title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Factors and Trends Affecting the Identification of a Reliable Biomarker for Diesel Exhaust Exposure. | The monitoring of human exposures to diesel exhaust continues to be a vexing problem for specialists seeking information on the potential health effects of this ubiquitous combustion product. Exposure biomarkers have yielded a potential solution to this problem by providing a direct measure of an individual's contact with key components in the exhaust stream. Spurred by the advent of new, highly sensitive, analytical methods capable of detecting substances at very low levels, there have been numerous attempts at identifying a stable and specific biomarker. Despite these new techniques, there is currently no foolproof method for unambiguously separating diesel exhaust exposures from those arising from other combustion sources. Diesel exhaust is a highly complex mixture of solid, liquid, and gaseous components whose exact composition can be affected by many variables, including engine technology, fuel composition, operating conditions, and photochemical aging. These factors together with those related to exposure methodology, epidemiological necessity, and regulatory reform can have a decided impact on the success or failure of future research aimed at identifying a suitable biomarker of exposure. The objective of this review is to examine existing information on exposure biomarkers for diesel exhaust and to identify those factors and trends that have had an impact on the successful identification of metrics for both occupational and community settings. The information will provide interested parties with a template for more thoroughly understanding those factors affecting diesel exhaust emissions and for identifying those substances and research approaches holding the greatest promise for future success. | 25,170,242 | [
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Safety and efficacy of fixed-combination travoprost/timolol in patients with open-angle glaucoma or ocular hypertension not controlled with timolol monotherapy. | To assess the intraocular pressure (IOP)-lowering effect of travoprost 0.004%/timolol 0.5% fixed-dose combination (TRAV/TIM-FC) in patients not achieving the target IOP of ≤18 mmHg while on timolol 0.5% (TIM) monotherapy. A multicenter, prospective, open-label study (NCT01336569) was conducted in patients with open-angle glaucoma or ocular hypertension. Eligible patients were receiving TIM monotherapy with a screening/baseline IOP of 19-35 mmHg in ≥1 eye. TIM was discontinued on the baseline visit day (no washout period) and TRAV/TIM-FC was initiated and administered once daily at 8 pm for 4-6 weeks. The primary efficacy variable was mean change in IOP from TIM-treated baseline to study end, measured by Goldmann applanation tonometry. Results were analyzed by analysis of variance and paired samples t-test (5% significance). A total of 49 patients were enrolled (mean age, 63 [range, 42-82] years; 55.1% White; 73.5% women), and 45 were included in the intent-to-treat (ITT) population. Mean duration of treatment with TRAV/TIM-FC was 31 days. Mean ± standard deviation IOP reduction from baseline (TIM) to the follow-up visit (TRAV/TIM-FC) was -5.0±3.6 mmHg. IOP decreased significantly (P<0.0001) from baseline (22.1±2.6 mmHg) to study end (17.1±3.9 mmHg) in the ITT population, with a mean IOP reduction of 22.3%. Most patients (n=33/45; 73.3%) achieved IOP ≤18 mmHg. Two patients experienced a total of four adverse events (AEs), including a patient who reported one serious AE (enterorrhagia) that was considered unrelated to treatment, and a patient who reported one event each of drug-related redness, pruritus, and foreign body sensation. Most patients (n=47/49; 95.9%) reported no AEs. TRAV/TIM-FC lowered IOP in patients who were not at target IOP while receiving TIM monotherapy, with most patients achieving an IOP ≤18 mmHg with TRAV/TIM-FC. TRAV/TIM-FC was well tolerated in this population. | 25,170,245 | [
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Advanced prostate cancer - patient survival and potential impact of enzalutamide and other emerging therapies. | The advent of exponential growth of novel agents tested and approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) has brought about a need for understanding of the mechanism of action, side-effects, and clinical efficacy of these drugs as they relate to these patients. This review will provide a synopsis of the treatment landscape in mCRPC as varying agents such as abiraterone acetate, cabazitaxel, sipuleucel-T, radium, and selected emerging agents are presented. A distinct focus on the utilization of enzalutamide, its mechanism of action, key pivotal trials that brought about its US Food and Drug Administration approval, as well as patient-focused perspectives and clinical implications are discussed herein. | 25,170,270 | [
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Profile of pacritinib and its potential in the treatment of hematologic disorders. | Pacritinib (previously known as SB-1518) is an innovative selective inhibitor of Janus kinase 2 and FMS-related tyrosine kinase 3 providing potential in the treatment of hematological malignancies such as myeloproliferative neoplasias, acute myeloid leukemia, and various lymphomas. Pacritinib has potent antiproliferative activity in Janus kinase 2 and/or FMS-related tyrosine kinase 3 activity-dependent cell lines and an ability to promote apoptosis and inhibit the signal transducers and activators of transcription (STAT) pathway. Pharmacokinetic studies have indicated a good per os bioavailability and favorable kinetic parameters. To date, promising results have been produced in five completed early-phase clinical trials in which pacritinib has been studied. Pacritinib displayed interesting activity and an acceptable safety profile, with mild to moderate gastrointestinal disorders being its most common adverse effects. | 25,170,285 | [
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AKR1C3 overexpression mediates methotrexate resistance in choriocarcinoma cells. | Chemotherapy is typically used to treat choriocarcinoma, but a small proportion of tumors develop resistance to chemotherapy. Similarly, methotrexate (MTX) is a first-line chemotherapy used to treat choriocarcinoma; although ~30% of patients are drug-resistant for MTX mono-therapy. Thus, we sought to elucidate the mechanism of chemotherapeutic-resistance of MTX. RNA interference technology, colony formation, and MTT assays were used to investigate the role of aldo-keto reductase family 1, member C3 (AKR1C3) in MTX resistance in choriocarcinoma cells. AKR1C3 expression was higher in JeG-3R cells compared to JeG-3 cells and targeted inhibition of AKR1C3 expression with shRNA suppresses growth of choriocarcinoma cells as measured by colony formation and MTT assays. Overexpression of AKR1C3 increased chemotherapeutic resistance in JeG-3 cells. Furthermore, AKR1C3 silencing increases sensitivity to MTX in JeG-3R choriocarcinoma cells. Increasing MTX sensitivity spears to be related to DNA damage induction by increased reactive oxygen species (ROS), apoptosis, and cell cycle arrest. Data show that AKR1C3 is critical to the development of methotrexate resistance in choriocarcinoma and suggest that AKR1C3 may potentially serve as a therapeutic marker for this disease. | 25,170,291 | [
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Abnormality in Wnt signaling is causatively associated with oxidative stress-induced intestinal tumorigenesis in MUTYH-null mice. | MUTYH is a DNA glycosylase that excises adenine paired with 8-oxoguanine to prevent mutagenesis in mammals. Biallelic germline mutations of MUTYH have been found in patients predisposed to a recessive form of familial adenomatous polyposis (MAP: MUTYH-associated polyposis). We previously reported that Mutyh-deficient mice showed a high susceptibility to spontaneous and oxidative stress-induced intestinal adenoma/carcinoma. Here, we performed mutation analysis of the tumor-associated genes including Apc, Ctnnb1, Kras and Trp53 in the intestinal tumors of Mutyh-deficient mice. In the 62 tumors, we identified 25 mutations in Apc of 18 tumors and 36 mutations in Ctnnb1 of 36 tumors. Altogether, 54 out of the 62 tumors (87.1%) had a mutation in either Apc or Ctnnb1; no tumor displayed mutations simultaneously in the both genes. Similar to MAP, 60 out of 61 mutations (98.3%) were identified as G:C to T:A transversions of which 85% occurred at either AGAA or TGAA sequences. Immunohistochemical analyses revealed the accumulation of β-catenin in the nuclei of tumors. No mutation was found in either Kras or Trp53 in the tumors. These results indicate that the uncontrolled activation of Wnt signaling pathway is causatively associated with oxidative stress-induced intestinal tumorigenesis in the Mutyh-deficient mice. | 25,170,306 | [
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Out-diffused silver island films for surface-enhanced Raman scattering protected with TiO2 films using atomic layer deposition. | We fabricated self-assembled silver nanoisland films using a recently developed technique based on out-diffusion of silver from an ion-exchanged glass substrate in reducing atmosphere. We demonstrate that the position of the surface plasmon resonance of the films depends on the conditions of the film growth. The resonance can be gradually shifted up to 100 nm towards longer wavelengths by using atomic layer deposition of titania, from 3 to 100 nm in thickness, upon the film. Examination of the nanoisland films in surface-enhanced Raman spectrometry showed that, in spite of a drop of the surface-enhanced Raman spectroscopy (SERS) signal after the titania spacer deposition, the Raman signal can be observed with spacers up to 7 nm in thickness. Denser nanoisland films show slower decay of the SERS signal with the increase in spacer thickness. 78.67.Sc (nanoaggregates; nanocomposites); 81.16.Dn (self-assembly); 74.25.nd (Raman and optical spectroscopy). | 25,170,333 | [
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E-cigarettes: online survey of UK smoking cessation practitioners. | Use of e-cigarettes (inhalable vapour producing battery powered devices that aim to simulate tobacco cigarettes), is rising in a number of countries, but as yet none of these products are regulated as medicinal devices or available as smoking cessation treatments. Smokers seeking support from health professionals to stop smoking are interested in e-cigarettes and may be buying them to aid a quit attempt. Determining what smokers are asking, and what health professionals think about these products may have implications for smoking treatment services in a number of countries. Stop smoking service advisors, managers and commissioners in the United Kingdom were asked to take part in two surveys on e-cigarettes. Data was analysed from 587 practitioners who completed a survey in 2011 and 705 practitioners who completed a repeat survey in 2013. Responses to multiple choice questions and free text comments were analysed. Responding practitioners reported that interest in, and use of, e-cigarettes is growing among adults seeking help to stop smoking in the UK. In 2013 91% of respondents reported that interest in e-cigarettes had grown in the past year and whilst in 2011, 2% of respondents reported a 'quarter to a half' of their clients saying that they were regularly using e-cigarettes, by 2013 this had increased to 23.5% (p < .001). Responding practitioners' views towards e-cigarettes became more positive between the first and second surveys (15% strongly agreed/agreed in 2011 that 'e-cigarettes are a good thing' rising to 26% in 2013). However, they continued to have concerns about the products. In particular, analysis of free text responses suggested practitioners were unsure about safety or efficacy for smoking cessation, and were worried that smokers may become dependent on the products. Practitioners were also aware of the potential of e-cigarettes to undermine smokers' willingness to use evidence-based methods to stop, and to challenge policies aiming to denormalise tobacco smoking. Health professionals are asking for reliable and accurate information on e-cigarettes to convey to smokers who want to quit. Randomized controlled trials and ongoing surveillance of e-cigarette use and its consequences for smoking cessation rates and smoking treatment services are required. | 25,170,337 | [
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Increasing sexually transmitted infection rates in young men having sex with men in the Netherlands, 2006-2012. | Men having sex with men (MSM) remain the largest high-risk group involved in on-going transmission of sexually transmitted infections (STI), including HIV, in the Netherlands. As risk behaviour may change with age, it is important to explore potential heterogeneity in risks by age. To improve our understanding of this epidemic, we analysed the prevalence of and risk factors for selected STI in MSM attending STI clinics in the Netherlands by age group. Analysis of data from the national STI surveillance system for the period 2006-2012. Selected STI were chlamydia, gonorrhoea, infectious syphilis and/or a new HIV infection. Logistic regression was used to identify factors associated with these selected STI and with overall STI positivity. Analyses were done separately for MSM aged younger than 25 years and MSM aged 25 years and older. In young MSM a significant increase in positivity rate was seen over time (p < 0.01), mainly driven by increasing gonorrhoea diagnoses, while in MSM aged 25 and older a significant decrease was observed (p < 0.01). In multivariate analyses for young MSM, those who were involved in commercial sex were at higher risk (OR: 1.5, 95% CI: 1.2-1.9). For MSM aged 25 years and older this was not the case. Having a previous negative HIV test was protective among older MSM compared to those not tested for HIV before (OR: 0.8, 95% CI: 0.8-0.8), but not among younger MSM. MSM visiting STI clinics remain a high-risk group for STI infections and transmission, but are not a homogenous group. While in MSM aged older than 25 years, STI positivity rate is decreasing, positivity rate in young MSM increased over time. Therefore specific attention needs to be paid towards targeted counselling and reaching particular MSM sub-groups, taken into account different behavioural profiles. | 25,170,341 | [
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Copy number variation in Han Chinese individuals with autism spectrum disorder. | Autism spectrum disorders (ASDs) are a group of neurodevelopmental conditions with a demonstrated genetic etiology. Rare (<1% frequency) copy number variations (CNVs) account for a proportion of the genetic events involved, but the contribution of these events in non-European ASD populations has not been well studied. Here, we report on rare CNVs detected in a cohort of individuals with ASD of Han Chinese background. DNA samples were obtained from 104 ASD probands and their parents who were recruited from Harbin, China. Samples were genotyped on the Affymetrix CytoScan HD platform. Rare CNVs were identified by comparing data with 873 technology-matched controls from Ontario and 1,235 additional population controls of Han Chinese ethnicity. Of the probands, 8.6% had at least 1 de novo CNV (overlapping the GIGYF2, SPRY1, 16p13.3, 16p11.2, 17p13.3-17p13.2, DMD, and NAP1L6 genes/loci). Rare inherited CNVs affected other plausible neurodevelopmental candidate genes including GRID2, LINGO2, and SLC39A12. A 24-kb duplication was also identified at YWHAE, a gene previously implicated in ASD and other developmental disorders. This duplication is observed at a similar frequency in cases and in population controls and is likely a benign Asian-specific copy number polymorphism. Our findings help define genomic features relevant to ASD in the Han Chinese and emphasize the importance of using ancestry-matched controls in medical genetic interpretations. | 25,170,348 | [
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Prevalence of erectile dysfunction and associated factors among diabetic men attending diabetic clinic at Muhimbili National Hospital in Dar-es-Salaam, Tanzania. | There has been an increase in the prevalence of erectile dysfunction (ED) in the general population especially among Diabetic patients. This seems to be neglected problem in low-income countries. This study aims at establishing the prevalence of ED and associated risk factors in diabetic patients attended at Diabetic Clinic at Muhimbili National Hospital. A cross-sectional hospital based study was conducted among 312 diabetic patients attending diabetic clinic at Muhimbili National Hospital between May and December 2011. More than half (55.1%) of the patients were found to have some form of ED (12.8% had mild dysfunction, 11.5% moderate and 27.9% severe dysfunction). The severity of ED was correlated with increased age. Multivariate logistic regression revealed that ED was significantly predicted by old age (odds ratio (OR) = 7.1, 95% CI 1.2-40.7), evidence of peripheral neuropathy (OR) =5.9, 95% CI 1.6-21.3), and evidence of peripheral vascular disease (OR =2.5, 95% CI 1.2-5.3). Also longer duration of DM was marginally associated with ED (p=0.056). Patients with ED were also more likely to suffer other sexual domains (p<0.001). No lifestyle factor was associated with ED. The prevalence of ED is high among DM patients. Interventions aimed at prevention, early diagnosis and detection of DM and its complications, and adherence to treatment to prevent complications should be implemented. Further studies should emphasize on temporal variation to show true causality of DM on erectile dysfunction. | 25,170,371 | [
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Stromal tumor of the lesser omentum : a case report. | Gastrointestinal stromal tumors (GISTs) represent the majority of primary non-epithelial neoplasms of the digestive tract, most frequently expressing the KIT protein detected by immunohistochemical staining for the CD117 antigen. Extragastrointestinal stromal tumors (EGISTs), neoplasms with immunohistological features overlapping those of GISTs, are found in the abdomen outside of the gastrointestinal tract with no connection to the gastric or intestinal wall. We report the clinical, macroscopic and immunohistological features of an EGIST arising in the lesser omentum of a 58-year-old woman. This is a very rare location of intra abdominal stromal tumors. | 25,170,380 | [
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Adherence to antiretroviral therapy among HIV-infected children receiving care at Kilimanjaro Christian Medical Centre (KCMC), Northern Tanzania: A cross- sectional analytical study. | Paediatric adherence to Highly Active Antiretroviral Therapy (HAART) is a dynamic process involving many factors. Adherence for the majority on therapy matters to prevent failure of 1(st) and 2(st) line therapy. The purpose of this study was to determine the rate of adherence to antiretroviral therapy in HIV infected children. We conducted a cross-sectional hospital based analytical study, from October 2011 to April 2012. HIV-infected children aged 2 to 17 years who had been on treatment for at least six months were enrolled. Data were collected by a standard questionnaire. Two-day self-report, one month self-recall report, and pill count were used to assess adherence. One hundred and eighty three respondents participated in this research. There were 92 (51%) males and 91 (49%) females. Only 45 (24.6%) had good adherence to their drug regimen when subjected to all three methods of assessment. Males were more adherent to ART than females (OR= 2.26, CI 1.05-4.87, p = 0.04). Adherence was worse among children who developed ART side effects (OR= 0.19, CI 0.07- 0.56;p = 0.01), could not attend clinic on regular basis (OR= 3.4, CI 1.60- 7.36, p = 0.01) and missed drug doses in the six months period prior to interview (OR= 0.40, CI 0.18-0.82, p= 0.01). Only 24.6% of paediatric patients had good adherence to ART when subjected to all three measures. Drug side-effects, missing drug doses in the six months period prior to study start, monthly income and affording transportation to the clinic were strong predictors of adherence. | 25,170,382 | [
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Gastrointestinal imaging-practical magnetic resonance imaging approach. | Over the past two decades, advances in cross-sectional imaging such as computed tomography and magnetic resonance imaging (MRI) have dramatically changed the concept of gastrointestinal imaging. MR is playing an increasing role in the evaluation of gastrointestinal disorders. MRI combines the advantages of excellent soft-tissue contrast, noninvasiveness, functional information and lack of ionizing radiation. Furthermore, recent developments of MRI have led to improved spatial and temporal resolution as well as decreased motion artifacts. In this article we describe the technical aspects of gastrointestinal MRI and present a practical approach for a well-known spectrum of gastrointestinal disease processes. | 25,170,393 | [
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Characterization of ureteral stents by dual-energy computed tomography: Clinical implications. | Dual-energy computed-tomography (DECT) has been suggested as the method of choice for imaging urinary calculi due to the modality's high sensitivity for detecting stones and its capability of accurately differentiating between uric-acid (UA) and non-UA (predominantly calcium) stones. The clinical significance of the latter feature relates to the differences in management of UA vs non-UA calculi. Like calculi, ureteral stents are assigned color by the dual-energy post-processing algorithm, which may lead to improved or worsened stone visualization based on the resulting stent/stone contrast. Herein we depict the case of a nephrolithiasis patient with bilateral stents, each with different color, clearly displaying the effect of stent color on stone visualization. Further, three-dimensional reconstruction of the DECT images illustrates advantages of this enhancement compared to conventional two-dimensional computed tomography. The resulting stent/stone contrast produces an unanticipated potential advantage of DECT in patients with urolithiasis and stents and may promote improved management decision-making. | 25,170,401 | [
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Predictors of reintubation in trauma intensive care unit: qatar experience. | To determine the causes, predictors and outcomes of re-intubation. Retrospective analysis of data collected from the trauma data base registry was conducted to identify the extubation failure cases in Trauma ICU at Hamad General Hospital, the only Level I trauma center in Qatar between January 2009 and December 2010. Demographics, mechanism of Injury, complications, injury severity score (ISS), Glasgow Coma Scale (GCS), ICU-length of stay (LOS), and mortality were analyzed among trauma patients who need reintubation within 48 hrs after extubation (group 1) compared to successfully extubated patients (group 2). A total of 954 patients were admitted to the trauma ICU, of which 343 were intubated orotracheally. The mean age of patients was 32±12 years with male predominance (95%). Motor vehicle crash (41%), pedestrian injury (20%) and falls (18%) were the most common mechanisms of injury. Reintubation (group 1) was required in 24 patients (7%). Patients in group 1 had higher rate of head injury mainly SAH (88%), pneumonia (79%) and pulmonary contusion (58%). The mean ICU-LOS was higher in the reintubated patients (p=0.010) in comparison to group 2. Forty-six percent of reintubated patients required tracheostomy. The mean age, ISS, GCS and tube size was comparable among the two groups. Furthermore, reintubation was not associated with higher mortality rate (p=0.910). However, Ventilator-associated pneumonia (VAP) (odd ratio=3.61 [95% CI 1.25-10.44]; p=0.020) and ventilator days (odd ratio=1.09 [95% CI 1.024-1.153]; p=0.006) were independent predictors of reintubation by multivariate analysis. Re-intubation is associated with increased ICU-LOS and need for tracheostomy. VAP and prolonged intubation are independent predictors of re-intubation. Our finding addresses the value of prevention and early treatment of infection in intubated patients. This study may represent an audit of local practice as well. | 25,170,412 | [
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Cadmium alters the formation of benzo[a]pyrene DNA adducts in the RPTEC/TERT1 human renal proximal tubule epithelial cell line. | Previously, we demonstrated the sensitivity of RPTEC/TERT1 cells, an immortalized human renal proximal tubule epithelial cell line, to two common environmental carcinogens, cadmium (Cd) and benzo[a]pyrene (B[a]P). Here, we measured BPDE-DNA adducts using a competitive ELISA method after cells were exposed to 0.01, 0.1, and 1 μM B[a]P to determine if these cells, which appear metabolically competent, produce BPDE metabolites that react with DNA. BPDE-DNA adducts were most significantly elevated at 1 μM B[a]P after 18 and 24 hours with 36.34 +/- 9.14 (n = 3) and 59.75 +/- 17.03 (n = 3) adducts/10<sup8</sup nucleotides respectively. For mixture studies, cells were exposed to a non-cytotoxic concentration of Cd, 1 μM, for 24 hours and subsequently exposed to concentrations of B[a]P for 24 hours. Under these conditions, adducts detected at 1 μM B[a]P after 24 hours were significantly reduced, 17.28 +/- 1.30 (n = 3) adducts/10<sup8</sup nucleotides, in comparison to the same concentration at previous time points without Cd pre-treatment. We explored the NRF2 antioxidant pathway and total glutathione levels in cells as possible mechanisms reducing adduct formation under co-exposure. Results showed a significant increase in the expression of NRF2-responsive genes, <iGCLC, HMOX1, NQO1</i, after 1 μM Cd × 1 μM B[a]P co-exposure. Additionally, total glutathione levels were significantly increased in cells exposed to 1 μM Cd alone and 1 μM Cd × 1 μM B[a]P. Together, these results suggest that Cd may antagonize the formation of BPDE-DNA adducts in the RPTEC/TERT1 cell line under these conditions. We hypothesize that this occurs through priming of the antioxidant response pathway resulting in an increased capacity to detoxify BPDE prior to BPDE-DNA adduct formation. | 25,170,436 | [
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Binge drinking and psychoactive drug use in a cohort of European youths. | TEN-D by Night is an international, multicentre, cross-sectional portal survey conducted on a large sample of young people in six European countries. This paper aims to investigate the alcohol and psychoactive drug consumption of this sample, with a focus on the prevalence of binge drinking and the poly-drug habits of the TEN-D cohort. The study population consisted of 4695 young people attending recreational sites on weekend nights. The intervention included two questionnaires and two psychoactive substance detection tests performed at the entry and exit of the recreational sites. A multivariate logistic regression model was used to predict the probability of binge drinking. Binge drinking was reported by 20% of the males and 13% of the females (P=0.001) before entry into the recreational sites and by 18% of the males and 11% of the females before entry into the clubs (P<0.001). Poly-drug use was reported by 71% of the males and 66% of the females. Living with a parent (OR 1.57; P=0.01), seeking employment (OR 1.66; P=0.005) and cannabis consumption (several times per month and several times per week, OR 1.94 and 3.66, respectively, P<0.05) were associated with binge drinking. Our survey showed that it is possible to identify individuals and groups at higher risk of binge drinking. This identification would allow for a focus on specific targets and would facilitate the redesign of prevention programmes. The increased use of psychoactive substances among youths should be studied extensively to promote successful prevention campaigns. | 25,170,451 | [
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Talking About Sex in Malawi: Toward a Better Understanding of Interpersonal Communication for HIV Prevention. | The generalised AIDS epidemic in Malawi presents many challenges. As communication and advice from parents, peers, and partners are important factors in influencing sexual behaviour, understanding communication may provide insights into behaviour change programming. This mixed-method study used a household survey (n=1812) and 15 focus group discussions from the southern districts of Malawi to explore communication about sex and sexuality. Quantitative study findings point to the idea that self-efficacy, perceived benefits, and injunctive norms about talking about condom use are important factors influencing intentions to discuss condom use with partners. Qualitative study findings found that communication regarding sex between parents and children, partners, and peers was not common, and when there was communication, messages about sex focused on negative consequences of sexual activity. In Malawi, there is a need to increase efficacy in talking about sex and protective sexual behaviours, including condom use. Interventions should include components to increase communication skills, shift norms about sexual communication, and provide alternative mechanisms for individuals to gather pertinent information regarding their sexual behaviour. | 25,170,453 | [
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What is Behind the Seeming Cessation of the Increase in Sleep Medicine Consumption in Finland During the Last Years? | In Finland, between 2003 and 2010 and parallel to the increase in the prevalence of insomnia-related symptoms among the general population, there has been a cessation of growth and even a decrease in the consumption of traditional hypnotics. The reasons behind this seemingly paradoxical situation are not known. We analyzed trends over the period 2000-2010 in the estimated consumption of traditional hypnotics and some new drugs that are destined for use in insomnia treatment. We used the annual wholesale statistical database compiled by the Finnish Medicine Agency, FIMEA, and data from the Finnish Drug Prescription Register. We found evidence to support two parallel trends in Finnish outpatient care. First, there seems to be a trend in which physicians increasingly comply with official guidelines for insomnia treatment, which partly accounts for the decrease in the consumption of traditional hypnotics. Second, at the same time, the first trend seems to be resulting in an increasing trend to treat insomnia patients with some new drugs that were not originally developed for insomnia treatment by prescribing these non-hypnotic drugs in small, sub-clinical doses. The current trend in practice may have contradictory effects on the treatment of insomnia. The long-term consequences of using low doses of drugs other than hypnotics to treat insomnia are not known and the situation should, therefore, be followed-up in subsequent studies. However, pharmacological treatment should never be a substitute for non-pharmacological treatments of insomnia. The authors gratefully acknowledge Ms. Maini Tulokas in the Social Insurance Institution for her skilled help in preparing the figures. | 25,170,458 | [
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Tuberculosis in quebec: a review of trends. | The aim of this research was to conduct a thorough review on the literature of tuberculosis in Canada and the Province of Quebec. To achieve this aim, an exhaustive literature review of tuberculosis in the Province of Quebec was undertaken. Data was collected with the goal of creating an epidemiological and public health evidence base to forecast the spread of tuberculosis. A keyword search strategy was used to find relevant articles from the peer-reviewed literature using the electronic search engine PubMed and a search of other relevant federal and provincial government databases. Twenty-nine peer-reviewed publications and twenty government reports containing information about the incidence or prevalence of tuberculosis in the Province of Quebec were included in the analysis. An analysis of the data revealed that while tuberculosis rates have been decreasing in both Canada and Quebec with an overall incidence below 3 per 100,000 of population in 2007, among immigrants and the Inuit communities in Quebec, the incidence and prevalence of the disease still remains high and reached 18 per 100,000 and 100 per 100,000, respectively in 2007. In general, while tuberculosis does not pose a significant burden to the general population, it does continue to affect certain sub-groups disproportionately, including select immigrants and Inuit communities in Quebec. Efforts to ensure that cost-effective healthcare interventions are delivered in a timely fashion should be pursued to reduce the associated morbidity and mortality of tuberculosis in the Province of Quebec. Funding for this research was provided to Medmetrics Inc., by McGill University, Montreal, Quebec, Génome Québec and the Ministère de Développement Economique, Innovation et Exportation du Gouvernement du Québec. The authors also wish to thank Drs. John White and Marcel Behr, both of McGill University and Dr Suneil Malik of the Infectious Disease Program in the Office of Biotechnology, Genomics and Population Health at the Public Health Agency of Canada for comments and suggestions on earlier drafts of this manuscript. | 25,170,460 | [
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Prevalence of vitamin d insufficiency in qatar: a systematic review. | Qatar has a high burden of chronic diseases including obesity, cardiovascular disease and type 2 diabetes mellitus. Low serum vitamin D levels have been implicated in the development and progression of a range of these chronic conditions. The prevalence of vitamin D insufficiency or deficiency in the general population of Qatar has still not been investigated. The aim of this study was to carry out a systematic review of published studies documenting the prevalence of vitamin D insufficiency or deficiency in the Qatari population. A search strategy was developed for online databases (PubMed, Ovid MEDLINE, Embase and Embase Classic) between 1980 to the last week of August 2012, and bibliographies of the included studies were further searched for additional reports. Search terms used were QATAR and VITAMIN D. Studies reporting the serum levels of vitamin D in several Qatari sub-populations were identified. Weighted-average vitamin D serum levels and prevalence of low vitamin D status (<75 nmol/L) were calculated. Subgroup analysis was carried out by age. The quality of each study was evaluated according to four criteria: national representativeness, representation of males and females, the sample size, and the sampling protocol. A total of 16 relevant publications were identified, and 8 of these (reporting from 7 unique studies) met our inclusion and exclusion criteria with a total number of 1,699 Qatari subjects. The pooled sample size weighted-average vitamin D concentration (±SD) was 45.3±14.3 nmol/L (95% CI: 44.6-46.0; range 29.2-66.9 nmol/L). The weighted-average prevalence of low vitamin D status was 90.4% (95% CI: 90.1-91.0; range 83%-91%). Age was inversely correlated with vitamin D levels and directly with its insufficiency/deficiency prevalence. There have only been a few studies on the prevalence of low vitamin D in Qatar a very high prevalence of vitamin D insufficiency/deficiency in Qatar that increases with age has been suggested. The present report underlines the need to develop a nationally representative study to further evaluate vitamin D status in Qatar. Given the growing evidence of the role of vitamin D in chronic disease, this study could help develop public health strategies for disease prevention in Qatar. | 25,170,469 | [
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The crisis of capitalism and the marketisation of health care: the implications for public health professionals. | The current economic crisis in Europe has challenged the basis of the economic model that currently prevails in much of the industrialised world. It has revealed a system that is managed not for the benefit of the people but rather for the corporations and the small elite who lead them, and which is clearly unsustainable in its present form. Yet, there is a hidden consequence of this system: an unfolding crisis in health care, driven by the greed of corporations whose profit-seeking model is also failing. Proponents of commodifying healthcare simultaneously argue that the cost of providing care for ageing populations is unaffordable while working to create demand for their health care products among those who are essentially healthy. Will healthcare be the next profit-fuelled investor bubble? In this paper, we call on health professionals to heed the warnings from the economic crisis and, rather than stand by while a crisis unfolds, act now to redirect increasingly market-oriented health systems to serve the common good. | 25,170,470 | [
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Intermittent attendance at breast cancer screening. | To determine why women skip rounds and factors influencing return of previous non attenders (PNAs) to breast screening. Retrospective, quantitative, structured questionnaire posted to 2500 women. First PNAs did not attend their first screening appointment in 2007/2008 but then attended in 2010; First Controls first attended in 2010 without missed previous appointments. Women who attended screening in 2006 or earlier then skipped a round but returned in 2010 were Subsequent PNAs; Subsequent Controls attended all appointments. More First Controls than First PNAs had family history of cancer (72.7% vs 63.2%; P=0.003); breast cancer (31.3% vs 24.8%; P=0.04). More PNAs lived rurally; more First PNAs had 3rd level education (33.2% vs 23.6%; P=0.002) and fewer had private insurance than First Controls (57.7% vs 64.8%; P=0.04). Excellent/good health was reported in First PNAs and First Controls (82.9% vs 83.2%), but fewer Subsequent PNAs than Subsequent Controls (72.7% vs 84.9%; P=0.000). Common considerations at time of missed appointment were had mammogram elsewhere (33% First PNA) and postponed to next round (16% First PNA, 18.8% Subsequent PNA). Considerations when returning to screening were similar for First PNAs and Subsequent PNAs: I am older (35.4%, 29.6%), I made sure I remembered (29%, 23.6%), could reschedule (17.6%, 20.6%), illness of more concern (16.5%, 19%). More First PNAs stated my family/friends advised (22.3% vs 15.2%) or my GP (12.6% vs 4.6%) advised me to attend, heard good things about BreastCheck (28.8% vs 13.6%). Intermittent attenders do not fit socio-demographic patterns of non-attenders; GP recommendation and word of mouth were important in women's return to screening. Fear and anxiety seem to act as a screening facilitator rather than an inhibitor. Significance for public healthAll breast cancer screening programmes strive to achieve and maintain a high level of attendance, as this is essential to reduce breast cancer mortality, together with cancer detection. While non-attendance has been widely studied, little is known about intermittent attenders. It is unclear why a woman chooses not to attend her breast screening appointment but then decides to respond positively to screening invitation two or more years later. The literature identifies many reasons why some women choose not to attend; but this study distinguishes those who then change their mind and return to screening. This study explores a sub-set of non-attenders which have, to date, been largely ignored, or grouped with people who never attend. This study will inform those struggling with non-attendance in their population based health programmes and will help to tackle the problem of non-attendance, which has adverse affects both economically and epidemiologically. | 25,170,485 | [
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Crisis Communication in the Area of Risk Management: The CriCoRM Project. | During the last H1N1 pandemic has emerged the importance of crisis communication as an essential part of health crisis management. The Project aims specifically to improve the understanding of crisis communication dynamics and effective tools and to allow public health institutions to communicate better with the public during health emergencies. THE PROJECT WILL PERFORM DIFFERENT ACTIVITIES: i) state of the art review; ii) identification of key stakeholders; iii) communicational analysis performed using data collected on stakeholder communication activities and their outcomes considering the lessons learnt from the analysis of the reasons for differing public reactions during pandemics; iv) improvement of the existing guidelines; v) development of Web 2.0 tools as web-platform and feed service and implementation of impact assessment algorithms; vi) organization of exercises and training on this issues. In the context of health security policies at an EU level, the project aims to find a common and innovative approach to health crisis communication that was displayed by differing reactions to the H1N1 pandemic policies. The focus on new social media tools aims to enhance the role of e-health, and the project aims to use these tools in the specific field of health institutions and citizens. The development of Web 2.0 tools for health crisis communication will allow an effective two-way exchange of information between public health institutions and citizens. An effective communication strategy will increase population compliance with public health recommendations. Significance for public healthThe specific aim of the project is to develop a European strategy approach on how to communicate with the population and with different stakeholders groups involved in the crisis management process, based on an analysis of the communication process during the H1N1 pandemic (content analysis of press releases, press coverage and forum discussions) and on interviews with key stakeholders in health crisis communication. The development of web 2.0 tools, providing rapid responses will allow real-time verification of awareness of social trends and citizens' response. Furthermore, the project would like to offer these resources to the EU Public Health Institutions and EU citizens to improve their interaction, and hence reinforce citizens' right to patient-centred health care. The project proposal has been designed in accordance with the general principles of ethics and the EU Charter of Fundamental Rights with regard to human rights, values, freedom, solidarity, and better protection of European citizens. | 25,170,491 | [
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Exploring the innate immunological response of an alternative nonhuman primate model of infectious disease; the common marmoset. | The common marmoset (Callithrix jacchus) is increasingly being utilised as a nonhuman primate model for human disease, ranging from autoimmune to infectious disease. In order to fully exploit these models, meaningful comparison to the human host response is necessary. Commercially available reagents, primarily targeted to human cells, were utilised to assess the phenotype and activation status of key immune cell types and cytokines in naive and infected animals. Single cell suspensions of blood, spleen, and lung were examined. Generally, the phenotype of cells was comparable between humans and marmosets, with approximately 63% of all lymphocytes in the blood of marmosets being T cells, 25% B-cells, and 12% NK cells. The percentage of neutrophils in marmoset blood were more similar to human values than mouse values. Comparison of the activation status of cells following experimental systemic or inhalational infection exhibited different trends in different tissues, most obvious in cell types active in the innate immune response. This work significantly enhances the ability to understand the immune response in these animals and fortifies their use as models of infectious disease. | 25,170,519 | [
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Roughness in lattice ordered effect algebras. | Many authors have studied roughness on various algebraic systems. In this paper, we consider a lattice ordered effect algebra and discuss its roughness in this context. Moreover, we introduce the notions of the interior and the closure of a subset and give some of their properties in effect algebras. Finally, we use a Riesz ideal induced congruence and define a function e(a, b) in a lattice ordered effect algebra E and build a relationship between it and congruence classes. Then we study some properties about approximation of lattice ordered effect algebras. | 25,170,523 | [
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Can primary failure of arteriovenous fistulas be anticipated? | Primary failure, early thrombosis, and inadequate maturation are the main complications encountered in arteriovenous fistulas. Doppler ultrasonographic assessment of flow-mediated dilatation (FMD) is currently used for the early diagnosis of atherosclerosis. Clinical experience in the use of FMD for preoperative assessment of vasculature is rather limited; therefore, we sought to elucidate the relationship between preoperative FMD and primary failure of the fistula. Thirty-three patients with end-stage renal disease who were admitted to our hospital between January and July 2005 were included in our study. Medical histories were established and the internal diameter, wall thickness, peak systolic flow rate, and resistive index (RI) were measured in the cephalic vein and radial and brachial arteries. Flow-mediated dilatation and nitrate-mediated dilatation (NMD) of the brachial artery were assessed. Fistulas were evaluated 48 hours and 30 days postoperatively. Brachial arterial internal diameter was lower in all fistulas that developed primary failure in 48 hours (0.4 ± 0.07 cm vs. 0.35 ± 0.07 cm, P = 0.016). The radial artery RI was found to be significantly elevated in fistulas with both early (48-hour) and late-term (30-day) failure (0.9 ± 0.08 vs. 0.68 ± 0.3, P = 0.01, and 0.86 ± 0.8 vs. 0.67 ± 0.3, P = 0.038, respectively). The brachial artery peak systolic flow rate was significantly reduced in patients in the radiocephalic fistula group that developed early and late-term failure (42.9 ± 12 cm/sec vs. 68.4 ± 10 cm/sec, P = 0.01, and 44.1 ± 13 cm/sec vs. 57.7 ± 16 cm/sec, P = 0.038, respectively). Our study, constrained by a smaller, older patient group, was unable to show a statistically significant correlation between FMD, NMD, and fistula success. Any single parameter may not be sufficient to assess vascular health preoperatively. A multifactorial approach incorporating parameters evaluating arterial and venous function might be more effective in predicting fistula success. Further studies on larger patient groups may indeed demonstrate the value of these assessments. | 25,170,532 | [
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Evaluation of serum perforin, caspase-3, sFasL and M-30 levels as apoptotic markers in children with Crimean-Congo hemorrhagic fever. | Apoptosis is a main regulator in responses of cellular immunity throughout systemic viral infections. Perforin, soluble Fas ligand, caspase-3 and caspase-cleaved cytokeratin-18 (M-30) are mediators of apoptosis. The aim of this study is the evaluation of Crimean-Congo hemorrhagic fever (CCHF) disease changes in the levels of these apoptotic markers and the relation of these changes with disease severity. Forty-nine hospitalized children with CCHF and 36 healthy controls were enrolled in this prospective study. The CCHF patients were classified into 2 groups based on disease severity (severe group and nonsevere group). Demographic characteristics and clinical and laboratory findings of all patients were recorded on admission. Serum perforin, caspase-3 and soluble Fas ligand levels were found to be significantly higher both in the severe and nonsevere CCHF groups than the healthy control group (P < 0.05), but there was no significant difference in these apoptotic markers between severe and nonsevere CCHF groups (P > 0.05). In addition, serum M-30 levels did not differ significantly among all groups (P > 0.05). There was a positive correlation between serum values for perforin, caspase-3 and M-30 and the disease's severity criteria such as aspartate aminotransferase and/or alanine aminotransferase. The serum levels of all these markers were negatively correlated with disease severity criteria such as the platelet count. In this study, we concluded that the interactions of cytolytic granules containing perforin and caspase cascade and Fas-FasL may play an important role in the pathogenesis of CCHF in children. | 25,170,551 | [
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From racemic alcohols to enantiopure amines: Ru-catalyzed diastereoselective amination. | A commercially available ruthenium(II) PNP-type pincer catalyst (Ru-Macho) promotes the formation of α-chiral tert-butanesulfinylamines from racemic secondary alcohols and Ellman's chiral tert-butanesulfinamide via a hydrogen borrowing strategy. The formation of α-chiral tert-butanesulfinylamines occurs in yields ranging from 31% to 89% with most examples giving >95:5 dr. | 25,170,560 | [
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Identification of species and geographical strains of Sitophilus oryzae and Sitophilus zeamais using the visible/near-infrared hyperspectral imaging technique. | Identifying stored-product insects is essential for granary management. Automated, computer-based classification methods are rapidly developing in many areas. A hyperspectral imaging technique could potentially be developed to identify stored-product insect species and geographical strains. This study tested and adapted the technique using four geographical strains of each of two insect species, the rice weevil and maize weevil, to collect and analyse the resultant hyperspectral data. Three characteristic images that corresponded to the dominant wavelengths, 505, 659 and 955 nm, were selected by multivariate image analysis. Each image was processed, and 22 morphological and textural features from regions of interest were extracted as the inputs for an identification model. We found the backpropagation neural network model to be the superior method for distinguishing between the insect species and geographical strains. The overall recognition rates of the classification model for insect species were 100 and 98.13% for the calibration and prediction sets respectively, while the rates of the model for geographical strains were 94.17 and 86.88% respectively. This study has demonstrated that hyperspectral imaging, together with the appropriate recognition method, could provide a potential instrument for identifying insects and could become a useful tool for identification of Sitophilus oryzae and Sitophilus zeamais to aid in the management of stored-product insects. | 25,170,577 | [
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Anti-vascular endothelial growth factor for neovascular age-related macular degeneration. | Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We analyzed outcomes as risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by The Cochrane Collaboration. We included 12 RCTs including a total of 5496 participants with neovascular AMD (the number of participants per trial ranged from 28 to 1208). One trial compared pegaptanib, three trials ranibizumab, and two trials bevacizumab versus controls; six trials compared bevacizumab with ranibizumab. Four trials were conducted by pharmaceutical companies; none of the eight studies which evaluated bevacizumab were funded by pharmaceutical companies. The trials were conducted at various centers across five continents (North and South America, Europe, Asia and Australia). The overall quality of the evidence was very good, with most trials having an overall low risk of bias.When compared with control treatments, participants who received any of the three anti-VEGF agents were more likely to have gained 15 letters or more of visual acuity, lost fewer than 15 letters of visual acuity, and had vision 20/200 or better after one year of follow up. Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same regimens were compared in the same RCTs, despite the substantially lower cost for bevacizumab compared with ranibizumab. No trial directly compared pegaptanib with other anti-VEGF agents; however, when compared with controls, ranibizumab or bevacizumab yielded larger improvements in visual acuity outcomes than pegaptanib.Participants treated with anti-VEGFs showed improvements in morphologic outcomes (e.g., size of CNV or central retinal thickness) compared with participants not treated with anti-VEGF agents. There was less reduction in central retinal thickness among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -13.97 μm; 95% confidence interval (CI) -26.52 to -1.41); however, this difference is within the range of measurement error and we did not interpret it as being clinically meaningful.Ocular inflammation and increased intraocular pressure after intravitreal injection were the most frequently reported serious ocular adverse events. Endophthalmitis was reported in fewer than 1% of anti-VEGF treated participants; no cases were reported in control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to detect a meaningful difference between groups. Data for visual function, quality of life, and economic outcomes were sparsely measured and reported. The results of this review indicate the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; ranibizumab and bevacizumab were also shown to improve visual acuity. The information available on the adverse effects of each medication do not suggest a higher incidence of potentially vision-threatening complications with intravitreal injection compared with control interventions; however, clinical trial sample sizes may not have been sufficient to detect rare safety outcomes. Research evaluating variable dosing regimens with anti-VEGF agents, effects of long-term use, combination therapies (e.g., anti-VEGF treatment plus photodynamic therapy), and other methods of delivering the agents should be incorporated into future Cochrane reviews. | 25,170,575 | [
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Functional hyperbranched polymers with advanced optical, electrical and magnetic properties. | As one kind of important functional material, those with advanced optical, electrical and magnetic characteristics have attracted increasing attention due to their essential and irreplaceable role in the daily life of humans. In particular, optical, electrical and magnetic hyperbranched polymers (HBPs) exhibit some unique properties, partially derived from their highly branched topological structures. This review summarizes the recent progress in the field of functional HBPs and their application in optics, electronics and magnetics, including light-emitting polymers, nonlinear optical materials, chemosensors, solar cells, magnetic materials, etc., and also gives some outlooks for further exploration in this field at the end of this paper. | 25,170,592 | [
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Maintaining tissue selenium species distribution as a potential defense mechanism against methylmercury toxicity in juvenile white sturgeon (Acipenser transmontanus). | Selenium (Se) has been shown to antagonize mercury (Hg) toxicity. We have previously demonstrated that orally intubated selenomethionine (SeMet) and methylmercury (MeHg) reduced tissue Se accumulation, as well as blood and kidney Hg concentrations in juvenile white sturgeon (Acipenser transmontanus). However, the form of Se accumulated is not known. In this study, three organoseleniums: selenocysteine (Sec), Se-methyl-selenocysteine (MSeCys), and SeMet and two inorganic Se species: selenate and selenite were determined and quantified in the blood at different post-intubation periods (12, 24, 48h) and in the muscle, liver, and kidneys at 48h in white sturgeon orally intubated with a single dose of control (carrier), SeMet (500μg Se/kg body weight; BW), MeHg (850μg Hg/kg BW), and both (Se+Hg; at 500μg Se/kg and 850μg Hg/kg BW). When only SeMet was intubated, the accumulative/unmodified pathway took precedent in the blood, white muscle, liver, and kidneys. In the presence of MeHg, however, active metabolic transformation and de novo synthesis of biologically active Se forms are seen in the liver and kidneys, as indicated by a gradual increase in blood Sec:SeMet ratios and Se metabolites. In the white muscle, mobilization of endogenous Se storage by MeHg is supported by the absence of tissue SeMet and detectable levels of blood SeMet. In contrast, co-intubation with SeMet increased muscle SeMet. The high levels of unknown Se metabolites and detectable levels of selenite in the kidney reflect its role as the major excretory organ for Se. Selenium metabolism is highly regulated in the kidneys, as Se speciation was not affected by MeHg or by its co-intubation with SeMet. In the Se+Hg group, the proportion of SeMet in the liver has decreased to nearly 1/8th of that of the SeMet only group, resulting in a more similar selenocompound distribution profile to that of the MeHg only group. This is likely due to the increased need for Se metabolites necessary for MeHg demethylation in the liver. Our study demonstrated that in the presence of MeHg, regulating tissue Se speciation, hence, Se bioavailability, is more an important strategy than maintaining total Se levels in major organs of juvenile white sturgeon. | 25,170,596 | [
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Doxorubicin-loaded magnetic gold nanoshells for a combination therapy of hyperthermia and drug delivery. | In the present work, nanohybrid of an anticancer drug, doxorubicin (Dox) loaded gold-coated superparamagnetic iron oxide nanoparticles (SPIONs@Au) were prepared for a combination therapy of cancer by means of both hyperthermia and drug delivery. The Dox molecules were conjugated to SPIONs@Au nanoparticles with the help of cysteamine (Cyst) as a non-covalent space linker and the Dox loading efficiency was investigated to be as high as 0.32 mg/mg. Thus synthesized particles were characterized by HRTEM, UV-Vis, FT-IR, SQUID magnetic studies and further tested for heat and drug release at low frequency oscillatory magnetic fields. The hyperthermia studies investigated to be strongly influenced by the applied frequency and the solvents used. The Dox delivery studies indicated that the drug release efficacy is strongly improved by maintaining the acidic pH conditions and the oscillatory magnetic fields, i.e. an enhancement in the Dox release was observed from the oscillation of particles due to the applied frequency, and is not effected by heating of the solution. Finally, the in vitro cell viability and proliferation studies were conducted using two different immortalized cell lines containing a cancerous (MCF-7 breast cancer) and non-cancerous H9c2 cardiac cell type. | 25,170,601 | [
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First-trimester screening for down syndrome with serum sampling at different gestational ages: the effect on screening performance. | The objective of this study was to evaluate the performance of first-trimester Down syndrome (DS) screening with serum sampling at different weeks of gestation. We studied 35,431 singleton pregnancies (2005-2011), including 145 DS cases. Screening performance was determined in different maternal age groups with serum sampling between weeks 9 + 0 and 13 + 6. No significant differences were found between the detection rates at different gestational weeks. The false-positive rate (FPR) in week 9 (6%) was comparable to the FPR in week 10 (6.5%; p = 0.214), whereas it was significantly lower compared to weeks 11 (7.2%; p = 0.007), 12 (7.4%; p = 0.003) and 13 (8.5%; p < 0.001). The odds of receiving a false-positive result was significantly increased with serum sampling in week 11 (OR 1.32, 95% CI 1.08-1.63; p = 0.008) for women ≥36 years and from week 12 onwards (OR 1.28, 95% CI 1.01-1.61; p = 0.04) for women <36 years. There were no differences in mean log10 multiple of the median values of pregnancy-associated plasma protein-A, free β-human chorionic gonadotrophin or nuchal translucency between both age groups, nor in mean maternal age between the different gestational weeks in either age group. Early serum sampling (<11 weeks) resulted in higher screening performance. The impact of the increase in the FPR was highest in women ≥36 years. | 25,170,623 | [
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Oligophrenin-1 is associated with cell adhesion and migration in prostate cancer. | We performed Escherichia coli ampicillin secretion trap (CAST) analysis in prostate cancer (PCa) to identify novel biomarkers. We show here that OPHN1, which encodes oligophrenin-1 protein, is upregulated in PCa. OPHN1 was first determined to be one of the genes associated with X-linked mental retardation; however, neither the gene's function nor the link between its expression and survival of patients has been investigated. We investigate the expression of oligophrenin-1 in 141 PCa tissue samples by immunohistochemistry and perform functional analysis using RNA interference. Immunohistochemical analysis of oligophrenin-1 demonstrated that 60 (43%) PCa cases were positive for oligophrenin-1. Positive oligophrenin-1 expression was significantly correlated with a high Gleason score (p = 0.0198). Furthermore, patients with oligophrenin-1-positive PCa had a worse biochemical recurrence-free survival rate than patients with oligophrenin-1-negative PCa (p = 0.0079). Cell adhesion to fibronectin was significantly reduced in OPHN1 small interfering (si)RNA-transfected LNCaP and PC3 cells in comparison to negative-control siRNA-transfected cells. Knockdown of OPHN1 reduced the expression of ITGA5 and stress fiber formation in LNCaP and PC3 cells. These results suggest that oligophrenin-1 is involved in tumor progression in PCa. | 25,170,626 | [
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Multicenter ALK testing in non-small-cell lung cancer: results of a round robin test. | The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has recently received approval for the treatment of patients with locally advanced or metastatic ALK-positive non-small-cell lung cancer (NSCLC). As the therapeutic prescription postulates the detection of ALK rearrangements, reliable diagnostic approaches are of utmost importance. With this study, we present the data of the first German ALK-round robin test based on genomic DNA in situ hybridization (ISH). The application of immunohistochemistry (IHC) for ALK protein detection was optional and not required for certification. Two tissue microarrays, each consisting of the same 10 NSCLC but in different arrangement of the cases, were generated (five unequivocally ALK-positive and five unequivocally ALK-negative cases). ISH-based results and optional IHC data had to be submitted within 10 working days. A successful participation (certification) was reached if at least 19 of the 20 possible points were scored (2 points for a correct case classification). Fifty-three of 59 participants (89.8%) provided their data for ISH-ALK detection within the submission period. Thirty-two of 53 participants (60.3%) received at least 19 points required for certification. Remarkably, the range of cells with aberrant ALK signal configuration was broad in ALK-negative (0-13%) and in ALK-positive cases (15-95%). Thirty-five participants supported the round robin test with optional ALK IHC results, which displayed a great heterogeneity in the ALK ISH-positive cases. In essence, our ALK ISH round robin test clearly demonstrates that there is accumulating need for improvement of ALK testing. Although ISH may be regarded as a well-established procedure, its broad application in a diagnostic setting is challenging and requires standardized methods and harmonized interpretation to achieve sound results for therapeutic decisions. The same is true for ALK IHC which, however if standardized, might improve the diagnostic approach. | 25,170,635 | [
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Noninvasive risk stratification of lung adenocarcinoma using quantitative computed tomography. | Lung cancer remains the leading cause of cancer-related deaths in the United States and worldwide. Adenocarcinoma is the most common type of lung cancer and encompasses lesions with widely variable clinical outcomes. In the absence of noninvasive risk stratification, individualized patient management remains challenging. Consequently a subgroup of pulmonary nodules of the lung adenocarcinoma spectrum is likely treated more aggressively than necessary. Consecutive patients with surgically resected pulmonary nodules of the lung adenocarcinoma spectrum (lesion size ≤3 cm, 2006-2009) and available presurgical high-resolution computed tomography (HRCT) imaging were identified at Mayo Clinic Rochester. All cases were classified using an unbiased Computer-Aided Nodule Assessment and Risk Yield (CANARY) approach based on the quantification of presurgical HRCT characteristics. CANARY-based classification was independently correlated to postsurgical progression-free survival. CANARY analysis of 264 consecutive patients identified three distinct subgroups. Independent comparisons of 5-year disease-free survival (DFS) between these subgroups demonstrated statistically significant differences in 5-year DFS, 100%, 72.7%, and 51.4%, respectively (p = 0.0005). Noninvasive CANARY-based risk stratification identifies subgroups of patients with pulmonary nodules of the adenocarcinoma spectrum characterized by distinct clinical outcomes. This technique may ultimately improve the current expert opinion-based approach to the management of these lesions by facilitating individualized patient management. | 25,170,645 | [
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Spine stereotactic body radiotherapy for renal cell cancer spinal metastases: analysis of outcomes and risk of vertebral compression fracture. | The aim of this study was to evaluate local control (LC) and the risk of vertebral compression fracture (VCF) after stereotactic body radiotherapy (SBRT) in patients with renal cell cancer spinal metastases. Prospectively collected data on 71 spinal segments treated with SBRT in 37 patients were reviewed. The median follow-up was 12.3 months (range 1.2-55.4 months). The LC rate was assessed based on each spinal segment treated and overall survival (OS) according to each patient treated. Sixty of 71 segments (85%) were radiation naive, 11 of 71 (15%) were previously irradiated, and 10 of 71 (14%) were treated with postoperative SBRT. The median SBRT total dose and number of fractions were 24 Gy and 2, respectively. The VCF analysis also included evaluation of the Spinal Instability Neoplastic Score criteria. The 1-year OS and LC rates were 64% and 83%, respectively. Multivariate analysis identified oligometastatic disease (13 of 37 patients) as a positive prognostic factor (p = 0.018) for OS. Of 61 non-postoperative spinal segments treated, 10 (16%) developed VCFs; 3 of 10 were de novo VCFs and 7 of 10 occurred as progression of an existing VCF. The 1-year VCF-free probability rate was 82%. Multivariate analysis identified single-fraction SBRT and baseline VCF as significant predictors of SBRT-induced VCF (p = 0.028 and p = 0.012, respectively). Spine SBRT yields high rates of local tumor control in patients with renal cell cancer. Baseline VCF and 18-24 Gy delivered in a single fraction were predictive of further collapse. Patients with oligometastatic disease may benefit most from such aggressive local therapy, given the prolonged survival observed. | 25,170,656 | [
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Steering matter wave superradiance with an ultranarrow-band optical cavity. | A superfluid atomic gas is prepared inside an optical resonator with an ultranarrow bandwidth on the order of the single photon recoil energy. When a monochromatic off-resonant laser beam irradiates the atoms, above a critical intensity the cavity emits superradiant light pulses with a duration on the order of its photon storage time. The atoms are collectively scattered into coherent superpositions of discrete momentum states, which can be precisely controlled by adjusting the cavity resonance frequency. With appropriate pulse sequences the entire atomic sample can be collectively accelerated or decelerated by multiples of two recoil momenta. The instability boundary for the onset of matter wave superradiance is recorded and its main features are explained by a mean field model. | 25,170,694 | [
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Modeling nanoscale inhomogeneities for quantitative HAADF STEM imaging. | High-angle annular dark-field scanning transmission electron microscopy in conjunction with image simulation is an important tool to determine the structure of nanomaterials. We show that molecular dynamics calculations can be combined with multislice image simulations to account for the large effects of surface-enhanced thermal vibrations and structural relaxation on image intensities. Application to a catalytically important gold cluster shows that the image intensity is sensitive to these surface dominated effects with important implications for three-dimensional structural characterizations. | 25,170,712 | [
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Breaking the theoretical scaling limit for predicting quasiparticle energies: the stochastic GW approach. | We develop a formalism to calculate the quasiparticle energy within the GW many-body perturbation correction to the density functional theory. The occupied and virtual orbitals of the Kohn-Sham Hamiltonian are replaced by stochastic orbitals used to evaluate the Green function G, the polarization potential W, and, thereby, the GW self-energy. The stochastic GW (sGW) formalism relies on novel theoretical concepts such as stochastic time-dependent Hartree propagation, stochastic matrix compression, and spatial or temporal stochastic decoupling techniques. Beyond the theoretical interest, the formalism enables linear scaling GW calculations breaking the theoretical scaling limit for GW as well as circumventing the need for energy cutoff approximations. We illustrate the method for silicon nanocrystals of varying sizes with N_{e}>3000 electrons. | 25,170,715 | [
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Non-Fermi-liquid manifold in a Majorana device. | We propose and study a setup realizing a stable manifold of non-Fermi-liquid states. The device consists of a mesoscopic superconducting island hosting N≥3 Majorana bound states tunnel coupled to normal leads, with a Josephson contact to a bulk superconductor. We find a nontrivial interplay between multichannel Kondo and resonant Andreev reflection processes, which results in the fixed point manifold. The scaling dimension of the leading irrelevant perturbation changes continuously within the manifold and determines the power-law scaling of the temperature-dependent conductance. | 25,170,717 | [
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Cooling a magnetic nanoisland by spin-polarized currents. | We investigate cooling of a vibrational mode of a magnetic quantum dot by a spin-polarized tunneling charge current exploiting the magnetomechanical coupling. The spin-polarized current polarizes the magnetic nanoisland, thereby lowering its magnetic energy. At the same time, Ohmic heating increases the vibrational energy. A small magnetomechanical coupling then permits us to remove energy from the vibrational motion and cooling is possible. We find a reduction of the vibrational energy below 50% of its equilibrium value. The lowest vibration temperature is achieved for a weak electron-vibration coupling and a comparable magnetomechanical coupling. The cooling rate increases at first with the magnetomechanical coupling and then saturates. | 25,170,723 | [
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Accurate predictions of C-SO2R bond dissociation enthalpies using density functional theory methods. | The dissociation of the C-SO2R bond is frequently involved in organic and bio-organic reactions, and the C-SO2R bond dissociation enthalpies (BDEs) are potentially important for understanding the related mechanisms. The primary goal of the present study is to provide a reliable calculation method to predict the different C-SO2R bond dissociation enthalpies (BDEs). Comparing the accuracies of 13 different density functional theory (DFT) methods (such as B3LYP, TPSS, and M05 etc.), and different basis sets (such as 6-31G(d) and 6-311++G(2df,2p)), we found that M06-2X/6-31G(d) gives the best performance in reproducing the various C-S BDEs (and especially the C-SO2R BDEs). As an example for understanding the mechanisms with the aid of C-SO2R BDEs, some primary mechanistic studies were carried out on the chemoselective coupling (in the presence of a Cu-catalyst) or desulfinative coupling reactions (in the presence of a Pd-catalyst) between sulfinic acid salts and boryl/sulfinic acid salts. | 25,170,742 | [
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The merits of unconscious thought in rule detection. | According to unconscious thought theory (UTT), unconscious thought is more adept at complex decision-making than is conscious thought. Related research has mainly focused on the complexity of decision-making tasks as determined by the amount of information provided. However, the complexity of the rules generating this information also influences decision making. Therefore, we examined whether unconscious thought facilitates the detection of rules during a complex decision-making task. Participants were presented with two types of letter strings. One type matched a grammatical rule, while the other did not. Participants were then divided into three groups according to whether they made decisions using conscious thought, unconscious thought, or immediate decision. The results demonstrated that the unconscious thought group was more accurate in identifying letter strings that conformed to the grammatical rule than were the conscious thought and immediate decision groups. Moreover, performance of the conscious thought and immediate decision groups was similar. We conclude that unconscious thought facilitates the detection of complex rules, which is consistent with UTT. | 25,170,756 | [
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Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders. | Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA) like propionic (PPA), and butyric acid (BA), which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD). Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal) or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH) mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s) was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals such as increased levels of SCFA's can epigenetically modulate cell function further supporting their role as environmental contributors to ASD. | 25,170,769 | [
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A non-neuronal cholinergic system regulates cellular ATP levels to maintain cell viability. | We previously suggested that a non-neuronal cholinergic system modulates energy metabolism through the mitochondria. However, the mechanisms responsible for making this system crucial remained undetermined. In this study, we developed a fusion protein expression vector containing a luciferase gene fused to the folic acid receptor-α gene. This protein of the vector was confirmed to target the plasma membrane of transfected HEK293 cells, and vector-derived luciferase activities and ATP levels in viable cells were positively correlated (r = 0.599). Using this luciferase vector, choline acetyltransferase (ChAT)-expressing cells (i.e., cells with an activated non-neuronal cholinergic system) had increased cellular ATP levels. ChAT-expressing cells also had upregulated IGF-1R and Glut-1 protein expressions as well as increased glucose uptake. This activated non-neuronal cholinergic system with efficient glucose metabolism rendered cells resistant to serum depletion-induced cell death. Our results indicate that a non-neuronal cholinergic system is involved in sustaining ATP levels to render cells resistant to a nutrient-deficient environment. | 25,170,772 | [
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Clinical implications of local field potentials for understanding and treating movement disorders. | Deep brain stimulation (DBS) for the treatment of movement disorders has provided researchers with an opportunity to record electrical oscillatory activity from electrodes implanted in deep brain structures. Extracellular activity recorded from a population of neurons, termed local field potentials (LFPs), has shed light on the pathophysiology of movement disorders and holds the potential to lead to refinement in existing treatments. This paper reviews the clinical significance of LFPs recorded from macroelectrodes implanted in basal ganglia and thalamic targets for the treatment of Parkinson's disease, essential tremor and dystonia. Neural population dynamics and subthreshold events, which are undetectable by single-unit recordings, can be examined with frequency band analysis of LFPs (frequency range: 1-250 Hz). Of clinical relevance, reliable correlations between motor symptoms and components of the LFP power spectrum suggest that LFPs may serve as a biomarker for movement disorders. In particular, Parkinson's rigidity has been shown to correlate with the power of beta oscillations (13-30 Hz), and essential tremor coheres with oscillations of 8-27 Hz. Furthermore, evidence indicates that the optimal contacts for DBS programming can be predicted from the anatomic location of beta and gamma bands (48-200 Hz). LFP analysis has implications for improved electrode targeting and the development of a real-time, individualized, 'closed-loop' stimulation system. | 25,170,784 | [
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Homogeneous hydrogenation of CO₂ to methyl formate utilizing switchable ionic liquids. | Combined capture of CO2 and subsequent hydrogenation allows for base/methanol-promoted homogeneous hydrogenation of CO2 to methyl formate. The CO2, captured as an amidinium methyl carbonate, reacts with H2 with no applied pressure of CO2 in the presence of a catalyst to produce sequentially amidinium formate, then methyl formate. The production of methyl formate releases the base back into the system, thereby reducing one of the flaws of catalytic hydrogenations of CO2: the notable consumption of one mole of base per mole of formate produced. The reaction proceeds under 20 atm of H2 with selectivity to formate favored by the presence of excess base and lower temperatures (110 °C), while excess alcohol and higher temperatures (140 °C) favor methyl formate. Known CO2 hydrogenation catalysts are active in the ionic liquid medium with turnover numbers as high as 5000. It is unclear as to whether the alkyl carbonate or CO2 is hydrogenated, as we show they are in equilibrium in this system. The availability of both CO2 and the alkyl carbonate as reactive species may result in new catalyst designs and free energy pathways for CO2 that may entail different selectivity or kinetic activity. | 25,170,785 | [
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Cognitive control predicts use of model-based reinforcement learning. | Accounts of decision-making and its neural substrates have long posited the operation of separate, competing valuation systems in the control of choice behavior. Recent theoretical and experimental work suggest that this classic distinction between behaviorally and neurally dissociable systems for habitual and goal-directed (or more generally, automatic and controlled) choice may arise from two computational strategies for reinforcement learning (RL), called model-free and model-based RL, but the cognitive or computational processes by which one system may dominate over the other in the control of behavior is a matter of ongoing investigation. To elucidate this question, we leverage the theoretical framework of cognitive control, demonstrating that individual differences in utilization of goal-related contextual information--in the service of overcoming habitual, stimulus-driven responses--in established cognitive control paradigms predict model-based behavior in a separate, sequential choice task. The behavioral correspondence between cognitive control and model-based RL compellingly suggests that a common set of processes may underpin the two behaviors. In particular, computational mechanisms originally proposed to underlie controlled behavior may be applicable to understanding the interactions between model-based and model-free choice behavior. | 25,170,791 | [
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Correlation between leucine rich domain and the stability of LRWD1 protein in human NT2/D1 cells. | LRWD1 is a protein that contains LRR and WDs domains and is important in regulating spermatogenesis. However, the roles of LRR or WDs domains in the expression of LRWD1 remain unclear. The NT2/D1 cells separately transfected with full length of LRWD1 gene (LRWD(WT)) or genes with deleted sequences in the LRR domain (LRWD1(ΔLRR)), WD1 domain (LRWD1(ΔWD1)), WD2 domain (LRWD1(ΔWD2)), WD3 domain (LRWD1(ΔWD3)) and entire three WD domains (LRWD1(Δ3×WD)) were applied to investigate the expression levels of LRWD1 protein by either Western blot or flow cytometry. The associated proteins in these mutated LRWD1 proteins were identified by mass spectrometry. Deletion of the LRR domain significantly decreased the expression of LRWD1 protein. With the treatment of MG132, the LRR domain may functions in preventing LRWD1 protein from proteasome-mediated degradation. In the co-immunoprecipitation analysis, protein receptor of tumor necrosis factor 2 (TNFR2) was specifically observed to be associated with LRR-deficient LRWD1 protein. The LRR domain is significantly correlated to the stability of LRWD1 protein. Determining if the stability is modulated by TNFR2 is worthy of further study. | 25,170,821 | [
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Umbelliferone and daphnetin ameliorate carbon tetrachloride-induced hepatotoxicity in rats via nuclear factor erythroid 2-related factor 2-mediated heme oxygenase-1 expression. | Among various phytochemicals, coumarins comprise a very large class of plant phenolic compounds that have good nutritive value, in addition to their antioxidant effects. The purpose of the present study was to investigate the protective effects of two coumarin derivatives, umbelliferone and daphnetin, against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats and elucidate the underlying mechanism. Treatment of rats with either umbelliferone or daphnetin significantly improved the CCl4-induced biochemical alterations. In addition, both compounds alleviated the induced-lipid peroxidation and boosted the antioxidant defense system. Moreover, the investigated compounds attenuated CCl4-induced histopathological alterations of the liver. Finally, umbelliferone and daphnetin induced the nuclear translocation of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and activity of the cytoprotective heme oxygenase-1 (HO-1). These results suggest that umbelliferone and daphnetin ameliorate oxidative stress-related hepatotoxicity via their ability to augment cellular antioxidant defenses by activating Nrf2-mediated HO-1 expression. | 25,170,823 | [
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Evaluation of an automated rapid diagnostic test for detection of Clostridium difficile. | The Verigene Clostridium difficile Nucleic Acid Test (Verigene CDF Test) (Nanosphere, Northbrook, IL, USA) is a new multiplex qualitative polymerase chain reaction (PCR) test used to detect C. difficile toxin genes in fecal specimens. To evaluate the performance of the new method, we tested 69 fecal samples from patients with suspected C. difficile infection using the Verigene CDF test, an enzyme immunoassay (EIA) and PCR following anaerobic fecal culture. The sensitivity, specificity, and accuracy of the Verigene CDF test were 96.7% (29/30), 97.4% (38/39), and 97.1% (67/69) respectively, using PCR following fecal culture as a reference method. We also analyzed the potential clinical impact of the Verigene CDF test using chart reviews of the 69 patients with suspected C. difficile infection and found that 11 of the 69 patients were incorrectly diagnosed, and the Verigene CDF test would have led to them receiving more appropriate management including practice of treatment and contact precaution, although, of the 69 patients, there are two whose samples were incorrectly identified with the Verigene CDF test. The Verigene CDF test will have a positive impact on patient care. | 25,170,836 | [
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Response of schizophrenic patients to dynamic facial expressions: an event-related potentials study. | Patients with schizophrenia have an impaired ability to respond to faces and may specifically show an impaired response to dynamic facial expressions. Here we investigated the responses of schizophrenic patients and healthy controls to dynamic facial images using event-related potentials (ERPs). We showed 13 schizophrenic patients and 13 healthy controls visual stimuli comprising facial expressions that continually changed from neutral to emotional. N200 latencies and P100-N200 peak-to-peak amplitudes in controls were prolonged or greater for dynamic emotions in comparison with those for static stimuli, but the group with schizophrenia showed no significant differences in responses to dynamic and static emotions. A significant negative correlation was observed between N200 latencies for dynamic negative emotion and PANSS (positive and negative syndrome scale) general psychopathology scale scores. A combination of hypersensitivity to static emotions and hyposensitivity to dynamic emotions in people with schizophrenia might underlie the absence of differences in response to these stimuli. A tendency in the schizophrenic group to hypersensitivity to static emotions might arise from the enhanced fear and arousal characteristics of this group; their hyposensitivity to dynamic emotions might result from controlled attentional bias away from facial expressions to reduce fear and anxiety. | 25,170,847 | [
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Prenatal Diagnosis of Congenital Absence of Aortic Valve: A Report of Two Cases with Different Outcomes and a Literature Review. | Congenital absence of aortic valve (AAV) is a rare cardiac anomaly associated with high mortality. We present 2 prenatally diagnosed cases of AAV. In both cases, fetal echocardiography showed no aortic valve tissue and free aortic regurgitation. At 24 weeks' gestation, case 1 showed a hypoplastic hypocontractile left ventricle and mitral atresia, but did not develop hydrops and was born at term. Bilateral pulmonary arterial banding was performed with continuous infusion of prostaglandin E1 at 5 days of age followed by Norwood and bidirectional Glenn procedures at 3 months of age. The hypoplastic non-compliant left ventricle and mitral atresia might have limited aortic regurgitation. Case 2 showed hydrops at 23 weeks' gestation. An enlarged hypocontractile left ventricle and massive mitral insufficiency were noted. The regurgitant flow was directed to the right atrium through a foramen ovale. This peculiar hemodynamic established a malignant circuit which was arbitrarily called 'inverse circulatory shunt'. Intrauterine death occurred at 28 weeks' gestation. An autopsy showed absent aortic valve leaflets but three tiny membranous remnants. Hemodynamic evaluation by fetal echocardiography should include the documentation of the presence of and assessment of the grade of aortic regurgitation, mitral regurgitation and blood flow through a foramen ovale as well as left ventricular function. | 25,170,850 | [
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Effectiveness and complications of ultrasound guided fine needle aspiration for primary liver cancer in a Chinese population with serum α-fetoprotein levels ≤200 ng/ml--a study based on 4,312 patients. | Hepatocellular carcinoma (HCC) can be diagnosed by noninvasive approaches with serum α-fetoprotein (AFP) levels >200 ng/ml and/or a radiological imaging study of tumor mass >2 cm in patients with chronic liver disease. Percutaneous fine needle aspiration (FNA) under ultrasound (US) guidance has a diagnostic specificity of 95% and is superior to radiological imaging studies. The aim of this study is to elucidate the effectiveness and complications of fine needle aspiration in a Chinese population with primary liver cancer and AFP levels ≤200 ng/ml. A retrospective study was conducted over a period of 28 years. This selection period included patients with a suspected diagnosis of primary liver cancer whose AFP levels were ≤200 ng/ml and who underwent US-FNA. This data was then analyzed with cytomorphological features correlating with medical history, radiological imaging, AFP, and follow-up information. Of the 1,929 cases with AFP ≤200 mg/ml, 1,756 underwent FNA. Of these, 1,590 cases were determined malignant and the remaining 166 were determined benign. Further, 1,478 malignant cases were diagnosed by FNA alone, and of these, 1,138 were diagnosed as PLC. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the diagnoses were 92.96%, 100%, 100%, 59.71%, and 93.62% respectively. There was no significant difference in the sensitivity, specificity, PPV and NPV between the subgroups with tumor size<2 cm and ≥2 cm. Major complications included implantation metastasis and hemorrhage. Patients with PLC, especially those who present with an AFP ≤200 ng/ml, should undergo FNA. If negative results are obtained by FNA, it still could be HCC and repeated FNA procedure may be needed if highly suspicious of HCC on imaging study. The superiority of FNA in overall accuracy may outweigh its potential complications, such like hemorrhage and implantation metastasis. | 25,170,868 | [
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Long-term low carbohydrate diet leads to deleterious metabolic manifestations in diabetic mice. | We investigated long-term effects of low carbohydrate diets on wild type mice, streptozotocin-injected and KKAy obese diabetic mice. These mice were pair-fed three different types of diets, standard chow (SC, C∶P∶F = 63∶15∶22), a low carbohydrate (LC, C∶P∶F = 38∶25∶37) diet and a severely carbohydrate restricted (SR, C∶P∶F = 18∶45∶37) diet for 16 weeks. Despite comparable body weights and serum lipid profiles, wild type and diabetic mice fed the low carbohydrate diets exhibited lower insulin sensitivity and this reduction was dependent on the amount of carbohydrate in the diet. When serum fatty acid compositions were investigated, monounsaturation capacity, i.e. C16:1/C16:0 and C18:1/C18:0, was impaired in all murine models fed the low carbohydrate diets, consistent with the decreased expression of hepatic stearoyl-CoA desaturase-1 (SCD1). Interestingly, both the hepatic expressions and serum levels of fibroblast growth factor 21 (FGF21), which might be related to longevity, were markedly decreased in both wild type and KKAy mice fed the SR diet. Taking into consideration that fat compositions did not differ between the LC and SR diets, we conclude that low carbohydrate diets have deleterious metabolic effects in both wild type and diabetic mice, which may explain the association between diets relatively low in carbohydrate and the elevated risk of cardiovascular events observed in clinical studies. | 25,170,869 | [
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Towards monitoring biodiversity in Amazonian forests: how regular samples capture meso-scale altitudinal variation in 25 km2 plots. | Ecological monitoring and sampling optima are context and location specific. Novel applications (e.g. biodiversity monitoring for environmental service payments) call for renewed efforts to establish reliable and robust monitoring in biodiversity rich areas. As there is little information on the distribution of biodiversity across the Amazon basin, we used altitude as a proxy for biological variables to test whether meso-scale variation can be adequately represented by different sample sizes in a standardized, regular-coverage sampling arrangement. We used Shuttle-Radar-Topography-Mission digital elevation values to evaluate if the regular sampling arrangement in standard RAPELD (rapid assessments ("RAP") over the long-term (LTER ["PELD" in Portuguese])) grids captured patters in meso-scale spatial variation. The adequacy of different sample sizes (n = 4 to 120) were examined within 32,325 km2/3,232,500 ha (1293×25 km2 sample areas) distributed across the legal Brazilian Amazon. Kolmogorov-Smirnov-tests, correlation and root-mean-square-error were used to measure sample representativeness, similarity and accuracy respectively. Trends and thresholds of these responses in relation to sample size and standard-deviation were modeled using Generalized-Additive-Models and conditional-inference-trees respectively. We found that a regular arrangement of 30 samples captured the distribution of altitude values within these areas. Sample size was more important than sample standard deviation for representativeness and similarity. In contrast, accuracy was more strongly influenced by sample standard deviation. Additionally, analysis of spatially interpolated data showed that spatial patterns in altitude were also recovered within areas using a regular arrangement of 30 samples. Our findings show that the logistically feasible sample used in the RAPELD system successfully recovers meso-scale altitudinal patterns. This suggests that the sample size and regular arrangement may also be generally appropriate for quantifying spatial patterns in biodiversity at similar scales across at least 90% (≈5 million km2) of the Brazilian Amazon. | 25,170,894 | [
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L-carnitine reduces in human conjunctival epithelial cells hypertonic-induced shrinkage through interacting with TRPV1 channels. | Ocular surface health depends on conjunctival epithelial (HCjE) layer integrity since it protects against pathogenic infiltration and contributes to tissue hydration maintenance. As the same increases in tear film hyperosmolarity described in dry eye disease can increase corneal epithelial transient receptor potential vanilloid type-1 (TRPV1) channel activity, we evaluated its involvement in mediating an osmoprotective effect by L-carnitine against such stress. Using siRNA gene silencing, Ca(2+) imaging, planar patch-clamping and relative cell volume measurements, we determined if the protective effects of this osmolyte stem from its interaction with TRPV1. TRPV1 activation by capsaicin (CAP) and an increase in osmolarity to ≈ 450 mOsM both induced increases in Ca(2+) levels. In contrast, blocking TRPV1 activation with capsazepine (CPZ) fully reversed this response. Similarly, L-carnitine (1 mM) also reduced underlying whole-cell currents. In calcein-AM loaded cells, hypertonic-induced relative cell volume shrinkage was fully blocked during exposure to L-carnitine. On the other hand, in TRPV1 gene-silenced cells, this protective effect by L-carnitine was obviated. The described L-carnitine osmoprotective effect is elicited through suppression of hypertonic-induced TRPV1 activation leading to increases in L-carnitine uptake through a described Na(+)-dependent L-carnitine transporter. | 25,170,901 | [
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Data mechanics and coupling geometry on binary bipartite networks. | We quantify the notion of pattern and formalize the process of pattern discovery under the framework of binary bipartite networks. Patterns of particular focus are interrelated global interactions between clusters on its row and column axes. A binary bipartite network is built into a thermodynamic system embracing all up-and-down spin configurations defined by product-permutations on rows and columns. This system is equipped with its ferromagnetic energy ground state under Ising model potential. Such a ground state, also called a macrostate, is postulated to congregate all patterns of interest embedded within the network data in a multiscale fashion. A new computing paradigm for indirect searching for such a macrostate, called Data Mechanics, is devised by iteratively building a surrogate geometric system with a pair of nearly optimal marginal ultrametrics on row and column spaces. The coupling measure minimizing the Gromov-Wasserstein distance of these two marginal geometries is also seen to be in the vicinity of the macrostate. This resultant coupling geometry reveals multiscale block pattern information that characterizes multiple layers of interacting relationships between clusters on row and on column axes. It is the nonparametric information content of a binary bipartite network. This coupling geometry is then demonstrated to shed new light and bring resolution to interaction issues in community ecology and in gene-content-based phylogenetics. Its implied global inferences are expected to have high potential in many scientific areas. | 25,170,903 | [
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Prolonged prophylactic protection from botulism with a single adenovirus treatment promoting serum expression of a VHH-based antitoxin protein. | Current therapies for most acute toxin exposures are limited to administration of polyclonal antitoxin serum. We have shown that VHH-based neutralizing agents (VNAs) consisting of two or more linked, toxin-neutralizing heavy-chain-only VH domains (VHHs), each binding distinct epitopes, can potently protect animals from lethality in several intoxication models including Botulinum neurotoxin serotype A1 (BoNT/A1). Appending a 14 amino acid albumin binding peptide (ABP) to an anti-BoNT/A1 heterodimeric VNA (H7/B5) substantially improved serum stability and resulted in an effective VNA serum half-life of 1 to 2 days. A recombinant, replication-incompetent, adenoviral vector (Ad/VNA-BoNTA) was engineered that induces secretion of biologically active VNA, H7/B5/ABP (VNA-BoNTA), from transduced cells. Mice administered a single dose of Ad/VNA-BoNTA, or a different Ad/VNA, via different administration routes led to a wide range of VNA serum levels measured four days later; generally intravenous > intraperitoneal > intramuscular > subcutaneous. Ad/VNA-BoNTA treated mice were 100% protected from 10 LD50 of BoNT/A1 for more than six weeks and protection positively correlated with serum levels of VNA-BoNTA exceeding about 5 ng/ml. Some mice developed antibodies that inhibited VNA binding to target but these mice displayed no evidence of kidney damage due to deposition of immune complexes. Mice were also successfully protected from 10 LD50 BoNT/A1 when Ad/VNA-BoNTA was administered up to 1.5 hours post-intoxication, demonstrating rapid appearance of the protective VNA in serum following treatment. Genetic delivery of VNAs promises to be an effective method of providing prophylactic protection and/or acute treatments for many toxin-mediated diseases. | 25,170,904 | [
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Individual- and neighborhood-level predictors of mortality in Florida colorectal cancer patients. | We examined individual-level and neighborhood-level predictors of mortality in CRC patients diagnosed in Florida to identify high-risk groups for targeted interventions. Demographic and clinical data from the Florida Cancer Data System registry (2007-2011) were linked with Agency for Health Care Administration and US Census data (n = 47,872). Cox hazard regression models were fitted with candidate predictors of CRC survival and stratified by age group (18-49, 50-64, 65+). Stratified by age group, higher mortality risk per comorbidity was found among youngest (21%), followed by middle (19%), and then oldest (14%) age groups. The two younger age groups had higher mortality risk with proximal compared to those with distal cancer. Compared with private insurance, those in the middle age group were at higher death risk if not insured (HR = 1.35), or received healthcare through Medicare (HR = 1.44), Medicaid (HR = 1.53), or the Veteran's Administration (HR = 1.26). Only Medicaid in the youngest (52% higher risk) and those not insured in the oldest group (24% lower risk) were significantly different from their privately insured counterparts. Among 18-49 and 50-64 age groups there was a higher mortality risk among the lowest SES (1.17- and 1.23-fold higher in the middle age and 1.12- and 1.17-fold higher in the older age group, respectively) compared to highest SES. Married patients were significantly better off than divorced/separated (HR = 1.22), single (HR = 1.29), or widowed (HR = 1.19) patients. Factors associated with increased risk for mortality among individuals with CRC included being older, uninsured, unmarried, more comorbidities, living in lower SES neighborhoods, and diagnosed at later disease stage. Higher risk among younger patients was attributed to proximal cancer site, Medicaid, and distant disease; however, lower SES and being unmarried were not risk factors in this age group. Targeted interventions to improve survivorship and greater social support while considering age classification may assist these high-risk groups. | 25,170,910 | [
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Lectin-like oxidized LDL receptor-1 is an enhancer of tumor angiogenesis in human prostate cancer cells. | Altered expression and function of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been associated with several diseases such as endothelial dysfunction, atherosclerosis and obesity. In these pathologies, oxLDL/LOX-1 activates signaling pathways that promote cell proliferation, cell motility and angiogenesis. Recent studies have indicated that olr1 mRNA is over-expressed in stage III and IV of human prostatic adenocarcinomas. However, the function of LOX-1 in prostate cancer angiogenesis remains to be determined. Our aim was to analyze the contribution of oxLDL and LOX-1 to tumor angiogenesis using C4-2 prostate cancer cells. We analyzed the expression of pro-angiogenic molecules and angiogenesis on prostate cancer tumor xenografts, using prostate cancer cell models with overexpression or knockdown of LOX-1 receptor. Our results demonstrate that the activation of LOX-1 using oxLDL increases cell proliferation, and the expression of the pro-angiogenic molecules VEGF, MMP-2, and MMP-9 in a dose-dependent manner. Noticeably, these effects were prevented in the C4-2 prostate cancer model when LOX-1 expression was knocked down. The angiogenic effect of LOX-1 activated with oxLDL was further demonstrated using the aortic ring assay and the xenograft model of tumor growth on chorioallantoic membrane of chicken embryos. Consequently, we propose that LOX-1 activation by oxLDL is an important event that enhances tumor angiogenesis in human prostate cancer cells. | 25,170,920 | [
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En bloc dual kidney transplantation from pediatric donors after cardiac death: initial experience in China. | To report 9 cases of en bloc kidney transplantation from pediatric donors in China and share the clinical experience. From February 2010 to February 2014, 9 pediatric donors (aged 5 months to 6 years) were assigned to us by the modern donation and allocation system after cardiac death. The en bloc kidneys were recovered in all 9 patients. The inferior vena cava and aorta of the donors were anastomosed to the external vein and artery of the recipients (7 adults and 2 children). Alprostadil or enoxaparin sodium was used for anticoagulation. The kidneys attained immediate perfusion after vascular anastomosis, except for one renal artery that developed thrombosis several minutes later, necessitating nephrectomy of the unilateral graft. The other eight en bloc grafts maintained normal function during the follow-up period of 1-50 months and all the patients survived. There were no rejections or other complications. Based on ultrasonography, the grafts increased in size during the follow-up period. These results indicate that en bloc renal transplantation from pediatric donors is an acceptable procedure, and more widespread use could increase the number of potential donors. Splitting of pediatric donor en bloc kidneys for transplantation into two recipients may also be feasible in well-matched cases. | 25,170,936 | [
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Evaluation of a modified Cefsulodin-Irgasan-Novobiocin agar for isolation of Yersinia spp. | Y. enterocolitica and Y. pseudotuberculosis are important food borne pathogens. However, the presence of competitive microbiota makes the isolation of Y. enterocolitica and Y. pseudotuberculosis from naturally contaminated foods difficult. We attempted to evaluate the performance of a modified Cefsulodin-Irgasan-Novobiocin (CIN) agar in the differentiation of Y. enterocolitica from non-Yersinia species, particularly the natural intestinal microbiota. The modified CIN enabled the growth of Y. enterocolitica colonies with the same efficiency as CIN and Luria-Bertani agar. The detection limits of the modified CIN for Y. enterocolitica in culture medium (10 cfu/ml) and in artificially contaminated pork (10(4) cfu/ml) were also comparable to those of CIN. However, the modified CIN provided a better discrimination of Yersinia colonies from other bacteria exhibiting Yersinia-like colonies on CIN (H2S-producing Citrobacter freundii, C. braakii, Enterobacter cloacae, Aeromonas hydrophila, Providencia rettgeri, and Morganella morganii). The modified CIN exhibited a higher recovery rate of Y. enterocolitica from artificially prepared bacterial cultures and naturally contaminated samples compared with CIN. Our results thus demonstrated that the use of modified CIN may be a valuable means to increase the recovery rate of food borne Yersinia from natural samples, which are usually contaminated by multiple types of bacteria. | 25,170,941 | [
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Three-dimensional flow of an Oldroyd-B nanofluid towards stretching surface with heat generation/absorption. | This article addresses the steady three-dimensional flow of an Oldroyd-B nanofluid over a bidirectional stretching surface with heat generation/absorption effects. Suitable similarity transformations are employed to reduce the governing partial differential equations into coupled nonlinear ordinary differential equations. These nonlinear ordinary differential equations are then solved analytically by using the homotpy analysis method (HAM). Graphically results are presented and discussed for various parameters, namely, Deborah numbers β1 and β2, heat generation/absorption parameter λ, Prandtl parameter Pr, Brownian motion parameters Nb, thermophoresis parameter Nt and Lewis number Le. We have seen that the increasing values of the Brownian motion parameter Nt and thermophoresis parameter Nt leads to an increase in the temperature field and thermal boundary layer thickness while the opposite behavior is observed for concentration field and concentration boundary layer thickness. To see the validity of the present work, the numerical results are compared with the analytical solutions obtained by Homotopy analysis method and noted an excellent agreement for the limiting cases. | 25,170,945 | [
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A comparative analysis of open surgery vs endoscopic balloon dilation for pediatric subglottic stenosis. | Minimally invasive endoscopic techniques are an appealing alternative to open surgical management of pediatric subglottic stenosis (SGS), but more information is needed to understand the comparative risks, benefits, and limitations of such interventions. To compare the effectiveness of endoscopic balloon dilation (EBD) and laryngotracheoplasty (LTP) in pediatric patients with SGS and to identify patient and disease factors that are associated with successful EBD. A retrospective medical record review of children undergoing EBD and LTP for SGS in a tertiary care children's hospital from 2006 through 2012. Success was defined as decannulation or tracheotomy avoidance. Additional outcomes were total number of procedures and number of unplanned procedures. Univariate χ2 analyses and multivariate regression analyses were performed to identify patient and disease factors statistically associated with success within treatment groups. Overall, 86 of 90 patients (96%) successfully avoided tracheotomy or were decannulated. Fourteen patients were successfully treated with EBD, but for 13 patients, EBD failed, and they underwent LTP. A total of 76 patients underwent LTP. In univariate analyses, patients for whom EBD was successful were more likely to have mild (grade 1 or 2; n = 10) than severe (grade 3 or 4; n = 4) SGS compared with patients for whom EBD failed (grade 1 or 2, n = 0 vs grade 3 or 4, n = 13) (P < .001). Three patients who underwent initial EBD had worsening stenosis. Patients initially treated with EBD were more likely to require unplanned surgical intervention during their treatment (6 of 27; 22%) than patients initially treated with LTP (3 of 63; 5%) (P = .01). Patients initially treated with EBD had a lower number of airway interventions and/or evaluations under anesthesia (mean, 6.7) during their course of treatment than patients initially treated with LTP (mean, 9.2) (P = .003). In multivariate analyses, only severe SGS was significantly associated with failure of initial EBD (13 of 13 [100%] with type 3 or 4 vs 4 of 14 with type 1 or 2 [29%]) (P = .002). For severe SGS, EBD has limited application compared with LTP, and in some cases failed EBD is even detrimental, increasing the risk of unplanned urgent interventions compared with LTP. | 25,170,960 | [
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Quantum Monte Carlo for noncovalent interactions: an efficient protocol attaining benchmark accuracy. | Reliable theoretical prediction of noncovalent interaction energies, which are important e.g. in drug-design and hydrogen-storage applications, is one of the longstanding challenges of contemporary quantum chemistry. In this respect, the fixed-node diffusion Monte Carlo (FN-DMC) method is a promising alternative to the commonly used "gold standard" coupled-cluster CCSD(T)/CBS method due to its benchmark accuracy and favourable scaling, in contrast to other correlated wave function approaches. This work is focused on the analysis of protocols and possible trade-offs for FN-DMC estimations of noncovalent interaction energies, and proposes an efficient yet accurate computational protocol using simplified explicit correlation terms with a favorable O(N(3)) scaling. It achieves results in excellent agreement (mean unsigned error ∼0.2 kcal mol(-1)) with respect to the CCSD(T)/CBS data on a number of complexes, including benzene/hydrogen, the T-shape benzene dimer, stacked adenine-thymine complex and a set of small noncovalent complexes (A24). The high accuracy and reduced computational costs predestinate the reported protocol for practical interaction energy calculations of large noncovalent complexes, where the CCSD(T)/CBS is prohibitively expensive. | 25,170,978 | [
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Contrasting light spectra constrain the macro and microstructures of scleractinian corals. | The morphological plasticity of scleractinian corals can be influenced by numerous factors in their natural environment. However, it is difficult to identify in situ the relative influence of a single biotic or abiotic factor, due to potential interactions between them. Light is considered as a major factor affecting coral skeleton morphology, due to their symbiotic relation with photosynthetic zooxanthellae. Nonetheless, most studies addressing the importance of light on coral morphological plasticity have focused on photosynthetically active radiation (PAR) intensity, with the effect of light spectra remaining largely unknown. The present study evaluated how different light spectra affect the skeleton macro- and microstructures in two coral species (Acropora formosa sensu Veron (2000) and Stylophora pistillata) maintained under controlled laboratory conditions. We tested the effect of three light treatments with the same PAR but with a distinct spectral emission: 1) T5 fluorescent lamps with blue emission; 2) Light Emitting Diodes (LED) with predominantly blue emission; and 3) Light Emitting Plasma (LEP) with full spectra emission. To exclude potential bias generated by genetic variability, the experiment was performed with clonal fragments for both species. After 6 months of experiment, it was possible to detect in coral fragments of both species exposed to different light spectra significant differences in morphometry (e.g., distance among corallites, corallite diameter, and theca thickness), as well as in the organization of their skeleton microstructure. The variability found in the skeleton macro- and microstructures of clonal organisms points to the potential pitfalls associated with the exclusive use of morphometry on coral taxonomy. Moreover, the identification of a single factor influencing the morphology of coral skeletons is relevant for coral aquaculture and can allow the optimization of reef restoration efforts. | 25,170,981 | [
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Anion radicals of isomeric [5,6] and [6,6] benzoadducts of Sc3N@C80: remarkable differences in endohedral cluster spin density and dynamics. | The anion radicals of isomeric [5,6] and [6,6] Sc3N@C80 benzoadducts were studied by electron spin resonance spectroscopy, density functional theory computations, and molecular dynamics. In both compounds the rotation of the Sc3N cluster is frozen and the spin density distribution of the cluster is highly anisotropic, with hyperfine coupling constants of 9.1 and 2 × 33.3 G for the [5,6] adduct and ∼0.6 and 2 × 47.9 G for the [6,6] adduct. Remarkably, the subtle variation of the position of the exohedral group on the surface of the cage results in very pronounced changes in the spin density distribution and the dynamics of the encapsulated Sc3N cluster. | 25,170,987 | [
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Establishment of neutralizing rat monoclonal antibodies for fibroblast growth factor-2. | Fibroblast growth factor-2 (FGF-2) plays a critical role in endothelial survival, proliferation, and angiogenesis and is localized on the cell membrane by binding to heparan sulfate proteoglycans. Here we established a neutralizing monoclonal antibody, 1B9B9, against FGF-2 using the rat medial iliac lymph node method. 1B9B9 blocked the binding of FGF-2 to its receptor, inhibiting FGF-2-induced proliferation and corresponding downstream signaling in endothelial cells. Treatment of human umbilical vein endothelial cells with 1B9B9 reduced the basal phosphorylation levels of Akt and MAPK. Furthermore, continued treatment with 1B9B9 induced cell death by apoptosis. Compared with FGF-2 knockdown, 1B9B9 significantly reduced cell survival. In addition, the combination of FGF-2 siRNA and 1B9B9 showed a synergistic effect. The data indicate that 1B9B9 established by the rat iliac lymph node method is a fully compatible neutralizing antibody. | 25,171,006 | [
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Sensorimotor training during expression of the leg extension response (LER) in 1-day-old rats. | In newborn rats, the leg extension response (LER) is a coordinated hyperextension of the hindlimbs that is shown in response to anogenital stimulation. Here we examined the influence of sensorimotor training on LER expression in postnatal day 1 rats. In Experiment 1, we examined if proprioceptive feedback facilitates LER expression. We did this by repeatedly stimulating the pup's anogenital region with a vibrotactile device, to experimentally evoke the LER, thus increasing LER-relevant hindlimb proprioceptive feedback during training. In trained subjects, the LER was evoked every 4 min for 15 trials, followed by a final LER test. Results indicated that proprioceptive feedback on its own did not alter later expression of the LER. In Experiment 2, we examined the effect of both proprioceptive and cutaneous feedback on LER expression, through the use of a range of motion (ROM) restriction during training. During ROM restriction, a Plexiglas plate was placed beneath the pup at 50% of limb length. After the 15th training trial, a final LER test occurred with no ROM restriction in place. Compared to controls, pups that experienced ROM restriction exhibited a significantly shorter LER duration, and smaller hip and ankle angles during the LER test (indicating greater limb flexion). Together these findings show that concurrent proprioceptive and cutaneous feedback, but not proprioceptive feedback alone, has persistent effects on expression of this newborn action pattern. | 25,171,018 | [
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Common misdiagnoses of biliary atresia. | Discrimination of biliary atresia (BA) from other causes of neonatal cholestasis (NC) is challenging. We aimed to analyze the clinicopathological findings in cholestatic infants who were provisionally diagnosed with BA and then excluded by intraoperative cholangiography compared with those with a definitive diagnosis of BA and to shed light on common misdiagnoses of BA. We retrospectively analyzed the data of infants diagnosed preoperatively with BA and referred to surgery between the years 2009 and 2013. On the basis of intraoperative cholangiography results, infants were divided into those with a definitive diagnosis of BA and those misdiagnosed with BA. Out of 147 infants, there was a misdiagnosis of BA in 10 (6.8%) infants. Alanine transaminase was significantly higher in the non-BA group, whereas other clinical and laboratory findings were comparable in both groups. Hepatomegaly and abnormal gallbladder in ultrasound, and ductular proliferation and advanced grades of portal fibrosis in liver biopsy were significantly higher in infants with BA. However, giant cells were more common in the non-BA infants. Nonetheless, the frequency of clay stool, hepatomegaly, abnormal gallbladder, ductular proliferation, and advanced portal fibrosis was remarkable (100, 70, 40, 70, and 50%, respectively) in the misdiagnosed infants. The misdiagnoses were idiopathic neonatal hepatitis, progressive familial intrahepatic cholestasis type 3, cytomegalovirus hepatitis, Alagille syndrome, and a cholangitic form of congenital hepatic fibrosis. A meticulous preoperative workup should be performed to exclude other causes of NC even if signs of BA are present, especially if features such as giant cells in histopathology are present. This involves completing the NC workup in parallel involving all common causes of NC rather than performing them in series to avoid loss of valuable time and efforts. | 25,171,020 | [
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-0.07716273,... |
Color stability of shade guides after autoclave sterilization. | This study evaluated the influence of 120 autoclave sterilization cycles on the color stability of two commercial shade guides (Vita Classical and Vita System 3D-Master). The specimens were evaluated by spectrophotometer before and after the sterilization cycles. The color was described using the three-dimensional CIELab system. The statistical analysis was performed in three chromaticity coordinates, before and after sterilization cycles, using the paired samples t test. All specimens became darker after autoclave sterilization cycles. However, specimens of Vita Classical became redder, while those of the Vita System 3D-Master became more yellow. Repeated cycles of autoclave sterilization caused statistically significant changes in the color coordinates of the two shade guides. However, these differences are considered clinically acceptable. | 25,171,040 | [
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Prospective observational study of the early loading of nanostructured calcium phosphate-coated tapered implants in the mandible and maxilla. | The purpose of this study was to evaluate the prospective clinical results of early loading. Implants were inserted in 11 maxillae (group I, 23 implants) and 12 mandibles (group II, 19 implants). Six months after prosthetic loading, several factors were investigated. Significant differences between the primary and secondary stability were not observed in groups I and II. The primary stability in the mandible was 81.1 implant stability quotient (ISQ), which was significantly higher than the 73.3 ISQ value observed in the maxilla (P = .003). The survival rates were 100% in group I and 94.7% in group II for 9 and 10.4 months, respectively. The marginal bone loss was 0.07 mm in group I and -0.07 mm in group II. After the placement of nanostructured calcium phosphate- coated implants, excellent primary and second stability was obtained. | 25,171,041 | [
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De novo design of functional oligonucleotides with acyclic scaffolds. | In this account, we demonstrate a new methodology for the de novo design of functional oligonucleotides with the acyclic scaffolds threoninol and serinol. Four functional motifs-wedge, interstrand-wedge, dimer, and cluster-have been prepared from natural DNA or RNA and functional base surrogates prepared from d-threoninol. The following applications of these motifs are described: (1) photoregulation of formation and dissociation of a DNA duplex modified with azobenzene, (2) sequence-specific detection of DNA using a fluorescent probe, (3) formation of fluorophore assemblies that mimic quantum dots, (4) improved strand selectivity of siRNA modified with a base surrogate, and (5) in vivo tracing of the RNAi pathway. Finally, we introduce artificial nucleic acids (XNAs) prepared from d-threoninol and serinol functionalized with each of the four nucleobases, which have unique properties compared with other acyclic XNAs. Functional oligonucleotides designed from acyclic scaffolds will be powerful tools for both DNA nanotechnology and biotechnology. | 25,171,046 | [
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Literacy effects on language and vision: emergent effects from an amodal shared resource (ASR) computational model. | Learning to read and write requires an individual to connect additional orthographic representations to pre-existing mappings between phonological and semantic representations of words. Past empirical results suggest that the process of learning to read and write (at least in alphabetic languages) elicits changes in the language processing system, by either increasing the cognitive efficiency of mapping between representations associated with a word, or by changing the granularity of phonological processing of spoken language, or through a combination of both. Behavioural effects of literacy have typically been assessed in offline explicit tasks that have addressed only phonological processing. However, a recent eye tracking study compared high and low literate participants on effects of phonology and semantics in processing measured implicitly using eye movements. High literates' eye movements were more affected by phonological overlap in online speech than low literates, with only subtle differences observed in semantics. We determined whether these effects were due to cognitive efficiency and/or granularity of speech processing in a multimodal model of speech processing - the amodal shared resource model (ASR, Smith, Monaghan, & Huettig, 2013a,b). We found that cognitive efficiency in the model had only a marginal effect on semantic processing and did not affect performance for phonological processing, whereas fine-grained versus coarse-grained phonological representations in the model simulated the high/low literacy effects on phonological processing, suggesting that literacy has a focused effect in changing the grain-size of phonological mappings. | 25,171,049 | [
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A comparative study of different aspects of manipulating ratio spectra applied for ternary mixtures: derivative spectrophotometry versus wavelet transform. | This work represents a comparative study of different aspects of manipulating ratio spectra, which are: double divisor ratio spectra derivative (DR-DD), area under curve of derivative ratio (DR-AUC) and its novel approach, namely area under the curve correction method (AUCCM) applied for overlapped spectra; successive derivative of ratio spectra (SDR) and continuous wavelet transform (CWT) methods. The proposed methods represent different aspects of manipulating ratio spectra of the ternary mixture of Ofloxacin (OFX), Prednisolone acetate (PA) and Tetryzoline HCl (TZH) combined in eye drops in the presence of benzalkonium chloride as a preservative. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulation containing the cited drugs. The proposed methods were validated according to the ICH guidelines. A comparative study was conducted between those methods regarding simplicity, limitation and sensitivity. The obtained results were statistically compared with those obtained from the reported HPLC method, showing no significant difference with respect to accuracy and precision. | 25,171,050 | [
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Renal denervation using focused infrared fiber lasers: a potential treatment for hypertension. | Renal denervation has recently become of great interest as a potential treatment for resistant hypertension. Denervation techniques using radio frequency (RF) or ultrasound energy sources have already been explored in literature. In this study, we investigate the use of lasers as a potential energy source for renal denervation. In vitro studies are performed in porcine/ovine renal arteries with focused laser beams at 980 nm, 1210 nm, and 1700 nm to study the ability to damage renal nerves without causing injury to non-target tissue structures like the endothelium. Then, a 980 nm laser catheter prototype is built and used to demonstrate in vivo renal denervation in ovine renal arteries. This study utilizes fiber coupled infrared lasers at 980 nm, 1210 nm, and 1700 nm. In vitro laser denervation studies at 980 nm are performed in both porcine and ovine renal arteries to study the ability of focused laser beams to damage renal nerves without injuring the endothelium. In vitro studies using lasers close to the lipid absorption lines at 1210 nm and 1700 nm are also performed in porcine renal arteries to study the possibility of selectively damaging the renal nerves by targeting the lipid myelin sheaths surrounding the nerves. Then, a laser catheter prototype is designed and built for in vivo renal denervation in ovine renal arteries using the 980 nm laser (powers ranging from 2 to 4 W, 5 seconds per exposure). Histochemical evaluations of the frozen sections are performed using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Histochemical analysis of in vitro laser treatments at 980 nm in porcine and ovine renal arteries show clear evidence of laser-induced renal nerve damage without injury to the endothelium and part of the media. No evidence of selective nerve damage is observed using the 1210 nm and 1700 nm lasers with the current treatment parameters. Histochemical analysis of in vivo laser treatments in ovine renal arteries using a focused 980 nm laser show clear evidence of renal nerve damage with depths of damage extending > 1.5 mm from the artery wall. Sections with laser-induced damage to the media/adventitia at depths of > 1 mm without injury to the endothelium are also observed. We demonstrate the use of focused lasers as an attractive energy source for causing renal nerve damage without injury to the artery wall and thus, may have potential therapeutic applications for conditions such as resistant hypertension, where renal denervation has been shown to be a promising form of treatment. | 25,171,055 | [
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Potential of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones against Leishmania (L.) infantum: biological activity and structure-activity relationships. | Naphtoquinones have been used as promising scaffolds for drug design studies against protozoan parasites. Considering the highly toxic and limited therapeutic arsenal, the global negligence with tropical diseases and the elevated prevalence of co-morbidities especially in developing countries, the parasitic diseases caused by various Leishmania species (leishmaniasis) became a significant public health threat in 98 countries. The aim of this work was the evaluation of antileishmanial in vitro potential of thirty-six 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones obtained by a three component reaction of lawsone, the appropriate aldehyde and thiols adequately substituted, exploiting the in situ generation of o-quinonemethides (o-QM) via the Knoevenagel condensation. The antileishmanial activity of the naphthoquinone derivatives was evaluated against promastigotes and intracellular amastigotes of Leishmania (Leishmania) infantum and their cytotoxicity was verified in mammalian cells. Among the thirty-six compounds, twenty-seven were effective against promastigotes, with IC50 values ranging from 8 to 189 µM; fourteen compounds eliminated the intracellular amastigotes, with IC50 values ranging from 12 to 65 µM. The compounds containing the phenyl groups at R1 and R2 and with the fluorine substituent at the phenyl ring at R2, rendered the most promising activity, demonstrating a selectivity index higher than 15 against amastigotes. A QSAR (quantitative structure activity relationship) analysis yielded insights into general structural requirements for activity of most compounds in the series. Considering the in vitro antileishmanial potential of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones and their structure-activity relationships, novel lead candidates could be exploited in future drug design studies for leishmaniasis. | 25,171,058 | [
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Single tyrosine mutation in AAV8 vector capsid enhances gene lung delivery and does not alter lung morphofunction in mice. | Vectors derived from adeno-associated viruses (AAVs) are important gene delivery tools for treating pulmonary diseases. Phosphorylation of surface-exposed tyrosine residues from AAV2 capsid targets the viral particles for ubiquitination and proteasome-mediated degradation, and mutations of these tyrosine residues lead to highly efficient vector transduction in vitro and in vivo in different organs. We evaluated the pulmonary transduction efficiency of AAV8 vectors containing point mutations in surface-exposed capsid tyrosine residues. Male C57BL/6 mice (20-25 g, n=24) were randomly assigned into three groups: control group animals received intratracheal (i.t.) instillation of saline (50 μl), wild-type AAV8 group, and capsid mutant Y733F AAV8 group, which received (i.t.) AAV8 vectors containing the DNA sequence of enhanced green fluorescence protein (eGFP). Four weeks after instillation, lung mechanics and morphometry, vector transduction (immunohistochemistry and mRNA expression of eGFP), and inflammatory cytokines and growth factor expression were analyzed. Tyrosine-mutant AAV8 vectors displayed significantly increased transduction efficiency in the lung compared with their wild-type counterparts. No significant differences were observed in lung mechanics and morphometry between experimental groups. There was no evidence of inflammatory response in any group. AAV8 vectors may be useful for new therapeutic strategies for the treatment of pulmonary diseases. | 25,171,090 | [
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Rapid fluorescent detection of (anti)androgens with spiggin-gfp medaka. | Widespread environmental antiandrogen contamination has been associated with negative impacts on biodiversity and human health. In particular, many pesticides are antiandrogenic, creating a need for robust and sensitive environmental monitoring. Our aim was to develop a sensitive and specific transgenic medaka (Oryzias latipes) model bearing an androgen responsive fluorescent reporter construct for whole organism-based environmental screening of pro- and antiandrogens. We analyzed the 5' regions of the androgen responsive three-spined stickleback (Gasterosteus aculeatus) spiggin genes in silico, revealing conserved blocks of sequence harboring androgen response elements. Identified putative promoters were cloned upstream of GFP. Germinal transgenesis with spg1-gfp led to stable medaka lines. GFP induction was exclusive to the kidney, the site of spiggin protein production in sticklebacks. Significant GFP expression was induced by three or four-day androgen treatment of newly hatched fry, but not by estrogens, mineralocorticoids, glucocorticoids or progestogens. The model responded dose-dependently to androgens, with highest sensitivity to 17MT (1.5 μg/L). In addition to flutamide, the biocides fenitrothion, vinclozolin and linuron significantly inhibited 17MT-induced GFP induction, validating the model for detection of antiandrogens. The spg1-gfp medaka model provides a sensitive, specific, and physiologically pertinent biosensor system for analyzing environmental androgen activity. | 25,171,099 | [
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Reduction of cardiac cell death after helium postconditioning in rats: transcriptional analysis of cell death and survival pathways. | Helium, a noble gas, has been used safely in humans. In animal models of regional myocardial ischemia/reperfusion (I/R) it was shown that helium conditioning reduces infarct size. Currently, it is not known how helium exerts its cytoprotective effects and which cell death/survival pathways are affected. The objective of this study, therefore, was to investigate the cell protective effects of helium postconditioning by PCR array analysis of genes involved in necrosis, apoptosis and autophagy. Male rats were subjected to 25 min of ischemia and 5, 15 or 30 min of reperfusion. Semiquantitative histological analysis revealed that 15 min of helium postconditioning reduced the extent of I/R-induced cell damage. This effect was not observed after 5 and 30 min of helium postconditioning. Analysis of the differential expression of genes showed that 15 min of helium postconditioning mainly caused upregulation of genes involved in autophagy and inhibition of apoptosis versus I/R alone. The results suggest that the cytoprotective effects of helium inhalation may be caused by a switch from pro-cell-death signaling to activation of cell survival mechanisms, which appears to affect a wide range of pathways. | 25,171,109 | [
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Use of selective serotonin-reuptake inhibitors during pregnancy and the risk of clubfoot. | Selective serotonin-reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. Previous studies have suggested that SSRIs may increase the risk of birth defects, including clubfoot. Using data from a population-based case-control study, we evaluated whether SSRI use increased the risk of clubfoot. Mothers were interviewed within 1 year after delivery about sociodemographic factors, pregnancy events, and exposures. They were specifically asked if they experienced depression or anxiety or if they took any of the following SSRIs: citalopram, escitalopram, fluvoxamine, paroxetine, sertraline, or fluoxetine. We used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We included a total of 622 clubfoot cases and 2002 nonmalformed controls born between 2006 and 2011 in Massachusetts, New York, and North Carolina. For the 2nd or 3rd lunar month of pregnancy (the relevant gestational period), SSRI use for a period of more than 30 days was higher in case mothers (5%) than control mothers (3%). After adjustment for maternal smoking and body mass index, the OR for any SSRI use and clubfoot was 1.8 (95% CI = 1.1-2.8). When individual SSRIs were examined, ORs were elevated for sertraline (1.6 [0.8-3.2]), paroxetine (9.2 [0.7-484.6]), and escitalopram (2.9 [1.1-7.2]). Our data suggest an increased risk of clubfoot occurrence in relation to SSRI use. Drug-specific risks varied widely, and some estimates were unstable. | 25,171,134 | [
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Siloxy alkynes in annulation reactions. | Siloxy alkynes are a family of versatile species in organic synthesis. This account reviews the annulation reactions of siloxy alkynes for the synthesis of a variety of carbo- and heterocyclic products. With various dipolarophiles or dipolarophile-like reaction partners, siloxy alkynes are capable of forming small (three- to six-membered) rings. Recently, we have expanded the scope to the synthesis of medium- and large-ring lactones, enabled by the design of new amphoteric molecules as well as a new ring-expansion strategy. These annulation reactions provide not only practically useful syntheses of cyclic molecules, but also important understanding of the fundamental reactivity of siloxy alkynes. | 25,171,137 | [
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Building robust carbon nanotube-interweaved-nanocrystal architecture for high-performance anode materials. | Rational design of electrode materials is essential but still a challenge for lithium-ion batteries. Herein, we report the design and fabrication of a class of nanocomposite architecture featured by hierarchically structured composite particles that are built from iron oxide nanocrystals and carbon nanotubes. An aerosol spray drying process was used to synthesize this architecture. Such nanoarchitecture enhanced the ion transport and conductivity that are required for high-power anodes. The large volume changes of the anodes during lithium insertion and extraction are accommodated by the particle's resilience and internal porosity. High reversible capacities, excellent rate capability, and stable performance are attained. The synthesis process is simple and broadly applicable, providing a general approach toward high-performance energy storage materials. | 25,171,139 | [
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Intrapolypeptide interactions between the GTPase effector domain (GED) and the GTPase domain form the bundle signaling element in dynamin dimers. | Biochemical and structural studies of dynamin have shown that the C-terminus of the GTPase effector domain (GED) folds back and docks onto a platform created by the N- and C-terminal α-helices of the GTPase domain to form a three-helix bundle. While cross-linking studies suggested that insect cell-expressed dynamin existed as a domain-swapped dimer, X-ray structures of protein expressed in Escherichia coli failed to detect evidence of this domain swap. Here, by cross-linking several cysteine pair replacements and analyzing cross-linked species by matrix-assisted laser desorption ionization Mega time of flight, we conclude that dynamin is not domain-swapped and that GED-GTPase domain interactions occur in cis. | 25,171,143 | [
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Synthesis of new chlorin e6 trimethyl and protoporphyrin IX dimethyl ester derivatives and their photophysical and electrochemical characterizations. | In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new chlorin e6 trimethyl ester and protoporphyrin IX dimethyl ester dyads as free bases and Zn(II) complexes. The synthesis of these molecules linked at the β-pyrrolic positions to pyrano[3,2-c]coumarin, pyrano[3,2-c]quinolinone, and pyrano[3,2-c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels-Alder reaction. The α-methylenechromanes, α-methylenequinoline, and ortho-quinone methides were generated in situ from a Knoevenagel reaction of 4-hydroxycoumarin, 4-hydroxy-6-methylcoumarin, 4-hydroxy-N-methylquinolinone, and 2-hydroxy-1,4-naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as Zn(II) complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time-correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one Zn(II) complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the Zn(II) complexes were also carried out to gain insights into their behavior for such applications. | 25,171,181 | [
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The advantages of unilateral pedal lymphography in the diagnosis of chyluria. | To evaluate the efficacy and safety of pedal lymphography (PLG) in the localization diagnosis of chyluria. Cystoscopy was performed in 153 patients and PLG in 121 cases. Unilateral or staged bilateral ligation and stripping of renal lymphatic vessel were performed according to the results of cystoscopy and/or PLG. Unilateral and bilateral urinary excretion of chyle was detected in 123 and 1 case by cystoscopy, respectively. In 121 cases receiving PLG, 100 cases of unilateral fistulous connection between the renal pelvis and the lymphatic system, 18 cases of bilateral fistulas and 1 case of lymphatic bladder fistula were demonstrated. PLG has a higher diagnostic rate for the detection of bilateral lymphatic renal pelvis fistulas than cystoscopy (p<0.05). 28 cases received renal pedicle lymphatic disconnection only according to the results of cystoscopy, and 3 of them failed (10.1%). While 121 cases had the same operation according to the results of PLG, only 1 case failed the operation (0.8%). PLG was efficient and safe for the localization diagnosis of chyluria, with a higher detection rate of bilateral fistulas than cystoscopy. PLG might benefit the selection of appropriate therapy and improve the surgical effect. | 25,171,183 | [
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Gate-induced carrier delocalization in quantum dot field effect transistors. | We study gate-controlled, low-temperature resistance and magnetotransport in indium-doped CdSe quantum dot field effect transistors. We show that using the gate to accumulate electrons in the quantum dot channel increases the "localization product" (localization length times dielectric constant) describing transport at the Fermi level, as expected for Fermi level changes near a mobility edge. Our measurements suggest that the localization length increases to significantly greater than the quantum dot diameter. | 25,171,186 | [
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Inhibition of hyperhomocysteinemia-induced inflammasome activation and glomerular sclerosis by NLRP3 gene deletion. | Hyperhomocysteinemia (hHcys) has been reported to initiate Nod-like receptor protein 3 (NLRP3) inflammasome formation and activation in podocytes, leading to glomerular dysfunction and sclerosis. However, it remains unknown whether Nlrp3 gene is critical for the formation and activation of inflammasomes in glomeruli of hHcys mice. Plasma homocysteine concentration was estimated utilizing HPLC, inflammasome formation and immunofluorescence expression from confocal microscopy, IL-1β production from ELISA. Uninephrectomized Nlrp3 knockout (Nlrp3(-/-)) and wild type (Nlrp3(+/+)) and intra renal Nlrp3 shRNA-transfected wild type mice (Nlrp3 shRNA) were fed a folate free (FF) diet or normal chow (ND) for 4 weeks to produce hHcys. The plasma Hcys levels were significantly elevated in both Nlrp3(-/-) and Nlrp3(+/+) mice fed a FF diet compared to ND fed mice. The FF diet significantly increased the colocalization of Nlrp3 with apoptosis-associated speck-like protein (ASC) or caspase-1, caspase-1 activity and IL-1β production in glomeruli of Nlrp3(+/+), but not in Nlrp3(-/-) mice and local Nlrp3 shRNA transfected mice. Correspondingly, the glomerular damage index (GDI) and urinary protein excretion were significantly higher in Nlrp3(+/+) mice compared to ND fed mice. However, the hHcys-induced increase in GDI and proteinuria were significantly lower in Nlrp3(-/-) and local Nlrp3 shRNA transfected mice than in Nlrp3(+/+) mice. Immunocytochemical analysis showed that hHcys decreased expression of podocin and nephrin, but increased desmin expression in glomeruli of Nlrp3(+/+) mice compared to Nlrp3(-/-) mice. Nlrp3 gene is an essential component of Nlrp3 inflammasomes and that targeting Nlrp3 may be important therapeutic strategy to prevent inflammasome activation and thereby protect podocytes and glomeruli from hHcys-induced injury. | 25,171,193 | [
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... |
Role of wickability on the critical heat flux of structured superhydrophilic surfaces. | While superhydrophilic coatings with enhanced wetting properties have been shown to increase the pool boiling critical heat flux (CHF), the role of nanostructures on its enhancement is not clear. Here, biological templates have been used to demonstrate that wickability is the single factor dictating CHF on structured superhydrophilic surfaces. The flexibility of biotemplating using the Tobacco mosaic virus has been leveraged to create surfaces with varying scales, morphologies, and roughness factors. Their wickabilities have been quantified via the wicked volume flux, a phenomenological parameter analogous to the contact angle, and the role of wickability on CHF has been demonstrated using data from over three dozen individual surfaces. These results are repeatable and independent of the substrate material, surface fouling, structure material, morphology, and contact angle as well as the structure scale. An experimentally validated correlation for CHF has been reported on the basis of the dimensionless wickability. Additionally, the surfaces have achieved a CHF of 257 W/cm(2) for water, representing the highest reported value to date for superhydrophilic surfaces. While the role of wickability on CHF has often been cited anecdotally, this work provides a quantitative measure of the phenomena and provides a framework for designing and optimizing coatings for further enhancement. | 25,171,197 | [
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Comparative study of n-dodecyl tetraethylene monoether lyotropic liquid crystals incorporated with graphene and graphene oxide. | Two kinds of carbon materials, i.e., graphene and graphene oxide (GO), were successfully incorporated into a lyotropic liquid crystal (LLC) matrix formed by n-dodecyl tetraethylene monoether (C12E4). The properties of graphene-C12E4 and GO-C12E4 LLC composites were characterized by UV-vis absorption, transmission electron microscopy (TEM) observations, polarized optical microscopy (POM) observations, small-angle X-ray scattering (SAXS) and rheological measurements. SAXS results indicate that both graphene and GO are well-dispersed in the C12E4 LLC matrix and some interactions occur between the C12E4 LLC matrix and graphene (or GO) sheets. Moreover, it is demonstrated that graphene interacts with the hydrophobic part of C12E4 LLC while GO mainly interacts with the hydrophilic part of C12E4 LLC because of the different properties of graphene and GO. Integration of graphene and GO into C12E4-PEG systems by a spontaneous phase separation method reveals the different interaction mechanisms of graphene and GO with C12E4 LLC. It can be concluded that the mechanical and electrical properties of the C12E4 LLC have been largely improved by the incorporation of graphene and GO, which opens the door for wide applications in nanotechnology, electrochemical and biochemical areas. | 25,171,198 | [
0.06624763,
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0.2645213,
0.1327662,
0.2550448,
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-0.235241... |
Biodegradation of complex hydrocarbons in spent engine oil by novel bacterial consortium isolated from deep sea sediment. | Complex hydrocarbon and aromatic compounds degrading marine bacterial strains were isolated from deep sea sediment after enrichment on spent engine (SE) oil. Phenotypic characterization and phylogenetic analysis of 16S rRNA gene sequences showed the isolates were related to members of the Pseudoalteromonas sp., Ruegeria sp., Exiguobacterium sp. and Acinetobacter sp. Biodegradation using 1% (v/v) SE oil with individual and mixed strains showed the efficacy of SE oil utilization within a short retention time. The addition of non-ionic surfactant 0.05% (v/v) Tween 80 as emulsifying agent enhanced the solubility of hydrocarbons and renders them more accessible for biodegradation. The degradation of several compounds and the metabolites formed during the microbial oxidation process were confirmed by Fourier transform infrared spectroscopy and Gas chromatography-mass spectrometry analyses. The potential of this consortium to biodegrade SE oil with and without emulsifying agent provides possible application in bioremediation of oil contaminated marine environment. | 25,171,211 | [
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0.07173073,
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0.07642431... |
Binding of TDP-43 to the 3'UTR of its cognate mRNA enhances its solubility. | TAR DNA binding protein of 43 kDa (TDP-43) has been implicated in the pathogenesis of a broad range of neurodegenerative diseases termed TDP-43 proteinopathies, which encompass a spectrum of diseases ranging from amyotrophic lateral sclerosis to frontotemporal dementia. Pathologically misfolded and aggregated forms of TDP-43 are found in cytoplasmic inclusion bodies of affected neurons in these diseases. The mechanism by which TDP-43 misfolding causes disease is not well-understood. Current hypotheses postulate that the TDP-43 aggregation process plays a major role in pathogenesis. We amplify that hypothesis and suggest that binding of cognate ligands to TDP-43 can stabilize the native functional state of the protein and ameliorate aggregation. We expressed recombinant TDP-43 containing an N-terminal Venus yellow fluorescent protein tag in Escherichia coli and induced its aggregation by altering solvent salt concentrations and examined the extent to which various oligonucleotide molecules affect its aggregation in vitro using aggregation-induced turbidity assays. We show that vYFP-TDP-43 binding to its naturally occurring RNA target that comprises a sequence on the 3'UTR region of its mRNA improves its solubility, suggesting interplay among TDP-43 solubility, oligonucleotide binding, and TDP-43 autoregulation. | 25,171,271 | [
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0.2366587,
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Oligohydramnios in women with preterm prelabor rupture of membranes and adverse pregnancy and neonatal outcomes. | To determine the association between the presence of oligohydramnios, determined as an amniotic fluid index ≤ 5 cm and the intra-amniotic inflammatory response, fetal inflammatory response and neonatal outcomes in actively managed preterm prelabor rupture of membranes (PPROM). Women with singleton pregnancies complicated by PPROM at a gestational age of between 24+0 and 36+6 weeks were included in the study. Ultrasound assessments of the amniotic fluid index and evaluation of the amniotic fluid interleukin (IL)-6 levels were performed at admission. The umbilical cord blood IL-6 levels were evaluated after delivery. In total, 74 women were included. The women with oligohydramnios did not have different amniotic fluid IL-6 levels [with oligohydramnios: median 342 pg/mL, interquartile range (IQR) 110-1809 vs. without oligohydramnios: median 256 pg/mL, IQR 122-748; p = 0.71] or umbilical cord blood IL-6 levels (with oligohydramnios: median 8.2 pg/mL, IQR 3.8-146.9 vs. without oligohydramnios: median 5.9 pg/mL, IQR 2.1-27.9; p = 0.14) than those without oligohydramnios. No association between oligohydramnios and neonatal morbidity was found. A correlation between the amniotic fluid index and the interval from rupture of membranes to amniocentesis was observed (rho = -0.34; p = 0.003). The presence of oligohydramnios is not associated with an adverse outcome in actively managed PPROM in singleton pregnancies in the absence of other complications. | 25,171,293 | [
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... |
Stereotactic Body Radiation Therapy (SBRT) Combined With Chemotherapy for Unresected Pancreatic Adenocarcinoma. | The role of radiation therapy in the management of unresectable pancreatic cancer is controversial. One concern about concurrent chemoradiation relates to the timing of chemotherapy. In contrast to conventional radiation therapy, stereotactic body radiation therapy (SBRT) delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here, we report our results of patients treated with SBRT and chemotherapy for inoperable pancreatic cancer. Thirty-eight patients treated with SBRT and chemotherapy for locally advanced, borderline resectable, and medically inoperable pancreatic cancer at our institution from January 2008 to December 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction over 5 days. Toxicities were scored using the Common Terminology Criteria for Adverse Events version 3. Survival was calculated using the Kaplan-Meier method. The median age was 70 years (range, 45 to 90 y). Eastern Cooperative Oncology Group performance status ranged from 0 to 3. Thirty-four patients received concurrent chemotherapy. Four patients received sequential chemotherapy. Median overall survival was 14.3 months and median progression-free survival was 9.2 months from diagnosis. From radiation, overall survival and progression-free survival were 12.3 and 6.8 months, respectively. The overall local control rate was 79%. Acute toxicity was minimal. Severe late SBRT-related toxicities included 1 grade 3 gastric outlet obstruction, 1 grade 4 biliary stricture, and 1 grade 5 gastric hemorrhage. SBRT combined with chemotherapy for unresectable pancreatic cancer is convenient, feasible, and generally well tolerated. Outcomes of SBRT combined with chemotherapy compare favorably to results obtained with chemotherapy and conventional radiation therapy. | 25,171,298 | [
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... |
Time to culture positivity and sputum smear microscopy during tuberculosis therapy. | Sputum smear microscopy is widely used for tuberculosis diagnosis and treatment monitoring. We evaluated the correlation between smear microscopy and time to liquid culture positivity during early tuberculosis treatment. The study included patients with smear-positive pulmonary tuberculosis hospitalized at a tuberculosis reference centre in Germany between 01/2012 and 05/2013. Patient records were reviewed and clinical, radiological and microbiological data were analysed. Sputum samples were collected before treatment initiation and weekly thereafter. A number of 310 sputum samples from 30 patients were analysed. Time to liquid culture positivity inversely correlated with smear grade (Spearman's rho -0.439, p<0.001). There was a better correlation within the first two months vs. after two months of therapy (-0.519 vs. -0.416) with a trend to a more rapid increase in time to positivity between baseline and week 2 in patients who culture-converted within the first two months (5.9 days vs. 9.4 days, p = 0.3). In conclusion, the numbers of acid-fast bacilli in sputum smears of patients with pulmonary tuberculosis and time to culture positivity for M. tuberculosis cultures from sputum are correlated before and during tuberculosis treatment. A considerable proportion of patients with culture conversion after two months of therapy continued to have detectable acid-fast bacilli on sputum smears. | 25,171,337 | [
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0.5293475,
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0.0245816... |
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