Mechanisms of Plasmodium-Enhanced Attraction of Mosquito Vectors.
Evidence is accumulating that Plasmodium-infected vertebrates are more attractive to mosquitoes than noninfected hosts, particularly when high levels of gametocytes are present. Changes in host odour have been suggested as a likely target for parasite manipulation because olfactory cues are crucial to mosquitoes in search of a bloodmeal host. This review discusses two routes that may lead to such changes: (i) direct emission of volatile products from malaria parasites, and (ii) changes in skin microbial composition that could lead to changes in the vertebrate odour profile. Here we synthesize what is known and suggest how further research can increase our understanding of the mechanisms of parasite manipulation of host attractiveness.


Isolation of two kinds of E. coli K-12 mutants for lysophospholipase L2: one with an elevated level of the enzyme and the other defective in it.
Two kinds of E. coli K-12 mutants for lysophospholipase L2 (located in the inner membrane) were isolated, using an improved version of the colony autoradiographic method developed by Raetz; these were, 1) strains carrying an elevated level of the enzyme and 2) strains defective or temperature-sensitive in the enzyme. Characterization of the crude lysates of these mutants revealed that the differences of lysophospholipase L2 activity are not due to the presence or absence of regulatory factors. Evidence was obtained, by using these mutants, that this lysophospholipase L2 transfers the acyl group of 2-acyl lysophospholipid to phosphatidylglycerol, forming acyl phosphatidylglycerol.


Dietary Isoflavones as Modulators of Drug Metabolizing Enzymes and Transporters: Effect on Prescription Medicines.
Isoflavones are the most widely consumed phytoestrogens. Besides being a dietary constituent, their consumption has been increasing in the form of herbal supplements and as promising alternatives to hormonal replacement therapy, in conjunction with prescription medicines. Isoflavones are extensively metabolized by phase I and II enzymes and are substrates of drug transporters. At high concentrations isoflavones may interact with drug metabolizing enzymes and drug transporters and modulate their activity, thus, altering the absorption, metabolism, distribution, excretion and toxicity profile of the co-administered drugs. This review summarizes the up-to-date literature of isoflavone-drug interactions giving insight into the possible mechanisms of interactions, in vitro-in vivo correlation and their implications on clinical outcomes.


Effect of different types of conditioning contraction on upper body postactivation potentiation.
Muscle contractions preceding an activity can result in increased force generation (postactivation potentiation [PAP]). Although the type of muscular contractions could affect subsequent strength and power performance, little information exists on their effects. The purpose of this study was to examine PAP effects produced by isometric (ISO), concentric (CON), eccentric (ECC), or concentric-eccentric (DYN) conditioning contractions on upper body force and power performance. Ten male, competitive rugby players (mean ± SD: age 20.4 ± 0.8 years, height 177.0 ± 8.1 cm, body mass 90.2 ± 13.8 kg) performed a ballistic bench press throw (BBPT) followed by a 10-minute rest and one of the conditioning contractions. After a 12-minute rest, the subjects performed another BBPT (post-BBPT). The conditioning contractions, applied on separate days and in counterbalanced randomized order, were a 7-second isometric barbell bench press for ISO and 1 set of 3 bench press repetitions at 3 repetition maximum for CON, ECC, and DYN (each repetition lasting 2 seconds for CON and ECC, overall execution time <7 seconds for DYN). Peak power (Ppeak), peak force (Fpeak), maximum distance (Dmax) and rate of force development (RFD) were measured using a linear position transducer. Electromyography (EMG) of the pectoralis major and triceps brachii was also recorded. The ISO produced significantly higher Ppeak (587 ± 116 and 605 ± 126 W for pre- and post-BBPT, respectively; p < 0.05). No significant differences in Ppeak were revealed for CON, ECC, and DYN (p > 0.05), and no significant differences existed in Fpeak, Dmax, and RFD for ISO, CON, ECC, and DYN (p > 0.05). Finally, EMG was not significantly different between pre- and post-BBPT for any of the conditioning contractions (p > 0.05). Isometric contractions appear to be the only conditioning contractions increasing upper body power output after long resting periods.


Altered hippocampal network excitability in the hypernoradrenergic mutant mouse tottering.
A latent, gene-linked alteration of hippocampal network excitability in tg/tg mutant mice was unmasked in vitro by convulsant-activated synchronous neuronal discharges. Exposure to elevated extracellular potassium ions or 4-aminopyridine, but not picrotoxin, revealed an abnormally prolonged network discharge duration in the mutant CA3 pyramidal cell region. In both phenotypes, noradrenaline, and a selective beta-noradrenergic receptor agonist, isoproterenol, reversibly accelerated the frequency of the discharges. These findings identify an intrinsic alteration in the excitability of an isolated neuronal network in a model of inherited generalized spike-wave epilepsy, and further implicate noradrenergic mechanisms in the temporal modulation of hippocampal synchronization and epileptogenesis.


Cloning and characterization of the glucagon receptor from cynomologous monkey.
The glucagon receptor was cloned from cynolomologous monkey. A frame-shift mutation at the 3' end of the monkey transcript results in a C-terminal extension of 14 amino acids. This extension is not observed in either the human or rodent glucagon receptors. Monkey glucagon receptor was expressed in CHO cells, either with (mkGCGR) or without (mkGCGRDelta14) the 14-amino acid C-terminal extension to approximate the human receptor. Both forms of the monkey receptor bound glucagon with similar affinity and showed glucagon-stimulated cAMP production, however the full-length form of the monkey receptor (mkGCGR) was less sensitive to glucagon in its ability to stimulate cAMP than the shortened form (mkGCGRDelta14). PCR of genomic DNA from baboon and rhesus monkeys suggests that they express a form of the receptor similar to that of cynomologous monkey, while in chimpanzee, the receptor is similar to the human form.


Does Yik Yak Promote Risky Health Behavior on College Campuses?
This study offers an analysis of how healthy and risky behaviors are discussed on an emerging social media platform. We sought to understand what behaviors are communicated and if they are encouraged or discouraged. We completed a content analysis of messages (n = 3,776) posted to Yik Yak captured three times a day on 4 days of the week across two separate weeks. We analyzed messages to determine the category of the behavior, an appraisal of the behavior, and normative voting feedback. Our results show that risky behaviors were discussed with greater frequency and received more user votes than healthy behaviors. Exposure to these messages could influence other students' perceptions of norms associated with these risky behaviors. We suggest further research to determine how Yik Yak may affect normative perceptions on college campuses.


Effect of a short-term treatment with alendronate on bone density and bone markers in patients with central diabetes insipidus.
The aim of this open prospective randomized study was to evaluate the effect of a 6-month treatment with alendronate on the bone mineral density (BMD) at lumbar spine in patients with central diabetes insipidus. Eighteen patients with central diabetes insipidus and 18 sex- and age-matched healthy subjects entered this study. At study entry, all subjects underwent BMD assessment at the lumbar spine and measurement of serum osteocalcin (OC) and cross-linked N-telopeptides of type I collagen (Ntx). Thereafter, 9 of the 18 patients were randomized to receive treatment with alendronate at a dose of 10 mg, orally, once daily for 6 months (group 1), whereas the remaining 9 patients did not receive any treatment affecting bone status during this period (group 2). After 6 months, bone metabolism and bone density study were repeated in all patients. At baseline, lumbar BMD values (0.86+/-0.03 vs. 1.01+/-0.02 g/cm2; P<0.001) and serum OC levels (4.7+/-0.3 vs. 7.9+/-0.2 microg/L; P<0.001) were significantly lower, whereas urinary Ntx levels were significantly higher [72.0+/-1.9 vs. 64.6+/-1.7 nmol bone collagen equivalents (BCE)/nmol creatinine (Cr); P<0.01] in patients than in controls. After randomization, no difference in lumbar BMD, serum OC, or urinary Ntx was found between patients of group 1 and group 2. At the 6 month follow-up, no difference in serum OC levels was found compared to baseline evaluation in patients of both group 1 and group 2. By contrast, a significant decrease in urinary Ntx levels was found in patients of group 1 (70.3+/-3.0 vs. 75.4+/-2.1 nmol BCE/nmol Cr; P<0.05), but not in patients of group 2 (68.8+/-3.3 vs. 68.5+/-3.0 nmol BCE/nmol Cr; P = NS). A significant increase in lumbar BMD values was found in patients of group 1 (0.88+/-0.04 vs. 0.83+/-0.04 g/cm2; P<0.05), whereas a significant decrease in lumbar BMD values was found in patients of group 2 (0.86+/-0.05 vs. 0.89+/-0.05 g/cm2; P<0.05). Lumbar BMD increased 7.0+/-1.5% in patients of group 1 and decreased 4.2+/-1.8% in patients of group 2 (P<0.001). In conclusion, this study demonstrated that a 6-month treatment with alendronate in patients with central diabetes insipidus was effective in significantly improving BMD at the lumbar spine, which was significantly worsened in untreated patients. Therefore, alendronate treatment could be used in patients with central diabetes insipidus with documented osteopenia or osteoporosis.


CEA-producing mucin-negative gastric signet-ring cell carcinoma with neuroendocrine markers: a case report.
Biopsy and autopsy materials excised from a 69-year-old woman were investigated. Serum carcinoembryonic antigen (CEA) showed a high value of 955 ng/mL. A plateaulike tumor was located in the gastric cardia and fundus to the entire gastric body. It showed severe proliferation and infiltration from the mucosa to the serosa. The tumor was comprised of signet-ring cells and poorly differentiated adenocarcinoma cells, which spread into the submucosa of the pylorus, duodenum, and jejunum. Signet-ring cells had a large, eccentric vesicular nucleus and a pale cytoplasmic inclusion. Poorly differentiated adenocarcinoma cells had a pleomorphic nucleus, small eosinophilic nucleolus, and abundant eosinophilic cytoplasm. Both neoplastic cells were positive for CEA, epithelial membrane antigen, Leu-7 (CD57), and neuron-specific enolase, and were negative for cytokeratin, vimentin, and periodic acid-Schiff, Alcian blue, and mucicarmine stains. Electron microscopy showed endocrine granules with a limiting membrane measuring approximately 238 nm in diameter in the cytoplasm. The authors diagnosed this patient as having mucin-negative gastric signet-ring cell carcinoma with neuroendocrine markers, which is suggested to exist among poorly differentiated adenocarcinoma, undifferentiated carcinoma, and signet-ring cell carcinoma.


Oral candidal carriage and infection in insulin-treated diabetic patients.
To evaluate candidal load and carriage of candidal species in 414 insulin-treated diabetes mellitus patients with and without clinical signs of infection. Host factors that could influence candidal load in diabetic patients with oral candidosis were also investigated. Candidal species were recovered from 414 insulin-treated diabetes mellitus patients attending two hospital diabetic clinics, using an oral rinse technique. Seventy-seven per cent of diabetic patients carried Candida species in their oral cavity, with C. albicans being the species most frequently isolated. C. dubliniensis was found for the first time in this patient group. Forty per cent of patients colonized with candidal species had no clinical signs of oral candidosis. Where oral candidosis was present, erythematous candidosis was the most common clinical presentation. Candidal load was not associated with age, sex or glycaemic control. However, it was significantly increased in those patients who were tobacco smokers, and non-significantly increased in those patients who wore dentures, or who had clinical signs of oral candidosis. The epidemiology of oral candidal carriage and infections in diabetic patients is complex and includes species which have not been previously reported in this group of patients. The development of oral candidosis in insulin-treated diabetes mellitus patients is not the result of a single entity, but rather, a combination of risk factors.


Stent implantation to ductus arteriosus in a patient with interrupted aortic arch guided by CT image overlay.
A 15-day-old premature patient with ventricular septal defect and interrupted aortic arch type B underwent "hybrid" initial treatment consisting of bilateral pulmonary artery banding followed by stenting of the ductus arteriosus. A pre-registered CT scan was re-purposed with a new three-dimensional image fusion software (VesselNavigator) to create a roadmap for stent delivery.


Production of rat protein disulfide isomerase in Saccharomyces cerevisiae.
Protein disulfide isomerase (PDI) is an abundant protein of the endoplasmic reticulum that catalyzes the oxidation of protein sulfhydryl groups and the isomerization and reduction of protein disulfide bonds. Saccharomyces cerevisiae cells lacking PDI are inviable. PDI is a component of many different protein processing complexes, and the actual activity of PDI that is required for cell viability is unclear. A cDNA that codes for rat PDI fused to the alpha-factor pre-pro segment was expressed in a protease-deficient strain of S. cerevisiae under the control of an ADH2-GAPDH hybrid promoter. The cells processed the resulting protein and secreted it into the medium as a monomer, despite having a KDEL or HDEL sequence at its C-terminus. The typical yield of isolated protein was 2 mg per liter of culture. The catalytic activity of the PDI from S. cerevisiae was indistinguishable from that of PDI isolated from bovine liver. This expression system is unique in allowing the same plasmid to be used both to complement pdi1 delta S. cerevisiae and to produce PDI for detailed in vitro analyses. Correlations of the in vivo behavior and in vitro properties of PDI are likely to reveal structure-function relationships of biological importance.


Influence of the anisotropy on zero-group velocity Lamb modes.
Guided waves in a free isotropic plate (symmetric S(n) and antisymmetric A(n) Lamb modes) exhibit a resonant behavior at frequencies where their group velocity vanishes while their phase velocity remains finite. Previous studies of this phenomenon were limited to isotropic materials. In this paper, the optical generation and detection of these zero-group velocity (ZGV) Lamb modes in an anisotropic plate is investigated. With a circular laser source, multiple local resonances were observed on a silicon wafer. Experiments performed with a line source demonstrated that the frequency and the amplitude of these resonances depend on the line orientation. A comparison between experimental and theoretical dispersion curves for waves propagating along the [100] and [110] directions of the silicon crystal verified that these resonances occur at the minimum frequency of the S(1) and A(2) Lamb modes. Simulations indicated that it is possible to deduce the three elastic constants of the plate material with good accuracy from these measurements.


Fat-soluble vitamin supplements for enterally fed preterm infants.
Fat-soluble vitamin requirements for the enterally fed premature infant are an important concern, both before and after discharge from the neonatal intensive care unit. Because preterm infants fed unsupplemented human milk receive deficient quantities of these vitamins (A, D, E, and K), supplements are very important for this population. Vitamin intakes with special formulas for low birth weight infants and human milk fortifiers are also reviewed.


Temporal abstraction and data mining with visualization of laboratory data.
To analyze the laboratory data by data mining, user-centered universal tools have not been available in medicine. We analyzed 1,565,877 laboratory data of 771 patients with viral hepatitis in order to find the difference of the temporal changes in laboratory test data between Hepatitis B and Hepatitis C by the combination of temporal abstraction and data mining. The data for one patient is temporal for more than 5 years. After pretreatment the data was converted to abstract patterns and then selected into sets of data combination and rules to identify Hepatitis B or C by D2MS and LUPC which were originally produced by ourselves. Not only data pattern, but also temporal relations were considered as a part of the rules. In the course of evaluating the results by domain experts, even though there were not so remarkable hypotheses, visualization tools made it easier for them to understand the relations of the complicated rules.


Relation of nonperfused myocardial volume and surface area to left ventricular performance in coronary microembolization.
After occlusion of an epicardial artery, left ventricular (LV) dysfunction is closely related to the volume of nonperfused myocardium (NPM). The impact of coronary microembolization (ME) on LV function, however, is larger relative to the total volume of NPM. We hypothesized that the total surface area (SA), rather than the total volume, of NPM is the major determinant of ME-induced LV dysfunction. We injected microspheres of 10-, 30-, or 100-microm diameter at each of 3 doses selectively into the left anterior descending coronary artery of 48 anesthetized pigs. Electron beam computed tomography (CT) was used to measure regional myocardial perfusion and changes in LV wall thickening (DeltaWT) and stroke volume (DeltaSV) after ME. At postmortem, a transmural "biopsy" of 1 to 2 cm3 of embolized myocardium was imaged by micro-CT, resulting in 3D images that provided volumes and SAs of the individual nonperfused foci. Additionally, in 9 pigs, creatine phosphokinase (CK) activity in embolized myocardium was measured as an index of washout of substances from the NPM. After ME, DeltaWT, DeltaSV, and CK washout were correlated more closely with the total SA (r=0.95, P<0.001; r=0.68, P<0.01; and r=0.88, P=0.01, respectively) than with the total NPM volume (r=0.59, P>0.05; 0.46, P>0.05; and r=0.69, P=0.04, respectively). After coronary ME, LV dysfunction is more closely related to the total SA than to the total volume of nonperfused microregions in the myocardium.


Contrasting land uses in Mediterranean agro-silvo-pastoral systems generated patchy diversity patterns of vascular plants and below-ground microorganisms.
The aims of this paper were (i) to define how contrasting land uses affected plant biodiversity in Mediterranean agro-silvo-pastoral-systems across a gradient of disturbance regimes: cork oak forests, secondary grasslands, hay crops, grass covered vineyards, tilled vineyards; (ii) to determine whether these patterns mirrored those of below-ground microorganisms and whether the components of γ-diversity followed a similar model. The disturbance regimes affected plant assemblage composition. Species richness decreased with increasing land use intensity, the Shannon index showed the highest values in grasslands and hay crops. Plant assemblage composition patterns mirrored those of Basidiomycota and Ascomycota. Richness in Basidiomycota, denitrifying bacteria and microbial biomass showed the same trend as that observed for vascular plant richness. The Shannon index pattern of below-ground microorganisms was different from that of plants. The plant γ-diversity component model weakly mirrored those of Ascomycota. Patchy diversity patterns suggest that the maintenance of contrasting land uses associated with different productions typical of agro-silvo-pastoral-systems can guarantee the conservation of biodiversity.


CardioVINEdb: a data warehouse approach for integration of life science data in cardiovascular diseases.
One of the major challenges in bioinfomatics is to integrate and manage data from different sources as well as experimental microarray data and present them in a user-friendly format. Therefore, we present CardioVINEdb, a data warehouse approach developed to interact with and explore life science data. The data warehouse architecture provides a platform independent web interface that can be used with any common web browser. A monitor component controls and updates the data from the different sources to guarantee up-todateness. In addition, the system provides a "static" and "dynamic" visualization component for interactive graphical exploration of the data.


International distance-learning outreach: the APEC EINet experience.
The Emerging Infections Network is a mature electronic network that links Public Health professionals in the Asia Pacific through regular e-mail bulletins and an extensive Web site (http://www.apec.org/infectious). Emerging infections is a new area of study; learning materials help foster education. Our objective is to quantify the response of the network to the introduction of distance-learning materials on the Web site. Distance-learning materials, developed by the University of Washington School of Public Health, were field tested and launched on the site. Publicity was carried out prior to the launch of the materials. Access was tracked prospectively using server counts of page downloads. Web access increased substantially during the month after the materials were launched, especially among Asia based computers. The effect was isolated to the distance-learning pages, and not general to the site. This Web site appears to be responsive to the advertisement and to the materials. Prospective Web-site monitoring proved useful.


A combined genotypic and phenotypic human immunodeficiency virus type 1 recombinant virus assay for the reverse transcriptase and integrase genes.
With the approval of the first HIV-1 integrase inhibitor raltegravir and a second one in phase III clinical development (elvitegravir), genotypic and phenotypic resistance assays are required to guide antiretroviral therapy and to investigate treatment failure. In this study, a genotypic and phenotypic recombinant virus assay was validated for determining resistance against integrase inhibitors. The assays are based on the amplification of a region encompassing not only HIV-1 integrase, but also reverse transcriptase and RNAseH. The overall amplification success was 85% (433/513) and increased to 93% (120/129) for samples with a viral load above 3 log(10) copies/ml. Both B and non-B HIV-1 subtypes could be genotyped successfully (93%; 52/56 and 100%; 49/49, respectively) and reproducibly. The phenotypic assay showed a high success rate (96.5%; 139/144) for subtype B (100%; 19/19) and non-B subtypes (92%; 45/49), and was found to be accurate and reproducible as assessed using well-characterized integrase mutants. Using both assays, baseline resistance to raltegravir and elvitegravir in subtype B and non-B HIV-1 strains selected at random was not observed, although integrase polymorphisms were present at varying prevalence. Biological cutoff values were found to be 2.1 and 2.0 for raltegravir and elvitegravir, respectively. In summary, a genotypic and phenotypic integrase resistance assay was validated successfully for accuracy, reproducibility, analytical and clinical sensitivity, and dynamic range.


Interleukin-6 and C-reactive protein as early markers of sepsis in patients with diabetic ketoacidosis or hyperosmosis.
An early diagnosis of sepsis in patients with diabetic ketoacidosis and hyperosmolar non-ketotic coma is crucial and could save lives. We studied serum C-reactive protein and interleukin-6 to find out how useful these might be for identifying sepsis. Sixty one diabetic patients with ketoacidosis or hyperosmolar non-ketotic coma were enrolled. Patients with signs and symptoms of systemic inflammatory response syndrome were identified. Acute-phase reactants, including C-reactive protein and interleukin-6, the main cytokine responsible for the induction of acute-phase proteins, were measured on admission and when patients had clinically improved and were euglycaemic. A total of 49 out of 61 patients with diabetic ketoacidosis or hyperosmosis had signs of systemic inflammatory response syndrome. Another 27 patients had systemic inflammatory response syndrome and no signs of infection and 22 patients had systemic inflammatory response syndrome due to proven infection. We detected a significant increase in serum C-reactive protein and interleukin-6 values in patients infected compared with patients not infected with systemic inflammatory response syndrome SIRS. Patients who finally died had much higher levels of these proteins, while there was a prompt reduction of serum C-reactive protein and interleukin-6 early during remission. Diabetic ketoacidosis and hyperosmolar non-ketotic coma can often cause a clinical syndrome resembling systemic inflammatory response syndrome. Determination of serum C-reactive protein and interleukin-6 levels is a useful way of excluding an underlying infection early on as well as confirming and monitoring sepsis.


Speech perception engages a general timer: evidence from a divided attention word identification task.
Time is essential to speech. The duration of speech segments plays a critical role in the perceptual identification of these segments, and therefore in that of spoken words. Here, using a French word identification task, we show that vowels are perceived as shorter when attention is divided between two tasks, as compared to a single task control condition. This temporal underestimation pattern is consistent with attentional models of timing and hence demonstrates that vowel duration is explicitly estimated using a central general-purpose timer.


Microtubule motors in spindle and chromosome motility.
Many of the kinesin microtubule motor proteins discovered during the past 8-9 years have roles in spindle assembly and function or chromosome movement during meiosis or mitosis. The discovery of kinesin motor proteins with a clear involvement in spindle and chromosome motility, together with recent evidence that cytoplasmic dynein plays a role in chromosome distribution, has attracted great interest. The identification of microtubule motors that function in chromosome distribution represents a major advance in understanding the forces that underlie chromosome and spindle movements during cell division.


External and interstitial radiation therapy of locally advanced carcinoma of the breast.
The present report concerns 164 cases of locally advanced breast cancer (stage III), treated between December 1977 and January 1987. The local therapy consisted exclusively of radiation therapy including external beam irradiation (60Co) up to 45-50 Gy supplemented with a boost, delivered either by interstitial 192Ir (30-40 Gy) or by external irradiation from limited fields (15-22 Gy). Eighty-one patients also received adjuvant systemic chemotherapy. A total of 51 local failures (31%) occurred. The actuarial rate of survival with local tumor control was 53% at 5 years and 49% at 6.5 years. A total of 69 patients developed distant metastases (42%). The actuarial survival without distant failure was 43% at 5 years and 37% at 6 years. The actuarial survival rate at 5 years was 53% and 38% at 7 years. The cosmetic results were excellent in 58 patients and poor in 13 patients (9.7%). The result suggests that stage III breast cancer can be satisfactorily treated with radiation therapy alone as local treatment.


Optical fiber-based biosensors.
This review outlines optical fiber-based biosensor research from January 2001 through September 2003 and was written to complement the previous review in this journal by Marazuela and Moreno-Bondi. Optical fiber-based biosensors combine the use of a biological recognition element with an optical fiber or optical fiber bundle. They are classified by the nature of the biological recognition element used for sensing: enzyme, antibody/antigen (immunoassay), nucleic acid, whole cell, and biomimetic, and may be used for a variety of analytes ranging from metals and chemicals to physiological materials.


Development of an integrative transformation system for the opportunistic pathogenic yeast Candida lusitaniae using URA3 as a selection marker.
The nucleotide sequence of the URA3 gene encoding orotidine-5'-phosphate decarboxylase (OMP DCase) of the human opportunistic pathogen yeast Candida lusitaniae was determined by degenerate PCR and chromosome walking. Deduced amino acid sequence showed strong homologies (59-85% identity) with OMP DCases of different Saccharomycetales and allowed identification of the known conserved domains. Very close upstream from the URA3 gene, the 3'-end of a gene encoding a Gea2-like protein was identified. A non-revertible C. lusitaniae ura3 mutant was selected on the basis of 5-fluoroorotic acid resistance. The mutation was a single point mutation resulting in the amino acid substitution D95V in a highly conserved domain, and in a concomitant EcoRV restriction site polymorphism. The mutant strain was successfully transformed to prototrophy following electroporation with the URA3 gene cloned in an integrative vector, with frequencies of 100-200 transformants per micro g of DNA. Southern blot analysis revealed that almost all transformants were derived from homologous recombination events at the resident locus. The GeneBank Accession No. for C. lusitaniae URA3 gene is AF450297.


Age Differences in Voice Evaluation: From Auditory-Perceptual Evaluation to Social Interactions.
The factors that influence the evaluation of voice in adulthood, as well as the consequences of such evaluation on social interactions, are not well understood. Here, we examined the effect of listeners' age and the effect of talker age, sex, and smoking status on the auditory-perceptual evaluation of voice, voice-related psychosocial attributions, and perceived speech tempo. We also examined the voice dimensions affecting the propensity to engage in social interactions. Twenty-five younger (age 19-37 years) and 25 older (age 51-74 years) healthy adults participated in this cross-sectional study. Their task was to evaluate the voice of 80 talkers. Statistical analyses revealed limited effects of the age of the listener on voice evaluation. Specifically, older listeners provided relatively more favorable voice ratings than younger listeners, mainly in terms of roughness. In contrast, the age of the talker had a broader impact on voice evaluation, affecting auditory-perceptual evaluations, psychosocial attributions, and perceived speech tempo. Some of these talker differences were dependent upon the sex of the talker and his or her smoking status. Finally, the results also show that voice-related psychosocial attribution was more strongly associated with the propensity of the listener to engage in social interactions with a person than auditory-perceptual dimensions and perceived speech tempo, especially for the younger adults. These results suggest that age has a broad influence on voice evaluation, with a stronger impact for talker age compared with listener age. While voice-related psychosocial attributions may be an important determinant of social interactions, perceived voice quality and speech tempo appear to be less influential. https://doi.org/10.23641/asha.5844102.


Muscle metabolism in track athletes, using 31P magnetic resonance spectroscopy.
We tested whether preferred running event in track athletes would correlate with the initial rate of phosphocreatine (PCr) resynthesis following submaximal exercise. PCr recovery was measured in the calf muscles of 16 male track athletes and 7 male control subjects following 5 min of repeated plantar flexion against resistance. Pi, PCr, and pH were measured using phosphorus magnetic resonance spectroscopy (31P MRS) with an 8-cm surface coil in a 1.8-T magnet. During exercise, work levels were gradually increased to deplete PCr to 50-60% of the initial value. No drop in pH was seen in any of the subjects during this exercise. The areas of the PCr peaks following exercise were fit to monoexponential curves. Two or three tests were performed on each subject and the results averaged. Athletes were divided into three groups based on their primary event: sprinters running 400 m or less, middle-distance athletes running 400-1500 m, and long-distance athletes running farther than 1500 m. The maximal rates of PCr resynthesis (mmol.min-1.kg-1 muscle weight) were 64.8 +/- 8.6, for long-distance runners; 41.4 +/- 11, for middle-distance runners; 32.0 +/- 7.0, for sprinters; and 38.6 +/- 10, for controls (mean +/- SE). The faster PCr recovery rates seen in long-distance runners compared with sprinters indicate greater oxidative capacity, which is consistent with the known differences between athletes in these events.


A dynamic account of self-efficacy in entrepreneurship.
We present a dynamic account of self-efficacy in entrepreneurship that integrates social-cognitive and control theory. According to our dynamic account, variability in self-efficacy energizes action because it involves self-motivation and discrepancy perception as competing motivational processes. We argue that variability and the average level in self-efficacy nascent entrepreneurs display over time support the enactment of entrepreneurial intentions and predict business ownership. The proposed positive effect of variability further implies an inverted u-shaped relationship between self-efficacy at a single point in time and business ownership. To test these hypotheses, we repeatedly assessed entrepreneurial self-efficacy of nascent African entrepreneurs during a 12-week entrepreneurship training program (total N = 241). Twelve months later, we assessed business ownership (total N = 190). We found that variability and the average level in entrepreneurial self-efficacy participants displayed during the training program were positively related to business ownership. Furthermore, for participants with strong entrepreneurial intentions, we found an inverted u-shaped relationship between entrepreneurial self-efficacy after the training program and business ownership. The study suggests that social-cognitive and control theory highlight different facets of self-regulation that both need to be accounted for to explain goal achievement in entrepreneurship. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Role and Operative Technique of Portal Venous Tumor Thrombectomy in Patients with Pancreatic Neuroendocrine Tumors.
Venous tumor thrombi have been reported in as many as 33 % of patients with pancreatic neuroendocrine tumors (pNETs). Surgical thrombectomy is often used to manage tumor thrombi that develop in association with cancers of the liver or kidney. We have likewise used thrombectomy to extract portal venous tumor thrombi in selected cases of pNET. We describe all cases of portal venous thrombectomy that were performed at our institution between 2007 and 2014 and illustrate the thrombectomy techniques we used in detail. In addition, we report the results of a PubMed search for English-language articles that were published between 1990 and 2014 and that described surgical therapy for portal venous thrombus developing in association with pNETs. Among 245 patients with pNET that underwent pancreatectomy at our institution, 26 (11 %) patients required surgical management of tumor involvement of the portal vein or its tributaries concomitant with pancreatectomy, including 9 (3.8 %) patients who underwent portal venous tumor thrombectomy. Eight cases describing surgical management of tumor thrombus including two additional cases of portal venous tumor thrombectomy were identified in the medical literature. Among patients with pNET who underwent thrombectomy at our institution, all nine had non-functioning tumors and eight (89 %) had tumors of the body and/or tail of the pancreas. Six (67 %) were treated with systemic therapy prior to pancreatectomy. Seven (78 %) patients are alive at a median follow-up of 33 months (range 3 to 97). Venous tumor thrombectomy may be used to safely and effectively extract thrombi from the portal venous system in selected patients with advanced pNET concomitant with pancreatectomy.


Pharmacokinetic evidence on the contribution of intestinal bacterial conversion to beneficial effects of astragaloside IV, a marker compound of astragali radix, in traditional oral use of the herb.
Astragaloside IV (AIV) is the most abundant saponin and a marker compound in Astragali Radix, a Chinese herb notable for its anti-aging and immune-enhancing effects. The present study investigated the role of intestinal bacterial conversion in the in vivo fate of AIV administered through a traditional oral route for the first time. When incubated anaerobically with rat intestinal bacteria, AIV generated five metabolites with three [monoglycosides brachyoside B and cyclogaleginoside B, the aglycone cycloastragenol (CA)] via stepwise deglycosylation and two from further epimerization (CA-iso) and dehydrogenation (CA-2H). Hydrolytic removal of C-6 glucose was a rate-limiting step for formations of CA and its derivatives. When AIV was orally administered to the rat, CA and CA-iso presented as the main components in plasma following AIV, and the AUC(0-∞) were 88.60 ± 9.66 (CA), 179.06 ± 28.53 (CA-iso) and 452.28 ± 43.33 nM·h (AIV). CA-2H was the predominant form in feces but was not detected in urine or plasma. This agreed well with in vitro data including rapid hepatic metabolism of CA-2H to form CA and CA-iso and reversible conversions between CA-2H and CA/CA-iso by intestinal bacteria. These findings support a crucial role of gut bacterial conversion of AIV in the traditional application of Astragali herb and warrant further investigational emphasis on CA and CA-iso.


The crude extract from the sea anemone, Bunodosoma caissarum elicits convulsions in mice: possible involvement of the glutamatergic system.
The crude extract from the sea anemone, Bunodosoma caissarum caused dose-dependent convulsions by i.c.v. route in mice. The involvement of the glutamatergic system in the convulsions was investigated. MK-801 and ketamine, non-competitive NMDA receptor antagonists, prolonged the latencies for convulsion onset. AP-5, a competitive NMDA receptor antagonist, reduced the number of animals convulsing and also increased the latency for convulsion onset. 7-Chlorokynurenic acid, an antagonist of the glycine site on the NMDA receptor, reduced the incidence of convulsions. GMP, a nucleotide known to antagonize some NMDA actions, reduced the incidence and the severity of convulsions and prolonged the latency for their onset. Riluzole, a neuroprotective and anticonvulsant agent, blocked the appearance of convulsions. In vitro, the crude extract inhibited [3H]glutamate binding to cerebral cortical membranes and enhanced [3H]glutamate release from cortical synaptosomes. Heating the crude extract to 100 degrees C for 30 min or preincubating it with sphingomyelin, abolished its effect on glutamate release, but did not alter its ability to induce convulsions and to inhibit glutamate binding. However, the convulsant action was inhibited when the crude extract was submitted to trypsin treatment. Our data suggest that the convulsions elicited by the crude extract are not due to the presence of cytolysin and are not related to an increase in glutamate release, but seem to be dependent on the interaction between a peptide component of the extract and NMDA receptors.


[Humoral and cellular immune responses to retinal S-antigen in uveitis patients].
Humoral and cellular immune responses to purified S-Ag were determined in 73 patients with anterior-, intermediate- and pan-uveitis and in 55 healthy subjects by ELISA and leucocyte migration inhibition test. The positive rates of humoral immune response to S-Ag in patients and controls were comparable; however, the positive rate of cellular immune response to S-Ag in the patients (54.6%) was significantly higher than that in the controls (3.3%), and that in pan-uveitis patients (69.4%) was significantly higher than in patients with anterior uveitis (15.4%), highly suggesting that the cellular immune response to S-Ag was involved in the onset of uveitis, especially when the choroid and retina were affected. The breakdown of anterior chamber associated immune deviation and abnormal expression of intraocular MHC-II antigens may contribute to the development of cellular immune response. More studies are needed.


Malaria medicines: a glass half full?
Despite substantial scientific progress over the past two decades, malaria remains a worldwide burden that causes hundreds of thousands of deaths every year. New, affordable and safe drugs are required to overcome increasing resistance against artemisinin-based treatments, treat vulnerable populations, interrupt the parasite life cycle by blocking transmission to the vectors, prevent infection and target malaria species that transiently remain dormant in the liver. In this Review, we discuss how the antimalarial drug discovery pipeline has changed over the past 10 years, grouped by the various target compound or product profiles, to assess progress and gaps, and to recommend priorities.


A bipartite recombinant yeast system for the identification of subtype-selective estrogen receptor ligands.
Since the estrogen receptor alpha (ERalpha) and beta (ERbeta) are thought to mediate different biological effects, there is intense interest in designing or screening subtype-selective ER ligands. Here, we constructed a biosensor identified as bipartite recombinant yeast system (BRYS) to screen and evaluate subtype-selective ER ligands. Uniform design and immunoblotting was used to determine an optimal dose of copper which control the expression of ERs through a copper inducible metallothionine promoter (CUP1). Some chemicals including natural estrogen (17beta-estradiol), specific estrogen receptor agonist (PPT and DPN), and phytoestrogens (genistein) were tested to validate this system. There was obvious and anticipative discrimination between the agonistic activities when these chemicals were identified and characterized. Furthermore, antagonist (ICI 182,780), which could antagonize the transactivation of estrogen, and chromatin immunoprecipitation (ChIP) were used to confirm that the agonistic effects were mediated through ERs. Comparative studies showed that this system was reproducible and sensitive. 4.7 pM (1.3 ng/l) estrogen was the lowest concentration that could be detected to ERalpha and 0.12 nM (33.5 ng/l) for ERbeta. The results from our study showed that in vitro screening for subtype-selective ER ligands could be conducted in a simple yeast system that is rapid, sensitive, reliable, and quantitative.


Allergenicity assessment of Buchanania lanzan protein extract in Balb/c mice.
Tree nuts are among "Big Eight" and have been reported globally for causing allergy. Buchanania lanzan (Bl) is one of the major tree nuts consumed by Indian population. However, very little is known about B. lanzan's induced allergic manifestation. Therefore, evaluation of it's allergenic potential was undertaken. Bl-crude protein extract sensitized BALB/c mice sera were used to identify the allergic proteins by it's IgE binding capability. The major IgE binding proteins found with molecular weight of 11, 20, 23, 25, 48, 54, and 65 kDa. Specific IgE, specific IgG1, MCPT-1, PGD2 and histamine were assessed in mice sera. Enormous amount of mast cell infiltration was noted in different organs. The levels of Th1/Th2 transcription factors GATA-3, SOCS3 and STAT-6 were found upregulated, whereas T-bet was downregulated. Furthermore, elevated Th1/Th2 cytokine responses were observed in mice sera. All together, these reactions developed systemic anaphylaxis upon Bl-CPE challenge in sensitized BALB/c mice. In order to confirm the evidences obtained from the studies carried out in BALB/c, the investigation was extended to human subjects as well. Control subjects and allergic patients were subjected to skin prick test (SPT). Later sera collected from those positive to SPT along with controls were used for IgE immunoblotting. The study evaluated the allergic manifestation associated with Bl, and identified it's proteins attributing Bl-mediated allergy. This work may help in managing tree nuts mediated allergies especially due to Buchanania lanzan sensitization.


Effects of two different treatments with continuous renal replacement therapy in patients with chronic renal dysfunction submitted to coronary invasive procedures.
Percutaneous coronary intervention (PCI) requires the use of iodinated contrast medium and consequently poses the risk of contrast-induced nephropathy (CIN), which can negatively impact on outcome. Patients with chronic kidney disease (CKD) are at particularly high risk of CIN. In this study, we investigated the role of continuous renal replacement therapy (CRRT) performed before and after versus only after PCI in patients with CKD. We studied 46 consecutive patients with CKD (mean creatinine >2 mg/dL) submitted to PCI: 21 (mean creatinine 2.7 ± 1.6 mg/dL) treated with CRRT only after PCI (CRRTpost) and 25 (mean creatinine 3.0 ± 1.3 mg/dL) with CRRT before and after PCI (CRRTpre-post). CRRT was performed with hemofiltration (creatinine <3 mg/dL) or hemodiafiltration (creatinine >3 mg/dL), initiated 6-8 hours before PCI and re-started immediately post PCI for 18-24 hours. Creatinine showed a greater reduction in CRRTpre-post (2.4 ± 1.0 vs. 3.0 ± 1.3 mg/dL; P=.002) with respect to CRRTpost (2.6 ± 1.3 vs 2.7 ± 1.6 mg/dL; P=.667). At median 14.7-month follow-up, CKD worsened in 3 patients (12%) of CRRTpre-post and in 9 (43%) of CRRTpost (P=.042). Kaplan-Meier analysis at 18 months showed a significantly higher overall mortality in patients treated with CRRTpre-post vs. CRRTpost (P=.041), which became even more significant during the entire follow-up period (P=.026) and an increase in cardiovascular deaths (5 vs. 0, respectively). Our results suggest that in CKD patients undergoing PCI, CRRT performed before and after is more effective in preventing a further deterioration of renal function and is associated with an improved long-term outcome when compared to CRRT performed only after.


[Efficiency of NaFeEDTA fortified soy sauce on anemia prevention].
Study the efficiency of the NaFeEDTA fortified soy sauce on anemia prevention among the children from iron deficiency anemia (IDA) prevalence region. A double blind controlled random intervention in Bijie, Guizhou was conducted for 18 months. The finger hemoglobin (Hb) was detected at baseline and after 6, 12, 18 months intervention. Anthropometrics were also taken at baseline and after 12 months intervention. The Hb level increased significantly in the intervention group [(111.08 +/- 11.31) g/L at baseline and (122.99 +/- 8.43) g/L after 12 months], the anemia prevalence decreased markedly (58.0% at baseline, 17.6% after 12 months). After 12 months intervention, a significantly gain of the weight for age Z-score (WAZ) was observed in the intervention group. The abdomen and triceps skin folders were thicker in the intervention group, and the intervention group had greater gains of the abdomen and triceps skin folders than those in the control group. The soy sauce fortified with NaFeEDTA can increase the Hb level and decrease the prevalence of anemia in the children, and the NaFeEDTA fortified soy sauce can enhance the weight gain and the pull up of the subcutaneous fat. It is suggested that using NaFeEDTA fortified soy sauce in high IDA prevalence population was an efficient way for IDA preventing.


Reduction in tracheal lumen due to endotracheal intubation and its calculated clinical significance.
The flow in the human trachea is turbulent. Thus, the tracheal resistance (R) and the pressure gradient (DeltaP) required to maintain a given flow across the trachea is inversely related to its radius raised to the fifth power. If the caliber reduction ratio (X) after endotracheal intubation is calculated as X = radius of the endotracheal tube (rETT)/radius of the trachea (rT), then DeltaP and/or R will be increased by (1/X)(5). To measure the actual ratio between rETT and rT following endotracheal intubation of pediatric patients with respiratory failure and to calculate the resulting increase in the tracheal R and DeltaP for a given inspiratory flow rate. Retrospective chart review. Pediatric ICU in a tertiary-care teaching children's medical center. PATIENT ENROLLMENT: Twenty consecutive pediatric patients (mean [+/- SD] age, 6.4 +/- 7.2 years) whose tracheas had been intubated for various causes of respiratory failure, and who had received a CT scan, were included in our study. All patients received an endotracheal tube the size of which was derived from the following formula: (age in years/4) + 4. rT and rETT were measured from CT scan sections at and around the level of the thoracic inlet, and the average values were used to calculate X. These values ranged from 0.33 to 0.65 (mean, 0. 55 +/- 0.8). The factor (1/X)(5) was calculated for each patient and then was multiplied by the known normal value for tracheal R for adolescents and adults (0.07 cm H(2)O/L/s) to obtain the value of R resulting from the artificial airway, (1/X)(5) x 0.07. Our results showed that tracheal R increased due to caliber reduction of the trachea after endotracheal intubation by 33.9 +/- 52.5-fold (range, 8.6- to 255.5-fold). In order to maintain an inspiratory flow of 1 L/s, the value of P for the intubated trachea would increase from 0. 07 cm H(2)O to a mean of 2.4 +/- 3.7 cm H(2)O (range, 0.6 to 18 cm H(2)O). In two of our patients, the rT/rETT ratios were < 0.5 (0.33 and 0.44, respectively); this translated into a more significant increase in the calculated DeltaPs, 18 and 4.2 cm H(2)O, respectively. : The common value of X due to endotracheal intubation is between 0.5 and 0.6, which in and of itself results in an increase in R across the intubated trachea up to 32-fold. The calculated increase in P as a result of this is between 2 and 3 cm H(2)O for adolescents or young adults. The addition of pressure support of at least 3 cm H(2)O during spontaneous ventilation via an endotracheal tube, which is common practice in pediatric critical care, should alleviate any respiratory distress emanating from the increased R. However, a value for X < 0.5, which was found in 10% of our patients (2 of 20 patients), results in a much higher calculated increase in the pressure gradient and, therefore, a higher level of pressure support is required to overcome this increase.


Comparison of low-technology and high-technology monitoring of clomiphene citrate ovulation induction.
To determine whether newer monitoring techniques, including urinary detection of the LH surge and vaginal ultrasound, offer an advantage over basal body temperature (BBT) charts alone in achieving pregnancy using clomiphene citrate (CC). Randomized clinical trial. Infertility patients in an academic research environment. Forty-five women undergoing ovulation induction with CC. The women were assigned randomly to receive either low- or high-technology ovulation monitoring for a total of 3 ovulatory cycles. Both groups were followed with BBT charts. The high-technology group also was monitored with urinary LH kits and vaginal ultrasound. Cycle fecundity rates for each technique were compared statistically with use of life-table analysis. Forty-five patients were studied during a total of 134 cycles. The overall cycle fecundity rate was 8%, 10% (8 of 81 cycles) for the low-technology monitoring group and 6% (3 of 53 cycles) for the high-technology monitoring group. These rates were not statistically significant when evaluated by Fisher's exact test (P = .53) or when using life-table analysis and a log-rank test (P = .48). These data suggest that, for initial attempts at ovulation induction with CC in unselected patients, high-technology monitoring of ovulation offers no increase in fecundity over low-technology monitoring.


Inhibition of IGF-I-related intracellular signaling pathways by proinflammatory cytokines in growth plate chondrocytes.
Children with chronic inflammatory diseases suffer from severe growth failure associated with resistance toward the anabolic action of insulin-like growth factor I (IGF-I). We hypothesized that proinflammatory cytokines interfere with IGF-I signaling. We used the mesenchymal chondrogenic cell line RCJ3.1C5.18 as a model of the growth plate. Cell proliferation was assessed by [(3)H]-thymidine-uptake and differentiation by gene expression (quantitative reverse-transcriptase PCR) of specific differentiation markers. Key signaling molecules of the respective IGF-I-related intracellular pathways were determined by western immunoblotting. Coincubation of the proinflammatory cytokines interleukin (IL)-1β (10 ng/ml), IL-6 (100 ng/ml), or tumor necrosis factor-α (50 ng/ml) with IGF-I inhibited IGF-I-driven cell proliferation by 50%, while baseline cell proliferation was not altered. These cytokines attenuated the IGF-I-induced phosphorylation of AKT as a key signaling molecule of the phosphatidylinositol-3 kinase pathway by 30-50% and the phosphorylation of ERK as a key signaling molecule of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by 50-75%. Also, IGF-I-enhanced chondrocyte differentiation was inhibited by these proinflammatory cytokines. The insensitivity toward the anabolic action of IGF-I in the growth plate in conditions of chronic inflammation is partially due to inhibition of IGF-I-specific signaling pathways by proinflammatory cytokines, which affect both IGF-I-driven chondrocyte proliferation and differentiation.


Costs will rather increase.
The purpose of this paper was to study the unfolding of an urgent and extensive decommissioning program in Sweden, focusing on the public's reactions and their arguments when opposing the decommissioning activities. The public's responses were studied through local media. Its content was surveyed and divided into actions and arguments. The arguments were further analyzed and categorized into inductively developed themes. Protest activities, such as demonstrations, meetings and petitions, were not coordinated, but mostly carried out for withdrawals of unique services and services in remote areas. The public questioned the decision makers' information, calculations and competence, the adequacy of the consequence analyses and whether the decommissioning activities would lead to any real savings. Patient and public safety, the vulnerable in society, and effects on the local areas were important topics. Thus, it seems the decision makers did not fully succeed in communicating the demonstrable benefits or create clarity of the rationales for decommissioning the particular services. Furthermore, it seems the public has a more inclusive approach to health services and their value compared to decision makers that need to keep the budget. Decommissioning is an emerging field of research, and this study of the unfolding of an urgent and extensive decommissioning program contributes with evidence that may improve decommissioning policy and practice. The study illustrates that it may be possible to implement a decommissioning program despite public protest, but that the longer-term effects on the health system's legitimacy need to be studied.


Peroxidase: a novel pathway for chemical oxidation in human term placenta.
Hydrogen peroxide-dependent oxidation of xenobiotics in a crude fraction of human term placental membranes (nuclei, mitochondria and microsomes) was investigated. Guaiacol was employed as a model substrate. The rate of its oxidation was found to be dependent on the concentration of protein, H2O2 and the substrate as well as the pH of the buffer. Several other classical substrates for peroxidases from different sources viz. pyrogallol, benzidine, p-PDA, DMBD, ABTS, TMPD and TMBD and endogenous chemicals such as bilirubin and epinephrine were also found to undergo oxidation. The xenobiotic oxidizing capacity of the membranes was retained by CaCl2 (0.5 M) extract as well as by the partially purified enzyme obtained by affinity (Con A) chromatography. The H2O2-dependent chemical oxidation by the partially purified peroxidase was inhibited by NaN3 and KCN (IC50 values 41 and 23 microM respectively). These results suggest that peroxidase may be a major enzyme in human term placenta capable of oxidation of endogenous chemicals and xenobiotics.


A crisis intervention program. Staff go the extra mile for client improvement.
1. Community mental health centers are faced with clients with dual and triple diagnoses who do not respond to traditional treatment. 2. A crisis team, with its inherent flexibility, may be able to engage multi-need clients and enable them to become connected to the Community mental health center. 3. Although these clients will continue to require inpatient services, provision of crisis team services can shorten inpatient length of stay. Plans to transition clients to more comprehensive services are necessary.


Publisher Correction: Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus.
This Article was mistakenly not made Open Access when originally published; this has now been amended, and information about the Creative Commons Attribution 4.0 International License has been added into the 'Additional information' section.


[Analysis of reports of cases of pesticide poisoning in Jiangsu Province, China, from 2006 to 2013].
To investigate the characteristics of pesticide poisoning in Jiangsu Province, China, and to provide a scientific basis for developing effective intervention measures and prevention strategies. The data from report cards of pesticide poisoning in Jiangsu Province from 2006 to 2013 were arranged using EXCEL tables, and assessed. Statistical analysis was applied to the epidemiological data using SPSS. From 2006 to 2013, a total of 32672 cases of pesticide poisoning were reported in Jiangsu Province. Most of the cases were caused by non-occupational poisoning (life poisoning) (72.78%). A majority of patients with pesticide poisoning were 35-54 years old (40.85%) or older than 65 years (15.69%). There were more female patients (58.22%) than male patients (41.78%). Among patients with occupational poisoning, male patients (50.90%) were more than female patients. Among patients with non-occupational poisoning, female patients were more than male patients (38.37%). Pesticide poisoning mainly occurred from July to September. The case-fatality rate of occupational poisoning (0.47%) was lower than that of non-occupational poisoning (7.10%). All 13 cities in Jiangsu Province reported cases of pesticide poisoning. There were more cases in the northern regions than in the southern regions. Pesticide poisoning was mainly caused by organophosphorus insecticides including methamidophos, dichlorvos, dimethoate, omethoate, and parathion, which accounted for 65.58%of all cases. Paraquat had the highest case-fatality rate (10.06%) among all pesticides, followed by tetramine (10.00%), dimethoate or omethoate (7.85%), methamidophos (7.79%), and dimehypo (7.68%). Pesticide poisoning cannot be ignored. The management and control should be improved in production and usage of highly toxic pesticides including organophosphorus insecticides, rodenticides, and herbicides. More attention should be paid to the protection of vulnerable groups including women, children, and the elderly.


Angular two-photon interference and angular two-qubit states.
Using angular-position-orbital-angular-momentum entangled photons, we study angular two-photon interference in a scheme in which entangled photons are made to pass through apertures in the form of double angular slits, and using this scheme, we demonstrate an entangled two-qubit state that is based on the angular-position correlations of entangled photons. The entanglement of the two-qubit state is quantified in terms of concurrence. These results provide an additional means for preparing entangled quantum states for use in quantum information protocols.


[High-yield agronomic measures of Curcuma longa L].
A method of orthogonal conic combinatorial design has been employed in the study of high-yield agronomic measures of C. longa. The results show that by increasing plants/mu and postponing sowing date, the yield is 50% higher than before, mathematical model of yield on plants/mu and sowing date were established, which can be used to predict the yield and explore optimal agronomic measures.


Lipid-bound factor Xa regulates tissue factor activity.
The activation of coagulation factor X by tissue factor (TF) and coagulation factor VIIa (VIIa) on a phospholipid surface is thought to be the key step in the initiation of blood coagulation. In this reaction, the product, fXa, is transiently and reversibly bound to the TF-VIIa enzyme complex. This in effect leads to a probabilistic inhibition of subsequent fX activations; a new fX substrate molecule cannot be activated until the old fXa molecule leaves. In this study, we demonstrate that benzamidine and soybean trypsin inhibitor-conjugated Sepharose beads, which bind fXa and sequester it away from the reaction, serve to enhance fX activation by the TF-VIIa complex. Thus, removal of fXa from the reactive zone, by either flow, fXa sequestration, or binding to distant lipid surfaces, can serve to enhance the levels of TF-VIIa activity. Using resonance energy transfer, we found the dissociation constants of fX and fXa for 100 nm diameter phospholipid vesicles to be on the order of 30-60 nM, consistent with previous measurements employing planar lipid surfaces. On the basis of the measurements of binding of fXa to phospholipid surfaces, we demonstrate that the rates of fX activation by the TF-VIIa complex under a variety of experimental conditions depend inversely on the amount of product (fXa) bound to the TF-phospholipid surface. These data support an inhibitory role for the reaction product, fXa, and indicate that models previously employed in understanding this initial coagulation reaction must now be re-evaluated to account for both the product occupancy of the phospholipid surface and the binding of the product to the enzyme. Moreover, the inhibitory properties of fXa can be described on the basis of the estimated surface density of fXa molecules on the TF-phospholipid surface.


Laboratory monitoring of rivaroxaban and assessment of its bleeding risk.
The aims of this study were to investigate the effects of rivaroxaban on routine coagulation assays using our local, widely available, reagents and to study the relationship between sensitive coagulation assays and bleeding risk caused by rivaroxaban. Prothrombin time (PT), activated partial thromboplastin time (APTT) and anti-factor Xa (FXa) chromogenic assays (Biophen DiXaI) and inhibition of FXa activity were performed in normal pooled plasma (NPP) spiked with rivaroxaban and plasma samples from patients treated with rivaroxaban. In vitro, the linear correlation coefficient of measured concentrations of rivaroxaban, by Biophen DiXaI, and spiked concentrations of rivaroxaban was 0.99. PT and APTT showed good linear correlation with rivaroxaban concentrations, while other assays showed poor correlation. In vivo, PT showed a moderate linear correlation with rivaroxaban concentrations while APTT had a weak correlation with rivaroxaban concentrations. In vitro and in vivo, the rivaroxaban concentrations, measured by Biophen DiXaI, always showed good correlation with the inhibition of FXa activity, and PT values showed moderate correlation with the inhibition of FXa activity. Biophen DiXaI can be considered as a quantitative method to monitor the anticoagulation activity of rivaroxaban, and could be used to evaluate bleeding risk caused by rivaroxaban. The PT reagent (Thrombosis S) could be considered as a rough method to monitor the anticoagulation activity of rivaroxaban and evaluate bleeding risk caused by rivaroxaban.


New chemical route for the synthesis of β-Na(0.33)V₂O₅ and its fully reversible Li intercalation.
To obtain good electrochemical performance and thermal stability of rechargeable batteries, various cathode materials have been explored including NaVS2, β-Na(0.33)V2O5, and Li(x)V2O5. In particular, Li(x)V2O5 has attracted attention as a cathode material in Li-ion batteries owing to its large theoretical capacity, but its stable electrochemical cycling (i.e., reversibility) still remains as a challenge and strongly depends on its synthesis methods. In this study, we prepared the Li(x)V2O5 from electrochemical ion exchange of β-Na(0.33)V2O5, which is obtained by chemical conversion of NaVS2 in air at high temperatures. Crystal structure and particle morphology of β-Na(0.33)V2O5 are characterized by using X-ray diffraction, scanning electron microscopy, and transmission electron microscopy techniques. Energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy, in combination with electrochemical data, suggest that Na ions are extracted from β-Na(0.33)V2O5 without irreversible structural collapse and replaced with Li ions during the following intercalation (i.e., charging) process. The thus obtained Li(x)V2O5 delivers a high discharge capacity of 295 mAh g(-1), which corresponds to x = 2, with crystal structural stability in the voltage range of 1.5-4.0 V versus. Li, as evidenced by its good cycling performance and high Coulombic efficiency (under 0.1 mA cm(-2)) at room temperature. Furthermore, the ion-exchanged Li(x)V2O5 from β-Na(0.33)V2O5 shows stable electrochemical behavior without structural collapse, even at a case of deep discharge to 1.5 V versus Li.


Use of extracorporeal photochemotherapy in heart transplant recipients during acute rejection: a case study.
Despite the growing availability of improved immunosuppressive agents, acute and chronic rejection episodes remain a major complication in heart transplant recipients. The rejection of allografts is a normal part of the body's response to foreign antigens. The key to controlling this response is to administer a regimen of multiple immunosuppressive drugs. Evidence indicates that by adding extracorporeal photochemotherapy to a standard immunomodulatory regimen, the rejection process can be reversed without significantly increasing patient risk. In this case study we examine extracorporeal photochemotherapy and the care of patients receiving this therapy.


Transcatheter therapy for aortic coarctation with severe systemic hypertension during pregnancy.
Aortic coarctation is an unusual cause of hypertension during pregnancy and its management is not clarified. We report transcatheter balloon dilatation and stenting for native aortic coarctation in a 22-year-old pregnant woman with severe and uncontrolled systemic hypertension. Arterial blood pressure could be successfully controlled with medical treatment during the rest of the pregnancy and the patient underwent uneventful delivery. No adverse events or recoarctation was observed during 24 months clinical follow-up. In conclusion, native aortic coarctation can be successfully treated during pregnancy with transcatheter therapy. More experience is needed to confirm the safety and efficacy of such management.


Root zone temperature affects the phytoextraction of Ba, Cl, Sn, Pt, and Rb using potato plants (Solanum tuberosum L. var. Spunta) in the field.
Three consecutive years of field experiments were conducted to investigate how different root-zone temperatures, manipulated by using different mulches, affect the phytoextraction of Ba, Cl, Sn, Pt and Rb in different organs of potato plants (roots, tubers, stems and leaves). Four different plastic covers were used (T1: transparent polyethylene; T2: white polyethylene; T3: white and black coextruded polyethylene, and T4: black polyethylene), using uncovered plants as control (T0). The different treatments had a significant effect on mean root zone temperatures (T0 = 16 degrees C, T1 = 20 degrees C, T2 = 23 degrees C, T3 = 27 degrees C and T4 = 30 degrees C) and induced a significantly different response in Ba, Cl, Sn, Pt and Rb concentration and accumulation. The T3 treatment gave rise to the greatest phytoextraction of Ba, Pt, Cl and Sn in the roots, leaflets and tubers. In terms of the relative distribution of the phytoaccumulated elements (as percentage of the total within the plant), Pt and Ba accumulated mainly in the roots whereas Rb, Sn and Cl accumulated primarily in tubers, establishing a close relationship between the biomass development of each organ and phytoaccumulation capacity of metals in response to temperature in the root zone.


Morphogenetic interaction of presumptive neural and mesodermal cells mixed in different ratios.
Cells of the presumptive forebrain region and axial mesoderm of Triturus neurulae were disaggregated and combined in different ratios. The differentiation of the central nervous systen in these explants was dependent on the relative amount of mesodermal cells present: an increase of mesodermal cells resulted in a corresponding increase in the frequency with which caudal structures of the central nervous system developed and a gradual loss of the forebrain formations.


Temperature-dependent increase in the DNA-binding activity of a heat shock factor in an extract of tobacco cultured cells.
The DNA-binding activity of a tobacco heat shock factor (HSF) was induced by heat treatment (37-40 degrees C) of a cell-free extract that contained extra-nuclear fraction, but not in an extract of isolated nuclei. These observations suggest that an inactive form of HSF can directly recognize and transduce the heat shock signal and that such transduction requires components of the extranuclear fraction. Addition of ATP or of most other nucleoside triphosphates reduced the binding of the HSF to the heat shock element (HSE) in the same extract, and removal of ATP by dialysis from the extract restored the ability of the HSF to bind to DNA. The restored activity of the HSF could be eliminated again by a second addition of ATP. Our observations provide the first example of the involvement of ATP in the regulation of the reversible changes in HSF that control its ability to bind to HSEs in a cell-free extract.


Magnetic resonance imaging findings in a red kangaroo (Macropus rufus) with otitis.
Magnetic resonance imaging (MRI) was performed on an adult, male Red kangaroo (Macropus rufus) with a history of nonspecific neurologic signs and acute discharge from the left ear. MRI revealed findings consistent with otitis and possible osteomyelitis of the temporal and mastoid bones. To the authors' knowledge, this is the first report of otitis and MRI findings in a kangaroo.


One-dimensional diffusion of colloids in polymer solutions.
For colloid-polymer systems confined in one-dimensional channels, the diffusion of the colloidal particles is obtained by tracking individual particles using enhanced video microscopy and digital image analysis. For short times, the diffusion is normal, of the Fickian type, with mean-squared displacement varying linearly with time. For long times, however, the mean-squared displacement is found to increase more slowly with time, being proportional to the square root of time, in agreement with the theoretical prediction for diffusion of hard rods in one dimension in which mutual crossing of the particles cannot take place. The crossover from short-time to long-time diffusion is observed and is found to depend on the colloid and polymer concentrations. Unexpectedly, for small polymer-to-colloid size ratios, it is the polymer rather than the colloid concentration which has a leading effect on the colloid diffusion.


Microscopic tubular discectomy for far lateral lumbar disc herniation.
Microscopic tubular discectomy (MTD) reduces muscle trauma associated with treatment of far lateral lumbar disc herniation (FLDH), but data from randomised controlled studies concerning its efficacy on posterolateral disc herniation, has failed to demonstrate its superiority over standard open techniques. Importantly concerns have been raised that it may be inferior in terms of relief of leg and back pain. Although several FLDH series show that MTD can deliver excellent outcomes, the volume of literature in this field has remained small and evidence based on health-related quality of life (HRQOL) measures, scarce. In this study we therefore evaluated the role of MTD for FLDH through analysing multiple HRQOL scores collected in a prospective database. We identified 24 patients who underwent MTD through a caudal approach, targeting directly the disc space to minimise traction on the dorsal root ganglion implicated in causing iatrogenic neuralgia. With a mean follow-up of 9.2months, the improvement in Oswestry Disability Index and Short Form 36 physical functioning and bodily pain scores was 32, (95% confidence interval [CI]: 21-43), 40 (95% CI: 30-51) and 35 (95% CI: 26-43) respectively. The improvement on the Visual Analogue Scale was 38mm (95% CI: 23-54) and 35mm (95% CI: 21-48) for leg pain and back pain respectively. There was no postoperative neuralgia noted and no reoperation required. Our data demonstrated clinically meaningful treatment effects and compare favourably with HRQOL surgical outcomes established for posterolateral disc herniation, supporting MTD as a valid treatment option for FLDH.


Risk factors for dementia in the cardiovascular health cognition study.
The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999. There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer's disease (AD). In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes. Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.


Bletilla striata as a vascular embolizing agent in interventional treatment of primary hepatic carcinoma.
To evaluate Bletilla striata as a vascular embolizing agent in interventional treatment of primary hepatic carcinoma. We made a vascular embolizing agent from a Chinese medicinal herb, Bletilla striata (bai ji). From October 1991 to January 1995, 56 patients with primary hepatic carcinoma were treated by hepatic arterial chemoembolization with Bletilla striata angioembolus, and 50 patients with primary hepatic carcinoma who were treated by conventional gelfoam embolization served as controls. All patients were followed up for 10-48 months. Embolization with the Bletilla striata powder produced extensive and permanent vascular obstruction, resulting in marked shrinkage of the tumor and significant decrease of serum alpha fetoprotein (AFP) level. After embolization, less collateral circulation formed later. The treatment interval was prolonged to an average of 7 months. The 1-, 2- and 3-year survival rates were 81.9%, 44.9%, and 33.6%, respectively, with a mean survival period of 19.8 months. All the clinical parameters were better than those in the control group treated by conventional gelfoam embolization. Bletilla striata angioembolus is a good vascular embolizing agent for treating PHC.


[Treatment of neonatal hyperbilirubinemia with BiliBed].
Phototherapy of the newborn is a common procedure in the neonatal ward. Different devices and lightsources are being used in the Scandinavian countries. In order to evaluate the safety and efficacy of a yet another new phototherapeutic device, the BiliBed, a randomised clinical, open cross-over study was undertaken. The study population comprised 22 newborn infants with non-haemolytic hyperbilirubinaemia. The effects of Bilibed on bilirubin elimination, fluid balance and restlessness during treatment were determined and compared to those obtained during conventional phototherapy. Heart rate and respiratory rate were used as a crude index of sympato-adrenerg tone during treatment. Both appliances were equally effective in reducing serum bilirubin concentration. Heart rate and respiratory rate were significantly lower during treatment with BiliBed. In spite of equal faecal/urinary output in conjunction with less ad libitum feeding volume, a trend towards better weight development was observed during BiliBed treatment. This may reflect differences in insensible water loss during treatment. The results suggest that BiliBed may be used without any disadvantages for the newborn compared to conventional phototherapy. Larger clinical trials are needed to determine its place in the clinical setting.


MicroRNA-374a protects against myocardial ischemia-reperfusion injury in mice by targeting the MAPK6 pathway.
Clinical treatment strategies for patients with myocardial ischemia typically include coronary artery recanalization to restore myocardial blood supply. However, myocardial reperfusion insult often induces oxidative stress and inflammation, which further leads to apoptosis and necrosis of myocardial cells. Increasing evidence suggests that microRNAs (miRNAs) participate in the pathological and physiological processes associated with myocardial ischemia reperfusion. In this study, we established a myocardial H/R H9C2 cell model and a mouse I/R model to detect molecules implicated in myocardial I/R regulation and to determine the underlying signal transduction pathways. Herein, we showed that the expression of miR-374a-5p decreased in a myocardial cell model (H9C2 cells) of hypoxia/reoxygenation (H/R) and mouse model of ischemia/reperfusion (I/R). Alternatively, overexpression of miR-374a-5p was found to ameliorate myocardial cell damage within both in vivo and in vitro models of ischemia. Further, mitogen-activated protein kinase 6 (MAPK6) was identified as a direct target of miR-374a-5p. Thus, by targeting MAPK6, miR-374a-5p was found to negatively regulate MAPK6 expression. However, up-regulation of MAPK6 functioned to inhibit the previously observed protective effect of miR-374a-5p in the H9C2 H/R model. Taken together, our study suggests that miR-374a-5p may have protective effects against cardiac I/R injury in vivo, and H/R injury in vitro, thereby providing novel insights into the molecular mechanisms associated with ischemia/reperfusion injury and a potential novel therapeutic target.


Synthesis of bottlebrush polystyrenes with uniform, alternating, and gradient distributions of brushes via living anionic polymerization and hydrosilylation.
By combining living anionic polymerization and hydrosilylation, densely grafted bottlebrush polymers with controlled spacing of branch points are prepared. Dimethyl(4-vinylphenyl)silane and dimethyl(4-(1-phenylvinyl)phenyl)silane are anionically (co)polymerized to synthesize uniform, alternating, and gradient in-chain silyl-hydride (Si-H) functionalized backbones. The spacing of branch points is controlled effectively by regulating the distribution of Si-H groups along the backbones. Three backbones with a similar number of Si-H groups but variable distributions are used to synthesize corresponding bottlebrush polymers via hydrosilylation between the backbones and chain-end vinyl functionalized polystyrene. The uniformly grafted bottlebrush exhibits the highest hydrodynamic radius (Rh ) of 5.6 nm and the lowest Tg of 79 °C which may be attributed to its compact grafted structure. This methodology exhibits high efficiency and convenience for the construction of bottlebrushes with controlled distribution of brushes.


INHIBITION OF SYNTHESIS OF THE CELL WALL OF STAPHYLOCOCCUS AUREUS BY CEPHALOTHIN.
Cephalothin, 7-(thiophene-2-acetamido)-cephalosporanic acid, suppresses synthesis of the cell of Staphylococcus aureus. Exposure to this agent led to a reduction in the degree of incorporation of carbon-14-lysine into the mucopeptide of the cell wall material and to an accumulation of N-acetyl glucosamine in the cell. The intensity of the lesions was comparable to that produced by penicillin.


Risk Factors for Daytime or Combined Incontinence in Children with Cerebral Palsy.
We identify risk factors for daytime or combined urinary incontinence in children with cerebral palsy. A cross-sectional case-control study was conducted including children with cerebral palsy with or without daytime or combined urinary incontinence from the CP-Reference Center at Ghent University Hospital and 2 associated special education schools. Factors were subdivided in 3 clusters of demographic and general medical data, cerebral palsy classification, and bladder and bowel dysfunction. Data were obtained using uroflowmetry with electromyography testing, a nonvalidated questionnaire and bladder diaries. Univariate and multivariate analyses were performed for variables and clusters, respectively. A final associative logistic model including all clusters was developed. The study included 34 incontinent children and 45 continent children. Daytime or combined urinary incontinence was associated with intellectual disability (OR 7.69), swallowing problems (OR 15.11), use of external aids (OR 27.50) and use of laxatives (OR 13.31). Daytime or combined urinary incontinence was positively associated with dyskinesia (OR 5.67) or combined spasticity and dystonia (OR 4.78), bilateral involvement (OR 4.25), Gross Motor Function Classification System level IV (OR 10.63) and V (OR 34.00), and severe impairment in manual (OR 24.27) or communication skills (OR 14.38). Lower maximum voided volume (OR 0.97) and oral fluid intake (OR 0.96) influenced daytime or combined urinary incontinence negatively. Pathological uroflow curves were not significantly associated with incontinence. The final model defined functional impairment, intellectual disability and oral fluid intake as predictive factors for daytime or combined urinary incontinence. Risk analysis revealed functional impairment, intellectual disability and fluid intake as important factors influencing continence in a child with cerebral palsy.


Effects of prenatal exposure to 50 Hz magnetic fields on development in mice: I. Implantation rate and fetal development.
Pregnant CD1 mice were exposed or sham-exposed from day 0 to day 17 of gestation to a 50 Hz sinusoidal magnetic field at 20 mT (rms). Preimplantation and postimplantation survival were assessed and fetuses examined for the presence of gross external, internal, and skeletal abnormalities. There were no statistically significant field-dependent effects on preimplantation or postimplantation survival, sex ratio, or the incidence of fetuses with internal or skeletal abnormalities. Magnetic field exposure was, however, associated with longer and heavier fetuses at term, with fewer external abnormalities. The results lend no support to suggestions of increased rates of spontaneous abortion or congenital malformation following prenatal exposure to power frequency magnetic fields.


Central nervous system action of TRH to stimulate gastric emptying in rats.
The effects of intracisternal injection of TRH on gastric emptying of a liquid meal was investigated in 24 h fasted rats using the phenol red method. Intracisternal injection of TRH, RX 77368, or [N-Val2]-TRH, an analog devoid of TSH-releasing activity, 5 min prior to a meal, stimulated gastric emptying measured 20 min later. TRH action was dose dependent (1-100 ng), and rapid in onset. The calculated time for emptying half of the meal was decreased from 16 +/- 3 min (control group) to 4 +/- 1 min (TRH 30 ng). The stable analog, RX 77368, unlike TRH, stimulated gastric emptying when the meal was given 60 min after peptide injection. Intravenous injection of atropine (2.5 micrograms) inhibited and that of carbachol (1 microgram) stimulated gastric emptying whereas i.v. injection of TRH (0.1-1 microgram) had no effect. Vagotomy but not adrenalectomy reversed the increase in gastric emptying induced by intracisternal TRH. Atropine blocked the stimulatory effect of TRH and carbachol. These results demonstrate that TRH acts within the brain to stimulate gastric emptying through vagus-dependent and cholinergic pathways whereas alterations of adrenal and pituitary-thyroid secretion do not play an important role.


Dosing considerations for rufinamide in patients with Lennox-Gastaut syndrome: Phase III trial results and real-world clinical data.
Lennox-Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, rufinamide dosing and titration may differ from the trial setting. Here, rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. Results demonstrated that a rapid titration schedule (7 or 14 days) of rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic-atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study - somnolence, vomiting, and pyrexia - occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of rufinamide in LGS.


Enantioselective synthesis of (+)-penostatin E.
The first enantioselective total synthesis of penostatin E has been accomplished. Two highly efficient and diastereoselective reactions, a Hosomi-Sakurai allylation and an intramolecular Pauson-Khand reaction, were utilized for the construction of the basic carbon framework of the target molecule as the key steps. A late-stage introduction of the side chain and a successful base-promoted elimination reaction afforded an efficient synthetic route to (+)-penostatin E.


Ketoconazole inhibits corticotropic cell function in vitro.
The effects of ketoconazole (KC) on secretion and biosynthesis of ACTH and generation of cAMP in rat anterior pituitary cells were investigated in vitro. KC inhibits CRF-stimulated ACTH release from rat anterior pituitary fragments in a dose-dependent fashion between 1.5 and 100 microM. The effect of CRF as a releaser of ACTH was fully restored after KC was removed from the medium. Similar effects were observed in primary cultures of rat anterior pituitary cells. KC dose-dependently decreased basal and CRF-stimulated ACTH release. In addition, basal and CRF-stimulated mRNA coding for the ACTH precursor were reduced after preincubation with KC. The effects of KC on ACTH release and biosynthesis seem to be mediated by cAMP, since KC inhibits basal and CRF-stimulated cAMP release and content within the same dose range. Since the stimulatory effects of cholera toxin, sodium fluoride, and forskolin were dose-dependently inhibited by KC and since the addition of (Bu)2cAMP abolished the inhibiting effect of KC, it is concluded that KC acts by inhibition of the catalytic component of the adenylate cyclase holoenzyme.


Acute inflammatory and immunologic responses against antigen in chronic bird-related hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is an immune-mediated lung disease induced by the inhalation of a wide variety of antigens and a persistent antigen exposure induces inevitably pulmonary fibrosis in chronic HP. Although neutrophils, Th1 and Th17 cells contribute to lung inflammation in acute phase of HP, there is no clear explanation as to how the immunological reaction occurs just after the inhalation of causative antigens in the chronic phase of HP. We examined the inflammatory and immunologic profiles before and after the inhalation provocation test (IPT) in serum and bronchoalveolar lavage fluid (BALF) from patients with chronic bird-related HP (BRHP) and other interstitial lung diseases (ILDs). We analyzed BALF samples from 39 patients (19 BRHP and 20 other ILDs) and serum samples from 25 consecutive patients (20 BRHP and 5 other ILDs) who underwent the IPT. A significant increase of neutrophils was observed in the BALF from the BRHP patients following the IPT. Neutrophil chemoattractants, namely, granulocyte colony-stimulating factor, IL-6, IL-8, IL-17, and CXCL2 significantly increased in both the serum and BALF of the BRHP patients after the IPT. Serum IFN-γ and CXCL10, cytokines/chemokines that contributed to Th1 inflammation, were also significantly increased in BRHP following the IPT. This study demonstrated the exposure to the causative antigen provoked acute neutrophilic and Th1 immunologic responses similar to acute HP even in the chronic phase of HP.


Buccinator myomucosal flap: clinical results and review of anatomy, surgical technique and applications.
The buccinator musculomucosal flap is an axial-pattern flap based on either the buccal or the facial artery. We present our experience with this flap and describe its surgical anatomy, the surgical techniques utilised to raise the flap and its clinical applications. We retrospectively reviewed all patients who had had buccinator myomucosal flaps created at the Groote Schuur Hospital between 1999 and 2004. Patients were also recalled to assess flap sensation and to record reduction of mouth opening as a consequence of donor site scarring. Of the 14 patients who had had a buccinator myomucosal flap created, there was one flap failure. Sensation was present in 71 per cent of flaps, and there was no trismus due to donor site scarring. The buccinator myomycosal flap is a dependable flap with good functional outcome and low morbidity.


Water and organic synthesis: a focus on the in-water and on-water border. Reversal of the in-water Breslow hydrophobic enhancement of the normal endo-effect on crossing to on-water conditions for Huisgen cycloadditions with increasingly insoluble organic liquid and solid 2π-dipolarophiles.
Measurements of the endo/exo product ratios for Huisgen cycloadditions with a series of vinyl ketones, alkyl acrylates, and substituted styrenes as dipolarophiles with phthalazinium and pyridazinium dicyanomethanide 1,3-dipoles in acetonitrile and water show that as the reactions change from in-water (large hydrophobic enhancement of endo-products) to on-water, the hydrophobic enhancement of the endo-products is reduced and partially reversed (relative to acetonitrile). An expected increase of the endo-effect with increasing hydrophobic character of the dipolarophile is overcome by decreasing water solubility causing changeover to on-water conditions. On-water reactions do not show increased cycloaddition endo-effects (relative to organic solvents) as do in-water reactions.


A new perspective for advanced positron emission tomography-based molecular imaging in neurodegenerative proteinopathies.
Recent studies in neurodegenerative conditions have increasingly highlighted that the same neuropathology can trigger different clinical phenotypes or, vice-versa, that similar phenotypes can be triggered by different neuropathologies. This evidence has called for the adoption of a pathology spectrum-based approach to study neurodegenerative proteinopathies. These conditions share brain deposition of abnormal protein aggregates, leading to aberrant biochemical, metabolic, functional, and structural changes. Positron emission tomography (PET) is a well-recognized and unique tool for the in vivo assessment of brain neuropathology, and novel PET techniques are emerging for the study of specific protein species. Today, key applications of PET range from early research and clinical diagnostic tools to their use in clinical trials for both participants screening and outcome evaluation. This position article critically reviews the role of distinct PET molecular tracers for different neurodegenerative proteinopathies, highlighting their strengths, weaknesses, and opportunities, with special emphasis on methodological challenges and future applications.


[Roentgenological aspects of polyarthritis in foals].
Radiographically, joint ill in foals is subdivided into four different types: Type P - osteomyelitis in the meta- and/or epiphysis adjacent to the physis. Type E - osteomyelitis in the epiphyseal subchondral bone. Type S - synovitis confined to the joint itself. Type T - osteomyelitis in the small tarsal bones. The radiographical features corresponding with the different types, the relationship between the radiological, pathological, bacterial and clinical findings, and the recommended radiographic procedure are discussed in detail.


Physical medicine and rehabilitation consultation: relationships with acute functional outcome, length of stay, and discharge planning after traumatic brain injury.
Patients hospitalized with traumatic brain injury comprise a large portion of the population treated at trauma centers, and physiatry consultants evaluate many traumatic brain injury patients in this setting. The purpose of this study was to delineate relationships between physical medicine and rehabilitation consultation in this population and acute functional outcome, length of stay, and discharge planning. Data were obtained for 1866 adult patients hospitalized with nonfatal traumatic brain injury. Functional outcome was determined using a modification of the FIM trade mark. Descriptive and regression analyses were used to determine the relationship of physical medicine and rehabilitation consultation to acute discharge FIM score, length of stay, and discharge disposition. Patients receiving physical medicine and rehabilitation consultation had more severe injuries, lower acute discharge FIM scores, and longer length of stay. However, multivariate analysis showed that earlier (<48 hr after admission) physical medicine and rehabilitation consultation resulted in significantly better FIM scores with transfers (odds ratio, 2.61; 95% confidence interval, 1.06-6.40) and locomotion (odds ratio, 3.54; 95% confidence interval, 1.34-9.32) and a significantly shorter acute length of stay (P = 0.001). Early physical medicine and rehabilitation consultation may positively impact functional status and length of stay for patients with traumatic brain injury during acute hospitalization. Additional work is needed to determine how physical medicine and rehabilitation consultation impacts rehabilitation-specific medical issues, long-term functional outcome, and healthcare costs.


Patterns and trends of drug use in the San Francisco Bay Area.
In December 2002, the author conducted a comprehensive review of indicators of use of illicit substances in the San Francisco Bay Area. Cocaine use prevalence appears to be rising again, after a significant decline in the late 1990s. The shift away from smoking crack and toward snorting powder cocaine persists. The former predominance of Blacks among users continues to ebb. Heroin use indicators consistently show a peak in 1999, followed by a significant decline. The average age of users keeps increasing. Local street prices of heroin have risen considerably since 2001. Marijuana indicators suggest a continued increase in prevalence. Methamphetamine indicators are mixed. Usage is still widespread, and risky injection practices among gay/bisexual men remain a major factor for HIV incidence. Incidence of new HIV infection declined between 1997 and 2001 for heterosexual drug injectors, but increased for gay male and transsexual injectors.


As others see us.
Another installment from the literary archives focuses on the public image of dentists and dentistry. The feedback is not exactly flattering.


[Myocardial localisation of tuberculosis: the diagnostic value of cardiac MRI].
Tuberculosis can be responsible for myocardial damage, the frequency of which is probably underestimated because of the difficulty in its diagnosis. We studied the contribution of cardiac magnetic resonance imaging (MRI) in three patients. Three patients were treated for disseminated tuberculosis. They had moderate cardiac abnormalities (tachycardia, dyspnoea on effort). The electrocardiogram was normal in 2 patients and the echocardiography showed localized hyperkinesias. Cardiac MRI revealed intra-myocardial nodular gadolinium enhancement and hyperkinesias. The clinical outcome in the 3 patients was favourable following anti-tuberculosis therapy; one patient was also administered corticosteroids. Cardiac MRI is a non-invasive examination that brought important arguments for the diagnosis of tubercular myocarditis in the 3 patients.