Clinical significance of prostatic-urethral angulation on the treatment outcome of patients with symptomatic benign prostatic hyperplasia treated with tamsulosin hydrochloride.
To evaluate the impact of the prostatic-urethral angulation (PUA) on the treatment efficacy of selective alpha-1A receptor blocker in male patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). A total of 80 patients with LUTS/BPH and with mean age 53.3 ± 6.3 (range 47-70) were included in our prospective comparative study. The patients were classified into 2 groups as a consecutive cases 40 in each one depending on the PUA either ≤ 35° (group A) or > 35° (group B). PUA and different prostatic parameters were measured using transrectal ultrasound. Prostate-specific antigen (PSA), the International Prostate Symptom Score and quality of life score (IPSS/QoL score), maximum flow rate (Qmax), and postvoid residual (PVR) volume were compared between the groups. The clinical significance of PUA was evaluated after 8 weeks of medical treatment with tamsulosin hydrochloride 0.4 mg daily. Baseline evaluation (pre-treatment) for both groups were comparable to each other with no clinically significant difference regarding age, PSA, IPSS/QoL score, Q(max) and PVR volume (P-value > 0.05). Comparison of parameters after 8 weeks showed that tamsulosin hydrochloride improved the total IPSS and all subscores (P < 0.001), QoL (P = 0.001), Q(max) (P = 0.002), and PVR (P = 0.04) in group A (Table 1). Tamsulosin hydrochloride appears to be less effective in improving IPSS/Qol score, Qmax and PVR in patients with lager PUA. The PUA might be a predictor for the treatment efficacy of α-blockers and more studies are warranted in the future before the final conclusion.


Effect of alpha-fluoromethylhistidine on brain histamine and noradrenaline in muricidal rats.
Rats maintained on a thiamine-deficient diet for 30 days showed mouse-killing aggression (muricide). Once the muricide tendency appeared, it remained during the entire experimental period, even after subsequent administration of thiamine hydrochloride for 30 days. The effect of alpha-fluoromethylhistidine (FMH) on muricide in this animal model was examined, and histamine and noradrenaline levels in several brain regions were measured. One hour after i.p. injection of 200 mg/kg of FMH, muricide was completely abolished. Significant decrease in histamine levels was found in the hypothalamus, thalamus, amygdala, striatum and pituitary of muricidal rats. Thus, the central histaminergic neuron system may be involved in the suppressive mechanism of muricide. On the other hand, it is noteworthy that the noradrenaline level was significantly decreased only in the hypothalamus. In conclusion, it seems likely that the suppression of muricide induced by FMH was attributable to both inhibition of the histaminergic system and activation of the noradrenergic system.


Effect of epinephrine on carbohydrate metabolism in exercising dogs.
Well-trained dogs with indwelling arterial and venous catheters ran on a treadmill (15%, 133 m/minute). A mixture of 3-3H: glucose and 14C-glucose (U) or 14C-lactate was infused at a constant rate. Hepatic glucose output (Ra), metabolic clearance rate of glucose (MCR), the percent participation of plasma glucose (G) in lactate production (%L comes from G), peripheral glycogenolysis (GLY) and lactate turnover (RaL) were calculated. Three types of experiments were conducted: (1) Type A, in which Epinephrine (E, 0.5 microgram/kg min) was infused mid-exercise for 75 min; (2) Type B, in which E was infused for three hours and exercise started mid-infusion for 75 min; and (3) Type C in which E and exercise began at the same time. In Type A, E increased G less (+15 mg/dL) than at rest (+50 mg/dL). Unlike at rest, during run E transiently decreased the Ra. The hyperglycemia was entirely due to a marked decrease of MCR. In Type B, E delayed the exercise-induced rise of Ra; and in Type C it delayed the rise of MCR. In all three types E reduced the %L comes from G from the usual 40% to 18% to 20%, and it potentiated the exercise-induced rise of GLY. In Type C, during the first hour, about five times as much lactate was produced (722 mg/kg) as in control runs (149 mg/kg). Beta-blockade abolished all the effects of E on glucose, lactate, MCR, GLY, %L comes from G and RaL. delta Ra and delta MCR rose faster, and they reached values that were approximately twice normal.(ABSTRACT TRUNCATED AT 250 WORDS)


From brain to neuro: the brain research association and the making of British neuroscience, 1965-1996.
This article explores the short history of "neuroscience" as a discipline in its own right as opposed to the much longer past of the brain sciences. It focuses on one historical moment, the formation of the first British "neuroscience" society, the Brain Research Association (BRA), renamed in 1996 to the British Neuroscience Association (BNA). It outlines the new thinking brought about by this new science of brain, mind, and behavior, it sketches the beginnings of the BRA and the institutionalization of neuroscience in the British context, and it further explores the ambiguous relation the association had towards some of the ethical, social, and political implications of this new area of research.


Role of the kallikrein-kinin system in the maturation of cardiovascular phenotype.
Recent studies indicate that during early phases of life the kallikrein-kinin system (KKS) plays a role in kidney development. In the rat kidney, the spatial and temporal pattern of expression of the genes encoding for kallikrein or bradykinin (BK) B2-receptors parallels postnatal nephrogenesis and blood flow redistribution from the inner to the outer renal cortex. Animal models with genetic dysfunction of the renal KKS show alterations in the functional maturation of the kidney, and ultimately develop salt-sensitive hypertension. Kininogen-deficient Brown Norway Katholiek rats have undetectable urinary kinin levels and show an exaggerated blood pressure sensitivity to chronic excess of salt or mineralocorticoids. Another rat model with genetic reduction in urinary kallikrein excretion is characterized by an altered pressure-natriuresis relationship, with this defect being corrected by infusion of purified rat tissue kallikrein. Knockout mice lacking the BK B2-receptor gene show elevated blood pressure and heart rate under basal conditions and enhanced blood pressure sensitivity to salt. In rats, prenatal blockade of the BK B2-receptor by icatibant leads to a cardiovascular phenotype similar to that of animals with genetic defects of the KKS. Delayed renal maturation is observed when high salt intake is associated with icatibant. Collectively, these findings indicate a relevant role of the KKS in the physiologic maturation of renal and cardiovascular phenotypes. Genetic or environmental factors, able to potentiate the activity of the renal KKS, could protect against the development of arterial hypertension.


Evaluation of the variety of plasmid profiles in S epidermidis isolates from hospital patients and staff.
Plasmid profiling was used to determine the variability of normal flora isolates of Staphylococcus epidermidis in order to evaluate the usefulness of plasmid profiling for identifying pathogens. Fifteen hospital staff members and patients repeatedly had cultures taken from the hands and nares, and multiple isolates were examined for plasmid profiles. S epidermidis isolated from the nares of 15 neonates were also examined. The total number of isolates examined for plasmid profiles was 726. Repetition of profiles was common among the different isolates from a single sampling (one swab). The frequency of re-isolating similar profiles on different days varied from 7% to 13%. Simultaneous isolation of similar profiles from nares and hands on the same individual varied from 0% to 11%, the percentage being lower for personnel. Isolation of the same plasmid profile from different individuals occurred only twice and resulted in an assignment probability of Pa = 0.002 for isolates obtained from different individuals. Significantly more isolates from nares contained plasmids (97%) compared with isolates from hands (89%). Patients who had two or more isolates of coagulase-negative staphylococci with similar profiles were judged, clinically, to have infections in 12 of 13 cases. However, the likelihood of re-isolating an S epidermidis strain with a similar plasmid profile twice from the same person at different times was sufficiently high to prevent plasmid profiling from being used as an absolute criterion for infection.


Blocking by the carcinogen, L-ethionine, of SOS functions in a tif-1 mutant of Escherichia coli B/r.
In Escherichia coli, DNA damage by carcinogenic agents results in the coordinate expression of a diversity of functions (SOS functions), many of which are thermally inducible without any damage to DNA in a tif-1 mutant. These include prophage induction, filamentous growth, and an error-prone DNA repair activity, which is responsible for ultraviolet-induced mutagenesis. Ethionine causes hepatic carcinoma in rats after prolonged feeding but is not a mutagen in the Ames test. The present study shows that 10 mM ethionine prevents the thermal induction of lambda-prophage in a tif-1 derivative of E. coli. The enhancement of mutation, which normally occurs at high temperature after a low dose of ultraviolet light, is also blocked by ethionine. Ethionine does not block, to any appreciable extent, the incorporation of radioactive precursors into RNA, DNA, or protein.


Influence of Musculoskeletal Manifestations as the Only Presenting Symptom in B-Cell Acute Lymphoblastic Leukemia.
To evaluate the clinical and prognostic impact of musculoskeletal manifestations as the only initial presenting symptom in childhood acute lymphoblastic leukemia (ALL). We retrospectively reviewed 158 children with precursor B-cell type ALL who were followed up for >2 years. The patients were assigned to the groups musculoskeletal manifestations (n = 24) or nonmusculoskeletal manifestations (n = 134) based on initial presenting symptom. The symptom duration (regarding any initial presenting symptom) and the leukemic symptom duration (regarding symptoms of systemic manifestation, such as fever, bleeding, or pallor) were assessed, along with other clinical characteristics. The musculoskeletal manifestations group exhibited a longer symptom duration than the nonmusculoskeletal manifestations group (43 days vs 22 days, P = .006), but overall survival did not significantly differ between the groups. Multivariate analysis indicated that a longer symptom duration did not affect prognosis but that a longer leukemic symptom duration was associated with a poorer prognosis (hazard ratio, 7.720; P = .048). Musculoskeletal manifestations are associated significantly with diagnostic delay, but this delay does not affect the prognosis. Diagnostic delay after the onset of leukemic symptoms, however, does appear to affect the prognosis. Intensive evaluations for hematologic malignancies may be unnecessary in children who complain of limb pain without any definite cause, unless they also present with accompanying leukemic symptoms.


Corneal power, thickness, and stiffness: results of a prospective randomized controlled trial of PRK and LASIK for myopia.
To compare the short-, medium-, and long-term changes in corneal optical power and corneal aberrations, central corneal thickness, and corneal "stiffness" assessed by pneumotonometry readings in patients having laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) for myopia. Department of Ophthalmology, Arhus University Hospital, Arhus, Denmark. One eye of each of 45 patients with myopia ranging from -6.00 to -8.00 diopters (D) (spherical equivalent spectacle refraction [SER]) was randomized to LASIK (n=25; mean SER -7.12 D +/- 0.57 [SD]) or PRK (n=20; mean SER -6.91 +/- 0.57 D). Data were collected prospectively before and 1, 3, 6, 12, and 36 months after surgery. Measurements included corneal topography (TMS-1, Tomey), corneal thickness (ultrasound pachymetry), and apparent intraocular pressure (IOP) (pneumotonometry). Retreatments were not performed during the first year, and retreated eyes were excluded from the 3-year follow-up. Changes in corneal power and aberrations, thickness, and apparent IOP were calculated in a pair-wise manner for 3 time periods: short term (preoperative to 1 month after surgery), medium term (1 to 12 months after surgery), and long term (1 to 3 years after surgery). In the short term, corneal power decreased equally in LASIK and PRK eyes. Spherical aberrations and coma-like aberrations increased equally, while corneal thickness decreased significantly less in LASIK eyes than in PRK eyes. The apparent IOP decreased more in LASIK eyes than in PRK eyes. In the medium term, corneal power increased significantly in both groups. Spherical aberrations decreased significantly in PRK eyes but not in LASIK eyes. From 1 to 12 months, corneal thickness increased more in PRK eyes than in LASIK eyes. During this period, the apparent IOP increased significantly in LASIK eyes. In the long term, corneal power and corneal aberrations did not change significantly in either group. Corneal thickness increased slightly but significantly in both groups. The apparent IOP increased significantly more in PRK eyes. Differences between LASIK and PRK related to time-dependent events affecting corneal shape and structural integrity were present. Peripheral changes in flap hydration in LASIK eyes and epithelial and/or stromal thickening in PRK eyes appeared to be the most important factors in optical power changes in the first year after treatment. The changes in apparent IOP suggest that some interlamellar healing occurred during the first year after LASIK. After LASIK and PRK, corneal bending stiffness seemed permanently decreased, although some restiffening may occur in PRK eyes in the long term.


Thyroid hormone resistance syndrome - own experiences.
Thyroid hormone resistance syndrome, also known as Refetoff syndrome, is a rare disease associated with decreased reaction of body tissues to thyroid hormones (TH). Patients with Refetoff syndrome tend to have elevated free TH concentrations and normal or inadequately elevated TSH (caused by thyrotropic cells in the pituitary gland insensitivity to TH). The cause of the disease is the mutation in TR-beta receptor gene. Depending on the clinical presentation generalised and pituitary resistance to TH are described. The syndrome is often misdiagnosed as hyperthyroidism and unnecessarily treated with anti-thyroid drugs. Some patients receive l-thyroxine treatment for apparent hypothyroidism. In this report, three patients are presented with a long history in our Clinic and Outpatient Clinic.


Effects of scopoletin and aflatoxin B1 on bovine hepatic mitochondrial respiratory complexes, 2: a-ketoglutarate cytochrome c and succinate cytochrome c reductases.
The in vitro effects of the toxin coumarin compounds scopoletin and aflatoxin B1 (AFB1) on bovine (Bos indicus) hepatic mitochondrial respiratory complex III enzymes, succinate cytochrome c and a-ketoglutarate cytochrome c reductases, were examined. Kinetic studies on the interaction of the toxins with the enzymes were also carried out. The results showed that although the observed inhibitory and stimulatory effects of the two toxins were consistent with the changes in the kinetic parameters (Km and Vmax values), these parameters were not consistent with the observed effects of the toxins at certain concentrations. These observations are discussed in terms of the relative locations of the enzymes in the mitochondria, and the previously reported inhibitory and uncoupling effects of the toxins on cow liver mitochondrial respiration.


Serum Tamm-Horsfall glycoprotein level in children with various renal diseases.
Serum Tamm-Horsfall glycoprotein (THGP) concentrations were measured by a competitive enzyme-linked immunosorbent assay using peroxidase-labeled THGP in 168 patients, aged 10.5 +/- 4.6 years, with various renal diseases. Using this method, THGP was determined in the concentration range of 10-10(3) micrograms/l. Serum THGP levels ranged from 130 to 350 micrograms/l in 32 control subjects, aged 1-16 years with normal renal function. In most patients with renal disease, the serum THGP levels were lower than those in control subjects. In particular, the serum THGP levels were more reduced according to the decrease in the clearance values of endogenous creatinine (CCR). These findings suggested that the measurement of serum THGP levels is helpful in the evaluation of renal function. On the other hand, 3 patients with vesicoureteric reflux showed higher serum THGP levels than control subjects, though the CCR values in 1 of these patients was lower. These high serum THGP levels may be the result of urinary backflow into circulation.


The biopersistence of Canadian chrysotile asbestos following inhalation.
Chrysotile asbestos is often included with other asbestos materials in evaluation and classification. However, chrysotile is a serpentine with markedly different physical and chemical characteristics in comparison to amphiboles (e.g., crocidolite, amosite, tremolite). In contrast to amphiboles, which are solid, rodlike fibers, chrysotile is composed like a rope of many fine fibrils, which tend to unwind. In order to quantify the dynamics and rate by which chrysotile is removed from the lung, the biopersistence of a sample of commercial chrysotile from the Eastern Townships area of Quebec, Canada, labeled QS Grade 3-F, which is the longest commercial grade intended for textile use, was studied. As the long fibers have been shown to have the greatest potential for pathogenicity, the chrysotile samples were specifically chosen to have more than 200 fibers/cm3 longer than 20 micro m present in the exposure aerosol. This publication presents the results of this study through 3 mo postexposure. The study design included: (1) Fiber clearance (lung digestions): At 1 day, 2 days, 7 days, 14 days, 1 mo, 3 mo, and 12 mo (to be reported) following a 5-day (6 h/day) inhalation exposure, the lungs from groups of animals were digested by low-temperature plasma ashing and subsequently analyzed by transmission electron microscopy for total chrysotile fibers number in the lungs and chrysotile fiber size (length and diameter) distribution in the lungs. (2) Fiber distribution (confocal microscopy): This procedure was included in order to identify the location of the fibers in the lung. At 1 day, 2 days, 7 days, 14 days, 1 month, and 3 months (to be reported) postexposure, the lungs from groups of animals were analyzed by confocal microscopy to determine the anatomic fate, orientation, and distribution of the retained chrysotile fibrils deposited on airways and in the parenchymal region. Chrysotile was found to be rapidly removed from the lung. Fibers longer than 20 micro m were cleared with T(1/2) = 16 days, most likely by dissolution and disintegration into shorter fibers. The shorter fibers were also rapidly cleared from the lung, with fibers 5-20 micro m clearing even faster (T(1/2) = 29.4 days) than those <5 micro m in length. The fibers <5 micro m in length cleared at a rate (T(1/2) = 107 days) that is within the range of clearance for insoluble nuisance dusts. The breaking apart of the longer fibers would be expected to increase the short fiber pool and therefore could account for this difference in clearance rates. The short fibers were not found clumped together but appeared as separate, fine fibrils, occasionally unwound at one end. Short free fibers appeared in the corners of alveolar septa, and fibers or their fragments were found within alveolar macrophages. The same was true of fibers in lymphatics, as they appeared free or within phagocytic lymphocytes. Neutrophil-mediated inflammatory response did not occur in the presence of chrysotile fibers at the time points examined. Taken in context with the scientific literature to date, this report provides new robust data that clearly support the difference seen epidemiologically between chrysotile and amphibole asbestos.


Alcohol and wine in relation to cancer and other diseases.
Heavy alcohol consumption is associated with increased overall mortality, cancer, liver, and cardiovascular diseases; but low doses of alcohol (up to one drink per day) are not associated with the risk of any cancer site with the exception of breast cancer and possibly of oral and pharyngeal cancers. Moreover, recent evidence indicates that moderate alcohol and specifically wine intake provides cardioprotection and neuroprotection and may increase longevity. Various experimental data hypothesize a potential cancer chemopreventive role of some grape extracts, and complete sequencing of the grapevine genome has revealed genes responsible for the synthesis of health-promoting compounds (resveratrol and other polyphenols), thus advocating the development of future potential nutraceutical strategies. This focuses on the pros and cons of moderate alcohol and wine consumption and opens a debate on this topic.


Three microporous metal-organic frameworks assembled from dodecanuclear {NiLn} subunits: synthesis, structure, gas adsorption and magnetism.
Three isostructural heterometallic metal-organic frameworks (MOFs) {[Ln2Ni(OAc)5(HL)(L)]·solvent molecules}n (H2L = 2-hydroxyimino-N-[1-(2-pyrazinyl)ethylidene]-propanohydrazone, Ln = Dy for 1, Tb for 2 and Gd for 3) were solvothermally synthesized by varying rare-earth metal ions with different electron configurations. Their crystal structures, gas adsorption and magnetic behaviors were fully investigated. The three isomorphous MOFs exhibit three-dimensional microporous frameworks with two different orientated dodecane metallic {NiIILnIII(HL)}6 metallomacrocycles alternately connected by {LnIII(L)} connectors, in which an empty one-dimensional channel decorated by the basic hydrazone interior is generated. Due to their LnIII-independent microporous nature, the activated sample of 1 as a representative example has a significant CO2 uptake up to 42.2 cm3 g-1 and an unusually high CO2/N2 and CO2/CH4 adsorption selectivity of up to 98.8 and 16.8 at 298 K and 100 kPa. Magnetically, apparent antiferromagnetic interactions for both 1 and 2 as well as ferromagnetic coupling for 3 are respectively observed at low temperature resulting from the competition of magnetic anisotropy and intermetallic ferromagnetic superexchange. Additionally, 1 with highly anisotropic DyIII spin shows slow magnetization relaxation under zero dc field, whereas 3 possessing isotropic GdIII ions displays a significant cryogenic magnetocaloric effect with a maximum entropy change of 26.6 J kg-1 K-1 at 3.0 K and 70 kOe. These interesting results can provide valuable information on gas separation-based multifunctional 3d-4f MOF materials.


Polymorphisms in DNA repair and multidrug resistance genes among Sindhis of Central India.
Polymorphisms in DNA repair and multidrug resistance genes might contribute to interindividual and interethnic differences in DNA repair capacity and drug disposition respectively. In the present study, we determined the allele and genotype frequencies of four single nucleotide polymorphisms (SNPs) located in the DNA repair genes, XRCC1, XRCC3, XPD, OGG1, namely XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, and OGG1 Ser326Cys, respectively and two SNPs located in the multidrug resistance gene, ABCB1, namely ABCB1 C3435T and ABCB1 C1236T, in 33-35 healthy and unrelated Sindhi individuals, residing in the Vidarbha region of Central India and compared them with the Maharashtrian population from the same geographical region and some other HapMap populations from the HapMap database. The study findings reveal that the Indian Sindhis are closely related to the Maharashtrians as well as Utah residents with Northern and Western European ancestry and Gujarati Indians in Houston, Texas in the HapMap database.


Can realtor education reduce lead exposures for vulnerable populations?
Lead is known for its devastating effects on people, particularly children under the age of six. Disturbed lead paint in homes is the most common source of lead poisoning of children. Preventive approaches including consumer education on the demand side of the housing market (purchasers and renters of housing units) and disclosure regulations on supply side of the housing market (landlords, homeowners, developers, and licensed realtors) have had mixed outcomes. The study described in this article considered whether a novel supply-side intervention that educates licensed real estate agents about the specific dangers of lead poisoning would result in better knowledge of lead hazards and improved behavior with respect to the information they convey to potential home buyers. Ninety-one licensed realtors were trained for four hours on lead hazards and their health impacts. Pre- and postsurveys and a six-month follow-up interview were conducted to assess the impact of the intervention on their knowledge and self-reported behaviors with clients. The findings suggest that supply-side education could have a salutary impact on realtor knowledge and behavior.


The origin of man: a chromosomal pictorial legacy.
Man, gorilla, and chimpanzee likely shared an ancestor in whom the fine genetic organization of chromosomes was similar to that of present man. A comparative analysis of high-resolution chromosomes from orangutan, gorilla, chimpanzee, and man suggests that 18 or 23 pairs of chromosomes of modern man are virtually identical to those of our "common hominoid ancestor", with the remaining pairs slightly different. From this lineage, gorilla separated fist, and three major chromosomal rearrangements presumably occurred in a progenitor of chimpanzee and man before the final divergence of these tow species. A precursor of the hominoid ancestor and orangutan is also assumed.


Written medicine information from English-speaking countries--how does it compare?
There has been an increasing drive from consumers for more information to be available about their medicines. However, the layout and presentation of such written information is variable, and the poor format and design discourages people from reading the documents. To identify, collate, and evaluate different formats of written medicine information (WMI). Three researchers evaluated 157 samples of WMI for 10 prescription and 3 over-the-counter medicines from 6 English-speaking countries compared with the United States Keystone Consensus Criterion 8 (USKCC8) and the Ten Key Principles (TKP) of Consumer Medicine Information. Readability was measured using Flesch-Kincaid Grade Level (FKGL) and Fog tests. Compliance (%) with the criteria was computed and examined using the median test. Overall median compliance with USKCC8 was 70%, and 74% to TKP. New Zealand leaflets achieved the highest compliance with USKCC8 (83%, Interquartile range (IQR) 70-89%), with US leaflets the lowest (55%, IQR 45-70%). Australian and New Zealand leaflets showed the highest compliance with TKP (90%, IQR 80-100% and 87-97%, respectively), while UK leaflets demonstrated the lowest (60%, IQR 52-71%). Overall median reading grades for the leaflets were 10 (Flesch-Kincaid Grade Level) and 11 (Fog). Compliance with USKCC8 and TKP varied greatly between countries, with readability grades exceeding the recommended range. International examples of WMI show wide variation in compliance with guidelines on recommended format and presentation. These examples of WMI require high literacy to read. Future WMI development should use more recommended formats and increase comprehensibility.


[Advances in male germline stem cell].
Stem cell can both self-renew and have the ability to differentiate into one or more cell types that perform normal tissue/organ function throughout life, including embryonic stem cell and adult stem cell. The treatment with stem cells will be widely used in the future. This article reviews recent advances in studies of the use of embryonic stem cells and spermatogonial stem cells in male reproduction.


Full Electric Control of Exchange Bias at Room Temperature by Resistive Switching.
Electric control of exchange bias (EB) is of vital importance in energy-efficient spintronics. Although many attempts have been made during the past decade, each has its own limitations for operation and thus falls short of full direct and reversible electrical control of EB at room temperature. Here, a novel approach is proposed by virtue of unipolar resistive switching to accomplish this task in a Si/SiO2 /Pt/Co/NiO/Pt device. By applying certain voltages, the device displays obvious EB in the high-resistance-state while negligible EB in the low-resistance state. Conductive filaments forming in the NiO layer and rupturing near the Co-NiO interface are considered to play dominant roles in determining the combined resistive switching and EB phenomena. This work paves a new way for designing multifunctional and nonvolatile magnetoelectric random access memory devices.


An allometric approach to quantify the extinction vulnerability of birds and mammals.
Methods to quantify the vulnerability of species to extinction are typically limited by the availability of species-specific input data pertaining to life-history characteristics and population dynamics. This lack of data hampers global biodiversity assessments and conservation planning. Here, we developed a new framework that systematically quantifies extinction risk based on allometric relationships between various wildlife demographic parameters and body size. These allometric relationships have a solid theoretical and ecological foundation. Extinction risk indicators included are (1) the probability of extinction, (2) the mean time to extinction, and (3) the critical patch size. We applied our framework to assess the global extinction vulnerability of terrestrial carnivorous and non-carnivorous birds and mammals. Irrespective of the indicator used, large-bodied species were found to be more vulnerable to extinction than their smaller counterparts. The patterns with body size were confirmed for all species groups by a comparison with IUCN data on the proportion of extant threatened species: the models correctly predicted a multimodal distribution with body size for carnivorous birds and a monotonic distribution for mammals and non-carnivorous birds. Carnivorous mammals were found to have higher extinction risks than non-carnivores, while birds were more prone to extinction than mammals. These results are explained by the allometric relationships, predicting the vulnerable species groups to have lower intrinsic population growth rates, smaller population sizes, lower carrying capacities, or larger dispersal distances, which, in turn, increase the importance of losses due to environmental stochastic effects and dispersal activities. Our study is the first to integrate population viability analysis and allometry into a novel, process-based framework that is able to quantify extinction risk of a large number of species without requiring data-intensive, species-specific information. The framework facilitates the estimation of extinction vulnerabilities of data-deficient species. It may be applied to forecast extinction vulnerability in response to a changing environment, by incorporating quantitative relationships between wildlife demographic parameters and environmental drivers like habitat alteration, climate change, or hunting.


Functional significance of collateral blood flow in patients with recent acute myocardial infarction. A study using myocardial contrast echocardiography.
We hypothesized that myocardial contrast echocardiography (MCE) can be used to both measure collateral blood flow as well as assess the functional significance of collaterals in patients with acute myocardial infarction (AMI). MCE was performed in 33 patients with recent AMI (12 +/- 7 days) and an occluded infarct-related artery (IRA), both before and after attempted percutaneous transluminal coronary angioplasty (PTCA). The size of the occluded bed was defined in patients with successful PTCA by injecting contrast directly into the opened IRA and expressed as a percent of the myocardium in the short-axis view. The percent of the perfusion bed supplied by collaterals before PTCA was determined. Transit rates of the microbubbles within the collateralized regions were also measured and were expressed as a percent of the transit rates in the normal adjacent beds. Regional function within the occluded bed was assessed using echocardiography and was graded as 1 (normal) to 5 (dyskinetic). Collaterals were graded on coronary angiography as 0 (none) to 3 (abundant). The perfusion bed size was larger for the left anterior descending (LAD) than for the right (RCA) and left circumflex (LCx) coronary arteries (37 +/- 6% versus 27 +/- 12% of the myocardium, p = 0.02). The percent of the occluded bed supplied by collateral flow was greater for RCA and LCx compared with the LAD (87 +/- 30% versus 72 +/- 22%, p less than 0.01). There was poor correlation between MCE-defined percent of occluded bed supplied by collaterals and angiographic collateral grade (r = 0.13). Regions supplied by collaterals were less likely to show confluent hypoperfused zones after reperfusion compared with those not supplied by collaterals. Similarly, the percent of myocardium not perfused by either anterograde or collateral flow correlated well (r = 0.67, p less than 0.01) with peak creatine kinase levels and was more likely to be associated with Q waves. Finally, although there was poor correlation between angiographic collaterals and regional function (r = 0.20), there was a significant negative correlation between MCE-defined spatial extent of collateral flow and regional function (r = -0.57, p less than 0.01). MCE can be used to measure collateral flow in patients with recent AMI and to assess the functional significance of collaterals in these patients. This technique may be ideally suited for the assessment of collateral perfusion in patients undergoing cardiac catheterization.


Transmit beamforming for optimal second-harmonic generation.
A simulation study of transmit ultrasound beams from several transducer configurations is conducted to compare second-harmonic imaging at 3.5 MHz and 11 MHz. Second- harmonic generation and the ability to suppress near field echoes are compared. Each transducer configuration is defined by a chosen f-number and focal depth, and the transmit pressure is estimated to not exceed a mechanical index of 1.2. The medium resembles homogeneous muscle tissue with nonlinear elasticity and power-law attenuation. To improve computational efficiency, the KZK equation is utilized, and all transducers are circular-symmetric. Previous literature shows that second-harmonic generation is proportional to the square of the transmit pressure, and that transducer configurations with different transmit frequencies, but equal aperture and focal depth in terms of wavelengths, generate identical second-harmonic fields in terms of shape. Results verify this for a medium with attenuation f1. For attenuation f1.1, deviations are found, and the high frequency subsequently performs worse than the low frequency. The results suggest that high frequencies are less able to suppress near-field echoes in the presence of a heterogeneous body wall than low frequencies.


[Research of the Raman Signal De-Noising Method Based on Feature Extraction].
To improve time resolution of the Raman measurement system, we need to adopt short scanning time. In this case, the weak Raman signal with vibrational spectrum of the molecular structure is easily to be buried by the high background noise, which influences the further analysis seriously. So it is necessary to de-noise the raw Raman signals. Conventional methods manage to de-noise signal by means of smoothing or averaging based on the difference between signal and noise in frequency characteristic or statistical features. They are commonly applied in the situation where the background noise is not so strong, and cannot give satisfactory results to the Raman signals with low signal-to-noise ratio. In this paper, the algorithm proposed detects peak positions and get peak half-width based on wavelet transform, and then reconstructs the Raman signals by least square fitting algorithm with characteristic parameters obtained, which extracts the useful signal from high background noise efficiently. In the simulation, the Raman curve fitted by the proposed algorithm was smooth, and the peak positions obtained were accurate, so the signal-to-noise ratio improved significantly. In the experiment, we adopted this algorithm to de-noise the tested Raman signal of Cefuroxime Axetil Tablets and Roxithromycin, respectively. The peak positions, peak half-width and amplitude were obtained and proved to be accurate. Therefore, the useful pure Raman signal could be recovered from the high background noise efficiently by the proposed algorithm, which improved the time resolution of Raman system. Both the simulation and the experiment showed that the proposed method could be easily performed with only a few parameters. Comparing with conventional methods, it could achieve satisfactory results under high background noise and provide accurate and reliable information for further analysis.


Physiologically based modeling of 2-butoxyethanol disposition in rats following different routes of exposure.
2-Butoxyethanol (BE) is widely used as a solvent in coatings and other consumer products and has shown hematotoxicity in laboratory animals. To provide a physiological basis for extrapolating toxicokinetic data observed in rats to humans, a blood flow rate-limited, physiologically based pharmacokinetic model was developed to describe the distribution and metabolism of BE in rats following drinking water, dermal, and inhalation exposures. The major urinary metabolite, butoxyacetic acid, represented 45 to 60% of the absorbed dose in all three routes of exposure. Other identified urinary metabolites in our studies included ethylene glycol and BE-glucuronide. A model formulation of the possible metabolic pathways based on the experimental data was proposed. The amounts of individual urinary metabolites were used to develop the model. Metabolic constants were estimated by fitting the data within the constraints of in vitro measurements. The model explained the change of profiles of urinary metabolites in different exposure routes by taking into account the differences in absorption rate and by incorporating a minor pathway for metabolism by skin. Sensitivity analysis showed that metabolic constants and blood flow rate to liver had a relatively larger influence on the production of urinary metabolites than the organ volume or the partition coefficient for BE.


Skin test with a timothy grass (Phleum pratense) pollen extract vs. IgE to a timothy extract vs. IgE to rPhl p 1, rPhl p 2, nPhl p 4, rPhl p 5, rPhl p 6, rPhl p 7, rPhl p 11, and rPhl p 12: epidemiological and diagnostic data.
The diagnostic approach to grass pollen allergy is now possible by detecting specific IgE to its allergenic components. To compare the IgE reactivity to a timothy grass pollen extract with the IgE reactivity to eight allergenic components from the same source (Phl p 1, 2, 4, 5, 6, 7, 11, 12). Both were compared with the skin test reactivity to a timothy grass extract. A population survey was carried out by means of the skin test to identify grass-allergic subjects, and to characterize them in terms of demographic and allergological parameters. Seven hundred and forty-nine sera were available for IgE detection to a timothy extract, to the recombinant Phl p 1, 2, 5, 6, 7, 11, 12, and to native Phl p 4 and bromelain. Results were stratified by means of demographic and allergy parameters. Ninety-five per cent of the sera had detectable IgE to the timothy extract. Prevalence of IgE reactivity increased from 86.8% to 93.3% as the number of combined reactive molecules rose from 2 to 8. Adjusted prevalences for each allergen were: rPhl p 1 = 83%, rPhl p 2 = 55%, nPhl p 4 = 70%, rPhl p 5 = 50%, rPhl p 6 = 44%, rPhl p 7 = 7%, rPhl p11 = 43%, rPhl p 12 = 15%. Isolated reactivity to rPhl p 1 was 6%, whereas it was negligible for the remaining molecules. IgE reactivity prevalence and mean values differed when patients were stratified on the basis of their associated pollen reactivity and their skin test reactivity grade. No differences were found when age, symptom type and duration were considered. Up to eight-fold higher IgE concentrations were found when the sum of IgE to molecules was compared with IgE to the extract. Testing for the IgE reactivity to the glycan of the native Phl p 4 allergen showed a possible interference with prevalence and value estimation. Higher prevalence values were found in previously immunotherapy-treated patients. The use of a complete panel of grass allergenic molecules can mimic the current use of allergenic extracts, but new relevant information, such as individual pattern of reactivity, adjusted prevalence, correct specific IgE concentration, can be achieved only by means of discrete allergenic molecules.


Polymorphisms and haplotypes across the osteoprotegerin gene associated with bone mineral density and osteoporotic fractures.
Osteoprotegerin plays a key role in bone remodelling. We studied the association between 24 polymorphisms and haplotypes on the OPG gene and bone mineral density and fractures. After multiple-testing correction, one SNP and two block-haplotypes were significantly associated with FN BMD. Two other block-haplotypes were associated with fracture. Osteoprotegerin (OPG) plays a key role in bone remodelling. Here we studied the association between polymorphisms and haplotypes on the OPG gene and bone mineral density (BMD) and fractures. Twenty-four single nucleotide polymorphisms (SNPs) were selected to cover six haplotypic blocks and were genotyped in 964 postmenopausal Spanish women. Haplotypes were established with HaploStats. Association was analysed by GLM (for BMD) and logistic regression (for fractures) both at single SNP and haplotype levels. Upon adjustment for multiple testing (p < 0.0073), one of the SNPs (SNP #17, rs1032129) remained significantly associated with FN BMD (p = 0.001). Four block-haplotypes stood multiple-testing correction. Two remained associated with FN BMD and two with fracture. The association of block-4 haplotype "AC" (of SNPs #18 and #17) with FN BMD (p = 0.0002) was stronger than that of SNP#17 alone and was the best result overall. A global assessment of the results indicated that all the alleles and haplotypes with a protective effect, at p < 0.05, belonged to a frequent long-range haplotype. In conclusion, these results provide a detailed picture of the involvement of common variants and haplotypes of the OPG gene in bone phenotypes.


Evidence for the intercalation of thalidomide into DNA: clue to the molecular mechanism of thalidomide teratogenicity?
The intercalation of thalidomide (alpha-phthalimidoglutarimide) into nucleic acids was studied by spectrophotometric titrations, displacement of known intercalators, viscosity changes of DNA solutions, and by phase partition analysis. Specific binding of thalidomide was found to DNA of various specimens (human placenta, calf thymus, salmon sperm), but not to RNA (from bakers yeast, torula yeast).


TRPV4 channels in the human urogenital tract play a role in cell junction formation and epithelial barrier.
The molecular interactions between transient receptor potential vanilloid subtype 4 channels (TRPV4) and cell junction formation were investigated in the human and mouse urogenital tract. A qualitative study was performed to investigate TRPV4 channels, adherence junctions (AJs) and tight junctions (TJs) in kidney, ureter and bladder tissues from humans and wild-type and transgenic TRPV4 knockout (-/-) mice with immunohistochemistry, Western blotting, immunoprecipitation and reverse trasnscription-PCR. Cell junction formation in the wild-type and TRPV4 knockout (-/-) mouse was evaluated with immunohistochemistry and transmission electron microscope (TEM) techniques. TRPV4 channels are predominantly located in membranes of epithelial cells of the bladder, ureter and the collecting ducts of the kidney. There is a molecular interaction between the TRPV4 channel and the AJ. TEM evaluation showed that AJ formation is disrupted in the TRPV4 -/- mouse resulting in deficient intercellular connections and integrity of the epithelium. TRPV4 is believed to be a mechanoreceptor in the bladder. This study demonstrates that TRPV4 is also involved in intercellular connectivity and structural integrity of the epithelium.


[Pain relief by means of continuous epidural analgesia after retroperitoneal lymph node dissection (author's transl)].
A retrospective study compares the effectiveness of postoperative epidural analgesia with conventional analgetic medication in cases of retroperitoneal lymph node dissection. Epidural analgesia is noted for its reduced need for additional medication and for its lower incidence of complications.


Psychosis proneness and ADHD in young relatives of schizophrenia patients.
Symptoms resembling the attentional deficit hyperactivity disorder (ADHD) are frequently observed in young relatives at risk for schizophrenia (HR). We examined the frequency of the ADHD syndrome and its relationship to psychosis related psychopathology and neurobehavioral abnormalities in young HR subjects (n=29) and healthy comparison subjects (HC; n=30). Thirty-one percent of HR subjects (n=9) had ADHD as a lifetime Axis-I diagnosis (HR-A). Compared to healthy comparison subjects, the HR-A group had impaired neurological function. The HR-A group but not the HR subjects without ADHD had higher scores on the Chapman's magical ideation and perceptual aberration scales. Thus, ADHD-like features are more prevalent in the HR population than the one described in the general population and are associated with more frequent psychosis-like clinical features. Longitudinal studies can clarify whether an "ADHD subgroup" within HR subjects predict an increased risk for future emergence of schizophrenia.


The "dense artery sign"--major cerebral artery thromboembolism demonstrated by computed tomography.
A 4 years review of high resolution thin slice (3-5 mm) computed tomography performed within 24 h after cerebral infarction revealed increased density in a major cerebral artery segment in 28 patients. Arteries affected were the vertebral and basilar artery in 6 and 8 patients, the sphenoid course of the middle cerebral artery in 13 cases and the extracranial internal carotid artery in 1 patient. In 35.7% of cases the so called "dense artery sign" provided earliest evidence of the ensuing infarction documented by CT controls in most patients. Angiography carried out in 8 patients, density calculations in the course of the affected vessel and resolution of the increased density on subsequent CT examinations suggest thrombembolism as the most likely etiology. In the clinical setting of acute stroke increased artery density encompassing the entire vessel diameter may serve as an early indicator of major cerebral artery occlusion and prompt angiographic investigation of a lesion potentially amenable to lysis.


Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells.
The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B(NF-κB) activity. To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF-κB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-κB activity.


Evidence-informed management of chronic low back pain with physical activity, smoking cessation, and weight loss.
The management of chronic low back pain (CLBP) has proven to be very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of The Spine Journal, titled Evidence-Informed Management of Chronic Low Back Pain Without Surgery. Articles in this special focus issue were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP.


Factors influencing choice of implants in total hip arthroplasty and total knee arthroplasty: perspectives of surgeons and patients.
To determine the factors influencing surgeons' choice of implants for total hip arthroplasty (THA) and total knee arthroplasty (TKA), 650 surveys were mailed to all active members of the American Association of Hip and Knee Surgeons practicing in the United States; 364 surveys (56%) were completed and returned. Analysis revealed that the average number of total hip and total knee replacements performed by the respondents in 1997 was 81 and 97; there was substantial regional variation. The average number of hip implant and knee implant brands used by these surgeons in 1997 was 2.4 and 1.8. Anticipated improvement in clinical results and cost of components were the most frequently listed reasons for changing brands. Surgeons were also queried about cost reduction programs at their particular institution. The most frequently listed strategies for cost reduction of implants included surgeon cost-awareness programs and volume discounting. More than half of the respondents (53.5%) anticipate manufacturers to decrease the cost of implants in the next 2 years. Most of the respondents (93.7%) currently have the ability to choose a particular implant. About half (46.7%) anticipate losing some or all control of this decision in the next 3 years. These respondents foresee their hospitals requiring the use of a discounted implant in the future. An additional survey was completed by 102 consecutive patients scheduled either for primary THA (64) or primary TKA (38) at our institution. When asked about implant selection, 93.1% responded that their orthopaedic surgeon should choose the prosthesis; 5.9% responded that their physician in consultation with the patient should choose the prosthesis. When asked what should be the primary determinant of implant choice, cost or quality, the overwhelming majority (97.1%) chose quality. A small percentage (2.9%) chose cost and quality. No patient chose cost alone. A large number of patients (84.8%) responded that they would pay additional costs if their insurance companies or health maintenance organizations refused to pay for a better but more expensive implant. Most patients realized how expensive components are, and 51% of the respondents correctly estimated the cost of an implant. Orthopaedic surgeons perceive that they are losing control of implant choice in THA and TKA. Cost of implants is one of the most significant factors influencing which implant is chosen. Patients (the true payors), however, overwhelmingly want their surgeons to choose the implant used at surgery, and they want quality, not cost, to be the primary determinant of this decision.


Evolutionary morphology of the hemolymph vascular system in scorpions: a character analysis.
Phylogenetically informative characters from the internal anatomy of scorpions were first reported more than 150 years ago, but the subject received little attention after the mid-1920s. Recent investigations, using traditional dissection, illustration and histological sectioning, microscopy, and innovative new methods for investigating complex soft tissue anatomy identified a new wealth of variation. Additionally, these investigations confirmed the phylogenetic significance of previously identified structures. Building on earlier work we present a more detailed description of the hemolymph vascular system (HVS) in scorpions, based on comparison of the vascular structures of the heart and the branching pattern of the prosomal arteries among 45 exemplar species representing most of the major scorpion lineages. Using corrosion-casting, MicroCT in combination with computer-aided 3D-reconstruction, and scanning electron microscopy, we conceptualize a series of phylogenetically informative characters for the anterior aorta system and characters of the heart and associated structures (e.g. arrangement of the ostia) of scorpions. Furthermore, we optimize the possible evolution of these new characters on a previous hypothesis of scorpion phylogeny, and discuss alternative character state transformations, their evolutionary consequences, and possible underlying evolutionary mechanisms acting on the HVS.


Efficacy and tolerability of liposomal heparin spraygel as an add-on treatment in the management of superficial venous thrombosis.
Superficial venous thrombosis usually resolves spontaneously in a few weeks. In most cases, treatment includes peroral analgesics or nonsteroidal anti-inflammatory drugs accompanied by the recommendation to wear elastic stockings and perform regular mild ambulation. In contrast to this "standard treatment," a recent ACCP guideline has recommended that patients affected by spontaneous superficial thrombophlebitis be treated with intermediate doses of unfractionated or low-molecular-weight heparin. This study was designed to assess the efficacy of topically applied heparin spraygel in terms of reduction of local symptoms and signs of superficial venous thrombosis.


Development of a Skill Acquisition Periodisation Framework for High-Performance Sport.
Unlike physical training, skill acquisition does not currently utilise periodisation to plan, monitor and evaluate programs. Development of a skill acquisition periodisation framework would allow for systematic investigation into the acute and longitudinal effectiveness of such interventions. Using the physical training literature as a reference point, a skill-training periodisation framework was developed for use in high-performance sport. Previous research undertaken in skill acquisition was used to provide support for the framework. The specificity, progression, overload, reversibility and tedium (SPORT) acronym was adopted. Each principle was then re-conceptualised so that it related to relevant skill acquisition principles. Methods for the measurement and analysis of each principle are provided and future directions for the longitudinal assessment of skill acquisition are discussed. The skill acquisition periodisation framework proposed in this study represents an opportunity for the principles relating to skill acquisition training to be measured in a systematic and holistic manner. This can also allow for a more sophisticated evaluation of the efficacy of longitudinal training programmes and interventions designed for sustained skill enhancement.


Experimental oligohydramnios decreases collagen in hypoplastic fetal rat lungs.
Neonates with premature rupture of the membrane and oligohydramnios have an increased risk of acute respiratory morbidity. The aims of this study are to investigate the effects of experimental oligohydramnios on transforming growth factor (TGF)-beta1 and connective tissue growth factor (CTGF) expressions and collagen level in fetal rat lungs. On day 16 of gestation, we anesthetized timed pregnant Sprague-Dawley dams, punctured the uterine wall and fetal membranes of each amniotic sac which resulted in oligohydramnios. Fetuses in the opposite uterine horn served as controls. On days 19 and 21 of gestation, fetuses were delivered by cesarean section. Rats exposed to oligohydramnios exhibited significantly lower lung weight/body weight ratios on days 19 and 21 of gestation than did the control rats. Lung type I collagen and TGF-beta1 mRNA expressions and lung collagen levels were significantly decreased in rats exposed to oligohydramnios on days 19 and 21 of gestation. Type I collagen and inhibitors of metalloproteinase-1 (TIMP-1) proteins were decreased and matrix metalloproteinase-1 (MMP-1) was increased in oligohydramnios-exposed rats on days 19 and 21 of gestation. CTGF mRNA expressions were comparable between control and oligohydramnios-exposed rats on days 19 and 21 of gestation. These data suggest that downregulation of collagen might be involved in the pathogenesis of oligohydramnios-induced respiratory morbidity.


[Long-term trials assessing pharmacological treatments in COPD: lessons and limitations].
Several long-term studies designed to assess pharmacological treatments for Chronic Obstructive Pulmonary Disease (COPD) have been published recently. Only such long-term studies allow an accurate analysis of the effect of treatments on criteria of effectiveness such as survival or decline in pulmonary function. A review of these studies is opportune. The high drop out rate, which is not a random event, leads to serious methodological problems that are of importance in the interpretation of these studies. Post hoc analysis of both the TORCH and UPLIFT trials suggest a positive effect of long-acting bronchodilators on survival. Up to now, no treatment has convincingly demonstrated an effect on the rate of decline of FEV(1). The treatments evaluated lead to a decrease in exacerbation rates and an improvement in quality of life although the effects of inhaled corticosteroids are subject to methodological concerns. The treatments are all well tolerated. The design of future studies should avoid the withdrawal of treatments at enrolment into a study in order to limit the number of drop outs. Long-term studies have made important progress in the knowledge, not only of the effects of the treatments assessed but also of the methodological issues which need to be addressed.


[Taxol and related diterpenoids of Taxus sp.: important acquisitions in the treatment of cancer].
Phytochemical and pharmacological studies on Taxus sp extracts have resulted in the isolation and the identification of several diterpenoids, and the discovery of the potent antitumor activity of taxol. This natural compound displays a unique mechanism of action as it stabilizes microtubules and inhibits their depolymerization into free tubulin. The emergence of taxol from the screening of natural products shows the benefits and the potent interest of these constituents in the search of drugs exhibiting novel mechanisms of action. The most pressing problem in taxol or taxol derivates commercialization is the drug supply. Alternative sources of taxol are now under investigation, mainly the total synthesis of taxol, the hemisynthesis of taxol or of taxotere from 10-deacetylbaccatine III, the in vitro production of taxol by cell or tissue cultures, and the prospection of new natural sources of taxol.


Steady-state modelling of metabolic flux between the tricarboxylic acid cycle and the glyoxylate bypass in Escherichia coli.
In this study, mathematical modelling, using the computer package MetaModel, was employed to calculate the steady-state fluxes and the concentration of various metabolites of the central pathways during growth of Escherichia coli on acetate. This package also enabled us to formulate the matrices of the elasticity coefficients and the control and response coefficients under different steady states. In this paper, we have assessed the relative contribution of the competing enzymes at the metabolic junction of isocitrate, i.e. isocitrate dehydrogenase (ICDH) and isocitrate lyase (ICL), to the overall distribution of carbon flux among the enzymes of the central pathways thus extending the pioneering work of Walsh and Koshland on the partition of carbon flux between the two metabolic cycles of the tricarboxylic acid and the glyoxylate bypass. This study revealed that ICDH is not 'rate limiting' during growth on acetate and that flux through ICL is essential not only to replenish the central pathways with biosynthetic precursors but also to sustain a high intracellular level of isocitrate. Furthermore, above certain threshold concentration of ICL, the Krebs cycle and the glyoxylate bypass work in concert and the partition of carbon flux between ICDH and ICL is no longer a problem.


Role of the middle residue in the triple tryptophan electron transfer chain of DNA photolyase: ultrafast spectroscopy of a Trp-->Phe mutant.
Photoreduction of the semi-reduced flavin adenine dinucleotide cofactor FADH* in DNA photolyase from Escherichia coli into FADH- involves three tryptophan (W) residues that form a closely spaced electron-transfer chain FADH*-W382-W359-W306. To investigate this process, we have constructed a mutant photolyase in which W359 is replaced by phenylalanine (F). Monitoring its photoproducts by femtosecond spectroscopy, the excited-state FADH* was found to decay in approximately 30 ps, similar as in wild type (WT) photolyase. In contrast to WT, however, in W359F mutant photolyase the ground-state FADH* fully recovered virtually concomitantly with the decay of its excited state and, despite the presence of the primary electron donor W382, no measurable flavin reduction was observed at any time. Thus, W359F photolyase appears to behave like many other flavoproteins, where flavin excited states are quenched by very short-lived oxidation of aromatic residues. Our analysis indicates that both charge recombination of the primary charge separation state FADH-W382*+ and (in WT) electron transfer from W359 to W382*+ occur with time constants <4 ps, considerably faster than the initial W382-->FADH* electron-transfer step. Our results provide a first experimental indication that electron transfer between aromatic residues can take place on the time scale of approximately 10(-12) s.


Quantitative analysis of intracellular calcium and mitochondrial kinetic fluorescence changes in GSNO-induced thymocyte early apoptosis.
A fluorescence microscopy imaging technique was applied to observe the single-cell kinetic changes of intracellular Ca(2+) concentration ([Ca(2+)](i)) and mitochondrial membrane potential (ΔΨ(m)) during the early stage of S-nitrosoglutathione (GSNO)-induced thymocytes apoptosis. The kinetic features of [Ca(2+)](i) and ΔΨ(m) were quantitatively analyzed and compared by fitting the fluorescence intensity data. The mathematical parameter, inflection point which indicated the time point when [Ca(2+)](i) or ΔΨ(m) changed the most rapidly, was proposed to analyze the fitting curve. The results revealed that the inflection point of [Ca(2+)](i) always appeared prior to that of ΔΨ(m) during apoptosis induced by a certain GSNO concentration. Both the [Ca(2+)](i) and ΔΨ(m) changed in a GSNO concentration-dependent manner. Another parameter, half-max effect point was also employed and displayed the similar results. Such quantitative analyses of real-time observations at the single-cell level are useful for interpreting the sequence of the biological events operating in GSNO-induced thymocyte apoptosis.


Monitoring human chorionic gonadotrophin level: evaluation of urine as an alternative specimen type.
Although urine has been used widely for the qualitative detection of human chorionic gonadotrophin (hCG), serum is chosen conventionally for the serial quantification of the hormone to monitor trophoblastic activity. In response to requests from both clinicians and patients regarding the use of urine as an alternative specimen type, we designed this comparative study to evaluate the possibility, taking into account both laboratory technique and the distribution of hCG within different body fluids. Using the Access Chemiluminescent Immunoassay System, total beta-hCG was measured in serum and urine (n = 30) collected from patients hospitalised for first-trimester abnormal pregnancy. Results obtained with normalised urine (corrected with urinary creatinine) and serum total beta-hCG correlated well (r = 0.98, P < 0.001), and we concluded that urine could be used as an alternative specimen type for the serial quantitation of hCG to monitor trophoblastic activity. However, the assay used must detect the common beta 2 epitope.


[Patient with stable ischaemic heart disease and essential thrombocythemia in Invasive Cardiology Laboratory -- role of the automated systems for estimation of platelet aggregation].
Patient with stable ischaemic heart disease and essential thrombocythemia in Invasive Cardiology Laboratory -- role of the automated systems for estimation of platelet aggregation. A case of a 63-year-old male patient with essential thrombocythemia and coronary artery disease is presented. The patient underwent elective coronary angiography and subsequent angioplasty of the intermediate branch. The procedure was complicated by a massive thrombosis of the right coronary artery. Tirofiban and subsequent stenting relieved anginal symptoms. Next, platelet activity was monitored using the platelet function analyser PFA-100 which enabled optimisation of the antiplatelet agent dosages. The usefulness of this device in the catheterisation laboratory is discussed.


Inhibition of tyrosine kinase signaling by tyrphostin AG126 downregulates the IL-21/IL-21R and JAK/STAT pathway in the BTBR mouse model of autism.
Autism spectrum disorder (ASD) comprises a broad range of neurodevelopmental disorders that are associated with deficits in social interaction and communication. The tyrosine kinase inhibitor tyrphostin AG126 represents a promising therapeutic agent for several neuroinflammatory disorders. There are currently no treatments available that can improve ASD and we previously showed that AG126 treatment exerts beneficial effects on BTBR T+ Itpr3tf/J (BTBR) mice, a model for autism that shows the core features of ASD; however, the immunological mechanisms and molecular targets associated with this effect were previously unclear. This study was undertaken to delineate the neuroprotective effect of AG126 on BTBR mice. Here, using this mouse model, we investigated the effects of AG126 administration on IL-21R, IL-21, IL-22, TNF-α, NOS2, STAT3, IL-27, and Foxp3 production by CD8+ T cells in the spleen by flow cytometry. We further explored the mRNA and protein expression of IL-21, IL-22, IL-1β, TNF-α, NOS2, JAK1, STAT3, IL-27, and Foxp3 in brain tissue by RT-PCR, and western blotting. We found that BTBR mice treated with AG126 exhibited significant decreases in IL-21R-, IL-21-, IL-22-, TNF-α-, NOS2-, STAT3-producing, and increases in IL-27- and Foxp3-producing, CD8+ T cells. Our results further demonstrated that AG126 treatment effectively decreased IL-21, IL-22, IL-1β, TNF-α, NOS2, JAK1, and STAT3, and increased IL-27 and Foxp3 mRNA and protein expression in brain tissues. Our findings suggest that AG126 elicits a neuroprotective response through downregulation of the IL-21/IL-21R and JAK/STAT pathway in BTBR mice, which could represent a promising novel therapeutic target for ASD treatment.


L-2-Hydroxyglutaric aciduria presenting with severe autistic features.
L-2-Hydroxyglutaric aciduria (L-2-HGA) is an autosomal recessive neurometabolic disorder characterized by psychomotor delay, ataxia, macrocephaly and typical neuroradiological findings of subcortical leucoencephalopathy. Recently, the disease causing gene has been discovered (L2HGDH) encoding L-2-hydroxyglutarate dehydrogenase. We present a 3-year-old boy with L-2-HGA, who demonstrated macrocephaly, noted already in utero with ultrasound. Cranial MRI demonstrated diffuse subcortical encephalopathy with increased signal of the subcortical white matter. Subsequent metabolic screening revealed increased levels of L-2-HGA, and genomic DNA analysis demonstrated two missense mutations in L-2-HGDG. Patient's further motor development was mildly impaired, whilst his speech development was profoundly impaired (first words at the age of 2 years). Since the age of 2 years he started demonstrating autistic repetitive behaviors and movements, increasing aloofness to his environment and limitations in the variety of spontaneous activity (CARS score: 44/60-severe autism). Autism has not so far been described in L-2-HGA and may be considered as an additional feature of the phenotypic spectrum.


Cancer-Cell-Specific Nuclear-Targeted Drug Delivery by Dual-Ligand-Modified Mesoporous Silica Nanoparticles.
Mesoporous silica nanoparticles are modified with dual targeting ligands, i.e., folic acid and dexamethasone, to construct a cancer-cell-specific nuclear-targeted delivery system. The resulting nanocarriers can not only enhance the inhibition efficacy of doxorubicin on Hela cells through active nucleus accumulation but also reduce toxic side effects on noncancer cells though receptor-mediated selective cellular uptake.


Different fractions in the normal and hypertrophied rat ventricular myocardium: an analysis of two models of hypertrophy.
Long-term hemodynamic overload of the heart leads to an increase in myocardial mass. In most cases it is not known to what degree the single components in the myocardium (water, protein, nonprotein substance) increase. As an answer to the overloading of the myocardium, many authors have established an intensification in the synthesis of myocardial proteins. It is, however, little known which proteins are then more intensively created and accumulated. This study examines the dynamics of the protein and nonprotein content as well as of single protein fractions (sarcoplasmic, myofibrillar, and stromal) in both hypertrophied and normal tissue from rat myocardia. The results revealed that in Goldblatt rats, 4-24 weeks after stenosis of one renal artery, no noteworthy differences in the relationships of protein and nonprotein content were caused by hypertrophy (34-54%) due to left ventricular pressure overload. The same is true of the tissue from moderately hypertrophied myocardia (12-17%) of rats exercised for several weeks by swimming training. Determination of hydroxyproline concentration showed that significant differences in the content of the collagen tissue in relation to control animals of the same age occurred only in Goldblatt rats 24 weels after operation. However, greater alterations in the concentrations of various protein fractions could be registered. The increase in the concentration of myofibrillar proteins in hypertrophied myocardial tissue is of particular significance and is to be considered as an adaption of the muscle to the increased mechanical demands. Certain changes regarding the relation of the single components within the myofibrillar fraction (relation of actomyosin concentration to T-fraction; relation of both components to total fraction), whose cause and significance is as yet unclear, could be observed.


Quantitative measurement of cerebrovascular reactivity by blood oxygen level-dependent MR imaging in patients with intracranial stenosis: preoperative cerebrovascular reactivity predicts the effect of extracranial-intracranial bypass surgery.
CVR is a measure of cerebral hemodynamic impairment. A recently validated technique quantifies CVR by using a precise CO(2) vasodilatory stimulus and BOLD MR imaging. Our aim was to determine whether preoperative CO(2) BOLD CVR predicts the hemodynamic effect of ECIC bypass surgery in patients with intracranial steno-occlusive disease. Twenty-five patients undergoing ECIC bypass surgery for treatment of intracranial stenosis or occlusion were recruited. CVR was measured preoperatively and postoperatively and expressed as %ΔBOLD MR signal intensity per mm Hg ΔPetCO(2). Using normative data from healthy subjects, we stratified patients on the basis of preoperative CVR into 3 groups: normal CVR, reduced CVR, and negative (paradoxical) CVR. Wilcoxon 2-sample tests (2-sided, α = 0.05) were used to determine whether the 3 groups differed with respect to change in CVR following bypass surgery. The group with normal preoperative CVR demonstrated no significant change in CVR following bypass surgery (mean, 0.22% ± 0.05% to 0.22% ± 0.01%; P = .881). The group with reduced preoperative CVR demonstrated a significant improvement following bypass surgery (mean, 0.08% ± 0.05% to 0.21 ± 0.08%; P < .001), and the group with paradoxical preoperative CVR demonstrated the greatest improvement (mean change, -0.04% ± 0.03% to 0.27% ± 0.03%; P = .028). Preoperative measurement of CVR by using CO(2) BOLD MR imaging predicts the hemodynamic effect of ECIC bypass in patients with intracranial steno-occlusive disease. The technique is potentially useful for selecting patients for surgical revascularization.


The Use of Multiparametric Magnetic Resonance Imaging (mpMRI) in the Detection, Evaluation, and Surveillance of Clinically Significant Prostate Cancer (csPCa).
With the long-standing controversy surrounding the use of prostate-specific antigen (PSA) for the detection, evaluation, and surveillance of prostate cancer, there is a need for a minimally invasive technique to identify and risk-stratify these patients. Additionally, in an effort to reduce the number of unnecessary biopsies and identify clinically significant prostate cancer (csPCa), there has been a shift in practice towards the use of multiparametric magnetic resonance imaging (mpMRI) in conjunction with decision-making regarding prostate cancer diagnosis and management. In the current review, we summarize the data regarding the use of mpMRI in the detection, evaluation, and surveillance of csPCa. Recent prospective clinical trials have determined that a pre-biopsy mpMRI may rule out insignificant prostate cancers, thereby reducing the number of patients who require a biopsy. The anatomic information gathered from these pre-biopsy mpMRI performed during MRI fusion biopsy in csPCa increases the accuracy of pathologic staging in terms of Gleason scores. In regard to active surveillance, prospective trials suggest little to no clinical utility for mpMRI and fusion biopsy in the surveillance of prostate cancer despite conflicting findings from retrospective studies. Recent trials suggest that mpMRI can play an important role in the detection and evaluation of csPCa. The ideal role for mpMRI in active surveillance remains limited.


Epidemiology of adults hospitalized with burns in Karachi, Pakistan.
Burns are a leading cause of adult death in Karachi slums, therefore we reviewed 1 year's logged experience (November 1992 to October 1993) at Karachi's two adult burn units for patient age, sex, burn severity and outcome. Also 47 inpatients were interviewed regarding their circumstances of injury. We grouped these using Haddon's Matrix. The log identified 832 patients. Females (57 per cent) outnumbered males and were younger on average (25.1 vs 27.6 years, P = 0.002). Females had more severe burns than males (57 per cent vs 50 per cent total body surface area (TBSA) burn, P = 0.002). At the unit with outcome data (n = 556), the case fatality was 56 per cent. The estimated adult mortality due to burns in Karachi was 10.2/100 000, 6.8/100 000 and 14.1/100 000 for men and women, respectively. Burns of interviewed patients were most often associated with flames (33/47), but stove bursts caused the most severe injury (52 per cent TBSA). These patients were predominantly young uneducated female houseworkers, clothed in loose attire who were injured during daylight at home around a floor-level stove, unaware of fire safety, and who received no first aid. It was concluded that the high burn severity and case fatality rates demand: (1) preventive measures, such as kitchen sand buckets, safer stove design and placement and education on fire safety and first aid, and (2) risk factor analysis to refine interventions.


Testing for antibodies to human aquaporin-4 by ELISA: sensitivity, specificity, and direct comparison with immunohistochemistry.
Several assays have been developed to detect antibodies to aquaporin-4 (NMO-IgG/AQP4-Ab). However, many of these assays require sophisticated techniques and are thus only available at specialized laboratories. This is problematic since NMO-IgG/AQP4-Ab testing has important prognostic and therapeutic implications. To evaluate a newly developed, commercial, enzyme-linked immunosorbent assay (ELISA) for detecting NMO-IgG/AQP4-Ab. Serum samples from 261 patients with NMO spectrum disorders (NMOSD; n=108) and controls (n=153) were tested for AQP4-Ab by using ELISA. Of these patients, 207 were tested in parallel using a standard immunohistochemical (IHC) assay. Fifty of 66 (75.8%) patients with NMO, 17/25 (68%) with LETM, 3/14 (21.4%) with ON, 2/3 (66.7%) with ON and non-extensive transverse myelitis, and 2/153 (1.3%) controls tested positive in the ELISA. Of those NMOSD patients tested by both ELISA and IHC, 10 were positive only in the ELISA and 3 exclusively in the IHC assay, suggesting that the overall sensitivity of the ELISA was higher than that of the standard IHC assay. The ELISA yielded very good intra- and inter-run reproducibility with regard to AQP4-Ab detection and good intrarun, but only moderate inter-run reproducibility with regard to AQP4-Ab quantification. Anti-AQP4 serum concentrations correlated with disease activity (p<0.00001), but did not differ between patients with NMO and patients with isolated LETM or ON. The ELISA evaluated here provides a relatively sensitive and easy-to-use diagnostic tool for detecting antibodies to AQP4 and could make AQP4-Ab testing, which is of high clinical relevance, more widely available.


Wild boar (Sus scrofa) - reservoir host of Toxoplasma gondii, Neospora caninum and Anaplasma phagocytophilum in Slovakia.
In Central Europe the wild boar population is permanently growing and consequently Cf foodborne infections. In this study serological and molecular detection of Toxoplasma gondii and Neospora caninum in wild boars was evaluated. Moreover, same samples were screened for the presence and genetic variability of tick-borne bacterium Anaplasma phagocytophilum. Blood samples collected from 113 wild boars from Southern Slovakia were examined for antibodies to T. gondii by indirect and to N. caninum by competitive ELISA. The presence of parasitic DNA in blood samples was determined by standard or real time PCR techniques. Antibodies against T. gondii and N. caninum were detected in 45 (39.8%) and 38 (33.6%) animals, respectively. Females were more frequently infected for both pathogens than males. The high seropositivity against both coccidia indicates a permanent occurrence of these pathogens in the studied locality. T. gondii DNA was confirmed in five seropositive boars (4.4%) and N. caninum in 23 blood samples (20.4%). Three out of 23 N. caninum PCR positive animals did not show seropositivity. Three out of 113 blood samples of wild boars were positive for A. phagocytophilum (2.7%). The obtained A. phagocytophilum sequences were 100% identical with GenBankTM isolates from Slovak dog (KC985242); German horse (JF893938) or wild boar (EF143810) and red deer (EF143808) from Poland. Coinfections of T. gondii with N. caninum and N. caninum with A. phagocytophilum were detected in single cases. Results suggest a potential zoonotic risk of toxoplasmosis transmission to humans and the spread of neosporosis to farm animals.


Evidence-based clinical practice guidelines for prostate cancer: the need for a unified approach.
Clinical practice guidelines are being increasingly recognized as critically important to an evidence-based practice. This article reviews the different approaches used by leading urological organizations to the development of prostate cancer guidelines. It further introduces the recommendations of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group as a unified approach to guideline development. Clinical guidelines on the management of prostate cancer demonstrate major methodological differences. Most notably, considerable discrepancies with regards to the systems used to grade the quality of the evidence and the strength of recommendation exist. The GRADE approach classifies the quality of evidence as high, moderate, low or very low, according to factors that include study design and execution, and the consistency of the results. It subsequently classifies recommendations as strong or weak, according to the balance between benefits and downsides and the degree of confidence in estimates of the downsides. There is an urgent need to standardize processes used to develop clinical guidelines for the management of patients with prostate cancer by leading urological organizations. Adoption of the GRADE approach would offer considerable rewards in terms of efficiency, guideline credibility and optimal clinical decision-making.


Tissue-specific profiling reveals modulation of cellular and mitochondrial oxidative stress in normal- and low-birthweight piglets throughout the peri-weaning period.
Weaning is known to induce important nutritional and energetic stress in piglets. Low-birthweight (LBW) piglets, now frequently observed in swine production, are more likely to be affected. The weaning period is also associated with dysfunctional immune responses, uncontrolled inflammation and oxidative stress conditions that are recognized risk factors for infections and diseases. Mounting evidence indicates that mitochondria, the main cellular sources of energy in the form of adenosine 5' triphosphate (ATP) and primary sites of reactive oxygen species production, are related to immunity, inflammation and bacterial pathogenesis. However, no information is currently available regarding the link between mitochondrial energy production and oxidative stress in weaned piglets. The objective of this study was to characterize markers of cellular and mitochondrial energy metabolism and oxidative status in both normal-birthweight (NBW) and LBW piglets throughout the peri-weaning period. To conduct the study, 30 multiparous sows were inseminated and litters were standardized to 12 piglets. All the piglets were weighted at day 1 and 120 piglets were selected and assigned to 1 of 2 experimental groups: NBW (n = 60, mean weight of 1.73 ± 0.01 kg) and LBW piglets weighing less than 1.2 kg (n = 60, 1.01 ± 0.01 kg). Then, 10 piglets from each group were selected at 14, 21 (weaning), 23, 25, 29 and 35 days of age to collect plasma and organ (liver, intestine and kidney) samples. Analysis revealed that ATP concentrations were lower in liver of piglets after weaning than during lactation (P < 0.05) thus suggesting a significant impact of weaning stress on mitochondrial energy production. Oxidative damage to DNA (8-hydroxy-2'-deoxyguanosine, 8-OHdG) and proteins (carbonyls) measured in plasma increased after weaning and this coincides with a rise in enzymatic antioxidant activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) (P < 0.05). Mitochondrial activities of both GPx and SOD are also significantly higher (P < 0.05) in kidney of piglets after weaning. Additionally, oxidative damage to macromolecules is more important in LBW piglets as measured concentrations of 8-OHdG and protein carbonyls are significantly higher (P < 0.05) in plasma and liver samples, respectively, than for NBW piglets. These results provide novel information about the nature, intensity and duration of weaning stress by revealing that weaning induces mitochondrial dysfunction and cellular oxidative stress conditions which last for at least 2 weeks and more severely impact smaller piglets.


Unexpected exit of a cochlear implant electrode through the wall of the basal turn of the cochlea - a report on two patients.
We describe the unusual complication of the cochlear implant electrode eroding through the lateral bony wall of the cochlear basal turn in 2 different patients. This complication, occurring during life, has not been previously described in the literature. Radiological investigations were vital in making this diagnosis. We also discuss the likely pathophysiology behind this complication.


Amino acid sequence of Japanese quail (Coturnix japonica) and northern bobwhite (Colinus virginianus) myoglobin.
Myoglobin has an important physiological role in vertebrates, and as the primary sarcoplasmic pigment in meat, influences quality perception and consumer acceptability. In this study, the amino acid sequences of Japanese quail and northern bobwhite myoglobin were deduced by cDNA cloning of the coding sequence from mRNA. Japanese quail myoglobin was isolated from quail cardiac muscles, purified using ammonium sulphate precipitation and gel-filtration, and subjected to multiple enzymatic digestions. Mass spectrometry corroborated the deduced protein amino acid sequence at the protein level. Sequence analysis revealed both species' myoglobin structures consist of 153 amino acids, differing at only three positions. When compared with chicken myoglobin, Japanese quail showed 98% sequence identity, and northern bobwhite 97% sequence identity. The myoglobin in both quail species contained eight histidine residues instead of the nine present in chicken and turkey.


Application of ultraviolet spectrophotometry to estimate occupational exposure to airborne polyaromatic compounds in asphalt pavers.
An ultraviolet (UV) spectrophotometric procedure was devised for the determination of polycyclic aromatic compound-oriented organic soluble matter in vapors and particulate collected from emissions of hot asphalt mix. Ultrasonic extraction was carried out with acetonitrile, followed by UV measurements at 254 nm. Polycyclic aromatic compounds (PACs) in volatile and particulate fraction were quantified as phenanthrene or benzo[k]fluoranthene equivalents. A comparison between UV and high-pressure liquid chromatography with fluorescence detection showed that PACs were one to three orders of magnitude higher than the sum of 15 priority polycyclic aromatic hydrocarbons (PAHs); still, significant correlations were found between volatile or particulate PACs and, respectively, total volatile or particulate PAHs. Moreover, in the particulate phase, PACs correlated with total particulate matter quantified by gravimetry. The proposed procedure was employed in a field study for monitoring personal exposure to asphalt emissions of workers engaged in road construction. Observed levels of acetonitrile-soluble PACs in air samples were very low (2-20 microg/m3); however, asphalt pavers were exposed to significantly higher concentrations of volatile PACs than construction workers (geometric mean, 5.9 microg/m3 vs. 4.1 microg/m3). This method for estimating the global content of volatile or particulate PACs in air samples satisfies our requirements of simplicity and is suitable for conducting an initial screening to assess exposure to airborne polyaromatic organics in asphalt pavers.


Control, Correction, and Modeling of Setup Errors and Organ Motion.
As advances in radiotherapy technology enable higher precision treatments, it becomes increasingly important to understand the factors that contribute to treatment uncertainty. The recent developments in imaging modalities and computer algorithms have made possible quantitative measurements of treatment uncertainties on statistically significant numbers of patients, which has led to new strategies for reducing as well as incorporating them into the treatment planning process. This article reviews the current literature on two sources of uncertainties deemed important in photon therapy, namely, patient localization (setup) errors and organ motion. In the area of patient localization there has been increasing work on protocols using electronic portal imaging devices to correct setup errors. These protocols are derived from probability analyses based on knowledge of setup errors for a population of patients in combination with defined clinical endpoints. Measurements of organ motion and methods to correct or control it have been more limited, due partly to the larger difficulties in imaging and motion characterization. We also review two paradigms for accounting for uncertainties in treatment plans: the conventional approach, which adds a margin around the tumor volume, and an alternative one, which includes uncertainties directly in the dose distributions of the tumor volume and nearby normal organs.


Deep Brain Stimulation for Memory Modulation: A New Frontier.
In the coming years the number of patients with cognitive disorders, such as Alzheimer disease and traumatic brain injury, is expected to dramatically increase, leading to an ever-increasing societal cost. Unfortunately, few medical and pharmacologic treatments have shown tangible benefit in the treatment of these diseases. Deep brain stimulation (DBS) is an established surgical technique to address multiple conditions, including Parkinson disease and essential tremor. Data from patients being treated with DBS, as well as those being monitored for seizures with depth electrodes, have suggested improvement in memory with electrical neuromodulation. MEDLINE was searched from inception through March 2018 using the keywords "DBS," "Deep Brain Stimulation," "Memory," "Memory Modulation," and "Cognition." Studies evaluating the effect of DBS on memory and learning were shortlisted and reviewed. Efforts to stimulate various nodes within the memory circuitry suggest that the variable effects may result from different mechanisms, including alteration of neural firing patterns, increased activity across several regions, and amplification of neural plasticity. Some of these targets, such as the entorhinal cortex, hippocampus, and nucleus basalis of Meynert, have shown promising results with regards to modulation of memory. Given the aging population and increasing numbers of patients with memory impairment from neurodegenerative diseases, interest in neuromodulation for memory enhancement will likely expand. Further work should employ more sophisticated responsive stimulation parameters and precise spatial targeting that may lead to an effective stimulation strategy for memory enhancement.


Binding of the endocrine disruptors 4-tert-octylphenol and 4-nonylphenol to human serum albumin.
Alkylphenols, considered to be endocrine disruptor chemicals and toxic environmental priority pollutants, pose great threats to humans with wide exposure from food and other potential sources. In this paper, to evaluate the toxicity of the alkylphenols at the protein level, the effects of 4-tert-octylphenol (OP) and 4-nonylphenol (NP) on human serum albumin (HSA) were characterized by molecular modeling, steady state and time-resolved fluorescence, ultraviolet-visible spectroscopy (UV-vis) and circular dichroism spectroscopy (CD). The enthalpy change (ΔH) and entropy change (ΔS) indicated that hydrophobic forces and hydrogen bonds were the dominant intermolecular forces in the binding of the alkylphenols to HSA. The binding constant of HSA-NP is much greater than that of HSA-OP, revealing that NP, which has a longer carbon chain, has a higher affinity than OP. The alterations of protein secondary structure in the presence of the alkylphenols were confirmed by UV-vis and CD spectroscopy. The time-resolved fluorescence study showed that the lifetimes of tryptophan (Trp) residue of HSA decreased after the addition of the alkylphenols, NP with longer carbon chain impact on the average lifetime of the Trp of HSA more than OP, which consistent with the conclusion drawn from the fluorescence date.


Chimeric RNAs generated by intergenic splicing in normal and cancer cells.
A hallmark of many neoplasias is chromosomal rearrangement, an event that commonly results in the fusion of two separate genes. The RNA and protein resulting from these gene fusions often play critical roles in cancer development, maintenance, and progression. Traditionally, these fusion products are thought to be produced solely due to DNA level changes and are therefore considered unique to cancer. Recent advances in microarray and deep-sequencing have revealed many more fusion transcripts. Surprisingly, some are without detectable rearrangement at the DNA level. Reports have demonstrated that at least some of these chimeric RNAs are generated via intergenic splicing. In this review, we highlight three examples of these noncanonical chimeric transcripts that are formed by trans-splicing or cis-splicing of adjacent genes and summarize the knowledge we have regarding these noncanonical fusions. We discuss the implications of the chimeric RNAs in both cancer and normal physiology, as some of these fusion transcripts are found in normal, noncancerous cells with sequences identical to those generated by canonical chromosomal translocation found in cancer cells. Finally, we present methods that are currently being used to discover additional chimeric RNAs.


The influence of age on learning a locomotor task.
Knowledge about locomotor task performance and learning in the elderly is important in optimizing rehabilitation strategies. The aim of this study was to evaluate differences between young and elderly subjects in the acquisition and performance of a precision locomotor task, with full and restricted vision. The subjects walked on a treadmill and had to step as low as possible over an obstacle, without touching it. They received acoustic warning and feedback signals, indicating obstacle appearance and foot clearance, respectively. Full vision was provided during the first two runs and became restricted during the third run. The number of obstacle hits and adaptations in foot clearance, leg muscle activity, range of motion of leg joints and swing phase duration were assessed. With vision, the performance improved in both groups. Restricted vision reduced the task accuracy in both the young and the elderly. However, only the young subjects regained optimal foot clearance with practice. Elderly subjects rely more on visual control when acquiring and performing a precision locomotor task. We suggest that this is due to an impaired function of proprioceptive feedback mechanisms, which can replace visual information in young subjects. In the elderly, therapeutical attention should be directed towards optimizing the use of the remaining proprioceptive inputs.


[Research of the extraction method of morphine from biological fluids].
A solid-phase extraction method of morphine from urine and blood has introduced. The effect of 5 SPE columns, 3 eluents and pH on morphine recovery has been investigated systematically. Derivative GC was used as a method of detection. The result showed that the column and the eluent of such as GDX-301, GDX-403 and C18 chloroform:isopropanol (9:1) had good behaviors to extraction of morphine. When GDX-301 was used as a sorbent, the recovery of morphine from urine was above 90% at pH 9, then went down with the increase of pH. While the recovery from blood was growing with the increase of pH, which reached above 90% in strong alkaline. The extraction method is simple, inexpensive, efficient and reproducible, which provides an effective and practical method to extract morphine and similar illicit drugs from biological fluids.


Approach of technical decision-making by element flow analysis and Monte-Carlo simulation of municipal solid waste stream.
This paper deals with the procedure and methodology which can be used to select the optimal treatment and disposal technology of municipal solid waste (MSW), and to provide practical and effective technical support to policy-making, on the basis of study on solid waste management status and development trend in China and abroad. Focusing on various treatment and disposal technologies and processes of MSW, this study established a Monte-Carlo mathematical model of cost minimization for MSW handling subjected to environmental constraints. A new method of element stream (such as C, H, O, N, S) analysis in combination with economic stream analysis of MSW was developed. By following the streams of different treatment processes consisting of various techniques from generation, separation, transfer, transport, treatment, recycling and disposal of the wastes, the element constitution as well as its economic distribution in terms of possibility functions was identified. Every technique step was evaluated economically. The Mont-Carlo method was then conducted for model calibration. Sensitivity analysis was also carried out to identify the most sensitive factors. Model calibration indicated that landfill with power generation of landfill gas was economically the optimal technology at the present stage under the condition of more than 58% of C, H, O, N, S going to landfill. Whether or not to generate electricity was the most sensitive factor. If landfilling cost increases, MSW separation treatment was recommended by screening first followed with incinerating partially and composting partially with residue landfilling. The possibility of incineration model selection as the optimal technology was affected by the city scale. For big cities and metropolitans with large MSW generation, possibility for constructing large-scale incineration facilities increases, whereas, for middle and small cities, the effectiveness of incinerating waste decreases.