id
stringlengths 10
13
| query
stringlengths 52
8.83k
| pos
stringclasses 1
value | neg
stringclasses 1
value |
|---|---|---|---|
Retriever1000
|
Social environment regulates corticotropin releasing factor, corticosterone and vasopressin in juvenile prairie voles.
Stressful social conditions, such as isolation, that occur during sensitive developmental periods may alter present and future social behavior. Changes in the neuroendocrine mechanisms closely associated with affiliative behaviors and stress reactivity are likely to underlie these changes in behavior. In the present study, we assessed the effects of post-weaning social housing conditions on the neuropeptides arginine vasopressin (AVP) and oxytocin (OT), and components of the hypothalamic-pituitary-adrenal axis (corticotropin releasing factor: [CRF], and corticosterone: [CORT]) in the prairie vole (Microtus ochrogaster), a socially monogamous bi-parental rodent. Following weaning at 21 days of age, prairie voles were maintained in one of three housing conditions: social isolation (isolate), paired with a same sex sibling (sibling) or paired with a stranger (stranger) of the same sex and age. Housing conditions were maintained for either 4 or 21 days. Central CRF, AVP and OT immunoreactivity (ir) were quantified and circulating plasma CORT, AVP and OT were assayed. Isolated voles had higher CRF-ir in the paraventricular nucleus of the hypothalamus (PVN) compared with sibling and stranger housed voles. Plasma CORT was significantly higher in isolates. AVP-ir was significantly lower in the PVN of isolate females compared to either sibling females or stranger females. However, AVP-ir was significantly higher in the supraoptic nucleus (SON) of isolates compared to siblings. There were no differences in central OT-ir or plasma OT. These results identify neuroendocrine mechanisms which respond to isolation and potentially modulate behavior.
|
No pos
|
No neg
|
Retriever1001
|
Psychiatric Diagnostic Uncertainty: Challenges to Patient-Centered Care.
In this case and commentary, a patient's request to be treated for depression without a stigmatizing diagnostic label of bipolar II disorder challenges a clinician's obligation to provide a clinically and ethically appropriate diagnosis and safe treatment consistent with the patient's family medical history. Sensitively recognizing and responding to patients' concerns and values, even when they might conflict with the delivery of reasonable psychiatric care, is essential when gauging the appropriateness of such therapeutic practices. Furthermore, developing honest and open communication; recognizing that patients, like some psychiatric diagnoses, do not fit into discrete boundaries or cannot be categorized by a single label; and placing the patient at the center of care can all serve to resolve value conflicts, protect patient privacy, and promote accurate diagnostic and treatment practices.
|
No pos
|
No neg
|
Retriever1002
|
A UNIFIED CONDITIONAL DISENTANGLEMENT FRAMEWORK FOR MULTIMODAL BRAIN MR IMAGE TRANSLATION.
Multimodal MRI provides complementary and clinically relevant information to probe tissue condition and to characterize various diseases. However, it is often difficult to acquire sufficiently many modalities from the same subject due to limitations in study plans, while quantitative analysis is still demanded. In this work, we propose a unified conditional disentanglement framework to synthesize any arbitrary modality from an input modality. Our framework hinges on a cycle-constrained conditional adversarial training approach, where it can extract a modality-invariant anatomical feature with a modality-agnostic encoder and generate a target modality with a conditioned decoder. We validate our framework on four MRI modalities, including T1-weighted, T1 contrast enhanced, T2-weighted, and FLAIR MRI, from the BraTS'18 database, showing superior performance on synthesis quality over the comparison methods. In addition, we report results from experiments on a tumor segmentation task carried out with synthesized data.
|
No pos
|
No neg
|
Retriever1003
|
Treatment preference for monthly oral ibandronate and weekly oral alendronate in women with postmenopausal osteoporosis: A randomized, crossover study (BALTO II).
OBJECTIVES
Patient preference strongly influences long-term medication use in chronic diseases such as postmenopausal osteoporosis.
METHODS
This 6-month, open-label, crossover, international study randomized 350 women with postmenopausal osteoporosis to monthly oral ibandronate 150mg for 3months followed by weekly alendronate 70mg for 12weeks, or vice versa.
RESULTS
Of patients expressing a preference (93.1%), more preferred the monthly ibandronate regimen (70.6%) than the weekly alendronate regimen (29.4%). The monthly ibandronate preference rate was statistically significant (P<0.0001). The most common reasons for ibandronate preference were ease of staying on treatment long-term (81.5%) and better lifestyle fit (75.4%). More women found the monthly ibandronate regimen more convenient (76.6%) than the weekly alendronate regimen (23.4%). The monthly ibandronate convenience rate was statistically significant (P<0.0001). The safety profiles of the two regimens were similar.
CONCLUSION
The strong patient preference for monthly ibandronate over weekly alendronate replicates previous study findings and may lead to improved treatment adherence in women with postmenopausal osteoporosis.
|
No pos
|
No neg
|
Retriever1004
|
In vitro permeation and penetration of ciclopirox olamine from poloxamer 407-based formulations--comparison of isolated human stratum corneum, bovine hoof plates and keratin films.
Fungal infections of skin and/or nails are common diseases resulting in major challenges in topical treatment. Therefore, the objective of the present study was to develop a dermal formulation targeting both tinea pedis and onychomycosis. The antifungal agent ciclopirox olamine (CPX) was incorporated into a variety of poloxamer 407-based formulations and analysed regarding its in vitro permeation and penetration behaviour across keratin films (KF) and bovine hoof plates as artificial nail models as well as human stratum corneum (SC). The novel compositions consisted of poloxamer 407 (P407), double distilled water, propylene glycol, isopropyl alcohol and medium chain triglycerides in given ratios. All the formulations exhibited semi-solid to liquid consistencies and were isotropic under a polarising microscope. Upon CPX incorporation, the formulations became softer and the yield stresses decreased. Increasing temperature led to higher complex viscosities. Permeation coefficients (P) from P407-based formulations across KF and bovine hoof plates and normalised retained CPX amounts in KF and bovine hoof plates were higher in comparison to the nail lacquer Ciclopoli(®) as a marketed reference. Data of KF and bovine hoof plates were comparable, therefore KF are suggested as artificial nail model for in vitro permeation studies besides the well-accepted nail model of bovine hoof plates. With regard to SC permeation, several liquid formulations indicated higher P in comparison to the references Ciclopoli(®) and the antimycotic skin formulation Selergo(®) 1% cream, while the normalised retained API amounts in SC were higher in comparison with Selergo(®) 1% cream or in the same range as Ciclopoli(®).
|
No pos
|
No neg
|
Retriever1005
|
From neurodevelopment to neurodegeneration: utilizing human stem cell models to gain insight into Down syndrome.
Down syndrome (DS), caused by triplication of chromosome 21, is the most frequent aneuploidy observed in the human population and represents the most common genetic form of intellectual disability and early-onset Alzheimer's disease (AD). Individuals with DS exhibit a wide spectrum of clinical presentation, with a number of organs implicated including the neurological, immune, musculoskeletal, cardiac, and gastrointestinal systems. Decades of DS research have illuminated our understanding of the disorder, however many of the features that limit quality of life and independence of individuals with DS, including intellectual disability and early-onset dementia, remain poorly understood. This lack of knowledge of the cellular and molecular mechanisms leading to neurological features of DS has caused significant roadblocks in developing effective therapeutic strategies to improve quality of life for individuals with DS. Recent technological advances in human stem cell culture methods, genome editing approaches, and single-cell transcriptomics have provided paradigm-shifting insights into complex neurological diseases such as DS. Here, we review novel neurological disease modeling approaches, how they have been used to study DS, and what questions might be addressed in the future using these innovative tools.
|
No pos
|
No neg
|
Retriever1006
|
Sexual Dimorphism of Metabolite Profiles in Pigs Depends on the Genetic Background.
The study aimed to investigate possible systematic effects in the basic underlying variability of individual metabolomic data. In this context, the extent of gender- and genotype-dependent differences reflected in the metabolic composition of three tissues in fattening pigs was determined. The 40 pigs belonged to the genotypes PIx(LWxGL) and PIxGL with gilts and boars, respectively. Blood and tissue samples from M. longissimus dorsi and liver were directly taken at the slaughtering plant and directed to GC × GC qMS metabolite analysis. Differences were observed for various metabolite classes like amino acids, fatty acids, sugars, or organic acids. Gender-specific differences were much more pronounced than genotype-related differences, which could be due to the close genetic relation of the fattening pigs. However, the metabolic dimorphism between gilts and boars was found to be genotype-dependent, and vice versa metabolic differences between genotypes were found to be gender-dependent. Most interestingly, integration into metabolic pathways revealed different patterns for carbon (C) and nitrogen (N) usage in boars and gilts. We suppose a stronger N-recycling and increased energy metabolism in boars, whereas, in gilts, more N is presumably excreted and remaining carbon skeletons channeled into lipogenesis. Associations of metabolites to meat quality factors confirmed the applicability of metabolomics approaches for a better understanding about the impact of drivers (e.g., gender, age, breed) on physiological processes influencing meat quality. Due to the huge complexity of the drivers-traits-network, the derivation of independent biomarkers for meat quality prediction will hardly be possible.
|
No pos
|
No neg
|
Retriever1007
|
Early detection of developing osteoarthritis by scintigraphy: an experimental study on rabbits.
Bone scintigraphy (99mTc-MDP) was used to study the development of experimental osteoarthritis produced by extension immobilization in rabbit knees. The purpose of the study was to determine a repeatable and noninvasive method for following the joint reaction leading to osteoarthritis. In comparison with the contralateral joints activity uptake in immobilized joints was already detectable in bone scintigraphy at 24 h, at the same time as the earliest changes in the biochemical reactions of joint tissues can be detected.
|
No pos
|
No neg
|
Retriever1008
|
Distance measurement between Tyr10 and Met35 in amyloid beta by site-directed spin-labeling ESR spectroscopy: implications for the stronger neurotoxicity of Abeta42 than Abeta40.
The neurotoxicity of the 42-mer and 40-mer amyloid beta peptides (Abeta42 and Abeta40) is closely related to the radicalization at both Tyr10 and Met35. Abeta42 is more neurotoxic than Abeta40. Our previous structural analyses of Abeta42 suggested that Tyr10 and Met35 are brought closer together by the turn at positions 22 and 23, and the S-oxidized radical cation at position 35, which is the ultimate toxic radical species, can be produced effectively through oxidation by the phenoxy radical at position 10. To verify this idea, their separation was measured by site-directed spin labeling (MTSSL) by using ESR spectroscopy. Among the three kinds of Abeta42 derivatives, which are doubly or singly spin-labeled at position 10 and 35, only 10,35-MTSSL-Abeta42 showed a clear dipole coupling in continuous-wave ESR; this suggests that the intramolecular spin labels at position 10 and 35 in Abeta42 are located within approximately 15 A. In contrast, 10,35-MTSSL-Abeta40 did not give such signals. The distance between Tyr10 and Met35 in 10,35-MTSSL-Abeta40, which was successfully measured by pulsed ESR spectroscopy was 30 A long. The difference in the distance between Abeta42 and Abeta40 could explain in part the stronger neurotoxicity of Abeta42 compared to Abeta40.
|
No pos
|
No neg
|
Retriever1009
|
Sound localization by human listeners.
In keeping with our promise earlier in this review, we summarize here the process by which we believe spatial cues are used for localizing a sound source in a free-field listening situation. We believe it entails two parallel processes: 1. The azimuth of the source is determined using differences in interaural time or interaural intensity, whichever is present. Wightman and colleagues (1989) believe the low-frequency temporal information is dominant if both are present. 2. The elevation of the source is determined from spectral shape cues. The received sound spectrum, as modified by the pinna, is in effect compared with a stored set of directional transfer functions. These are actually the spectra of a nearly flat source heard at various elevations. The elevation that corresponds to the best-matching transfer function is selected as the locus of the sound. Pinnae are similar enough between people that certain general rules (e.g. Blauert's boosted bands or Butler's covert peaks) can describe this process. Head motion is probably not a critical part of the localization process, except in cases where time permits a very detailed assessment of location, in which case one tries to localize the source by turning the head toward the putative location. Sound localization is only moderately more precise when the listener points directly toward the source. The process is not analogous to localizing a visual source on the fovea of the retina. Thus, head motion provides only a moderate increase in localization accuracy. Finally, current evidence does not support the view that auditory motion perception is anything more than detection of changes in static location over time.
|
No pos
|
No neg
|
Retriever1010
|
A Haplotype of Two Novel Polymorphisms in δ-Sarcoglycan Gene Increases Risk of Dilated Cardiomyopathy in Mongoloid Population.
The role of genetic abnormality of δ-sarcoglycan (δ-SG) gene in dilated (DCM) and hypertrophied (HCM) cardiomyopathy patients is still unfolding. In this study we first defined the promoter region and then searched for polymorphisms/mutations among the promoter, 5'-untranslated region, and the encoding exons in δ-SG gene in 104 Chinese patients with DCM, 145 with HCM, and 790 normal controls. Two novel polymorphisms were found, an 11 base-pair (bp) deletion (c.-100~-110; -) in the promoter region and a missense polymorphism of A848G resulting in p.Q283R in the highly conserved C-terminus. The prevalence of homozygous genotype -/- of c.-100~-110 was slightly higher in DCM (14.42%) and HCM patients (14.48%), as compared with normal controls (11.01%). The prevalence of genotype of 848A/G was significantly higher in DCM (6.73%; OR = 9.43; p = 0.0002), but not in HCM patients (1.38%; OR = 1.37; p = 0.62), as compared with controls (0.76%). Haplotype -_G consisting c.-100~-110 and A848G was associated with increased risk of DCM (OR = 17.27; 95%CI = 3.19-93.56; p = 0.001) but not associated with HCM (OR = 1.90; 95%CI = 0.38-9.55; p = 0.44). Co-occurrence of the genotypes -/- of c.-100~-110 and 848A/G was found in 5 patients with DCM (4.81%; OR = 39.85; p = 0.0001), none of HCM patients, and only 1 of the controls (0.13%). Both polymorphisms were also found in the Japanese population, but not in the Africans and Caucasians. C.-100~-110 resulted in a decrease of δ-SG promoter activity to 64±3% of the control level (p<0.01). Both co-immunoprecipitation and in vitro protein pull-down assays demonstrated that δ-SG-283R interacts normally to β- and γ-SG, but significantly decreased localization of β/δ/γ-SG on the plasma membrane. In conclusion, haplotype -_G composed of c.-100~-110 and A848G confers higher susceptibility to DCM in the Mongoloid population.
|
No pos
|
No neg
|
Retriever1011
|
An Evaluation of High Preprocedural Anxiety and Venipuncture Pain Experienced by Young Children.
OBJECTIVE
The aim of this study was to determine if young children with high preprocedural anxiety experience increased pain at venipuncture.
METHODS
This was secondary analysis of prospectively obtained data from a randomized controlled trial comparing vapocoolant spray with jet-injected lidocaine for venipuncture pain. Children aged 1 to 6 years were enrolled and videotaped. Videos were reviewed and scored for anxiety using the modified Yale Preoperative Anxiety Scale score for preprocedural anxiety (score range, 23-100). High anxiety was defined as greater than 40. Pain at the time of venipuncture was scored using the Face, Legs, Activity, Cry, and Consolability scale (score range 0-10). Moderate to severe pain was defined as greater than 3. Logistic regression assessed patient factors associated with high preprocedural anxiety and evaluated the relationship between preprocedural anxiety and pain during venipuncture.
RESULTS
Two hundred five patients were enrolled; 59.5% of patients were male, and 53.7% were White. Mean age was 3.2 years. Prior to the procedure, 67% of patients had high anxiety. Patient age, race, sex, and previous venipuncture were not associated with increased odds of high anxiety. Moderate to severe pain at venipuncture was observed in 65% of children. High preprocedural anxiety was associated with increased odds of moderate to severe pain at venipuncture when controlled for patient characteristics (adjusted odds ratio, 4.62; 95% confidence interval, 2.03-8.54).
CONCLUSIONS
Most young children undergoing venipuncture experienced high preprocedural anxiety. Children with high preprocedural anxiety had increased odds of moderate to severe pain at venipuncture. Anxiety-reducing interventions should be explored to reduce pain experienced during venipuncture.
|
No pos
|
No neg
|
Retriever1012
|
Development and validation of a standardized tool for reporting retinal findings in abusive head trauma.
PURPOSE
To develop and validate a robust standardized reporting tool for describing retinal findings in children examined for suspected abusive head trauma.
DESIGN
A prospective interobserver and intraobserver agreement study.
METHOD
An evidence-based assessment pro forma was developed, recording hemorrhages (location, layer, severity) and additional features. Eight consultant pediatric ophthalmologists and 7 ophthalmology residents assessed a series of 105 high-quality RetCam images of 21 eyes from abusive head trauma cases with varying degrees of retinal hemorrhage and associated findings. The pediatric ophthalmologists performed a repeat assessment of the randomized images. The images were observed simultaneously with standardized display settings. Interobserver and intraobserver agreement was assessed using free-marginal multirater kappa, intraclass correlation coefficients, and concordance coefficients.
RESULTS
Almost-perfect interobserver agreement was observed for residents and pediatric ophthalmologists recording the presence and number of fundus hemorrhages (intraclass correlation coefficients 0.91 and 0.87, respectively) and the location of hemorrhages (concordance coefficients 0.86 and 0.85, respectively). Substantial agreement was observed by both groups regarding size of hemorrhage (concordance coefficients 0.73 and 0.76), moderate agreement for hemorrhage morphology (concordance coefficients 0.53 and 0.52), and other findings (concordance coefficients 0.48 and 0.59). Intraobserver agreement for pediatric ophthalmologists varied by question, ranging from substantial to perfect for the presence, number, location, size, and morphology of fundus hemorrhage.
CONCLUSION
We have developed and validated a standardized clinical reporting tool for ophthalmic findings in suspected abusive head trauma, which has excellent interobserver and intraobserver agreement among consultant specialists and residents. We suggest that its use will improve standardized clinical reporting of such cases.
|
No pos
|
No neg
|
Retriever1013
|
Clear-air turbulence: simultaneous observations by radar and aircraft.
Ultrasensitive radars and uninstrumented jet aircraft in concert have probed regions of the clear atmosphere in search of clear-air turbulence. All sources of clear-air radar echoes above 6 kilometers that were probed simultaneously by the aircraft were found to be turbulent.
|
No pos
|
No neg
|
Retriever1014
|
Homosexuality and bisexuality in different populations.
The general public as well as the scientific community have use for accurate data on the size(s) of the heterosexual, homosexual, and bisexual populations. Uses include political, legal, medical, and social. The data upon which the typically used figures are dependent have come under scrutiny. This review of studies from the U.S. and elsewhere indicate that it is unreasonable to consider the often-used figure of 10% of the male population as more or less regularly engaging in same-sex activities. The figure is closer to half that. And the figure for the lesbian population is even smaller. Further, routinely exclusive or predominantly exclusive homosexual activities are more common than bisexual activities.
|
No pos
|
No neg
|
Retriever1015
|
The impact of environmental and demographic factors on nursing job satisfaction.
OBJECTIVE
This study aims to evaluate all aspects of job satisfaction in registered nurses working in different hospitals in Shiraz, Iran.
METHODS
This cross-sectional study was performed during February to August 2015 in Shiraz, Iran. It comprised of 371 registered nurses working in government and private hospitals using multi-stage cluster sampling. Job satisfaction was evaluated using 5 items of the Job Descriptive Index (JDI) consisting of 63 questions developed by Smith, Kendall, and Hulin (1969). Statistical tests including independent sample t test and one-way analysis of variance (ANOVA) were used in order to identify the relation between job satisfaction, and demographic features and work environment. Data were analyzed by SPSS version 15.0, using descriptive statistics, independent-samples t-test, and ANOVA.
RESULTS
Our findings showed no relationship between demographic variables and job satisfaction. However, a significant association was observed between environmental aspects such as work rotation (fixed versus rotating) nurse's status (staff vs. supervisors), type of hospitals (governmental vs. private) and work (p<0.01), promotion (p<0.02) and pay (p<0.01) items respectively; however, type of hospital was deemed exempt regarding promotion. Also regarding the number of shifts per week, nurses with more than eight shifts present a lower mean score of satisfaction about pay significantly (p=0.03).
CONCLUSION
The results concerning younger nurses have different types of satisfaction based on several environmental factors. Nurses' policy makers must pay more attention to nurses' satisfaction and focus on reducing the various inequalities.
|
No pos
|
No neg
|
Retriever1016
|
Skyrmion motion driven by oscillating magnetic field.
The one-dimensional magnetic skyrmion motion induced by an electric current has attracted much interest because of its application potential in next-generation magnetic memory devices. Recently, the unidirectional motion of large (20 μm in diameter) magnetic bubbles with two-dimensional skyrmion topology, driven by an oscillating magnetic field, has also been demonstrated. For application in high-density memory devices, it is preferable to reduce the size of skyrmion. Here we show by numerical simulation that a skyrmion of a few tens of nanometres can also be driven by high-frequency field oscillations, but with a different direction of motion from the in-plane component of the tilted oscillating field. We found that a high-frequency field for small skyrmions can excite skyrmion resonant modes and that a combination of different modes results in a final skyrmion motion with a helical trajectory. Because this helical motion depends on the frequency of the field, we can control both the speed and the direction of the skyrmion motion, which is a distinguishable characteristic compared with other methods.
|
No pos
|
No neg
|
Retriever1017
|
Simplified coagglutination test for serological grouping of beta-hemolytic streptococci.
A new coagglutination kit consisting of a plastic slide with dried antibody-coated staphylococci was evaluated for the grouping of beta-hemolytic streptococci of groups A, B, C, and G. The test was compared with the classical precipitation test, using hot formamide antigen extracts with 224 strains of groups A, B, C, and G streptococci. An agreement of 100% was found between the new coagglutination and the classical precipitation procedures. No false-positive results were obtained with group F and D streptococci; however, group L streptococci reacted with the group A reagent. The test procedure could be shortened by using suspensions of colonies from overnight cultures on blood agar plates in small volumes of Todd-Hewitt broth without further incubation. All 74 strains of groups A, B, C, and G were correctly identified from suspensions in Todd-Hewitt broth; however, suspending the colonies in 0.9% saline or phosphate-buffered saline resulted in lower sensitivities.
|
No pos
|
No neg
|
Retriever1018
|
Establishment of reference range of CD4 T-lymphocyte in healthy Nepalese adults.
OBJECTIVE
CD4 T lymphocytes are the most widely used cellular markers to assess the course of HIV infection, clinical staging and, monitoring the effect of antiretroviral therapy. The regional reference range for Eastern, Central and Western development region of Nepal had already been established whereas the same was still lacking in Mid-western and Far-western development region. The objective of this study was to establish reference range of CD4 T lymphocyte in the remaining two development regions and finally the national reference range using data from previous study.
RESULTS
The average values (mean ± SD) of CD4 and CD3 T cell in present study was (819 ± 294) cells/μl and (1546 ± 532) cells/μl, respectively. The absolute CD4 T cell (914 ± 303) and CD3 T cell (1671 ± 560) count in female were significantly higher than those from male, CD4 (757 ± 270) and CD3 (1465 ± 499) (p value-0.000). National reference value of CD4 was determined to be (798 ± 335) cells/μl for healthy Nepalese adults.
|
No pos
|
No neg
|
Retriever1019
|
Early- and late-onset breast cancer types among women in the United States and Japan.
BACKGROUND
Although differences in breast cancer incidence among Occidental and Asian populations are often attributed to variations in environmental exposures and/or lifestyle, fewer studies have systematically examined the effect of age-related variations.
METHODS
To further explore age-related geographic breast cancer variations, we compared age-specific incidence patterns among cases of female invasive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) program and the Osaka Cancer Registry (1978-1997).
RESULTS
In SEER, there were 236,130 Whites, 21,137 Blacks, and 3,304 Japanese-Americans in Hawaii with invasive breast cancer. In Osaka, there were 25,350 cases. Incidence rates per 100,000 woman-years ranged from 87.6 among Whites to 21.8 in Osaka. Age-specific incidence rates increased rapidly until age 50 years for all race/ethnicity groups, and then continued to increase more slowly for Whites, Blacks, and Japanese-Americans in Hawaii but plateaud for Osaka. Age-specific incidence rates in SEER reflected bimodal (early-onset and late-onset) breast cancer populations, whereas Osaka had only an early-onset age distribution. These age-specific differences in incidence among SEER and Osaka persisted after adjustment for calendar-period and birth-cohort effects using age-period-cohort models.
CONCLUSIONS
Results confirm striking age-specific differences among Occidental and native Japanese breast cancer populations, probably due to complex age-related biological and/or environmental variations among Occidental and Asian breast cancer populations.
|
No pos
|
No neg
|
Retriever1020
|
Effects of the isoform-specific characteristics of ATF6 alpha and ATF6 beta on endoplasmic reticulum stress response gene expression and cell viability.
The endoplasmic reticulum (ER)-transmembrane proteins, ATF6 alpha and ATF6 beta, are cleaved during the ER stress response (ERSR). The resulting N-terminal fragments (N-ATF6 alpha and N-ATF6 beta) have conserved DNA-binding domains and divergent transcriptional activation domains. N-ATF6 alpha and N-ATF6 beta translocate to the nucleus, bind to specific regulatory elements, and influence expression of ERSR genes, such as glucose-regulated protein 78 (GRP78), that contribute to resolving the ERSR, thus, enhancing cell viability. We previously showed that N-ATF6 alpha is a rapidly degraded, strong transcriptional activator, whereas beta is a slowly degraded, weak activator. In this study we explored the molecular basis and functional impact of these isoform-specific characteristics in HeLa cells. Mutants in the transcriptional activation domain or DNA-binding domain of N-ATF6 alpha exhibited loss of function and increased expression, the latter of which suggested decreased rates of degradation. Fusing N-ATF6 alpha to the mutant estrogen receptor generated N-ATF6 alpha-MER, which, without tamoxifen exhibited loss-of-function and high expression, but in the presence of tamoxifen N-ATF6 alpha-MER exhibited gain-of-function and low expression. N-ATF6 beta conferred loss-of-function and high expression to N-ATF6 alpha, suggesting that ATF6 beta is an endogenous inhibitor of ATF6 alpha. In vitro DNA binding experiments showed that recombinant N-ATF6 beta inhibited the binding of recombinant N-ATF6 alpha to an ERSR element from the GRP78 promoter. Moreover, siRNA-mediated knock-down of endogenous ATF6 beta increased GRP78 promoter activity and GRP78 gene expression, as well as augmenting cell viability. Thus, the relative levels of ATF6 alpha and -beta, may contribute to regulating the strength and duration of ATF6-dependent ERSR gene induction and cell viability.
|
No pos
|
No neg
|
Retriever1021
|
A combination of long term fragmentation and glacial persistence drove the evolutionary history of the Italian wall lizard Podarcis siculus.
BACKGROUND
The current distribution of genetic diversity is the result of a vast array of microevolutionary processes, including short-term demographic and ecological mechanisms and long-term allopatric isolation in response to Quaternary climatic fluctuations. We investigated past processes that drove the population differentiation and spatial genetic distribution of the Italian wall lizard Podarcis siculus by means of sequences of mitochondrial cytb (n = 277 from 115 localities) and nuclear mc1r and β-fibint7genes (n = 262 and n = 91, respectively) from all its distribution range. The pattern emerging from the genetic data was compared with current and past (last glacial maximum) species distribution modeling (SDM).
RESULTS
We identified seven deeply divergent parapatric clades which presumably remained isolated in different refugia scattered mainly throughout the Tyrrhenian coast. Conversely, the Adriatic coast showed only two haplogroups with low genetic variability. These results appear to agree with the SDM prediction at the last glacial maximum (LGM) indicating a narrow area of habitat suitability along the Tyrrhenian coast and much lower suitability along the Adriatic one. However, the considerable land exposure of the Adriatic coastline favored a glacial colonization of the Balkan Peninsula.
CONCLUSIONS
Our population-level historical demography showed a common trend consistent with glacial expansions and regional persistence during the last glacial maximum. This complex genetic signature appears to be inconsistent with the expectation of the expansion-contraction model and post-LGM (re)colonizations from southern refugia. Hence it is one of an increasing number of cases in which these assumptions are not met, indicating that long-term fragmentation and pre-LGM events such as glacial persistence were more prominent in shaping genetic variation in this temperate species.
|
No pos
|
No neg
|
Retriever1022
|
Isotherm, kinetics, and adsorption mechanism studies of diethylenetriaminepentaacetic acid-modified banana/pomegranate peels as efficient adsorbents for removing Cd(II) and Ni(II) from aqueous solution.
Two novel absorbents were synthesized for the first time by banana and pomegranate peels using diethylenetriaminepentaacetic acid (DTPA) modification to eliminate Cd(II) and Ni(II) of sewage. The DTPA-modified peels performed significantly higher adsorption capacity than unmodified materials. The maximum adsorption capacities of DTPA-modified banana/pomegranate peel were 46.729/46.296 mg/g for Cd(II), and 29.240/16.611 mg/g for Ni(II). Adsorption isotherm and kinetics models were simulated to determine their removal efficiency and potential for recovery of these two heavy metals. As the results, the adsorption reached equilibrium within 5 min and was well described by the pseudo-second order model and Langmuir isotherm. The surface morphology analysis of the synthetic materials by Scanning Electron Microscopy-Energy Dispersive X-ray spectroscopy, Fourier Transform Infrared spectroscopy, and X-ray Photoelectron Spectroscopy, implied that ion exchange, complexation, and physical adsorption may together contribute to Cd(II) and Ni(II) loading on DTPA-modified peels. This study demonstrates the feasibility of waste peels as cost-efficient bio-absorbents to remove Cd(II) and Ni(II) in sewage systems, and discovers potential adsorption mechanism of efficiency improvements after DTPA modification.
|
No pos
|
No neg
|
Retriever1023
|
Functional magnetic resonance imaging of motor activation in the human cervical spinal cord.
Functional magnetic resonance imaging (fMRI) at 1.5 T of a 30-mm segment of the human spinal cord, centered at the seventh cervical cord segment, showed mean blood-oxygenation-dependent contrast changes in image intensity of 4.8% associated with a unilateral hand-closing task in normal human volunteers. The observed locale of activation in the ipsilateral intermediate and ventral gray matter of the cervical cord contains motoneurons, corticospinal axonal terminations from the hand area of the brain motor cortex, and capillaries supplying the spinal neurons. This noninvasive observation of focal activation within the human spinal cord is consistent with neuronal cooperation over more than one cord segment and suggests that fMRI of the human central nervous system may have wider clinical applications outside of the brain.
|
No pos
|
No neg
|
Retriever1024
|
Role of the interleukin-6 -174 G>C gene polymorphism in retinal artery occlusion.
BACKGROUND AND PURPOSE
Proinflammatory cytokines including interleukin-6 (IL-6) are supposed to play a pivotal role in the development of atherosclerosis. A common polymorphism in the promoter of the IL-6 gene (IL-6 -174G>C) affects plasma IL-6 concentrations and has been suggested as a risk factor for cardiovascular disease. The aim of the present case-control study was to investigate the role of this polymorphism for retinal artery occlusion (RAO).
METHODS
One hundred eighty-two patients with RAO and 307 control subjects were genotyped for the IL-6 -174G>C polymorphism. Genotypes were determined by fluorogenic exonuclease (TaqMan) assay.
RESULTS
The prevalence of the CC genotype was significantly lower in patients with RAO than in control subjects (10.4% versus 19.9%; P=0.006). Homozygosity for the C allele was associated with an odds ratio of 0.50 (95% CI, 0.28 to 0.89) for RAO.
CONCLUSIONS
The CC genotype of the IL-6 -174G>C polymorphism may be associated with a protective effect against RAO.
|
No pos
|
No neg
|
Retriever1025
|
Re-evaluation of the diagnostic performance of 11C-methionine PET/CT according to the 2016 WHO classification of cerebral gliomas.
PURPOSE
We evaluated the usefulness of 11C-methionine (MET) positron emission tomography/computed tomography (PET/CT) for grading cerebral gliomas according to the 2016 WHO classification with special emphasis on the presence of the isocitrate dehydrogenase 1 (IDH1) gene mutation and 1p/19q codeletion.
METHODS
In total, 144 patients underwent MET PET/CT before surgery. The ratios of the maximum standardized uptake value (SUV) of the gliomas to the mean SUV of the contralateral cortex on MET PET/CT (MET TNR) were calculated.
RESULTS
The median MET TNRs in IDH1-mutant and IDH1-wildtype tumours were 1.95 and 3.35, respectively. From among 74 IDH1-mutant tumours, the oligodendrogliomas showed a higher median MET TNR than the astrocytic tumours (2.90 vs. 1.40, P < 0.001). In grade II, III and IV IDH1-mutant astrocytic tumours, the median MET TNRs were 1.20, 2.05 and 2.20, respectively (grade II vs. grade III, P < 0.0001; grade II vs. grade IV, P = 0.023). In oligodendrogliomas, the MET TNR was lower fin grade II tumours than in grade III tumours (2.30 vs. 3.30 P = 0.008). In differentiating low-grade (grade II) from high-grade (grade III and IV) gliomas, receiver operating characteristic analysis showed a higher area under the curve for wildtype tumours (0.976) than for all tumours (0.852; P < 0.001) and IDH1-mutant tumours (0.817; P = 0.004).
CONCLUSION
IDH1-mutant tumours showed lower MET uptake than IDH1-wildtype tumours. Regardless of IDH1 mutation status, oligodendrogliomas with 1p/19q codeletion showed MET uptake as high as that in high-grade IDH1-wildtype tumours. Therefore, MET uptake for glioma grading was more consistent for IDH1-wildtype tumours than for IDH1-mutant tumours.
|
No pos
|
No neg
|
Retriever1026
|
Effect of Body Type on Renal Injury: Major Renal Trauma Following an Insignificant Common-in-Everyday-Life Incident.
A blunt renal trauma (RT) diagnosis can present challenges. It demands increased clinical suspicion, taking into consideration patient history, mechanism of injury, and clinical and laboratory findings. Final diagnosis may be confirmed radiographically or intraoperatively. A thin, 22-year-old female with severe right flank pain appeared ambulatory in the emergency department. The pain appeared 1 h previously, following a common incident in a city bus, where the patient was as a standing passenger. The bus was moving in an urban area at low speed and decelerated rapidly. Another standing passenger fell on the patient, causing her right flank area to be compressed onto the bus banister for a few seconds. Clinical findings were insignificant. Laboratory examinations revealed only a nonvisible hematuria. Chest X-ray and abdominal ultrasonography were normal. Due to pain severity, an abdominal computed tomography scan was performed and revealed a grade-4, parenchymal RT with extravasation of contrast medium in delayed images. The patient underwent double-J stent insertion and had an uneventful recovery. She presented no complications at 5 mo postinjury. Major RT can be a result of an insignificant, blunt injury in a thin patient; thus, taking into consideration body habitus is of paramount importance in diagnostic evaluation.
|
No pos
|
No neg
|
Retriever1027
|
Aberrant expression of HIF3A in plasma of patients with non-small cell lung cancer and its clinical significance.
BACKGROUND
Hypoxia-inducible factors (HIFs) have been evaluated in various cancers and diseases. However, the specific role of hypoxia-inducible factor 3 alpha (HIF3A) in non-small cell lung cancer (NSCLC) remains controversial.
MATERIALS AND METHODS
We investigated HIF3A mRNA expression in the plasma and tumor tissues of patients with NSCLC and explored its clinical significance. Plasma samples from 103 cases of lung adenocarcinoma (LUAD) and 96 cases of lung squamous cell carcinoma (LUSC), and tumor-adjacent normal tissues from 58 LUAD and 62 LUSC cases were retrospectively evaluated at the No.8 People's Hospital of Qing Dao. HIF3A expression was explored using RT-qPCR. The clinical significance of HIF3A was evaluated in the plasma and tumor tissues using the receiver operating curve (ROC) and the area under the curve (AUC).
RESULTS
Hypoxia-inducible factor 3 alpha expression was notably downregulated in the plasma or tumor tissues of patients with LUAD and LUSC, compared with the healthy control group or adjacent normal tissues. Furthermore, HIF3A expression had a significant positive correlation in the plasma and tumor tissues of LUAD and LUSC patients. Meanwhile, the ROC-AUCs achieved a significantly higher range, from 0.84 to 0.93, with the plasma or tumor tissues of NSCLC patients. Thus, HIF3A expression was not only correlated with plasma and tumor tissues, but also showed potential significance in NSCLC.
CONCLUSION
Hypoxia-inducible factor 3 alpha is aberrantly detectable in NSCLC patients in the plasma and tumor tissues. HIF3A may be involved in hypoxic responses during the development and occurrence of NSCLC.
|
No pos
|
No neg
|
Retriever1028
|
Cancer incidence following treatment for infertility at a clinic in the UK.
BACKGROUND
There is concern about the long-term health impact of ovarian stimulation treatment for infertility, in particular the effect on cancer risk. The aim of this study was to investigate the incidence of cancer in a cohort of women attending a large infertility clinic in the UK.
METHODS
Women who were UK residents attending the clinic between January 1, 1975 and December 31, 1989 were identified for the study. The cohort was followed-up and cancer incidence rates calculated.
RESULTS
The study cohort was made up of 5556 women of whom 75% had received ovarian stimulation drug treatment at the clinic. A total of 118 cancers (including 55 breast, four corpus uteri and six ovarian) were incident in the cohort from the beginning of 1990 to the end of 1997. The incidence rates of cancer of the breast, corpus uteri and ovary were not significantly different from expectation based on national cancer rates, and were similar for women who had received hormonal treatment to stimulate their ovaries and those who had not.
CONCLUSIONS
These data do not support a hypothesis linking infertility treatment involving ovarian stimulation with increased breast, uterine and ovarian cancer over the follow-up period studied.
|
No pos
|
No neg
|
Retriever1029
|
Amprenavir inhibits the migration in human hepatocarcinoma cell and the growth of xenografts.
The introduction of HAART (highly-active-antiretroviral-therapy) has resulted in extended survival of HIV positive patients. Conversely, due to the prolonged expectancy of life and the ageing of the HIV positive population, tumors are now one of the major cause of death, and among them hepatocellular carcinoma (HCC) has become a growing concern in these patients. Considering the potential anti-tumoral effects of HIV protease inhibitors, we decided to evaluate the anti-tumoral activity of Amprenavir on liver carcinoma and to evaluate its potential synergistic effects in combination with standard chemoterapic drugs, such as Doxorubicin. Our results indicate that Amprenavir had direct inhibitory effects on invasion of Huh-7 hepatocarcinoma cell lines, inhibiting MMP proteolytic activation. Amprenavir was able to delay the growth of hepatocarcinoma xenografts in nude mice and had a synergistic effect with Doxorubicin. Furthermore, Amprenavir was able to promote regression of hepatocarcinoma growth in vivo by anti-angiogenetic and overall anti-tumor activities, independently by PI3K/AKT related pathways that at today is one of the more suggestive hypothesis to explain the anti-tumor effects of the different protease inhibitors. In summary these findings suggest novel anti-neoplastic action of Amprenavir on liver cancer showing the possibility of novel combination therapies.
|
No pos
|
No neg
|
Retriever1030
|
Neuroendocrine differentiation in pure type mammary mucinous carcinoma is associated with favorable histologic and immunohistochemical parameters.
Mucinous carcinoma of the breast is a specific good prognostic type malignancy occurring in elderly patients. Neuroendocrine differentiation has long been described in mucinous carcinoma, but the significance of such finding is uncertain. We evaluated the neuroendocrine differentiation profiles of 38 cases of pure mucinous carcinoma and compared the clinicopathological differences between those with and those without neuroendocrine differentiation. The parameters assessed included patients' age, tumor size, nuclear grade, axillary lymph node status at time of diagnosis, percentage area of intratumoral mucin, and the expression of estrogen and progesterone receptors, cerbB2 oncoprotein, and three neuroendocrine markers, namely neurone-specific enolase, chromogranin, and synaptophysin by immunohistochemistry. Patients' outcome and follow-up period were also documented. Of the 38 cases of pure mucinous carcinoma, 28, 11 and six cases showed positive staining for 1, 2 and 3 of the neuroendocrine markers. For all the groups with variable neuroendocrine differentiation and compared to those without such differentiation, they all showed older patients' age, higher proportion of tumors with lower nuclear grade, lower incidence of axillary lymph node metastasis, a higher progesterone receptor, and lower cerbB2 oncoprotein expression. No difference was detected between tumor size, intratumoral mucinous area, and estrogen receptor status. In all, 37 patients did not have distant metastases or local recurrences at the end of follow-up period, while one patient with coexisting high-grade ductal carcinoma in situ at time of diagnosis died of breast carcinoma. Our findings suggest that the identification of neuroendocrine differentiation in pure mucinous carcinoma is associated with more favorable histologic and immunohistochemical parameters.
|
No pos
|
No neg
|
Retriever1031
|
Prediction of Optimal Drug Schedules for Controlling Autophagy.
The effects of molecularly targeted drug perturbations on cellular activities and fates are difficult to predict using intuition alone because of the complex behaviors of cellular regulatory networks. An approach to overcoming this problem is to develop mathematical models for predicting drug effects. Such an approach beckons for co-development of computational methods for extracting insights useful for guiding therapy selection and optimizing drug scheduling. Here, we present and evaluate a generalizable strategy for identifying drug dosing schedules that minimize the amount of drug needed to achieve sustained suppression or elevation of an important cellular activity/process, the recycling of cytoplasmic contents through (macro)autophagy. Therapeutic targeting of autophagy is currently being evaluated in diverse clinical trials but without the benefit of a control engineering perspective. Using a nonlinear ordinary differential equation (ODE) model that accounts for activating and inhibiting influences among protein and lipid kinases that regulate autophagy (MTORC1, ULK1, AMPK and VPS34) and methods guaranteed to find locally optimal control strategies, we find optimal drug dosing schedules (open-loop controllers) for each of six classes of drugs and drug pairs. Our approach is generalizable to designing monotherapy and multi therapy drug schedules that affect different cell signaling networks of interest.
|
No pos
|
No neg
|
Retriever1032
|
Characterizing the Transport and Surface Affinity of Extracellular Vesicles Isolated from Yeast and Bacteria in Well-Characterized Porous Media.
Extracellular vesicles (EVs) are membrane-bounded, nanosized particles, produced and secreted by all biological cell types. EVs are ubiquitous in the environment, operating in various roles including intercellular communication and plant immune modulation. Despite their ubiquity, the role of EV surface chemistry in determining transport has been minimally investigated. Using the zeta (ζ)-potential as a surrogate for surface charge, this work considers the deposition of EVs from the yeast, Saccharomyces cerevisiae, and two bacterial species, Staphylococcus aureus and Pseudomonas fluorescens, in well-characterized porous medium under various background conditions shown to influence the transport of other environmental colloidal particles: ionic strength and humic acid concentration. The affinity of S. cerevisiae EVs for the porous medium (glass beads) appeared to be sensitive to changes in ionic strength, as predicted by colloid stability (Derjaguin, Landau, Verwey, and Overbeek or DLVO) theory, and humic acid concentration, while P. fluorescens EVs deviated from DLVO predictions, suggesting that mechanisms other than charge stabilization may control the deposition of P. fluorescens. Calculations of attachment efficiency from these deposition studies were used to estimate EV transport using a clean-bed filtration model. Based on these calculations, EVs could be transported through such homogeneous porous media up to 15 m.
|
No pos
|
No neg
|
Retriever1033
|
Effects of terpinen-4-ol fumigation on protein levels of detoxification enzymes in Tribolium confusum.
Terpinen-4-ol has high fumigating activity to stored-grain pests including Tribolium confusum. To understand the detoxification of terpinen-4-ol in insects, proteomic analysis was performed to identify related proteins and pathways in response to terpinen-4-ol fumigation in T. confusum. By using isobaric tags for relative and absolute quantitation (iTRAQ)-based strategy, 4,618 proteins were obtained from T. confusum adults in the present study. Comparative proteomic analysis showed that 148 proteins were upregulated and 137 proteins were downregulated in beetles under the LC50 of terpinen-4-ol treatment for 24 hr. According to functional classifications, differentially expressed proteins (DEPs) were enriched in xenobiotic metabolism pathways. In the detoxification pathway, the levels of 25 cytochrome P450s, 5 glutathione S-transferases, and 2 uridine diphosphate (UDP)-glucuronosyltransferases were changed, most of which were upregulated in T. confusum exposed to terpinen-4-ol. The results indicated that terpinen-4-ol was potentially metabolized and detoxified by enzymes like P450s in T. confusum.
|
No pos
|
No neg
|
Retriever1034
|
The NIFS protein can function as a selenide delivery protein in the biosynthesis of selenophosphate.
The NIFS protein from Azobacter vinelandii is a pyridoxal phosphate-containing homodimer that catalyzes the formation of equimolar amounts of elemental sulfur and L-alanine from the substrate L-cysteine (Zheng, L., White, R. H., Cash, V. L., Jack, R. F., and Dean, D. R. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 2754-2758). A sulfur transfer role of NIFS in which the enzyme donates sulfur for iron sulfur center formation in nitrogenase was suggested. The fact that NIFS also can catalyze the decomposition of L-selenocysteine to elemental selenium and L-alanine suggested the possibility that this enzyme might serve as a selenide delivery protein for the in vitro biosynthesis of selenophosphate. In agreement with this hypothesis, we have shown that replacement of selenide with NIFS and L-selenocysteine in the in vitro selenophosphate synthetase assay results in an increased rate of formation of selenophosphate. These results thus support the view that a selenocysteine-specific enzyme similar to NIFS may be involved as an in vivo selenide delivery protein for selenophosphate biosynthesis. A kinetic characterization of the two NIFS catalyzed reactions carried out in the present study indicates that the enzyme favors L-cysteine as a substrate compared with its selenium analog. A specific activity for L-cysteine of 142 nmol/min/mg compared with 55 nmol/min/mg for L-selenocysteine was determined. This level of enzyme activity on the selenoamino acid substrate is adequate to deliver selenium to selenophosphate synthetase in the in vitro assay system described.
|
No pos
|
No neg
|
Retriever1035
|
Molecular and immunohistochemical studies on epidermal responses in Atlantic salmon Salmo salar L. induced by Gyrodactylus salaris Malmberg, 1957.
Various strains of Atlantic salmon exhibit different levels of susceptibility to infections with the ectoparasitic monogenean Gyrodactylus salaris. The basic mechanisms involved in this differential ability to respond to this monogenean were elucidated using controlled and duplicated challenge experiments. Highly susceptible East Atlantic salmon allowed parasite populations to reach up to 3000 parasites per host within 6 weeks, whereas less susceptible Baltic salmon never reached larger parasite burdens than 122 parasites per host during the same period. The present study, comprising immunohistochemistry and gene expression analyses, showed that highly susceptible salmon erected a response mainly associated with an increased expression of interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma), IL-10 and infiltration of CD3-positive cells in the epidermis of infected fins. Less susceptible salmon showed no initial response in fins but 3-6 weeks post-infection a number of other genes (encoding the immune-regulating cytokine IL-10, cell marker MHC II and the pathogen-binding protein serum amyloid A) were found to be up-regulated. No proliferation of epithelial cells was seen in the skin of less susceptible salmon, and IL-10 may play a role in this regard. It can be hypothesized that resistant salmon regulate the parasite population by restricting nutrients (sloughed epithelial cells and associated material) and thereby starve the parasites. In association with this 'scorched-earth strategy', the production of pathogen-binding effector molecules such as serum amyloid A (SAA) (or others still not detected) may contribute to the resistance status of the fish during the later infection phases.
|
No pos
|
No neg
|
Retriever1036
|
Formation of topographic maps.
The catalogue of data presented here form many systems demonstrates that multiple mechanisms are involved in the formation of topographic maps. We are not yet in a position to explain why a particular mechanism appears to dominate in some situations and not in others. Certain generalizations can be made, however. First, at least some form of chemospecificity can be invoked to help explain connectivity in all of the experiments we have cited. Often, the differential identities of a population of neurons can be reflected in an orderly pattern of axon outgrowth and in the actively maintained preservation of neighbor relations as the axons grow toward their targets; such orderly arrangements are not obligatory, but, where present, they facilitate the speedy establishment of orderly maps when the axons reach their target nuclei. Within a terminal zone, chemospecific cues may dominate and constrain a given axon to terminate in a specific location, but axon-axon interactions commonly supercede chemospecific matching. At least two forms of axon-axon interaction occur, one based on some sort of biochemical properties related to the axon's embryological identity and another based on the axons' electrical activity. Tasks for the future are to identify the cellular bases of each of these mechanisms and to understand the situations in which each is manifested.
|
No pos
|
No neg
|
Retriever1037
|
Citrate and renal calculi.
Potassium citrate is a new and exciting therapeutic approach which has considerably broadened our capability for the medical control of stone disease. The discussion summarizes the data supporting utility of potassium citrate in the management of renal tubular acidosis with calcium stones, hypocitraturic calcium oxalate nephrolithiasis ('idiopathic', or secondary to chronic diarrheal syndrome or thiazide therapy) and uric acid lithiasis with or without calcium stones.
|
No pos
|
No neg
|
Retriever1038
|
Phenotypic predictors of suicide subtypes from pre-to postdeployment in active duty military personnel.
Military service members are at increased risk for suicide, but there are few strategies for detecting those who are at highest risk after a deployment. Using all available data collected from 4119 Military service members before and after their deployment to Iraq for Operation Iraqi Freedom, we tested whether predeployment characteristics clustered together to predict postdeployment suicidal risk. Latent class analysis showed that three classes best characterized the sample at predeployment. Class 1 had significantly higher scores on PTSD severity pre- and postdeployment than Classes 2 and 3 (Ps < .001). At postdeployment, Class 1 also had a greater proportion of endorsement of lifetime and past year suicidal ideation than Classes 2 and 3 (Ps < .05) and a greater proportion of lifetime suicide attempts than Class 3 (P < .001). Class 1 also had a greater proportion of endorsement of past-30-days intention to act on suicidal thoughts than Classes 2 and 3 (Ps < .05) and past-30-days specific plan for suicide than Classes 2 and 3 (Ps < .05). The study showed that based only on predeployment data, it is possible to determine which service members might be at highest risk for suicidal ideation and behavior at postdeployment.
|
No pos
|
No neg
|
Retriever1039
|
Water quality assessment of a small peri-urban river using low and high frequency monitoring.
The biogeochemical behaviors of small rivers that pass through suburban areas are difficult to understand because of the multi-origin inputs that can modify their behavior. In this context, a monitoring strategy has been designed for the Marque River, located in Lille Metropolitan area of northern France, that includes both low-frequency monitoring over a one-year period (monthly sampling) and high frequency monitoring (measurements every 10 minutes) in spring and summer. Several environmental and chemical parameters are evaluated including rainfall events, river flow, temperature, dissolved oxygen, turbidity, conductivity, nutritive salts and dissolved organic matter. Our results from the Marque River show that (i) it is impacted by both urban and agricultural inputs, and as a consequence, the concentrations of phosphate and inorganic nitrogen have degraded the water quality; (ii) the classic photosynthesis/respiration processes are disrupted by the inputs of organic matter and nutritive salts; (iii) during dry periods, the urban sewage inputs (treated or not) are more important during the day, as indicated by higher river flows and maximal concentrations of ammonium; (iv) phosphate concentrations depend on oxygen contents in the river; (v) high nutrient concentrations result in eutrophication of the Marque River with lower pH and oxygen concentrations in summer. During rainfalls, additional inputs of ammonium, biodegradable organic matter as well as sediment resuspension result in anoxic events; and finally (vi) concentrations of nitrate are approximately constant over the year, except in winter when higher inputs can be recorded. Having better identified the processes responsible for the observed water quality, a more informed remediation effort can be put forward to move this suburban river to a good status of water quality.
|
No pos
|
No neg
|
Retriever1040
|
Nanoparticle delivery of suicide DNA for epithelial ovarian cancer therapy.
Intraperitoneal administration of polymeric nanoparticles to deliver DNA encoding suicide genes holds much promise as an effective therapy for advanced epithelial ovarian cancer. Poly(beta-amino ester)s, a class of cationic, biodegradable polymers complex to DNA to form nanoparticles that deliver DNA to cells in ovarian tumors. Modifications to poly(beta-amino ester)s can improve both the efficiency and specificity with which DNA is delivered to tumor cells. Preclinical studies to test therapeutic efficacy of gene therapy strategies that are under development make use of mouse models for epithelial ovarian cancer and new imaging technologies.
|
No pos
|
No neg
|
Retriever1041
|
Clinical and psychological characteristics of TMD patients with trauma history.
OBJECTIVE
The purpose of this study was to investigate clinical and psychological characteristics of temporomandibular disorders (TMD) patients with trauma history.
MATERIALS AND METHODS
The clinical and psychological characteristics of 34 TMD patients with trauma history were compared with those of 340 TMD patients without trauma history. Craniomandibular index (CMI) was used for clinical characteristics of TMD patients. Symptom severity index (SSI) was used to assess the multiple dimensions of pain. Symptom checklist-90-revision (SCL-90-R) was used for psychological evaluation.
RESULTS
Temporomandibular disorders patients with trauma history displayed significantly higher CMI and palpation index. TMD patients with trauma history also exhibited higher values in duration, sensory intensity, affective intensity, tolerability, scope of symptom, and total SSI score. In addition, these patients showed significantly higher values in symptom dimensions of somatization, depression, anxiety, phobic anxiety, and paranoid ideation. Among the symptom dimensions of SCL-90-R, somatization showed the most significant correlations with CMI and SSI.
CONCLUSIONS
Temporomandibular disorders patients with trauma history displayed more severe subjective, objective, and psychological dysfunction than those without trauma history. Pain of myogenous origin, history of physical trauma, and psychosocial dysfunction were all closely related.
|
No pos
|
No neg
|
Retriever1042
|
Can educational video resources improve learning when used to augment traditional teaching of clinical examination? A randomized control trial of novice medical students.
BACKGROUND
Good clinical examination skills can both increase the quality of patient care and reduce its cost. A previous study by our group demonstrated that face-to-face training is the gold standard for teaching these skills. It is unclear if high quality educational videos can augment this teaching.
METHODS
Forty-two Medical Students naïve to large joint examination were recruited and block randomised to two groups. The control group had face-to-face teaching alone. The intervention group had their teaching augmented with a custom educational video accessed via a web portal. Participants were assessed on their examination of a large joint using a previously standardised assessment tool at baseline and 7 days post intervention. Assessors were blinded to intervention type.
RESULTS
There was no significant difference in the mean baseline scores. Mean baseline scores were 3.35 (11.2%, SD = 2.2, SE = 0.49) for the face-to-face only group and 2.65 (8.8%, SD = 1.39, SE = 0.31) for the video adjunct group [p = 0.137]. There was a significant difference in the improvement in score after intervention between each group [p = 0.005]. The mean improvement in score was 15.42 (SD = 5.64, SE = 1.29) for the face-to-face only group and 20.68 (SD = 4.33,SE = 0.99) for the video adjunct group.
CONCLUSION
When used as an adjunct to more traditional face-to-face teaching methods, a custom-made educational video significantly improves the teaching of clinical examination skills and there is a role for these resources in augmenting traditional teaching methods.
|
No pos
|
No neg
|
Retriever1043
|
Tumor necrosis factor-alpha as trigger of platelet activation in patients with heart failure.
The clinical history of patients with heart failure (HF) is complicated by arterial thromboembolism. Platelet activation is reported in this population, but the underlying mechanism has not been clarified. Forty-two patients with HF scored according to New York Heart Association (NYHA) classification had higher levels of collagen-induced platelet aggregation, platelet tumor necrosis factor-alpha (TNF-alpha) receptor expression, and serum thromboxane B2 and higher circulating levels of TNF-alpha than 20 healthy subjects. Coincubation of platelets from HF patients with an inhibitor of TNF-alpha receptors significantly reduced collagen-induced platelet aggregation. In vitro study demonstrated that TNF-alpha amplified the platelet response to collagen; this effect was inhibited by TNF-alpha receptor antagonist and inhibitors of arachidonic acid metabolism. This study showed that TNF-alpha behaves as a trigger of platelet activation through stimulation of the arachidonic acid pathway.
|
No pos
|
No neg
|
Retriever1044
|
Intercellular junctions in the human developing preovulatory follicle and corpus luteum.
Using the lanthanum tracer and freeze-fracture techniques, the cell contacts of human ovarian cells were examined. The cell contacts between theca interna cells are similar to those seen between luteal cells are composed of septate-like cell contacts and gap junctions. On the other hand granulosa cells are connected by desmosomes and gap junctions. Thus, at least from the viewpoint of cell junctions, it is suggested that the main precursory cells of the luteal cells are the theca interna cells, although there is a general agreement that the luteal cells are derived from the granulosa cells.
|
No pos
|
No neg
|
Retriever1045
|
Chronic stress influences nociceptive sensitivity of female rats in an estrous cycle-dependent manner.
Exposure to chronic stress can influence nociception and further induce hyperalgesia. Whether stress modulation of pain in female animals occurs in an estrous cycle-specific manner is still unclear. We profiled the changes in nociception (thermal, mechanical, formalin-evoked acute and inflammatory pain) of female Sprague-Dawley rats after treatment with chronic unpredictable mild stress (CUMS) and investigated whether these changes occur in an estrous cycle-dependent manner. The results showed that CUMS female rats exhibited a lower mechanical withdrawal threshold in proestrus and estrus, a longer formalin-evoked licking time in metestrus and diestrus, but no changes in the latency time on the tail-flick test. The present study findings suggest that chronic stress induces mechanical and formalin-evoked acute hyperalgesia of female rats in an estrous cycle-dependent manner.SUMMARYOur studies showed that chronic stress increased nociceptive sensitivity of female rats. Furthermore females had different stress-induced pain responses in different estrous phases: mechanical hyperalgesia in proestrus and estrus, formalin-evoked acute hyperalgesia in metestrus and diestrus.
|
No pos
|
No neg
|
Retriever1046
|
Enhanced production of (R,R)-2,3-butanediol by metabolically engineered Klebsiella oxytoca.
Microbial fermentation produces a racemic mixture of 2,3-butanediol ((R,R)-BD, (S,S)-BD, and meso-BD), and the compositions and physiochemical properties vary from microorganism to microorganism. Although the meso form is much more difficult to transport and store because of its higher freezing point than those of the optically active forms, most microorganisms capable of producing 2,3-BD mainly yield meso-2,3-BD. Thus, we developed a metabolically engineered (R,R)-2,3-BD overproducing strain using a Klebsiella oxytoca ΔldhA ΔpflB strain, which shows an outstanding 2,3-BD production performance with more than 90 % of the meso form. A budC gene encoding 2,3-BD dehydrogenase in the K. oxytoca ΔldhA ΔpflB strain was replaced with an exogenous gene encoding (R,R)-2,3-BD dehydrogenase from Paenibacillus polymyxa (K. oxytoca ΔldhA ΔpflB ΔbudC::PBDH strain), and then its expression level was further amplified with using a pBBR1MCS plasmid. The fed-batch fermentation of the K. oxytoca ΔldhA ΔpflB ΔbudC::PBDH (pBBR-PBDH) strain with intermittent glucose feeding allowed the production of 106.7 g/L of (R,R)-2,3-BD [meso-2,3-BD, 9.3 g/L], with a yield of 0.40 g/g and a productivity of 3.1 g/L/h, which should be useful for the industrial application of 2,3-BD.
|
No pos
|
No neg
|
Retriever1047
|
Ultrasound-Triggered on Demand Lidocaine Release Relieves Postoperative Pain.
Safe and non-invasive on-demand relief is a crucial and effective treatment for postoperative pain because it considers variable timing and intensity of anesthetics. Ultrasound modulation is a promising technique for this treatment because it allows convenient timed and non-invasive controlled drug release. Here, we created an ultrasound-triggered lidocaine (Lido) release platform using an amino acid hydrogel functioning as three-dimensional (3D) scaffold material (Lido-PPIX@ER hydrogel). It allows control of the timing, intensity and duration of lidocaine (Lido) to relieve postoperative pain. The hydrogel releases Lido due to the elevated reactive oxygen species (ROS) levels generated by PPIX under ultrasound triggering. The Lido-PPIX@ER hydrogel under individualized ultrasound triggering released lidocaine and provided effective analgesia for more than 72 h. The withdrawal threshold was higher than that in the control group at all time points measured. The hydrogel showed repeatable and adjustable ultrasound-triggered nerve blocks in vivo, the duration of which depended on the extent and intensity of insonation. On histopathology, no systemic effect or tissue reaction was observed in the ultrasound-triggered Lido-PPIX@ER hydrogel-treated group. The Lido-PPIX@ER hydrogel with individualized (highly variable) ultrasound triggering is a convenient and effective method that offers timed and spatiotemporally controlled Lido release to manage postoperative pain. This article presents the delivery system for a new effective strategy to reduce pain, remotely control pain, and offer timed and spatiotemporally controlled release of Lido to manage postoperative pain.
|
No pos
|
No neg
|
Retriever1048
|
Personal factors and baseline function in patients undergoing non-operative management for chronic hip-related groin pain: a cross-sectional study.
Aim
Little is known about the relationship between personal factors and perception of hip-related function among patients with chronic hip-related groin pain (HRGP) seeking non-operative management. This analysis was performed to determine if depressive symptoms, central sensitisation, movement evoked pain (MEP), pressure hypersensitivity and activity level were associated with patients' perception of hip-related function, represented by the International Hip Outcome Tool (iHOT-33).
Methods
This cross-sectional study used baseline data from a pilot randomised clinical trial. Participants had anterior hip symptoms for at least 3 of the past 12 months reproduced on examination. Depressive symptoms, central sensitisation and activity level were quantified with self-report questionnaires. MEP was assessed during step down and squat. Pain pressure threshold (PPT) was used to assess pressure hypersensitivity. Statistical analysis was performed to assess bivariate association between variables and independent association of variables with iHOT-33.
Results
Data from 33 participants (aged 18-40 years) with HRGP were analysed. Greater depressive symptoms (rs=-0.48, p=0.005), higher MEP during step down (rs=-0.36, p=0.040) and squat (rs=-0.39, p=0.024), and greater central sensitisation (rs=-0.33, p=0.058) were associated with lower (worse) iHOT-33 scores. Greater depressive symptoms (β=-0.47, 95% CI -0.76 to -0.17; p=0.003) and higher MEP during squat (β=-0.38, 95% CI -0.68 to -0.08; p=0.014) accounted for 37% of variability in iHOT-33. After adjusting for depressive symptoms and MEP, PPT, central sensitisation symptoms and activity level were not associated iHOT-33.
Conclusions
In patients with HRGP seeking non-operative management, greater depressive symptoms and MEP are independently associated with worse self-perceived hip function.
Trial registration number
NCT03959319.
|
No pos
|
No neg
|
Retriever1049
|
Association of Obesity Indicators with Hypertension in Type 2 Diabetes Mellitus Patients.
OBJECTIVES
To study the association of waist circumference (WC), waist to hip ratio (WHR) and body mass index (BMI) with hypertension in type 2 diabetes mellitus (DM) patients in a tertiary care hospital.
METHODS
The anthropometric measures of patients were recorded in the Diabetic Outdoor of Nishtar Hospital Multan from 2013 to 2018 after taking approval from the Institutional Ethical Review Committee. All patients were evaluated in detail after obtaining informed consent. Data was entered and analyzed in SPSS version 20 (IBM Corp., Armonk, NY, USA).
RESULTS
Data of 4556 type 2 DM patients, 2549 (55.9%) females, and 2007 (44.1%) males, was analyzed. Mean age of the study population was 47.72 years. Mean age of females was 47.32 years, while of males was 48.23 years. A total of 3393 (74.5%) of the patients had hypertension, 1912 females and 1481 males. The mean systolic blood pressure (SBP) was 130.84 mmHg, while the mean diastolic blood pressure (DBP) was 82.65 mmHg. Mean WC was 102.85 cm. Mean hip circumference was 100.33 cm. Mean weight was 66.93 kg. Mean height was 1.59 m. Mean WHR was 1.02. Mean BMI was 26.37 kg/m2. Obesity (BMI >27 kg/m2) was found in 1,891 (41.5%) of patients. Central obesity was found in 80.7% and 94.7% of type 2 DM patients according to the WC and WHR cutoff, respectively. Hypertension was significantly associated with all the obesity indicators (p<0.001). Type 2 DM patients with a high WHR were more likely to be hypertensive as compared to those with normal WHR (75% versus 65%, odds ratio (OR) 1.6, p<0.001). A higher than normal WC was also significantly associated with hypertension (79% versus 56%, OR 2.9, p<0.001). Similarly, obese type 2 DM patients with a BMI >27 kg/m2 were more likely to be hypertensive as compared to those with a normal range (18.5 to 22.9 kg/m2) BMI (83.1% versus 64.4%, OR 2.7, p<0.001).
CONCLUSION
Diabetes is more prevalent in females and middle-aged people. Hypertension and obesity are two very common comorbidities of diabetes. Hypertension is strongly associated with all the parameters (WC, WHR, and BMI) of obesity.
|
No pos
|
No neg
|
Retriever1050
|
Microprobe analysis of human otoconia.
Utricular and saccular otoconia (N = 510) from 1 fetus (39th gestational week; Trisomy-18), 2 babies (1 1/2 and 2 months) and 3 adults (58, 61 and 77 years) were analysed with an energy dispersive X-ray microprobe. In all otoconia the elemental composition showed an extremely high concentration of Ca but also Na, Mg, P, S, Cl and K were identified. The presence of non-Ca elements was interpreted as being due to a protein nucleus of the otoconia. Non-Ca elements are more prominent during fetal age and early post-natally than later in life. Old age otoconia contained high concentrations of P which indicates that a ' phosphatization ' of aging otoconia occurs, i.e. calcite otoconia are transformed in situ into apatite by reaction with phosphate ions. The elemental composition of otoconia in Trisomy-18 was similar to that in early postnatal inner ears.
|
No pos
|
No neg
|
Retriever1051
|
Purification and characterization of tyrosylprotein sulfotransferase.
Tyrosylprotein sulfotransferase (TPST) is a Golgi membrane enzyme involved in the post-translational modification of secretory and membrane proteins. Here we describe the 140,000-fold purification of this enzyme from bovine adrenal medulla to apparent homogeneity and determine its substrate specificity. The key step in the purification was affinity chromatography on a substrate peptide to which the enzyme bound in the presence of nucleotide cosubstrate. TPST is a 54-50 kd integral membrane glycoprotein. The presence of sialic acid strongly suggests that within the Golgi complex, TPST is localized in the trans-most subcompartment. TPST was found to specifically sulfate tyrosine residues adjacent to acidic amino acids. These results define a major determinant for the specificity of protein sulfation in the trans Golgi.
|
No pos
|
No neg
|
Retriever1052
|
Thermographic of the Microcirculation in Healthy Children Aged 3-10 Months as an Objective and Noninvasive Method of Assessment.
BACKGROUND
The aim of this study was to assess if thermography as an objective and non-invasive research tool is capable of identifying the changes in the surface temperature of the body as a response to muscle stimulation in Vojta therapy. The research group consisted of children aged 3-10 months with slight abnormalities of the motor pattern, subjected to individually selected stimulation elements according to Vojta.
METHODS
The Vojta method of spontaneous motor assessment and the thermovision method of assessing the microcirculation properties of muscles were used for the evaluation.
RESULTS
In the study group, changes in the microcirculation parameters of the extensor muscles of the back occurred immediately after the therapy at the first examination.
CONCLUSIONS
The analysis featuring an objective assessment allows physiotherapists to diagnose local temperature changes based on the effect of microcirculation parameters in the musculofascial structures.
TRIAL REGISTRATION
The research was conducted as a pilot study for a scientific project approved by the Commission for Scientific Research of the University of Health and Sport Sciences in Wroclaw No 24/2021. The study is currently in the registration process with the Australian New Zealand Clinical Trials Registry.
|
No pos
|
No neg
|
Retriever1053
|
[Congenital encephalomyelopathy as a possible slow infection in humans].
A slow influenzal congenital infection of man (in a child aged 2.5 years) is described for the first time. The infection manifests itself by encephalomyelopathy (retarded psychomotor development, sluggish spinal pareses of the limbs) and resembles Werdnig-Hoffmann amyotrophy. Besides, one can ses neuroendocrine disorders (hypophyseal nanism, hypogonadism ) and the signs of immunodeficiency. The long-term persistence of influenza A virus, its defective form was detected in the blood and CSF by means of molecular hybridization. In addition, the summarized data on the clinical studies of congenital influenzal injuries to the CNS in children, carried out by the author are provided. The theoretical evidence for the work was experimental slow influenzal infection in mice obtained for the first time at the N.F.Gamaleia Institute of Epidemiology and Microbiology (Moscow).
|
No pos
|
No neg
|
Retriever1054
|
Gastric adenocarcinoma of fundic gland type: report of three cases.
Recently, fundic gland type gastric adenocarcinoma (GA-FG) has been reported as a new entity. This report describes GA-FG among Koreans for the first time. From March 2008 to July 2010 we identified only three cases of GA-FG out of over 6,000 GAs resected by endoscopy or surgery. Cell differentiation by mucin proteins, pepsinogen-I, and H+/K+-ATPase was evaluated. All three cases were male patients and diagnosed as early stage GA. Histologically, GA-FGs were well-differentiated adenocarcinoma with pale gray-blue, basophilic columnar or cuboidal cells and mildly enlarged nuclei, resembling chief cells. All three cases were positive for pepsinogen-I and were classified as gastric mucin phenotype. Among three histologic subtypes of GA-FG, since tumors were mainly composed of chief cells, our three cases were classified as chief cell predominant type. In conclusion, GA-FG is very rare among Koreans and pepsinogen-I and MUC6 expression are typical immunohistochemical findings in GA-FG suggesting differentiation toward fundic glands.
|
No pos
|
No neg
|
Retriever1055
|
The physiological effect of a 'climb assist' device on vertical ladder climbing.
'Climb assist' claims to reduce strain when climbing ladders; however, no research has yet substantiated this. The purpose of this study was to assess the physiological and psychophysical effects of climb assist on 30 m ladder climbing at a minimum acceptable speed. Eight participants (six male and two female) climbed a 30 m ladder at 24 rungs per minute with and without climb assist, and were monitored for heart rate (HR), [Formula: see text]O2 and rate of perceived exertion (RPE). All three variables decreased significantly (p < 0.05) with climb assist with [Formula: see text]O2 decreasing by 22.5%, HR by 14.8% and RPE decreasing by a mean of 2.3 units on the 10-point Borg scale. When descending the ladder [Formula: see text]O2 decreased by a mean of 42% compared to that ascending. At the minimal acceptable climbing speed climb assist decreases the physiological strain on climbers, as demonstrated by reduced [Formula: see text]O2, HR and perceived exertion. Practitioner Summary: 'Climb assist' systems claim to reduce strain when climbing, however; no research has yet been published to substantiate this. A crossover study compared [Formula: see text]O2, HR and RPE at a minimal acceptable climbing speed with and without climb assist. Climb assist significantly reduced all variables confirming it reduces strain when climbing.
|
No pos
|
No neg
|
Retriever1056
|
Reaction with DNA and mutagenic specificity of syn-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide.
The spectroscopic characterization of purine deoxyribonucleoside adducts derived from the fjord-region syn-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide and the mutagenic specificity of the latter compound for the supF gene in the pSP189 shuttle vector are described. This dihydrodiol epoxide preferentially forms adducts with deoxyadenosine residues in DNA and is preferentially opened trans in reactions with DNA or with deoxyribonucleotides. In common with other fjord-region syn-dihydrodiol epoxides, the most frequently observed mutational changes were A-->T and G-->T changes. This hydrocarbon dihydrodiol epoxide is structurally similar to syn-benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide but has an additional benzene ring annelated distant from the reaction center. As anticipated, there were some common features in the chemistry and mutagenicities of these two compounds, but there were also substantive differences which indicate factors of importance in controlling reactions of these kinds of compounds with DNA.
|
No pos
|
No neg
|
Retriever1057
|
Leisure-time physical activity sustained since midlife and preservation of cognitive function: The Atherosclerosis Risk in Communities Study.
INTRODUCTION
We tested the hypotheses that higher levels of and persistence of midlife leisure-time physical activity (LTPA) are associated long-term with lower cognitive decline and less incident dementia.
METHODS
A total of 10,705 participants (mean age: 60 years) had LTPA (no, low, middle, or high) measured in 1987-1989 and 1993-1995. LTPA was assessed in relation to incident dementia and 14-year change in general cognitive performance.
RESULTS
Over a median follow-up of 17.4 years, 1063 dementia cases were observed. Compared with no LTPA, high LTPA in midlife was associated with lower incidence of dementia (hazard ratio [95% confidence interval], 0.71 [0.61, 0.86]) and lower declines in general cognitive performance (-0.07 standard deviation difference [-0.12 to -0.04]). These associations were stronger when measured against persistence of midlife LTPA over 6 years.
DISCUSSION
LTPA is a readily modifiable factor associated inversely with long-term dementia incidence and cognitive decline.
|
No pos
|
No neg
|
Retriever1058
|
Fluidigm2PURC: Automated processing and haplotype inference for double-barcoded PCR amplicons.
PREMISE OF THE STUDY
Targeted enrichment strategies for phylogenomic inference are a time- and cost-efficient way to collect DNA sequence data for large numbers of individuals at multiple, independent loci. Automated and reproducible processing of these data is a crucial step for researchers conducting phylogenetic studies.
METHODS AND RESULTS
We present Fluidigm2PURC, an open source Python utility for processing paired-end Illumina data from double-barcoded PCR amplicons. In combination with the program PURC (Pipeline for Untangling Reticulate Complexes), our scripts process raw FASTQ files for analysis with PURC and use its output to infer haplotypes for diploids, polyploids, and samples with unknown ploidy. We demonstrate the use of the pipeline with an example data set from the genus Thalictrum (Ranunculaceae).
CONCLUSIONS
Fluidigm2PURC is freely available for Unix-like operating systems on GitHub (https://github.com/pblischak/fluidigm2purc) and for all operating systems through Docker (https://hub.docker.com/r/pblischak/fluidigm2purc).
|
No pos
|
No neg
|
Retriever1059
|
Response of the sand fly Phlebotomuspapatasi to visual, physical and chemical attraction features in the field.
In this study, 27 CDC traps were modified with various attractive features and compared with a CDC trap with no light source or baits to evaluate the effects on attraction to Phlebotomus papatasi (Scopoli) north of the Dead Sea near Jericho. Attractive features included CO2, lights, colored trap bodies, heat, moisture, chemical lures and different combinations of the same. Traps were placed 20m apart and rotated from one trap location to the next after 24h trapping periods. The most significant attractive feature was CO2, which attracted more sand flies than any other feature evaluated. Ultraviolet light was the next most attractive feature, followed by incandescent light. When evaluated alone, black or white trap bodies, heat and moisture, all influenced trap catch but effects were greater when these attractive features were used together. The results of this study suggest that traps with CO2 and UV light could be used in batteries as control interventions if suitable CO2 sources become available.
|
No pos
|
No neg
|
Retriever1060
|
Using Stakeholder Involvement, Expert Knowledge and Naturalistic Implementation to Co-Design a Complex Intervention to Support Children's Inclusion and Participation in Schools: The CIRCLE Framework.
Whist inclusion is recommended for most children most of the time it remains difficult to implement. In this paper, we present the process undertaken to review and redesign a pre-existing complex intervention (The CIRCLE Framework) which was designed to enhance teachers confidence and competence in provision of universal first level supports for 5-12 year old children with additional support needs. The approach presented draws on the Medical Research Council guidance for the development of complex interventions. A series of ten co-design workshops with 70 stakeholders was completed, applying interactive and participatory methods. Analysing outputs of each workshop revealed recurring design ideas that became the main aspects of the new framework and associated manuals. Intervention content, theoretical frameworks, manuals to support use in practice and implementation strategies were developed. On completion, the updated intervention was extended up to 18 years of age and redistributed to all teachers in the participating local authority. We present the main conclusions and interpretations around the design and naturalistic implementation of the framework, and reflections on use in practice, including a detailed list of recommendations for implementation across schools and staff.
|
No pos
|
No neg
|
Retriever1061
|
Two-barrel bile-acids-sensitive microelectrodes based on liquid ion exchanger.
Several liquid membrane microelectrodes sensitive to bile acids (two barrel, tip diameter about 0.5 micron) are described. The results of different liquid ion exchangers such as Aliquat 336/decanol, trioctylmethylammonium/decanol, hexadecyltrimethylammonium/decanol, benzyldimethylhexadecylammonium/decanol, hexadecyltributylammonium/5% hexachlorobenzene + 0.5% bromoacetanilide in o-dichlorobenzene are compared with each other, and the better one among them is the mixture of benzyldimethylhexadecylammonium cholate/decanol with hexadecyltributylammonium taurocholate/5% hexachlorobenzene + 0.5% bromoacetanilide in o-dichlorobenzene because of its quicker response time and low drift. The calibration curves, slopes, test limits, selective coefficients, drifts, and response times of the various bile-acids-sensitive microelectrodes in different calibration solutions were demonstrated and compared with each other.
|
No pos
|
No neg
|
Retriever1062
|
The progressive systemic sclerosis/systemic lupus overlap: an unusual clinical progression.
Three patients with the unusual combinations of discoid lupus, systemic lupus erythematosus (SLE), and progressive systemic sclerosis (PSS) are reported. The first patient developed PSS eight years after a diagnosis of discoid lupus had been made and this was complicated by myositis six years later. The second patient developed PSS more than 20 years after being diagnosed as having SLE. The third patient developed SLE with predominant features of urticarial vasculitis six years after PSS. Mild myositis also ensued. There were no antibodies to U1RNP demonstrable in any of these patients. The clinical progression of SLE to PSS or vice versa in the absence of features of mixed connective tissue disease is distinctly uncommon.
|
No pos
|
No neg
|
Retriever1063
|
International Commission for Protection Against Environmental Mutagens and Carcinogens. Dosimetry of genotoxic agents and dose-response relationships of their effects.
Dose-response relationships and determination of dose of mutagens and carcinogens are summarized and discussed on the basis of conceptual and kinetic aspects. Different dose definitions may be referred to steps in the chain of events from exposure (or emission) to observed effects. A system is applied to show the influence of various processes on the kinetics of the transfers between consecutive steps. The same system illustrates processes influenced by protraction and fractionation of dose, synergists, comutagens/cocarcinogens, heritable factors, etc. The response at a given dose is expected to depend on the product of consecutive transfer functions. An application of general rules of chemical kinetics shows that when a chemical is introduced at a sufficiently low level, all processes affecting the transfers and therefore the transfer functions themselves become first-order, provided the induction status of enzymes and the cell-division rate remain constant. Under the same conditions, dose-response relationships are expected to be linear, i.e. without "safe" thresholds. However, present knowledge of the kinetics of repair at low levels of DNA damage and of the kinetics of induction of repair functions is not enough complete to be decisive. These considerations and the fact that observed dose-response data in some cases indicate the existence of thresholds but in others appear able to reject the threshold hypothesis lead to the conclusion that, generally, dose-response curves are most probably linear down to dose zero. However, certain mutagens/carcinogens give rise to lesions repaired so effectively that quasi-thresholds appear in certain subpopulations or organs.
|
No pos
|
No neg
|
Retriever1064
|
Automated hippocampal segmentation in 3D MRI using random undersampling with boosting algorithm.
The automated identification of brain structure in Magnetic Resonance Imaging is very important both in neuroscience research and as a possible clinical diagnostic tool. In this study, a novel strategy for fully automated hippocampal segmentation in MRI is presented. It is based on a supervised algorithm, called RUSBoost, which combines data random undersampling with a boosting algorithm. RUSBoost is an algorithm specifically designed for imbalanced classification, suitable for large data sets because it uses random undersampling of the majority class. The RUSBoost performances were compared with those of ADABoost, Random Forest and the publicly available brain segmentation package, FreeSurfer. This study was conducted on a data set of 50 T1-weighted structural brain images. The RUSBoost-based segmentation tool achieved the best results with a Dice's index of [Formula: see text] ([Formula: see text]) for the left (right) brain hemisphere. An independent data set of 50 T1-weighted structural brain scans was used for an independent validation of the fully trained strategies. Again the RUSBoost segmentations compared favorably with manual segmentations with the highest performances among the four tools. Moreover, the Pearson correlation coefficient between hippocampal volumes computed by manual and RUSBoost segmentations was 0.83 (0.82) for left (right) side, statistically significant, and higher than those computed by Adaboost, Random Forest and FreeSurfer. The proposed method may be suitable for accurate, robust and statistically significant segmentations of hippocampi.
|
No pos
|
No neg
|
Retriever1065
|
Kaempferol inhibits thrombosis and platelet activation.
The objectives of the present study were to investigate whether kaempferol affects pro-coagulant proteinase activity, fibrin clot formation, blood clot and thrombin (or collagen/epinephrine)-stimulated platelet activation, thrombosis, and coagulation in ICR (Imprinting Control Region) mice and SD (Sprague-Dawley) rats. Kaempferol significantly inhibited the enzymatic activities of thrombin and FXa by 68 ± 1.6% and 52 ± 2.4%, respectively. Kaempferol also inhibited fibrin polymer formation in turbidity. Microscopic analysis was performed using a fluorescent conjugate. Kaempferol completely attenuated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and phosphoinositide 3-kinase (PI3K)/PKB (AKT) in thrombin-stimulated platelets and delayed aggregation time (clotting) by 34.6% in an assay of collagen/epinephrine-stimulated platelet activation. Moreover, kaempferol protected against thrombosis development in 3 animal models, including collagen/epinephrine- and thrombin-induced acute thromboembolism models and an FeCl3-induced carotid arterial thrombus model. The ex vivo anticoagulant effect of kaempferol was further confirmed in ICR mice. This study demonstrated that kaempferol may be clinically useful due to its ability to reduce or prevent thrombotic challenge.
|
No pos
|
No neg
|
Retriever1066
|
Melanoma of the female urethra.
Primary melanoma of the female urethra is a very rare malignant tumor with high mortality. Due to its rarity, there are no guidelines and recommendations on the diagnosis and treatment of such patients, so we aimed to review the reported cases and case series, their treatment, and outcome. We searched through PubMed for all articles reporting on female urethral melanoma. We found 73 articles (case reports and case series) reporting on 112 patients. There are no clinical trials on the topic due to the rarity of the condition. Median patient age at presentation is 68 years. Due to the late presentation, the prognosis of the disease is poor, and median survival is 16 months, with 5-year survival in around 10 % (12 reported patients). Regarding treatment, most authors use either less radical approach (partial or total urethrectomy) or radical approach (anterior pelvic exenteration). We found no evidence that either of the treatment modalities results with higher survival. In local excision, there are indications that margins less than 2-2.5 cm result in high percentage of local recurrence suggesting that resection width should be at least 2.5 cm. For localized urethral melanoma, local resection with margins of 2.5 cm can be recommended and there is no foundation to support radical surgery in such patients. Chemotherapy and immunotherapy can also recommend. For locally advanced disease, the prognosis is poor, and radical surgery will not improve survival significantly.
|
No pos
|
No neg
|
Retriever1067
|
Simultaneous exposure to Escherichia coli heat-labile and heat-stable enterotoxins increases fluid secretion and alters cyclic nucleotide and cytokine production by intestinal epithelial cells.
Enterotoxigenic Escherichia coli (ETEC) is a significant cause of diarrheal disease and death, especially in children in developing countries. ETEC causes disease by colonizing the small intestine and producing heat-labile toxin (LT), heat-stable toxin (ST), or both LT and ST (LT+ST). The majority of ETEC strains produce both ST and LT. Despite the prevalence of LT+ST-producing organisms, few studies have examined the physiologic or immunologic consequences of simultaneous exposure to these two potent enterotoxins. In the current report, we demonstrate that when LT and ST are both present, they increase water movement into the intestinal lumen over and above the levels observed with either toxin alone. As expected, cultured intestinal epithelial cells increased their expression of intracellular cyclic GMP (cGMP) when treated with ST and their expression of intracellular cyclic AMP (cAMP) when treated with LT. When both toxins were present, cGMP levels but not cAMP levels were synergistically elevated compared with the levels of expression caused by the corresponding single-toxin treatment. Our data also demonstrate that the levels of inflammatory cytokines produced by intestinal epithelial cells in response to LT are significantly reduced in animals exposed to both enterotoxins. These findings suggest that there may be complex differences between the epithelial cell intoxication and, potentially, secretory outcomes induced by ETEC strains expressing LT+ST compared with strains that express LT or ST only. Our results also reveal a novel mechanism wherein ST production may reduce the hosts' ability to mount an effective innate or adaptive immune response to infecting organisms.
|
No pos
|
No neg
|
Retriever1068
|
Why eating star fruit is prohibited for patients with chronic kidney disease?
New studies have shown the mechanism by which the star fruit (Averrhoa carambola) becomes toxic to individuals with chronic kidney disease (CKD). The aim of this study was to review the current literature on the topic. This is a review article, with publications from 2000 to 2014 available in scientific database. There are reports that neurotoxicity is due to the presence of oxalate in star fruit, but recent findings show that the neurotoxic effect of the toxin is by caramboxin, which appears to inhibit the GABAergic system which is the major inhibitory system in the central nervous system (CNS), involving changes as sobs and confusion, to more serious conditions such as seizures and death. It is important to multidisciplinary action to alert patients with CKD as the prohibition of the star fruit consumption.
|
No pos
|
No neg
|
Retriever1069
|
The guardians' perspective on paediatric cancer treatment in Malawi and factors affecting adherence.
BACKGROUND
Abandonment of paediatric cancer treatment is a common problem in developing countries. Little is known about the guardians' perspective on cancer treatment in these countries, especially the factors that affect adherence.
METHODS
Following a pilot study enquiring into the possible causes of abandonment, a problem analysis diagram was drawn which helped to develop the questionnaires. Semi-structured interviews (n = 83) and focus group discussions (n = 8) were held with the guardians of 25 Burkitt lymphoma patients and 7 Wilms tumour patients at different phases of therapy in Malawi.
RESULTS
Parents in Malawi are very motivated to continue treatment if they think that it will cure their child. Financial costs are important concerns. Not all tasks at home are assumed by other household members. The diagnosis of cancer was unknown before being told about it in hospital and caused fear of recurrence and death. Guardians are reluctant to ask the health personnel questions. They worry that taking frequent blood samples will weaken their child. The side effects of the chemotherapy are seen as a proof of efficacy.
CONCLUSION
It is important to appreciate the guardians' concerns when offering treatment that requires their sustained commitment. It is necessary to provide not only medical treatment, but also travel allowances and adequate nutritional support during long hospital stays to impoverished families. Information should be given proactively.
|
No pos
|
No neg
|
Retriever1070
|
Factors Associated With Sputum Culture-Negative vs Culture-Positive Diagnosis of Pulmonary Tuberculosis.
Importance
Recognition of active tuberculosis (TB) in its earliest stages could reduce morbidity and prevent advancement to transmissible disease. Little is published about the occurrence and presentation of sputum culture-negative pulmonary TB (PTB), an early paucibacillary but often underrecognized disease state.
Objective
To assess differences between culture-negative and culture-positive PTB regarding occurrence, clinical presentation, radiographic findings, demographics, and comorbidities.
Design, Setting, and Participants
Cross-sectional study in which surveillance data of adult patients with PTB reported to the New York City Department of Health in New York, New York, from 2011 through 2013, ie, years for which demographic, clinical, and radiographic data were collected. Patients were aged 18 years or older, had signs of pulmonary disease, and had mycobacterial sputum culture results; those with HIV coinfection or a TB diagnosis within 2 years prior to presentation were excluded. Culture-negative PTB was defined as clinical and radiographic presentation consistent with TB, 3 negative results on sputum culture, and improvement with antituberculous treatment. The analyses were performed between 2015 and 2016; notably, the proportion of reported patients with culture-negative PTB has remained consistent during the past 2 decades.
Main Outcomes and Measures
The occurrence of culture-negative PTB among all patients with PTB was calculated, and demographics, comorbidities, symptoms, and radiographic findings were compared between culture-negative and culture-positive PTB.
Results
Of the 796 patients with PTB (median [interquartile range] age, 41 [29-54] years; 499 [63%] men) who met criteria for analysis, 116 (15%) had negative results on sputum culture. Patients with culture-negative PTB compared with culture-positive PTB were less frequently male (53% vs 64%; P = .03) and presented with a significantly lower frequency of cough (68% vs 89%; P < .001), weight loss (39% vs 51%; P = .03), and cavitation on both chest radiograph (7% vs 28%; P < .001) and chest computed tomographic scan (26% vs 59%; P < .001).
Conclusions and Relevance
Given the lack of criterion-standard test confirmation and the relative paucity of symptoms and radiological abnormalities, culture-negative PTB is likely underdiagnosed and its occurrence underestimated globally. Awareness of these findings, enhanced diagnostic approaches, and, ideally, better biomarkers could improve detection and treatment of this early disease and reduce the development of transmissible TB.
|
No pos
|
No neg
|
Retriever1071
|
Reward sensitivity in impulsivity.
Impulsive individuals choose immediate small over delayed larger rewards, suggesting reward hypersensitivity. Single-unit studies have shown increased ventral tegmental activity to rewards and reward predictors and decreased activity when predicted rewards are withheld. The orbitofrontal ventral tegmental cortical target also responds to reward and expectation in single-unit and neuroimaging studies. The anterior P2a event-related potential component is a proposed index of reward-related orbitofrontal activity. In this reward prediction study in high and low impulsive subjects, the P2a localized to orbitofrontal cortex and was largest to non-predicted rewards and smallest in the absence of predicted rewards in subjects higher on self-reported impulsiveness, consistent with a P2a index of orbitofrontal reward processing and with reward hypersensitivity in impulsivity.
|
No pos
|
No neg
|
Retriever1072
|
Content and distribution of glycogen in oral epithelial dysplasia.
Forty-four oral lesions with epithelial dysplasia and 25 other benign and malignant lesions of the oral mucosa were examined after staining with hematoxylin-eosin and diastase controlled PAS. The intensity of the PAS-positivity for glycogen, the grade of dysplasia, the type of keratinization and the degree of subepithelial inflammation were recorded. Histologically normal epithelium at the margins of the lesions were used as controls. The presence and amount of glycogen in normal epithelium at the margins of the lesions were used as controls. The presence and amount of glycogen in normal epithelium at the margin of the lesions were used as controls. The presence and amount of glycogen in normal epithelium varied with the form of keratinization in that non- or parakeratinized epithelium was rich in glycogen whereas there was a negative glycogen-reaction in orthokeratinized epithelium. The most striking feature was an abrupt limitation of the glycogen at the junction between nondysplastic and dysplastic epithelium. The difference in the amount of glycogen in normal and dysplastic epithelium as assessed semiquantitatively, was statistically significant. There was no statistically significant difference in glycogen content with different degrees of dysplasia. The diastase controlled PAS-staining may therefore be a useful method of distinguishing dysplastic from nondysplastic epithelium in doubtful cases. Pseudoepitheliomatous hyperplastic epithelium covering granular cell myoblastoma did not contain any glycogen. Five of six squamous cell carcinomas and four verrucous carcinomas contained no demonstrable glycogen. Glycogen was present in the epithelium of the cases of lichen planus and "denture hyperplasia" investigated.
|
No pos
|
No neg
|
Retriever1073
|
Statin use and 30-day mortality in patients with acute symptomatic pulmonary embolism.
BACKGROUND
Statins possess antithrombotic and profibrinolytic properties. The association between statin use and short-term outcomes in patients with acute pulmonary embolism (PE) remains unknown.
METHODS
We used the data from the Registro Informatizado de Pacientes con Enfermedad TromboEmbólica registry to compare the 30-day all-cause mortality in patients with acute PE according to the use of statins. Secondary outcome was fatal PE. We used cancer-related mortality as a falsification endpoint.
RESULTS
From January 2009 to April 2021, 31 169 patients with PE were recruited. Of these, 5520 (18%) were using statins at baseline: low intensity: 829, moderate: 3636, high intensity: 1055. Statin users were older and had a higher frequency of diabetes, hypertension, or atherosclerotic disease than non-users (P <0.001 for all comparisons). During the first 30 days, 1475 patients died (fatal PE, 255). On multivariable analysis, statin users had a lower risk of all-cause death (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.56-0.76) and fatal PE (OR: 0.42; 95% CI: 0.28-0.62) than non-users. The risk for death was lower in patients using either low- (OR: 0.51; 95% CI: 0.34-0.77), moderate- (OR: 0.68; 95% CI: 0.57-0.81), or high-intensity statins (OR: 0.68; 95% CI: 0.51-0.92). Results did not change in mixed effects logistic regression models with hospitals as a random effect. Statins were not associated with a significant chance in cancer mortality (falsification endpoint).
CONCLUSIONS
PE patients using statins at baseline had a significantly lower risk of dying within the first 30 days than non-users. Randomized trials are needed to confirm these data.
|
No pos
|
No neg
|
Retriever1074
|
Irrelevance of figural identity for resolving ambiguities in apparent motion.
In order to examine the degree to which form perception affects the formation of apparent-motion experience, subjects were presented with nine ambiguous apparent-motion situations, where the elements of each single flash were various figures. One of the interpretations of each situation preserved the figural identity of the figures across flashes. It was found that figural identity does not have any effect on determining the type of motion experienced, except when the figural analysis involved is relatively simple.
|
No pos
|
No neg
|
Retriever1075
|
Depressive rumination alters cortisol decline in Major Depressive Disorder.
Depressive rumination - a central characteristic of Major Depressive Disorder (MDD) - is a maladaptive emotion regulation strategy that prolongs sad mood and depressive episodes. Considerable research demonstrates the emotional and behavioral consequences of depressive rumination, yet few studies investigate its effect on neuroendocrine functioning. The current study examined the effect of an emotion regulation manipulation on the trajectory of cortisol concentrations among individuals with MDD and healthy controls (CTL). Sadness was induced via forced failure. Participants then were randomly assigned to a depressive rumination or distraction emotion regulation induction. MDDs in the rumination condition exhibited less cortisol decline compared to MDDs in the distraction condition and compared to CTLs in either condition. Findings suggest that depressive rumination alters the trajectory of cortisol secretion in MDD and may prolong cortisol production. Results thereby provide important insights into the interaction of biological and psychological factors through which distress contributes to MDD.
|
No pos
|
No neg
|
Retriever1076
|
Satiety: have we neglected dietary non-nutrients?
Satiety, which is the inhibition of eating following the end of a meal, is influenced by a number of food characteristics, including compositional and structural factors. An increased understanding of these factors and the mechanisms whereby they exert their effects on satiety may offer a food-based approach to weight management. Water and gas, which are often neglected in nutrition, are major components of many foods and contribute to volume, and to sensory and other characteristics. A review of previous short-term studies that evaluated the effects of water or gas in foods on satiety showed that while satiety was generally increased, effects on subsequent intakes were not always apparent. These studies were diverse in terms of design, timings and food matrices, which precludes definitive conclusions. However, the results indicate that solids may be more effective at increasing satiety than liquids, but gas may be as effective as water. Although increased gastric distension may be the main mechanism underlying these effects, pre-ingestive and ingestive impacts on cognitive, anticipatory and sensory responses also appear to be involved. Furthermore, there is limited evidence that water on its own may be effective at increasing satiety and decreasing intakes when drunk before, but not with, a meal. Longer-term extrapolation suggests that increasing food volumes with water or gas may offer weight-management strategies. However, from a practical viewpoint, the effects of water and gas on satiety may be best exploited by using these non-nutrients to manipulate perceived portion sizes, without increasing energy contents.
|
No pos
|
No neg
|
Retriever1077
|
Expression, signaling and function of Egr transcription factors in pancreatic β-cells and insulin-responsive tissues.
Egr-1 and the related zinc finger transcription factors Egr-2, Egr-3, and Egr-4 are stimulated by many extracellular signaling molecules and represent a convergence point for intracellular signaling cascades. Egr-1 expression is induced in insulinoma cells and pancreatic β-cells following stimulation with either glucose, or pregnenolone sulfate. Moreover, stimulation of Gαq and Gαs-coupled receptors enhances EGR-1 gene transcription. Functional studies revealed that Egr transcription factors control insulin biosynthesis via regulation of Pdx-1 expression. Glucose homeostasis and pancreatic islet size are regulated by Egr transcription factors, indicating that these proteins control central physiological parameters regulated by pancreatic β-cells. In addition, Egr-1 is an integral part of the insulin receptor signaling cascade in insulin-responsive tissues and influences insulin resistance.
|
No pos
|
No neg
|
Retriever1078
|
Comparative evaluation of the Bruker Biotyper and Vitek MS matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry systems for identification of yeasts of medical importance.
We report the first comparative evaluation between the Bruker Biotyper MS (BMS) and the Vitek MS (VMS) for the identification of yeasts. The rate of correct identifications at the species level was comparable using the commercial databases (89.8% versus 84.3%; P = 0.712), but higher for BMS using an in-house-extended database (100% versus 84.3%; P = 0.245). Importantly, the rate of misidentification was significantly higher for VMS (1% versus 12.1%; P < 0.0001), including the rate of major errors (0% versus 4.5%; P = 0.0036).
|
No pos
|
No neg
|
Retriever1079
|
Effects of normoxic and hypoxic exercise regimens on monocyte-mediated thrombin generation in sedentary men.
Exercise and hypoxia paradoxically modulate vascular thrombotic risks. The shedding of procoagulant-rich microparticles from monocytes may accelerate the pathogenesis of atherothrombosis. The present study explores the manner in which normoxic and hypoxic exercise regimens affect procoagulant monocyte-derived microparticle (MDMP) formation and monocyte-promoted thrombin generation (TG). Forty sedentary healthy males were randomized to perform either normoxic (NET; 21% O2, n=20) or hypoxic (HET; 15% O2, n=20) exercise training (60% VO(2max)) for 30 min/day, 5 days/week for 5 weeks. At rest and immediately after HET (100 W under 12% O2 for 30 min), the MDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. The results demonstrated that acute 12% O2 exercise (i) increased the release of coagulant factor V (FV)/FVIII-rich, phosphatidylserine (PS)-exposed and tissue factor (TF)-expressed microparticles from monocytes, (ii) enhanced the peak height and rate of TG in monocyte-rich plasma (MRP) and (iii) elevated concentrations of norepinephrine/epinephrine, myeloperoxidase (MPO) and interleukin-6 (IL-6) in plasma. Following the 5-week intervention, HET exhibited higher enhancements of peak work-rate and cardiopulmonary fitness than NET did. Moreover, both NET and HET decreased the FV/FVIII-rich, PS-exposed and TF-expressed MDMP counts and the peak height and rate of TG in MRP following the HET. However, HET elicited more suppression for the HE (hypoxic exercise)-enhanced procoagulant MDMP formation and dynamic TG in MPR and catecholamine/peroxide/pro-inflammatory cytokine levels in plasma than NET. Hence, we conclude that HET is superior to NET for enhancing aerobic capacity. Furthermore, HET effectively suppresses procoagulant MDMP formation and monocyte-mediated TG under severe hypoxic stress, compared with NET.
|
No pos
|
No neg
|
Retriever1080
|
Computational modeling of amylin-induced calcium dysregulation in rat ventricular cardiomyocytes.
Hyperamylinemia is a condition that accompanies obesity and precedes type II diabetes, and it is characterized by above-normal blood levels of amylin, the pancreas-derived peptide. Human amylin oligomerizes easily and can deposit in the pancreas [1], brain [2], and heart [3], where they have been associated with calcium dysregulation. In the heart, accumulating evidence suggests that human amylin oligomers form moderately cation-selective [4,5] channels that embed in the cell sarcolemma (SL). The oligomers increase membrane conductance in a concentration-dependent manner [5], which is correlated with elevated cytosolic Ca2+. These findings motivate our core hypothesis that non-selective inward Ca2+ conduction afforded by human amylin oligomers increase cytosolic and sarcoplasmic reticulum (SR) Ca2+ load, which thereby magnifies intracellular Ca2+ transients. Questions remain however regarding the mechanism of amylin-induced Ca2+ dysregulation, including whether enhanced SL Ca2+ influx is sufficient to elevate cytosolic Ca2+ load [6], and if so, how might amplified Ca2+ transients perturb Ca2+-dependent cardiac pathways. To investigate these questions, we modified a computational model of cardiomyocytes Ca2+ signaling to reflect experimentally-measured changes in SL membrane permeation and decreased sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) function stemming from acute and transgenic human amylin peptide exposure. With this model, we confirmed the hypothesis that increasing SL permeation alone was sufficient to enhance Ca2+ transient amplitudes. Our model indicated that amplified cytosolic transients are driven by increased Ca2+ loading of the SR and that greater fractional release may contribute to the Ca2+-dependent activation of calmodulin, which could prime the activation of myocyte remodeling pathways. Importantly, elevated Ca2+ in the SR and dyadic space collectively drive greater fractional SR Ca2+ release for human amylin expressing rats (HIP) and acute amylin-exposed rats (+Amylin) mice, which contributes to the inotropic rise in cytosolic Ca2+ transients. These findings suggest that increased membrane permeation induced by oligomeratization of amylin peptide in cell sarcolemma contributes to Ca2+ dysregulation in pre-diabetes.
|
No pos
|
No neg
|
Retriever1081
|
Electronic Structure of Liquid Alkanes: A Representative Case of Liquid Hexanes and Cyclohexane Studied Using Polarization-Dependent Two-Photon Absorption Spectroscopy.
Two-photon absorption (2PA) spectra of liquid cyclohexane and hexanes are reported for the energy range 6.4-8.5 eV (177-145 nm), providing detailed information about their electronic structures in bulk liquid. Using a broadband pump-probe fashion, we measured the continuous 2PA spectra by simultaneous absorption of a 266 nm (4.6 eV) pump photon and one UV-vis probe photon from the white-light continuum (1.8-3.9 eV). Theoretical one-photon absorption (1PA) and 2PA cross sections of isolated gas phase molecules are computed by the equation of motion coupled-cluster method with single and double substitutions (EOM-CCSD) to substantiate the assignment of the experimental spectra, and the natural transition orbital (NTO) analysis provides visualization of the participating orbitals in a transition. Our analysis suggests that upon solvation transitions at the lowest excitation energy involving promotion of electron to the 3s Rydberg orbitals are blue-shifted (∼0.55 eV for cyclohexane and ∼0.18 eV for hexanes) to a greater extent as compared to those involving other Rydberg orbitals, which is similar to the behavior observed for water and alcohols. All other transitions experience negligible (cyclohexane) or minor red-shift by ∼0.15-0.2 eV (hexane) upon solvation. In both alkanes, the spectra are entirely dominated by Rydberg transitions: the most intense bands in 1PA and 2PA spectra are due to the excitation of electrons to the Rydberg "p" and "d" type orbitals, respectively, although one transition terminating in the 3s Rydberg has significant 2PA strength. This work demonstrates that the gas phase electronic transition properties in alkanes are not significantly altered upon solvation. In addition, electronic structure calculations using an isolated-molecule framework appear to provide a reasonable starting point for a semiquantitative picture for spectral assignment and also to analyze the solvatochromic shifts for liquid phase absorption spectra.
|
No pos
|
No neg
|
Retriever1082
|
Long-Term Patient-Related Quality of Life after Knee Periprosthetic Joint Infection.
BACKGROUND
We aimed to evaluate the impact of knee periprosthetic joint infection (PJI) by assessing the patients' long-term quality of life and explicitly their psychological wellbeing after successful treatment.
METHODS
Thirty-six patients with achieved eradication of infection after knee PJI were included. Quality of life was evaluated with the EQ-5D and SF-36 outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data.
RESULTS
At a follow-up of 4.9 ± 3.5 years the mean SF-36 score was 24.82 ± 10.0 regarding the physical health component and 46.16 ± 13.3 regarding the mental health component compared to German normative values of 48.36 ± 9.4 (p < 0.001) and 50.87 ± 8.8 (p = 0.003). The mean EQ-5D index reached 0.55 ± 0.33 with an EQ-5D VAS rating of 52.14 ± 19.9 compared to reference scores of 0.891 (p < 0.001) and 68.6 ± 1.1 (p < 0.001). Mean scores of the ISR revealed the psychological symptom burden on the depression scale.
CONCLUSION
PJI patients still suffer from significantly lower quality of life compared to normative data, even years after surgically successful treatment. Future clinical studies should focus on patient-related outcome measures. Newly emerging treatment strategies, prevention methods, and interdisciplinary approaches should be implemented to improve the quality of life of PJI patients.
|
No pos
|
No neg
|
Retriever1083
|
Gold Nanoparticles Compromise TNF-α-Induced Endothelial Cell Adhesion Molecule Expression Through NF-κB and Protein Degradation Pathways and Reduce Neointima Formation in A Rat Carotid Balloon Injury Model.
The aim of this study was to investigate the anti-inflammatory effects and mechanism of action of the gold nanoparticles (AuNPs) on vascular injury. In vitro vascular endothelial cell (EC) inflammation and in vivo rat carotid balloon injury models were used. The expression of TNF-α-induced cell adhesion molecules (CAMs) was suppressed by the AuNPs in human umbilical vein ECs and aortic ECs. The AuNPs reduced TNF-α-induced intracellular ROS production and NF-κB signaling pathways and enhanced CAM protein degradation by increasing their ubiquitination. However, they did not interfere with the mTOR pathway for protein synthesis and TNF-αbinding to ECs. These effects led to a reduction of monocyte adhesion to EC monolayers in vitro and endothelial CAM expression and monocyte/macrophage level in the vascular injured areas, contributing to a substantial decrease of arterial neointima formation in the rat carotid balloon injury model. The serum gold concentration was 99.5±18 ng/ml after three-day oral administration. Moreover, incubation of the AuNPs with serum and albumin led to an increase of particle sizes of the AuNPs. Collectively, we provide the first evidence that demonstrates that AuNPs possess anti-inflammatory bioactivity on vascular ECsin vitro and can reduce arterial neointima hyperplasia during vascular injury in vivo.
|
No pos
|
No neg
|
Retriever1084
|
Treadmilling of a prokaryotic tubulin-like protein, TubZ, required for plasmid stability in Bacillus thuringiensis.
Prokaryotes rely on a distant tubulin homolog, FtsZ, for assembling the cytokinetic ring essential for cell division, but are otherwise generally thought to lack tubulin-like polymers that participate in processes such as DNA segregation. Here we characterize a protein (TubZ) from the Bacillus thuringiensis virulence plasmid pBtoxis, which is a member of the tubulin/FtsZ GTPase superfamily but is only distantly related to both FtsZ and tubulin. TubZ assembles dynamic, linear polymers that exhibit directional polymerization with plus and minus ends, movement by treadmilling, and a critical concentration for assembly. A point mutation (D269A) that alters a highly conserved catalytic residue within the T7 loop completely eliminates treadmilling and allows the formation of stable polymers at a much lower protein concentration than the wild-type protein. When expressed in trans, TubZ(D269A) coassembles with wild-type TubZ and significantly reduces the stability of pBtoxis, demonstrating a direct correlation between TubZ dynamics and plasmid maintenance. The tubZ gene is in an operon with tubR, which encodes a putative DNA-binding protein that regulates TubZ levels. Our results suggest that TubZ is representative of a novel class of prokaryotic cytoskeletal proteins important for plasmid stability that diverged long ago from the ancient tubulin/FtsZ ancestor.
|
No pos
|
No neg
|
Retriever1085
|
Effects of temperature on orthophosphate absorption by excised corn roots.
The uptake of orthophosphate ((32)P) by excised corn roots, Zea mays L. was studied using roots grown on 0.2 mm CaSO(4). Nine concentrations of KH(2)PO(4) from 1 to 256 mum were used at temperatures of 20 degrees , 30 degrees , and 40 degrees . Enzyme kinetic analysis was applied to the data obtained. Two apparent mechanisms (sites) of phosphate uptake were observed, 1 dominating at high P concentrations and 1 at low P concentrations. A Km of 1.36 x 10(-4) and a Vmax of 177 x 10(-9) moles per gram of roots per hour at 30 degrees was calculated for the mechanism dominating at high P concentrations. Similar calculations gave a Km of 6.09 x 10(-6) and a Vmax of 162 x 10(-9) moles per gram of roots per hour at 30 degrees for the mechanism dominating at low P concentrations. The Q(10) for both mechanisms was approximately 2. Calculation of thermodynamic values from the data gave DeltaF of - 5200 cal, DeltaH of - 950 to - 1400 cal, and a enthalpy of activation (A) of 10,300 to 13,800 cal per mole for the mechanism dominating at high P concentrations. Similar calculations from the data for the mechanism dominating at low P concentrations gave a DeltaF of - 7300 cal, DeltaH of - 10,700 to - 8200 cal, and a A of 9300 to 18,900 cal per mole. If the dual mechanism interpretation of this kind of data adequately describes this system, then both mechanisms of P absorption by corn roots involve chemical reactions.
|
No pos
|
No neg
|
Retriever1086
|
Personalization of renal replacement therapy initiation: a secondary analysis of the AKIKI and IDEAL-ICU trials.
BACKGROUND
Trials comparing early and delayed strategies of renal replacement therapy in patients with severe acute kidney injury may have missed differences in survival as a result of mixing together patients at heterogeneous levels of risks. Our aim was to evaluate the heterogeneity of treatment effect on 60-day mortality from an early vs a delayed strategy across levels of risk for renal replacement therapy initiation under a delayed strategy.
METHODS
We used data from the AKIKI, and IDEAL-ICU randomized controlled trials to develop a multivariable logistic regression model for renal replacement therapy initiation within 48 h after allocation to a delayed strategy. We then used an interaction with spline terms in a Cox model to estimate treatment effects across the predicted risks of RRT initiation.
RESULTS
We analyzed data from 1107 patients (619 and 488 in the AKIKI and IDEAL-ICU trial respectively). In the pooled sample, we found evidence for heterogeneous treatment effects (P = 0.023). Patients at an intermediate-high risk of renal replacement therapy initiation within 48 h may have benefited from an early strategy (absolute risk difference, - 14%; 95% confidence interval, - 27% to - 1%). For other patients, we found no evidence of benefit from an early strategy of renal replacement therapy initiation but a trend for harm (absolute risk difference, 8%; 95% confidence interval, - 5% to 21% in patients at intermediate-low risk).
CONCLUSIONS
We have identified a clinically sound heterogeneity of treatment effect of an early vs a delayed strategy of renal replacement therapy initiation that may reflect varying degrees of kidney demand-capacity mismatch.
|
No pos
|
No neg
|
Retriever1087
|
Data bases for the assessment of medical technologies. Examples from Europe.
The assessment of medical technologies has to answer several questions ranging from safety and effectiveness to complex economical, social, and health policy issues. The type of data needed to carry out such evaluation depends on the specific questions to be answered, as well as on the stage of development of a technology. Basically two types of data may be distinguished: (a) general demographic, administrative, or financial data which has been collected not specifically for technology assessment; (b) the data collected with respect either to a specific technology or to a disease or medical problem. On the basis of a pilot inquiry in Europe and bibliographic research, the following categories of type (b) data bases have been identified: registries, clinical data bases, banks of factual and bibliographic knowledge, and expert systems. Examples of each category are discussed briefly. The following aims for further research and practical goals are proposed: criteria for the minimal data set required, improvement to the registries and clinical data banks, and development of an international clearinghouse to enhance information diffusion on both existing data bases and available reports on medical technology assessments.
|
No pos
|
No neg
|
Retriever1088
|
Remnant Liver Ischemia as a Prognostic Factor for Cancer-Specific Survival After Resection of Colorectal Liver Metastases.
IMPORTANCE
Ischemia-reperfusion injury during hepatic resection has been shown to accelerate progression of liver cancer. However, the prognostic relevance of remnant liver ischemia (RLI) after resection of colorectal liver metastases (CLMs) is unknown to date.
OBJECTIVES
To assess the prognostic influence of RLI after resection of CLMs and to identify correlates of greater extent of RLI.
DESIGN, SETTING, AND PARTICIPANTS
This study was a retrospective analysis at The University of Texas MD Anderson Cancer Center based on prospectively collected data. The study identified 202 patients who underwent curative resection of CLMs between January 1, 2008, and December 31, 2014, and had enhanced computed tomographic images obtained within 30 days after surgery.
MAIN OUTCOMES AND MEASURES
Remnant liver ischemia was defined as reduced or absent contrast enhancement during the portal phase. Postoperative RLI was classified as grade 0 (none), 1 (marginal), 2 (partial), 3 (segmental), or 4 (necrotic) as previously defined. Experienced members of the surgical team retrospectively performed imaging assessments. Team members were masked to the postoperative outcomes. Survival after resection was stratified by RLI grade. Predictors of RLI grade 2 or higher and survival were identified.
RESULTS
Among 202 patients (median [range] age, 56 [27-87] years; 84 female), the RLI grades were as follows: grade 0 (105 patients), grade 1 (47 patients), grade 2 (45 patients), grade 3 (5 patients), and grade 4 (0 patients). Recurrence-free survival (RFS) and cancer-specific survival (CSS) rates after hepatic resection were worse in patients with RLI grade 2 or higher vs grade 1 or lower (RFS at 3 years, 6.4% [3 of 50] vs 39.2% [60 of 152]; P < .001 and CSS at 5 years, 20.7% [10 of 50] vs 63.7% [97 of 152]; P < .001). A largest metastasis at least 3 cm (OR, 2.74; 95% CI, 1.35-5.70; P = .005), multiple CLMs (OR, 2.51; 95% CI, 1.25-5.24; P = .009), and nonanatomic resection (odds ratio [OR], 3.29; 95% CI, 1.52-7.63; P = .002) were associated with RLI grade 2 or higher. A largest metastasis at least 3 cm (hazard ratio [HR], 1.70; 95% CI, 1.01-2.88; P = .045), mutant RAS (HR, 2.15; 95% CI, 1.27-3.64; P = .005), and RLI grade 2 or higher (HR, 2.90; 95% CI, 1.69-4.84; P < .001) were associated with worse CSS.
CONCLUSIONS AND RELEVANCE
In this study, remnant liver ischemia grade 2 or higher was associated with worse CSS after resection of CLMs. High-quality anatomic surgery to minimize RLI after resection is essential.
|
No pos
|
No neg
|
Retriever1089
|
Type-1 interferons contribute to the neuroinflammatory response and disease progression of the MPTP mouse model of Parkinson's disease.
Type-1 interferons (IFNs) are pleiotropic cytokines with a critical role in the initiation and regulation of the pro-inflammatory response. However, the contribution of the type-1 IFNs to CNS disorders, specifically chronic neuropathologies such as Parkinson's disease is still unknown. Here, we report increased type-1 IFN signaling in both post mortem human Parkinson's disease samples and in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model. In response to MPTP, mice lacking the type-1 IFN receptor (IFNAR1(-/-) ) displayed decreased type-1 IFN signaling, an attenuated pro-inflammatory response and reduced loss of dopaminergic neurons. The neuroprotective potential of targeting the type-1 IFN pathway was confirmed by reduced neuroinflammation and DA cell death in mice treated with a blocking monoclonal IFNAR1 (MAR-1) antibody. The MPTP/MAR-1 treated mice also displayed increased striatal dopamine levels and improved behavioural outcomes compared to their MPTP/IgG controls. These data, implicate for the first time, a deleterious role for the type-1 IFNs as key modulators of the early neuroinflammatory response and therefore the neuronal cell death in Parkinson's disease. GLIA 2016;64:1590-1604.
|
No pos
|
No neg
|
Retriever1090
|
Design, Synthesis, and Biological Evaluation of C-2 Substituted 3Hthieno[ 2,3-d]pyrimidin-4-one Derivatives as Novel FGFR1 Inhibitors.
BACKGROUND
Thienopyrimidinone is a newly designed, selective fibroblast growth factor receptor 1 (FGFR1) inhibitor with an excellent anticancer effect.
OBJECTIVE
The goal of the present study was to design and synthesize better FGFR1 inhibitors through modifications of the lead compound thienopyrimidinone.
METHODS
In the present study, a series of C-2 substituted derivatives of thienopyrimidinone, namely L1-L16, were synthesized, and their inhibitory effects on FGFR1 were evaluated. The anti-proliferative activities of these compounds were assessed by MTT assay.
RESULTS
Among the novel derivatives, L11 was found to exert remarkable FGFR1 inhibitory activity (79.93% at 10 µM) and anti-proliferative activity, with IC50 values of 2.1, 2.5, and 3.5 .M in the FGFR1-overexpressing cell lines, H460, HT-1197, and B16F10, respectively.
CONCLUSION
Our newly synthesized thienopyrimidinone derivatives may be candidate FGFR1 inhibitors for future development as novel anticancer agents.
|
No pos
|
No neg
|
Retriever1091
|
Evaluating Sensory Processing in Fragile X Syndrome: Psychometric Analysis of the Brain Body Center Sensory Scales (BBCSS).
Individuals with fragile X syndrome (FXS), especially those co-diagnosed with autism spectrum disorder (ASD), face many sensory processing challenges. However, sensory processing measures informed by neurophysiology are lacking. This paper describes the development and psychometric properties of a parent/caregiver report, the Brain-Body Center Sensory Scales (BBCSS), based on Polyvagal Theory. Parents/guardians reported on 333 individuals with FXS, 41% with ASD features. Factor structure using a split-sample exploratory-confirmatory design conformed to neurophysiological predictions. Internal consistency, test-retest, and inter-rater reliability were good to excellent. BBCSS subscales converged with the Sensory Profile and Sensory Experiences Questionnaire. However, data also suggest that BBCSS subscales reflect unique features related to sensory processing. Individuals with FXS and ASD features displayed more sensory challenges on most subscales.
|
No pos
|
No neg
|
Retriever1092
|
Influence of the implantation site on the sensitivity of patient pancreatic tumor xenografts to Apo2L/TRAIL therapy.
OBJECTIVES
We have previously demonstrated activity of Apo2L/TRAIL against patient pancreatic tumor xenografts. Here, we have examined the influence of the tumor implantation site on therapeutic response of orthotopic tumors and their metastases to Apo2L/TRAIL.
METHODS
Sensitivity of 6 patient pancreatic tumor xenografts to Apo2L/TRAIL was determined in a subcutaneous model. To compare the response of orthotopic tumors, cells from subcutaneous xenografts were injected into the pancreas. Tumor growth was confirmed by histological examination of selected mice, and then treatment was started. When all control mice developed externally palpable tumors, the experiment was terminated, and pancreatic weights compared between control and treated groups. Magnetic resonance imaging was used to quantitate the response of orthotopic and metastatic tumors.
RESULTS
The sensitivity to Apo2L/TRAIL observed in subcutaneous tumors was maintained in orthotopic tumors. Metastatic spread was observed with orthotopic tumor implantation. In an orthotopic model of a sensitive tumor, primary and metastatic tumor burden was significantly reduced, and median survival significantly extended by Apo2L/TRAIL therapy.
CONCLUSIONS
Our data provide evidence that the site of tumor engraftment does not alter the inherent sensitivity of patient xenografts to Apo2L/TRAIL, and these results highlight the potential of Apo2L/TRAIL therapy against primary and metastatic pancreatic cancer.
|
No pos
|
No neg
|
Retriever1093
|
Supramolecular tetrads containing Sn(IV) porphyrin, Ru(II) porphyrin, and expanded porphyrins assembled using complementary metal-ligand interactions.
Two examples of supramolecular tetrads containing Sn(IV) porphyrin, expanded thiaporphyrins such as sapphyrin and rubyrin, and Ru(II) porphyrin assembled using non-interfering cooperative tin(IV)-oxygen and ruthenium(II)-nitrogen coordination properties are described. These are the first examples in which the expanded porphyrins are used as axial ligands. The tetrads were prepared by adopting one step as well as stepwise approaches. In a one pot approach, the mono meso-pyridyl dihydroxy Sn(IV) porphyrin, meso-hydroxyphenyl expanded thiaporphyrin, and Ru(II) porphyrin were reacted in benzene under refluxing conditions followed by column chromatographic purification on alumina to afford tetrads. In a stepwise approach, the axial bonding type of triads containing Sn(IV)porphyrin as central unit and expanded thiaporphyrins as axial ligands were synthesized first by reacting meso-pyridyl dihydroxy Sn(IV) porphyrin with meso-hydroxyphenyl expanded thiaporphyrin in benzene at refluxing temperature. In the next step, the triads were reacted with Ru(II) porphyrin under mild reaction conditions to afford tetrads in decent yields. Both methods worked efficiently and produced stable, soluble tetrads in decent yields. One-dimensional (1D) and two-dimensional (2D) NMR techniques were used to confirm the identity of these novel tetrads. Absorption and electrochemical studies indicated that the components in tetrads interact weakly and retain their individual characteristic features. The steady state photophysical studies revealed that the quantum yield of Sn(IV) porphyrin in tetrads was reduced significantly because of non-radiative decay pathways operating in these systems.
|
No pos
|
No neg
|
Retriever1094
|
Paper-Based Fluidic Sensing Platforms for β-Adrenergic Agonist Residue Point-of-Care Testing.
The illegal use of β-adrenergic agonists during livestock growth poses a threat to public health; the long-term intake of this medication can cause serious physiological side effects and even death. Therefore, rapid detection methods for β-adrenergic agonist residues on-site are required. Traditional detection methods such as liquid chromatography have limitations in terms of expensive instruments and complex operations. In contrast, paper methods are low cost, ubiquitous, and portable, which has led to them becoming the preferred detection method in recent years. Various paper-based fluidic devices have been developed to detect β-adrenergic agonist residues, including lateral flow immunoassays (LFAs) and microfluidic paper-based analytical devices (μPADs). In this review, the application of LFAs for the detection of β-agonists is summarized comprehensively, focusing on the latest advances in novel labeling and detection strategies. The use of μPADs as an analytical platform has attracted interest over the past decade due to their unique advantages and application for detecting β-adrenergic agonists, which are introduced here. Vertical flow immunoassays are also discussed for their shorter assay time and stronger multiplexing capabilities compared with LFAs. Furthermore, the development direction and prospects for the commercialization of paper-based devices are considered, shedding light on the development of point-of-care testing devices for β-adrenergic agonist residue detection.
|
No pos
|
No neg
|
Retriever1095
|
Dietary intake and urinary excretion of methylated arsenicals of Japanese adults consuming marine foods and rice.
Dietary intake and urinary excretion of monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine (AsB) were measured in 150 adult Japanese subjects. Duplicate diet (DD) samples and first void of urine on the next morning of DD sampling day were collected and analysed for arsenic species with liquid chromatography-ICP mass spectrometry. Median (min-max) intakes of MMA, DMA and AsB were <2.3 (<2.3-<2.3), 4.57 (<2.3-24.3), and 13.6 (<2.4-231) μg As/day, respectively, and median urinary concentrations were 1.90 (<0.37-26.), 21.9 (<0.27-141) and 19.6 (<0.37-1063) ng As/mg creatinine, respectively. Interrelationships between intake levels and urinary concentrations were mostly significant with positive coefficients indicating mutual association due to co-exposure, metabolism and/or dietary habit. Urinary concentrations and intake levels of AsB were also positively correlated confirming the applicability of urine analysis as biomarker of exposure. The present descriptive results provide with essential piece of information in assessing health risk of methylated arsenicals for population who consume marine products and rice.
|
No pos
|
No neg
|
Retriever1096
|
Design of a multiplex quantitative reverse transcription-PCR system to simultaneously detect 16 pathogens associated with bovine respiratory and enteric diseases.
AIM
Bovine respiratory disease (BRD) and bovine enteric disease (BED) are two major diseases in cattle, resulting in severe economic losses in the dairy and beef industries. The two major diseases are associated with several factors such as viruses, bacteria, the health condition of the host and environmental factors. We aimed to design a new efficient diagnostic method, which rapidly detect causative pathogens, minimizing economic loss due to BRD and BED.
METHODS AND RESULTS
We designed a multiplex quantitative reverse transcription-PCR (qRT-PCR) system for the simultaneous diagnosis of 16 pathogens, including 12 viruses and 4 bacteria related to BRD and BED, based on single qRT-PCR assays in previous studies. The designed multiplex qRT-PCR was highly sensitive and has minimal detection levels which will be no different from those of single qRT-PCR. Moreover, the multiplex qRT-PCR could more efficiently detect the causative pathogens than conventional RT-PCR in test using a part of BRD and BED clinical samples. Furthermore, our data revealed that the multiplex qRT-PCR had high performance in its specificity and reproducibility tests.
CONCLUSIONS
Our system can effectively detect multiple BRD or BED related pathogens from each animal while testing several clinical samples via the multiplex qRT-PCR. It is more time-, cost- and labour-efficient than other diagnostic methods.
SIGNIFICANCE AND IMPACT OF THE STUDY
Rapid detection of infected animals from the herd using our system will greatly contribute to infection control and prompt treatment in field.
|
No pos
|
No neg
|
Retriever1097
|
Novel trihydroxamate-containing peptides: design, synthesis, and metal coordination.
Novel trihydroxamate-containing peptides were designed to mimic desferrioxamine (Desferal(R), DFO, a naturally occurring siderophore) but possess distinct conformational restrictions and varied lipophilicity to probe structure vs. metal coordination. The synthesis was performed via fragment condensation of hydroxamate-containing oligopeptides such as Fmoc-Leu- Psi[CON(OBz)]-Phe-Ala-Pro-OH and H-Leu-Psi[CON(OBz)]-Phe-Ala-Pro-OBu(t) (Fmoc: 9-fluor enylmethoxycarbonyl; OBz: benzyl; OBu(t): tert-butyl) either in solution or on a solid support. The metal-binding properties were studied by electrospray ionization-mass spectroscopy (ESI-MS), ultraviolet (UV)-visible spectroscopy, and (1)H nuclear magnetic resonance (NMR). Similar to the dihydroxamate analogs previously explored [Biopolymers (Peptide Science), 2003, Vol. 71, pp. 489-515], the compounds with three hydroxamates arrayed at 10-atom intervals, i.e., H-[Leu-Psi[CON(OH)]-Phe-Ala-Pro](3)-OH (P1), cyclo[Leu-Psi[CON(OH)]-Phe-Ala-Pro](3) (P2), and H-[Leu-Psi(CONOH)-Phe-Ala-Pro](2)-Leu-NHOH (P7), exhibited high affinities for intramolecular coordination with Fe(III) and Ga(III). As expected, both P1 and P2 showed higher relative Fe(III)-binding affinities than the corresponding dihydroxamate-containing peptide analogs (P11 and P12). Even though both P1 and P2 did not compete with DFO in the relative metal-binding affinity in both solution and gas phases, P1, P2, and DFO exhibited similar relative binding selectivities to 11 different metal ions including Fe(III), Fe(II), Al(III), Ga(III), In(III), Zn(II), Cu(II), Co(II), Ni(II), Gd(III), and Mn(II). Compared to the other metal ions, they had higher relative binding affinities with Fe(III), Fe(II), Al(III), Ga(III), and In(III). The decreased metal-binding affinities of P1 and P2 in comparison with DFO suggested the conformational restrictions of their backbones perturb their three hydroxamate groups from optimal hexadentate orientations for metal coordination. As detected by ESI-MS, P2 was distinguished from both P1 and DFO by solvation of its Ga(III) and Fe(III) complexes (such as acetonitrile or water), thereby stabilizing the resulting complexes in the gas phase. Noteworthy, P2 led to 69% death rate in Hela cells at a concentration of 50 microM, exhibiting higher cytotoxicity than DFO in vitro despite its much lower affinity for iron. This enhanced toxicity may simply reflect the increased lipophilicity of the cyclic trihydroxamate (P2) together with the improvements in its cell penetration, and/or subsequent intracellular molecular recognition of both side chains and hydroxamate groups. The cytotoxicity was significantly suppressed by precoordination with Ga(III) or Fe(III), suggesting a mechanism of toxicity via sequestration of essential metal ions as well as the importance of curbing the metal coordination before targeting. The potential of such siderophore-mimicking peptides in oncology needs further exploration.
|
No pos
|
No neg
|
Retriever1098
|
Complement biosynthesis in vitro by rat hepatoma cell strains.
Four separate rat hepatoma strains were examined for their capacity to synthesize complement (C). None of the strains synthesized detectable amounts of the first components (C-1), and only one strain (7800C-1) produced the fourth component (C4). However, each of the strains synthesized significant amounts of biologically active C-2 and C-3. Three of the four strains also produced C-5 and the natural inhibitor of C-1 (C1 INH). Two control rat cell strains (fibroblast and pituitary) did not synthesize any detectable C components. Production of C, studied extensively in 7800C-1 and H-4, was reversibly inhibited by cycloheximide (2 mug/ml) and [ 14-C ] amino acids were incorporated into C-2, C-3, and C-1 INH. As assessed by gel filtration, the elution positions of the C components synthesized by the cells in culture were similar to those of the corresponding proteins in normal rat serum. Hydrocortisone (10-6 to 10-7 M) stimulated the production of C-3 by H-4 but C-2 and C-5 production were not affected. These C-producing hepatoma cells may prove useful for studies of the control of C biosynthesis.
|
No pos
|
No neg
|
Retriever1099
|
Treatment and survival in children with pulmonary arterial hypertension: the UK Pulmonary Hypertension Service for Children 2001-2006.
OBJECTIVE
A retrospective study of the UK Pulmonary Hypertension Service for Children for the first 5-year period of its existence.
DESIGN AND PATIENTS
Records of 216 children with idiopathic pulmonary arterial hypertension (IPAH) and associated pulmonary arterial hypertension (APAH) were reviewed. Kaplan-Meier survival curves were constructed for different diagnostic groups and for different therapies.
RESULTS
At cardiac catheterisation only 7.4% of those with IPAH and 6% of those with APAH responded positively to vasodilator testing and so were treated with nifedipine. Others needing treatment were given continuous intravenous epoprostenol, bosentan or sildenafil singly or in combination. For IPAH survival rates were 85.6%, 79.9% and 71.9% at 1, 3 and 5 years, respectively, compared with a survival time of less than a year in historical untreated controls. A combination of intravenous epoprostenol with either bosentan or sildenafil, or both, appeared to achieve the best outcome. Six children underwent lung transplantation. In APAH survival rates were 92.3%, 83.8% and 56.9% at 1, 3 and 5 years, respectively, postoperative congenital heart disease with severe pulmonary hypertension having the worst outcome.
CONCLUSION
New pulmonary hypertension-specific medicines have improved survival in children as in adults. Outcome in this series compares favourably with international outcome data.
|
No pos
|
No neg
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.