title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Stress and resilience in military mortuary workers: care of the dead from battlefield to home. | The death of a military service member in war provokes feelings of distress and pride in mortuary workers who process the remains. To further understand their reactions, the authors interviewed 34 military and civilian personnel to learn more about their work stresses and rewards. They review stresses of anticipation, exposure, and experience in handling the dead and explore the personal, supervisory, and leadership strategies to reduce negative effects and promote personal growth. These results can be applied to many other situations requiring planning, implementing, and supervising mortuary operations involving mass death. | 25,140,840 | [
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Comparison of bilateral and unilateral contractions between swimmers and nonathletes during leg press and hand grip exercises. | The bilateral limb deficit (BLD) is defined as the reduction in force production during bilateral compared with summed unilateral contractions of homologous muscles. The underlying mechanism for the BLD has been elusive to determine. The purpose of this study was to examine the presence of the BLD during maximal isometric leg press and handgrip exercises in female swimmers (n = 9, mean age = 20.1 ± 1.3 years) and nonathletes (n = 9, mean age = 21.7 ± 1.3 years) to gain further insight into this phenomenon. Force and electromyography (EMG) measures were collected from participants under bilateral and unilateral conditions for handgrip and leg press exercises. Bilateral limb ratios (BLR) were calculated for swimmers (BLRS) and nonathletes (BLRNA). A deficit was found for swimmers and nonathletes in leg force (BLRS = 79.84% ± 13.09% and BLRNA = 81.44% ± 19.23%) and leg EMG (BLRS = 88.45% ± 15.41% and BLRNA = 94.66% ± 13.62%); however, no BLD was seen in hand force (BLRS = 98.30% ± 11.21% and BLRNA = 95.91% ± 11.04%) and hand EMG (BLRS = 102.42% ± 11.20% and BLRNA = 103.30% ± 16.50%). Furthermore, no significant differences were found between groups for leg force, leg EMG, hand force, and hand EMG. In conclusion, a BLD was detected for both groups during bilateral isometric leg press. This suggests that while the BLD may be affected by neural influences, there may other factors involved such as postural stability requirements to perform the exercise. | 25,140,863 | [
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Synthetic antibodies with a human framework that protect mice from lethal Sudan ebolavirus challenge. | The ebolaviruses cause severe and rapidly progressing hemorrhagic fever. There are five ebolavirus species; although much is known about Zaire ebolavirus (EBOV) and its neutralization by antibodies, little is known about Sudan ebolavirus (SUDV), which is emerging with increasing frequency. Here we describe monoclonal antibodies containing a human framework that potently inhibit infection by SUDV and protect mice from lethal challenge. The murine antibody 16F6, which binds the SUDV envelope glycoprotein (GP), served as the starting point for design. Sequence and structural alignment revealed similarities between 16F6 and YADS1, a synthetic antibody with a humanized scaffold. A focused phage library was constructed and screened to impart 16F6-like recognition properties onto the YADS1 scaffold. A panel of 17 antibodies were characterized and found to have a range of neutralization potentials against a pseudotype virus infection model. Neutralization correlated with GP binding as determined by ELISA. Two of these clones, E10 and F4, potently inhibited authentic SUDV and conferred protection and memory immunity in mice from lethal SUDV challenge. E10 and F4 were further shown to bind to the same epitope on GP as 16F6 with comparable affinities. These antibodies represent strong immunotherapeutic candidates for treatment of SUDV infection. | 25,140,871 | [
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Biogeographic distribution patterns and their correlates in the diverse frog fauna of the Atlantic Forest hotspot. | Anurans are a highly diverse group in the Atlantic Forest hotspot (AF), yet distribution patterns and species richness gradients are not randomly distributed throughout the biome. Thus, we explore how anuran species are distributed in this complex and biodiverse hotspot, and hypothesize that this group can be distinguished by different cohesive regions. We used range maps of 497 species to obtain a presence/absence data grid, resolved to 50×50 km grain size, which was submitted to k-means clustering with v-fold cross-validation to determine the biogeographic regions. We also explored the extent to which current environmental variables, topography, and floristic structure of the AF are expected to identify the cluster patterns recognized by the k-means clustering. The biogeographic patterns found for amphibians are broadly congruent with ecoregions identified in the AF, but their edges, and sometimes the whole extent of some clusters, present much less resolved pattern compared to previous classification. We also identified that climate, topography, and vegetation structure of the AF explained a high percentage of variance of the cluster patterns identified, but the magnitude of the regression coefficients shifted regarding their importance in explaining the variance for each cluster. Specifically, we propose that the anuran fauna of the AF can be split into four biogeographic regions: a) less diverse and widely-ranged species that predominantly occur in the inland semideciduous forests; b) northern small-ranged species that presumably evolved within the Pleistocene forest refugia; c) highly diverse and small-ranged species from the southeastern Brazilian mountain chain and its adjacent semideciduous forest; and d) southern species from the Araucaria forest. Finally, the high congruence among the cluster patterns and previous eco-regions identified for the AF suggests that preserving the underlying habitat structure helps to preserve the historical and ecological signals that underlie the geographic distribution of AF anurans. | 25,140,882 | [
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Unexpected metal ion-assisted transformations leading to unexplored bridging ligands in Ni(II) coordination chemistry: the case of PO3F(2-) group. | The initial 'accidental', metal ion-assisted hydrolysis of PF6(-) to PO3F(2-) has been evolved in a systematic investigation of the bridging affinity of the latter group in Ni(II)/oximate chemistry; mono-, di- and trinuclear complexes have been prepared and confirmed both the rich reactivity of PO3F(2-) and its potential for further use as bridging ligand in high-nuclearity 3d-metal cluster chemistry. | 25,140,887 | [
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4-1BBL enhances CD8+ T cell responses induced by vectored vaccines in mice but fails to improve immunogenicity in rhesus macaques. | T cells play a central role in the immune response to many of the world's major infectious diseases. In this study we investigated the tumour necrosis factor receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its ability to increase T cell immunogenicity induced by a variety of recombinant vectored vaccines. To efficiently test this hypothesis, we assessed a number of promoters and developed a stable bi-cistronic vector expressing both the antigen and adjuvant. Co-expression of 4-1BBL, together with our model antigen TIP, was shown to increase the frequency of murine antigen-specific IFN-γ secreting CD8(+) T cells in three vector platforms examined. Enhancement of the response was not limited by co-expression with the antigen, as an increase in CD8(+) immunogenicity was also observed by co-administration of two vectors each expressing only the antigen or adjuvant. However, when this regimen was tested in non-human primates using a clinical malaria vaccine candidate, no adjuvant effect of 4-1BBL was observed limiting its potential use as a single adjuvant for translation into a clinical vaccine. | 25,140,889 | [
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Deciphering the glycolipid code of Alzheimer's and Parkinson's amyloid proteins allowed the creation of a universal ganglioside-binding peptide. | A broad range of microbial and amyloid proteins interact with cell surface glycolipids which behave as infectivity and/or toxicity cofactors in human pathologies. Here we have deciphered the biochemical code that determines the glycolipid-binding specificity of two major amyloid proteins, Alzheimer's β-amyloid peptide (Aβ) and Parkinson's disease associated protein α-synuclein. We showed that both proteins interact with selected glycolipids through a common loop-shaped motif exhibiting little sequence homology. This 12-residue domain corresponded to fragments 34-45 of α-synuclein and 5-16 of Aβ. By modulating the amino acid sequence of α-synuclein at only two positions in which we introduced a pair of histidine residues found in Aβ, we created a chimeric α-synuclein/Aβ peptide with extended ganglioside-binding properties. This chimeric peptide retained the property of α-synuclein to recognize GM3, and acquired the capacity to recognize GM1 (an Aβ-inherited characteristic). Free histidine (but not tryptophan or asparagine) and Zn2+ (but not Na+) prevented this interaction, confirming the key role of His-13 and His-14 in ganglioside binding. Molecular dynamics studies suggested that the chimeric peptide recognized cholesterol-constrained conformers of GM1, including typical chalice-shaped dimers, that are representative of the condensed cholesterol-ganglioside complexes found in lipid raft domains of the plasma membrane of neural cells. Correspondingly, the peptide had a particular affinity for raft-like membranes containing both GM1 and cholesterol. The chimeric peptide also interacted with several other gangliosides, including major brain gangliosides (GM4, GD1a, GD1b, and GT1b) but not with neutral glycolipids such as GlcCer, LacCer or asialo-GM1. It could inhibit the binding of Aβ1-42 onto neural SH-SY5Y cells and did not induce toxicity in these cells. In conclusion, deciphering the glycolipid code of amyloid proteins allowed us to create a universal ganglioside-binding peptide of only 12-residues with potential therapeutic applications in infectious and neurodegenerative diseases that involve cell surface gangliosides as receptors. | 25,140,899 | [
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Driving forces for the self-assembly of graphene oxide on organic monolayers. | Graphene oxide (GO) flakes were self-assembled from solution on surfaces of self-assembled monolayers (SAMs), varying in the chemical structure of their head groups. The coverage density of GO relates to strength of attractive interaction, which is largest for Coulomb interaction provided by positively charged SAM head groups and negatively charged GO. A rough surface enhances the coverage density but with the same trend in driving force dependency. The self-assembly approach was used to fabricate field-effect transistors with reduced GO (rGO) as active layer. The SAMs as attractive layer for self-assembly remain almost unaffected by the reduction from GO to rGO and serve as ultra-thin gate dielectrics in devices, which operate at low voltages of maximum 3 V and exhibit a shift of the Dirac voltage related to the dipole moment of the SAMs. | 25,140,920 | [
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Oral GS-5806 activity in a respiratory syncytial virus challenge study. | Respiratory syncytial virus (RSV) is a common cause of infant hospitalizations and is increasingly recognized as a cause of considerable morbidity and mortality. No accepted antiviral treatment exists. We conducted a double-blind, placebo-controlled study of GS-5806, an oral RSV-entry inhibitor, in healthy adults who received a clinical challenge strain of RSV intranasally. Participants were monitored for 12 days. At the time of a positive test for RSV infection or 5 days after inoculation, whichever occurred first, participants were randomly assigned to receive GS-5806 or placebo in one of seven sequential cohorts. Cohorts 1 to 4 received a first dose of 50 mg of GS-5806 and then 25 mg daily for the next 4 days, cohort 5 received a first dose of 50 mg and then 25 mg daily for the next 2 days, cohort 6 received one 100-mg dose, and cohort 7 received a first dose of 10 mg and then 5 mg daily for the next 4 days. Dose selection for cohorts 5, 6, and 7 occurred after an interim analysis of data for cohorts 1 to 4. The primary end point was the area under the curve (AUC) for the viral load, which was assessed after administration of the first dose through the 12th day after inoculation. Secondary end points were mucus weight and symptom scores. Among the 54 participants in cohorts 1 to 4 who were infected with RSV, active treatment was associated with a lower viral load (adjusted mean, 250.7 vs. 757.7 log10 plaque-forming-unit equivalents [PFUe] × hours per milliliter; P<0.001), lower total mucus weight (mean, 6.9 g vs. 15.1 g; P=0.03), and a lower AUC for the change from baseline in symptom scores (adjusted mean, -20.2 vs. 204.9 × hours; P=0.005). The results were similar in cohorts 5, 6, and 7. Adverse events, including low neutrophil counts and increased levels of alanine aminotransferase, were more common among participants receiving GS-5806. Treatment with GS-5806 reduced the viral load and the severity of clinical disease in a challenge study of healthy adults. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01756482.). | 25,140,957 | [
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Computer-assisted surgery in orthopedic oncology. | In orthopedic oncology, computer-assisted surgery (CAS) can be considered an alternative to fluoroscopy and direct measurement for orientation, planning, and margin control. However, only small case series reporting specific applications have been published. We therefore describe possible applications of CAS and report preliminary results in 130 procedures. We conducted a retrospective cohort study of all oncological CAS procedures in a single institution from November 2006 to March 2013. Mean follow-up time was 32 months. We categorized and analyzed 130 procedures for clinical parameters. The categories were image-based intralesional treatment, image-based resection, image-based resection and reconstruction, and imageless resection and reconstruction. Application to intralesional treatment showed 1 inadequate curettage and 1 (other) recurrence in 63 cases. Image-based resections in 42 cases showed 40 R0 margins; 16 in 17 pelvic resections. Image-based reconstruction facilitated graft creation with a mean reconstruction accuracy of 0.9 mm in one case. Imageless CAS was helpful in resection planning and length- and joint line reconstruction for tumor prostheses. CAS is a promising new development. Preliminary results show a high number of R0 resections and low short-term recurrence rates for curettage. | 25,140,984 | [
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Tandem ring-closing metathesis/transfer hydrogenation: practical chemoselective hydrogenation of alkenes. | An operationally simple chemoselective transfer hydrogenation of alkenes using ruthenium metathesis catalysts is presented. Of great practicality, the transfer hydrogenation reagents can be added directly to a metathesis reaction and effect hydrogenation of the product alkene in a single pot at ambient temperature without the need to seal the vessel to prevent hydrogen gas escape. The reduction is applicable to a range of alkenes and can be performed in the presence of aryl halides and benzyl groups, a notable weakness of Pd-catalyzed hydrogenations. Scope and mechanistic considerations are presented. | 25,140,991 | [
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Chimpanzees and humans mimic pupil-size of conspecifics. | Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes). We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals. | 25,140,998 | [
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An early warning system based on syndromic surveillance to detect potential health emergencies among migrants: results of a two-year experience in Italy. | Profound geopolitical changes have impacted the southern and eastern Mediterranean since 2010 and defined a context of instability that is still affecting several countries today. Insecurity combined with the reduction of border controls has led to major population movements in the region and to migration surges from affected countries to southern Europe, especially to Italy. To respond to the humanitarian emergency triggered by this migration surge, Italy implemented a syndromic surveillance system in order to rapidly detect potential public health emergencies in immigrant reception centres. This system was discontinued after two years. This paper presents the results of this experience detailing its strengths and weaknesses in order to document the applicability and usefulness of syndromic surveillance in this specific context. | 25,140,999 | [
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Hawthorne effect with transient behavioral and biochemical changes in a randomized controlled sleep extension trial of chronically short-sleeping obese adults: implications for the design and interpretation of clinical studies. | To evaluate the effects of study participation per se at the beginning of a sleep extension trial between screening, randomization, and the run-in visit. Subjects were screened, returned for randomization (Comparison vs. Intervention) after 81 days (median), and attended run-in visit 121 days later. Outpatient. Obese (N = 125; M/F, 30/95; Blacks/Whites/Other, N = 73/44/8), mean weight 107.6±19.7 kg, <6.5 h sleep/night. Non-pharmacological sleep extension. Sleep duration (diaries and actigraphy watch), sleep quality (Pittsburgh Sleep Quality Index), daily sleepiness (Epworth Sleepiness Scale), fasting glucose, insulin and lipids. Prior to any intervention, marked improvements occurred between screening and randomization. Sleep duration increased (diaries: 357.4 ±51.2 vs. 388.1±48.6 min/night; mean±SD; P<0.001 screening vs. randomization; actigraphy: 344.3 ±41.9 vs. 358.6±48.2 min/night; P<0.001) sleep quality improved (9.1±3.2 vs. 8.2±3.0 PSQI score; P<0.001), sleepiness tended to improve (8.9±4.6 vs. 8.3±4.5 ESS score; P = 0.06), insulin resistance decreased (0.327±0.038 vs. 0.351±0.045; Quicki index; P<0.001), and lipids improved, except for HDL-C. Abnormal fasting glucose (25% vs. 11%; P = 0.007), and metabolic syndrome (42% vs. 29%; P = 0.007) both decreased. In absence of intervention, the earlier metabolic improvements disappeared at the run-in visit. Relatively small sample size. Improvements in biochemical and behavioral parameters between screening and randomization changed the "true" study baseline, thereby potentially affecting outcome. While regression to the mean and placebo effect were considered, these findings are most consistent with the "Hawthorne effect", according to which behavior measured in the setting of an experimental study changes in response to the attention received from study investigators. This is the first time that biochemical changes were documented with respect to the Hawthorne effect. The findings have implications for the design and conduct of clinical research. ClinicalTrials.gov NCT00261898. | 25,141,012 | [
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Asthma during pregnancy in a population-based study--pregnancy complications and adverse perinatal outcomes. | Asthma is one of the most common chronic diseases, and prevalence, severity and medication may have an effect on pregnancy. We examined maternal asthma, asthma severity and control in relation to pregnancy complications, labour characteristics and perinatal outcomes. We retrieved data on all singleton births from July 1, 2006 to December 31, 2009, and prescribed drugs and physician-diagnosed asthma on the same women from multiple Swedish registers. The associations were estimated with logistic regression. In total, 266 045 women gave birth to 284 214 singletons during the study period. Maternal asthma was noted in 26 586 (9.4%) pregnancies. There was an association between maternal asthma and increased risks of pregnancy complications including preeclampsia or eclampsia (adjusted OR 1.15; 95% CI 1.06-1.24) and premature contractions (adj OR 1.52; 95% CI 1.29-1.80). There was also a significant association between maternal asthma and emergency caesarean section (adj OR 1.29; 95% CI 1.23-1.34), low birth weight, and small for gestational age (adj OR 1.23; 95% CI 1.13-1.33). The risk of adverse outcomes such as low birth weight increased with increasing asthma severity. For women with uncontrolled compared to those with controlled asthma the results for adverse outcomes were inconsistent displaying both increased and decreased OR for some outcomes. Maternal asthma is associated with a number of serious pregnancy complications and adverse perinatal outcomes. Some complications are even more likely with increased asthma severity. With greater awareness and proper management, outcomes would most likely improve. | 25,141,021 | [
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Investigation of the role of protonation of benzophenone and its derivatives in acidic aqueous solutions using time-resolved resonance Raman spectroscopy: how are ketyl radicals formed in aqueous solutions? | The formation mechanism of ketyl radicals and several other selective photoreactions of benzophenone and its derivatives are initiated by the protonation of their triplet state and have been investigated using nanosecond time-resolved resonance Raman spectroscopy (ns-TR(3)) in solutions of varying conditions. Evidence is found that the ketyl radical is generated by the combined action of a ketone protonation and a subsequent electron transfer based on the results from previous studies on the photochemistry and photophysics of benzophenone and the ns-TR(3) results reported here for benzophenone, 1,4-dibenzoylbenzene, 3-(hydroxymethyl)benzophenone, and ketoprofen in neutral and acidic solution. In order to better understand the role of the protonated ketone, results are summarized for some selective photochemical reactions of benzophenone and its derivatives induced by protonation in acidic solutions. For the parent benzophenone, the protonation of the ketone leads to the photohydration reactions at the ortho- and meta-positions of the benzene ring in acidic aqueous solutions. For 3-(hydroxymethyl)benzophenone, the protonation promotes an interesting photoredox reaction to become very efficient and the predominant reaction in a pH = 2 aqueous solution. While for ketoprofen, the protonation can initiate a solvent-mediated excited-state intramolecular proton transfer (ESIPT) from the carboxyl group to the carbonyl group that then leads to a decarboxylation reaction in a pH = 0 acidic aqueous solution. We briefly discuss the key role of the protonation of the ketone in the photochemistry of these aromatic ketones. | 25,141,023 | [
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Cultured neonatal rat cardiomyocytes display differences in glucose uptake and sensitivity to dexamethasone related to maternal diet. | Feeding a low protein (LP) diet in rat pregnancy is associated with impaired cardiovascular health and function, possibly as a result of tissue remodelling. To assess whether cardiomyocytes retain differences induced by protein restriction, cells from neonatal rats exposed to control or LP diets in utero were cultured for a period of 10 days. At the end of this period, no differences in cell size, proliferation differentiation or metabolic function were noted. When treated with dexamethasone (0.1-10 μM) for 2 days, it was noted that insulin-stimulated glucose uptake was enhanced, but only in cells from LP rats. Increased glucocorticoid sensitivity of cardiomyocytes from LP rats could not be explained by differential expression of the glucocorticoid receptor or the glucose transporters, GLUT1 and GLUT4. The findings of the study suggest that sensitivity to endocrine signals may be permanently programmed by undernutrition through mechanisms that are preserved in vitro. | 25,141,045 | [
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Mechanistic investigation of the cleavage of phosphodiester catalyzed by a symmetrical oxyimine-based macrocyclic dinuclear zinc complex: a DFT study. | Density functional theory (DFT) was utilized to investigate the hydrolysis reaction mechanisms of phosphodiester BNPP (BNPP = bis(4-nitrophenyl)phosphate) catalyzed by a symmetrical oxyimine-based macrocyclic dinuclear zinc(ii) complex. We examined the nature of the nucleophilic reagent and the active form of the catalyst. The coordination and binding models of the catalyst-substrate complex were explored and we investigated two catalyst configurations (a ridge configuration and a plane configuration), four basic catalyst-substrate binding models (a mono-point-binding model, a dual-point-binding model, an OH-bridging model and a mono-center-dual-binding model) and two alternate roles for the metal-coordinated hydroxide ion (whether it acts as a nucleophile or as a general base to facilitate the deprotonation of a solvent molecule). The one-point-binding mode was found to be preferred to construct a starting reactant. Nine plausible reaction mechanisms were proposed and investigated. Mechanism 1, a stepwise SN2-type addition-substitution reaction involving a para-position nucleophilic attack and the configuration inversion of the phosphate, was found to be the most favorable pathway. All of the proposed pathways are derived from alternate mechanisms such as a ping-pong mechanism and an AP mechanism. The ping-pong mechanism in combination with the role of the metal-coordinated hydroxide ion acting as a nucleophile was found to be more competitive than the other mechanisms examined. Results reported in this paper are consistent with, and can be utilized to systematically interpret, the experimental observations in the literature. | 25,141,046 | [
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RandomForest4Life: a Random Forest for predicting ALS disease progression. | We describe a method for predicting disease progression in amyotrophic lateral sclerosis (ALS) patients. The method was developed as a submission to the DREAM Phil Bowen ALS Prediction Prize4Life Challenge of summer 2012. Based on repeated patient examinations over a three- month period, we used a random forest algorithm to predict future disease progression. The procedure was set up and internally evaluated using data from 1197 ALS patients. External validation by an expert jury was based on undisclosed information of an additional 625 patients; all patient data were obtained from the PRO-ACT database. In terms of prediction accuracy, the approach described here ranked third best. Our interpretation of the prediction model confirmed previous reports suggesting that past disease progression is a strong predictor of future disease progression measured on the ALS functional rating scale (ALSFRS). We also found that larger variability in initial ALSFRS scores is linked to faster future disease progression. The results reported here furthermore suggested that approaches taking the multidimensionality of the ALSFRS into account promise some potential for improved ALS disease prediction. | 25,141,076 | [
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Effects of mental and physical practice on a finger opposition task among children. | We sought to compare the effects of physical practice (PP) and mental practice (MP) on the immediate and long-term learning of the finger-to-thumb opposition sequence task (FOS) in children; in addition, we investigated the transfer of this learning to an untrained sequence of movements and to the contralateral untrained hand. This study included thirty-six 9- and 10-year-old children who were randomly allocated into 3 groups: MP, PP, and no practice (NP). The MP and PP groups were subjected to a single session of training with the dominant trained hand. MP participants were trained by mentally rehearsing the movements, PP participants were trained by executing the movements, and the NP group had no training. The performance of the trained sequence (TS) and untrained reverse sequence (URS) by each of the 3 groups was evaluated under identical conditions before training, after 5 min, and at 4 days, 7 days, and 28 days after training. Whereas both trained groups (MP and PP) showed statistically significant improvement in TS using the trained hand at all assessment points after the training, only MP participants were able to transfer the performance gains from the TS to the URS and from the trained hand to the untrained opposite hand. Children were able to learn the FOS through MP or PP with a similar level of performance. Unlike PP, MP allowed for the transfer of performance gain to the URS and to the opposite hand, suggesting that the internal representations developed by MP were effector-independent. | 25,141,084 | [
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Sixth-grade physical education: an acculturation of bullying and fear. | Although bullying is recognized as a serious problem among adolescents, more information is needed regarding bullying within the context of physical education. Grounded in a social-ecological framework, the purpose of this investigation was to discover the perceptions students and teachers have about bullying in physical education and about peer and adult support. Data collection included formal and informal interviews with 24 students and 4 teachers and 20 observations of 6th-grade physical education classes in 1 Midwestern school. Data were analyzed using a constant-comparative process. The results indicate that adults acculturate students to support a bullying climate by providing mixed information regarding social interactions, ignoring nonphysical instances of bullying, and promoting inappropriate curricular selections. Participants also report that perceived differences such as appearance, body size, physical ability, and personal attire ignite most episodes of harassment in physical education. Further, students perceive that fear prevents many from (a) reporting instances of bullying to those in authority, (b) assisting bullied friends, and (c) feeling safe in certain physical education locations. Finally, students and teachers report that bullying impacts students' desire to participate in physical education. Overall, evidence from this investigation suggests that an efficacious support system does not exist for addressing the magnitude of the bullying problem. Although this study provided an initial step toward understanding the social-ecological factors affecting peer harassment in physical education, additional research is warranted. | 25,141,091 | [
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Thiol-activated gem-dithiols: a new class of controllable hydrogen sulfide donors. | A class of novel thiol-activated H2S donors has been developed on the basis of the gem-dithiol template. These donors release H2S in the presence of cysteine or GSH in aqueous solutions as well as in cellular environments. | 25,141,097 | [
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Treatment priorities in oncology: do we want to live longer or better? | Despite the progress achieved in the fight against cancer over the past several years, assessing the needs, goals and preferences of patients with cancer is of the utmost importance for the delivery of health care. We sought to assess priorities regarding quantity versus quality of life among Brazilian patients, comparing them with individuals without cancer. Using a questionnaire presenting four hypothetical cancer cases, we interviewed cancer patients, oncology health-care professionals and laypersons, most of whom had administrative functions in our hospital. A total of 214 individuals participated: 101 patients, 44 health-care professionals and 69 laypersons. The mean ages in the three groups were 56, 34 and 31 years old, respectively (p<0.001). The patients had gastrointestinal (25%), breast (22%), hematologic (10%), lung (8%) or other tumors (36%) and the tumor-node- metastasis (TNM) stage was I, II, III or IV in 22%, 13%, 34% and 31% of cases, respectively. Treatment priorities differed significantly among the three groups (p = 0.005), with survival time being a higher priority for patients than for the other two groups and with opposite trends regarding quality of life. In multivariate analysis, the age and sex distributions were not associated with the choice to maximize quality of life. In this limited sample of cancer patients, there were no associations between treatment priorities and disease stages. Both survival time and quality of life appeared to be important to cancer patients, oncology health-care professionals and laypersons, but survival time seemed to have higher priority for people diagnosed with cancer than for healthy people. Additionally, survival seemed to be more important than quality of life for all three groups assessed. | 25,141,108 | [
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Fluid distribution kinetics during cardiopulmonary bypass. | The purpose of this study was to examine the isovolumetric distribution kinetics of crystalloid fluid during cardiopulmonary bypass. Ten patients undergoing coronary artery bypass grafting participated in this prospective observational study. The blood hemoglobin and the serum albumin and sodium concentrations were measured repeatedly during the distribution of priming solution (Ringer's acetate 1470 ml and mannitol 15% 200 ml) and initial cardioplegia. The rate of crystalloid fluid distribution was calculated based on 3-min Hb changes. The preoperative blood volume was extrapolated from the marked hemodilution occurring during the onset of cardiopulmonary bypass. Clinicaltrials.gov: NCT01115166. The distribution half-time of Ringer's acetate averaged 8 minutes, corresponding to a transcapillary escape rate of 0.38 ml/kg/min. The intravascular albumin mass increased by 5.4% according to mass balance calculations. The preoperative blood volume, as extrapolated from the drop in hemoglobin concentration by 32% (mean) at the beginning of cardiopulmonary bypass, was 0.6-1.2 L less than that estimated by anthropometric methods (p<0.02). The mass balance of sodium indicated a translocation from the intracellular to the extracellular fluid space in 8 of the 10 patients, with a median volume of 236 ml. The distribution half-time of Ringer's solution during isovolumetric cardiopulmonary bypass was 8 minutes, which is the same as for crystalloid fluid infusions in healthy subjects. The intravascular albumin mass increased. Most patients were hypovolemic prior to the start of anesthesia. Intracellular edema did not occur. | 25,141,112 | [
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The association of vitamin D deficiency with non-alcoholic fatty liver disease. | Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl). In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed. | 25,141,113 | [
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Silyl phosphorus and nitrogen donor chelates for homogeneous ortho borylation catalysis. | Ir catalysts supported by bidentate silyl ligands that contain P- or N-donors are shown to effect ortho borylations for a range of substituted aromatics. The substrate scope is broad, and the modular ligand synthesis allows for flexible catalyst design. | 25,141,136 | [
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Quantitative estimation of renal function with dynamic contrast-enhanced MRI using a modified two-compartment model. | To establish a simple two-compartment model for glomerular filtration rate (GFR) and renal plasma flow (RPF) estimations by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A total of eight New Zealand white rabbits were included in DCE-MRI. The two-compartment model was modified with the impulse residue function in this study. First, the reliability of GFR measurement of the proposed model was compared with other published models in Monte Carlo simulation at different noise levels. Then, functional parameters were estimated in six healthy rabbits to test the feasibility of the new model. Moreover, in order to investigate its validity of GFR estimation, two rabbits underwent acute ischemia surgical procedure in unilateral kidney before DCE-MRI, and pixel-wise measurements were implemented to detect the cortical GFR alterations between normal and abnormal kidneys. The lowest variability of GFR and RPF measurements were found in the proposed model in the comparison. Mean GFR was 3.03±1.1 ml/min and mean RPF was 2.64±0.5 ml/g/min in normal animals, which were in good agreement with the published values. Moreover, large GFR decline was found in dysfunction kidneys comparing to the contralateral control group. Results in our study demonstrate that measurement of renal kinetic parameters based on the proposed model is feasible and it has the ability to discriminate GFR changes in healthy and diseased kidneys. | 25,141,138 | [
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Asynchrony of seasons: genetic differentiation associated with geographic variation in climatic seasonality and reproductive phenology. | Many organisms exhibit distinct breeding seasons tracking food availability. If conspecific populations inhabit areas that experience different temporal cycles in food availability spurred by variation in precipitation regimes, then they should display asynchronous breeding seasons. Thus, such populations might exhibit a temporal barrier to gene flow, which may potentially promote genetic differentiation. We test a central prediction of this hypothesis, namely, that individuals living in areas with more asynchronous precipitation regimes should be more genetically differentiated than individuals living in areas with more similar precipitation regimes. Using mitochondrial DNA sequences, climatic data, and geographical/ecological distances between individuals of 57 New World bird species mostly from the tropics, we examined the effect of asynchronous precipitation (a proxy for asynchronous resource availability) on genetic differentiation. We found evidence for a positive and significant cross-species effect of precipitation asynchrony on genetic distance after accounting for geographical/ecological distances, suggesting that current climatic conditions may play a role in population differentiation. Spatial asynchrony in climate may thus drive evolutionary divergence in the absence of overt geographic barriers to gene flow; this mechanism contrasts with those invoked by most models of biotic diversification emphasizing physical or ecological changes to the landscape as drivers of divergence. | 25,141,144 | [
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Nutrient limitation and physiology mediate the fine-scale (de)coupling of biogeochemical cycles. | Nutrients in the environment are coupled over broad timescales (days to seasons) when organisms add or withdraw multiple nutrients simultaneously and in ratios that are roughly constant. But at finer timescales (seconds to days), nutrients become decoupled if physiological traits such as nutrient storage limits, circadian rhythms, or enzyme kinetics cause one nutrient to be processed faster than another. To explore the interactions among these coupling and decoupling mechanisms, we introduce a model in which organisms process resources via uptake, excretion, growth, respiration, and mortality according to adjustable trait parameters. The model predicts that uptake can couple the input of one nutrient to the export of another in a ratio reflecting biological demand stoichiometry, but coupling occurs only when the input nutrient is limiting. Temporal nutrient coupling may, therefore, be a useful indicator of ecosystem limitation status. Fine-scale patterns of nutrient coupling are further modulated by, and potentially diagnostic of, physiological traits governing growth, uptake, and internal nutrient storage. Together, limitation status and physiological traits create a complex and informative relationship between nutrient inputs and exports. Understanding the mechanisms behind that relationship could enrich interpretations of fine-scale time-series data such as those now emerging from in situ solute sensors. | 25,141,147 | [
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Unexpected primary reactions for thermolysis of 1,1-diamino-2,2-dinitroethylene (FOX-7) revealed by ab initio calculations. | The primary thermolysis reactions of a promising insensitive explosive 1,1-diamino-2,2-dinitroethylene (DADNE, FOX-7) have been studied in the gas phase at a high level of theory (CCSD(T)-F12/aVTZ). Our calculations revealed that none of the conventional reactions (C-NO2 bond fission, nitro-nitrite and nitro-aci-nitro rearrangements) dominate thermolysis of FOX-7. On the contrary, two new decomposition pathways specific for this particular species that commenced with enamino-imino isomerization and intramolecular cyclization were found instead to be more feasible energetically. The activation barriers of these primary isomerization reactions were calculated to be 48.4 and 28.8 kcal/mol, while the activation energies of the overall decomposition pathways are predicted to be ∼49 and ∼56 kcal/mol, respectively. The new pathways can also be relevant for a wide series of unsaturated hydrocarbons substituted with both nitro- and amino-groups (e.g., triaminotrinitrobenzene, TATB). | 25,141,156 | [
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The lack of impact of peri-implantation or late gestation nutrient restriction on ovine fetal renal development and function. | Unbalanced nutrition during critical windows of development is implicated in determining the susceptibility to hypertension and cardiovascular disease in adult life, but the underlying mechanisms during fetal life have not been fully elucidated. We investigated the effects of moderate nutritional restriction during critical windows in gestation on late gestation fetal sheep growth, cardiovascular and renal renin-angiotensin system function. Ewes were fed 100% nutrient requirements (control), or 40-50% nutrient requirements during the peri-implantation period (1-31 days gestation (dGA), PI40 and PI50), or 50% nutrient requirements in late gestation (104-127 dGA). At 125 ± 2 dGA, fetal cardiovascular and renal function were measured at baseline, and during frusemide, angiotensin II (Ang II), phenylephrine and hypoxia challenges. Maternal undernutrition had no effect on fetal biometry, kidney weight, nephron number, basal cardiovascular function or cardiovascular and renal responses to frusemide. Fetal blood pressure response to Ang II was blunted in PI50 (P < 0.05), but not in PI40 groups. There was no difference between groups in the cardiovascular or endocrine response to hypoxia. The lack of effect of moderate undernutrition within key developmental windows of fetal kidney development on fetal renal structure and function suggests that renal mechanisms do not underlie our previous observations of cardiovascular dysfunction in adulthood following early-life undernutrition. | 25,141,168 | [
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Influence of bismuth oxide concentration on the pH level and biocompatibility of white Portland cement. | To investigate if there is a relation between the increase of bismuth oxide and the decrease of pH levels and an intensification of toxicity in the Portland cement. White Portland cement (WPC) was mixed with 0, 15, 20, 30 and 50% bismuth oxide, in weight. For the pH level test, polyethylene tubes were filled with the cements and immersed in Milli-Q water for 15, 30 and 60 days. After each period, the increase of the pH level was assessed. For the biocompatibility, two polyethylene tubes filled with the cements were implanted in ninety albino rats (n=6). The analysis of the intensity of the inflammatory infiltrate was performed after 15, 30 and 60 days. The statistical analysis was performed using the Kruskal-Wallis, Dunn and Friedman tests for the pH level and the Kruskal-Wallis and Dunn tests for the biological analysis (p<0.05). The results showed an increase of the pH level after 15 days, followed by a slight increase after 30 days and a decrease after 60 days. There were no significant statistical differences among the groups (p>0.05). For the inflammatory infiltrates, no significant statistical differences were found among the groups in each period (p>0.05). The 15% WPC showed a significant decrease of the inflammatory infiltrate from 15 to 30 and 60 days (p<0.05). The addition of bismuth oxide into Portland cement did not affect the pH level and the biological response. The concentration of 15% of bismuth oxide resulted in significant reduction in inflammatory response in comparison with the other concentrations evaluated. | 25,141,197 | [
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Clues for minimal hepatic encephalopathy in children with noncirrhotic portal hypertension. | In children with noncirrhotic extrahepatic portal vein obstruction (EHPVO), minimal hepatic encephalopathy (MHE) was reported in a few series, but neither is it routinely investigated nor does consensus about its diagnosis exist. In this prospective observational study we aimed at detecting the prevalence of MHE in children with EHPVO and providing a practical diagnostic protocol. A consecutive sample of 13 noncirrhotic children (age range 4-18 years) with EHPVO underwent a screening for MHE based on level of fasting ammonia, quantified electroencephalogram (EEG) evaluation, and a wide battery of 26 psychometric tests exploring learning ability, abstract reasoning, phonemic and semantic fluency, selective attention, executive functions, short-term verbal and visual memory, long-term verbal memory, and visuopractic ability. Five children had at least 2 altered psychometric tests. Selective attention, executive function, and short-term visual memory were the domains more frequently altered, and 4 tests were enough to detect 80% of these children. Fasting ammonia plasma level was increased in 6 children. EEG mean dominant frequency adjusted for age was associated with serum ammonia concentration (β = -0.44 ± 0.19, P < 0.05). As a whole, children with EHPVO showed trends for lower α (median 41% vs 49%) and higher θ power than controls (median 41% vs 49% and 29% vs 20%, respectively). MHE affects approximately 50% of children with EHPVO and, therefore, is worthwhile to be investigated. Three simple tools, serum ammonia, quantified EEG, and neuropsychological examination, focused on selective attention, executive function, and short-term visual memory can be used effectively in the evaluation of MHE in this setting. | 25,141,228 | [
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Gut microbiota and inflammatory bowel disease: the role of antibiotics in disease management. | Imbalances in the composition and number of bacteria in the gut microbiota have been implicated in inflammatory bowel disease (IBD), and modulation of the gut microbiota by probiotics and antibiotics in IBD has been an active area of research, with mixed results. This narrative review summarizes the findings of relevant publications identified using the PubMed database. Although antibiotics have been associated with an increased risk of IBD development and flares, several meta-analyses demonstrate that antibiotics are efficacious for the induction of remission and treatment of flares in patients with IBD. Data supporting their use include a large number of antibiotic studies in Crohn's disease and evidence suggests antibiotics are efficacious in both Crohn's disease and ulcerative colitis, although there are fewer studies of the latter. For Crohn's disease, antibiotics have been shown to be useful for the induction of remission and in the postoperative management of patients undergoing surgery. Additionally, patients with fistulizing disease, particularly perianal, can benefit from antibiotics administered short term. Both antimicrobials and probiotics have been shown to be useful for the treatment of pouchitis. Additional randomized controlled trials are needed to further elucidate the role of bacteria in IBD and to better inform clinicians about appropriate antibiotic therapies. | 25,141,239 | [
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A semipermeable enzymatic nanoreactor as an efficient modulator for reversible pH regulation. | Here we propose a new concept for the fabrication of a semipermeable enzymatic nanoreactor as an efficient modulator to reversibly switch the pH of an aqueous environment. We used amino-functionalized, expanded mesoporous silica nanoparticles (EMSN) as a model nanocarrier to load enzymes. In order to protect enzymes from the interference of a complicated environment, polyelectrolyte multilayers (PEMs) were coated on the surface of the EMSN through layer by layer (LbL) assembly. These PEMs can serve as semipermeable membranes, allowing small molecules to diffuse in and out freely while trapping the enzymes in the nanoreactors. Compared with traditional electrochemical stimulation or optical control methods, our enzymatic regulation platform is easy to operate without complicated instruments. In addition, this system can cover a wide range of pH values and conveniently regulate pH values by simply controlling the concentrations of catalysts or reactants. Meanwhile, this strategy could be generalized to other enzymes or nanocarriers to achieve reversible pH regulation for different purposes. The switched pH values can be implemented for the modulation of the conformational changes of nucleic acids and activation of the charge conversion in drug delivery applications. | 25,141,270 | [
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Risk of bias in trial-based economic evaluations: identification of sources and bias-reducing strategies. | The objectives of this article are first to give an overview of the risks of bias in trial-based economic evaluations and, second, to identify how key sources for bias can be revealed and overcome (i.e. what bias-reducing strategies might be employed) in future trial-based economic evaluations in the field of health psychology. Narrative review discussing sources of bias in trial-based economic evaluations and bias-reducing strategies. We identified 11 biases and assigned them to a particular trial phase. A distinction is made between pre-trial biases, biases during the trial and biases that are relevant after the actual trial. All potential forms of bias are discussed in detail and strategies are shown to detect and overcome these biases. In order to avoid bias in trial-based economic evaluations, one has to be aware of all the possible forms of bias. All stakeholders have to examine trial-based economic evaluations in a rigorous and stringent manner. This article can be helpful in this examination as it gives an overview of the possible biases which researchers should take into account. | 25,141,273 | [
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Relationship of preexisting influenza hemagglutination inhibition, complement-dependent lytic, and antibody-dependent cellular cytotoxicity antibodies to the development of clinical illness in a prospective study of A(H1N1)pdm09 Influenza in children. | The hemagglutination inhibition (HAI) antibody titer is considered the primary immune correlate of protection for influenza. However, recent studies have highlighted the limitations on the use of the HAI titer as a correlate in at-risk populations such as children and older adults. In addition to the neutralization of cell-free virus by antibodies to hemagglutinin and interference of virus release from infected cells by antibodies to neuraminidase, influenza virus-specific antibodies specifically can bind to infected cells and lyse virus-infected cells through the activation of complement or natural killer (NK) cells, via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent lysis (CDL). We evaluated preexisting HAI, CDL, and ADCC antibodies in young children enrolled in a prospective cohort study of dengue during the epidemic with influenza A(H1N1)pdm09 virus to determine associations between preexisting antibodies and the occurrence of clinical or subclinical influenza virus infection. Though both preexisting HAI and CDL antibodies were associated with protection against clinical influenza, our data suggested that CDL was not a better correlate than HAI. We found that ADCC antibodies behaved differently from HAI and CDL antibodies. Unlike HAI and CDL antibodies, preexisting ADCC antibodies did not correlate with protection against clinical influenza. In fact, ADCC antibodies were detected more frequently in the clinical influenza group than the subclinical group. In addition, in contrast to HAI and CDL antibodies, HAI and the ADCC antibodies titers did not correlate. We also found that ADCC, but not CDL or HAI antibodies, positively correlated with the ages of the children. | 25,141,276 | [
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Generation and Evaluation of a Genome-Scale Metabolic Network Model of Synechococcus elongatus PCC7942. | The reconstruction of genome-scale metabolic models and their applications represent a great advantage of systems biology. Through their use as metabolic flux simulation models, production of industrially-interesting metabolites can be predicted. Due to the growing number of studies of metabolic models driven by the increasing genomic sequencing projects, it is important to conceptualize steps of reconstruction and analysis. We have focused our work in the cyanobacterium Synechococcus elongatus PCC7942, for which several analyses and insights are unveiled. A comprehensive approach has been used, which can be of interest to lead the process of manual curation and genome-scale metabolic analysis. The final model, iSyf715 includes 851 reactions and 838 metabolites. A biomass equation, which encompasses elementary building blocks to allow cell growth, is also included. The applicability of the model is finally demonstrated by simulating autotrophic growth conditions of Synechococcus elongatus PCC7942. | 25,141,288 | [
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Predicting progression of Alzheimer's disease using ordinal regression. | We propose a novel approach to predicting disease progression in Alzheimer's disease (AD)--multivariate ordinal regression--which inherently models the ordered nature of brain atrophy spanning normal aging (CTL) to mild cognitive impairment (MCI) to AD. Ordinal regression provides probabilistic class predictions as well as a continuous index of disease progression--the ORCHID (Ordinal Regression Characteristic Index of Dementia) score. We applied ordinal regression to 1023 baseline structural MRI scans from two studies: the US-based Alzheimer's Disease Neuroimaging Initiative (ADNI) and the European based AddNeuroMed program. Here, the acquired AddNeuroMed dataset was used as a completely independent test set for the ordinal regression model trained on the ADNI cohort providing an optimal assessment of model generalizability. Distinguishing CTL-like (CTL and stable MCI) from AD-like (MCI converters and AD) resulted in balanced accuracies of 82% (cross-validation) for ADNI and 79% (independent test set) for AddNeuroMed. For prediction of conversion from MCI to AD, balanced accuracies of 70% (AUC of 0.75) and 75% (AUC of 0.81) were achieved. The ORCHID score was computed for all subjects. We showed that this measure significantly correlated with MMSE at 12 months (ρ = -0.64, ADNI and ρ = -0.59, AddNeuroMed). Additionally, the ORCHID score can help fractionate subjects with unstable diagnoses (e.g. reverters and healthy controls who later progressed to MCI), moderately late converters (12-24 months) and late converters (24-36 months). A comparison with results in the literature and direct comparison with a binary classifier suggests that the performance of this framework is highly competitive. | 25,141,298 | [
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Role of serum myeloperoxidase, CPK, CK-MB, and cTnI tests in early diagnosis of myocardial ischemia during ERCP. | Some patients may experience retrosternal pain during ERCP, which may be a pioneer of a serious myocardial problem, and early diagnosis is very important for the prognosis and management. In the study, we aimed to investigate the role of serum cardiac biomarkers, such as myeloperoxidase (MPO), creatine phospokinase (CPK), creatine kinase- myocardial band (CK-MB), and cTnI, on early diagnosis of myocardial ischemia during endoscopic retrograde cholangio pancreaticograpy (ERCP) procedures. In this prospective observational study, ERCP patients were separated into ischemic cardiac (n:48) and non-ischemic (n:76) groups. Serious cardiac, kidney, and liver disease patients were excluded from the study. Changes in electrocardigrapy (ECG), blood pressure, pulse rate, oxygen saturation, and serum MPO, CPK, CK-MB, and cTnI levels were investigated before and after the ERCP. Results were evaluated statistically (p<0.05). Mean age was 59.76±16.62 (55♀, 69♂). Only one patient had clinically unimportant retrosternal pain (0.8%). ST-elevation was detected in 10.4% (n:5), ST-depression in 12.5% (n:6), and negative-T in 31.3% (n:15) of ischemic patients during ERCP. Systolic and diastolic blood pressure and pulse rates in both groups and oxygen saturations in the ischemic group were reduced after ERCP. Significance was not detected with MPO and CPK tests. CK-MB levels showed an increase after the ERCP in the non-ischemic group (p<0.001). cTnI means were higher among the ischemics when pre- and post-ERCP periods (p:0.001) were compared. Clinically unimportant retrosternal pain, T negativity, and ST segment changes as well as reduced systolic, diastolic blood pressure, and heart rates can be seen during ERCP. MPO and CPK levels remain insignificant if myocardial injury does not develop. Increased CK-MB levels in non-ischemic patients and increased cTnI levels in ischemics may be seen. | 25,141,318 | [
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Mutatis mutandis: are we diagnosing too many people with non-celiac gluten sensitivity? Multiple case report. | We report three patients presenting with gluten-related signs and symptoms. Since villous height/crypt depth ratio, intraepithelial lymphocyte count, and serum antibody tests were not diagnostic for celiac disease (CD), a diagnosis of non-celiac gluten sensitivity (NCGS) was suggested. On the other hand, antibodies suggestive for CD surprisingly showed positive results in the duodenal biopsy organ culture of all three cases. The reported cases suggest the precious potential role that organ culture systems may play in differentiating CD from NCGS. This method should be recommended when gluten-related disorders are suspected in order to reduce the inappropriate diagnosis of NCGS. | 25,141,323 | [
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Could thermal sensitivity of mitochondria determine species distribution in a changing climate? | For many aquatic species, the upper thermal limit (Tmax) and the heart failure temperature (THF) are only a few degrees away from the species' current environmental temperatures. While the mechanisms mediating temperature-induced heart failure (HF) remain unresolved, energy flow and/or oxygen supply disruptions to cardiac mitochondria may be impacted by heat stress. Recent work using a New Zealand wrasse (Notolabrus celidotus) found that ATP synthesis capacity of cardiac mitochondria collapses prior to T(HF). However, whether this effect is limited to one species from one thermal habitat remains unknown. The present study confirmed that cardiac mitochondrial dysfunction contributes to heat stress-induced HF in two additional wrasses that occupy cold temperate (Notolabrus fucicola) and tropical (Thalassoma lunare) habitats. With exposure to heat stress, T. lunare had the least scope to maintain heart function with increasing temperature. Heat-exposed fish of all species showed elevated plasma succinate, and the heart mitochondria from the cold temperate N. fucicola showed decreased phosphorylation efficiencies (depressed respiratory control ratio, RCR), cytochrome c oxidase (CCO) flux and electron transport system (ETS) flux. In situ assays conducted across a range of temperatures using naive tissues showed depressed complex II (CII) and CCO capacity, limited ETS reserve capacities and lowered efficiencies of pyruvate uptake in T. lunare and N. celidotus. Notably, alterations of mitochondrial function were detectable at saturating oxygen levels, indicating that cardiac mitochondrial insufficiency can occur prior to HF without oxygen limitation. Our data support the view that species distribution may be related to the thermal limits of mitochondrial stability and function, which will be important as oceans continue to warm. | 25,141,346 | [
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Evaluating the efficacy of Tui Na in treatment of childhood anorexia: a meta-analysis. | Medical practitioners are now seeing more children younger than 15 y who are developing childhood anorexia. Hua Tuo chiropractic treatments are an ancient and practical massage therapy and are a type of Tui Na therapy, which has been used for curing childhood anorexia for thousands of years in China. Research literature suggests that chiropractic care produces outcomes at least comparable with alternative treatments. The research team intended to perform a systematic review to identify and synthesize evidence on the efficacy of Tui Na for treatment of childhood anorexia. Systematic searches were conducted for studies evaluating Tui Na therapy in electronic databases MEDLINE, EMBASE, PsychINFO, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, the Midwives Information and Resource Service, the Health Management Information Consortium, the Health Management and Information Service, PubMed, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), the Chinese Scientific Journal Database VIP, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Chinese Clinical Trial Register-from inception to November 2011. The research team hand-searched reference lists and journals, extracted data from the papers, and assessed the quality of the research. Participants of the reviewed studies were infants and children younger than 15 y. Of the 109 papers identified, 3 papers reported on randomized, controlled trials (RCTs) involving 332 patients; 45 covered cohort or quasi-experimental studies; and 61 discussed nonintervention studies. Meta-analysis results from the 3 RCTs showed that Tui Na can improve the curative effect compared with oral medicine that is used for infants and young children with anorexia and can also increase a child's weight. The level of evidence reported was mixed, but given the available evidence, the research team concluded that Tui Na therapy was a viable intervention that could benefit infants and young children with anorexia. No serious adverse events were reported. Larger randomized, controlled trials are required to explore the effects of Tui Na therapy for treatment of childhood anorexia further. | 25,141,371 | [
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The use of bioimpedance spectroscopy to monitor therapeutic intervention in patients treated for breast cancer related lymphedema. | We performed a multi-institutional analysis to evaluate the ability of bioimpedance spectroscopy (BIS) to capture the impact of lymphedema treatment compared with observation alone in the management of breast cancer related lymphedema (BCRL). We utilized a retrospective review of 50 patients with breast cancer who were evaluated with BIS at baseline and following loco-regional treatment. An analysis was performed comparing changes in L-Dex scores for those patients undergoing treatment for BCRL (n=13) versus those not undergoing intervention (n=37). A second (subset) analysis was also performed on all patients with elevated L-Dex scores compared to baseline prior to undergoing loco-regional treatment (n=32). When comparing the cohort treated for BCRL to those not treated, L-Dex scores were significantly reduced (-4.3 v. 0.1, p=0.005) in the period following intervention (for treated patients). For the subset of patients with elevated L-Dex scores postoperation, the change in L-Dex score following BCRL treatment was significantly reduced (-5.8 v. 0.1, p=0.001) compared with the group observed that had elevated postsurgical L-Dex scores. In this analysis, BIS was able to detect early onset lymphedema and subsequently significant changes (reductions) in L-Dex scores directly related to intervention for BCRL compared with observation alone. | 25,141,461 | [
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Structural relationship between microlymphatic and microvascullar blood vessels in the rabbit ventricular myocardium. | We investigated the distribution and relationship between draining lymphatic vessels, lymphatic capillaries, and microvascular blood vessels in rabbit ventricular tissue. The left and right ventricular tissue from 15 healthy adult rabbits was obtained, processed, and sectioned for analysis. 5'-nucleotidase-alkaline phosphatase (5'-Nase-Alpase) double staining was first used to identify lymphatic and blood vessels. Dual fluorescent immunohistochemical technique was then utilized with lymphatic endothelial cell marker podoplanin and blood vascular marker PAL-E. In addition, five ventricular samples were examined for ultrastructure using transmission electron microscopy (TEM). Draining lymphatic vessels and both lymphatic and blood capillaries were observed in the ventricular tissue. The lumens of draining lymphatic vessels were larger and irregular while the lymphatic capillaries were small in diameter and abundant. All lymphatic vessels were located among blood capillaries in the myocardium and aligned with the longitudinal axis of myocardial cells. The immunofluorescence double staining demonstrated that draining lymphatic vessels, lymphatic capillaries, and microvascular blood vessels were adjacent to each other and the cardiac myocyte with a ratio of lymphatic to microvascular blood vessels of approximately 1:1. This study suggests that lymphatic and blood capillaries exist in abundance and in nearly identical numbers in the ventricular myocardium and that they interweave with each other to comprise a complicated vessel network. | 25,141,462 | [
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Intracranial venous drainage through spinal veins. | There is extensive collateral networking at the craniocervical junction with a substantial anatomical and functional continuity between the veins, venous sinuses, and venous plexuses of the brain and spine. The predominant pathway for intracranial blood outflow may depend on the level and degree of obstruction. We are presenting an unusual case of predominant egress of intracranial blood through enlarged spinal canal venous collaterals due to thrombosis of the intracranial venous sinuses. Awareness of this unique pattern of venous drainage of the cranium is important and should be considered in the differential diagnosis of spinal arteriovenous malformation (AVM) or arteriovenous fistula (AVF). Magnetic Resonance Venography (MRV) of the brain should be considered to exclude intracranial thrombosis in these cases. | 25,141,475 | [
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Therapy-resistant metastasizing anaplastic spermatocytic seminoma: a cytogenetic hybrid: a case report. | Anaplastic spermatocytic seminoma is a rare variant of the conventional spermatocytic seminoma, with only 6 cases reported up to now. The anaplastic variant contains only the medium-sized cell type, hallmarked by large-sized nucleoli, whereas the small lymphocyte-like and giant cells typical of the conventional spermatocytic seminoma are lacking. We report herein an unusual case of a 40-year-old man with an anaplastic spermatocytic seminoma which metastasized first to the retroperitoneal lymph nodes and, something never before reported, subsequently to the lung and other organs. The immunophenotype with c-kit and SALL4 positive and PLAP, as well OCT 3/4 negative tumor cells were identical to those of conventional spermatocytic seminoma. Cytogenetically the tumor cells showed a gain of chromosome 9, typical for spermatocytic seminoma, but simultaneously also the short arm 12p were overexpressed--an overexpression crucial to the aggressive behavior of seminomas and other nonseminomatous tumors but never before encountered in spermatocytic seminoma. The current opinion is that seminoma and nonseminomatous germ cell tumors develop from a common primitive progenitor cell, whereas spermatocytic seminomas develop from differentiated spermatogonia. The herein presented cytogenetic hybrid tumor shows that a crossover between the two different histogenetic "tracks" is possible. | 25,141,494 | [
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Walking and stair climbing abilities in individuals after chronic stroke with and without mental health problem. | To compare muscle strength, balance, walking and stair climbing abilities among individuals after chronic stroke with or without mental health problems; to describe their physiological response after stress stimulation. Subjects who had their first stroke more than one year ago were classified for mental health problems according to the Depression Anxiety Stress Scale-21. Lower extremity muscle strength of the quadriceps and plantar flexors, was measured by dynamometer Balance and walking performance was measured by the Berg Balance Scale (BBS), 10-m walk test and timing of stair climbing. Community participation and spiritual well-being were measured. The physiological response of stress stimulation was assessed by the long stress test protocol of the biofeedback device. Forty-five subjects with chronic stroke aged 40-80 years were grouped by with (n = 25) and without mental health problems (n = 20). Significant differences were found in quadriceps muscle strength, BBS, walking and stair climbing speed, community participation and spiritual well-being between two groups. In the stress stimulus phase, the electromyography and heart rate variability demonstrated significant difference between those with and without stress. Individuals with chronic stroke with mental health problems demonstrated decreased quadriceps muscle strength, balance and locomotor performances. | 25,141,520 | [
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Weight and body mass index in men and age and height in women relate to difficulty and ability in performing activities in community-living Thai elders. | To compare difficulty between male and female community-living elderly in performing activities (DDA), ability in performing living activities (ADA) and balance, and to explore associations among them related to age, weight, height and body mass index (BMI). In all, 1,964 participants (646 men, 1,318 women) aged 60 or over reported their age, weight, height, DDA, ADA, and performed the Berg balance scale (BBS). Male and female elderly were divided into low and high BBS groups (BBS cutoff point score: male = 26,female = 28.5). The Mann-Whitney U test was conducted to compare age, weight, height, BMI, DDA, ADA and the BBS. Associations among them were tested using Spearman's rank correlation. A low BBS score represented high risk of falling and vice versa for a high BBS score. No difference in DDA, ADA, and BBS was found associated with sex. Weight and BMI correlated to DDA, ADA, and BBS in elderly men with high fall risk, while age and height was related to DDA and ADA, respectively in elderly women with low fall risk. Male and female community-dwelling Thai elders were similar in ability in performing activities and balance. Weight and BMI was important among elderly men, whereas age and height was significant among women. | 25,141,523 | [
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Online self-report questionnaire on computer work-related exposure (OSCWE): validity and internal consistency. | To develop an online, self-report questionnaire on computer work-related exposure (OSCWE) and to determine the internal consistency, face and content validity of the questionnaire. The online, self-report questionnaire was developed to determine the risk factors related to musculoskeletal disorders in computer users. It comprised five domains: personal, work-related, work environment, physical health and psychosocial factors. The questionnaire's content was validated by an occupational medical doctor and three physical therapy lecturers involved in ergonomic teaching. Twenty-five lay people examined the feasibility of computer-administered and the user-friendly language. The item correlation in each domain was analyzed by the internal consistency (Cronbach's alpha; alpha). The content of the questionnaire was considered congruent with the testing purposes. Eight hundred and thirty-five computer users at the PTT Exploration and Production Public Company Limited registered to the online self-report questionnaire. The internal consistency of the five domains was: personal (alpha = 0.58), work-related (alpha = 0.348), work environment (alpha = 0.72), physical health (alpha = 0.68) and psychosocial factor (alpha = 0.93). The findings suggested that the OSCWE had acceptable internal consistency for work environment and psychosocial factors. The OSCWE is available to use in population-based survey research among computer office workers. | 25,141,533 | [
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Immediate effects of trunk stabilizer muscles training on muscle response time in individuals with non-specific chronic low back pain. | To investigate immediate effects of biofeedback training on motor control performance in participants with nonspecific chronic low back pain. RCT was conducted. The training group received isolated and co-contraction training of trunk stabilizers in lying on the left side, sitting on stool and sitting on a gymnastic ball, while the control group was asked to rest comfortably on a chair. Trunk muscles response time during rapid arm movement test was recorded using surface electromyography. Two-way ANOVA and Bonferroni post hoc test were used to detect changes within and between groups. In the training group, the trunk muscles response times were significantly decreased after training when compared with those in the control group (p<0.05). Trunk stabilizer training has a beneficial effect on motor response time of the trunk muscles. The long-term effects of exercise should be further considered with a larger sample size. | 25,141,535 | [
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The role of number of tasks in determining the relevance of information. | Our objective was to explore the value of considering the number of tasks that use a piece of information when calculating the relevance information has to an operator. Whereas frequency and criticality of information are often identified as information attributes, the number of tasks that use the information is rarely considered. We calculated the relevance of pieces of information in air traffic control using criticality and frequency, and compared it to a formula that also considered the number of tasks. Including number of tasks resulted in information ranking that better accounted for aircraft relevant information, and better supported the information needs of air traffic controllers as determined by judgments of controllers. The attribute of number of tasks is valuable in calculating the relevance of information. Application: Interface designers should consider the number of tasks that use a particular piece of information when determining the placement of information within a display. | 25,141,598 | [
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Emergency medical equipment storage: benefits of visual cues tested in field and simulated settings. | We tested the effectiveness of an illustrated divider ("the divider") for bedside emergency equipment drawers in an intensive care unit (ICU). In Study I, we assessed whether the divider increases completeness and standardizes the locations of emergency equipment within the drawer. In Study 2, we investigated whether the divider decreases nurses' restocking and retrieval times and decreases their workload. Easy access to fully stocked emergency equipment is important during emergencies. However, inefficient equipment storage and cognitively demanding work settings might mean that drawers are incompletely stocked and access to items is slow. A pre-post-post study investigated drawer completeness and item locations before and after the introduction of the divider to 30 ICU drawers. A subsequent experiment measured item restocking time, item retrieval time, and subjective workload for nurses. At 2 weeks and 10 weeks after the divider was introduced, the completeness of the drawer increased significantly compared with before the divider was introduced. The divider decreased the variability of the locations of the 17 items in the drawer to 16% of its original value. Study 2 showed that restocking times but not retrieval times were significantly faster with the divider present For both tasks, nurses rated their workload lower with the divider. The divider improved the standardization and completeness of emergency equipment. In addition, restocking times and workload were decreased with the divider. Redesigning storage for certain equipment using human factors design principles can help to speed and standardize restocking and ease access to equipment. | 25,141,599 | [
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Steering in a random forest: ensemble learning for detecting drowsiness-related lane departures. | The aim of this study was to design and evaluate an algorithm for detecting drowsiness-related lane departures by applying a random forest classifier to steering wheel angle data. Although algorithms exist to detect and mitigate driver drowsiness, the high rate of false alarms and missed detection of drowsiness represent persistent challenges. Current algorithms use a variety of data sources, definitions of drowsiness, and machine learning approaches to detect drowsiness. We develop a new approach for detecting drowsiness-related lane departures using steering wheel angle data that employ an ensemble definition of drowsiness and a random forest algorithm. Data collected from 72 participants driving the National Advanced Driving Simulator are used to train and evaluate the model. The model's performance was assessed relative to a commonly used algorithm, percentage eye closure (PERCLOS). The random forest steering algorithm had a higher classification accuracy and area under the receiver operating characteristic curve than PERCLOS and had comparable positive predictive value. The algorithm succeeds at identifying two key scenarios associated with the drowsiness detection task. These two scenarios consist of instances when drivers depart their lane because they fail to modulate their steering behavior according to the demands of the simulated road and instances when drivers correctly modulate their steering behavior according to the demands of the road. The random forest steering algorithm is a promising approach to detect driver drowsiness. The algorithm's ties to consequences of drowsy driving suggest that it can be easily paired with mitigation systems. | 25,141,601 | [
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Domestication of Mahseer (Tor soro) in Indonesia. | Mahseer is an economically important fish in the world with a distribution from the Himalayan Mountains up to Southeast Asia. One species of Masheer is Tor soro in the Indonesian Archipelago. For a long time, T. soro has been collected from the wild and now is becoming rare. In addition, the degradation of its habitat is another problem. Hence, it is urgent that this species is saved from extinction. Domestication of T. soro from North Sumatra has been conducted since 1996. This paper reports the results of domestication of T. soro starting from collecting live specimens, genetic and morphometric characterizations, evaluation to breeding, and growing out. In 2010, domestication was successful to produce a second generation of young broodstocks and now the breeding technology is being shared with several provinces where T. soro exist. | 25,141,656 | [
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Diverse thermoresponsive behaviors of uncharged UCST block copolymer micelles in physiological medium. | Three amphiphilic diblock copolymers, representative of three types of block copolymer (BCP) design, were synthesized using reversible addition-fragmentation chain-transfer (RAFT) polymerization. All of them have a same uncharged block of a random copolymer of commercially available acrylamide and acrylonitrile, P(AAm-co-AN), and exhibit a composition-tunable upper critical solution temperature (UCST). We show that by coupling a common P(AAm-co-AN) block with either hydrophobic polystyrene (PS) or hydrophilic poly(dimethylacrylamide) (PDMA) or the lower critical solution temperature (LCST) polymer of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), the BCP micelles formed in water or in phosphate buffered saline (PBS) can display diverse and UCST-dictated changes in response to temperature variations, such as the reversible dispersion-aggregation of micelles, dissolution-formation of micelles, and reversal of micelle core and corona. The results point out that P(AAm-co-AN) is a robust UCST polymer that can be introduced into controlled polymer architectures producible by RAFT, the same way as using the extensively studied LCST counterparts like poly(N-isopropylacrylamide) (PNIPAM). This ability should make the door wide open to exploring new thermosensitive polymers based on the thermosensitivity opposite to the LCST. | 25,141,758 | [
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XacR - a novel transcriptional regulator of D-xylose and L-arabinose catabolism in the haloarchaeon Haloferax volcanii. | The haloarchaeon Haloferax volcanii degrades D-xylose and L-arabinose via oxidative pathways to α-ketoglutarate. The genes involved in these pathways are clustered and were transcriptionally upregulated by both D-xylose and L-arabinose suggesting a common regulator. Adjacent to the gene cluster, a putative IclR-like transcriptional regulator, HVO_B0040, was identified. It is shown that HVO_B0040, designated xacR, encodes an activator of both D-xylose and L-arabinose catabolism: in ΔxacR cells, transcripts of genes involved in pentose catabolism could not be detected; transcript formation could be recovered by complementation, indicating XacR dependent transcriptional activation. Upstream activation promoter regions and nucleotide sequences that were essential for XacR-mediated activation of pentose-specific genes were identified by in vivo deletion and scanning mutagenesis. Besides its activator function XacR acted as repressor of its own synthesis: xacR deletion resulted in an increase of xacR promoter activity. A palindromic sequence was identified at the operator site of xacR promoter, and mutation of this sequence also resulted in an increase and thus derepression of xacR promoter activity. It is concluded that the palindromic sequence represents the binding site of XacR as repressor. This is the first report of a transcriptional regulator of pentose catabolism in the domain of archaea. | 25,141,768 | [
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Lower heart rate variability predicts increased level of C-reactive protein 4 years later in healthy, nonsmoking adults. | Inflammation and vagally mediated heart rate variability (vmHRV) have been implicated in a number of conditions including diabetes and cardiovascular disease. Consistent with the inflammatory reflex termed the 'cholinergic anti-inflammatory pathway', numerous cross-sectional studies have demonstrated negative associations between vmHRV and inflammatory markers such as C-reactive protein (CRP). The only prospective study, however, showed the opposite: higher CRP at baseline predicted higher high-frequency heart rate variability (HF-HRV) at follow-up. Thus, additional studies are needed to examine the prospective association between vmHRV and CRP. Healthy employees participated in a voluntary on-site health assessment. Blood samples and ambulatory heart rate recordings were obtained, and night-time HF-HRV was calculated. Useable heart rate data were available in 2007 for 106 nonsmoking employees (9% women; age 44.4 ± 8 years), all of whom returned for an identical follow-up health assessment in 2011. Bootstrapped (500 replications) bivariate (r) and partial Pearson's correlations (ppc) adjusting for sex, age and body mass index at baseline (2007) were calculated. Zero-order correlations indicated that higher HF-HRV was associated with lower levels of CRP at both time-points (2007: r = -0.19, P < 0.05; 2011: r = -0.34, P < 0.001). After adjustment, HF-HRV remained a significant predictor of CRP (ppc = -0.20, P < 0.05). In this study, we have provided in vivo support for the cholinergic anti-inflammatory pathway in humans. Cardiac vagal modulation at baseline predicts level of CRP 4 years later. Our findings have important implications for the role of vmHRV as a risk factor for cardiovascular disease morbidity and mortality. Interventions targeted at vmHRV might be useful in the prevention of diseases associated with elevated systemic inflammation. | 25,141,771 | [
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Prevalence and validity of self-reported smoking in Indigenous and non-Indigenous young adults in the Australian Northern Territory. | In this study, we used data from Australia's Northern Territory to assess differences in self-reported smoking prevalence between the Indigenous and non-Indigenous populations. We also used urinary cotinine data to assess the validity of using self-reported smoking data in these populations. The Aboriginal Birth Cohort (ABC) is a prospective study of 686 Aboriginal babies born in Darwin 1987-90. The Top End Cohort (TEC) is a study of non-Indigenous adolescents, all born in Darwin 1987-91. In both studies, participants aged between 16 and 21 years, were asked whether they smoked. Urinary cotinine measurements were made from samples taken at the same visits. Self-reported smoking prevalence was 68% in the ABC and 14% in the TEC. Among the self-reported non-smokers, the median cotinine levels were higher in the ABC (33 ng/ml) than in the TEC (5 ng/ml), with greater percentages of reported non-smokers in the under 50 ng/ml group in the TEC than in the ABC CONCLUSIONS: Prevalence of smoking was much higher in the ABC than in the TEC. The higher cotinine levels in ABC non-smokers may reflect an underestimated prevalence, but is also likely to reflect higher levels of passive smoking. A broader approach encompassing social, cultural and language factors with increased attention to smoking socialisation factors is required. | 25,141,772 | [
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Evaluation of a new person-centered integrated care model in psychiatry. | The present study evaluated a new integrated treatment concept offering inpatient care, acute psychiatric day hospital and outpatient treatment by the same therapeutic team. 178 patients participated in this randomized controlled trial. Data on psychopathology, global and social functioning, patient satisfaction, continuity of care and administrative data was gathered on admission, throughout the course of treatment, upon discharge and at 1-year follow-up. In addition, the physicians in charge rated the therapeutic relationship. The data analysis consists of group-wise comparisons and regression analyses (cross-tabulations and χ(2) test statistics for categorical data and Mann-Whitney U tests for continuous data). Differences between groups over time were analyzed with a series of generalized linear mixed model. The integrated care group showed a significant reduction in psychopathological impairment (20.7%) and an improvement of psychosocial functioning (36.8%). The mean number of days before re-admission was higher in the control group when compared to the integrated care group (156.8 vs. 91.5). There was no difference in the number of re-admissions and days spent in psychiatric institutions. This new approach offers a treatment model, which facilitates continuity of care. Beside it improves psychopathological outcome measures and psychosocial functioning in patients with mental illness. | 25,141,779 | [
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The developmental origins of sarcopenia: from epidemiological evidence to underlying mechanisms. | Sarcopenia is defined as the loss of skeletal muscle mass and strength with age. There is increasing recognition of the serious health consequences in terms of disability, morbidity and mortality as well as major healthcare costs. Adult determinants of sarcopenia including age, gender, size, levels of physical activity and heritability have been well described. Nevertheless, there remains considerable unexplained variation in muscle mass and strength between older adults that may reflect not only the current rate of loss but the peak attained earlier in life. To date most epidemiological studies of sarcopenia have focused on factors modifying decline in later life; however, a life course approach to understanding sarcopenia, additionally, focuses on factors operating earlier in life including developmental influences. The epidemiological evidence linking low birth weight with lower muscle mass and strength is strong and consistent with replication in a number of different groups including children, young and older adults. However, most of the evidence for the cellular, hormonal, metabolic and molecular mechanisms underlying these associations comes from animal models. The next stage is to translate the understanding of mechanisms from animal muscle to human muscle enabling progress to be made not only in earlier identification of individuals at risk of sarcopenia but also in the development of beneficial interventions across the life course. | 25,141,783 | [
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Searching for very early precursors of autism spectrum disorders: the Hamamatsu Birth Cohort for Mothers and Children (HBC). | Autism spectrum disorders (ASD) are life-long neurodevelopmental conditions. The pathophysiology is poorly understood, and the clinical diagnosis can only be made through behavioural assessments. The prevalence of ASD has increased eight-fold over the last three decades. Paralleling this rise, research interest in the disorder has been accumulating, centering on two aspects: risk factors that would explain the increase in prevalence, and precursors that could predict an emergence of ASD prior to 2 years of age. As regard factors responsible for the increased prevalence, an increasing trend of low birthweight (4.2% in 1980 v. 9.6% in 2006 at Japan) and advanced paternal age at birth are potentially implicated. To explore these issues, and to yield an early diagnostic algorithm for ASD, the authors initiated the ongoing Hamamatsu Birth Cohort for Mothers and Children (HBC) in 2007. The strengths of the HBC include frequent, direct face-to-face assessments of all the participating mothers and children during the first 4 years of life (12 assessments); this depth of assessments will disclose subtle changes in the developmental domains of individuals with ASD, which might otherwise be overlooked. A total of 1200 pregnant women are to be recruited by the end of 2010. Assembled information comprises a range of variables related to the mother's characteristics and child development. The comprehensiveness of the HBC will provide an informative data source that will elucidate early trajectories of children with ASD in addition to revealing detailed, developmental properties of typically developing children. | 25,141,784 | [
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Study protocol: the JEU cohort study--transversal multiaxial evaluation and 5-year follow-up of a cohort of French gamblers. | There is abundant literature on how to distinguish problem gambling (PG) from social gambling, but there are very few studies of the long-term evolution of gambling practice. As a consequence, the correlates of key state changes in the gambling trajectory are still unknown. The objective of the JEU cohort study is to identify the determinants of key state changes in the gambling practice, such as the emergence of a gambling problem, natural recovery from a gambling problem, resolution of a gambling problem with intermediate care intervention, relapses or care recourse. The present study was designed to overcome the limitations of previous cohort study on PG. Indeed, this longitudinal case-control cohort is the first which plans to recruit enough participants from different initial gambling severity levels to observe these rare changes. In particular, we plan to recruit three groups of gamblers: non-problem gamblers, problem gamblers without treatment and problem gamblers seeking treatment.Recruitment takes place in various gambling places, through the press and in care centers. Cohort participants are gamblers of both sexes who reported gambling on at least one occasion in the previous year and who were aged between 18 and 65. They were assessed through a structured clinical interview and self-assessment questionnaires at baseline and then once a year for five years. Data collection comprises sociodemographic characteristics, gambling habits (including gambling trajectory), the PG section of the DSM-IV, the South Oaks Gambling Screen, the Gambling Attitudes and Beliefs Survey - 23, the Mini International Neuropsychiatric Interview, the Wender-Utah Rating Scale-Child, the Adult ADHD Self-report Scale, somatic comorbidities (especially current treatment and Parkinson disease) and the Temperament and Character Inventory - 125. The JEU cohort study is the first study which proposes to identify the predictive factors of key state changes in gambling practice. This is the first case-control cohort on gambling which mixes non-problem gamblers, problem gamblers without treatment and problem gamblers seeking treatment in almost equal proportions. This work may help providing a fresh perspective on the etiology of pathological gambling, which may provide support for future research, care and preventive actions. (ClinicalTrials.gov): NCT01207674. | 25,141,820 | [
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Direct measurement of interaction forces between charged multilamellar vesicles†. | Depletion-attraction induced adhesion of two giant (∼ 40 μm), charged multilamellar vesicles is studied using a new Cantilevered-Capillary Force Apparatus, developed in this laboratory. The specific goal of this work is to investigate the role of dynamics in the adhesion and de-adhesion processes when the vesicles come together or are pulled apart at a constant velocity. Hydrodynamic effects are found to play an important role in the adhesion and separation of vesicles at the velocities that are studied. Specifically, a period of hydrodynamically controlled drainage of the thin film between vesicles is observed prior to adhesion, and it is shown that the force required to separate a pair of tensed, adhering vesicles increases with increasing separation velocity and membrane tension. It is also shown that the work done to separate the vesicles increases with separation velocity, but exhibits a maximum as the membrane tension is varied. | 25,141,827 | [
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Metal artifact reduction sequence MRI abnormalities occur in metal-on-polyethylene hips. | To determine the importance of MRI abnormalities in metal-on-metal (MoM) bearings, it is important to understand the baseline features of this diagnostic tool in conventional metal-on-polyethylene (MoP) bearings. What are the frequency, size, and types of MRI-documented adverse local tissue reactions in asymptomatic patients with MoP bearings? We recruited 50 patients 5 years after a MoP total hip arthroplasty from a pool of patients in our joint registry who had a Harris hip score of >90. To be included, patients had to be without pain and have adequate radiographs. Our data set included 50 asymptomatic patients with MoP bearings who underwent a metal artifact reduction sequence MRI. MRI abnormalities were seen in 14 of 50 (28%) asymptomatic patients who were studied. Thirteen of the 14 abnormalities were cystic thin-walled lesions with a mean of 18 cm3 (range, 1-79 cm3). MRI abnormalities were noted in nearly one-third of asymptomatic patients with MoP bearings. Decisions concerning revision of MoM bearings should not be based on isolated MRI findings because MRI abnormalities are commonly seen regardless of bearing type. A number of factors should determine the need for intervention including pain, mechanical symptoms, abductor weakness, component type, component position, and ion levels as well as MRI findings. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. | 25,141,843 | [
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Partner notification among men who have sex with men and heterosexuals with STI/HIV: different outcomes and challenges. | Partner notification effectiveness among index clients diagnosed with HIV, syphilis and/or gonorrhoea at sexually transmitted infection (STI) clinics was evaluated between 2010 and 2012. We explored percentages of identifiable, notified and tested partners by sexual preference and gender. Partner notification trends were studied using the national STI database. Men who have sex with men (n = 304), heterosexual men (n = 33) and women (n = 35) reported, respectively, 6.7, 3.8 and 2.3 partners per index. Percentages of identifiable partners differed between groups (men who have sex with men: 46%, heterosexual men: 63%, women: 87%, p < 0.001). The percentage of notified partners (of those identifiable) was lowest for heterosexual men (76%; men who have sex with men: 92%; women: 83%; p < 0.001). STI positivity rates among notified partners were high: 33%-50% depending on sexual preference. Among men who have sex with men, having HIV was associated with not notifying all identifiable partners. Percentages of notified clients at STI clinics increased between 2010 and 2012: from 13% to 19% among men who have sex with men, from 13% to 18% among heterosexual men and from 8% to 11% among women (p < 0.001 for all groups). The percentage of STI/HIV detected through partner notification increased among men who have sex with men (from 22% to 30%) and women (from 25% to 29%; p < 0.001). Unidentifiable partners among men who have sex with men, lower partner notification effectiveness for HIV and the relative large proportion of heterosexual men not notifying their partners appear to be important partner notification challenges. | 25,141,854 | [
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Potential importance of transition metals in the induction of DNA damage by sperm preparation media. | What are the mechanisms by which the preparation of spermatozoa on discontinuous density gradients leads to an increase in oxidative DNA damage? The colloidal silicon solutions that are commonly used to prepare human spermatozoa for assisted reproduction technology (ART) purposes contain metals in concentrations that promote free radical-mediated DNA damage. Sporadic reports have already appeared indicating that the use of colloidal silicon-based discontinuous density gradients for sperm preparation is occasionally associated with the induction of oxidative DNA damage. The cause of this damage is however unknown. This study comprised a series of experiments designed to: (i) confirm the induction of oxidative DNA damage in spermatozoa prepared on commercially available colloidal silicon gradients, (ii) compare the levels of damage observed with alterative sperm preparation techniques including an electrophoretic approach and (iii) determine the cause of the oxidative DNA damage and develop strategies for its prevention. The semen samples employed for this analysis involved a cohort of >50 unselected donors and at least three independent samples were used for each component of the analysis. The setting was a University biomedical science laboratory. The major techniques employed were: (i) flow cytometry to study reactive oxygen species generation, lipid peroxidation and DNA damage, (ii) computer-aided sperm analysis to measure sperm movement and (iii) inductively coupled mass spectrometry to determine the elemental composition of sperm preparation media. Oxidative DNA damage is induced in spermatozoa prepared on PureSperm(®) discontinuous colloidal silicon gradients (P < 0.001 versus repeated centrifugation) because this medium contains metals, particularly Fe, Al and Cu, which are known to promote free radical generation in the immediate vicinity of DNA. This damage can be significantly accentuated by reducing agents, such as ascorbate (P < 0.001) and inhibited by selective chelation (P < 0.001). This problem is not confined to PureSperm(®); analysis of additional commercial sperm preparation media revealed that metal contamination is a relatively constant feature of such products. While the presence of metals, particularly transition metals, may exacerbate the levels of oxidative DNA damage seen in human spermatozoa, the significance of such damage has not yet been tested in suitably powered clinical trials. The results explain why the preparation of spermatozoa on discontinuous colloidal silicon gradients can result in oxidative DNA damage. The results are of immediate relevance to the development of safe, effective protocols for the preparation of spermatozoa for ART purposes. The study was funded by the Australian Health and Medical Research Council. One of the authors (R.J.A.) has had a consultantship with a biotechnology company, NuSep, interested in the development of electrophoretic methods of sperm preparation. He has no current financial interest in this area. None of the other authors have a conflict of interest to declare. | 25,141,857 | [
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Maternal supplementation with vitamin A or β-carotene and cardiovascular risk factors among pre-adolescent children in rural Nepal. | Vitamin A plays an important role in fetal renal and cardiovascular development, yet there has been little research on its effects on cardiovascular risk factors later in childhood. To examine this question, we followed the children of women who had been participants in a cluster-randomized, double blind, placebo-controlled trial of weekly supplementation with 7000 μg retinol equivalents of preformed vitamin A or 42 mg of β-carotene from 1994 to 1997 in rural Nepal. Women received their assigned supplements before, during and after pregnancy. Over a study period of 3 years, 17,531 infants were born to women enrolled in the trial. In 2006-2008, we revisited and assessed 13,118 children aged 9-13 years to examine the impact of maternal supplementation on early biomarkers of chronic disease. Blood pressure was measured in the entire sample of children. In a subsample of 1390 children, venous blood was collected for plasma glucose, Hb1Ac and lipids and a morning urine specimen was collected to measure the ratio of microalbumin/creatinine. Detailed anthropometry was also conducted in the subsample. The mean ± s.d. systolic and diastolic blood pressure was 97.2 ± 8.2 and 64.6 ± 8.5 mm Hg, respectively, and about 5.0% had high-blood pressure (⩾120/80 mm Hg). The prevalence of microalbuminuria (⩾30 mg/g creatinine) was also low at 4.8%. There were no differences in blood pressure or the risk of microalbuminuria between supplement groups. There were also no group differences in fasting glucose, glycated hemoglobin, triglycerides or cholesterol. Maternal supplementation with vitamin A or β-carotene had no overall impact on cardiovascular risk factors in this population at pre-adolescent age in rural Nepal. | 25,141,874 | [
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Inferior mesenteric vein serves as an alternative guide for transection of the pancreatic body during pancreaticoduodenectomy with concomitant vascular resection: a comparative study evaluating perioperative outcomes. | Tumors of the pancreatic head often involve the superior mesenteric and portal veins. The purpose of this study was to assess perioperative outcomes after pancreaticoduodenectomy (PD) with concomitant vascular resection using the inferior mesenteric vein (IMV) as a guide for transection of the pancreatic body (Whipple at IMV, WATIMV). One hundred thirty-seven patients had segmental vein resection during PD between January 2006 and June 2013. Depending on whether the standard approach of creating a tunnel anterior to the mesenterico-portal vein (MPV) axis was achieved for pancreatic transection, patients were subjected to a standard PD with vein resection procedure (s-PD + VR, n = 75) or a modified procedure (m-PD + VR, n = 62). Within the m-PD + VR group, 28 patients underwent the WATIMV procedure, while 34 patients underwent the usual procedure of transection, or 'central pancreatectomy' (c-PD + VR). The volume of intraoperative blood loss and the blood transfusion requirements were significantly greater, and the venous wall invasion and neural invasion frequency were significantly higher in the m-PD + VR group compared with the s-PD + VR group. There were no significant differences in the length of hospitalization, postoperative morbidity, and grades of complications between the two groups. Multivariate logistic regression identified intraoperative blood transfusion (P = 0.004) and vascular invasion (P = 0.008) as the predictors of postoperative morbidity. Further stratification of the entire cohort of 62 (45%) patients who underwent m-PD + VR showed a higher rate of negative resection margins (96.4%) in the WATIMV group compared with the c-PD + VR group (76.5%) (P = 0.06). The volume of intraoperative blood loss (P = 0.013), and intraoperative blood transfusion requirements (P = 0.07) were significantly greater in the c-PD + VR group compared with the WATIMV group. Furthermore, high intraoperative blood loss and tumor stage were predictive of a positive resection margin. 'Whipple at the IMV (WATIMV)' has comparable postoperative morbidity with standard PD + VR. If IMV runs into the splenic vein, it could serve as an alternative guide for transection of the pancreatic body during PD + VR. | 25,141,915 | [
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Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma. | Mesothelioma is inherently chemo-resistant with only 50% of patients responding to the standard of care treatments, and consequently it has a very grim prognosis. The aim of this study was to establish a panel of chemo-resistant mesothelioma models with clinically relevant levels of resistance as tools for investigating chemo-resistance and identifying new treatments for mesothelioma. Chemo-resistant cell lines were established in vitro and characterized in vivo using syngeneic Fischer rats. Tumors derived from all chemo-resistant cell lines were immunohistochemically classified as mesothelioma. Homozygous deletion of p16(INK4A)/p14(ARF) and increased expression of several ATP-binding cassette transporters were demonstrated, consistent with findings in human mesothelioma. Further, the acquisition of chemo-resistance in vitro resulted in changes to tumor morphology and overall survival. In conclusion, these models display many features corresponding with the human disease, and provide the first series of matched parental and chemo-resistant models for in vitro and in vivo mesothelioma studies. | 25,141,917 | [
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Early infancy - a critical period for development of obesity. | Abundant epidemiologic evidence from the developed world now shows that more rapid weight gain during the first half of infancy predicts later obesity and cardio-metabolic risk. In countries in transition, in which stunting is still prevalent, distinguishing the effects of gain in weight from linear growth remains a challenge. Moreover, very few studies to date have incorporated body composition measures during infancy, which is key to understanding determinants of infant weight gain that also predict later obesity. In addition to infant feeding type, potential determinants include the perinatal endocrine milieu. Animal and emerging human data raise the possibility that ensuring adequate leptin exposure to the growing fetus may regulate energy balance as the infant grows. Understanding these pathways, as well as examining the balance between cardiovascular and cognitive effects in both term and preterm infants, will point the way toward effective interventions to alter infant growth to prevent later obesity. | 25,141,932 | [
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The interleukins IL-6 and IL-1Ra: a mediating role in the associations between BMI and birth weight? | The biological mechanisms in the association between maternal body mass index (BMI) and birth weight are not well understood, but are likely to involve maternal plasma glucose levels and nutrient transport across the placenta, both important modulators of fetal growth. Adipose tissue contributes to circulating levels of interleukins that may affect glucose metabolism and possibly also placental transport of nutrients. We investigated possible mediating roles of Interleukin 6 (IL-6) and Interleukin 1 Receptor antagonist (IL-1Ra) in 208 pregnant women. Known and hypothesized dependencies between BMI in early pregnancy and fasting glucose, IL-1Ra and IL-6 at gestational weeks 30-32, and birth weight were specified in a path diagram. Standardized regression coefficients, expressing direct, indirect and total effects, were estimated by Bayesian path analysis. Mean (s.d.) BMI was 24.9 kg/m2 (4.2) and mean (s.d.) birth weight 3748 g (454). The total effect of BMI on birth weight was 0.24 (95% credibility interval (CrI) [0.12, 0.36]). The direct effect of IL-1Ra on birth weight was not statistically significant, but significant effects of BMI on IL-1Ra (0.61, 95% CrI [0.51, 0.72]), of IL-1Ra on fasting glucose (0.17, 95% CrI [0.01, 0.34]) and of fasting glucose on birth weight (0.14, 95% CrI [0.01, 0.27]) implied an indirect pathway from BMI via IL-1Ra on birth weight. Approximately 20% of the effect of BMI on birth weight was mediated through IL-1Ra. For IL-6, no such effects were found. Our results indicate that IL-1Ra may be a mediator in the association between BMI and birth weight. | 25,141,934 | [
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Copper-catalyzed decarboxylative C-P cross-coupling of alkynyl acids with H-phosphine oxides: a facile and selective synthesis of (E)-1-alkenylphosphine oxides. | A novel and efficient copper-catalyzed decarboxylative cross-coupling of alkynyl acids for the stereoselective synthesis of E-alkenylphosphine oxides has been developed. In the presence of 10 mol % of CuCl without added ligand, base, and additive, various alkynyl acids reacted with H-phosphine oxides to afford E-alkenylphosphine oxides with operational simplicity, broad substrate scope, and the stereoselectivity for E-isomers. | 25,141,945 | [
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Genetic markers of cisplatin-induced hearing loss in children. | This journal recently published a Commentary by Ratain and colleagues at the University of Chicago that criticizes our work on cisplatin-induced hearing loss in children. It is unfortunate that neither the authors nor the editors of Clinical Pharmacology & Therapeutics corresponded with us to provide an earlier opportunity to address these questions. Here we correct the authors' inaccuracies and provide additional analyses that further strengthen our published findings. | 25,141,953 | [
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PSI showed higher tolerance to Sb(V) than PSII due to stimulation of cyclic electron flow around PSI. | The knowledge of the effects of Sb(V) on the physiological characteristics of cyanobacteria was still limited. In the present study, responses of photosystem I and II (PSI and PSII), cyclic electron flow (CEF), and interphotosystem electron transport of Microcystis aeruginosa to 5-100 mg/l Sb(V) were synchronously measured using the Dual-PAM-100. 5 mg/l Sb (V) significantly inhibited PSII activity, but had no significant effects on PSI activity. At higher concentrations of Sb(V), the quantum yield and electron transport of PSI were less affected compared to PSII. The ratio of Y(II)/Y(I) significantly decreased with increasing Sb(V) concentration. It decreased from 0.7 for control to 0.4 for 100 mg/l Sb(V)-treated cells, indicating that the change of the distribution of quantum yields between two photosystems and more serious inhibition of PSII under stress of Sb(V) compared to PSI. CEF was activated associated with the inhibition of linear electron flow after exposure to Sb(V). The contribution of Y(CEF) to the quantum yield and activity of PSI increased with increasing Sb(V) concentrations. The cyclic electron transport rate made a significant contribution to electron transport rate of PSI, especially at high Sb(V) concentration (100 mg/l) and high illumination (above 555 μmol photons/m(2)/s). The stimulation of CEF was essential for the higher tolerance of PSI than PSII to Sb(V). | 25,141,964 | [
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Impaired erythrocyte deformability in transgenic HO-1G143H mutant mice. | To investigate the potential effects of variation of HO-1 activity on hemorheology, this study compared the hemorheological properties between transgenic HO-1G143H mutant mice and wild-type (WT) control mice. Fresh blood samples were obtained from mice via the ocular venous sinus. The whole blood viscosity was measured using a cone-plate viscometer. Erythrocyte deformability and aggregation was measured using ektacytometry. The elongation index was significantly reduced in the HO-1G143H mutant mice compared to the WT mice at the shear rates of 600, 800, and 1,000 s(-1). The integrated elongation index was decreased in the HO-1G143H mutant mice compared to the WT mice. There was no statistically significant difference between the HO-1G143H mutant mice and the WT mice in terms of whole blood viscosity, aggregation index, amplitude of aggregation, and aggregation half time. The present study demonstrated that a reduction in HO-1 activity results in an impaired erythrocyte deformability. Although the mechanism underlying this effect remains unclear, our study brings to light the participation of HO-1 in the variations of hemorheology. | 25,141,966 | [
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Burden of stroke in Puerto Rico. | Stroke is the fifth leading cause of death and the first cause of long-term disability in Puerto Rico. Trained staff reviewed and independently validated the medical records of patients who had been hospitalized with possible stroke at any of the 20 largest hospitals located in Puerto Rico during 2007, 2009, and 2011. The mean age of the 5005 newly diagnosed stroke patients (51·2% female) was 70 years. At the time of hospitalization, women were 4½ years older, were less likely to be married (60·2% vs. 39·9%, P < 0·001), smoked less (5·8% vs. 13·4%, P < 0·001), and had significantly higher proportion of diabetes (56·0% vs. 54·8%), hypertension (89·1% vs. 85·0%), and low density lipoprotein-cholesterol (LDL-Chol) > 100 mg/dL (65·7% vs. 57·5%) P < 0·05. Ischemic stroke represented 75% of all types of strokes. Atrial fibrillation was mentioned in 7·9% of the medical records. The risk for dying before discharge was similar for both genders, but was 40% higher for women than for men at one-year follow-up: age-adjusted odds ratio = 1·4 (95% confidence interval = 1·2-1·5). | 25,141,980 | [
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Construction of an uricase nanoparticles modified au electrode for amperometric determination of uric acid. | A method is described for preparation of uricase nanoparticles (100 nm in size) and their direct immobilization onto the Au electrode. The enzyme electrode along with Ag/AgCl as reference and Pt as auxiliary electrode were connected through potentiostat/galvanostat to construct an amperometric uric acid biosensor. The enzyme electrode was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and electrochemical impedance spectroscopy (EIS). The enzyme electrode detected uric acid level as low as 5.0 μM at a signal-to-noise ratio of 3, within 7 s at pH 8.5 and 40 °C. The biosensor showed a linear working range, 0.005 to 0.8 mM for uric acid with a sensitivity of 0.03 mA μM(-1) cm(-2). The biosensor was evaluated. The biosensor lost only 15 % of its initial activity over a period of 7 months, when stored at 4 °C. The fabricated biosensor was successfully employed for determination of uric acid in human serum and urine. | 25,141,984 | [
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A metabolic trade-off between phosphate and glucose utilization in Escherichia coli. | Getting the most out of available nutrients is a key challenge that all organisms face. Little is known about how they optimize and balance the simultaneous utilization of multiple elemental resources. We investigated the effects of long-term phosphate limitation on carbon metabolism of the model organism Escherichia coli using chemostat cultures. We profiled metabolic changes in the growth medium over time and found evidence for an increase in fermentative metabolism despite the aerobic conditions. Using full-genome sequencing and competition experiments, we found that fitness under phosphate-limiting conditions was reproducibly increased by a mutation preventing flux through succinate in the tricarboxylic acid cycle. In contrast, these mutations reduced competitive ability under carbon limitation, and thus reveal a conflicting metabolic benefit in the role of the TCA cycle in environments limited by inorganic phosphate and glucose. | 25,141,987 | [
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Beyond birthweight: the maternal and placental origins of chronic disease. | New findings on the maternal and placental programming of chronic disease lead to four conclusions: (1) Growth of the placental surface is polarized from the time of implantation, so that growth along the major axis, the length, is qualitatively different from growth along the minor axis, the breadth. (2) The human fetus may attempt to compensate for undernutrition by expansion of the placental surface along its minor axis. This only occurs if the mother was well nourished before conception, and may have long-term costs that include hypertension. (3) The effects of placental size on long-term health are conditioned by the mother's nutritional state, as indicated by her socio-economic status, height and body mass index. (4) The maternal-placental programming of chronic disease differs in boys and girls. Boys invest less than girls in placental growth but more readily expand the placental surface if they become undernourished in mid-late gestation. Boys are more responsive to their mothers' current diets while girls respond more to their mothers' lifetime nutrition and metabolism. | 25,142,007 | [
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Altered microglial phagocytosis in GPR34-deficient mice. | GPR34 is a Gi/o protein-coupled receptor (GPCR) of the nucleotide receptor P2Y12 -like group. This receptor is highly expressed in microglia, however, the functional relevance of GPR34 in these glial cells is unknown. Previous results suggested an impaired immune response in GPR34-deficient mice infected with Cryptococcus neoformans. Here we show that GPR34 deficiency results in morphological changes in retinal and cortical microglia. RNA sequencing analysis of microglia revealed a number of differentially expressed transcripts involved in cell motility and phagocytosis. We found no differences in microglial motility after entorhinal cortex lesion and in response to laser lesion. However, GPR34-deficient microglia showed reduced phagocytosis activity in both retina and acutely isolated cortical slices. Our study identifies GPR34 as an important signaling component controlling microglial function, morphology and phagocytosis. | 25,142,016 | [
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Expansion of a 2 + 2 macrocycle into a 6 + 6 macrocycle: template effect of cadmium(II). | The reaction of trans-1,2-diaminocyclopentane with 2,6-diformylpyridine results in formation of 2 + 2, 3 + 3, and 4 + 4 Schiff base macrocycles as well as trace amounts of 6 + 6 and 8 + 8 macrocycles. In contrast, the 6 + 6 Schiff base macrocycle is a dominant product of the reaction of the isolated 2 + 2 macrocycle with excess of cadmium(II) chloride. The X-ray crystal structure of the protonated amine derivative of the 6 + 6 macrocycle reveals an unusual container-like conformation with the S6 axis. | 25,142,027 | [
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Monodisperse carboxyl-functionalized poly(ethylene glycol)-coated magnetic poly(glycidyl methacrylate) microspheres: application to the immunocapture of β-amyloid peptides. | Identification and evaluation of small changes in β-amyloid peptide (Aβ) levels in cerebrospinal fluid is of crucial importance for early detection of Alzheimer's disease. Microfluidic detection methods enable effective preconcentration of Aβ using magnetic microparticles coated with Aβ antibodies. Poly(glycidyl methacrylate) microspheres are coated with α-amino-ω-methoxy-PEG5000 /α-amino-ω-Boc-NH-PEG5000 Boc groups deprotected and NH2 succinylated to introduce carboxyl groups. Capillary electrophoresis with laser-induced fluorescence detection confirms the efficient capture of Aβ 1-40 peptides on the microspheres with immobilized monoclonal anti-Aβ 6E10. The capture specificity is confirmed by comparing Aβ 1-40 levels on the anti-IgG-immobilized particles used as a control. | 25,142,028 | [
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Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment. | Biomarkers have great potential to improve the diagnosis and treatment of sepsis. The available literature supports the potential utility of sTREM-1, IL-27, suPAR, neutrophil CD64, presepsin, cfDNA and miRNAs as novel diagnostic, prognostic and treatment response biomarkers. The future of sepsis biomarkers lies in extensive validation studies of such novel biomarkers across heterogeneous populations and exploration of their power in combination. Furthermore, the use of a companion diagnostics model may augment the ability of investigators to identify novel sepsis biomarkers and develop specific therapeutic strategies based on biomarker information. | 25,142,036 | [
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The effect of different concentrations of linseed oil or fish oil in the maternal diet on the fatty acid composition and oxidative status of sows and piglets. | N-3 polyunsaturated fatty acids (PUFA) are essential for foetal development. Hence, including n-3 PUFA in the sow diet can be beneficial for reproduction. Both the amount and form (precursor fatty acids vs. long chain PUFA) of supplementation are important in this respect. Furthermore, including n-3 PUFA in the diet can have negative effects, such as decreased arachidonic acid (ARA) concentration and increased oxidative stress. This study aimed to compare the efficacy to increase eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations in the piglet, when different concentrations of linseed oil (LO, source of precursor α-linolenic acid) or fish oil (FO, source of EPA and DHA) were included in the maternal diet. Sows were fed a palm oil diet or a diet including 0.5% or 2% LO or FO from day 45 of gestation until weaning. Linoleic acid (LA) was kept constant in the diets to prevent a decrease in ARA, and all diets were supplemented with α-tocopherol acetate (150 mg/kg) and organic selenium (0.4 mg/kg) to prevent oxidative stress. Feeding 0.5% LO or 0.5% FO to the sows resulted in comparable EPA concentrations in the 5-day old piglet liver, but both diets resulted in lower EPA concentrations than when 2% LO was fed. The highest EPA concentration was obtained when 2% FO was fed. The DHA level in the piglet liver could only be increased when FO, but not LO, was fed to the sows. The 2% FO diet had no advantage over the 0.5% FO diet to increase DHA in the piglet. Despite the constant LA concentration in the sow diet, a decrease in ARA could not be avoided when LO or FO were included in the diet. Feeding 2% FO to the sows increased the malondialdehyde concentration (marker for lipid peroxidation) in sow plasma, but not in piglets. | 25,142,040 | [
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Environmental and genetic effects on weight and visual score traits at postweaning in Suffolk sheep. | This study aimed to investigate the following environmental effects in Suffolk lambing: contemporary groups, type of birth, and age of animal and age of dam at lambing on conformation (C), precocity (P), musculature (M), and body weight at postweaning (W), and the heritability coefficients and genetic correlations among these traits. Contemporary groups, type of birth, and age of animal and age of dam at lambing were significant for W. For C, all the effects studied were significant, except linear and quadratic effects of age of the animal. For P, all effects studied were significant, except the quadratic effect of age of the animal. For M, the effects of contemporary group, type of birth, and the linear effect of the age of the animal were significant. Heritability estimates were 0.07 ± 0.03, 0.14 ± 0.03, 0.09 ± 0.03, and 0.11 ± 0.03 for C, P, M, and W, respectively, indicating a positive low response for direct selection. Estimates of genetic correlations among the visual scores (C, P, and M) and W were moderate to highly favorable and positive, ranging from 0.48 to 0.90. These results indicate that selection for visual scores will increase body weight. | 25,142,054 | [
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IRBIS: a systematic search for conserved complementarity. | IRBIS is a computational pipeline for detecting conserved complementary regions in unaligned orthologous sequences. Unlike other methods, it follows the "first-fold-then-align" principle in which all possible combinations of complementary k-mers are searched for simultaneous conservation. The novel trimming procedure reduces the size of the search space and improves the performance to the point where large-scale analyses of intra- and intermolecular RNA-RNA interactions become possible. In this article, I provide a rigorous description of the method, benchmarking on simulated and real data, and a set of stringent predictions of intramolecular RNA structure in placental mammals, drosophilids, and nematodes. I discuss two particular cases of long-range RNA structures that are likely to have a causal effect on single- and multiple-exon skipping, one in the mammalian gene Dystonin and the other in the insect gene Ca-α1D. In Dystonin, one of the two complementary boxes contains a binding site of Rbfox protein similar to one recently described in Enah gene. I also report that snoRNAs and long noncoding RNAs (lncRNAs) have a high capacity of base-pairing to introns of protein-coding genes, suggesting possible involvement of these transcripts in splicing regulation. I also find that conserved sequences that occur equally likely on both strands of DNA (e.g., transcription factor binding sites) contribute strongly to the false-discovery rate and, therefore, would confound every such analysis. IRBIS is an open-source software that is available at http://genome.crg.es/~dmitri/irbis/. | 25,142,064 | [
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Prospective, randomized, double-blinded trial of bone marrow cell transplantation combined with coronary surgery - perioperative safety study. | We present here a sub-study of our prospective, randomized, double-blinded trial of bone marrow mononuclear cell (BMMC) transplantation with coronary artery bypass surgery (CABG) (ClinicalTrials.gov Identifier: NCT00418418), evaluating our secondary end-point concerning hospital stay as well as perioperative morbidity. Injecting a substantial amount of biologically active cells into a diseased myocardium inspires concerns for safety, a concern overlooked in previous trials. We evaluated the immediate perioperative effects of intramyocardial injection of autologous BMMCs combined with CABG. In a randomized double-blinded manner, 39 patients received injections either of BMMCs (n = 20) or of vehicle medium (n = 19). The patients' haemodynamics, arterial blood gases, systemic vein oxygen level, blood glucose, acid-base balance, lactate, haemoglobin, body temperature and diuresis, as well as medications needed, were recorded in the operating theatre and in the intensive care unit (ICU) every 4 h throughout the first postoperative 24 h. No dissimilarities in these parameters were detectable. In the ICU, the median need for adrenaline was 0.0086 µg/kg/min (first quartile 0.0000, third quartile 0.0204) for controls and 0.0090 µg/kg/min (0.0000, 0.0353) for BMMC patients (P = 0.757); for noradrenaline, 0.0586 µg/kg/min (0.0180, 0.0888) for controls and 0.0279 µg/kg/min (0.0145, 0.0780) for BMMC patients (P = 0.405). The median stay at the ICU was 2 days for both groups (1, 2 for controls; 1, 3 for BMMCs; P = 0.967). Within the first postoperative day, one control patient had an elevated level of creatine kinase-myocardial band fraction mass (CK-MBm) up to >100 µg/l; no BMMC patient showed elevated CK-MBm levels (P = 0.474). Both intramyocardial BMMC and placebo injections appear safe during surgery and immediate ICU stay after treatment of heart failure. | 25,142,068 | [
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Replication competent virus as an important source of bias in HIV latency models utilizing single round viral constructs. | The central memory T cell (TCM) model forms a unique HIV-1 latency model based on primary cells that closely resemble in vivo TCM. The virus employed in this model is based on an engineered vector incapable of replication after initial infection. We show that despite this strategy, replication competent viral particles are released into the culture medium due to recombination between overlapping sequences of the env deleted HIV genome that is co-transfected with intact env. This finding emphasizes the need for careful data analysis and interpretation if similar constructs are employed and urges for additional caution during laboratory work. | 25,142,072 | [
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Mild copper-TBAF-catalyzed N-arylation of sulfoximines with aryl siloxanes. | An efficient copper-TBAF-catalyzed C-N bond formation of sulfoximines with arylsiloxanes in dichloromethane at room temperature, affording the desired N-aryl sulfoximines in good to excellent yields under an oxygen atmosphere, is reported. This method complements the existing synthetic approaches due to some advantageous properties of arylsiloxanes such as availability, low toxicity, ease of handling, high stability, and environmental benignity under mild reaction conditions, thus opening a new approach to practical C-N bond formation. | 25,142,135 | [
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High and prolonged sulfamidase secretion by the liver of MPS-IIIA mice following hydrodynamic tail vein delivery of antibiotic-free pFAR4 plasmid vector. | Mucopolysaccharidosis type IIIA (MPS-IIIA) or Sanfilippo A syndrome is a lysosomal storage genetic disease that results from the deficiency of the N-sulfoglucosamine sulfohydrolase (SGSH) protein, a sulfamidase required for the degradation of heparan sulfate glycosaminoglycans (GAGs). The accumulation of these macromolecules leads to somatic organ pathologies, severe neurodegeneration and death. To assess a novel gene therapy approach based on prolonged secretion of the missing enzyme by the liver, mediated by hydrodynamic gene delivery, we first compared a kanamycin and an antibiotic-free expression plasmid vector, called pFAR4. Thanks to the reduced vector size, pFAR4 derivatives containing either a ubiquitous or a liver-specific promoter mediated a higher reporter gene expression level than the control plasmid. Hydrodynamic delivery of SGSH-encoding pFAR4 into MPS-IIIA diseased mice led to high serum levels of sulfamidase protein that was efficiently taken up by neighboring organs, as shown by the correction of GAG accumulation. A similar reduction in GAG content was also observed in the brain, at early stages of the disease. Thus, this study contributes to the effort towards the development of novel biosafe non-viral gene vectors for therapeutic protein expression in the liver, and represents a first step towards an alternative gene therapy approach for the MPS-IIIA disease. | 25,142,140 | [
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Migraine and restless legs syndrome: a systematic review. | Restless legs syndrome (RLS) is increasingly being reported as a comorbidity of migraine. We conducted a systematic review and meta-analysis of studies investigating RLS in headache/migraine and vice versa. We calculated the prevalence and 95% confidence intervals (CI) of RLS in headache/migraine, of headache/migraine in RLS and controls, and odds ratios (ORs) of the association between the conditions. We then determined pooled effect estimates for the associations. We identified 24 studies. RLS prevalence in migraine ranged from 8.7% to 39.0% with no apparent differences based on gender and aura status. Prevalence among controls was compatible with the literature. Migraine prevalence in RLS ranged from 15.1% to 62.6%. We did not pool prevalence data because of high unexplained heterogeneity. High heterogeneity with respect to the association between any migraine and RLS could be explained by study design. Pooled analyses showed substantially higher effect estimates in case-control studies (pooled OR = 4.19, 95% CI 3.07-5.71; I (2) = 0.0%) than in cohort studies (pooled OR = 1.22, 95% CI 1.14-1.30; I (2) = 0.0%). Our results support the concept of RLS as an important comorbidity of migraine. However, the degree of association appears to be strongly determined by study design. Potential effects by gender and aura status and the role of RLS in other headache disorders remain unclear. | 25,142,142 | [
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Disposal of iNKT cell deficiency and an increase in expression of SLAM signaling factors characterizes sarcoidosis remission: a 4-year longitudinal study. | Invariant NKT (iNKT) cells are regulatory lymphocytes that may be important in disorders with increased Th1 responses. We utilized a 4-year longitudinal observational study of iNKT cells and SLAM signaling pathway factors, which are important for iNKT development in patients with newly diagnosed sarcoidosis. Detailed clinical, functional, and radiographic evaluation and determination of iNKT peripheral blood cell counts and expression of SLAM signaling factors was carried out at presentation and after 3 months, 1 year, and 4 years of disease follow-up in 29 patients with pulmonary sarcoidosis. At presentation, we also evaluated the frequencies of pulmonary BALF iNKT cells. We also included 37 control subjects. We demonstrated a marked deficiency of blood and lung iNKT cells and decreased expression of SLAM signaling factors in patients with newly diagnosed sarcoidosis. During 4 years of disease follow-up, there was a significant increase in blood iNKT cell numbers and in expression of SLAM signaling factors, mainly SLAMF1, SLAMF6, and FYN. This increase clearly correlated with improvement in patients' clinical symptoms. At the 4-year endpoint, the disease had gone into remission in the great majority of patients and thus also iNKT cell deficiency. Moreover, at the 4-year endpoint iNKT level reached the iNKT level of the control subjects. Our longitudinal study showed that a disposal of iNKT deficiency in parallel with an increase in expression of SLAM signaling factors characterizes the clinical remission of sarcoidosis. | 25,142,143 | [
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Involvement of patients with lung and gynecological cancer and their relatives in psychosocial cancer rehabilitation: a narrative review. | Getting cancer is stressful for most patients and their relatives, and research has shown that psychosocial support is needed. Still, cancer care fails to appropriately address psychosocial problems associated with cancer. Research on this topic is often seen from the perspective of either the patient or the relative, even though it is suggested that psychosocial support is beneficial for the patient and the relative as a pair. Furthermore, research on the need for psychosocial support rarely involves patients with gynecological and lung cancer and their relatives, even though they often suffer from isolation and stigmatization. The aim of this review was therefore to summarize knowledge about psychosocial support with regard to individual needs, involvement of significant others, and providers of psychosocial support focusing on this specific population. A narrative review procedure was chosen. This method is a specific kind of review, which summarizes, explains, and interprets evidence on a selected topic. The review process was structured according to typical scholarly articles with attention to the search and review process. A total of 16 studies were included in the review. The studies were divided into two main categories: (1) studies focusing on needs for psychosocial support; and (2) studies focusing on interventions. The needs studies were analyzed, and three themes emerged: the needs of the patient and the significant other across the cancer trajectory; the needs of the significant other as a carer; and needs and ongoing and tailored support. The intervention studies were directed toward the patient and the relative, the patient, or the relative. Five interventions comprising various forms of support that were purely supportive and were carried out by healthcare professionals were identified. There were overlaps between the needs of the patient and the relative, but there were also distinctive characteristics of the needs in the two groups. The needs varied during the cancer trajectory, and we therefore recommend that support be offered continuously. It was also evident that the relatives should be involved in the patients' care and that the involvement was beneficial for both the patient and the relative. | 25,142,155 | [
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0.1160311,
0.04635535,
0.2430317,
-0.0129762... |
Characterization of the frhAGB-encoding hydrogenase from a non-methanogenic hyperthermophilic archaeon. | The F420-reducing hydrogenase has been known as a key enzyme in methanogenesis. Its homologs have been identified in non-methanogenic hyperthermophilic archaea, including Thermococcus onnurineus NA1, but neither physiological function nor biochemical properties have been reported to date. The enzyme of T. onnurineus NA1 was distinguished from those of other methanogens and the members of the family Desulfurobacteriaceae with respect to the phylogenetic distribution of the α and β subunits, organization of frhAGB genes and conservation of F420-coordinating residues. RT-qPCR and Western blot analyses revealed frhA gene is not silent but is expressed in T. onnurineus NA1 grown in the presence of sulfur, carbon monoxide, or formate. The trimeric enzyme complex was purified to homogeneity via affinity chromatography from T. onnurineus NA1 and exhibited catalytic activity toward the electron acceptors such as viologens and flavins but not the deazaflavin coenzyme F420. This is the first biochemical study on the function of the frhAGB-encoding enzyme from a non-methanogenic archaea. | 25,142,159 | [
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... |
A depletion layer in polymer solutions at an interface oscillating at the subnano- to submicrometer scale. | The mobility of segments of the polymer mesh in a solution determines the dynamic response of the depletion layer (DL) to mechanical stimuli. This phenomenon can be used to vastly decrease the local viscosity experienced by any device performing periodic motion at the nano- and microscale in complex liquids. We refined the vibrating quartz tuning fork (QTF) method to probe the viscosity of model aqueous solutions of polyethylene glycol, covering a broad range of molecular weights (3 kDa to 1 MDa) and QTF oscillation amplitudes (50 pm to 100 nm). For semidilute solutions of PEGs of high molecular weight, we found a drop of local viscosity, up to two orders of magnitude below the bulk value. We propose a simple explanation based on the motion of the depletion layer, strongly supported by rheometry and dynamic light scattering results. We show that it is possible to directly probe the viscosity of the DL and increase its thickness far above the equilibrium value. The key role is played by the rate of relaxation of the entangled system. The relevance of this paradigm ranges from the basic research on dynamics of entangled systems to design of energy-efficient nanomachines operating in a crowded environment. | 25,142,160 | [
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0.170393,
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0.004... |
Dietary requirement for serum-derived bovine immunoglobulins in the clinical management of patients with enteropathy. | A variety of human disease conditions are associated with chronic intestinal disorders or enteropathies that are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Such disruptions in the homeostasis of the gastrointestinal (GI) tract can lead to symptoms of abdominal pain and discomfort, bloating, abnormal bowel function, and malabsorption of nutrients. While significant advances have been made in understanding the factors that influence the complex and fragile balance between the gut microbiota, intestinal epithelial cell integrity, and the underlying immune system, effective therapies for restoring intestinal balance during enteropathy are still not available. Numerous studies have demonstrated the ability of oral immunoglobulins to improve weight gain, support gut barrier function, and reduce the severity of enteropathy in animals. More recently, studies in humans provide evidence that serum-derived bovine immunoglobulin/protein isolate is safe and improves nutritional status and GI symptoms in patients with enteropathy associated with irritable bowel syndrome or infection with the human immunodeficiency virus. This review summarizes studies showing the impact of enteropathy on nutritional status and how specially formulated bovine immunoglobulins may help restore intestinal homeostasis and nutritional status in patients with specific enteropathies. Such protein preparations may provide distinct nutritional support required for the dietary management of patients who, because of therapeutic or chronic medical needs, have limited or impaired capacity to digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or other special medically determined nutrient requirements that cannot be satisfied by changes to the normal diet alone. | 25,142,170 | [
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... |
Expansive open-door laminoplasty secured with titanium miniplates is a good surgical method for multiple-level cervical stenosis. | Laminoplasty is an effective procedure for treating cervical spondylotic myelopathy (CSM). Little information is available regarding the surgical outcomes of expansive open-door laminoplasty (EOLP) when securing with titanium miniplates without bone grafting. This study is aimed to elucidate the efficacy of and problems associated with EOLP secured with titanium miniplates without bone grafting, thereby enhancing future surgical outcomes. This is a retrospective study. The study participants comprised 104 patients who underwent cervical EOLP secured with titanium miniplates without bone graft for CSM treatment between August 2005 and March 2011. The clinical results were evaluated based on the Japanese Orthopedic Association (JOA) and Nurick scores. The radiographic outcomes were determined based on plain film and magnetic resonance imaging findings, which were assessed and compared. Lateral cervical spine X-rays exhibited improvement in the Pavlov ratio of the spinal canal at 1 day postoperation, and this ratio did not change at 1 year postoperation. The mean cervical curvature from C2 to C7 decreased 0.21° ± 10.09° and the mean cervical range of motion was deteriorated by 35% at 12 months (P < 0.05). The Nurick score improved from 3.19 ± 1.06 to 0.92 ± 1.32 (P < 0.05). The mean JOA recovery rate was 75% ± 21.1% at 1 year. The mean level of postoperative neck pain at 3 months was 3.09 ± 2.31, as determined using the visual analogue scale (VAS). Increased age, concomitant thoracolumbar stenosis, depression disorder, and preexisting myelomalacia negatively affected the JOA recovery rate (P < 0.05). A decreased preoperative Nurick score and superior sensory function in the upper extremities were powerful predictors of an enhanced JOA recovery rate. The postoperative complications involved hematoma formation 0.9%, reversible C5 nerve palsy 2.8%, and moderate to severe neck pain (VAS ≥ 4) 42%. No cases of lamina closure or collapse were observed. EOLP secured with titanium miniplates without bone grafting is a safe and effective surgical method for treating most patients with CSM. | 25,142,174 | [
0.1485159,
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0.0777055,
0.1377774,
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CXCL16 haplotypes in patients with human carotid atherosclerosis: preliminary results. | Chemokine CXC ligand 16 (CXCL16) has chemoattractive, adhesive and scavenging properties and may play a role in the formation of atherosclerotic lesions. However, studies of CXCL16 polymorphisms in patients with atherosclerosis are scarce. The missense polymorphisms I123T and A181V are potentially important factors in the regulation of presentation and shedding of the CXCL16 chemokine domain. The aim of this study was to analyze the association between I123T and A181V polymorphism haplotypes and the accumulation of carotid plaque as well as the effect of the haplotype on the CXCL16 mRNA expression in carotid plaques in patients with advanced atherosclerosis. Additionally, we performed a bioinformatic prediction analysis of the impact of CXCL16 protein sequence variation on CXCL16-CXCR6 interactions and analyzed the soluble CXCL16 plasma levels according to the CXCL16 haplotype. This study evaluated a total of 733 participants, including 283 controls and 450 patients with carotid atherosclerosis (CA) undergoing endarterectomy. Analyses of the polymorphisms and the gene expression were performed using real-time PCR. The soluble CXCL16 levels were measured with ELISA. The missense allele haplotype, T123V181, was found to be significantly and independently associated with the occurrence of CA plaque (OR=1.27;1.02-1.57, p=0.03). This haplotype was predicted to significantly change the CXCL16-CXCR6 interaction, compared to I123A181. Neither the CXCL16 mRNA expression in the human plaques nor the soluble CXCL16 plasma levels differed according to the haplotype. These results indicate that the CXCL16 T123V181 haplotype is a moderate genetic risk factor for the development of carotid plaque. Further functional and replication studies are needed to clarify the mechanisms by which this combination of alleles promotes advanced CA and validate its impact on disease progression. | 25,142,184 | [
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0.02603098,
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In vitro and in vivo metabolism of 14C-AZ11, a novel inhibitor of bacterial DNA gyrase/type II topoisomerase. | 1. (2R,4S,4aS)-11-Fluoro-2,4-dimethyl-8-((S)-4-methyl-2-oxooxazolidin-3-yl)-2,4,4a,6-tetrahydro-1H,1'H-spiro [isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione (AZ11) is a novel mode-of-inhibition bacterial topoisomerase inhibitor that entered preclinical development for the treatment of Gram-positive bacteria infection. 2. The in vitro biotransformation studies of AZ11 using mouse, rat, dog and human hepatocytes showed low-intrinsic clearance in all species attributed to microsomal metabolism. 3. After a single intravenous administration of [14C]AZ11 in bile duct cannulated rats, the mean percentage of dose recovered in rat urine, bile and feces was approximately 18, 36 and 42%, respectively. Unchanged AZ11 recovered in rat urine and bile was less than 9% of the dose, indicating that AZ11 underwent extensive metabolism in rats. 4. The most abundant in vivo metabolite detected in urine and bile was M1 formed via ring opening on the piperidine and morpholine rings accounting for 20% of the administered dose. The major fecal metabolite was M5, which accounted for approximately 32% of administered dose. M5 was not formed when AZ11 incubated with rat intestinal microsomes and cytosol but was formed when incubated with fresh rat feces, suggesting that unchanged AZ11 was directly excreted into gut lumen where M5 formed as an intestinal microflora-mediated product. This process could have significant impact on bioavailability or exposure of AZ11 in rat. | 25,142,218 | [
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0.1833484,
0.2332373,
-0.00999732... |
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