title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Eimeria tenella: 14-3-3 protein interacts with telomerase. | Telomerase, consisting of telomerase RNA and telomerase reverse transcriptase (TERT), is responsible for the maintenance of the end of linear chromosomes. TERT, as the catalytic subunit of telomerase, plays a critical role in telomerase activity. Researches indicate TERT-associated proteins participate in the regulation of telomerase assembly, posttranslational modification, localization, and enzymatic function. Here, the telomerase RNA-binding domain of Eimeria tenella TERT (EtTRBD) was cloned into pGBKT7 and performed as the bait. α-Galactosidase assay showed that the bait plasmid did not activate Gal4 reporter gene. Further, we isolated an EtTRBD-associated protein, 14-3-3, by yeast two-hybrid screening using the constructed bait plasmid. To confirm the interaction, EtTRBD and 14-3-3 were expressed by prokaryotic and eukaryotic expression systems. Pull-down assays by purified proteins demonstrated a direct bind between EtTRBD and 14-3-3. Co-immunoprecipitation techniques successfully validated that 14-3-3 interacted with EtTRBD in 293T cells. The protein-protein interaction provides a starting point for more in-depth studies on telomerase and telomere regulation in E. tenella. | 25,216,780 | [
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Is closed suction drainage effective in early recovery of hip joint function? Comparative evaluation in one-stage bilateral total hip arthroplasty. | One-stage primary bilateral cementless total hip arthroplasty with unilateral closed suction drainage (CSD) was prospectively performed for 51 patients (102 hips), and local effects of CSD were quantitatively evaluated. Postoperatively, pain scores evaluated by visual analog scale and periwound temperatures measured by thermography were lower in the CSD side than the non-CSD side. CT measurements also showed that postoperative cross-sectional area of the thigh was smaller in the CSD side. Active straight leg raising and weight bearing were more accelerated in the CSD side., showing earlier recovery of hip joint function. CSD for hip arthroplasty has an advantage in reducing postoperative local inflammation and be recommended from the viewpoint of postoperative pain relief and early recovery of hip joint function. | 25,216,791 | [
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Light and electron microscopic features of surgically excised left atrial appendage in rheumatic heart disease patients with atrial fibrillation and sinus rhythm. | There are few studies comparing the pathology of the remodeled substrate in patients of rheumatic heart disease with atrial fibrillation (AF) and normal sinus rhythm (NSR). The study group comprised 30 patients with rheumatic heart disease undergoing mitral valve replacement. Excised left atrial appendages of these patients [17 with persistent AF and 13 NSR (control group)] were subjected to light and electron microscopic examination. The histopathological findings of the myocardium were characterized by cardiomyocyte hypertrophy (CH), nuclear enlargement (NE), perinuclear clearing (PC), sarcoplasmic vacuolation (SV), fibrosis, and inflammation in the patients with AF and NSR. NE (17/17 vs. 4/13; P=.004), PC (17/17 vs. 4/13; P=.004), SV (17/17 vs. 9/13; P=.06), and fibrosis (15/17 vs. 3/13; P=.001) were all significantly more common in patients with AF. Inflammatory cells were observed in 9/17 patients of AF as compared to 1 in NSR patients (9/17 vs. 1/13; P=.02). CH was common in the patients with AF as compared with those in NSR (17/17 vs. 10/13; P=.103). In AF patients, electron microscopy revealed cardiomyocytes with depletion of the contractile elements (Z-bands), glycogen particle accumulation, and an increase in mitochondria. Cells severely affected by AF showed loss of contractile elements with extensive areas of SV, presence of myelin figures, and mitochondrial aggregates. Majority of AF cases showed extensive fibrosis in the form of collagen bundles in the interstitium. The left atrial substrate in AF as compared with NSR, in rheumatic heart disease patients, is associated with significant degenerative remodeling and ongoing inflammation that is associated with extensive fibrosis. | 25,216,788 | [
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Social stress and escalated drug self-administration in mice II. Cocaine and dopamine in the nucleus accumbens. | Social defeat stress results in escalation of cocaine taking and long-term neural adaptations in rats. How the intensity and timing of social defeat stress determine these effects, particularly in mice, have not been well characterized. This study investigated the effects of mild vs. moderate intensities and durations of social stress on intravenous cocaine self-administration as well as on dopamine (DA) release in the nucleus accumbens shell (NAcSh) by using in vivo microdialysis. Adult male Swiss Webster (CFW) mice experienced 10 days of social defeat stress, either mild (15 attack bites in ca. 1.8 min) or moderate (30 attack bites in ca. 3.6 min), and compared to controls that were handled daily. Subsequently, the socially stressed mice were assessed for either (1) intravenous cocaine self-administration, using several unit doses (0, 0.3, 0.6, 1.0 mg/kg/infusion) under limited access conditions, or (2) neural sensitization, as determined by in vivo microdialysis of DA in the NAcSh in response to acute d-amphetamine challenge. Social defeat stress resulted in escalated cocaine self-administration in both mild and moderate socially stressed groups. In addition, social defeat stress led to increased DA release after d-amphetamine challenge. These data suggest that both mild and moderate socially stressed mice exhibit increased cocaine taking compared to controls, and this increase is associated with escalated dopaminergic responses in the NAcSh. | 25,216,798 | [
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Optimising the production of succinate and lactate in Escherichia coli using a hybrid of artificial bee colony algorithm and minimisation of metabolic adjustment. | Metabolic engineering is a research field that focuses on the design of models for metabolism, and uses computational procedures to suggest genetic manipulation. It aims to improve the yield of particular chemical or biochemical products. Several traditional metabolic engineering methods are commonly used to increase the production of a desired target, but the products are always far below their theoretical maximums. Using numeral optimisation algorithms to identify gene knockouts may stall at a local minimum in a multivariable function. This paper proposes a hybrid of the artificial bee colony (ABC) algorithm and the minimisation of metabolic adjustment (MOMA) to predict an optimal set of solutions in order to optimise the production rate of succinate and lactate. The dataset used in this work was from the iJO1366 Escherichia coli metabolic network. The experimental results include the production rate, growth rate and a list of knockout genes. From the comparative analysis, ABCMOMA produced better results compared to previous works, showing potential for solving genetic engineering problems. | 25,216,804 | [
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The concentration of carbon monoxide in the breathing areas of workers during logging operations at the motor-manual level. | This article compares 2 variants of logging technologies at the motor-manual level: variant A - cutting and delimbing by means of a petrol chainsaw, skidding with the use of a cable winch mounted on a tractor (67-74 kW); variant B - cutting by means of a petrol chainsaw, skidding, debranching and cutting to length by means of a processor aggregated with a farm tractor (61 kW). Direct dosimetry and non-parametric (moving block bootstrap) methods were used in order to specify the characteristics of the collected sets. Bootstrap average values show that the average CO concentration at a skidding tractor operator's station during early thinning was 2.54 mg×m(-3). At processor operator's station it amounted to 10.35 mg×m(-3). Such results allow to conclude that a higher CO concentration at the above-mentioned 2 work stations was observed during early thinning. In the case of a petrol chainsaw operator, it was observed that the permissible exposure limit (23 mg×m(-3)) was exceeded and the short-term permissible exposure limit (117 mg×m(-3)) was not. The average concentration value for a chainsaw operator working individually during late thinning interventions was substantially lower (15.01 mg×m(-3)), which results from the lack of technological pressure that can be observed while cooperating with a processor operator. The risk increases along with conditions that generate the concentration of exhaust produced by 2-stroke petrol chainsaw engines. | 25,216,817 | [
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Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study. | The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia. Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method. Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean ± SEM: 0.29 ± 0.030 versus 0.20 ± 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma. The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF. | 25,216,821 | [
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Diffusion-weighted magnetic resonance imaging for non-neoplastic conditions in the hepatobiliary and pancreatic regions: pearls and potential pitfalls in imaging interpretation. | Potentially, diffusion-weighted magnetic resonance imaging (DWI) can assess the functional information on concerning the status of tissue cellularity, because increased cellularity is associated with impeded diffusion. DWI in the hepatobiliary and pancreatic regions has demonstrated the usefulness to detect malignant lesions and differentiate them from benign lesions. However, it has been shown more recently that there is some overlap in ADC values for benign and malignant neoplasms. Moreover, some non-neoplastic lesions in the hepatobiliary and pancreatic regions exhibit restricted diffusion on DWI, because of pus, inflammation, or high cellularity. Focal eosinophilic liver disease, hepatic inflammatory myofibroblastic tumor, granulomatous liver disease, acute cholecystitis, xanthogranulomatous cholecystitis, focal pancreatitis, or autoimmune pancreatitis frequently exhibit restricted diffusion on DWI, which may be confused with malignancy in the hepatobiliary and pancreatic regions. Thus, DWI should not be interpreted in isolation, but in conjunction with other conventional images, to avoid the diagnostic pitfalls of DWI. Nevertheless, the presence of diffusion restriction in the non-neoplastic lesions sometimes provides additional information regarding the diagnosis, in problematic patients where conventional images have yielded equivocal findings. DWI may help differentiate hepatic abscess from malignant necrotic tumors, gallbladder empyema from dense bile or sludge in the gallbladder, and pylephlebitis from bland thrombosis in the portal vein. Therefore, knowledge of DWI findings to conventional imaging findings of diffusion-restricted non-neoplastic conditions in the hepatobiliary and pancreatic regions helps establishing a correct diagnosis. | 25,216,848 | [
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Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in colorectal cancer. | Dysregulation of microRNA-100 (miR-100) has been shown to be involved in cancer tumorigenesis and progression of several cancer types. However, its expression patterns in tumors are controversial. The aim of this study was to investigate the expression and clinical significance of miR-100 in colorectal cancer (CRC). Quantitative real-time PCR was used to analyze the expression of miR-100 in 138 pairs of human CRC and adjacent normal tissues. The prognostic values of miR-100 in CRC were also analyzed. The results showed that the miR-100 expression was significantly downregulated in CRC tissues when compared to adjacent normal tissues (P<0.001). Also, low miR-100 expression was observed to be significantly correlated with larger tumor size (P=0.023), higher incidence of lymph node metastasis (P=0.009), and advanced TNM stage (P=0.016). More importantly, Kaplan-Meier analysis showed that CRC patients with low miR-100 expression tended to have shorter overall survival. In multivariate analysis stratified for known prognostic variables, low miR-100 expression was identified as an independent prognostic factor for overall survival. In conclusion, our data indicated for the first time that the downregulation of miR-100 was associated with advanced clinical features and poor prognosis of CRC patients, suggesting that miR-100 downregulation may serve as an unfavorable prognostic biomarker in CRC. | 25,216,869 | [
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WWP2: a multifunctional ubiquitin ligase gene. | The ubiquitin-proteasome system plays an important role in various celluar processes. WWP2, a recently identified ubiquitin E3 ligase, has been proved a multifunctional gene by degradation a series of targets via ubiquitin-dependent proteasome system, including PETN, Smads, Oct4, EGR2, TIRF and so. Hereafter, we reviewed the recent research process about the function of WWP2. | 25,216,927 | [
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Direct interaction of actin filaments with F-BAR protein pacsin2. | Two mechanisms have emerged as major regulators of membrane shape: BAR domain-containing proteins, which induce invaginations and protrusions, and nuclear promoting factors, which cause generation of branched actin filaments that exert mechanical forces on membranes. While a large body of information exists on interactions of BAR proteins with membranes and regulatory proteins of the cytoskeleton, little is known about connections between these two processes. Here, we show that the F-BAR domain protein pacsin2 is able to associate with actin filaments using the same concave surface employed to bind to membranes, while some other tested N-BAR and F-BAR proteins (endophilin, CIP4 and FCHO2) do not associate with actin. This finding reveals a new level of complexity in membrane remodeling processes. | 25,216,944 | [
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Pulse pressure variation is not a valid predictor of fluid responsiveness in patients with elevated left ventricular filling pressure. | The purpose of this study was to test the hypothesis that the predictive ability of pulse pressure variation (PPV) for fluid responsiveness would be altered in patients with elevated left ventricular (LV) filling pressure. According to the preoperative echocardiographic assessment of the ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/E'), patients undergoing surgical coronary revascularization were classified into normal (n=34, E/E'<8) and high (n=34, E/E'>15) LV filling pressure group. After anesthetic induction, PPV and hemodynamic data were measured before and after 6 mL/kg of colloid administration. Fluid responsiveness was defined as 12% or more increase in stroke volume index assessed by pulmonary artery catheter and tested by the area under the receiver operating characteristic curve (AUROC). The AUROCs of PPV in the normal and high filling pressure group were 0.829 (95% confidence interval [CI], 0.661-0.963; P<.001) and 0.583 (95% CI, 0.402-0.749; P=.110), respectively. The AUROCs of cardiac filling pressures and right ventricular end-diastolic volume index did not show statistical significance in both groups. None of the assessed preload indices including PPV were able to predict fluid responsiveness in patients with elevated LV filling pressure. | 25,216,949 | [
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Evaluation of the ecotoxicity of pollutants with bioluminescent microorganisms. | This chapter deals with the use of bioluminescent microorganisms in environmental monitoring, particularly in the assessment of the ecotoxicity of pollutants. Toxicity bioassays based on bioluminescent microorganisms are an interesting complement to classical toxicity assays, providing easiness of use, rapid response, mass production, and cost effectiveness. A description of the characteristics and main environmental applications in ecotoxicity testing of naturally bioluminescent microorganisms, covering bacteria and eukaryotes such as fungi and dinoglagellates, is reported in this chapter. The main features and applications of a wide variety of recombinant bioluminescent microorganisms, both prokaryotic and eukaryotic, are also summarized and critically considered. Quantitative structure-activity relationship models and hormesis are two important concepts in ecotoxicology; bioluminescent microorganisms have played a pivotal role in their development. As pollutants usually occur in complex mixtures in the environment, the use of both natural and recombinant bioluminescent microorganisms to assess mixture toxicity has been discussed. The main information has been summarized in tables, allowing quick consultation of the variety of luminescent organisms, bioluminescence gene systems, commercially available bioluminescent tests, environmental applications, and relevant references. | 25,216,953 | [
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Rapid in-vitro testing for chemotherapy sensitivity in leukaemia patients. | Bioluminescent bacterial biosensors can be used in a rapid in vitro assay to predict sensitivity to commonly used chemotherapy drugs in acute myeloid leukemia (AML). The nucleoside analog cytarabine (ara-C) is the key agent for treating AML; however, up to 30 % of patients fail to respond to treatment. Screening of patient blood samples to determine drug response before commencement of treatment is needed. To achieve this aim, a self-bioluminescent reporter strain of Escherichia coli has been constructed and evaluated for use as an ara-C biosensor and an in vitro assay has been designed to predict ara-C response in clinical samples. Transposition mutagenesis was used to create a cytidine deaminase (cdd)-deficient mutant of E. coli MG1655 that responded to ara-C. The strain was transformed with the luxCDABE operon and used as a whole-cell biosensor for development an 8-h assay to determine ara-C uptake and phosphorylation by leukemic cells. Intracellular concentrations of 0.025 μmol/L phosphorylated ara-C were detected by significantly increased light output (P < 0.05) from the bacterial biosensor. Results using AML cell lines with known response to ara-C showed close correlation between the 8-h assay and a 3-day cytotoxicity test for ara-C cell killing. In retrospective tests with 24 clinical samples of bone marrow or peripheral blood, the biosensor-based assay predicted leukemic cell response to ara-C within 8 h. The biosensor-based assay may offer a predictor for evaluating the sensitivity of leukemic cells to ara-C before patients undergo chemotherapy and allow customized treatment of drug-sensitive patients with reduced ara-C dose levels. The 8-h assay monitors intracellular ara-CTP (cytosine arabinoside triphosphate) levels and, if fully validated, may be suitable for use in clinical settings. | 25,216,956 | [
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Mass-spectrometry-based microbial metabolomics: recent developments and applications. | Metabolomics is an omics technique aiming at qualitatively and quantitatively describing a metabolome by various analytical platforms. It is an indispensable component of modern systems biology. Microbial metabolomics can be roughly classified as metabolic footprint analysis and metabolic fingerprint analysis depending on the analyte origins. Both of them have been beneficial to microbiological research for different reasons. Mass spectrometry and nuclear magnetic resonance spectroscopy techniques are popular analytical strategies prevailing in the metabolomics field. In this review, chromatography-mass-spectrometry-based microbial metabolomic analysis steps are summarized, including sample collection, metabolite extraction, instrument analysis, and data analysis. Moreover, their applications in some representative fields are discussed as examples. The aim of this review is to present briefly recent technical advances in mass-spectrometry-based analysis, and to highlight the value of modern applications of microbial metabolomics. | 25,216,964 | [
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Spatial point processes and moment dynamics in the life sciences: a parsimonious derivation and some extensions. | Mathematical models of dynamical systems in the life sciences typically assume that biological systems are spatially well mixed (the mean-field assumption). Even spatially explicit differential equation models typically make a local mean-field assumption. In effect, the assumption is that diffusive movement is strong enough to destroy spatial structure or that interactions between individuals are sufficiently long-range that the effects of spatial structure are weak. However, many important biophysical processes, such as chemical reactions of biomolecules within cells, disease transmission among humans, and dispersal of plants, have characteristic spatial scales that can generate strong spatial structure at the scale of individuals, with important effects on the behaviour of biological systems. This calls for mathematical methods that incorporate spatial structure. Here, we focus on one method, spatial-moment dynamics, which is based on the idea that important information about a spatial point process is held in its low-order spatial moments. The method goes beyond the dynamics of the first moment, i.e. the mean density or concentration of agents in space, in which no information about spatial structure is retained. By including the dynamics of at least the second moment, the method retains some information about spatial structure. Whereas mean-field models effectively use a closure assumption for the second moment, spatial-moment models use a closure assumption for the third (or a higher-order) moment. The aim of the paper was to provide a parsimonious and intuitive derivation of spatial-moment dynamic equations that is accessible to non-specialists. The derivation builds naturally from the first moment to the second, and we show how it can be extended to higher-order moments. Rather than tying the model to a specific biological example, we formulate a general model of movement, birth, and death of multiple types of interacting agents. This model can be applied to problems from a range of disciplines, some of which we discuss. The derivation is performed in a spatially non-homogeneous setting, to facilitate future investigations of biological scenarios, such as invasions, in which the spatial patterns are non-stationary over space. | 25,216,969 | [
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A 10-year prospective study of respiratory disease and depression and anxiety in adulthood. | Several cross-sectional studies have found an association between respiratory disease and increased mood or anxiety disorders among adults. Little is known about the nature of these associations over time or the role of potential confounders in these links. To investigate the association between respiratory disease and incident and persistent depression or anxiety disorders 10 years later and to examine potential pathways of these associations. Data were drawn from the Midlife Development in the United States survey, a representative sample of adults in the United States ages 18 to 74 years. Participants (N = 2,101) were interviewed on a range of health domains at baseline at wave 1 (1994) and again at wave 2 (2005). Respiratory disease was associated with increased odds of depression and anxiety disorders cross-sectionally at both time points. Respiratory disease at wave 1 was not associated with incident depression or anxiety disorders at wave 2. Respiratory disease at wave 1 was associated with increased odds of persistent depression or anxiety disorders 10 years later among those with depression or anxiety disorders at wave 1. Associations were not explained by differences in demographic characteristics, secondhand smoke exposure, cigarette smoking, or history of exposure to childhood maltreatment. Findings shed new light on the association between respiratory disease and depression or anxiety disorders. Individuals with respiratory disease appear to have higher prevalence of concurrent depression or anxiety disorders and persistent depression or anxiety disorders compared with those without respiratory disease. However, a history of respiratory disease does not appear to confer increased risk of new onset of depression or anxiety disorders. | 25,216,970 | [
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Medication errors in ED: Do patient characteristics and the environment influence the nature and frequency of medication errors? | Medication safety is of increasing importance and understanding the nature and frequency of medication errors in the Emergency Department (ED) will assist in tailoring interventions which will make patient care safer. The challenge with the literature to date is the wide variability in the frequency of errors reported and the reliance on incident reporting practices of busy ED staff. A prospective, exploratory descriptive design using point prevalence surveys was used to establish the frequency of observed medication errors in the ED. In addition, data related to contextual factors such as ED patients, staffing and workload were also collected during the point prevalence surveys to enable the analysis of relationships between the frequency and nature of specific error types and patient and ED characteristics at the time of data collection. A total of 172 patients were included in the study: 125 of whom patients had a medication chart. The prevalence of medication errors in the ED studied was 41.2% for failure to apply patient ID bands, 12.2% for failure to document allergy status and 38.4% for errors of omission. The proportion of older patients in the ED did not affect the frequency of medication errors. There was a relationship between high numbers of ATS 1, 2 and 3 patients (indicating high levels of clinical urgency) and increased rates of failure to document allergy status. Medication errors were affected by ED occupancy, when cubicles in the ED were over 50% occupied, medication errors occurred more frequently. ED staffing affects the frequency of medication errors, there was an increase in failure to apply ID bands and errors of omission when there were unfilled nursing deficits and lower levels of senior medical staff were associated with increased errors of omission. Medication errors related to patient identification, allergy status and medication omissions occur more frequently in the ED when the ED is busy, has sicker patients and when the staffing is not at the minimum required staffing levels. | 25,216,984 | [
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Calcifying fibrous pseudotumour of the tongue: report of a rare case. | We describe a rare case of calcifying fibrous pseudotumour of the tongue in a 33-year-old woman. | 25,216,986 | [
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Climate change and land management in the rangelands of central Oregon. | Climate change, along with exotic species, disturbances, and land use change, will likely have major impacts on sagebrush steppe ecosystems in the western U.S. over the next century. To effectively manage sagebrush steppe landscapes for long-term goals, managers need information about the interacting impacts of climate change, disturbances and land management on vegetation condition. Using a climate-informed state-and-transition model, we evaluated the potential impacts of climate change on rangeland condition in central Oregon and the effectiveness of multiple management strategies. Under three scenarios of climate change, we projected widespread shifts in potential vegetation types over the twenty-first century, with declining sagebrush steppe and expanding salt desert shrub likely by the end of the century. Many extreme fire years occurred under all climate change scenarios, triggering rapid vegetation shifts. Increasing wildfire under climate change resulted in expansion of exotic grasses but also decreased juniper encroachment relative to projections without climate change. Restoration treatments in warm-dry sagebrush steppe were ineffective in containing exotic grass, but juniper treatments in cool-moist sagebrush steppe substantially reduced the rate of juniper encroachment, particularly when prioritized early in the century. Overall, climate-related shifts dominated future vegetation patterns, making management for improved rangeland condition more difficult. Our approach allows researchers and managers to examine long-term trends and uncertainty in rangeland vegetation condition and test the effectiveness of alternative management actions under projected climate change. | 25,216,989 | [
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Improving survival and growth of planted Austrocedrus chilensis seedlings in disturbed patagonian forests of Argentina by managing understory vegetation. | This study was aimed at determining, under field conditions, early interactions between planted cypress seedlings and their associated shrubs in a mesic area of Andean Patagonia and, in a nursery, the effects of increasing light availability on cypress performance when soil water was not a limiting factor. The field experiment was performed in a former cypress-coihue mixed forest (42°02'S, 71°33'W), which was replaced in the 1970s by a plantation of radiata pine. In 2005, 800 cypress seedlings were planted under maqui shrubs in a clear-cut area of the pine stand. In 2007, two treatments were set: no-competition treatment ([NCT] i.e., the surrounding aboveground biomass was removed) and competition treatment ([CT] i.e., without disturbance). The nursery experiment (42°55'S, 71°21'W) consisted of two groups: "shade" (grown under shade cloth) and "sun" (grown at full sun) cypress seedlings. After one growing season, seedling survival and stem growth (in height and diameter) were determined at both sites. Furthermore, the growth rate of leaves, stems, and roots was determined in the nursery. In the field experiment, height growth and survival in NCT were significantly greater than in CT, and a competition process occurred between cypress and surrounding shrubs. In the nursery, sun plants grew more in diameter and increased root weight more than shade plants. Results also showed that in mesic areas of Patagonia, decreasing competition and increasing light levels produced stouter seedlings better adapted to support harsh environmental conditions. Therefore, the removal of protecting shrubs could be a good management practice to improve seedling establishment. | 25,216,990 | [
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Hemicrania continua: major shortcomings in the new classification. | Hemicrania continua ( HC) was described and coined by Sjaastad and Spierings in 1984. Later cases, carrying this appellation should, grossly, conform to this original description. The proposed classification criteria (ICHD, 3rd edition beta version) for HC has major shortcomings, and ordinary HC cases do not fulfill the proposed criteria. Relatively rare symptoms and signs are e.g. made obligatory (point C 1). And the recommended dosage of indomethacin- both test and long-term dosages-is unallowably high. In this way, bogus HC cases are systematically created. This irrational diagnostic system is in urgent need of a major revision. | 25,216,994 | [
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[Clinical relevance of the K-ras oncogene in colorectal cancer: experience in a Mexican population]. | Colorectal cancer is frequent in the developed countries, with a cancer-specific mortality rate of 33%. Different biomarkers are associated with overall survival and the prediction of monoclonal treatment effectiveness. The presence of mutations in the K-ras oncogene alters the response to target therapy with cetuximab and could be an independent prognostic factor. To analyze the difference in survival between patients with mutated K-ras and those with K-ras wild-type status. Thirty-one clinical records were retrospectively analyzed of patients presenting with colorectal cancer that underwent K-ras sequencing through real-time polymerase chain reaction within the time frame of 2009 to 2012 at the Hospital de Alta Especialidad de Veracruz of the Instituto para la Salud y Seguridad Social de los Trabajadores del Estado (HAEV-ISSSTE). Survival analysis for patients with and without K-ras mutation was performed using the Kaplan Meier method. Contrast of covariates was performed using logarithmic transformations. No statistically significant difference was found in relation to survival in the patients with mutated K-ras vs. those with K-ras wild-type (P=.416), nor were significant differences found when analyzing the covariants and survival in the patients with mutated K-ras: ECOG scale (P=.221); age (less than, equal to or greater than 65years, P=.441); clinical stage according to the AJCC (P=.057), and primary lesion site (P=.614). No relation was found between the K-ras oncogene mutation and reduced survival, in contrast to what has been established in the international medical literature. Further studies that include both a larger number of patients and those receiving monoclonal treatment, need to be conducted. There were only 5 patients in the present study that received cetuximab, resulting in a misleading analysis. | 25,216,999 | [
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Effects of Nicotine on Streptococcus gordonii Growth, Biofilm Formation, and Cell Aggregation. | Streptococcus gordonii is a commensal species of human oral flora. It initiates dental biofilm formation and provides binding sites for later colonizers to attach to and generate mature biofilm. Smoking is the second highest risk factor for periodontal disease, and cigarette smoke extract has been reported to facilitate Porphyromonas gingivalis-S. gordonii dual-species biofilm formation. Our hypothesis is that nicotine, one of the most important and active components of tobacco, stimulates S. gordonii multiplication and aggregation. In the present study, S. gordonii planktonic cell growth (kinetic absorbance and CFU), biofilm formation (crystal violet stain and confocal laser scanning microscopy [CLSM]), aggregation with/without sucrose, and 11 genes that encode binding proteins or regulators of gene expression were investigated. Results demonstrated planktonic cell growth was stimulated by 1 to 4 mg/ml nicotine treatment. Biofilm formation was increased at 0.5 to 4 mg/ml nicotine. CLSM indicated bacterial cell mass was increased by 2 and 4 mg/ml nicotine, but biofilm extracellular polysaccharide was not significantly affected by nicotine. Cell aggregation was upregulated by 4, 8, and 16 mg/ml nicotine with sucrose and by 16 mg/ml nicotine without sucrose. Quantitative reverse transcriptase PCR indicated S. gordonii abpA, scaA, ccpA, and srtA were upregulated in planktonic cells by 2 mg/ml nicotine. In conclusion, nicotine stimulates S. gordonii planktonic cell growth, biofilm formation, aggregation, and gene expression of binding proteins. Those effects may promote later pathogen attachment to tooth surfaces, the accumulation of tooth calculus, and the development of periodontal disease in cigarette smokers. | 25,217,021 | [
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Therapeutic window for striatal dopamine D(2/3) receptor occupancy in older patients with schizophrenia: a pilot PET study. | In younger patients with schizophrenia, positron emission tomography (PET) studies have identified a therapeutic window of striatal dopamine D(2/3) receptor occupancy of 65%-80%. This type of empirical information is not available in late life. Our primary aim was to assess the effect of changes in D(2/3) relative receptor occupancy (RRO) on clinical outcomes in this population. Open-label intervention. Centre for Addiction and Mental Health, Toronto. Subjects with schizophrenia age 50 years or more who were clinically stable and previously maintained on oral risperidone for D(2/3) RRO in dorsal putamen was assessed, using the region of interest analysis of [¹¹C]raclopride PET scans, before and after the dose reduction. Clinical assessments included the Positive and Negative Syndrome Scale and the Simpson-Angus Scale. Nine subjects (mean ± SD age: 58 ± 7 years; mean ± SD baseline risperidone dose: 3.4 ± 1.6 mg/day) participated in the study. Extrapyramidal symptoms (EPS) were present in six subjects and were associated with 70% or more D(2/3) RRO in the putamen (range: 70%-87%). Following the dose reduction, EPS resolved in five subjects. Two subjects experienced a clinical worsening at 52% and at less than 50% D(2/3) RRO. EPS diminished less than 70% D(2/3) RRO, which suggests a lower therapeutic window for older patients with schizophrenia than that for younger patients. Although these findings have to be replicated in a larger sample, they have important implications for future drug development and clinical guidelines in late-life schizophrenia. | 25,217,025 | [
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Diet shift induced rapid evolution of size and function in a predatory bird. | A predator's body size correlates with its prey size. Change in the diet may call for changes in the hunting mode and traits determining hunting success. We explored long-term trends in sternum size and shape in the northern goshawk by applying geometric morphometrics. Tetraonids, the primary prey of the goshawk, have decreased and been replaced by smaller birds in the diet. We expected that the size of the goshawk has decreased accordingly more in males than females based on earlier observations of outer morphology. We also expected changes in sternum shape as a function of changes in hunting mode. Size of both sexes has decreased during the preceding decades (1962-2008), seemingly reflecting a shift in prey size and hunting mode. Female goshawks hunting also mammalian prey tend to have a pronouncedly "Buteo-type" sternum compared to males preying upon birds. Interestingly, the shrinkage of body size resulted in an increasingly "Buteo-type" sternum in both sexes. In addition, the sternum shape in birds that died accidentally (i.e., fit individuals) was more Buteo-type than in starved ones, hinting that selection was towards a Buteo-type sternum shape. We conclude that these observed patterns are likely due to directional selection driven by changes in the diet towards smaller and more agile prey. On the other hand, global warming is predicted to also cause a decrease in size, thus these two scenarios are inseparable. Because of difficulties in studying fitness-related phenotypic changes of large raptors in the field, time series of museum exemplars collected over a wide geographical area may give answers to this conundrum. | 25,217,047 | [
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Why brain death is considered death and why there should be no confusion. | Neurologic determination of brain death is a complex assessment that may be misunderstood by nonspecialists and families. Recent guidelines clarify how to proceed with such an examination and are available to physicians, with the time of death in adults and children being determined by the last defining test-the apnea test. This core principle in neurology has been challenged recently in court and resulted in an unprecedented continuation of care in a 13-year-old child declared dead. This review comments on the medical, legal, and ethical quandaries introduced by this case and highlights the major elements of consensus on matters related to brain death that have been forged over 3 decades of sustained medical and societal debate. A clear appreciation by physicians and the public of the diagnostic determination of death following loss of brain function will help to prevent similar conflicts from occurring in the future. | 25,217,058 | [
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Effect of femtosecond laser-assisted cataract surgery on the corneal endothelium. | To compare the effect on the corneal endothelium of femtosecond laser-assisted cataract surgery and conventional phacoemulsification cataract surgery. Private clinic, Tasmania, Australia. Prospective comparative cohort study. Femtosecond laser-assisted cataract surgery (study group) or conventional phacoemulsification (control group) was performed. The central corneal thickness, central 3.0 mm corneal volume, volume stress index, and central endothelial cell density (ECD) were measured preoperatively and 1 day, 3 weeks, and 6 months postoperatively. The study group comprised 405 eyes and the control group, 215 eyes. Postoperative corneal edema was significantly less in the study group at 1 day and 3 weeks. However, the difference was negligible at 6 months. The study group had significant reductions in ECD loss compared with the control group [corrected] at 3 weeks but not at 6 months (6-month mean -150 cells/mm(2) ± 244 [SD] versus -149 cells/mm(2) ± 233). Eyes in the study group with laser-automated corneal incisions had greater endothelial cell loss at 6 months than eyes in the study group with manual corneal incisions and eyes in the control group (P<.0001). Eyes in the study group with zero effective phaco time and manually created corneal incisions had statistically significantly less endothelial cell loss at 6 months than the other groups (P<.0001). Femtosecond laser pretreatment for cataract surgery was associated with a significant reduction in early postoperative corneal edema and endothelial cell loss compared with conventional phacoemulsification; however, the difference diminished with time. Laser-automated corneal incisions seemed to adversely affect the corneal endothelial cells. No author has a financial or proprietary interest in any material or method mentioned. | 25,217,072 | [
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Analysis of selected risk factors for nodal metastases in head and neck cutaneous squamous cell carcinoma. | Cutaneous squamous cell carcinoma (cSCC) accounts for 20% of all skin malignancies and 20% of deaths. In contrast to mucosal SCC, treatment results are very good. However, regional metastases are present in 5-20% of cases, and the prognosis for patients with metastases is 50% lower. It has been reported that several risk factors are responsible for the head and neck lymph node regional metastasis, such as: poor cell differentiation, local recurrence, immunosuppression, and tumour dimension. Multivariate analysis of metastatic neck lesions in head and neck cSCC. Retrospective analysis of patients treated at our department for head and neck cSCC. The study includes 100 patients: 66 males (66%) and 34 females (34%), aged 26-98 years (mean age 74.6). The tumour was evaluated for: sex predilection, local recurrence, stage (according to 7th edition of American Joint Committee on Cancer TNM staging), differentiation, and site. Most patients (79 cases; 79%) were treated for primary cSCC, while the other 21 patients presented local recurrence of cSCC. Neck metastases were diagnosed in five patients with primary cSCC and in three with recurrent cSCC. No distant metastasis was observed. The most common tumour location was the auricle (29 cases; 29%). Neck dissection was performed most frequently in patients with lip tumours (17/22 cases; 77%). Neck metastasis was diagnosed most often in patients with cSCC on the lip (2 patients) and buccal region (2 patients). The most common tumour location in males was the auricle (25/66 cases; 38%) whereas in females the nasal and buccal regions were the most common locations, with 8 patients each (8/34 cases; 23%). Neck dissection was performed in 20 of the 66 males (30%) and in 12 of the 34 females (35%). Neck metastasis was confirmed in 5 females (15%) and 3 males (5%). The most common histopathological tumour stage was G2 (57 cases; 57%). Of the eight patients with confirmed neck metastasis, four had poorly-differentiated (histopathological stage G3). Thus, 4 of the 24 patients (17%) with stage G3 tumours experienced metastasis. Our findings suggest that factors such as local recurrence, degree of cell differentiation, tumour dimension and/or location, can increase the risk of neck metastases. For this reason, in patients with such risk factors, neck dissection should be considered to evaluate for metastatic lesions. | 25,217,080 | [
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Intratympanic steroids as a salvage treatment for sudden sensorineural hearing loss? A meta-analysis. | Sudden sensorineural hearing loss is typically treated with systemic steroids. The aim of this meta-analysis was to evaluate the efficacy of salvage intratympanic steroid treatment in patients who have initial treatment failure with systemic steroids. A MEDLINE literature search was performed, supported by searches of Web of Science, Biosis, and Science Direct. Articles of all languages were included. Selection of relevant publications was conducted independently by three authors. Only randomized controlled trials were considered. In one arm of the studies, the patients received salvage intratympanic steroids. In the other arm, patients did not receive further treatment. The standard difference in mean (SDM) amount of improvement in hearing threshold between patients who did and did not receive salvage intratympanic steroids was calculated. From an initial 184 studies found via the search strategy, 5 studies met inclusion criteria and were included. There was a statistically significant greater reduction in hearing threshold on pure-tone audiometry in patients who received salvage intratympanic steroids than in those who did not (SDM = -0.401, p = 0.005). Subgroup analysis showed that administration by intratympanic injection (SDM = -0.375, p = 0.013) rather than a round window catheter (SDM = -0.629, p = 0.160) yielded significant improvement in outcome. The usage of dexamethasone yielded better outcomes (SDM = -0.379, p = 0.039) than the use of methylprednisolone (SDM = -0.459, p = 0.187). No serious side effect of treatment was reported. In patients who have failed initial treatment with systemic steroids, additional treatment with salvage intratympanic dexamethasone injections demonstrate a statistically significant reduction in the hearing thresholds as compared to controls. | 25,217,083 | [
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[Successful treatment of Bowen disease with ingenol mebutate]. | Ingenol mebutate is a novel cytotoxic drug extracted from the plant Euphorbia peplus. Since November 2012 it is approved in Germany for the treatment of superficial actinic keratoses. We report the successful treatment of Bowen disease with ingenol mebutate in a patient being treated with the multikinase inhibitor sunitinib for to metastatic clear cell renal carcinoma. | 25,217,087 | [
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Editorial: ASD and illegal behaviors. | The last decade has seen significant advances in our understanding of autism spectrum disorder, from both biological and clinical perspectives. Outcome runs the gamut from complete independence to relative dependence. Of particular interest, among those described with poor outcome are a small number of individuals, male and female, who have engaged in unlawful behavior. This special issue of the Journal of Autism and Developmental Disorders presents a number of papers providing further insight into this issue. | 25,217,089 | [
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Single-incision versus conventional multiport laparoscopic colorectal surgery-systematic review and pooled analysis. | The aim of this pooled analysis is to determine the effect of single-incision laparoscopic colorectal surgery (SILC) on short-term clinical and oncological outcomes compared with conventional multiport laparoscopic colorectal surgery (CLC). An electronic search of Embase, Medline, Web of Science, and Cochrane databases was performed. Weighted mean differences (WMD) were calculated for the effect size of SILC on continuous variables and pooled odds ratios (POR) were calculated for discrete variables. No significant differences between the groups were noted for mortality or morbidity including anastomotic leak, reoperation, pneumonia, wound infection, port-site hernia, and operative time. The benefits of a SILC approach included reduction in time to return of bowel function (WMD = -1.11 days; 95 % C.I. -2.11 to -0.13; P = 0.03), and length of hospital stay (WMD = -1.9 days; 95 % C.I. -2.73 to -1.07; P < 0.0001). Oncological surgical quality was also shown for SILC for the treatment of colorectal cancer with a similar average lymph node harvest, proximal and distal resection margin length compared to CLC. SILC can be performed safely by experienced laparoscopic surgeons with similar short-term clinical and oncological outcomes to CLC. SILC may further enhance some of the benefits of minimally invasive surgery with a reduction in blood loss and length of hospital stay. | 25,217,093 | [
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Sutured repair of primary small umbilical and epigastric hernias: concomitant rectus diastasis is a significant risk factor for recurrence. | Umbilical and epigastric hernias are common in the adult population and prompt repair is advised. We aimed to evaluate the impact of concomitant rectus diastasis on the outcome of patients who underwent primary sutured fascia closure of a hernia without mesh. We performed a retrospective analysis of 231 consecutive adult patients who had undergone elective suture-based repair of small (<2 cm) and primary umbilical or epigastric hernias with respect to complications, recurrence, and chronic pain. Patients with rectus diastasis suffered from a significantly increased rate of hernia recurrence (29/93 vs. 9/108; p < 0.001). The use of absorbable sutures also had a negative influence on the recurrence rate (26/90 vs. 12/111; p = 0.001). Obesity (body mass index > 35 kg/m(2)) was associated with more complications (p = 0.02). Wound infections following hernia repair also were associated with a higher rate of recurrence (p = 0.08) and chronic pain (p = 0.02). The mean follow-up via a structured questionnaire was 31 months (range 3-59) and data were available for 201 of 231 patients (87 %). We strongly recommend preoperatively checking for rectus diastasis and using nonabsorbable sutures as an alternative to mesh repair only when repairing small umbilical or epigastric hernias (<2 cm) and there is no concomitant rectus diastasis. Patients with coexistent rectus diastasis definitely benefit from mesh-based repair of the midline to decrease the recurrence rate. | 25,217,109 | [
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Chondromyxoid fibroma management: a single institution experience of 22 cases. | Several different strategies have been reported for the treatment of chondromyxoid fibromas, all with variable outcomes and high recurrence rates. We report on 22 consecutive cases of chondromyxoid fibromas treated by intralesional curettage, four of which had adjuvant cementation at our institution between 2003 and 2010. We assessed the functional outcome using the Musculoskeletal Tumour Society (MSTS) scoring system. Nine males and 16 females with a mean age of 36.5 years (range 11 to 73) and a mean follow-up of 60.7 months were included in the study. Local recurrence occurred in two patients (9%) within the first 2 years following the index procedure. This was treated by re-curettage only of the residual defect. Two postoperative complications occurred: a superficial wound infection in one patient and a transient deep peroneal nerve neurapraxia in the other. The mean postoperative MSTS score was 96.7%. Intralesional curettage and cementation is as an effective treatment strategy for chondromyxoid fibromas, providing satisfactory functional results with a low recurrence rate. Careful case selection with stringent clinical and radiographic follow-up is recommended. | 25,217,119 | [
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Predictors for mortality following acute pancreatitis in children. | Although there are several studies focusing on pancreatitis etiology and clinical outcome, no previous report has examined the risk factors for death in children. We reviewed the medical records of all children (ages 0-18 years) admitted to West China Hospital with acute pancreatitis between 2002 and 2012. Independent predictors for death following acute pancreatitis in children were identified using a multivariate logistic regression analysis. Biliary diseases (23%), medications (20%), idiopathic (19%), and trauma (11%) were the most common etiologies for acute pancreatitis in children. The death rate was 5% and the mean duration of hospital stay was 13 days. Organ failure during admission occurred in 24 of 371 patients and most of them started in 3 days of onset (19/24). Multivariate analysis with logistic regression confirmed that occurrence of SIRS in the first week of onset (OR = 2.12, 95% CI 1.14-6.32, P < 0.001), occurrence of organ failure within 3 days of onset (OR = 8.0, 95% CI 2.2-12.3, P < 0.001), occurrence of MOF in the first week of onset (OR = 9.4, 95% CI 2.3-14.6, P < 0.001), infected necrosis (OR = 1.28, 95% CI 1.08-1.52, P = 0.02), and idiopathic cause (OR = 17.3, 95% CI 2.0-60.5, P < 0.001) were independent risk factors for death in cases with pancreatitis. Mortality rate and complication rate of acute pancreatitis in children remains low. Patients with SIRS, early organ failure, MOF, infected necrosis, or idiopathic cause should be well evaluated because they have higher risk of death. | 25,217,139 | [
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The area and attachment abnormalities of the gubernaculum in patients with undescended testes in comparison with those with retractile testes. | In order to evaluate the gubernaculum (GN) abnormalities quantitatively in patients with undescended testes (UDT), the area and attachment site of the gubernaculum were evaluated. Sixty-seven testes from 61 patients with an undescended testis treated in the past 11 years at our institution were examined. Using intraoperative photographs or DVDs, the area of the GN inside the processus vaginalis was measured, and the ratio to that of the testis was determined. When the GN was attached to the vas deferens, the GN distance from the testis was also measured, and the ratio to that of the transverse length of the testis (deviation index) was calculated. Reference values were obtained from 23 testes from 15 patients with mobile testes. In cases with mobile testes, the GN attached to the bottom of the testis, and involved the lower pole of the epididymis. Even though the GN was attached to the bottom of the testis in 43 testes in the UDT patients (64 %), the GN was found to be elongated. The mean GN area ratio was 1.58 (1SD, 0.6) in the UDT cases, in comparison to 0.47 (0.2) in the cases with mobile testes. The GN was attached to the vas deferens in 24 testes (36 %). The deviation index was 1.34 (1.0), but the GN area ratio of these cases was 1.56 (0.7), which was similar to that of the GN attached to the bottom of the testis. The present study revealed that an increase in the GN area ratio was the most common imaging abnormality in cases with UDT. | 25,217,140 | [
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The Affordable Care Act, health care reform, prescription drug formularies and utilization management tools. | The U.S. Patient Protection and Affordable Care Act (hence, Affordable Care Act, or ACA) was signed into law on March 23, 2010. Goals of the ACA include decreasing the number of uninsured people, controlling cost and spending on health care, increasing the quality of care provided, and increasing insurance coverage benefits. This manuscript focuses on how the ACA affects pharmacy benefit managers and consumers when they have prescriptions dispensed. PBMs use formularies and utilization control tools to steer drug usage toward cost-effective and efficacious agents. A logic model was developed to explain the effects of the new legislation. The model draws from peer-reviewed and gray literature commentary about current and future U.S. healthcare reform. Outcomes were identified as desired and undesired effects, and expected unintended consequences. The ACA extends health insurance benefits to almost 32 million people and provides financial assistance to those up to 400% of the poverty level. Increased access to care leads to a similar increase in overall health care demand and usage. This short-term increase is projected to decrease downstream spending on disease treatment and stunt the continued growth of health care costs, but may unintentionally exacerbate the current primary care physician shortage. The ACA eliminates limitations on insurance and increases the scope of benefits. Online health care insurance exchanges give patients a central location with multiple insurance options. Problems with prescription drug affordability and control utilization tools used by PBMs were not addressed by the ACA. Improving communication within the U.S. healthcare system either by innovative health care delivery models or increased usage of health information technology will help alleviate problems of health care spending and affordability. | 25,217,142 | [
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Prevalence, incidence, clearance, and associated factors of genital human papillomavirus infection among men: a population-based cohort study in rural China. | The natural history of human papillomavirus (HPV) infection in men on a population base has rarely been studied in general, particularly among Chinese men. A total of 1,286 men ages 25 to 65 years from rural China were enrolled during 2009-2010 and their genital HPV infection status was assessed biannually for up to seven visits using PCR and sequencing methods. Prevalence analysis was performed among men with at least one valid HPV result (N = 1,279) and men with at least two consecutive HPV results (N = 1,059) were included in incidence and clearance analyses (median follow-up time, 31.8 months; interquartile range, 15.4-37.9 months). The prevalence and incidence of any HPV type, oncogenic, and nononcogenic HPV were 17.8%, 6.4%, 12.4%, and 14.6, 4.9, 10.8 per 1,000 person months, respectively. The median duration of infection with any HPV type, oncogenic, and nononcogenic HPV was 11.5, 6.8, and 11.5 months, respectively. The number of lifetime sexual partners was consistently associated with increased risk of prevalent and incident infection of HPV. Men ages 25 to 50 years had a higher incidence and longer duration of HPV infection than older men (51-65 years). This epidemiologic investigation provides basic information of genital HPV infection among the Chinese male population; these data are crucial for the consideration of primary strategies against HPV-related carcinoma in the Chinese male and female population. | 25,217,154 | [
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TRAIL-receptor costimulation inhibits proximal TCR signaling and suppresses human T cell activation and proliferation. | The TRAIL-receptor/TRAIL system originally described to induce apoptosis preferentially in malignant cells is also known to be involved in T cell homeostasis and the response to viral infections and autoimmune diseases. Whereas the expression of TRAIL on activated NK and T cells increases their cytotoxicity, induction of TRAIL on APCs can turn them into apoptosis inducers but might also change their immunostimulatory capacity. Therefore, we analyzed how TRAIL-receptor (TRAIL-R) costimulation is modulating TCR-mediated activation of human T cells. T cells triggered by rTRAIL in combination with anti-CD3 and -CD28 Abs exhibited a strong decrease in the expression of activation markers and Th1 and Th2 cytokines compared with CD3/CD28-activated T cells. Most importantly, proliferation of TRAIL-R costimulated T cells was strongly impaired, but no apoptosis was induced. Addition of exogenous IL-2 could not rescue T cells silenced by TRAIL-R costimulation, and TRAIL-mediated inhibition of T cell proliferation only prevented TCR-triggered proliferation but was ineffective if T cells were activated downstream of the TCR. Inhibition of T cell proliferation was associated with abrogation of proximal TCR signaling by inhibiting recruitment of TCR-associated signaling molecules to lipid rafts, followed by abrogation of protein tyrosine phosphorylation of ZAP70, phospholipase C-γ1, and protein kinase C-θ, and impaired nuclear translocation of NFAT, AP-1, and NF-κB. Most importantly, TRAIL-R costimulation efficiently inhibited alloantigen-induced T cell proliferation and CD3/28-induced activation and proliferation of autoreactive T cells derived from patients with Omenn syndrome, indicating that coactivation of TRAIL-R and TCR represents a mechanism to downmodulate T cell immune responses. | 25,217,163 | [
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Aging delays resolution of acute inflammation in mice: reprogramming the host response with novel nano-proresolving medicines. | Aging is associated with an overt inflammatory phenotype and physiological decline. Specialized proresolving lipid mediators (SPMs) are endogenous autacoids that actively promote resolution of inflammation. In this study, we investigated resolution of acute inflammation in aging and the roles of SPMs. Using a self-resolving peritonitis and resolution indices coupled with lipid mediator metabololipidomics, we found that aged mice had both delayed resolution and reduced SPMs. The SPM precursor docosahexaenoic acid accelerated resolution via increased SPMs and promoted human monocyte reprogramming. In aged mice, novel nano-proresolving medicines carrying aspirin-triggered resolvins D1 and D3 reduced inflammation by promoting efferocytosis. These findings provide evidence for age-dependent resolution pathways in acute inflammation and novel means to activate resolution. | 25,217,168 | [
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White matter microstructure and cognition in adolescents with congenital heart disease. | To describe the relationship between altered white matter microstructure and neurodevelopment in children with dextro-transposition of the great arteries (d-TGA). We report correlations between regional white matter microstructure as measured by fractional anisotropy (FA) and cognitive outcome in a homogeneous group of adolescents with d-TGA. Subjects with d-TGA (n = 49) and controls (n = 29) underwent diffusion tensor imaging and neurocognitive testing. In the group with d-TGA, we correlated neurocognitive scores with FA in 14 composite regions of interest in which subjects with d-TGA had lower FA than controls. Among the patients with d-TGA, mathematics achievement correlated with left parietal FA (r = 0.39; P = .006), inattention/hyperactivity symptoms correlated with right precentral FA (r = -0.39; P = .006) and left parietal FA (r = -0.30; P = .04), executive function correlated with right precentral FA (r = -0.30; P = .04), and visual-spatial skills correlated with right frontal FA (r = 0.30; P = .04). We also found an unanticipated correlation between memory and right posterior limb of the internal capsule FA (r = 0.29; P = .047). Within the group with d-TGA, regions of reduced white matter microstructure are associated with cognitive performance in a pattern similar to that seen in healthy adolescents and adults. Diminished white matter microstructure may contribute to cognitive compromise in adolescents who underwent open-heart surgery in infancy. | 25,217,200 | [
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All-cause mortality and cardiovascular events with nicorandil in patients with IHD: systematic review and meta-analysis of the literature. | Nicorandil is able to protect the cardiomyocytes from ischemic damage, but clear benefits of nicorandil in all-cause mortality and cardiovascular events were not consistently reported in patients with ischemic heart disease (IHD). Cochrane, PubMed, EMBASE, CBM, CNKI and Wangfang databases were searched for randomized controlled trials. Data on all-cause mortality and cardiovascular events were collected. Nicorandil groups were pooled to perform a comparison with control groups and to get the pooled odds ratios (ORs) and associated 95% confidence intervals (CIs) for all-cause mortality, relative risks (RRs), and associated 95% CIs for cardiovascular events. STATA 11.0 software was used for all-cause mortality and cardiovascular events statistics. We retrieved 17 randomized controlled studies enrolling a total of 7305 patients. The addition of nicorandil treatment significantly reduced cardiovascular events (13.83% versus 18.01%; RR, 0.77; 95% CI, 0.69 to 0.86). No differences in all-cause mortality (3.83% versus 4.70%; OR, 0.81; 95% CI, 0.64 to 1.02), and repeat revascularization rate (13.06% versus 13.54%; RR, 0.95; 95% CI, 0.70 to 1.29) were observed. There was a weak linear association between cardiovascular events and nicorandil in IHD with diabetes (P=0.099). The results suggest that nicorandil as an adjunct therapy to IHD is associated with reduced cardiovascular events in patients with IHD. | 25,217,220 | [
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Cathepsin B is involved in the heat shock induced cardiomyocytes apoptosis as well as the anti-apoptosis effect of HSP-70. | Cathepsin B is one of the major lysosomal cysteine proteases that plays an important role in apoptosis. Herein, we investigated whether Cathepsin B is involved in cardiomyocyte apoptosis caused by hyperthermic injury (HI) and heat shock protein (HSP)-70 protects these cells from HI-induced apoptosis mediated by Cathepsin. HI was produced in H9C2 cells by putting them in a circulating 43 °C water bath for 120 min, whereas preinduction of HSP-70 was produced in H9C2 cells by mild heat preconditioning (or putting them in 42 °C water bath for 30 min) 8 h before the start of HI. It was found that HI caused both cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. E-64-c, in addition to reducing Cathepsin B activity, significantly attenuated HI-induced cardiomyocyte apoptosis (evidenced by increased apoptotic cell numbers, increased tuncated Bid (t-Bid), increased cytochrome C, increased caspase-9/-3, and decreased Bcl-2/Bax) in H9C2 cells. In addition, preinduction of HSP-70 by mild heat preconditioning or inhibition of HSP-70 by Tripolide significantly attenuated or exacerbated respectively both the cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. Furthermore, the beneficial effects of pre-induction of HSP-70 by mild heat production in reducing both cardiomyocyte apoptosis and increased Cathepsin B activity caused by HI can be significantly reduced by Triptolide preconditioning. These results indicate that Cathepsin B is involved in HI-induced cardiomyocyte apoptosis in H9C2 cells and HSP-70 protects these cells from HI-induced cardiomyocyte apoptosis through Cathepsin B pathways. | 25,217,222 | [
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The p53 control of apoptosis and proliferation: lessons from Drosophila. | The canonical role of p53 in preserving genome integrity and limiting carcinogenesis has been well established. In the presence of acute DNA-damage, oncogene deregulation and other forms of cellular stress, p53 orchestrates a myriad of pleiotropic processes to repair cellular damages and maintain homeostasis. Beside these well-studied functions of p53, recent studies in Drosophila have unraveled intriguing roles of Dmp53 in promoting cell division in apoptosis-induced proliferation, enhancing fitness and proliferation of the winner cell in cell competition and coordinating growth at the organ and organismal level in the presence of stress. In this review, we describe these new functions of Dmp53 and discuss their relevance in the context of carcinogenesis. | 25,217,223 | [
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Prognostic impact of intraocular involvement in primary CNS lymphoma: experience from the G-PCNSL-SG1 trial. | The impact of intraocular involvement (IOL) in primary CNS lymphoma (PCNSL) has not been sufficiently evaluated. Here, we present the analysis of IOL in the only completed randomized phase III trial in PCNSL. The G-PCNSL-SG1 study evaluated the role of whole-brain radiotherapy in primary therapy of PCNSL. Data of the 526 eligible study patients were checked, and clinical characteristics, therapy, and outcome of patients with IOL diagnosed at study inclusion were analyzed. Ophthalmologic examination at study inclusion was performed in 297 patients (56.5 %) of whom IOL was diagnosed in 19 (6.4 %). Clinical characteristics did not significantly differ between patients with IOL (IOL+) and those without (IOL-). The median progression-free survival (PFS) in the IOL+ group was 3.5 months (95 % CI 0.0-7.07) as compared to 8.3 months (95 % CI 4.78-11.78) in the IOL- group (P = 0.004), the median overall survival (OS) was 13.2 months (95 % CI 0.86-25.62) and 20.5 months (95 % CI 15.56-25.5), respectively (P = 0.155). In multivariate analysis, a significantly inferior PFS and OS for IOL+ patients were found. IOL at diagnosis of PCNSL was an independent negative prognostic indicator for PFS and OS in this analysis. | 25,217,230 | [
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Disease control for patients with psoriasis receiving continuous versus interrupted therapy with adalimumab or etanercept: a clinical practice study. | Studies analyzing the efficacy and safety of interrupted psoriasis therapy with biologic drugs have not reported clear benefits in routine clinical practice. To identify differences in the disease control of psoriasis patients undergoing continuous or interrupted therapy with adalimumab or etanercept. This retrospective 3-year cohort study (interrupted vs. continuous therapy) involved 77 patients (47 adalimumab, 30 etanercept) who were managed under clinical practice conditions. The proportion of episodes with a Physician Global Assessment (PGA) ≥ 3 during the follow-up in each study cohort was the primary effectiveness endpoint. The relative risk of PGA ≥ 3 episodes in the interrupted therapy cohort was analyzed. Twenty-one patients receiving adalimumab were included in the interrupted therapy cohort (44.7 %), and 26 were included in the continuous therapy cohort (55.3 %). In the group of etanercept, 21 patients received continuous treatment (70.0 %), and nine patients started at least one interruption period (30.0 %). The proportion of PGA ≥ 3 episodes in continuous and interrupted groups were 19.2 % vs. 33.3 % for adalimumab patients (p = 0.27), and 42.9 % vs. 55.6 % in patients treated with etanercept (p = 0.52). The relative risk of PGA ≥ 3 episodes with interrupted therapy was 1.73 (95 % confidence interval 0.64-4.68; p = 0.27), and 1.30 (95 % confidence interval 0.60-2.79; p = 0.52) in the adalimumab and etanercept groups, respectively. In routine clinical practice, interrupted therapy with adalimumab or etanercept can provide adequate disease control for a subgroup of patients with excellent response to biologic drugs. | 25,217,234 | [
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Progenitor cells and podocyte regeneration. | The very limited ability of adult podocytes to proliferate in vivo is clinically significant because podocytes form a vascular barrier that is functionally critical to the nephron, podocyte hypoplasia is a characteristic of disease, and inadequate regeneration of podocytes is a major cause of persistent podocyte hypoplasia. Excessive podocyte loss or inadequate replacement leads to glomerulosclerosis in many progressive kidney diseases. Thus, restoration of podocyte cell density almost certainly is reliant on regeneration by podocyte progenitors. However, such putative progenitors have remained elusive until recently. In this review, we describe the developmental processes leading to podocyte and parietal epithelial cell (PEC) formation during glomerulogenesis. We compare evidence that in normal human kidneys PECs expressing progenitor markers CD133 and CD24 can differentiate into podocytes in vitro and in vivo, with evidence from animal models suggesting a more limited role of the PEC's capacity to serve as a podocyte progenitor in adults. We highlight tantalizing new evidence that specialized vascular wall cells of afferent arterioles, including those that produce renin in healthy kidney, provide a novel local progenitor source of new PECs and podocytes in response to podocyte hypoplasia in the adult, and draw comparisons with glomerulogenesis. | 25,217,270 | [
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Large-scale monitoring and assessment of metal contamination in surface water of the Selenga River Basin (2007-2009). | An extensive and year-round survey was conducted to assess metal pollution in vast watershed areas of the Selenga River Basin (2007-2009), which provided baseline heavy metal database for the future management. Sources and environmental hazard and risk indices associated with metal pollution were evidenced across the countries of Mongolia and Russia (Buryatia Republic). In general, the concentrations of heavy metals in river water of Mongolia were greater than those of Russia, expect for the upstream of the Dzhida River in Russia. The spatial distribution generally indicated that metal pollution in the Selenga River was mainly associated with the activities in the Mongolian upstream regions. Similar pollution sources of metals between river water and wastewater associated with surrounding activities were found across the industrial and mining areas. Compositional patterns of metals suggested their sources were independent of each other, with hot spots in certain sites. Our measurements indicated that about 63 % of the locations surveyed (48 of 76) exceeded the critical heavy metal pollution index of 100, identifying possible harmful effects on aquatic ecosystems through metal pollution. Zinc was found to be the chemical of priority concern, as more than half of the locations exceeded the corresponding water quality guideline. Other metals including Mn, Fe, Cr, Cu, and As might be problematic in the Selenga River Basin considering the occurrence and their concentrations. Results of our extensive survey during the period of 3 years indicated that urgent action would be necessary in timely manner to improve water quality and mitigate the impact of heavy metals on aquatic environment of the Selenga River Basin. | 25,217,283 | [
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Ghrelin negatively affects the function of ovarian follicles in mature pigs by direct action on basal and gonadotropin-stimulated steroidogenesis. | We previously showed that expression of ghrelin messenger RNA is significantly increased in the ovaries of cycling pigs but not in prepubertal animals and that ghrelin stimulates estradiol (E2) secretion by ovarian follicles in prepubertal animals. The present study investigated in vitro the role of ghrelin in regulating the ovarian steroidogenesis during estrus cycle in mature pigs. Small (SFs), medium (MFs), and large (LFs) ovarian follicles were collected on days 4 to 6, 10 to 12, and 16 to 18 of the estrous cycle from cycling pigs and exposed to 20, 100, and 500 pg/mL ghrelin for 24 hours. In additional experiments, MFs were exposed to ghrelin plus 100 ng/mL follicle-stimulating hormone (FSH) or luteinizing hormone (LH). Levels of progesterone (P4), testosterone (T), and E2 in culture medium were determined by enzyme-linked immunosorbent assay, and the expression of the steroid pathway enzymes 3β hydroxysteroid dehydrogenase (HSD), 17β-HSD, and cytochrome P450 aromatase (CYP19) was evaluated by Western blotting. Ghrelin had no effect on steroid secretion when present at 20 pg/mL, its concentration in follicular fluid, whereas at 100 pg/mL and 500 pg/mL, its concentration in serum, ghrelin significantly decreased secretion of P4, T, and E2. Moreover, all concentrations of ghrelin decreased steroid secretion in FSH- and LH-stimulated follicles. Western blot analysis showed that ghrelin inhibited expression of 3β-HSD, 17β-HSD, and CYP19 proteins. These results suggest that ghrelin, by direct inhibition of 3β-HSD, 17β-HSD, and CYP19 protein expression, inhibits LH- and FSH-stimulated steroid secretion by ovarian follicles, thus negatively affecting ovarian steroidogenesis in mature pigs. | 25,217,306 | [
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Population data of 15 autosomal STR markers from Afro-Bolivians of Nor Yungas Province (Bolivia). | Allele frequencies and forensic parameters for 15 autosomal loci included in the AmpFlSTR® Identifiler kit were estimated in a sample of 57 unrelated Afro-descendants from Nor Yungas (Bolivia). Buccal swabs samples were obtained from voluntary donors, after consent was given. All loci were in Hardy-Weinberg equilibrium after Bonferroni correction. D21S11 was the most informative locus, while the least discriminating locus was D3S1358. The combined power of discrimination and the combined probability of exclusion were >0.99999999 and >0.99997, respectively. The multidimensional scaling (MDS) plot generated by Rst matrix supported that Afro-Bolivians of Nor Yungas preserved a stronger African descent compared to other admixed Latin American populations. These results amplified the Bolivian databases of autosomal STR loci and may provide a useful tool for human identification tests and population genetic studies. | 25,217,341 | [
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Fiscal incentives, behavior change and health promotion: what place in the health-in-all-policies toolkit? | Taxes, subsidies and welfare benefits may provide financial incentives to encourage healthy behaviors or discourage less healthy ones. Historically, taxes have been used in many countries to deter behaviors like tobacco smoking or harmful alcohol use. More recently, an increasing number of governments have sought to expand the scope for the use of fiscal measures in health promotion to foods and beverages high in fat, salt or sugar. A strong public health rationale, supported by a growing body of evidence of the health impacts of taxes and other fiscal measures, adds to the more traditional rationale for the use of commodity taxes, which hinges on their revenue-generating potential and their ability to address the costs imposed by consumers of health-related commodities on other individuals. Despite limitations in the existing evidence base, reviewed in this paper, taxes have been shown to generate significant health gains when applied to tobacco products and alcoholic beverages. In the case of foods and non-alcoholic beverages, the effects tend to build up over time and are stronger in people with lower socio-economic status. However, a number of potentially undesirable effects suggest that governments should exercise caution in planning and implementing taxes on health-related commodities. In particular, commodity taxes are generally regressive, and this is especially the case for taxes on tobacco, foods and non-alcoholic beverages, although the actual size of the tax burden involved is relatively modest. In addition, taxes may negatively impact on economic efficiency and social welfare, and may incentivize illicit activities. | 25,217,345 | [
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Evaluation of Health in All Policies: concept, theory and application. | This article describes some of the crucial theoretical, methodological and practical issues that need to be considered when evaluating Health in All Policies (HiAP) initiatives. The approaches that have been applied to evaluate HiAP in South Australia are drawn upon as case studies, and early findings from this evaluative research are provided. The South Australian evaluation of HiAP is based on a close partnership between researchers and public servants. The article describes the South Australian HiAP research partnership and considers its benefits and drawbacks in terms of the impact on the scope of the research, the types of evidence that can be collected and the implications for knowledge transfer. This partnership evolved from the conduct of process evaluations and is continuing to develop through joint collaboration on an Australian National Health & Medical Research Council grant. The South Australian research is not seeking to establish causality through statistical tests of correlations, but instead by creating a 'burden of evidence' which supports logically coherent chains of relations. These chains emerge through contrasting and comparing findings from many relevant and extant forms of evidence. As such, program logic is being used to attribute policy change to eventual health outcomes. The article presents the preliminary program logic model and describes the early work of applying the program logic approach to HiAP. The article concludes with an assessment of factors that have accounted for HiAP being sustained in South Australia from 2008 to 2013. | 25,217,350 | [
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Impact of hypocapnia and cerebral perfusion on orthostatic tolerance. | We examined two novel hypotheses: (1) that orthostatic tolerance (OT) would be prolonged when hyperventilatory-induced hypocapnia (and hence cerebral hypoperfusion) was prevented; and (2) that pharmacological reductions in cerebral blood flow (CBF) at baseline would lower the 'CBF reserve', and ultimately reduce OT. In study 1 (n = 24; aged 25 ± 4 years) participants underwent progressive lower-body negative pressure (LBNP) until pre-syncope; end-tidal carbon dioxide (P ET , CO 2) was clamped at baseline levels (isocapnic trial) or uncontrolled. In study 2 (n = 10; aged 25 ± 4 years), CBF was pharmacologically reduced by administration of indomethacin (INDO; 1.2 mg kg(-1)) or unaltered (placebo) followed by LBNP to pre-syncope. Beat-by-beat measurements of middle cerebral artery blood flow velocity (MCAv; transcranial Doppler), heart rate (ECG), blood pressure (BP; Finometer) and end-tidal gases were obtained continuously. In a subset of subjects' arterial-to-jugular venous differences were obtained to examine the independent impact of hypocapnia or cerebral hypoperfusion (following INDO) on cerebral oxygen delivery and extraction. In study 1, during the isocapnic trial, P ET , CO 2 was successfully clamped at baseline levels at pre-syncope (38.3 ± 2.7 vs. 38.5 ± 2.5 mmHg respectively; P = 0.50). In the uncontrolled trial, P ET , CO 2 at pre-syncope was reduced by 10.9 ± 3.9 mmHg (P ≤ 0.001). Compared to the isocapnic trial, the decline in mean MCAv was 15 ± 4 cm s(-1) (35%; P ≤ 0.001) greater in the uncontrolled trial, yet the time to pre-syncope was comparable between trials (544 ± 130 vs. 572 ± 180 s; P = 0.30). In study 2, compared to placebo, INDO reduced resting MCAv by 19 ± 4 cm s(-1) (31%; P ≤ 0.001), but time to pre-syncope remained similar between trials (placebo: 1123 ± 138 s vs. INDO: 1175 ± 212 s; P = 0.53). The brain extracted more oxygen in face of hypocapnia (34% to 53%) or cerebral hypoperfusion (34% to 57%) to compensate for reductions in delivery. In summary, cerebral hypoperfusion either at rest or induced by hypocapnia at pre-syncope does not impact OT, probably due to a compensatory increase in oxygen extraction. | 25,217,373 | [
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Single unit hyperactivity and bursting in the auditory thalamus of awake rats directly correlates with behavioural evidence of tinnitus. | Tinnitus is an auditory percept without an environmental acoustic correlate. Contemporary tinnitus models hypothesize tinnitus to be a consequence of maladaptive plasticity-induced disturbance of excitation-inhibition homeostasis, possibly convergent on medial geniculate body (MGB, auditory thalamus) and related neuronal networks. The MGB is an obligate acoustic relay in a unique position to gate auditory signals to higher-order auditory and limbic centres. Tinnitus-related maladaptive plastic changes of MGB-related neuronal networks may affect the gating function of MGB and enhance gain in central auditory and non-auditory neuronal networks, resulting in tinnitus. The present study examined the discharge properties of MGB neurons in the sound-exposure gap inhibition animal model of tinnitus. MGB single unit responses were obtained from awake unexposed controls and sound-exposed adult rats with behavioural evidence of tinnitus. MGB units in animals with tinnitus exhibited enhanced spontaneous firing, altered burst properties and increased rate-level function slope when driven by broadband noise and tones at the unit's characteristic frequency. Elevated patterns of neuronal activity and altered bursting showed a significant positive correlation with animals' tinnitus scores. Altered activity of MGB neurons revealed additional features of auditory system plasticity associated with tinnitus, which may provide a testable assay for future therapeutic and diagnostic development. | 25,217,380 | [
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Delayed anemia assessment in patients treated with oral artemisinin derivatives for uncomplicated malaria: a pooled analysis of clinical trials data from Mali. | In sub-Saharan Africa, artemisinin-based combination therapy (ACT) and injectable artesunate are the first-line treatments for uncomplicated and severe Plasmodium falciparum malaria, respectively. However, recent studies suggest that delayed anaemia is associated with these treatments in non-immune travellers. This paper aimed to assess the risk factors associated with delayed anaemia after falciparum malaria treatment with artemisinin-containing drugs in malaria-endemic populations. Pooled, individual malaria patient data were extracted from 13 clinical trials performed from 2002 to 2011 in various settings of Mali. Treatment regimens were artemether-lumefantrine, artesunate plus amodiaquine, artesunate plus sulphadoxine-pyrimethamine, artesunate plus sulphamethoxypyrazine-pyrimethamine, artesunate plus mefloquine, artesunate-pyronaridine, artesunate monotherapy, chloroquine, sulphadoxine-pyrimethamine, amodiaquine and sulphadoxine-pyrimethamine plus amodiaquine. Univariate and multivariate analyses were performed using the generalized linear and latent mixed model procedures to assess risk factors associated with haemoglobin concentration evolution and anaemia during the treatment follow-up. A total of 5,990 participants were recruited and followed from day 0 to day 28. The participants' median age was five years, ranging from three months to 70 years. There was a decrease in haemoglobin level on day 7 in all treatment arms, but the magnitude varied across treatments. There was a significant risk of haemoglobin level decrease on day 7 in the artemisinin-based therapy compared to the non-artemisinin treatments. The risk of haemoglobin concentration drop was associated with age group < five years old (0.61 g/dL 95% CI (0.71 to 0.51), p < 0.001), baseline high parasite density (0.43 g/dL 95% CI (0.51 to 0.35), p < 0.001) and treatment failure (0.40 g/dL 95% CI (0.59 to 0.20), p = 0.018), while high haemoglobin level at baseline was a protective factor (0.53 to 0.59) p < 0.001). No association was found between artemisinin-based therapy and severe delayed anaemia. Oral artemisinin derivative treatments for uncomplicated P. falciparum malaria are associated with a transient and clinically moderate haemoglobin decrease by day 7 but not associated with a delayed severe anaemia. | 25,217,396 | [
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Progression to multi-scale models and the application to food system intervention strategies. | The aim of this article is to discuss how the systems science approach can be used to optimize intervention strategies in food animal systems. It advocates the idea that the challenges of maintaining a safe food supply are best addressed by integrating modeling and mathematics with biological studies critical to formulation of public policy to address these challenges. Much information on the biology and epidemiology of food animal systems has been characterized through single-discipline methods, but until now this information has not been thoroughly utilized in a fully integrated manner. The examples are drawn from our current research. The first, explained in depth, uses clinical mastitis to introduce the concept of dynamic programming to optimize management decisions in dairy cows (also introducing the curse of dimensionality problem). In the second example, a compartmental epidemic model for Johne's disease with different intervention strategies is optimized. The goal of the optimization strategy depends on whether there is a relationship between Johne's and Crohn's disease. If so, optimization is based on eradication of infection; if not, it is based on the cow's performance only (i.e., economic optimization, similar to the mastitis example). The third example focuses on food safety to introduce risk assessment using Listeria monocytogenes and Salmonella Typhimurium. The last example, practical interventions to effectively manage antibiotic resistance in beef and dairy cattle systems, introduces meta-population modeling that accounts for bacterial growth not only in the host (cow), but also in the cow's feed, drinking water and the housing environment. Each example stresses the need to progress toward multi-scale modeling. The article ends with examples of multi-scale systems, from food supply systems to Johne's disease. Reducing the consequences of foodborne illnesses (i.e., minimizing disease occurrence and associated costs) can only occur through an understanding of the system as a whole, including all its complexities. Thus the goal of future research should be to merge disciplines such as molecular biology, applied mathematics and social sciences to gain a better understanding of complex systems such as the food supply chain. | 25,217,407 | [
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Raman spectroscopy for a rapid diagnosis of sickle cell disease in human blood samples: a preliminary study. | Raman spectroscopy has been proposed as a tool for diagnosis of human blood diseases aiming a quick and accurate diagnosis. Sickle cell disease arises in infancy and causes a severe anemia; thus, an early diagnosis may avoid pathological complications such as vasoocclusion, hemolytic anemia, retinopathy, cardiovascular disease, and infections. This work evaluated spectral differences between hemoglobin S (HbS) and hemoglobin A (HbA) to be used in a diagnostic model based on principal components analysis. Blood samples of patients with a previous diagnosis of sickle cell disease were hemolyzed with water, centrifuged, and the pellet was collected with a pipette. Near-infrared Raman spectra (830 nm, 200 mW) were obtained from these samples, and a model based on principal components analysis and Mahalanobis distance were used to discriminate HbA from HbS. Differences were found in the spectra of HbS and HbA, mainly in the 882 and 1,373 cm(-1) (valine, HbA) and 1,547 and 1,622 cm(-1) (glutamic acid, HbS). The spectral model could correctly discriminate 100% of the samples in the correspondent groups. Raman spectroscopy was able to detect the subtle changes in the polypeptide chain (valine and glutamic acid substitution) due to the sickle cell disease and could be used to discriminate blood samples with HbS from HbA with minimum sample preparations (hemolysis with water and centrifugation). | 25,217,409 | [
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Vitritis in pediatric genetic retinal disorders. | To determine which types of pediatric retinal degeneration are associated with inflammatory cells in the anterior vitreous. Retrospective, observational study in humans. Retrospective chart review was performed for pediatric patients with suspected retinal degeneration presenting to a single examiner from 2008 to 2013. Age, visual acuity (VA), slit-lamp examination of anterior vitreous (SLAV), and clinical and molecular genetic diagnoses were documented. Anterior vitreous cells were graded clinically with SLAV from rare cells (1-4) to 1+ (5-9), 2+ (10-30), or 3+ (>30). Cells were also counted in magnified slit beam photographs masked to molecular diagnosis when obtainable. Cell counts in SLAV, best-corrected VA, and molecular and clinical diagnoses. We evaluated 105 charts, 68 of which (64.8%) included SLAV data. Numerous (1+ or greater) cells were present in 22 of 68 patients (32.4%), whereas 4 of 68 (5.9%) had rare cells and 42 of 68 (61.8%) had no cells. The average age between patients with cells, no cells, and rare cells did not differ significantly (P = 0.25). The VA averaged 20/124 in patients with cells, 20/143 in patients with no cells, and 20/68 in patients with rare cells (P = 0.70). The most frequent diagnoses with cells included Bardet Biedl syndrome (BBS), Leber congenital amaurosis (LCA), and retinitis pigmentosa. The most frequent diagnoses without cells included congenital stationary night blindness (CSNB), LCA, Stargardt disease, and blue cone monochromacy. A nonrandom subset of pediatric retinal degenerations exhibit vitritis. Cells were present in 5 of 5 BBS patients (a progressive degeneration), whereas cells were not detected in any of the 12 patients with CSNB (a stable dysfunction). Studying vitritis in pediatric retinal degenerations may reveal whether inflammation accompanies progressive vision loss in certain subtypes. Potentially, inflammation could be treated. In addition, SLAV may aid in clinical diagnosis. | 25,217,415 | [
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Propensity-weighted long-term risk of urinary adverse events after prostate cancer surgery, radiation, or both. | Prostate cancer is the second most common cancer in men and has high survivorship, yet little is known about the long-term risk of urinary adverse events (UAEs) after treatment. To compare the long-term UAE incidence across treatment and control groups. Using a matched-cohort design, we identified elderly men treated with external-beam radiotherapy (EBRT; n=44 318), brachytherapy (BT; n=14 259), EBRT+BT (n=11 835), radical prostatectomy (RP; n=26 970), RP+EBRT (n=1557), or cryotherapy (n=2115) for non-metastatic prostate cancer and 144 816 non-cancer control individuals from the population-based Surveillance, Epidemiology, and End Results-Medicare linked data from 1992-2007 with follow-up through 2009. The incidence of treated UAEs and time from cancer treatment to first UAE were analyzed in terms of propensity-weighted survival. Median follow-up was 4.14 yr. At 10 yr, all treatment groups experienced higher propensity-weighted cumulative UAE incidence than the control group (16.1%; hazard risk [HR] 1.0), with the highest incidence for RP+EBRT (37.8%; HR 3.19, 95% confidence interval [CI] 2.79-3.66), followed by BT+EBRT (28.4%; HR 1.97, CI 1.85-2.10), RP (26.6%; HR 2.44, CI 2.34-2.55), cryotherapy (23.4%; HR 1.56, CI 1.30-1.87), BT (19.8%; HR 1.43, CI 1.33-1.53), and EBRT (19.7%; HR 1.11, CI 1.07-1.16). Bladder outlet obstruction was the most common event. Men undergoing RP, RP+EBRT, and BT+EBRT experienced the highest UAE risk at 10 yr, although UAEs accrued differently over extended follow-up. The significant background UAE rate among non-cancer control individuals yields a risk attributable to prostate cancer treatment that is 17% lower than prior estimates. We show that treatment for prostate cancer, especially combinations of two treatments such as radiation and surgery, carries a significant risk of urinary adverse events such as urethral stricture. This risk increases with time since treatment, emphasizing that treatments have long-term effects. | 25,217,421 | [
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Management strategies for heart failure with preserved ejection fraction. | The management of heart failure with preserved ejection fraction (HFpEF) is challenging and requires an accurate diagnosis. Although currently there is no convincing therapy that prolongs survival in patients with HFpEF, treatment of fluid retention and of comorbidities, such as hypertension, myocardial ischemia, and atrial fibrillation, may improve symptoms and quality of life. Future outcome trials testing the efficacy of promising new agents will have better characterization of patient phenotype to maximize the potential response to therapies. This article provides current management strategies available for HFpEF, gives an overview of previous trials that have failed to prove the benefit of therapies to improve outcomes, and highlights promising novel therapies. | 25,217,434 | [
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Why do they keep coming back? Psychosocial etiology of persistence of frequent attendance in primary care: a prospective cohort study. | Patients who visit their General Practitioner (GP) very frequently over extended periods of time often have multimorbidity and are costly in primary and specialist healthcare. We investigated the impact of patient-level psychosocial and GP-level factors on the persistence of frequent attendance (FA) in primary care. Two-year prospective cohort study in 623 incident adult frequent attenders (>90th attendance centile; age and sex-adjusted) in 2009. Information was collected through questionnaires (patients, GPs) and GPs' patient data. We used multilevel, ordinal logistic regression analysis, controlling for somatic illness and demographic factors with FA in 2010 and/or 2011 as the outcome. Other anxiety (odds ratio (OR) 2.00; 95% confidence interval from 1.29 to 3.10) over 3years and the number of life events in 3years (OR 1.06; 1.01-1.10 per event; range of 0 to 12) and, at baseline, panic disorder (OR 5.40; 1.67-17.48), other anxiety (OR 2.78; 1.04-7.46), illness behavior (OR 1.13; 1.05-1.20 per point; 28-point scale) and lack of mastery (OR 1.08; 1.01-1.15 per point; 28-point scale) were associated with persistence of FA. We found no evidence of synergistic effects of somatic, psychological and social problems. We found no strong evidence of effects of GP characteristics. Panic disorder, other anxiety, negative life events, illness behavior and lack of mastery are independently associated with persistence of frequent attendance. Effective intervention at these factors, apart from their intrinsic benefits to these patients, may reduce attendance rates, and healthcare expenditures in primary and specialist care. | 25,217,448 | [
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Isoprenoid biosynthesis in Plasmodium falciparum. | Malaria kills nearly 1 million people each year, and the protozoan parasite Plasmodium falciparum has become increasingly resistant to current therapies. Isoprenoid synthesis via the methylerythritol phosphate (MEP) pathway represents an attractive target for the development of new antimalarials. The phosphonic acid antibiotic fosmidomycin is a specific inhibitor of isoprenoid synthesis and has been a helpful tool to outline the essential functions of isoprenoid biosynthesis in P. falciparum. Isoprenoids are a large, diverse class of hydrocarbons that function in a variety of essential cellular processes in eukaryotes. In P. falciparum, isoprenoids are used for tRNA isopentenylation and protein prenylation, as well as the synthesis of vitamin E, carotenoids, ubiquinone, and dolichols. Recently, isoprenoid synthesis in P. falciparum has been shown to be regulated by a sugar phosphatase. We outline what is known about isoprenoid function and the regulation of isoprenoid synthesis in P. falciparum, in order to identify valuable directions for future research. | 25,217,461 | [
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Surviving catastrophic disintegration of a large left atrial myxoma: the importance of multi-disciplinary team. | Atrial myxomas are the most common primary cardiac tumors, representing ∼50% of all benign cardiac tumors. Patients with a left atrial myxoma (LAM) generally present with symptoms of mechanical obstruction of blood flow, systemic emboli or constitutional symptoms. Embolic complications may occur any time with progression of the tumor; therefore, myxoma is usually considered an indication for urgent surgery. This report describes a patient with mobile large LAM who survived multiple emboli to the brain, spleen, kidneys, abdominal aorta and lower limbs during hospitalization for surgery, illustrating the critical nature of this finding and its possible catastrophic complications and demonstrating the importance of multi-disciplinary team in the decision-making process and the management of such complications and supporting the hypothesis that intravenous thrombolysis may be safely used in the treatment of embolic stroke due to cardiac myxoma. | 25,217,477 | [
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Evidence that environmental and genetic risks for psychotic disorder may operate by impacting on connections between core symptoms of perceptual alteration and delusional ideation. | Relational models of psychopathology propose that symptoms are dynamically connected and hypothesize that genetic and environmental influences moderate the strength of these symptom connections. Previous findings suggest that the interplay between hallucinations and delusions may play a crucial role in the development of psychotic disorder. The current study examined whether the connection between hallucinations and delusions is impacted by proxy genetic and environmental risk factors. Hallucinations and delusions at baseline and at 3-year follow-up were assessed in a sample of 1054 healthy siblings and 918 parents of 1109 patients with psychosis, and in 589 healthy controls (no familial psychosis risk). Environmental factors assessed were cannabis use, childhood trauma, and urbanicity during childhood. Logistic regression analyses tested whether familial psychosis risk predicted increased risk of delusions, given presence of hallucinations. Moderating effects of environmental factors on the hallucination-delusion association were tested in a similar fashion, restricted to the control and sibling groups. The risk of delusions, given hallucinations, was associated with proxy genetic risk: 53% in parents, 47% in siblings, and 36% in controls. The hallucination-delusion association was stronger in those reporting cannabis use (risk difference: 32%) and childhood trauma (risk difference: 15%) although not all associations were statistically conclusive (respectively: p = .037; p = .054). A directionally similar but nonsignificant effect was found for urb anicity during childhood (risk difference: 14%, p =.357). The strength of the connection between delusions and hallucinations is associated with familial and environmental risks for psychotic disorder, suggesting that specific symptom connections in the early psychosis psychopathology network are informative of underlying mechanisms. | 25,217,481 | [
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Transcatheter aortic valve implantation combined with elective coronary artery stenting: a simultaneous approach†. | Many patients referred for transcatheter aortic valve implantation (TAVI) also require percutaneous coronary intervention (PCI). The aim of the study was to identify whether combined treatment of patients with aortic stenosis and coronary artery disease (CAD) with TAVI and PCI has comparable results to treatment of patients with no CAD or with CAD with non-significant lesions who receive only TAVI. Between April 2008 and August 2013, 730 consecutive patients underwent transapical TAVI at our institution. In our study population of 593 patients, 285 (48.1%) had no CAD and received TAVI only (Group I); 232 (39.1%) presented with CAD but no highly significant coronary artery lesion(s) and also received TAVI only (Group II), and 76 (12.8%) had CAD and highly significant coronary lesion(s) and underwent combined, single-staged TAVI and PCI (Group III). Three transapical TAVI patients who received PCI because of iatrogenic coronary artery obstruction during TAVI and 134 transapical TAVI patients with previous CABG were excluded from this study. Group II showed a calculated mean SYNTAX score of 5.7 ± 7.4. However, Group III showed a statistically significantly higher mean SYNTAX score of 8.0 ± 5.7 than Group II (P < 0.001) before the combined procedure. Combined TAVI and PCI reduced the mean SYNTAX score significantly from 8.0 ± 5.7 to 3.0 ± 4.9 (P < 0.001) in those patients presenting with severe aortic stenosis and highly significant CAD (Group III). The thirty-day all-cause mortality rate was 5.3, 3.9 and 2.6% for Group I, II and III, respectively (P = 0.609). Patients with highly significant CAD undergoing TAVI and PCI had similar survival up to 3 years as patients without CAD undergoing TAVI only. Radiation time and amount of contrast agent were higher during combined treatment in Group III (P < 0.05). However, no difference in acute kidney injury post-procedurally was observed. Single-stage combined treatment of severe aortic stenosis and highly relevant coronary lesions is a safe and feasible procedure. Early survival and survival up to 3 years are comparable to that observed in patients presenting without CAD who received TAVI only. PCI effectively reduces the complexity of coronary lesions. Although more contrast agent is applied during the combined treatment, the rate of acute kidney injury was not higher. | 25,217,500 | [
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The Notch pathway inhibits TGFβ signaling in breast cancer through HEYL-mediated crosstalk. | Acquired resistance to TGFβ is a key step in the early stages of tumorigenesis. Mutations in TGFβ signaling components are rare, and little is known about the development of resistance in breast cancer. On the other hand, an activated Notch pathway is known to play a substantial role in promoting breast cancer development. Here, we present evidence of crosstalk between these two pathways through HEYL. HEYL, a basic helix-loop-helix transcription factor and a direct target of Notch signaling, is specifically overexpressed in breast cancer. HEYL represses TGFβ activity by binding to TGFβ-activated Smads. HeyL(-/-) mice have defective mammary gland development with fewer terminal end buds. On the other hand, HeyL transgenic mice show accelerated mammary gland epithelial proliferation and 24% of multiparous mice develop mammary gland cancer. Therefore, repression of TGFβ signaling by Notch acting through HEYL may promote initiation of breast cancer. | 25,217,524 | [
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Evaluation of laser diode thermal desorption-tandem mass spectrometry (LDTD-MS-MS) in forensic toxicology. | Many forensic laboratories experience backlogs due to increased drug-related cases. Laser diode thermal desorption (LDTD) has demonstrated its applicability in other scientific areas by providing data comparable with instrumentation, such as liquid chromatography-tandem mass spectrometry, in less time. LDTD-MS-MS was used to validate 48 compounds in drug-free human urine and blood for screening or quantitative analysis. Carryover, interference, limit of detection, limit of quantitation, matrix effect, linearity, precision and accuracy and stability were evaluated. Quantitative analysis indicated that LDTD-MS-MS produced precise and accurate results with the average overall within-run precision in urine and blood represented by a %CV <14.0 and <7.0, respectively. The accuracy for all drugs in urine ranged from 88.9 to 104.5% and 91.9 to 107.1% in blood. Overall, LDTD has the potential for use in forensic toxicology but before it can be successfully implemented that there are some challenges that must be addressed. Although the advantages of the LDTD system include minimal maintenance and rapid analysis (∼10 s per sample) which makes it ideal for high-throughput forensic laboratories, a major disadvantage is its inability or difficulty analyzing isomers and isobars due to the lack of chromatography without the use of high-resolution MS; therefore, it would be best implemented as a screening technique. | 25,217,542 | [
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Equine total carbon dioxide testing in Illinois in 2012. | During prolonged strenuous exercise, racehorses can experience acidemia. To counteract this phenomenon, trainers can administer blood alkalizing agents that raise the plasma pH and total carbon dioxide (TCO2) concentration. In Illinois, the administrative threshold for TCO2 in plasma is 37.0 mmol/L. Because accuracy in the reported measurement of TCO2 must be ensured, uncertainty measurements are often issued alongside the reported concentrations. We report a validated method for measuring TCO2 levels in equine plasma using the Beckman UniCel DxC 600. A six-point calibration curve ranging from 5 to 50 mmol/L is analyzed along with controls at four TCO2 levels with each set of samples. Using this method, we collected data from 5,199 race samples during 2012, with 134 being from thoroughbred horses and 5,065 from standardbred horses. During method validation, uncertainty was determined using the simplified Guide to the Expression of Uncertainty in Measurement approach and was found to be 3% at 99.7% confidence level with eight measurements. Additionally, to investigate other variables that could have an effect on TCO2 levels, we collected the gender, breed, Lasix(®) status, strong ion concentration, pre- or post-race collection time and track location of all horses tested during that year. The samples had an overall mean TCO2 concentration of 30.5 ± 2.0 mmol/L. The other physiological and environmental data were analyzed using analysis of covariance tables. These results indicate gender, breed, furosemide status, collection time and track location to be strongly correlated (P < 0.0001) to TCO2 levels. Thoroughbred status was found to have no effect. Finally, TCO2 concentrations were highly correlated (P < 0.0001) to sodium and chloride ion concentrations. No correlation was found between TCO2 and potassium concentrations. The results show that there are several environmental and physiological factors that can affect TCO2 concentrations. The concentration of other strong ions present in the blood may indicate doping status. | 25,217,543 | [
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XLR-11 and UR-144 in Washington state and state of Alaska driving cases. | The case reports for 18 driving cases positive for the synthetic cannabinoid substances XLR-11 and/or UR-144 are discussed. Eleven of these cases had drug recognition expert evaluations performed. Slurred speech, lack of convergence and body and eyelid tremors were the most consistently noted interview characteristic. Pulse and blood pressure of the subjects were within the expected range. Most of the drivers contacted demonstrated poor driving; however, their performance on the standardized field sobriety tests yielded inconsistent diagnostic information. All cases were negative for other commonly detected drugs that affect the central nervous system, although one case was additionally positive for other synthetic cannabinoids. Of the studied cases, six were positive for only UR-144, whereas eight contained only XLR-11. Four cases were found to have both. | 25,217,547 | [
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Improved rat genome gene prediction by integration of ESTs with RNA-Seq information. | RNA-Seq (also called whole-transcriptome sequencing) is an emerging technology that uses the capabilities of next-generation sequencing to detect and quantify entire transcripts. One of its important applications is the improvement of existing genome annotations. RNA-Seq provides rapid, comprehensive and cost-effective tools for the discovery of novel genes and transcripts compared with expressed sequence tag (EST), which is instrumental in gene discovery and gene sequence determination. The rat is widely used as a laboratory disease model, but has a less well-annotated genome as compared with humans and mice. In this study, we incorporated deep RNA-Seq data from three rat tissues-bone marrow, brain and kidney-with EST data to improve the annotation of the rat genome. Our analysis identified 32 197 transcripts, including 13 461 known transcripts, 13 934 novel isoforms and 4802 new genes, which almost doubled the numbers of transcripts in the current public rat genome database (rn5). Comparisons of our predicted protein-coding gene sets with those in public datasets suggest that RNA-Seq significantly improves genome annotation and identifies novel genes and isoforms in the rat. Importantly, the large majority of novel genes and isoforms are supported by direct evidence of RNA-Seq experiments. These predicted genes were integrated into the Rat Genome Database (RGD) and can serve as an important resource for functional studies in the research community. The predicted genes are available at http://rgd.mcw.edu. | 25,217,576 | [
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The role of microRNAs in the control of innate immune response in cancer. | Ligands for receptors of natural killer (NK) cells and CD8(+) cytotoxic T lymphocytes (CTL), such as the inhibitory nonclassical HLA-G, the activating stress-induced major histocompatibility complex class I-related antigens MICA and MICB, and/or the UL16-binding proteins (ULBPs), are often aberrantly expressed upon viral infection and neoplastic transformation, thereby preventing virus-infected or malignant-transformed cells from elimination by immune effector cells. Recently, it has been shown that ligands of both NK and CD8(+) T cells are regulated by a number of cellular and/or viral microRNAs (miRs). These miRs are involved in shaping the antiviral and/or antitumoral immune responses as well as neoplastic growth properties. This review summarizes the expression pattern and function of miRs directed against selected NK and T cell receptor ligands, their putative role in shaping immune surveillance and tumorigenicity, and their clinical relevance. In addition, the potential role of RNA-binding proteins in the post-transcriptional gene regulation of these ligands will be discussed. | 25,217,579 | [
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The RIG-I ATPase core has evolved a functional requirement for allosteric stabilization by the Pincer domain. | Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor expressed in metazoan cells that is responsible for eliciting the production of type I interferons and pro-inflammatory cytokines upon detection of intracellular, non-self RNA. Structural studies of RIG-I have identified a novel Pincer domain composed of two alpha helices that physically tethers the C-terminal domain to the SF2 helicase core. We find that the Pincer plays an important role in mediating the enzymatic and signaling activities of RIG-I. We identify a series of mutations that additively decouple the Pincer motif from the ATPase core and show that this decoupling results in impaired signaling. Through enzymological and biophysical analysis, we further show that the Pincer domain controls coupled enzymatic activity of the protein through allosteric control of the ATPase core. Further, we show that select regions of the HEL1 domain have evolved to potentiate interactions with the Pincer domain, resulting in an adapted ATPase cleft that is now responsive to adjacent domains that selectively bind viral RNA. | 25,217,590 | [
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Regulation of retinal oxygen metabolism in humans during graded hypoxia. | Animal experiments indicate that the inner retina keeps its oxygen extraction constant despite systemic hypoxia. For the human retina no such data exist. In the present study we hypothesized that systemic hypoxia does not alter inner retinal oxygen extraction. To test this hypothesis we included 30 healthy male and female subjects aged between 18 and 35 years. All subjects were studied at baseline and during breathing 12% O₂ in 88% N₂ as well as breathing 15% O₂ in 85% N₂. Oxygen saturation in a retinal artery (SO₂art) and an adjacent retinal vein (SO₂vein) were measured using spectroscopic fundus reflectometry. Measurements of retinal venous blood velocity using bidirectional laser Doppler velocimetry and retinal venous diameters using a Retinal Vessel Analyzer (RVA) were combined to calculate retinal blood flow. Oxygen and carbon dioxide partial pressure were measured from earlobe arterialized capillary blood. Retinal blood flow was increased by 43.0 ± 23.2% (P < 0.001) and 30.0 ± 20.9% (P < 0.001) during 12% and 15% O₂ breathing, respectively. SO₂art as well as SO₂vein decreased during both 12% O₂ breathing (SO₂art: -11.2 ± 4.3%, P < 0.001; SO₂vein: -3.9 ± 8.5%, P = 0.012) and 15% O₂ breathing (SO₂art: -7.9 ± 3.6%, P < 0.001; SO₂vein: -4.0 ± 7.0%, P = 0.010). The arteriovenous oxygen difference decreased during both breathing periods (12% O2: -28.9 ± 18.7%; 15% O₂: -19.1 ± 16.7%, P < 0.001 each). Calculated oxygen extraction did, however, not change during our experiments (12% O₂: -2.8 ± 18.9%, P = 0.65; 15% O₂: 2.4 ± 15.8%, P = 0.26). Our results indicate that in healthy humans, oxygen extraction of the inner retina remains constant during systemic hypoxia. | 25,217,648 | [
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Oxidative stress associated with middle aging leads to sympathetic hyperactivity and downregulation of soluble guanylyl cyclase in corpus cavernosum. | Impairment of nitric oxide (NO)-mediated cavernosal relaxations in middle age contributes to erectile dysfunction. However, little information is available about the alterations of sympathetic neurotransmission and contraction in erectile tissue at middle age. This study aimed to evaluate the alterations of the contractile machinery associated with tyrosine hydroxylase (TH) in rat corpus cavernosum (RCC) at middle age, focusing on the role of superoxide anion. Male Wistar young (3.5-mo) and middle-aged (10-mo) rats were used. Electrical-field stimulation (EFS)- and phenylephrine-induced contractions were obtained in RCC strips. Levels of reactive-oxygen species (ROS) and TH mRNA expression, as well as protein expressions for α₁/β₁-subunits of soluble guanylyl cyclase (sGC), in RCC were evaluated. The neurogenic contractile responses elicited by EFS (4-32 Hz) were greater in RCC from the middle-aged group that was accompanied by elevated TH mRNA expression (P < 0.01). Phenylephrine-induced contractions were also greater in the middle-aged group. A 62% increase in ROS generation in RCC from middle-aged rats was observed. The mRNA expression for the α₁A-adrenoceptor remained unchanged among groups. Protein levels of α₁/β₁-sGC subunits were decreased in RCC from the middle-aged compared with young group. The NADPH oxidase inhibitor apocynin (85 mg·rat(-1)·day(-1), 4 wk) fully restored the enhanced ROS production, TH mRNA expressions, and α₁/β₁-subunit sGC expression, indicating that excess of superoxide anion plays a major role in the sympathetic hyperactivity and hypercontractility in erectile tissue at middle age. Reduction of oxidative stress by dietary antioxidants may be an interesting approach to treat erectile dysfunction in aging population. | 25,217,652 | [
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MicroRNA-146a and microRNA-146b expression and anti-inflammatory function in human airway smooth muscle. | MicroRNA (miR)-146a and miR-146b are negative regulators of inflammatory gene expression in lung fibroblasts, epithelial cells, monocytes, and endothelial cells. The abundance of cyclooxygenase-2 (COX-2) and IL-1β is negatively regulated by the miR-146 family, suggesting miR-146a and/or miR-146b might modulate inflammatory mediator expression in airway smooth muscle thereby contributing to pathogenesis of asthma. To test this idea we compared miR-146a and miR-146b expression in human airway smooth muscle cells (hASMCs) from nonasthmatic and asthmatic subjects treated with cytomix (IL-1β, TNF-α, and IFNγ) and examined the miRNAs' effects on COX-2 and IL-1β expression. We found that cytomix treatment elevated miR-146a and miR-146b abundance. Induction with cytomix was greater than induction with individual cytokines, and asthmatic cells exhibited higher levels of miR-146a expression following cytomix treatment than nonasthmatic cells. Transfection of miR-146a or miR-146b mimics reduced COX-2 and IL-1β expression. A miR-146a inhibitor increased COX-2 and IL-1β expression, but a miR-146b inhibitor was ineffective. Repression of COX-2 and IL-1β expression by miR-146a correlated with reduced abundance of the RNA-binding protein human antigen R. These results demonstrate that miR-146a and miR-146b expression is inducible in hASMCs by proinflammatory cytokines and that miR-146a expression is greater in asthmatic cells. Both miR-146a and miR-146b can negatively regulate COX-2 and IL-1β expression at pharmacological levels, but loss-of-function studies showed that only miR-146a is an endogenous negative regulator in hASMCs. The results suggest miR-146 mimics may be an attractive candidate for further preclinical studies as an anti-inflammatory treatment of asthma. | 25,217,662 | [
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Is it safe to use inhaled corticosteroids in pregnancy? | A healthy woman with mild to moderate asthma came to my clinic today after learning that she was pregnant. She inquired about continuing her inhaled corticosteroid (ICS) medication and whether there would be any risks to her unborn child if she were to do so. What would you advise? Given the published evidence, ICSs should be continued throughout pregnancy at low to moderate doses sufficient to control asthma symptoms and prevent exacerbations. However, caution must be taken with doses greater than 1000 µg/d (chlorofluorocarbon beclomethasone equivalent), although whether such doses cause adverse effects is currently still questionable. Patient education on proper ICS administration and adherence, including during the first trimester, must be ongoing. Well controlled asthma will reduce the need for higher ICS doses and possible exposure to systemic corticosteroids, and might decrease the risk of adverse pregnancy or perinatal outcomes. | 25,217,675 | [
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JAK2V617F+ myeloproliferative neoplasm clones evoke paracrine DNA damage to adjacent normal cells through secretion of lipocalin-2. | Genetic instability is strongly involved in cancer development and progression, and elucidating the mechanism could lead to novel therapeutics for preventing carcinogenesis. Philadelphia-negative myeloproliferative neoplasms (MPNs) are clonal myeloid disorders with a high prevalence of JAK2V617F mutation, and transformation to acute myeloid leukemia through accumulation of additional mutations is a major complication in MPNs. Here, we showed that JAK2V617F(+) cells conferred paracrine DNA damage to neighboring normal cells as well as to themselves through increased reactive oxygen species (ROS). We screened candidate factors responsible for the effect and found that lipocalin-2 (Lcn2) is overexpressed in JAK2V617F(+) cells and that short hairpin RNA-mediated knockdown of Lcn2 significantly alleviated the paracrine DNA damage. Normal hematopoietic cells showed elevated ROS levels through increased intracellular iron levels when treated with lipocalin-2, which led to p53 pathway activation, increased apoptosis, and decreased cellular proliferation. In contrast, JAK2V617F(+) cells did not suffer from lipocalin-2-induced growth suppression resulting from attenuated p53 pathway activation, which conferred a relative growth advantage to JAK2V617F(+) clones. In summary, we demonstrated that JAK2V617F-harboring cells cause paracrine DNA damage accumulation through secretion of lipocalin-2, which gives proliferative advantage to themselves and an increased risk for leukemic transformation to both JAK2V617F(+) and JAK2V617F(-) clones. | 25,217,696 | [
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Complete debromination of decabromodiphenyl ether using the integration of Dehalococcoides sp. strain CBDB1 and zero-valent iron. | This study investigated the effects of nano- and micro-scale zero-valent iron (nZVI and mZVI) particles on Dehalococcoides sp. strain CBDB1 participating in anaerobic reduction of polybrominated diphenyl ethers. nZVI (>0.25 g L(-)(1)) had an inhibitory effect upon this strain, whereas 1.0 g L(-1) mZVI showed no negative impact on bacterial growth. Strain CBDB1 could only utilize lower brominated congeners (<7 bromines) as electron acceptor. In the bio-ZVI system, decabromodiphenyl ether (BDE-209) was first reduced by ZVI to lower brominated congeners, which were then dehalogenated to diphenyl ether by CBDB1. Within 30 d, a BDE-209 debromination efficiency of 16% and 24% was obtained in the bio-nZVI (0.25 g L(-1)) and bio-mZVI (1.0 g L(-1)) systems with a corresponding diphenyl ether yield efficiency of 14% and 19%, respectively. The debromination efficiency increased significantly from 8% to 24% with an increase of mZVI dosage from 0.25 to 1.0 g L(-1) in the bio-mZVI system. | 25,217,713 | [
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Integration of RAFT polymerization and click chemistry to fabricate PAMPS modified macroporous polypropylene membrane for protein fouling mitigation. | A copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) grafting-to method was used to tether alkyne-terminated poly(2-acrylamido-2-methyl propane sulfonic acid) (alkyne-PAMPS) to the azide functionalized macroporous polypropylene membrane (MPPM-N3). Alkyne-PAMPS was synthesized by the reversible addition-fragmentation chain transfer polymerization (RAFT) of AMPS with an alkyne-terminated trithiocarbonate served as a chain transfer agent. The combination of RAFT polymerization with click chemistry to graft polymer to the surface of polypropylene membrane produced relatively high grafting density and controllable grafting chain length. The structure and composition of the modified and unmodified MPPM surfaces were analyzed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR/FT-IR), X-ray photoelectron spectroscopy (XPS); field emission scanning electron microscopy (FE-SEM) was employed to observe the morphological changes on the membrane surface. The permeation performances were tested by the filtration of protein dispersion. The experimental results show that with the grafting degree going up, the relative flux reduction decreases, while the relative flux recovery ratio increases, and the protein fouling is obviously mitigated by tethering PAMPS to the membrane surface. The modified membranes can be potentially applied for fouling reduction during the filtration of proteins. | 25,217,729 | [
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Does maternal intrapartum antibiotic treatment prolong the incubation time required for blood cultures to become positive for infants with early-onset sepsis? | We hypothesized that maternal intrapartum antibiotic treatment delays the growth of the organism in the blood culture obtained during the work-up for infants with suspected early-onset sepsis (EOS). Single center, retrospective review of infants with blood culture-proven EOS over 13.5 years period. EOS was defined by isolation of a pathogen from blood culture obtained within 72 hours of birth and antibiotic treatment for ≥ 5 days. Among 81 infants with positive blood cultures, 38 were deemed to have EOS and 43 were deemed contaminants. The organisms grown were as follows: Escherichia coli in 17 infants, Group B streptococcus in 10 infants, and others in 11 infants. Overall, 17 infants with EOS did not receive intrapartum antibiotics and had blood cultures drawn for being symptomatic after birth. The other 21 infants who received intrapartum antibiotics had blood culture drawn primarily for maternal chorioamnionitis. The median (interquartile range [IQR]) incubation time to blood culture positivity was not different in infants who received intrapartum antibiotics compared with infants who did not (19.6 hours, IQR 16-28 hours vs. 19.5 hours, IQR 17.2-21.6 hours, p = 0.7489). Maternal intrapartum antibiotic treatment did not delay the time to blood culture positivity in infants with EOS. | 25,217,736 | [
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Cover crops influence soil microorganisms and phytoextraction of copper from a moderately contaminated vineyard. | We investigated the ability of summer (Avena sativa [oat], Trifolium incarnatum [crimson clover], Chenopodium [goosefoot]) and winter (Vicia villosa [hairy vetch], Secale Cereale L. [Rye], Brassica napus L. partim [rape]) cover crops, including a mixed species treatment, to extract copper from an organic vineyard soil in situ and the microbial communities that may support it. Clover had the highest copper content (14.3mgCukg(-1) DM). However, it was the amount of total biomass production that determined which species was most effective at overall copper removal per hectare. The winter crop rye produced significantly higher amounts of biomass (3532kgDMha(-1)) and, therefore, removed significantly higher amounts of copper (14,920mgCuha(-1)), despite less accumulation of copper in plant shoots. The maximum annual removal rate, a summation of best performing summer and winter crops, would be 0.033kgCuha(-1)y(-1). Due to this low annual extraction efficiency, which is less than the 6kgCuha(-1)y(-1) permitted for application, phytoextraction cannot be recommended as a general method of copper extraction from vineyards. Copper concentration did not influence aboveground or belowground properties, as indicated by sampling at two distances from the grapevine row with different soil copper concentrations. Soil microorganisms may have become tolerant to the copper levels at this site. Microbial biomass and soil enzyme activities (arylsulfatase and phosphatase) were instead driven by seasonal fluxes of resource pools. Gram+ bacteria were associated with high soil moisture, while fungi seemed to be driven by extractable carbon, which was linked to high plant biomass. There was no microbial group associated with the increased phytoextraction of copper. Moreover, treatment did not influence the abundance, activity or community structure of soil microorganisms. | 25,217,742 | [
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Field study on the impact of nocturnal road traffic noise on sleep: the importance of in- and outdoor noise assessment, the bedroom location and nighttime noise disturbances. | The aim of this field study is to gain more insight into the way nocturnal road traffic noise impacts the sleep of inhabitants living in noisy regions, by taking into account several modifying variables. Participants were tested during five consecutive nights in their homes and comparisons between effective indoor and outdoor noise levels (LAeq, LAmax, number of noise events), sleep (actigraphy and sleep logs) and aspects of well-being (questionnaires) were made. Also, we investigated into what extent nocturnal noise exposure - objectively measured as well as perceived - directly relates to sleep outcomes and how the bedroom location influenced our measurements. We found that subjects living and sleeping in noisy regions correctly perceive their environment in terms of noise exposure and reported an overall discomfort due to traffic noise. In the evaluation of the objective noise levels, the inside noise levels did not follow the outside noise levels, though the different noise patterns could be described as characteristic for a noise and quiet environment. The impact on sleep, however, was only modest and we did not find any influence of noise intrusion on mood or pre-sleep arousal levels. Concerning the subjectively reported noise disturbances during the night, a clear relationship between noise and sleep outcomes could be established; with sleep onset latencies and judged sleep quality being particularly affected. The importance of inside and outside noise assessment as well as the use of multiple noise indicators in a home environment is further described. Additional emphasis is put on the determination of quiet control regions and the bedroom location, as this can alter noise levels and sleep outcomes. Also, including subjective noise evaluations during the night might not only provide crucial information on how participants experience the noise, but also allows for a more qualitative interpretation of the actual noise situation. | 25,217,747 | [
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Occurrence of phthalate esters in river sediments in areas with different land use patterns. | Phthalate esters (PAEs) are widely used as plasticizers in both industrial and commercial products and have aroused considerable concern over their widespread distribution and potentially hazardous impacts on the environment. The present study investigated the distribution (concentrations at different sites) of PAEs in typical riverine sediments in southern Jiangsu Province and its relationship with the physical and chemical properties of the sediments. PAEs were detected in all 34 sediment samples analyzed, and the total concentrations of the six priority control PAEs in sediments ranged from 2.3 to 80.1 mg kg(-1) with a mean concentration of 13.2 ± 14.7 mg kg(-1). Land use significantly (p<0.05) influenced the PAE concentrations in the river sediments. The average PAE concentrations in mixed industrial and commercial districts were 27.8 ± 18.2 mg kg(-1), three and eight times higher than those in suburban areas (8.8 ± 3.7 mg kg(-1)) and an agricultural field (3.4 ± 0.9 mg kg(-1)), respectively. The concentrations of PAEs showed significant linear positive correlations with sediment organic matter and phosphorus but no significant correlation with sediment pH. Di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) were the dominant PAE compounds present in all examined sediment samples. These PAEs have relatively high ecotoxicology, but the potential risk of their transfer to the food chain needs further study. | 25,217,750 | [
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Dynamic mass balance model for mercury in the St. Lawrence River near Cornwall, Ontario, Canada. | A dynamic mass balance model was developed for the St. Lawrence River near Cornwall, Ontario that predicts and hindcasts mercury concentrations and fluxes in three forms, elemental Hg (Hg(0)), divalent mercury (Hg(2+)), and methyl mercury (MeHg), in a six compartment environment (air, water, porewater, sediment, periphyton, and benthic invertebrates). Our objective was to construct a dynamic mass balance model for mercury in the St. Lawrence River near Cornwall, Ontario based on the framework and results of a steady-state mass balance model developed previously for this site. The second objective was to estimate industrial mercury emissions based on mercury residues deposited in sediments prior to 1970, the year when regulations were implemented to reduce mercury pollution in the environment. We compiled mercury concentrations, fluxes, and transformation rates from previous studies completed in this section of the river (area of approximately 100km(2)) to develop the model. Estimated mercury concentrations in all media were similar to measured data (R(2)=0.99), with only minor exceptions, providing a satisfactory overall description of the mercury loadings and transformation rates of the different mercury species. The estimated historical emissions prior to 1970 from local industries along the Cornwall waterfront were approximately 400kgyear(-1). A storm sewer discharge of 5000m(3)/day resulted in a significant increase in mercury concentrations, particularly in sediment (617ngg(-1) to 624ngg(-1); p=0.004). Model results suggest that discharges of mercury from sources such as local industries and storm sewers have an impact on mercury in media such as sediment and water. This model should provide a basis for predicting and hindcasting mercury concentrations in other river environments as well, because it considers three distinct forms of mercury, and contains environmental media common to all rivers, including some (e.g. periphyton) not typically included in previous mercury models. | 25,217,751 | [
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How "lucky" we are that the Fukushima disaster occurred in early spring: predictions on the contamination levels from various fission products released from the accident and updates on the risk assessment for solid and thyroid cancers. | The present paper studies how a random event (earthquake) and the subsequent disaster in Japan affect transport and deposition of fallout and the resulting health consequences. Therefore, except for the original accident in March 2011, three additional scenarios are assessed assuming that the same releases took place in winter 2010, summer 2011 and autumn 2011 in order to cover a full range of annual seasonality. This is also the first study where a large number of fission products released from the accident are used to assess health risks with the maximum possible efficiency. Xenon-133 and (137)Cs are directly estimated within the model, whereas 15 other radionuclides are calculated indirectly using reported isotopic ratios. As much as 85% of the released (137)Cs would be deposited in continental regions worldwide if the accident occurred in winter 2010, 22% in spring 2011 (when it actually happened), 55% in summer 2011 and 48% if it occurred during autumn 2011. Solid cancer incidents and mortalities from Fukushima are estimated to be between 160 and 880 and from 110 to 640 close to previous estimations. By adding thyroid cancers, the total number rises from 230 to 850 for incidents and from 120 to 650 for mortalities. Fatalities due to worker exposure and mandatory evacuation have been reported to be around 610 increasing total estimated mortalities to 730-1260. These estimates are 2.8 times higher than previously reported ones for radiocaesium and (131)I and 16% higher than those reported based on radiocaesium only. Total expected fatalities from Fukushima are 32% lower than in the winter scenario, 5% that in the summer scenario and 30% lower than in the autumn scenario. Nevertheless, cancer fatalities are expected to be less than 5% of those from the tsunami (~20,000). | 25,217,754 | [
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The new sulfated O-specific polysaccharide from marine bacterium Cobetia pacifica KMM 3878, containing 3,4-O-[(S)-1-carboxyethylidene]-D-galactose and 2,3-O-disulfate-D-galactose. | The O-specific polysaccharide was isolated from the lipopolysaccharide of Cobetia pacifica KMM 3878 and studied by chemical methods along with (1)H and (13)C NMR spectroscopy, including, 1D TOCSY and 2D (1)H, (1)H COSY, (1)H, (13)C HSQC, (1)H, (1)H ROESY, (1)H, (13)C HMBC and (1)H, (13)C H2BC experiments. The following new structure of the sulfated O-polysaccharide from C. pacifica KMM 3878 containing 3,4-O-[(S)-1-carboxyethylidene]-D-galactose and 2,3-O-disulfate-D-galactose was established: →4)-β-D-Gal2,3R-(1→6)-β-D-Gal3,4(S-Pyr)-(1→6)-β-D-Gal-(1→ Where R is -SO3H. | 25,217,756 | [
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Development of a risk-screening tool for cancer survivors to participate in unsupervised moderate- to vigorous-intensity exercise: results from a survey study. | The health benefits of exercise increase in dose-response fashion among cancer survivors. However, it is unclear how to identify cancer survivors who may require a pre-exercise evaluation before they progress from the common recommendation of walking to unsupervised moderate- to vigorous-intensity exercise. To clarify how to identify cancer survivors who should undergo a pre-exercise evaluation before they progress from the common recommendation of walking to unsupervised moderate- to vigorous-intensity exercise. Electronic survey. Forty-seven (n = 47) experts in the field of exercise physiology, rehabilitation medicine, and cancer survivorship. Not applicable. We synthesized peer-reviewed guidelines for exercise and cancer survivorship and identified 82 health factors that may warrant a pre-exercise evaluation before a survivor engages in unsupervised moderate- to vigorous-intensity exercise. The 82 health factors were classified into 3 domains: (1) clinical health factors; (2) comorbidity and device health factors; and (3) medications. We surveyed a sample of experts asking them to identify which of the 82 health factors among cancer survivors would indicate the need for a pre-exercise evaluation before they engaged in moderate- to vigorous-intensity exercise. The response rate to our survey was 75% (n = 47). Across the 3 domains of health factors, acute symptoms, comorbidities, and medications related to cardiovascular disease were agreed on to indicate a pre-exercise evaluation for survivors before they engaged in unsupervised moderate- to vigorous-intensity exercise. Other health factors in the survey included hematologic, musculoskeletal, systemic, gastrointestinal, pulmonary, and neurological symptoms and comorbidities. Eighteen experts (38%) said it was difficult to provide absolute answers because no 2 patients are alike, and their decisions are made on a case-by-case basis. The results from this expert survey will help to identify which cancer survivors should undergo a pre-exercise evaluation before they engage in unsupervised moderate- to vigorous-intensity exercise. | 25,217,819 | [
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Peripheral myopization and visual performance with experimental rigid gas permeable and soft contact lens design. | To evaluate the performance of two experimental contact lenses (CL) designed to induce relative peripheral myopic defocus in myopic eyes. Ten right eyes of 10 subjects were fitted with three different CL: a soft experimental lens (ExpSCL), a rigid gas permeable experimental lens (ExpRGP) and a standard RGP lens made of the same material (StdRGP). Central and peripheral refraction was measured using a Grand Seiko open-field autorefractometer across the central 60° of the horizontal visual field. Ocular aberrations were measured with a Hartman-Shack aberrometer, and monocular contrast sensitivity function (CSF) was measured with a VCTS6500 without and with the three contact lenses. Both experimental lenses were able to increase significantly the relative peripheral myopic defocus up to -0.50 D in the nasal field and -1.00 D in the temporal field (p<0.05). The ExpRGP induced a significantly higher myopic defocus in the temporal field compared to the ExpSCL. ExpSCL induced significantly lower levels of Spherical-like HOA than ExpRGP for the 5mm pupil size (p<0.05). Both experimental lenses kept CSF within normal limits without any statistically significant change from baseline (p>0.05). RGP lens design seems to be more effective to induce a significant myopic change in the relative peripheral refractive error. Both lenses preserve a good visual performance. The worsened optical quality observed in ExpRGP was due to an increased coma-like and spherical-like HOA. However, no impact on the visual quality as measured by CSF was observed. | 25,217,826 | [
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The great divide: septation and malformation of the cloaca, and its implications for surgeons. | The anorectal and urogenital systems arise from a common embryonic structure termed cloaca. Subsequent development leads to the division/septation of the cloaca into the urethra, urinary bladder, vagina, anal canal, and rectum. Defective cloacal development and the resulting anorectal and urogenital malformations are some of the most severe congenital anomalies encountered in children. In the most severe form in females, the rectum, vagina, and urethra fail to develop separately and drain via a single common channel known as a cloaca into the perineum. In this review, we summarize our current knowledge of embryonic cloaca development and malformation, and compare them to what has already been described in the literature. We describe the use of mouse models of cloaca malformation to understand which signaling pathways and cellular mechanisms are involved in the process of normal cloaca development. We also discuss the embryological correlation of the epithelial and stromal histology found in step sections of the common channel in 14 human cloaca malformations. Finally, we highlight the significance of these findings, compare them to prior studies, and discuss their implications for the pediatric surgeons. Understanding and identifying the molecular basis for cloaca malformation could provide foundation for tissue engineering efforts that in the future would reflect better surgical reconstruction and improved quality of life for patients. | 25,217,828 | [
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Small nucleolar RNA 113-1 suppresses tumorigenesis in hepatocellular carcinoma. | Emerging evidence suggests that small nucleolar RNAs (snoRNAs) are involved in tumorigenesis. The roles of small nucleolar RNA 113-1 (SNORD113-1) on the development of hepatocellular carcinoma (HCC) remain unknown. The expression of SNORD113-1 was measured in 112 HCC tumor tissues using quantitative RT-PCR and compared with expression levels from with paired non-tumor tissues. The effects of SNORD113-1 on HCC tumorigenesis were investigated in HepG2 and Huh7 cells as well as a xenograft nude mouse model. CpG methylation within the promoter region of the SNORD113-1 gene was identified using Sodium bisulfite sequencing. Cancer pathway reporter investigate the mechanism by which SNORD113-1 suppressed tumorigenesis. SNORD113-1 expression was significantly downregulated in HCC tumors compared with adjacent non-tumor tissues, and downregulation of SNORD113-1 in HCC tumors was significantly associated with worse survival of patients. In addition, CpG methylation at the promoter region of the SNORD113-1 gene was higher in HCC tumors than adjacent non-tumor tissues. Functionally, SNORD113-1 suppressed cancer cell growth in HepG2 and Huh7 cells and in a xenograft nude mouse model. Furthermore, SNORD113-1 inactivated the phosphorylation of ERK1/2 and SMAD2/3 in MAPK/ERK and TGF-β pathways. SNORD113-1 functions as a tumor suppressor role in HCC and may be important as a potential diagnostic and therapeutic target for HCC. | 25,217,841 | [
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0.02561468,
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0.08044803,
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0.4990821,
0.09666868,
-0.06437103,
-0.00179567,
-0.1510409,
-0.001... |
Female cystic fibrosis mutation carriers and assisted reproductive technology: does carrier status affect reproductive outcomes? | To evaluate the association between female cystic fibrosis (CF) carrier status and in vitro fertilization (IVF) response and outcomes. The presence of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in male carriers has been associated with infertility, yet possible adverse effects on the ovarian function and reproductive outcomes of female carriers have not been studied to date. Retrospective cohort study. Private academic, clinical reproductive center. Females<40 years of age who were screened for CFTR mutations and received IVF treatment between July 2002 and March 2013. Patients initiated controlled ovarian hyperstimulation with frequent monitoring, vaginal oocyte retrieval, fertilization, embryo transfer, and a pregnancy test. Various measures of IVF stimulation response and cycle outcome were evaluated for both carriers and noncarriers. Analysis was performed by logistic regression and Poisson regression. IVF cycles (n=199) from CFTR mutation carrier patients (n=112) were analyzed. No significant differences in outcome were noted when carriers of different mutation loci were compared in aggregate with the noncarrier group (n=6,420 cycles from 3,555 patients). Significant differences were noted for some metrics when the carriers were grouped by mutation loci. Overall, no significant differences in stimulation response and cycle outcome were noted between female CFTR mutation carriers and noncarriers. Further research is needed to investigate whether the differences noted between specific CFTR mutation loci are clinically relevant and whether CFTR mutations may impact reproductive outcomes outside the context of assisted reproductive technologies. | 25,217,870 | [
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A case of right renal artery originating from the thoracic aorta. | The renal arteries normally originate from the abdominal aorta between the first and second lumbar vertebrae. The main renal artery arising from the thoracic aorta is an uncommon anomaly. Here we report a rare case of a right renal artery originating above the celiac axis. A 38-year-old male underwent computed tomographic angiography in preparation for being a renal donor, and two right renal arteries were observed. A main renal artery arose from the thoracic aorta at the 11th thoracic vertebral level, and an accessory renal artery originated from the abdominal aorta at the renal hilum. | 25,217,879 | [
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... |
Communication: Low-temperature approximation of the virial series for the Lennard-Jones and modified Lennard-Jones models. | The regularity of the existing data on the virial coefficients for the Lennard-Jones and modified Lennard-Jones models has allowed a rough extrapolation to the coefficients of higher orders. The corresponding approximation of the infinite virial series has been proposed for the limited temperature interval: 0.4-0.8 of the critical temperature. The loci of zero points of isothermal bulk modulus obtained on the basis of this approximation are close to the vapor-liquid branch of the experimental binodal rather than spinodal. In addition, those points ((dP/dV)T = 0) almost coincide with the divergence points of the approximated virial series that may eliminate some disputable questions about the boundaries of adequacy for the virial equation of state and makes the theoretical isotherms qualitatively similar to the real in the condensation region. | 25,217,895 | [
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... |
Analytic first derivatives for a spin-adapted open-shell coupled cluster theory: evaluation of first-order electrical properties. | An analytic scheme is presented for the evaluation of first derivatives of the energy for a unitary group based spin-adapted coupled cluster (CC) theory, namely, the combinatoric open-shell CC (COSCC) approach within the singles and doubles approximation. The widely used Lagrange multiplier approach is employed for the derivation of an analytical expression for the first derivative of the energy, which in combination with the well-established density-matrix formulation, is used for the computation of first-order electrical properties. Derivations of the spin-adapted lambda equations for determining the Lagrange multipliers and the expressions for the spin-free effective density matrices for the COSCC approach are presented. Orbital-relaxation effects due to the electric-field perturbation are treated via the Z-vector technique. We present calculations of the dipole moments for a number of doublet radicals in their ground states using restricted open-shell Hartree-Fock (ROHF) and quasi-restricted HF (QRHF) orbitals in order to demonstrate the applicability of our analytic scheme for computing energy derivatives. We also report calculations of the chlorine electric-field gradients and nuclear quadrupole-coupling constants for the CCl, CH2Cl, ClO2, and SiCl radicals. | 25,217,899 | [
0.2072375,
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Testing time-dependent density functional theory with depopulated molecular orbitals for predicting electronic excitation energies of valence, Rydberg, and charge-transfer states and potential energies near a conical intersection. | Kohn-Sham (KS) time-dependent density functional theory (TDDFT) with most exchange-correlation functionals is well known to systematically underestimate the excitation energies of Rydberg and charge-transfer excited states of atomic and molecular systems. To improve the description of Rydberg states within the KS TDDFT framework, Gaiduk et al. [Phys. Rev. Lett. 108, 253005 (2012)] proposed a scheme that may be called HOMO depopulation. In this study, we tested this scheme on an extensive dataset of valence and Rydberg excitation energies of various atoms, ions, and molecules. It is also tested on a charge-transfer excitation of NH3-F2 and on the potential energy curves of NH3 near a conical intersection. We found that the method can indeed significantly improve the accuracy of predicted Rydberg excitation energies while preserving reasonable accuracy for valence excitation energies. However, it does not appear to improve the description of charge-transfer excitations that are severely underestimated by standard KS TDDFT with conventional exchange-correlation functionals, nor does it perform appreciably better than standard TDDFT for the calculation of potential energy surfaces. | 25,217,903 | [
0.06748189,
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On the full exploitation of symmetry in periodic (as well as molecular) self-consistent-field ab initio calculations. | Use of symmetry can dramatically reduce the computational cost (running time and memory allocation) of self-consistent-field ab initio calculations for molecular and crystalline systems. Crucial for running time is symmetry exploitation in the evaluation of one- and two-electron integrals, diagonalization of the Fock matrix at selected points in reciprocal space, reconstruction of the density matrix. As regards memory allocation, full square matrices (overlap, Fock, and density) in the Atomic Orbital (AO) basis are avoided and a direct transformation from the packed AO to the symmetry adapted crystalline orbital basis is performed, so that the largest matrix to be handled has the size of the largest sub-block in the latter basis. Quantitative examples, referring to the implementation in the CRYSTAL code, are given for high symmetry families of compounds such as carbon fullerenes and nanotubes. | 25,217,905 | [
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A new ab initio potential energy surface and infrared spectra for the Ar-CS₂ complex. | We report a new three-dimensional potential energy surface for Ar-CS2 involving the Q3 normal mode for the υ3 antisymmetric stretching vibration of the CS2 molecule. The potential energies were calculated using the supermolecular method at the coupled-cluster singles and doubles level with noniterative inclusion of connected triples, using augmented correlation-consistent quadruple-zeta basis set plus midpoint bond functions. Two vibrationally averaged potentials with CS2 at both the ground (υ = 0) and the first excited (υ = 1)υ3 vibrational states were generated from the integration of the three-dimensional potential over the Q3 coordinate. Each potential was found to have a T-shaped global minimum and two equivalent linear local minima. The radial discrete variable representation /angular finite basis representation method and the Lanczos algorithm were applied to calculate the rovibrational energy levels. The calculated band origin shift of the complex (0.0622 cm(-1)) is very close to the observed one (0.0671 cm(-1)). The predicted infrared spectra and spectroscopic parameters based on the two averaged potentials are in excellent agreement with the available experimental data. | 25,217,915 | [
0.05024164,
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0.04820183,
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Detailed mechanism of the CH₂I + O₂ reaction: yield and self-reaction of the simplest Criegee intermediate CH₂OO. | The application of a new reaction scheme using CH2I + O2 to generate the simplest Criegee intermediate, CH2OO, has stimulated lively research; the Criegee intermediates are extremely important in atmospheric chemistry. The detailed mechanism of CH2I + O2 is hence important in understanding kinetics involving CH2OO. We employed ultraviolet absorption to probe simultaneously CH2I2, CH2OO, CH2I, and IO in the reaction system of CH2I + O2 upon photolysis at 248 nm of a flowing mixture of CH2I2, O2, and N2 (or SF6) in the pressure range 7.6-779 Torr to investigate the reaction kinetics. With a detailed mechanism to model the observed temporal profiles of CH2I, CH2OO, and IO, we found that various channels of the reaction CH2I + O2 and CH2OO + I play important roles; an additional decomposition channel of CH2I + O2 to form products other than CH2OO or ICH2OO becomes important at pressure less than 60 Torr. The pressure dependence of the derived rate coefficients of various channels of reactions of CH2I + O2 and CH2OO + I has been determined. We derived a rate coefficient also for the self-reaction of CH2OO as k = (8 ± 4) × 10(-11) cm(3) molecule(-1) s(-1) at 295 K. The yield of CH2OO from CH2I + O2 was found to have a pressure dependence on N2 and O2 smaller than in previous reports; for air under 1 atm, the yield of ~30% is about twice of previous estimates. | 25,217,917 | [
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... |
A diabatic state model for double proton transfer in hydrogen bonded complexes. | Four diabatic states are used to construct a simple model for double proton transfer in hydrogen bonded complexes. Key parameters in the model are the proton donor-acceptor separation R and the ratio, D1/D2, between the proton affinity of a donor with one and two protons. Depending on the values of these two parameters the model describes four qualitatively different ground state potential energy surfaces, having zero, one, two, or four saddle points. Only for the latter are there four stable tautomers. In the limit D2 = D1 the model reduces to two decoupled hydrogen bonds. As R decreases a transition can occur from a synchronous concerted to an asynchronous concerted to a sequential mechanism for double proton transfer. | 25,217,923 | [
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0.1682283,
0.04093586,
-0.08791225,... |
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