsequent non-aiming movement.Conclusion: Taken together, information regarding the previous response functions as noise interfering with the processes contributing to the subsequent non-aiming movement.


Cosensitization in Dye-Sensitized Solar Cells.
Dye-sensitized solar cells (DSCs) are a next-generation photovoltaic technology, whose natural transparency and good photovoltaic output under ambient light conditions afford them niche applications in solar-powered windows and interior design for energy-sustainable buildings. Their ability to be fabricated on flexible substrates, or as fibers, also makes them attractive as passive energy harvesters in wearable devices and textiles. Cosensitization has emerged as a method that affords efficiency gains in DSCs, being most celebrated via its role in nudging power conversion efficiencies of DSCs to reach world-record values; yet, cosensitization has a much wider potential for applications, as this review will show. Cosensitization is a chemical fabrication method that produces DSC working electrodes that contain two or more different dyes with complementary optical absorption characteristics. Dye combinations that collectively afford a panchromatic absorption spectrum emulating that of the solar emission spectrum are ideal, given that such combinations use all available sunlight. This review classifies existing cosensitization efforts into seven distinct ways that dyes have been combined in order to generate panchromatic DSCs. Seven cognate molecular-engineering strategies for cosensitization are thereby developed, which tailor optical absorption toward optimal DSC-device function.


Purification and characterization of chitinase from Alcaligenes faecalis AU02 by utilizing marine wastes and its antioxidant activity.
Marine waste is an abundant renewable source for the recovery of several value added metabolites with potential industrial applications. This study describes the production of chitinase on marine waste, with the subsequent use of the same marine waste for the extraction of antioxidants. A chitinase-producing bacterium isolated from seafood effluent was identified as Alcaligenes faecalis AU02. Optimal chitinase production was obtained in culture conditions of 37°C for 72 h in 100 ml medium containing 1% shrimp and crab shell powder (1:1) (w/v), 0.1% K(2)HPO(4), and 0.05% MgSO(4)·7H(2)O. The molecular weight of chitinase was determined by SDS-PAGE to be 36 kDa. The optimum pH, temperature, pH stability, and thermal stability of chitinase were about 8, 37°C, 5-12, and 40-80°C, respectively. The antioxidant activity of A. faecalis AU02 culture supernatant was determined through scavenging ability on 1,1-diphenyl-2-picrylhydrazyl (DPPH) as 84%, and the antioxidant compound was characterized by TLC and its FT-IR spectrum. The present study proposed that marine wastes can be utilized to generate a high-value-added product and that pharmacological studies can extend its use to the field of medicine.


Skin preparation for preventing infection following caesarean section.
The risk of maternal mortality and morbidity (particularly postoperative infection) is higher for caesarean section than for vaginal birth. With the increase in caesarean section, it is important that the risks to the mother are minimised as far as possible. This review focuses on different forms and methods for preoperative skin preparation to prevent infection. To compare the effects of different agent forms and methods of preoperative skin preparation for preventing postcaesarean infection. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 January 2012) and the reference lists of all included studies and review articles Randomised and quasi-randomised trials, including cluster-randomised trials, evaluating any type of preoperative skin preparation agents, forms and methods of application for caesarean section. Three review authors independently assessed all potential studies for inclusion, assessed risk of bias and extracted the data using a predesigned form. Data were checked for accuracy. We included five trials with a total of 1462 women. No difference was found in the primary outcomes of either wound infection or endometritis. Two trials of 1294 women, compared drape with no drape (one trial using iodine and the other using chlorhexidine) and found no significant difference in wound infection (risk ratio (RR) 1.29; 95% confidence interval (CI) 0.97 to 1.71). One trial of 79 women comparing alcohol scrub and iodophor drape with iodophor scrub without drape reported no wound infection in either group. One trial of 50 women comparing parachlorometaxylenol plus iodine with iodine alone reported no significant difference in wound infection (RR 0.33; 95% CI 0.04 to 2.99).Two trials reported endometritis, one trial comparing alcohol scrub and iodophor drape with iodophor scrub only found no significant difference (RR 1.62; 95% CI 0.29 to 9.16). The other trial of 50 women comparing parachlorometaxylenol plus iodine with iodine alone reported no significant difference in endometritis (RR 0.88; 95% CI 0.56 to 1.38). No difference was found in the secondary outcome of either length of stay or reduction of skin bacteria colony count. No trial reported other maternal outcomes, i.e. maternal mortality, repeat surgery and re-admission resulting from infection. One trial, which was only available as an abstract, investigated the effect of skin preparation on neonatal adverse events and found cord blood iodine concentration to be significantly higher in the iodine group. Little evidence is available from the included randomised controlled trials to evaluate different agent forms, concentrations and methods of skin preparation for preventing infection following caesarean section. Therefore, it is not yet clear what sort of skin preparation may be most efficient for preventing postcaesarean wound and surgical site infection. There is a need for high-quality, properly designed randomised controlled trials with larger sample sizes in this field. High priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), the timing and duration of applying the antiseptic (especially previous night versus day of surgery, and application methods (scrubbing, swabbing and draping).


Vascular and inflammatory actions of P2X receptors in renal injury.
P2 purinergic receptors are activated by extracellular ATP and subserve a plethora of roles in the body, including metabolism, inflammation and neuronal signalling. This review focuses on renal purinergic receptors and how different roles that they play may contribute to renal dysfunction and the progression of chronic kidney disease. Numerous studies have linked P2 receptors, particularly the P2X4R and P2X7R subtypes, to kidney injury and damage. However, the mechanisms underlying this association are not fully defined. Several studies show that activation of P2X4R and particularly P2X7R can have a pro-inflammatory effect, causing or exacerbating damage to renal tissue. However, clinical trials aiming to utilise P2X7R antagonists to treat inflammatory disease have been unsuccessful, and it is possible that other mechanisms besides inflammation tie P2X7R activation to disease progression. In this context, purinergic signalling is also involved in the control of vascular tone and our recent studies suggest that activation of P2X4R/P2X7R causes renal vascular dysfunction and contributes to chronic kidney disease. This brief review aims to summarise the complementary inflammatory and vascular roles of P2X receptors in the kidney, with emphasis on the subtypes P2X4R and P27XR, and how each contributes to and presents therapeutic targets in the progression of chronic kidney disease.


[Caspase-9 (-Ex5+32 G/A) gene polymorphism is associated with caspase-9 expression in degenerative nucleus pulposus of lumbar intervertebral disc].
Objective To investigate the relationship between caspase-9 (-Ex5+32 G/A) gene polymorphisms, Schneiderman score of magnetic resonance imaging (MRI) in lumbar disc degeneration and the expression of caspase-9 in degenerative nucleus pulposus. Methods The peripheral venous blood and prominent nucleus pulposus were obtained from 105 patients with lumbar disc herniation. Genomic DNA was extracted and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The caspase-9(-Ex5+32 G/A) gene polymorphisms were analyzed in all DNA samples. The expression of caspase-9 in the tissues was detected by immunohistochemical SP staining. The t test was used to analyze the difference between the genotypes and the expression of caspase-9 in intervertebral disc nucleus. Pearson correlation analysis was performed to assess the association between caspase-9 expression in nucleus pulposus and the MRI score of lumbar disc. Results MRI analysis showed that the patients with AA genotype had the highest MRI scores, but there were no significant differences in MRI scores among patients with AA, GA, and GG genotypes. Compared with GG genotype carriers, AA genotype carriers had a statistically significant difference in the expression of caspase-9 in nucleus pulposus. There was no correlation between the MRI score of lumbar disc degeneration and the expression of caspase-9 in the degenerated nucleus pulposus. Conclusion The caspase-9(-Ex5+32 G/A) gene polymorphism is associated with the expression of caspase-9 in the degenerative nucleus pulposus. However, the MRI Schneiderman score is not significantly correlated with the expression of caspase-9 in degenerative nucleus pulposus.


MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype.
To determine the frequency, mutation spectrum and phenotype of the recently described autosomal recessive MUTYH-associated polyposis (MAP), we performed a systematic search for MUTYH (MYH) mutations by sequencing the complete coding region of the gene in 329 unselected APC mutation-negative index patients with the clinical diagnosis of familial adenomatous polyposis (FAP) or attenuated FAP (AFAP). Biallelic germline mutations in MUTYH were identified in 55 of the 329 unselected patients (17%) and in another 9 selected index cases. About one-fifth (20%) of the 64 unrelated MAP patients harboured none of the 2 hot-spot missense mutations Y165C and/or G382D. Including 7 affected relatives, almost all MAP patients presented with either an attenuated (80%) or with an atypical phenotype (18%). Fifty percentage of the MAP patients had colorectal cancer at diagnosis. Duodenal polyposis was found in 18%, thyroid and stomach cancer in 1 case, other extraintestinal manifestations associated with FAP were not observed. In 8 families, vertical segregation was suspected; in 2 of these families, biallelic mutations were identified in 2 generations. Monoallelic changes with predicted functional relevance were found in 0.9% of the 329 patients, which is in accordance with the carrier frequency in the general population. In conclusion, biallelic MUTYH mutations are the underlying genetic basis in a substantial fraction of patients with adenomatous polyposis. The phenotype of MAP is best characterised as attenuated or atypical, respectively. Colorectal surveillance starting at about 18 years of age is recommended for biallelic mutation carriers and siblings of MAP patients, who refuse predictive testing.


Portable recording in the assessment of obstructive sleep apnea. ASDA standards of practice.
The objective assessment of patients with a presumptive diagnosis of obstructive sleep apnea (OSA) has primarily used attended polysomnographic study. Recent technologic advances and issues of availability, convenience and cost have led to a rapid increase in the use of portable recording devices. However, limited scientific information has been published regarding the evaluation of the efficacy, accuracy, validity, utility, cost effectiveness and limitations of this portable equipment. Attaining a clear assessment of the role of portable devices is complicated by the multiplicity of recording systems and the variability of clinical settings in which they have been analyzed. This paper reviews the current knowledge base regarding portable recording in the assessment of OSA, including technical considerations, validation studies, potential advantages and disadvantages, issues of safety, current clinical usage and areas most in need of further study.


Comparison of the Respiratory Toxicity and Total Cholinesterase Activities in Dimethyl Versus Diethyl Paraoxon-Poisoned Rats.
The chemical structure of organophosphate compounds (OPs) is a well-known factor which modifies the acute toxicity of these compounds. We compared ventilation at rest and cholinesterase activities in male Sprague-Dawley rats poisoned with dimethyl paraoxon (DMPO) and diethyl paraoxon (DEPO) at a subcutaneous dose corresponding to 50% of the median lethal dose (MLD). Ventilation at rest was recorded by whole body plethysmography. Total cholinesterase activities were determined by radiometric assay. Both organophosphates decreased significantly the respiratory rate, resulting from an increase in expiratory time. Dimethyl-induced respiratory toxicity spontaneously reversed within 120 min post-injection. Diethyl-induced respiratory toxicity was long-lasting, more than 180 min post-injection. Both organophosphates decreased cholinesterase activities from 10 to 180 min post-injection with the same degree of inhibition of total cholinesterase within an onset at the same times after injection. There were no significant differences in residual cholinesterase activities between dimethyl and diethyl paraoxon groups at any time. The structure of the alkoxy-group is a determinant factor of the late phase of poisoning, conditioning duration of toxicity without significant effects on the magnitude of alteration of respiratory parameters. For same duration and magnitude of cholinesterase inhibition, there was a strong discrepancy in the time-course of effects between the two compounds.


Asymmetric Construction of 3-Azabicyclo[3.1.0]hexane Skeleton with Five Contiguous Stereogenic Centers by Cu-Catalyzed 1,3-Dipolar Cycloaddition of Trisubstituted Cyclopropenes.
A highly diastereo- and enantioselective desymmetrization of prochiral cyclopropenes via a Cu(CH3CN)4BF4/Ph-Phosferrox complex catalyzed 1,3-dipolar cycloaddition of azomethine ylides was described. A variety of complex 3-azabicyclo[3.1.0]hexane derivatives bearing five contiguous stereogenic centers and two all-carbon quaternary stereogenic centers were directly synthesized as a single isomer in excellent yields (up to 99%) and enantioselectivities (97 → 99% ee). Notably, various functional groups (CO2R, CN, CONMe2, and Ph) of cyclopropenes were found to be well-tolerated in this transformation. The cycloadduct was conveniently converted to a biologically important GABA derivative via LiAlH4 reduction and subsequent hydrolysis.


[Sialadenitis at an unusual site in acute infectious mononucleosis].
Infectious mononucleosis is found worldwide. The clinical manifestations vary widely. We report a case with impressive swelling of the hard and soft palate. Inflammation in the region of the efferent ducts of the palatinal glands resulted in congestion in the region of the mucinous salivary glands. The subsequent secretory stasis caused degeneration of the acini and rupture of a salivary retention cyst. The surrounding connective tissue was soaked with mucin, and unspecific chronic granular inflammation was found. Immunohistochemical examination with a monoclonal EBV antibody was necessary to show that the exceptional clinical picture was due to infectious mononucleosis.


Intercluster reactions show that (CH3)2S(+)CH2CO2H is a better methyl cation donor than (CH3)3N(+)CH2CO2H.
The intrinsic methylating abilities of the known biological methylating zwitterionic agents, dimethylsulfonioacetate (DMSA), (CH(3))(2)S⁺CH(2)CO(2)(-) (1) and glycine betaine (GB), (CH(3))(3)N⁺CH(2)CO(2)(-) (2), have been examined via a range of gas phase experiments involving collision-induced dissociation (CID) of their proton-bound homo- and heterodimers, including those containing the amino acid arginine. The relative yields of the products of methyl cation transfer are consistent in all cases and show that protonated DMSA is a more potent methylating agent than protonated GB. Since methylation can occur at more than one site in arginine, the [M+CH(3)](+) ion of arginine, formed from the heterocluster [DMSA+Arg+H](+), was subject to an additional stage of CID. The resultant CID spectrum is virtually identical to that of an authentic sample of protonated arginine-O-methyl ester but is significantly different to that of an authentic sample of protonated N(G)-methyl arginine. This suggests that methylation has occurred within a salt bridge complex of [DMSA+Arg+H](+), in which the arginine exists in the zwitterionic form. Finally, density functional theory calculations on the model salts, (CH(3)CO(2)(-))[(CH(3))(3)S(+)] and (CH(3)CO(2)(-))[(CH(3))(4)N(+)], show that methylation of CH(3)CO(2)(-) by (CH(3))(3)S(+) is both kinetically and thermodynamically preferred over methylation by (CH(3))(4)N(+).


Seizure prediction: methods.
Epilepsy, one of the most common neurological diseases, affects over 50 million people worldwide. Epilepsy can have a broad spectrum of debilitating medical and social consequences. Although antiepileptic drugs have helped treat millions of patients, roughly a third of all patients have seizures that are refractory to pharmacological intervention. The evolution of our understanding of this dynamic disease leads to new treatment possibilities. There is great interest in the development of devices that incorporate algorithms capable of detecting early onset of seizures or even predicting them hours before they occur. The lead time provided by these new technologies will allow for new types of interventional treatment. In the near future, seizures may be detected and aborted before physical manifestations begin. In this chapter we discuss the algorithms that make these devices possible and how they have been implemented to date. We also compare and contrast these measures, and review their individual strengths and weaknesses. Finally, we illustrate how these techniques can be combined in a closed-loop seizure prevention system. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.


Stereological analysis of non-Hodgkins lymphomas.
A detailed stereological analysis was carried out on 30 lymph nodes at 2 ultrastructural levels. They were classified as follows: 10 were reactive lymph nodes, 10 were of low-grade non-Hodgkins lymphomas and 10 were of high-grade non-Hodgkins lymphomas. The mean and median values and interquartile ranges of nuclear profile diameter, nuclear volume, volume of cytoplasm, cell volume and absolute number of ribosomes were recorded for each case. The model proved very efficient in establishing several significant differences between the highgrade and lowgrade lymphomas and between the highgrade lymphomas and reactive lymph nodes but did not discriminate between lowgrade lymphomas and reactive nodes, nor did it distinguish neoplastic cells from reactive cells in the neoplastic group. The significance of these findings is discussed.


Bumetanide/amiloride ('Burinex A'): a new combined preparation for the control of patients with congestive cardiac failure.
Two hundred and thirty-three patients (66 males and 167 females), aged 24 to 92 years, with congestive cardiac failure were entered into a long-term study to evaluate the efficacy and tolerability of treatment with a fixed dose combination tablet containing 1 mg bumetanide and 5 mg amiloride. One hundred and fifty-five patients were treated for 52 weeks. The daily dosages were 1 tablet (113 patients), 2 tablets (35 patients), 3 or 4 tablets (7 patients). Treatment was associated with a marked reduction in the prevalence of ankle oedema, dyspnoea and pulmonary crepitations, and with statistically significant decreases in body weight, pulse rate and calf measurement. Mean serum potassium showed a small but statistically significant increase, but serious hyperkalaemia was not encountered. Although serum sodium decreased, serious hyponatraemia did not occur. No clinically significant effects on hepatic, renal or haemopoietic function were observed. Minor adverse effects, most of which resolved spontaneously, were reported by 60 patients. Only 14 (6.0%) patients ceased treatment because of adverse effects.


Surgical treatment results of Iranian abdominal trauma casualties in the Iran and Iraq war.
Military medicine is a field to which a great deal of manpower, time, and effort is devoted. Abdominal traumatic injuries in field hospitals are among the major lesions to be treated, and laparotomies have a special role in the treatment of these injuries. This study was performed to assess the care of abdominal lesions in Iranian troops so that the results can be used in future planning programs. In a cross-sectional descriptive-analytical study, 522 cases of laparotomies were studied by the census method. These troops were injured from 1982 to 1987. Primary site of injury, general medical condition, location of the hospitals, and ensuing complications were studied. Most of the patients were younger than 30 years, and the mortality rate was greater in rearward hospitals. Seventy-four patients had poor general condition at the time of admission; 30% of them ultimately died, which showed a statistically significant difference between the patients in field hospitals and those in rearward hospitals with regard to final prognosis (p > 0.05). The colon, small intestine, and thorax were the most common sites of injuries. The trend of complications somewhat followed the trend of the primary lesions, with some specific variations. This study offers a full review of a great number of the abdominal surgical cases, their modes of treatment, and the ensuing complications. Also, the role of field hospitals is emphasized. Patients with poor initial general conditions should receive vigorous attention. In all patients, even the least common sites of injury should not be neglected or lethal complications could ensue.