title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Hepatitis C virus genotype distribution in Turkey remains unchanged after a decade: performance of phylogenetic analysis of the NS5B, E1, and 5'UTR regions in genotyping efficiency. | Hepatitis C virus (HCV) genotyping has a considerable effect on therapy. The aim was to determine the change in prevalence of HCV genotypes in Turkey during the last decade and to compare the performance of DNA sequencing of different targets in the HCV genome (NS5B, E1, and 5'UTR). Five hundred HCV RNA-positive patients (226 males, 274 females) were included in the study. The NS5B, E1, and 5'UTR regions of the HCV genome were amplified by polymerase chain reaction (PCR) in patients where possible. Amplified PCR products were sequenced directly, and phylogenetic analysis was performed. A commonly used database, namely www.hcv.lanl.gov, was also used to determine the genotypes. Phylogenetic analysis of the NS5B, E1, and 5'UTR regions showed that 1b was the most frequent genotype, with percentages of 92.5%, 93.5%, and 87.7%, respectively. Genotype 1a was the second most prevalent genotype, with ratios of 6.7%, 5.6%, and 6.6%, whereas genotype 2a was detected in proportions of 0.4%, 0.2%, and 0.8%, respectively. Genotype 5 or 6 was not detected among patients. The phylogenetic analysis showed discordant results with 18 patients' genotypes for different targets. The phylogenetic analysis showed similar results with the hcv.lanl.gov database for the E1 and NS5B sequences. There has been no change in genotyping profiles of Turkey during the last decade, representing 1b as the most prevalent subtype, followed by 1a. Phylogenetic analysis of HCV indicated high performance compared with the hcv.lanl.gov database when sequences of E1 and NS5B regions were analyzed. | 25,254,523 | [
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Treatment with a combination of bosentan and sildenafil allows for successful liver transplantation in a patient with portopulmonary hypertension. | Pulmonary arterial hypertension (PAH) that occurs in the setting of cirrhosis and portal hypertension is referred to as portopulmonary hypertension (PPHTN). Liver transplantation (LTx) is curative, but the presence of moderate-to-severe PPHTN may be a contraindication for transplantation because of the elevated risk of peri- and post-transplantation morbidity and mortality. We report a successful liver transplantation in a patient with liver cirrhosis after treatment of moderate-to-severe PPHTN with a combination of the dual endothelin receptor antagonist bosentan and the specific phosphodiesterase-5 inhibitor sildenafil. | 25,254,528 | [
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Immunolocalization of corticotropin-releasing hormone (CRH) and its receptors (CRHR1 and CRHR2) in human endometrial carcinoma: CRHR1 as a potent prognostic factor. | Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2). CRH, CRHR1, and CRHR2 have recently been reported in several types of carcinoma, but the significance of these proteins has remained largely unknown in human endometrial carcinoma. A total of 87 endometrial carcinoma specimens were obtained from Japanese female patients who underwent surgical treatment, fixed in 10% formalin, and embedded in paraffin wax. Immunohistochemistry for CRH, CRHR1, and CRHR2 was performed, and clinical data were obtained from the medical records. Immunopositivity of CRH, CRHR1, and CRHR2 in the specimens was 26%, 15%, and 10%, respectively. Univariate analysis revealed that immunohistochemical CRH status was positively associated with CRHR1 and CRHR2 status and that CRHR1 status was significantly associated with the risk of recurrence and poorer clinical outcome, whereas CRHR2 status was marginally associated with better prognosis for overall survival. Multivariate analysis demonstrated CRHR1 status as an independent prognostic factor for both disease-free and overall survival. These results suggest that intratumoral CRH-CRHR1 signaling plays an important role in the progression of endometrial carcinoma and that CRHR1 is a potent prognostic factor in patients with this disease. | 25,254,562 | [
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The association of direct thrombin inhibitor anticoagulants with cardiac thromboses. | Direct thrombin inhibitor (anti-factor IIa) anticoagulants, now established for treatment and prevention of cardiac thromboembolism and VTE, have been repeatedly associated with a significantly increased frequency of thrombosis on abnormal cardiac endothelium when compared head-to-head with indirectly acting therapeutic anticoagulants in studies of sufficient patient number and duration. Although there is uncertainty as to the mechanism, the weight of evidence as a class effect warrants prescribing effective anticoagulants other than direct thrombin inhibitors. | 25,254,608 | [
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Suicide by gases in England and Wales 2001-2011: evidence of the emergence of new methods of suicide. | Increases in suicide deaths by gassing, particularly carbon monoxide poisoning from burning barbecue charcoal, have occurred in many parts of East Asia and resulted in rises in overall suicide rates in some countries. Recent trends in gas poisoning suicides outside Asia have received little attention. We analysed suicides by gassing in England and Wales (2001-2011) using national suicide mortality data enhanced by free text searching of information sent by coroners to the Office for National Statistics (ONS). We conducted specific searches for suicides involving barbecue charcoal gas, helium, and hydrogen sulphide. We analysed coroners' records of eight people who used helium as a method of suicide, identified from systematic searches of the records of four coroners. Gassing accounted for 5.2% of suicide deaths in England and Wales during 2001-2011. The number of gas suicides declined from 368 in 2001 to 174 by 2011 (a 53% reduction). The fall was due to a decline in deaths involving car exhaust and other sources of carbon monoxide. There was a rapid rise in deaths due to helium inhalation over the period, from five deaths in the two year period 2001-2002 to 89 in 2010-2011 (a 17-fold increase). There were small rises in deaths involving hydrogen sulphide (0 cases in 2001-2002 versus 14 cases in 2010-2011) and barbecue charcoal gas (1 case in 2001-2002 versus 11 cases in 2010-2011). Compared to individuals using other methods, those suicides adopting new types of gas for suicide were generally younger and from more affluent socioeconomic groups. The corones' records of four of the eight individuals dying by helium inhalation whose records were reviewed showed evidence of Internet involvement in their choice of method. We were not able to identify the source of carbon monoxide (car exhaust or barbecue charcoal) for over 50% of cases. Increases in helium inhalation as a method of suicide have partially offset recent decreases in suicide by the use of car exhaust. Public health measures are urgently needed to prevent a potential epidemic rise in the use of helium similar to the recent rises in charcoal burning suicides in East Asia. | 25,254,616 | [
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Novel approaches to combat bacterial biofilms. | Biofilms formed by pathogenic bacteria and fungi are associated with a wide range of diseases, from device-related infections (such as catheters or prosthetic joints) to chronic infections occurring on native tissues (such as lung infections in cystic fibrosis patients). Biofilms are therefore responsible for an important medical and economic burden. Currently used antibiotics have mostly been developed to target exponentially growing microorganisms and are poorly effective against biofilms. In particular, even high concentrations of bactericidal antibiotics are inactive against a subset of persistent biofilm bacteria, which can cause infection recurrence despite prolonged treatments. While the search for a magic bullet antibiotic effective against both planktonic and biofilm bacteria is still active, alternative preventive and curative approaches are currently being developed either limiting adhesion or biofilm formation or targeting biofilm tolerance by killing persister bacteria. Most of these approaches are adjunctive using new molecules in combination with antibiotics. This review presents promising approaches or strategies that could improve our ability to prevent or eradicate bacterial biofilms in medical settings. | 25,254,624 | [
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A rapid, sensitive and selective electrochemical biosensor with concanavalin A for the preemptive detection of norovirus. | Norovirus (NoV) is a foodborne pathogen that can cause sporadic and epidemic gastrointestinal diseases. Rapid screening is crucial to promptly identify the presence of NoV and prevent food poisoning. Here, we present a sensitive, selective, and rapid electrochemical biosensor for the detection of NoV. The proposed electrochemical biosensor is composed of a nanostructured gold electrode conjugated with concanavalin A (ConA). ConA functions as a recognition element that selectively captures NoV. Cyclic voltammetry revealed a linear relationship (R(2) = 0.998) between the current and concentration of NoV (in the range of 10(2) and 10(6) copies/mL), with a relatively short assay time (1h) and a good detection limit (35 copies/mL). Additionally, the signals of Hepatitis A and E in the selectively test were found to be only 2.0% and 2.8% of the NoV signal at an identical concentration of 10(3) copies/mL, proving that the electrochemical biosensor has a selectively of approximately 98%. Moreover, the concentration of NoV was measured in a realistic environment, i.e., a sample solution extracted from lettuce, to demonstrate a potential application of the proposed biosensor (LoD = 60 copies/mL). | 25,254,625 | [
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Glutamine deprivation stimulates mTOR-JNK-dependent chemokine secretion. | The non-essential amino acid, glutamine, exerts pleiotropic effects on cell metabolism, signalling and stress resistance. Here we demonstrate that short-term glutamine restriction triggers an endoplasmic reticulum (ER) stress response that leads to production of the pro-inflammatory chemokine, interleukin-8 (IL-8). Glutamine deprivation-induced ER stress triggers colocalization of autophagosomes, lysosomes and the Golgi into a subcellular structure whose integrity is essential for IL-8 secretion. The stimulatory effect of glutamine restriction on IL-8 production is attributable to depletion of tricarboxylic acid cycle intermediates. The protein kinase, mTOR, is also colocalized with the lysosomal membrane clusters induced by glutamine deprivation, and inhibition of mTORC1 activity abolishes both endomembrane reorganization and IL-8 secretion. Activated mTORC1 elicits IL8 gene expression via the activation of an IRE1-JNK signalling cascade. Treatment of cells with a glutaminase inhibitor phenocopies glutamine restriction, suggesting that these results will be relevant to the clinical development of glutamine metabolism inhibitors as anticancer agents. | 25,254,627 | [
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Intra- and inter-pandemic variations of antiviral, antibiotics and decongestants in wastewater treatment plants and receiving rivers. | The concentration of eleven antibiotics (trimethoprim, oxytetracycline, ciprofloxacin, azithromycin, cefotaxime, doxycycline, sulfamethoxazole, erythromycin, clarithromycin, ofloxacin, norfloxacin), three decongestants (naphazoline, oxymetazoline, xylometazoline) and the antiviral drug oseltamivir's active metabolite, oseltamivir carboxylate (OC), were measured weekly at 21 locations within the River Thames catchment in England during the month of November 2009, the autumnal peak of the influenza A[H1N1]pdm09 pandemic. The aim was to quantify the pharmaceutical response to the pandemic and compare this to drug use during the late pandemic (March 2010) and the inter-pandemic periods (May 2011). A large and small wastewater treatment plant (WWTP) were sampled in November 2009 to understand the differential fate of the analytes in the two WWTPs prior to their entry in the receiving river and to estimate drug users using a wastewater epidemiology approach. Mean hourly OC concentrations in the small and large WWTP's influent were 208 and 350 ng/L (max, 2070 and 550 ng/L, respectively). Erythromycin was the most concentrated antibiotic measured in Benson and Oxford WWTPs influent (max=6,870 and 2,930 ng/L, respectively). Napthazoline and oxymetazoline were the most frequently detected and concentrated decongestant in the Benson WWTP influent (1650 and 67 ng/L) and effluent (696 and 307 ng/L), respectively, but were below detection in the Oxford WWTP. OC was found in 73% of November 2009's weekly river samples (max=193 ng/L), but only in 5% and 0% of the late- and inter-pandemic river samples, respectively. The mean river concentration of each antibiotic during the pandemic largely fell between 17-74 ng/L, with clarithromycin (max=292 ng/L) and erythromycin (max=448 ng/L) yielding the highest single measure. In general, the concentration and frequency of detecting antibiotics in the river increased during the pandemic. OC was uniquely well-suited for the wastewater epidemiology approach owing to its nature as a prodrug, recalcitrance and temporally- and spatially-resolved prescription statistics. | 25,254,643 | [
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The comparative photodegradation activities of pentachlorophenol (PCP) and polychlorinated biphenyls (PCBs) using UV alone and TiO2-derived photocatalysts in methanol soil washing solution. | Photochemical treatment is increasingly being applied to remedy environmental problems. TiO2-derived catalysts are efficiently and widely used in photodegradation applications. The efficiency of various photochemical treatments, namely, the use of UV irradiation without catalyst or with TiO2/graphene-TiO2 photodegradation methods was determined by comparing the photodegadation of two main types of hydrophobic chlorinated aromatic pollutants, namely, pentachlorophenol (PCP) and polychlorinated biphenyls (PCBs). Results show that photodegradation in methanol solution under pure UV irradiation was more efficient than that with either one of the catalysts tested, contrary to previous results in which photodegradation rates were enhanced using TiO2-derived catalysts. The effects of various factors, such as UV light illumination, addition of methanol to the solution, catalyst dosage, and the pH of the reaction mixture, were examined. The degradation pathway was deduced. The photochemical treatment in methanol soil washing solution did not benefit from the use of the catalysts tested. Pure UV irradiation was sufficient for the dechlorination and degradation of the PCP and PCBs. | 25,254,664 | [
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Maximal strength, muscular endurance and inflammatory biomarkers in young adult men. | The aim was to study associations of maximal strength and muscular endurance with inflammatory biomarkers independent of cardiorespiratory fitness in those with and without abdominal obesity. 686 young healthy men participated (25±5 years). Maximal strength was measured via isometric testing using dynamo-meters to determine maximal strength index. Muscular endurance index consisted of push-ups, sit-ups and repeated squats. An indirect cycle ergometer test until exhaustion was used to estimate maximal aerobic capacity (VO2max). Participants were stratified according to those with (>102 cm) and those without abdominal obesity (<102 cm) based on waist circumference. Inflammatory factors (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were analysed from serum samples. Maximal strength and muscular endurance were inversely associated with IL-6 in those with (β=-0.49, -0.39, respectively) (p<0.05) and in those without abdominal obesity (β=-0.08, -0.14, respectively) (p<0.05) adjusted for smoking and cardio-respiratory fitness. After adjusting for smoking and cardiorespiratory fitness, maximal strength and muscular endurance were inversely associated with CRP only in those without abdominal obesity (β=-0.11, -0.26, respectively) (p<0.05). This cross-sectional study demonstrated that muscular fitness is inversely associated with C-reactive protein and IL-6 concentrations in young adult men independent of cardiorespi-ratory fitness. | 25,254,894 | [
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A method of analysis for T-2 toxin and neosolaniol by UPLC-MS/MS in apple fruit inoculated with Trichothecium roseum. | Trichothecenes are one of the most important groups of mycotoxins produced by Trichothecium roseum, which causes core rot of apple. A reliable and sensitive method was developed and successfully applied for the rapid detection of trichothecenes including T-2 toxin and neosolaniol in harvested apple using UPLC-MS/MS. After the extraction of the two mycotoxins from the apple matrix with methanol/water (80/20, v/v), the concentrated extracts were cleaned-up by PriboFast M270 columns and then analysed by UPLC-MS/MS. T-2 toxin and neosolaniol were effectively separated as unique peaks. The validity of this method was established by its linearity (R(2) ≥ 0.9995), precision (relative standard deviation ≤ 3.6%), accuracy, selectivity, limit of detection of 2-5 μg kg(-1), limit of quantification of 5-10 μg kg(-1) and average recovery of 73-96%. Levels of T-2 toxin were found in the range 7.1-128.4 µg kg(-1) in the core rot lesion of three cultivars apple (cvs. Red Delicious, Fuji and Ralls). T-2 was detected not only in the lesion, but also in the tissue without any disease symptoms. However, neosolaniol was only detected in the lesion on 'Red Delicious' apples. In addition, the concentration of T-2 toxin in the susceptible cultivar (cv. Fuji) was significantly higher than that in the resistant one (cv. Ralls). This method proved to be suitable at detecting T-2 and neosolaniol simultaneously in apples infected with T. roseum. | 25,254,921 | [
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Strengthening global health security by developing capacities to deploy medical countermeasures internationally. | In 2014, the United States in partnership with international organizations and nearly 30 partner countries launched the Global Health Security Agenda (GHSA) to accelerate progress to improve prevention, detection, and response capabilities for infectious disease outbreaks that can cause public health emergencies. Objective 9 of the GHSA calls for improved global access to medical countermeasures and establishes as a target the development of national policy frameworks for sending and receiving medical countermeasures from and to international partners during public health emergencies. The term medical countermeasures refers to vaccines, antimicrobials, therapeutics, and diagnostics that address the public health and medical consequences of chemical, biological, radiological, and nuclear events; pandemic influenza; and emerging infectious diseases. They are stockpiled by a few countries to protect their own populations and by international organizations, such as the World Health Organization (WHO), for the international community, typically for recipients with limited resources. However, as observed during the 2009 H1N1 influenza pandemic, legal, regulatory, logistical, and funding barriers slowed the ability of WHO and countries to quickly deploy or receive vaccine. Had the 2009 H1N1 influenza pandemic been more severe, the world would have been ill prepared to cope with the global demand for rapid access to medical countermeasures. This article summarizes the US government efforts to develop a national framework to deploy medical countermeasures internationally and a number of engagements to develop regional and international mechanisms, thus increasing global capacity to respond to public health emergencies. | 25,254,917 | [
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Mixtec Mexican Amerindians: an HLA alleles study for America peopling, pharmacogenomics and transplantation. | HLA-A, -B and -DRB1 alleles have been studied in a Mixtec Mexican Amerindian population by indirect DNA sequencing. HLA relatedness has been tested by comparing results with other Amerindians and worldwide populations; a total of 15,681 chromosomes have been used. Genetic distances between populations, Neighbour Joining (NJ) dendrograms and correspondence analyses have been carried out. Conclusions are: 1) Our Mixtec sample from Oaxaca Coastal Mexican area shows an HLA profile different to that of Oaxaca Central Mountains area showing that genes and languages do not correlate which is inferred both by plane genetic distances and NJ dendrograms and correspondence analyses. 2) Genetic distances and NJ dendrograms join together Mazatecan Mexican Amerindians with our studied Coastal Mixtec group; it fits with the historical relationship between Mixtec and Mazatecans. 3) A*24:02-B*35:14-DRB1*04:11, A*02:01-B*15:15-DRB1*04:11 and A*68:03-B*39:08-DRB1*08:02 extended HLA haplotypes have been "de novo" found in our Mixtec Coastal sample. 4) Shared HLA alleles are found between our Pacific Coast Mixtec Amerindians and Pacific Islanders. 5) These results are useful for establishing a future area transplantation waiting list, for the study of HLA linked diseases epidemiology and for pharmacogenomics in certain drug therapy. | 25,254,939 | [
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Adsorption of zwitterionic surfactant on limestone measured with high-performance liquid chromatography: micelle-vesicle influence. | Herein is presented a new methodology to determine the static adsorption of a zwitterionic surfactant on limestone in three different aqueous media [high-performance liquid chromatography (HPLC) water, seawater, and connate water] with the use of HPLC at room temperature and 70 °C. The results showed that, in both HPLC water and seawater, the surfactant adsorption followed a monolayer Langmuir tendency. In contrast, for connate water, the surfactant presented a new adsorption profile, characterized by two regions: (i) At surfactant concentrations below 1500 mg L(-1), an increase of adsorption is observed as the amount of divalent cations increases in the aqueous media. (ii) At surfactant concentrations above 1500 mg L(-1), the adsorption decreases because the equilibrium, monomer ⇆ micelle ⇆ vesicle, is shifted to the formation of vesicles, giving as a result a decrease in the concentration of monomers, thus reducing the interaction between the surfactant and the rock, and therefore, lower adsorption values were obtained. The behavior of the surfactant adsorption under different concentrations of divalent cations was well-described by the use of a new modified Langmuir model: (dΓ/dt)ads = k(ads)c(Γ∞ - Γ) - k(cmc)(c - c(cmc))(n)ΓH(c - c(cmc)). It was also observed that, as the temperature increases, the adsorption is reduced because of the exothermic nature of the adsorption processes. | 25,254,947 | [
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Low-temperature solution growth of ZnO nanocone/highly oriented nanorod arrays on copper. | Solution-phase approaches to one-dimensional (1D) ZnO nanostructure arrays are appealing because of their good potential for scale-up. Allowing for a wide variety of substrate material compatibility and saving energy, it is very essential to further research the low-temperature growth process of 1D ZnO nanostructure arrays and its detailed growth mechanism. In this study, large-scale misaligned hexagonal ZnO nancone arrays were synthesized on bare copper foil, while large-scale well-aligned, and highly oriented ZnO nanorod arrays were grown on seeded copper foil through a facile solution processing method at normal atmospheric pressure at 35 °C. X-ray diffraction analysis verified the crystalline nature of the ZnO nanocone/nanorods, and transmission electron microscopy further confirmed the single-crystal nature and the preferential growth direction of the ZnO nanocone/nanorods. The room-temperature photoluminescence measurement qualitatively identified the intrinsic point defects in the ZnO nanocones/nanorods. Besides, the detailed growth behavior of ZnO was discussed with and without a ZnO seed layer, which provides useful information to propose the growth mechanism of the nanocone/nanorods in the low-temperature solution. The method developed here can be easily scaled up to fabricate ZnO nanostructures for many important applications in field emission display, gas sensors, and superhydrophobic surfaces. | 25,254,950 | [
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Muscle atrophy in response to cytotoxic chemotherapy is dependent on intact glucocorticoid signaling in skeletal muscle. | Cancer cachexia is a syndrome of weight loss that results from the selective depletion of skeletal muscle mass and contributes significantly to cancer morbidity and mortality. The driver of skeletal muscle atrophy in cancer cachexia is systemic inflammation arising from both the cancer and cancer treatment. While the importance of tumor derived inflammation is well described, the mechanism by which cytotoxic chemotherapy contributes to cancer cachexia is relatively unexplored. We found that the administration of chemotherapy to mice produces a rapid inflammatory response. This drives activation of the hypothalamic-pituitary-adrenal axis, which increases the circulating level of corticosterone, the predominant endogenous glucocorticoid in rodents. Additionally, chemotherapy administration results in a significant loss of skeletal muscle mass 18 hours after administration with a concurrent induction of genes involved with the ubiquitin proteasome and autophagy lysosome systems. However, in mice lacking glucocorticoid receptor expression in skeletal muscle, chemotherapy-induced muscle atrophy is completely blocked. This demonstrates that cytotoxic chemotherapy elicits significant muscle atrophy driven by the production of endogenous glucocorticoids. Further, it argues that pharmacotherapy targeting the glucocorticoid receptor, given in concert with chemotherapy, is a viable therapeutic strategy in the treatment of cancer cachexia. | 25,254,959 | [
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Pd-catalyzed α-arylation of trimethylsilyl enolates of α,α-difluoroacetamides. | We report the arylation and heteroarylation of α,α-difluoro-α-(trimethylsilyl)acetamides with aryl and heteroaryl bromides catalyzed by an air- and moisture-stable palladacyclic complex containing P(t-Bu)2Cy as ligand. A broad range of electronically varied aryl and heteroaryl bromides underwent this transformation to afford α-aryl-α,α-difluoroacetamides in high yields. Due to the electrophilicity of the fluorinated amide, this palladium-catalyzed cross-coupling reaction provides a versatile platform to generate a range of α,α-difluoro carbonyl compounds, such as α-aryl-α,α-difluoroketones, -acetaldehydes, -acetates, and acetic acids, and difluoroalkyl derivatives, such as 2-aryl-2,2-difluoroethanols and -ethylamines, under mild conditions. | 25,254,966 | [
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Neurospora WC-1 recruits SWI/SNF to remodel frequency and initiate a circadian cycle. | In the negative feedback loop comprising the Neurospora circadian oscillator, the White Collar Complex (WCC) formed from White Collar-1 (WC-1) and White Collar-2 (WC-2) drives transcription of the circadian pacemaker gene frequency (frq). Although FRQ-dependent repression of WCC has been extensively studied, the mechanism by which the WCC initiates a circadian cycle remains elusive. Structure/function analysis of WC-1 eliminated domains previously thought to transactivate frq expression but instead identified amino acids 100-200 as essential for frq circadian expression. A proteomics-based search for coactivators with WCC uncovered the SWI/SNF (SWItch/Sucrose NonFermentable) complex: SWI/SNF interacts with WCC in vivo and in vitro, binds to the Clock box in the frq promoter, and is required both for circadian remodeling of nucleosomes at frq and for rhythmic frq expression; interestingly, SWI/SNF is not required for light-induced frq expression. These data suggest a model in which WC-1 recruits SWI/SNF to remodel and loop chromatin at frq, thereby activating frq expression to initiate the circadian cycle. | 25,254,987 | [
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Putting it all together: recommendations for improving pain management in plastic surgical procedures-surgical facial rejuvenation. | Postoperative pain is a major concern for patients undergoing facial aesthetic surgery. Aggressive efforts to reduce postoperative pain while avoiding adverse sequelae, such as nausea and vomiting, will result in an improved patient experience. Newer pharmaceuticals, medical devices, and longer-acting local anesthetics offer the potential to reduce pain and enhance patient satisfaction. The purpose of this report is to review the options and apply them to 3 specific facial aesthetic procedures: face-lift, brow lift, and blepharoplasty. Our review investigates methods used for pain control in the surgical facial rejuvenation patient. We highlight those techniques that have been documented efficacy. We share specific methods of pain management for the more common surgical facial rejuvenation procedures that we perform. In an effort to maximize patient comfort, we assess the effectiveness of various devices, technologies, and treatment modalities available for pain control after surgical facial rejuvenation. These include local anesthetics, topical creams, intravenous acetaminophen, perioperative ketorolac, local anesthetic wound catheter delivery systems, liposomal bupivacaine, tarsorrhaphy/frost sutures, postoperative pharmacologic therapeutics, prophylactic steroids, and tricks to eliminate pain with suture removal. Additionally, we summarize the primary investigator's preferred method of pain management for the common surgical facial rejuvenation procedures performed. Recent advances in postoperative pain control can significantly improve the patient's surgical experience. This multimodal therapy includes new pharmaceuticals, longer-acting local anesthetics, and devices designed to minimize postoperative pain. Adoption of these techniques may also reduce the need for narcotics and prevent postoperative adverse sequelae. | 25,254,992 | [
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Cardiac evaluation and management before vascular surgery. | The most common and significant morbidity and mortality of vascular surgical procedures remain coronary artery disease, arrhythmia, and heart failure. Cardiac evaluation and medical optimization provide the groundwork for best medical practice in an otherwise high-risk surgical population. The goal of this study is to review the most current literature and guidelines for evaluating patients prior to vascular surgical interventions. From this, we have made our own recommendations regarding both the preoperative and perioperative management of vascular surgical patients. Risk stratification using a modified Lee index may be best to assess perioperative cardiac risk. Coronary revascularization should be reserved for those patients with significant coronary disease irrespective of symptoms. β-blockers, statins, and antiplatelet agents should be considered for all patients with peripheral vascular disease. The preoperative management of vascular surgical patients requires a complete understanding of the patient's medical history as it relates to their perioperative cardiac risk. Overwhelming data support the use of medical therapy as adjunct to minimize or prevent the risk of future cardiovascular events. As vascular surgery transitions to the outpatient setting, further studies will be required to better elucidate cardiac evaluation in this patient population. | 25,255,034 | [
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Quantitative profiling of oxylipins through comprehensive LC-MS/MS analysis of Fusarium verticillioides and maize kernels. | Fusarium verticillioides is one of the most important fungal pathogens causing ear and stalk rot in maize, even if frequently asymptomatic, producing a harmful series of compounds named fumonisins. Plant and fungal oxylipins play a crucial role in determining the outcome of the interaction between the pathogen and its host. Moreover, oxylipins result as signals able to modulate the secondary metabolism in fungi. In keeping with this, a novel, quantitative LC-MS/MS method was designed to quantify up to 17 different oxylipins produced by F. verticillioides and maize kernels. By applying this method, we were able to quantify oxylipin production in vitro - F. verticillioides grown into Czapek-Dox/yeast extract medium amended with 0.2% w/v of cracked maize - and in vivo, i.e. during its growth on detached mature maize ears. This study pinpoints the role of oxylipins in a plant pathogen such as F. verticillioides and sets up a novel tool aimed at understanding the role oxylipins play in mycotoxigenic pathogens during their interactions with respective hosts. | 25,255,035 | [
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Capture of heliophobic atoms by (4)He nanodroplets: the case of cesium. | Within Density Functional Theory (DFT), we address the capture of a Cs atom by a superfluid helium nanodroplet using models of different complexity. In the simplest model, the Cs-droplet potential is obtained in two extreme approximations, namely the sudden approximation in which one assumes that the density of the droplet is not relaxed as Cs approaches it, and the adiabatic approximation in which one assumes that it does. Next, a more complex approach in which the collision is described within a time-dependent DFT approach is employed. Depending on the energy and impact parameter of the impinging Cs atom, a rich variety of dynamical phenomena appears that is discussed in some detail. | 25,255,044 | [
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Hypothalamic S1P/S1PR1 axis controls energy homeostasis. | Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats. | 25,255,053 | [
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Effects of analgesic use on inflammation and hematology in a murine model of venous thrombosis. | Venous thrombosis (VT) is a significant cause of morbidity and mortality in humans. Surgical animal models are crucial in studies investigating the pathogenesis of this disease and evaluating VT therapies. Because inflammation is critical to both the development and resolution of VT, analgesic medications have the potential to adversely affect multiple parameters of interest in VT research. The objective of this study was to determine how several common analgesics affect key variables in a murine ligation model of deep vein thrombosis. Male C57BL/6 mice were randomly assigned to receive either local (bupivacaine) or systemic parenteral analgesia (buprenorphine, tramadol, or carprofen) or 0.9% NaCl (control). All mice underwent laparotomy and ligation of the inferior vena cava, and treatment was continued until euthanasia at 6 or 48 h after surgery. Analysis of harvested tissues and blood included: hematology, thrombus weight, serum and vein-wall cytokines (IL1β, IL6, IL10, TNFα), soluble P-selectin, and vein-wall leukocyte infiltration. Compared with 0.9% NaCl, all of the analgesics affected multiple parameters important to VT research. Carprofen and tramadol affected the most parameters and should not be used in murine models of VT. Although they affected fewer parameters, a single dose of bupivacaine increased thrombus weight at 6 h, and buprenorphine was associated with reduced vein wall macrophages at 48 h. Although we cannot recommend the use of any of the evaluated analgesic dosages in this mouse model of VT, buprenorphine merits additional investigation to ensure the highest level of laboratory animal care and welfare. | 25,255,071 | [
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A lysosome-targeted fluorescent chemodosimeter for monitoring endogenous and exogenous hydrogen sulfide by in vivo imaging. | A lysosome-targeted fluorescent chemodosimeter, 1, was developed for monitoring endogenous and exogenous H2S by in vivo imaging of HeLa cells, D. melanogaster and C. elegans. In the tests of mutated C. elegans (SRP-6 nulls), chemodosimeter 1 could trace the accumulation of lysosome and lysosomal injury with a high resolution. | 25,255,077 | [
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Gastroesophageal reflux disease and risk for bipolar disorder: a nationwide population-based study. | Studies have shown that chronic inflammation may play a vital role in the pathophysiology of both gastroesophageal reflux disease (GERD) and bipolar disorder. Among patients with GERD, the risk of bipolar disorder has not been well characterized. We explored the relationship between GERD and the subsequent development of bipolar disorder, and examined the risk factors for bipolar disorder in patients with GERD. We identified patients who were diagnosed with GERD in the Taiwan National Health Insurance Research Database. A comparison cohort without GERD was matched according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts based on diagnosis and the prescription of medications. The GERD cohort consisted of 21,674 patients, and the comparison cohort consisted of 21,674 matched control patients without GERD. The incidence of bipolar disorder (incidence rate ratio [IRR] 2.29, 95% confidence interval [CI] 1.58-3.36, P<.001) was higher among GERD patients than among comparison cohort. Multivariate, matched regression models showed that the female sex (hazard ratio [HR] 1.78, 95% CI 1.76-2.74, P = .008), being younger than 60 years old (HR 2.35, 95% CI 1.33-4.16, P = .003), and alcohol use disorder (HR 4.89, 95% CI 3.06-7.84, P = .004) were independent risk factors for the development of bipolar disorder among GERD patients. GERD may increase the risk of developing bipolar disorder. Based on our data, we suggest that attention should be focused on female patients younger than 60 years, and patients with alcohol use disorder, following a GERD diagnosis. | 25,255,080 | [
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A widely used in vitro biofilm assay has questionable clinical significance for enterococcal endocarditis. | Biofilm formation may play an important role in the pathogenesis of infections caused by Enterococcus faecalis, including endocarditis. Most biofilm studies use a polystyrene dish assay to quantify biofilm biomass. However, recent studies of E. faecalis strains in tissue and animal models suggest that polystyrene dish results need to be interpreted with caution. We evaluated 158 clinical E. faecalis isolates using a polystyrene dish assay and found variation in biofilm formation, with many isolates forming little biofilm even when different types of media were used. However, all tested clinical isolates were able to form biofilms on porcine heart valve explants. Dextrose-enhanced biofilm formation in the polystyrene dish assay was found in 6/12 (50%) of clinical isolates tested and may explain some, but not all of the differences between the polystyrene dish assay and the heart valve assay. These findings suggest that in studies assessing the clinical relevance of enterococcal biofilm-forming ability, ex vivo biofilm formation on a relevant tissue surface may be warranted to validate results of in vitro assays. | 25,255,085 | [
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Nipbl and mediator cooperatively regulate gene expression to control limb development. | Haploinsufficiency for Nipbl, a cohesin loading protein, causes Cornelia de Lange Syndrome (CdLS), the most common "cohesinopathy". It has been proposed that the effects of Nipbl-haploinsufficiency result from disruption of long-range communication between DNA elements. Here we use zebrafish and mouse models of CdLS to examine how transcriptional changes caused by Nipbl deficiency give rise to limb defects, a common condition in individuals with CdLS. In the zebrafish pectoral fin (forelimb), knockdown of Nipbl expression led to size reductions and patterning defects that were preceded by dysregulated expression of key early limb development genes, including fgfs, shha, hand2 and multiple hox genes. In limb buds of Nipbl-haploinsufficient mice, transcriptome analysis revealed many similar gene expression changes, as well as altered expression of additional classes of genes that play roles in limb development. In both species, the pattern of dysregulation of hox-gene expression depended on genomic location within the Hox clusters. In view of studies suggesting that Nipbl colocalizes with the mediator complex, which facilitates enhancer-promoter communication, we also examined zebrafish deficient for the Med12 Mediator subunit, and found they resembled Nipbl-deficient fish in both morphology and gene expression. Moreover, combined partial reduction of both Nipbl and Med12 had a strongly synergistic effect, consistent with both molecules acting in a common pathway. In addition, three-dimensional fluorescent in situ hybridization revealed that Nipbl and Med12 are required to bring regions containing long-range enhancers into close proximity with the zebrafish hoxda cluster. These data demonstrate a crucial role for Nipbl in limb development, and support the view that its actions on multiple gene pathways result from its influence, together with Mediator, on regulation of long-range chromosomal interactions. | 25,255,084 | [
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Gamma delta T cells recognize haptens and mount a hapten-specific response. | The ability to recognize small organic molecules and chemical modifications of host molecules is an essential capability of the adaptive immune system, which until now was thought to be mediated mainly by B cell antigen receptors. Here we report that small molecules, such as cyanine 3 (Cy3), a synthetic fluorescent molecule, and 4-hydroxy-3-nitrophenylacetyl (NP), one of the most noted haptens, are γδ T cell antigens, recognized directly by specific γδ TCRs. Immunization with Cy3 conjugates induces a rapid Cy3-specific γδ T cell IL-17 response. These results expand the role of small molecules and chemical modifications in immunity and underscore the role of γδ T cells as unique adaptive immune cells that couple B cell-like antigen recognition capability with T cell effector function. | 25,255,099 | [
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Where the road ends, yaws begins? The cost-effectiveness of eradication versus more roads. | A disabling and disfiguring disease that "begins where the road ends", yaws is targeted by WHO for eradication by the year 2020. The global campaign is not yet financed. To evaluate yaws eradication within the context of the post-2015 development agenda, we perform a somewhat allegorical cost-effectiveness analysis of eradication, comparing it to a counterfactual in which we simply wait for more roads (the end of poverty). We use evidence from four yaws eradication pilot sites and other mass treatment campaigns to set benchmarks for the cost of eradication in 12 known endemic countries. We construct a compartmental model of long-term health effects to 2050. Conservatively, we attribute zero cost to the counterfactual and allow for gradual exit of the susceptible (at risk) population by road (poverty reduction). We report mean, 5th and 95th centile estimates to reflect uncertainty about costs and effects. Our benchmark for the economic cost of yaws eradication is uncertain but not high -US$ 362 (75-1073) million in 12 countries. Eradication would cost US$ 26 (4.2-78) for each year of life lived without disability or disfigurement due to yaws, or US$ 324 (47-936) per disability-adjusted life year (DALY). Excluding drugs, existing staff and assets, the financial cost benchmark is US$ 213 (74-522) million. The real cost of waiting for more roads (poverty reduction) would be 13 (7.3-20) million years of life affected by early-stage yaws and 2.3 (1.1-4.2) million years of life affected by late-stage yaws. Endemic countries need financing to begin implementing and adapting global strategy to local conditions. Donations of drugs and diagnostics could reduce cost to the public sector and catalyze financing. Resources may be harnessed from the extractive industries. Yaws eradication should be seen as complementary to universal health coverage and shared prosperity on the post-2015 development agenda. | 25,255,131 | [
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Efficacy and safety of systemic tacrolimus in high-risk penetrating keratoplasty after graft failure with systemic cyclosporine. | The aim of this study was to investigate the efficacy and safety of systemic tacrolimus for the treatment of eyes that developed graft failure despite treatment with cyclosporine (CsA). Ten eyes of 10 patients who underwent high-risk penetrating keratoplasty (PKP) and developed graft failure despite treatment with systemic CsA were included in this study. The patients underwent PKP and were treated with systemic tacrolimus according to the standardized protocol. Treatment with tacrolimus was continued for 18.1 ± 13.9 months. The median duration of corneal graft clarity was 34.5 months. Graft rejection occurred in 2 of 10 eyes during a mean follow-up period of 48.9 ± 22.9 months. Kaplan-Meier survival plots showed significantly fewer graft rejection episodes (P = 0.033) and longer graft survival (P = 0.042) after treatment with tacrolimus compared those with CsA. Tacrolimus was discontinued in 2 patients; 1 had renal dysfunction and the other had muscle pain and fatigue. These side effects subsided after discontinuation of tacrolimus. Treatment with systemic tacrolimus is possibly safe and effective in reducing graft rejection and prolonging graft survival in patients with high-risk PKP after graft failure with systemic CsA. | 25,255,133 | [
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Instrument development of the UNC Dry Eye Management Scale. | Dry eye disease (DED) is a common ocular disease that can have adverse effects on quality of life. Our aim was to develop a single-item questionnaire that is reliable, patient-driven, and clinic friendly to assess DED symptoms and their effect on quality of life to help support the management of patients with DED. An initial dry eye questionnaire was created and administered to 18 patients with DED followed by a 15-minute cognitive interviewing session. This questionnaire was then refined using feedback obtained from the cognitive interview and was termed the University of North Carolina Dry Eye Management Scale (UNC DEMS). Field testing was then performed on 66 patients (46 with DED and 20 without DED) to determine the validity and test-retest reliability of the UNC DEMS compared with the current gold standard, the Ocular Surface Disease Index (OSDI). Pearson correlation coefficients were calculated between the UNC DEMS, OSDI, and other DED measures to assess criterion-related validity. Reliability coefficients were estimated for test-retest reliability. Comparing the UNC DEMS with the OSDI across all study participants, the correlation coefficient was 0.80 (P < 0.001). Comparing the UNC DEMS with the OSDI in the DED group, the correlation coefficient was 0.69 (P < 0.001). The test-retest reliability coefficient of the UNC DEMS was estimated to be 0.90. The UNC DEMS is a valid, reliable questionnaire that can be efficiently administered in a busy clinical practice and can be used to support the management of patients with DED. | 25,255,135 | [
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Extraorbital lacrimal gland excision: a reproducible model of severe aqueous tear-deficient dry eye disease. | The aim of this study was to establish and characterize extraorbital lacrimal gland excision (LGE) as a model of aqueous tear-deficient dry eye disease in mice. Female C57BL/6 mice at 6 to 8 weeks of age were randomized to extraorbital LGE, sham surgery, or scopolamine groups. Mice that underwent extraorbital LGE or sham surgery were housed in the standard vivarium. Scopolamine-treated mice were housed in a controlled environment chamber that allowed for the continuous regulation of airflow (15 L/min), relative humidity (30%), and temperature (21-23°C). Clinical disease severity was assessed over the course of 14 days using the phenol red thread test and corneal fluorescein staining. Real-time polymerase chain reaction was performed to assess corneal mRNA expression of interleukin 1β, tumor necrosis factor α, and matrix metalloproteinase 9. Flow cytometry was used to assess T helper cell frequencies in the conjunctivae and draining lymph nodes. Extraorbital LGE markedly reduced aqueous tear secretion as compared with the sham procedure and induced a more consistent decrease in aqueous tear secretion than was observed in mice that received scopolamine while housed in the controlled environment chamber. Extraorbital LGE significantly increased corneal fluorescein staining scores as compared with those of both the sham surgery and scopolamine-treated groups. Extraorbital LGE significantly increased the corneal expression of interleukin 1β, tumor necrosis factor α, and matrix metalloproteinase 9. Further, extraorbital LGE increased T helper 17-cell frequencies in the conjunctivae and draining lymph nodes. Extraorbital LGE induces aqueous tear-deficient dry eye disease in mice as evidenced by decreased aqueous tear secretion, increased corneal epitheliopathy, and induced ocular surface inflammation and immunity. | 25,255,136 | [
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Chemical fingerprint and metabolic profile analysis of Citrus reticulate 'Chachi' decoction by HPLC-PDA-IT-MS(n) and HPLC-Quadrupole-Orbitrap-MS method. | A method incorporating HPLC-PDA-IT-MS(n) with HPLC-Quadrupole-Orbitrap-MS was developed for the investigation of chemical fingerprint of Citrus reticulate 'Chachi' decoction (CRCD) and metabolic profile of SD rat plasma sample after oral administration of CRCD (1.5 g herb/kg). A total of 27 chemical constituents of CRCD were identified from their MW, UV spectra, MS(n) data and retention behavior by comparing the results with those of the reference standards or literature. And 43 compounds were detected in dosed SD rat plasma samples, including 9 prototypes which were identified as hesperetin, isosinensetin, sinensetin, tetramethyl-O-isoscutellarein, nobiletin, tetramethyl-O-scutellarein, HMF (3,5,6,7,8,3',4'-heptamethoxyflavone), tangeretin and 5-demethylnobiletin and 34 metabolites underwent metabolic process of demethylation, glucuronide conjugation, sulfate conjugation or mixed modes. This is the first research for the metabolic profile of CRCD in SD rats, which could lay a foundation for the further studies of CRC or its formulation. | 25,255,155 | [
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Constipation after thoraco-lumbar fusion surgery. | Thoraco-lumbar posterior fusion surgery is a frequent procedure used for patients with spinal instability due to tumor, trauma or degenerative disease. In the perioperative phase, many patients may experience vomiting, bowel irritation, constipation, or may even show symptoms of adynamic ileus possibly due to immobilization and high doses of opioid analgesics and narcotics administered during and after surgery. Retrospective single-center study on patients undergoing thoraco-lumbar fusion surgery for degenerative lumbar spine disease with instability in 2012. Study groups were built according to presence/absence of postoperative constipation, with postoperative constipation being defined as no bowel movement on postoperative days 0-2. Ninety-nine patients (39 males, 60 females) with a mean age of 57.1 ± 17.3 years were analyzed, of which 44 patients with similar age, gender, BMI and ASA-grades showed constipation (44.4%). Occurrence of constipation was associated with longer mean operation times (247 ± 62 vs. 214 ± 71 min; p=0.012), higher estimated blood loss (545 ± 316 vs. 375 ± 332 ml; p<0.001), and higher mean morphine dosages in the postoperative days 0-7 (the difference being significant on postoperative days 1 (48 mg vs. 30.9 mg, p=0.041) and 2 (43.2mg vs. 29.1mg, p=0.028). The equivalence dose of morphine administered during surgery was similar (339 ± 196 vs. 285 ± 144 mg; p=0.286). The use of laxatives in the postoperative days 0-7 was generally high in both study groups, while it was more frequent in patients experiencing constipation. One patient with constipation developed a sonographically confirmed paralytic ileus. Patients with constipation showed a tendency toward longer postoperative hospitalization (7.6 vs. 6.7 days, p=0.136). The rate of constipation was high after thoraco-lumbar fusion surgery. Moreover, it was associated with longer surgery time, higher blood loss, and higher postoperative morphine doses. Further trials are needed to prove if the introduction of faster and less invasive surgery techniques may have a positive side effect on bowel movement after spine surgery as they may reduce operation times, blood loss and postoperative morphine use. | 25,255,157 | [
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Comparison of echocardiographic measurements in elite and nonelite Arabian endurance horses. | To determine whether echocardiographic variables differed between successful (elite) and less successful (nonelite) Arabian endurance horses. 34 Arabian horses that competed in endurance racing. Horses were assigned to either an elite or nonelite group on the basis of results of a previous competition, and a standardized echocardiographic examination was performed on each horse within 1 to 4 weeks after that competition. Multivariable logistic regression with backward stepwise elimination was used to create a prediction model for the determination of horse status (elite or nonelite) as a function of the measured echocardiographic variables. The elite and nonelite groups consisted of 23 and 11 horses, respectively. One horse in the nonelite group had a frequent ventricular dysrhythmia that could have negatively affected its performance and rider's safety, whereas none of the horses in the elite group had remarkable cardiac abnormalities. The left ventricular internal diameter during systole and diastole and left ventricular mass and stroke volume were significantly greater for horses in the elite group, compared with those for horses in the nonelite group. The final logistic regression model correctly predicted the horse status for all of the horses in the elite group and 8 of 11 horses in the nonelite group. Results indicated that heart size was significantly associated with performance for Arabian endurance horses in a manner similar to findings for Thoroughbred and Standardbred racehorses in active competition. | 25,255,178 | [
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Expression of epidermal growth factor receptor and human epidermal growth factor receptor 2 in periocular squamous cell carcinomas of horses. | To determine whether epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are expressed in periocular squamous cell carcinomas (SCCs) of horses. Biopsy specimens of SCCs from 46 horses. Pathology records were searched retrospectively for biopsy specimens of periocular SCCs obtained from horses. Slides of the specimens were reviewed histologically to confirm the SCC diagnosis and stained for EGFR and HER2 by immunohistochemical methods. For both EGFR and HER2, the immunohistochemical staining intensity and percentage of stain-positive cells on the slides were determined. 43 of 46 (93%) SCCs were immunoreactive for EGFR. The median score for EGFR staining intensity was 4 (range, 2 to 12), and the median number of mitotic figures was 8 mitotic figures/10 hpfs (range, 0 to 34 mitotic figures/10 hpfs). Mitotic index was not correlated with the percentage of EGFR stain-positive cells or staining intensity. Of the 43 EGFR-immunoreactive SCCs, 38 had stain present primarily in the cytoplasm and 5 had stain equally distributed between the cytoplasm and cell membranes. Thirty-five of 46 (76%) SCCs were immunoreactive for HER2. Mitotic index was not correlated with the percentage of HER2 stain-positive cells or staining intensity. Of the 35 HER2-immunoreactive SCCs, the stain was present primarily in the cytoplasm and 7 had stain equally distributed between the cytoplasm and cell membranes. Results indicated that most periocular SCCs of horses expressed EGFR and HER2, which suggested that equine periocular SCCs might respond to treatment with EGFR inhibitors. | 25,255,181 | [
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Highly-efficient enzymatic conversion of crude algal oils into biodiesel. | Energy-intensive chemical conversion of crude algal oils into biodiesel is a major barrier for cost-effective algal biofuel production. To overcome this problem, we developed an enzyme-based platform for conversion of crude algal oils into fatty acid methyl esters. Crude algal oils were extracted from the oleaginous microalga Nannochloropsis oceanica IMET1 and converted by an immobilized lipase from Candida antarctica. The effects of different acyl acceptors, t-butanol as a co-solvent, oil to t-butanol ratio, oil to methanol ratio, temperature and reaction time on biodiesel conversion efficiency were studied. The conversion efficiency reached 99.1% when the conversion conditions were optimized, i.e., an oil to t-butanol weight ratio of 1:1, an oil to methanol molar ratio of 1:12, and a reaction time of 4h at 25°C. The enzymatic conversion process developed in this study may hold a promise for low energy consumption, low wastewater-discharge biochemical conversion of algal feedstocks into biofuels. | 25,255,191 | [
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Tracing the origin of suspended sediment in a large Mediterranean river by combining continuous river monitoring and measurement of artificial and natural radionuclides. | Delivery of suspended sediment from large rivers to marine environments has important environmental impacts on coastal zones. In France, the Rhone River (catchment area of 98,000 km(2)) is by far the main supplier of sediment to the Mediterranean Sea and its annual solid discharge is largely controlled by flood events. This study investigates the relevance of alternative and original fingerprinting techniques based on the relative abundances of a series of radionuclides measured routinely at the Rhone River outlet to quantify the relative contribution of sediment supplied by the main tributaries during floods. Floods were classified according to the relative contribution of the main subcatchments (i.e., Oceanic, Cevenol, extensive Mediterranean and generalised). Between 2000 and 2012, 221 samples of suspended sediment were collected at the outlet and were shown to be representative of all flood types that occurred during the last decade. Three geogenic radionuclides (i.e., (238)U, (232)Th and (40)K) were used as fingerprints in a multivariate mixing model in order to estimate the relative contribution of the main subcatchment sources-characterised by different lithologies-in sediment samples collected at the outlet. Results showed that total sediment supply originating from Pre-Alpine, Upstream, and Cevenol sources amounted to 10, 7 and 2.10(6)tons, respectively. These results highlight the role of Pre-Alpine tributaries as the main sediment supplier (53%) to the Rhone River during floods. Other fingerprinting approaches based on artificial radionuclide activity ratios (i.e., (137)Cs/(239+240)Pu and (238)Pu/(239+240)Pu) were tested and provided a way to quantify sediment remobilisation or the relative contributions of the southern tributaries. In the future, fingerprinting methods based on natural radionuclides should be further applied to catchments with heterogeneous lithologies. Methods based on artificial radionuclides should be further applied to catchments characterised by heterogeneous post-Chernobyl (137)Cs deposition or by specific releases of radioactive effluents. | 25,255,199 | [
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A distinct tethering step is vital for vacuole membrane fusion. | Past experiments with reconstituted proteoliposomes, employing assays that infer membrane fusion from fluorescent lipid dequenching, have suggested that vacuolar SNAREs alone suffice to catalyze membrane fusion in vitro. While we could replicate these results, we detected very little fusion with the more rigorous assay of lumenal compartment mixing. Exploring the discrepancies between lipid-dequenching and content-mixing assays, we surprisingly found that the disposition of the fluorescent lipids with respect to SNAREs had a striking effect. Without other proteins, the association of SNAREs in trans causes lipid dequenching that cannot be ascribed to fusion or hemifusion. Tethering of the SNARE-bearing proteoliposomes was required for efficient lumenal compartment mixing. While the physiological HOPS tethering complex caused a few-fold increase of trans-SNARE association, the rate of content mixing increased more than 100-fold. Thus tethering has a role in promoting membrane fusion that extends beyond simply increasing the amount of total trans-SNARE complex. | 25,255,215 | [
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Quantifying the impact and extent of undocumented biomedical synonymy. | Synonymous relationships among biomedical terms are extensively annotated within specialized terminologies, implying that synonymy is important for practical computational applications within this field. It remains unclear, however, whether text mining actually benefits from documented synonymy and whether existing biomedical thesauri provide adequate coverage of these linguistic relationships. In this study, we examine the impact and extent of undocumented synonymy within a very large compendium of biomedical thesauri. First, we demonstrate that missing synonymy has a significant negative impact on named entity normalization, an important problem within the field of biomedical text mining. To estimate the amount synonymy currently missing from thesauri, we develop a probabilistic model for the construction of synonym terminologies that is capable of handling a wide range of potential biases, and we evaluate its performance using the broader domain of near-synonymy among general English words. Our model predicts that over 90% of these relationships are currently undocumented, a result that we support experimentally through "crowd-sourcing." Finally, we apply our model to biomedical terminologies and predict that they are missing the vast majority (>90%) of the synonymous relationships they intend to document. Overall, our results expose the dramatic incompleteness of current biomedical thesauri and suggest the need for "next-generation," high-coverage lexical terminologies. | 25,255,227 | [
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Choosing Wisely: a neurosurgical perspective on neuroimaging for headaches. | Multiple national initiatives seek to curb spending to address increasing healthcare costs in the United States. The Choosing Wisely initiative is a popular initiative that focuses on reducing healthcare spending by setting guidelines to limit tests and procedures requested by patients and ordered by physicians. To reduce spending on neuroimaging, the Choosing Wisely initiative and other organizations have offered guidelines to limit neuroimaging for headaches. Although the intentions are laudable, these guidelines are inconsistent with the neurosurgeon's experience with patients with brain tumor. If adopted by governing or funding organizations, these guidelines threaten to negatively affect the care and outcomes of patients with brain tumors, who frequently present with minimal symptoms or isolated headaches syndromes. As physicians grapple with the difficult conflict between evidence-based cost-cutting guidelines and individualized patient-tailored medicine, they must carefully balance the costs and benefits of discretionary services such as neuroimaging for headaches. By participating in the development of validated clinical decision rules on neuroimaging for headaches, neurosurgeons can advocate for their patients and improve their patients' outcomes. | 25,255,253 | [
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Domestic harm and neglect among lesbian, gay, and bisexual older adults. | This study examined harm, hurt, and neglect by caregivers as well as self-neglect and physical and mental health status among 113 lesbian, gay, and bisexual (LGB) older adults aged 60-88 years, who attended community-based social and recreation programs or groups in the United States. Reporting on their experiences with caregivers, 22.1% of the participants experienced at least one type of harm, including physical, emotional, verbal, sexual, financial, and neglectful; additionally, 25.7% of the participants reported they knew LGB older adults who experienced at least one type of harm from his or her caregiver. With regard to self-neglect, 62.8% reported experiencing it; those indicating positive psychological health reported fewer experiences with self-neglect. | 25,255,273 | [
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Discovery and characterization of MAPK-activated protein kinase-2 prevention of activation inhibitors. | Two structurally distinct series of novel, MAPK-activated kinase-2 prevention of activation inhibitors have been discovered by high throughput screening. Preliminary structure-activity relationship (SAR) studies revealed substructural features that influence the selective inhibition of the activation by p38α of the downstream kinase MK2 in preference to an alternative substrate, MSK1. Enzyme kinetics, surface plasmon resonance (SPR), 2D protein NMR, and X-ray crystallography were used to determine the binding mode and the molecular mechanism of action. The compounds bind competitively to the ATP binding site of p38α but unexpectedly with higher affinity in the p38α-MK2 complex compared with p38α alone. This observation is hypothesized to be the origin of the substrate selectivity. The two lead series identified are suitable for further investigation for their potential to treat chronic inflammatory diseases with improved tolerability over previously studied p38α inhibitors. | 25,255,283 | [
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Clinical validation and implications of dried blood spot sampling of carbamazepine, valproic acid and phenytoin in patients with epilepsy. | To facilitate therapeutic monitoring of antiepileptic drugs (AEDs) by healthcare professionals for patients with epilepsy (PWE), we applied a GC-MS assay to measure three AEDs: carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) levels concurrently in one dried blood spot (DBS), and validated the DBS-measured levels to their plasma levels. 169 PWE on either mono- or polytherapy of CBZ, PHT or/and VPA were included. One DBS, containing ∼15 µL of blood, was acquired for the simultaneous measurement of the drug levels using GC-MS. Simple Deming regressions were performed to correlate the DBS levels with the plasma levels determined by the conventional immunoturbimetric assay in clinical practice. Statistical analyses of the results were done using MedCalc Version 12.6.1.0 and SPSS 21. DBS concentrations (Cdbs) were well-correlated to the plasma concentrations (Cplasma): r=0.8381, 0.9305 and 0.8531 for CBZ, PHT and VPA respectively, The conversion formulas from Cdbs to plasma concentrations were [0.89×CdbsCBZ+1.00]µg/mL, [1.11×CdbsPHT-1.00]µg/mL and [0.92×CdbsVPA+12.48]µg/mL respectively. Inclusion of the red blood cells (RBC)/plasma partition ratio (K) and the individual hematocrit levels in the estimation of the theoretical Cplasma from Cdbs of PHT and VPA further improved the identity between the observed and the estimated theoretical Cplasma. Bland-Altman plots indicated that the theoretical and observed Cplasma of PHT and VPA agreed well, and >93.0% of concentrations was within 95% CI (±2SD); and similar agreement (1∶1) was also found between the observed Cdbs and Cplasma of CBZ. As the Cplasma of CBZ, PHT and VPA can be accurately estimated from their Cdbs, DBS can therefore be used for drug monitoring in PWE on any of these AEDs. | 25,255,292 | [
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Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer. | A hypermutated subtype of advanced prostate cancer was recently described, but prevalence and mechanisms have not been well-characterized. Here we find that 12% (7 of 60) of advanced prostate cancers are hypermutated, and that all hypermutated cancers have mismatch repair gene mutations and microsatellite instability (MSI). Mutations are frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 epigenetic silencing. Our findings identify parallels and differences in the mechanisms of hypermutation in prostate cancer compared with other MSI-associated cancers. | 25,255,306 | [
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Hybrid and rogue kinases encoded in the genomes of model eukaryotes. | The highly modular nature of protein kinases generates diverse functional roles mediated by evolutionary events such as domain recombination, insertion and deletion of domains. Usually domain architecture of a kinase is related to the subfamily to which the kinase catalytic domain belongs. However outlier kinases with unusual domain architectures serve in the expansion of the functional space of the protein kinase family. For example, Src kinases are made-up of SH2 and SH3 domains in addition to the kinase catalytic domain. A kinase which lacks these two domains but retains sequence characteristics within the kinase catalytic domain is an outlier that is likely to have modes of regulation different from classical src kinases. This study defines two types of outlier kinases: hybrids and rogues depending on the nature of domain recombination. Hybrid kinases are those where the catalytic kinase domain belongs to a kinase subfamily but the domain architecture is typical of another kinase subfamily. Rogue kinases are those with kinase catalytic domain characteristic of a kinase subfamily but the domain architecture is typical of neither that subfamily nor any other kinase subfamily. This report provides a consolidated set of such hybrid and rogue kinases gleaned from six eukaryotic genomes-S.cerevisiae, D. melanogaster, C.elegans, M.musculus, T.rubripes and H.sapiens-and discusses their functions. The presence of such kinases necessitates a revisiting of the classification scheme of the protein kinase family using full length sequences apart from classical classification using solely the sequences of kinase catalytic domains. The study of these kinases provides a good insight in engineering signalling pathways for a desired output. Lastly, identification of hybrids and rogues in pathogenic protozoa such as P.falciparum sheds light on possible strategies in host-pathogen interactions. | 25,255,313 | [
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Distinct contributions of adverse childhood experiences and resilience resources: a cohort analysis of adult physical and mental health. | Although evidence is rapidly amassing as to the damaging potential of early life adversities on physical and mental health, as yet few investigations provide comparative snapshots of these patterns across adulthood. This population-based study addresses this gap, examining the relationship of adverse childhood experiences (ACEs) to physical and mental health within a representative sample (n = 19,333) of adults, comparing the prevalence and explanatory strength of ACEs among four birth cohorts spanning ages 18-79. This assessment accounts for demographic and socioeconomic factors, as well as both direct and moderating effects of resilience resources (social/emotional support, life satisfaction, and sleep quality). Findings demonstrate (1) increasing trends of reported ACEs across younger cohorts, including time period shifts such as more prevalent family incarceration, substance abuse, and divorce, (2) significant bivariate as well as independent associations of ACEs with poor health within every cohort, controlling for multiple covariates (increasing trends in older age for physical health), and (3) robust patterns wherein resilience resources moderated ACEs, indicating buffering pathways that sustained into old age. Theoretical and practice implications for health professionals are discussed. | 25,255,340 | [
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Coagulation phenotypes in septic shock as evaluated by calibrated automated thrombography. | Sepsis induces alterations of coagulation suggesting both hypercoagulable or hypocoagulable features. The result of their combination remains unknown, making it difficult to predict whether one prevails over the other. Thrombin generation tests (TGTs) stand as an interesting tool to establish an integrative phenotype of coagulation. It has been reported that septic patients display a hypocoagulable trait using TGT. However, protein C (PC) system response was not evaluated. We aimed at describing the thrombin generation profile in patients with septic shock under conditions that are sensitive to PC system to evaluate the net results of coagulation abnormalities and to determine whether hypercoagulable or hypocoagulable traits coexist within a given individual. Thrombin generation was studied in plasma from patients presenting with septic shock at diagnosis and 6 h after a conventional therapeutic management using calibrated automated thrombography with or without thrombomodulin (TM) addition. Patients exhibit clear alterations of TGT that present as both consumption-related hypocoagulability (evidenced without TM addition) but also hypercoagulability by decreased sensitivity to the PC system evidenced with TM addition. No difference could be demonstrated between survivors and nonsurvivors at Day 28, but patients who do not respond to therapeutics at 6 h seem to be more hypercoagulable. More importantly, if our results evidence heterogeneity between patients, we show that alterations of coagulation result in an equilibrium in the majority of patients, thus suggesting "normocoagulability"; but, in the presence of a biological imbalance between baseline thrombin generation and sensitivity to TM, the global effect mostly tends toward hypercoagulability. Thus, TGT may help identify distinct biological coagulation phenotypes in the complex alterations induced by sepsis. | 25,255,379 | [
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Potential cost-effectiveness of therapeutic drug monitoring in patients with resistant hypertension. | Nonadherence to drug therapy poses a significant problem in the treatment of patients with presumed resistant hypertension. It has been shown that therapeutic drug monitoring (TDM) is a useful tool for detecting nonadherence and identifying barriers to treatment adherence, leading to effective blood pressure (BP) control. However, the cost-effectiveness of TDM in the management of resistant hypertension has not been investigated. A Markov model was used to evaluate life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios in resistant hypertension patients receiving either TDM optimized therapy or standard best medical therapy. The model ran from the age of 30 to 100 years or death, using a cycle length of 1 year. Efficacy of TDM was modeled by reducing risk of hypertension-related morbidity and mortality. Cost analyses were performed from a payer's perspective. Deterministic and probabilistic sensitivity analyses were conducted. In the age group of 60-year olds, TDM gained 1.07 QALYs in men and 0.97 QALYs in women at additional costs of €3854 and €3922, respectively. Given a willingness-to-pay threshold of €35,000 per QALY gained, the probability of TDM being cost-effective was 95% or more in all age groups from 30 to 90 years. Results were influenced mostly by the frequency of TDM testing, the rate of nonresponders to TDM, and the magnitude of effect of TDM on BP. Therapeutic drug monitoring presents a potential cost-effective healthcare intervention in patients diagnosed with resistant hypertension. Importantly, this finding is valid for a wide range of patients, independent of sex and age. | 25,255,395 | [
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Outcome of regional lymphadenectomy in accordance with primary tumor location on laparoscopic nephroureterectomy for urothelial carcinoma of the upper urinary tract: a prospective study. | To determine the appropriate template of regional lymph node dissection (LND) at the time of laparoscopic nephroureterectomy (LNU) for patients with clinically node- negative urothelial carcinoma of the upper urinary tract. This prospective study included 45 patients undergoing LND with LNU in accordance with our prospective rules regarding the area of LND. Perioperative, pathologic, and follow-up data were collected. Micrometastasis in lymph nodes (LNs) was later evaluated by immunohistochemistry (IHC). Recurrence-free survival (RFS) was calculated with the Kaplan-Meier method. The median number of LNs removed was 14 (range 1-33). One patient with pT3 disease had node metastasis based on routine pathologic examination, and IHC revealed micrometastases in two additional patients (pT2 in one and pT3 in one). Therefore, 15% (3/20) of patients with ≥pT2 disease had node disease. After surgery, six patients experienced minor complications (Grade 1 or 2), and Grade 5 gastrointestinal bleeding after aspiration pneumonia developed in one elderly male patient on the 45th postoperative day, which was not considered to be associated with LND. At the last follow-up, lung metastasis developed in four patients (pT1 in one, pT2 in one, and pT3 in two), and presacral lymph node metastasis developed in one patient with a lower ureteral tumor (pT2), which was not included in our prospective template for a lower ureteral tumor. LN recurrence within/ near the LND area was not observed in patients with pelvic/upper ureteral carcinoma. The 2-year nonurothelial RFS rate was 84%. We consider that the present template represents regional LNs for patients with clinically node-negative pelvic/upper ureteral carcinoma, while presacral LNs may be incorporated into the regional LND template for patients with clinically node-negative lower ureteral carcinoma. | 25,255,401 | [
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A cost analysis of the impact of a new intravenous antihypertensive in managing perioperative blood pressure during cardiac surgery. | To examine the impact of intravenous antihypertensive selection on hospital health resource utilization using data from the Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events (ECLIPSE) trials. Analysis of ECLIPSE trial data comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine and unit costs based on the Premier Hospital database to assess surgery duration, time to extubation, and length of stay (LOS) with the associated cost. A total of 1414 patients from the ECLIPSE trials and the Premier hospital database were included for analysis. The duration of surgery and postoperative LOS were similar across groups. The time from chest closure to extubation was shorter in patients receiving clevidipine group compared with the pooled comparator group (median 7.0 vs 7.6 hours, P = 0.04). There was shorter intensive care unit (ICU) LOS in the clevidipine group versus the nitroglycerin group (median 27.2 vs 33.0 hours, P = 0.03). A trend toward reduced ICU LOS was also seen in the clevidipine compared with the pooled comparator group (median 32.3 vs 43.5 hours, P = 0.06). The costs for ICU LOS and time to extubation were lower with clevidipine than with the comparators, with median cost savings of $887 and $34, respectively, compared with the pooled comparator group, for a median cost savings of $921 per patient. Health resource utilization across therapeutic alternatives can be derived from an analysis of standard costs from hospital financial data to matched utilization metrics as part of a randomized controlled trial. In cardiac surgical patients, intravenous antihypertensive selection was associated with a shorter time to extubation in the ICU and a shorter ICU stay compared with pooled comparators, which in turn may decrease total costs. | 25,255,404 | [
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Management of hemorrhage with the target-specific oral anticoagulants. | The target-specific oral anticoagulants have recently been introduced as alternatives to warfarin for both prophylactic and therapeutic indications. Although their efficacy and side-effect profiles have been favorable, there is significant concern about management of hemorrhage with these agents as there is no direct reversal agent available. It is important for clinicians to be aware of these agents and the issues that surround them. Most of the management of hemorrhage is based on expert opinion and case reviews. Given the potentially catastrophic consequences of acute hemorrhage while patients are on anticoagulation, specific treatments are needed. Some methods that have been described include activated charcoal, hemodialysis, prohemostatic agents, and transfusions. Target-specific therapies have been shown to be effective in early studies in animal models; however, the effects in humans are still under investigation. More investigation is needed on the management of bleeding complications from target-specific oral anticoagulants. | 25,255,409 | [
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0.2628356,
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The likelihood of achieving quantified road safety targets: a binary logistic regression model for possible factors. | In past several decades, many countries have set quantified road safety targets to motivate transport authorities to develop systematic road safety strategies and measures and facilitate the achievement of continuous road safety improvement. Studies have been conducted to evaluate the association between the setting of quantified road safety targets and road fatality reduction, in both the short and long run, by comparing road fatalities before and after the implementation of a quantified road safety target. However, not much work has been done to evaluate whether the quantified road safety targets are actually achieved. In this study, we used a binary logistic regression model to examine the factors - including vehicle ownership, fatality rate, and national income, in addition to level of ambition and duration of target - that contribute to a target's success. We analyzed 55 quantified road safety targets set by 29 countries from 1981 to 2009, and the results indicate that targets that are in progress and with lower level of ambitions had a higher likelihood of eventually being achieved. Moreover, possible interaction effects on the association between level of ambition and the likelihood of success are also revealed. | 25,255,417 | [
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Investigation of various types of inverse micelles in nonpolar liquids using transient current measurements. | Transient current measurements are used to characterize a wide variety of charge carriers in nonpolar liquids. The transient current method allows us to obtain both the concentration and mobility of charge carriers and therefore also the hydrodynamic radius using Stokes' law. In this article, five different surfactants in dodecane are investigated: OLOA11K, Solsperse13940, Span80, Span85, and AOT. We show that different types of currents are observed depending on the size of the inverse micelles. For large inverse micelles such as for OLOA11K, Solsperse13940, and Span80, the measurement of the transient current is straightforward because of the low steady-state current level. However, for small inverse micelles such as AOT and Span85, the current from the generation of charges is much larger such that high voltages, a small distance between the electrodes, and dielectric coatings on the electrodes are required to measure the signal related to the initially present charged inverse micelles. The estimated hydrodynamic radii of AOT and Span85, the two smallest inverse micelles, are in good agreement with the values reported in the literature. The comparison of the transient currents with simulations indicates that the dynamics of the charge transport are well-understood. | 25,255,418 | [
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First step into space: performance and morphological evolution of P3HT:PCBM bulk heterojunction solar cells [corrected] under AM0 illumination. | P3HT (poly(3-hexylthiophene-2,5-diyl)):PC61BM ([6,6]-phenyl-C61 butyric acid methyl ester) bulk heterojunction solar cells are fabricated and characterized as a function of solar intensity, temperature, and aging at vacuum conditions under illumination with AM0 illumination for testing potential use in space applications. The evolution of the inner film morphology is probed with grazing incidence X-ray scattering techniques and correlated with the evolution of the efficiency during aging. Grazing incidence wide-angle X-ray scattering shows almost no change of the crystalline structure of the P3HT:PCBM films due to aging. In contrast, the morphological evolution on the mesoscale extracted from grazing incidence small-angle X-ray scattering can explain the observed decay of the overall efficiency. The behavior at high solar intensities as well as elevated temperatures suggests that organic solar cells have high potential for space applications in the future. | 25,255,423 | [
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Single-dose etomidate does not increase mortality in patients with sepsis: a systematic review and meta-analysis of randomized controlled trials and observational studies. | The effect of single-dose etomidate on mortality in patients with sepsis remains controversial. We systematically reviewed the literature to investigate whether a single dose of etomidate for rapid sequence intubation increased mortality in patients with sepsis. PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched for randomized controlled trials (RCTs) and observational studies regarding the effect of single-dose etomidate on mortality in adults with sepsis. The primary outcome was all-cause mortality. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled relative risks (RRs) and 95% CIs. Eighteen studies (two RCTs and 16 observational studies) in 5,552 patients were included. Pooled analysis suggested that single-dose etomidate was not associated with increased mortality in patients with sepsis in both the RCTs (RR, 1.20; 95% CI, 0.84-1.72; P = .31; I(2) = 0%) and the observational studies (RR, 1.05; 95% CI, 0.97-1.13; P = .23; I(2) = 25%). When only adjusted RRs were pooled in five observational studies, RR for mortality was 1.05 (95% CI, 0.79-1.39; P = .748; I(2) = 71.3%). These findings also were consistent across all subgroup analyses for observational studies. Single-dose etomidate increased the risk of adrenal insufficiency in patients with sepsis (eight studies; RR, 1.42; 95% CI, 1.22-1.64; P < .00001). Current evidence indicates that single-dose etomidate does not increase mortality in patients with sepsis. However, this finding largely relies on data from observational studies and is potentially subject to selection bias; hence, high-quality and adequately powered RCTs are warranted. | 25,255,427 | [
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Geographical variation in health-related physical fitness and body composition among Chilean 8th graders: a nationally representative cross-sectional study. | In addition to excess adiposity, low cardiorespiratory fitness (CRF) and low musculoskeletal fitness (MSF) are important independent risk factors for future cardio-metabolic disease in adolescents, yet global fitness surveillance in adolescents is poor. The objective of this study was to describe and investigate geographical variation in levels of health-related physical fitness, including CRF, MSF, body mass index (BMI), and waist circumference (WC) in Chilean 8th graders. This cross-sectional study was based on a population-based, representative sample of 19,929 8th graders (median age = 14 years) in the 2011 National Physical Education Survey from Chile. CRF was assessed with the 20-meter shuttle run test, MSF with standing broad jump, and body composition with BMI and WC. Data were classified according to health-related standards. Prevalence of levels of health-related physical fitness was mapped for each of the four variables, and geographical variation was explored at the country level by region and in the Santiago Metropolitan Area by municipality. Girls had significantly higher prevalence of unhealthy CRF, MSF, and BMI than boys (p<0.05). Overall, 26% of boys and 55% of girls had unhealthy CRF, 29% of boys and 35% of girls had unhealthy MSF, 29% of boys and 44% of girls had unhealthy BMI, and 31% of adolescents had unhealthy WC. High prevalence of unhealthy fitness levels concentrates in the northern and middle regions of the country and in the North and Southwest sectors for the Santiago Metropolitan Area. Prevalence of unhealthy CRF, MSF, and BMI is relatively high among Chilean 8th graders, especially in girls, when compared with global estimates. Identification of geographical regions and municipalities with high prevalence of unhealthy physical fitness presents opportunity for targeted intervention. | 25,255,442 | [
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Cardiac-specific inhibition of kinase activity in calcium/calmodulin-dependent protein kinase kinase-β leads to accelerated left ventricular remodeling and heart failure after transverse aortic constriction in mice. | The mechanism of cardiac energy production against sustained pressure overload remains to be elucidated. We generated cardiac-specific kinase-dead (kd) calcium/calmodulin-dependent protein kinase kinase-β (CaMKKβ) transgenic (α-MHC CaMKKβkd TG) mice using α-myosin heavy chain (α-MHC) promoter. Although CaMKKβ activity was significantly reduced, these mice had normal cardiac function and morphology at baseline. Here, we show that transverse aortic binding (TAC) in α-MHC CaMKKβkd TG mice led to accelerated death and left ventricular (LV) dilatation and dysfunction, which was accompanied by significant clinical signs of heart failure. CaMKKβ downstream signaling molecules, including adenosine monophosphate-activated protein kinase (AMPK), were also suppressed in α-MHC CaMKKβkd TG mice compared with wild-type (WT) mice. The expression levels of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, which is a downstream target of both of CaMKKβ and calcium/calmodulin kinases, were also significantly reduced in α-MHC CaMKKβkd TG mice compared with WT mice after TAC. In accordance with these findings, mitochondrial morphogenesis was damaged and creatine phosphate/β-ATP ratios assessed by magnetic resonance spectroscopy were suppressed in α-MHC CaMKKβkd TG mice compared with WT mice after TAC. These data indicate that CaMKKβ exerts protective effects on cardiac adaptive energy pooling against pressure-overload possibly through phosphorylation of AMPK and by upregulation of PGC-1α. Thus, CaMKKβ may be a therapeutic target for the treatment of heart failure. | 25,255,457 | [
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Tracheal Epstein-Barr virus-associated smooth muscle tumour in an HIV-positive patient. | Epstein-Barr virus-related smooth muscle tumours (EBV-SMTs) are a rare but well recognized non-AIDS-defining malignancy that can also be found in several other immunosuppressed states. Pulmonary involvement of EBV-SMTs is not uncommon, but it can present with multifocal lesions in any anatomical site. The present article describes an HIV-positive woman with dyspnea who was found to have a large tracheal EBV-SMT. The authors discuss their approach to diagnosis and management, and present unique follow-up bronchoscopic imaging. | 25,255,459 | [
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Correlation of the interleukin-29 levels in crevicular fluid and plasma with the genetic polymorphism in chronic and aggressive periodontitis patients. | To assess the effect of single nucleotide polymorphism (SNP) on the Interleukin (IL-29) quantity in gingival crevicular fluid (GCF) and plasma of chronic and aggressive periodontitis patients. Patients with periodontal health (n=30), chronic generalized periodontitis (n=30) and generalized aggressive periodontitis (n=30) were subjected to IL-29 quantity estimation in GCF and plasma using enzyme linked immunosorbent assay and was correlated with IL-29 SNP (rs30461) using polymerase chain reaction. IL-29 concentration in GCF and plasma was highest in aggressive periodontitis patients (114.17 ± 95.07pg/ml and 149.69 ± 109.90pg/ml respectively). The least concentration was found in subjects with healthy periodontium (47.50 ± 37.75pg/ml and 54.52 ± 37.53pg/ml) and in chronic periodontitis it was found to be 65.01 ± 41.26pg/ml and 81.17 ± 46.23pg/ml. The difference in the quantity of IL-29 in GCF and plasma among different groups was statistically significant (p<0.001 and p<0.001 respectively). rs30461 polymorphism of IL-29 analysis revealed that difference in the prevalence of A/A, A/G and G/G genotype among three groups was not statistically significant (p=0.097). Increased quantity of IL-29 in GCF and plasma of subjects with periodontitis suggests a role in pathogenesis of periodontitis and the SNP (rs30461) is not related to susceptibility to periodontitis in this population of Indian individuals. | 25,255,471 | [
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Besides fibrillization: putative role of the peptide fragment 71-82 on the structural and assembly behavior of α-synuclein. | The fibrillization of α-synuclein (α-syn) is involved in Parkinson's disease, a neurodegenerative disorder that affects four million people in the world. The amino acid sequence 71-82 of this protein (VTGVTAVAQKTV) has appeared to be essential for fibril formation. In the present study, we have investigated the secondary structure and thermal stability of the peptide fragment 71-82, α-syn71-82, as a function of concentration and temperature, as well as its interactions with phospholipid model membranes using various spectroscopic techniques. The data show that α-syn71-82 is mainly disordered in solution with the presence of a few β-sheet structure elements. The peptide reversibly forms intermolecular β-sheets with increasing concentration and decreasing temperature, suggesting that it is subjected to a thermodynamic equilibrium between a monomeric and an oligomeric form. This equilibrium seems to be affected by the presence of zwitterionic membranes. Conversely, the influence of the peptide on zwitterionic lipid bilayers is small and concentration-dependent. By contrast, α-syn71-82 is strongly affected by anionic vesicles. The peptide indeed exhibits a dramatic conformational change, reflecting an extensive and irreversible self-aggregation, the majority of the amino acids being involved in a parallel β-sheet conformation. The aggregates appear to be located near the membrane surface but do not perturb significantly the membrane order. Comparing these results with the literature, it appears that α-syn71-82 shares several general properties and structural similarities with its parent protein. These common points suggest that the sequence 71-82 may overall contribute to the behavior and properties of α-syn. | 25,255,476 | [
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Payment or reimbursement for certain medical expenses for Camp Lejeune family members. Interim final rule. | The Department of Veterans Affairs (VA) is promulgating regulations to implement statutory authority to provide payment or reimbursement for hospital care and medical services provided to certain veterans' family members who resided at Camp Lejeune, North Carolina, for at least 30 days during the period beginning on January 1, 1957, and ending on December 31, 1987. Under this rule, VA will reimburse family members, or pay providers, for medical expenses incurred as a result of certain illnesses and conditions that may be attributed to exposure to contaminated drinking water at Camp Lejeune during this time period. Payment or reimbursement will be made within the limitations set forth in statute and Camp Lejeune family members will receive hospital care and medical services that are consistent with the manner in which we provide hospital care and medical services to Camp Lejeune veterans. | 25,255,501 | [
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[Determination of eight bisphenol diglycidyl ethers in water by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry]. | A solid phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method was developed for the determination of eight bisphenol diglycidyl ethers, including bisphenol A diglycidyl ether (BADGE), bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE x HCl), bisphenol A bis (3-chloro-2-hydroxypropyl) ether (BADGE x 2HCl), bisphenol A (2, 3-dihydroxypropyl) glycidyl ether (BADGE x H2O), bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE x 2H2O), bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) ether (BADGE x HCl x H2O), bisphenol F diglycidyl ether (BFDGE) and bisphenol F bis (3-chloro-2-hydroxypropyl) ether (BFDGE 2HCl) in water. A total of ten samples were collected from the leaching of the coatings for drinking water supply system. Then, 200 mL exposure water was preconcentrated on C18 solid-phase extraction cartridge. The eight compounds were analyzed by liquid chromatography-tandem mass spectrometry method on a C18 column by the gradient elution with methanol, water and 5 mmol/L ammonium acetate as mobile phases in the multiple reaction monitoring (MRM) scan mode. The external matrix standard solutions were used for the quantitative determination and the calibration curves of the eight compounds showed good linearity in the range of 0.007-5.00 microg/L with the correlation coefficients more than 0.999 0. The limits of quantification (LOQs) of the method were 7-91 ng/L. The spiked recoveries ranged from 79.1% to 101% with the relative standard deviations of 4.0% - 12%. The method is sensitive and accurate, and is applicable to the determination of bisphenol diglycidyl ethers in water. | 25,255,565 | [
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Salmonella bacteraemia among healthcare workers and their dependents. | To determine the incidence and resistance pattern of Salmonella infection in healthcare workers and their dependents. The retrospective analysis was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and comprised records of employees and their dependents with bacteraemia from January 2007 to December 2011. Person-years were calculated using data from the human resources department. SPSS 19 was used for statistical analyses. Of the total 2532 records available, 82 (3.23%) patients were identified with Salmonella bacteraemia. Of them, 34 (41.5%) patients were in age group 1-10, 15 (18.3%) in 11-20, 26 (31.7%) in 21-30, and 7 (8.5%) were above 30 years. Besides, 48 (58.5%) were males. Salmonella typhi was found in 44 (53.7%) patients, Salmonella paratyphiA in 35 (42.7%) and Salmonella species in 3 (3.7%) patients. The yearly incidence of Salmonella infection in the study population ranged from 206 to 596 per 100000 person-years. Ciprofloxacin resistance was noted to be 56 (68.2%) followed by Ampicillin 29 (35.3%) and Co-trimoxazole 24 (29.2%). No strains were resistant to Cefiximeor Ceftriaxone. The yearly incidence of Salmonella bacteraemia ranged from 200 to 600 per 100000 person years. There was significant quinolone resistance among the isolates. | 25,255,579 | [
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Perforation of Meckel's diverticulum by foreign body. | Meckel's diverticulum (MD) is a congenital disorder of the gastrointestinal tract that is usually asymptomatic. Perforation of an MD by foreign bodies is an extremely rare cause of acute abdomen in children. We present a rare case of perforation of an MD in a child after eating melon seeds. The patient was treated successfully with segmental resection and primary anastomosis and had an uneventful postoperative recovery. | 25,255,595 | [
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[Drainage pathways of the frontal sinus on oblique multi-planar reconstruction CT scans]. | Oblique reconstruction CT images of frontal sinus drainage pathways were created with ONIS which is free DICOM viewer software. By placing the slice line of the cross sectional image on the drainage pathway of the frontal sinus in the sagittal view, the key oblique CT image could be generated in 96.9% of 65 normal paranasal sinuses that showed the frontal sinus and its drainage pathway simultaneously in one slice. The route of the drainage pathway was divided by the line of the uncinate process, and three variations were defined as follows: (1) inside, (2) outside to inside, and (3) outside. Additionally, three variations of the upper attachment site of the uncinate process were defined as follows: (1) outside: orbital wall, (2) upside: skull base or intersinus septum of the frontal sinus, and (3) inside: middle turbinate. The uncinate process was attached to the "outside" in 66.7%, and all of them had the "inside" pathway of drainage. The rest of them in whom the uncinate process was attached to the "upside" or "inside" had a drainage pathway of "outside to inside" or "outside." The anatomical relations between the frontal sinus and the anterior ethmoid cells such as agger nasi cell, frontal ethmoidal cell and intersinus septal cell were reasonably explained with these variations in the drainage pathway. The key oblique CT image showing the frontal sinus drainage pathway is the imaginary plane of the surgical pathway of instruments while they are inserted into the frontal sinus. Therefore, using the oblique CT image together with the sagittal CT image, we can get valuable information about the three dimensional anatomy of the frontal sinus before and during frontal sinusotomy. | 25,255,645 | [
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[Utilization of ultrasonography in the fields of critical care medicine and anesthesiology: preface and comments ]. | Recently, with the development of technology, opportunities for the clinical use of ultrasonography are increasing. Regarding this circumstance, the current issue highlights the use of ultrasonography in critical care and anesthesia Chapters include cardiac, lung and abdominal echography, and various perioperative use of ultrasonography including ultrasound-guided procedures. Every author emphasizes that "Seeing the image of ultrasonography is believing". Finally, I hope the current issue help the readers get cutting edge knowledge of the utilization of ultrasonography in the clinical practice. | 25,255,655 | [
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[FAST for abdominal trauma]. | Japanese Association for Acute Medicine and Japanese Association for The Surgery of Trauma developed JATEC (Japan Advanced Trauma Evaluation and Care) course as an off-the-job training to improve trauma care in Japan. In this course, the trauma patients undergo primary survey and secondary survey. FAST (focused assessment with sonography for trauma) is performed to detect hemoperitoneum during primary survey. In this article, we describe FAST in the evaluation and care for abdominal trauma. If the patient becomes hemodynamically unstable during the survey or the intraoperative period, we have to repeat primary survey and FAST. | 25,255,658 | [
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[Transesophageal and intracardiac echocardiography in therapeutic cardiac catheterizations of structural heart disease]. | Recently clinical indication of therapeutic cardiac catheterization (CC) is being developed in the field of structural heart disease (SHD) along with the advance and refinement of medical equipment for interventional CC. Echocardiography is an indispensable imaging tool as well as fluoroscopy as a guidance of CC. Transesophageal echocardiography (TEE) is one of the most widely used imaging modalities in diagnosis and treatment of SHD. Although TEE provides high-quality imaging of intra-cardiovascular structures including three-dimensional imaging, it requires general anesthesia when it is performed along with therapeutic CC. Intracardiac echocardiography (ICE) is a useful alternative in this setting since it can be performed intravenously only under local anesthesia during CC and displays excellent cardiovascular imaging similar to TEE. We herein discuss the clinical utility of both TEE and ICE during the procedure of device closure of atrial septal defect. | 25,255,660 | [
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Multifunctional Au-ZnO plasmonic nanostructures for enhanced UV photodetector and room temperature NO sensing devices. | In this study we report the enhancement of UV photodetection and wavelength tunable light induced NO gas sensing at room temperature using Au-ZnO nanocomposites synthesized by a simple photochemical process. Plasmonic Au-ZnO nanostructures with a size less than the incident wavelength have been found to exhibit a localized surface plasmon resonance (LSPR) that leads to a strong absorption, scattering and local field enhancement. The photoresponse of Au-ZnO nanocomposite can be effectively enhanced by 80 times at 335 nm over control ZnO. We also demonstrated Au-ZnO nanocomposite's application to wavelength tunable gas sensor operating at room temperature. The sensing response of Au-ZnO nancomposite is enhanced both in UV and visible region, as compared to control ZnO. The sensitivity is observed to be higher in the visible region due to the LSPR effect of Au NPs. The selectivity is found to be higher for NO gas over CO and some other volatile organic compounds (VOCs), with a minimum detection limit of 0.1 ppb for Au-ZnO sensor at 335 nm. | 25,255,700 | [
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Congenital central diabetes insipidus and optic atrophy in a Wolfram newborn: is there a role for WFS1 gene in neurodevelopment? | Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder characterized by diabetes mellitus (DM), optic atrophy (OA), central diabetes insipidus (CDI) and deafness (D). The phenotype of the disease has been associated with several mutations in the WFS1 gene, a nuclear gene localized on chromosome 4. Since the discovery of the association between WFS1 gene and Wolfram syndrome, more than 150 mutations have been identified in WS patients. We previously described the first case of perinatal onset of Wolfram syndrome newborn carrying a segmental uniparental heterodysomy affecting the short arm of chromosome 4 responsible for a significant reduction in wolframin expression. Here we review and discuss the pathophysiological mechanisms that we believe responsible for the perinatal onset of Wolfram syndrome as these data strongly suggest a role for WFS1 gene in foetal and neonatal neurodevelopment. We described a male patient of 30 weeks' gestation with intrauterine growth restriction and poly-hydramnios. During the first days of life, the patient showed a 19% weight loss associated with polyuria and hypernatremia. The presence of persistent hypernatremia (serum sodium 150 mEq/L), high plasma osmolarity (322 mOsm/L) and low urine osmolarity (190 mOsm/l) with a Uosm/Posm ratio < 1 were consistent with CDI. The diagnosis of CDI was confirmed by the desmopressin test and the brain magnetic resonance imaging (MRI) at 34 weeks of age, that showed the lack of posterior pituitary hyperintense signal. In addition, a bilateral asymmetrical optic nerve hypoplasia associated with right orbital bone hypoplasia was observed, suggesting the diagnosis of WF. During the five years follow-up the patient did not developed glucose intolerance or diabetes mellitus. By the end of the second year of life, primary non-autoimmune central hypothyroidism and mild neurodevelopment retardation were diagnosed. The analysis of our case, in the light of the most recent literature, suggests a possible role for WFS1 gene in the development of certain brain structures during the fetal period. Wolfram syndrome should be considered in the differential diagnosis of the rare cases of congenital central diabetes insipidus developed in the neonatal period. | 25,255,707 | [
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Long-term oncologic outcomes of radical prostatectomy compared with brachytherapy-based approaches for intermediate- and high-risk prostate cancer. | To review the recently published contemporary long-term outcomes from tertiary care urologic practices comparing brachytherapy-based management strategies and radical prostatectomy (RP) across intermediate- and high-risk groups. Literature was reviewed for the past 5 years under the search terms localized prostate cancer, outcomes, brachytherapy, and adical prostatectomy. Abstracts were reviewed and excluded if results were not reported according to the recognized risk groupings or if followup was less than 5 years. A total of 1237 abstracts concerning adical prostatectomy and 600 concerning brachytherapy were retrieved in the initial search. Of these, 80 met the inclusion criteria, and the articles were retrieved and reviewed in detail. For intermediate- and high-risk prostate cancer, brachytherapy-based approaches provide superior long-term oncologic and functional outcomes. Irritative and obstructive symptoms are prominent in the first 6-12 months but resolve by 3 years for all but <5%. High-risk patients do very well with multimodality treatment combining external beam radiotherapy, a brachytherapy boost, and androgen deprivation for 9-12 months. | 25,255,713 | [
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Toxic myopathy and acute hepatic necrosis in cattle caused by ingestion of Senna obtusifolia (sicklepod; coffee senna) in Brazil. | The epidemiological, clinical and pathological findings of field and experimental Senna obtusifolia (sicklepod; coffee senna) poisoning in cattle are described. The low availability of good quality forage and high rate of infestation of pastures by S. obtusifolia were the factors that led to poisonous plant ingestion. In this study, the morbidity ranged between 2% and 27.9%, and the lethality was 100%. For the experimental study, six cattle were fed with the aerial parts of S. obtusifolia collected in three different seasons at 9%-38% of the animal's body weight. The experimental and field diseases were similar. The main clinical signs were diarrhea, reluctance to move, muscular weakness and recumbency. The gross findings included pale discoloration of the skeletal muscle. Microscopically, the affected cattle showed degeneration and necrosis of the skeletal muscles and occasionally of the cardiac muscles. Additionally, two cattle showed centrilobular hepatic necrosis. In this study, S. obtusifolia collected from the same farm showed seasonal variation in toxicity. Poisoning by S. obtusifolia is an important cause of death of cattle in the Central Western region of Brazil. The toxicosis caused by this plant is similar to S. occidentalis poisoning; however, in S. obtusifolia poisoning, acute hepatic necrosis is sometimes present. | 25,255,730 | [
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Embryological and molecular development of the adrenal glands. | In this mini review, the embryological and functional development of the adrenal glands is presented from a molecular perspective. While acknowledging that this is a highly complex series of events, the processes are described in simple and broad strokes in a single text for the reader who is interested in this field but is not an active researcher. The origin of the adrenal glands is in the mesodermal ridge as early as the fourth week of gestation. Between the eighth and ninth weeks of gestation, the adrenal glands are encapsulated and this results in the presence of a distinct organ. There have been great strides in deciphering the very complicated molecular aspects of adrenal gland development in which multiple transcription factors have been identified, directing the adrenogonadal primordium into the adrenal cortex, kidney, or bipotential gonad. Adrenocorticotrophic hormone is critical for early development of the hypothalamic-pituitary adrenal axis. Several mutations in transcription factors, responsible for normal adrenal gland development have been found to induce the familial syndrome of congenital adrenal hypoplasia or neoplasia. | 25,255,746 | [
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Fermented broth in tyrosinase- and melanogenesis inhibition. | Fermented broth has a long history of applications in the food, pharmaceutical and cosmetic industries. Recently, the use of fermented broth in skin care products is in ascendance. This review investigates the efficacy of fermented broth in inhibiting tyrosinase and melanogenesis. Possible active ingredients and hypopigmentation mechanisms of fermented broth are discussed, and potential applications of fermented broth in the cosmetic industry are also addressed. | 25,255,749 | [
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Structure and absolute configuration of 20β-Hydroxyprednisolone, a biotransformed product of predinisolone by the marine endophytic fungus Penicilium lapidosum. | The anti-inflammatory drug predinisolone (1) was reduced to 20β-hydroxyprednisolone (2) by the marine endophytic fungus Penicilium lapidosum isolated from an alga. The structural elucidation of 2 was achieved by 1D- and 2D-NMR, MS, IR data. Although, 2 is a known compound previously obtained through microbial transformation, the data provided failed to prove the C20 stereochemistry. To solve this issue, DFT and TD-DFT calculations have been carried out at the B3LYP/6-31+G (d,p) level of theory in gas and solvent phase. The absolute configuration of C20 was eventually assigned by combining experimental and calculated electronic circular dichroism spectra and 3JHH chemical coupling constants. | 25,255,760 | [
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Challenge and opportunity in evaluating a diffusion-based active bystanding prevention program: Green Dot in high schools. | Increasing attention has recently been paid to the development of prevention programs designed to actively engage bystanders in prevention efforts to reduce the risk of sexual and dating violence; yet, few evaluations have been conducted. Our proposed plan to rigorously evaluate a randomized intervention trial of the Green Dot bystander program as it is implemented in high schools across Kentucky is presented. We highlight the value of measuring violence victimization and perpetration outcomes, capturing actual and observed student bystander behaviors, and testing the diffusion of Green Dot training through students' social networks. | 25,255,794 | [
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Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer. | Sipuleucel-T is a US Food and Drug Administration-approved immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its mechanism of action is not fully understood. This prospective trial evaluated the direct immune effects of systemically administered sipuleucel-T on prostatic cancer tissue in the preoperative setting. Patients with untreated localized prostate cancer were treated on an open-label Phase II study of sipuleucel-T prior to planned radical prostatectomy (RP). Immune infiltrates in RP specimens (posttreatment) and in paired pretreatment biopsies were evaluated by immunohistochemistry (IHC). Correlations between circulating immune response and IHC were assessed using Spearman rank order. Of the 42 enrolled patients, 37 were evaluable. Adverse events were primarily transient, mild-to-moderate and infusion related. Patients developed T cell proliferation and interferon-γ responses detectable in the blood following treatment. Furthermore, a greater-than-three-fold increase in infiltrating CD3(+), CD4(+) FOXP3(-), and CD8(+) T cells was observed in the RP tissues compared with the pretreatment biopsy (binomial proportions: all P < .001). This level of T cell infiltration was observed at the tumor interface, and was not seen in a control group consisting of 12 concurrent patients who did not receive any neoadjuvant treatment prior to RP. The majority of infiltrating T cells were PD-1(+) and Ki-67(+), consistent with activated T cells. Importantly, the magnitude of the circulating immune response did not directly correlate with T cell infiltration within the prostate based upon Spearman's rank order correlation. This study is the first to demonstrate a local immune effect from the administration of sipuleucel-T. Neoadjuvant sipuleucel-T elicits both a systemic antigen-specific T cell response and the recruitment of activated effector T cells into the prostate tumor microenvironment. | 25,255,802 | [
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Variations in CYP78A13 coding region influence grain size and yield in rice. | Grain size is one of the most important determinants of crop yield in cereals. Here, we identified a dominant mutant, big grain2 (bg2-D) from our enhancer-trapping population. Genetic analysis and SiteFinding PCR (polymerase chain reaction) revealed that BG2 encodes a cytochrome P450, OsCYP78A13. Sequence search revealed that CYP78A13 has a paralogue Grain Length 3.2 (GL3.2, LOC_Os03g30420) in rice with distinct expression patterns, analysis of transgenic plants harbouring either CYP78A13 or GL3.2 showed that both can promote grain growth. Sequence polymorphism analysis with 1529 rice varieties showed that the nucleotide diversity at CYP78A13 gene body and the 20 kb flanking region in the indica varieties were markedly higher than those in japonica varieties. Further, comparison of the genomic sequence of CYP78A13 in the japonica cultivar Nipponbare and the indica cultivar 9311 showed that there were three InDels in the promoter region and eight SNPs (single nucleotide polymorphism) in its coding sequence. Detailed examination of the transgenic plants with chimaeric constructs suggested that variation in CYP78A13 coding region is responsible for the variation of grain yield. Taken together, our results suggest that the variations in CYP78A13 in the indica varieties hold potential in rice breeding for application of grain yield improvement. | 25,255,828 | [
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An exploratory study of domains of parenting concern among mothers who are childhood sexual abuse survivors. | This study conducted an exploratory factor analysis and initial validation of Ruscio's (2001) parenting attitudes questionnaire, which assessed parenting concerns among child sexual abuse survivors. Child sexual abuse survivor mothers (N = 60) reported on their abuse experiences and completed the parenting attitudes questionnaire, the Center for Epidemiologic Studies Depression Scale, and subscales of the Parenting Stress Index and the Parent-Child Relationship Inventory. Three primary factors emerged: (a) concerns regarding the child's sexuality and safety, (b) boundary disturbances within the child-survivor relationship, and (c) lack of energy for parenting due to recovery issues. Concerns about safety and sexuality and lack of energy for parenting were robust predictors of parenting outcomes. Assessment of such concerns may facilitate discussion of the balance between recovery work and parenting challenges. | 25,255,840 | [
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An optimal transition time to extracorporeal cardiopulmonary resuscitation for predicting good neurological outcome in patients with out-of-hospital cardiac arrest: a propensity-matched study. | Prolonged conventional cardiopulmonary resuscitation (CCPR) is associated with a poor prognosis in out-of-hospital cardiac arrest (OHCA) patients. Alternative methods can be needed to improve the outcome in patients with prolonged CCPR and extracorporeal cardiopulmonary resuscitation (ECPR) can be considered as an alternative method. The objectives of this study were to estimate the optimal duration of CPR to consider ECPR as an alternative resuscitation method in patients with CCPR, and to find the indications for predicting good neurologic outcome in OHCA patients who received ECPR. This study is a retrospective analysis based on a prospective cohort. We included patients ≥ 18 years of age without suspected or confirmed trauma and who experienced an OHCA from May 2006 to December 2013. First, we determined the appropriate cut-off duration for CPR based on the discrimination of good and poor neurological outcomes in the patients who received only CCPR, and then we compared the outcome between the CCPR group and ECPR group by using propensity score matching. Second, we compared CPR related data according to the neurologic outcome in matched ECPR group. Of 499 patients suitable for inclusion, 444 and 55 patients were enrolled in the CCPR and ECPR group, respectively. The predicted duration for a favorable neurologic outcome (CPC1, 2) is < 21 minutes of CPR in only CCPR patients. The matched ECPR group with ≥ 21 minutes of CPR duration had a more favorable neurological outcome than the matched CCPR group at 3 months post-arrest. In matched ECPR group, younger age, witnessed arrest without initial asystole rhythm, early achievement of mean arterial pressure ≥ 60 mmHg, low rate of ECPR-related complications, and therapeutic hypothermia were significant factors for expecting good neurologic outcome. ECPR should be considered as an alternative method for attaining good neurological outcomes in OHCA patients who required prolonged CPR, especially of ≥ 21 minutes. Younger or witnessed arrest patients without initial asystole were good candidates for ECPR. After implantation of ECPR, early hemodynamic stabilization, prevention of ECPR-related complications, and application of therapeutic hypothermia may improve the neurological outcome. | 25,255,842 | [
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The modulating effects of endogenous substances on drug metabolising enzymes and implications for inter-individual variability and quantitative prediction. | The cytochrome P450 family of enzymes play an important role in the metabolism of drugs and other xenobiotics. While genotypic variation can contribute to the inter-individual variability in drug metabolism, individuals sharing the same genotype for an enzyme can still show considerable variability in drug metabolising capacity by that enzyme. It is well recognised that in some disease states (e.g. inflammation, infection, diabetes) or other physiological conditions (e.g. pregnancy), the clearance of drugs may significantly alter, possibly via modulation of drug metabolising enzymes by varying levels of endogenous substances. This review investigates the current knowledge on the modulating effects of various endogenous substances on DMEs in vitro and possible utility of available in vitro data for quantitative prediction of clinical outcome. It is postulated that understanding and estimating the inter-individual variability in DMEs within each population might be possible by application of in vitro in vivo extrapolation linked physiologically-based pharmacokinetic modelling. However, in vitro information for building such quantitative relationships is currently not abundant. | 25,255,874 | [
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Geometrical and optical benchmarking of copper(II) guanidine-quinoline complexes: insights from TD-DFT and many-body perturbation theory (part II). | Ground- and excited-state properties of copper(II) charge-transfer systems have been investigated starting from density-functional calculations with particular emphasis on the role of (i) the exchange and correlation functional, (ii) the basis set, (iii) solvent effects, and (iv) the treatment of dispersive interactions. Furthermore (v), the applicability of TD-DFT to excitations of copper(II) bis(chelate) charge-transfer systems is explored by performing many-body perturbation theory (GW + BSE), independent-particle approximation and ΔSCF calculations for a small model system that contains simple guanidine and imine groups. These results show that DFT and TD-DFT in particular in combination with hybrid functionals are well suited for the description of the structural and optical properties, respectively, of copper(II) bis(chelate) complexes. Furthermore, it is found an accurate theoretical geometrical description requires the use of dispersion correction with Becke-Johnson damping and triple-zeta basis sets while solvent effects are small. The hybrid functionals B3LYP and TPSSh yielded best performance. The optical description is best with B3LYP, whereby heavily mixed molecular transitions of MLCT and LLCT character are obtained which can be more easily understood using natural transition orbitals. An natural bond orbital analysis sheds light on the donor properties of the different donor functions and the intraguanidine stabilization during coordination to copper(I) and (II). | 25,255,876 | [
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Stable small quantum dots for synaptic receptor tracking on live neurons. | We developed a coating method to produce functionalized small quantum dots (sQDs), about 9 nm in diameter, that were stable for over a month. We made sQDs in four emission wavelengths, from 527 to 655 nm and with different functional groups. AMPA receptors on live neurons were labeled with sQDs and postsynaptic density proteins were visualized with super-resolution microscopy. Their diffusion behavior indicates that sQDs access the synaptic clefts significantly more often than commercial QDs. | 25,255,882 | [
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Multiwall carbon nanotubes directly promote fibroblast-myofibroblast and epithelial-mesenchymal transitions through the activation of the TGF-β/Smad signaling pathway. | A number of studies have demonstrated that MWCNTs induce granuloma formation and fibrotic responses in vivo, and it has been recently reported that MWCNT-induced macrophage activation and subsequent TGF-β secretion contribute to pulmonary fibrotic responses. However, their direct effects against alveolar type-II epithelial cells and fibroblasts and the corresponding underlying mechanisms remain largely unaddressed. Here, MWCNTs are reported to be able to directly promote fibroblast-to-myofibroblast conversion and the epithelial-mesenchymal transition (EMT) through the activation of the TGF-β/Smad signaling pathway. Both of the cell transitions may play important roles in MWCNT-induced pulmonary fibrosis. Firstly, in-vivo and in-vitro data show that long MWCNTs can directly interact with fibroblasts and epithelial cells, and some of them may be uptaken into fibroblasts and epithelial cells by endocytosis. Secondly, long MWCNTs can directly activate fibroblasts and increase both the basal and TGF-β1-induced expression of the fibroblast-specific protein-1, α-smooth muscle actin, and collagen III. Finally, MWCNTs can induce the EMT through the activation of TGF-β/Smad2 signaling in alveolar type-II epithelial cells, from which some fibroblasts involved in pulmonary fibrosis are thought to originate. These observations suggest that the activation of the TGF-β/Smad2 signaling plays a critical role in the process of the fibroblast-to-myofibroblast transition and the EMT induced by MWCNTs. | 25,255,886 | [
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The clinical anatomy of the conal artery. | Coronary arteries have been extensively described and recognized by gross anatomic studies. However, in the clinical setting, the recognition of the conal artery is essential during coronary angiography, as well as certain congenital heart conditions such as tetralogy of Fallot. In order to provide a complete anatomic and physiologic correlation of the actual incidence and distribution of the conal artery we examined 300 formalin fixed hearts with gross dissections and 300 coronary angiograms. The conal artery was identified in all hearts examined and five main patterns were recognized. In Type A (193, 32.1%), the conal artery arose as a branch of the right coronary artery (RCA); in Type B (96, 16%), the conal artery arose from the common coronary ostium with the RCA; in Type C (242, 40.3%), the conal artery took origin from the right aortic sinus as an independent artery; in Type D (48, 8%), multiple conal arteries were present and arose from the RCA as separate branches (32, 66.6%), from a common ostium with the RCA (8, 16.6%) or from the aortic sinus (8, 16.6%); in Type E (22, 3.6%), the conal artery arose as a branch of the right ventricular branch (17, 2.8%) or acute marginal artery (5, 0.8%). The relative prevalence of the five patterns as well as the morphology and the topography of the conal artery varied significantly with the degree of coronary luminal stenosis (as observed during angiography) and also with the degree of hypertrophied ventricular wall (as observed during gross dissections). | 25,255,889 | [
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Effect of diabetes on hospitalization for ischemic stroke and related in-hospital mortality: a study in Tuscany, Italy, over years 2004-2011. | Incidence of ischemic stroke and associated in-hospital mortality is decreasing in Western populations, while the prevalence of diabetes, a well-known risk factor for ischemic stroke, is progressively rising. This study was aimed at evaluating the effect of diabetes on ischemic stroke hospitalization and in-hospital mortality after ischemic stroke. Discharges with diagnosis of ischemic stroke were identified in a database containing all hospitalizations of resident population of Tuscany, Italy, over years 2004-2011. Cases with diabetes were identified through specific drug prescriptions, official certifications or previous hospital diagnosis. Rates of annual ischemic stroke incidence and related in-hospital mortality were separately calculated for gender and age class, in subjects with and without diabetes. Sixty-five thousand one hundred sixty-five hospital discharges with ischemic stroke diagnosis were identified. Diabetes was associated with increased risk of stroke odds ratio(95% confidence interval):1.31(1.28-1.34) in men and 1.24(1.21-1.37) in women. Diabetic women, compared with men, had a higher in-hospital mortality risk after ischemic stroke (odds ratio:1.32; 1.06-1.64), whereas in non-diabetic subjects, there was no difference between genders. Incidence of ischemic stroke has declined in non-diabetic subjects, except for women aged ≤70 years; a similar reduction was observed for in-hospital mortality. Among diabetic patients, conversely, annual incidence of ischemic stroke rose by 3% in the elderly people (>70 years), and annual mortality trend remained unchanged. In the last decade, the incidence of ischemic stroke and of related in-hospital mortality declined in persons without diabetes, while increasing among diabetic patients of advanced age. Women with diabetes, compared with men, had a higher in-hospital mortality risk. | 25,255,901 | [
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Evidence on access to medicines for chronic diseases from household surveys in five low- and middle-income countries. | The 2011 United Nations (UN) General Assembly Political Declaration on Prevention and Control of Non-Communicable Diseases (NCDs) brought NCDs to the global health agenda. Essential medicines are central to treating chronic diseases such as hypertension and diabetes. Our study aimed to quantify access to essential medicines for people with chronic conditions in five low- and middle-income countries and to evaluate how household socioeconomic status and perceptions about medicines availability and affordability influence access. We analysed data for 1867 individuals with chronic diseases from national surveys (Ghana, Jordan, Kenya, Philippines and Uganda) conducted in 2007-10 using a standard World Health Organization (WHO) methodology to measure medicines access and use. We defined individuals as having access to medicines if they reported regularly taking medicine for a diagnosed chronic disease and data collectors found a medicine indicated for that disease in their homes. We used logistic regression models accounting for the clustered survey design to investigate determinants of keeping medicines at home and predictors of access to medicines for chronic diseases. Less than half of individuals previously diagnosed with a chronic disease had access to medicines for their condition in every country, from 16% in Uganda to 49% in Jordan. Other than reporting a chronic disease, higher household socioeconomic level was the most significant predictor of having any medicines available at home. The likelihood of having access to medicines for chronic diseases was higher for those with medicines insurance coverage [highest adjusted odds ratio (OR) 3.12 (95% confidence intervals (CI): 1.38, 7.07)] and lower for those with past history of borrowing money to pay for medicines [lowest adjusted OR 0.56 (95% CI: 0.34, 0.92)]. Our study documents poor access to essential medicines for chronic conditions in five resource-constrained settings. It highlights the importance of financial risk protection and consumer education about generic medicines in global efforts towards improving treatment of chronic diseases. | 25,255,920 | [
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Silencing of PNPLA6, the neuropathy target esterase (NTE) codifying gene, alters neurodifferentiation of human embryonal carcinoma stem cells (NT2). | Neuropathy target esterase (NTE) is a protein involved in the development of a polyneuropathy caused by exposure to certain organophosphorus compounds. In vivo and in vitro studies have also associated NTE with embryonic development since NTE null mice embryos are non-viable, and silencing the NTE-codifying gene (Pnpla6) in mouse embryonic stem cells strongly alters the differentiation of vascular and nervous systems. In this paper, human embryonal carcinoma stem cells human-derived NTera2/D1 (hNT2) are used as an in vitro neurodifferentiation model to determine whether PNPLA6 silencing is able to alter the differentiation process. In control cultures, PNPLA6 mRNA levels increased in parallel with other neuroectodermal markers during neurodifferentiation. PNPLA6 silencing with specific interference RNA reached a 97% decrease in gene expression 3days after transfection and with a maximum reduction in NTE enzymatic activity (50%), observed on day 4. Silencing PNPLA6 showed an 80% decrease in quantifiable neuronal cells after 13days in vitro (DIV) compared to controls and absence of different neuronal markers after 66DIV. Microarray data analysis of the PNPLA6-silenced cells showed alterations in several developmental processes, mainly neurogenesis and epithelium tube morphogenesis. PNPLA6 silencing also led to a reduction in electrical activity and an altered neuronal phenotype. This work is the first proof supporting the hypothesis that NTE plays a role in human early neurodevelopment using a human cell differentiation model. | 25,255,935 | [
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Identification and expression of GnRH2 and GnRH3 in the black sea bass (Centropristis striata), a hermaphroditic teleost. | We cloned two cDNAs for two gonadotropin-releasing hormones, GnRH2 (chicken GnRH-II) and GnRH3 (salmon GnRH), respectively, from the black sea bass (Centropristis striata). Black sea bass are protogynous hermaphroditic teleosts that change from females to males between 2 and 5 years of age. Similar to other GnRH precursors, the precursors of black sea bass GnRH2 and GnRH23 consisted of a signal peptide, decapeptide, a downstream processing site, and a GnRH-associated peptide. Our analyses failed to identify GnRH1. GnRH3 precursor transcript was more widely distributed in a variety of tissues compared with GnRH2. Further examination of GnRH expression and gonadal histology was done in black sea bass from three different size groups: small (11.4-44.1 g), medium (179.4-352.2 g) and large (393.8-607.3 g). Interestingly, GnRH3 expression occurred only in the pituitaries of males in the small and medium groups compared with expression of GnRH2. Future functional studies of the sea bass GnRHs will be valuable in elucidating the potential underlying neuroendocrine mechanisms of black sea bass reproduction and may ultimately contribute to management advances in this commercially important fish. | 25,255,937 | [
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3D GABA imaging with real-time motion correction, shim update and reacquisition of adiabatic spiral MRSI. | Gamma-aminobutyric acid (GABA) and glutamate (Glu) are the major neurotransmitters in the brain. They are crucial for the functioning of healthy brain and their alteration is a major mechanism in the pathophysiology of many neuro-psychiatric disorders. Magnetic resonance spectroscopy (MRS) is the only way to measure GABA and Glu non-invasively in vivo. GABA detection is particularly challenging and requires special MRS techniques. The most popular is MEscher-GArwood (MEGA) difference editing with single-voxel Point RESolved Spectroscopy (PRESS) localization. This technique has three major limitations: a) MEGA editing is a subtraction technique, hence is very sensitive to scanner instabilities and motion artifacts. b) PRESS is prone to localization errors at high fields (≥3T) that compromise accurate quantification. c) Single-voxel spectroscopy can (similar to a biopsy) only probe steady GABA and Glu levels in a single location at a time. To mitigate these problems, we implemented a 3D MEGA-editing MRS imaging sequence with the following three features: a) Real-time motion correction, dynamic shim updates, and selective reacquisition to eliminate subtraction artifacts due to scanner instabilities and subject motion. b) Localization by Adiabatic SElective Refocusing (LASER) to improve the localization accuracy and signal-to-noise ratio. c) K-space encoding via a weighted stack of spirals provides 3D metabolic mapping with flexible scan times. Simulations, phantom and in vivo experiments prove that our MEGA-LASER sequence enables 3D mapping of GABA+ and Glx (Glutamate+Gluatmine), by providing 1.66 times larger signal for the 3.02ppm multiplet of GABA+ compared to MEGA-PRESS, leading to clinically feasible scan times for 3D brain imaging. Hence, our sequence allows accurate and robust 3D-mapping of brain GABA+ and Glx levels to be performed at clinical 3T MR scanners for use in neuroscience and clinical applications. | 25,255,945 | [
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Transcriptome profiling of the testis reveals genes involved in spermatogenesis and marker discovery in the oriental fruit fly, Bactrocera dorsalis. | The testis is a highly specialized tissue that plays a vital role in ensuring fertility by producing spermatozoa, which are transferred to the female during mating. Spermatogenesis is a complex process, resulting in the production of mature sperm, and involves significant structural and biochemical changes in the seminiferous epithelium of the adult testis. The identification of genes involved in spermatogenesis of Bactrocera dorsalis (Hendel) is critical for a better understanding of its reproductive development. In this study, we constructed a cDNA library of testes from male B. dorsalis adults at different ages, and performed de novo transcriptome sequencing to produce a comprehensive transcript data set, using Illumina sequencing technology. The analysis yielded 52 016 732 clean reads, including a total of 4.65 Gb of nucleotides. These reads were assembled into 47 677 contigs (average 443 bp) and then clustered into 30 516 unigenes (average 756 bp). Based on BLAST hits with known proteins in different databases, 20 921 unigenes were annotated with a cut-off E-value of 10(-5). The transcriptome sequences were further annotated using the Clusters of Orthologous Groups, Gene Orthology and the Kyoto Encyclopedia of Genes and Genomes databases. Functional genes involved in spermatogenesis were analysed, including cell cycle proteins, metalloproteins, actin, and ubiquitin and antihyperthermia proteins. Several testis-specific genes were also identified. The transcripts database will help us to understand the molecular mechanisms underlying spermatogenesis in B. dorsalis. Furthermore, 2913 simple sequence repeats and 151 431 single nucleotide polymorphisms were identified, which will be useful for investigating the genetic diversity of B. dorsalis in the future. | 25,255,964 | [
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... |
Protecting worker and public health during responses to catastrophic disasters-learning from the World Trade Center experience. | Despite incremental lessons learned since 9/11, responder and community health remain at unnecessary risk during responses to catastrophic disasters, as evidenced during the BP Deepwater Horizon spill and Hurricanes Katrina, Rita, and Sandy. Much of the health harm that occurs during disaster response, as distinct from during the disaster event itself, is avoidable. Protection of public health should be an integral component of disaster response, which should "do no additional harm." This commentary examines how challenges and gaps the World Trade Center response resulted in preventable occupational and environmental health harm. It proposes changes in disaster response policies to better protect the health of rescue and recovery workers, volunteers, and impacted worker and residential communities. | 25,255,981 | [
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Construction of 3D polymer brushes by dip-pen nanodisplacement lithography: understanding the molecular displacement for ultrafine and high-speed patterning. | Dip-pen nanodisplacement lithography (DNL) is a versatile scanning probe-based technique that can be employed for fabricating ultrafine 3D polymer brushes under ambient conditions. Many fundamental studies and applications require the large-area fabrication of 3D structures. However, the fabrication throughput and uniformity are still far from satisfactory. In this work, the molecular displacement mechanism of DNL is elucidated by systematically investigating the synergistic effect of z extension and contact time. The in-depth understanding of molecular displacement results in the successful achievement of ultrafine control of 3D structures and high-speed patterning at the same time. Remarkably, one can prepare arbitrary 3D polymer brushes on a large area (1.3 mm × 1.3 mm), with <5% vertical and lateral size variations, and a patterning speed as much as 200-fold faster than the current state-of-the-art. | 25,256,006 | [
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Association between MTHFR C677T polymorphism and congenital heart disease. A family-based meta-analysis. | Congenital heart disease (CHD) is the most common type of birth defect. It is suspected that polymorphisms in folate metabolism are associated with an increased risk of CHD, but the conclusion remains unclear. Studies have reported that the MTHFR C677T polymorphism was associated with the development of structural congenital heart malformations. The objective of this study was to conduct a meta-analysis of available studies to identify common polymorphisms in the MTHFR gene in children with CHD and their mothers and to test for an association between genotype and disease. In all, 19 eligible studies comprising 4,219 cases and 20,123 controls were included in this meta-analysis. A significant association was found between the MTHFR C677T polymorphism and CHD risk (OR: 1.26; 95 % CI = 1.06-1.51; p = 0.009) with no strong evidence of heterogeneity (I(2) = 39 %) in the fetal analysis. In the maternal analysis, the MTHFR C677T polymorphism was significantly associated with CHD risk (OR = 1.52; 95 % CI = 1.09-2.11; p = 0.01) with significant heterogeneity (I(2) = 63 %). | 25,256,053 | [
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... |
Multiple independent colonization of the Canary Islands by the winged grasshopper genus Sphingonotus Fieber, 1852. | Volcanic archipelagos represent ideal systems to study processes of colonization, differentiation and speciation. The Canary Islands are one of the best studied archipelagos, being composed of seven main islands with a well-known geological history. Most taxa have colonized these islands stepwise from the African or Iberian mainland from east to west, following their geological origin as well as the predominating wind direction and ocean currents. Furthermore, within-island radiations have been reported for several taxa. The grasshopper genus Sphingonotus is species-rich and occurs with nine fully winged species on the Canary Islands, seven of which are endemic to single or few islands. We inferred a phylogeny of these species and their North African and Iberian relatives based upon sequences of three mitochondrial genes and one nuclear gene of 136 specimens. Surprisingly, our results suggest that almost all Sphingonotus species colonized the archipelago independently from the mainland and nearly no inter-island colonization occurred. Despite their strong flight capabilities, only one pair of endemic species are closely related (S. sublaevis from Gran Canary and S. pachecoi from Lanzarote). Moreover, no within-island speciation events were detected. We hypothesize that passive wind dispersal from the African mainland was the main driver of the colonization process and that most Sphingonotus species are not able to cover inter-island distances by active flight. This, together with strong intrageneric niche overlap might explain the lack of within-island speciation in this taxon. | 25,256,055 | [
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Excretion of tectoridin metabolites in rat urine and bile orally administrated at different dosages and their inhibitory activity against aldose reductase. | This study investigated the urinary and biliary excretion of tectoridin, a major active isoflavonoid found in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. Using UHPLC/Q-TOFMS, seven glucuronides and/or sulfated metabolites and four Phase I metabolites were simultaneously quantified in rat urine after oral administration of tectoridin at 100 and 200 mg/kg. Over a 72-h period, 14.2% and 14.7% of the tectoridin were excreted as eleven metabolites in urine, among which, two major metabolites tectorigenin-7-O-β-D-glucuronide (Te-7G) and tectorigenin accounted for 5.5-5.5% and 4.3-4.4%. Furthermore, the cumulative excretion of four glucuronides and sulfated metabolites in bile accounted for 7.3% and 3.9% of the dose within 60 h, among which, Te-7G and tectorigenin-7-O-glucuronide-4'-O-sulfate (Te-7G-4'S) accounted for 2.3-3.0% and 1.4-3.9%, respectively. The results indicate that the urine was the primary elimination route, and glucuronidation after deglycosylation at C-7 position was the major metabolic pathway of tectoridin in vivo. Moreover, the inhibitory activities of tectoridin and its five metabolites on rat lens aldose reductase were confirmed (IC₅₀: 1.4-15.5 μM), whereas irisolidone-7-O-glucuronide (Ir-7G) and irisolidone showed little activity. | 25,256,063 | [
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Microinjection of cocaine- and amphetamine-regulated transcript 55-102 peptide into the nucleus accumbens could modulate anxiety-related behavior in rats. | Cocaine- and amphetamine-regulated transcript (CART) peptide is abundantly expressed in the nucleus accumbens (NAcc) and is involved in stress, anxiety and reward responses. To examine the role of CART peptide in anxiety-related behavior, naïve rats were bilaterally injected with CART 55-102 peptide (0.5, 1.0 or 2.5 µg/0.5 µl/side) or vehicle into the NAcc. Following this, their anxiety-related behavior was assessed using the elevated plus maze and the open field tests with a one-week interval between the tests. There was no difference in the time spent in open arms, or number of entries into open arms on the elevated plus maze in the CART-treated animals at any dose, when compared with the vehicle-treated group. However, there was a significant increase in the time spent in the center of the open field with administration of the low dose of CART peptide (0.5 µg/0.5 µl/side), although this effect disappeared at the high dose (2.5 µg/0.5 µl/side). None of the doses of CART peptide altered total locomotion in these tests. To further determine the possible anxiety-modulating effect of CART peptide at low dosages, the light and dark test was performed. Additional groups of rats given doses of 0.01 µg/0.5 µl/side or 0.5 µg/0.5 µl/side of CART peptide showed increased exploration time in the light side. These results suggest that accumbal-CART peptide reduces anxiety-like behavior in a dose-dependent manner. | 25,256,086 | [
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0.007099156,
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0.01654808,
0.229402... |
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