title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Predictors of loneliness among older women and men in Sweden: A national longitudinal study. | Longitudinal research on loneliness in old age has rarely considered loneliness separately for men and women, despite gender differences in life experiences. The objective of this study was to examine the extent to which older women and men (70+) report feelings of loneliness with a focus on: (a) changes in reported loneliness as people age, and (b) which factors predict loneliness. Data from the 2004 and 2011 waves of SWEOLD, a longitudinal national survey, was used (n = 587). The prediction of loneliness in 2011 by variables measured in 2004 and 2004-2011 variable change scores was examined in three logistic regression models: total sample, women and men. Variables in the models included: gender, age, education, mobility problems, depression, widowhood and social contacts. Older people moved into and out of frequent loneliness over time, although there was a general increase in loneliness with age. Loneliness at baseline, depression increment and recent widowhood were significant predictors of loneliness in all three multivariable models. Widowhood, depression, mobility problems and mobility reduction predicted loneliness uniquely in the model for women; while low level of social contacts and social contact reduction predicted loneliness uniquely in the model for men. This study challenges the notion that feelings of loneliness in old age are stable. It also identifies important gender differences in prevalence and predictors of loneliness. Knowledge about such differences is crucial for the development of effective policy and interventions to combat loneliness in later life. | 25,126,996 | [
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Association between anticoagulant treatment duration and risk of venous thromboembolism recurrence and bleeding in clinical practice. | This retrospective observational study examined whether anticoagulant treatment duration varies by risks of venous thromboembolism (VTE) recurrence and bleeding. VTE patients naïve to anticoagulants were identified from the HealthCore Integrated Research Database between 06/01/2007 and 09/30/2011 and categorized into three groups: provoked, cancer-related, and unprovoked VTE. Treatment duration was from initiation to discontinuation of anticoagulation, based on a 60-day gap in prescription fill unless there was an international normalized ratio test every 42 days. Bleeding risk was estimated using RIETE score, and VTE risk categories were based on ACCP guidelines. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate association between VTE recurrence/bleeding and anticoagulation duration. Of 2002 patients identified (52.3% males, mean age 57 ±15 years), 21.4% had provoked, 16.4% had cancer-related, and 62.1% had unprovoked VTE. Average anticoagulant treatment duration was 294 ± 261 days. After adjusting for demographics and clinical characteristics, provoked and cancer-related VTE patients were 32% (95% CI=14-54%, P<0.001) and 35% (95% CI=7-70%, P=0.013) more likely, respectively, to discontinue anticoagulants than unprovoked VTE patients. No differences were observed between provoked and cancer-related VTE patients. Patients with an intermediate/high bleeding risk were 26% (95% CI=14-36%, P<0.001) less likely to discontinue treatment than those with a low bleeding risk. The observed anticoagulation duration for VTE may not be concordant with guidelines, due to the challenge of counterbalancing risks of VTE recurrence and bleeding. Further studies are needed to explore this. | 25,127,013 | [
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Delirium screening anchored in child development: The Cornell Assessment for Pediatric Delirium. | The recently validated Cornell Assessment for Pediatric Delirium (CAPD) is a new rapid bedside nursing screen for delirium in hospitalized children of all ages. The present manuscript provides a "developmental anchor points" reference chart, which helps ground clinicians' assessment of CAPD symptom domains in a developmental understanding of the presentation of delirium. During the development of this CAPD screening tool, it became clear that clinicians need specific guidance and training to help them draw on their expertise in child development and pediatrics to improve the interpretative reliability of the tool and its accuracy in diagnosing delirium. The developmental anchor points chart was formulated and reviewed by a multidisciplinary panel of experts to evaluate content validity and include consideration of sick behaviors within a hospital setting. The CAPD developmental anchor points for the key ages of newborn, 4 weeks, 6 weeks, 8 weeks, 28 weeks, 1 year, and 2 years served as the basis for training bedside nurses in scoring the CAPD for the validation trial and as a multifaceted bedside reference chart to be implemented within a clinical setting. In the current paper, we discuss the lessons learned during implementation, with particular emphasis on the importance of collaboration with the bedside nurse, the challenges of establishing a developmental baseline, and further questions about delirium diagnosis in children. The CAPD with developmental anchor points provides a validated, structured, and developmentally informed approach to screening and assessment of delirium in children. With minimal training on the use of the tool, bedside nurses and other pediatric practitioners can reliably identify children at risk for delirium. | 25,127,028 | [
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IGFBP3 methylation is a novel diagnostic and predictive biomarker in colorectal cancer. | Aberrant hypermethylation of cancer-related genes has emerged as a promising strategy for the development of diagnostic, prognostic and predictive biomarkers in human cancer, including colorectal cancer (CRC). The aim of this study was to perform a systematic and comprehensive analysis of a panel of CRC-specific genes as potential diagnostic, prognostic and predictive biomarkers in a large, population-based CRC cohort. Methylation status of the SEPT9, TWIST1, IGFBP3, GAS7, ALX4 and miR137 genes was studied by quantitative bisulfite pyrosequencing in a population-based cohort of 425 CRC patients. Methylation levels of all genes analyzed were significantly higher in tumor tissues compared to normal mucosa (p<0.0001); however, cancer-associated hypermethylation was most frequently observed for miR137 (86.7%) and IGFBP3 (83%) in CRC patients. Methylation analysis using the combination of these two genes demonstrated greatest accuracy for the identification of colonic tumors (sensitivity 95.5%; specificity 90.5%). Low levels of IGFBP3 promoter methylation emerged as an independent risk factor for predicting poor disease free survival in stage II and III CRC patients (HR = 0.49, 95% CI: 0.28-0.85, p = 0.01). Our results also suggest that stage II & III CRC patients with high levels of IGFBP3 methylation do not benefit from adjuvant 5FU-based chemotherapy. By analyzing a large, population-based CRC cohort, we demonstrate the potential clinical significance of miR137 and IGFBP3 hypermethylation as promising diagnostic biomarkers in CRC. Our data also revealed that IGFBP3 hypermethylation may serve as an independent prognostic and predictive biomarker in stage II and III CRC patients. | 25,127,039 | [
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Youth, friendship, and gaming: a network perspective. | With digital games being part of the leisure of a multitude of young people, it is important to understand to what extent gaming-related practices such as talking about games or playing games together are associated with the quality of friendship relations with players and nonplayers. Based on 100 friendship networks, this study explored to what extent those practices permeated the everyday life of youngsters and whether they could be considered as a part of doing friendship. Results indicated that gaming as a conversational topic was widespread within and between networks. Furthermore, regardless of gender, this was significantly associated with friendship quality in almost all of the networks. When considering playing games together, a somewhat different picture emerged. In contrast to conversational practices, playing together was less widespread. Moreover, both the occurrence and the effect of co-play and friendship quality was gendered. The findings of this study show that a focus on gaming-related practices yields a fruitful starting point when considering the role of digital games in a social context that is not limited to people playing (online) games. Furthermore, they also feed into the ongoing debate of possible effects of digital games in that it shows that the way in which games influence the lives of young people goes beyond a direct effects approach. | 25,127,060 | [
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Partial purification and characterization of chromate reductase of a novel Ochrobactrum sp. strain Cr-B4. | Hexavalent chromium contamination is a serious problem due to its high toxicity and carcinogenic effects on the biological systems. The enzymatic reduction of toxic Cr(VI) to the less toxic Cr(III) is an efficient technology for detoxification of Cr(VI)-contaminated industrial effluents. In this regard, a chromate reductase enzyme from a novel Ochrobactrum sp. strain Cr-B4, having the ability to detoxify Cr(VI) contaminated sites, has been partially purified and characterized. The molecular mass of this chromate reductase was found to be 31.53 kD, with a specific activity 14.26 U/mg without any addition of electron donors. The temperature and pH optima for chromate reductase activity were 40°C and 8.0, respectively. The activation energy (Ea) for the chromate reductase was found to be 34.7 kJ/mol up to 40°C and the activation energy for its deactivation (Ed) was found to be 79.6 kJ/mol over a temperature range of 50-80°C. The frequency factor for activation of chromate reductase was found to be 566.79 s(-1), and for deactivation of chromate reductase it was found to be 265.66 × 10(3) s(-1). The reductase activity of this enzyme was affected by the presence of various heavy metals and complexing agents, some of which (ethylenediamine tetraacetic acid [EDTA], mercaptoethanol, NaN3, Pb(2+), Ni(2+), Zn(2+), and Cd(2+)) inhibited the enzyme activity, while metals like Cu(2+) and Fe(3+) significantly enhanced the reductase activity. The enzyme followed Michaelis-Menten kinetics with Km of 104.29 µM and a Vmax of 4.64 µM/min/mg. | 25,127,065 | [
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Semicarbazide - from state-of-the-art analytical methods and exposure to toxicity: a review. | This review assesses the state of the art concerning semicarbazide (SEM). Originally, SEM was primarily detected as a nitrofurazone veterinary metabolite, but over time scientists gradually found that azodicarbonamide in sealed cans and flour could also lead to the generation of SEM. This discovery makes the study of SEM particularly interesting. At present, an increasing number of researchers are investigating the toxicity of SEM and developing more and better analytical methods for the determination of SEM. In recent years, many researchers have focused on exposure from different foods, the public awareness of hazards and analytical detection methods for SEM in different foods. Although there have been significant achievements, these results have not been summarised in a review. The exposure from different foods, toxicity and methods of detection for SEM are comprehensively reviewed here. This review will provide not only others with a better understanding of SEM but also background information to facilitate future research. | 25,127,068 | [
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Gynecologic care for transgender youth. | To provide an overview of the care of the adolescent transgender patient with regard to the guidelines and recommendations that currently exist, and to review the role of the clinician caring for transgender youth. The World Professional Association for Transgender Health and the Endocrine Society continue to provide comprehensive guidelines for the care of adolescent transgender patients. The decision to perform surgery on a patient who is a minor remains a complex one, and a case-by-case approach should be taken with important ethical principles in mind. Cross-sex steroid use places transgender adolescents at risk for metabolic disorders, and careful surveillance is necessary. In addition, transgender teens are at high risk for depression, anxiety and suicidality and have been shown to engage in more high-risk behaviors compared with their nontransgender heterosexual counterparts. Clinicians who care for adolescents can play an important role in the counseling, screening, health maintenance and support of their patients through the transition process. | 25,127,077 | [
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Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum. | Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration. | 25,127,095 | [
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Supportive care needs of cancer patients: A literature review. | This review of the research literature explored the supportive care needs of cancer patients of varying ages and genders at varying stages of cancer treatment. We conducted a search of online databases of peer-reviewed studies published in the English language between 2009 and 2014. This paper reviews research studies that explored the supportive care needs of cancer patients through focus groups, surveys, and interviews. The samples addressed varied in age, ethnicity, and gender. One major need identified was the requirement of informational support. Other essential needs included emotional, spiritual, and financial support. Supportive care can be administered in various ways—for example, by religious communities or caregivers as well as providers. However, healthcare providers must recognize the supportive care needs of their patients and incorporate effective resources and interventions into treatment plans. | 25,127,108 | [
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Trans-axillary approach for breast implant exchange in high risk cases of irradiated or attenuated skin. | Breast reconstruction with implants after tissue expansion is one of the most common methods of reconstruction. Although this approach is generally reliable, exchange of breast tissue expander for implant through the standard anterior incision presents a challenge in cases with attenuated soft tissue envelope due to radiation, thin anatomy, prior surgery, or combination of the above. We propose that a trans-axillary approach is a safe and alternate approach for implant exchange in the high-risk patients. A case series of 16 patients with multiple risk factors for compromised soft tissue that underwent a trans-axillary approach for implant exchange is reported. The trans-axillary implant exchange technique involves use of a standard 4 cm axillary incision, removal of the expander, judicious capsulotomy, placement of permanent implant, and closure in three separate tissue layers. All trans-axillary cases were successful and all incisions were well healed without dehiscence, infection, or seroma. The average patient age was 49.4 years, and 50% of patients had received or were scheduled to receive radiation therapy. Nine patients underwent unilateral trans-axillary expander exchange while 7 patients were bilateral. Median implant size was 360 cc (mean 369 cc, range 150-600 cc), and mean follow-up for all patients was over 24 months. There were no cases of implant extrusion, capsular contracture requiring re-operation, or lymphedema. Six patients underwent concurrent or subsequent nipple reconstruction. This approach illustrates application of a technique commonly used in breast aesthetic augmentation to address a common reconstructive dilemma, which we believe to be a useful tool in prosthesis-based breast reconstruction, especially in patients with compromised soft tissue envelopes. | 25,127,109 | [
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Sex-dependent gene expression in human pluripotent stem cells. | Males and females have a variety of sexually dimorphic traits, most of which result from hormonal differences. However, differences between male and female embryos initiate very early in development, before hormonal influence begins, suggesting the presence of genetically driven sexual dimorphisms. By comparing the gene expression profiles of male and X-inactivated female human pluripotent stem cells, we detected Y-chromosome-driven effects. We discovered that the sex-determining gene SRY is expressed in human male pluripotent stem cells and is induced by reprogramming. In addition, we detected more than 200 differentially expressed autosomal genes in male and female embryonic stem cells. Some of these genes are involved in steroid metabolism pathways and lead to sex-dependent differentiation in response to the estrogen precursor estrone. Thus, we propose that the presence of the Y chromosome and specifically SRY may drive sex-specific differences in the growth and differentiation of pluripotent stem cells. | 25,127,145 | [
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Co-infection with 'Candidatus Neoehrlichia mikurensis' and Borrelia afzelii in an Ixodes ricinus tick that has bitten a human in Romania. | Despite the vast importance of ticks as disease vectors, the infectious agents transmitted by ticks are still incompletely known in many areas. Here, we report for the first time the detection of the bacterium 'Candidatus Neoehrlichia mikurensis' in Romania, in an Ixodes ricinus tick obtained from a human. Furthermore, the tick also had a co-infection with Borrelia afzelii. 'Candidatus Neoehrlichia mikurensis' is one of the most recent discoveries of a tick-borne agent, and has been found in human patients in several European countries as well as in China. | 25,127,158 | [
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Repurposing human PDE4 inhibitors for neglected tropical diseases: design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors. | A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4) inhibitor cilomilast (1) was undertaken in order to identify inhibitors of phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the parasite which causes African sleeping sickness, a neglected tropical disease that affects thousands each year, and TbrPDEB1 has been shown to be an essential target of therapeutic relevance. Noting that 1 is a weak inhibitor of TbrPDEB1, we report the design and synthesis of analogs of this compound, culminating in 12b, a sub-micromolar inhibitor of TbrPDEB1 that shows modest inhibition of T. brucei proliferation. | 25,127,163 | [
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Glycemic effect of oat and barley beta-glucan when incorporated into a snack bar: a dose escalation study. | The blood glucose-lowering effects of β-glucan from oats and barley depend on the amounts consumed and their rheological properties. This has been recently challenged with growing evidence that the food matrix may also be an important factor in predicting its physiological response. The objective of this study was to examine the effects of varying doses of β-glucan from oats and barley and added to a snack bar on postprandial glycemia. In a randomized crossover study, 12 healthy males and females consumed one of 8 snack bars containing 0 (control), 1.5, 3, and 6 g of β-glucan derived from oats or barley or 3 white bread controls. All treatments contained 50 g of available carbohydrate. Blood glucose concentrations were measured after ingestion of the treatments over 2 hours. Incorporation of 1.5 to 6 g of β-glucan into snack bars had no additional glucose-lowering benefits irrespective of dose and source compared to the control bars (0 g β-glucan), suggesting that both the solid food matrix and composition of the bars may play a role in their effects on glycemic response. All bars reduced blood glucose area under the curve (AUC) by an average of 25% (p < 0.05) compared to the mean of the 3 white bread controls. Adding β-glucan from oats and barley to the snack bar formulation used in this study did not yield any additional benefits beyond the glucose-lowering effects of the snack bars themselves. | 25,127,170 | [
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Laser-induced nondestructive patterning of a thin ferroelectric polymer film with controlled crystals using Ge8Sb2Te11 alloy layer for nonvolatile memory. | We present a simple but robust nondestructive process for fabricating micropatterns of thin ferroelectric polymer films with controlled crystals. Our method is based on utilization of localized heat arising from thin Ge(8)Sb(2)Te(11) (GST) alloy layer upon exposure of 650 nm laser. The heat was generated on GST layer within a few hundred of nanosecond exposure and subsequently transferred to a thin poly(vinylidene fluoride-co-trifluoroethylene) film deposited on GST layer. By controlling exposure time and power of the scanned laser, ferroelectric patterns of one or two microns in size are fabricated with various shape. In the micropatterned regions, ferroelectric polymer crystals were efficiently controlled in both degree of the crystallinity and the molecular orientations. Nonvolatile memory devices with laser scanned ferroelectric polymer layers exhibited excellent device performance of large remnant polarization, ON/OFF current ratio and data retention. The results are comparable with devices containing ferroelectric films thermally annealed at least for 2 h, making our process extremely efficient for saving time. Furthermore, our approach can be conveniently combined with a number of other functional organic materials for the future electronic applications. | 25,127,181 | [
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Direct synthesis of α-trifluoromethyl ketone from (hetero)arylacetylene: design, intermediate trapping, and mechanistic investigations. | Regioselective addition across the alkynes has been achieved in a silver-catalyzed protocol utilizing Langlois reagent (CF3SO2Na) and molecular O2 to access medicinally active α-trifluoromethyl ketone compounds. This method was successful in producing α-trifluoromethyl ketone in heterocyclic scaffolds, which are incompatible with earlier strategies. Experimental findings suggest a mechanism involving α-styrenyl radical intermediate and 1-methyl-2-pyrrolidinone (NMP) solvent, which leads to crystallographically characterized N-methylsuccinimide. Isotope labeling, kinetic studies, and intermediate trapping further helped to gain insight into this energy-demanding process. | 25,127,202 | [
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Chemical and mechanical defenses vary among maternal lines and leaf ages in Verbascum thapsus L. (Scrophulariaceae) and reduce palatability to a generalist insect. | Intra-specific variation in host-plant quality affects herbivore foraging decisions and, in turn, herbivore foraging decisions mediate plant fitness. In particular, variation in defenses against herbivores, both among and within plants, shapes herbivore behavior. If variation in defenses is genetically based, it can respond to natural selection by herbivores. We quantified intra-specific variation in iridoid glycosides, trichome length, and leaf strength in common mullein (Verbascum thapsus L, Scrophulariaceae) among maternal lines within a population and among leaves within plants, and related this variation to feeding preferences of a generalist herbivore, Trichopulsia ni Hübner. We found significant variation in all three defenses among maternal lines, with T. ni preferring plants with lower investment in chemical, but not mechanical, defense. Within plants, old leaves had lower levels of all defenses than young leaves, and were strongly preferred by T. ni. Caterpillars also preferred leaves with trichomes removed to leaves with trichomes intact. Differences among maternal lines indicate that phenotypic variation in defenses likely has a genetic basis. Furthermore, these results reveal that the feeding behaviors of T. ni map onto variation in plant defense in a predictable way. This work highlights the importance of variation in host-plant quality in driving interactions between plants and their herbivores. | 25,127,229 | [
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A method for predicting the number of active bubbles in sonochemical reactors. | Knowledge of the number of active bubbles in acoustic cavitation field is very important for the prediction of the performance of ultrasonic reactors toward most chemical processes induced by ultrasound. The literature in this field is scarce, probably due to the complicated nature of the phenomena. We introduce here a relatively simple semi-empirical method for predicting the number of active bubbles in an acoustic cavitation field. By coupling the bubble dynamics in an acoustical field with chemical kinetics occurring in the bubble during oscillation, the amount of the radical species OH and HO2 and molecular H2O2 released by a single bubble was estimated. Knowing that the H2O2 measured experimentally during sonication of water comes from the recombination of hydroxyl (OH) and perhydroxyl (HO2) radicals in the liquid phase and assuming that in sonochemistry applications, the cavitation is transient and the bubble fragments at the first collapse, the number of bubbles formed per unit time per unit volume is then easily determined using material balances for H2O2, OH and HO2 in the liquid phase. The effect of ultrasonic frequency on the number of active bubbles was examined. It was shown that increasing ultrasonic frequency leads to a substantial increase in the number of bubbles formed in the reactor. | 25,127,247 | [
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Cognitive functioning among patients with diabetic foot. | Using diabetic foot (DF) as an indicator of severe diabetes, we aimed to investigate the cognitive profile of DF patients and the relations between cognitive functioning and both diabetes complications and comorbidities. Dementia-free patients with DF aged 30-90 (n=153) were assessed through medical records and a cognitive battery. Information on diabetes complications and comorbidities was collected via interview; glycated hemoglobin (HbA1c) was tested. Data were analyzed using robust logistic or quantile regression adjusted for potential confounders. The mean Mini-Mental Examination (MMSE) score of patients was 24.6 (SD=3.6), and 40% had global cognitive dysfunction (MMSE ≤24). Among elderly patients (aged ≥65), MMSE impairment was related to amputation (OR 3.59, 95% CI 1.07-12.11). Episodic memory impairment was associated with foot amputation (OR 4.13, 95% CI 1.11-15.28) and microvascular complications (OR 9.68, 95% CI 1.67-56.06). Further, elderly patients with HbA1c <7% had increased odds of psychomotor slowness (OR 7.75, 95% CI 1.55-38.73) and abstract reasoning impairment (OR 4.49, 95% CI: 1.15-17.46). However, such significant associations were not shown in adult patients aged <65. Amputation, microvascular diseases and glycemic control were associated with impaired global cognitive function and its domains among patients aged ≥65. | 25,127,250 | [
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Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence. | The events leading to breast cancer (BC) progression or recurrence are not completely understood and new prognostic markers aiming at identifying high risk-patients and to develop suitable therapy are highly demanded. Experimental evidences found in cancer cells a deregulated expression of some genes involved in governance of stem cell properties and demonstrated a relationship between stemness genes overexpression and poorly differentiated BC subtypes. In the present study 140 primary invasive BC specimens were collected. The expression profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT-PCR were analyzed and any correlation between their expression and the BC clinic-pathological features (CPfs) and prognosis was investigated. In our cohort (117 samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes negative status and higher KI67 proliferation index, respectively (p=0.019, p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004) as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035). Our study provides further proof of the suitable use of stemness genes in BC management. Interestingly, a prognostic role of SOX2, which seems to be a suitable marker of early recurrence irrespective of other clinicopathological features. | 25,127,259 | [
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Measuring behaviors of individual adolescents during group-based substance abuse intervention. | Group treatment is delivered in youth correctional facilities, yet groups may be iatrogenic. Few measures with demonstrated psychometric properties exist to track behaviors of individuals during groups. The authors assessed psychometrics for the Group Process-Individual Level measure (GP-IL) of group treatment. N = 152 teens were randomized to 1 of 2 groups (10 sessions each). Adolescents, counselors, and observers rated teen behaviors at sessions 3 and 10. GP-IL assesses reinforcement for deviancy and positive behaviors, member rejection, and counselor connection and praise. Internal consistency and 1-month stability were demonstrated. Concurrent validity is supported by correlations with measures expected to be associated with group behavior (e.g., coping skills). Counselors and observers rated more deviancy during interactive skills-building groups versus didactic psychoeducational groups (P ≤ .005). Scales evidenced incremental validity. GP-IL offers a sound method of tracking adolescent behaviors for professionals working with groups. Counselors ratings were most reliable and valid overall. | 25,127,289 | [
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Evaluation of ototoxicity in patients treated with hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin and sodium thiosulfate. | Ototoxic hearing loss associated with intravenous or intra-arterial administration of cisplatin is well documented. However, there is limited data regarding the ototoxic effect of cisplatin when perfused into the abdominal cavity using hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this study is to assess and describe ototoxicity in patients treated with HIPEC with cisplatin and sodium thiosulfate for peritoneal surface malignancies. We performed a retrospective chart review (2007-2012) of patients treated for advanced peritoneal malignancies at a tertiary care center using HIPEC with cisplatin and sodium thiosulfate infusion. Thirteen patients (12 males, 1 female) met study criteria. Audiometric thresholds were compared before and after treatment. A 20 dB loss at any single frequency, 10 dB decrease at any two adjacent frequencies, or loss of response at three consecutive test frequencies defined a significant ototoxic change (). Despite minimal hearing change in six patients, none of the 13 patients in our study exhibited a significant ototoxic change in hearing sensitivity post HIPEC with cisplatin at any test interval in any test frequency. Our findings represent the first objective assessment of ototoxic effect after HIPEC with cisplatin and sodium thiosulfate infusion. Our results suggest that peritoneal perfusion of cisplatin with intravenous perfusion of sodium thiosulfate is not associated with ototoxic changes in hearing sensitivity. Further investigation of the administration and systemic mechanism of absorption of sodium thiosulfate as a potential protection against cisplatin ototoxicity is needed to confirm these findings. | 25,127,324 | [
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The SOX transcription factors as key players in pluripotent stem cells. | Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), and induced PSCs (iPSCs) are able to self-renew and differentiate into a multitude of specialized cellular lineages. In these cells, the pluripotential identity is maintained by a group of transcription factors (TFs). Among these factors, SOX TFs play an essential role, not only in regulating pluripotency but also in mediating self-renewal and differentiation. Some SOX TFs are highly expressed in undifferentiated PSCs, while others are upregulated upon differentiation to promote specific lineage differentiation. Further roles of SOX factors in pluripotency are highlighted through their critical involvement in iPSCs generation. To perform these multiple functions and activities, SOX TFs are strongly associated with a complex regulatory network(s) that involves the binding of SOX factors to variant trans-acting partners to activate or suppress specific genes. Although, SOX2 has attracted special attention as a critical factor in maintaining PSCs characteristics and as an integral component that is required to reprogram somatic cells into pluripotency, new reports widely appreciated that other SOX TFs, such as SOX1, SOX3, or reengineered SOX7 and SOX17, can compensate for the absence of SOX2 and thus play a fundamental role during the reprogramming process and maintaining pluripotency. These findings indicate that the recent progress has greatly expanded our knowledge about the role of SOX factors in PSCs. Thus, in this review we summarize what is currently known about the roles of SOX factors in PSCs and their role in somatic cell reprogramming. Also, we intend to provide an update on their relationship with other factors in regulating the characteristics and early differentiation of PSCs. | 25,127,330 | [
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FS4, FS4-p, and FSP: a 4-month crossover study of 3 fine structure sound-coding strategies. | The aim of the present study was to compare two novel fine structure strategies "FS4" and "FS4-p" with the established fine structure processing (FSP) strategy. FS4 provides fine structure information on the apical four-electrode channels. With FS4-p, these electrodes may be stimulated in a parallel manner. The authors evaluated speech perception, sound quality, and subjective preference. A longitudinal crossover study was done on postlingually deafened adults (N = 33) who were using FSP as their default strategy. Each participant was fitted with FS4, FS4-p, and FSP, for 4 months in a randomized and blinded order. After each run, an Adaptive Sentence test in noise (Oldenburger Sentence Test [OLSA]) and a Monosyllable test in quiet (Freiburger Monosyllables) were performed, and subjective sound quality was determined with a Visual Analogue Scale. At the end of the study the preferred strategy was noted. Scores of the OLSA did not reveal any significant differences among the three strategies, but the Freiburger test showed a statistically significant effect (p = 0.03) with slightly worse scores for FS4 (49.7%) compared with FSP (54.3%). Performance of FS4-p (51.8%) was comparable with the other strategies. Both audiometric tests depicted a high variability among subjects. The number of best-performing strategies for each participant individually was as follows: (a) for the OLSA: FSP, N = 10.5; FS4, N = 10.5; and FS4-p, N = 12; and (b) for the Freiburger test: FSP, N = 14; FS4, N = 9; and FS4-p, N = 10. A moderate agreement was found in the best-performing strategies of the Speech tests within the participants. For sound quality, speech in quiet, classical, and pop music were assessed. No significant effects of strategy were found for speech in quiet and classical music, but auditory impression of pop music was rated as more natural in FSP compared with FS4 (p = 0.04). It is interesting that at the end of the study, a majority of the participants favored the new coding strategies over their previous default FSP (FSP, N = 13; FS4, N = 13; FS4-p, N = 7). In summary, FS4 and FS4-p offer new and further options in audio processor fitting, with similar levels of speech understanding in noise as FSP. This is an interesting result, given that the strategies' presentation of temporal fine structure differs from FSP. At the end of the study, 20 of 33 subjects chose either FS4 or FS4-p over their previous default strategy FSP. | 25,127,325 | [
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Real-time photoacoustic imaging system for burn diagnosis. | We have developed a real-time (8 to 30 fps) photoacoustic (PA) imaging system with a linear-array transducer for burn depth assessment. In this system, PA signals originating from blood in the noninjured tissue layer located under the injured tissue layer are detected and imaged. A compact home-made high-repetition-rate (500 Hz) 532-nm fiber laser was incorporated as a light source. We used an alternating arrangement for the fibers and sensor elements in the probe, which improved the signal-to-noise ratio, reducing the required laser energy power for PA excitation. This arrangement also enabled a hand-held light-weight probe design. A phantom study showed that thin light absorbers embedded in the tissue-mimicking scattering medium at depths >3 mm can be imaged with high contrast. The maximum error for depth measurement was 140 μm. Diagnostic experiments were performed for rat burn models, including superficial dermal burn, deep dermal burn, and deep burn models. Injury depths (zones of stasis) indicated by PA imaging were compared with those estimated by histological analysis, showing discrepancies 200 μm. The system was also used to monitor the healing process of a deep dermal burn. The results demonstrate the potential usefulness of the present system for clinical burn diagnosis. | 25,127,338 | [
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Perfluorochemicals and human semen quality: the LIFE study. | The relation between persistent environmental chemicals and semen quality is evolving, although limited data exist for men recruited from general populations. We examined the relation between perfluorinated chemicals (PFCs) and semen quality among 501 male partners of couples planning pregnancy. Using population-based sampling strategies, we recruited 501 couples discontinuing contraception from two U.S. geographic regions from 2005 through 2009. Baseline interviews and anthropometric assessments were conducted, followed by blood collection for the quantification of seven serum PFCs (perfluorosulfonates, perfluorocarboxylates, and perfluorosulfonamides) using tandem mass spectrometry. Men collected a baseline semen sample and another approximately 1 month later. Semen samples were shipped with freezer packs, and analyses were performed on the day after collection. We used linear regression to estimate the difference in each semen parameter associated with a one unit increase in the natural log-transformed PFC concentration after adjusting for confounders and modeling repeated semen samples. Sensitivity analyses included optimal Box-Cox transformation of semen quality end points. Six PFCs [2-(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), perfluorooctane sulfonamide (PFOSA), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA)] were associated with 17 semen quality end points before Box-Cox transformation. PFOSA was associated with smaller sperm head area and perimeter, a lower percentage of DNA stainability, and a higher percentage of bicephalic and immature sperm. PFDeA, PFNA, PFOA, and PFOS were associated with a lower percentage of sperm with coiled tails. Select PFCs were associated with certain semen end points, with the most significant associations observed for PFOSA but with results in varying directions. | 25,127,343 | [
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Transcriptional landscape of glomerular parietal epithelial cells. | Very little is known about the function of glomerular parietal epithelial cells (PECs). In this study, we performed genome-wide expression analysis on PEC-enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the transcriptional state of PECs under normal conditions. We identified hundreds of differentially expressed genes that mapped to distinct biologic modules including development, tight junction, ion transport, and metabolic processes. Since developmental programs were highly enriched in PECs, we characterized several of their candidate members at the protein level. Collectively, our findings confirm that PECs are multifaceted cells and help define their diverse functional repertoire. | 25,127,402 | [
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Virulence attributes in Brazilian clinical isolates of Pseudomonas aeruginosa. | Pseudomonas aeruginosa is an opportunistic human pathogen responsible for causing a huge variety of acute and chronic infections with significant levels of morbidity and mortality. Its success as a pathogen comes from its genetic/metabolic plasticity, intrinsic/acquired antimicrobial resistance, capacity to form biofilm and expression of numerous virulence factors. Herein, we have analyzed the genetic variability, antimicrobial susceptibility as well as the production of metallo-β-lactamases (MBLs) and virulence attributes (elastase, pyocyanin and biofilm) in 96 strains of P. aeruginosa isolated from different anatomical sites of patients attended at Brazilian hospitals. Our results revealed a great genetic variability, in which 86 distinct RAPD types (89.6% of polymorphisms) were detected. Regarding the susceptibility profile, 48 strains (50%) were resistant to the antimicrobials, as follows: 22.92% to the three tested antibiotics, 12.5% to both imipenem and meropenem, 11.46% to ceftazidime only, 2.08% to imipenem only and 1.04% to both ceftazidime and meropenem. Out of the 34 clinical strains of P. aeruginosa resistant to both imipenem and meropenem, 25 (73.53%) were MBL producers by phenotypic method while 12 (35.29%) were PCR positive for the MBL gene SPM-1. All P. aeruginosa strains produced pyocyanin, elastase and biofilm, although in different levels. Some associations were demonstrated among the susceptibility and/or production of these virulence traits with the anatomical site of strain isolation. For instance, almost all strains isolated from urine (85.71%) were resistant to the three antibiotics, while the vast majority of strains isolated from rectum (95%) and mouth (66.67%) were susceptible to all tested antibiotics. Urine isolates produced the highest pyocyanin concentration (20.15±5.65 μg/ml), while strains isolated from pleural secretion and mouth produced elevated elastase activity (1441.43±303.08 FAU) and biofilm formation (OD590 0.676±0.32), respectively. Also, MBL-positive strains produced robust biofilm compared to MBL-negative strains. Collectively, the production of site-dependent virulence factors can be highlighted as potential therapeutic targets for the treatment of infections caused by heterogeneous and resistant strains of P. aeruginosa. | 25,127,423 | [
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2-Phenylaminonaphthoquinones and related compounds: synthesis, trypanocidal and cytotoxic activities. | A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the synthesized quinones were tested against cancer cells and normal fibroblasts, showing that certain chemical modifications on the naphthoquinone moiety induce and excellent increase the selectivity index of the cytotoxicity (4g and 10). The results presented here show that the anti-T. cruzi activity of 2-aminonaphthoquinones derivatives can be improved by the replacement of the benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed elements that should lead to the discovery of more selective cytotoxic and trypanocidal compounds. | 25,127,463 | [
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Development of highly sensitive electrochemical genosensor based on multiwalled carbon nanotubes-chitosan-bismuth and lead sulfide nanoparticles for the detection of pathogenic Aeromonas. | In this paper, we reported the construction of new high sensitive electrochemical genosensor based on multiwalled carbon nanotubes-chitosan-bismuth complex (MWCNT-Chi-Bi) and lead sulfide nanoparticles for the detection of pathogenic Aeromonas. Lead sulfide nanoparticles capped with 5'-(NH2) oligonucleotides thought amide bond was used as signalizing probe DNA (sz-DNA) and thiol-modified oligonucleotides sequence was used as fixing probe DNA (fDNA). The two probes hybridize with target Aeromonas DNA (tDNA) sequence (fDNA-tDNA-szDNA). The signal of hybridization is detected by differential pulse voltammetry (DPV) after electrodeposition of released lead nanoparticles (PbS) from sz-DNA on the surface of glass carbon electrode decorated with MWCNT-Chi-Bi, which improves the deposition and traducing electrical signal. The optimization of incubation time, hybridization temperature, deposition potential, deposition time and the specificity of the probes were investigated. Our results showed the highest sensibility to detect the target gene when compared with related biosensors and polymerase chain reaction (PCR). The detection limit for this biosensor was 1.0×10(-14) M. We could detect lower than 10(2) CFU mL(-1) of Aeromonas in spiked tap water. This method is rapid and sensitive for the detection of pathogenic bacteria and would become a potential application in biomedical diagnosis, food safety and environmental monitoring. | 25,127,474 | [
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N-acetyl-4-aminophenol (paracetamol) in urine samples of 6-11-year-old Danish school children and their mothers. | Recent studies indicate an association between the use of paracetamol during pregnancy and reproductive disorders in male offspring. Furthermore, N-acetyl-4-aminophenol (NAAP, paracetamol) has been shown to be ubiquitously excreted in urine samples of the general population. To investigate the internal body burden of the Danish population to NAAP for the first time, 288 morning urine samples from 6- to 11-year-old Danish school children and their mothers were analyzed for NAAP. NAAP was measurable in all mothers and all of the children except for one child. Results showed that there is a ubiquitous body burden of NAAP in Danish mothers and children even when paracetamol analgesics have not been used recently. Hence, several unknown sources of NAAP/paracetamol exposure have to exist. We found an association in NAAP excretion between the mothers and their children which could indicate common lifestyle related exposure (e.g. via food or indoor air sources). However, we did not detect any association between lifestyle data from questionnaires and levels of NAAP excretion in this study. The knowledge about possible sources of exposure leading to this omnipresent paracetamol excretion is limited and further investigation is wanted. | 25,127,489 | [
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Analysis of muscle activation patterns during transitions into and out of high knee flexion postures. | Increased risk of medial tibiofemoral osteoarthritis (OA) is linked to occupations that require frequent transitions into and out of postures which require high knee flexion (>90°). Muscle forces are major contributors to joint loading, and an association between compressive forces due to muscle activations and the degeneration of joint cartilage has been suggested. The purpose of this study was to evaluate muscle activation patterns of muscles crossing the knee during transitions into and out of full-flexion kneeling and squatting, sitting in a low chair, and gait. Both net and co-activation were greater when transitioning out of high flexion postures, with maximum activation occurring at knee angles greater than 100°. Compared to gait, co-activation levels during high flexion transitions were up to approximately 3 times greater. Co-activation was significantly greater in the lateral muscle group compared to the medial group during transitions into and out of high flexion postures. These results suggest that compression due to activation of the medial musculature of the knee may not be the link between high knee flexion postures and increased medial knee OA observed in occupational settings. Further research on a larger subject group and workers with varying degrees of knee OA is necessary. | 25,127,491 | [
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Reliability of telemetric electromyography and near-infrared spectroscopy during high-intensity resistance exercise. | This study quantified the inter- and intra-test reliability of telemetric surface electromyography (EMG) and near infrared spectroscopy (NIRS) during resistance exercise. Twelve well-trained young men performed high-intensity back squat exercise (12 sets at 70-90% 1-repetition maximum) on two occasions, during which EMG and NIRS continuously monitored muscle activation and oxygenation of the thigh muscles. Intra-test reliability for EMG and NIRS variables was generally higher than inter-test reliability. EMG median frequency variables were generally more reliable than amplitude-based variables. The reliability of EMG measures was not related to the intensity or number of repetitions performed during the set. No notable differences were evident in the reliability of EMG between different agonist muscles. NIRS-derived measures of oxyhaemoglobin, deoxyhaemoglobin and tissue saturation index were generally more reliable during single-repetition sets than multiple-repetition sets at the same intensity. Tissue saturation index was the most reliable NIRS variable. Although the reliability of the EMG and NIRS measures varied across the exercise protocol, the precise causes of this variability are not yet understood. However, it is likely that biological variation during multi-joint isotonic resistance exercise may account for some of the variation in the observed results. | 25,127,493 | [
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Persistent organic pollutants in liver of Brazilian sharpnose shark (Rhizoprionodon lalandii) from southeastern coast of Brazil. | In the present study, persistent organic pollutants (POPs) were determined in 14 livers from specimens of the Brazilian sharpnose shark (Rhizoprionodon lalandii), which is an important economic resource for small-scale fisheries on the southeastern coast of Brazil. The following concentrations (lipid weight) of POPs were found: ∑PCBs: 1019±267 ng g(-1); ∑DDTs: 111±40 ng g(-1) and ∑PBDEs: 10.4±4.78. PCB 153 made the greatest contribution to ∑PCB (21.4%), followed by PCB 138 (14.6%) and PCB 180 (9.94%). Among chlorinated pesticides, only the p,p'-DDE and p,p'-DDD isomers had concentrations above the detection limit. Moreover, levels above the detection limit were found only for PBDE congeners 47 and 100 (BDEs 47>99). On average, BDE 47 accounted for 88% of the total PBDE load. The feeding habits of the Brazilian sharpnose shark close to the Brazilian coastline are likely the most important difference regarding the accumulation of POPs in comparison to oceanic species that feed in deeper waters. Thus, this species may be used to evaluate the pollution of coastal areas as well as human exposure to contaminants, as the Brazilian sharpnose shark is a frequently used for human consumption. Further studies in other areas of Brazil and involving other species are needed to clarify the mechanisms and potential impact of POPs, which can affect the biology of different organisms and cause population declines. | 25,127,497 | [
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Changes in the concentration and relative abundance of alkanes and PAHs from the Deepwater Horizon oiling of coastal marshes. | We determined changes of 28 alkanes and 43 different PAHs in 418 wetland soil samples collected on ten sampling trips to three Louisiana estuaries before and after they were oiled from the 2010 Deepwater Horizon disaster. There was a significant decline in 22 of the 28 alkane analytes (0.42% day(-1)), no change in 6, over 2.5 years. The concentration of five aromatic petroleum hydrocarbons (PAHs) increased (range 0.25-0.70% day(-1)), whereas the total PAH pool did not change. Of these five, naphthalene and C-1-naphthalenes are suggested to be of higher toxicity than the other three because of their relatively higher volatility or solubility. The relative proportions of alkane analytes, but not PAHs, does not yet resemble that in the pre-oiled marshes after 3 years, The trajectories of nine indicators for degradation/weathering were either inconclusive or misleading (alkanes) or confirmed the relatively meager degradation of PAHs. | 25,127,500 | [
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[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter. | Positron emission tomography (PET) imaging of the norepinephrine transporter (NET) is still hindered by the availability of useful PET imaging probes. The present study describes the radiosynthesis and pre-clinical evaluation of a new compound, exo-3-(6-methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. Labeling of NS8880 with [(11)C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [(11)C]methanolate in a Boc-protected precursor. The isolated [(11)C]NS8880 was evaluated pre-clinically both in a pig model (PET scanning) and in a rat model (μPET scanning) and compared to (S,S)-[(11)C]-O-methylreboxetine ([(11)C]MeNER). The radiolabeling technique yielded [(11)C]NS8880 in low (<10%) but still useful yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [(11)C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [(11)C]NS8880. Based on the pre-clinical results obtained so far [(11)C]NS8880 displays promising properties for PET imaging of NET. | 25,127,515 | [
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Temperature-related mortality in 17 large Chinese cities: how heat and cold affect mortality in China. | Few multicity studies have been conducted to investigate the acute health effects of cold and hot temperatures in China. We aimed to examine the relationship between temperature and daily mortality in 17 large Chinese cities. We first calculated city-specific effect of temperature using time-series regression models combined with distributed lag nonlinear models; then we pooled the city-specific estimates with the Bayesian hierarchical models. The cold effects lasted longer than the hot effects. For the cold effects, a 1 °C decrease from the 25th to 1st percentiles of temperature over lags 0-14 days was associated with increases of 1.69% [95% posterior intervals (PI): 1.01%, 2.36%], 2.49% (95% PI: 1.53%, 3.46%) and 1.60% (95% PI: 0.32%, 2.87%) in total, cardiovascular and respiratory mortality, respectively. For the hot effects, a 1 °C increase from the 75th to 99th percentiles of temperature was associated with corresponding increases of 2.83% (95% PI: 1.42%, 4.24%), 3.02% (95% PI: 1.33%, 4.71%) and 4.64% (95% PI: 1.96%, 7.31%). The latitudes, number of air conditioning per household and disposable income per capita were significant modifiers for cold effects; the proportion of the elderly was a significant modifier for hot effects. This largest epidemiological study of temperature to date in China suggested that both cold and hot temperatures were associated with increased mortality. Our findings may have important implications for the public health policies in China. | 25,127,523 | [
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Nonylphenol in pregnant women and their matching fetuses: placental transfer and potential risks of infants. | As the predominant environmental biodegradation product of nonylphenol (NP) ethoxylates and with proven estrogenic effects, NP is formed during the alkylation process of phenols. The purposes of this study were (1) to examine maternal and prenatal exposure to NP in Taiwan, (2) to determine the level of placental protection against NP exposure as well as the level of NP in breast milk, and (3) to assess the potential risk for breastfed newborns exposed to NP through the milk. Thirty pairs of maternal and fetal blood samples, placenta, and breast milk during the 1st and the 3rd months of lactation were collected. External NP exposures of these specimens were then analyzed by using high-performance liquid chromatography coupling with fluorescence detection. Next, the socio-demographics, lifestyle, delivery method, dietary and work history were collected using a questionnaire. In addition, the daily intake of NP from consuming breast milk in the 1st and 3rd months for newborns was studied through deterministic and probabilistic risk assessment methods. The geometric means and geometric standard deviation of NP levels in maternal blood, fetal cord blood, placenta, and breast milk in the 1st and 3rd months were 14.6 (1.7) ng/ml, 18.8 (1.8) ng/ml, 19.8 (1.9) ng/g, 23.5 (3.2) ng/ml, and 57.3 (1.4) ng/ml, respectively. The probabilistic percentiles (50th, 75th, and 95th) of daily intake NP in breast milk were 4.33, 7.79, and 18.39 μg/kg-bw/day in the 1st month, respectively, and were 8.11, 10.78, 16.08 μg/kg-bw/day in the 3rd month, respectively. The probabilistic distributions (5th, 25th, and 50th) of risk for infants aged 1 month old were 0.27, 0.64, and 1.15, respectively, and that for infants aged 3 month old were 0.31, 0.46, and 0.62, respectively. Through repeated exposure from the dietary intake of expectant mothers, fetuses could encounter a high NP exposure level due to transplacental absorption, partitioning between the maternal and fetal compartments. Daily NP intake via breast milk in three month-old babies exceeded the tolerable daily intake (TDI) of 5 µg/kg bw/day indicated a potential risk for Taiwan infants. | 25,127,525 | [
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Immigrant and refugee health: common infectious diseases. | Immigrants and refugees are at risk of infectious diseases (IDs) that are rare in the United States. Screening and treatment before entry into the United States are required for some of these diseases, whereas quarantine is mandated for others. The Centers for Disease Control and Prevention has published specific recommendations for the evaluation and treatment of immigrants and refugees before and after they arrive in the United States. In addition, immigrants and refugees who return to their home countries are at greater risk of IDs than other travelers. Health care professionals are required to report certain IDs to state or local health departments. | 25,127,537 | [
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Non-covalent conjugation of CdTe QDs with lysozyme binding DNA for fluorescent sensing of lysozyme in complex biological sample. | Water-soluble cysteamine (CA) capped CdTe quantum dots (QDs) conjugated with lysozyme binding DNA (LBD) was constructed for luminescent sensing of lysozyme by forming a ternary self-assembly complex. Addition of negatively charged lysozyme binding DNA to the positively charged CA capped CdTe QDs buffer solution (Tris-HCl pH 7.4) could lead to the formation of QDs-LBD complex through electrostatic interactions. Once lysozyme was introduced into the CdTe QDs-LBD system, it could bind specifically with the QDs-LBD complex, resulting in fluorescence emission enhancement of the QDs due to the surface inert of QDs. At a given amount of LBD and CdTe QDs (LBD: QDs=2: 1), the fluorescence intensity enhancement of QDs was linear with lysozyme concentration over the range of 8.9-71.2 nM, with a detection limit of 4.3 nM. Due to the specific binding of LBD with lysozyme, this approach displayed high selectivity for lysozyme recognition. The sensing mechanism was confirmed by DLS and zeta potential measurement, and agarose gel electrophoresis experiment. Furthermore, the proposed CA-capped CdTe QDs-LBD sensor was applied to lysozyme detection in mouse serum and human morning urine samples, which showed high sensitivity and selectivity in the complex biological sample. | 25,127,568 | [
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An in-needle extraction technique in determination of organic compounds released from dental tissue conditioners incubated in artificial saliva. | The use of an in-needle technique for direct isolation of analytes from real liquid samples is a new proposal. The in-needle technique has been relatively seldom used for direct sampling of liquid matrix through the needle. In this work the in-needle technique has been applied for the determination of compounds evolved to artificial saliva from dental prosthetic materials. It has been shown that results from the experiment with in-needle device were at least comparable with those obtained with using well known solid phase extraction (SPE). It is worth to mention that in-needle extraction offers some advantages: lower consumption of solvent, shorter step-preparation time and reduced costs. The compounds released from prosthetic materials may affect the stability of tissue conditioners and limit their long-term use in the oral cavity. Examined soft dental materials have been found to be stable as minor amount of various species have been emitted from them. Results of the stability tests of soft dental materials with the use of in-needle device on sample preparation step enable their quick evaluation and estimations of their quality. | 25,127,585 | [
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Glucose biosensor based on multisegment nanowires exhibiting reversible magnetic control. | We describe the amperometric detection of glucose using oriented nanowires with magnetic switching of the bioelectrochemical process. The fabrication process of the nanowires was prepared through controlled nucleation and growth during a stepwise electrochemical deposition, and it was characterized using scanning electron microscopy. Cyclic voltammetry and amperometry were used to study the magnetoswitchable property; this control was accomplished by changing the surface orientation of nanowires. Under the optimal condition, the amperometric response was also linear up to a glucose concentration of 0.1-16.0 mmol L(-1) with a sensitivity of 81 μA mM(-1). The detection limit was estimated for 4.8×10(-8) mol L(-1), defined from a signal/noise ratio of 3. It also exhibits good reproducibility and high selectivity with insignificant interference from ascorbic acid, acetoaminophen, and uric acid. The resulting biosensor was applied to detect the blood sugar in human serum samples without any pretreatment, and the results were comparatively in agreement with the clinical assay. | 25,127,595 | [
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Cytochrome P450 2D6 based electrochemical sensor for the determination of codeine. | Considering the enzymatic activity of the cytochrome P450 2D6 on substrates such as codeine, the current paper includes the development of an enzymatic biosensor for detection of this drug. Home-made screen-printed electrodes were used as electrochemical transducers of the biosensor, in which the enzyme was covalently attached to the carbon surface of the working electrode, this type of modification being the most suitable for the immobilization of the biological element. Chronoamperometric measurements were carried out under optimum conditions of pH and working potential, pH 7 and +200 mV vs. screen-printed Ag/AgCl electrode, giving a reduction signal related to the concentration of codeine in solution. Consecutive additions of a solution of codeine were performed to obtain calibration curves in order to validate the electrochemical method in terms of precision and calculate its capability of detection. These biosensors were used for the determination of codeine in urine and commercial pharmaceutical samples. | 25,127,601 | [
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A novel restricted access material combined to molecularly imprinted polymers for selective solid-phase extraction and high performance liquid chromatography determination of 2-methoxyestradiol in plasma samples. | A feasibility study was performed in order to ensure the possibilities in using a restricted access material combined to molecularly imprinted polymers (RAM-MIP) as sorbent material in solid phase extraction (SPE) for clean-up of 2-methoxyestradiol (2-ME) from plasma samples. The MIP with hydrophilic external layer was designed by precipitation polymerization. The polymer was characterized by thermogravimetric analysis (TGA) and scanning electron microscope (SEM). The use of analogs of 2-ME as templates, in combination with a chromatographic separation of the analytes in the sample, overcame the problem of the template bleeding. To demonstrate the property of the RAM-MIP obtained, a comparison of commercially available C18 SPE was performed. The results showed that the RAM-MISPE recoveries were significantly higher than that of C18 SPE for 2-ME in trace concentration. During the extraction process, 2-ME was sufficiently cleaned for further chromatographic analysis with no interferences from template leakage and matrix. Good linearity was obtained from 0.06 to 20 μg mL(-1) with the correlation coefficient r>0.9991. The coefficient of variation of the inter-assay precision was less than 11.9%. The recoveries of 2-ME in rat plasma at three spiked levels were in the range of 99.10-101.00%. Based on the analytical validation results, the proposed method (RAM-MIP off-line SPE/HPLC) can be a useful tool to determine 2-ME in rat plasma samples. | 25,127,620 | [
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Application of neodymium isotope ratio measurements for the origin assessment of uranium ore concentrates. | A novel procedure has been developed for the measurement of (143)Nd/(144)Nd isotope ratio in various uranium-bearing materials, such as uranium ores and ore concentrates (UOC) in order to evaluate the usefulness and applicability of variations of (143)Nd/(144)Nd isotope ratio for provenance assessment in nuclear forensics. Neodymium was separated and pre-concentrated by extraction chromatography and then the isotope ratios were measured by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). The method was validated by the measurement of standard reference materials (La Jolla, JB-2 and BCR-2) and the applicability of the procedure was demonstrated by the analysis of uranium samples of world-wide origin. The investigated samples show distinct (143)Nd/(144)Nd ratio depending on the ore type, deposit age and Sm/Nd ratio. Together with other characteristics of the material in question, the Nd isotope ratio is a promising signature for nuclear forensics and suggests being indicative of the source material, the uranium ore. | 25,127,625 | [
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Assessment of gas chromatography time-of-flight accurate mass spectrometry for identification of volatile and semi-volatile compounds in honey. | The performance of gas chromatography (GC) combined with a hybrid quadrupole time-of-flight (QTOF) mass spectrometry (MS) system for the determination of volatile and semi-volatile compounds in honey samples is evaluated. After headspace (HS) solid-phase microextraction (SPME) of samples, the accurate mass capabilities of the above system were evaluated for compounds identification. Accurate scan electron impact (EI) MS spectra allowed discriminating compounds displaying the same nominal masses, but having different empirical formulae. Moreover, the use of a mass window with a width of 0.005 Da provided highly specific chromatograms for selected ions, avoiding the contribution of interferences to their peak areas. Additional information derived from positive chemical ionization (PCI) MS spectra and ion product scan MS/MS spectra permitted confirming the identity of novel compounds. The above possibilities are illustrated with examples of honey aroma compounds, belonging to different chemical classes and containing different elements in their molecules. Examples of compounds whose structures could not be described are also provided. Overall, 84 compounds, from a total of 89 species, could be identified in 19 honey samples from 3 different geographic areas in the world. The suitability of responses measured for selected ions, corresponding to above species, for authentication purposes is assessed through principal components analysis. | 25,127,626 | [
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High-performance liquid chromatographic and mass spectrometric analysis of fluorescent carbon nanodots. | Amino/hydroxyl-functionalized fluorescent carbon nanodots (C-NanoD) are conveniently synthesized based on hydrothermal carbonization of chitosan at 180°C. Dialysis membranes with small cut-off masses (500-1000 Da) were found useful for removing the side-products and low molecular mass species to purify the C-NanoD product. Herein, reversed-phase high-performance liquid chromatography (RP-HPLC) has been successfully applied to fractionate the C-NanoD product. The elution order of the C-NanoD species present in the sample follows approximately their core sizes from small to large. The separated C-NanoD fractions are collected and characterized by UV absorption spectroscopy, photoluminescence (PL) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and transmission electron microscopy (TEM). All the C-NanoD fractions display a distinctive absorption band at 300 nm, attributing to the n→π* transition of C=O bond. The PL spectra of the fractions display emission peaks at 400-415 nm which are slightly red-shifted with their increase in relative molecular masses. The C-NanoD fractions are fully anatomized by MALDI-TOF MS, displaying their fragmentation mass ion features. The core sizes of some selected C-NanoD are determined as 1.6, 1.8, 2.5, and 3.1 nm by TEM which are in consistent with their HPLC elution order. The findings highlight the virtues of RP-HPLC to fractionate and reveal the unique characteristics of individual C-NanoD species present in an as-synthesized C-NanoD product which may have potential applications in the fields of bioanalysis, bioimaging, catalysis, chemosensing, energy storage, and optoelectronics device. | 25,127,629 | [
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Application of the diffusive gradients in thin films technique for available potassium measurement in agricultural soils: effects of competing cations on potassium uptake by the resin gel. | The utilization of Amberlite (IRP-69 ion-exchange resin, 100-500 wet mesh) as the binding phase in the diffusive gradients in thin films (DGT) technique has shown potential to improve the assessment of plant-available K in soils. The binding phase has recently been optimized by using a mixed Amberlite and ferrihydrite (MAF) gel which results in linear K uptake over extended deployment periods and in solutions with higher K concentrations. As restriction of K uptake by Ca on the Amberlite based resin gel has been previously proposed, potential competing effects of Ca(2+), Mg(2+) and NH(4+) on K uptake by the MAF gel were investigated. These cations had no effect on K elution efficiency which was 85%. However, K uptake by the MAF gel was restricted in the presence of competing cations in solution. Consequently, the diffusion coefficient of K decreased in the presence of cations compared to previous studies but was stable at 1.12×10(-5)cm(2)s(-1) at 25°C regardless of cation concentrations. Uptake of K by the DGT device was affected by the presence of excessive Ca in more than 30% of twenty typical Australian agricultural soils. However, this problem could be circumvented by using a shorter deployment time than the normal 24 h. Moderate correlation of concentrations of K extracted by DGT with Colwell K (extracted by NaHCO(3), R(2)=0.69) and NH4OAc K (R(2)=0.61) indicates that DGT measures a different pool of K in soils than that measured by the standard extractants used. In addition, the MAF gel has the ability to measure Ca and Mg simultaneously. | 25,127,648 | [
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Text recycling: acceptable or misconduct? | Text recycling, also referred to as self-plagiarism, is the reproduction of an author's own text from a previous publication in a new publication. Opinions on the acceptability of this practice vary, with some viewing it as acceptable and efficient, and others as misleading and unacceptable. In light of the lack of consensus, journal editors often have difficulty deciding how to act upon the discovery of text recycling. In response to these difficulties, we have created a set of guidelines for journal editors on how to deal with text recycling. In this editorial, we discuss some of the challenges of developing these guidelines, and how authors can avoid undisclosed text recycling. | 25,127,654 | [
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Plasma and platelet serotonin concentrations in healthy dogs and dogs with myxomatous mitral valve disease. | Serotonin has been implicated in canine myxomatous mitral valve disease (MMVD); however, the sources of serotonin have not been fully elucidated. This study compared the concentration of serotonin in plasma and platelets of normal healthy small breed dogs with predisposition to MMVD and dogs with naturally occurring MMVD. 43 small-breed client-owned dogs with an approximate weight of <10 kg and age of 6 years or above were divided into 2 groups: a healthy control group (n = 20) and a group with echocardiographic evidence of MMVD (n = 23). 5 ml samples of blood were collected. Plasma and platelets were separated by centrifugation and assayed for serotonin measured by enzyme linked immunosorbent assay (ELISA). Median plasma serotonin concentration was not significantly different (p = 0.3630) between normal healthy dogs (3.7 ng/ml) and dogs with MMVD (4.3 ng/ml). Males had higher plasma serotonin concentration than females (4.7 and 2.9 ng/ml respectively, p = 0.0043). Platelet serotonin concentration was not different between healthy dogs and dogs with MMVD (128.6 ng/10⁹ platelets and 176.6 ng/10⁹ platelets respectively, p = 0.4575). Age, echocardiographic indices and platelet count showed no correlation with plasma or platelet serotonin concentration. Circulating plasma serotonin is unlikely a major source of serotonin signaling in canine MMVD. Platelets could be a source of serotonin in canine MMVD through platelet adhesion to the mitral valve; however, the amount of serotonin stored in platelets of healthy dogs and dogs with MMVD is not different. | 25,127,665 | [
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Cardiac vignette: isolated pulmonary regurgitation. | Isolated pulmonary regurgitation (PR) is a rare occurrence with only a handful of documented cases worldwide. Though usually well tolerated in childhood, chronic PR can eventually lead to RV dysfunction and ventricular arrhythmias. In this cardiac vignette, we describe a case of isolated PR in a young female presenting with syncope and explore the natural history, different investigative modalities as well as issues in clinical management of this rare condition. | 25,127,669 | [
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Changes in the loading conditions induced by vagal stimulation modify the myocardial infarct size through sympathetic-parasympathetic interactions. | In a previous research, we described that vagal stimulation increases the infarct size by sympathetic co-activation. The aim of this study was to determine if hemodynamic changes secondary to the vagal stimulation are able to activate sympathetic compensatory neural reflexes, responsible for increasing the infarct size. A second goal was to determine if intermittent vagal stimulation avoids sympathetic activation and reduces infarct size by muscarinic activation of the Akt/glycogen synthase kinase 3 β (GSK-3β) pathway. Rabbits were subjected to 30 min of regional myocardial ischemia and 3 h of reperfusion without vagal stimulation, or the following protocols of right vagus nerve stimulation for 10 min before ischemia: (a) continuous vagal stimulation and (b) intermittent vagal stimulation (cycles of 10 s ON/50 s OFF). Continuous vagal stimulation increased the infarct size (70.7 ± 4.3 %), even after right vagal section (68.6 ± 4.1 %) compared with control group (52.0 ± 3.7 %, p < 0.05). Bilateral vagotomy, pacing, and esmolol abolished the deleterious effect, reaching an infarct size of 43.3 ± 5.1, 43.5 ± 2.1, and 46.0 ± 4.6 % (p < 0.05), respectively. Intermittent stimulation reduced the infarct size to 29.8 ± 3.0 % (p < 0.05 vs I/R). This effect was blocked with atropine (50.2 ± 3.6 %, p < 0.05). Continuous vagal stimulation induced bradycardia and increased the loading conditions and wall stretching of the atria. These changes provoked the co-activation reflex of the sympathetic nervous system, observed by the rise in plasmatic catecholamine levels, which increased the infarct size. Sympathetic co-activation was abolished by continuous vagal stimulation with constant heart rate or parasympathetic deafferentation. Intermittent vagal stimulation attenuated the sympathetic tone and reduced the infarct size by the muscarinic activation of the Akt pathway and GSK-3β inhibition. Continuous stimulation only phosphorylated Akt and GSK-3β when esmolol was administered. | 25,127,674 | [
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Nicotine promotes initiation and progression of KRAS-induced pancreatic cancer via Gata6-dependent dedifferentiation of acinar cells in mice. | Although smoking is a leading risk factor for pancreatic ductal adenocarcinoma (PDAC), little is known about the mechanisms by which smoking promotes initiation or progression of PDAC. We studied the effects of nicotine administration on pancreatic cancer development in Kras(+/LSLG12Vgeo);Elas-tTA/tetO-Cre (Ela-KRAS) mice, Kras(+/LSLG12D);Trp53+/LSLR172H;Pdx-1-Cre (KPC) mice (which express constitutively active forms of KRAS), and C57/B6 mice. Mice were given nicotine for up to 86 weeks to produce blood levels comparable with those of intermediate smokers. Pancreatic tissues were collected and analyzed by immunohistochemistry and reverse transcriptase polymerase chain reaction; cells were isolated and assayed for colony and sphere formation and gene expression. The effects of nicotine were also evaluated in primary pancreatic acinar cells isolated from wild-type, nAChR7a(-/-), Trp53(-/-), and Gata6(-/-);Trp53(-/-) mice. We also analyzed primary PDAC cells that overexpressed GATA6 from lentiviral expression vectors. Administration of nicotine accelerated transformation of pancreatic cells and tumor formation in Ela-KRAS and KPC mice. Nicotine induced dedifferentiation of acinar cells by activating AKT-ERK-MYC signaling; this led to inhibition of Gata6 promoter activity, loss of GATA6 protein, and subsequent loss of acinar differentiation and hyperactivation of oncogenic KRAS. Nicotine also promoted aggressiveness of established tumors as well as the epithelial-mesenchymal transition, increasing numbers of circulating cancer cells and their dissemination to the liver, compared with mice not exposed to nicotine. Nicotine induced pancreatic cells to acquire gene expression patterns and functional characteristics of cancer stem cells. These effects were markedly attenuated in K-Ras(+/LSL-G12D);Trp53(+/LSLR172H);Pdx-1-Cre mice given metformin. Metformin prevented nicotine-induced pancreatic carcinogenesis and tumor growth by up-regulating GATA6 and promoting differentiation toward an acinar cell program. In mice, nicotine promotes pancreatic carcinogenesis and tumor development via down-regulation of Gata6 to induce acinar cell dedifferentiation. | 25,127,677 | [
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Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine. | A large body of evidence suggests that peroxisome proliferator-activated receptor (PPAR) agonists may improve some of the pathological features of Parkinson's disease (PD). In the present study, we evaluated the effects of the PPAR-α agonist fenofibrate (100mg/kg) and PPAR-γ agonist pioglitazone (30mg/kg) in a rat model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (MPTP). Male Wistar rats were pretreated with both drugs for 5 days and received an infusion of MPTP. The experiments were divided into two parts. First, 1, 7, 14, and 21 days after surgery, the animals were submitted to the open field test. On days 21 and 22, the rats were subjected to the forced swim test and two-way active avoidance task. In the second part of the study, 24h after neurotoxin administration, immunohistochemistry was performed to assess tyrosine hydroxylase activity. The levels of dopamine and its metabolites in the striatum were determined using high-performance liquid chromatography, and fluorescence detection was used to assess caspase-3 activation in the substantia nigra pars compacta (SNpc). Both fenofibrate as pioglitazone protected against hypolocomotion, depressive-like behavior, impairment of learning and memory, and dopaminergic neurodegeneration caused by MPTP, with dopaminergic neuron loss of approximately 33%. Fenofibrate and pioglitazone also protected against the increased activation of caspase-3, an effector enzyme of the apoptosis cascade that is considered one of the pathological features of PD. Thus, PPAR agonists may contribute to therapeutic strategies in PD. | 25,127,682 | [
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Centrally-administered oxytocin promotes preference for familiar objects at a short delay in ovariectomized female rats. | Oxytocin has been previously associated with social attachment behaviors in various species, however, most studies focused on partner preference in the socially-monogamous prairie vole. In these, oxytocin treatment was shown to promote partner preference, such that females receiving either central or pulsatile peripheral administration would spend more time with a familiar male. This behavioral outcome was blocked by oxytocin receptor antagonist treatment. The aim of the current study was to further explore the preference-inducing properties of oxytocin by examining its effects on object preference on ovariectomized female rats. In other words, we assessed whether these effects would apply to objects and if they would be persistent across species. Eight rats were infused with oxytocin into the left ventricle and object preference was assessed at two delays: 30min and 4h. At the 30min delay, oxytocin-treated animals showed preference for the familiar object, whereas saline-treated controls exhibited preference for the novel object. At the 4h delay, both groups showed novel-object preference. Our findings show that oxytocin modulates object preference in the female rat at a shorter delay, similar to the findings from partner-preference studies in the prairie vole, suggesting that the mechanisms driving object preference might be in part similar to those responsible for partner preference. | 25,127,685 | [
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Spatial-explicit modeling of social vulnerability to malaria in East Africa. | Despite efforts in eradication and control, malaria remains a global challenge, particularly affecting vulnerable groups. Despite the recession in malaria cases, previously malaria free areas are increasingly confronted with epidemics as a result of changing environmental and socioeconomic conditions. Next to modeling transmission intensities and probabilities, integrated spatial methods targeting the complex interplay of factors that contribute to social vulnerability are required to effectively reduce malaria burden. We propose an integrative method for mapping relative levels of social vulnerability in a spatially explicit manner to support the identification of intervention measures. Based on a literature review, a holistic risk and vulnerability framework has been developed to guide the assessment of social vulnerability to water-related vector-borne diseases (VBDs) in the context of changing environmental and societal conditions. Building on the framework, this paper applies spatially explicit modeling for delineating homogeneous regions of social vulnerability to malaria in eastern Africa, while taking into account expert knowledge for weighting the single vulnerability indicators. To assess the influence of the selected indicators on the final index a local sensitivity analysis is carried out. Results indicate that high levels of malaria vulnerability are concentrated in the highlands, where immunity within the population is currently low. Additionally, regions with a lack of access to education and health services aggravate vulnerability. Lower values can be found in regions with relatively low poverty, low population pressure, low conflict density and reduced contributions from the biological susceptibility domain. Overall, the factors characterizing vulnerability vary spatially in the region. The vulnerability index reveals a high level of robustness in regard to the final choice of input datasets, with the exception of the immunity indicator which has a marked impact on the composite vulnerability index. We introduce a conceptual framework for modeling risk and vulnerability to VBDs. Drawing on the framework we modeled social vulnerability to malaria in the context of global change using a spatially explicit approach. The results provide decision makers with place-specific options for targeting interventions that aim at reducing the burden of the disease amongst the different vulnerable population groups. | 25,127,688 | [
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Surgical outcomes of progressive tractional retinal detachment associated with familial exudative vitreoretinopathy. | To evaluate various surgeries for treating retinal detachment (RD) associated with familial exudative vitreoretinopathy (FEVR). Retrospective, interventional case series. The charts of 22 patients who underwent surgery were reviewed. A complete ophthalmic examination was performed including wide-field fundus images with fluorescein angiography. The primary and secondary outcomes were fundus features (vascular activity of the fibrovascular proliferation and extent of tractional RD) and visual acuity (VA), respectively. Thirty-one eyes were included (12 eyes underwent scleral buckling, 1 scleral buckling and vitrectomy, 7 vitrectomy alone, and 11 lensectomy and vitrectomy). Twenty-six eyes were reattached during 1 surgery. Scleral buckling resulted in cessation of fibrovascular proliferation and retinal reattachment; only 1 of these eyes required vitrectomy. Lens-sparing vitrectomy resulted in stabilized fibrovascular proliferation and retinal reattachment. Vitrectomy with lensectomy did not achieve retinal reattachment in 4 eyes. Fibrovascular proliferation has a rich vascular component in patients younger than 3 years, and collagen fibers were present mainly with more advanced age. The postoperative VA improved in 5 of 8 eyes examined, was unchanged in 1 eye, and decreased in 2 eyes with macular involvement. FEVR-induced RDs are highly variable and require careful preoperative evaluation to determine the best surgical procedure. Vitrectomy with release of posterior traction is essential in younger patients with vascularly active fibrovascular proliferation, whereas scleral buckling may be important for cases with peripheral traction anterior to the equator. In all cases, peripheral thermal treatment applied to all ischemic areas contributed to reduced peripheral neovascularization. | 25,127,701 | [
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Ocular tolerability and efficacy of a cationic emulsion in patients with mild to moderate dry eye disease - a randomised comparative study. | The purpose of this study was to compare the safety and efficacy of a new cationic emulsion (CE) with a formulation of polyvinyl alcohol and povidone (PVA-P) for the treatment of mild to moderate dry eye disease. This was a multicenter, open-label, comparative study. Patients were randomised to receive CE (Cationorm) or PVA-P (Refresh) (1:1). The following objective criteria were assessed to compare the two eye drops: tear Break-up Time (TBUT), Schirmer's test, lissamine green staining (Van Bijsterveld score), corneal fluorescein staining (Oxford scale) and oculopalpebral examination, on D7 and D28 (end of study). At these visits, ocular symptoms and safety were also assessed. Seventy-nine patients were randomised: CE: 44 patients; PVA-P: 35 patients. At D28, improvement was significantly better for TBUT [CE: 1.7 ± 2.4 s; PVA-P: 0.6 ± 1.8 s; P=0.015] and for the Van Bijsterveld score [CE: -1.4 ± 1.2; PVA-P: -0.9 ± 1.2; P=0.046] in the CE group. The same applied for the palpebral erythema score (P=0.023), overall efficacy assessed by the investigators (P<0.001), and symptoms not related to eye drop instillation (P=0.021). Improvement was observed from D7. No difference was observed between the two treatments with regard to ocular safety. These results suggest that in patients with mild to moderate dry eye, Cationorm, in addition to its moisturizing and lubricating properties, also helps stabilize the tear film due to its oily component. This study demonstrates the benefit of this new pharmaceutical form for the treatment of mild to moderate dry eye disease. | 25,127,703 | [
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Insulin-like growth factor binding protein 5 (IGFBP5) mediates methamphetamine-induced dopaminergic neuron apoptosis. | Overexposure to methamphetamine (METH), a psychoactive drug, induces a variety of adverse effects to the nervous system, including apoptosis of dopaminergic neurons. Insulin-like growth factor binding protein 5 (IGFBP5), a member of insulin-like growth factor (IGF) system, is a pro-apoptotic factor that plays important roles in neuronal apoptosis. To test the hypothesis that IGFBP5 can mediate METH-induced neuronal apoptosis, we examined IGFBP5 mRNA and protein expression changes in PC12 cells exposed to METH (3.0mM) for 24h and in the striatum of rats following 15 mg/kg × 8 intraperitoneal injections of METH at 12h interval. We also checked the effect on neuronal apoptosis after silencing IGFBP5 expression with TUNEL staining and flow cytometry; Western blot was used for detecting the expression of apoptotic markers active-caspase3 and PARP. To elucidate the mechanisms underlying IGFBP5-mediated neuronal apoptosis, we determined the release of cytochrome c (cyto c), an apoptogenic factor, from the mitochondria after METH treatment with or without IGFBP5 knockdown. Our results showed that IGFBP5 expression was increased significantly after METH exposure in PC12 cells and in the METH-treated rats' striatum. Further, METH-exposed PC12 cells exhibited higher apoptosis-positive cell number and activity of caspase3 and PARP compared with control cells, while these changes can be blocked by silencing IGFBP5 expression. In addition, a significant increase of cyto c release from mitochondria after METH exposure was observed and it was inhibited after silencing IGFBP5 expression in PC12 cells. These results indicate that IGFBP5 plays key roles in METH-induced neuronal apoptosis and may be a potential gene target for therapeutics in METH-caused neurotoxicity. | 25,127,757 | [
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Differences in the transduction of canonical Wnt signals demarcate effector and memory CD8 T cells with distinct recall proliferation capacity. | Protection against reinfection is mediated by Ag-specific memory CD8 T cells, which display stem cell-like function. Because canonical Wnt (Wingless/Int1) signals critically regulate renewal versus differentiation of adult stem cells, we evaluated Wnt signal transduction in CD8 T cells during an immune response to acute infection with lymphocytic choriomeningitis virus. Whereas naive CD8 T cells efficiently transduced Wnt signals, at the peak of the primary response to infection only a fraction of effector T cells retained signal transduction and the majority displayed strongly reduced Wnt activity. Reduced Wnt signaling was in part due to the downregulation of Tcf-1, one of the nuclear effectors of the pathway, and coincided with progress toward terminal differentiation. However, the correlation between low and high Wnt levels with short-lived and memory precursor effector cells, respectively, was incomplete. Adoptive transfer studies showed that low and high Wnt signaling did not influence cell survival but that Wnt high effectors yielded memory cells with enhanced proliferative potential and stronger protective capacity. Likewise, following adoptive transfer and rechallenge, memory cells with high Wnt levels displayed increased recall expansion, compared with memory cells with low Wnt signaling, which were preferentially effector-like memory cells, including tissue-resident memory cells. Thus, canonical Wnt signaling identifies CD8 T cells with enhanced proliferative potential in part independent of commonly used cell surface markers to discriminate effector and memory T cell subpopulations. Interventions that maintain Wnt signaling may thus improve the formation of functional CD8 T cell memory during vaccination. | 25,127,860 | [
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Concomitant TLR/RLH signaling of radioresistant and radiosensitive cells is essential for protection against vesicular stomatitis virus infection. | Several studies indicated that TLR as well as retinoic acid-inducible gene I-like helicase (RLH) signaling contribute to vesicular stomatitis virus (VSV)-mediated triggering of type I IFN (IFN-I) responses. Nevertheless, TLR-deficient MyD88(-/-)Trif(-/-) mice and RLH-deficient caspase activation and recruitment domain adaptor inducing IFN-β (Cardif)(-/-) mice showed only marginally enhanced susceptibility to lethal VSV i.v. infection. Therefore, we addressed whether concomitant TLR and RLH signaling, or some other additional mechanism, played a role. To this end, we generated MyD88(-/-)Trif(-/-)Cardif(-/-) (MyTrCa(-/-)) mice that succumbed to low-dose i.v. VSV infection with similar kinetics as IFN-I receptor-deficient mice. Three independent approaches (i.e., analysis of IFN-α/β serum levels, experiments with IFN-β reporter mice, and investigation of local IFN-stimulated gene induction) revealed that MyTrCa(-/-) mice did not mount IFN-I responses following VSV infection. Of note, treatment with rIFN-α protected the animals, qualifying MyTrCa(-/-) mice as a model to study the contribution of different immune cell subsets to the production of antiviral IFN-I. Upon adoptive transfer of wild-type plasmacytoid dendritic cells and subsequent VSV infection, MyTrCa(-/-) mice displayed significantly reduced viral loads in peripheral organs and showed prolonged survival. On the contrary, adoptive transfer of wild-type myeloid dendritic cells did not have such effects. Analysis of bone marrow chimeric mice revealed that TLR and RLH signaling of radioresistant and radiosensitive cells was required for efficient protection. Thus, upon VSV infection, plasmacytoid dendritic cell-derived IFN-I primarily protects peripheral organs, whereas concomitant TLR and RLH signaling of radioresistant stroma cells as well as of radiosensitive immune cells is needed to effectively protect against lethal disease. | 25,127,863 | [
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D-beta-hydroxybutyrate extends lifespan in C. elegans. | The ketone body beta-hydroxybutyrate (βHB) is a histone deacetylase (HDAC) inhibitor and has been shown to be protective in many disease models, but its effects on aging are not well studied. Therefore we determined the effect of βHB supplementation on the lifespan ofC. elegans nematodes. βHB supplementation extended mean lifespan by approximately 20%. RNAi knockdown of HDACs hda-2 or hda-3 also increased lifespan and further prevented βHB-mediated lifespan extension. βHB-mediated lifespan extension required the DAF-16/FOXO and SKN-1/Nrf longevity pathways, the sirtuin SIR-2.1, and the AMP kinase subunit AAK-2. βHB did not extend lifespan in a genetic model of dietary restriction indicating that βHB is likely functioning through a similar mechanism. βHB addition also upregulated ΒHB dehydrogenase activity and increased oxygen consumption in the worms. RNAi knockdown of F55E10.6, a short chain dehydrogenase and SKN-1 target gene, prevented the increased lifespan and βHB dehydrogenase activity induced by βHB addition, suggesting that F55E10.6 functions as an inducible βHB dehydrogenase. Furthermore, βHB supplementation increased worm thermotolerance and partially prevented glucose toxicity. It also delayed Alzheimer's amyloid-beta toxicity and decreased Parkinson's alpha-synuclein aggregation. The results indicate that D-βHB extends lifespan through inhibiting HDACs and through the activation of conserved stress response pathways. | 25,127,866 | [
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A novel sonochemical synthesis of antlerite nanorods. | Antlerite - Cu3(OH)4SO4 was prepared, for the first time, by the sonochemical method from an aqueous solution of CuSO4, without any additives. The source of OH(-) is a result of protonation of SO4(2-) forming HSO4(-) and OH(-). The extreme local conditions inside the cavity that are developed during the bubble collapse (pressure is above 1000atm and the temperature is higher than 5000K) lead to the formation of the crystalline mineral. A suggested mechanism for the mineral formation is proposed. Due to the collapse of the bubbles, the distances between the opposite charge Cu(2+) and SO4(2-) ions is shortened and a crystallization process is initiated. In addition, the reaction is a one-step process with short irradiation time of less than 30min. The chemo-physical analysis of the sonochemically obtained product has revealed the presence of single phase antlerite nanorods. | 25,127,893 | [
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The diagnosis of febrile urinary tract infection in children may be facilitated by urinary biomarkers. | We prospectively assessed the feasibility of two urinary markers of renal injury as potential diagnostic tests for acute febrile urinary tract infection (UTI) and subsequent renal scarring. The patient cohort comprised children aged 0 to 4 years who visited the emergency room. The children were divided into three groups, namely, a febrile UTI (fUTI), febrile control (FC) and a non-febrile control (NFC) group, respectively, which were matched for sex and age. An enzyme-linked immunosorbent assay for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) was performed on urine collected from each child. The urine levels of both markers were compared between the three groups, and the diagnostic accuracy was determined based on the area under the receiver-operator characteristic curve (AUC). In the fUTI group, the predictability of subsequent renal scarring was assessed by associating urinary levels with dimercaptosuccinic acid findings 6 months after an UTI episode. Significantly elevated levels of urinary NGAL and KIM-1 were observed in the fUTI group, as well as with increased urine esterase, serum C-reactive protein, and pyuria. The AUC was 72 % for KIM-1 and 96 % for NGAL. The AUC of KIM-1 for the prediction of scarring was 71 % (p < 0.05). The diagnosis of febrile UTI and the prediction of subsequent scarring may be facilitated by assaying urine biomarkers with acceptable accuracy. | 25,127,917 | [
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Indicators of pulmonary exacerbation in cystic fibrosis: A Delphi survey of patients and health professionals. | There is uncertainty about the most important indicators of pulmonary exacerbations in CF. Two parallel Delphi surveys in 13 CF centres (UK and Ireland). Delphi 1: 31 adults with CF, ≥ one exacerbation over 12 months. Delphi 2: 38 CF health professionals. Rounds 1 and 2 participants rated their level of agreement with statements relating to indicators of exacerbation; Round 3 participants rated the importance of statements which were subsequently placed in rank order. Objective measurements were of higher importance to health professionals. Feelings of increased debility were rated most important by adults with CF. There were clear differences in perspectives between the two groups as to the most important indicators of an exacerbation. This highlights that CF health professionals should take more cognisance of specific signs and symptoms reported by adults with CF, especially since these may be a precursor to an exacerbation. | 25,127,921 | [
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Sterol carrier protein 2 regulates proximal tubule size in the Xenopus pronephric kidney by modulating lipid rafts. | The kidney is a homeostatic organ required for waste excretion and reabsorption of water, salts and other macromolecules. To this end, a complex series of developmental steps ensures the formation of a correctly patterned and properly proportioned organ. While previous studies have mainly focused on the individual signaling pathways, the formation of higher order receptor complexes in lipid rafts is an equally important aspect. These membrane platforms are characterized by differences in local lipid and protein compositions. Indeed, the cells in the Xenopus pronephric kidney were positive for the lipid raft markers ganglioside GM1 and Caveolin-1. To specifically interfere with lipid raft function in vivo, we focused on the Sterol Carrier Protein 2 (scp2), a multifunctional protein that is an important player in remodeling lipid raft composition. In Xenopus, scp2 mRNA was strongly expressed in differentiated epithelial structures of the pronephric kidney. Knockdown of scp2 did not interfere with the patterning of the kidney along its proximo-distal axis, but dramatically decreased the size of the kidney, in particular the proximal tubules. This phenotype was accompanied by a reduction of lipid rafts, but was independent of the peroxisomal or transcriptional activities of scp2. Finally, disrupting lipid micro-domains by inhibiting cholesterol synthesis using Mevinolin phenocopied the defects seen in scp2 morphants. Together these data underscore the importance for localized signaling platforms in the proper formation of the Xenopus kidney. | 25,127,994 | [
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Urine YKL-40 is associated with progressive acute kidney injury or death in hospitalized patients. | A translational study in renal transplantation suggested YKL-40, a chitinase 3-like-1 gene product, plays an important role in acute kidney injury (AKI) and repair, but data are lacking about this protein in urine from native human kidneys. This is an ancillary study to a single-center, prospective observational cohort of patients with clinically-defined AKI according to AKI Network serum creatinine criteria. We determined the association of YKL -40 ≥ 5 ng/ml, alone or combined with neutrophil gelatinase-associated lipocalin (NGAL), in urine collected on the first day of AKI with a clinically important composite outcome (progression to higher AKI stage and/or in-hospital death). YKL-40 was detectable in all 249 patients, but urinary concentrations were considerably lower than in previously measured deceased-donor kidney transplant recipients. Seventy-two patients (29%) progressed or died in-hospital, and YKL-40 ≥ 5 ng/ml had an adjusted odds ratio (95% confidence interval) for the outcome of 3.4 (1.5-7.7). The addition of YKL-40 to a clinical model for predicting the outcome resulted in a continuous net reclassification improvement of 29% (P = 0.04). In patients at high risk for the outcome based on NGAL concentrations in the upper quartile, YKL-40 further partitioned the cohort into moderate-risk and very high-risk groups. Urine YKL-40 is associated with AKI progression and/or death in hospitalized patients and improves clinically determined risk reclassification. Combining YKL-40 with other AKI biomarkers like NGAL may further delineate progression risk, though additional studies are needed to determine whether YKL-40 has general applicability and to define its association with longer-term outcomes in AKI. | 25,128,003 | [
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[Sudden cardiac death in individuals with normal hearts: an update]. | Sudden death (SD) is a tragic event and a world-wide health problem. Every year, near 4-5 million people experience SD. SD is defined as the death occurred in 1h after the onset of symptoms in a person without previous signs of fatality. It can be named "recovered SD" when the case received medical attention, cardiac reanimation effective defibrillation or both, surviving the fatal arrhythmia. Cardiac channelopathies are a group of diseases characterized by abnormal ion channel function due to genetic mutations in ion channel genes, providing increased susceptibility to develop cardiac arrhythmias and SD. Usually the death occurs before 40 years of age and in the autopsy the heart is normal. In this review we discuss the main cardiac channelopathies involved in sudden cardiac death along with current management of cases and family members that have experienced such tragic event. | 25,128,006 | [
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A cross-sectional retrospective analysis of the regionalization of complex surgery. | The Veterans Health Administration (VHA) system has assigned a surgical complexity level to each of its medical centers by specifying requirements to perform standard, intermediate or complex surgical procedures. No study to similarly describe the patterns of relative surgical complexity among a population of United States (U.S) civilian hospitals has been completed. single year, retrospective, cross-sectional. the study used Florida Inpatient Discharge Data from short-term acute hospitals for calendar year 2009. Two hundred hospitals with 2,542,920 discharges were organized into four quartiles (Q 1, 2, 3, 4) based on the number of complex procedures per hospital. The VHA surgical complexity matrix was applied to assign relative complexity to each procedure. The Clinical Classification Software (CCS) system assigned complex procedures to clinically meaningful groups. For outcome comparisons, propensity score matching methods adjusted for the surgical procedure, age, gender, race, comorbidities, mechanical ventilator use and type of admission. in-hospital mortality and length-of-stay (LOS). Only 5.2% of all inpatient discharges involve a complex procedure. The highest volume complex procedure hospitals (Q4) have 49.8% of all discharges but 70.1% of all complex procedures. In the 133,436 discharges with a primary complex procedure, 374 separate specific procedures are identified, only about one third of which are performed in the lowest volume complex procedure (Q1) hospitals. Complex operations of the digestive, respiratory, integumentary and musculoskeletal systems are the least concentrated and proportionately more likely to occur in the lower volume hospitals. Operations of the cardiovascular system and certain technology dependent miscellaneous diagnostic and therapeutic procedures are the most concentrated in high volume hospitals. Organ transplants are only done in Q4 hospitals. There were no significant differences in in-hospital mortality rates and the longest lengths of stay were found in higher volume hospitals. Complex surgery in Florida is effectively regionalized so that small volume hospitals operating within the range of complex procedures appropriate to their capabilities provide no increased risk of post surgical mortality. | 25,128,011 | [
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Cost-effectiveness models for chronic obstructive pulmonary disease: cross-model comparison of hypothetical treatment scenarios. | To compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios. COPD modeling groups simulated four hypothetical interventions with their model and compared the results with a reference scenario of no intervention. The four interventions modeled assumed 1) 20% reduction in decline in lung function, 2) 25% reduction in exacerbation frequency, 3) 10% reduction in all-cause mortality, and 4) all these effects combined. The interventions were simulated for a 5-year and lifetime horizon with standardization, if possible, for sex, age, COPD severity, smoking status, exacerbation frequencies, mortality due to other causes, utilities, costs, and discount rates. Furthermore, uncertainty around the outcomes of intervention four was compared. Seven out of nine contacted COPD modeling groups agreed to participate. The 5-year incremental cost-effectiveness ratios (ICERs) for the most comprehensive intervention, intervention four, was €17,000/quality-adjusted life-year (QALY) for two models, €25,000 to €28,000/QALY for three models, and €47,000/QALY for the remaining two models. Differences in the ICERs could mainly be explained by differences in input values for disease progression, exacerbation-related mortality, and all-cause mortality, with high input values resulting in low ICERs and vice versa. Lifetime results were mainly affected by the input values for mortality. The probability of intervention four to be cost-effective at a willingness-to-pay value of €50,000/QALY was 90% to 100% for five models and about 70% and 50% for the other two models, respectively. Mortality was the most important factor determining the differences in cost-effectiveness outcomes between models. | 25,128,045 | [
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An updated method for risk adjustment in outcomes research. | To demonstrate why meta-analytic methods need modification before they can be used to aggregate rates or effect sizes in outcomes research, under the constraint of no common underlying effect or rate. Studies are presented that require different types of risk adjustment. First, we demonstrate using rates that external risk adjustment through standardization can be achieved using modified meta-analytic methods, but only with a model that allows input of user-defined weights. Next, we extend these observations to internal risk adjustment of comparative effect sizes. We show that this procedure produces identical results to conventional age standardization if a rate is being standardized for age. We also demonstrate that risk adjustment of effect sizes can be achieved with this modified method but cannot be done using standard meta-analysis. We conclude that this method allows risk adjustment to be performed in situations in which currently the fixed- or random-effects methods of meta-analysis are inappropriately used. The latter should be avoided when the underlying aim is risk adjustment rather than meta-analysis. | 25,128,057 | [
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Increased cardiovascular disease mortality associated with excessive exercise in heart attack survivors. | To test whether greater exercise is associated with progressively lower mortality after a cardiac event. We used Cox proportional hazard analyses to examine mortality vs estimated energy expended by running or walking measured as metabolic equivalents (3.5 mL O2/kg per min per day or metabolic equivalent of task-h/d [MET-h/d]) in 2377 self-identified heart attack survivors, where 1 MET-h/d is the energy equivalent of running 1 km/d. Mortality surveillance via the National Death Index included January 1991 through December 2008. A total of 526 deaths occurred during an average prospective follow-up of 10.4 years, 376 (71.5%) of which were related to cardiovascular disease (CVD) (International Statistical Classification of Diseases, 10th Revision codes I00-I99). CVD-related mortality compared with the lowest exercise group decreased by 21% for 1.07 to 1.8 MET-h/d of running or walking (P=.11), 24% for 1.8 to 3.6 MET-h/d (P=.04), 50% for 3.6 to 5.4 MET-h/d (P=.001), and 63% for 5.4 to 7.2 MET-h/d (P<.001) but decreased only 12% for ≥7.2 MET-h/d (P=.68). These data represent a 15% average risk reduction per MET-h/d for CVD-related mortality through 7.2 MET-h/d (P<.001) and a 2.6-fold risk increase above 7.2 MET-h/d (P=.009). Relative to the risk reduction at 7.2 MET-h/d, the risk for ≥7.2 MET-h/d increased 3.2-fold (P=.006) for all ischemic heart disease (IHD)-related mortalities but was not significantly increased for non-IHD-CVD, arrhythmia-related CVD, or non-CVD-related mortalities. Running or walking decreases CVD mortality risk progressively at most levels of exercise in patients after a cardiac event, but the benefit of exercise on CVD mortality and IHD deaths is attenuated at the highest levels of exercise (running: above 7.1 km/d or walking briskly: 10.7 km/d). | 25,128,072 | [
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Coexistence of neurofibroma and meningioma at exactly the same level of the cervical spine. | We report a case of the coexistence of different spinal tumors at the same level of the cervical spine, without neurofibromatosis (NF), which was successfully treated with surgery. A 72-year-old female presented with right upper-limb clumsiness and weakness. Magnetic resonance imaging revealed an intradural, extramedullary tumor mass at the right C3-4 level with extradural extension into the intervertebral foramen. The extradural tumor was removed, and the pathology showed neurofibroma. After incision of the dura, the intradural tumor was removed, and was identified as meningioma in the pathological report. The patient did not meet the criteria of NF. Coexistence of neurofibroma and meningioma at exactly the same level of the spine without NF is extremely rare. Exploration of the intradural space may be necessary after resection of an extradural tumor if the surgical finding does not correlate well with the preoperative images. | 25,128,077 | [
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Dentin-smear remains at self-etch adhesive interface. | The bonding potential of 'mild' self-etch adhesives may be compromised due to smear interference, as they may not dissolve/penetrate the smear layer effectively due to their relatively low acidity. We observed that the thickness of the dentin smear layer differed depending on the surface-preparation methodology used. The interaction of an (ultra-)mild self-etch adhesive (Clearfil S3 Bond, Kuraray Noritake) with human dentin, prepared either using a medium-grit diamond bur ('thick', clinically relevant smear layer) or 600-grit SiC-paper ('thin' smear layer), or just fractured (smear-free), was evaluated using high-resolution transmission electron microscopy (TEM). Non-demineralized/demineralized 30-100nm interfacial cross-sections were prepared following common TEM-specimen processing and diamond-knife ultra-microtomy. The adhesive did not dissolve the bur-cut, nor the SiC-ground smear layer, but impregnated it. Within this 'resin-smear complex', hydroxyapatite was abundantly present. At fractured dentin, this complex was not present, while the actual layer of interaction of the adhesive was limited to about 100nm. Non-demineralized 'ultra-thin' (30-50nm) sections confirmed the interfacial ultra-structure to differ for the three surface-preparation methods. An electron dense band was consistently disclosed at the adhesive interface, most likely representing the documented chemical interaction of the functional monomer 10-MDP with Ca. The dentin surface-preparation method significantly affects the nature of the smear layer and the interaction with the ultra-mild self-etch adhesive. | 25,128,080 | [
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Stents in paediatric and adult congenital interventional cardiac catheterization. | A 'stent' is a tubular meshed endoprosthesis that has contributed to the development of interventional catheterization over the past 30 years. In congenital heart diseases, stents have offered new solutions to the treatment of congenital vessel stenosis or postsurgical lesions, to maintain or close shunt patency, and to allow transcatheter valve replacement. First, stents were made of bare metal. Then, stent frameworks evolved to achieve a better compromise between radial strength and flexibility. However, almost all stents used currently in children have not been approved for vascular lesions in children and are therefore used 'off-label'. Furthermore, the inability of stents to follow natural vessel growth still limits their use in low-weight children and infants. Recently, bioresorbable stents have been manufactured and may overcome this issue; they are made from materials that may dissolve or be absorbed in the body. In this review, we aim to describe the history of stent development, the technical characteristics of stents used currently, the clinical applications and results, and the latest technological developments and perspectives in paediatric and adult congenital cardiac catheterization. | 25,128,078 | [
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SENP5, a SUMO isopeptidase, induces apoptosis and cardiomyopathy. | Cardiomyopathy presents a major health issue and is a leading cause of heart failure. Although a subset of familial cardiomyopathy is associated with genetic mutations, over 50% of cardiomyopathy is defined as idiopathic, the mechanisms underlying which are under intensive investigation. SUMO conjugation is a dynamic posttranslational modification that can be readily reversed by the activity of sentrin-specific proteases (SENPs). However, whether SENPs are implicated in heart disease pathophysiology remains unexplored. We observed a significant increase in the level of SENP5, a SUMO isopeptidase, in human idiopathic failing hearts. To reveal whether it plays a role in the pathogenesis of cardiac muscle disorders, we used a gain-of-function approach to overexpress SENP5 in murine cardiomyocytes (SENP5 transgenic, SENP5-Tg). Overexpression of SENP5 led to cardiac dysfunction, accompanied by decreased cardiomyocyte proliferation and elevated apoptosis. The increase in apoptosis preceded other detectable pathological changes, suggesting its causal link to cardiomyopathy. Further examination of SENP5-Tg hearts unveiled a decrease in SUMO attachment to dynamin related protein (Drp1), a factor critical for mitochondrial fission. Correspondingly, the mitochondria of SENP5-Tg hearts at an early developmental stage were significantly larger compared with those in the control hearts, suggesting that desumoylation of Drp1 at least partially accounts for the cardiac phenotypes observed in the SENP5-Tg mice. Finally, overexpression of Bcl2 in SENP5-Tg hearts improved cardiac function of SENP5-Tg mice, further supporting the notion that SENP5 mainly targets mitochondrial function in vivo. Our findings demonstrate an important role of the desumoylation enzyme SENP5 in the development of cardiac muscle disorders, and point to the SUMO conjugation pathway as a potential target in the prevention/treatment of cardiomyopathy. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". | 25,128,087 | [
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Effects of chronic administration of arachidonic acid on lipid profiles and morphology in the skeletal muscles of aged rats. | Arachidonic acid (20:4n-6, ARA) is a major component of the cell membrane, whereas ARA-derived eicosanoids are formed when cells are damaged. Aging is associated with an accretion of oxidative stress in skeletal muscles. In this study, we examined the effects of chronic administration (13 weeks) of ARA (240 mg/kg/day) on fatty acid composition, antioxidative status, and morphology of slow (soleus muscles) and fast (extensor digitorum longus muscles; EDL)-twitch muscles in aged rats (21 months old). The level of reactive oxygen species was higher in the EDL of ARA-administered rats than in that of control rats. ARA administration decreased the muscle cell volumes and increased the number of slow myosin heavy chain (MHC)-positive cells in the EDL. The relative content of MHC2X was increased whereas the relative content of MHC2B was decreased in the EDL of ARA-administered rats. These results suggest that ARA deposition in the fast-twitch muscle of aged rats reduced cell volume with an increase in oxidative stress. | 25,128,088 | [
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Cosmetic fat augmentation following breast reconstruction: sonographic appearance with cytopathologic correlation. | This series presents the history and imaging of patients who had cosmetic fat augmentation following mastectomy and reconstruction. The cases provide the useful reminder that a complete surgical history is essential when assessing the imaging of a post-operative breast patient and that speaking directly with patients can be a critical step in putting together a complete clinical picture and adding value to their care. | 25,128,090 | [
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Identification, characterization, immobilization of a novel type hydrolase (LmH) from Listeria monocytogenes. | A novel type of hydrolase (LmH) from Listeria monocytogenes was identified, characterized, and immobilized for biotechnological applications. Primary sequence analysis indicated that LmH had a catalytic triad (Ser(91)-Asp(192)-His(222)) with a molecular weight of 27.8 kDa. Homologs of this enzyme are produced by many Gram-positive bacteria including Bacillus, Staphylococcus, and Enterococcus. Biochemical properties of LmH were investigated by performing mass spectrometry, dynamic light scattering (DLS), enzyme assays, enantioselective analysis, circular dichroism (CD) spectroscopy, fluorescence analysis, and macroscopic hydrogel formations. Interestingly, cross-linked enzyme aggregates (CLEAs) of LmH exhibited enhanced stability and good recycling abilities compared to free LmH. These molecular characteristics of LmH highlight its great potential for the pharmaceutical, biotechnological, and chemical industries. | 25,128,099 | [
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Clinimetric properties of the Tinetti Mobility Test, Four Square Step Test, Activities-specific Balance Confidence Scale, and spatiotemporal gait measures in individuals with Huntington's disease. | Individuals with Huntington's disease (HD) experience balance and gait problems that lead to falls. Clinicians currently have very little information about the reliability and validity of outcome measures to determine the efficacy of interventions that aim to reduce balance and gait impairments in HD. This study examined the reliability and concurrent validity of spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step Test (FSST), and Activities-specific Balance Confidence (ABC) Scale in individuals with HD. Participants with HD [n = 20; mean age ± SD=50.9 ± 13.7; 7 male] were tested on spatiotemporal gait measures and the TMT, FSST, and ABC Scale before and after a six week period to determine test-retest reliability and minimal detectable change (MDC) values. Linear relationships between gait and clinical measures were estimated using Pearson's correlation coefficients. Spatiotemporal gait measures, the TMT total and the FSST showed good to excellent test-retest reliability (ICC > 0.75). MDC values were 0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively, four points for the TMT, and 3s for the FSST. The TMT and FSST were highly correlated with most spatiotemporal measures. The ABC Scale demonstrated lower reliability and less concurrent validity than other measures. The high test-retest reliability over a six week period and concurrent validity between the TMT, FSST, and spatiotemporal gait measures suggest that the TMT and FSST may be useful outcome measures for future intervention studies in ambulatory individuals with HD. | 25,128,156 | [
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Aldosterone augments Na+-induced reduction of cardiac norepinephrine reuptake. | Impairment of the cardiac norepinephrine (NE) reuptake by the neuronal NE transporter contributes to enhanced cardiac NE net release in congestive heart failure. Elevated plasma levels of aldosterone (AL) promote sympathetic overstimulation in failing hearts by unclear mechanisms. Our aim was to evaluate if elevated AL and/or alterations in Na(+) intake regulate cardiac NE reuptake. To test the effects of AL and Na(+) on cardiac NE reuptake, Wistar rats were fed a normal-salt (NS) diet (0.2% NaCl), a low-salt (LS) diet (0.015% NaCl), or a high-salt (HS) diet (8% NaCl). Another group of animals received AL infusion alone (0.75 μg/h) or AL infusion plus HS diet. Specific cardiac [(3)H]NE uptake via the NE transporter in a Langendorff preparation and AL plasma levels were measured at different time points between 5 and 42 days of treatment. To compare these findings from healthy animals with a disease model, Dahl salt-sensitive rats were investigated as a model of congestive heart failure with endogenously elevated AL. In summary, neither exogenous nor endogenous elevations of AL alone were sufficient to reduce cardiac NE reuptake. Only the HS diet induced a reduction of NE reuptake by 26%; additional infusion of AL augmented this effect to a further reduction of NE reuptake by 36%. In concordance, Dahl salt-sensitive rats treated with a HS diet displayed elevated AL and a marked reduction of NE reuptake. We conclude that exogenous or endogenous AL elevations alone do not reduce cardiac NE reuptake, but AL serves as an additional factor that negatively regulates cardiac NE reuptake in concert with HS intake. | 25,128,164 | [
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Rare embryonal rhabdomyosarcoma of external acoustic canal: a case report and literature review. | Embryonal rhabdomyosarcoma of external ear canal is very rare, even in the pediatric population. We report an embryonal rhabdomyosarcoma of external acoustic canal, occurring in a 12-year-old Chinese girl who presented with left ear canal mass. Wide local excision of the mass was done under local anesthesia. Histopathological examination revealed the diagnosis. She then underwent 20 cycles of radiotherapy. CECT scan post treatment showed clearance of tumor cell. Now, patient is disease free for 5 years. We believe that early diagnosis followed by complete resection of the tumor with clear margin and radiotherapy improves the prognosis of the disease. | 25,128,187 | [
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Receiver operating characteristic curve analysis to determine the diagnostic performance of serum haptoglobin concentration for the diagnosis of acute puerperal metritis in dairy cows. | Acute puerperal metritis (APM) in dairy cows is characterized by fever and fetid vaginal discharge within 21 days in milk (DIM). Increased serum haptoglobin concentration (Hp) can support the diagnosis of APM. However, there is a dearth of information of the test performance of Hp as a measure for APM with a consistent definition and considering parity. The objective of this trial was to study the test performance of Hp to distinguish healthy cows from cows with APM. A total of 33 of 60 (55.0%) primiparous cows and 43 of 133 (32.3%) multiparous cows developed APM. Primiparous cows with APM had the greatest Hp. However, in primiparous cows Hp did not significantly differ between healthy cows (DIM 2: 1.49 ± 0.64 mg/mL; DIM 5: 2.13 ± 0.66 mg/mL; DIM 10: 1.46 ± 0.85 mg/mL) and cows with APM (DIM 2: 1.78 ± 0.62 mg/mL; DIM 5: 2.48 ± 0.64 mg/mL; DIM 10: 1.60 ± 0.81 mg/mL). In multiparous cows, Hp was greater in cows with APM (DIM 2: 1.27 ± 0.68 mg/mL; DIM 5: 1.89 ± 0.94 mg/mL; DIM 10: 1.23 ± 0.78 mg/mL) than in healthy cows (DIM 2: 0.99 ± 0.68 mg/mL; DIM 5: 1.10 ± 0.80 mg/mL; DIM 10: 0.83 ± 0.68 mg/mL). Sensitivity and specificity of Hp to diagnose APM in multiparous cows ranged from 72% to 79% and 54% to 71% on DIM 2, 5 and 10, respectively. | 25,128,191 | [
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The radiosensitising effect of gemcitabine and its main metabolite dFdU under low oxygen conditions is in vitro not dependent on functional HIF-1 protein. | Regions within solid tumours often experience oxygen deprivation, which is associated with resistance to chemotherapy and irradiation. The aim of this study was to evaluate the radiosensitising effect of gemcitabine and its main metabolite dFdU under normoxia versus hypoxia and to determine whether hypoxia-inducible factor 1 (HIF-1) is involved in the radiosensitising mechanism. Stable expression of dominant negative HIF-1α (dnHIF) in MDA-MB-231 breast cancer cells, that ablated endogenous HIF-1 transcriptional activity, was validated by western blot and functionality was assessed by HIF-1α activity assay. Cells were exposed to varying oxygen environments and treated with gemcitabine or dFdU for 24 h, followed by irradiation. Clonogenicity was then assessed. Using radiosensitising conditions, cells were collected for cell cycle analysis. HIF-1 activity was significantly inhibited in cells stably expressing dnHIF. A clear radiosensitising effect under normoxia and hypoxia was observed for both gemcitabine and dFdU. No significant difference in radiobiological parameters between HIF-1 proficient and HIF-1 deficient MDA-MB-231 cells was demonstrated. For the first time, radiosensitisation by dFdU, the main metabolite of gemcitabine, was demonstrated under low oxygen conditions. No major role for functional HIF-1 protein in radiosensitisation by gemcitabine or dFdU could be shown. | 25,128,202 | [
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Fluoroscopic findings post-peroral esophageal myotomy. | Natural orifice transluminal endoscopic surgery (NOTES) is a surgical technique that has been evolving rapidly. Endoscopic submucosal dissection was initiated in 1999, in Japan, for en-bloc resection of large lesions of the stomach (Zhou et al., World J Gastroenterol 19:6962-6968, 2013, ; Kobara et al., Clin Exp Gastroenterol 7:67-74, 2014). Since then, many additional therapies utilizing natural transluminal endoscopic approach have evolved. Peroral endoscopic myotomy (POEM) is a minimally invasive type of transluminal endoscopic surgery that was recently developed for the treatment of achalasia and esophageal motility disorders. The peroral endoscopic myotomy is a less invasive surgical treatment that is suitable for all types of achalasia and used as an alternate to the Heller myotomy. The radiographic findings of achalasia and surgical changes after Heller myotomy have been described, however, very little is available on the post-POEM esophagram appearance. The purpose of this article is to illustrate the anatomy, surgical procedure, and normal and abnormal findings seen on esophagrams in patients who have undergone a POEM. | 25,128,214 | [
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ABT-724 alleviated hyperactivity and spatial learning impairment in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder. | Dysfunction of dopamine D4 receptor (D4R) is linked to attention-deficit/hyperactivity disorder (ADHD) as well as ADHD associated cognitive impairment. Here, we tested the possible therapeutic benefit of the D4R-selective agonist ABT-724 in adolescent spontaneously hypertensive rats (SHRs). ABT-724-treated SHRs were administered ABT-724 (0.04mg/kg, 0.16mg/kg or 0.64mg/kg) from postnatal day (P) 28 to P32. Control SHRs and Sprague-Dawley (SD) rats were injected with saline. Then two cohorts of rats were tested in the open field and Làt maze that measured locomotion and non-selective attention (NSA), respectively. Another cohort of rats was subjected to water maze task for evaluation of spatial learning and memory. We found that control SHRs displayed hyperactivity as well as impaired NSA and spatial learning compared with normotensive SD rats. ABT-724 (0.16 and 0.64mg/kg) treatment alleviated hyperactivity and spatial learning impairment in SHRs. No dose of ABT-724 tested altered NSA in SHRs. Our results raise the possibility that ABT-724 may be used as a therapeutic intervention for ADHD patients during adolescence. | 25,128,216 | [
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The relationships between insomnia, sleep apnoea and depression: findings from the American National Health and Nutrition Examination Survey, 2005-2008. | To determine the association between insomnia, obstructive sleep apnoea (OSA), and comorbid insomnia-OSA and depression, while controlling for relevant lifestyle and health factors, among a large population-based sample of US adults. We examined a sample of 11,329 adults (≥18 years) who participated in the National Health and Nutrition Examination Survey (NHANES) during the years 2005-2008. Insomnia was classified via a combination of self-reported positive physician diagnosis and high-frequency 'trouble falling asleep', 'waking during the night', 'waking too early', and 'feeling unrested during the day'. OSA was classified as a combination of a positive response to a physician-diagnosed condition, in addition to a high frequency of self-reported nocturnal 'snoring', 'snorting/stopping breathing' and 'feeling overly sleepy during the day'. Comorbid insomnia-OSA was further assessed by combining a positive response to either insomnia (all), or sleep apnoea (all), as classified above. Depressive symptomology was assessed by the Patient Health Questionnaire-9 (PHQ-9), with scores of >9 used to indicate depression. Odds ratios (ORs) and 95% confidence intervals (CIs) for sleep disorders and depression were attained from logistic regression modelling adjusted for sex, age, poverty level, smoking status and body mass index (BMI). Those who reported insomnia, OSA or comorbid insomnia-OSA symptoms reported higher rates of depression (33.6%, 22.2%, 27.1%, respectively), and consistently reported poorer physical health outcomes than those who did not report sleep disorders. After adjusting for sex, age, poverty level, smoking status and BMI (kg/m(2)), insomnia (OR 6.57, 95% CI 3.89-11.11), OSA (OR 5.14, 95% CI 3.14-8.41) and comorbid insomnia-OSA (OR 6.67, 95% CI 4.44-10.00) were associated with an increased likelihood of reporting depression. Insomnia, OSA and comorbid insomnia-OSA are associated with significant depressive symptomology among this large population-based sample of adults. | 25,128,225 | [
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Prostate cancer with Paneth cell-like neuroendocrine differentiation has recognizable histomorphology and harbors AURKA gene amplification. | Aurora kinase A (AURKA) gene amplification has been documented in 67% of hormone-naive prostate cancer cases that progress to a highly aggressive variant of castrate-resistant disease, clinically referred to as "neuroendocrine" prostate cancer, "small cell" prostate carcinoma, or "anaplastic" prostate cancer. Therefore, AURKA amplification is a potential prognostic biomarker that may help to identify patients with prostate cancer who are at high risk for developing castrate-resistant disease with clinical features of small cell carcinoma. Furthermore, AURKA inhibitors are currently being tested in clinical trials. In a previous study, we found AURKA amplification in 6 cases of prostate cancer with Paneth cell-like cells. This morphologic pattern has been suggested to represent low-grade neuroendocrine differentiation (NED) with generally favorable prognosis. We sought to investigate the frequency of AURKA amplification and the histologic characteristics of prostate cancer with Paneth cell-like NED. Twenty-five cases from 172 prostatectomies were evaluated for the presence of 18 morphologic features and AURKA amplification. Most prostate cancers with Paneth cell-like NED had macronucleoli (92%), basophilic appearance (88%), perineural invasion (72%), and nuclear stratification (76%). The frequency of AURKA amplification was 45%, present throughout the examined tumor nodule including areas without Paneth cell-like cells. When histologically similar cases with and without AURKA amplification were compared, this gene alteration was associated with larger extent of Paneth cell-like NED identified at magnification ×20 (P = .015), higher percentage of Paneth cell-like NED throughout the tumor nodule (P = .033), ductal features (P = .02), and higher overall Gleason grade (P = .039). AURKA amplification was not associated with age, serum prostate specific antigen, or tumor stage. The high frequency of AURKA amplification (45%) in localized prostate cancer with Paneth cell-like NED and its potential prognostic significance warrant further investigation. | 25,128,228 | [
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Analysis of natural and induced variation in tomato glandular trichome flavonoids identifies a gene not present in the reference genome. | Flavonoids are ubiquitous plant aromatic specialized metabolites found in a variety of cell types and organs. Methylated flavonoids are detected in secreting glandular trichomes of various Solanum species, including the cultivated tomato (Solanum lycopersicum). Inspection of the sequenced S. lycopersicum Heinz 1706 reference genome revealed a close homolog of Solanum habrochaites MOMT1 3'/5' myricetin O-methyltransferase gene, but this gene (Solyc06g083450) is missing the first exon, raising the question of whether cultivated tomato has a distinct 3' or 3'/5' O-methyltransferase. A combination of mining genome and cDNA sequences from wild tomato species and S. lycopersicum cultivar M82 led to the identification of Sl-MOMT4 as a 3' O-methyltransferase. In parallel, three independent ethyl methanesulfonate mutants in the S. lycopersicum cultivar M82 background were identified as having reduced amounts of di- and trimethylated myricetins and increased monomethylated myricetin. Consistent with the hypothesis that Sl-MOMT4 is a 3' O-methyltransferase gene, all three myricetin methylation defective mutants were found to have defects in MOMT4 sequence, transcript accumulation, or 3'-O-methyltransferase enzyme activity. Surprisingly, no MOMT4 sequence is found in the Heinz 1706 reference genome sequence, and this cultivar accumulates 3-methyl myricetin and is deficient in 3'-methyl myricetins, demonstrating variation in this gene among cultivated tomato varieties. | 25,128,240 | [
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Auto-fluorescence of the bone and its use for delineation of bone necrosis. | Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication of long-term bisphosphonate treatment. Currently, the drawback in the surgical management of BRONJ is the difficulty distinguishing between viable and necrotic bone. Intraoperative bone fluorescence induced by tetracyclines has been shown to be a valuable aid to overcome this problem. In this technical note we report the finding that viable bone is auto-fluorescent using the VELscope Vx fluorescence lamp. Necrotic bone shows an altered fluorescence pattern (pale or no fluorescence). Thus it is suggested that auto-fluorescence of bone might be of similar use during the surgical therapy of BRONJ. | 25,128,260 | [
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... |
Airbrushed composite polymer Zr-ACP nanofiber scaffolds with improved cell penetration for bone tissue regeneration. | Electrospun polymer nanofibers have multiple applications in the tissue engineering field despite limited cell penetration within the scaffolds and slow synthesis rates. Airbrushing, a proposed alternative to traditional electrospinning, is a technique capable of synthesizing open structure nanofiber scaffolds at high rates. In this study, three biocompatible polymers-poly-D,L-lactic acid (P-DL-LA), polycaprolactone (PCL), and poly(methyl methacrylate) (PMMA), were airbrushed to form networks for bone tissue regeneration. All three polymers were loaded with up to 20% (w/w) zirconium-modified amorphous calcium phosphate (Zr-ACP). A simple one-step mix and straightforward material deposition yielded open structure networks with well-distributed Zr-ACP. Cell penetration within the airbrushed scaffolds was found to be more than twice the cell penetration within conventional electrospun networks. The airbrushed polymer network supported cell growth and differentiation. Cells grown on the Zr-ACP in P-DL-LA fibers exhibited improved levels of osteocalcin protein with an increase in the Zr-ACP content by day 16. This airbrushing method promises to be a viable and attractive alternative to currently used electrospinning techniques in the formation of composite 3D nanofiber scaffolds for tissue engineering applications. | 25,128,269 | [
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0.6368531,
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0.1006875,
0.059... |
Bilateral Ankle and Subtalar Joint Fusion Secondary to Guillain Barré-Induced Foot Drop. | Guillain-Barré syndrome is a serious disorder that occurs when the body's immune system mistakenly attacks the peripheral nervous system. This leads to nerve inflammation and damage that can cause muscle weakness and/or paralysis, including foot drop. Therapy ranges from supportive measures, such as physical therapy, to surgical intervention. It appears from the published data that these patients, generally, have been left to their own devices, because no known cure is available, necessitating reliance on others for their daily activities and ambulation. We present a unique surgical option, with a follow-up period of 24 months, in which bilateral subtalar and ankle fusion allowed unassisted ambulation to a patient who might otherwise have never walked again. | 25,128,306 | [
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Infectious Spondylodiscitis, Epidural Phlegmon, and Psoas Abscess Complicating Diabetic Foot Infection: A Case Report. | Few published case reports have cited vertebral osteomyelitis as a sequela of a diabetic foot infection. The purpose of the present report is to increase awareness of a potentially severe complication of diabetic foot ulceration: vertebral osteomyelitis and associated pathologic features. We present the case of a 63-year-old male with right calcaneal osteomyelitis who developed acute onset lower back pain with concomitant fever and chills. Magnetic resonance imaging revealed L4-L5 vertebral osteomyelitis, a T9-L1 epidural abscess, and a right psoas muscle abscess secondary to hematogenous seeding from the calcaneus. The patient underwent right partial calcanectomy, spinal and right psoas abscess incision and drainage, and direct lumbar interbody fusion of L4-L5 with a right iliac crest allograft. All bone, blood, and abscess cultures were positive for methicillin-resistant Staphylococcus aureus. After the surgery, the patient's pain resolved in his back and hip and he regained full right lower extremity function. The 1-year follow-up examination revealed that the patient had vertebral arthritis but was able to perform his activities of daily living with a walker and cane. It is important to recognize the potential complications of diabetic foot ulcerations and be aware of the identifying symptoms and treatment options for this condition to prevent significant morbidity and mortality. | 25,128,309 | [
0.09136627,
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0.107897,
0.08784237,
0.2169252,
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Treatment of Calcaneal Fracture With Severe Soft Tissue Injury and Osteomyelitis: A Case Report. | Advancements in surgical technique have resulted in the ability to reconstruct lower extremity injuries that would have previously been treated by amputation. Currently, a paucity of data is available specifically addressing limb amputation versus reconstruction for calcaneal fractures with severe soft tissue compromise. Reconstruction leaves the patient with their native limb; however, multiple surgeries, infections, chronic pain, and a poor functional outcome are very real possibilities. We present the case of a complex calcaneal fracture complicated by soft tissue injury and osteomyelitis that highlights the importance of shared decision-making between patient and surgeon when considering reconstruction versus amputation. This case exemplifies the need for open communication concerning the risks and benefits of treatment modalities while simultaneously considering the patient's expectations and desired outcomes. | 25,128,313 | [
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0.1001411,
0.0917131,
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0.002598118,
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... |
Torque-stiffness-controlled dynamic walking with central pattern generators. | Walking behavior is modulated by controlling joint torques in most existing passivity-based bipeds. Controlled Passive Walking with adaptable stiffness exhibits controllable natural motions and energy efficient gaits. In this paper, we propose torque-stiffness-controlled dynamic bipedal walking, which extends the concept of Controlled Passive Walking by introducing structured control parameters and a bio-inspired control method with central pattern generators. The proposed walking paradigm is beneficial in clarifying the respective effects of the external actuation and the internal natural dynamics. We present a seven-link biped model to validate the presented walking. Effects of joint torque and joint stiffness on gait selection, walking performance and walking pattern transitions are studied in simulations. The work in this paper develops a new solution of motion control of bipedal robots with adaptable stiffness and provides insights of efficient and sophisticated walking gaits of humans. | 25,128,320 | [
-0.1798386,
0.333606,
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0.113389,
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0.1144731,
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0.0... |
Mitochondrial function/dysfunction in white adipose tissue. | The role of mitochondria in white adipocytes has long been neglected due in part to their lower abundance in these cells. However, accumulating evidence suggests that mitochondria are vital for maintaining metabolic homeostasis in white adipocytes because of their involvement in adipogenesis, fatty acid synthesis and esterification, branched-chain amino acid catabolism and lipolysis. It is therefore not surprising that white adipose tissue function can be perturbed by altering mitochondrial components or oxidative capacity. Moreover, studies in humans and animals with significantly altered fat mass, such as in obesity or lipoatrophy, indicate that impaired mitochondrial function in adipocytes may be linked directly to the development of metabolic diseases such as diabetes and insulin resistance. However, recent studies that specifically targeted mitochondrial function in adipocytes indicated dissociation between impaired mitochondrial oxidative capacity and systemic insulin sensitivity. | 25,128,326 | [
-0.1809268,
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0.01328536,
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0.1096444,
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0.1166384,
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Analysis of the xplAB-containing gene cluster involved in the bacterial degradation of the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine. | Repeated use of the explosive compound hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) on military land has resulted in significant soil and groundwater pollution. Rates of degradation of RDX in the environment are low, and accumulated RDX, which the U.S. Environmental Protection Agency has determined is a possible human carcinogen, is now threatening drinking water supplies. RDX-degrading microorganisms have been isolated from RDX-contaminated land; however, despite the presence of these species in contaminated soils, RDX pollution persists. To further understand this problem, we studied RDX-degrading species belonging to four different genera (Rhodococcus, Microbacterium, Gordonia, and Williamsia) isolated from geographically distinct locations and established that the xplA and xplB (xplAB) genes, which encode a cytochrome P450 and a flavodoxin redox partner, respectively, are nearly identical in all these species. Together, the xplAB system catalyzes the reductive denitration of RDX and subsequent ring cleavage under aerobic and anaerobic conditions. In addition to xplAB, the Rhodococcus species studied here share a 14-kb region flanking xplAB; thus, it appears likely that the RDX-metabolizing ability was transferred as a genomic island within a transposable element. The conservation and transfer of xplAB-flanking genes suggest a role in RDX metabolism. We therefore independently knocked out genes within this cluster in the RDX-degrading species Rhodococcus rhodochrous 11Y. Analysis of the resulting mutants revealed that XplA is essential for RDX degradation and that XplB is not the sole contributor of reducing equivalents to XplA. While XplA expression is induced under nitrogen-limiting conditions and further enhanced by the presence of RDX, MarR is not regulated by RDX. | 25,128,343 | [
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0... |
Enhanced uranium immobilization and reduction by Geobacter sulfurreducens biofilms. | Biofilms formed by dissimilatory metal reducers are of interest to develop permeable biobarriers for the immobilization of soluble contaminants such as uranium. Here we show that biofilms of the model uranium-reducing bacterium Geobacter sulfurreducens immobilized substantially more U(VI) than planktonic cells and did so for longer periods of time, reductively precipitating it to a mononuclear U(IV) phase involving carbon ligands. The biofilms also tolerated high and otherwise toxic concentrations (up to 5 mM) of uranium, consistent with a respiratory strategy that also protected the cells from uranium toxicity. The enhanced ability of the biofilms to immobilize uranium correlated only partially with the biofilm biomass and thickness and depended greatly on the area of the biofilm exposed to the soluble contaminant. In contrast, uranium reduction depended on the expression of Geobacter conductive pili and, to a lesser extent, on the presence of the c cytochrome OmcZ in the biofilm matrix. The results support a model in which the electroactive biofilm matrix immobilizes and reduces the uranium in the top stratum. This mechanism prevents the permeation and mineralization of uranium in the cell envelope, thereby preserving essential cellular functions and enhancing the catalytic capacity of Geobacter cells to reduce uranium. Hence, the biofilms provide cells with a physically and chemically protected environment for the sustained immobilization and reduction of uranium that is of interest for the development of improved strategies for the in situ bioremediation of environments impacted by uranium contamination. | 25,128,347 | [
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0.1979537,
0.400559,
0.093622... |
Comparison of NaF and FDG PET/CT for assessment of treatment response in castration-resistant prostate cancers with osseous metastases. | Assessment of skeletal metastases' response to therapy is a highly relevant but unresolved clinical problem. The main goal of this work was to compare pharmacodynamic responses to therapy assessed with positron emission tomography-computed tomography (PET/CT) using fluorine-18 sodium fluoride (NaF) and fluorine-18 fluorodeoxyglucose (FDG) as the tracers. Patients with prostate cancer with known osseous metastases were treated with zibotentan (ZD4054) and imaged with combined dynamic NaF/FDG PET/CT before therapy (baseline), after 4 weeks of therapy (week 4), and after 2 weeks of treatment break (week 6). Kinetic analysis allowed comparison of the voxel-based tracer uptake rate parameter Ki, the vasculature parameters K1 (measuring perfusion/permeability) and Vb (measuring vasculature fraction in the tissue), and the standardized uptake values (SUVs). Correlations were high for the NaF and FDG peak uptake parameters (Ki and SUV correlations ranged from 0.57 to 0.88) and for vasculature parameters (K1 and Vb correlations ranged from 0.61 to 0.81). Correlation was low between the NaF and FDG week 4 Ki responses (ρ = 0.35; P = .084) but was higher for NaF and FDG week 6 Ki responses (ρ = 0.72; P < .0001). Correlations for vasculature responses were always low (ρ < 0.35). NaF and FDG uptakes in the osseous metastases were spatially dislocated, with overlap in the range from 0% to 80%. This study found that late NaF and FDG uptake responses are consistently correlated but that earlier uptake responses and all vasculature responses can be unrelated. This study also confirmed that FDG and NaF uptakes are spatially dislocated. Although treatment responses assessed with NaF and FDG may be correlated, using both tracers provides additional information. | 25,128,349 | [
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0.4056625,
0.1894563,
0.2013634,
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