Bayesian target optimisation for high-precision holographic optogenetics.
Two-photon optogenetics has transformed our ability to probe the structure and function of neural circuits. However, achieving precise optogenetic control of neural ensemble activity has remained fundamentally constrained by the problem of off-target stimulation (OTS): the inadvertent activation of nearby non-target neurons due to imperfect confinement of light onto target neurons. Here we propose a novel computational approach to this problem called Bayesian target optimisation. Our approach uses nonparametric Bayesian inference to model neural responses to optogenetic stimulation, and then optimises the laser powers and optical target locations needed to achieve a desired activity pattern with minimal OTS. We validate our approach in simulations and using data from in vitro experiments, showing that Bayesian target optimisation considerably reduces OTS across all conditions we test. Together, these results establish our ability to overcome OTS, enabling optogenetic stimulation with substantially improved precision.


Free fruit at workplace intervention increases total fruit intake: a validation study using 24 h dietary recall and urinary flavonoid excretion.
To validate 24 h dietary recall of fruit intake by measuring the total 24 h excretion of 10 different flavonoids in 24 h urine during an intervention with free fruit at workplaces. Employees at workplaces offering a free-fruit program, consisting of daily free and easy access to fresh fruit, and controls employees at workplaces with no free-fruit program were enrolled in this validation study (n=103). Dietary intake was assessed by using a 24 h dietary recall questionnaire at baseline and approximately 5 months later. Ten flavonoids, quercetin, isorhamnetin, tamarixetin, kaempferol, hesperetin, naringenin, eriodictyol, daidzein, genistein, and phloretin, were measured using HPLC-electrospray ionization-MS. The 24 h urinary excretion of total flavonoids and the estimated intake of fruits were significantly correlated (r (s)=0.31, P<0.01). The dietary intake of citrus fruits and citrus juices was significantly correlated with total excretion of citrus specific flavonoids (r (s)=0.28, P<0.01), and orange was positively correlated with naringenin (r (s)=0.24, P<0.01) and hesperetin (r (s)=0.24, P<0.01). Phloretin in urine was correlated with apple intake (r (s)=0.22, P<0.01) and also with overall estimated intake of fruit (r (s)=0.22, P<0.01). This study shows that a 24 h dietary recall can be used as a valid estimate of the intake of fruits in agreement with an objective biomarker of fruit intake in free fruit at workplace interventions.


The effects of HEMA-monomer and air atmosphere treatment of glass fibre on the transverse strength of a provisional fixed partial denture resin.
This study focused on some mechanical properties such as the transverse strength, the maximal deflection, and the modulus of elasticity of resin reinforced with two different types of agents-treated and with untreated glass fibre, and without fibre. A Teflon mould was used to prepare six groups of specimens. Two different types of chemical modification agents, hydroxyethyl-methacrylate (HEMA)-monomer and air atmosphere were applied to create hydrophilic surfaces on the glass fibres. The flow rate was kept at two different levels, 25 and 60 mL min-1. The discharge powers of the surface treatment process were 15 or 20 W. The fibres were exposed to glow discharge conditions for the periods of 10 or 15 min. Without fibre specimens were the control group. The provisional resin was same in all groups. All the specimens were subjected to transverse testing with a cross-head speed of 5 mm min-1. The three-point load test was used to record the load of the fracture for each specimens. The Kruskal-Wallis analysis of variance was used to compare the transverse strength, the maximal deflection and the modulus of elasticity. The differences in the transverse strength and the maximal deflection between the six groups were found statistically significant but the modulus of elasticity was not statistically significant. The transverse strength of HEMA-monomer (group A) was shown the highest value (66.3 MPa). For without-fibre group, the value was 52.9 MPa. This difference was statistically significant when the Mann-Whitney U-test was used for comparing. Repairing or remaking provisional restorations can be a time-consuming endeavour. The added strength of the polymethyl methacrylate with the fibre can reduce clinical failures of provisional fixed partial dentures. The surface treatment process was increased the transverse strength and the maximal deflection. The clinical implication of chemical modification agents-coated fibres is reduced incidence of fixed provisional restoration failure.


[Experimental study of the pharmacological properties of amikacin].
The general toxic and organotropic properties of amikacin were studied in acute and chronic experiments. The antibiotic was administered to the experimental animals in the doses equivalent to the therapeutic ones for humans or exceeding them 2-3 times. No unfavourable effect of amikacin in the above doses on hearing was observed. A certain increase in the level of urea nitrogen in the blood serum and leukopenia were registered only after administration of the highest drug dose exceeding 2 times the equivalent treatment dose of amikacin for humans (15 g). After the use of this dose separate microfocal necrotic lesions were detected morphologically in the proximal tubules of the kidneys. The lesions were of a transitory nature. It is concluded that amikacin has a wide range of therapeutic doses and the level of its safety is rather high.


Obesity and the risk of new-onset atrial fibrillation.
Obesity is associated with atrial enlargement and ventricular diastolic dysfunction, both known predictors of atrial fibrillation (AF). However, it is unclear whether obesity is a risk factor for AF. To examine the association between body mass index (BMI) and the risk of developing AF. Prospective, community-based observational cohort in Framingham, Mass. We studied 5282 participants (mean age, 57 [SD, 13] years; 2898 women [55%]) without baseline AF (electrocardiographic AF or arterial flutter). Body mass index (calculated as weight in kilograms divided by square of height in meters) was evaluated as both a continuous and a categorical variable (normal defined as <25.0; overweight, 25.0 to <30.0; and obese, > or =30.0). In addition to adjusting for clinical confounders by multivariable techniques, we also examined models including echocardiographic left atrial diameter to examine whether the influence of obesity was mediated by changes in left atrial dimensions. Association between BMI or BMI category and risk of developing new-onset AF. During a mean follow-up of 13.7 years, 526 participants (234 women) developed AF. Age-adjusted incidence rates for AF increased across the 3 BMI categories in men (9.7, 10.7, and 14.3 per 1000 person-years) and women (5.1, 8.6, and 9.9 per 1000 person-years). In multivariable models adjusted for cardiovascular risk factors and interim myocardial infarction or heart failure, a 4% increase in AF risk per 1-unit increase in BMI was observed in men (95% confidence interval [CI], 1%-7%; P = .02) and in women (95% CI, 1%-7%; P = .009). Adjusted hazard ratios for AF associated with obesity were 1.52 (95% CI, 1.09-2.13; P = .02) and 1.46 (95% CI, 1.03-2.07; P = .03) for men and women, respectively, compared with individuals with normal BMI. After adjustment for echocardiographic left atrial diameter in addition to clinical risk factors, BMI was no longer associated with AF risk (adjusted hazard ratios per 1-unit increase in BMI, 1.00 [95% CI, 0.97-1.04], P = .84 in men; 0.99 [95% CI, 0.96-1.02], P = .56 in women). Obesity is an important, potentially modifiable risk factor for AF. The excess risk of AF associated with obesity appears to be mediated by left atrial dilatation. These prospective data raise the possibility that interventions to promote normal weight may reduce the population burden of AF.


Extensible behavior of titin in the miniswine left ventricle.
The sarcomeric protein titin is a molecular spring responsible for passive tension and restoring forces of cardiomyocytes. Extension of titin as a function of sarcomere length (SL) has been studied in rodents, which predominantly express the smaller, stiffer N2B titin isoform. Large mammals coexpress roughly equal proportions of N2B and N2BA titin, the larger, more compliant isoform. We hypothesized that extension of titin in relation to SL differs in large mammals and that this difference is functionally important. We characterized the filling pressure-SL relation in diastolic-arrested miniswine left ventricles. SL was 2.15 to 2.25 mum at a filling pressure of approximately 0 mm Hg and reached a maximum of approximately 2.50 mum with overfilling. In the normal filling pressure range, SL ranged from approximately 2.32 to approximately 2.40 mum. We assessed titin extension as a function of SL using immunoelectron microscopy, which allowed delineation of the behavior of specific spring segments. The major isoform difference was that the N2B-Us segment extended approximately 4-fold more as a function of SL in N2B compared with N2BA titin. Using this segment, we estimated sarcomeric force development with a worm-like chain model and found that N2B develops markedly greater force than N2BA titin. The resulting force with coexpression of N2B and N2BA titin is intermediate. In light of murine studies showing that operating SLs are shorter than in miniswine, our results indicate that coexpression of the 2 titin isoforms in large mammals allows longer SLs without the development of excessive diastolic tension.


The development of sensitivity to biological motion in noise.
We investigated developmental changes in sensitivity to biological motion by asking 6-year-olds, 9-year-olds, and adults (twenty-four in each group) to discriminate point-light biological motion displays depicting one of a variety of human movements from scrambled versions of the same displays. When tested without noise dots, participants at all ages performed near ceiling levels and no differences in accuracy were found among the three age groups. Age differences emerged in the second task, in which we used a staircase procedure to determine threshold values of the number of noise dots that could be tolerated in producing a percentage correct value corresponding to a d' value of 1.4. Sensitivity to biological motion improved linearly with age (p < 0.01), with 6-year-olds performing significantly more poorly than adults. This immature performance contrasts with adult-like accuracy by 4 years of age for sensitivity to global motion (Parrish et al, 2005 Vision Research 45 827-837). The comparison implies an immaturity at 6 years of age in the neural networks involved specifically in the processing of biological motion, networks that may include the superior temporal sulcus (STS).


AMPylation: Something Old is New Again.
The post-translational modification AMPylation is emerging as a significant regulatory mechanism in both prokaryotic and eukaryotic biology. This process involves the covalent addition of an adenosine monophosphate to a protein resulting in a modified protein with altered activity. Proteins capable of catalyzing AMPylation, termed AMPylators, are comparable to kinases in that they both hydrolyze ATP and reversibly transfer a part of this primary metabolite to a hydroxyl side chain of the protein substrate. To date, only four AMPylators have been characterized, though many more potential candidates have been identified through amino acid sequence analysis and preliminary in vitro studies. This modification was first discovered over 40 years ago by Earl Stadtman and colleagues through the modification of glutamine synthetase by adenylyl transferase; however research into this mechanism has only just been reenergized by the studies on bacterial effectors. New AMPylators were revealed due to the discovery that a bacterial effector having a conserved Fic domain transfers an AMP group to protein substrates. Current research focuses on identifying and characterizing various types of AMPylators homologous to Fic domains and adenylyl transferase domains and their respective substrates. While all AMPylators characterized thus far are bacterial proteins, the conservation of the Fic domain in eukaryotic organisms suggests that AMPylation is omnipresent in various forms of life and has significant impact on a wide range of regulatory processes.


Conservation of adjacency as evidence of paralogous operons.
Most of the analyses on the conservation of gene order are limited to orthologous genes. However, the organization of genes into operons might also result in the conservation of gene order of paralogous genes. Thus, we sought computational evidence that conservation of gene order of paralogous genes represents another level of conservation of genes in operons. We found that pairs of genes within experimentally characterized operons of Escherichia coli K12 and Bacillus subtilis tend to have more adjacently conserved paralogs than pairs of genes at transcription unit boundaries. The fraction of same strand gene pairs corresponding to conserved paralogs averages 0.07 with a maximum of 0.22 in Borrelia burgdorferi. The use of evidence from the conservation of adjacency of paralogous genes can improve the prediction of operons in E.coli K12 by approximately 0.27 over predictions using conservation of adjacency of orthologous genes alone.


Ketoroloac tromethamine loaded nanodispersion incorporated into thermosensitive in situ gel for prolonged ocular delivery.
The present study was designed to improve the ocular availability of ketorolac tromethamine and to prolong its precorneal residence time for the treatment of postoperative ocular inflammation. Ketorolac tromethamine nanodispersions were successfully prepared by nanoprecipitation method using Eudragit(®) RL100. These nanodispersions were characterized in terms of particle size, zeta potential, entrapment efficiency and in vitro release. Consequently, the optimum nanodispersion was incorporated into thermosensitive in situ gel. The optimum gelling capacity was obtained by 20% Pluronic(®) F-127 and 14% Pluronic(®) F-127/1.5% HPMC K4m. The gelling temperature and gelation time of the in situ gels increased by decreasing the concentration of Pluronic(®) F-127. The mucoadhesive strength was significantly improved by the addition of HPMC. Incorporation of ketorolac tromethamine loaded nanodispersions into in situ gel bases sustained the release of ketorolac tromethamine, improved its ocular availability and prolonged its residence time without causing irritation to eye.


Accuracy and Speed Improvement of Event Camera Motion Estimation Using a Bird's-Eye View Transformation.
Event cameras are bio-inspired sensors that have a high dynamic range and temporal resolution. This property enables motion estimation from textures with repeating patterns, which is difficult to achieve with RGB cameras. Therefore, motion estimation of an event camera is expected to be applied to vehicle position estimation. An existing method, called contrast maximization, is one of the methods that can be used for event camera motion estimation by capturing road surfaces. However, contrast maximization tends to fall into a local solution when estimating three-dimensional motion, which makes correct estimation difficult. To solve this problem, we propose a method for motion estimation by optimizing contrast in the bird's-eye view space. Instead of performing three-dimensional motion estimation, we reduced the dimensionality to two-dimensional motion estimation by transforming the event data to a bird's-eye view using homography calculated from the event camera position. This transformation mitigates the problem of the loss function becoming non-convex, which occurs in conventional methods. As a quantitative experiment, we created event data by using a car simulator and evaluated our motion estimation method, showing an improvement in accuracy and speed. In addition, we conducted estimation from real event data and evaluated the results qualitatively, showing an improvement in accuracy.


Comparison of EGS4 and MCNP Monte Carlo codes when calculating radiotherapy depth doses.
The Monte Carlo codes EGS4 and MCNP have been compared when calculating radiotherapy depth doses in water. The aims of the work were to study (i) the differences between calculated depth doses in water for a range of monoenergetic photon energies and (ii) the relative efficiency of the two codes for different electron transport energy cut-offs. The depth doses from the two codes agree with each other within the statistical uncertainties of the calculations (1-2%). The relative depth doses also agree with data tabulated in the British Journal of Radiology Supplement 25. A discrepancy in the dose build-up region may by attributed to the different electron transport algorithims used by EGS4 and MCNP. This discrepancy is considerably reduced when the improved electron transport routines are used in the latest (4B) version of MCNP. Timing calculations show that EGS4 is at least 50% faster than MCNP for the geometries used in the simulations.


Genome-Wide Diversity, Population Structure and Demographic History of Dromedaries in the Central Desert of Iran.
The development of camel husbandry for good production in a desert climate is very important, thus we need to understand the genetic basis of camels and give attention to genomic analysis. We assessed genome-wide diversity, linkage disequilibrium (LD), effective population size (Ne) and relatedness in 96 dromedaries originating from five different regions of the central desert of Iran using genotyping-by-sequencing (GBS). A total of 14,522 Single Nucleotide Polymorphisms (SNPs) with an average minor allele frequency (MAF) of 0.19 passed quality control and filtering steps. The average observed heterozygosity in the population was estimated at 0.25 ± 0.03. The mean of LD at distances shorter than 40 kb was low (r2 = 0.089 ± 0.234). The camels sampled from the central desert of Iran exhibited higher relatedness than Sudanese and lower than Arabian Peninsula dromedaries. Recent Ne of Iran's camels was estimated to be 89. Predicted Tajima's D (1.28) suggested a bottleneck or balancing selection in dromedary camels in the central desert of Iran. A general decrease in effective and census population size poses a threat for Iran's dromedaries. This report is the first SNP calling report on nearly the chromosome level and a first step towards understanding genomic diversity, population structure and demography in Iranian dromedaries.


Monitoring ligand-induced conformational changes for the identification of estrogen receptor agonists and antagonists.
Nuclear receptors are transcription factors that are important targets for current drug discovery efforts as they play a role in many pathological processes. Their activity can be regulated by small molecules like hormones and drugs that can have agonistic or antagonistic functions. These ligands bind to the receptor and account for diverse conformational changes that are crucial determinants for the receptor activity. Here, we set out to develop FLiN (fluorescent labels in nuclear receptors), a direct binding assay that detects conformational changes in the estrogen receptor. The assay is based on the introduction of a cysteine residue and subsequent specific labeling of the receptor with a thiol-reactive fluorophore. Changes in the receptor conformation upon ligand binding lead to differences in the microenvironment of the fluorophore and alter its emission spectrum. The FLiN assay distinguishes between different binding modes and is suitable for high-throughput screening.


Prediction of breast cancer metastasis risk using circulating tumor markers: A follow-up study.
Distant organ tumor dissemination is a major cause of breast cancer-related deaths. In 2010, we analyzed the prognostic importance of the circulating tumor markers (CTMs) cytokeratin 19 (CK19), CK20, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in relation to the clinical and pathological characteristics of patients with breast cancer (BC). To assess the clinical utility of CK19, CK20 and EGFR in predicting distant metastasis in BC, here we report 7-year follow-up results of 77 patients. The patients with at least one positive CTM were classified as CTM(+) and those negative for all CTMs were assigned to CTM(-) group. In patients who received no treatment following CTM analysis, 25.0% had metastasis in CTM(+) and 10.0% in CTM(-) group. In patients who received one of the following therapies: chemotherapy, radiotherapy or hormone therapy, or the combinations of these therapies, the rate of metastasis was 33.3% in CTM(+) and 20.0% in CTM(-) group. Disease-free time was shorter in CTM(+) patients compared to CTM(-) group (28.83 ± 10.76 and 41.38 ± 9.5 months, respectively). According to multivariate Cox proportional hazard regression analysis, the presence of regional lymph node metastasis, Ki-67 expression, higher tumor grade and CTM expression status were predictors of poor prognosis associated with distant metastasis (p < 0.05). Also, CTM positivity was a factor associated with metastasis-related poor prognosis (HR = 0.492, p = 0.026). The mean survival for CTM(+) patients was shorter than that for CTM(-) patients (90.671 ± 2.66 and 101.23 ± 3.92 months, respectively; p > 0.05). Our findings demonstrate that CTM positivity may indicate a high metastasis risk; however, CTM negativity does not guarantee low metastasis risk. These results may encourage further preclinical investigation of CTMs, to evaluate the possible implications of these findings to the clinical setting.


Energetics and kinetics of the reaction of HOCO with hydrogen atoms.
The potential energy surface for the reaction of HOCO radicals with hydrogen atoms has been explored using the CCSD(T)/aug-cc-pVQZ ab initio method. Results show that the reaction occurs via a formic acid (HOC(O)H) intermediate, and produces two types of products: H(2)O+CO and H(2)+CO(2). Reaction enthalpies (0 K) are obtained as -102.0 kcalmol for the H(2)+CO(2) products, and -92.7 kcalmol for H(2)O+CO. Along the reaction pathways, there exists a nearly late transition state for each product channel. However, the transition states locate noticeably below the reactant asymptote. Direct ab initio dynamics calculations are also carried out for studying the kinetics of the H+HOCO reaction. At room temperature, the rate coefficient is predicted to be 1.07x10(-10)cm(3) molec(-1) s(-1) with a negligible activation energy E(a)=0.06 kcalmol, and the branching ratios are estimated to be 0.87 for H(2)+CO(2), and 0.13 for H(2)O+CO. In contrast, the product branching ratios have a strong T dependence. The branching ratio for H(2)O+CO could increase to 0.72 at T=1000 K.


Analysis of CLCN2 as candidate gene for megalencephalic leukoencephalopathy with subcortical cysts.
Mutations in the gene MLC1 are found in approximately 80% of the patients with the inherited childhood white matter disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC). Genetic linkage studies have not led to the identification of another disease gene. We questioned whether mutations in CLCN2, coding for the chloride channel protein 2 (ClC-2), are involved in MLC. Mice lacking this protein develop white matter abnormalities, which are characterized by vacuole formation in the myelin sheaths, strikingly similar to the intramyelinic vacuoles in MLC. Sequence analysis of CLCN2 at genomic DNA and cDNA levels in 18 MLC patients without MLC1 mutations revealed some nucleotide changes, but they were predicted to be nonpathogenic. Further, in electrophysiological experiments, one of the observed amino acid changes was shown to have no effect on the ClC-2-mediated currents. In conclusion, we found no evidence suggesting that the CLCN2 gene is involved in MLC.


Massive obstructive urolithiasis in a bull used for artificial insemination.
A seven-year-old Jersey bull used for artificial insemination showed clinical signs of obstructive urolithiasis. This was confirmed by catheterisation and subsequent urethrotomy over the site of obstruction distal to the sigmoid flexure. Although urine flow was elicited after removal of the calculi, this was only temporary and the animal had to be killed 24 hours later. On post mortem examination about 2 kg of round, smooth, pearl-like calculi were found in the urinary bladder and the urethra of the sigmoid flexure was studded with similar calculi. It was concluded that urethrotomy at the sigmoid flexure or penectomy post scrotally would not have alleviated this condition.


Initiatives to enhance the quality and efficiency of statin and PPI prescribing in the UK: impact and implications.
To assess the impact of a range of national and regional initiatives introduced in the North Lancashire Teaching Primary Care Trust (NLTPCT) since 2004 to enhance the quality and efficiency of prescribing proton pump inhibitors (PPIs), statins and ezetimibe. In addition, to suggest additional measures that could be introduced in NLTPCT to further enhance the quality and efficiency of prescribing based on initiatives in other European countries. A before-and-after observational study was undertaken on the utilization and expenditure of prescriptions dispensed in ambulatory care in NLTPCT from 2004 to 2007. Utilization was assessed using 'defined daily doses' (DDDs) and 'DDDs/1000 inhabitants per day' and compared over the study period. Reimbursed expenditure was assessed in terms of overall expenditure, expenditure/DDD, as well as expenditure/1000 inhabitants per year. The combination of measures and initiatives enhanced the utilization of generic PPIs. International Nonproprietary Name (INN) prescribing of omeprazole reached 98% of all omeprazole by 2007. The measures also resulted in limited utilization of esomeprazole and lowered reimbursed expenditure/DDD of generic omeprazole to GB pound0.13 by 2007. This was 87% below 2004 originator prices, leading to a 41% fall in PPI expenditure during the study period despite increased utilization. Utilization of statins grew by over 130% during the study period enhanced by increased utilization of high doses of simvastatin and atorvastatin following the introduction of the quality and outcomes framework. Simvastatin dominated statin utilization by 2007, with generic simvastatin accounting for over 99.5% of total simvastatin. Reimbursed expenditure/DDD for generic simvastatin was pound0.03 in 2007, 95% below 2004 originator prices, leading to a fall in overall expenditure on statins. It proved difficult to undertake an impact analysis as, typically, a range of measures were introduced sequentially and simultaneously during the study period. The findings are in line with expectations and do provide examples to other European countries. This includes a high rate of INN prescribing, low reimbursed prices for generic simvastatin and omeprazole and growing utilization of higher strength statins. The high rate of INN prescribing reduces the need for additional measures that have been instigated in other European countries to further enhance the prescribing and dispensing of generics to fully realize the resource benefits. Additional demand side measures are feasible and have already been instigated to conserve resources.


Immunocytochemical characterization of extracellular matrix proteins expressed by cultured glioma cells.
The immunolocalization of type I, III and IV collagens and fibronectin in two rat glioma cell lines in vitro (BT4C and BT4Cn) is described. In addition, antibodies against denatured type I and III collagens were used to study breakdown products of native type I and III collagens. For the BT4C cells, the extracellular matrix expression in monolayer cultures and in multicellular tumor spheroids was compared. Type IV collagen was strongly expressed in BT4C tumor spheroids but was negative in the corresponding monolayer cultures. Denatured type I collagen was found both in monolayers and in spheroids of BT4C, suggesting either a rapid turnover (i.e., synthesis and immediate breakdown) of type I collagen or an altered collagen gene transcription. Both cell lines were negative for native type I and III and denatured type III collagen. Fibronectin was strongly expressed in both cell lines. Supporting the immunofluorescence data, the hydroxyproline content in the tumor spheroids was twice the amount found in monolayer cultures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with immunoblotting also verified the immunostaining experiments, showing that glioma spheroids and injected tumor cells have the potential for fibronectin and collagen production, given the appropriate growth conditions.


High prevalence of HIV/AIDS risky sexual behaviors among street youth in Gondar town: a community based cross sectional study.
Street youth are vulnerable to HIV/AIDS and all kinds of health risks. This study assessed HIV/AIDS risky sexual behaviors and its predictors among street youth in Gondar town, Northwest Ethiopia. A community based cross sectional study was conducted on 467 street youth living in Gondar town. A pre tested and structured questionnaire via interview was used to collect data. Logistic regression analysis was used to identify predictors. Odds ratio with 95% CI was computed to assess the strength of associations. A total of 288 (61.7%) respondents had sexual intercourse in their life time. Among these 264 (91.7%) had more than one lifetime sexual partners. In addition, 80.5% of them used condom inconsistently in the last 12 months. Khat chewing was found to be predictor of having multiple sexual partners. Rural former residence and longer duration of stay on the street are also identified as predictors of inconsistent condom use. High prevalence of HIV/AIDS risky sexual behaviors were observed among street youth in Gondar town. Interventions aimed at reducing sexual risky behaviors among street youth should focus on reducing the duration of stay on the street and chat chewing.


[Partial nephrectomy in lithiasis].
To analyze our series of patients with renal lithiasis who underwent partial nephrectomy from 1980-1999. 28 patients who underwent partial nephrectomy were analyzed (22 females; mean age 48.09 years, and 6 males; mean age 60 years). Surgery for lithiasis had been previously performed in 5 renal units. Nine patients had previously undergone ESWL (more than 3 sessions), all of whom subsequently developed multiple residual calculi. Twelve patients had a microbiologically confirmed positive urine culture. The renal lithiasis amenable to treatment by partial nephrectomy was frequently localized in the lower calyces (17 cases). Histopathological analysis of the nephrectomy specimen showed a prevalence of signs of chronic parenchymal atrophy (25 cases). Three cases showed segmental renal dysplasia (those in whom a superior heminephrectomy was performed for duplex excretory system). Fifty percent of the stone fragments analyzed showed calcium phosphocarbonate. Eight patients had postoperative complications; the most important were two cases of renal cutaneous fistula and one subphrenic abscess. At 9 1/2 years' mean follow-up, renal function is normal in 25 patients. Lithiasis developed in the contralateral unit in 6 cases and in the same renal unit in one case. Partial nephrectomy continues to be a therapeutic option for lithiasis. Its indication depends on the morphological and functional characteristics of the compromised renal unit, especially in those cases in whom renal preservation can be obviated due to its scanty significance.


Snacking is associated with reduced risk of overweight and reduced abdominal obesity in adolescents: National Health and Nutrition Examination Survey (NHANES) 1999-2004.
Snacking is common in adolescents; however, it is unclear if there is an association between snacking and overweight or obesity within the context of the overall diet. This study examined the associations of snacking with weight status and abdominal obesity in adolescents 12-18 y of age (n = 5811). We conducted secondary analyses of 24-h diet recalls and anthropometric data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. We classified adolescents by frequency of snack consumption (0, 1, 2, 3, and > or =4 snacks/d) and by the percentage of energy intake from snacks (0%, <10%, 10-19%, 20-29%, 30-39%, and > or =40%). We classified adolescents who had a body mass index (BMI) > or =85th percentile of BMI-for-age as overweight or obese. We defined abdominal obesity as a waist circumference > or =90th percentile. We determined covariate-adjusted prevalences of overweight or obesity and abdominal obesity and odds ratios with SUDAAN software (release 9.0.1; Research Triangle Institute, Research Triangle Park, NC). Mean values of all obesity indicators studied were inversely associated with snacking frequency and percentage of energy from snacks. The prevalence of overweight or obesity and of abdominal obesity decreased with increased snacking frequency and with increased percentage of energy from snacks. Odds ratios (95% CIs) for overweight or obesity and for abdominal obesity ranged from 0.63 (0.48, 0.85) to 0.40 (0.29, 0.57) and from 0.61 (0.43, 0.86) to 0.36 (0.21, 0.63) for 2 to > or =4 snacks/d, respectively. Reduced risks of overweight or obesity and abdominal obesity were associated with snacking. Snackers, compared with nonsnackers, were less likely to be overweight or obese and less likely to have abdominal obesity.


Forest restoration treatments in a ponderosa pine forest enhance physiological activity and growth under climatic stress.
As the climate warms, drought will increasingly occur under elevated temperatures, placing forest ecosystems at growing risk of extensive dieback and mortality. In some cases, increases in tree density following early 20th-century fire suppression may exacerbate this risk. Treatments designed to restore historical stand structure and enhance resistance to high-severity fire might also alleviate drought stress by reducing competition, but the duration of these effects and the underlying mechanisms remain poorly understood. To elucidate these mechanisms, we evaluate tree growth, mortality, and tree-ring stable-carbon isotope responses to stand-density reduction treatments with and without prescribed fire in a ponderosa pine forest of western Montana. Moderate and heavier cutting experiments (basal area reductions of 35% and 56%, respectively) were initiated in 1992, followed by prescribed burning in a subset of the thinned units. All treatments led to a growth release that persisted to the time of resampling. The treatments had little effect on climate-growth relationships, but they markedly altered seasonal carbon isotope signals and their relationship to climate. In burned and unburned treatments, carbon isotope discrimination (Δ13 C) increased in the earlywood (EW) and decreased in the latewood (LW) relative to the control. The sensitivity of LW Δ13 C to late-summer climate also increased in all treatments, but not in the control. Such increased sensitivity indicates that the reduction in competition enabled trees to continue to fix carbon for new stem growth, even when the climate became sufficiently stressful to stop new assimilation in slower-growing trees in untreated units. These findings would have been masked had we not separated EW and LW. The importance of faster growth and enhanced carbon assimilation under late-summer climatic stress became evident in the second decade post-treatment, when mountain pine beetle activity increased locally, and tree mortality rates in the controls of both experiments increased to more than twice those in their respective treatments. These findings highlight that, when thinning is used to restore historical forest structure or increase resistance to high-severity fire, there will likely be additional benefits of enhanced growth and physiological activity under climatic stress, and the effects may persist for more than two decades.


Oligosaccharide binding to barley alpha-amylase 1.
Enzymatic subsite mapping earlier predicted 10 binding subsites in the active site substrate binding cleft of barley alpha-amylase isozymes. The three-dimensional structures of the oligosaccharide complexes with barley alpha-amylase isozyme 1 (AMY1) described here give for the first time a thorough insight into the substrate binding by describing residues defining 9 subsites, namely -7 through +2. These structures support that the pseudotetrasaccharide inhibitor acarbose is hydrolyzed by the active enzymes. Moreover, sugar binding was observed to the starch granule-binding site previously determined in barley alpha-amylase isozyme 2 (AMY2), and the sugar binding modes are compared between the two isozymes. The "sugar tongs" surface binding site discovered in the AMY1-thio-DP4 complex is confirmed in the present work. A site that putatively serves as an entrance for the substrate to the active site was proposed at the glycone part of the binding cleft, and the crystal structures of the catalytic nucleophile mutant (AMY1D180A) complexed with acarbose and maltoheptaose, respectively, suggest an additional role for the nucleophile in the stabilization of the Michaelis complex. Furthermore, probable roles are outlined for the surface binding sites. Our data support a model in which the two surface sites in AMY1 can interact with amylose chains in their naturally folded form. Because of the specificities of these two sites, they may locate/orient the enzyme in order to facilitate access to the active site for polysaccharide chains. Moreover, the sugar tongs surface site could also perform the unraveling of amylose chains, with the aid of Tyr-380 acting as "molecular tweezers."


Supervisory attentional system in patients with focal frontal lesions.
The aim of this study was to re-examine the hypothesis of a link between frontal cortex and the Supervisory Attentional System (SAS; Shallice, 1988). Contrary to previous studies that examined patients with lesions extending beyond the frontal lobes (Shallice, 1982; Burgess & Shallice, 1996a, 1996b), SAS or executive functions were evaluated in a group of patients with strict frontal lesions. Three tasks (Tower of London -TOL-, Hayling and Brixton tests) designed to assess specific SAS processes (planning, inhibition and abstraction of logical rules respectively) were administered. In the TOL test, although frontal patients were slower than control participants, the two groups did not differ in their ability to solve problems. Furthermore, the two groups did not differ in terms of performance in the Hayling and Brixton tests either. These results are discussed in terms of the SAS model and are compared to those observed by Shallice (1982) and Burgess & Shallice (1996a, 1996b). Additionally, the issue of the neural subtract of executive functions is addressed.


Systems, economics, and neoliberal politics: Theories to understand missed nursing care.
The phenomenon of missed nursing care is endemic across all sectors. Nurse leaders have drawn attention to the implications of missed care for patient outcomes, with calls to develop clear political, methodological, and theoretical approaches. As part of this call, we describe three structural theories that inform frameworks of missed care: systems theory, economic theory, and neoliberal politics. The final section provides commentary on the strengths and limitations of these three theories, in the light of structuration theory and calls to balance this research agenda by reinstating nurse agency and examining the interactions between nurses as agents and the health systems as structures. The paper argues that a better understanding of variations in structure-agency interaction across the healthcare system might lead to more effective interventions at strategic leverage points.


Long-term effects of high nitrogen loads on cation and carbon riverine export in agricultural catchments.
The intensification of agriculture in recent decades has resulted in extremely high nitrogen inputs to ecosystems. One effect has been H(+) release through NH(4)(+) oxidation in soils, which increases rock weathering and leads to acidification processes such as base-cation leaching from the soil exchange complex. This study investigated the evolution of cation concentrations over the past 50 years in rivers from the Armorican crystalline shield (Brittany, western France). On a regional scale, acidification has resulted in increased base-cation riverine exports (Ca(2+), Mg(2+), Na(+), K(+)) correlated with the increased NO(3)(-) concentration. The estimated cation increase is 0.7 mmol(+)/L for Ca(2+) + Mg(2+) and 0.85 mmol(+)/L for total cations. According to mass balance, cation loss represents >30% of the base-cation exchange capacity of soils. Long-term acidification thus contributes to a decline in soil productivity. Estimates of the total organic nitrogen annually produced worldwide indicate that acidification may also constitute an additional carbon source in crystalline catchments if compensated by liming practices.


Nurses' descriptions of caring for culturally diverse clients.
The nursing profession has responded to today's cultural diversity through theory development, association statements, research, and inclusion of cultural content in nursing curricula. This qualitative study was completed to explore whether this increased attention to cultural diversity is resulting in culturally sensitive nursing care. In this preliminary description of cross-cultural care, eight recently graduated nurses were each interviewed twice. Caring for culturally diverse clients is reflected by these participants as complex and challenging, due to the interrelatedness of multiple personal and contextual factors. Nurses' commitment to caring for culturally diverse clients varies, ranging from "resistant" to "generalist" to "impassioned." Contextual factors include the setting of health care, the support of colleagues, the institutional climate, the foundation of education, and the presence of racism. Despite the nursing profession's attention directed toward issues of cultural diversity, it seems that the goal of culturally sensitive care remains a distant ideal.


Advances in the therapy of idiopathic inflammatory myopathies.
To review progress in areas pertinent to the development of better therapies for the idiopathic inflammatory myopathies. New classification criteria for the idiopathic inflammatory myopathies have been proposed in an effort to define disease subsets with more uniform prognoses and responses to therapy. Diseases that may mimic the idiopathic inflammatory myopathies can be differentiated more accurately with molecular testing and biochemical and immunohistochemical analysis of muscle tissue. Advances in our understanding of the pathogenesis of the idiopathic inflammatory myopathies have served to identify potential new therapeutic targets. International collaborative study groups have reached consensus on outcome measures and on the optimal design of clinical trials in the idiopathic inflammatory myopathies. Tumor necrosis factor-alpha antagonists, rituximab, and the calcineurin inhibitors are being used to treat the idiopathic inflammatory myopathies, but their efficacy has not yet been tested in randomized clinical trials. Future advances in the development of therapies for the idiopathic inflammatory myopathies have been enabled by recent progress in myositis classification, differential diagnosis, basic science, and clinical trial design. Preliminary studies suggest that calcineurin inhibitors, tumor necrosis factor antagonists, and rituximab may be effective treatments.


Prevalence of psychological distress and associated factors in tuberculosis patients in public primary care clinics in South Africa.
Psychological distress has been rarely investigated among tuberculosis patients in low-resource settings despite the fact that mental ill health has far-reaching consequences for the health outcome of tuberculosis (TB) patients. In this study, we assessed the prevalence and predictors of psychological distress as a proxy for common mental disorders among tuberculosis (TB) patients in South Africa, where over 60 % of the TB patients are co-infected with HIV. We interviewed 4900 tuberculosis public primary care patients within one month of initiation of anti-tuberculosis treatment for the presence of psychological distress using the Kessler-10 item scale (K-10), and identified predictors of distress using multiple logistic regressions. The Kessler scale contains items associated with anxiety and depression. Data on socio-demographic variables, health status, alcohol and tobacco use and adherence to anti-TB drugs and anti-retroviral therapy (ART) were collected using a structured questionnaire. Using a cut off score of ≥28 and ≥16 on the K-10, 32.9 % and 81 % of tuberculosis patients had symptoms of distress, respectively. In multivariable analysis older age (OR = 1.52; 95 % CI = 1.24-1.85), lower formal education (OR = 0.77; 95 % CI = 0.65-0.91), poverty (OR = 1.90; 95 % CI = 1.57-2.31) and not married, separated, divorced or widowed (OR = 0.74; 95 % CI = 0.62-0.87) were associated with psychological distress (K-10 ≥28), and older age (OR = 1.30; 95 % CI = 1.00-1.69), lower formal education (OR = 0.55; 95 % CI = 0.42-0.71), poverty (OR = 2.02; 95 % CI = 1.50-2.70) and being HIV positive (OR = 1.44; 95 % CI = 1.19-1.74) were associated with psychological distress (K-10 ≥16). In the final model mental illness co-morbidity (hazardous or harmful alcohol use) and non-adherence to anti-TB medication and/or antiretroviral therapy were not associated with psychological distress. The study found high rates of psychological distress among tuberculosis patients. Improved training of providers in screening for psychological distress, appropriate referral to relevant health practitioners and providing comprehensive treatment for patients with TB who are co-infected with HIV is essential to improve their health outcomes. It is also important that structural interventions are promoted in order to improve the financial status of this group of patients.


PSKR1 and PSY1R-mediated regulation of plant defense responses.
Plant peptide signaling is an upcoming topic in many areas of plant research. Our recent findings show that the tyrosine sulfated peptide receptors PSKR1 and PSY1R are not only involved in growth and development but also in plant defense. They modulate salicylate- and jasmonate-dependent defense pathways in an antagonistic manner and this phenomenon might be dependent on the age and developmental stage of the plant. Here we discuss how the endogenous peptides might integrate growth, wounding, senescence and the opposing defense pathways against biotrophic and necrotrophic pathogens for increased fitness of the plant.


Activated T cell subsets in human type 1 diabetes: evidence for expansion of the DR+ CD30+ subpopulation in new-onset disease.
An important limitation in T cell studies of human autoimmune (type 1) diabetes is lack of direct access to cells infiltrating the pancreas. We hypothesized that cells recently released from the pancreas into the blood might express a characteristic combination of markers of activation. We therefore examined the recently activated circulating T cell population [CD3+, human leucocyte antigen D-related (HLA-DR+)] using cytokine production and 10 additional subset markers [CD69, CD25, CD122, CD30, CD44v6, CD57, CD71, CCR3 (CD193), CCR5 (CD195) or CXCR3 (CD183)], comparing newly diagnosed adult (ND) (age 18-40 years) patients (n=19) to patients with diabetes for >10 years [long-standing (LS), n=19] and HLA-matched controls (C, n=16). CD3+ DR+ cells were enriched by two-step immunomagnetic separation. No differences in basal or stimulated production of interleukin (IL)-4, IL-10, IL-13 or interferon (IFN)-gamma by CD3+ DR+ enriched cells were observed between the different groups of subjects. However, among the CD3+ DR+ population, significant expansions appeared to be present in the very small CD30+, CD69+ and CD122+ subpopulations. A confirmatory study was then performed using new subjects (ND=26, LS=15), three-colour flow cytometry, unseparated cells and three additional subset markers (CD38, CD134, CD4/CD25). This confirmed the expansion of the CD3+ DR+ CD30+ subpopulation in ND subjects. We conclude that a relative expansion in the T cell subpopulation with the activated phenotype CD3+ DR+ CD30+ is seen in the peripheral blood of subjects with newly diagnosed type 1 diabetes. This subpopulation represents less than 0 x 7% of circulating T cells and may provide a rich source of disease-specific T cells that can be isolated from blood.


Simple analysis of diphenylmethane antihistaminics and their analogues in bodily fluids by headspace solid-phase microextraction-capillary gas chromatography.
Thirteen antihistaminic drugs and their analogues are tested for their extraction by headspace solid-phase microextraction from human whole blood and urine. Their determination is made by using capillary gas chromatography with flame ionization detection. Relatively high recoveries are obtained for terodiline, diphenhydramine, diphenylpyraline, and orphenadrine in urine; but the recoveries in blood extracts are 4-51 times lower than those in urine extracts for all drugs. Benactyzine and piperilate are not suited for the extraction method. The calibration curves are drawn for four drugs spiked to whole blood and for eleven drugs spiked to urine; excellent linearity is confirmed for the drugs. The detection limits for the drugs are 76-473 ng/mL in blood and 13-186 ng/mL in urine. Diphenhydramine is determined for whole blood obtained from a male subject who had received oral administration of 30 mg diphenhydramine-HCl 150 min before the sampling; the concentrations of the drug are 0.12 and 1.22 micrograms/mL for blood and urine, respectively.


Enhancing Agrichemical Delivery and Plant Development with Biopolymer-Based Stimuli Responsive Core-Shell Nanostructures.
The inefficient delivery of agrichemicals in agrifood systems is among the leading cause of serious negative planetary and public health impacts. Such inefficiency is mainly attributed to the inability to deliver the agrichemicals at the right place (target), right time, and right dose. In this study, scalable, biodegradable, sustainable, biopolymer-based multistimuli responsive core-shell nanostructures were developed for smart agrichemical delivery. Three types of responsive core/shell nanostructures incorporated with model agrichemicals (i.e., CuSO4 and NPK fertilizer) were synthesized by coaxial electrospray, and the resulting nanostructures showed spherical morphology with an average diameter about 160 nm. Tunable agrichemical release kinetics were achieved by controlling the surface hydrophobicity of nanostructures. The pH and enzyme responsiveness was also demonstrated by the model analyte release kinetics (up to 7 days) in aqueous solution. Finally, the efficacy of the stimuli responsive nanostructures was evaluated in soil-based greenhouse studies using soybean and wheat in terms of photosynthesis efficacy and linear electron flow (LEF), two important metrics for seedling development and health. Findings confirmed plant specificity; for soybean, the nanostructures resulted in 34.3% higher value of relative chlorophyll content and 41.2% higher value of PS1 centers in photosystem I than the ionic control with equivalent agrichemical concentration. For wheat, the nanostructures resulted in 37.6% higher value of LEF than the ionic agrichemicals applied at 4 times higher concentration, indicating that the responsive core-shell nanostructure is an effective platform to achieve precision agrichemical delivery while minimizing inputs. Moreover, the Zn and Na content in the leaves of 4-week-old soybean seedlings were significantly increased with nanostructure amendment, indicating that the developed nanostructures can potentially be used to modulate the accumulation of other important micronutrients through a potential biofortification strategy.


Increased lactate threshold after five weeks of treadmill aerobic training in rats.
The aim of the present study was to analyse the lactate threshold (LT) changes in rats submitted to an aerobic treadmill-training programme. Twenty-five Wistar rats were divided into two groups: a sedentary control group (CG), and a trained group (TG) submitted to an aerobic training during 5 weeks. All the animals were submitted to an incremental treadmill exercise test in order to determine LT. There was an increase in the maximum running speed in the TG (from 32.25 ± 1.27 to 47.75 ± 3.13 m.min-1 - p = 0.001), and running speed at LT (from 26.21 ± 1.15 to 35.30 ± 2.24 m.min-1 - p = 0.004), a part from the reduction in blood lactate at LT. LT can be determined in rats, and aerobic training induced positive oxidative physiological adaptations in the animals.


Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial.
The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was designed to test the hypothesis that for the same blood-pressure control, valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk. 15?245 patients, aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a randomised, double-blind, parallel-group comparison of therapy based on valsartan or amlodipine. Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint, defined as a composite of cardiac mortality and morbidity. Patients from 31 countries were followed up for a mean of 4.2 years. Blood pressure was reduced by both treatments, but the effects of the amlodipine-based regimen were more pronounced, especially in the early period (blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month; 1.5/1.3 mm Hg after 1 year; p<0.001 between groups). The primary composite endpoint occurred in 810 patients in the valsartan group (10.6%, 25.5 per 1000 patient-years) and 789 in the amlodipine group (10.4%, 24.7 per 1000 patient-years; hazard ratio 1.04, 95% CI 0.94-1.15, p=0.49). The main outcome of cardiac disease did not differ between the treatment groups. Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes. The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk.


Influence of advanced age and related comorbidity on the course and outcome of acute pancreatitis.
Aging process and comorbidity have been held to influence the course and outcome of acute pancreatitis in elderly patients. The aim of the present study was to investigate this issue in a large series of patients > or = 70 years of age suffering from acute pancreatitis. A retrospectively study was carried out on 439 patients with a first episode of AP. The patients were divided into two age groups: < or = 69 years (n = 340) and > or = 70 years (n = 99). Differences in general characteristics, aetiological factors, blood tests and laboratory data, severity of the disease and outcome were evaluated. The presence of intercurrent diseases was also investigated in the two age groups. No significant difference was observed in the distribution of the various aetiological factors in the two age groups considered. The percentage of patients with necrotizing forms of AP, Ranson prognostic score for severity, local and systemic complications, the number of patients requiring surgical intervention or endoscopic sphincterotomy, as well as length of hospital stay were similar in the two groups. Considering the patients suffering from necrotizing acute pancreatitis, a significant increase (p = 0.01) in mortality was observed in > or = 70-year-old patients (25.8 vs 7.8%). Associated diseases were significantly more frequent in advanced age (63.6 vs 41.4%; p = 0.0004), but comorbidity did not correlate with the presence of pancreatic necrosis, the need for surgery or endoscopic sphincterotomy, and with mortality. The results of this study suggest that advanced age and related comorbidity have only a limited influence on the course and outcome of acute pancreatitis.


Self-management support in routine primary care by nurses.
To examine how and to what extent self-management support, including behaviour change support, is provided by primary care nurses in routine consultations with chronically ill patients. Observational study design. Routine consultations of primary care nurses in the Netherlands with chronically ill patients were audio-taped and analysed. The analysis identified health topics addressed according to health care standards, self-management topics addressed using a validated set of topics, and behaviour change techniques (BCTs) using the Behaviour Change Techniques Taxonomy v1. Seventy-eight routine consultations of 17 primary care nurses with chronically ill patients were included in the analysis. Nurses addressed both health topics and self-management topics in brief, fragmented, and often inconsistent manners. Dietary intake and physical activity were the most frequently addressed topics. Nurses applied 21 BCTs to target behaviour change, but the use of these techniques was mainly inconsistent and implicit. The most consistently used BCTs were review behaviour goal(s) (56.4%) and feedback on behaviour (51.3%). Nurses addressed both health topics and self-management topics in their routine consultations. The duration, frequency, and number of addressed topics differed throughout the consultations. Nurses tended to prioritize the monitoring and optimization of patients' medical treatment and provided limited self-management support. Nurses seldom deepened their focus on behaviour change and infrequently used effective techniques to support this change. Adoption of self-management in primary care, including behaviour change, might be enhanced if nurses consistently and explicitly use effective BCTs in their consultations. Statement of contribution What is already known on this subject? Primary care nurses play a pivotal role in self-management support for patients with a chronic condition. Adequate self-management support requires nurses to activate patients and enhance behaviour change. Little is known regarding to what extent nurses provide self-management support in routine primary care. What does this study add? Self-management support is brief, fragmented, and inconsistently provided by nurses. Nurses tend to prioritize medical treatment optimization and seldom focus on behavioural change. Nurses' use of effective behaviour change techniques is low and should be enhanced.


A universal model for solar eruptions.
Magnetically driven eruptions on the Sun, from stellar-scale coronal mass ejections to small-scale coronal X-ray and extreme-ultraviolet jets, have frequently been observed to involve the ejection of the highly stressed magnetic flux of a filament. Theoretically, these two phenomena have been thought to arise through very different mechanisms: coronal mass ejections from an ideal (non-dissipative) process, whereby the energy release does not require a change in the magnetic topology, as in the kink or torus instability; and coronal jets from a resistive process involving magnetic reconnection. However, it was recently concluded from new observations that all coronal jets are driven by filament ejection, just like large mass ejections. This suggests that the two phenomena have physically identical origin and hence that a single mechanism may be responsible, that is, either mass ejections arise from reconnection, or jets arise from an ideal instability. Here we report simulations of a coronal jet driven by filament ejection, whereby a region of highly sheared magnetic field near the solar surface becomes unstable and erupts. The results show that magnetic reconnection causes the energy release via 'magnetic breakout'-a positive-feedback mechanism between filament ejection and reconnection. We conclude that if coronal mass ejections and jets are indeed of physically identical origin (although on different spatial scales) then magnetic reconnection (rather than an ideal process) must also underlie mass ejections, and that magnetic breakout is a universal model for solar eruptions.


Physical therapy modalities and rehabilitation techniques in the management of neuropathic pain.
Neuropathic pain is an important problem because of its complex natural history, unclear etiology, and poor response to standard physical therapy agents. It causes severe disability unrelated to its etiology. The primary goals of the management of neuropathic pain are to detect the underlying cause, to define the differential diagnosis and eliminate risk factors, and to reduce the pain. The physician should also know the functional and psychologic conditions of the patient. Therefore, a multimodal management plan in neuropathic pain is essential. This review aimed to reflect a diverse point of view about various physical therapy modalities and rehabilitation techniques. Physical therapy modalities and rehabilitation techniques are important options and must be considered when pharmacotherapy alone is not sufficient. In addition, psychosocial support and cognitive behavioral therapy could also be taken into consideration. It has been suggested that the importance of pain rehabilitation techniques will increase in time and these will take a larger part in the management of neuropathic pain. However, it is now early to comment on these methods because of the lack of adequate publications.


Diabetes mellitus and sudden cardiac death: what are the data?
Diabetes mellitus has long been linked to an increased risk of sudden cardiac death. However, the magnitude of this association, and the mechanism accounting for this phenomenon, have not been precisely defined. In this review, we evaluate the epidemiological data pertaining to the association between diabetes mellitus and sudden cardiac death and discuss various proposed mechanisms that may account for this relationship. Potential factors contributing to the increased risk of sudden cardiac death observed in patients with diabetes mellitus include silent myocardial ischemia, autonomic nervous system dysfunction, abnormal cardiac repolarization, hypoglycemia, a hypercoaguable state secondary to diabetes mellitus, diabetic cardiomyopathy, and impaired respiratory response to hypoxia and hypercapnea. We conclude that diabetes mellitus does appear to be associated with an increased risk of sudden cardiac death. Although this increased risk is relatively modest, given the large number of diabetic patients worldwide, the absolute number of sudden cardiac deaths attributable to diabetes mellitus remains significant. Little evidence exists to support any specific mechanism(s) accounting for this association. Further investigation into the pathophysiology of sudden cardiac death in diabetes mellitus may yield improved risk stratification tools as well as identify novel therapeutic targets.


Auditory motor integration in oral and manual effectors.
Sensorimotor integration of auditory feedback for oral and manual force control was compared in 10 healthy participants. Based on the notion that auditory-to-motor integration is a more typical form of feedback for oral articulators given their role in speech and singing, it was predicted that oral force generation would be more accurate and less variable on an auditory-motor task compared to manual force generation. However, finger force production showed similar accuracy and lower variability than lip force production. The authors propose that auditory feedback can be used for fine force control of both oral and manual effectors. Differences in performance are considered to arise from physiological differences between the effectors that are reflected in their typical functions. This novel study of oral and manual force control under auditory feedback is an important step in understanding how auditory information can be associated with fine force control.


Quantifying interface and bulk contributions to spin-orbit torque in magnetic bilayers.
Spin-orbit interaction-driven phenomena such as the spin Hall and Rashba effect in ferromagnetic/heavy metal bilayers enables efficient manipulation of the magnetization via electric current. However, the underlying mechanism for the spin-orbit interaction-driven phenomena remains unsettled. Here we develop a sensitive spin-orbit torque magnetometer based on the magneto-optic Kerr effect that measures the spin-orbit torque vectors for cobalt iron boron/platinum bilayers over a wide thickness range. We observe that the Slonczewski-like torque inversely scales with the ferromagnet thickness, and the field-like torque has a threshold effect that appears only when the ferromagnetic layer is thinner than 1 nm. Through a thickness-dependence study with an additional copper insertion layer at the interface, we conclude that the dominant mechanism for the spin-orbit interaction-driven phenomena in this system is the spin Hall effect. However, there is also a distinct interface contribution, which may be because of the Rashba effect.


Eukaryotic cytosine methyltransferases.
Large-genome eukaryotes use heritable cytosine methylation to silence promoters, especially those associated with transposons and imprinted genes. Cytosine methylation does not reinforce or replace ancestral gene regulation pathways but instead endows methylated genomes with the ability to repress specific promoters in a manner that is buffered against changes in the internal and external environment. Recent studies have shown that the targeting of de novo methylation depends on multiple inputs; these include the interaction of repeated sequences, local states of histone lysine methylation, small RNAs and components of the RNAi pathway, and divergent and catalytically inert cytosine methyltransferase homologues that have acquired regulatory roles. There are multiple families of DNA (cytosine-5) methyltransferases in eukaryotes, and each family appears to be controlled by different regulatory inputs. Sequence-specific DNA-binding proteins, which regulate most aspects of gene expression, do not appear to be involved in the establishment or maintenance of genomic methylation patterns.


MoSART: Mobile Spatial Augmented Reality for 3D Interaction With Tangible Objects.
In this paper we introduce MoSART, a novel approach for Mobile Spatial Augmented Reality on Tangible objects. MoSART is dedicated to mobile interaction with tangible objects in single or collaborative situations. It is based on a novel "all-in-one" Head-Mounted Display (AMD) including a projector (for the SAR display) and cameras (for the scene registration). Equipped with the HMD the user is able to move freely around tangible objects and manipulate them at will. The system tracks the position and orientation of the tangible 3D objects and projects virtual content over them. The tracking is a feature-based stereo optical tracking providing high accuracy and low latency. A projection mapping technique is used for the projection on the tangible objects which can have a complex 3D geometry. Several interaction tools have also been designed to interact with the tangible and augmented content, such as a control panel and a pointer metaphor, which can benefit as well from the MoSART projection mapping and tracking features. The possibilities offered by our novel approach are illustrated in several use cases, in single or collaborative situations, such as for virtual prototyping, training or medical visualization.


Embryonic corneal epithelial actin alters distribution in response to laminin.
In the current study, laser scanning confocal image analysis was used to investigate the actin distribution in whole-mount preparations of freshly isolated and cultured corneal epithelia. Actin staining defined the cell borders and microvilli of the periderm cells. The actin was prominent as an organized network at the interface between the basal and periderm cells and in the basal compartment of the basal cells (actin cortical mat) when isolated with the basal lamina (BL). In epithelia isolated without BL, the actin in the periderm cells and the network at the periderm-basal cell interface was the same as in epithelia isolated with BL. However, the actin in the basal compartment of the basal cells was localized in the cellular blebs that projected from the basal cell surface. Epithelia isolated without BL and cultured in the presence of laminin reorganized the actin cortical mat within 2 hours. However, epithelia isolated without BL and cultured without BL proteins continued to have basal cell projections, sometimes into the pores of the filter. Treatment of epithelia with 2 microM cytochalasin D prevented the reorganization of the actin by laminin. In conclusion, the use of confocal analysis increased our understanding of actin distribution in the epithelial sheets. These results confirmed and extended previous studies using electron microscopy to determine that corneal epithelial cells respond to extracellular matrix molecules by an actin-dependent mechanism.


Identification of Caffeic Acid Phenethyl Ester (CAPE) as a Potent Neurodifferentiating Natural Compound That Improves Cognitive and Physiological Functions in Animal Models of Neurodegenerative Diseases.
Cell-based screening of bioactive compounds has served as an important gateway in drug discovery. In the present report, using human neuroblastoma cells and enrolling an extensive three-step screening of 57 phytochemicals, we have identified caffeic acid phenethyl ester (CAPE) as a potent neurodifferentiating natural compound. Analyses of control and CAPE-induced neurodifferentiated cells revealed: (i) modulation of several key proteins (NF200, MAP-2, NeuN, PSD95, Tuj1, GAP43, and GFAP) involved in neurodifferentiation process; and (ii) attenuation of neuronal stemness (HOXD13, WNT3, and Msh-2) and proliferation-promoting (CDC-20, CDK-7, and BubR1) proteins. We anticipated that the neurodifferentiation potential of CAPE may be beneficial for the treatment of neurodegenerative diseases and tested it using the Drosophila model of Alzheimer's disease (AD) and mice model of amnesia/loss of memory. In both models, CAPE exhibited improved disease symptoms and activation of physiological functions. Remarkably, CAPE-treated mice showed increased levels of neurotrophin-BDNF, neural progenitor marker-Nestin, and differentiation marker-NeuN, both in the cerebral cortex and hippocampus. Taken together, we demonstrate the differentiation-inducing and therapeutic potential of CAPE for neurodegenerative diseases.


Multiple Intravitreal Ranibizumab Injections for Persistant Choroidal Neovascularization Associated with Presumed Ocular Histoplasmosis Syndrome.
Presumed ocular histoplasmosis syndrome (POHS) is a clinical entity that is characterized by small, round, discrete, macular or mid peripheral atrophic (punched out) chorioretinal lesions (histo spots), peripapillary scarring, choroidal neovascularization (CNV), and the absence of anterior uveitis and vitritis. Diagnosis of this disorder is based upon characteristic clinical findings and a positive histoplasmin skin test or residence in an endemic region for Histoplasma capsulatum. There is no active systemic disease during diagnosis of POHS. Disciform scarring and macular CNV secondary to POHS is a well-known complication which leads to loss of visual acuity or visual disturbance. Without therapy, the visual prognosis in these patients is unfavorable. Submacular surgery, radiation, steroids, photodynamic therapy, and most recently anti-vascular endothelial growth factor therapy are current therapeutic options for this condition. We report a case with persistent CNV secondary to POHS in a middle-aged woman with moderate myopia and the clinical course of treatment with multiple intravitreal ranibizumab (Lucentis®, Novartis) injections.


Vid24p, a novel protein localized to the fructose-1, 6-bisphosphatase-containing vesicles, regulates targeting of fructose-1,6-bisphosphatase from the vesicles to the vacuole for degradation.
Glucose regulates the degradation of the key gluconeogenic enzyme, fructose-1,6-bisphosphatase (FBPase), in Saccharomyces cerevisiae. FBPase is targeted from the cytosol to a novel type of vesicle, and then to the vacuole for degradation when yeast cells are transferred from medium containing poor carbon sources to fresh glucose. To identify proteins involved in the FBPase degradation pathway, we cloned our first VID (vacuolar import and degradation) gene. The VID24 gene was identified by complementation of the FBPase degradation defect of the vid24-1 mutant. Vid24p is a novel protein of 41 kD and is synthesized in response to glucose. Vid24p is localized to the FBPase-containing vesicles as a peripheral membrane protein. In the absence of functional Vid24p, FBPase accumulates in the vesicles and fails to move to the vacuole, suggesting that Vid24p regulates FBPase targeting from the vesicles to the vacuole. FBPase sequestration into the vesicles is not affected in the vid24-1 mutant, indicating that Vid24p acts after FBPase sequestration into the vesicles has occurred. Vid24p is the first protein identified that marks the FBPase-containing vesicles and plays a critical role in delivering FBPase from the vesicles to the vacuole for degradation.


A deep learning-based tool for the automated detection and analysis of caveolae in transmission electron microscopy images.
Caveolae are nanoscopic and mechanosensitive invaginations of the plasma membrane, essential for adipocyte biology. Transmission electron microscopy (TEM) offers the highest resolution for caveolae visualization, but provides complicated images that are difficult to classify or segment using traditional automated algorithms such as threshold-based methods. As a result, the time-consuming tasks of localization and quantification of caveolae are currently performed manually. We used the Keras library in R to train a convolutional neural network with a total of 36,000 TEM image crops obtained from adipocytes previously annotated manually by an expert. The resulting model can differentiate caveolae from non-caveolae regions with a 97.44% accuracy. The predictions of this model are further processed to obtain caveolae central coordinate detection and cytoplasm boundary delimitation. The model correctly finds negligible caveolae predictions in images from caveolae depleted Cav1-/- adipocytes. In large reconstructions of adipocyte sections, model and human performances are comparable. We thus provide a new tool for accurate caveolae automated analysis that could speed up and assist in the characterization of the cellular mechanical response.


Screening for antimalarial maculopathy in rheumatology clinics.
Ophthalmoscopy and three tests of visual function were undertaken in 39 patients with rheumatoid arthritis receiving treatment with antimalarial drugs and in a control group of 16 patients with rheumatoid arthritis who were not receiving such treatment. Visual contrast sensitivity, macular threshold to red light, and central visual fields to red targets were not significantly different in treated patients and controls. There were no abnormalities in visual acuity, but 11 of 76 eyes of treated patients showed minor macular abnormalities on ophthalmoscopy that were not seen in control patients, suggesting that ophthalmoscopy may be the most sensitive measure of early drug toxicity. Five rheumatologists were able to identify 52 of 65 minor changes detected by an ophthalmologist. These studies, and a critical review of published reports, suggest that in clinical practice antimalarial drugs can be administered safely to patients with rheumatoid arthritis without the need for repetitive routine examination by an ophthalmologist or the use of complicated physiological tests. Recording of visual acuity in each eye and ophthalmoscopy by the prescribing doctor may be all that are required to detect early antimalarial maculopathy.


Community sexual health providers' views on immediate postpartum provision of intrauterine contraception.
Increasing access to effective postpartum contraceptive methods can reduce the risk of unintended pregnancy and short inter-birth intervals. The need for an additional postpartum visit can be a barrier to women accessing intrauterine contraception after childbirth. Immediate postpartum intrauterine contraception (PPIUC) provision is known to be safe, but is not routinely available in the UK. Establishing this service requires multidisciplinary support, including from community and maternity stakeholders. The aim of this study was to determine the views of community sexual health providers towards PPIUC implementation. A questionnaire was distributed to attendees at two UK sexual health conferences. Research questions focused on (1) views on PPIUC (2) perceived role of the sexual health provider in PPIUC service and (3) potential challenges anticipated in providing PPIUC aftercare. Free-text boxes were provided for further comment. Analysis was by a mixed methods approach. A total of 240 questionnaires were distributed with 156 completed (response rate 65%). Some 128 respondents (82%) felt 'positive' towards the PPIUC implementation. Most respondents (67.9%) indicated they would be happy to promote PPIUC and provide thread checks. Perceived challenges in providing PPIUC aftercare included staff time, experience in managing clinical issues, and access to ultrasound. Community sexual health providers were positive towards PPIUC implementation, and perceived their role predominantly in the aftercare of women. Several clinical and practical challenges were identified, some of which differ from those previously expressed by other groups. Stakeholder involvement is key to successful implementation of PPIUC, and wider recognition of potential barriers can assist in developing strategies to overcome these.


Diabetes and coronary heart disease in Filipino-American women: role of growth and life-course socioeconomic factors.
To investigate associations between adult markers of childhood growth and the prevalence of diabetes and coronary heart disease (CHD) in Filipino-American women and to determine the role of social and educational differences, including the influence of social mobility between childhood and adulthood. Socioeconomic disadvantage and poor infant growth, resulting in short leg length, may contribute to the dramatically increased risk of diabetes and CHD in Filipino-American women, but this has not been investigated. This study is a cross-sectional study of 389 Filipino-American women (age 58.7 +/- 9.4 years [mean +/- SD]). Diabetes was defined by 1999 World Health Organization criteria and CHD by ischemic electrocardiogram changes, Rose angina, a history of myocardial infarction, or revascularization surgery. A score of social mobility (0-4) was calculated by summarizing childhood and adult financial circumstances. Diabetes prevalence (31.4%) was not associated with measures of growth but was significantly lower in women with greater education, childhood and adult income, or social mobility score. Compared with Filipinas who were poorest in childhood and adulthood, respective odds ratios (95% CI) for diabetes were 0.55 (0.18-1.68), 0.19 (0.06-0.62), and 0.11 (0.03-0.42), down to 0.07 (0.01-0.51) in the most advantaged women (P < 0.0001). Family history of diabetes [5.14 (2.72-9.70)] and larger waist [1.07 per cm (1.03-1.10)] were also significant predictors in multiple adjusted models. In contrast, CHD prevalence (22.4%) was most strongly associated with leg length, but not trunk length; compared with individuals with the shortest legs, respective odds ratios (95% CI) for CHD were 0.60 (0.31-1.19), 0.53 (0.26-1.05), and 0.44 (0.22-0.91) in the tallest group, in age- (P(trend) = 0.02) and multiple-adjusted models (P(trend) = 0.01). Socioeconomic disadvantage contributes to the high prevalence of diabetes in Filipinas. Factors limiting early growth of the legs may increase the risk of CHD in this comparatively short population.


Estrogen sulfotransferase is expressed in subcutaneous adipose tissue of obese humans in association with TNF-alpha and SOCS3.
Estrogen sulfotransferase (EST) catalyzes the inactivation of estrone and estradiol in numerous tissues. Animal studies suggest that EST modulates glucose and lipid metabolism in adipose tissue, but it is unknown whether EST is expressed in human adipose tissue and, if so, how its expression relates to features of the metabolic syndrome. Cross-sectional data from 16 obese men and women with metabolic dysregulation were collected as part of a larger randomized trial at an academic medical center. Participants underwent assessment of body composition, oral glucose tolerance testing, measurement of serum hormones and inflammatory markers, and sc fat biopsy to assess adipose expression of TNF-α, suppressor of cytokine signaling 3 (SOCS3), leptin, adiponectin, and EST. EST expression was detectable in sc adipose tissue from both men and women. Log(10) EST mRNA was not significantly associated with age, race, sex or menopausal status, or circulating levels of estrogen or testosterone. In univariate analysis, log(10) EST mRNA was significantly associated with visceral adipose tissue area (r = 0.57, P = 0.02) as well as adipose tissue expression of TNF-α (r = 0.94, P < 0.0001) and SOCS3 mRNA (r = 0.93, P < 0.0001). The associations between EST expression and TNF-α and SOCS3 held in multivariate modeling controlling for age, race, sex and menopausal status, and visceral adiposity. EST expression was not significantly associated with the adipose tissue levels of leptin or adiponectin expression. EST is expressed in abdominal sc adipose tissue of both obese males and females in association with expression of TNF-α and SOCS3, suggesting potential roles in inflammation. Further studies are needed to determine the specific metabolic roles of EST expression in human adipose tissue.


Action-based cognitive remediation for individuals with serious mental illnesses: Effects of real-world simulations and goal setting on functional and vocational outcomes.
Cognitive remediation programs often have larger effects on cognition compared with everyday outcomes. We compared changes across cognitive, functional competence, and vocational domains in 2 cognitive remediation programs. A sequential enrollment, nonrandom design with 50 individuals with serious mental illnesses (psychotic and mood disorders) from a community vocational rehabilitation program. Action-Based Cognitive Remediation (ABCR), a new program that combines traditional cognitive training techniques with simulated workplace situations and goal setting for engaging with cognitively demanding activities (N = 24; 19 completers) was compared with traditional cognitive remediation (tCR; N = 26; 15 completers). Both groups met twice-weekly for 2-hr sessions over 10 weeks. Repeated measures analysis of variance was used to examine effects pre- and posttreatment and 10 weeks after treatment. Univariate analysis of variance and chi-square tests were used to compare work outcomes 6 months after intervention. Significantly more ABCR participants (83%) were retained in the intervention compared with tCR (57%) and reported greater increases in perceived competence with cognitively challenging tasks (η2 = .23). ABCR effects were significantly larger than tCR on functional competence (η2 = .53), with smaller, nonsignificant differences in social cognition (η2 = .14) and neurocognition (η 2 = .16). ABCR participants were marginally more likely to be competitively employed (68.4% vs. 40%) and, among those employed, ABCR participants experienced less job-related stress (η2 = .37). Cognitive rehabilitative programs for serious mental illness that rely on computer-based training for neuroplasticity should ensure opportunities for active skill development and therapist-supported techniques to overcome challenges with generalizing cognitive effects to everyday outcomes. (PsycINFO Database Record


Changes in endothelial function before and after renal transplantation.
Endothelial dysfunction is an early key event in the development of atherosclerotic cardiovascular disease observed in chronic renal failure patients. The role of renal transplantation (RTx) on endothelial dysfunction is still unclear. The aim of this study was to evaluate the endothelial function of chronic renal failure patients before RTx (while they were on hemodialysis, HD), and after RTx (at the 6th and 12th months) by a noninvasive method, brachial arterial ultrasound. A total of 22 (17 male, mean age: 33.9 +/- 11.6 years) RTx recipients were enrolled in the study. Endothelium-dependent vasodilation (EDD) was assessed by establishing reactive hyperemia. EDD prior to transplantation was significantly lower when compared with EDD measured at the 6th and 12th months after RTx (EDD pretransplantation: 6 +/- 3.7%, EDD at the 6th month of RTx: 8.3 +/- 2.3% and EDD at the 12th month of RTx: 12.1 +/- 3.6%, P < 0.001). When the EDD values measured at the 6th and 12th months of RTx were compared, measurements of the 12th month were found significantly higher than those of the 6th month (P < 0.001). Our results also showed that RTx has provided improvement in endothelial function by eliminating the uremic environment although not in the early post-RTx period.


Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice.
Tuberculosis is the leading cause of death in the world resulting from a single bacterial infection. Despite its enormous burden on world health, little is known about the molecular mechanisms of pathogenesis of Mycobacterium tuberculosis. Bacterial multiplication and concomitant tissue damage within an infected host, including experimentally infected mice, occurs primarily in the lungs-the favoured niche of M. tuberculosis. Although it has been proposed that the distinctive cell wall of M. tuberculosis is important for virulence, rigorous genetic proof has been lacking. Here, using signature-tagged mutagenesis, we isolated three attenuated M. tuberculosis mutants that cannot synthesize or transport a complex, cell wall-associated lipid called phthiocerol dimycocerosate (PDIM) which is found only in pathogenic mycobacteria. Two mutants have transposon insertions affecting genes implicated in PDIM synthesis; the third has a disruption in a gene encoding a large transmembrane protein required for proper subcellular localization of PDIM. Synthesis and transport of this complex lipid is only required for growth in the lung; all three mutants are unaffected for growth in the liver and spleen. This clearly shows that a lipid is required for M. tuberculosis virulence.


Modulation of Sex Pheromone Discrimination by A UDP-Glycosyltransferase in Drosophila melanogaster.
The detection and processing of chemical stimuli involve coordinated neuronal networks that process sensory information. This allows animals, such as the model species Drosophila melanogaster, to detect food sources and to choose a potential mate. In peripheral olfactory tissues, several classes of proteins are acting to modulate the detection of chemosensory signals. This includes odorant-binding proteins together with odorant-degrading enzymes (ODEs). These enzymes, which primarily act to eliminate toxic compounds from the whole organism also modulate chemodetection. ODEs are thought to neutralize the stimulus molecule concurrently to its detection, avoiding receptor saturation thus allowing chemosensory neurons to respond to the next stimulus. Here, we show that one UDP-glycosyltransferase (UGT36E1) expressed in D. melanogaster antennal olfactory sensory neurons (OSNs) is involved in sex pheromone discrimination. UGT36E1 overexpression caused by an insertion mutation affected male behavioral ability to discriminate sex pheromones while it increased OSN electrophysiological activity to male pheromones. Reciprocally, the decreased expression of UGT36E1, controlled by an RNAi transgene, improved male ability to discriminate sex pheromones whereas it decreased electrophysiological activity in the relevant OSNs. When we combined the two genotypes (mutation and RNAi), we restored wild-type-like levels both for the behavioral discrimination and UGT36E1 expression. Taken together, our results strongly suggest that this UGT plays a pivotal role in Drosophila pheromonal detection.


Hemoglobin Great Lakes (beta 68 [E12] leucine replaced by histidine): a new high-affinity hemoglobin.
Hemoglobin Great Lakes, beta 68 (E12) Leu replaced by His is a new high oxygen affinity hemoglobin variant discovered in a 29-yr-old female having numerous hospitalizations for thrombophlebitis associated with mild erythrocytosis. The mutant hemoglobin has normal stability and normal electrophoretic mobility, but increased oxygen affinity (P-50 16.1 mm Hg at 37 degrees C, pH 7.4) and reduced cooperativity. The abnormal beta-chain could be separated on globin chain chromatography on carboxymethyl/cellulose in spite of the normal electrophoretic mobility of the intact hemoglobin. The leucyl residue at beta 68th position (E12) is in the middle of E-helix, which is part of the heme pocket and next to the valine (E11), which is the heme binding site. The substitution of proline for leucine in hemoglobin Mizuho resulted in the distortion of tertiary structure of the beta-chains and lead to a serious instability of hemoglobin molecule. However, the substitution of this residue by histidine in hemoglobin Great Lakes is not associated with hemoglobin instability.


[Minimal inhibitory concentrations of Candida species to five antifungals by using the reference dilution micromethod and the E-test.].
It is accepted that the frequency of candidosis has increased during the last decade, specially in hospitalized patients. The more frequent use of azole antifungals and the recognition of isolates of Candida sp resistant to these and other drugs such as 5-fluorocytosine constitute a great need for a reproducible and useful C. albicans in vitro susceptibility testing method for monitoring antifungal therapy in clinical mycological laboratories. The E-test is a novel agar diffussion technique for testing the susceptibility of yeasts against a defined continous gradient of drug and could be used by most clinical laboratories. In this study the E-test and the NCCLS reference microbroth method (M27-P guidelines) were used to determine the MICs of amphotericin B, 5-flucytosine, itraconazole, fluconazole and ketoconazole for 50 clinical isolates of Candida albicans, Torulopsis glabrata, C. tropicalis and Hansenula anomala and five reference ATCC strains. The main purpose of the study was to compare the results obtained by the two methods. In general good agreement (+/- 1 dilution) was otained between both methods, despite differences observed for some species-antifungal combinations in which the MICs were lower by the E-test than by the microbroth method. MICs for C. albicans and T. glabrata to amphotericin B were < 0.50 microg/mL. Two isolates of C. albicans and two others of H. anomala, showed MIC < 8 microg/mL for 5- flucytosine. All isolates of T. glabrata and 40% of C. albicans showed MICs > 16 microg/mL for fluconazole. The results of this study indicate that E-test is an alternative for susceptibility testing to the NCCLS reference method. Because its simplicity it seems to be an easier test for routine clinical laboratories.


[The levels of health justice and the distribution of resources].
The right to health care is a social achievement of democratic states based on law. In order for this to become effective in a just way, it is necessary for many elements to come together. This article analyses these elements in their different moments: the state as a guarantor of this right and to limit assistance; the health institutions, direct managers of care, which must combine efficiency and equity; and, finally, the health professionals, who are in the final instance the real distributors of resources. Traditionally medicine always omitted evaluation of the socio-economic factors from its sphere. It even came to consider that these questions were opposed to good medical practice. Today such an assertion is unsustainable. For a health professional the path to efficiency passes by way of assuring clinical effectiveness, in this way guaranteeing both the patient's interest and the suitable distribution of resources.


Uniformly sized molecularly imprinted polymers for d-chlorpheniramine: influence of a porogen on their morphology and enantioselectivity.
Uniformly sized molecularly imprinted polymers (MIPs) for d-chlorpheniramine have been prepared by a multi-step swelling and polymerization method using methacrylic acid (MAA) or 2-(trifluoromethyl)acrylic acid (TFMAA) as a functional monomer and toluene, phenylacetonitrile, benzylacetonitrile or chloroform as a porogen. From measurement of their scanning electron microscopy images and physical properties in the dry state, the MIP prepared using TFMAA and chloroform as the functional monomer and porogen, respectively, seemed to be non-porous and had extremely low specific surface areas and pore volumes, while the other MIPs were porous beads with high specific surface areas and pore volumes. All the MIPs prepared were evaluated using hydro-organic mobile phases in HPLC. As a result, they showed the similar retentive and enantioselective properties for chlorpheniramine, brompheniramine and pheniramine. This result suggests the presence of enantioselective binding sites in the swollen state for all the MIPs.


Relationships among dietary fiber components and the digestibility of energy, dietary fiber, and amino acids and energy content of nine corn coproducts fed to growing pigs.
An experiment was conducted to determine a best fitting dietary fiber (DF) component to estimate the effect of DF concentration on the digestibility of energy, DF, and AA and energy value of 9 corn coproducts: corn bran (37.0% total nonstarch polysaccharides [NSP]); corn bran with solubles (17.1% NSP); cooked corn distillers dried grains with solubles (DDGS; 20.4% NSP); reduced oil DDGS (25.0% NSP); uncooked DDGS (22.0% NSP); high protein distillers dried grains (21.9% NSP); dehulled, degermed corn (1.1% NSP); corn germ meal (44.4% NSP); and corn gluten meal (4.9% NSP). A total of 20 growing pigs (initial BW: 25.9 ± 2.5 kg) were fitted with a T-cannula in the distal ileum and allotted to 10 dietary treatment groups in a 4-period incomplete block design with 8 observations per treatment. Treatments included a corn-soybean meal-based basal diet and 9 diets obtained by mixing 70% of the basal diet with 30% of the test ingredient. In tested ingredients, 11 DF components were determined: 1) ADF, 2) NDF, 3) total dietary fiber, 4) hemicellulose, 5) total NSP, 6) NSP arabinose, 7) NSP xylose, 8) NSP mannose, 9) NSP glucose, 10) NSP galactose, and 11) arabinoxylan. The apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of GE, DM, and NDF and the AID of AA of ingredients were measured. A single best fitting DF component was assessed and ranked for each trait, showing that arabinoxylan concentration best explained variance in AID of GE (R(2) = 0.65; cubic, P < 0.01) and DM (R(2) = 0.67; cubic, P < 0.01). The NSP xylose residue best explained variance in ATTD of GE (R(2) = 0.80; cubic, P < 0.01), DM (R(2) = 0.78; cubic, P < 0.01), and NDF (R(2) = 0.63; cubic, P < 0.01); AID of Met (R(2) = 0.40; cubic, P = 0.02), Met + Cys (R(2) = 0.44; cubic, P = 0.04), and Trp (R(2) = 0.11; cubic, P = 0.04); and DE (R(2) = 0.66; linear, P = 0.02) and ME (R(2) = 0.71; cubic, P = 0.01) values. The AID of Lys was not predictable (P > 0.05) from the DF concentration. In conclusion, the arabinoxylan and NSP xylose residue were the DF components that best explained variation due to DF concentration and, with the exception of AID of Lys, can be used to predict the digestibility of energy and DF and the DE and ME values in corn coproducts.


[Extraovarian peritoneal serous papillary carcinoma: an unusual surgical case].
The extraovarian peritoneal serous papillary carcinoma (EPSPC) is a multicentric peritoneal tumor with minimal or absent involvement of the ovaries. The actual treatment regimen consists of a cytoreductive surgery followed by a combination chemotherapy. Few studies have compared outcome of EPSPC to papillary serous ovarian cancer (PSOC). Several authors have documented similar clinical behavior between EPSPC and PSOC, but this finding has not been universal. A 64-year-old female patient with symptomatic gall stone disease underwent elective laparoscopic cholecystectomy. Unexpectedly we found some uncommon small nodular structures on the serosa of the right colon. The histological findings suggested a poorly differentiated peritoneal serous papillary carcinoma. Biopsies of both ovaries showed no signs of tumor infiltration and the diagnosis of EPSPC was established. After surgery, a combination chemotherapeutic regimen with carboplatin and cyclophosphamid was given. Laparoscopic reassessment 7 months after the first procedure showed no tumor. 3 identical cycles completed chemotherapy. Normal ovaries and no other tumor sites were found in a final laparoscopic look after 11 months.