title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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The polar high molecular weight fraction of the Agaricus blazei Murill extract, AndoSan™, reduces the activity of the tumor-associated protease, legumain, in RAW 264.7 cells. | AndoSan™ is an extract of Agaricus blazei Murill (AbM; 82.4%), Hericium erinaceum (14.7%), and Grifola frondosa (2.9%). The main ingredient of AndoSan, AbM, is rich in different forms of β-glucans. Since these exhibit potent antitumor activity and have immunomodulatory effects, the stimulatory effect of AndoSan on the production of different cytokines, chemokines, and leukocyte growth factors has predominantly been attributed to β-glucans. AndoSan has been claimed to consist of 90% carbohydrate, of which 2.8% is β-glucans, but in this study, we show that the carbohydrate content is only 2% of the dry weight, corresponding to 0.09% β-glucan per mL of AndoSan. Fractionation of AndoSan, followed by carbohydrate analysis and HPLC analysis revealed that most of the glucose was concentrated in the polar high molecular weight fraction of AndoSan (ethanol insoluble water extract [EIWE]-A) and that this extract was able to significantly inhibit the activity of the tumor-associated protease, legumain, in RAW 264.7 cells. Legumain is synthesized as a zymogen and undergoes pH-dependent autoactivation of the proform to reach an enzymatically active form. In this study, we demonstrate that both the polar and nonpolar AndoSan fractions are able to inhibit the autoactivation of prolegumain, and that the polar fractions of AndoSan are the most potent inhibitors of the active form of the enzyme. | 25,136,950 | [
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Inside money, procyclical leverage, and banking catastrophes. | We explore a model of the interaction between banks and outside investors in which the ability of banks to issue inside money (short-term liabilities believed to be convertible into currency at par) can generate a collapse in asset prices and widespread bank insolvency. The banks and investors share a common belief about the future value of certain long-term assets, but they have different objective functions; changes to this common belief result in portfolio adjustments and trade. Positive belief shocks induce banks to buy risky assets from investors, and the banks finance those purchases by issuing new short-term liabilities. Negative belief shocks induce banks to sell assets in order to reduce their chance of insolvency to a tolerably low level, and they supply more assets at lower prices, which can result in multiple market-clearing prices. A sufficiently severe negative shock causes the set of equilibrium prices to contract (in a manner given by a cusp catastrophe), causing prices to plummet discontinuously and banks to become insolvent. Successive positive and negative shocks of equal magnitude do not cancel; rather, a banking catastrophe can occur even if beliefs simply return to their initial state. Capital requirements can prevent crises by curtailing the expansion of balance sheets when beliefs become more optimistic, but they can also force larger price declines. Emergency asset price supports can be understood as attempts by a central bank to coordinate expectations on an equilibrium with solvency. | 25,136,959 | [
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A model for implementing guidelines for person-centered care in a nursing home setting. | Systematic evaluations of knowledge translation interventions in nursing homes to improve practice are scarce. There is also a lack of studies focusing on creating sustainable evidence-based practice in the setting of residential dementia care. The aim of this paper is to describe a model for implementing national evidence-based guidelines for care of persons with dementia in nursing homes. The secondary aim is to outline the nursing home staff experiences during the first year of the implementation process. The intervention had a participatory action research approach. This included educational activities such as: (i) thematic seminars introducing national guidelines for dementia care, (ii) regular unit-based seminars; and (iii) later dissemination of information in reflective seminars and several days of poster-exhibitions. Areas of practice development were selected on each of the 24 units, based on unit-specific needs, and a quality improvement strategy was applied and evaluated. Each unit met ten times during a period of eight months. Data for this study were extracted from the reflective seminars and poster presentations, analyzed using a qualitative content analysis. Findings showed that implementation of guidelines were perceived by staff as beneficial for both staff and the residents. However, barriers to identification of relevant sources of evidence and barriers to sustainable implementation were experienced. One of our assumptions was that dementia nursing homes can benefit from becoming knowledge driven, with care practices founded in evidence-based sources. Our findings show that to be partly true, even though most staff units found their efforts to pursue and utilize knowledge adversely impacted by time-logistics and practical workload challenges. | 25,136,961 | [
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Transcriptional profiling in rat hair follicles following simulated Blast insult: a new diagnostic tool for traumatic brain injury. | With wide adoption of explosive-dependent weaponry during military activities, Blast-induced neurotrauma (BINT)-induced traumatic brain injury (TBI) has become a significant medical issue. Therefore, a robust and accessible biomarker system is in demand for effective and efficient TBI diagnosis. Such systems will also be beneficial to studies of TBI pathology. Here we propose the mammalian hair follicles as a potential candidate. An Advanced Blast Simulator (ABS) was developed to generate shock waves simulating traumatic conditions on brains of rat model. Microarray analysis was performed in hair follicles to identify the gene expression profiles that are associated with shock waves. Gene set enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) were used to identify cell processes and molecular signaling cascades affected by simulated bomb blasts. Enrichment analyses indicated that genes with altered expression levels were involved in central nervous system (CNS)/peripheral nervous system (PNS) responses as well as signal transduction including Ca2+, K+-transportation-dependent signaling, Toll-Like Receptor (TLR) signaling and Mitogen Activated Protein Kinase (MAPK) signaling cascades. Many of the pathways identified as affected by shock waves in the hair follicles have been previously reported to be TBI responsive in other organs such as brain and blood. The results suggest that the hair follicle has some common TBI responsive molecular signatures to other tissues. Moreover, various TBI-associated diseases were identified as preferentially affected using a gene network approach, indicating that the hair follicle may be capable of reflecting comprehensive responses to TBI conditions. Accordingly, the present study demonstrates that the hair follicle is a potentially viable system for rapid and non-invasive TBI diagnosis. | 25,136,963 | [
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Age-stratified 5-year risks of cervical precancer among women with enrollment and newly detected HPV infection. | It is unclear whether a woman's age influences her risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) upon detection of HPV. A large change in risk as women age would influence vaccination and screening policies. Among 972,029 women age 30-64 undergoing screening with Pap and HPV testing (Hybrid Capture 2, Qiagen, Germantown, MD) at Kaiser Permanente Northern California (KPNC), we calculated age-specific 5-year CIN3+ risks among women with HPV infections detected at enrollment, and among women with "newly detected" HPV infections at their second screening visit. Women (57,899, 6.0%) had an enrollment HPV infection. Among the women testing HPV negative at enrollment with a second screening visit, 16,724 (3.3%) had a newly detected HPV infection at their second visit. Both enrollment and newly detected HPV rates declined with age (p < 0.001). Women with enrollment versus newly detected HPV infection had higher 5-year CIN3+ risks: 8.5% versus 3.9%, (p < 0.0001). Risks did not increase with age but declined slightly from 30-34 years to 60-64 years: 9.4% versus 7.4% (p = 0.017) for enrollment HPV and 5.1% versus 3.5% (p = 0.014) for newly detected HPV. Among women age 30-64 in an established screening program, women with newly detected HPV infections were at lower risk than women with enrollment infections, suggesting reduced benefit vaccinating women at older ages. Although the rates of HPV infection declined dramatically with age, the subsequent CIN3+ risks associated with HPV infection declined only slightly. The CIN3+ risks among older women are sufficiently elevated to warrant continued screening through age 65. | 25,136,967 | [
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Registration of 2D histological sections with 3D micro-CT datasets from small animal vertebrae and tibiae. | The aim of this study was the registration of digitized thin 2D sections of mouse vertebrae and tibiae used for histomorphometry of trabecular bone structure into 3D micro computed tomography (μCT) datasets of the samples from which the sections were prepared. Intensity-based and segmentation-based registrations (SegRegs) of 2D sections and 3D μCT datasets were applied. As the 2D sections were deformed during their preparation, affine registration for the vertebrae was used instead of rigid registration. Tibiae sections were additionally cut on the distal end, which subsequently undergone more deformation so that elastic registration was necessary. The Jaccard distance was used as registration quality measure. The quality of intensity-based registrations and SegRegs was practically equal, although precision errors of the elastic registration of segmentation masks in tibiae were lower, while those in vertebrae were lower for the intensity-based registration. Results of SegReg significantly depended on the segmentation of the μCT datasets. Accuracy errors were reduced from approximately 64% to 42% when applying affine instead of rigid transformations for the vertebrae and from about 43% to 24% when using B-spline instead of rigid transformations for the tibiae. Accuracy errors can also be caused by the difference in spatial resolution between the thin sections (pixel size: 7.25 μm) and the μCT data (voxel size: 15 μm). In the vertebrae, average deformations amounted to a 6.7% shortening along the direction of sectioning and a 4% extension along the perpendicular direction corresponding to 0.13-0.17 mm. Maximum offsets in the mouse tibiae were 0.16 mm on average. | 25,136,982 | [
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Sequential inclusion of two berberine cations in cucurbit[8]uril cavity: kinetic and thermodynamic studies. | A combination of absorption and fluorescence spectroscopic studies with isothermal calorimetric titrations and stopped-flow measurements is a powerful way to reveal the thermodynamics and kinetics of inclusion complex formation with cucurbit[8]uril (CB8). The unique photophysical characteristics of berberine (B(+)), a pharmaceutically important natural alkaloid, were exploited to distinguish the consecutive encapsulation processes, and to examine the confinement in the CB8 cavity. The highly environment sensitive fluorescence lifetime of B(+) permitted the selective detection of various cucurbituril complexes, and indicated to what extent the embedded guest was available for interaction with water. Highly stable 1 : 1 and 2 : 1 B(+) : CB8 complexes were produced due to the release of the high energy water molecules from the CB8 interior, and the second binding step proved to be almost 3 times more exothermic. The favorable entropy change contributed appreciably to the driving force of 1 : 1 encapsulation. In contrast, the embedment of the second B(+) in CB8 led to substantial entropy diminution. The kinetics of encapsulation was followed in real time by recording the fluorescence intensity change after rapid mixing of B(+) and CB8. No evidence was found for intermediates. The rate constants of (64 ± 9) × 10(6), and (5.0 ± 0.5) × 10(6) M(-1) s(-1) were found for the 1 : 1 and 2 : 1 associations, whereas 3.8 ± 0.6, and 0.6 ± 0.1 s(-1) were obtained as the rate constants of the reverse processes at 283 K, respectively. | 25,136,985 | [
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The potential impact of a 20% tax on sugar-sweetened beverages on obesity in South African adults: a mathematical model. | The prevalence of obesity in South Africa has risen sharply, as has the consumption of sugar-sweetened beverages (SSBs). Research shows that consumption of SSBs leads to weight gain in both adults and children, and reducing SSBs will significantly impact the prevalence of obesity and its related diseases. We estimated the effect of a 20% tax on SSBs on the prevalence of and obesity among adults in South Africa. A mathematical simulation model was constructed to estimate the effect of a 20% SSB tax on the prevalence of obesity. We used consumption data from the 2012 SA National Health and Nutrition Examination Survey and a previous meta-analysis of studies on own- and cross-price elasticities of SSBs to estimate the shift in daily energy consumption expected of increased prices of SSBs, and energy balance equations to estimate shifts in body mass index. The population distribution of BMI by age and sex was modelled by fitting measured data from the SA National Income Dynamics Survey 2012 to the lognormal distribution and shifting the mean values. Uncertainty was assessed with Monte Carlo simulations. A 20% tax is predicted to reduce energy intake by about 36 kJ per day (95% CI: 9-68 kJ). Obesity is projected to reduce by 3.8% (95% CI: 0.6%-7.1%) in men and 2.4% (95% CI: 0.4%-4.4%) in women. The number of obese adults would decrease by over 220 000 (95% CI: 24 197-411 759). Taxing SSBs could impact the burden of obesity in South Africa particularly in young adults, as one component of a multi-faceted effort to prevent obesity. | 25,136,987 | [
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Non-injection synthesis of doped zinc oxide plasmonic nanocrystals. | Plasmonic metal oxide nanocrystals bridge the optoelectronic gap between semiconductors and metals. In this study, we report a facile, non-injection synthesis of ZnO nanocrystals doped with Al, Ga, or In. The reaction readily permits dopant/zinc atomic ratios of over 15%, is amenable to high precursor concentrations (0.2 M and greater), and provides high reaction yields (>90%). The resulting colloidal dispersions exhibit high transparency in the visible spectrum and a wavelength-tunable infrared absorption, which arises from a dopant-induced surface plasmon resonance. Through a detailed investigation of reaction parameters, the reaction mechanism is fully characterized and correlated to the optical properties of the synthesized nanocrystals. The distinctive optical features of these doped nanocrystals are shown to be readily harnessed within thin films that are suitable for optoelectronic applications. | 25,136,989 | [
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Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery. | Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion. | 25,137,021 | [
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Comparison of interferon-γ release assay to two cut-off points of tuberculin skin test to detect latent Mycobacterium tuberculosis infection in primary health care workers. | An interferon-γ release assay, QuantiFERON-TB (QFT) test, has been introduced an alternative test for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Here, we compared the performance of QFT with tuberculin skin test (TST) measured at two different cut-off points among primary health care work (HCW) in Brazil. A cross-sectional study was carried out among HCWs in four Brazilian cities with a known history of high incidence of TB. Results of the QFT were compared to TST results based on both ≥5 mm and ≥10 mm as cut-off points. We enrolled 632 HCWs. When the cut-off value of ≥10 mm was used, agreement between QFT and TST was 69% (k = 0.31), and when the cut-off of ≥5 mm was chosen, the agreement was 57% (k = 0.22). We investigated possible factors of discordance of TST vs QFT. Compared to the TST-/QFT- group, risk factors for discordance in the TST+/QFT- group with TST cut-off of ≥5 mm included age between 41-45 years [OR = 2.70; CI 95%: 1.32-5.51] and 46-64 years [OR = 2.04; CI 95%: 1.05-3.93], BCG scar [OR = 2.72; CI 95%: 1.40-5.25], and having worked only in primary health care [OR = 2.30; CI 95%: 1.09-4.86]. On the other hand, for the cut-off of ≥10 mm, BCG scar [OR = 2.26; CI 95%: 1.03-4.91], being a household contact of a TB patient [OR = 1.72; CI 95%: 1.01-2.92] and having had a previous TST [OR = 1.66; CI 95%: 1.05-2.62], were significantly associated with the TST+/QFT- group. No statistically significant associations were found among the TST-/QFT+ discordant group with either TST cut-off value. Although we identified BCG vaccination to contribute to the discordance at both TST cut-off measures, the current Brazilian recommendation for the initiation of LTBI treatment, based on information gathered from medical history, TST, chest radiograph and physical examination, should not be changed. | 25,137,040 | [
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Coupling of X-chromosome reactivation with the pluripotent stem cell state. | X-chromosome inactivation (XCI) in female mammals is a dramatic example of epigenetic gene regulation, which entails the silencing of an entire chromosome through a wide range of mechanisms involving noncoding RNAs, chromatin-modifications, and DNA-methylation. While XCI is associated with the differentiated cell state, it is reversed by X-chromosome reactivation (XCR) ex vivo in pluripotent stem cells and in vivo in the early mouse embryo and the germline. Critical in the regulation of XCI vs. XCR is the X-inactivation center, a multigene locus on the X-chromosome harboring several long noncoding RNA genes including, most prominently, Xist and Tsix. These genes, which sit at the top of the XCI hierarchy, are by themselves controlled by pluripotency factors, coupling XCR with the naïve pluripotent stem cell state. In this point-of-view article we review the latest findings regarding this intricate relationship between cell differentiation state and epigenetic control of the X-chromosome. In particular, we discuss the emerging picture of complex multifactorial regulatory mechanisms, ensuring both a fine-tuned and robust X-reactivation process. | 25,137,047 | [
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Diabetes mellitus as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. | To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG). This is a systematic review and meta-analysis of case-control and cohort studies. The literature search included two databases (PubMed and Embase) and the reference lists of the retrieved studies. Separate meta-analyses for case-control studies and cohort studies were conducted using random-effects models, with results reported as adjusted odds ratios (ORs) and relative risks (RRs), respectively. Thirteen studies--seven case-control studies and six population-based cohort studies--were included in this meta-analysis. The pooled RR of the association between DM and POAG based on the risk estimates of the six cohort studies was 1.40 (95% CI, 1.25-1.57). The pooled OR of the association between DM and POAG based on the risk estimates of the seven case-control studies was 1.49 (95% CI, 1.17-1.88). There was considerable heterogeneity among the case-control studies that reported an association between DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort studies (P = 0.377). After omitting the case-control study that contributed significantly to the heterogeneity, the pooled OR for the association between DM and POAG was 1.35 (95% CI, 1.06-1.74). Individuals with DM have an increased risk of developing POAG. | 25,137,059 | [
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Genomic inverse PCR for exploration of ligated breakpoints (GIPFEL), a new method to detect translocations in leukemia. | Here we present a novel method "Genomic inverse PCR for exploration of ligated breakpoints" (GIPFEL) that allows the sensitive detection of recurrent chromosomal translocations. This technique utilizes limited amounts of DNA as starting material and relies on PCR based quantification of unique DNA sequences that are created by circular ligation of restricted genomic DNA from translocation bearing cells. Because the complete potential breakpoint region is interrogated, a prior knowledge of the individual, specific interchromosomal fusion site is not required. We validated GIPFEL for the five most common gene fusions associated with childhood leukemia (MLL-AF4, MLL-AF9, MLL-ENL, ETV6-RUNX1, and TCF3-PBX1). A workflow of restriction digest, purification, ligation, removal of linear fragments and precipitation enriching for circular DNA was developed. GIPFEL allowed detection of translocation specific signature sequences down to a 10-4 dilution which is close to the theoretical limit. In a blinded proof-of-principle study utilizing DNA from cell lines and 144 children with B-precursor-ALL associated translocations this method was 100% specific with no false positive results. Sensitivity was 83%, 65%, and 24% for t(4;11), t(9;11) and t(11;19) respectively. Translocation t(12;21) was correctly detected in 64% and t(1;19) in 39% of the cases. In contrast to other methods, the characteristics of GIPFEL make it particularly attractive for prospective studies. | 25,137,060 | [
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High proton conduction at above 100 °C mediated by hydrogen bonding in a lanthanide metal-organic framework. | A lanthanide metal-organic framework (MOF) compound of the formulation [Eu2(CO3)(ox)2(H2O)2]·4H2O (1, ox = oxalate) was prepared by hydrothermal synthesis with its structure determined crystallographically. Temperature-dependent but humidity-independent high proton conduction was observed with a maximum of 2.08 × 10(-3) S cm(-1) achieved at 150 °C, well above the normal boiling point of water. Results from detailed structural analyses, comparative measurements of conductivities using regular and deuterated samples, anisotropic conductivity measurements using a single-crystal sample, and variable-temperature photoluminescence studies collectively establish that the protons furnished by the Eu(III)-bound and activated aqua ligands are the charge carriers and that the transport of proton is mediated along the crystallographic a-axis by ordered hydrogen-bonded arrays involving both aqua ligands and adjacent oxalate groups in the channels of the open framework. Proton conduction was enhanced with the increase of temperature from room temperature to about 150 °C, which can be rationalized in terms of thermal activation of the aqua ligands and the facilitated transport between aqua and adjacent oxalate ligands. A complete thermal loss of the aqua ligands occurred at about 160 °C, resulting in the disintegration of the hydrogen-bonded pathway for proton transport and a precipitous drop in conductivity. However, the structural integrity of the MOF was maintained up to 350 °C, and upon rehydration, the original structure with the hydrogen-bonded arrays was restored, and so was its high proton-conduction ability. | 25,137,095 | [
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Germination shifts of C3 and C4 species under simulated global warming scenario. | Research efforts around the world have been increasingly devoted to investigating changes in C3 and C4 species' abundance or distribution with global warming, as they provide important insight into carbon fluxes and linked biogeochemical cycles. However, changes in the early life stage (e.g. germination) of C3 and C4 species in response to global warming, particularly with respect to asymmetric warming, have received less attention. We investigated germination percentage and rate of C3 and C4 species under asymmetric (+3/+6°C at day/night) and symmetric warming (+5/+5°C at day/night), simulated by alternating temperatures. A thermal time model was used to calculate germination base temperature and thermal time constant. Two additional alternating temperature regimes were used to test temperature metrics effect. The germination percentage and rate increased continuously for C4 species, but increased and then decreased with temperature for C3 species under both symmetric and asymmetric warming. Compared to asymmetric warming, symmetric warming significantly overestimated the speed of germination percentage change with temperature for C4 species. Among the temperature metrics (minimum, maximum, diurnal temperature range and average temperature), maximum temperature was most correlated with germination of C4 species. Our results indicate that global warming may favour germination of C4 species, at least for the C4 species studied in this work. The divergent effects of asymmetric and symmetric warming on plant germination also deserve more attention in future studies. | 25,137,138 | [
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Surgical treatment of large abdominally involved primary dumbbell tumor in the lumbar region. | This was a retrospective clinical study. The aim of this study was to assess the efficacy of a combined anterior and posterior approach, or single-stage posterior extensive approach for resection of large abdominally involved dumbbell tumor in the lumbar region. Resection of the large spinal-retroperitoneal involved dumbbell tumor is particularly controversial and challenging because of unique exposure requirements. From June 2006 to October 2011, 18 consecutive patients suffering from large dumbbell tumors in the lumbar region were involved. In the initial 8 patients, a combined posterior and anterior surgical approach was applied. The remaining 10 patients were surgically treated with a single posterior extensive approach to excise both the intraspinal and intra-abdominal tumors. Reconstruction with bone or mesh grafts was also performed simultaneously in 3 of the 10 patients in this group. The perioperative period was uneventful for 7 of 8 patients who underwent combined surgery. However, 1 patient encountered right nephrectomy because of a ruptured renal vein and refractory bleeding during anterior tumor exposure. Histopathology revealed the presence of schwannoma (n=4), neurofibroma (n=3), and neuroblastoma (n=1). With the mean of 52 months of follow-up, metastasis occurred in 1 patient with neuroblastoma. In the 10 patients with only the posterior approach, histopathology demonstrated schwannoma (n=5), neurofibroma (n=3), small round cell mesenchymal tumor (n=1), and benign fibrous histiocytoma (n=1). No recurrence was detected at the mean follow-up of 24 months. The posterior extensive approach is safe and effective to remove the large abdominally involved dumbbell tumors, and also facilitates simultaneously reconstruction of the vertebral body, as compared with the combined posterior and anterior approach. | 25,137,145 | [
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Stereoselective synthesis of C-fused pyranoindoles, pyranobenzofurans and pyranobenzothiophene scaffolds using oxa-Pictet-Spengler type reaction of vinylogous carbonates. | C-fused pyranoheterocycles can be readily assembled using an intramolecular oxa-Pictet-Spengler type reaction of vinylogous carbonates in a highly stereoselective manner. Required indole and benzofuran rings tethered to vinylogous carbonates are prepared by a tandem Sonogashira coupling-nucleopalladation reaction. The entire process can also be carried out in a 'one-pot' manner starting from homopropargyl alcohol. The C-fused pyranoindoles could be converted to spirooxindoles as well as to ring expanded products under oxidative conditions. | 25,137,156 | [
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[Intravenous drugs infusion safety through smart pumps]. | To analyze the role of smart infusion pumps in reducing errors related with the administration of intravenous medications. Retrospective, observational study analyzing the implementation of a system with smart intravenous infusion pumps (Hospira MedNetTM) and the role of the safety system for the detection of errors during the administration of drugs, sera, and blood. We included infusions administered at the day-care hospitals of hematology, oncology, rheumatology, and oncopediatrics. We analyzed adherence to the safety system, the number of programming errors detected, the commonly implicated drugs in these errors, and improvement actions. During the study period, 120 smart pumps were implemented and data on 70,028 infusions were gathered. The rate of adherence to the safety program was 62.30% in hematology (6,887 infusions), 60,30% in oncology (28,127 infusions), 46,50% in rheumatology (1,950 infusions) and 1.8% in oncopediatrics (139 infusions). 3,481 out of the established limits programming alerts were generated by the pumps: 2,716 of relative limit and 765 of absolute limit. En 807 infusions (2.17%), errors that could have had consequences for the patients could be prevented. These findings allowed implementing a series of strategies aimed at minimizing these errors in the future. The Hospira MedNetTM system detects deviations from the established protocols of intravenous infusion, preventing in this way potential adverse events for the patients. It also allows establishing correction measures and implementing the improvement strategies. | 25,137,160 | [
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Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC patients by next generation sequencing: toward a real-time liquid biopsy for treatment. | Assessment of EGFR mutation in non-small cell lung cancer (NSCLC) patients is mandatory for optimization of pharmacologic treatment. In this respect, mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient's disease status. Blood samples were collected from 37 patients enrolled in the TRIGGER study, a prospective phase II multi-center trial of erlotinib treatment in advanced NSCLC patients with activating EGFR mutations in tumor tissue. 10 CTC preparations from breast cancer patients without EGFR mutations in their primary tumors and 12 blood samples from healthy subjects were analyzed as negative controls. CTC preparations, obtained by the Veridex CellSearch System, were subjected to ultra-deep next generation sequencing (NGS) on the Roche 454 GS junior platform. CTCs fulfilling all Veridex criteria were present in 41% of the patients examined, ranging in number between 1 and 29. In addition to validated CTCs, potential neoplastic elements were seen in 33 cases. These included cells not fulfilling all Veridex criteria (also known as "suspicious objects") found in 5 (13%) of 37 cases, and isolated or clustered large naked nuclei with irregular shape observed in 33 (89%) cases. EGFR mutations were identified by NGS in CTC preparations of 31 (84%) patients, corresponding to those present in matching tumor tissue. Twenty-five (96%) of 26 deletions at exon 19 and 6 (55%) of 11 mutations at exon 21 were detectable (P = 0.005). In 4 (13%) cases, multiple EGFR mutations, suggesting CTC heterogeneity, were documented. No mutations were found in control samples. We report for the first time that the CellSearch System coupled with NGS is a very sensitive and specific diagnostic tool for EGFR mutation analysis in CTC preparations with potential clinical impact. | 25,137,181 | [
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[Patient safety -- mission for the future: Managing complications: what do I tell to the patients and what to the relatives?]. | In cases of unintended treatment courses an adequate communication is mandatory. Empathetic conversations expressing human warmth can pave the way to the avoidance of forensic consequences. The laws on patient's rights obligate the responsible physician to inform on request the patient about all recognizable circumstances that may lead to the assumption of a treatment error and to avoid hazards to health. The patient has a right to view his or her complete patient records and to demand that copy be made at the patient's expense. In the case of information to relatives the physician must observe the content and scope of his/her obligation to medical confidentiality. | 25,137,204 | [
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Deposition of Particles in Human Mouth-Throat Replicas and a USP Induction Port. | Oral inhalation is the common route of drug delivery to pulmonary airways. In general, deposition in the oropharyngeal airways from a drug-delivery device makes up a substantial portion of the emitted dose, which affects the dose delivered to the lung. Studies with airway replicas made from cadaver or magnetic resonance imaging scans show that for micrometer-sized particles, impaction is the dominant deposition mechanism. Several deposition studies in oropharyngeal replicas found that the deposition efficiency can be correlated with the mouth inlet velocity and inlet mouthpiece diameter. Other studies show that the deposition efficiency is best correlated with the mean diameter of internal geometry and the mean velocity based on the mean diameter. We investigated the mouth inlet diameter, as well as internal airway dimensions and their influence on oropharyngeal deposition based on experimental data from this study. Several human oropharyngeal replicas with different mouth inlet diameters and the USP induction port were used. We found that the aerosol deposition increased with decreasing mouth inlet diameter. Several mathematical expressions were tried to correlate the deposition efficiency with the Stokes number calculated based on (1) mouth inlet diameter and inlet velocity, (2) mean diameter of internal geometry and mean velocity, (3) mouth inlet velocity and mean diameter, and (4) mouth inlet velocity and minimum diameter in the oropharyngeal replica. The best correlation was obtained in case 4. This correlation could explain the intra-subject variation when deposition was found to vary with mouth inlet diameter, such as in some aerosol drug-delivery devices. It could also explain the intersubject variability in oropharyngeal deposition when human volunteers with different airway geometries and mouth openings were studied. | 25,137,223 | [
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Sex-specific relationships of physical activity, body composition, and muscle quality with lower-extremity physical function in older men and women. | This study aims to determine the sex-specific relationships of physical activity, body composition, and muscle quality with lower-extremity physical function in older men and women. Seventy-nine community-dwelling men (n = 39; mean [SD] age, 76.1 [6.2] y; mean [SD] body mass index, 27.3 [3.8] kg/m(2)) and women (n = 40; mean [SD] age, 75.8 [5.5] y; mean [SD] body mass index, 27.0 [3.8] kg/m(2)) were assessed for physical activity via questionnaire, body composition via dual-energy x-ray absorptiometry scanning, leg extension power using the Nottingham power rig, and muscle quality (W/kg; the ratio of leg extension power [W] to lower-body mineral-free lean mass [kg]). A composite measure of physical function was obtained by summing Z scores from the 6-minute walk, 8-ft up-and-go test, and 30-second chair-stand test. As expected, men had significantly greater levels of physical activity, lower adiposity, greater lean mass, higher leg extension power, and greater muscle quality compared with women (all P < 0.05). In linear regression analyses, muscle quality and physical activity were the strongest predictors of lower-extremity physical function in men and independently explained 42% and 29% of the variance, respectively. In women, muscle quality (16%) and percent body fat (12%) were independent predictors after adjustment for covariates. Muscle quality is the strongest predictor of lower-extremity physical function in men and women, but sex impacts the importance of physical activity and adiposity. These findings suggest that older men and women may benefit from different intervention strategies for preventing physical disability and also highlight the importance of weight management for older women to preserve physical function. | 25,137,244 | [
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Thrombopoietin treatment of one graft in a double cord blood transplant provides early platelet recovery while contributing to long-term engraftment in NSG mice. | Human cord blood (CB) hematopoietic stem cell (HSC) transplants demonstrate delayed early neutrophil and platelet recovery and delayed longer term immune reconstitution compared to bone marrow and mobilized peripheral blood transplants. Despite advances in enhancing early neutrophil engraftment, platelet recovery after CB transplantation is not significantly altered when compared to contemporaneous controls. Recent studies have identified a platelet-biased murine HSC subset, maintained by thrombopoietin (TPO), which has enhanced capacity for short- and long-term platelet reconstitution, can self-renew, and can give rise to myeloid- and lymphoid-biased HSCs. In previous studies, we have shown that transplantation of human CB CD34(+) cells precultured in TPO as a single graft accelerates early platelet recovery as well as yielding long-term repopulation in immune-deficient mice. In this study, using a double CB murine transplant model, we investigated whether TPO cultured human CB CD34(+) cells have a competitive advantage or disadvantage over untreated human CB CD34(+) cells in terms of (1) short-term and longer term platelet recovery and (2) longer term hematological recovery. Our studies demonstrate that the TPO treated graft shows accelerated early platelet recovery without impairing the platelet engraftment of untreated CD34(+) cells. Notably, this was followed by a dominant contribution to platelet production through the untreated CD34(+) cell graft over the intermediate to longer term. Furthermore, although the contribution of the TPO treated graft to long-term hematological engraftment was reduced, the TPO treated and untreated grafts both contributed significantly to long-term chimerism in vivo. | 25,137,252 | [
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Hypertriglyceridemic waist phenotype: association with metabolic disorders and visceral fat in adults. | To evaluate the association of Hypertriglyceridemic waist with metabolic disorders and visceral fat in adults. Cross-sectional study with 191 individuals of both sexes. Subjects were grouped according to Waist Circumference (WC) ratings (Men: > 90 cm; Women: > 80 cm) and triglycerides (TG) (> 150 mg/dl) in Group 1 (HTW Phenotype): elevated WC and TG; Group 2 (absence of HTW Phenotype): elevated WC and normal TG or normal WC and elevated TG or normal WC and TG. Metabolic alternations, visceral adipose tissue (VAT) and visceral/subcutaneous fat index (VF/SF) measured by computed tomography were evaluated as cardiovascu - lar risk factors between the groups. Individuals with HTW phenotype, 82% had three or more cardiovascular risk factors. The association between cardiovascular risk factors with HTW phenotype revealed that among men 73.7% had hypercholesterolemia, 94.9% elevated non-HDLc and 78.9% excess of VAT area (p = 0.001). Among women, 65% had elevated Sistolic Blood Plessure, 80% hypercholesterolemia and 90% elevated non-HDLc (p < 0.02). The HTW phenotype associated with the metabolic alternations and VAT excess. Individuals with HTW had higher number of cardiovascular risk factors. The Hypertriglyceridemic waist can be used in clinical practice for investigating cardiovascular risk and visceral adipose tissue in individuals. | 25,137,258 | [
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Psychological well-being in a sample of obese patients compared with a control group. | The literature has found that obese patients usually report more depression and anxiety than normal weight individuals. However, not many investigations have studied the relationship between obesity and quality of life from a Positive Psychology approach. In this study it is analyzed if obese patients have less psychological well-being than a control group (normal weight participants). A total of 221 participants (111 obese individuals and 110 controls) were selected to conduct the study. To measure psychological well-being, the Spanish version of the Ryff's Scales was used. To measure mental health, the Spanish version of the mental health component of the Short Form 36 Health Survey (SF-36) was used. It was found that obese participants reported less psychological well-being than normal weight individuals, but that there were not statistically significant differences in the case of mental health measured with the SF-36. According to the results, it can be concluded that reports of psychological well-being problems were much more common in participants with weight problems than in the control group. | 25,137,259 | [
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Fat-soluble vitamin deficiencies after bariatric surgery could be misleading if they are not appropriately adjusted. | To evaluate the differences in frequency of fat-soluble vitamin deficiencies if we adjust their levels by its main carriers in plasma in patients undergoing Biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGB). We recruited 178 patients who underwent RYGB (n = 116 patients) and BPD (n = 62 patients) in a single centre. Basal data information and one-year after surgery included: anthropometric measurements, fat-soluble vitamins A, E and D, retinol binding protein (RBP) and total cholesterol as carriers of vitamin A and E respectively. Continuous data were compared using T-Student and proportions using chisquare test. There was a vitamin D deficiency of 96% of all patients, 10% vitamin A deficiency and 1.2% vitamin E deficiency prior to surgery. One year after surgery, 33% of patients were vitamin A deficient but the frequency reduced to 19% when we adjusted by RBP. We found a vitamin E deficiency frequency of 0% in RYGB and 4.8% in DBP one year after surgery. However, when we adjusted the serum levels to total cholesterol, we found an increased frequency of 8.7% in RYGB group for vitamin E deficiency and 21.4% in DBP (p = 0.04). We have found a different frequency of deficit for fat-soluble vitamin both in BPD and RYGB once we have adjusted for its main carriers. This is clinically relevant to prevent from overexposure and toxicity. We suggest that carrier molecules should be routinely requested when we assess fat-soluble vitamin status in patients who undergo malabsorptive procedures. | 25,137,270 | [
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[Body composition and heart rate variability in patients with chronic obstructive pulmonary disease pulmonary rehabilitation candidates]. | Body composition is a non-invasive method, which gives us information about the distribution of tissues in the body structure, it is also an indicator of the risk of mortality in patients with chronic obstructive pulmonary disease. The heart rate variability is a technique that gives us information of autonomic physiological condition, being recognized as an indicator which is decreased in a number of diseases. The purpose of this study was to assess body composition and heart rate variability. The methodology used is that of Debora Kerr (1988) endorsed by the International Society for advances in Cineantropometría for body composition and heart rate variability of the guidelines described by the American Heart Association (1996). Roscraff equipment, caliper Slimguide and watch Polar RS 800CX was used. , BMI 26.7 ± 3.9 kg / m²; Muscle Mass 26.1 ± 6.3 kg ; Bone Mass 1.3 kg ± 8.1 76 ± 9.9 years Age : 14 candidates for pulmonary rehabilitation patients were evaluated , Adipose mass 16.4 ± 3.6 kg ; FEV1 54 ± 14%. Increased waist circumference and waist hip ratio was associated with a lower overall heart rate variability. The bone component was positively related to the variability of heart rate and patients with higher forced expiratory volume in one second had lower high frequency component in heart rate variability. In these patients, the heart rate variability is reduced globally and is associated with cardiovascular risk parameters. | 25,137,278 | [
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Molecular characterization and expression analysis of the critical floral genes in hickory (Carya cathayensis Sarg.). | The full ORFs of three floral genes in hickory (Carya cathayensis Sarg.), CcAGL24 (the AGAMOUS-LIKE24 homolog), CcSOC1 (the SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 homolog) and CcAP1 (the APETALA1 homolog) are derived using a 5' RACE PCR protocol. Through sequence alignment and phylogenetic analysis, it is demonstrated that the three genes belong to the MADS-Box family. According to the evolutionary trees of the three genes, the homologous genes from the same family cluster well together, while those from different orders doesn't match evolutionary regularity of individual organisms. The result of Quantitative RT-PCR analysis shows that the transcriptional levels of the three genes are up-regulated in early stage and down-regulated in late stage in pistillate floral development. However, it takes different time to reach respective expression peak among the three genes. In staminate floral development, the transcription trend of the three genes is up-regulated, subsequently down-regulated, and then up-regulated again. Nevertheless, those trajectories, peaks, expression levels, inflection points are different in pistillate floral development. The result suggests that their functions are different in between pistillate and staminate floral development. The probable ordinal site of the three genes in the flowering network from top down is CcAGL24, CcSOC1, and CcAP1, which is identical to that in herbaceous plants. Moreover, several adverse environmental factors trigger several negative genes and then confine the development of staminate floral buds. Our results suggest the possible relationship among the three critical floral genes and their functions throughout the floral development in hickory. | 25,137,292 | [
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[Intravascular papillary endothelial hyperplasia of the lung]. | We report a rare case of pulmonary intravascular papillary endothelial hyperplasia. The patient was a 63-year-old male. Multiple lung nodules were noted on chest computed tomography( CT) at preoperative check for gastric cancer. Metastatic lung tumor was suspected, and partial resection of the right lung was performed. Histopathologic examination revealed papillary proliferation lined by endothelial cells and a hematoma. Immunohistochemically, the endothelial cells were positive for CD31/CD34 and factor VIII related antigen. | 25,137,319 | [
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... |
Reconstructing Austronesian population history in Island Southeast Asia. | Austronesian languages are spread across half the globe, from Easter Island to Madagascar. Evidence from linguistics and archaeology indicates that the 'Austronesian expansion,' which began 4,000-5,000 years ago, likely had roots in Taiwan, but the ancestry of present-day Austronesian-speaking populations remains controversial. Here, we analyse genome-wide data from 56 populations using new methods for tracing ancestral gene flow, focusing primarily on Island Southeast Asia. We show that all sampled Austronesian groups harbour ancestry that is more closely related to aboriginal Taiwanese than to any present-day mainland population. Surprisingly, western Island Southeast Asian populations have also inherited ancestry from a source nested within the variation of present-day populations speaking Austro-Asiatic languages, which have historically been nearly exclusive to the mainland. Thus, either there was once a substantial Austro-Asiatic presence in Island Southeast Asia, or Austronesian speakers migrated to and through the mainland, admixing there before continuing to western Indonesia. | 25,137,359 | [
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Development of an organic lateral resolution test device for imaging mass spectrometry. | An organic lateral resolution test device has been developed to measure the performance of imaging mass spectrometry (IMS) systems. The device contains periodic gratings of polyethylene glycol (PEG) and lipid bars covering a wide range of spatial frequencies. Microfabrication technologies were employed to produce well-defined chemical interfaces, which allow lateral resolution to be assessed using the edge-spread function (ESF). In addition, the design of the device allows for the direct measurement of the modulation transfer function (MTF) to assess image quality. Scanning electron microscopy (SEM) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) were used to characterize the device. TOF-SIMS imaging was used to measure the chemical displacement of biomolecules in matrix-assisted laser desorption/ionization (MALDI) matrix crystals. In a proof-of-concept experiment, the platform was also used to evaluate MALDI matrix application methods, specifically aerosol spray and sublimation methods. | 25,137,365 | [
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Reconciling "stress" and "health" in physical anthropology: what can bioarchaeologists learn from the other subdisciplines? | The concepts of "stress" and "health" are foundational in physical anthropology as guidelines for interpreting human behavior and biocultural adaptation in the past and present. Though related, stress and health are not coterminous, and while the term "health" encompasses some aspects of "stress," health refers to a more holistic condition beyond just physiological disruption, and is of considerable significance in contributing to anthropologists' understanding of humanity's lived experiences. Bioarchaeological interpretations of human health generally are made from datasets consisting of skeletal markers of stress, markers that result from (chronic) physiological disruption (e.g., porotic hyperostosis; linear enamel hypoplasia). Non-specific indicators of stress may measure episodes of stress and indicate that infection, disease, or nutritional deficiencies were present in a population, but in assessing these markers, bioarchaeologists are not measuring "health" in the same way as are human biologists, medical anthropologists, or primatologists. Rather than continue to diverge on separate (albeit parallel) trajectories, bioarchaeologists are advised to pursue interlinkages with other subfields within physical anthropology toward bridging "stress" and "health." The papers in this special symposium set include bioarchaeologists, human biologists, molecular anthropologists, and primatologists whose research develops this link between the concepts of "stress" and "health," encouraging new avenues for bioarchaeologists to consider and reconsider health in past human populations. | 25,137,366 | [
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Accelerometer adherence and performance in a cohort study of US Hispanic adults. | This study described participant adherence to wearing the accelerometer and accelerometer performance in a cohort study of adults. From 2008 to 2011, 16,415 US Hispanic/Latino adults age 18-74 yr enrolled in the Hispanic Community Health Study/Study of Latinos. Immediately after the baseline visit, participants wore an Actical accelerometer for 1 wk. This study explored correlates of accelerometer participation and adherence, defined as wearing it for at least three of a possible six days for ≥10 h·d. Accelerometer performance was assessed by exploring the number of different values of accelerometer counts per minute for each participant. Overall, 92.3% (n = 15,153) had at least 1 d with accelerometer data and 77.7% (n = 12,750) were adherent. Both accelerometer participation and adherence were higher among participants who were married or partnered, reported a higher household income, were first-generation immigrants, or reported lower sitting time. Participation was also higher among those with no stair limitations. Adherence was higher among participants who were male, older, employed or retired, not US born, preferred Spanish over English, reported higher work activity or lower recreational activity, and with a lower body mass index. Among the sample that met the adherence definition, the maximum recorded count per minute was 12,000, and there were a total of 5846 different counts per minute. On average, participants had 112.5 different counts per minute over 6 d (median, 106; interquartile range, 91-122). The number of different counts per minute was higher among men, younger ages, normal weight, and those with higher accelerometer-assessed physical activity. Several correlates differed between accelerometer participation and adherence. These characteristics could be targeted in future studies to improve accelerometer wear. The performance of the accelerometer provided insight into creating a more accurate nonwear algorithm. | 25,137,369 | [
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Long-term fertilization modifies the structures of soil fulvic acids and their binding capability with Al. | The binding characteristics of organic ligands and minerals in fulvic acids (FAs) with Al are essential for understanding soil C sequestration, remain poorly understood. In this study, Fourier transform infrared (FTIR) spectroscopy combined with two-dimensional correlation spectroscopy (2DCOS) analysis was applied for the first time to explore the binding of Al with organic ligands and minerals in soil FAs. For these analyses, two contrasting treatments were selected from a long-term (i.e., 22-year) fertilization experiment: chemical (NPK) fertilization and swine manure (SM) fertilization. The results showed that the long-term application of organic and inorganic fertilizers to soils had little effect on the compositions of the fluorescent substances and organic ligands in the soil FAs. However, long-term SM fertilization increased the weathered Al and Si concentrations in the soil FAs compared with long-term chemical fertilization. Furthermore, organic ligands in the soil FAs were mainly bound with Al in the NPK treatment, whereas both organic ligands and minerals (Al-O-Si, Si-O) were bound with Al under the M fertilization conditions. Both transmission electron microscopy (TEM) images and X-ray diffraction spectra demonstrated that amorphous and short-range-ordered nanominerals were abundant in the soil FAs from the SM plot in contrast to the soil FAs from the NPK plot. This result illustrates the role nanominerals play in the preservation of soil FAs by during long-term organic fertilization. In summary, the combination of FTIR and 2D correlation spectroscopy is a promising approach for the characterization of the binding capability between soil FAs and Al, and a better understanding FA-Al binding capability will greatly contribute to global C cycling. | 25,137,372 | [
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Discovery of covalent inhibitors of glyceraldehyde-3-phosphate dehydrogenase, a target for the treatment of malaria. | We developed a new class of covalent inhibitors of Plasmodium falciparum glyceraldehyde-3-phosphate dehydrogenase, a validated target for the treatment of malaria, by screening a small library of 3-bromo-isoxazoline derivatives that inactivate the enzyme through a covalent, selective bond to the catalytic cysteine, as demonstrated by mass spectrometry. Substituents on the isoxazolinic ring modulated the potency up to 20-fold, predominantly due to an electrostatic effect, as assessed by computational analysis. | 25,137,375 | [
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Susceptibility-weighted imaging in heat stroke. | To assess the role of susceptibility-weighted imaging in the detection of intracranial hemorrhage after heat stroke and in the prognosis. The study group consisted of eight patients after heat stroke, with a score of 3 to 9 in Glasgow Coma Scale. The MR studies were performed with a 1.5 T scanner. Susceptibility-weighted imaging data were collected within 2-5 days after heat stroke. The study was approved by ethics committee, and written informed consents were obtained from family members of the patients. Punctate hemorrhages were detected in brain stem, corona radiata and frontal lobe by susceptibility-weighted imaging for three patients. Among the three cases, two patients came to death in the 5th day and the 25th day after heat stroke respectively. Another patient became a persistent vegetative state and died about 3 months later. Five patients with no hemorrhage detected gradually recovered and cerebellar dysfunction remained to various degrees. Heat stroke is a life-threatening condition characterized by hyperthermia and accompanied by various complications such as disseminated intravascular coagulation. Susceptibility-weighted imaging is a very useful tool for detection of intracranial hemorrhage and may probably evaluate the prognosis after heat stroke. | 25,137,376 | [
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Impact of fresh organic matter incorporation on PAH fate in a contaminated industrial soil. | The impacts of fresh organic matter (OM) incorporation in an industrial PAH-contaminated soil on its structure and contaminant concentrations (available and total) were monitored. A control soil and a soil amended with the equivalent of 10 years maize residue input were incubated in laboratory-controlled conditions over 15 months. The structure of the amended soil showed an aggregation process trend which is attributable to (i) the enhanced microbial activity resulting from fresh OM input itself and (ii) the fresh OM and its degradation products. Initially the added organic matter was evenly distributed among all granulodensimetric fractions, and then rapidly degraded in the sand fraction, while stabilizing and accumulating in the silts. PAH degradation remained slight, despite the enhanced microbial biomass activity, which was similar to kinetics of the turnover rate of OM in an uncontaminated soil. The silts stabilized the anthropogenic OM and associated PAH. The addition of fresh OM tended to contribute to this stabilization process. Thus, in a context of plant growth on this soil two opposing processes might occur: rhizodegradation of the available contaminant and enhanced stabilization of the less available fraction due to carbon input. | 25,137,382 | [
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AgONO-assisted direct C-H arylation of heteroarenes with anilines. | A novel copper-catalyzed C-H arylation of heteroarenes with anilines by an in situ diazonium reaction is established by using silver nitrite (AgONO) as an unconventional nitrosating reagent under acid-free conditions. It provides a complementary approach for the C-H arylation of electron-rich heteroarenes with aromatic amines affording a variety of heterobiaryls in moderate to good yields. | 25,137,410 | [
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Letrozole vs anastrozole for height augmentation in short pubertal males: first year data. | Aromatase inhibitors are used off-label to treat short stature in peripubertal boys. To investigate short- and long-term hormonal and auxologic differences in short pubertal boys treated with letrozole (L) or anastrozole (A). PATIENTS are seen for laboratory evaluation and physical examination every 6 months, bone age yearly, DEXA and spine film every 2 years. They will be followed until they reach their final height. This is a preliminary report after 1 year of treatment. A single academic children's hospital outpatient clinic. Boys with age >10 years, bone age ≤ 14 years, clinical and hormonal evidence of central puberty, and either height < fifth percentile or predicted adult height (PAH) more than 10 cm below mid-parental height (MPH). Letrozole (2.5 mg) or anastrozole (1 mg) was administered orally each day. Hormonal and clinical parameters, growth velocity, and change in bone age and PAH. Thirty-nine boys have completed 1 year of treatment. Baseline means were age 14.1 years, PAH 166 cm, and testosterone 198 ng/dL. At 1 year, letrozole resulted in higher LH (L 6.1 ± 2.5 vs A 3.2 ± 1.7 IU/L) and testosterone (1038 ± 348 vs 536 ± 216 ng/dL) with lower estradiol (2.8 ± 2.8 vs 5.6 ± 2.9 pg/mL) and IGF-1 (237 ± 51 vs 331 ± 79 ng/mL). First year growth velocities were identical (7.2 cm/year), but an increase in PAH was greater in the anastrozole group (4.2 ± 3.5 vs 1.4 ± 4.4 cm, p = 0.03) after 1 year. We present first-year data from a direct comparison of anastrozole and letrozole for height augmentation in short pubertal boys. Letrozole was more potent in hormonal manipulation than anastrozole. First-year growth velocities were comparable, but improvement in PAH was greater in the anastrozole group. It remains to be seen if positive PAH trends will translate to increase in final height in either group. | 25,137,428 | [
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Amide proton transfer-weighted imaging of the head and neck at 3 T: a feasibility study on healthy human subjects and patients with head and neck cancer. | The aim of this study was to explore the feasibility and repeatability of amide proton transfer-weighted (APTw) MRI for the head and neck on clinical MRI scanners. Six healthy volunteers and four patients with head and neck tumors underwent APTw MRI scanning at 3 T. The APTw signal was quantified by the asymmetric magnetization transfer ratio (MTRasym) at 3.5 ppm. Z spectra of normal tissues in the head and neck (masseter muscle, parotid glands, submandibular glands and thyroid glands) were analyzed in healthy volunteers. Inter-scan repeatability of APTw MRI was evaluated in six healthy volunteers. Z spectra of patients with head and neck tumors were produced and APTw signals in these tumors were analyzed. APTw MRI scanning was successful for all 10 subjects. The parotid glands showed the highest APTw signal (~7.6% average), whereas the APTw signals in other tissues were relatively moderate. The repeatability of APTw signals from the masseter muscle, parotid gland, submandibular gland and thyroid gland of healthy volunteers was established. Four head and neck tumors showed positive mean APTw ranging from 1.2% to 3.2%, distinguishable from surrounding normal tissues. APTw MRI was feasible for use in the head and neck regions at 3 T. The preliminary results on patients with head and neck tumors indicated the potential of APTw MRI for clinical applications. | 25,137,521 | [
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Method to simultaneously determine the sphingosine 1-phosphate breakdown product (2E)-hexadecenal and its fatty acid derivatives using isotope-dilution HPLC-electrospray ionization-quadrupole/time-of-flight mass spectrometry. | Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various physiological processes, can be irreversibly degraded by the membrane-bound S1P lyase (S1PL) yielding (2E)-hexadecenal and phosphoethanolamine. It is discussed that (2E)-hexadecenal is further oxidized to (2E)-hexadecenoic acid by the long-chain fatty aldehyde dehydrogenase ALDH3A2 (also known as FALDH) prior to activation via coupling to coenzyme A (CoA). Inhibition or defects in these enzymes, S1PL or FALDH, result in severe immunological disorders or the Sjögren-Larsson syndrome, respectively. Hence, it is of enormous importance to simultaneously determine the S1P breakdown product (2E)-hexadecenal and its fatty acid metabolites in biological samples. However, no method is available so far. Here, we present a sensitive and selective isotope-dilution high performance liquid chromatography-electrospray ionization-quadrupole/time-of-flight mass spectrometry method for simultaneous quantification of (2E)-hexadecenal and its fatty acid metabolites following derivatization with 2-diphenylacetyl-1,3-indandione-1-hydrazone and 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. Optimized conditions for sample derivatization, chromatographic separation, and MS/MS detection are presented as well as an extensive method validation. Finally, our method was successfully applied to biological samples. We found that (2E)-hexadecenal is almost quantitatively oxidized to (2E)-hexadecenoic acid, that is further activated as verified by cotreatment of HepG2 cell lysates with (2E)-hexadecenal and the acyl-CoA synthetase inhibitor triacsin C. Moreover, incubations of cell lysates with deuterated (2E)-hexadecenal revealed that no hexadecanoic acid is formed from the aldehyde. Thus, our method provides new insights into the sphingolipid metabolism and will be useful to investigate diseases known for abnormalities in long-chain fatty acid metabolism, e.g., the Sjögren-Larsson syndrome, in more detail. | 25,137,547 | [
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Distorted subjective reports of stimulus onsets under dual-task conditions: Delayed conscious perception or estimation bias? | We investigated whether selecting a response for one task delays the conscious perception of another stimulus (delayed conscious perception hypothesis). In two experiments, participants watched a revolving clock hand while performing two tasks in close succession (i.e. a dual-task). Two stimuli were presented with varying stimulus onset asynchrony (SOA). After each trial, participants separately estimated the onsets of the two stimuli on the clock face. Across two experiments and four conditions, we manipulated response requirements and assessed their impact on perceived stimulus onsets. Results showed that (a) providing speeded responses to the stimuli did lead to greater SOA-dependent misperceptions of both stimulus onsets as compared to a solely perceptual condition, and (b) that response grouping reduced these misperceptions. Overall, the results provide equivocal evidence for the delayed conscious perception hypothesis. They rather suggest that participants' estimates of the two stimulus onsets are biased by the interval between their responses. | 25,137,569 | [
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Singly protonated dehydronorcantharidin silver coordination polymer induces apoptosis of lung cancer cells via reactive oxygen species-mediated mitochondrial pathway. | Silver complexes have been shown to possess antimicrobial and anticancer properties. Ag-SP-DNC, a novel silver and singly protonated dehydronorcantharidin complex, was synthesized in our previous study. In this study, we offer evidence that Ag-SP-DNC elicits a reactive oxygen species (ROS)-mediated mitochondrial apoptosis in lung cancer cells. Ag-SP-DNC inhibited the growth of A549 cells by inducing G2/M phase cell cycle arrest and apoptosis. Ag-SP-DNC induced apoptosis was associated with the levels of intracellular ROS. The further study revealed that Ag-SP-DNC disrupted the mitochondrial membrane potential, induced the caspase-3 activation and led to the translocation of apoptosis inducing factor and endonucleaseG to the nucleus. These findings have important implications for the development of silver complexes for anticancer applications. | 25,137,572 | [
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Object perception: where do we see the weight? | A new study of the response of the human brain as subjects view objects of different weights they are about to lift shows that the weight of objects, which influences the way we act upon them, is represented in the ventral stream of the visual cortex. | 25,137,583 | [
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Behavioral sequencing: competitive queuing in the fly CNS. | A study of grooming behaviors in Drosophila suggests a neuronal mechanism for how animals produce complex motor patterns from ordered interactions among modules of different motor acts. This mechanism may be a common one in many nervous systems. | 25,137,585 | [
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Genetics: finding genes for schizophrenia. | New studies have substantially advanced our understanding of the genetic architecture of schizophrenia, but we are far from identifying the underlying mutations. We may require new approaches to understand the biological implications of insights into the genetics of psychiatric disease. | 25,137,590 | [
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Aberrant regulation and function of microRNAs in cancer. | Malignant neoplasms are consistently among the top four leading causes of death in all age groups in the United States, despite a concerted effort toward developing novel therapeutic approaches. Our understanding of and therapeutic strategy for treating each of these neoplastic diseases have been improved through decades of research on the genetics, signaling pathways, and cellular biology that govern tumor cell initiation, progression and maintenance. Much of this work has concentrated on post-translational modifications and abnormalities at the DNA level, including point mutations, amplifications/deletions, and chromosomal translocations, and how these aberrant events affect the expression and function of protein-coding genes. Only recently has a novel class of conserved gene regulatory molecules been identified as a major contributor to malignant neoplastic disease. This review focuses on how these small non-coding RNA molecules, termed microRNAs (miRNAs), can function as oncogenes or tumor suppressors, and how the misexpression of miRNAs and dysregulation of factors that regulate miRNAs contribute to the tumorigenic process. Specific focus is given to more recently discovered regulatory mechanisms that go awry in cancer, and how these changes alter miRNA expression, processing, and function. | 25,137,592 | [
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Effective ion mobility calculations for macromolecules by scattering on electron clouds. | Broad commercialization and increasing resolving power of ion mobility spectrometry/mass spectrometry (IMS/MS) platforms have engendered an explosion of IMS applications to structural characterization of gas-phase biomolecules. That has renewed interest in more accurate and rapid ion mobility calculations that are needed to elicit ion geometries from the measurements. An approach based on scattering on electron density isosurfaces (SEDI) that mirrors the physics of molecular collisions was proven superior to the common methods involving atomic coordinates a decade ago but has remained impractical for large ions because of extreme computational demands. Here, we accelerate SEDI by up to ∼500 times using the fragment molecular orbital approach for surface generation and the multiplexed scattering algorithm in conjunction with the new grid extrapolation procedure for cross section evaluations. Parallelization of the code on a supercomputer has produced major further speed gains, allowing SEDI calculations for proteins (defined by over a million surface points) with a precision of <0.1% in 1 min. Initial tests reveal the anticipated dependence of mobility on the ion charge state and lower cross sections in view of reduced surface roughness. Present developments are expected to lead to broad application of SEDI in IMS studies of macromolecules, enabling more accurate and reliable structural assignments. | 25,137,627 | [
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Low-density lipoprotein-mimicking nanoparticles for tumor-targeted theranostic applications. | This study introduces multifunctional lipid nanoparticles (LNPs), mimicking the structure and compositions of low-density lipoproteins, for the tumor-targeted co-delivery of anti-cancer drugs and superparamagnetic nanocrystals. Paclitaxel (4.7 wt%) and iron oxide nanocrystals (6.8 wt%, 11 nm in diameter) are co-encapsulated within folate-functionalized LNPs, which contain a cluster of nanocrystals with an overall diameter of about 170 nm and a zeta potential of about -40 mV. The folate-functionalized LNPs enable the targeted detection of MCF-7, human breast adenocarcinoma expressing folate receptors, in T2 -weighted magnetic resonance images as well as the efficient intracellular delivery of paclitaxel. Paclitaxel-free LNPs show no significant cytotoxicity up to 0.2 mg mL(-1) , indicating the excellent biocompatibility of the LNPs for intracellular drug delivery applications. The targeted anti-tumor activities of the LNPs in a mouse tumor model suggest that the low-density lipoprotein-mimetic LNPs can be an effective theranostic platform with excellent biocompatibility for the tumor-targeted co-delivery of various anti-cancer agents. | 25,137,631 | [
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Healthcare system and the wealth-health gradient: a comparative study of older populations in six countries. | The present study provides a comparative analysis of the association between wealth and health in six healthcare systems (Sweden, the United Kingdom, Germany, the Czech Republic, Israel, the United States). National samples of individuals fifty years and over reveal considerable cross-country variations in health outcomes. In all six countries wealth and health are positively associated. The findings also show that state-based healthcare systems produce better population health outcomes than private-based healthcare systems. The results indicate that in five out of the six countries studied, the wealth-health gradients were remarkably similar, despite significant variations in healthcare system type. Only in the United States was the association between wealth and health substantially different from, and much greater than that in the other five countries. The findings suggest that private-based healthcare system in the U.S. is likely to promote stronger positive associations between wealth and health. | 25,137,644 | [
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Maximal entropy random walk for region-based visual saliency. | Visual saliency is attracting more and more research attention since it is beneficial to many computer vision applications. In this paper, we propose a novel bottom-up saliency model for detecting salient objects in natural images. First, inspired by the recent advance in the realm of statistical thermodynamics, we adopt a novel mathematical model, namely, the maximal entropy random walk (MERW) to measure saliency. We analyze the rationality and superiority of MERW for modeling visual saliency. Then, based on the MERW model, we establish a generic framework for saliency detection. Different from the vast majority of existing saliency models, our method is built on a purely region-based strategy, which is able to yield high-resolution saliency maps with well preserved object shapes and uniformly highlighted salient regions. In the proposed framework, the input image is first over-segmented into superpixels, which are taken as the primary units for subsequent procedures, and regional features are extracted. Then, saliency is measured according to two principles, i.e., uniqueness and visual organization, both implemented in a unified approach, i.e., the MERW model based on graph representation. Intensive experimental results on publicly available datasets demonstrate that our method outperforms the state-of-the-art saliency models. | 25,137,693 | [
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Four-class classification of skin lesions with task decomposition strategy. | This paper proposes a new computer-aided method for the skin lesion classification applicable to both melanocytic skin lesions (MSLs) and nonmelanocytic skin lesions (NoMSLs). The computer-aided skin lesion classification has drawn attention as an aid for detection of skin cancers. Several researchers have developed methods to distinguish between melanoma and nevus, which are both categorized as MSL. However, most of these studies did not focus on NoMSLs such as basal cell carcinoma (BCC), the most common skin cancer and seborrheic keratosis (SK) despite their high incidence rates. It is preferable to deal with these NoMSLs as well as MSLs especially for the potential users who are not enough capable of diagnosing pigmented skin lesions on their own such as dermatologists in training and physicians with different expertise. We developed a new method to distinguish among melanomas, nevi, BCCs, and SKs. Our method calculates 828 candidate features grouped into three categories: color, subregion, and texture. We introduced two types of classification models: a layered model that uses a task decomposition strategy and flat models to serve as performance baselines. We tested our methods on 964 dermoscopy images: 105 melanomas, 692 nevi, 69 BCCs, and 98 SKs. The layered model outperformed the flat models, achieving detection rates of 90.48%, 82.51%, 82.61%, and 80.61% for melanomas, nevi, BCCs, and SKs, respectively. We also identified specific features effective for the classification task including irregularity of color distribution. The results show promise for enhancing the capability of the computer-aided skin lesion classification. | 25,137,721 | [
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A dual-population differential evolution with coevolution for constrained optimization. | Inspired by the fact that in modern society, team cooperation and the division of labor play important roles in accomplishing a task, this paper proposes a dual-population differential evolution (DPDE) with coevolution for constrained optimization problems (COPs). The COP is treated as a bi-objective optimization problem where the first objective is the actual cost or reward function to be optimized, while the second objective accounts for the degree of constraint violations. At each generation during the evolution process, the whole population is divided into two based on the solution's feasibility to treat the both objectives separately. Each subpopulation focuses on only optimizing the corresponding objective which leads to a clear division of work. Furthermore, DPDE makes use of an information-sharing strategy to exchange search information between the different subpopulations similar to the team cooperation. The comparison of the proposed method on a number of benchmark functions with selected state-of-the-art constraint-handling algorithms indicates that the proposed technique performs competitively and effectively. | 25,137,739 | [
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Taste dysfunction and eating behaviors in survivors of head and neck cancer treatment. | Radiation, chemotherapy, and surgery result in eating problems for patients with head and neck cancer. Eating is essential to physical and social functioning. Strategies for head and neck cancer survivors to cope with eating and taste impairments are reported in this study. | 25,137,792 | [
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[Therapeutic effect of Astragalus and Angelica mixture on the renal function and TCM syndrome factors in treating stage 3 and 4 chronic kidney disease patients]. | To compare the therapeutic effect of Astragalus and Angelica Mixture (AAM) on treating CKD patients according to different CKD primary diseases, staging and TCM syndromes. A multicentre, open-label, and self control clinical design was used, and thirty-two patients in line with inclusive criteria were recruited. Based on maintaining their previous basic CKD treatment, patients additionally took AAM (Astragalus and Angelica each 30 g), once a day, three months consisted of one therapeutic course. Serum creatinine (SCr), estimated glomerular filtration rate (eG- FR), 24 h urinary total protein (UTP), plasma albumin (ALB), hemoglobin (Hb), and changes of TCM syndrome factor integrals were compared before treatment, at the end of month 1, 2, and 3. The differences in the aforesaid indices were compared between CKD patients with different CKD primary diseases (chronic glomerulonephritis, chronic renal tubulointerstitial disease, hypertensive renal damage), different CKD stages (CKD 3 and CKD 4), and patients of qi-blood deficiency syndrome (QBDS) and non-QBDS. AAM could improve 78.12% (25/32) patients' renal function. Compared with before treatment, SCr decreased (12.08% +/- 10.11%), eGFR increased (21.14% +/- 18.55%), and ALB increased (2.76% +/- 1.97%) at the end of 3-month treatment (all P < 0.05). As for TCM syndrome factor integrals, compared with before treatment, the integrals for qi deficiency syndrome, blood deficiency syndrome, and yin deficiency syndrome decreased, while the integrals for dampness heat syndrome and turbid-toxin syndrome increased (all P < 0.05). There was no obvious difference in all indices except the integral for hypertensive renal damage patients of yin deficiency syndrome (P > 0.05). The SCr decreasing percent was 19.82% +/- 8.30% for patients of non-QBDS and 5.24% +/- 10.75% for patients of QBDS. The latter was higher with statistical difference (P < 0.05). As for TCM syndrome factor integrals, the integral differences of qi deficiency and blood deficiency were obviously higher in patients of QBDS, when compared with patients of non-QBDS (P < 0.05). AAM could improve the renal function of CKD patients, elevate their ALB levels, and ameliorate associated qi deficiency syndrome, blood deficiency syndrome, and yin deficiency syndrome, especially for CKD patients of QBDS. | 25,137,839 | [
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[Renal protection of Tangke Decoction on rats with diabetes and its effect on the expression of TGF-beta1/Smad4]. | To observe the effect of Tangke Decoction (TD) on the expression of TGF-beta1/Smad4 of rats with early diabetes and to explore the effect and mechanism of TD against the renal injury induced by diabetes. SD rats were randomly divided into the normal control group (n = 12), the model group (n = 10), the Chinese herbs prevented group (n =10), the Chinese herbs treated group (n = 10), and the Western medicine control group (n = 10). TD (18 mg/kg) was given by gastrogavage to rats in the Chinese herbs prevented group immediately after successful modeling for 12 weeks, once daily. At the 4th week of successful modeling, rats in the rest 4 groups were administered by gastrogavage. Equal volume of normal saline was given to rats in the model group and the normal control group. Benazepril suspension (1 mg/kg) was administered by gastrogavage to rats in the Western medicine control group for 8 weeks, once daily. TD (18 mg/kg) was given by gastrogavage to rats in the Chinese herbs treated group for 8 weeks, once daily. The body weight, kidney weight, index of kidney weight, fasting blood sugar, 24 h urinary albumin excretion rate were examined after experiment. The pathological changes of the renal tissue were observed by HE staining, Masson staining, and electron microscope. The expression of renal transforming growth factor-beta1, (TGF-beta1) and Smad4 were detected using immunohistochemical assay. Compared with the normal control group, the body weight of rats decreased significantly; the kidney weight, index of kidney weight, blood sugar, 24 h urinary protein excretion, the urinary albumin excretion rate,TGF-beta1 and Smad4 expression increased significantly in the model group (all P < 0.01). Compared with the model group, the aforesaid indices were improved in each treatment group with statistical difference (P < 0.05, P < 0.01). Compared with the Western medicine control group, the kidney weight, index of kidney weight, blood sugar, 24 h urinary protein excretion, and the urinary albumin excretion rate were obviously improved in the Chinese herbs prevented group (P < 0.01). The renal pathological changes were most obvious in the model group significantly, but they were improved in all treatment groups. TD could obviously improve the symptoms of diabetes and down-regulate the expression of renal TGF-beta1 and Smad4 of early diabetic nephropathy rats, which suggested that TD had certain preventive effect on early diabetic nephropathy. | 25,137,849 | [
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[Effect of advanced glycation end products on the function and angiogenesis of adipose tissue-derived stem cells and the protective effect of danhong injection: an experimental study]. | OBJECTIVE To investigate the effect of Nepsilon-(carboxymethyl) lysine albumin (CMLs), a primary advanced glycation end products (AGEPs) isoform in diabetic body, on the function and angiogenesis of adipose tissue-derived stem cells (ADSCs) and the protective effect of Danhong Injection (DH). METHODS Human ADSCs were cultured and separated from human subcutaneous fatty tissue using enzymatic digestion and centrifugation. The morphology was observed using optical microscope and differentiation capacities assessed. Cells were exposed to 5 different interventions respectively for 24 h, i.e., PBS, 60 1 microg/mL BSA, 60 microg/mL CML-BSA, 100 microL/mL DH, and 60 micro./mL CML-BSA +100 microL/mL DH. Their effect on the proliferation, migration, apoptosis, and secretion were observed using WST-1 assay, Transwell assay, Annexin V-FITC/PI flow meter test reagent kit, human VEGF reagent kit, ELISA reagent kit, respectively. The effect on ADSCs angiogenesis was observed by in vitro angiogenesis test. Compared with the BSA group, the capacities of proliferation and migration could be significantly inhibited by CML-BSA, the apoptosis promoted, the secretion of VEGF reduced, and the angiogenesis of ADSCs weakened (P < 0.05). Compared with the blank control group, 100 microL/mL DH could significantly promote the proliferation and migration capacities of ADSCs, inhibit apoptosis of ADSCs, increase the secretion of VEGF, and improve the angiogenesis of ADSCs (P < 0.05). Compared with the CML-BSA group, the inhibition of CML-BSA on the proliferation and migration capacities of ADSCs could be significantly reversed, the promotion of CML-BSA on the apoptosis of ADSCs improved, the secretion of VEGF increased, and the angiogenesis of ADSCs elevated (P < 0.05). clusion CMLs could significantly inhibit the proliferation and migration capacities of ADSCs, promote their apoptosis, and inhibit their angiogeneses, which could be improved by DH. | 25,137,851 | [
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[Effect of zhenqing recipe on non-alcoholic fatty liver in type 2 diabetes rats and the expression of SIK1]. | To observe the effect of Zhenqing Recipe (ZQR) on non-alcoholic fatty liver (NAFL), and the expression of hepatic salt-inducible kinase 1 (SIK1) and sterol-regulatory element binding protein-ic (SREBP-lc) in type 2 diabetes rats. A rat model of type 2 diabetes was established by high fat/sucrose diet combined with intraperitoneal injection of small dose streptozotocin (STZ) . Modeled rats were randomly divided into the model group, the ZQR group, and the metformin group, 8 in each group. Eight rats were recruited as a normal control group. ZQR at the daily dose of 12 g crude drugs/kg was administered to rats in the ZQR group by gastrogavage. Metformin suspension at the daily dose of 150 mg/kg was administered to rats in the metformin group by gastrogavage. Equal volume of distilled water was administered to rats in the normal control group and the model group. All medication lasted for 12 weeks. The levels of fasting blood glucose (FBG), free fatty acid (FFA), serum triglyceride (TG), serum total cholesterol (TC), serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected. The body weight and wet liver weight were weighed, and the liver weight index calculated. The liver TG content was measured. The pathological changes of liver and the expression of SIK1 were observed by HE staining and immunohistochemistry. The mRNA and protein expression of SIK1 and SREBP-1c were detected using RT-PCR and Western blot. Compared with the normal control group, FBG, FFA, TG, TC, ALT, AST, liver weight index, and liver TG contents significantly increased (P < 0.01); liver steatosis was severe, the mRNA and protein expression of SIK1 obviously decreased (P < 0.01); mRNA and protein expression of SREBP-1c increased (P < 0.01). After drug therapy, compared with the model group, FBG, FFA, TG, TC, ALT, AST, and liver weight index significantly decreased, liver TG contents significantly decreased, the mRNA and protein expression of SIK1 obviously increased, while mRNA and protein expression of SREBP-1c obviously decreased (P < 0.05, P < 0.01) in the ZQR group and the metformin group (P < 0.05, P < 0.01); and the pathological changes were also improved. All the indices were improved more in the ZQR group (all P < 0.05). In this experiment, we found that the expression of SIK1 decreased in NAFL rats with type 2 diabetes. ZQR could alleviate lesion of NAFL type 2 diabetes rats possibly by up-regulating hepatic SIK1 expression at mRNA and protein levels. | 25,137,852 | [
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[Effect of Mudan Granule on islets beta cell function in monosodium glutamate induced obese mice with insulin resistance: an experimental study]. | To study the effect of Mudan Granule (MD) on the glucose metabolism and beta cell function in monosodium glutamate (MSG) induced obese mice with insulin resistance (IR). MSG obese mice were induced by subcutaneous injecting MSG (4 g/kg for 7 successive days in neonatal ICR mice). Forty MSG mice with IR features were recruited and divided into four groups according to body weight, fasting blood glucose, triglyceride (TG), total cholesterol (TC), and the percentage of blood glucose decreased within 40 min in the IR test, i.e., the model group (Con), the low dose MD group, the high dose MD group, and the Metformin group (Met). Besides, another 10 ICR mice were recruited as the normal control group (Nor). The water solvent of 2.5 g/kg MD or 5 g/kg MD was respectively administered to mice in the low dose MD group and the high dose MD group. Metformin hydrochloride was given to mice in the Met group at 0.2 g/kg body weight. Equal dose solvent distilled water was administered to mice in the Nor group and the Con group by gastrogavage, once per day. All medication was lasted for 15 weeks. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were performed after 6 weeks of treatment. Beta cell function was assessed by hyperglycemic clamp technique. The morphological changes in the pancreas were evaluated by hematoxylin-eosin (HE) staining. Changes of iNOS, NF-kappaB p65, and p-NF-kappaB p65 in the pancreas were tested. Compared with the Nor group, the blood glucose level, AUC, and fasting blood insulin, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, pNF-kappaB p65 subunit obviously increased; decreased percentage of blood glucose within 40 min in ITT, glucose infusion rate (GIR), Clamp 1 min insulin, and Max-Insulin obviously decreased in the Con group (P < 0.05, P < 0.01). Compared with the Con group, the aforesaid indices could be improved in the Met group (P < 0.05, P < 0.01). In the low dose MD group, AUC, iNOS activities, and the expression of iNOS and p-NF-kappaB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT and GIR obviously increased (P < 0.05, P < 0.01). In the high dose MD group, AUC, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, and p-NF-KB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT, Max-Insulin, and GIR obviously increased (P < 0.05, P < 0.01). MD could significantly improve IR and functional disorder of 3 cells in MSG obese mice, which might be associated with lowering inflammatory reaction in the pancreas. | 25,137,853 | [
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Acetabular cup placement in navigated and non-navigated total hip arthroplasty (THA): results of two consecutive series using a cementless short stem. | Acetabular component malposition has been linked to increased rates of dislocation, impingement, pelvic osteolysis, cup migration, leg length discrepancy and polyethylene wear in patients undergoing total hip arthroplasty (THA). Compare the acetabular component positioning and the operative time in two consecutive short-stem cementless THA series without and with using an imageless navigation. The retrospective study consisted of 31 cases of short-stem cementless THA without navigation (NNAV) and 30 cases with navigation (NAV). CT scans were performed in all cases at two-month or later postoperatively. The abduction and anteversion angles measured on postoperative CT were compared between two groups using t-test. The percentage of cup placement (abduction, anteversion and combined) within the safe zone for each group was compared using Chi-square test at a 0.05 level of significance. The operative time was compared between two groups using t-test. The mean abduction was 43.97 (range, 33-52, SD 4.44) in NNAV group and 41.37 (range, 37-45, SD 2.01) in NAV group. This difference was significant (p = 0.004). The mean anteversion was 22.58 (range, 2-39, SD 10.68) in NNAV group and 13.57 (range, 7-18, SD 3.28) in NAV group. This difference was significant (p < 0.001). According to the criteria of Lewinnek et al, 96.8% in NNAV group were placed within the safe zone for abduction, 51.6% for anteversion, and 48.4% for both abduction and anteversion. In NAV group, all 30 cups (100%) were placed within the safe zone for abduction, anteversion, and both. There were significant differences in the percentage of cup placement within the safe zone for anteversion (p < 0.001), for both abduction and anteversion (p < 0.001) but not significant for abduction (p = 0.32) between two groups. The mean operative time was 107.09 and 110.67 minutes for NNAV and NAV group respectively, this difference was not significant (p = 0.49). The present study demonstrated a significant increase in the placement of acetabular cups within the safe zone using imageless navigation compared to freehand technique, especially at anteversion angle. | 25,137,880 | [
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Diagnostic properties of the STOP-Bang and its modified version in screening for obstructive sleep apnea in Thai patients. | To test the diagnostic properties of the original and a modified STOP-Bang, as well as testing the additional use of a waist-to-height ratio (WHtR) of > or = 0.55 in screening for obstructive sleep apnea (OSA) in Thai patients. Three hundred and three patients (186 males and 117 females) who underwent anthropometric measurement and standard polysomnography were asked to complete the STOP-Bang questionnaire. Subjects were considered high-risk if their scores were > or = 3. Patients with significant co-morbidities were excluded. Screening for OSA involved measurements of STOP-Bang sensitivity, specificity, positive predictive value, and negative predictive value at several apnea-hypopnea index (AHI) cut-off points. At AHI 5, these values were 87.3%, 48.1%, 82.2%, and 52.2%, respectively. At AHI 15, these values were 92.6%, 36.4%, 58.5%, and 83.6%, respectively. The modified STOP-Bang (using a cut-off of BMI > 30 kg/m2) showed slightly increased sensitivities at the AHI cut-off points of 5 and 15 with values of 88.7% and 93.2%, respectively, with improved area under the curves. Furthermore, by applying the WHtR of > or = 0.55 to those patients who were classified as high-risk by the questionnaires, the specificities for predicting OSA were improved to 85.2% and 76.1% for the aforementioned cut-off points, respectively. Both STOP-Bang and its modified version were highly sensitive measures for OSA screening in medical or dental clinics. However, the modified version might be more suitable for Thais and Asians, and the additional use of WHtR > or = 0.55 might be useful for reducing the unnecessary sleep investigation or management in those who were classified as high-risk patients. | 25,137,882 | [
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[Leukoaraiosis as a cause of non-arteritic anterior ischemic optic neuropathy--a case report]. | The paper presents the case of a 61-year-old man with specific symptoms of non-arteritic anterior ischemic optic neuropathy. The head computed tomographyscans revealed multiple leukoaraiotic lesions. Leukoaraiosis is a disease affecting small cerebral vessels. Its pathogenesis is associated with a chronic inflammatory process and ischemic vascular endothelial dysfunction which reduce the cerebral blood flow. It cannot be ruled out that this process, alongside with Horton disease, hypertension, diabetes and atherosclerosis, may also be involved in the pathogenesis of non-arteritic anterior ischemic optic neuropathy. leukoaraiosis, non-arteritic anterior ischemic optic neuropathy. | 25,137,919 | [
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[Terson syndrome--a literature review]. | Tersone syndrome was first described in 1900 as haemorrhages in the eye that occur as a consequence of intracranial hemorrhage. The main cause of the syndrome in adults is a subarachnoid hemorrhage following the rupture of intracranial aneurysm. The pathogenesis has not been fully understood. It is believed that the increase of intracranial pressure results in the hemodynamic changes in ocular vessels. Reported symptoms include decrease of visual acuity following generalized symptoms such as headache, loss of consciousness and meningealsigns. Physical examination usually reveals vitreous hemorrhage (classic Terson's syndrome) and other forms of intraocular hemorrhage. The authors reviewed the available literature on the Terson's Syndrome. Clinical presentation, pathogenesis, diagnosis, and available treatment options are presented and discussed, considering the rare occurrence of this disease. | 25,137,925 | [
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[A simple tool to measure the immediate wellbeing of elderly people in nursing homes]. | Immediate wellbeing and quality of life in an institution are of paramount importance. The assessment of the quality of life of elderly people is both complex and poorly adapted to daily practices. The instant assessment of wellbeing tool (EVIBE), developed in the field, is an original and practical alternative. This tool allows caregivers to carry out an immediate assessment and a qualitative approach with residents while involving professionals in a well-treatment approach improving daily practices. | 25,137,958 | [
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An overview of the sequence features of N- and C-terminal segments of the human chemokine receptors. | Chemokine receptors play a crucial role in the cellular signaling enrolling extracellular ligands chemotactic proteins which recruit immune cells. They possess seven trans-membrane helices, an extracellular N-terminal region with three extracellular hydrophilic loops being important for search and recognition of specific ligand(s), and an intracellular C-terminal region with three intracellular loops that couple G-proteins. Although the functional aspects of the terminal segments of the extra-and intra-cellular G proteins are universally identified, the molecular basis on which they rest are still unclear because they are not definable by means of X-rays due to their high mobility and are not easy to study in the membrane. The purpose of this work is to define which physical-chemical properties of the terminal segments of the human chemokine receptors are at the basis of their functional mechanisms. Therefore, we have evaluated their physical-chemical properties in terms of amino acid composition, local flexibility, disorder propensity, net charge distribution and putative sites of post-translational modifications. Our results support the conclusion that all 19 C-terminal and N-terminal segments of human chemokine receptors are very flexible due to the systematic presence of intrinsic disorder. Although, the purpose of this plasticity clearly appears that of controlling and modulating the binding of ligands, we provide evidence that the overlap of linearly charged stretches, intrinsic disorder and post-translational modification sites, consistently found in these motives, is a necessary feature to exert the function. The role of the intrinsic disorder has been discussed considering the structural information coming from intrinsically disordered model compounds which support the view that the chemokine terminals have to be considered as strong polyampholytes or polyelectrolytes where conformational ensembles and structural transitions between them are modulated by charge fraction variations. Also the role of post-translational modifications has been found coherent with this view because, changing the charge fraction, they guide structural transitions between ensembles. Moreover, we have also considered our results from an evolutionary point of view in order to understand if the features found in humans were also present in other species. Our data evidenced that the structural features of the human terminals of the chemokine receptors were shared and evolutionarily conserved particularly among mammals. This means that the various organisms not only tolerate but select intrinsic disorder for the terminal regions of their receptors, reflecting constraints that point to molecular recognition. In conclusion the terminal segments of chemokine receptors must be considered as strong polyampholytes where the charge fraction variations induced by post-translational modifications are the driving physico-chemical feature able to adapt the conformations of the terminal segments to their functions. | 25,138,014 | [
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Repeating pulmonary rehabilitation: prevalence, predictors and outcomes. | Pulmonary rehabilitation (PR) is a cornerstone of care in chronic respiratory diseases; yet its benefits diminish over time. Repeating PR may be beneficial; however, little is known about the characteristics and outcomes of repeaters. This study aimed to establish the proportion of repeaters, identify characteristics that predict repetition and compare the magnitude of benefits achieved between initial and subsequent programmes. Patients with stable chronic respiratory diseases who attended PR over a 9-year period were included. Outcome measures included the 6-min walk distance (6MWD) and the Chronic Respiratory Disease Questionnaire-Self-Reported (CRDQ-SR). Independent predictors of repeating were identified. Of 296 patients, 59 (20%) repeated PR, most within 1-3 years. Following the initial programme, repeaters had significant decline in 6MWD (-96.1 ± 84.6 m; P < 0.001) and CRDQ-SR scores (mean decline -3.6 points, range -0.1 to -7.9 points; P < 0.005). The improvement in 6MWD was less in the repeat programme compared with the first (38.4 ± 50.7 m vs 67 ± 40.4 m; P = 0.005), while the change in CRDQ-SR was similar in all domains. A chronic obstructive pulmonary disease diagnosis increased the odds of repeating PR (odds ratio (OR) 4.8; P = 0.005) while improved mastery in the initial programme reduced the odds (OR 0.9; P = 0.033). One in five patients repeated PR, achieving clinically significant improvements in exercise tolerance and quality of life. Patients with small improvements in disease mastery after initial PR were more likely to repeat the programme and may benefit from earlier intervention or longer duration PR. | 25,138,020 | [
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The reliability of fetal MRI in the assessment of brain malformations. | To assess the inter- and intraobserver reliability of different fetal MRI measurements in cases of fetal brain malformations and to examine the concordance between ultrasonography (US) and MRI findings. Fetal brain MRIs and US findings of 56 pregnant women were retrieved from the institutional database. Standardized fetal brain MRI measurements were performed by 4 observers, and the inter- and intraobserver reliability was determined. Additionally, US and MRI findings were retrospectively compared. The interobserver intraclass correlation coefficient (ICC) was above 0.9 for the cerebellum and posterior horn of the lateral ventricle. The measurements regarding the third ventricle (0.50), the fourth ventricle (0.58), and the corpus callosum (0.63) showed poor reliability. Overall, the intraobserver reliability was greater than the interobserver reliability. US and MRI findings were discordant in 29% of the cases with MRI rendering an extended diagnosis in 18%, a change of diagnosis in 3.6%, and excluding pathological findings suspected on US in 7.1%. Fetal MRI is a valuable complement to US in the investigation of fetal brain malformations. The reliability of most parameters was high, except for the measurements of the third and fourth ventricles and the corpus callosum. | 25,138,047 | [
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Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma. | Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid (ZOL) represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, ZOL triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), which could enhance tumor cell survival and treatment resistance. We hypothesized that targeting CLU using siRNA or the antisense drug, OGX-011, will suppress treatment-induced CLU induction and enhance ZOL-induced cell death in osteosarcoma (OS) cells. The combined effects of OGX-011 and ZOL were investigated in vitro on cell growth, viability, apoptosis and cell cycle repartition of ZOL-sensitive or -resistant human OS cell lines (SaOS2, U2OS, MG63 and MNNG/HOS). In OS cell lines, ZOL increased levels of HSPs, especially CLU, in a dose- and time-dependent manner by mechanism including increased HSF1 transcription activity. The OS resistant cells to ZOL exhibited higher CLU expression level than the sensitive cells. Moreover, CLU overexpression protects OS sensitive cells to ZOL-induced cell death by modulating the MDR1 and farnesyl diphosphate synthase expression. OGX-011 suppressed treatment-induced increases in CLU and synergistically enhanced the activity of ZOL on cell growth and apoptosis. These biologic events were accompanied by decreased expression of HSPs, MDR1 and HSF1 transcriptional activity. In vivo, OGX-011, administered 3 times a week (IP, 20mg/kg), potentiated the effect of ZOL (s.c; 50µg/kg), significantly inhibiting tumor growth by 50% and prolonging survival in MNNG/HOS xenograft model compared to ZOL alone. These results indicate that ZOL-mediated induction of CLU can be attenuated by OGX-011, with synergistic effects on delaying progression of osteosarcoma. | 25,138,053 | [
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Ranolazine as a promising treatment option for atrial fibrillation: electrophysiologic mechanisms, experimental evidence, and clinical implications. | Currently available agents for pharmacologic management of atrial fibrillation (AF) are limited by their suboptimal efficacy and nonnegligible proarrhythmic risk. Ranolazine (RN) is a novel antianginal agent with increasingly appreciated antiarrhythmic properties that can suppress ventricular and supraventricular arrhythmias including AF. In this review, we describe the electrophysiological properties of RN, focusing on atrial-selective inhibition of a number of ion channels implicated in the development of AF, particularly the sodium current. We further summarize evidence from experimental studies that demonstrate a potent AF-suppressing effect of RN, alone or in combination with other antiarrhythmic drugs. Of clinical relevance, we present growing evidence from preliminary clinical investigations indicating the safety and efficacy of RN for prevention and treatment of AF in various clinical settings including prevention of AF in patients with acute coronary syndromes, prevention and conversion of postoperative AF after surgical coronary revascularization, sinus rhythm maintenance in drug-resistant recurrent AF, and facilitating of electrical or pharmacological cardioversion in cardioversion-resistant patients. While current experimental and clinical evidence points to RN as a potentially promising agent for suppression of AF, well-designed, large-scale trials will be required before RN can be considered for pharmacological treatment of AF in clinical practice. | 25,138,058 | [
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Exsheathment and midgut invasion of nocturnally subperiodic Brugia malayi microfilariae in a refractory vector, Aedes aegypti (Thailand strain). | Exsheathment and midgut invasion of nocturnally subperiodic Brugia malayi microfilariae were analyzed using light and scanning electron microscopy in a refractory vector, Aedes aegypti (Thailand strain). Results showed that exsheathed microfilariae represented only approximately 1% of the total microfilaria midguts dissected at 5-min post-infected blood meal (PIBM). The percentage of exsheathed microfilariae found in midguts progressively increased to about 20, 60, 80, 90, and 100% at 1-, 2-5-, 6-12-, 18-36-, and 48-h PIBM, respectively. Importantly, all the microfilariae penetrating the mosquito midguts were exsheathed. Midgut invasion by the exsheathed microfilariae was observed between 2- and 48-h PIBM. SEM analysis revealed sheathed microfilariae surrounded by small particles and maceration of the microfilarial sheath in the midguts, suggesting that the midguts of the refractory mosquitoes might have protein(s) and/or enzyme(s) and/or factor(s) that induce and/or accelerate exsheathment. The microfilariae penetrated the internal face of the peritrophic matrix (PM) by their anterior part and then the midgut epithelium, before entering the hemocoel suggesting that PM was not a barrier against the microfilariae migrating towards the midgut. Melanized microfilariae were discovered in the hemocoel examined at 96-h PIBM suggesting that the refractory mosquitoes used melanization reactions against this parasite. This study provided evidence that A. aegypti (Thailand strain) has refractory mechanisms against B. malayi in both midgut and hemocoel. | 25,138,070 | [
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Inhibitory effect of plantaricin peptides (Pln E/F and J/K) against Escherichia coli. | Plantaricins are small bioactive peptides produced by Lactobacillus plantarum strains that exhibit significant antimicrobial activity against closely-related Gram-positive bacteria, including food spoilage organisms. In comparison, bacteriocins including plantaricins, are usually less effective against Gram-negative organisms. In this study, we demonstrate that heterologously expressed and purified plantaricins, Pln E, -F, -J, and -K when tested against Gram negative model organism Escherichia coli K-12 were highly effective under certain conditions. The apparent tolerance of Gram-negative members to these peptides has been explained on the basis of the presence of the outer membrane (OM) that acts as a protective barrier. We have shown that agents and/or conditions that destabilize OM of E. coli K-12, make it susceptible to plantaricin peptides. In order to further strengthen this conclusion, an OM lipoprotein-defective lpp mutant strain of E. coli K-12 was also studied and compared. A significant loss of cell viability both in terms of CFU/ml as well as with live-dead dual staining combined with flow cytometry, could be demonstrated with the lpp mutant in comparison to the wild type strain. The results indicate that plantaricins can inhibit Gram-negative bacteria if the outer-membrane is weakened and it can be used in preservation of food with the help of some food-grade chelating agents. | 25,138,074 | [
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Proteomic investigation of the hippocampus in prenatally stressed mice implicates changes in membrane trafficking, cytoskeletal, and metabolic function. | Prenatal stress influences the development of the fetal brain and so contributes to the risk of the development of psychiatric disorders in later life. The hippocampus is particularly sensitive to prenatal stress, and robust abnormalities have been described in the hippocampus in schizophrenia and depression. The aim of this study was to determine whether prenatal stress is associated with distinct patterns of differential protein expression in the hippocampus using a validated mouse model. We therefore performed a comparative proteomic study assessing female hippocampal samples from 8 prenatally stressed mice and 8 control mice. Differential protein expression was assessed using 2-dimensional difference in gel electrophoresis and subsequent mass spectrometry. The observed changes in a selected group of differentially expressed proteins were confirmed by Western blotting. In comparison to controls, 47 protein spots (38 individual proteins) were found to be differentially expressed in the hippocampus of prenatally stressed mice. Functional grouping of these proteins revealed that prenatal stress influenced the expression of proteins involved in brain development, cytoskeletal composition, stress response, and energy metabolism. Western blotting was utilized to validate the changes in calretinin, hippocalcin, profilin-1 and the signal-transducing adaptor molecule STAM1. Septin-5 could not be validated via Western blotting due to methodological issues. Closer investigation of the validated proteins also pointed to an interesting role for membrane trafficking deficits mediated by prenatal stress. Our findings demonstrate that prenatal stress leads to altered hippocampal protein expression, implicating numerous molecular pathways that may provide new targets for psychotropic drug development. | 25,138,076 | [
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Drug targeting systems for cancer therapy: nanotechnological approach. | Progress in cancer treatment remains challenging because of the great nature of tumor cells to be drug resistant. However, advances in the field of nanotechnology have enabled the delivery of drugs for cancer treatment by passively and actively targeting to tumor cells with nanoparticles. Dramatic improvements in nanotherapeutics, as applied to cancer, have rapidly accelerated clinical investigations. In this review, drug-targeting systems using nanotechnology and approved and clinically investigated nanoparticles for cancer therapy are discussed. In addition, the rationale for a nanotechnological approach to cancer therapy is emphasized because of its promising advances in the treatment of cancer patients. | 25,138,089 | [
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Bioinspired design and assembly of layered double hydroxide/poly(vinyl alcohol) film with high mechanical performance. | Inspired by the hierarchical structure and excellent mechanical performance of nacre, LDH nanosheets with an appropriate aspect ratio to withstand significant loads and at the same time allow for rupture under the pull-out mode were synthesized as artificial building blocks for the fabrication of nacre-like films. Multilayered PVA/LDH films with a high tensile strength and ductility were prepared for the first time by bottom-up layer-by-layer assembly of pretreated LDH nanosheets and spin-coating of PVA. The weight fraction of inorganic LDH platelets in the hybrid PVA/LDH films (wp) was controlled by changing the concentration of PVA solution applied in the spin-coating process. The resulting films revealed that the PVA/LDH hybrid films were piled close together to form a well-defined stratified structure resembling the brick-and-mortar structure of natural nacre. In the hybrid films, the content of inorganic LDH platelets was comparable to the value in nacre, up to 96.9 wt %. It could be clearly seen that the mechanical performance of the as-prepared PVA/LDH films was greatly improved by increasing the rigid building-block LDHs. The tensile strength of the 2 wt % PVA/LDH hybrid film reached a value of 169.36 MPa, thus exceeding the strength of natural nacre and reaching 4 times that of a pure PVA film. Meanwhile, its elastic modulus was comparable to that of lamellar bone. | 25,138,146 | [
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Vocal fold paresis accompanying vocal fold polyps. | The aim of this study was to evaluate patients with vocal fold polyps using laryngeal electromyography (LEMG) for the presence of vocal fold paresis and to compare transnasal fiberoptic and rigid stroboscopic findings between polyp patients with normal LEMG and with vocal fold paresis. Thirty-five patients with a vocal fold polyp underwent transnasal fiberoptic laryngoscopy, rigid laryngostroboscopy, and LEMG. The findings were compared between the LEMG-confirmed vocal fold paresis patients and the normal LEMG patients. LEMG resulted in a diagnosis of unilateral or bilateral vocal fold paresis in 17 of 35 patients (48.6 %). More men than women with vocal fold polyps had vocal fold paresis (p < 0.05). The vocal fold paresis group had higher presence of axial rotation and hypomobility of vocal folds, higher asymmetry of vertical height of vocal folds, and less presence of longitudinal stretch of vocal folds (p < 0.05). Medial-lateral compression of the false vocal folds and anterior-posterior approximation of the larynx did not show any difference between the groups. No significant difference was found in vibratory wave characteristics between the groups through rigid laryngostroboscopy. Vocal fold paresis was present in almost half of the patients with vocal fold polyps. Paresis can only be accurately diagnosed with LEMG. Transnasal fiberoptic laryngoscopic examination is helpful to recognize vocal fold paresis in vocal fold polyp patients, while stroboscopic examination is not useful to identify it in vocal fold polyp patients. | 25,138,152 | [
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The CAP1/Prss8 catalytic triad is not involved in PAR2 activation and protease nexin-1 (PN-1) inhibition. | Serine proteases, serine protease inhibitors, and protease-activated receptors (PARs) are responsible for several human skin disorders characterized by impaired epidermal permeability barrier function, desquamation, and inflammation. In this study, we addressed the consequences of a catalytically dead serine protease on epidermal homeostasis, the activation of PAR2 and the inhibition by the serine protease inhibitor nexin-1. The catalytically inactive serine protease CAP1/Prss8, when ectopically expressed in the mouse, retained the ability to induce skin disorders as well as its catalytically active counterpart (75%, n=81). Moreover, this phenotype was completely normalized in a PAR2-null background, indicating that the effects mediated by the catalytically inactive CAP1/Prss8 depend on PAR2 (95%, n=131). Finally, nexin-1 displayed analogous inhibitory capacity on both wild-type and inactive mutant CAP1/Prss8 in vitro and in vivo (64% n=151 vs. 89% n=109, respectively), indicating that the catalytic site of CAP1/Prss8 is dispensable for nexin-1 inhibition. Our results demonstrate a novel inhibitory interaction between CAP1/Prss8 and nexin-1, opening the search for specific CAP1/Prss8 antagonists that are independent of its catalytic activity. | 25,138,159 | [
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Pepper: cytoscape app for protein complex expansion using protein-protein interaction networks. | We introduce Pepper (Protein complex Expansion using Protein-Protein intERactions), a Cytoscape app designed to identify protein complexes as densely connected subnetworks from seed lists of proteins derived from proteomic studies. Pepper identifies connected subgraph by using multi-objective optimization involving two functions: (i) the coverage, a solution must contain as many proteins from the seed as possible, (ii) the density, the proteins of a solution must be as connected as possible, using only interactions from a proteome-wide interaction network. Comparisons based on gold standard yeast and human datasets showed Pepper's integrative approach as superior to standard protein complex discovery methods. The visualization and interpretation of the results are facilitated by an automated post-processing pipeline based on topological analysis and data integration about the predicted complex proteins. Pepper is a user-friendly tool that can be used to analyse any list of proteins. Pepper is available from the Cytoscape plug-in manager or online (http://apps.cytoscape.org/apps/pepper) and released under GNU General Public License version 3. | 25,138,169 | [
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Comparison of bivalirudin and heparin in patients undergoing rotational atherectomy: a subanalysis of the randomised ROTAXUS trial. | Bivalirudin has emerged as a meaningful alternative to heparin in patients undergoing percutaneous coronary intervention (PCI). To date, it is unclear whether bivalirudin has advantages in patients undergoing rotational atherectomy (RA). The current subgroup analysis of the ROTAXUS trial compared patients receiving bivalirudin (n=129) to those receiving unfractionated heparin (UFH) (n=111). Efficacy was assessed by the frequency of periprocedural myocardial infarction (MI) and safety by the frequency of major access-site bleeding (ASB). Baseline characteristics were similar. Periprocedural MI occurred less frequently in the bivalirudin group (22% vs. 37.5%, p=0.02), while ASB did not differ significantly (2.3% vs. 5.5%, p=0.20). This effect was larger in the RA group, where bivalirudin significantly reduced periprocedural MI (15.7% vs. 38.7%, p=0.01) with a trend towards reduced major ASB (2.9% vs. 10.2%, p=0.09). In the control group without RA, bivalirudin was not superior to UFH regarding periprocedural MI (28.6% vs. 36.6%, p=0.42) and major ASB (1.7% vs. 1.7%, p=0.99). This analysis suggests a differential benefit of bivalirudin in patients treated with RA. Patients receiving bivalirudin during RA showed significantly less periprocedural MI and fewer ASB compared to patients treated with UFH. | 25,138,183 | [
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Hospice Comics: Representations of Patient and Family Experience of Illness and Death in Graphic Novels. | Non-fiction graphic novels about illness and death created by patients and their loved ones have much to teach all readers. However, the bond of empathy made possible in the comic form may have special lessons for healthcare providers who read these texts and are open to the insights they provide. | 25,138,207 | [
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Waveband selection of reagent-free determination for thalassemia screening indicators using Fourier transform infrared spectroscopy with attenuated total reflection. | A reagent-free determination method for the thalassemia screening indicators hemoglobin (Hb), mean corpuscular Hb (MCH), and mean corpuscular volume (MCV) was developed based on Fourier transform infrared spectrometers equipped with an attenuated total reflection accessory. A random and stability-dependent rigorous process of calibration, prediction, and validation was conducted. Appropriate wavebands were selected using the improved moving window partial least squares method with stability and equivalence. The obtained optimal wavebands were 1722 to 1504 cm⁻¹ for Hb, 1653 to 901 cm⁻¹ for MCH, and 1562 to 964 cm⁻¹ for MCV. A model set equivalent to the optimal model was proposed for each indicator; the public waveband of Hb equivalent wavebands was 1717 to 1510 cm⁻¹, and the public equivalent waveband for MCH and MCV was 1562 to 901 cm⁻¹. All selected wavebands were within the MIR fingerprint region and achieved high validation effects. The sensitivity and specificity were 100.0% and 96.9% for the optimal wavebands and 100.0% and 95.3% for the equivalent wavebands, respectively. Thus, the spectral prediction was highly accurate for determining negative and positive for thalassemia screening. This technique is rapid and simple in comparison with conventional methods and is a promising tool for thalassemia screening in large populations. | 25,138,209 | [
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Secretoneurin as a marker for hypoxic brain injury after cardiopulmonary resuscitation. | The neuropeptide secretoneurin (SN) shows widespread distribution in the brain. We evaluated whether SN is elevated after cardiopulmonary resuscitation (CPR) and could serve as a potential new biomarker for hypoxic brain injury after CPR. This was a prospective observational clinical study. All patients admitted to a tertiary medical intensive care unit after successful CPR with expected survival of at least 24 h were consecutively enrolled from September 2008 to April 2013. Serum SN and neuron-specific enolase were determined in 24 h intervals starting with the day of CPR for 7 days. Neurological outcome was assessed with the Cerebral Performance Categories Scale (CPC) at hospital discharge. A total of 134 patients were included with 49 % surviving to good neurological outcome (CPC 1-2). SN serum levels peaked within the first 24 h showing on average a sixfold increase above normal. SN levels were significantly higher in patients with poor (CPC 3-5) than in patients with good neurological outcome [0-24 h: 75 (43-111) vs. 38 (23-68) fmol/ml, p < 0.001; 24-48 h: 45 (24-77) vs. 23 (16-39) fmol/ml, p < 0.001]. SN determined within the first 48 h showed a receiver operating characteristic (ROC) area under the curve (AUC) of 0.753 (0.665-0.841). NSE in the first 72 h had a ROC-AUC of 0.881 (0.815-0.946). When combining the two biomarkers an AUC of 0.925 (0.878-0.972) for outcome prediction could be reached. SN is a promising early biomarker for hypoxic brain injury. Further studies will be required for confirmation of these results. | 25,138,227 | [
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Impaired left atrial function in heart failure with preserved ejection fraction. | Left atrial (LA) enlargement is present in the majority of heart failure with preserved ejection fraction (HFpEF) patients and is a marker of risk. However, the importance of LA function in HFpEF is less well understood. The PARAMOUNT trial enrolled HFpEF patients (LVEF ≥45%, NT-proBNP >400 pg/mL). We assessed LA reservoir, conduit, and pump function using two-dimensional volume indices and speckle tracking echocardiography in 135 HFpEF patients in sinus rhythm at the time of echocardiography and 40 healthy controls of similar age and gender. Systolic LA strain was related to clinical characteristics and measures of cardiac structure and function. Compared with controls, HFpEF patients had worse LA reservoir, conduit, and pump function. The differences in systolic LA strain (controls 39.2 ± 6.6% vs. HFpEF 24.6 ± 7.3%) between groups remained significant after adjustments and even in the subsets of HFpEF patients with normal LA size or without a history of AF. Among HFpEF patients, lower systolic LA strain was associated with higher prevalence of prior HF hospitalization and history of AF, as well as worse LV systolic function, and higher LV mass and LA volume. However, NT-proBNP and E/E' were similar across the quartiles of LA function. In this HFpEF cohort, we observed impairment in all phases of LA function, and systolic LA strain was decreased independent of LA size or history of AF. LA dysfunction may be a marker of severity and play a pathophysiological role in HFpEF. NCT00887588. | 25,138,249 | [
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Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ hydrogel based on poloxamer 407 and carrageenan. | The objective of this study was to construct a new in situ gel system based on the combination of poloxamer 407 and carrageenan (carrageenan-poloxamer 407 hydrogel, CPH) for intranasal delivery of ketorolac tromethamine. CPH showed potassium ion concentration - dependent erosion characteristics which ensured slow erosion in aqueous environment containing potassium ion at the physiological level. Loading with ketorolac tromethamine influenced erosion, drug release and thermosensitive properties of CPH. CPH containing 15% ketorolac tromethamine showed suitable gelation temperature (near 35°C) and in vitro sustained release profiles. Pharmacokinetic study of intranasal CPH containing 15% ketorolac tromethamine in rats demonstrated enhanced absolute bioavailability (68.8 ± 23.3%) and prolonged mean residence time (8.8 ± 3.5h) in comparison with the intranasal solution group (24.8 ± 13.8%, 3.9 ± 0.6h). Nasal ciliotoxicity evaluation on an in situ toad palate model preliminarily showed the safety of CPH for intranasal use. All results suggested the potential of CPH as a new sustained - release platform for the intranasal delivery of ketorolac tromethamine. | 25,138,250 | [
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Amorphous isradipine nanosuspension by the sonoprecipitation method. | The aims of this study are to increase and explain the mechanism of dissolution enhancement of isradipine using the sonoprecipitation method for stable nanosuspensions. There have been still few of published researches on formulation of isradipine using nanoparticle engineering. Nanosuspension systems were prepared upon various factors including amplitude and the time length of ultrasonication. The dissolution test was performed according to the USP paddle method in intestinal fluid (pH 6.8). The crystalline structure of drug, the molecular interaction, morphology and size of nanosuspension were also investigated to determine the mechanism of dissolution enhancement. The sonoprecipitation method with use of HPMC 6 showed its potential in enhancement of the drug release rate. Stable nanosuspension was significantly depended on amplitude and time of ultrasonication since these factors affected on the size of nanoparticles. The synergistic effects of reduction of drug crystallinity and particle size could increase the dissolution rate of isradipine by providing a stable nanosuspension. This work may contribute to a new strategy for improvement dissolution rate of isradipine. | 25,138,256 | [
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Why did the proton cross the road? Humour and science communication. | The use of humour in public discourse about science has grown remarkably over the past few years, and when used in science communication activities is being seen as a great way to bring science to the public through laughter. However, barely any research has been published either on the often-assumed beneficial learning effects of humour in informal science education, or on the wider social functions and effects of humour about science and how humorous public discourse about science can influence the public understanding of science and the science-society relationship. This research note reviews some of the literature on the psychology and sociology of humour and comedy and tries to apply some of its insights to the effects humour might have when used in science communication. Although not intended to be anti-humour, this note attempts at least to start a more critical conversation on the value of humour in the communication of science. | 25,138,269 | [
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Etanercept restores normal insulin signal transduction in β2-adrenergic receptor knockout mice. | Inhibition of TNFα protects the retina against diabetic-like changes in rodent models. The mechanism by which TNFα induces deleterious retinal changes is not known. Previously, we have shown that TNFα can inhibit normal insulin signal transduction, leading to increased apoptosis in both retinal endothelial cells (REC) and Müller cells. Additionally, β2-adrenergic receptor knockout mice (β2KO) have increased TNFα levels and decreased insulin receptor activity. In this study, we hypothesized that inhibition of TNFα in β2KO mice would increase normal insulin signaling, leading to improved retinal function. C57BL6 or β2KO mice were left untreated or treated with etanercept (0.3 mg/kg subcutaneously, 3× a week) for 2 months. Electroretinogram analyses were done before treatment was initiated and after two months of treatment with etanercept on all mice. Western blot or ELISA analyses were done on whole retinal lysates from all four groups of mice for TNFα, suppressor of cytokine signaling 3 (SOCS3), insulin receptor, and apoptotic proteins. Etanercept significantly reduced TNFα levels in β2KO mice, leading to increased insulin receptor phosphorylation on tyrosine 1150/1151. SOCS3 levels were increased in β2KO mice, which were reduced after etanercept treatment. Pro-apoptotic proteins were reduced in etanercept-treated β2KO mice. Etanercept improved ERG amplitudes in β2KO mice. Inhibition of TNFα by etanercept protects the retina likely through reduced TNFα-mediated insulin resistance, leading to reduced apoptosis. | 25,138,272 | [
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Agar-supported cultivation of Halorubrum sp. SSR, and production of halocin C8 on the scale-up prototype Platotex. | Halorubrum sp. SSR was isolated from a solar saltern in Algeria. The strain exhibited a high antibiotic activity against the indicator strain Natronorubrum aibiense G23, and the bioactive compound showed thermal, acid and alkali stability. SSR was grown on agar-supported cultivation (AgSF) to compare yields and applicability with traditional submerged cultivation. AgSF scale-up was implemented taking benefit from the solid-state cultivation prototype Platotex. This technology leads to high amounts of the target Halocin and facilitate the downstream steps. The antibiotic compound was purified according to a fast efficient procedure including ion exchange chromatography followed by a fractionation on C18 Sep-Pack cartridge. The compound was identified as Halocin C8 according to N-terminal amino acid sequencing and high-resolution mass spectrometry. | 25,138,277 | [
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Dual role of Tlx3 as modulator of Prrxl1 transcription and phosphorylation. | The proper establishment of the dorsal root ganglion/spinal cord nociceptive circuitry depends on a group of homeodomain transcription factors that includes Prrxl1, Brn3a and Tlx3. By the use of epistatic analysis, it was suggested that Tlx3 and Brn3a, which highly co-localize with Prrxl1 in these tissues, are required to maintain Prrxl1 expression. Here, we report two Tlx3-dependent transcriptional mechanisms acting on Prrxl1 alternative promoters, referred to as P3 and P1/P2 promoters. We demonstrate that (i) Tlx3 induces the transcriptional activity of the TATA-containing promoter P3 by directly binding to a bipartite DNA motif and (ii) it synergistically interacts with Prrxl1 by indirectly activating the Prrxl1 TATA-less promoters P1/P2 via the action of Brn3a. The Tlx3 N-terminal domain 1-38 was shown to have a major role on the overall Tlx3 transcriptional activity and the C-terminus domain (amino acids 256-291) to mediate the Tlx3 effect on promoters P1/P2. On the other hand, the 76-111 domain was shown to decrease Tlx3 activity on the TATA-promoter P3. In addition to its action on Prrxl1 alternative promoters, Tlx3 proved to have the ability to induce Prrxl1 phosphorylation. The Tlx3 domain responsible for Prrxl1 hyperphosphorylation was mapped and encompasses amino acid residues 76 to 111. Altogether, our results suggest that Tlx3 uses distinct mechanisms to tightly modulate Prrxl1 activity, either by controlling its transcriptional levels or by increasing Prrxl1 phosphorylation state. | 25,138,281 | [
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Enrichment options for African painted dogs (Lycaon pictus). | Best practices for carnivore enrichment encourage the diversity of species-typical behaviors, increased activity, and reduced stereotypic behavior; ideally considering the life-history and behavior of each species. African wild dogs (Lycaon pictus), or painted dogs, are social carnivores that have large home ranges and complex pack dynamics (e.g., variation in group size, relatedness, etc.). As there are relatively few studies on painted dog enrichment, the goal of this study was to compile a list of enrichment options used by institutions participating in the species survival plan (SSP). Representatives were asked to describe social groups (n = 45), enclosures (n = 21), enrichment practices (options, delivery frequency, perceived success), and overall best practices. Respondents (61%, n = 23) reported using options for all six enrichment categories recommended by the Canid Taxon Advisory Group: environmental enrichment devices, habitat, sensory, food, behavioral, and social. Perceived success was significantly higher for the food category, followed by the sensory and behavioral categories. All respondents reported delivering enrichment at least multiple times a month, and most reported multiple times per week. Enclosure size did not differ significantly for mixed-sex groups (n = 28) compared to single-sex groups (n = 17). We discuss respondents' suggestions for best practices and the need to record data to compare perceived success with actual behavioral effects, controlling for variation in group size and composition. Overall, respondents recommended a flexible approach, since not all painted dogs and groups respond in the same way to the enrichment options. | 25,138,282 | [
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Evaluation and validation of a serum bactericidal antibody assay for Haemophilus influenzae type b and the threshold of protection. | Prior to routine immunisation, Haemophilus influenzae serotype b (Hib) was a major cause of serious bacterial infections, particularly in young children. In the United Kingdom, introduction of the Hib conjugate vaccine into the national childhood immunisation schedule has led to a sustained decline in invasive Hib disease across all age-groups. Evaluation of the immune response to Hib conjugate vaccines involves measurement of serum IgG antibodies against the capsular polyribosyl-ribitol-phosphate (PRP) polysaccharide by enzyme-linked immunosorbent assay (ELISA), with accepted short-term and long-term protective thresholds of ≥0.15μg/mL and ≥1.0μg/mL, respectively. These levels were derived by passive immunisation or immunisation with pure polysaccharide, and their relevance for protection following immunisation with conjugate vaccines remains unclear. This study aimed to modify and optimise a serum bactericidal antibody (SBA) assay to evaluate the functional activity of Hib antibodies generated following Hib conjugate vaccination. Validation of the Hib SBA assay was deemed acceptable for all assay parameters tested. A strong correlation between anti-PRP IgG concentrations and SBA titres was observed in vaccinated adults (r=0.81), as well as infants after primary immunisation at 2, 3, and 4 months (r=0.635) and after the 12-month booster (r=0.746). The assay identified some children with high anti-PRP IgG but low SBA activity and vice versa. The predictive protective SBA titre corresponding to a post-booster anti-PRP IgG of 1.0μg/mL was 8. Thus, the optimised Hib SBA assay was specific and reproducible and correlated with anti-PRP IgG. Such assays may have a role in evaluating immune responses to conjugate vaccines in addition to measuring capsular antibodies. | 25,138,290 | [
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Temporary replacement of missing maxillary lateral incisors with orthodontic miniscrew implants in growing patients: rationale, clinical technique, and long-term results. | The missing maxillary lateral incisor in adolescent patients presents an orthodontic challenge. Historically, there have been three treatment options to address this clinical problem: (1) canine substitution, (2) tooth auto-transplantation, and (3) dental restoration. Unfortunately, these methods are not without limitation. A novel treatment concept, originating in 2003 and utilizing orthodontic miniscrew implants, is presented along with the rationale, clinical technique and 8 years of follow-up. | 25,138,368 | [
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... |
Translational mini-screw implant research. | It is important to thoroughly test new materials as well as techniques when these innovations are to be utilized in the human clinical situation. Translational research fills this important niche. The purpose of translational research is to establish the continuity of evidence from the laboratory to the clinic and in so-doing, provide evidence that the material is functioning appropriately and that the process in the human will be successful. This concept applies to the mini-screw implant; which, has been very successfully introduced into the orthodontic armamentarium over the last decade for application as a temporary anchorage device. The examples of translational research that will be illustrated in this paper have paved the way to ensure that clinicians have evidence to confidently utilize mini-screw implants in orthodontic practice. Needless to say, more studies are needed to ensure a safe, effective and efficient manner to practice orthodontics. | 25,138,369 | [
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Non-HLA genes PTPN22, CDK6 and PADI4 are associated with specific autoantibodies in HLA-defined subgroups of rheumatoid arthritis. | Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serves as a helpful discriminator in genetic studies and today anti-citrullinated cyclic peptide (anti-CCP) antibody positivity is employed for diagnosis of disease. The HLA-DRB1 locus is known as the most important genetic contributor for the risk of RA, but is not sufficient to drive autoimmunity and additional genetic and environmental factors are involved. Hence, we addressed the association of previously discovered RA loci with disease-specific autoantibody responses in RA patients stratified by HLA-DRB1*04. We investigated 2178 patients from three RA cohorts from Sweden and Spain for 41 genetic variants and four autoantibodies, including the generic anti-CCP as well as specific responses towards citrullinated peptides from vimentin, alpha-enolase and type II collagen. Our data demonstrated different genetic associations of autoantibody-positive disease subgroups in relation to the presence of DRB1*04. Two specific subgroups of autoantibody-positive RA were identified. The SNP in PTPN22 was associated with presence of anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Cochran-Mantel-Haenszel test P = 0.0001, P corrected <0.05), whereas SNPs in CDK6 and PADI4 were associated with anti-CCP status in DRB1*04 negative patients (Cochran-Mantel-Haenszel test P = 0.0004, P corrected <0.05 for both markers). Additionally we see allelic correlation with autoantibody titers for PTPN22 SNP rs2476601 and anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02) and between CDK6 SNP rs42041 and anti-CCP in non-carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02). These data point to alternative pathways for disease development in clinically similar RA subgroups and suggest an approach for study of genetic complexity of disease with strong contribution of HLA. | 25,138,370 | [
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... |
Early erythropoietin in post-diarrheal hemolytic uremic syndrome: a case-control study. | Although erythropoietin (EPO) deficiency has been reported in children with post-diarrheal hemolytic uremic syndrome (D + HUS), very limited clinical data on EPO use in this disease are currently available. In this case-control study we examined whether EPO administration would reduce the number of red blood cell (RBC) transfusions in D + HUS patients under our care. Data from children treated exclusively with RBC transfusions (controls; n = 21) were retrospectively compared with data on those who also received EPO for the treatment of anemia (cases; n = 21). Both patient groups were similar in age (p = 0.9), gender (p = 0.12), weight (p = 1.00) and height (p = 0.66). Acute phase severity was also comparable, as inferred by the need for dialysis (p = 0.74), the duration of dialysis (p = 0.3), length of hospitalization (p = 0.81), presence of severe bowel (p = 1.00) or neurological injury (p = 0.69), arterial hypertension (p = 1.00) and death (p = 1.00). No differences in the hemoglobin level at admission (p = 0.51) and discharge (p = 0.28) were noted. Three children treated with EPO and two controls did not require any RBC transfusion (p = 1.00). Median number of RBC transfusions needed by cases and controls was 2 (p = 0.52). Treatment with EPO did not reduce the number of RBC transfusions in D + HUS children. Assessment of EPO efficacy in D + HUS merits further studies. | 25,138,373 | [
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0.03954582,
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Hematologic findings predictive of bone marrow disease in dogs with multicentric large-cell lymphoma. | Evaluation of the bone marrow is needed for complete staging in dogs with multicentric large-cell lymphoma, but is often omitted in clinical practice. The objective was to determine if routine peripheral blood findings, including microscopic evaluation of blood smears, can predict the presence of bone marrow involvement in dogs with lymphoma. Hematologic data including evaluation of blood smears and bone marrow aspirates from 107 dogs newly diagnosed with large-cell lymphoma were retrospectively evaluated. Neoplastic lymphocytes were identified based on cell size, nuclear size, chromatin pattern, and the presence of nucleoli. Positive specimens were defined as having ≥ 10% neoplastic lymphocytes. Two groups were established based on the presence or absence of lymphoma in the bone marrow. Variables (positive blood smear, HCT, platelet count, and total and differential WBC counts) were evaluated to determine if they were predictive of bone marrow involvement using univariate and multivariate logistic models. Thrombocytopenia and the presence of > 10% neoplastic lymphocytes on blood smears were identified as significant variables for predicting the presence of bone marrow involvement. When considered independently, either a positive blood smear or thrombocytopenia had low sensitivity (60%) and moderate specificity (89% and 87%, respectively). Sensitivity increased when these variables were evaluated together (80%). In dogs with multicentric large-cell lymphoma, thrombocytopenia or the presence of neoplastic lymphocytes in circulation is suggestive of bone marrow involvement, but not definitive. Normal peripheral blood findings do not exclude the possibility of lymphoma in the bone marrow. | 25,138,384 | [
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Age-related pattern and monocyte-acquired haemozoin associated production of erythropoietin in children with severe malarial anaemia in Ghana. | Malaria continues to be a global health challenge, affecting more than half the world's population and causing approximately 660,000 deaths annually. The majority of malaria cases are caused by Plasmodium falciparum and occur in sub-Saharan Africa. One of the major complications asscociated with malaria is severe anaemia, caused by a cycle of haemoglobin digestion by the parasite. Anaemia due to falciparum malaria in children has multifactorial pathogenesis, which includes suppression of bone marrow activity. Recent studies have shown that haemozoin, which is a by-product of parasite haemoglobin digestion, may play an important role in suppression of haemoglobin production, leading to anaemia. In this study we correlated the levels of erythropoietin (EPO), as an indicator of stimulation of haemoglobin production, to the levels of monocyte acquired haemozoin in children with both severe and uncomplicated malaria. There was a significantly negative correlation between levels of haemozoin-containing monocytes and EPO, which may suggest that haemozoin suppresses erythropoiesis in severe malaria. A multiple linear regression analysis and simple bar was used to investigate associations between various haematological parameters. To examine the levels of erythropoietin in the age categories, the levels of erythropoietin was measured using a commercial Enyme-Linked Immunosorbent Assay (ELISA). Giemsa-stained blood smears were used to determine percentage pigment containing monocytes. The haemozoin containing monocytes was expressed as a percentage of the total number of monocytes. To obtain the number of haemozoin containing monocytes/μL the percentage of haemozoin containing monocytes was multiplied by the absolute number of monocytes/μL from the automated haematology analyzer. The levels of erythropoietin in younger children (<3 years) was significantly higher than in older children with a similar degree of malaria anaemia (Hb levels) (p < 0.005). Haemozoin-containing monocytes were relatively higher in severe malaria anaemia patients compared to those with uncomplicated malaria (p < 0.001). Age purportedly has a direct effect on background levels of erythropoietin. With corresponding decreased levels of erythropoietin in older children with the same degree of severe malarial anaemia, conceivably, the bone marrows of younger children with acute malaria may be less sensitive to erythropoietin. | 25,138,388 | [
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... |
[Citation analysis of research articles from Norwegian health enterprises, 2005-2011]. | The citation frequency of a publication is often interpreted as an expression of its scientific impact. Previous citation analyses of Norwegian medical research have either focused on universities and university hospitals or on subject areas at the national level. Such analyses have paid little attention to other health enterprises, despite a strong increase in their research activity during the last decade. For all health enterprises with more than 25 publications in the Web of Science during the period 2005-2011 we have calculated field normalized citation indexes at the institution and subject levels. On the whole, research undertaken by the health enterprises is frequently cited, and some medium-sized health enterprises stand out in terms of their high average citation indexes: Helse Stavanger Health Enterprise, Diakonhjemmet Hospital and Helse Nord-Trøndelag Health Enterprise, although Oslo University Hospital Health Enterprise and Helse Bergen Health Enterprise account for more than half of the most cited articles. In citation analyses at the aggregated level, highly and infrequently cited research groups/departments may balance each other. This appears to be the case in the largest health enterprises. Some medium-sized health enterprises that have a more concentrated research portfolio will thus accumulate higher average citation indexes than the largest university hospitals. | 25,138,404 | [
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Molecular imaging to predict ventricular arrhythmia in heart failure. | Ventricular tachycardia (VT) is a major cause of sudden cardiac death (SCD) in patients with heart failure (HF). Left ventricular ejection fraction (LVEF) and heart failure class according to the New York Heart association (NYHA) are in most common use to identify patients that may benefit from implantable cardioverter defibrillator (ICD) therapy. But during 3 years of follow up only 35% of patients receive appropriate ICD action. Therefore, there is a continued need for refinement of selection criteria for ICD implantation. In this regard, molecular imaging of the autonomic nervous system, which plays a central role in HF progression and cardiac electro-mechanical regulation, can make a substantial contribution. This article reviews the currently available literature concerning the value of molecular neuronal cardiac imaging for prediction of ventricular arrhythmias in HF patients. | 25,138,427 | [
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Pathologic changes associated with suspected hypovitaminosis A in amphibians under managed care. | Vitamin A deficiency is a recently recognized nutritional disease in amphibians fed insect-based diets. The classic pathologic lesion that has been associated with hypovitaminosis A in amphibians is squamous metaplasia of the lingual and oral mucosa. In an attempt to further characterize the range of lesions that may be associated with vitamin A deficiency, we reviewed archived amphibian necropsy reports from three facilities. As previously reported, the tongue was the most commonly affected site in animals presenting with squamous metaplasia. However, metaplastic changes were also observed in a variety of locations that included the oral cavity, nasal cavity, pharynx, esophagus, stomach, cloaca, skin, urinary bladder, ureter, and reproductive tract. In addition, species and age-specific differences were noted in the development of squamous metaplasia. This review highlights the need to establish standardized guidelines for optimal postmortem tissue sampling of amphibians in order to maximize the accurate diagnosis of pathologic lesions that may be associated with hypovitaminosis A. Zoo Biol. 33:508-515, 2014. © 2014 Wiley Periodicals Inc. | 25,138,440 | [
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