title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Carbapenem-resistant Klebsiella pneumoniae infections in kidney transplant recipients: a case-control study. | Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections have emerged as a significant challenge in solid organ transplantation. CRKP infections in other patient populations have been associated with higher mortality, when compared to infections caused by carbapenem-sensitive K. pneumoniae (CSKP). The aim of this study was to evaluate possible risk factors, clinical characteristics, and outcomes of CRKP infections compared with CSKP infections in kidney transplant recipients (KTR). We retrospectively investigated 13 CRKP infections and 39 CSKP infections in KTR (2006-2010). CRKP was not significantly associated with age, gender, or comorbidities. CRKP infections were significantly associated with recent exposure to broad-spectrum antibiotics and were more likely to have been managed on an inpatient basis and to have required source control. CRKP was significantly associated with earlier mortality. Six of 13 (46%) patients with CRKP infection, and none of the patients with CSKP infection, died within 6.5 months of infection onset. Although cases and controls did not differ significantly with respect to diabetes, all patients (100%, n = 9) who died during the study had diabetes, while 58% of the 43 survivors had diabetes (P = 0.02). In conclusion, CRKP compared with CSKP is associated with greater risk of mortality. Investigations on ways to better prevent CRKP are urgently needed. | 25,092,500 | [
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Promoting Female Condom Use Among Female University Students in KwaZulu-Natal, South Africa: Results of a Randomized Behavioral Trial. | Relatively few interventions have tested the efficacy of female condom promotion either alone or in combination with other barrier methods. We evaluated the efficacy of a two-session (enhanced) cognitive-behavioral intervention (EI) (n = 147) against a one-session control (minimal) educational intervention (MI) (n = 149) to promote female condom (FC) use among female students aged 18-28 at a South African university. We assessed change from baseline to 2.5 and 5 months in number of vaginal intercourse occasions unprotected by male or female condoms in EI versus MI using generalized linear models with a log link function and GEE. Both groups reported significant reductions in number of unprotected vaginal intercourse occasions from baseline to each follow-up, with no significant difference between the two-session and single-session intervention. Introduction of a brief group-based MI FC promotion intervention with FC access holds promise for delivery in clinics and other community venues. | 25,092,513 | [
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Individual-Level and Partner-Level Predictors of Newly Diagnosed HIV Infection Among Black and White Men Who Have Sex with Men in Baltimore, MD. | Black MSM continue to be the group most disproportionately impacted by HIV in the United States. This study assesses the relationship between partner-level and respondent-level characteristics and newly diagnosed HIV infection among a sample of MSM. Ego-centric data were gathered using venue-based time-space sampling on 335 men who reported on a total of 831 male anal sex partners. In multivariate analyses, age of partner, HIV status of partner, and respondent having had an STD in the past twelve months were associated with a newly diagnosed HIV infection among black MSM. Efforts for black MSM are needed that aim to increase HIV and STD testing, foster open communication between partners about HIV status, and address social determinants of health. | 25,092,514 | [
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Inhibition of key markers linked with spermatogenesis and cellular ATP by subchronic exposure to leachate in a rat model. | Few or no studies have measured the toxic effects of subchronic exposure to leachate using key markers linked with spermatogenesis and cellular adenosine triphosphate (ATP) in an experimental rat model. This study was undertaken to evaluate the toxic effects of leachate obtained from the Elewi Odo municipal battery-recycling site (EOMABRL) on male reproductive function using testicular hormones and biomarker of cellular ATP. EOMABRL was administered at 0, 20, 40, 60, 80, and 100% concentrations to adult male rats for 60 days. After exposure, serum was collected for hormonal biochemistry assays, and testes were collected to determine the activity of xanthine oxidase (XO) and lactate dehydrogenase (LDH). Exposure of animals to EOMABRL resulted in a 519.7, 285.7, 569.1, 606.1, and 1,793.2% increase in XO activity with a sequential decrease in LDH activity (marker of cellular ATP) by 44.1, 55.9, 61.4, 69.3, and 89.7%, respectively, compared with the control. Furthermore, EOMABRL caused a significant inhibitory effect on serum luteinizing hormone, follicle-stimulating hormone, and testosterone levels. We conclude that some possible mechanisms by which EOMABRL elicits toxicity in male rat testes could be through inhibition of LDH activity and depletion of serum hormone levels. | 25,092,531 | [
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Comparison between results of high tibial osteotomy above and below tibial tubercle in relation to future total knee arthroplasty. | This prospective study included 50 patients with medial compartment osteoarthritis and varus knees. Twenty-five patients had high tibial closed wedge osteotomy above the tibial tubercle (TT) (group I), and the other 25 had the osteotomy just below it (group II). The two groups were matched. The osteotomies in both groups were fixed with plates and screws. All patients were followed up radiographically and clinically for more than 12 months. Clinical and radiographic results of both groups are comparable. Regarding factors that will affect future knee arthroplasty (TKA), osteotomies below TT are more advantageous. That is because soft tissues and bony changes of the knees in group II are minimal, and the issue of slower union rates can be diminished by using rigid plate fixation. | 25,092,563 | [
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Anti-C1q autoantibodies from active lupus nephritis patients could inhibit the clearance of apoptotic cells and complement classical pathway activation mediated by C1q in vitro. | Anti-C1q antibodies are prevalent in patients with active lupus nephritis and were found to be closely associated with renal involvement and predictive for a flare of nephritis. However, the pathogenesis of anti-C1q antibodies involved in human lupus nephritis remains unclear. C1q, which plays a key role in apoptotic cell and immune complex removal, is a very important functional molecule in the pathogenesis of SLE. The aim of this study was to investigate the influence of anti-C1q autoantibodies from active lupus nephritis patients on the bio-functions of C1q in vitro. We purified IgG autoantibodies against C1q from lupus nephritis patients, and found that they could recognize C1q bound on early apoptotic cells at 30 μg/ml, and could significantly decrease the phagocytosis by macrophages of early apoptotic cells opsonized by 50 μg/ml C1q in comparison with normal IgG. Levels of circulating immune complexes of the ten patients were measured by a circulating immune complexes (CIC)-C1q Enzyme Immunoassay Kit. Anti-C1q autoantibodies affinity purified by microtiter plates could significantly inhibit the deposition of C3c on CIC-C1q in a dose dependent manner in comparison with IgG from 10 healthy blood donors. The binding of opsonized immune complexes to RBCs was significantly inhibited by anti-C1q autoantibodies purified by microtiter plates in a dose dependent manner. Our observations suggest that serum anti-C1q autoantibodies from active lupus nephritis patients could interfere with some biological function of C1q in vitro. | 25,092,568 | [
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Accuracy and reliability of pulp/tooth area ratio in upper canines by peri-apical X-rays. | Due to the real need for careful staff training in age assessment, in order to improve capacity, consistency and competence, new research on the reliability and repeatability of methods frequently used in age assessment are required. The aim of this study was twofold: first, to test the accuracy of this method for age estimation; second, to obtain data on the reliability of this technique. A sample of 81 peri-apical radiographs of upper canines (44 men and 37 women), aged between 19 and 74years, was used; the teeth were taken from the osteological collection of Sassari (Sardinia, Italy). Three blinded observers used the technique in order to perform the age estimation. The mean real age of the 81 observations was 37.21 (CI95% 34.37 40.05), and estimated ages ranged from 36.65 to 38.99 (CI95%-Ex1 35.42; 41.28; CI95%-Ex2 33.89; 39.41; CI95%-Ex3 35.92; 42.06). The module differences found by the three observers were 3.43, 4.24 and 4.45, respectively for Ex1×Ex2, Ex1×Ex3 and Ex2×Ex3. The module differences observed among real and observed ages were 2.55 (CI95% 1.90; 3.20), 2.22 (CI95% 1.65; 2.78) and 4.39 (CI95% 3.80; 5.75), respectively for Ex1, Ex2 and Ex3. No differences were observed among measurements. This technique can be reproduced and repeated after proper training, since it was found high reliability and accuracy. | 25,092,574 | [
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Molecular weight distribution characterization of hydrophobe-modified hydroxyethyl cellulose by size-exclusion chromatography. | Size-exclusion chromatography (SEC) of hydrophobe-modified hydroxyethyl cellulose (HmHEC) is challenging because polymer chains are not isolated in solution due to association of hydrophobic groups and hydrophobic interaction with column packing materials. An approach to neutralize these hydrophobic interactions was developed by adding β-cyclodextrin (β-CD) to the aqueous eluent. SEC mass recovery, especially for the higher molecular weight chains, increased with increasing concentration of β-CD in the eluent. A β-CD concentration of 0.75wt% in the eluent was determined to be optimal for the HmHEC polymers studied. These conditions enabled precise determinations of apparent molecular weight distributions exhibiting less than 2% relative standard deviation in the measured weight-average molecular weight (MW) for five injections on three studied samples and showed no significant differences in MW determined on two different days. The developed technology was shown to be very robust for characterizing HmHEC having MW from 500kg/mol to 2000kg/mol, and it can be potentially applied to other hydrophobe-modified polymers. | 25,092,594 | [
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Obesity in autoimmune diseases: not a passive bystander. | In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of "adipokines", involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental and pathophysiological data on the relationship between obesity, adipokines - namely leptin, adiponectin, resistin, visfatin - and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis (HT). The strongest levels of evidence support an increased risk of RA (OR=1.2-3.4), MS (OR=2), psoriasis and PsA (OR=1.48-6.46) in obese subjects. A higher risk of IBD, T1D and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis and PsA, and impairs the treatment response of RA, IBD, psoriasis and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases. | 25,092,612 | [
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The pig as an animal model for human pathologies: A proteomics perspective. | Traditional biomedical models are easy to manage in experimental facilities and allow fast and affordable basic genetic studies related to human disorders, but in some cases they do not always represent the complexity of their physiology. Translational medicine demands selected models depending on the particularities of the human disease to be investigated, reproducing as closely as possible the evolution, clinical symptoms and molecular pathways, cells or tissues involved in the dysfunction. Thus, pig models offer an alternative because of their anatomical and physiological similarities to humans and the availability of genomic, transcriptomic and, progressively more, proteomic tools for analysis of this species. Furthermore, there is a wide range of natural, selected and transgenic porcine breeds. The present review provides a summary of the applications of the pig as a model for metabolic, cardiovascular, infectious diseases, xenotransplantation and neurological disorders and an overview of the possibilities that the diverse proteomic techniques offer to study these pathologies in depth. | 25,092,613 | [
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The prevalence of undiagnosed diabetes mellitus and the association of baseline glycemic control on mortality in the intensive care unit: a prospective observational study. | Hyperglycemia is common during critical illness and can adversely affect clinical outcomes. We sought to determine the prevalence of undiagnosed diabetes among medical intensive care unit (MICU) patients with stress hyperglycemia and the association between baseline glycemic control and mortality. A prospective, observational cohort study was performed at a tertiary care MICU. Hemoglobin A1c (HbA1c) levels were obtained from any patient who developed hyperglycemia and all known diabetic patients. We assessed the prevalence of undiagnosed diabetes (defined by HbA1c) among patients with stress hyperglycemia, and the association between baseline glycemic control and mortality. We enrolled 299 patients. One hundred two (34.1%) had no history and 197 (65.9%) had a history of diabetes. Of the nondiabetic patients, 14 (13.7%) had an HbA1c of at least 6.5%. There was a significant difference in mortality between patients with HbA1c less than 6.5% and those with HbA1c of at least 6.5% (19.3% vs 11.7%, P=.038), despite similar Acute Physiology and Chronic Health Evaluation II scores. There was no significant difference in demographic characteristics between these groups. Multivariable logistic regression revealed lower HbA1c levels to be significantly associated with increased hospital mortality (odds ratio, 1.92; 95% confidence interval, 1.30-2.85; P=.001). A significant number of MICU patients with stress hyperglycemia have undiagnosed diabetes. Hyperglycemia with lower baseline HbA1c was associated with increased mortality. | 25,092,614 | [
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Establishment of multiple pesticide biodegradation capacities from pesticide-primed materials in on-farm biopurification system microcosms treating complex pesticide-contaminated wastewater. | On-farm biopurification systems (BPSs) treat pesticide-containing wastewater at farms by biodegradation and sorption processes. The inclusion of pesticide-primed material carrying a pesticide-degrading microbial community is beneficial for improving biodegradation, but no data exist for treating wastewater containing multiple pesticides, as often occurs on farms. In a microcosm set-up, an examination was carried out to determine whether multiple pesticide degradation activities could be simultaneously established in the matrix of a BPS by the simultaneous inclusion of different, appropriate pesticide-primed materials. The microcosms were fed with a mixture of pesticides including the fungicide metalaxyl and the herbicides bentazon, isoproturon, linuron and metamitron, and pesticide-degrading activities were monitored over time. The strategy immediately provided the microcosms with a multiple pesticide degradation/mineralisation capacity, which improved during feeding of the pesticide mixture. Not only did the degradation of the parent compound improve but also that of the produced metabolites and compound mineralisation. The time to achieve maximum degradation/mineralisation capacity depended on the pesticide degradation capacity of the pesticide-primed materials. The data obtained show that the addition of pesticide-primed materials into the matrix of a BPS as an approach to improve biodegradation can be extended to the treatment of pesticide mixtures. | 25,092,626 | [
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Experiences with provider and parental attitudes and practices regarding the administration of multiple injections during infant vaccination visits: lessons for vaccine introduction. | An increasing proportion of childhood immunization visits include administration of multiple injections. Future introduction of vaccines to protect against multiple diseases will further increase the number of injections at routine immunization childhood visits, particularly in developing countries that are still scaling up introductions. Parental and healthcare provider attitudes toward multiple injections may affect acceptance of recommended vaccines, and understanding these attitudes may help to inform critical decisions about vaccine introduction. We conducted a systematic review of the literature to examine factors underlying reported parental and healthcare provider concerns and practices related to administration of multiple injections during childhood vaccination visits. Forty-four articles were identified; 42 (95%) were from high income countries, including 27 (61%) from the USA. Providers and parents report concerns about multiple injections, which tend to increase with increasing numbers of injections. Common parental and provider concerns included apprehension about the pain experienced by the child, worry about potential side effects, and uncertainty about vaccine effectiveness. Multiple studies reported that a positive provider recommendation to the parent and a high level of concern about the severity of the target disease were significantly associated with parental acceptance of all injections. Providers often significantly overestimated parental concerns about multiple injections. Providers may play a critical role in the decision for a child to receive all recommended injections. Their overestimation of parental concerns may lead them to postpone recommended vaccinations, which may result in extra visits and delayed vaccination. More research is needed on interventions to overcome provider and parental concern about multiple injections, particularly in developing countries. | 25,092,632 | [
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Trials in the prevention of type 1 diabetes: current and future. | A major thrust in type 1 diabetes research is stopping the destruction of beta cells that leads to type 1 diabetes. Research over the past 30 years has defined genetic factors and evidence of autoimmunity that have led to the development of robust prediction models in those at high risk for type 1 diabetes. The ability to identify those at risk and the development of new agents and of collaborative research networks has led to multiple trials aimed at preventing beta cell loss. Trials at all stages of beta cell loss have been conducted: primary prevention (prior to the development of autoimmunity); secondary prevention (after autoantibodies are found) and tertiary prevention (intervening after diagnosis to maintain remaining beta cells). Studies have shown mixed results; evidence of maintained insulin secretion after the time of diagnosis has been described in a number of studies, and primary and secondary prevention is proving to be elusive. Much has been learned from the increasing number of studies in the field in terms of network creation, study design and choice of intervention that will facilitate new avenues of investigation. | 25,092,646 | [
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Modulation of a cytoskeletal calpain-like protein induces major transitions in trypanosome morphology. | Individual eukaryotic microbes, such as the kinetoplastid parasite Trypanosoma brucei, have a defined size, shape, and form yet transition through life cycle stages, each having a distinct morphology. In questioning the structural processes involved in these transitions, we have identified a large calpain-like protein that contains numerous GM6 repeats (ClpGM6) involved in determining T. brucei cell shape, size, and form. ClpGM6 is a cytoskeletal protein located within the flagellum along the flagellar attachment zone (FAZ). Depletion of ClpGM6 in trypomastigote forms produces cells with long free flagella and a shorter FAZ, accompanied by repositioning of the basal body, the kinetoplast, Golgi, and flagellar pocket, reflecting an epimastigote-like morphology. Hence, major changes in microbial cell form can be achieved by simple modulation of one or a few proteins via coordinated association and positioning of membrane and cytoskeletal components. | 25,092,656 | [
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Two sources of meaning in infant communication: preceding action contexts and act-accompanying characteristics. | How do infants communicate before they have acquired a language? This paper supports the hypothesis that infants possess social-cognitive skills that run deeper than language alone, enabling them to understand others and make themselves understood. I suggested that infants, like adults, use two sources of extralinguistic information to communicate meaningfully and react to and express communicative intentions appropriately. In support, a review of relevant experiments demonstrates, first, that infants use information from preceding shared activities to tailor their comprehension and production of communication. Second, a series of novel findings from our laboratory shows that in the absence of distinguishing information from preceding routines or activities, infants use accompanying characteristics (such as prosody and posture) that mark communicative intentions to extract and transmit meaning. Findings reveal that before infants begin to speak they communicate in meaningful ways by binding preceding and simultaneous multisensory information to a communicative act. These skills are not only a precursor to language, but also an outcome of social-cognitive development and social experience in the first year of life. | 25,092,662 | [
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How arbitrary is language? | It is a long established convention that the relationship between sounds and meanings of words is essentially arbitrary--typically the sound of a word gives no hint of its meaning. However, there are numerous reported instances of systematic sound-meaning mappings in language, and this systematicity has been claimed to be important for early language development. In a large-scale corpus analysis of English, we show that sound-meaning mappings are more systematic than would be expected by chance. Furthermore, this systematicity is more pronounced for words involved in the early stages of language acquisition and reduces in later vocabulary development. We propose that the vocabulary is structured to enable systematicity in early language learning to promote language acquisition, while also incorporating arbitrariness for later language in order to facilitate communicative expressivity and efficiency. | 25,092,667 | [
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Origin of symbol-using systems: speech, but not sign, without the semantic urge. | Natural language--spoken and signed--is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint. | 25,092,671 | [
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Linezolid manifests a rapid and dramatic therapeutic effect for patients with life-threatening tuberculous meningitis. | We conducted a retrospective cohort study of patients with MRC grade II/III tuberculous meningitis (TBM) who accepted a background antitubercular regimen (BR) with or without linezolid (LZD). At the 4th week, the LZD-BR group achieved a faster and higher percentage of Glasgow coma scale recovery and temperature recovery, a higher cerebrospinal fluid (CSF)/blood glucose ratio, and lower CSF white blood cell counts than did the BR group. Short-term linezolid supplementation may be a more effective treatment for life-threatening TBM. | 25,092,692 | [
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The activity of glycopeptide antibiotics against resistant bacteria correlates with their ability to induce the resistance system. | Glycopeptide antibiotics containing a hydrophobic substituent display the best activity against vancomycin-resistant enterococci, and they have been assumed to be poor inducers of the resistance system. Using a panel of 26 glycopeptide derivatives and the model resistance system in Streptomyces coelicolor, we confirmed this hypothesis at the level of transcription. Identification of the structural glycopeptide features associated with inducing the expression of resistance genes has important implications in the search for more effective antibiotic structures. | 25,092,694 | [
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High prevalence of extended-spectrum β-lactamase, plasmid-mediated AmpC, and carbapenemase genes in pet food. | We evaluated the pet food contained in 30 packages as a potential origin of extended-spectrum cephalosporin-resistant Gram-negative organisms and β-lactamase genes (bla). Live bacteria were not detected by selective culture. However, PCR investigations on food DNA extracts indicated that samples harbored the blaCTX-M-15 (53.3%), blaCMY-4 (20%), and blaVEB-4-like (6.7%) genes. Particularly worrisome was the presence of blaOXA-48-like carbapenemases (13.3%). The original pet food ingredients and/or the production processes were highly contaminated with bacteria carrying clinically relevant acquired bla genes. | 25,092,703 | [
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Physiologically based pharmacokinetic prediction of telmisartan in human. | A previously developed physiologically based pharmacokinetic model for hepatic transporter substrates was extended to an organic anion transporting polypeptide substrate, telmisartan. Predictions used in vitro data from sandwich culture human hepatocyte and human liver microsome assays. We have developed a novel method to calibrate partition coefficients (Kps) between nonliver tissues and plasma on the basis of published human positron emission tomography (PET) data to decrease the uncertainty in tissue distribution introduced by in silico-predicted Kps. With in vitro data-predicted hepatic clearances, published empirical scaling factors, and PET-calibrated Kps, the model could accurately recapitulate telmisartan pharmacokinetic (PK) behavior before 2.5 hours. Reasonable predictions also depend on having a model structure that can adequately describe the drug disposition pathways. We showed that the elimination phase (2.5-12 hours) of telmisartan PK could be more accurately recapitulated when enterohepatic recirculation of parent compound derived from intestinal deconjugation of glucuronide metabolite was incorporated into the model. This study demonstrated the usefulness of the previously proposed physiologically based modeling approach for purely predictive intravenous PK simulation and identified additional biologic processes that can be important in prediction. | 25,092,714 | [
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Quality-of-life measures for use within care homes: a systematic review of their measurement properties. | the aims of this review were (i) to identify quality-of-life (QoL) measures which have had their measurement properties validated in people residing in care homes or nursing homes, and to critically compare and summarise these instruments and (ii) to make recommendations for measurement instruments. bibliographic databases PsycINFO, PubMed, Cochrane, CINAHL and Embase were searched for articles evaluating measurement properties of QoL instruments in people residing in care homes. Methodological quality of studies was assessed using the consensus-based standards for the selection of health measurement instruments checklist. Measurement properties of instruments were appraised using a systematic checklist. the search strategy resulted in 3252 unique citations, of which 15 articles were included in this review. These articles assessed 13 instruments, 8 of which were dementia or Alzheimer specific instruments. The QUALIDEM, a dementia-specific observational instrument, had the widest array of information available on its measurement properties, which were mostly satisfactory. Most measurement instruments lacked information on hypotheses testing and content validity. Information on responsiveness and measurement error was not available for any instrument. for people with dementia living in care homes, the QUALIDEM is recommended for measuring QoL. For residents without dementia, we recommend Kane et al.'s Psychosocial Quality of Life Domains questionnaire. Studies of higher methodological quality, assessing a wider range of measurement properties are needed to allow a more fully informed choice of QoL instrument. | 25,092,719 | [
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Statin use after colorectal cancer diagnosis and survival: a population-based cohort study. | To investigate whether statins used after colorectal cancer diagnosis reduce the risk of colorectal cancer-specific mortality in a cohort of patients with colorectal cancer. A cohort of 7,657 patients with newly diagnosed stage I to III colorectal cancer were identified from 1998 to 2009 from the National Cancer Data Repository (comprising English cancer registry data). This cohort was linked to the United Kingdom Clinical Practice Research Datalink, which provided prescription records, and to mortality data from the Office of National Statistics (up to 2012) to identify 1,647 colorectal cancer-specific deaths. Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% CIs by postdiagnostic statin use and to adjust these HRs for potential confounders. Overall, statin use after a diagnosis of colorectal cancer was associated with reduced colorectal cancer-specific mortality (fully adjusted HR, 0.71; 95% CI, 0.61 to 0.84). A dose-response association was apparent; for example, a more marked reduction was apparent in colorectal cancer patients using statins for more than 1 year (adjusted HR, 0.64; 95% CI, 0.53 to 0.79). A reduction in all-cause mortality was also apparent in statin users after colorectal cancer diagnosis (fully adjusted HR, 0.75; 95% CI, 0.66 to 0.84). In this large population-based cohort, statin use after diagnosis of colorectal cancer was associated with longer rates of survival. | 25,092,779 | [
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Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. | To improve survival rates in children with acute myeloid leukemia (AML), we evaluated gemtuzumab-ozogamicin (GO), a humanized immunoconjugate targeted against CD33, as an alternative to further chemotherapy dose escalation. Our primary objective was to determine whether adding GO to standard chemotherapy improved event-free survival (EFS) and overall survival (OS) in children with newly diagnosed AML. Our secondary objectives examined outcomes by risk group and method of intensification. Children, adolescents, and young adults ages 0 to 29 years with newly diagnosed AML were enrolled onto Children’s Oncology Group trial AAML0531 and then were randomly assigned to either standard five-course chemotherapy alone or to the same chemotherapy with two doses of GO (3 mg/m2/dose) administered once in induction course 1 and once in intensification course 2 (two of three). There were 1,022 evaluable patients enrolled. GO significantly improved EFS (3 years: 53.1% v. 46.9%; hazard ratio [HzR], 0.83; 95% CI, 0.70 to 0.99; P.04) but not OS (3 years: 69.4% v. 65.4%; HzR, 0.91; 95% CI, 0.74 to 1.13; P = .39). Although remission was not improved (88% v. 85%; P = .15), posthoc analyses found relapse risk (RR) was significantly reduced among GO recipients overall (3 years: 32.8% v. 41.3%; HzR, 0.73; 95% CI, 0.58 to 0.91; P = .006). Despite an increased postremission toxic mortality (3 years: 6.6% v. 4.1%; HzR, 1.69; 95% CI, 0.93 to 3.08; P = .09), disease-free survival was better among GO recipients (3 years: 60.6% v. 54.7%; HzR, 0.82; 95% CI, 0.67 to 1.02; P = .07). GO added to chemotherapy improved EFS through a reduction in RR for children and adolescents with AML. | 25,092,781 | [
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Early activation of the kynurenine pathway predicts early death and long-term outcome in patients resuscitated from out-of-hospital cardiac arrest. | The kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post-cardiac arrest shock, early death, and long-term outcome. Plasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12-month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3-hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3-hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3-hydroxyanthranilic acid had lower 24-hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3-hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12-month poor outcome and significantly improved risk reclassification. KP is activated early after cardiac arrest and is associated with severity of post-cardiac arrest shock, early death, and poor long-term outcome. | 25,092,787 | [
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The use of crowdsourcing for dietary self-monitoring: crowdsourced ratings of food pictures are comparable to ratings by trained observers. | Crowdsourcing dietary ratings for food photographs, which uses the input of several users to provide feedback, has potential to assist with dietary self-monitoring. This study assessed how closely crowdsourced ratings of foods and beverages contained in 450 pictures from the Eatery mobile app as rated by peer users (fellow Eatery app users) (n = 5006 peers, mean 18.4 peer ratings/photo) using a simple 'healthiness' scale were related to the ratings of the same pictures by trained observers (raters). In addition, the foods and beverages present in each picture were categorized and the impact on the peer rating scale by food/beverage category was examined. Raters were trained to provide a 'healthiness' score using criteria from the 2010 US Dietary Guidelines. The average of all three raters' scores was highly correlated with the peer healthiness score for all photos (r = 0.88, p<0.001). Using a multivariate linear model (R(2) = 0.73) to examine the association of peer healthiness scores with foods and beverages present in photos, peer ratings were in the hypothesized direction for both foods/beverages to increase and ones to limit. Photos with fruit, vegetables, whole grains, and legumes, nuts, and seeds (borderline at p = 0.06) were all associated with higher peer healthiness scores, and processed foods (borderline at p = 0.06), food from fast food restaurants, refined grains, red meat, cheese, savory snacks, sweets/desserts, and sugar-sweetened beverages were associated with lower peer healthiness scores. The findings suggest that crowdsourcing holds potential to provide basic feedback on overall diet quality to users utilizing a low burden approach. | 25,092,793 | [
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Patterns of innervation of the lacrimal gland with clinical application. | Parasympathetic stimulation of the lacrimal gland is responsible for tear production, and this innervation originates from fibers conveyed in the facial nerve. After synapse in the pterygopalatine ganglion, postsynaptic parasympathetic fibers travel within the zygomatic and zygomaticotemporal nerves (ZTN) into the orbit. As described in most anatomy texts, ZTN communicates with the lacrimal nerve (LN) posterior to the gland and then secretomotor fibers enter the gland. This study was performed to gain a better understanding of the innervation of the lacrimal gland. Seventeen cadaver heads were bisected for a total of 34 sides, which then underwent dissection of the superolateral orbital region to observe the course for the LN and ZTN. Three variations of the course of the LN and ZTN were found. In 20 (60.6%) dissections it was documented that the ZTN entered directly into the lacrimal gland with no communication with the LN. In 12 (36.4%) of the bisected heads, ZTN had both a direct connection into the gland and a communicating branch with the LN. In only one (3.0%) bisected head, ZTN communicated with the LN before entering the gland as it is commonly described in anatomy texts. Our study reveals that the ZTN usually takes a different course than is classically described in most anatomy textbooks. A greater understanding of the typical course these nerves take may help surgeons identify them more easily and avoid damaging them. | 25,092,807 | [
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Medicaid admissions and readmissions: understanding the prevalence, payment, and most common diagnoses. | Reducing hospital readmissions is a way to improve care and reduce avoidable costs. However, there have been few studies of readmissions in the Medicaid population. We sought to characterize acute care hospital admissions and thirty-day readmissions in the Medicaid population through a retrospective analysis in nineteen states. We found that Medicaid readmissions were both prevalent (9.4 percent of all admissions) and costly ($77 million per state) and that they represented 12.5 percent of Medicaid payments for all hospitalizations. Five diagnostic groups appeared to drive Medicaid readmissions, accounting for 57 percent of readmissions and 49 percent of hospital payments for readmissions. The most prevalent diagnostic categories were mental and behavioral disorders and diagnoses related to pregnancy, childbirth, and their complications, which together accounted for 31.2 percent of readmissions. This analysis, conducted through the Medicaid Medical Directors Learning Network, allows Medicaid medical directors to better understand the nature and prevalence of hospital use in the Medicaid population and provides a baseline for measuring improvement. | 25,092,834 | [
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Children's health insurance program premiums adversely affect enrollment, especially among lower-income children. | Both Medicaid and the Children's Health Insurance Program (CHIP), which are run by the states and funded by federal and state dollars, offer health insurance coverage for low-income children. Thirty-three states charged premiums for children at some income ranges in CHIP or Medicaid in 2013. Using data from the 1999-2010 Medical Expenditure Panel Surveys, we show that the relationship between premiums and coverage varies considerably by income level and by parental access to employer-sponsored insurance. Among children with family incomes above 150 percent of the federal poverty level, a $10 increase in monthly premiums is associated with a 1.6-percentage-point reduction in Medicaid or CHIP coverage. In this income range, the increase in uninsurance may be higher among those children whose parents lack an offer of employer-sponsored insurance than among those whose parents have such an offer. Among children with family incomes of 101-150 percent of poverty, a $10 increase in monthly premiums is associated with a 6.7-percentage-point reduction in Medicaid or CHIP coverage and a 3.3-percentage-point increase in uninsurance. In this income range, the increase in uninsurance is even larger among children whose parents lack offers of employer coverage. | 25,092,836 | [
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Exploring regional differences in the reading competencies of Italian students. | Recently, the study of territorial differences in educational outcomes has assumed a particular importance for the policy strategies related to the socioeconomic conditions of different geographical areas. In Italy, international surveys for student assessments have introduced a regional stratification only recently, and regular national student assessments started only in 2008. In this article, the reading performances of Italian students based on OECD-PISA 2009 are investigated, taking into account regional and macro-area partition. Student outcomes are explored by using a multilevel analysis, where school membership, socioeconomic and cultural background of students, and regional gross domestic product are introduced. The results show that, despite the existence of a unified educational system in Italy, regional and macro-area differences in student reading achievements are consolidated and variability in performances among schools is especially noticeable. Comparisons based on national assessments by INVALSI at the end of compulsory school confirm these findings. Italian policy makers are advised to take into account these results to improve learning opportunities and to reduce educational gaps. In particular, targeted regional policies are needed to improve the mean performance especially in the Southern regions of Calabria, Campania, and Sicilia, and to strengthen the system equity in several regions, such as Emilia-Romagna. To decrease the school differences, possible suggestions are to postpone the choice of the school type (currently, at age 14) and to motivate good teachers to work in schools located in the worst socioeconomic and cultural environments. | 25,092,864 | [
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RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development. | Ligation of erythropoietin (EPO) receptor (EPOR) JAK2 kinase complexes propagates signals within erythroid progenitor cells (EPCs) that are essential for red blood cell production. To reveal hypothesized novel EPOR/JAK2 targets, a phosphotyrosine (PY) phosphoproteomics approach was applied. Beyond known signal transduction factors, 32 new targets of EPO-modulated tyrosine phosphorylation were defined. Molecular adaptors comprised one major set including growth factor receptor-bound protein 2 (GRB2)-associated binding proteins 1-3 (GAB1-3), insulin receptor substrate 2 (IRS2), docking protein 1 (DOK1), Src homology 2 domain containing transforming protein 1 (SHC1), and sprouty homologue 1 (SPRY1) as validating targets, and SPRY2, SH2 domain containing 2A (SH2D2A), and signal transducing adaptor molecule 2 (STAM2) as novel candidate adaptors together with an ORF factor designated as regulator of human erythroid cell expansion (RHEX). RHEX is well conserved in Homo sapiens and primates but absent from mouse, rat, and lower vertebrate genomes. Among tissues and lineages, RHEX was elevated in EPCs, occurred as a plasma membrane protein, was rapidly PY-phosphorylated >20-fold upon EPO exposure, and coimmunoprecipitated with the EPOR. In UT7epo cells, knockdown of RHEX inhibited EPO-dependent growth. This was associated with extracellular signal-regulated kinase 1,2 (ERK1,2) modulation, and RHEX coupling to GRB2. In primary human EPCs, shRNA knockdown studies confirmed RHEX regulation of erythroid progenitor expansion and further revealed roles in promoting the formation of hemoglobinizing erythroblasts. RHEX therefore comprises a new EPO/EPOR target and regulator of human erythroid cell expansion that additionally acts to support late-stage erythroblast development. | 25,092,874 | [
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Dietary manipulation of oncogenic microRNA expression in human rectal mucosa: a randomized trial. | High red meat (HRM) intake is associated with increased colorectal cancer risk, while resistant starch is probably protective. Resistant starch fermentation produces butyrate, which can alter microRNA (miRNA) levels in colorectal cancer cells in vitro; effects of red meat and resistant starch on miRNA expression in vivo were unknown. This study examined whether a HRM diet altered miRNA expression in rectal mucosa tissue of healthy volunteers, and if supplementation with butyrylated resistant starch (HRM+HAMSB) modified this response. In a randomized cross-over design, 23 volunteers undertook four 4-week dietary interventions; an HRM diet (300 g/day lean red meat) and an HRM+HAMSB diet (HRM with 40 g/day butyrylated high amylose maize starch), preceded by an entry diet and separated by a washout. Fecal butyrate increased with the HRM+HAMSB diet. Levels of oncogenic mature miRNAs, including miR17-92 cluster miRNAs and miR21, increased in the rectal mucosa with the HRM diet, whereas the HRM+HAMSB diet restored miR17-92 miRNAs, but not miR21, to baseline levels. Elevated miR17-92 and miR21 in the HRM diet corresponded with increased cell proliferation, and a decrease in miR17-92 target gene transcript levels, including CDKN1A. The oncogenic miR17-92 cluster is differentially regulated by dietary factors that increase or decrease risk for colorectal cancer, and this may explain, at least in part, the respective risk profiles of HRM and resistant starch. These findings support increased resistant starch consumption as a means of reducing risk associated with an HRM diet. | 25,092,886 | [
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Potential immune mechanisms associated with anemia in Plasmodium vivax malaria: a puzzling question. | The pathogenesis of malaria is complex, generating a broad spectrum of clinical manifestations. One of the major complications and concerns in malaria is anemia, which is responsible for considerable morbidity in the developing world, especially in children and pregnant women. Despite its enormous health importance, the immunological mechanisms involved in malaria-induced anemia remain incompletely understood. Plasmodium vivax, one of the causative agents of human malaria, is known to induce a strong inflammatory response with a robust production of immune effectors, including cytokines and antibodies. Therefore, it is possible that the extent of the immune response not only may facilitate the parasite killing but also may provoke severe illness, including anemia. In this review, we consider potential immune effectors and their possible involvement in generating this clinical outcome during P. vivax infections. | 25,092,911 | [
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Automated conversation system before pediatric primary care visits: a randomized trial. | Interactive voice response systems integrated with electronic health records have the potential to improve primary care by engaging parents outside clinical settings via spoken language. The objective of this study was to determine whether use of an interactive voice response system, the Personal Health Partner (PHP), before routine health care maintenance visits could improve the quality of primary care visits and be well accepted by parents and clinicians. English-speaking parents of children aged 4 months to 11 years called PHP before routine visits and were randomly assigned to groups by the system at the time of the call. Parents' spoken responses were used to provide tailored counseling and support goal setting for the upcoming visit. Data were transferred to the electronic health records for review during visits. The study occurred in an urban hospital-based pediatric primary care center. Participants were called after the visit to assess (1) comprehensiveness of screening and counseling, (2) assessment of medications and their management, and (3) parent and clinician satisfaction. PHP was able to identify and counsel in multiple areas. A total of 9.7% of parents responded to the mailed invitation. Intervention parents were more likely to report discussing important issues such as depression (42.6% vs 25.4%; P < .01) and prescription medication use (85.7% vs 72.6%; P = .04) and to report being better prepared for visits. One hundred percent of clinicians reported that PHP improved the quality of their care. Systems like PHP have the potential to improve clinical screening, counseling, and medication management. | 25,092,938 | [
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Axial length measurement acquisition rates of two optical biometers in cataractous eyes. | To compare the ability of two optical biometers to acquire the axial length (AL) measurement in cataractous eyes. This prospective, comparative, single-center study comprised 105 eyes (63 patients). AL was acquired by the composite mean value of 20 measurements (composite-20 IM) and five measurements (composite-5 IM) (IOLMaster(®) 500 version 7.1 software), and the standard mean value of the first five measurements (standard-5 LS, Lenstar LS 900(®)). Anterior chamber depth (ACD) and average keratometry (K) readings were acquired. AL was acquired in 83.8%, 92.4%, and 84.8% of eyes for the composite-5 IM, composite-20 IM, and standard-5 LS, respectively. Standard-5 LS AL measurements were significantly shorter (P<0.001). IOLMaster(®) 500-acquired ACD (corneal epithelium to lens) measurements were significantly shorter (P<0.001). IOLMaster(®) 500 average K measurements were significantly steeper (P<0.001). The composite-20 IM had the highest AL acquisition success rate of the three versions evaluated. AL, ACD, and average Ks were statistically different between the two biometers, although the differences were clinically insignificant. | 25,092,960 | [
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Cerebellar dysregulation and heterogeneity of mood disorders. | This paper discusses diverse studies to consider the hypothesis that cerebellar pathology supports the heterogeneous metabolic pathologies of mood disorders. The evidence presented includes studies selected from the following areas of scientific research: magnetic resonance imaging, histology, clinical syndromes, comparative anatomy, neuronal connections, and mitochondrial dysfunction. The gamut of different scientific study methods confirms the validity of the involvement of the cerebellum in mood disorders. | 25,092,983 | [
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High expression of HEF1 is associated with poor prognosis in urinary bladder carcinoma. | Human enhancer of filamentation 1 (HEF1) is a multidomain scaffolding protein that has been thought to play an important role in the tumor progression of various cancers. HEF1 expression has not previously been reported in urinary bladder carcinoma, and little is known about its prognostic significance. The aim of this study was to evaluate the expression patterns of HEF1 in urinary bladder carcinoma and to investigate its prognostic significance. HEF1 expression was analyzed by immunohistochemistry using tissue microarray. A significant relationship between HEF1 expression and sex, tumor size, number of tumors, invasion depth, lymph node metastasis, and distant metastasis was found, and high expression of HEF1 was associated with worse overall survival when compared to low expression of HEF1. Multivariate analysis showed that HEF1 expression was an independent prognostic factor for overall survival in urinary bladder carcinoma. We investigated HEF1 expression in urinary bladder carcinoma and found that high HEF1 expression was associated with advanced stage, large tumor size, and shortened progression-free survival. Although the biologic function of HEF1 in urinary bladder carcinoma remains unknown, the expression of HEF1 can provide new prognostic information for disease progression. | 25,092,988 | [
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Pioglitazone improves the cardio-ankle vascular index in patients with type 2 diabetes mellitus treated with metformin. | Type 2 diabetes is known to be associated with elevated cardiovascular mortality. Pioglitazone improves blood pressure (BP) and pulse wave velocity (PWV), which is an arterial stiffness parameter. Arterial stiffness is closely associated with cardiovascular disease. However, PWV is correlated with BP. The cardio-ankle vascular index (CAVI) reflects arterial stiffness independent of BP. Pioglitazone improves PWV but reduces blood pressure. The aim of this study was to re-evaluate the effect of pioglitazone on arterial stiffness with CAVI. Sixty patients with type 2 diabetes mellitus and already on 500 mg/day of metformin received add-on therapy of pioglitazone 15 mg/day or glimepiride 1 mg/day for 6 months, during which time changes in their metabolic parameters and CAVI were observed. After 6 months of treatment, both pioglitazone (n=30) and glimepiride (n=30) improved fasting blood glucose and glycated hemoglobin. The changes in fasting blood glucose and glycated hemoglobin between the two groups were greater in the pioglitazone group. Systolic and diastolic BP was decreased in both groups, with no significant between-group differences. Only pioglitazone increased serum adiponectin levels, and the change in adiponectin between the pioglitazone and glimepiride groups was significantly different. CAVI was decreased significantly by pioglitazone but remained unchanged after treatment with glimepiride. The change in CAVI between the two groups was significantly different. These results suggest that pioglitazone improves CAVI, a BP-independent arterial stiffness parameter, in patients with type 2 diabetes mellitus treated with metformin. | 25,092,992 | [
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Cognitive control in bilinguals: Advantages in Stimulus-Stimulus inhibition. | Bilinguals have been shown to outperform monolinguals at suppressing task-irrelevant information and on overall speed during cognitive control tasks. Here, monolinguals' and bilinguals' performance was compared on two nonlinguistic tasks: a Stroop task (with perceptual Stimulus-Stimulus conflict among stimulus features) and a Simon task (with Stimulus-Response conflict). Across two experiments testing bilinguals with different language profiles, bilinguals showed more efficient Stroop than Simon performance, relative to monolinguals, who showed fewer differences across the two tasks. Findings suggest that bilingualism may engage Stroop-type cognitive control mechanisms more than Simon-type mechanisms, likely due to increased Stimulus-Stimulus conflict during bilingual language processing. Findings are discussed in light of previous research on bilingual Stroop and Simon performance. | 25,093,009 | [
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The effects of a multi-ingredient dietary supplement on body composition, adipokines, blood lipids, and metabolic health in overweight and obese men and women: a randomized controlled trial. | The present study investigated the effects of a multi-ingredient dietary supplement (MIDS) containing caffeine, conjugated linoleic acid (CLA), green tea, and branched-chain amino acids (BCAA) taken for 8 weeks on body composition, blood lipid profile, glucose, insulin, adiponectin, leptin, and high-sensitivity C-reactive protein (hs-CRP) in overweight and obese men and women. Twenty-two participants completed the study (PL, n = 11; 7 women, 4 men; age, 34 ± 3.5 years; height, 169.2 ± 3.3 cm; body mass, 96.9 ± 6.8 kg; BMI, 34.1 ± 1.8 kg/m(2); MIDS, n = 11; 9 women, 2 men; age, 36 ± 3.4 years; height, 173.2 ± 2.9 cm; body mass, 91.9 ± 5.6 kg; BMI, 30.0 ± 1.5 kg/m(2)). Participants were randomly assigned and stratified by body fat percentage to two groups: 1) a soybean oil placebo (PL) or 2) MIDS. Each group consumed two pills with breakfast and two pills with lunch. Body composition and android fat, waist and hip circumferences, blood pressure and heart rate were measured at baseline and after 8 weeks of supplementation. There were no significant changes for any of the variables of body composition. Feelings of hunger were significantly higher in MIDS versus PL with no changes observed in satiety or desire to eat. Heart rate and blood pressure were unaltered in MIDS after 8 weeks of supplementation. Furthermore, lipid profile, food intake, mood state variables, fasting blood glucose, and endocrine markers did not significantly change regardless of group. MIDS intake does not appear to alter body composition or markers of cardiovascular health versus PL. Moreover, MIDS may actually increase feelings of hunger versus PL. | 25,093,015 | [
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Electrophoretic Deposition of Carbon Nanotubes over TiO2 Nanotubes: Evaluation of Surface Properties and Biocompatibility. | Titanium (Ti) is often used as an orthopedic and dental implant material due to its better mechanical properties, corrosion resistance, and excellent biocompatibility. Formation of TiO2 nanotubes (TiO2 NTs) on titanium is an interesting surface modification to achieve controlled drug delivery and to promote cell growth. Carbon nanotubes (CNTs) possess excellent chemical durability and mechanical strength. The use of CNTs in biomedical applications such as scaffolds has received considerable attention in recent years. The present study aims to modify the surface of titanium by anodizing to form TiO2 NTs and subsequently deposit CNTs over it by electrophoretic deposition (EPD). Characteristic, biocompatibility, and apatite forming ability of the surface modified samples were evaluated. The results of the study reveal that CNTs coating on TiO2 nanotubes help improve the biological activity and this type of surface modification is highly suitable for biomedical applications. | 25,093,017 | [
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Large deletion causing von Hippel-Lindau disease and hereditary breast cancer syndrome. | Patients with intragenic mutations of the VHL gene have a typical disease presentation. However in cases of large VHL gene deletions which involve other genes in the proximity of the VHL gene a presentation of the disease can be different. To investigate whether large VHL deletions that remove the FANCD2 gene have an effect on the disease phenotype, we studied a family with a 50 kb large deletion encompassing these two genes. Four patients in this family were affected by VHL-related lesions. However one carrier of the deletion also had bilateral ductal breast cancer at age 46 and 49. Both tumors were of ~2 cm in diameter. On one side lymph nodes were affected. One tumor was ER- and PR-negative (HER2 s unknown) and the second was ER- and PR-positive, and HER2-negative. Our study suggests that a deletion of FANCD2 gene, an important gene in the DNA repair pathway, may be associated with an increased risk of breast cancer, but further studies are needed in this regard. | 25,093,046 | [
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The SNPs (-1654C/T, -1641A/G and -1476A/T) of protein C promoter are associated with susceptibility to pulmonary thromboembolism in a Chinese population. | Pulmonary thromboembolism (PTE) is a common and potentially lethal disease. It is significant to investigate the gene mutations of protein C for clarifying the etiology of PTE. In this present study, we investigated the promoter region polymorphism sites including -1654C/T, -1641A/G and -1476A/T of the protein C gene in a Chinese population. A total of 110 cases of PTE and one hundred and ninety healthy controls in a Chinese population were genotyped for three polymorphisms (-1654C/T, -1641A/G and -1476A/T) of the protein C promoter. The statistical analysis was performed by Stata 11.0. The single nucleotide polymorphisms (SNPs) (-1654C/T, -1641A/G and -1476A/T) in protein C gene were associated with the susceptibility to PTE in Chinese population. According to the binary logistic regression analysis, the independently significant risk factors for PTE were the complications of deep vein thrombosis (DVT) or cancer, history of operation or injury, and the homozygous carriers of the TT genotype (protein C -1654C/T). The SNPs (-1654C/T, -1641A/G and -1476A/T) of protein C promoter gene are associated with the susceptibility to PTE in a Chinese population. Especially, the homozygous carriers of genotype TT (-1654C/T) increase the risk of PTE in a Chinese population. Confirmation of our preliminary observations in a larger scale study is needed. | 25,093,091 | [
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Predictive value of lactate in unselected critically ill patients: an analysis using fractional polynomials. | Hyperlactatemia has long been associated with poor clinical outcome in varieties of intensive care unit (ICU) patients. However, the impact of temporal changes in lactate has not been well established and there are some shortcomings in model building in previous studies. The present study aims to investigate the association of initial lactate and normalization time with hazard by using fractional polynomial Cox proportional hazard model. A large clinical database named Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) was employed for analysis. Demographics, comorbidities, laboratory findings were extracted and were compared between survivors and non-survivors by using univariable analysis. Cox proportional hazard model was built by purposeful selection of covariate with initial lactate (L0) and normalization time (T) remaining in the model. Best fit model was selected by using deviance difference test and comparisons between fractional polynomial regression models of different degrees were performed by using closed test procedure. A total of 6,291 ICU patients were identified to be eligible for the present study, including 1,675 non-survivors and 4,616 survivors (mortality rate: 26.6%). Patients with lactate normalization had significantly reduced hazard rate as compared to those without normalization (log-rank test: P<0.05). The best powers of L0 in the model were -2 and -1 with the deviance of 19,944.51, and the best powers of T were 0.5 and 3 with the deviance of 7,965.63. The adjusted hazard ratio for the terms L0(-2) and L0(-1) were 1.13 (95% CI: 1.09-1.18) and 0.43 (95% CI: 0.34-0.54); and the adjusted hazard ratio for the terms T(0.5) and T(3) were 7.42 (95% CI: 2.85-19.36) and 3.06×10(-6) (95% CI: 3.01×10(-11)-0.31). Initial lactate on ICU admission is associated with death hazard and the relationship follows a fractional polynomial pattern with the power of -2 and -1. Delayed normalization of lactate is predictive of high risk of death when it is measured within 150 hours after ICU admission. | 25,093,098 | [
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Structural Features of the Telomerase RNA Gene in the Naked Mole Rat Heterocephalus glaber. | Telomere length, an important feature of life span control, is dependent on the activity of telomerase (a key enzyme of the telomere-length-maintaining system). Telomerase RNA is a component of telomerase and, thus, is crucial for its activity. The structures of telomerase RNA genes and their promoter regions were compared for the long-living naked mole rat and different organisms. Two rare polymorphisms in Heterocephalus glaber telomerase RNA (hgTER) were identified: A→G in the first loop of pseudoknot P2b-p3 (an equivalent of 111nt in hTR) and G→A in the scaRNA domain CR7-p8b (an equivalent of 421nt in hTR). Analysis of TER promoter regions allowed us to identify two new transcription factor binding sites. The first one is the ETS family site, which was found to be a conserved element for all the analyzed TER promoters. The second site is unique for the promoter region of TER of the naked mole rat and is a binding site for the SOX17 transcription factor. The absence of one Sp1 site in the TER promoter region of the naked small rat is an additional specific feature of the promoter area of hgTER. Such variation in the hgTER transcription regulation region and hgTER itself could provide increased telomerase activity in stem cells and an extended lifespan to H. glaber. | 25,093,110 | [
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High-throughput Method of One-Step DNA Isolation for PCR Diagnostics of Mycobacterium tuberculosis. | The efficiency of one-step and multi-step protocols of DNA isolation from lysed sputum samples containing the Mycobacterium tuberculosis complex has been compared. DNA was isolated using spin-cartridges containing a special silica-based sorbent modified with fluoroplast and polyaniline, or using an automated isolation system. One-step isolation using the obtained sorbent has been shown to ensure a significantly lower DNA loss and higher sensitivity in the PCR detection of Mycobacterium tuberculosis as compared to a system based on sorption and desorption of nucleic acids during the isolation. | 25,093,111 | [
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Lipid-protein nanodiscs offer new perspectives for structural and functional studies of water-soluble membrane-active peptides. | Lipid-protein nanodiscs (LPNs) are nanoscaled fragments of a lipid bilayer stabilized in solution by the apolipoprotein or a special membrane scaffold protein (MSP). In this work, the applicability of LPN-based membrane mimetics in the investigation of water-soluble membrane-active peptides was studied. It was shown that a pore-forming antimicrobial peptide arenicin-2 from marine lugworm (charge of +6) disintegrates LPNs containing both zwitterionic phosphatidylcholine (PC) and anionic phosphatidylglycerol (PG) lipids. In contrast, the spider toxin VSTx1 (charge of +3), a modifier of Kv channel gating, effectively binds to the LPNs containing anionic lipids (POPC/DOPG, 3 : 1) and does not cause their disruption. VSTx1 has a lower affinity to LPNs containing zwitterionic lipids (POPC), and it weakly interacts with the protein component of nanodiscs, MSP (charge of -6). The neurotoxin II (NTII, charge of +4) from cobra venom, an inhibitor of the nicotinic acetylcholine receptor, shows a comparatively low affinity to LPNs containing anionic lipids (POPC/DOPG, 3 : 1 or POPC/DOPS, 4 : 1), and it does not bind to LPNs/POPC. The obtained data show that NTII interacts with the LPN/POPC/DOPS surface in several orientations, and that the exchange process among complexes with different topologies proceeds fast on the NMR timescale. Only one of the possible NTII orientations allows for the previously proposed specific interaction between the toxin and the polar head group of phosphatidylserine from the receptor environment (Lesovoy et al., Biophys. J. 2009. V. 97. № 7. P. 2089-2097). These results indicate that LPNs can be used in structural and functional studies of water-soluble membrane-active peptides (probably except pore-forming ones) and in studies of the molecular mechanisms of peptide-membrane interaction. | 25,093,115 | [
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Construction of a pIX-modified Adenovirus Vector Able to Effectively Bind to Nanoantibodies for Targeting. | Current targeting strategies for genetic vectors imply the creation of a specific vector for every targeted receptor, which is time-consuming and expensive. Therefore, the development of a universal vector system whose surface can specifically bind molecules to provide efficient targeting is of particular interest. In this study, we propose a new approach in creating targeted vectors based on the genome of human adenovirus serotype 5 carrying the modified gene of the capsid protein pIX (Ad5-EGFP-pIX-ER): recombinant pseudoadenoviral nanoparticles (RPANs). The surfaces of such RPANs are able to bind properly modified chimeric nanoantibodies that specifically recognize a particular target antigen (carcinoembryonic antigen (CEA)) with high affinity. The efficient binding of nanoantibodies (aCEA-RE) to the RPAN capsid surfaces has been demonstrated by ELISA. The ability of the constructed vector to deliver target genes has been confirmed by experiments with the tumor cell lines A549 and Lim1215 expressing CEA. It has been shown that Ad5-EGFP-pIX-ER carrying aCEA-RE on its surface penetrates into the tumor cell lines A549 and Lim1215 via the CAR-independent pathway three times more efficiently than unmodified RPAN and Ad5-EGFP-pIX-ER without nanoantibodies on the capsid surface. Thus, RPAN Ad5-EGFP-pIX-ER is a universal platform that may be useful for targeted gene delivery in specific cells due to "nanoantibody-modified RPAN" binding. | 25,093,116 | [
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Idelalisib for the treatment of chronic lymphocytic leukemia. | Chronic lymphocytic leukemia is the most common leukemia in the United States. It is a slowly progressive disease, with an 82% five-year survival rate. The treatment strategies are highly individualized with patients in the early and stable stages typically not requiring treatment. However, those with progressive or clinically advanced disease will require treatment. Cytotoxic drugs, such as the alkylating agents, purine nucleoside antagonists, and immunotherapeutic agents, have been the mainstay of chemotherapeutic treatment in CLL. However, given the lack of therapeutic specificity, these medications (especially older ones) have limited tolerability due to side effects. In this paper, we will discuss the data on the use of phosphatidylinositol 3 kinase inhibitor Idelalisib in the management of patients with chronic lymphocytic leukemia. The preclinical and clinical data thus far demonstrate that Idelalisib produces a dramatic and durable response in patients with chronic lymphocytic leukemia and without causing significant toxicity. Moving forward, the ongoing clinical trials will help address the various questions currently being raised regarding the long-term application and safety of Idelalisib. With greater clinical experience following more widespread use of Idelalisib, we will be able to determine the optimal combination therapies in treatment-naïve and relapsed/refractory patients, resulting in more individualized therapeutic strategies for patients with chronic lymphocytic leukemia. | 25,093,123 | [
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Severe Hypercholesterolemia: A Unique Presentation of Non-Hodgkin's Lymphoma in a Patient with Neurofibromatosis Type 1. | We report a case of non-Hodgkin's lymphoma (NHL) with an unusual initial manifestation as severe hypercholesterolemia and obstructive jaundice in a patient with neurofibromatosis type 1 (NF 1). NHL should be considered in the evaluation of obstructive jaundice alone or in combination with severe hypercholesterolemia. Relief of biliary obstruction led to the resolution of hypercholesterolemia in our 59-year-old male patient, followed by doxorubicin-based chemotherapy for the underlying lymphoma. NF 1 is a genetic condition that results from a defect in a tumor-suppressor gene and it is likely that this led to the development of NHL in our patient. It is important that clinicians are familiar with the gastrointestinal manifestations of NF 1, especially its association with intra-abdominal malignancies, when treating patients with a personal or family history. To the best of our knowledge, this is the first case of NHL presenting initially as severe hypercholesterolemia and it is also one of the few instances where NHL has been reported in association with NF 1. | 25,093,126 | [
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Unusual relapse of primary central nervous system lymphoma at site of lumbar puncture. | Primary CNS lymphoma (PCNSL) is a rare non-Hodgkin's lymphoma confined to the CNS. Local relapse of this disease is common, but extracranial or subcutaneous metastasis is rare with only a few cases being reported in literature. We report a 63-year-old male patient, who responded well to treatment for PCNSL but relapsed two and half years later with a lumbosacral nodule at the site of a previous lumbar puncture due to microscopic tumor seeding. Clinicians treating patients with PCNSL must remain alert to the possibility of extracranial solitary relapse even after the resolution of initial disease because prompt treatment can result in a good outcome. | 25,093,130 | [
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Extended inferior turbinate flap for endoscopic reconstruction of skull base defects. | Objective When the use of the nasoseptal flap for endoscopic skull base reconstruction has been precluded, the posterior pedicle inferior turbinate flap is a viable option for small midclival defects. Limitations of the inferior turbinate flap include its small surface area and limited arc of rotation. We describe a novel extended inferior turbinate flap that expands the reconstructive applications of this flap. Design Cadaveric anatomical study. Participants Cadaveric specimens. Main Outcome Measures Flap size, arc of rotation, and reconstructive applications were assessed. Results The average width of the flap was 5.46 ± 0.58 cm (7.32 ± 0.59 cm with septal mucosa). The average length of the flap was 5.01 ± 0.58 cm (5.28 ± 0.37 cm with septal mucosa). The average surface area of the flap was ∼ 27.26 ± 3.65 cm(2) (40.53 ± 6.45 cm(2) with septal mucosa). The extended inferior turbinate flap was sufficient to cover clival defects extending between the paraclival internal carotid arteries. The use of the flap in 22 cadavers and 5 clinical patients is described. Conclusion The extended inferior turbinate flap presents an additional option for reconstruction of skull base defects when the nasoseptal flap is unavailable. | 25,093,144 | [
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Curcumin loaded microsponges for colon targeting in inflammatory bowel disease: fabrication, optimization, and in vitro and pharmacodynamic evaluation. | The present study was aimed to develop and optimize the microsponges of curcumin for colon specific drug delivery in a view to bypass the upper gastrointestinal tract (GIT) for enhanced therapeutic effect. Microsponges were developed by quasi emulsion solvent diffusion method using 3(2) full factorial design. Prepared microsponges were optimized in order to analyze the effects of independent variables (volume of ethanol and Eudragit L100) on the encapsulation efficiency, particle size, and drug release. The optimized formulation was subjected to in vivo study using acetic acid induced colitis model in rats. The F7 was selected as optimized formulation based on particle size of 41.63 μm, % entrapment efficiency of 78.13%, and % cumulative drug release of 84.12%, and desirability factor of 0.83. Release studies revealed that microsponges prevented the premature release of curcumin in upper GIT and specifically released the drug at colonic pH. The drug release profile of F7 formulation was subjected to different kinetic models and based upon the best correlation coefficient (r(2) = 0.9927) the release was found to follow Higuchi model, which suggested diffusion as the main mechanism of drug release. Pharmacodynamic study showed that curcumin loaded microsponges causes a significant decrease in edema, necrosis, and hemorrhage of colon as compared to free curcumin. This study proves that curcumin loaded microsponges may act as a promising drug delivery system for treatment of ulcerative colitis. | 25,093,165 | [
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Predictive factors affecting the short term and long term exodrift in patients with intermittent exotropia after bilateral rectus muscle recession and its effect on surgical outcome. | To determine the predictive factors that affect short term and long term postoperative drift in intermittent exotropia after bilateral lateral rectus recession and to evaluate its effect on surgical outcome. Retrospective review of 203 patients with diagnosis of intermittent exotropia, who had surgical corrections with more than 3 years of followup. Different preoperative parameters were obtained and evaluated using Pearson's correlation analysis. The proportion of exodrift increased from 62% at 6 weeks to 84% at 3 years postoperatively. The postoperative drift was 4.3 ± 8.1 PD at 6 weeks, 5.8 ± 8.4 PD at 6 months, 7.2 ± 8.3 PD at 1 year, 7.4 ± 8.4 PD at 2 years, and 7.7 ± 8.5 PD at 3 years. Preoperative deviation and initial overcorrection were significant factors affecting the postoperative drift at 3 years (r = 0.177, P = 0.011, r = -0.349, and P < 0.001, resp.). Postoperative exodrift along three years occurs in a majority of patients after bilateral lateral rectus recession for intermittent exotropia. The long term surgical success is significantly affected by this postoperative exodrift. A larger preoperative deviation and a larger initial overcorrection are associated with a larger early and late postoperative exodrift. | 25,093,170 | [
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Neuroendocrine differentiation is a prognostic factor for stage II poorly differentiated colorectal cancer. | Neuroendocrine differentiation (NED) in colorectal cancer is an indistinct phenomenon and may define a new cancer subtype, especially in the poorly differentiated colorectal cancer (PDCRC). The clinical features of PDCRC with NED remain controversial, thus confusing the implementation of individualized treatment. This study included 171 patients who underwent surgery from 2000 to 2011 and had pathology-confirmed PDCRC. Each sample was examined by immunohistochemistry for the biological markers of NED, synaptophysin (Syn), and chromogranin (CgA). Patients with Syn(+) and/or CgA(+) cells were classified as NED(+); otherwise, they were NED(-). Data were collected for patients who were followed up for at least two years. NED(+) staining was present in 71 (41.5%) patients. The median survival time was 36.9 months. No survival differences existed between the NED(-) and NED(+) groups (P > 0.05). However, stage II NED(+) patients had a significantly worse prognosis than NED(-) patients (P = 0.018). For the NED(+) group, the median survival was 38.56 months, and the 5-year survival was 65%. For the NED(-) group, the median survival was 53.18 months, and the 5-year survival was 90%. NED is a common event in primary PDCRC. For stage II PDCRC, NED(+) indicates a poor prognosis. | 25,093,184 | [
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Mutational analysis of oculocutaneous albinism: a compact review. | Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by either complete lack of or a reduction of melanin biosynthesis in the melanocytes. The OCA1A is the most severe type with a complete lack of melanin production throughout life, while the milder forms OCA1B, OCA2, OCA3, and OCA4 show some pigment accumulation over time. Mutations in TYR, OCA2, TYRP1, and SLC45A2 are mainly responsible for causing oculocutaneous albinism. Recently, two new genes SLC24A5 and C10orf11 are identified that are responsible to cause OCA6 and OCA7, respectively. Also a locus has been mapped to the human chromosome 4q24 region which is responsible for genetic cause of OCA5. In this paper, we summarized the clinical and molecular features of OCA genes. Further, we reviewed the screening of pathological mutations of OCA genes and its molecular mechanism of the protein upon mutation by in silico approach. We also reviewed TYR (T373K, N371Y, M370T, and P313R), OCA2 (R305W), TYRP1 (R326H and R356Q) mutations and their structural consequences at molecular level. It is observed that the pathological genetic mutations and their structural and functional significance of OCA genes will aid in development of personalized medicine for albinism patients. | 25,093,188 | [
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Role of rutin on nitric oxide synthesis in human umbilical vein endothelial cells. | Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a major antiatherogenic factor in the blood vessel. Oxidative stress plays an important role in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Decreased availability of endothelial NO promotes the progression of endothelial dysfunction and atherosclerosis. Rutin is a flavonoid with multiple cardiovascular protective effects. This study aimed to investigate the effects of rutin on eNOS and NO production in cultured human umbilical vein endothelial cells (HUVEC). HUVEC were divided into four groups: control; oxidative stress induction with 180 μM H₂O₂; treatment with 300 μM rutin; and concomitant induction with rutin and H₂O₂ for 24 hours. HUVEC treated with rutin produced higher amount of NO compared to control (P < 0.01). In the oxidative stress-induced HUVEC, rutin successfully induced cells' NO production (P < 0.01). Rutin promoted NO production in HUVEC by inducing eNOS gene expression (P < 0.05), eNOS protein synthesis (P < 0.01), and eNOS activity (P < 0.05). Treatment with rutin also led to increased gene and protein expression of basic fibroblast growth factor (bFGF) in HUVEC. Therefore, upregulation of eNOS expression by rutin may be mediated by bFGF. The results showed that rutin may improve endothelial function by augmenting NO production in human endothelial cells. | 25,093,198 | [
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Distribution of subsequent primary invasive melanomas following a first primary invasive or in situ melanoma Queensland, Australia, 1982-2010. | Melanoma survivors are known to have a highly elevated risk of subsequent primary melanomas. To determine the relative risk of subsequent primary invasive melanomas following a first primary invasive or in situ melanoma, with a focus on body site. A retrospective cohort study was conducted using population-based administrative data for melanoma diagnoses collected by the Queensland Cancer Registry, Queensland, Australia. Deidentified records of all cases of melanoma among Queensland residents during the period 1982-2005 were obtained and reviewed to December 31, 2010. There were 39,668 eligible cases of first primary invasive melanoma and 22,845 cases of first primary in situ melanoma. Standardized incidence ratios (SIRs), a proxy measure for relative risk, were calculated by dividing the observed number of subsequent primary invasive melanomas by the product of the strata-specific incidence rates that occurred in the general population and the cumulative time at risk for the cohort. Synchronous subsequent melanomas (diagnosed within 60 days of the first primary melanoma) were excluded. Differences between SIRs were assessed using multivariate negative binomial regression adjusted for sex, age group, time to second diagnosis, and body site and expressed in terms of adjusted SIR ratios with corresponding 95% CIs. There were 5358 subsequent primary invasive melanomas diagnosed, resulting in SIRs of 5.42 (95% CI, 5.23-5.61) and 4.59 (4.37-4.82) for persons with a first primary invasive or in situ melanoma, respectively. The SIRs remained elevated throughout the follow-up period. In general, subsequent primary invasive melanomas were more likely to occur at the same body site as the initial invasive or in situ melanoma. The largest relative risk was for females with a first primary invasive melanoma on the head followed by a subsequent primary invasive melanoma also on the head (SIR, 13.32; 95% CI, 10.28-16.98). Melanoma survivors require ongoing surveillance, with particular attention required for the body site of the initial lesion. Clinical practice guidelines have recognized the importance of monitoring for people with invasive melanoma; the results of the present study highlight the need for similar levels of supervision for those with a diagnosis of in situ melanoma. | 25,093,216 | [
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Depressive symptoms precede memory decline, but not vice versa, in non-demented older adults. | To determine whether depressive symptoms typically precede or follow memory declines. An autoregressive latent trajectory model was used to examine the direction of the relationship between depressive symptoms and memory decline observed over 12 years. Washington/Hamilton Heights Inwood Columbia Aging Project, a community-based longitudinal study of aging and dementia in northern Manhattan. Older adults initially without dementia(n = 2,425). Memory composite scores were computed from three subscores of the Selective Reminding Test. Depressive symptoms were assessed using a 10-item version of the Center for Epidemiologic Studies Depression Scale. Analyses controlled for age, sex, recruitment wave,education, black race, and Hispanic ethnicity measured at baseline and chronic disease burden measured at each study visit. Initial depressive symptoms predicted worse memory scores at the second study visit (B weight = − 0.03; P = .003) and accelerated memory decline over the entire study period (B weight = − 0.02; P = .03). Memory scores did not predict subsequent depressive symptoms. These findings suggest that depressive symptoms precede memory decline, but not vice versa, in late life. This pattern of results is consistent with hypotheses that depression is a prodrome of dementia or a causal contributor to memory decline. Clinicians should be aware that depressive symptoms may represent an early indicator not only of dementia, as reported previously, but also of memory decline more generally. | 25,093,232 | [
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Guiding brain tumor resection using surface-enhanced Raman scattering nanoparticles and a hand-held Raman scanner. | The current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients. Here, we evaluated the ability of a hand-held Raman scanner, guided by surface-enhanced Raman scattering (SERS) nanoparticles, to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model. In a simulated intraoperative scenario, we tested both a static Raman imaging device and a mobile, hand-held Raman scanner. We show that SERS image-guided resection is more accurate than resection using white light visualization alone. Both methods complemented each other, and correlation with histology showed that SERS nanoparticles accurately outlined the extent of the tumors. Importantly, the hand-held Raman probe not only allowed near real-time scanning, but also detected additional microscopic foci of cancer in the resection bed that were not seen on static SERS images and would otherwise have been missed. This technology has a strong potential for clinical translation because it uses inert gold-silica SERS nanoparticles and a hand-held Raman scanner that can guide brain tumor resection in the operating room. | 25,093,240 | [
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A few positively charged residues slow movement of a polypeptide chain across the endoplasmic reticulum membrane. | Many polypeptide chains are translocated across and integrated into the endoplasmic reticulum membrane through protein-conducting channels. During the process, amino acid sequences of translocating polypeptide chains are scanned by the channels and classified to be retained in the membrane or translocated into the lumen. We established an experimental system with which the kinetic effect of each amino acid residue on the polypeptide chain movement can be analyzed with a time resolution of tens of seconds. Positive charges greatly slow movement; only two lysine residues caused a remarkable slow down, and their effects were additive. The lysine residue was more effective than arginine. In contrast, clusters comprising three residues of each of the other 18 amino acids had little effect on chain movement. We also demonstrated that a four lysine cluster can exert the effect after being fully exposed from the ribosome. We concluded that as few as two to three residues of positively charged amino acids can slow the movement of the nascent polypeptide chain across the endoplasmic reticulum membrane. This effect provides a fundamental basis of the topogenic function of positively charged amino acids. | 25,093,244 | [
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Responsive Design, Weighting, andVariance Estimation in the 2006-2010 National Survey of Family Growth. | Objective-The National Survey of Family Growth (NSFG) collects data on pregnancy, childbearing, men's and women's health, and parenting from a national sample of men and women aged 15-44 in the United States. The 2006-2010 NSFG design was a significant departure from the previous periodic design, used in 1973-2002. This report shows fieldwork results and weighting, imputation, and variance estimation procedures. The report should be useful to users of the 2006-2010 public-use data file and to survey methodologists wishing to learn how the NSFG was conducted. Methods-NSFG's new design is based on an independent national probability sample of men and women aged 15-44. The University of Michigan's Institute for Social Research conducted fieldwork under a contract with the National Center for Health Statistics. Professional female interviewers conducted in-person, face-to-face interviews using laptop computers. A responsive design approach was used in planning and managing the fieldwork for NSFG to control costs and reduce nonresponse bias. Results-The 2006-2010 NSFG is based on 22,682 completed interviews-10,403 interviews with men and 12,279 with women. Interviews with men lasted an average of 52 minutes, and for women, 71 minutes. Weighted response rates were 75% among men, 78% among women, and 77% overall. Analysis of NSFG data requires the use of sampling weights and estimation of sampling errors that account for the complex sample design and estimation features of the survey. Sampling weights are provided on the data files. The rate of missing data in the survey is generally low. | 25,093,250 | [
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The sensitivity of the Kleihauer-Betke test for placental abruption. | The Kleihauer-Betke (KB) test evaluates fetal blood in the maternal circulation, and is often used when placental abruption is suspected. At our centre, it is the protocol to perform a KB test in all suspected cases of abruption. We carried out a retrospective study of all cases of abruption that occurred at our centre over 6 years. Of the 68 confirmed cases of placental abruption, only three had positive KB tests, giving a sensitivity of only 4.4%. Thus, in the overwhelming majority of cases of confirmed abruption, the KB test was negative. Our findings indicate that the KB test has poor sensitivity for placental abruption and should not be used in the detection of abruption. | 25,093,255 | [
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Molecular cloning and expression analysis of tea plant aquaporin (AQP) gene family. | The role of aquaporin proteins (AQPs) has been extensively studied in plants. However, the information of AQPs in the tea plant (Camellia sinensis) is unclear. In this manuscript, we isolated 20 full-length AQP cDNAs from the tea plant, and these sequences were classified into five subfamilies. The genes in these subfamilies displayed differential expression profiles in the studied tissues. The CsAQP expression patterns correlated with flower development and opening (FDO) and bud endodormancy (BED). To better understand the short-term expression patterns of CsAQPs in response to abiotic stress, tea plants were treated with abscisic acid (ABA), cold, salt or drought. ABA treatment down-regulated the expression of various CsAQPs. Salt up-regulated the transcription of most CsAQP genes. Cold treatment resulted in a complicated transcriptional regulation pattern for various CsAQPs. The expression of CsAQPs, especially plasma membrane intrinsic proteins (CsPIPs) and tonoplast intrinsic proteins (CsTIPs), was induced by drought and remained relatively high after rehydration in leaves, whereas almost all the CsAQPs were repressed in roots. Our results highlighted the diversity of CsAQPs in the tea plant and demonstrated that the CsPIP and CsTIP genes play a vital role in the stress response as well as in FDO and BED. Furthermore, certain CsSIPs (small basic intrinsic proteins), CsNIPs (NOD26-like intrinsic proteins) and CsXIPs (X intrinsic proteins) may regulate BED and FDO. | 25,093,260 | [
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Directed evolution of squalene synthase for dehydrosqualene biosynthesis. | Squalene synthase (SQS) catalyzes the first step of sterol/hopanoid biosynthesis in various organisms. It has been long recognized that SQSs share a common ancestor with carotenoid synthases, but it is not known how these enzymes selectively produce their own product. In this study, SQSs from yeast, human, and bacteria were independently subjected to directed evolution for the production of the C30 carotenoid backbone, dehydrosqualene. This was accomplished via high-throughput screening with Pantoea ananatis phytoene desaturase, which can selectively convert dehydrosqualene into yellow carotenoid pigments. Genetic analysis of the resultant mutants revealed various mutations that could effectively convert SQS into a "dehydrosqualene synthase." All of these mutations are clustered around the residues that have been proposed to be important for NADPH binding. | 25,093,296 | [
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[Pathogenesis of HIV-1]. | The human immunodeficiency virus type 1 (HIV-1) establishes a chronic, lifelong infection finally leading to the acquired immunodeficiency syndrome (AIDS), which is characterized by the onset of opportunistic infections and tumors. The natural course of HIV-1 infections is very variable and depends on the virus and its replication competence as well as the host. This review summarizes our current knowledge on HIV-1 and host factors influencing the pathogenesis of HIV-1. | 25,093,308 | [
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Isolation and characterization of CD34+ blast-derived exosomes in acute myeloid leukemia. | Exosomes are membrane-bound vesicles found in all biological fluids. AML patients' plasma collected at diagnosis contains elevated exosome levels relative to normal donor (ND) plasma. The molecular profile of AML exosomes changes in the course of therapy and may serve as a measure of disease progression or response to therapy. However, plasma contains a mix of exosomes derived from various cell types. To be able to utilize blast-derived exosomes as biomarkers for AML, we have developed an immunoaffinity-based capture method utilizing magnetic microbeads coated with anti-CD34 antibody (Ab). This Ab is specific for CD34, a unique marker of AML blasts. The capture procedure was developed using CD34+ exosomes derived from Kasumi-1 AML cell culture supernatants. The capture capacity of CD34microbeads was shown to linearly correlate with the input exosomes. A 10 uL aliquot of CD34 microbeads was able to capture all of CD34+ exosomes present in 100-1,000 uL of AML plasma. The levels of immunocaptured CD34+ exosomes correlated with the percentages of CD34+ blasts in the AML patients' peripheral blood. The immunocaptured exosomes had a typical cup-shaped morphology by transmission electron microscopy, and their molecular cargo was similar to that of parental blasts. These exosomes were biologically-active. Upon co-incubation with natural killer (NK) cells, captured blast-derived exosomes down-regulated surface NKG2D expression, while non-captured exosomes reduced expression levels of NKp46. Our data provide a proof-of-principle that blast-derived exosomes can be quantitatively recovered from AML patients' plasma, their molecular profile recapitulates that of autologous blasts and they retain the ability to mediate immune suppression. These data suggest that immunocaptured blast-derived exosomes might be useful in diagnosis and/or prognosis of AML in the future. | 25,093,329 | [
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A new 2α,5α,10β,14β-tetraacetoxy-4(20),11-taxadiene (SIA) derivative overcomes paclitaxel resistance by inhibiting MAPK signaling and increasing paclitaxel accumulation in breast cancer cells. | Tumor resistance due to multiple mechanisms seriously hinders the efficacy of chemotherapy drugs such as paclitaxel. The most widely studied P-glycoprotein inhibitors still have limited ability to reverse resistance in the clinic. In this study, NPB304, a novel Sinenxan A (SIA) derivative, was found to significantly sensitize resistant breast cancer cells to paclitaxel in vitro and in vivo. Treatment with NPB304 increased paclitaxel-induced apoptosis in a p53-dependent manner through PARP cleavage. Importantly, NPB304 enhanced the antitumor effect of paclitaxel in resistant breast tumor xenografts in nude mice without significantly affecting weight loss. NPB304 regulated cell resistance through inhibition of MAPK pathway components, including p-ERK and p-p38. Moreover, NPB304 increased paclitaxel accumulation by affecting P-gp function. In addition to increasing Rhodamine 123 accumulation, NPB304 promoted bidirectional permeability but decreased the efflux ratio of paclitaxel in a Caco-2 monolayer model, thereby increasing the intracellular concentration of paclitaxel. Similarly, NPB304 increased the concentration of paclitaxel in the resistant tumor tissue. Hence, NPB304 is a novel compound that promotes the sensitization of resistant cells to paclitaxel through multiple mechanisms and has the potential for use in combination therapies to treat resistant breast cancer. | 25,093,335 | [
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Electronic structure, novel synthesis, and O-H...O and C-H...O interactions in two 6-oxopiperidine-2-carboxylic acid derivatives. | Molecules of (S)-6-oxo-1-(thiophen-2-ylmethyl)piperidine-2-carboxylic acid, C11H13NO3S, crystallize as single enantiomers in the space group P21 and the thiophene ring is disordered over two positions, while (S)-6-oxo-1-(thiophen-3-ylmethyl)piperidine-2-carboxylic acid, C11H13NO3S, crystallizes as a single enantiomer in the space group P212121. Their absolute configurations were confirmed by anomalous dispersion effects in diffraction measurements on the crystals. The molecules of each compound are linked by a combination of strong O-H...O hydrogen bonds and weak C-H...O interactions, resulting in two- and three-dimensional networks, respectively, in the crystal structures. | 25,093,366 | [
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Topological analysis of the three-dimensional coordination polymer poly[(μ4-azido)[μ4-5-(pyridin-4-yl)tetrazolido]disilver(I)]. | The title compound, [Ag2(C6H4N4)(N3)]n, was obtained under hydrothermal conditions at 433 K. The asymmetric unit of the orthorhombic space group (Pna21) consists of two Ag(+) cations, an anionic 5-(pyridin-4-yl)tetrazolide (4-ptz(-)) ligand and an anionic azide ligand. Both Ag(+) centres are coordinated by four N atoms, forming a distorted tetrahedral coordination environment. When all the component ions are viewed as 4-connected nodes, the whole three-dimensional network can be regarded topologically as a new kind of 4,4,4,4-connected net with the Schläfli symbol (4.8(5))(4(2).8(4))(4(3).8(3))2. | 25,093,367 | [
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Homoleptic 2,2'-bipyridine metalates(-I) of iron and cobalt, one cocrystallized with an anthracene radical anion and the other with neutral anthracene. | Homoleptic 2,2'-bipyridine (bipy) metalates of iron and cobalt have been synthesized directly from the corresponding homoleptic anthracene metalates. In the iron structure, bis[([2.2.2]cryptand)potassium(I)] tris(2,2'-bipyridine)ferrate(-I) anthracene(-I), [K(C18H36N2O6)]2[Fe(C10H8N2)3](C14H10), the asymmetric unit contains one potassium complex cation in a general position, the Fe center and one and a half bipy ligands of the ferrate complex on a crystallographic twofold axis that includes the Fe atom, and one half of an anthracene radical anion whose other half is generated by a crystallographic inversion center. The cations and anions are well separated and the geometry about the Fe center is essentially octahedral. In the cobalt structure, ([2.2.2]cryptand)potassium(I) bis(2,2'-bipyridine)cobaltate(-I) anthracene hemisolvate tetrahydrofuran (THF) disolvate, [K(C18H36N2O6)][Co(C10H8N2)2]·0.5C14H10·2C4H8O, the asymmetric unit contains the cation, anion, and both cocrystallized THF solvent molecules in general positions, and one half of a cocrystallized anthracene molecule whose other half is generated by a crystallographic inversion center. The cation and anion are well separated and the ligand planes in the cobaltate anion are periplanar. Each anthracene molecule is midway between and is oriented perpendicular to a pair of symmetry-related bipy ligands such that aromatic donor-acceptor interactions may play a role in the packing arrangement. The lengths of the bonds that connect the bipy rings support the assertion that the ligands are bipy radical anions in the iron structure. However, in the case of cobalt, these lengths are between the known ranges for a bipy radical anion and a bipy dianion, and therefore no conclusion can be made from the crystallography alone. One cocrystallized THF solvent molecule in the cobalt structure was modeled as disordered over three positions with appropriate geometric and thermal restraints, which resulted in a refined component mass ratio of 0.412 (4):0.387 (3):0.201 (3). | 25,093,368 | [
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Web search behavior and information needs of people with multiple sclerosis: focus group study and analysis of online postings. | Multiple sclerosis (MS) patients and their family members increasingly seek health information on the Internet. There has been little exploration of how MS patients integrate health information with their needs, preferences, and values for decision making. The INtegrating and Deriving Evidence, Experiences, and Preferences (IN-DEEP) project is a collaboration between Italian and Australian researchers and MS patients, aimed to make high-quality evidence accessible and meaningful to MS patients and families, developing a Web-based resource of evidence-based information starting from their information needs. The objective of this study was to analyze MS patients and their family members' experience about the Web-based health information, to evaluate how they asses this information, and how they integrate health information with personal values. We organized 6 focus groups, 3 with MS patients and 3 with family members, in the Northern, Central, and Southern parts of Italy (April-June 2011). They included 40 MS patients aged between 18 and 60, diagnosed as having MS at least 3 months earlier, and 20 family members aged 18 and over, being relatives of a person with at least a 3-months MS diagnosis. The focus groups were audio-recorded and transcribed verbatim (Atlas software, V 6.0). Data were analyzed from a conceptual point of view through a coding system. An online forum was hosted by the Italian MS society on its Web platform to widen the collection of information. Nine questions were posted covering searching behavior, use of Web-based information, truthfulness of Web information. At the end, posts were downloaded and transcribed. Information needs covered a comprehensive communication of diagnosis, prognosis, and adverse events of treatments, MS causes or risk factors, new drugs, practical, and lifestyle-related information. The Internet is considered useful by MS patients, however, at the beginning or in a later stage of the disease a refusal to actively search for information could occur. Participants used to search on the Web before or after their neurologist's visit or when a new therapy was proposed. Social networks are widely used to read others' stories and retrieve information about daily management. A critical issue was the difficulty of recognizing reliable information on the Web. Many sources were used but the neurologist was mostly the final source of treatment decisions. MS patients used the Internet as a tool to integrate information about the illness. Information needs covered a wide spectrum, the searched topics changed with progression of the disease. Criteria for evaluating Internet accuracy and credibility of information were often lacking or generic. This may limit the empowerment of patients in health care choices. | 25,093,374 | [
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Obesity-related genomic loci are associated with type 2 diabetes in a Han Chinese population. | Obesity is a well-known risk factor for type 2 diabetes. Genome-wide association studies have identified a number of genetic loci associated with obesity. The aim of this study is to examine the contribution of obesity-related genomic loci to type 2 diabetes in a Chinese population. We successfully genotyped 18 obesity-related single nucleotide polymorphisms among 5338 type 2 diabetic patients and 4663 controls. Both individual and joint effects of these single nucleotide polymorphisms on type 2 diabetes and quantitative glycemic traits (assessing β-cell function and insulin resistance) were analyzed using logistic and linear regression models, respectively. Two single nucleotide polymorphisms near MC4R and GNPDA2 genes were significantly associated with type 2 diabetes before adjusting for body mass index and waist circumference (OR (95% CI) = 1.14 (1.06, 1.22) for the A allele of rs12970134, P = 4.75×10(-4); OR (95% CI) = 1.10 (1.03, 1.17) for the G allele of rs10938397, P = 4.54×10(-3)). When body mass index and waist circumference were further adjusted, the association of MC4R with type 2 diabetes remained significant (P = 1.81×10(-2)) and that of GNPDA2 was attenuated (P = 1.26×10(-1)), suggesting the effect of the locus including GNPDA2 on type 2 diabetes may be mediated through obesity. Single nucleotide polymorphism rs2260000 within BAT2 was significantly associated with type 2 diabetes after adjusting for body mass index and waist circumference (P = 1.04×10(-2)). In addition, four single nucleotide polymorphisms (near or within SEC16B, BDNF, MAF and PRL genes) showed significant associations with quantitative glycemic traits in controls even after adjusting for body mass index and waist circumference (all P values<0.05). This study indicates that obesity-related genomic loci were associated with type 2 diabetes and glycemic traits in the Han Chinese population. | 25,093,408 | [
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Length and GC content variability of introns among teleostean genomes in the light of the metabolic rate hypothesis. | A comparative analysis of five teleostean genomes, namely zebrafish, medaka, three-spine stickleback, fugu and pufferfish was performed with the aim to highlight the nature of the forces driving both length and base composition of introns (i.e., bpi and GCi). An inter-genome approach using orthologous intronic sequences was carried out, analyzing independently both variables in pairwise comparisons. An average length shortening of introns was observed at increasing average GCi values. The result was not affected by masking transposable and repetitive elements harbored in the intronic sequences. The routine metabolic rate (mass specific temperature-corrected using the Boltzmann's factor) was measured for each species. A significant correlation held between average differences of metabolic rate, length and GC content, while environmental temperature of fish habitat was not correlated with bpi and GCi. Analyzing the concomitant effect of both variables, i.e., bpi and GCi, at increasing genomic GC content, a decrease of bpi and an increase of GCi was observed for the significant majority of the intronic sequences (from ∼ 40% to ∼ 90%, in each pairwise comparison). The opposite event, concomitant increase of bpi and decrease of GCi, was counter selected (from <1% to ∼ 10%, in each pairwise comparison). The results further support the hypothesis that the metabolic rate plays a key role in shaping genome architecture and evolution of vertebrate genomes. | 25,093,416 | [
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Pneumococcal vaccines for cystic fibrosis. | Invasive pneumococcal disease is associated with significant mortality and many countries have introduced routine pneumococcal vaccination into their childhood immunisation programmes. Whilst pneumococcal disease in cystic fibrosis is uncommon, pneumococcal immunisation may offer some protection against pulmonary exacerbations caused by this pathogen. In the USA and UK pneumococcal vaccination is currently recommended for all children and adults with cystic fibrosis. To assess the efficacy of pneumococcal vaccines in reducing morbidity in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. In addition, the pharmaceutical manufacturers of the polysaccharide and conjugate pneumococcal vaccines were approached.Date of the most recent search: 15 May 2014. Randomised and quasi-randomised controlled trials comparing pneumococcal vaccination (with either a polysaccharide or conjugate pneumococcal vaccine) with non-vaccination or placebo in children or adults with cystic fibrosis were eligible for inclusion. No relevant trials were identified. There are no trials included in this review. As no trials were identified we cannot draw conclusions on the efficacy of routine pneumococcal immunisation in people with cystic fibrosis in reducing their morbidity or mortality. As many countries now include pneumococcal immunisation in their routine childhood vaccination schedule it is unlikely that future randomised controlled trials will be initiated. Rigorously conducted epidemiological studies may offer the opportunity to evaluate the efficacy of pneumococcal vaccination in reducing morbidity and mortality in people with cystic fibrosis. | 25,093,421 | [
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A novel method for non-transferrin-bound iron quantification by chelatable fluorescent beads based on flow cytometry. | The reliable measurement of non-transferrin-bound iron (NTBI) in serum has proved to be difficult and generally time consuming. We have sought a simple and fast method for such a determination. We adopted a fluorescence assay and designed a fluorescent dye with a chelating agent attached to sense iron. To avoid autofluorescence from serum samples, the iron probes were linked to beads and the autofluorescence could be separated and excluded from the measurement by flow cytometry due to the size difference between beads and serum proteins. Fluorescent beads containing both fluorescent and chelating moieties have been synthesized. The nature of the chelating function has been systematically investigated using four different chelators: bidentate hydroxypyranone, bidentate hydroxypyridinone, hexadentate hydroxypyranone and hexadentate hydroxypyridinone, each with different iron affinity constants. Competition studies demonstrate that the hexadentate hydroxypyridinone-based beads are capable of scavenging most of low molecular mass and albumin-bound iron but negligible amounts of iron from transferrin and ferritin. Serum samples from 30 patients with different types of disease and normal volunteers were measured. The concentrations of NTBI fall in the range -0.41 to +6.5 μM. The data have been compared with those obtained from the traditional 'NTA' method. | 25,093,426 | [
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A Novel Approach to Realizing Routine HIV Screening and Enhancing Linkage to Care in the United States: Protocol of the FOCUS Program and Early Results. | The United States health care system remains far from implementing the Centers for Disease Control and Prevention's recommendation of routine human immunodeficiency virus (HIV) screening as part of health care for adults. Although consensus for the importance of screening has grown, innovations in implementing routine screening are still lacking. HIV on the Frontlines of Communities in the United States (FOCUS) was launched in 2010 to provide an environment for testing innovative approaches to routine HIV screening and linkage to care. The strategy of the FOCUS program was to develop models that maximize the use of information systems, fully integrate HIV screening into clinical practice, transform basic perceptions about routine HIV screening, and capitalize on emerging technologies in health care settings and laboratories. In 10 of the most highly impacted cities, the FOCUS program supports 153 partnerships to increase routine HIV screening in clinical and community settings. From program launch in 2010 through October 2013, the partnerships have resulted in a total of 799,573 HIV tests and 0.68% (5425/799,573) tested positive. The FOCUS program is a unique model that will identify best practices for HIV screening and linkage to care. | 25,093,431 | [
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Classification of sequential swallowing types using videoendoscopy with high reproducibility and reliability. | This study aimed to classify sequential swallowing types using videoendoscopy (VE) avoiding radiation exposure and compare the results using videofluoroscopy (VF). Twenty-one healthy adults simultaneously underwent VF and VE during sequential straw drinking. Each discrete swallow was classified into an L-segmental type (laryngeal vestibule opens after swallow) or L-continuous type (laryngeal vestibule closure continues after swallow) using VF and a V-segmental type (velopharynx opens after swallow) or V-continuous type (velopharynx closure continues after swallow) using VE. Test-retest reproducibility and interrater and intrarater reliability were evaluated in ten healthy adults. Of 128 swallows, 94 were L-segmental and 34 were L-continuous types as per VF, whereas 95 were V-segmental and 33 were V-continuous types as per VE. The leading edge of the bolus at swallow onset was significantly deeper in L-continuous types (P = 0.001). Laryngeal vestibule closure on VF images corresponded to velopharyngeal closure on VE images for 127 of 128 swallows (κ = 0.98, P < 0.001). All subjects showed the same types of swallows in the first and the second studies. Both interrater and intrarater reliability were high. VE showed high reproducibility and reliability in the classification of sequential swallowing types. | 25,093,442 | [
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Pharmacokinetics and toxicity predictors of new s-triazines, herbicide candidates, in correlation with chromatogrpahic retention constants. | Herbicides, which are ubiquitously present in soil and food, have been proven to cause human health hazard effects, hence development of new herbicide-active compounds is recommended. In this paper, nine 2,4-bis(cycloalkyl)-6-chloro-s-triazines were considered as herbicide candidates and their pharmacokinetics and toxicity were reviewed on the basis of in silico descriptors. Both, pharmacokinetic and toxicity predictors were presented as functions of their lipophilicity, quantified with retention constants that were obtained by liquid chromatography. None of the candidates investigated has functional groups for genotoxicity hazards and endocrine disruptions; they have acceptable toxicity and favorable pharmacokinetic properties based on computer-aided analyses. Two candidates have been selected as lead compounds for further research. | 25,093,448 | [
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Unambiguous Determination of the Absolute Configuration of Dimeric Stilbene Glucosides from the Rhizomes of Gnetum africanum. | Dimeric stilbene glucosides 1-3 [two diastereomers of (-)-gnemonoside A (1a and 1b), (-)-gnemonoside C (2), and (-)-gnemonoside D (3)] as well as a mixture of the two enantiomers of gnetin C (4) were isolated from the rhizomes of Gnetum africanum. The two enantiomers of gnetin C, (+)-4 and (-)-4, were obtained from the aglycones of 1a and 1b, respectively. The configurations of these stilbenoids were investigated by NMR and vibrational circular dichroism (VCD) experiments. The absolute configurations of (-)-1a, (-)-2, (-)-3, and (-)-4 were established as 7aS,8aS by VCD spectroscopy in combination with density functional theory calculations. The antiamyloidogenic activity of the isolated stilbenes was also evaluated versus beta-amyloid fibrils. The four glucosides of gnetin C (1a, 1b, 2, and 3) were found to be the most active compounds, with inhibition percentages of 56, 56, 58, and 54 at 10 μM, respectively. | 25,093,453 | [
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In vitro study of a novel nanogold-collagen composite to enhance the mesenchymal stem cell behavior for vascular regeneration. | Novel nanocomposites based on type I collagen (Col) containing a small amount (17.4, 43.5, and 174 ppm) of gold nanoparticles (AuNPs, approximately 5 nm) were prepared in this study. The pure Col and Col-AuNP composites (Col-Au) were characterized by the UV-Vis spectroscopy (UV-Vis), surface-enhanced raman spectroscopy (SERS) and atomic force microscopy (AFM). The interaction between Col and AuNPs was confirmed by infrared (IR) spectra. The effect of AuNPs on the biocompatibility of Col, evaluated by the proliferation and reactive oxygen species (ROS) production of mesenchymal stem cells (MSCs) as well as the activation of monocytes and platelets, was investigated. Results showed that Col-Au had better biocompatibility than Col. Upon stimulation by vascular endothelial growth factor (VEGF) and stromal derived factor-1α (SDF-1α), MSCs expressed the highest levels of αvβ3 integrin/CXCR4, focal adhesion kinase (FAK), matrix metalloproteinase-2 (MMP-2), and Akt/endothelial nitric oxide synthase (eNOS) proteins when grown on the Col-Au (43.5 ppm) nanocomposite. Taken together, Col-Au nanocomposites may promote the proliferation and migration of MSCs and stimulate the endothelial cell differentiation. These results suggest that Col-Au may be used to construct tissue engineering scaffolds for vascular regeneration. | 25,093,502 | [
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Self-reported spatial hearing abilities across different cochlear implant profiles. | The goal of this study was to determine how self-reported spatial hearing abilities differ across various cochlear implant (CI) profiles and to examine the degree of subjective benefit following cochlear implantation across different groups of CI users. This was a retrospective study of subjective spatial hearing ability of CI recipients. The subjects consisted of 99 unilateral CI users, 49 bilateral CI users, 32 subjects with a CI and contralateral hearing aid (bimodal users), and 37 short-electrode CI users. All subjects completed the Spatial Hearing Questionnaire (Tyler, Perreau, & Ji, 2009), a questionnaire assessing spatial hearing ability, after implantation, and a subset of the subjects completed the questionnaire pre- and postimplantation. Subjective spatial hearing ability was rated higher for the bilateral and short electrode CI users compared to the unilateral and bimodal users. There was no significant difference in subjective spatial hearing performance between the bilateral and short electrode CI users and the unilateral CI and bimodal users. A separate analysis of pre- and postimplant performance revealed that all CI groups reported significant improvements in spatial hearing ability after implantation. This study suggests that there are substantial differences in perceived spatial hearing ability among unilateral and bimodal CI users compared with bilateral and short electrode CI users. | 25,093,507 | [
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Anterior Chamber Depth, Lens Thickness, and Related Measures in African American Females With Long Anterior Zonules: A Matched Study With Control for Refractive Error. | To investigate anterior chamber depth (ACD), lens thickness (LT), vitreous body length (VBL), and axial length (AL) in African American females with long anterior zonules (LAZ) while controlling for refractive error. The eyes of 50 African American females with LAZ were compared with 50 controls matched with age, race, sex, and refractive error. Central ACD, LT, VBL, and AL measurements were obtained in a masked manner using a-scan ultrasonography. LAZ cases had a mean age±SD of 67.1±7.6 years (range, 52 to 85 y) and a mean refractive error of +1.85±1.41 D (-1.75 to +4.75 D). Parameters were similar for controls. Mean ACD for cases was 2.45±0.34 mm and 2.57±0.38 mm for controls. Mean LT for cases was 4.94±0.43 mm and 4.83±0.45 mm for controls. Mean VBL for cases was 15.00±0.72 mm and 15.17±0.76 mm for controls. Mean AL for cases was 22.39±0.82 mm and 22.57±0.76 mm for controls. Using multiple logistic regression to control for any residual differences in age and refractive error, no significant differences were present between LAZ eyes and control eyes relative to the a-scan variables (P>0.1). When refractive error was controlled for, this group of African American females with LAZ did not exhibit clinically significant differences in ACD, LT, VBL, and AL as compared with controls. | 25,093,521 | [
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Reminiscence functions and the health of Israeli Holocaust survivors as compared to other older Israelis and older Canadians. | Existing research with English-speaking samples indicates that various ways in which older adults recall their past affect both their physical and mental health. Self-positive reminiscence functions (i.e. identity, problem-solving, death preparation) correlate and predict mental health in later life whereas self-negative functions (i.e. bitterness revival, boredom reduction, intimacy maintenance) correlate and predict the physical health of older adults. For this study, we recruited 295 Israeli Holocaust survivors to ascertain if early life trauma affects these associations between reminiscence and health. In order to distinguish cross-national differences from survivor-specific effects, we also recruited two comparative samples of other older Israelis (not Holocaust survivors; n = 205) and a second comparative sample of 335 older Canadians. Three separate structural equation models were computed to replicate this tripartite reminiscence and health model. Coefficients for self-negative functions significantly differed between survivors and both Canadians and other older Israelis, and between Canadians and both Israeli samples. However, no differences were found between prosocial and self-positive functions. Moreover, the higher order structure of reminiscence and health appears largely indistinguishable across these three groups. Early life trauma does not appear to fundamentally affect associations between reminiscence and health. These findings underscore the resilience of Holocaust survivors. | 25,093,526 | [
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Interplay between longitudinal and transverse contrasts in Fe3O4 nanoplates with (111) exposed surfaces. | Iron oxide has been developed as either T1 or T2 magnetic resonance imaging (MRI) contrast agents by controlling the size and composition; however, the underlying mechanism of T1 and T2 contrasts in one iron oxide entity is still not well understood. Herein, we report that freestanding superparamagnetic magnetite nanoplates with (111) exposed facets have significant but interactional T1 and T2 contrast effects. We demonstrate that the main contribution of the T1 contrast of magnetic nanoplates is the chemical exchange on the iron-rich Fe3O4(111) surfaces, whereas the T2 relaxation is dominated by the intrinsic superparamagnetism of the nanoplates with an enhanced perturbation effect. We are able to regulate the balance of T1 and T2 contrasts by controlling structure and surface features, including morphology, exposed facets, and surface coating. This study provides an insightful understanding on the T1 and T2 contrast mechanisms, which is urgently needed to allow more sophisticated design of high-performance MRI contrast agents. | 25,093,532 | [
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Differentiation of bel-7402 human hepatocarcinoma cells induced by aqueous extracts of fresh gecko (AG) and its anti-tumor activity in vivo. | Gecko, a kind of reptile, has been widely used as a traditional Chinese medicine to treat various diseases including cancer in China for thousands of years. The aim of this study was to investigate the anti-tumor effect of AG (aqueous extracts of fresh gecko) on human hepatocellular carcinoma cell Bel-7402 in vitro and mouse H22 hepatocellular in vivo. Further to underlie the molecular mechanism of AG inducing the differentiation of Bel-7402 cells. AG was obtained by water extracting method and qualitatively analyzed through High Performance Liquid Chromatography. The total protein concentration of AG was measured by BCA (bicinchoninic acid disodium) assay. The anti-tumor activities in vivo were analyzed through H22 (mouse hepatocellular carcinoma cell line H22) tumor xenografts mice. The cytotoxic activity of AG on Bel-7402 cells was evaluated by MTT assays. AFP (alpha fetoprotein) was detected by radioimmunoassay. ALB (albumin), ALP (alkaline phosphatase) and γ-GT (γ-glutamyl transpeptidase) were detected by biochemical methods with commercial kits. While morphological changes were observed through an inverted microscope. Moreover, the expression level of the proteins involved in MAPK (mitogen-activated protein kinase) signal pathway which was closely related to cellular differentiation was assessed by Western blot. AG showed obviously anti-tumor activity in vivo and anti-proliferative activity on Bel-7402 cells in vitro both dose-dependently. The number of clones of Bel-7402 cells treated with AG reduced and the cells were displaying differentiation state such as relatively bigger size and dispersed growth. The biochemical function markers of the cells were significantly changed after being treated with AG. The data showed that AFP secretion of the cells decreased 42.5%, ALB secretion increased 58.9%, the activity of ALP and γ-GT markedly decreased 67.0% and 48.5% separately when the concentration of AG was 10μl/ml, and those effects were all in a dose-dependent manner. The major original and phosphorylated signal proteins (ERK1/2 (extracellular sigal-regualted kinase 1/2), P38 (p38 MAPK) and JNK1/2 (c-Jun N-terminal kinase 1/2)) involved in MAPK signal pathway were measured and the results showed that AG activated the ERK1/2 of Bel-7402 cells. AG has anti-tumor activity in vivo and inhibits Bel-7402 cell proliferation in vitro through inducing cell differentiation, and the mechanism involves the activation of ERK1/2. | 25,093,547 | [
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2-Nitrophenol reduction promoted by S. putrefaciens 200 and biogenic ferrous iron: the role of different size-fractions of dissolved organic matter. | The reduction of nitroaromatic compounds (listed as a priority pollutant) in natural subsurface environments typically coexists with dissimilatory reduction of iron oxides effected by dissolved organic matter (DOM). Investigating the impact of the DOM that influences those reduction processes is crucial for understanding and predicting the geochemical fate of these environmental species. This study investigated the impact of different molecular weight DOM fractions (DMWDs) on the 2-nitrophenol (2-NP) reduction by S. putrefaciens 200 (SP200) and α-Fe2O3 with lactate (excluding electron donor interference). Kinetic measurements demonstrated that 2-NP reduction rates were affected by the redox reactivity of active species under DMWDs (denoted as L-DOM, M-DOM, and H-DOM). The enhanced reduction rates are consistent with the negative shifts in peak oxidation potential values, the increases in HA-like/FA-like values, aromaticity index values and electron transfer capacity values. L-DOM acted mainly as ligands to complex Fe(II), whereas the significant role of H-DOM in reductive reactions should be acting as an electron shuttle, transferring electrons from SP200 to Fe(III) and 2-NP and from biogenic Fe(II) to 2-NP, further accelerating the 2-NP reductions. Those observations provide valuable insights into the role of DOM in the biogeochemical redox processes and the remediation of contaminated soil in a natural environment. | 25,093,552 | [
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Morphogenesis: a Mob rules from the rear. | The giant ciliated protozoan Stentor coeruleus is re-emerging as a model organism for morphogenesis and patterning in unicellular organisms. A new study provides evidence that cytokinesis and morphogenesis are mechanistically linked through the Mob1 protein. | 25,093,564 | [
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Reproductive technology and the life course: current debates and research in social egg freezing. | While there are currently few confirmed births from previously frozen eggs in the UK, the improved outcomes of new technologies of vitrification and intra-cytoplasmic sperm injection (ICSI) have led to the marketing of egg freezing for non-medical reasons, whereby women are offered the possibility of preserving their eggs until such time as they wish to have a child. Non-academic commentary on this phenomenon has commonly constructed it within a neo-liberal discourse of 'choice', whereby women are positioned as choosing to 'delay motherhood,' often for reasons relating to their careers. However, there have been relatively few research studies which explore either women's awareness and understandings of social egg freezing or the reasons why women consider or undertake egg freezing. This paper summarises the current academic discussion surrounding social egg freezing and outlines the limited body of empirical literature identified from a systematic search of relevant databases. The potential benefits and harms of social egg freezing and the ethical issues it raises are well rehearsed in existing literature, but there is limited empirical evidence about who is accessing social egg freezing, why they are taking this option and what their experiences and future intentions are. | 25,093,571 | [
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"Let's talk about sex": a qualitative study of Rwandan adolescents' views on sex and HIV. | This qualitative study explored the views and experiences of adolescents with perinatally acquired HIV in Kigali, Rwanda, regarding sex, love, marriage, children and hope for the future. The study enrolled 42 adolescents who had received combination antiretroviral therapy for at least 12 months, and a selection of their primary caregivers. Study methods included 3 multiple day workshops consisting of role-playing and focus group discussions (FGDs) with adolescents, 8 in-depth interviews with adolescents, and one FGD with caregivers. The adolescents reported experiencing similar sexual needs and dilemmas as most other adolescents, but with an added layer of complexity due to fears related to HIV transmission and/or rejection by partners. They desired more advice from their parents/caregivers on these topics. Although they struggled with aspects of sex, love, marriage and having children, most agreed that they would find love, be married and have children in the future. The two most discussed HIV-related anxieties were how and when to disclose to a (potential) sex/marriage partner and whether to have children. However, most adolescents felt that they had a right to love and be loved, and were aware of prevention-of-mother-to-child-transmission (PMTCT) options in Rwanda. Adolescents generally spoke about their future role in society in a positive manner. Strengthening the life skills of HIV-positive adolescents, especially around HIV disclosure and reduction of HIV transmission, as well as the support skills of parents/caregivers, may not only reduce onward HIV transmission but also improve quality of life by reducing anxiety. | 25,093,572 | [
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Precipitation regime shift enhanced the rain pulse effect on soil respiration in a semi-arid steppe. | The effect of resource pulses, such as rainfall events, on soil respiration plays an important role in controlling grassland carbon balance, but how shifts in long-term precipitation regime regulate rain pulse effect on soil respiration is still unclear. We first quantified the influence of rainfall event on soil respiration based on a two-year (2006 and 2009) continuously measured soil respiration data set in a temperate steppe in northern China. In 2006 and 2009, soil carbon release induced by rainfall events contributed about 44.5% (83.3 g C m(-2)) and 39.6% (61.7 g C m(-2)) to the growing-season total soil respiration, respectively. The pulse effect of rainfall event on soil respiration can be accurately predicted by a water status index (WSI), which is the product of rainfall event size and the ratio between antecedent soil temperature to moisture at the depth of 10 cm (r2 = 0.92, P<0.001) through the growing season. It indicates the pulse effect can be enhanced by not only larger individual rainfall event, but also higher soil temperature/moisture ratio which is usually associated with longer dry spells. We then analyzed a long-term (1953-2009) precipitation record in the experimental area. We found both the extreme heavy rainfall events (>40 mm per event) and the long dry-spells (>5 days) during the growing seasons increased from 1953-2009. It suggests the shift in precipitation regime has increased the contribution of rain pulse effect to growing-season total soil respiration in this region. These findings highlight the importance of incorporating precipitation regime shift and its impacts on the rain pulse effect into the future predictions of grassland carbon cycle under climate change. | 25,093,573 | [
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Structural modeling of iron halogenases: synthesis and reactivity of halide-iron(IV)-oxo compounds. | A structural synthetic model of the iron(IV)-oxo-halide active species of non-heme iron dependent halogenases is reported. Compounds with general formula [Fe(IV)(O)(X)(Pytacn)](+) (1-X, X = Cl, Br) have been prepared and characterized spectroscopically and chemically with regard to their oxidizing ability. 1-X performs hydrogen-atom abstraction of C-H bonds at reaction rates 2-3 times faster than the corresponding solvato dicationic species, thus modelling the first step in C-H functionalization taking place in natural halogenation. | 25,093,575 | [
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Use of the ADOS for assessing spontaneous expressive language in young children with ASD: a comparison of sampling contexts. | The current study compared the spontaneous expressive language of children with autism spectrum disorder (ASD) across multiple language sampling contexts: the Autism Diagnostic Observation Schedule (ADOS; Lord, Rutter, DiLavore, & Risi, 1999) and play with an examiner or parent. Participants were children with ASD (n = 63; 55 boys) with a mean age of 45 months (SD = 3.94, range = 37-53). The number of utterances produced; percentage of intelligible utterances; number of different words; mean length of utterance; and the number of requests, comments, and instances of turn-taking were calculated for the ADOS, examiner-child play, and parent-child play. Children were categorized into Tager-Flusberg et al.'s (2009) developmental language phases for each context. Effects of sampling context were identified for all variables examined. The ADOS resulted in fewer utterances and lower structural and pragmatic language performance than examiner-child play and/or parent-child play. Categorization of children into language phases differed across contexts. Use of the ADOS as a language sampling context may lead to underestimating the abilities of young children with ASD relative to play with an examiner or parent. Researchers and clinicians should be aware of context effects, particularly for assessments designed to observe autism symptoms. | 25,093,577 | [
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Meta-analysis of operative mortality and complications in patients from minority ethnic groups. | Insight into the effects of ethnic disparities on patients' perioperative safety is necessary for the development of tailored improvement strategies. The aim of this study was to review the literature on safety differences between patients from minority ethnic groups and those from the ethnic majority undergoing surgery. PubMed, CINAHL, the Cochrane Library and Embase were searched using predefined inclusion criteria for available studies from January 1990 to January 2013. After quality assessment, the study data were organized on the basis of outcome, statistical significance and the direction of the observed effects. Relative risks for mortality were calculated. After screening 3105 studies, 26 studies were identified. Nine of these 26 studies showed statistically significant higher mortality rates for patients from minority ethnic groups. Meta-analysis demonstrated a greater risk of mortality for these patients compared with patients from the Caucasian majority in studies performed both in North America (risk ratio 1·22, 95 per cent confidence interval 1·05 to 1·42) and outside (risk ratio 2·25, 1·40 to 3·62). For patients from minority groups, the length of hospital or intensive care unit stay was significantly longer in five studies, and complication rates were significantly higher in ten. Methods used to identify patient ethnicity were not described in 14 studies. Patients from minority ethnic groups, in North America and elsewhere, have an increased risk of perioperative death and complications. More insight is needed into the causes of ethnic disparities to pursue safer perioperative care for patients of minority ethnicity. | 25,093,587 | [
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Solvent reorganization plays a temperature-dependent role in antibiotic selection by a thermostable aminoglycoside nucleotidyltransferase-4'. | The aminoglycoside nucleotidyltransferase-4' (ANT) is an enzyme that causes resistance to a large number of aminoglycoside antibiotics by nucleotidylation of the 4'-site on these antibiotics. The effect of solvent reorganization on enzyme-ligand interactions was investigated using a thermophilic variant of the enzyme resulting from a single-site mutation (T130K). Data showed that the binding of aminoglycosides to ANT causes exposure of polar groups to solvent. However, solvent reorganization becomes the major contributor to the enthalpy of the formation of enzyme-aminoglycoside complexes only above 20 °C. The change in heat capacity (ΔCp) shows an aminoglycoside-dependent pattern such that it correlates with the affinity of the ligand for the enzyme. Differences in ΔCp values determined in H2O and D2O also correlated with the ligand affinity. The temperature-dependent increase in the offset temperature (Toff), the temperature difference required to observe equal enthalpies in both solvents, is also dependent on the binding affinity of the ligand, and the steepest increase was observed with the tightest binding aminoglycoside, neomycin. Overall, these data, together with earlier observations with a different enzyme, the aminoglycoside N3-acetyltransferase-IIIb [Norris, A. L., and Serpersu, E. H. (2011) Biochemistry 50, 9309], show that solvent reorganization or changes in soft vibrational modes of the protein are interchangeable with respect to the role of being the major contributor to complex formation depending on temperature. These data suggest that such effects may more generally apply to enzyme-ligand interactions, and studies at a single temperature may provide only a part of the whole picture of thermodynamics of enzyme-ligand interactions. | 25,093,604 | [
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Posttraumatic administration of luteolin protects mice from traumatic brain injury: implication of autophagy and inflammation. | Secondary brain insult induced by traumatic brain injury (TBI), including excitotoxicity, oxidative stress, inflammatory response, and neuronal degeneration, is sensitive to therapeutic interventions; therefore, searching for neuroprotective agents represents a promising therapeutic strategy for TBI treatment. Luteolin, a member of the flavonoid family, has recently been proven to modulate autophagy. However, whether it activates autophagy after TBI thereby alleviating the secondary insult is not yet understood. Here, we aimed to evaluate the neuroprotection of luteolin against TBI and the potential role of autophagy where it is involved. For this purpose, mice were randomly divided into four groups and then subjected to TBI. The treatment mice received luteolin at a dose of 30mg/kg 30min post-TBI based on our previous study. We employed western blot, immunofluorescence and quantitative real-time PCR to determine autophagy process and inflammatory response among different groups. Autophagy was found to be enhanced after luteolin treatment according to the expressions of autophagic markers. Furthermore, luteolin decreased nuclear accumulation of p65 induced by TBI, indicating attenuation of inflammation. In line with these observations, luteolin decreased mRNA and protein expressions of pro-inflammatory factors IL-1b and TNF-a. At last, luteolin reduced neuronal degeneration, and alleviated brain edema and blood-brain barrier (BBB) disruption. In conclusion, these results implied that luteolin protected mice brain from traumatic brain injury by inhibiting inflammatory response, and luteolin-induced autophagy might play a pivotal role in its neuroprotection. | 25,093,609 | [
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Estimating healthy life expectancies using longitudinal survey data: methods and techniques in population health measures. | Objective-Summary measures of population health are statistics that combine mortality and morbidity to represent overall population health in a single index. Such measures include healthy life expectancy, also called disability-free life expectancy and active life expectancy. Healthy life expectancy can be calculated using cross-sectional or longitudinal survey data. This report presents a comprehensive discussion of a method for calculating healthy life expectancy using data from longitudinal surveys. Methods-Healthy life expectancies are calculated using the multistate life table model. Expected life in various states of health is estimated using data from the Second Longitudinal Study of Aging and the Medicare Current Beneficiary Survey to illustrate the calculation of the statistics and the discussion of data and methodology related issues. Results-The study shows that estimating summary measures of population health using longitudinal survey data provides the opportunity of using incidence rather than prevalence rates. Health measures estimated based on incidence reflect the most recent health status of the population. Models that use longitudinal survey data measure transitions from good to poor health as well as poor to good health. That is, the models account for recovery from morbidity or illness. Longitudinal survey data canalsobeusedtocalculate healthy or active life expectancies by initial health states. | 25,093,608 | [
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... |
Human paraoxonase 1 hydrolysis of nanomolar chlorpyrifos-oxon concentrations is unaffected by phenotype or Q192R genotype. | The organophosphorus insecticide chlorpyrifos has been widely used. Its active metabolite chlorpyrifos-oxon (CPO) is a potent anticholinesterase and is detoxified by paraoxonase 1 (PON1). PON1 activity is influenced by numerous factors including a Q192R polymorphism. Using forty human blood samples bearing homozygous genotypes and either high or low activity phenotypes (as determined by high concentration assays of paraoxon and diazoxon hydrolysis) the serum PON1 hydrolysis of high (320 μM) and low (178 nM) CPO concentrations was assessed using direct or indirect spectrophotometric methods, respectively. PON1 activity at high CPO concentration reflected the phenotype and genotype differences; subjects with the high activity phenotype and homozygous for the PON1R192 alloform hydrolyzed significantly more CPO than subjects with the low activity phenotype and/or PON1Q192 alloform (high RR=11023±722, low RR=9467±798, high QQ=8809±672, low QQ=6030±1015 μmol CPO hydrolyzed/min/L serum). However, PON1 hydrolysis of CPO at the lower, more environmentally relevant concentration showed no significant differences between the PON1192 genotypes and/or between high and low activity phenotypes (high RR=231±27, low RR=219±52, high QQ=193±59, low QQ=185±43 nmol CPO/min/L serum). Low CPO concentrations were probably not saturating, so PON1 did not display maximal velocity and the PON1 genotype/phenotype might not influence the extent of metabolism at environmental exposures. | 25,093,614 | [
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The polycystic ovary syndrome evolutionary paradox: a genome-wide association studies-based, in silico, evolutionary explanation. | Polycystic ovary syndrome (PCOS) is a common female endocrine disorder characterized by phenotypes ranging from hyperandrogenism to metabolic disorders, more prevalent in people of African/Caucasian and Asian ancestry. Because PCOS impairs fertility without diminishing in prevalence, it was considered an evolutionary paradox. Genome-Wide Association Studies identified 17 single nucleotide polymorphisms (SNPs) associated with PCOS, with different allele frequencies, ethnicity-related, in 11 susceptibility loci. In this study we analyze the PCOS phenotype-genotype relationship in silico, using SNPs of representative genes for analysis of genetic clustering and distance, to evaluate the degree of genetic similarity. 1000 Genomes, HapMap, and Human Genome Diversity Project databases were used as source of allele frequencies of the SNPs, using data from male and female individuals grouped according to their geographical ancestry. Genetic clustering was calculated from SNPs data by Bayesian inference. The inferred ancestry of individuals was matched with PCOS phenotype data, extracted from a previous meta-analysis. The measure of genetic distance was plotted against the geographic distance between the populations. The individuals were assigned to five genetic clusters, matching with different world regions (Kruskal-Wallis/Dunn's post test; P < .0001), and converging in two main PCOS phenotypes in different degrees of affinity. The overall genetic distance increased with the geographic distance among the populations (linear regression; R(2) = 0.21; P < .0001), in a phenotype-unrelated manner. Phenotype-genotype correlations were demonstrated, suggesting that PCOS genetic gradient results from genetic drift due to a serial founder effect occurred during ancient human migrations. The overall prevalence of the disease supports intralocus sexual conflict as alternative to the natural selection of phenotypic traits in females. | 25,093,623 | [
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0.2609645,
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0.1964538,
-0.235765... |
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