Changes in prescription patterns before and after reporting of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial (ENHANCE) results and expected effects on low-density lipoprotein-cholesterol reduction.
Recent trends suggest a decreased use of ezetimibe/simvastatin combination and coadministered ezetimibe plus statin therapies. This analysis evaluated changes in prescription patterns for ezetimibe/simvastatin, ezetimibe plus statins, and statin therapies and expected effects on low-density lipoprotein cholesterol (LDL-C) lowering during 2007 to 2008. Prescription pattern changes were assessed by the use of patient-level data from the IMS Health Longitudinal Rx database during two time periods, July 14, 2007 to January 13, 2008 (n = 8,813,674) and January 14, 2008 to July 13, 2008 (n = 9,131,030), 6 months before and after reporting of the results of The Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial (ENHANCE) trial on January 14, 2008. Expected LDL-C reductions were estimated using data from previous controlled clinical trials. During 6 months post-ENHANCE, greater proportions of patients were switched from ezetimibe/simvastatin and ezetimibe plus statins to other lipid-lowering therapies by health care providers than 6 months pre-ENHANCE (21.1% vs 6.0% and 46.9% vs 38.5%, differences: -15.06% [95% confidence interval -15.14%, -14.97%] and -8.43% [95% confidence interval -8.70%, -8.17%], respectively). Greater proportions of these patients switched to statin monotherapy in the later than earlier period. Prescription patterns were similar for statins during both time periods, although fewer patients switched to ezetimibe/simvastatin and ezetimibe plus statin therapies post-ENHANCE. In both time periods, greater proportions of patients on ezetimibe/simvastatin and ezetimibe plus statins switched to less-than-equivalent LDL-C lowering efficacy doses of statins than those on statin therapy. On the basis of previous clinical data for these therapies, smaller LDL-C reductions would be expected in patients who switched from ezetimibe/simvastatin and ezetimibe plus statins to statins, despite a trend toward switching to greater statin doses in the later time period. More patients switched from ezetimibe/simvastatin and ezetimibe plus statin to statin monotherapy 6 months after the reporting of the ENHANCE trial, the majority of which were prescribed less potent, LDL-C-lowering therapies. On the basis of the known LDL-C lowering efficacies for these therapies, such changes would be expected to increase LDL-C levels in these patients and may reduce the proportion of patients who achieve guideline-recommended LDL-C goals.


Cooperative transcription factor associations discovered using regulatory variation.
Regulation of gene expression at the transcriptional level is achieved by complex interactions of transcription factors operating at their target genes. Dissecting the specific combination of factors that bind each target is a significant challenge. Here, we describe in detail the Allele Binding Cooperativity test, which uses variation in transcription factor binding among individuals to discover combinations of factors and their targets. We developed the ALPHABIT (a large-scale process to hunt for allele binding interacting transcription factors) pipeline, which includes statistical analysis of binding sites followed by experimental validation, and demonstrate that this method predicts transcription factors that associate with NFκB. Our method successfully identifies factors that have been known to work with NFκB (E2A, STAT1, IRF2), but whose global coassociation and sites of cooperative action were not known. In addition, we identify a unique coassociation (EBF1) that had not been reported previously. We present a general approach for discovering combinatorial models of regulation and advance our understanding of the genetic basis of variation in transcription factor binding.


Cooperative regulation of the interferon regulatory factor-1 tumor suppressor protein by core components of the molecular chaperone machinery.
Our understanding of the post-translational processes involved in regulating the interferon regulatory factor-1 (IRF-1) tumor suppressor protein is limited. The introduction of mutations within the C-terminal Mf1 domain (amino acids 301-325) impacts on IRF-1-mediated gene repression and growth suppression as well as the rate of IRF-1 degradation. However, nothing is known about the proteins that interact with this region to modulate IRF-1 function. A biochemical screen for Mf1-interacting proteins has identified an LXXLL motif that is required for binding of Hsp70 family members and cooperation with Hsp90 to regulate IRF-1 turnover and activity. These conclusions are supported by the finding that Hsp90 inhibitors suppress IRF-1-dependent transcription shortly after treatment, although at later time points inhibition of Hsp90 leads to an Hsp70-dependent depletion of nuclear IRF-1. Conversely, the half-life of IRF-1 is increased by Hsp90 in an ATPase-dependent manner leading to the accumulation of nuclear but not cytoplasmic IRF-1. This study begins to elucidate the role of the Mf1 domain of IRF-1 in orchestrating the recruitment of regulatory factors that can impact on both its turnover and transcriptional activity.


Microorganisms from the Late Precambrian of Central Australia.
An assemblage of structurally and organically well preserved microorganisms, interpreted as both green and blue-green algae, has been found in chert facies of the Bitter Springs limestone from the upper Precambrian of central Australia. This appears to be the earliest known occurrence of green algae in the fossil record. These organisms are among the oldest known multicellular and unicellular fossils exhibiting distinct histological preservation.


Breast Milk Cytokines and Early Growth in Gambian Infants.
Background: Breast milk provides nutrition for infants but also delivers other bioactive factors that have key protective and developmental benefits. In particular, cytokines are thought to play a role in immunomodulation, although little is known about their impact on health outcomes in early life. Objective: The purpose of this pilot study was to evaluate the relationship between cytokines in breast milk and infant growth outcomes in a low-income setting. Methods: 100 mother-infant pairs were followed up to 2-3 months postpartum as part of a prospective longitudinal cohort study in urban Gambia, West Africa. The concentrations of 9 pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNFα), IGF-1 and TGFβ2 were measured in colostrum within 12 h of birth and in breast milk at the final visit, scheduled between day 60 and 89 postpartum. Infant weight was recorded and converted to weight-for-age Z-scores (WAZ) at the same time points. Growth outcomes were defined in our study as (a) change in WAZ between birth and final visit (b) WAZ at final visit. Linear regression analysis was used to determine the ability of colostrum and breast milk cytokine concentrations to predict growth outcomes up to 2-3 months postpartum. Results: Gambian infants demonstrated growth faltering across the first 2-3 months postpartum. There was no significant relationship between cytokines in colostrum and subsequent change in WAZ between birth and the final visit, in either unadjusted or adjusted models. However, cytokines in mature breast milk, TNFα, IFNγ, IL1β, IL2, IL4, and IL6, were weak negative predictors of WAZ scores at the final visit, in unadjusted models (p < 0.05). When adjusted for maternal anemia (as a proxy for maternal nutrition), TNFα and IL6 remained significant predictors (p < 0.05). Conclusions: Variations in breast milk cytokine levels do not play a substantial role in the growth faltering observed across early infancy. The potential contribution of other factors, such as micronutrients, hormones or human milk oligosaccharides, must be elucidated. Cytokine levels in mature breast milk were weakly predictive of poor infant growth, possibly reflecting a "read-out" of suboptimal maternal health and nutrition.


Purification and immunological characterization of a calcium pump from bovine brain synaptosomal vesicles.
In previous work ( Papazian , D., H. Rahamimoff , and S. M. Goldin (1979) Proc. Natl. Acad. Sci. U. S. A. 76: 3708-3712), an ATP-dependent calcium transport activity derived from rat brain synaptosomes was reconstituted into artificial lipid vesicles and substantially purified by transport-specific fractionation. When this procedure was applied to bovine brain synaptosomes, the approximately 70-fold purified, reconstituted Ca2+ uptake system contained two major polypeptides of Mr = 230,000 (" C230 ") and 94,000 (" C94 ") as observed on sodium dodecyl sulfate (SDS) gels. Evidence is presented here that these polypeptides are immunologically related to one another and that the synaptosomal Ca2+ pump is immunologically distinct from Ca2+ pumps in non-neuronal cells. Antisera and monoclonal antibodies to the purified, reconstituted protein did not significantly cross-react with the Ca2+ pumps or any other components of bovine sarcoplasmic reticulum or erythrocytes. However, these antibodies did cross-react with a component of bovine brain axolemma-enriched membranes. A monoclonal antibody was produced that immunoprecipitated the Ca2+ transport activity, both in native, synaptosomal vesicles and in liposomes containing the reconstituted transport system. This antibody bound C230 more prominently than C94 on Western blots of SDS gels. An antiserum raised against C94 alone, obtained by elution from SDS gels, was also found to bind most prominently to C230 on Western blots. These results suggest that this synaptosomal Ca2+ pump is specific to nerve tissue and that C94 and C230 are structurally homologous components of this transport activity.


Association between willingness to use snus to quit smoking and perception of relative risk between snus and cigarettes.
Smokers are often incorrect in their assessment of the relative risk of snus and cigarettes. We have studied how perception of risks of snus compared with cigarettes was associated with the willingness of trying snus as a quit-smoking method. Fourteen thousand seven hundred and forty-four Norwegian men aged 20-50 years were selected at random from a national representative web panel and sent a questionnaire by e-mail. Of the 7,170 (48.6%) who responded, there were 1,155 former daily smokers who reported method for quitting smoking and 1,213 current daily smokers who stated their willingness to try different methods for quitting smoking. They were also asked to assess the relative risk between daily use of snus and cigarettes. Adjusted odds ratio (AOR) for reporting willingness to try snus in future quit attempts was significantly higher (AOR = 4.82, p < .001) for the 22.9% of the current smokers who, consistent with scientific evidence, believed that the health risks were "far lower" for snus than for cigarettes compared with the 39.8% who incorrectly perceived the health risks to be "equal or higher" for snus (reference AOR = 1). About 37.2% of the daily smokers believed that the risk was "somewhat lower" for snus than for cigarettes and had a significantly higher AOR of reporting willingness to try snus (AOR = 2.31, p < .001) compared with the reference group. Devising a way to inform smokers about the risk continuum of tobacco products could be an important research priority in countries where snus is allowed to compete with cigarettes for market share.


Quantitative trait loci associated with functional stay-green SNU-SG1 in rice.
During monocarpic senescence in higher plants, functional stay-green delays leaf yellowing, maintaining photosynthetic competence, whereas nonfunctional stay-green retains leaf greenness without sustaining photosynthetic activity. Thus, functional stay-green is considered a beneficial trait that can increase grain yield in cereal crops. A stay-green japonica rice 'SNU-SG1' had a good seed-setting rate and grain yield, indicating the presence of a functional stay-green genotype. SNU-SG1 was crossed with two regular cultivars to determine the inheritance mode and identify major QTLs conferring stay-green in SNU-SG1. For QTL analysis, linkage maps with 100 and 116 DNA marker loci were constructed using selective genotyping with F2 and RIL (recombinant inbred line) populations, respectively. Molecular marker-based QTL analyses with both populations revealed that the functional stay-green phenotype of SNU-SG1 is regulated by several major QTLs accounting for a large portion of the genetic variation. Three main-effect QTLs located on chromosomes 7 and 9 were detected in both populations and a number of epistatic-effect QTLs were also found. The amount of variation explained by several digenic interactions was larger than that explained by main-effect QTLs. Two main-effect QTLs on chromosome 9 can be considered the target loci that most influence the functional stay-green in SNU-SG1. The functional stay-green QTLs may help develop low-input high-yielding rice cultivars by QTL-marker-assisted breeding with SNU-SG1.


The Stepping Threshold Test for Reactive Balance: Validation of Two Observer-Based Evaluation Strategies to Assess Stepping Behavior in Fall-Prone Older Adults.
Introduction: Measurement of reactive balance is critical for fall prevention but is severely underrepresented in the clinical setting due to the lack of valid assessments. The Stepping Threshold Test (STT) is a newly developed instrumented test for reactive balance on a movable platform, however, it has not yet been validated for fall-prone older adults. Furthermore, different schemes of observer-based evaluation seem possible. The aim of this study was to investigate validity with respect to fall risk, interpretability, and feasibility of the STT using two different evaluation strategies. Methods: This study involved 71 fall-prone older adults (aged ≥ 65) who underwent progressively increasing perturbations in four directions for the STT. Single and multiple-step thresholds for each perturbation direction were determined via two observer-based evaluation schemes, which are the 1) consideration of all steps (all-step-count evaluation, ACE) and 2) consideration of those steps that extend the base of support in the direction of perturbation (direction-sensitive evaluation, DSE). Established balance measures including global (Brief Balance Evaluations Systems Test, BriefBEST), proactive (Timed Up and Go, TUG), and static balance (8-level balance scale, 8LBS), as well as fear of falling (Short Falls Efficacy Scale-International, FES-I) and fall occurrence in the past year, served as reference measurements. Results: The sum scores of STT correlated moderately with the BriefBEST (ACE: r = 0.413; DSE: r = 0.388) and TUG (ACE: r = -0.379; DSE: r = -0.435) and low with the 8LBS (ACE: r = 0.173; DSE: r = 0.246) and Short FES-I (ACE: r = -0.108; DSE: r = -0.104). The sum scores did not distinguish between fallers and non-fallers. No floor/ceiling effects occurred for the STT sum score, but these effects occurred for specific STT thresholds for both ACE (mean floor effect = 13.04%, SD = 19.35%; mean ceiling effect = 4.29%, SD = 7.75%) and DSE (mean floor effect = 7.86%, SD = 15.23%; mean ceiling effect = 21.07%, SD = 26.08). No severe adverse events occurred. Discussion: Correlations between the STT and other balance tests were in the expected magnitude, indicating convergent validity. However, the STT could not distinguish between fallers and non-fallers, referring to a need for further studies and prospective surveys of falls to validate the STT. Current results did not allow a definitive judgment on the advantage of using ACE or DSE. Study results represented a step toward a reactive balance assessment application in a clinical setting.


[Use of immunospecific methods for quantitative estimation of microsomal epoxide hydrolase].
Antiserum, specific to rat liver microsomal epoxide hydrolase, was produced. Three methods for quantitative estimation of the epoxide hydrolase, base on the principle of antigen-antiserum immunoprecipitation, were used: electroimmune analysis by Laurell, radial immunodiffusion, enzyme-linked immunoassay. Distinct correlation between specific enzyme activity and its content in microsomal preparation was demonstrated using a simple and stable procedure of radial immunodiffusion. In the enzyme-linked assay conjugate of protein A with alkaline phosphate served as the secondary antibody. Sensitivity of the procedure described was about 1,000-fold higher as compared with radial immunodiffusion method.


Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge.
Colorectal cancer (CRC) has been shown to acquire RAS and EGFR ectodomain mutations as mechanisms of resistance to epidermal growth factor receptor (EGFR) inhibition (anti-EGFR). After anti-EGFR withdrawal, RAS and EGFR mutant clones lack a growth advantage relative to other clones and decay; however, the kinetics of decay remain unclear. We sought to determine the kinetics of acquired RAS/EGFR mutations after discontinuation of anti-EGFR therapy. We present the post-progression circulating tumor DNA (ctDNA) profiles of 135 patients with RAS/BRAF wild-type metastatic CRC treated with anti-EGFR who acquired RAS and/or EGFR mutations during therapy. Our validation cohort consisted of an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling. A separate retrospective cohort of 80 patients was used to evaluate overall response rate and progression free survival during re-challenge therapies. Our analysis showed that RAS and EGFR relative mutant allele frequency decays exponentially (r2=0.93 for RAS; r2=0.94 for EGFR) with a cumulative half-life of 4.4 months. We validated our findings using an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling, confirming exponential decay with an estimated half-life of 4.3 months. A separate retrospective cohort of 80 patients showed that patients had a higher overall response rate during re-challenge therapies after increasing time intervals, as predicted by our model. These results provide scientific support for anti-EGFR re-challenge and guide the optimal timing of re-challenge initiation.


The tissue-type plasminogen activator inhibitor ETIa from Erythrina variegata: structural basis for the inhibitory activity by cloning, expression, and mutagenesis of the cDNA encoding ETIa.
Erythrina variegata trypsin inhibitor ETIa belongs to the Kunitz inhibitor family, but is unique in its ability to bind and inhibit tissue-type plasminogen activator (tPA). A cDNA clone encoding ETIa was isolated from the lambda gt11 cDNA library using specific antiserum as a probe and characterized by nucleotide sequencing. The cloned ETIa cDNA consists of 762 nucleotides and includes an open reading frame encoding a polypeptide of 198 amino acids. Comparison of the deduced protein sequence and the determined protein sequence indicated the presence of two signal peptides composed of 24 and 2 amino acids at the N- and C-termini, respectively. The cDNA encoding mature ETIa was amplified by polymerase chain reaction (PCR), ligated into the expression vector pET-22b, and expressed in Escherichia coli BL21(DE3). The recombinant ETIa (rETIa) was expressed in E. coli as inclusion bodies; it was purified to homogeneity by gel filtration on Sephadex G-75. The rETIa exhibited almost the same inhibitory activity toward trypsin and tPA as ETIa. Six mutants, in which the amino acids Arg61, Leu62, Arg63, and Ala65 were replaced by Pro, Phe, Leu/Asp, and Tyr, respectively, were constructed by site-specific mutagenesis and expressed in E. coli. The site-specific mutation of Arg63 to Leu (aR63L) or Asp (aR63D) in ETIa resulted in abolition of the inhibitory activities toward both trypsin and tPA. The mutants aR61P and aL62F showed significantly reduced tPA-inhibitory activity, and furthermore the double mutant aR61P/L62F lacked tPA-inhibitory activity, despite retaining the trypsin-inhibitory activity. In contrast, the mutant aA65Y exhibited tPA-inhibitory activity to the same extent as rETIa. This result suggests that Arg61 and Leu62 in ETIa, in addition to Arg63, may play an important role in the interaction with tPA.


Non-invasive coronary physiology based on computational analysis of intracoronary transluminal attenuation gradient.
Invasive procedure is a prerequisite for studying coronary physiology. We established the measurement of non-invasive physiological parameters including coronary blood flow (CBF), flow velocity, and microvascular resistance using coronary computed tomography angiography (CCTA). Vessel-specific CBF was derived from transluminal attenuation flow encoding (TAFE) and then tested using three separate datasets consisted of computational simulation, human perfusion CT, and human CCTA. TAFE-derived CBF correlated well with measured vessel-specific myocardial blood flow and CBF. TAFE-derived CBF per myocardial mass consistently decreased with the progressive severity of stenosis, and it was found to better to detect significant stenosis than transluminal attenuation gradient (TAG). With the addition of vessel anatomy, TAFE-derived CBF could calculate flow velocity and microvascular resistance. The results of non-invasively acquired parameters according to the severity of stenosis were similar to those obtained through invasive physiology studies. Our study demonstrated that non-invasive comprehensive coronary physiology parameters can be derived from CCTA without any pre-specified condition or performing complex heavy computational processes. Our findings are expected to expand the clinical coverage of CCTA and coronary physiology.


Video-assisted thoracoscopic surgery: The preferred method to manage pulmonary sequestration.
This study aims at describing the feasibility and safety of video-assisted thoracic surgery (VATS) in benign diseases such as pulmonary sequestrations (PSs) and report the surgical outcomes. This is a retrospective analysis of prospectively maintained data of 25 patients who were operated for PS over 7 years at a dedicated thoracic surgery centre in India. Pre-operative details, operative technique and details, post-operative details and complications were recorded and analysed. There were 15 (60%) males and 10 (40%) females, with a median age of 22.28 years (range, 16-28 years). All patients had intra-lobar type of sequestration. The most commonly involved was left lower lobe (n = 15 patients, 60%) followed by the right lower lobe (n = 10 patients, 40%). The origin of blood supply was from the descending thoracic aorta in 18 patients (72%), the abdominal aorta in 5 (20%) and the coeliac trunk and the inferior phrenic artery in one patient (4%) each. All patients underwent complete lobar resection. One patient was converted because of dense hilar adhesion. The average duration of surgery was 179 min and the average blood loss was 204 ml. The median hospital stay and chest tube duration were 4 and 3 days, respectively. One patient was re-explored because of post-operative bleeding. Only one patient had an air leak for >7 days. The median follow-up was 42 months (range, 6-90 months) without any recurrence. VATS is a safe, feasible and effective option for PS at experienced centres.


Evidence for Sequential Performance Effects in Professional Darts.
Objectives: The study of sequential effects in aiming tasks might shed light on the organization of repetitive motor performances over time. To date, investigations of such effects in sports have been limited and yielded mixed results. Given the relatively short time intervals between successive attempts, and the absence of defensive interventions, dart throwing provides a potentially fruitful testing ground for examining the presence of sequential performance effects in the motor domain. Methods and Results: A total of 80 competitive darts matches of 10 of the world's best players were scored from publicly available video footage in terms of sequences of hits and misses of triple 20. In darts, throws are organized in legs, i.e., a rapid succession of three throws by the same player, allowing us to investigate various transitions in performance (throw 1 → 2, 2 → 3, and 3 → 1). The resulting binary sequences were analyzed statistically in terms of independence and stationarity. Across players significant statistical evidence was found for sequential dependence from the first throw in a leg to the second throw, but not for the other transitions. As regards to stationarity, a significant decline in performance was observed in the course of the match. Conclusions: In professional darts, evidence can be found for both sequential dependence as well as for non-stationarity, implying that performance does not, or at least not always, constitute a stationary random independent process. More research is needed on the motor control mechanisms underlying the observed carry-over effects within triplets as well as the possible causes of non-stationarity.


A smart micro-drill for cochleostomy formation: a comparison of cochlear disturbances with manual drilling and a human trial.
Cochleostomy formation is a key stage of the cochlear implantation procedure. Minimizing the trauma sustained by the cochlea during this step is thought to be a critical feature in hearing preservation cochlear implantation. The aim of this paper is firstly, to assess the cochlea disturbances during manual and robotic cochleostomy formation. Secondly, to determine whether the use of a smart micro-drill is feasible during human cochlear implantation. The disturbances within the cochlea during cochleostomy formation were analysed in a porcine specimen by creating a third window cochleostomy, preserving the underlying endosteal membrane, on the anterior aspect of the basal turn of the cochlea. A laser vibrometer was aimed at this third window, to assess its movement while a traditional cochleostomy was performed. Six cochleostomies were performed in total, three manually and three with a smart micro-drill. The mean and peak membrane movement was calculated for both manual and smart micro-drill arms, to represent the disturbances sustained within cochlea during cochleostomy formation. The smart micro-drill was further used to perform live human robotic cochleostomies on three adult patients who met the National Institute of Health and Clinical Excellence criteria for undergoing cochlear implantation. In the porcine trial, the smart micro-drill preserved the endosteal membrane in all three cases. The velocity of movement of the endosteal membrane during manual cochleostomy is approximately 20 times higher on average and 100 times greater in peak velocity, than for robotic cochleostomy. The robot was safely utilized in theatre in all three cases and successfully created a bony cochleostomy while preserving the underlying endosteal membrane. Our experiments have revealed that controlling the force of drilling during cochleostomy formation and opening the endosteal membrane with a pick will minimize the trauma sustained by the cochlea by a factor of 20. Additionally, the smart micro-drill can safely perform a bony cochleostomy in humans under operative conditions and preserve the integrity of the underlying endosteal membrane.


Effects of cytochalasin B and colchicine on the morphology of SW-13 human adrenal cortical tumor cells in culture.
Human adrenal cortical tumor cells (SW-13) grow into a typical epithelial cell monolayer when seeded onto culture dishes. The cells of the SW-13 population monolayer appear flattened with few conspicuous surface features. The cells are attached to one another at their lateral borders and are arranged in a cobblestone-like manner. Following Triton X-100 extraction, the distribution of the cytoskeletal elements was observed with scanning electron microscopic techniques to correspond to the shape of the non-extracted cell. Changes in the distribution and morphology of projections on the cell surface as well as changes in cell shape were revealed after treatment of the cultures with compounds which bring about microtubular and microfilament disruption. Following 60 minute treatment of the cell population with cytochalasin B (10 micrograms/ml), 90% of the cells became round while remaining attached to neighboring cells and to the substrate by slender cell processes and filopodia. Some bleeding could be seen on the cell surfaces of cytochalasin B treated cultures and an increase in the number of microvilli was evident. When the cytoskeletal elements were observed with scanning electron microscopic techniques after Triton X-100 extraction, the amount of peripheral cytoskeletal elements was decreased and only slender projections of the microfilaments and microtubules were evident. Colchicine (0.06 micrograms/ml) treatment of the SW-13 adrenal cell population resulted in the appearance of surface blebs within 10 minutes of the initiation of treatment. The changes in surface projections are discussed in relationship to the loss of microtubules and microfilaments from the cytoplasm of the cell.


Effect of Feeding Diets Combining Whole-Grain Paddy Rice and High Levels of Fat on Broiler Chicken Growth.
Previously, we showed that the growth of chicks fed a diet containing 43% whole-grain paddy rice and 10% soybean oil was retarded relative to a control group fed a corn-based diet containing 6% soybean oil. However, feeding chicks with 43% whole-grain paddy rice containing 6% soybean oil resulted in normal growth. It is possible that the observed growth retardation was caused by the high soybean oil content or resulted from the combination of whole-grain paddy rice and the high level of soybean oil which was added to the diet to maintain the overall energy content. The present study was therefore carried out to identify the reasons for the observed growth retardation. Thirty-six chicks (0-day-old) were divided into six equal-sized groups that were fed one of the following six experimental diets ad libitum for 28 d: two kinds of dehulled rice-based diets containing 5% or 10% soybean oil (DS5% or DS10%), another three whole-grain paddy rice-based diets containing 10% soybean oil, corn oil, or rendering oil (WS10%, WC10%, WR10%, respectively), and a WS10% diet supplemented with vitamin B12, methionine and ethoxyquin. The body weight gain of groups fed the WS10% and WC10% diets was significantly lower than the weight gain of birds fed the DS5% diet (control). In addition, the liver of birds fed the WS10% and WC10% diet exhibited significantly higher lipid peroxidation than that of the control group. In comparison, supplementation of the WS10% diet with vitamin B12, methionine and ethoxyquin dramatically improved growth and hepatic oxidation status. These results indicate that diets combining whole-grain paddy rice and high levels of soybean and corn oil adversely affect performance, presumably via lipid peroxidation in the liver.


Genetic localization and characterization of a pKM101-coded endonuclease.
The genetic and biochemical properties of an endonuclease mediated by the mutagenesis-enhancing plasmid pKM101 have been investigated. Taking advantage of the observation that this endonuclease, unlike host-coded DNases, is active in the presence of EDTA, we have developed an assay with nondenaturing acrylamide gels containing DNA. We have localized the plasmid DNA sufficient for nuclease expression to a 0.8-kilobase sequence that is near regions of DNA necessary for conjugal transfer, and we have determined that this gene is transcribed clockwise on the pKM101 map. The pKM101 gene mediating this activity codes for a 16,000-dalton protein, which is the same molecular mass as the nuclease monomer, leading us to conclude that this gene codes for the nuclease itself rather than for an activator of some host-coded enzyme. Cellular fractionation experiments have shown that the enzyme is localized in the periplasm. We have not been able to demonstrate any physiological role for the enzyme, but we have ruled out a direct involvement of the nuclease in any of the following known plasmid-associated phenotypes: (i) mutagenesis enhancement, (ii) conjugal transfer, (iii) entry exclusion, (iv) fertility inhibition of coresident P-group plasmids, (v) killing of Klebsiella pneumoniae used as conjugal recipients, and (vi) plasmid curing induced by treatment of cells with fluorodeoxyuridine. In addition, we have shown that the enzyme does not restrict bacteriophage or affect the ability of the host to utilize DNA as a source of thymine. Finally, we have shown that 11 of the 26 other plasmids tested also elaborated EDTA-resistant DNases.


Multidrug-resistant Acinetobacter infection mortality rate and length of hospitalization.
Acinetobacter infections have increased and gained attention because of the organism's prolonged environmental survival and propensity to develop antimicrobial drug resistance. The effect of multidrug-resistant (MDR) Acinetobacter infection on clinical outcomes has not been reported. A retrospective, matched cohort investigation was performed at 2 Baltimore hospitals to examine outcomes of patients with MDR Acinetobacter infection compared with patients with susceptible Acinetobacter infections and patients without Acinetobacter infections. Multivariable analysis controlling for severity of illness and underlying disease identified an independent association between patients with MDR Acinetobacter infection (n = 96) and increased hospital and intensive care unit length of stay compared with 91 patients with susceptible Acinetobacter infection (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2-5.2 and OR 2.1, 95% CI 1.0-4.3] respectively) and 89 uninfected patients (OR 2.5, 95% CI 1.2-5.4 and OR 4.2, 95% CI 1.5-11.6] respectively). Increased hospitalization associated with MDR Acinetobacter infection emphasizes the need for infection control strategies to prevent cross-transmission in healthcare settings.


Fibroblasts maintain the phenotype and viability of the rat heparin-containing mast cell in vitro.
Rat serosal heparin-containing mast cells (HP-MC) were maintained in vitro for as long as 30 days when co-cultured with mouse skin-derived 3T3 fibroblasts. In contrast, when the mast cells were cultured alone, on fibronectin-, gelatin-, or dermal-collagen-coated dishes, on acid and heat-killed fibroblasts in the presence or absence of 24 hr fibroblast-conditioned medium, or on a monolayer of mouse serosal macrophages, they failed to adhere to the dishes, released significant amounts of their histamine and lactate dehydrogenase, and stained with trypan blue, indicating a loss of viability. The rat serosal HP-MC cultured with the 3T3 fibroblasts became so adherent to the fibroblasts that the two cell types could be separated from one another only by trypsinization. The cultured HP-MC stained with both alcian blue and safranin and continued to synthesize proteoglycan at a rate comparable to that of freshly isolated cells. The 35S-labeled proteoglycan synthesized by these cultured cells, like that produced by freshly isolated rat serosal HP-MC, was a 750,000 to 1,000,000 m.w. proteoglycan containing only heparin glycosaminoglycans of 50,000 to 100,000 m.w. When HP-MC were cultured for 1 wk with the fibroblasts and were then incubated for 5 min with a 1/20 dilution of rabbit anti-rat IgE, they generated and released an average of 22 +/- 10 ng (mean +/- SD, n = 5) of prostaglandin D2 per 10(6) cells and exocytosed a higher net percentage of their total histamine content (44 +/- 11% [mean +/- SD, n = 8]) than did cells just isolated from the animal (6 +/- 4% [mean +/- SD, n = 4]). As assessed by electron microscopy, many of the cultured HP-MC resembled freshly isolated cells except that some secretory granules had fused with one another in some cells. Morphologically, after activation the cultured HP-MC underwent compound exocytosis like freshly isolated cells. These results demonstrate that the in vivo differentiated rat HP-MC maintain their histology, morphology, immunologic responsiveness, histamine content, and ability to synthesize heparin proteoglycan when co-cultured with living fibroblasts.


Phenotype-genotype analysis of dystrophinopathy caused by duplication mutation in Dystrophin gene in an African patient.
The dystrophinopathies, duchenne muscular dystrophy (DMD) and Becker muscular dystrophy are common X-linked genetic myopathies resulting from mutations in the dystrophin gene. Duplication is an uncommon mechanism of mutation occurring in about 5% of DMD cases. The global prevalence of DMD is reported as 1/18,000 males. There is little clinical or epidemiological data on African patients. To present the genotype-phenotype analysis of dystrophinopathy with an exon 8 through 9 duplication mutation in a patient of African/Ghanaian descent and his asymptomatic mother. Investigations including a biopsy of the vastus lateralis muscle and genetic testing of the patient and his mother. Genetic testing demonstrated a duplication of exons 8 through 9 of the dystrophin gene in both the patient and his mother. The muscle biopsy of the patient showed partial expression of the dystrophin protein. In the absence of a family history of dystrophinopathy, we hypothesize that this is a sporadic mutation occurring in the grand maternal lineage. This case extends the world wide epidemiology of this disease to include the African/Ghanaian population and confirms the vulnerability of the dystrophin gene to recurrent spontaneous mutations at the exon 8 and 9 site.


Effects of synthetic peptides on the inflammatory response and their therapeutic potential.
Recently, interest in small peptide molecules as potential drug candidates has revived. In this review, two series of synthetic peptides and their selective effects on the inflammatory response have been described, focusing on the intracellular pathways involved and on their therapeutic potential. A series of F(D)LF(D)LF analogs has been synthesized, including either N- t-Boc or different N-ureido substituents. The free acid derivatives as they are good candidates as antiinflammatory drugs are able to antagonize the multiple neutrophil functions evoked by N-formyl-L-methionyl-L-leucyl-Lphenylalanine (fMLF), i.e. chemotaxis, superoxide anion production and lysozyme release. Their methyl-ester derivatives are ineffective. The second series of peptides derives from the endogenous protein kinase C (PKC) inhibitor PKI55, a 55-amino acid protein, whose synthesis is induced by PKC activation, so that a feedback loop of inhibition is established. In vitro experiments showed that PKI55 inhibits recombinant PKC isoforms α, β1, β2, γ, δ, ζ, ; to identify the minimal amino acid sequence of PKI55 protein maintaining the inhibitory effects on PKC, peptides derived from both C- and N-terminal sequences have been synthesized. The N-terminal peptides 5 (MLYKLHDVCRQLWFSC), 8 (CRQLWFSC) and 9 (CRQLW), that in human neutrophils retain the inhibitory activity on PKC, decrease the chemotaxis, and, in mice, display anti-inflammatory and analgesic action, after both central and peripheral administration of very low doses. Furthermore, the peptide 5 shows neuroprotective activity in a model of cerebral ischemia in vitro, favouring the recovery of synaptic function. These findings suggest interesting possible therapeutic applications for these peptides.


Does feeding of hexachlorobenzene promote structural changes in rat-liver porphyrinogen carboxy-lyase?
This study aimed to determine whether drug treatment produced structural changes in porphyrinogen carboxy-lyase enzymatic protein, leading to altered properties. Rat-liver enzyme was obtained from normal animals and from those with hexachlorobenzene (HCB)-induced porphyria, and several of its properties were comparatively studied. The enzymes from both sources were purified 110-fold. They were similar in subcellular distribution, ammonium sulfate fractionation, calcium phosphate gel adsorption, storage stability, requirements of incubation media, effects of salts and photo-oxidizing agents. The enzymes differed with respect to effect of incubation temperature, pH, aerobiosis, chelating agents, dithiothreitol, methylene blue, heat stability and chromatographic behaviour on DEAE-cellulose and Sephadex G-100. These differences would appear to indicate structural differences between the two types of enzymatic protein. Since the porphyrinogenic action of HCB can be mediated through a metabolite, structural differences could arise through the binding of an inhibitory metabolite to the whole enzyme or through modifications to the protein during its synthesis.


Experimental and Theoretical Investigation of the Function of 4- tert-Butyl Pyridine for Interface Energy Level Adjustment in Efficient Solid-State Dye-Sensitized Solar Cells.
4- tert-Butylpyridine ( t-BP) is commonly used in solid state dye-sensitized solar cells (ssDSSCs) to increase the photovoltaic performance. In this report, the mechanism how t-BP functions as a favorable additive is investigated comprehensively. ssDSSCs were prepared with different concentrations of t-BP, and a clear increase in efficiency was observed up to a maximum concentration and for higher concentrations the efficiency thereafter decreases. The energy level alignment in the complete devices was measured using hard X-ray photoelectron spectroscopy (HAXPES). The results show that the energy levels of titanium dioxide are shifted further away from the energy levels of spiro-OMeTAD as the t-BP concentration is increased. This explains the higher photovoltage obtained in the devices with higher t-BP concentration. In addition, the electron lifetime was measured for the devices and the electron lifetime was increased when adding t-BP, which can be explained by the recombination blocking effect at the surface of TiO2. The results from the HAXPES measurements agree with those obtained from density functional theory calculations and give an understanding of the mechanism for the improvement, which is an important step for the future development of solar cells including t-BP.


Cone Photoreceptor Irregularity on Adaptive Optics Scanning Laser Ophthalmoscopy Correlates With Severity of Diabetic Retinopathy and Macular Edema.
To determine whether cone density, spacing, or regularity in eyes with and without diabetes (DM) as assessed by high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) correlates with presence of diabetes, diabetic retinopathy (DR) severity, or presence of diabetic macular edema (DME). Participants with type 1 or 2 DM and healthy controls underwent AOSLO imaging of four macular regions. Cone assessment was performed by independent graders for cone density, packing factor (PF), nearest neighbor distance (NND), and Voronoi tile area (VTA). Regularity indices (mean/SD) of NND (RI-NND) and VTA (RI-VTA) were calculated. Fifty-three eyes (53 subjects) were assessed. Mean ± SD age was 44 ± 12 years; 81% had DM (duration: 22 ± 13 years; glycated hemoglobin [HbA1c]: 8.0 ± 1.7%; DM type 1: 72%). No significant relationship was found between DM, HbA1c, or DR severity and cone density or spacing parameters. However, decreased regularity of cone arrangement in the macular quadrants was correlated with presence of DM (RI-NND: P = 0.04; RI-VTA: P = 0.04), increasing DR severity (RI-NND: P = 0.04), and presence of DME (RI-VTA: P = 0.04). Eyes with DME were associated with decreased density (P = 0.04), PF (P = 0.03), and RI-VTA (0.04). Although absolute cone density and spacing don't appear to change substantially in DM, decreased regularity of the cone arrangement is consistently associated with the presence of DM, increasing DR severity, and DME. Future AOSLO evaluation of cone regularity is warranted to determine whether these changes are correlated with, or predict, anatomic or functional deficits in patients with DM.


Correlation between ultrasound-diagnosed non-alcoholic fatty liver and periodontal condition in a cross-sectional study in Japan.
This cross-sectional study investigated the relationship between periodontal condition and ultrasound-diagnosed non-alcoholic fatty liver disease (NAFLD) in a Japanese oral health check population. A total of 1226 consecutive participant were enrolled in the study. Abdominal ultrasonography was applied to diagnose NAFLD. Of the study participants, 339 (27.7%) had ultrasonography-diagnosed NAFLD. The participants with NAFLD had a significantly higher prevalence of probing pocket depth (PPD) ≥ 4 mm (86.7%) than those without NAFLD (72.9%) (p < 0.05). After adjusting for gender, age, Brinkman index, regular exercise habits, body mass index, number of teeth present, presence of periodontitis, blood pressure, and serum parameters, there was a statistically significant difference in the adjusted odds ratios of having PPD ≥ 4 mm for NAFLD (Odds ratio = 1.881, 95% confidence interval 1.184-2.987, p < 0.01). Having PPD ≥ 4 mm may be a risk factor for ultrasound-diagnosed NAFLD in this cross-sectional study of a Japanese oral health check population.


Broad chromosomal domains of histone modification patterns in C. elegans.
Chromatin immunoprecipitation identifies specific interactions between genomic DNA and proteins, advancing our understanding of gene-level and chromosome-level regulation. Based on chromatin immunoprecipitation experiments using validated antibodies, we define the genome-wide distributions of 19 histone modifications, one histone variant, and eight chromatin-associated proteins in Caenorhabditis elegans embryos and L3 larvae. Cluster analysis identified five groups of chromatin marks with shared features: Two groups correlate with gene repression, two with gene activation, and one with the X chromosome. The X chromosome displays numerous unique properties, including enrichment of monomethylated H4K20 and H3K27, which correlate with the different repressive mechanisms that operate in somatic tissues and germ cells, respectively. The data also revealed striking differences in chromatin composition between the autosomes and between chromosome arms and centers. Chromosomes I and III are globally enriched for marks of active genes, consistent with containing more highly expressed genes, compared to chromosomes II, IV, and especially V. Consistent with the absence of cytological heterochromatin and the holocentric nature of C. elegans chromosomes, markers of heterochromatin such as H3K9 methylation are not concentrated at a single region on each chromosome. Instead, H3K9 methylation is enriched on chromosome arms, coincident with zones of elevated meiotic recombination. Active genes in chromosome arms and centers have very similar histone mark distributions, suggesting that active domains in the arms are interspersed with heterochromatin-like structure. These data, which confirm and extend previous studies, allow for in-depth analysis of the organization and deployment of the C. elegans genome during development.


Beta-adrenergic desensitization reduces the sensitivity of adenylate cyclase for magnesium in permeabilized lymphocytes.
Magnesium modulates hormone-sensitive adenylate cyclase activation. In the present studies, we have examined the magnesium requirement of beta-adrenergic-stimulated adenylate cyclase activity in permeabilized human lymphocytes. Following isoproterenol pretreatment, under conditions that lead to homologous beta-adrenergic desensitization, the EC50 of magnesium for beta-adrenergic-stimulated adenylate cyclase activity was significantly increased [control; 1.99 (+0.81/-0.57) mM; desensitized; 3.82 (+0.31/-0.29) mM]. Further, when assays were performed at high Mg2+ concentrations following agonist pretreatment, we detected only small and inconsistant reductions in beta-adrenergic-stimulated adenylate cyclase activity and in beta-adrenergic cAMP-dependent protein kinase activity. In contrast, the detection of agonist-induced beta-adrenergic receptor sequestration and alterations in receptor affinity for agonists was not qualitatively affected by changes in magnesium concentrations. The data demonstrate that the functional consequences of beta-adrenergic desensitization may be obscured at high magnesium concentrations. Furthermore, in this system desensitization may be viewed as a beta-receptor-specific reduction in magnesium sensitivity.


Green tea polyphenols attenuate hepatic steatosis, and reduce insulin resistance and inflammation in high-fat diet-induced rats.
Non‑alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and inflammation; however, the exact pathogenesis of NAFLD is not fully understood. Green tea polyphenols (GTP) exhibit beneficial effects against metabolic syndrome. However, the effect of GTP on NAFLD remains largely unknown. The aim of the present study was to investigate the effects of GTP on NAFLD in high‑fat diet (HFD)‑induced rats. The NAFLD rat model was induced with a HFD for 8 weeks. A total of 30 adult male Sprague Dawley rats were randomly divided into three groups: i) Normal control group; ii) HFD group; and iii) HFD with GTP group. Hematoxylin and eosin and Oil Red O analyses were performed. The levels of alanine aminotransferase (ALT), aspartate amino-transferase (AST) and inflammatory cytokines in the serum, as well as oxidative stress markers and hepatic lipids in the liver were measured. In addition, parameters associated with glucose metabolism were also assessed. Western blotting and RT‑qPCR were used to determine the expression levels of 5' adenosine monophosphate‑activated protein kinase (AMPK). HFD‑induced rats exhibited features associated with NAFLD. GTP intervention significantly reduced serum ALT and AST levels. Fasting serum glucose, insulin resistance and hepatic lipid levels were all decreased in the GTP‑treated rats. GTP also significantly decreased the levels of TNF‑α, IL‑6 and malondialdehyde. In contrast, superoxide dismutase levels were increased in the liver. Furthermore, GTP also significantly increased phosphorylation of AMPK and attenuated histopathological changes indicative of injury in liver tissue. GTP has a protective effect on HFD‑induced hepatic steatosis, insulin resistance and inflammation, and the underlying mechanism may involve the AMPK pathway.


Bibliometric analysis on the adoption of artificial intelligence applications in the e-health sector.
Artificial Intelligent (AI) applications in e-health have evolved considerably in the last 25 years. To track the current research progress in this field, there is a need to analyze the most recent trend of adopting AI applications in e-health. This bibliometric analysis study covers AI applications in e-health. It differs from the existing literature review as the journal articles are obtained from the Scopus database from its beginning to late 2021 (25 years), which depicts the most recent trend of AI in e-health. The bibliometric analysis is employed to find the statistical and quantitative analysis of available literature of a specific field of study for a particular period. An extensive global literature review is performed to identify the significant research area, authors, or their relationship through published articles. It also provides the researchers with an overview of the work evolution of specific research fields. The study's main contribution highlights the essential authors, journals, institutes, keywords, and states in developing the AI field in e-health.


Extra osseous primary Ewing's sarcoma.
The case of 20 years old boy with an extra osseous Ewing's sarcoma is described. He was initially diagnosed as a case of infiltrative malignant tumour of left suprarenal gland on the basis of preoperative workup but postoperative biopsy of surgically excised specimen confirmed Extra-osseous Ewing's Sarcoma (EES) suprarenal gland with no evidence of malignancy on skeletal scintiscan, bone marrow aspirate and histopathology Suprarenal location of primary EES is unknown and probably has not been reported in literature. We report a unique case of EES.


Geographic risk for lyme disease and human granulocytic ehrlichiosis in southern New York state.
Ixodes scapularis, the tick vector of Lyme disease and human granulocytic ehrlichiosis (HGE), is prevalent in much of southern New York state. The distribution of this species has increased, as have reported cases of both Lyme disease and HGE. The unreliability of case reports, however, demonstrates the need for tick and pathogen surveillance in order to accurately define areas of high risk. In this study, a total of 89,550 m2 at 34 study sites was drag sampled in 1995 and a total of 51,540 m2 at 40 sites was sampled in 1996 to determine tick and pathogen distribution in southern New York state. I. scapularis was collected from 90% of the sites sampled, and regionally, a 2.5-fold increase in nymphal abundance occurred from 1995 to 1996. I. scapularis individuals from all sites were infected with Borrelia burgdorferi in 1995, while an examination of ticks for both B. burgdorferi and the agent of HGE in 1996 confirmed that these organisms were present in all counties; the average coinfection rate was 1.9%. No correlation was found between estimated risk and reported cases of Lyme disease. The geographic disparity of risk observed among sites in this study underscores the need for vector and pathogen surveillance on a regional level. An entomologic risk index can help identify sites for targeted tick control efforts.


Comparison of electroacupuncture and medical treatment for functional constipation: a systematic review and meta-analysis.
To assess the effectiveness of electroacupuncture (EA) relative to conventional medication in functional constipation (FC). Systematic review and meta-analysis. To be included, studies needed to: (1) have been randomised controlled trials; (2) have recruited adult patients diagnosed with FC according to the Rome II/III criteria or the American Gastroenterological Association guideline for chronic FC; and (3) have randomised patients to be treated with EA or anti-constipation medication. We searched Medline, the Cochrane Library and Embase databases for articles published up to 30 June 2016. EA or anti-constipation medication. The primary outcome was the change in the number of weekly spontaneous bowel movements. Secondary outcomes were total response rate (or total effective rate), symptom reduction and Cleveland Clinic constipation scores. The pooled results showed significantly more improvement in the frequency of spontaneous bowel movements in the EA treatment group compared with the medicine-treated group (pooled SMD 0.244, 95% CI 0.065 to 0.424, P=0.008). Deep-needling EA was significantly more effective than treatment with medication at increasing the frequency of spontaneous bowel movements (p=0.019). Significantly greater improvement was also seen for total response rates (p=0.018) and reductions in symptom score (p<0.001) in EA-treated patients. EA was more effective than medication at improving spontaneous bowel movements and total response rate, and reducing the symptoms of FC.


Morphology and identification of first instar larvae of Australian blowflies of the genus Chrysomya of forensic importance.
Light microscopy photographs, line illustrations and scanning electron microscopy micrographs are provided for first instar larvae of six Australian species of Chrysomya. All species have confirmed or potential in forensic investigations given their carrion-breeding habits. Morphology of the first instar larvae of Ch. nigripes, Ch. rufifacies, Ch. saffranea and Ch. varipes is revised, while larvae of Ch. incisularis and Ch. latifrons are described for the first time. The following morphological structures are documented: pseudocephalon, antennal complex, maxillary palpus, facial mask, thoracic and abdominal spinulation, spiracular field, posterior spiracles and cephaloskeleton. New diagnostic features of the cephaloskeleton and the spinulation of the abdominal segments are described. Verification of earlier descriptions revealed major discrepancies between published data, especially in the case of Ch. nigripes. The present results allow clarification, correction and, especially, complementation of the existing information provided by numerous authors. Finally, an identification key for first instar larvae of Australian necrophagous Chrysomya is presented.


Determining Dark-Matter-Electron Scattering Rates from the Dielectric Function.
We show that the rate for dark-matter-electron scattering in an arbitrary material is determined by an experimentally measurable quantity, the complex dielectric function, for any dark matter interaction that couples to electron density. This formulation automatically includes many-body effects, eliminates all systematic theoretical uncertainties on the electronic wave functions, and allows a direct calibration of the spectrum by electromagnetic probes such as infrared spectroscopy, x-ray scattering, and electron energy-loss spectroscopy. Our formalism applies for several common benchmark models, including spin-independent interactions through scalar and vector mediators of arbitrary mass. We discuss the consequences for standard semiconductor and superconductor targets and find that the true reach of superconductor detectors for light mediators exceeds previous estimates by several orders of magnitude, with further enhancements possible due to the low-energy tail of the plasmon. Using a heavy-fermion superconductor as an example, we show how our formulation allows a rapid and systematic investigation of novel electron scattering targets.


N-Acetylcysteine improves the disturbed thiol redox balance after methionine loading.
Methionine loading seems to be accompanied by increased oxidative stress and damage. However, it is not known how this oxidative stress is generated. We performed the present crossover study to further elucidate the effects of methionine loading on oxidative stress in the blood of healthy volunteers, and to examine possible preventative effects of N -acetylcysteine (NAC) administration. A total of 18 healthy subjects were given two oral methionine loads of 100 mg/kg body weight, 4 weeks apart, one without NAC (Met group), and one in combination with supplementation with 2x900 mg doses of NAC (Met+NAC group). Blood samples were collected before and 2, 4, 8 and 24 h after methionine loading for measurements of thiol levels, protein carbonyls, lipid peroxidation, cellular fibronectin and ferric reducing ability of plasma (FRAP; i.e. antioxidant capacity). After methionine loading, whole-blood levels of free and oxidized cysteine and homocysteine were increased in both groups. Furthermore, the total plasma levels of homocysteine were higher, whereas those of cysteine were lower, after methionine loading in both groups. Lower levels of oxidized homocysteine and a higher free/oxidized ratio were found in the Met+NAC group compared with the Met group. Although the antioxidant capacity decreased after methionine loading, no major changes over time were found for protein carbonyls or cellular fibronectin in either group. Our results suggest that methionine loading may initiate the generation of reactive oxygen species by the (auto)-oxidation of homocysteine. In addition, supplementation with NAC seems to be able to partially prevent excessive increases in the levels of homocysteine in plasma and of oxidized homocysteine in whole blood, and might thereby contribute to the prevention of oxidative stress.


Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity.
Like other tumors, aggressive soft tissue sarcomas (STS) use glycolysis rather than mitochondrial oxidative phosphorylation (OXPHOS) for growth. Given the importance of the cofactor coenzyme A (CoA) in energy metabolism, we investigated the impact of Vnn1 pantetheinase-an enzyme that degrades pantetheine into pantothenate (vitamin B5, the CoA biosynthetic precursor) and cysyteamine-on tumor growth. Using two models, we show that Vnn1+ STS remain differentiated and grow slowly, and that in patients a detectable level of VNN1 expression in STS is associated with an improved prognosis. Increasing pantetheinase activity in aggressive tumors limits their growth. Using combined approaches, we demonstrate that Vnn1 permits restoration of CoA pools, thereby maintaining OXPHOS. The simultaneous production of cysteamine limits glycolysis and release of lactate, resulting in a partial inhibition of STS growth in vitro and in vivo. We propose that the Warburg effect observed in aggressive STS is reversed by induction of Vnn1 pantetheinase and the rewiring of cellular energy metabolism by its products.


Influences of the bark economics spectrum and positive termite feedback on bark and xylem decomposition.
The plant economics spectrum integrates trade-offs and covariation in resource economic traits of different plant organs and their consequences for pivotal ecosystem processes, such as decomposition. However, in this concept stems are often considered as one unit ignoring the important functional differences between wood (xylem) and bark. These differences may not only affect the performance of woody plants during their lifetime, but may also have important "afterlife effects." Specifically, bark quality may strongly affect deadwood decomposition of different woody species. We hypothesized that (1) bark quality strongly influences bark decomposability to microbial decomposers, and possibly amplifies the interspecific variation in decomposition by invertebrate consumption, especially termites; and (2) bark decomposition has secondary effects on xylem mass loss by providing access to decomposers including invertebrates such as termites. We tested these hypotheses across 34 subtropical woody species representing five common plant functional types, by conducting an in situ deadwood decomposition experiment over 12-month in two sites in subtropical evergreen broad-leaved forest in China. We employed visual examination and surface density measurement to quantify termite consumption to both bark and the underlying xylem, respectively. Using principal component analysis, we synthesized seven bark traits to provide the first empirical evidence for a bark economics spectrum (BES), with high BES values (i.e., bark thickness, nitrogen, phosphorus, and cellulose contents) indicating a resource acquisitive strategy and low BES values (i.e., carbon, lignin, and dry matter contents) indicating a resource conservative strategy. The BES affected interspecific variation in bark mass loss and this relationship was strongly amplified by termites. The BES also explained nearly half of the interspecific variation in termite consumption to xylem, making it an important contributor to deadwood decomposition overall. Moreover, the above across-species relationships manifested also within plant functional types, highlighting the value of using continuous variation in bark traits rather than categorical plant functional types in carbon cycle modeling. Our findings demonstrate the potent role of the BES in influencing deadwood decomposition including positive invertebrate feedback thereon in warm-climate forests, with implications for the role of bark quality in carbon cycling in other woody biomes.


Io's atmospheric response to eclipse: UV aurorae observations.
The New Horizons (NH) spacecraft observed Io's aurora in eclipse on four occasions during spring 2007. NH Alice ultraviolet spectroscopy and concurrent Hubble Space Telescope ultraviolet imaging in eclipse investigate the relative contribution of volcanoes to Io's atmosphere and its interaction with Jupiter's magnetosphere. Auroral brightness and morphology variations after eclipse ingress and egress reveal changes in the relative contribution of sublimation and volcanic sources to the atmosphere. Brightnesses viewed at different geometries are best explained by a dramatic difference between the dayside and nightside atmospheric density. Far-ultraviolet aurora morphology reveals the influence of plumes on Io's electrodynamic interaction with Jupiter's magnetosphere. Comparisons to detailed simulations of Io's aurora indicate that volcanoes supply 1 to 3% of the dayside atmosphere.


NMR analyses of the conformations of L-isoleucine and L-valine bound to Escherichia coli isoleucyl-tRNA synthetase.
The 400-MHz 1H NMR spectra of L-isoleucine and L-valine were measured in the presence of Escherichia coli isoleucyl-tRNA synthetase (IleRS). Because of chemical exchange of L-isoleucine or L-valine between the free state and the IleRS-bound state, a transferred nuclear Overhauser effect (TRNOE) was observed among proton resonances of L-isoleucine or L-valine. However, in the presence of isoleucyl adenylate tightly bound to the amino acid activation site of IleRS, no TRNOE for L-isoleucine or L-valine was observed. This indicates that the observed TRNOE is due to the interaction of L-isoleucine or L-valine with the amino acid activation site of IleRS. The conformations of these amino acids in the amino acid activation site of IleRS were determined by the analyses of time dependences of TRNOEs and TRNOE action spectra. The IleRS-bound L-isoleucine takes the gauche+ form about the C alpha-C beta bond and the trans form about the C beta-C gamma 1 bond. The IleRS-bound L-valine takes the gauche- form about the C alpha-C beta bond. Thus, the conformation of IleRS-bound L-valine is the same as that of IleRS-bound L-isoleucine except for the delta-methyl group. The side chain of L-isoleucine or L-valine lies in an aliphatic hydrophobic pocket of the active site of IleRS. Such hydrophobic interaction with IleRS is more significant for L-isoleucine than for L-valine. The TRNOE analysis is useful for studying the amino acid discrimination mechanism of aminoacyl-tRNA synthetases.


Clear cell "sugar" tumor of the lung: a case report and review of the literature.
Clear cell "sugar" tumor of the lung is a rare benign tumor that is often an incidental finding during histopathologic workup. It strikingly has a similar resemblance to renal cell carcinoma (RCC) cells. Under the microscope, it is composed of thin cell walls and high levels of glycogen. Therefore, when diagnosed, it is important to rule out metastatic RCC. Here, in this case report, we present a case of clear cell "sugar" tumor of the lung and review the literature that has been published. Clear cell tumor of the lung needs to be studied more extensively as it can present with unique signs and symptoms. It has also occurred in the presence of systemic diseases. This has led researchers to theorize about its etiology which we discuss in this case report.


Prokaryotic SPHINX 1.8 REP protein is tissue-specific and expressed in human germline cells.
Small circular DNAs of 1.8 and 2.4 kb were initially discovered in highly infectious Creutzfeldt-Jakob Disease (CJD) and scrapie particles from mammalian brain and cultured cells. Surprisingly, these protected cytoplasmic "SPHINX" DNAs contained replication (REP) initiation sequences resembling those of Acinetobacter phage viruses. An antibody was generated against a REP peptide encoded by the SPHINX 1.8 open reading frame (ORF) that was not present in mammals. It bound to a 41kd "spx1" protein on Western blots. Cytologically, spx1 concentrated in spinal cord synapses and pancreatic islet, but not exocrine cells. We hypothesized that circular SPHINX DNAs are ancient symbiotic elements that can participate in functional differentiation and neurodegeneration. Cell and tissue-specific patterns of spx1 expression shown below implicate somatic cell-to-cell communication and differentiation functions that would favor conservation of SPHINX 1.8 in evolution. Remarkably, primary human oocytes and spermatogonia, but not mature sperm, displayed intense cytoplasmic spx1 signals that underscore the maternal inheritance of SPHINX 1.8. These findings should encourage investigations of unexplored networks of incorporated environmental infectious agents that can be key actors in progressive neurodegeneration, immunity, and cancer.


Optimization of cotton variety registration criteria aided with a genotype-by-trait biplot analysis.
China is one of the largest cotton producing countries in the world thanks to high yields, on which a variety registration system has mainly focused, so that a lack of quality is nowadays acknowledged as a weak point of the cotton industry in that country. The objective of this study was to check the hypothesis that bias in cultivar selection in favor of yield has been maintained through the application of an imperfect selection index (SI), but that a better outcome is possible. Our demonstration is based on an analysis of the data from ten years of cotton variety trials using genotype-by-trait biplots, implemented both for the cultivar selection index (SI) currently applied in China and for an adjusted selection index (ASI) that more effectively took into account the antagonism between yield and quality traits. The main findings were: 1) significant negative associations between yield and fiber quality hindered their simultaneous improvement; 2) registered genotypes were mainly determined by the SI which was primarily yield-oriented; 3) no progress in fiber quality was recorded unlike yield; 4) balanced progress in yield and quality is possible through an adjusted selection index (ASI) guided by genotype-by-trait biplot analysis.


The role of bacteria in oral cancer.
Despite the widening interest in the possible association between bacteria and different stages of cancer development, our knowledge in its relation to oral cancers remains inadequate. The aim of this review article is to derive a better understanding on the role of various micro-organisms in the etiogenesis of oral cancers through all the available data on the pubmed. Different bacteria have been proposed to induce carcinogenesis either through induction of chronic inflammation or by interference, either directly or indirectly, with eukaryotic cell cycle and signaling pathways, or by metabolism of potentially carcinogenic substances like acetaldehyde causing mutagenesis. Studies have shown diversity of isolated bacterial taxa between the oral cancer tissue specimens and the control, with Exiguobacterium oxidotolerans, Prevotella melaninogenica, Staphylococcus aureus and Veillonella parvula being specific for tumorogenic tissues. Most isolates are saccharolytic and acid tolerant. Streptococcus anginosus, commonly linked with esophageal and pharyngeal cancers, is not of significance in oral cancers. Similarly, significant salivary specificity is noted for three bacteria, namely, Capnocytophaga gingivalis, P. melaninogenica, and Streptococcus mitis in oral cancer patients, making these species salivary markers for the early detection of oral cancers and thus improving the survival rate significantly. Also, such high degree of bacterial specificity in oral cancers has also provoked the designing of new treatment options for cancer prevention by way of vaccine delivery. However, for the success of these steps, a deeper exploration into this subject with a greater understanding is warranted.


Reduced hepatic injury in Toll-like receptor 4-deficient mice following D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.
Liver transplantation is the only therapy of proven benefit in fulminant hepatic failure (FHF). Lipopolysaccharide (LPS), D-galactosamine (GalN)-induced FHF is a well established model of liver injury in mice. Toll-Like Receptor 4 (TLR4) has been identified as a receptor for LPS. The aim of this study was to investigate the role of TLR4 in FHF induced by D-GalN/LPS administration in mice. Wild type (WT) and TLR4 deficient (TLR4ko) mice were studied in vivo in a fulminant model induced by GalN/LPS. Hepatic TLR4 expression, serum liver enzymes, hepatic and serum TNF-α and interleukin-1β levels were determined. Apoptotic cells were identified by immunohistochemistry for caspase-3. Nuclear factor-kappaβ (NF-κ β) and phosphorylated c-Jun hepatic expression were studied using Western blot analysis. All WT mice died within 24 hours after administration of GalN/LPS while all TLR4ko mice survived. Serum liver enzymes, interleukin-1β, TNF-α level, TLR4 mRNA expression, hepatic injury and hepatocyte apoptosis all significantly decreased in TLR4ko mice compared with WT mice. A significant decrease in hepatic c-Jun and IκB signaling pathway was noted in TLR4ko mice compared with WT mice. In conclusion, following induction of FHF, the inflammatory response and the liver injury in TLR4ko mice was significantly attenuated through decreased hepatic c-Jun and NF-κB expression and thus decreased TNF-α level. Down-regulation of TLR4 expression plays a pivotal role in GalN/LPS induced FHF. These findings might have important implications for the use of the anti TLR4 protein signaling as a potential target for therapeutic intervention in FHF.


Daidzein prevents the increase in CD4+CD28null T cells and B lymphopoesis in ovariectomized mice: a key mechanism for anti-osteoclastogenic effect.
Estrogen deficiency leads to an upregulation of TNF-α producing T cells and B-lymphopoesis which augments osteoclastogenesis. Estrogen deficiency also increases the population of premature senescent CD4⁺ CD28null T cells which secrete a higher amount of TNF-α thus leading to enhanced osteoclastogenesis. Isoflavonoids like daidzein and genistein are found mostly in soybeans, legumes, and peas. These share structural similarity with 17β-stradiol (E2) and have osteoprotective role. This study explores the effect of daidzein (Daid) on the proliferation of TNF-α producing T cells, premature senescent T cells and B cell lymphopoesis under estrogen deficient conditions. For this study adult Balb/c mice were treated with Daid at 10 mg/kg body weight dose by oral gavage daily post ovariectomy (Ovx). After six weeks animals were autopsied and bone marrow and spleen cells were collected for FACS analysis. Blood serum was collected for ELISA. It was observed that Ovx mice treated with Daid for six weeks show reduction in Ovx induced expansion of CD4⁺ T cells in bone marrow and spleen when analysed by flow cytometry. Estrogen deficiency led to increased prevalence of TNF-α secreting CD4⁺CD28null T cells, however, treatment with Daid increased the percentage of CD4⁺CD28⁺ T cells. Co-culture of CD4⁺CD28null T cells and bone marrow resulted in enhanced osteoclastogenesis as evident by increased tartarate resistant acid phosphatase (TRAP) expression, an osteoclast marker. However, treatment with Daid resulted in reduced osteoclastogenesis in CD4⁺CD28null T cells and bone marrow cell co-culture. Daid also regulated B lymphopoesis and decreased mRNA levels of RANKL in B220⁺ cells. Taken together, we propose that one of the mechanisms by which Daid prevents bone loss is by reversing the detrimental immune changes as a result of estrogen deficiency.


Influence of pizotifen and ergotamine on the venoconstrictor effect of 5-hydroxytryptamine and noradrenaline in man.
The influence of locally infused pizotifen (80 ng) and ergotamine (16 ng and 4 ng) on the compliance of superficial hand veins in man, and their interactions with the venoconstrictor effects of noradrenaline and 5-hydroxytryptamine (5-HT), were investigated in a placebo-controlled study in healthy volunteers. Pizotifen alone reduced venous compliance and produced a parallel displacement to the right of the 5-HT dose-response curve suggestive of competitive antagonism. The venoconstrictor effect of noradrenaline was not influenced by pizotifen. This confirms the selective antagonism of 5-HT by pizotifen and supports the existence of specific 5-HT receptors on human veins. After infusion of 16 ng ergotamine, which by itself reduced venous compliance, the venoconstrictor effects of the lower doses of 5-HT and of all doses of noradrenaline were larger but still never exceeded the arithmetic sum of the separate effects of noradrenaline or 5-HT and ergotamine. A lower dose of ergotamine (4 ng) induced only a small venoconstriction and did not influence the constrictor effect of noradrenaline. Therefore, in contrast to previous observations, no potentiation of the venoconstrictor effect of noradrenaline by ergotamine was observed under the present experimental conditions. The additive effect of noradrenaline and ergotamine may well explain its therapeutic action in the treatment of migraine.


The influence of processing and preservation on the retention of health-promoting compounds in broccoli.
In this work the effects of common household practices such as chilling, freezing, and cooking on vitamin C retention in broccoli (Marathon cv.), as well as their influence on the release of sulforaphane upon enzymatic hydrolysis of glucoraphanin by the endogenous enzyme myrosinase, were investigated. When chilled at 6 degrees C and 95% R.H. for 35 d, broccoli showed a vitamin C and sulforaphane loss of about 39% and 29%, respectively, while storage at -18 degrees C for 60 d resulted in similar losses, but mainly due to the blanching step. Boiling, steaming, microwaving, pressure-cooking, and the combined use of pressure and microwaves were the cooking methods investigated. Boiling and steaming caused significant vitamin C losses, 34% and 22%, respectively, while with the other treatments more than 90% retention was observed. Sulforaphane was no more detectable after boiling or steaming, while pressure/microwave cooking did not cause any significant loss. The quantitative distribution of these moieties in the florets and stems of fresh and chilled broccoli was also investigated.


Differential effect of age on hippocampal subfields assessed using a new high-resolution 3T MR sequence.
Recent advances in neuroimaging have highlighted the interest to differentiate hippocampal subfields for cognitive neurosciences and more notably in assessing the effects of normal and pathological aging. The main goal of the present study is to investigate the effects of normal aging onto the volume of the different hippocampal subfields. For this purpose, we developed a new magnetic resonance sequence together with reliable tracing guidelines to assess the volume of different subfields of the hippocampus using a 3 Tesla scanner, and estimated the validity of a simpler and less time-consuming method based on the widely-used automatic Voxel-Based Morphometry (VBM) technique. Three hippocampal regions of interest were delineated on the right and left hippocampi of 50 healthy subjects between 18 and 68 years old corresponding to the CA1, subiculum and other (including CA2-3-4 and Dentate Gyrus) subfields. A strong effect of age was found on the volume of the subiculum only, with a decrease paralleling that of the global gray matter volume, while CA1 and other subfields seemed relatively spared. Although less precise than the ROI-tracing technique, the VBM-based method appeared as a reliable alternative especially to distinguish CA1 and subiculum subfields. Our findings of a specific effect of age on the subiculum are consistent with the developmental hypothesis ("last-in first-out" theory). This contrasts with the predominant vulnerability of the CA1 subfield to Alzheimer's disease reported in several previous studies, suggesting that the assessment of hippocampal subfields may improve the discrimination between normal and pathological aging.


Glucose utilization and role of blood in endotoxin shock.
The present study was conducted to explore influences modifying glucose uptake in canine blood administered LD100 E. coli endotoxin. Particular emphasis was given to assay the role of the white blood cell (WBC) in glucose utilization. Significant increases in glucose uptake and lactic acid production, attributed to increased activity of the WBC, were observed 1-3 h after endotoxin was added to blood in vitro. Although a net increase in glucose utilization was noted, endotoxin simultaneously exerted adverse effects by depressing glucose uptake below predicted values (Q10 = 2.12 with LD100 endotoxin vs. 2.78 in saline controls) and increasing WBC mortality rate. Blood from dogs pretreated with sublethal doses of endotoxin in vivo utilized glucose at an accelerated rate when subjected to endotoxin in vitro. Excess glucose was consumed because of elevated numbers of white blood cells although additional glucose requirements after endotoxin were independent of temperature between the ranges of 34-41 degrees C. All animals pretreated with daily sublethal injections of endotoxin for 3 days survived superlethal doses of endotoxin.


Comparison of urinary bladder and ear biopsy samples for determining prevalence of Borrelia burgdorferi in rodents in central Europe.
PCR was used to compare urinary bladder and ear biopsy samples from four European species of wild rodents for the presence of Borrelia burgdorferi sensu lato. From 60 paired comparisons of bladder and ear biopsy samples, the PCR results were concordantly positive or negative in 43 samples (71.7%). Of the 17 which differed, 14 bladder samples were positive and ear samples were negative while the converse occurred for three samples. Thus ear biopsy samples led to a significantly lower estimate of infection than bladder biopsy samples. This suggests that the use of ear biopsy samples in epidemiological studies of B. burgdorferi in Central European rodents is likely to lead to underestimates of the prevalence.


Therapeutic dose from a pyroelectric electron accelerator.
Simple heating of pyroelectric crystals has been used as the basis for compact sources of X rays, electrons, ions and neutrons. We report on the evaluation of the feasibility of using a portable pyroelectric electron accelerator to deliver a therapeutic dose to tissue. Such a device could be mass produced as a handheld, battery-powered instrument. Experiments were conducted with several crystal sizes in which the crystal was heated inside a vacuum chamber and the emitted electrons were allowed to penetrate a thin beryllium window into the surrounding air. A Faraday cup was used to count the number of electrons that exited the window. The energy of these electrons was determined by measuring the energy spectrum of the X rays that resulted from the electron interactions with the Faraday cup. Based on these measurements, the dose that this source could deliver to tissue was calculated using Monte Carlo calculations. It was found that 10(13) electrons with a peak energy of the order of 100 keV were emitted from the beryllium window and could deliver a dose of 1664 Gy to a 2-cm-diameter, 110-microm-deep region of tissue located 1.5 cm from the window with air between the window and the tissue. This dose level is high enough to consider this technology for medical applications in which shallow energy deposition is beneficial.


An explosive innovation: Phylogenetic relationships of Solanum section Gonatotrichum (Solanaceae).
Solanum is one of the largest plant genera and exhibits a wide range of morphological diversity. Solanum section Gonatotrichum, the focus of this study, is unique within the genus because of its fruits that swell with turgor pressure and explosively dehisce to disperse the seeds. We infer phylogenetic relationships within section Gonatotrichum using DNA sequence data from two nuclear regions (ITS and the granule-bound starch synthase gene [GBSSI or waxy]) and the chloroplast region trnT-F. The resulting phylogenetic trees support the monophyly of the section with the inclusion of Solanum lignescens, a species not previously thought to belong to the group due to the presence of stellate hairs. This inclusion of this species in section Gonatotrichum suggests that the simple, often geniculate hairs of species in the group may represent reduced stellate hairs. The presence of heterantherous flowers appears to be derived in the section, but this character is largely lost in Solanum parcistrigosum.


Superior Changes in Jump, Sprint, and Change-of-Direction Performance but Not Maximal Strength Following 6 Weeks of Velocity-Based Training Compared With 1-Repetition-Maximum Percentage-Based Training.
To compare the effects of velocity-based training (VBT) and 1-repetition-maximum (1RM) percentage-based training (PBT) on changes in strength, loaded countermovement jump (CMJ), and sprint performance. A total of 24 resistance-trained males performed 6 weeks of full-depth free-weight back squats 3 times per week in a daily undulating format, with groups matched for sets and repetitions. The PBT group lifted with fixed relative loads varying from 59% to 85% of preintervention 1RM. The VBT group aimed for a sessional target velocity that was prescribed from pretraining individualized load-velocity profiles. Thus, real-time velocity feedback dictated the VBT set-by-set training load adjustments. Pretraining and posttraining assessments included the 1RM, peak velocity for CMJ at 30%1RM (PV-CMJ), 20-m sprint (including 5 and 10 m), and 505 change-of-direction test (COD). The VBT group maintained faster (effect size [ES] = 1.25) training repetitions with less perceived difficulty (ES = 0.72) compared with the PBT group. The VBT group had likely to very likely improvements in the COD (ES = -1.20 to -1.27), 5-m sprint (ES = -1.17), 10-m sprint (ES = -0.93), 1RM (ES = 0.89), and PV-CMJ (ES = 0.79). The PBT group had almost certain improvements in the 1RM (ES = 1.41) and possibly beneficial improvements in the COD (ES = -0.86). Very likely favorable between-groups effects were observed for VBT compared to PBT in the PV-CMJ (ES = 1.81), 5-m sprint (ES = 1.35), and 20-m sprint (ES = 1.27); likely favorable between-groups effects were observed in the 10-m sprint (ES = 1.24) and nondominant-leg COD (ES = 0.96), whereas the dominant-leg COD (ES = 0.67) was possibly favorable. PBT had small (ES = 0.57), but unclear differences for 1RM improvement compared to VBT. Both training methods improved 1RM and COD times, but PBT may be slightly favorable for stronger individuals focusing on maximal strength, whereas VBT was more beneficial for PV-CMJ, sprint, and COD improvements.


Psychometric properties of the portuguese version of the Pain Self-Efficacy Questionnaire.
This study sought to translate and evaluate the psychometric properties of a European Portuguese version of the Pain Self-Efficacy Questionnaire (P-PSEQ), in order to enable its use in clinical and cross-cultural studies. The Pain Self-Efficacy Questionnaire was translated into European Portuguese and then back-translated into English. A consensus version of the translated version was pre-tested with a pilot sample, followed by cognitive debriefing, resulting in a final version of the measure. A convenience sample of 174 Portuguese adults with chronic musculoskeletal pain completed the Portuguese Pain Self-Efficacy Questionnaire (P-PSEQ) and criterion measures of pain intensity (Numerical Ratings Scale), pain interference (Portuguese Brief Pain Inventory Interference Scale), quality of life and general health (SF-12), and psychological functioning (Hospital Anxiety and Depression Scale). Cronbach's alpha and composite reliability coefficients were computed as measures of reliability, and confirmatory factor analysis was performed. Pearson correlation coefficients between the P-PSEQ score and the criterion measures were computed to evaluate the construct validity of the scale. The P-PSEQ demonstrated good to excellent reliability (Cronbach's alpha = 0.88 and Composite reliability = 0.92), and showed moderately strong associations with the criterion measures in the hypothesized directions, supporting its construct validity. Additionally, the confirmatory factor analysis supported a single factor solution, as hypothesized. The findings provide strong support for the reliability and validity of the P-PSEQ. Research is needed to determine the responsivity of the P-PSEQ and to establish the generalizability of the results in other samples of Portuguese patients with chronic pain.


Electrical ventricular defibrillation.
Ventricular fibrillation is the condition in which all of the muscle fibers in the ventricles of the heart contract and relax randomly and do not propel blood from the heart. This condition, which is the major cause of sudden death from a heart attack, can be reversed by passage of a single pulse of current through the heart using electrodes applied to the chest wall; this technique is known as ventricular defibrillation. World-wide clinical experience has shown that with existing defibrillators, successful defibrillation of subjects weighing over 100 kg is infrequent. It should not be concluded, however, that defibrillation cannot be achieved in such subjects. To illustrate this point, data will be presented to show that it is possible to establish a dose concept in which the output required from a defibrillator can be specified in terms of the weight of the subject. This dose concept evolved slowly from studies reported by investigators in various countries. For example, the present-day techniques of ventricular defibrillation are due to the investigations of researchers all over the world. Prevost and Battelli (1898) in Switzerland first showed that electric current can both induce ventricular fibrillation and achieve defibrillation. The studies of Kouwenhoven in the 1930's in the USA showed that 60 Hz alternating current can be used for defibrillation. The first human defibrillations in 1947 and 1952 used this type of current; these studies were reported by Beck and Zoll in the USA. The present-day technique for defibrillation derives from the animal studies reported by Gurvich and Yuniev 1946 in Russia. Finally, Lown et al. in the early 1960's applied the technique to man. Exciting new developments are underway in ventricular defibrillation. Not only are higher output defibrillators beginning to appear, but automatic and fully implantable defibrillators are being involved. In this paper, the present state of the art of defibrillation will be reported and future trends will be described.


Genotypic selection following coinfection of cultured cells with subgroup 1 and subgroup 2 human rotaviruses.
The purpose of this study was to determine why identifiable reassortants between subgroup 1 and subgroup 2 rotaviruses have been so rarely isolated from human specimens. Cultured cells were coinfected with pairs of subgroup 1 and 2 human rotaviruses and passaged multiple times to simulate natural reassortant formation and selection in vivo. After coinfection of MA-104 cells with subgroup 1 (DS-1) and subgroup 2 (either Wa or P) strains, approximately 14% of the plaque-picked progeny were shown to be reassortants. During multiple passages of these coinfected cultures, however, complete (Wa virus coinfection) or nearly complete (P virus coinfection) loss of detectable DS-1 segments from progeny was observed. Thus, when all segments of the subgroup 2 viruses were present in coinfected cultures, these segments dominated in the selected progeny. Coinfection with subgroup 1-subgroup 2 rotavirus reassortants and the DS-1 strain followed by multiple passages, however, resulted in complete loss of some segments from the subgroup 2 strains originally present in the reassortants. Therefore, segments from the parental subgroup 2 viruses appeared to be selected in toto during multiple passages because they were dominant as a group, not because individual segments of these viruses were consistently favoured over their subgroup 1 virus counterparts.


A retrospective analysis of risk factors associated with bovine respiratory disease treatment failure in feedlot cattle.
The objective of this project was to identify risk factors associated with the probability of failing to resolve clinical signs of bovine respiratory disease (BRD) after initial antimicrobial treatment. A retrospective data analysis was performed with 194,062 animals treated for BRD with an antimicrobial from 10 U.S. feedlots from 2005 to 2009. A binary variable classified cattle as a treatment failure if they were retreated for BRD or died following an initial BRD treatment. A generalized logistic mixed model was created to evaluate associations of quarter of the year at feedlot arrival, arrival weight, sex, risk classification (high vs. low), days on feed at first BRD treatment, and rectal temperature at first BRD treatment and all 2-way interactions with the probability of first treatment failure for BRD. A total of 64,683 out of 194,062 (33.3%) of cattle initially treated for BRD were classified as treatment failures due to death or retreatment. Multiple 2-way interactions were present. High-risk calves had greater probability of first treatment failure compared with low-risk calves, but this effect was modified by quarter of arrival, days on feed at first treatment, and rectal temperature category. The effect of arrival weight category was modified by days on feed at first treatment of BRD and quarter of arrival for probability of first treatment failure. Multiple arrival and treatment characteristics were associated with the probability of first BRD treatment failure. Knowledge of these factors can lead future prospective studies to improve the prediction of treatment failure and provide baseline results for the industry.


Nevirapine induced Stevens-Johnson syndrome in an HIV infected patient.
Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is widely prescribed as a part of the combination therapy of human immunodeficiency virus (HIV) infection because of its efficacy and good tolerability. Here, we report a case of Stevens-Johnson syndrome (SJS) secondary to nevirapine. The patient had a diffuse, exfoliating exanthema with generalized bullous eruptions that involved the face, trunk and both extremities with elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme activities. The condition improved with stoppage of nevirapine-based highly active antiretroviral therapy (HAART) regimen, so we attributed this adverse event to nevirapine. A strict vigilance of adverse drug reaction is required in HAART.


Comparison of the thymidine kinase genes from three entomopoxviruses.
The entomopoxviruses (insect poxviruses) of eastern spruce budworm (Choristoneura fumiferana), two year cycle spruce budworm (C. biennis) and the Indian red army worm (Amsacta moorei) are being studied in our laboratory for their potential as biological insecticides and expression vectors. These viruses characteristically replicate in the cytoplasm of insect cells and produce occlusion bodies that serve to protect the virion from the environment. By analogy to mammalian poxviruses, they should also contain a viral thymidine kinase (TK) that functions in viral DNA synthesis. The replication of the A. moorei entomopoxvirus was inhibited by bromodeoxyuridine whereas the baculovirus of Autographa californica was insensitive to this drug. This result was a biochemical indication that entomopoxviruses contained a kinase that phosphorylated this nucleoside analogue and thus viral DNA synthesis was inhibited. TK genes from the three different insect poxviruses were identified, cloned and sequenced. The sequences of the TK genes of the entomopoxviruses were closely related and exhibited 63.2% identity and 9.9% similarity at the protein level. However, there was only 36.7% identity and 13.6% similarity when these enzymes were compared to their mammalian poxvirus counterpart in vaccinia virus. Finally, one entomopoxvirus TK gene was expressed in Escherichia coli mutants lacking the enzyme. These bacteria were converted to a phenotype that could incorporate radioactive thymidine into their chromosomal DNA. The results presented in this paper provide impetus for the design of a recombinant entomopoxvirus expression system in which foreign genes could be introduced into the viral TK locus under selective pressure from bromodeoxyuridine.


Lithium-angiotensin interaction in rat neurohypophysis.
The effects of various concentrations of lithium upon basal and angiotensin-stimulated cyclic AMP accumulation were studied in isolated rat neurohypophysis. High doses of lithium diminished significantly the spontaneous accumulation of the nucleotide. This effect was not influenced by pre-incubation. Angiotensin-stimulated accumulation was inhibited by lithium at a dose which did not interfere with the basal accumulation of cyclic AMP. The possible physiological significance and mechanism of action are discussed.


Transluminal dilatation in the management of mesenteric angina: a report of two cases.
Two patients with typical clinical and angiographic findings of mesenteric angina are reported. Both remain asymptomatic seven and 11 months respectively, after transluminal dilatation of superior mesenteric artery stenoses.


[Intimate partner physical violence: an obstacle to initiation of childcare in primary healthcare units in Rio de Janeiro, Brazil?].
The aim of this study was to evaluate whether intimate partner physical violence is a risk factor for late initiation of childcare in primary healthcare units (PHCU). This cross-sectional study included 927 mothers and their infants less than six months of age seen at 27 PHCU in Rio de Janeiro, Brazil. The target outcome was delay in first visit to the service (at 60 days of age or later). Interactions between intimate partner physical violence, maternal employment, and quality of prenatal care were explored using multivariate logistic regression. Postpartum intimate partner physical violence was an independent risk factor for late initiation of children's healthcare when mothers had no formal occupation (OR = 3.1, 95%CI: 1.5-6.3) or reported inadequate prenatal care (OR = 4.8, 95%CI: 2.4-9.5). The results emphasize the need for better training of health professionals to detect cases of intimate partner violence during prenatal and pediatric care, which themselves are important steps for reducing such occurrence and thus promoting adequate maternal and child care.