title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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LiftingWiSe: a lifting-based efficient data processing technique in wireless sensor networks. | Monitoring thousands of objects which are deployed over large-hard-to-reach areas, is an important application of the wireless sensor networks (WSNs). Such an application requires disseminating a large amount of data within the WSN. This data includes, but is not limited to, the object's location and the environment conditions at that location. WSNs require efficient data processing and dissemination processes due to the limited storage, processing power, and energy available in the WSN nodes. The aim of this paper is to propose a data processing technique that can work under constrained storage, processing, and energy resource conditions. The proposed technique utilizes the lifting procedure in processing the disseminated data. Lifting is usually used in discrete wavelet transform (DWT) operations. The proposed technique is referred to as LiftingWiSe, which stands for Lifting-based efficient data processing technique for Wireless Sensor Networks. LiftingWiSe has been tested and compared to other relevant techniques from the literature. The test has been conducted via a simulation of the monitored field and the deployed wireless sensor network nodes. The simulation results have been analyzed and discussed. | 25,116,902 | [
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Expression of vesicular glutamate transporter 3 mRNA in the brain and retina of the pigeon. | Vesicular glutamate transporters (vGluTs), which accumulate glutamate into synaptic vesicles, are classified into three subtypes in mammalian brains: vGluT1, vGluT2, and vGluT3. VGluT3 is localized in non-glutamatergic neurons of the brain and retinal amacrine cells. In birds, the vGluT3 genome is found, but its distribution in the brain or retina is unknown. The present study was conducted to analyze vGluT3 cDNA sequence and elucidate its distribution in the pigeon brain and retina. The vGluT3 cDNA comprises 1761bp and showed 95% and 88% identity to the chicken and zebra finch vGluT3 cDNAs, respectively, and 74% identity to human vGluT3 cDNA. In situ hybridization revealed that the vGluT3 mRNA was expressed in neurons of the caudal linear nucleus (LC) of the brain and in amacrine cells of the inner nuclear layer of the retina. A combination of in situ hybridization and serotonin immunohistochemistry revealed three types of stained cells in LC and retina: vGluT3(+)/serotonin(+), vGluT3(+)/serotonin(-), and vGluT3(-)/serotonin(+). The vGluT3(+)/serotonin(+) cells were approximately 22% in LC and 16% in the retina. The present results suggest that the pigeon vGluT3 mRNA is comparable with the mammalian type. | 25,116,931 | [
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Value of water mazes for assessing spatial and egocentric learning and memory in rodent basic research and regulatory studies. | Maneuvering safely through the environment is central to survival of all animals. The ability to do this depends on learning and remembering locations. This capacity is encoded in the brain by two systems: one using cues outside the organism (distal cues), allocentric navigation, and one using self-movement, internal cues and sometimes proximal cues, egocentric navigation. Allocentric navigation involves the hippocampus, entorhinal cortex, and surrounding structures (e.g., subiculum); in humans this system encodes declarative memory (allocentric, semantic, and episodic, i.e., memory for people, places, things, and events). This form of memory is assessed in laboratory animals by many methods, but predominantly the Morris water maze (MWM). Egocentric navigation involves the dorsal striatum and connected structures; in humans this system encodes routes and integrated paths and when over-learned becomes implicit or procedural memory. Several allocentric methods for rodents are reviewed and compared with the MWM with particular focus on the Cincinnati water maze (CWM). MWM advantages include minimal training, no food deprivation, ease of testing, reliable learning, insensitivity to differences in body weight and appetite, absence of non-performers, control methods for performance effects, repeated testing capability and other factors that make this test well-suited for regulatory studies. MWM limitations are also reviewed. Evidence-based MWM design and testing methods are presented. On balance, the MWM is arguably the preferred test for assessing learning and memory in basic research and regulatory studies and the CWM is recommended if two tests can be accommodated so that both allocentric (MWM) and egocentric (CWM) learning and memory can be effectively and efficiently assessed. | 25,116,937 | [
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Main trunk crossover stenting in a patient with left internal thoracic artery--protected single coronary artery. | A 74-year-old man with single coronary artery and history of previous coronary artery bypass graft (CABG) was admitted to our hospital with worsening angina. Because of high risk of redo-CABG, we performed transradial percutaneous coronary intervention against the just proximal left anterior descending coronary artery (LAD) stenosis coexisting with short main trunk, anomalous right coronary artery deriving from the mid LAD and patent left internal thoracic artery-distal LAD graft. Under the guidance of IVUS, we successfully implanted an everolimus-eluting stent from the main trunk ostium to the proximal LAD without complications. | 25,117,026 | [
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Toxicity of naturally occurring Bio-fly and chitosan compounds to control the Mediterranean fruit fly Ceratitis capitata (Wiedemann). | The efficacy of five compounds of a biopolymer chitosan and Bio-fly (Beauveria bassiana fungus) as biopesticide was evaluated on Ceratitis capitata under laboratory conditions. The inhibitory effects on acetylcholinesterase (AChE) and adenosinetriphosphatase (ATPase) as biochemical indicators were also determined in vivo. The results indicated that B. bassiana based Bio-fly exhibited significant toxicity against C. capitata (LC50 = 3008 and 3126 mg/L after 48 h in females and males, respectively) followed by the derivatives of chitosan, N-(4-propylbenzyl)chitosan and N-(2-nitrobenzyl)chitosan. Bio-fly displayed remarkable inhibition of AChE activity (IC50 = 2220 mg/L) while N-(2-chloro,6-flourobenzyl)chitosan, N-(4-propylbenzyl)chitosan and N-(3,4-methylenedioxybenzyl) chitosan had no significant difference in inhibitory action. In adult males, N-(2-nitrobenzyl)chitosan exhibited the highest inhibitory action (IC50 = 6569 mg/L). In addition, the toxic effects of the tested compounds on the activity of ATPase indicated that highly significant inhibition was found with N-(4-propylbenzyl)chitosan with an IC50 of 8194 and 8035 mg/L, in females and males, respectively. | 25,117,027 | [
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[Factors associated with health promoting behaviors among Chilean adolescents]. | Health-promoting behaviors are important to prevent diseases and prolong life in the population. People develop these behaviors throughout life. However, better benefits for health are obtained with an early development. To determine the prevalence of health-promoting behaviors among early adolescents and its associated factors. Cross-sectional survey performed in 1,465 students of high, medium and low socio-economic status, attending fifth to eighth grades of schools located in a small Chilean city. Participants answered a questionnaire that gathered information about frequency of health-promoting behaviors such as health responsibility and nutrition, physical exercise and stress management, life appreciation, social support and different personal, school and familial factors. A higher frequency of health-promoting behaviors was associated with better academic achievement, better school commitment, and higher perception of school membership. It also was associated with a better perception of health status and a higher conformity with physical appearance. Health promoting behaviors in these children are related to a better academic achievement and a higher integration with school environment. | 25,117,031 | [
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[A proposal for the definitive reform of the private health insurance system in Chile]. | Private health insurance should be able to provide coverage to people considered as high risk, such as women and the elderly. The only way to do that is to organize implicit or explicit cross-subsidies from low to high-risk individuals. This paper examines how European private health insurance companies introduced regulatory measures that could be introduced in Chile such as open enrollment, community-rated premiums, lifetime coverage, a package of minimum benefits and a risk equalization scheme. | 25,117,041 | [
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Real-time analysis of endogenous protoporphyrin IX fluorescence from δ-aminolevulinic acid and its derivatives reveals distinct time- and dose-dependent characteristics in vitro. | Photodynamic therapy (PDT) and photodiagnosis based on the intracellular production of the photosensitizer protoporphyrin IX (PPIX) by administration of its metabolic precursor -aminolevulinic acid (ALA) achieved their breakthrough upon the clinical approval of MAL (ALA methyl ester) and HAL (ALA hexyl ester). For newly developed ALA derivatives or application in new tumor types, in vitro determination of PPIX formation involves multiparametric experiments covering variable pro-drug concentrations, medium composition, time points of analysis, and cell type(s). This study uses a fluorescence microplate reader with a built-in temperature and atmosphere control to investigate the high-resolution long-term kinetics (72 h) of cellular PPIX fueled by administration of either ALA, MAL, or HAL for each 10 different concentrations. For simultaneous proliferation correction, A431 cells were stably transfected with green fluorescent protein. The results indicate that the peak PPIX level is a function of both, incubation concentration and period: maximal PPIX is generated with 1 to 2-mM ALA/MAL or 0.125-mM HAL; also, the PPIX peak shifts to longer incubation periods with increasing pro-drug concentrations. The results underline the need for detailed temporal analysis of PPIX formation to optimize ALA (derivative)-based PDT or photodiagnosis and highlight the value of environment-controlled microplate readers for automated in vitro analysis. | 25,117,078 | [
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Identification of cancer stem cells and a strategy for their elimination. | It has been established previously that up to 40% of mouse CD34(+) hematopoietic stem cells are capable of internalizing exogenous dsDNA fragments both in vivo and ex vivo. Importantly, when mice are treated with a combination of cyclophosphamide and dsDNA, the repair of interstrand crosslinks in hematopoietic progenitors is attenuated, and their pluripotency is altered. Here we show for the first time that among various actively proliferating mammalian cell populations there are subpopulations capable of internalizing dsDNA fragments. In the context of cancer, such dsDNA-internalizing cell subpopulations display cancer stem cell-like phenotype. Furthermore, using Krebs-2 ascites cells as a model, we found that upon combined treatment with cyclophosphamide and dsDNA, engrafted material loses its tumor-initiating properties which we attribute to the elimination of tumor-initiating stem cell subpopulation or loss of its tumorigenic potential. | 25,117,082 | [
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Correlation between low folate levels and hyperhomocysteinemia, but not with vitamin B12 in hypertensive patients. | Hypertension is considered to be among the most important risk factors for cardiovascular and cerebrovascular diseases. In recent years, several investigators have reported that high plasma levels of total homocysteine (t-hcy) has a key role in the development of hypertension, and the deficiency of B complex vitamins could increase the risk of hypertension. The purpose of this study was to investigate the relationship between plasma homocysteine, folate and vitamin B12 in hypertensive patients. In 116 patients with hypertension and 81 healthy subjects, total plasma homocysteine, vitamin B12 and folate levels were measured. Homocysteine was significantly higher in patients than in control subjects (22.9±3.5 versus 9.0±2.3 μmol/L respectively, p<0.001); the folate plasma concentrations in hypertensive patients were significantly lower than in control subjects (6.7±5.0 ng/ml and 9.0±4.4 ng/ml respectively, p<0.05). Moreover, no differences in vitamin B12 plasma levels were observed when comparing the levels of hypertensive patients and those of the controls (440±223 pg/ml vs 491±185 pg/ml respectively, p>0.05). Our results confirmed that, as previously observed, elevated t-hcy levels and low folate levels, but not vitamin B12 levels, are significantly associated with hypertension. | 25,117,099 | [
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Novel ABCC8 (SUR1) gene mutations in Asian Indian children with congenital hyperinsulinemic hypoglycemia. | Congenital hyperinsulinemic hypoglycemia (HI) is a heterogeneous genetic disorder of insulin secretion characterized by persistent hypoglycemia, most commonly associated with inactivating mutations of the β-cell ATP-sensitive K(+) channel (K(ATP) channel) genes ABCC8 (encoding SUR1) and KCNJ11(encoding Kir6.2). This study aimed to screen the mutations in the genes associated with congenital HI in Asian Indian children. Recessive mutations of these genes cause hyperinsulinism that is unresponsive to treatment with channel agonists like diazoxide. Dominant K(ATP) mutations have been associated with diazoxide-responsive disease. The KCNJ11, ABCC8, GCK, HNF4A, and GLUD1 genes were analyzed by sequence analysis in 22 children with congenital HI. We found 10 novel mutations (c.1delA, c.61delG, c.267delT, c.619-629delCCCGAGGACCT, Gln444*, Leu724Pro, Ala847Thr, Trp898*, IVS30-2A>C, and Leu1454Arg) and two known mutations (Gly111Arg and Arg598*) in the ABCC8 gene. This study describes novel and known ABCC8 gene mutations in children with congenital HI. This is the first large genetic screening study on HI in India and our results will help clinicians in providing optimal treatment for patients with hyperinsulinemia and in assisting affected families with genetic counseling. | 25,117,148 | [
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Dermatological toxicity associated with targeted therapies in cancer: optimal management. | Targeted therapies have developed rapidly over the last few years in the field of oncology thanks to a better understanding of carcinogenesis. They target pathways involved in signal transduction (EGFR, HER2, HER3, HER4, FLT3, RAS, RAF, MEK, KIT, RET, mTOR, SRC, EPH, SCF), tumor angiogenesis (VEGFR, TIE2), and tumor microenvironment (PDGFR, FGFR). They rarely cause the systemic adverse reactions generally associated with chemotherapy, but frequently cause disabling and specific skin toxicity. The impact on patient quality of life can be important both in terms of symptoms caused and of potentially aesthetic consequences. Inappropriate management can increase the risk of dose reduction or discontinuation of the cancer treatment. In this review, we will discuss skin toxicity associated with the main drug classes-EGFR, BRAF, MEK, mTOR, c-KIT, CTLA4, and SMO inhibitors, and anti-angiogenic agents. Targeted therapy-induced skin toxicities will be detailed in terms of symptoms, frequency, evolution, complications, and topical and oral treatments in order to improve their diagnosis and management. | 25,117,153 | [
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Neuropsychological Assessment of Children With Reading Disabilities From 8 to 10 Years Old: An Exploratory Portuguese Study. | Reading disabilities are one of the most significant causes of school failure and may result from different causes and cognitive processes. A comprehensive battery of neuropsychological tests was applied to a control group of 102 children (46 girls, 56 boys) with no history of learning disabilities and 32 children (13 girls, 19 boys) with poor reading achievement (PRA) to characterize their cognitive profile. A principal component analysis of the cognitive measures was undertaken to identify cognitive domains. Age-adjusted normative data were computed from controls for verbal and visuospatial abilities, psychomotor skills, executive functions, and a total score. Significant differences were found between the 2 groups. Although single tests could not identify children with PRA, measures of oral and written language, immediate and working memory, calculation, and verbal learning discriminated the 2 groups. A logistic regression model using these factors allowed us to identify 91.2% of healthy children and 96.9% of children with PRA. PRA may result from different patterns of cognitive difficulties, and it is more common in children with oral language and working-memory deficits. Wide-range cognitive testing is necessary to identify strong and weak areas to plan personalized intervention programs. | 25,117,206 | [
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NMR analysis of carbohydrate-binding interactions in solution: an approach using analysis of saturation transfer difference NMR spectroscopy. | One of the most commonly used ligand-based NMR methods for detecting ligand binding is saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy. The STD NMR method is an invaluable technique for assessing carbohydrate-lectin interactions in solution, because STD NMR can be used to detect weak ligand binding (Kd ca. 10(-3)-10(-8) M). STD NMR spectra identify the binding epitope of a carbohydrate ligand when bound to lectin. Further, the STD NMR method uses 1H-detected NMR spectra of only the carbohydrate, and so only small quantities of non-labeled lectin are required. In this chapter, I describe a protocol for the STD NMR method, including the experimental procedures used to acquire, process, and analyze STD NMR data, using STD NMR studies for methyl-β-D-galactopyranoside (β-Me-Gal) binding to the C-terminal domain of an R-type lectin from earthworm (EW29Ch) as an example. | 25,117,260 | [
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Structural basis for constitutive activity and agonist-induced activation of the enteroendocrine fat sensor GPR119. | GPR119 is a Gαs-coupled 7TM receptor activated by endogenous lipids such as oleoylethanolamide (OEA) and by the dietary triglyceride metabolite 2-monoacylglycerol. GPR119 stimulates enteroendocrine hormone and insulin secretion. But despite massive drug discovery efforts in the field, very little is known about the basic molecular pharmacology of GPR119. GPR119 receptor signalling was studied in transfected cells. Mutational mapping (30 mutations in 23 positions) was performed on residues required for ligand-independent and agonist-induced GPR119 activation (AR231453 and OEA). Novel Rosetta-based receptor modelling was applied, using a composite template approach with segments from different X-ray structures and fully flexible ligand docking. The increased signalling induced by increasing the cell surface expression of GPR119 in the absence of agonist and the inhibitory effect of two synthetic inverse agonists demonstrated that GRP119 signals with a high degree of constitutive activity through the Gαs pathway. The mutational maps for AR231453 and OEA were very similar and, surprisingly, also similar to the mutational map for residues affecting the constitutive signalling - albeit with key differences. Surprisingly, almost all residues in extracellular loop-2b were important for the constitutive activity. The molecular modelling and docking demonstrated that AR231453 binds in a 'vertical' pocket in between mutational hits reaching from the centre of the receptor out to extracellular loop-2b. The high constitutive activity of GPR119 should be taken into account in future drug discovery efforts, which can now be guided by the detailed knowledge of the physiochemical properties of the extended ligand-binding pocket. | 25,117,266 | [
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Chemical genomics screening for biomodulators of endomembrane system trafficking. | Cell proteins traffic through complex and tightly regulated pathways. Although the endomembrane system is essential, its different pathways are still not well understood. In order to dissect protein trafficking pathways, chemical genomic screenings have been performed. This strategy has been utilized to successfully discover bioactive chemicals with a specific cellular action and in most cases, tunable and reversible effects. Once the bioactive chemical is identified, further strategies can be used to find the target proteins that are important for functionality of trafficking pathways. This approach can be combined with the powerful genetic tools available for model organisms. Drug-hypersensitive and drug-resistant mutant isolation can lead to the identification of cellular pathways affected by a bioactive chemical and reveal its protein target(s). Here, we describe an approach to look for hypersensitive and resistant mutants to a specific bioactive chemical that affects protein trafficking in yeast. This approach can be followed and adapted to any other pathway or cellular process that can be screened phenotypically, serving as a guide for novel screens in yeast. More importantly, information provided by this approach can potentially be extrapolated to other organisms like plants. Thus, the method described can be of broad utility to plant biologists. | 25,117,289 | [
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Increased serum levels of GDF-15 associated with mortality and subclinical atherosclerosis in patients on maintenance hemodialysis. | Increased carotid intima-media thickness (CIMT) was shown to be an independent predictor of cardiovascular (CV) mortality in dialysis patients and the general population. Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor superfamily, is produced by cardiomyocytes and atherosclerotic lesions under stress conditions such as inflammation. We assessed associations between serum concentrations of GDF-15, mortality, and CIMT for subclinical atherosclerosis in hemodialysis (HD) patients. A total of 87 patients on maintenance hemodialysis and 45 sex- and age-matched healthy controls were included in this prospective study. Serum GDF-15 levels were measured by ELISA. CIMT was assessed by Doppler ultrasonography. The association between serum GDF-15 levels and mortality was assessed using Cox regression analysis with serum levels categorized into two groups according to the median value (328.18 pg/ml). Patients were followed for 2 years and cause-specific and all-cause mortality were determined. The median level of serum GDF-15 was significantly higher in HD patients than controls [328 (198-522) vs. 176 (101-289) pg/ml, p < 0.01, respectively]. Serum GDF-15 levels were correlated to CIMT (r = 0.607, p < 0.001), C-reactive protein (CRP; r = 0.250, p = 0.010), HD duration (r = 0.376, p = 0.004), and serum albumin (r = - 0.156, p = 0.030). The multivariate analysis revealed that GDF-15 was found to be an independent variable of CIMT in HD patients. In the study, the serum GDF-15 level was an independent marker of all-cause of mortality when adjusted for age, CRP, and history of diabetes mellitus. The relationship between serum GDF-15, mortality, and carotid artery thickening suggests that GDF-15 may be a novel marker of atherosclerosis, inflammation, and malnutrition in HD patients. | 25,117,302 | [
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Development of polymorphic expressed sequence tag-single sequence repeat markers in the common Chinese cuttlefish, Sepiella maindroni. | The common Chinese cuttlefish (Sepiella maindroni) is one of the popular edible cephalopod consumed across Asia. To facilitate the population genetic investigation of this species, we developed fourteen polymorphic microsatellite makers from expressed sequence tags of S. maindroni. The number of alleles at each locus ranged from 6 to 10 with an average of 7.9 alleles per locus. The ranges of observed and expected heterozygosity were from 0.615 to 0.962 and 0.685 to 0.888, respectively. Four loci were found deviated significantly from Hardy-Weinberg equilibrium. The polymorphism information content ranged from 0.638 to 0.833. These polymorphic microsatellite loci will be helpful for the population genetic, genetic linkage map, and other genetic studies of S. maindroni. | 25,117,305 | [
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Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation. | Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients. | 25,117,323 | [
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Effect of Jianpi Bushen prescription on the expression of SHP-1 and apoptosis-related genes in chemically damaged model mice. | We investigated the effect of Jianpi Bushen prescription (JBP) on the expression of the SHP-1 and apoptosis-related genes in chemically damaged model mice and a compound e-jiao slurry (EJS) group (positive control). Kunming mice received an abdominal injection of 100 mg/kg cyclophosphamide once a day for 3 consecutive days to induce chemical damage. The mice underwent lavage at a suspension of 0.1 g/kg low-dose JBP (100%), high-dose JBP (200%), and 0.2 mL/10 g EJS twice a day for 9 days. mRNA and protein expression of SHP-1 in bone marrow mononuclear cells was detected using real-time polymerase chain reaction and Western blot; mRNA expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax) protein was detected by in situ hybridization. Expression of SHP-1 and Bax mRNA was significantly upregulated in the model group compared to the control group (P < 0.05). Expression in the low-dose JBP, high-dose JBP, and EJS groups was significantly downregulated compared with the model group (P < 0.05). The low-dose JBP group exhibited much lower SHP-1 and Bax mRNA expression levels. Compared with controls, Bcl-2 mRNA expression was significantly reduced in the model group (P < 0.05). Expression in the low-dose JBP, high-dose JBP, and EJS groups significantly increased compared with the model group (P < 0.05). The low-dose JBP group showed much higher Bcl-2 mRNA expression. Therefore, JBP regulates the expression of the SHP- 1, Bax, and Bcl-2 genes in chemically damaged mice. | 25,117,354 | [
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Effects of simulated weightlessness on cellular morphology and biological characteristics of cell lines SGC-7901 and HFE-145. | We investigated the effects of simulated weightlessness on cellular morphology, proliferation, cell cycle, and apoptosis of the human gastric carcinoma cell line SGC-7901 and the human gastric normal cell line HFE-145. A rotating clinostat was used to simulate weightlessness. The Image-Pro4.5 image analysis system was used for morphometric analysis. Proliferating cell nuclear antigen expression was examined by immunohistochemical staining. Changes in the cell cycle were examined using a cytometer. Apoptosis was measured using the terminal dUTP nick-end labeling (TUNEL) method. When subjected to simulated weightlessness, the cellular morphology of SGC-7901 cells was changed at 12, 24, 48, and 72 h, cell conversion from the G1 to S phase was blocked, proliferation was inhibited at 48 and 72 h, and the apoptosis index was increased at 72 h. The same changes were observed for HFE-145 cells at 12 h when subjected to simulated weightlessness, but no significant changes were found afterward compared with controls. SGC-7901 cells change their cellular morphology and biological characteristics during clinostat-simulated weightlessness at 72 h, but HFE-145 cells only change at 12 h and adapt to simulated weightlessness after that point. | 25,117,363 | [
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Influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. | We examined the influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. Sixty rats with spinal cord injury were divided into an experimental group and a control group and given neural stem cells or an equivalent amount of phosphate-buffered saline by intravenous transplantation, respectively. Basso, Beattie, and Bresnahan (BBB) motor function assessment was performed in rats at different times after transplantation, and von Willebrand factor (vWF) immunofluorescence and Western blot analysis of vascular endothelial growth factor (VEGF) protein were also performed. The BBB scores of rats in the 2 groups were both zero before transplantation. The BBB score gradually increased over time. The BBB score of the experimental group showed no significant difference compared with that of the control group (P > 0.05) 7 days after transplantation. The BBB score of the experimental group was significantly improved compared with that of the control group 14 days after transplantation (P < 0.05). vWF-positive cells and VEGF protein expression in the experimental group were significantly increased compared with those in the control group 7 and 14 days after transplantation, respectively (P < 0.05). Neural stem cell transplantation may promote angiogenesis by inducing VEGF expression as well as improve functional recovery of limb movements. | 25,117,366 | [
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Variants -250G/A and -514C/T in the LIPC gene are associated with hypertensive disorders of pregnancy in Chinese women. | We examined the influence of the promoter polymorphisms -250G/A (rs2070895) and -514C/T (rs1800588) in the human hepatic lipase (LIPC) gene on dyslipidemia and hypertensive disorders complicating pregnancy (HDCP) in a Chinese population. Clinically defined HDCP patients (N = 321) and healthy pregnant women (N = 331) were recruited and genotyped using polymerase chain reaction-restriction fragment length polymorphism for the two LIPC single nucleotide polymorphisms (SNPs). The results showed significant relationships between HDCP and triglycerides, apolipoprotein A1, and high-density lipoprotein cholesterol (P < 0.05), which confirmed that HDCP was accompanied by dyslipidemia. The results also demonstrated that in gestational hypertension (GH) patients, both total cholesterol (TC) and systolic blood pressure (SBP) levels were related to the two SNPs (P ≤ 0.004), although no significant association was found between HDCP and LIPC genotypes or alleles. Significant linkage disequilibrium of the two SNPs was found in both HDCP patients (R(2) = 0.867) and controls (R(2) = 0.91). Body mass index (BMI) was associated with -250G/A in women with mild preeclampsia (MPE) (P = 0.01). Carriers of the mutant homozygote -250AA genotype presented higher BMI in the MPE group. In conclusion, the LIPC -250G/A and -514C/T variants influenced TC and SBP levels in GH patients and the BMI level in the MPE group, although there was no evidence to validate an association between HDCP and LIPC allele, genotype, or haplotype frequencies. | 25,117,371 | [
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Incontinentia Pigmenti in 22-month Old Afro-Caribbean Fraternal Twin Girls. A Case Report. | Incontinentia pigmenti is a rare X-linked dominant condition characterized by cutaneous, neural, ocular and dental manifestations. The condition has mainly been reported in Caucasian females. The aim of this case report is to highlight the clinical presentation in Afro-Caribbean twin girls. The girls demonstrated abnormal hair distribution, pigmented limbs and torso, small conical or missing teeth with delayed dental eruption. | 25,117,394 | [
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Double bag or Y-set versus standard transfer systems for continuous ambulatory peritoneal dialysis in end-stage kidney disease. | Peritonitis is the most frequent serious complication of continuous ambulatory peritoneal dialysis (CAPD). It has a major influence on the number of patients switching from CAPD to haemodialysis and has probably restricted the wider acceptance and uptake of CAPD as an alternative mode of dialysis.This is an update of a review first published in 2000. This systematic review sought to determine if modifications of the transfer set (Y-set or double bag systems) used in CAPD exchanges are associated with a reduction in peritonitis and an improvement in other relevant outcomes. We searched the Cochrane Renal Group's Specialised Register through contact with the Trials Search Co-ordinator. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE. Date of last search: 22 October 2013. Randomised controlled trials (RCTs) or quasi-RCTs comparing double bag, Y-set and standard peritoneal dialysis (PD) exchange systems in patients with end-stage kidney disease. Data were abstracted by a single investigator onto a standard form and analysed by Review Manager. Analysis was by a random effects model and results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). Twelve eligible trials with a total of 991 randomised patients were identified. Despite the large total number of patients, few trials covered the same interventions, small numbers of patients were enrolled in each trial and the methodological quality was suboptimal. Y-set and twin-bag systems were superior to conventional spike systems (7 trials, 485 patients, RR 0.64, 95% CI 0.53 to 0.77) in preventing peritonitis in PD. Disconnect systems should be the preferred exchange systems in CAPD. | 25,117,423 | [
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Draft genome sequence of Rhodomicrobium udaipurense JA643T with special reference to hopanoid biosynthesis. | Hopanoids are present in vast amounts as integral components of bacteria and plants with their primary function to strengthen rigidity of the plasma membrane. To establish their roles more precisely, we conducted sequencing of the whole genome of Rhodomicrobium udaipurense JA643(T) isolated from a fresh water stream of Udaipur in Himachal Pradesh, India, by using the Illumina HiSeq pair end chemistry of 2 × 100 bp platform. Determined genome showed a high degree of similarity to the genome of R. vannielii ATCC17100(T) and the 13.7 million reads generated a sequence of 3,649,277 bp possessing 3,611 putative genes. The genomic data were subsequently investigated with respect to genes involved in various features. The machinery required for the degradation of aromatic compounds and resistance to solvents as well as all that required for photosynthesis are present in this organism. Also, through extensive functional annotation, 18 genes involved in the biosynthesis of hopanoids are predicted, namely those responsible for the synthesis of diploptene, diplopterol, adenosylhopane, ribosylhopane, aminobacteriohopanetriol, glycosyl group containing hopanoids and unsaturated hopanoids. The hopanoid biosynthetic pathway was then inferred based on the genes identified and through experimental validation of individual hopanoid molecules. The genome data of R. udaipurense JA643(T) will be useful in understanding the functional features of hopanoids in this bacterium. | 25,117,430 | [
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Inhibition of N-acetylglucosaminyltransferase V enhances sensitivity of radiotherapy in human prostate cancer. | The purpose of this study was to investigate the relationship between N-acetylglucosaminyltransferase V (GnT-V) and radiation sensitivity of prostate cancer (PCa) cells both in vitro and in vivo. Firstly, the GnT-V expression was studied in 84 cases of PCa tissues, in which higher level of GnT-V was detected more frequently in the advanced tumors. Secondly, the GnT-V stably suppressed cell lines PCa/1079 (Lncap/1079 and PC3/1079) were constructed from PCa cell lines (Lncap and PC3) in vitro. Attenuation of GnT-V inhibited cell proliferation, migration and increased apoptosis, which resulted in enhanced radiation sensitivity of PCa cells. The underlying mechanism may be relevant to the increasing ratio of Bax/Bcl-2, the blocking transcription of NF-κB and the reduction of cell cycle G2-M arrest. Finally, in in vivo study, compared with control groups, the irradiated PCa xenograft nude mice of PCa/1079 indicated to reduce tumor-growth rate and enhance survival time. Summary, our studies showed that inhibition of GnT-V probably improved PCa cells' radiation sensitivity. | 25,117,443 | [
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Ten weeks of aerobic training does not result in persistent changes in VLDL triglyceride turnover or oxidation in healthy men. | Very low density lipoprotein triglyceride (VLDL-TG) and free fatty acids (FFA) constitute a substantial proportion of human energy supply both at rest and during exercise. Exercise acutely decreases VLDL-TG concentration, and VLDL-TG clearance is increased after an exercise bout. However, the effects of long-term training are not clear. The aim was to investigate long-term effects of training by direct assessments of VLDL-TG and palmitate kinetics and oxidation in healthy lean men (n=9) at rest, before and after a 10-week training program, compared with a non-training control group (n=9). VLDL-TG kinetics were assessed by a primed constant infusion of [1-14C]VLDL-TG, and VLDL-TG oxidation by specific activity (14CO2) in expired air. The metabolic study days were placed 60-72 h after the last exercise bout. Palmitate kinetics and oxidation were assessed by a 2 h constant infusion of [9,10-(3)H]palmitate. In the training group (n=9), maximal oxygen uptake increased significantly by ≈20% (P<0.05), and the insulin sensitivity (assessed by the hyperinsulinemic-euglycemic clamp) improved significantly (P<0.05). Despite these metabolic improvements, no changes were observed in VLDL-TG secretion, clearance, or oxidation or in palmitate kinetics. We conclude that 10 weeks of exercise training did not induce changes in VLDL-TG and palmitate kinetics in healthy lean men. | 25,117,466 | [
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Identification of threshold prostate specific antigen levels to optimize the detection of clinically significant prostate cancer by magnetic resonance imaging/ultrasound fusion guided biopsy. | Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater. | 25,117,476 | [
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Correlation of gross urine color with diagnostic findings in male cats with naturally occurring urethral obstruction. | Seventy-five male cats with urethral obstruction were prospectively enrolled to evaluate gross urine color at urinary catheter placement for correlation with diagnostic findings. Cats with darker red urine were more likely to be azotemic (serum creatinine concentration >2.0 mg/dl [177 µmol/l]), and urine color correlated well with serum creatinine and serum potassium concentrations. Darker urine color was negatively correlated with urine specific gravity. Urine color was not associated with the presence or absence of lower urinary tract stones on radiographs or ultrasound. Cats with darker red urine at the time of urinary catheter placement are likely to have more significant metabolic derangements and may require more aggressive supportive care. | 25,117,491 | [
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Advantages of crystallographic fragment screening: functional and mechanistic insights from a powerful platform for efficient drug discovery. | X-ray crystallography has been an under-appreciated screening tool for fragment-based drug discovery due to the perception of low throughput and technical difficulty. Investigators in industry and academia have overcome these challenges by taking advantage of key factors that contribute to a successful crystallographic screening campaign. Efficient cocktail design and soaking methodologies have evolved to maximize throughput while minimizing false positives/negatives. In addition, technical improvements at synchrotron beamlines have dramatically increased data collection rates thus enabling screening on a timescale comparable to other techniques. The combination of available resources and efficient experimental design has resulted in many successful crystallographic screening campaigns. The three-dimensional crystal structure of the bound fragment complexed to its target, a direct result of the screening effort, enables structure-based drug design while revealing insights regarding protein dynamics and function not readily obtained through other experimental approaches. Furthermore, this "chemical interrogation" of the target protein crystals can lead to the identification of useful reagents for improving diffraction resolution or compound solubility. | 25,117,499 | [
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Building safety into active living initiatives. | Efforts to promote environmental designs that facilitate opportunities for physical activity should consider the fact that injuries are the leading cause of death for Americans ages 1 to 44, with transportation-related injuries the most common cause. Drawing on the latest research and best practices in the field of injury prevention, the purpose of this article is to provide those working to promote physical activity with evidence-based recommendations on building in safety while designing active environments. A systematic review of the peer-reviewed and grey literature published from 1995 to 2012 was conducted to identify injury prevention strategies applicable to objectives in the Active Design Guidelines (ADG), which present design strategies for active living. Injury prevention strategies were rated according to the strength of the research evidence. We identified 18 urban design strategies and 9 building design strategies that promote safety. Evidence was strong or emerging for 14/18 urban design strategies and 7/9 building design strategies. ADG strategies are often wholly compatible with well-accepted injury prevention principles. By partnering with architects and planners, injury prevention and public health professionals can help ensure that new and renovated spaces maximize both active living and safety. | 25,117,526 | [
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... |
Endophytic fungi: expanding the arsenal of industrial enzyme producers. | Endophytic fungi, mostly belonging to the Ascomycota, are found in the intercellular spaces of the aerial plant parts, particularly in leaf sheaths, sometimes even within the bark and root system without inducing any visual symptoms of their presence. These fungi appear to have a capacity to produce a wide range of enzymes and secondary metabolites exhibiting a variety of biological activities. However, they have been only barely exploited as sources of enzymes of industrial interest. This review emphasizes the suitability and possible advantages of including the endophytic fungi in the screening of new enzyme producing organisms as well as in studies aiming to optimize the production of enzymes through well-known culture processes. Apparently endophytic fungi possess the two types of extracellular enzymatic systems necessary to degrade the vegetal biomass: (1) the hydrolytic system responsible for polysaccharide degradation consisting mainly in xylanases and cellulases; and (2) the unique oxidative ligninolytic system, which degrades lignin and opens phenyl rings, comprises mainly laccases, ligninases and peroxidases. The obvious ability of endophytic fungi to degrade the complex structure of lignocellulose makes them useful in the exploration of the lignocellulosic biomass for the production of fuel ethanol and other value-added commodity chemicals. In addition to this, endophytic fungi may become new sources of industrially useful enzymes such as lipases, amylases and proteases. | 25,117,531 | [
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Label-free colorimetric detection of cadmium ions in rice samples using gold nanoparticles. | A simple and label-free colorimetric method for cadmium ions (Cd(2+)) detection using unmodified gold nanoparticles (AuNPs) is reported. The unmodified AuNPs easily aggregate in a high concentration of NaCl solution, but the presence of glutathione (GSH) can prevent the salt-induced aggregation of AuNPs. When Cd(2+) is added to the stable mixture of AuNPs, GSH, and NaCl, Cd(2+) can coordinate with 4× GSH as a spherical shaped complex, which decreases the amount of free GSH on the surface of gold nanoparticles to weaken the stability of AuNPs, and AuNPs will easily aggregate in high-salt conditions. On the basis of the mechanism, we design a simple, label-free colorimetric method using AuNPs accompanied by GSH in a high-salt environment to detect Cd(2+) in water and digested rice samples. | 25,117,533 | [
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The energy allocation function of sleep: a unifying theory of sleep, torpor, and continuous wakefulness. | The energy allocation (EA) model defines behavioral strategies that optimize the temporal utilization of energy to maximize reproductive success. This model proposes that all species of the animal kingdom share a universal sleep function that shunts waking energy utilization toward sleep-dependent biological investment. For endotherms, REM sleep evolved to enhance energy appropriation for somatic and CNS-related processes by eliminating thermoregulatory defenses and skeletal muscle tone. Alternating REM with NREM sleep conserves energy by decreasing the need for core body temperature defense. Three EA phenotypes are proposed: sleep-wake cycling, torpor, and continuous (or predominant) wakefulness. Each phenotype carries inherent costs and benefits. Sleep-wake cycling downregulates specific biological processes in waking and upregulates them in sleep, thereby decreasing energy demands imposed by wakefulness, reducing cellular infrastructure requirements, and resulting in overall energy conservation. Torpor achieves the greatest energy savings, but critical biological operations are compromised. Continuous wakefulness maximizes niche exploitation, but endures the greatest energy demands. The EA model advances a new construct for understanding sleep-wake organization in ontogenetic and phylogenetic domains. | 25,117,535 | [
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First report of a direct surface plasmon resonance immunosensor for a small molecule seafood toxin. | Tetrodotoxin (TTX), a small molecular weight neurotoxin, is responsible for poisoning events that traditionally occur from consumption of contaminated puffer fish. Recent studies have shown a growing number of foods contaminated with TTX and a larger number of waters and associated countries where the toxin may occur. The apparent expanding prevalence of TTX supports a growing need for screening assays that can be used to detect potentially harmful food. In the past few years, surface plasmon resonance (SPR) biosensors have been developed for rapid, robust detection of TTX; however, these assays focus on detection of unbound antibody from an inhibition reaction with the toxin. This manuscript introduces the first direct immunoassay for a seafood toxin, specifically TTX. Major advantages of this assay compared to indirect assays include increased speed of analysis, decreased use of biological reagents, and improved confidence in the detection of the toxin, along with the ability to characterize the antibody/toxin interaction. The analytical method introduced in this paper could be applied to other seafood toxins, as well as to a wide range of low molecular weight targets. | 25,117,539 | [
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Polyethylenimine carbon nanotube fiber electrodes for enhanced detection of neurotransmitters. | Carbon nanotube (CNT)-based microelectrodes have been investigated as alternatives to carbon-fiber microelectrodes for the detection of neurotransmitters because they are sensitive, exhibit fast electron transfer kinetics, and are more resistant to surface fouling. Wet spinning CNTs into fibers using a coagulating polymer produces a thin, uniform fiber that can be fabricated into an electrode. CNT fibers formed in poly(vinyl alcohol) (PVA) have been used as microelectrodes to detect dopamine, serotonin, and hydrogen peroxide. In this study, we characterize microelectrodes with CNT fibers made in polyethylenimine (PEI), which have much higher conductivity than PVA-CNT fibers. PEI-CNT fibers have lower overpotentials and higher sensitivities than PVA-CNT fiber microelectrodes, with a limit of detection of 5 nM for dopamine. The currents for dopamine were adsorption controlled at PEI-CNT fiber microelectrodes, independent of scan repetition frequency, and stable for over 10 h. PEI-CNT fiber microelectrodes were resistant to surface fouling by serotonin and the metabolite interferant 5-hydroxyindoleacetic acid (5-HIAA). No change in sensitivity was observed for detection of serotonin after 30 flow injection experiments or after 2 h in 5-HIAA for PEI-CNT electrodes. The antifouling properties were maintained in brain slices when serotonin was exogenously applied multiple times or after bathing the slice in 5-HIAA. Thus, PEI-CNT fiber electrodes could be useful for the in vivo monitoring of neurochemicals. | 25,117,550 | [
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Reference gene selection for quantitative real-time PCR normalization in Reaumuria soongorica. | Despite its superiority for evaluating gene expression, real-time quantitative polymerase chain reaction (qPCR) results can be significantly biased by the use of inappropriate reference genes under different experimental conditions. Reaumuria soongorica is a dominant species of desert ecosystems in arid central Asia. Given the increasing interest in ecological engineering and potential genetic resources for arid agronomy, it is important to analyze gene function. However, systematic evaluation of stable reference genes should be performed prior to such analyses. In this study, the stabilities of 10 candidate reference genes were analyzed under 4 kinds of abiotic stresses (drought, salt, dark, and heat) within 4 accessions (HG010, HG020, XGG030, and XGG040) from 2 different habitats using 3 algorithms (geNorm, NormFinder, and BestKeeper). After validation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large unite (rbcL) expression pattern, our data suggested that histone H2A (H2A) and eukaryotic initiation factor 4A-2 (EIF4A2) were the most stable reference genes, cyclophilin (CYCL) was moderate, and elongation factor 1α (EF1α) was the worst choice. This first systematic analysis for stably expressed genes will facilitate future functional analyses and deep mining of genetic resources in R. soongorica and other species of the Reaumuria genus. | 25,117,551 | [
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Engineering bacterial microcompartment shells: chimeric shell proteins and chimeric carboxysome shells. | Bacterial microcompartments (BMCs) are self-assembling organelles composed entirely of protein. Depending on the enzymes they encapsulate, BMCs function in either inorganic carbon fixation (carboxysomes) or organic carbon utilization (metabolosomes). The hallmark feature of all BMCs is a selectively permeable shell formed by multiple paralogous proteins, each proposed to confer specific flux characteristics. Gene clusters encoding diverse BMCs are distributed broadly across bacterial phyla, providing a rich variety of building blocks with a predicted range of permeability properties. In theory, shell permeability can be engineered by modifying residues flanking the pores (symmetry axes) of hexameric shell proteins or by combining shell proteins from different types of BMCs into chimeric shells. We undertook both approaches to altering shell properties using the carboxysome as a model system. There are two types of carboxysomes, α and β. In both, the predominant shell protein(s) contain a single copy of the BMC domain (pfam00936), but they are significantly different in primary structure. Indeed, phylogenetic analysis shows that the two types of carboxysome shell proteins are more similar to their counterparts in metabolosomes than to each other. We solved high resolution crystal structures of the major shell proteins, CsoS1 and CcmK2, and the presumed minor shell protein CcmK4, representing both types of cyanobacterial carboxysomes and then tested the interchangeability. The in vivo study presented here confirms that both engineering pores to mimic those of other shell proteins and the construction of chimeric shells is feasible. | 25,117,559 | [
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Secretoglobin 3A2 attenuates lipopolysaccharide-induced inflammation through inhibition of ERK and JNK pathways in bronchial epithelial cells. | Secretoglobin (SCGB) 3A2, previously known as uteroglobin-related protein 1, is a secreted protein highly expressed in the epithelial cells of the airways. It has been demonstrated that SCGB3A2 is involved in allergic airway inflammation such as bronchial asthma. However, the role of SCGB3A2 in lipopolysaccharide (LPS)-induced airway inflammation has yet to be reported. The goal of this study was therefore to clarify the role of SCGB3A2 in LPS-induced airway inflammation. We stimulated BEAS-2B, human bronchial epithelial cells, with LPS and analyzed messenger RNA (mRNA) expression of tumor necrosis factor (TNF)-α and CXCL8 with or without pre-incubation of SCGB3A2. The mRNA expression of TNF-α and CXCL8 was clearly upregulated 3 h after LPS stimulation, and pre-incubation of SCGB3A2 significantly inhibited the upregulation of the mRNA expression. The pre-incubation of SCGB3A2 also inhibited LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase in BEAS-2B cells. Furthermore, PD98059, a specific inhibitor for ERK, as well as SP600125, a specific inhibitor for JNK, inhibited LPS-induced mRNA upregulation of inflammatory mediators. These results demonstrate the novel biological activity of SCGB3A2, which is that it attenuates LPS-induced inflammation in bronchial epithelial cells through inhibition of ERK and JNK activation. | 25,117,566 | [
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Interleukin-6 and other inflammatory markers in diagnosis of periprosthetic joint infection. | The purpose of this study was to evaluate the diagnostic value of interleukin-6 (IL-6) and other inflammatory markers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WCC) in diagnosis of PJI. The study group included 40 patients (21 males, 19 females) admitted for surgical intervention after knee or hip arthroplasties. Patients were subjected to careful history taking, thorough clinical examination and pre-operative laboratory investigations including serum IL-6, CRP, WCC and ESR. Peri-implant tissue specimens were subjected to microbiological culture and histopathological examination. The mean age of patients was 58.4 years (range, 38-72 years). Intra-operative cultures and histopathological examination revealed 11 patients had been infected (PJI) and 29 patients were aseptic failure of prosthesis. Four presumed markers of infection were tested preoperatively: ESR, CRP, WCC, and IL-6. ESR (p = 0.0001), CRP (p = 0.004), WCC (0.0001), and IL-6 (p = 0.0001) were significantly higher in patients with septic revision than those with aseptic failure of the prosthesis. Serum IL-6 (>10.4 pg/ml) reportedly had a sensitivity of 100%, a specificity of 90.9%, a PPV of 79%, a NPV of 100%, and accuracy of 92.5%. The present study demonstrated that IL-6 has been found to be the most accurate laboratory marker for diagnosing PJI when compared to ESR, CRP, and WCC. IL-6 above 10.4 pg/ml and CRP level above 18 mg/L will identify all patients with PJI and the combination of CRP + IL-6 is an excellent screening test to identify all such patients (sensitivity 100%, NPV 100%). | 25,117,573 | [
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Prevalence of femoro-acetabular impingement in international competitive track and field athletes. | The aim of our study was to analyse the prevalence of femoro-acetabular impingement (FAI) in national elite track and field athletes compared to peers using magnetic resonance imaging (MRI) and clinical examination including impingement tests. A total of 44 participants (22 national elite track and field athletes and 22 non-athletes) underwent an MRI for radiological findings associated with FAI, including alpha angle, lateral centre edge angle (CEA), findings of labral and cartilage lesions. The study group was furthermore investigated by the hip outcome score (HOS) and a clinical hip examination including range of motion (ROM) and impingement tests. Concerning the cam impingement, there was a significant difference measured by mean alpha angle between the athlete group (52.2 ± 7.29°) and the control group (48.1 ± 5.45°, P = 0.004). Eleven athletes showed a cam impingement, while two probands of the control group had a pincer impingement and one a mixed form (P = 0.0217). There was no statistically significant difference concerning the CEA upon evaluating pincer impingement. Seven track and field athletes had a positive impingement test, whereof three had an increased alpha angle >55°. No participant of the control group showed pathological results in the impingement test (P = 0.0121). MRI evidence and clinical examination suggest that cam impingement is more common in elite athletes in comparison to non-athletes. At a professional level, the intense practice of track and field athletics is susceptible for FAI. | 25,117,575 | [
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Effect of multilevel laboratory rat caging system on the well-being of the singly-housed Sprague Dawley rat. | Current regulations emphasize that good husbandry practices allow animals to engage in species appropriate postural adjustments without touching the enclosure walls. This study evaluated the well-being of rats housed in a commercially available multilevel rat caging system, with or without access to the upper level of the caging. The evaluation methodologies included assessment of behavioral observations in the home cage, physiological assessment of metabolism and immune function, and determination of the affective state using a spatial cognitive bias assay. The study determined that rats that were provided access to the full multilevel cage during testing after initial restriction to the lower level of the cage demonstrated behavioral changes consistent with a positive affective state, while those with no changes to their housing situation had no significant differences in their affective states. Rats that were consistently housed with access restricted to the lower level of the cage exhibited a tendency to increased neutrophil:lymphocyte ratios as compared with those provided with access to all levels of the multilevel cage. There were no differences in body weight demonstrated between the experimental groups. Overall use of the cage space, as documented through analysis of behavioral observations in the home cage, demonstrated no significant differences in preferred location in the cage during the light or dark cycles, though rats with access to both levels of the cage were significantly more active during the light cycle. The results of this study suggest that the use of a multilevel caging system may improve the well-being of rats used in research. | 25,117,586 | [
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Urodynamics before stress urinary incontinence surgery. | In patients with symptoms of stress urinary incontinence, there is still a debate regarding the benefit of a multichannel urodynamic investigation prior to surgical management. The purpose of this article is to review recent evidence on this topic. Results of two large randomized controlled trials provided evidence that preoperative urodynamics do not improve outcome of incontinence surgery in women with uncomplicated stress urinary incontinence. Furthermore, in this selected group of women, urodynamics hardly lead to deviation of surgery as a primary treatment in case of an indication for operation based on symptoms and signs. Low urethral closure pressures and detrusor overactivity are urodynamic parameters which were associated with impaired cure of symptoms of stress urinary incontinence after surgery. Preoperative urodynamics do not improve outcome in women with complaints of stress incontinence and do hardly alter the treatment plan. It remains questionable whether a more accurate counselling on the postoperative perspectives counterbalances the disadvantages attended with urodynamics. The routine use in women with uncomplicated stress incontinence should no longer be advised. Preoperative urodynamic evaluation should only be used to answer a specific clinical question or if the results are likely to influence the choice of treatment. | 25,117,607 | [
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Phase-1 study of abiraterone acetate in chemotherapy-naïve Japanese patients with castration-resistant prostate cancer. | Persistent androgen synthesis under castration status in adrenal gland, testes and tumor cells is thought to be one of the major causes of development and progression of castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA), the prodrug of abiraterone, which is an inhibitor of androgen synthesis enzymes, was evaluated for pharmacokinetics, pharmacodynamics, preliminary efficacy and safety in Japanese patients with CRPC in a phase-1, open-label and dose-escalation study. Chemotherapy-naïve Japanese CRPC patients (N = 27) received one of four AA daily doses (250 mg [n = 9], 500 mg [n = 6], 1000 [1 h premeal] mg [n = 6] and 1000 [2 h postmeal] mg [n = 6]) continuously through 28-day treatment cycles. In the first cycle, AA monotherapy was given on days 1-7 for pharmacokinetics, and AA plus prednisone (5 mg twice daily) from days 8 to 28. Of 27 patients, 9 continued treatment with AA until the data cut-off date (18 July 2013). Over the evaluated dose range, plasma abiraterone concentrations increased with dose, with median tmax 2-3 h. At each dose level, mean serum corticosterone concentrations increased, while testosterone and dehydroepiandrosterone sulfate concentrations rapidly decreased following a single AA dose and were further reduced to near the quantification limit on day 8 regardless of the dose. At least 3 patients from each dose-group experienced ≥50% prostate-specific antigen reduction, suggesting clinical benefit from AA in Japanese CRPC patients. AA was generally well-tolerated, and, therefore, the recommended AA dosage regimen in Japanese CRPC patients is 1000 mg oral dose under modified fasting conditions (at least 1 h premeal or 2 h postmeal). This study is registered at ClinicalTrials.gov: NCT01186484. | 25,117,615 | [
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Transforming growth factor alpha is a critical mediator of radiation lung injury. | Radiation fibrosis of the lung is a late toxicity of thoracic irradiation. Epidermal growth factor (EGF) signaling has previously been implicated in radiation lung injury. We hypothesized that TGF-α, an EGF receptor ligand, plays a key role in radiation-induced fibrosis in lung. Mice deficient in transforming growth factor (TGF-α(-/-)) and control C57Bl/6J (C57-WT) mice were exposed to thoracic irradiation in 5 daily fractions of 6 Gy. Cohorts of mice were followed for survival (n ≥ 5 per group) and tissue collection (n = 3 per strain and time point). Collagen accumulation in irradiated lungs was assessed by Masson's trichrome staining and analysis of hydroxyproline content. Cytokine levels in lung tissue were assessed with ELISA. The effects of TGF-α on pneumocyte and fibroblast proliferation and collagen production were analyzed in vitro. Lysyl oxidase (LOX) expression and activity were measured in vitro and in vivo. Irradiated C57-WT mice had a median survival of 24.4 weeks compared to 48.2 weeks for irradiated TGF-α(-/-) mice (P = 0.001). At 20 weeks after irradiation, hydroxyproline content was markedly increased in C57-WT mice exposed to radiation compared to TGF-α(-/-) mice exposed to radiation or unirradiated C57-WT mice (63.0, 30.5 and 37.6 μg/lung, respectively, P = 0.01). C57-WT mice exposed to radiation had dense foci of subpleural fibrosis at 20 weeks after exposure, whereas the lungs of irradiated TGF-α (-/-) mice were largely devoid of fibrotic foci. Lung tissue concentrations of IL-1β, IL-4, TNF-α, TGF-β and EGF at multiple time points after irradiation were similar in C57-WT and TGF-α(-/-) mice. TGF-α in lung tissue of C57-WT mice rose rapidly after irradiation and remained elevated through 20 weeks. TGF-α(-/-) mice had lower basal LOX expression than C57-WT mice. Both LOX expression and LOX activity were increased after irradiation in all mice but to a lesser degree in TGF-α(-/-) mice. Treatment of NIH-3T3 fibroblasts with TGF-α resulted in increases in proliferation, collagen production and LOX activity. These studies identify TGF-α as a critical mediator of radiation-induced lung injury and a novel therapeutic target in this setting. Further, these data implicate TGF-α as a mediator of collagen maturation through a TGF-β independent activation of lysyl oxidase. | 25,117,621 | [
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Modeling dose deposition and DNA damage due to low-energy β(-) emitters. | One of the main issues of low-energy internal emitters concerns the very short ranges of the beta particles, versus the dimensions of the biological targets. Depending on the chemical form, the radionuclide may be more concentrated either in the cytoplasm or in the nucleus of the target cell. Consequently, since in most cases conventional dosimetry neglects this issue it may overestimate or underestimate the dose to the nucleus and hence the biological effects. To assess the magnitude of these deviations and to provide a realistic evaluation of the localized energy deposition by low-energy internal emitters, the biophysical track-structure code PARTRAC was used to calculate nuclear doses, DNA damage yields and fragmentation patterns for different localizations of radionuclides in human interphase fibroblasts. The nuclides considered in the simulations were tritium and nickel-63, which emit electrons with average energies of 5.7 (range in water of 0.42 μm) and 17 keV (range of 5 μm), respectively, covering both very short and medium ranges of beta-decay products. The simulation results showed that the largest deviations from the conventional dosimetry occur for inhomogeneously distributed short-range emitters. For uniformly distributed radionuclides selectively in the cytoplasm but excluded from the cell nucleus, the dose in the nucleus is 15% of the average dose in the cell in the case of tritium but 64% for nickel-63. Also, the numbers of double-strand breaks (DSBs) and the distributions of DNA fragments depend on subcellular localization of the radionuclides. In the low- and medium-dose regions investigated here, DSB numbers are proportional to the nuclear dose, with about 50 DSB/Gy for both studied nuclides. In addition, DSB numbers on specific chromosomes depend on the radionuclide localization in the cell as well, with chromosomes located more peripherally in the cell nucleus being more damaged by short-ranged emitters in cytoplasm compared with chromosomes located more centrally. These results illustrate the potential for over- or underestimating the risk associated with low-energy emitters, particularly for tritium intake, when their distribution at subcellular levels is not appropriately considered. | 25,117,624 | [
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Hierarchically porous three-dimensional electrodes of CoMoO₄ and ZnCo₂O₄ and their high anode performance for lithium ion batteries. | Ternary metal oxides have been receiving wide attention in electrochemical energy storage due to their rich redox reactions and tuneable conductivity. We present a simple solution-based method to prepare a 3D interconnected porous network of ternary metal oxide (CoMoO₄ and ZnCo₂O₄) nanostructures on macroporous nickel foam. The open-structured networks with different degrees of porosity endow them with high surface areas of electro-active sites. The Li ion storage properties of both anodes are investigated. High rate capability and long term cycling stability are achieved for both systems. | 25,117,647 | [
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Oxidative stress and antioxidant status in patients with autoimmune liver diseases. | To estimate oxidative stress and antioxidant components during different stages of autoimmune liver diseases and assess their possible implication on disease progression. We determined several markers of oxidative injury (isoprostane, aldehydes, protein carbonyls, 3-nitrotyrosine, and myeloperoxidase) and antioxidant components (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase) in whole blood, serum, and urine in 49 patients with autoimmune cholestatic liver diseases (AC) and 36 patients with autoimmune hepatitis (AIH) and healthy subjects matched for sex and age. Both AC and AIH patients had increased levels of all lipid and protein oxidative injury products and significantly decreased whole blood glutathione levels compared to controls. AIH patients had significantly higher levels of aldehydes and glutathione peroxidase activity and significantly lower protein carbonyl levels compared to AC patients. Protein carbonyl and isoprostane levels increased and glutathione levels decreased gradually with progression from mild fibrosis to severe fibrosis and cirrhosis in both AC and AIH patients. In addition, both cirrhotic AC and AIH patients had significantly higher protein carbonyls compared to non-cirrhotics. We provide novel findings in support of a major contribution of oxidant/antioxidant imbalance in the progression of liver injury in AC and AIH. | 25,117,650 | [
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Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients. | Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as 'unfavourable neurological outcome'. Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use. | 25,117,654 | [
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Utilization of stem cells to treat congenital heart disease: hype and hope. | Surgical advances over the past few decades have transformed the clinical management of congenital heart disease, such as hypoplastic left heart syndrome. Congenital heart disease affects more than 1% of liveborn infants and accounts for more than 2.5 million affected children per year worldwide. The cost and availability of complex medical management for these children becomes bluntly realized when heart failure progresses and only palliative options remain. Cell-based cardiac regeneration has been the focus of intensive efforts in adult heart disease for more than a decade and now has promise for pediatrics. Innate cardiac regeneration in the pediatric setting is measurable and potentially modifiable in the early stages of development. Repurposing cell-based manufactured products to promote cardiac regeneration in congenital heart disease has demonstrated significant improvement in cases of dilated cardiomyopathy and structural heart disease in infants. A focus on preemptive cardiac regeneration in the pediatric setting may offer new insights into the timing of surgery, location of cell-based delivery, and type of cell-based regeneration that could further inform acquired cardiac disease applications. The concept of cell-based pediatric cardiac regenerative surgery could transform the management of congenital heart disease when cost-effective strategies produce a valuable adjunctive solution to improve outcomes of cardiac surgery. | 25,117,663 | [
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Genetic variation in dihydropyrimidine dehydrogenase (DPYD) gene in a healthy adult Indian population. | Dihydropyrimidine dehydrogenase (DPD) encoded by DPYD gene is the major enzyme involved in metabolism of 5-flurouracil (5-FU), a pyrimidine analogue used in cancer chemotherapy. Although very effective as a cancer therapeutic drug, if not rapidly metabolized, 5-FU may prove lethal. Single nucleotide variants (SNVs) within DPYD that modulate DPD enzyme activity contribute to 5-FU toxicity. This study looked for DPYD SNVs common in the Indian population that might be associated with variable DPD activity and drug toxicity. To achieve this, sequencing analysis was performed of all 23 exons and flanking intronic regions of the DPYD gene in a cohort of 50 healthy adult Indians. This study detected 22 SNVs including intronic, synonymous and non-synonymous changes in the DPYD gene, of which six have not been documented before. Allelic frequency was calculated for the observed variants and linkage disequilibrium (LD) analysis was performed on variants with frequency ≥0.1 to identify haplotypes. This study provides a brief overview of the genetic polymorphism in DPYD in Indians and emphasizes the need for a large scale extensive study to establish markers associated with the frequently observed variable drug metabolism. | 25,117,664 | [
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Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non-alcoholic steatohepatitis. | Non-alcoholic steatohepatitis (NASH) has emerged as a common cause of chronic liver disease and virus-independent hepatocellular carcinoma (HCC) in patients with obesity, diabetes, and metabolic syndrome. To reveal the molecular mechanism underlying hepatocarcinogenesis from NASH, microRNA (miRNA) expression profiles were analyzed in STAM mice, a NASH-HCC animal model. MicroRNA expression was also examined in 42 clinical samples of HCC tissue. Histopathological images of the liver of STAM mice at the ages of 6, 8, 12, and 18 weeks showed findings compatible with fatty liver, NASH, liver cirrhosis (LC), and HCC, respectively. Expression of miR-122 in non-tumor LC at the age of 18 weeks was significantly lower than that in LC at the age of 12 weeks. Expression of miR-122 was further decreased in HCCs relative to non-tumor LC at the age of 18 weeks. Expression of miR-122 was also decreased in clinical samples of liver tissue showing macrovesicular steatosis and HCC, being consistent with the findings in the NASH model mice. DNA methylation analysis revealed that silencing of miR-122 was not mediated by DNA hypermethylation of the promoter region. These results suggest that silencing of miR-122 is an early event during hepatocarcinogenesis from NASH, and that miR-122 could be a novel molecular marker for evaluating the risk of HCC in patients with NASH. | 25,117,675 | [
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Closing the gap between glia and neuroblast proliferation. | Reporting in this issue of Developmental Cell, Spéder and Brand (2014) show that gap junctions are required in blood-brain barrier glial cells to reactivate proliferation of quiescent neuroblasts. Gap junctions allow synchronous Ca(2+) waves and control insulin-like protein Dipl6 expression and secretion to trigger neuroblast division. | 25,117,678 | [
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A role for β3-integrins in linking breast development and cancer. | Pregnancy induces a rapid and controlled expansion of mammary stem cells. In this issue of Developmental Cell, Desgrosellier et al. (2014) show that β3-integrin is required downstream of hormonal signaling and TGFβ2 to regulate mammary stem cell number and alveolar development specifically during early pregnancy. | 25,117,679 | [
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N-cadherin locks left-right asymmetry by ending the leftward movement of Hensen's node cells. | The stereotypic left-right (LR) asymmetric distribution of internal organs is due to an asymmetric molecular cascade in the lateral plate mesoderm (LPM) that is originated at the embryonic node. In chicken embryos, molecular asymmetries at Hensen's node are created by leftward cell movements that occur transiently. What terminates these movements, and, moreover, what is the impact of prolonging them on the LR asymmetry cascade? We show that leftward movements last longer when N-cadherin function is blocked and cease prematurely when N-cadherin is overexpressed on the right side of the node. The prolonged leftward movements lead to loss of asymmetric expression of fgf8 and nodal at the node region. This originates an abnormal expression of the asymmetric genes cer1 and snai1 in the LPM, resulting in mispositioned hearts. We conclude that N-cadherin stops the leftward cell movements and that this termination is an essential step in the establishment of LR asymmetry. | 25,117,685 | [
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YAPping about differentiation therapy in muscle cancer. | Overcoming a presumed differentiation block in the childhood muscle cancer embryonal rhabdomyosarcoma is often thought to hold promise as an approach to replace cytotoxic chemotherapy with molecularly-targeted differentiation therapies. In this issue of Cancer Cell, Tremblay and colleagues implicate YAP1 and the Hippo signaling pathway in the maintenance of differentiation-arrested and proliferative phenotypes for embryonal rhabdomyosarcoma. | 25,117,705 | [
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Multiparametric magnetic resonance imaging for the differentiation of low and high grade clear cell renal carcinoma. | To retrospectively evaluate the ability of magnetic resonance (MR) imaging to differentiate low from high Fuhrman grade renal cell carcinoma (RCC). MR images from 80 consecutive pathologically proven RCC (57 clear cell, 16 papillary and 7 chromophobe) were evaluated. Double-echo chemical shift, dynamic contrast-enhanced T1- and T2-weighted images and apparent diffusion coefficient (ADC) maps were reviewed independently. Signal intensity index (SII), tumour-to-spleen SI ratio (TSR), ADC ratio, wash-in (WiI) and wash-out indices (WoI) between different phases were calculated and compared to pathological grade and size. The Fuhrman scoring system was used. Low grade (score ≤ 2) and high grade (score ≥ 3) tumours were compared using univariate and multivariate analyses. No associations between grade and imaging factors were found for papillary and chromophobe RCCs. For clear cell RCCs, there was a significant association between the grade and parenchymal WiI (WiI2) (P = 0.02) or ADCr (P = 0.03). A significant association between tumour grade and size (P = 0.01), WiI2 (P = 0.02) and ADCr (P = 0.05) remained in multivariate analysis. Multiparametric MRI can be used to accurately differentiate low Fuhrman grade clear cell RCC from high grade. High Fuhrman grade (≥ 3) RCCs were larger, had lower parenchymal wash-in indices and lower ADC ratios than low grade. • Fuhrman grade of clear cell RCC can be differentiated with multiparametric MR imaging. • Fuhrman grade significantly differed for size, parenchymal wash-in index and ADC ratio. • No significant associations were found for papillary and chromophobe renal cell carcinoma. | 25,117,747 | [
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Seasonal variations of vitamin D concentrations in pregnant women and neonates in Slovenia. | While foreign research shows a high prevalence of vitamin D deficiency in pregnant women and consequently in neonates, we do not have any data on vitamin D concentration in these risk groups for Slovenia. We performed a prospective study to evaluate vitamin D concentration in pregnant women and neonates in Maribor region. We determined 25-hydroxy-vitamin D concentration from blood samples taken before delivery from 100 pregnant women who gave birth in Maribor University Clinical Centre in September and December 2013, respectively, and from the cord blood of their neonates. We collected data on nutrition and sun exposure during pregnancy. We calculated the vitamin D concentrations in pregnant women and neonates according to season of birth and use of nutrition supplements, determined the vitamin D levels in some pregnancy complications and checked the correlation of maternal and neonatal vitamin D concentrations. The average vitamin D concentration in the September group was 54.3±25.2nmol/L, and in the December group 33.3±18.6nmol/L (p<0.001). Optimal vitamin D concentration (>80nmol/L) was reached by 12.0% of pregnant women in September and by only 2.0% in December. Women who took nutrition supplements containing vitamin D during pregnancy had significantly higher vitamin D levels than those who did not (September 68.9±27.0nmol/L vs. 46.5±20.3nmol/L, p<0.001; December 38.7±17.9nmol/L vs. 30.2±18.4nmol/L, p=0.028). Neonates had higher average levels of vitamin D than their mothers but there was a good correlation between maternal and neonatal vitamin D values. Vitamin D deficiency is very common in pregnant women in Slovenia as well, especially in winter and in those women who do not take nutrition supplements containing vitamin D. | 25,117,752 | [
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Disease-specific T-helper cell polarizing function of lesional dendritic cells in different types of chronic rhinosinusitis with nasal polyps. | Although eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) exhibit distinct T-helper (Th) responses, the underlying mechanisms remain unclear. To clarify the phenotypes and Th-cell polarizing functions of dendritic cells (DCs) in different types of CRSwNP. DC subsets, their surface phenotypes, and Th-cell subsets were studied by means of immunohistochemistry and flow cytometry. The sorted lesional DCs were activated or cultured with autologous naive CD4(+) T cells, and cytokine production was determined by ELISA. Thymic stromal lymphopoietin and osteopontin expression were detected by means of reverse-transcriptase polymerase chain reaction. Although elevated local Th1 and Th17 cells were noted in both eosinophilic and noneosinophilic CRSwNP, increased Th2 cells were found only in eosinophilic CRSwNP. Increased numbers of myeloid DCs, plasmacytoid DCs, and their activated subsets were found in both types of CRSwNP, but only myeloid DCs and plasmacytoid DCs from eosinophilic CRSwNP demonstrated an up-regulation of OX40 ligand (OX40L) and programmed death ligand 1(PD-L1) expression. Lesional DCs from both types of CRSwNP produced enhanced levels of IL-12, IL-6, and transforming growth factor-β, and induced increased Th1 and Th17 responses; in contrast, only DCs from eosinophilic CRSwNP induced obviously enhanced Th2 responses, when cocultured with naive CD4(+) T cells. Blockade of OX40L and PD-L1 on lesional DCs from eosinophilic CRSwNP suppressed Th2 responses, but promoted Th1 responses in DC-T cell coculture. Distinct subsets of lesional DCs were found in eosinophilic and noneosinophilic CRSwNP, where OX40L/PD-L1(+) lesional DCs in eosinophilic CRSwNP could prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells. | 25,117,756 | [
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Predictors of health-related quality of life over time among adolescents and young adults with sickle cell disease. | Little is known about what factors affect the health-related quality of life (HRQoL) of adolescents and young adults (AYAs) with sickle cell disease (SCD), and how their HRQoL changes over time. This retrospective study included 87 AYAs attending a SCD Adolescent Clinic who completed a measure of HRQoL at each visit over the course of approximately 1.3 years. Results suggested that the following were associated with poorer physical HRQoL: being female, more healthcare utilization events, and presence of internalizing symptoms. Internalizing and externalizing symptoms were the only factors correlated with poorer psychosocial HRQoL. Generalized linear mixed models indicated that physical and psychosocial HRQoL improved among all participants during the assessment period, and those with externalizing behaviors reported faster improvement in physical HRQoL over time. AYAs with SCD may benefit from early mental health screening and intervention to optimize clinical care. | 25,117,764 | [
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A short peptide from frog skin accelerates diabetic wound healing. | Delayed wound healing will result in the development of chronic wounds in some diseases, such as diabetes. Amphibian skins possess excellent wound-healing ability and represent a resource for prospective wound-healing promoting compounds. A potential wound-healing promoting peptide (CW49; amino acid sequence APFRMGICTTN) was identified from the frog skin of Odorrana grahami. It promotes wound healing in a murine model with a full-thickness dermal wound in both normal and diabetic animals. In addition to its strong angiogenic ability with respect to the upregulation of some angiogenic proteins, CW49 also showed a significant anti-inflammatory effect in diabetic wounds, which was very important for healing chronic wounds. CW49 had little effect on re-epithelialization, resulting in no significant effect on wound closure rate compared to a vehicle control. Altogether, this indicated that CW49 might accelerate diabetic wound healing by promoting angiogenesis and preventing any excessive inflammatory response. Considering its favorable traits as a small peptide that significantly promotes angiogenesis, CW49 might be an excellent candidate or template for the development of a drug for use in the treatment of diabetic wounds. | 25,117,795 | [
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The selective adsorption of tellurium in the aluminosilicate regions of AFI- and MOR-type microporous crystals. | Attempts have been made to load tellurium (Te) atoms into the one-dimensional nano-channels of microporous crystals of aluminophosphate AlPO4-5 and of aluminosilicate mordenites of the Na(+) form (Na-MOR) and the H(+)-form (H-MOR) at 673 K. The density of the atoms adsorbed was in the sequence 0 ∼ AlPO4-5 ≪ H-MOR < Na-MOR. AlPO4-5 provides a shallow potential of periodical charge fluctuation for Te atoms, from the alternate ordering of Al and P atoms through O atoms. Mordenite offers a sufficiently strong potential for Te adsorption, but the magnitude varies with the type of cation. Dipoles between framework AlO2(-) anion sites and their Na(+) counter-ions in Na-MOR provide a stronger potential than the Brønsted acid points in H-MOR. The adsorption of Te atoms in the silico-aluminophosphate SAPO-5 was between that of AlPO4-5 and H-MOR, leading us to suspect that Te atoms are selectively adsorbed in the aluminosilicate regions accompanying the Brønsted acid points distributed in the major aluminophosphate network. The aluminosilicate regions in SAPO-5 are below 500 nm in size and are distributed throughout a single crystal. | 25,117,797 | [
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Identification of 33 candidate oncogenes by screening for base-specific mutations. | Genes with recurrent codon-specific somatic mutations are likely drivers of tumorigenesis and potential therapeutic targets. Hypermutable cancers may represent a sensitive system for generation and selection of oncogenic mutations. We utilised exome-sequencing data on 25 sporadic microsatellite-instable (MSI) colorectal cancers (CRCs) and searched for base-specific somatic mutation hotspots. We identified novel mutation hotspots in 33 genes. Fourteen genes displayed mutations in the validation set of 254 MSI CRCs: ANTXR1, MORC2, CEP135, CRYBB1, GALNT9, KRT82, PI15, SLC36A1, CNTF, GLDC, MBTPS1, OR9Q2, R3HDM1 and TTPAL. A database search found examples of the hotspot mutations in multiple cancer types. This work reveals a variety of new recurrent candidate oncogene mutations to be further scrutinised as potential therapeutic targets. | 25,117,815 | [
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Person-to-person transmission of norovirus resulting in an outbreak of acute gastroenteritis at a summer camp. | A significant proportion of norovirus (NV) gastroenteritis outbreaks described in the Spanish literature have been because of contaminated food or water. This study describes an outbreak of acute gastroenteritis because of NV in which there was person-to-person transmission. A retrospective cohort study was carried out; we established the case definition for primary and secondary cases. An epidemiological survey was designed, including possible food exposures, and clinical and laboratory data. Water and stool samples were taken from affected individuals and food handlers. The presence of NV was detected using a reverse transcription-PCR assay. We analyzed the risk of gastroenteritis using relative risk and its 95% confidence interval as the measure of association, and estimated the basic reproductive number (R0). The primary attack rate was 45.0%, with no significant differences between sexes. The secondary attack rate during the camp stay was 22.7%. The basic reproductive number for 5 days was R0=2.62. The most frequent symptoms were abdominal pain (85.7%) and vomiting (81.9%). Epidemiological analysis showed no association with food or drinking water. A total of 66.6% (8/12) of stool samples tested positive for NV (genogroup II). Control measures in general, and hand hygiene in particular, should be extended to the families once the children return home, to prevent secondary cases in NV outbreaks. | 25,117,826 | [
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Species variation in the enantioselective metabolism of tegafur to 5-fluorouracil among rats, dogs and monkeys. | Tegafur (FT), a pro-drug of 5-fluorouracil (5-FU), is a racemate consisting of two enantiomers, R and S-FT. The aim of this study was to clarify interspecies variation in the enantioselective metabolism of FT. Plasma concentrations of FT enantiomers were determined in rats, dogs and monkeys following intravenous and oral dosing of the racemate (5 mg/kg). In addition, the enzymatic conversion of FT enantiomers to 5-FU was assayed using hepatic preparations. Metabolic clearance of R-FT was higher than that of S-FT in rats and monkeys, but S-FT was the preferential substrate for dogs. An inhibition study revealed that cytochrome P450 is primarily responsible for the enantioselective metabolism of FT in rats and dogs. In contrast, in monkeys, thymidine phosphorylase was a determinant of the enantioselectivity in FT metabolism. Although oral bioavailability was not enantioselective, in-vitro and in-vivo kinetic studies suggested that the enantioselectivity in the hepatic intrinsic clearance of FT directly influences the body clearance in all animal species examined. The interspecies variations were observed in the enantioselective pharmacokinetics of FT, and the in-vivo enantioselectivity could be extrapolated from the in-vitro metabolic activities. | 25,117,829 | [
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Laparoscopic myomectomy: clinical outcomes and comparative evidence. | Laparoscopic myomectomy is a common surgical treatment for symptomatic uterine leiomyomas. Proponents of the laparoscopic approach to myomectomy propose that the advantages include shorter length of hospital stay and recovery time. Others suggest longer operative time, greater blood loss, increased risk of recurrence, risk of uterine rupture in future pregnancies, and potential dissemination of cells with use of morcellation. This review outlines techniques for performance of laparoscopic myomectomy and critically appraises the available evidence for operative data, short-term and long-term complications, and reproductive outcomes. | 25,117,840 | [
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A latent growth curve analysis of alcohol-use specific parenting and adolescent alcohol use. | This study investigates how changes in alcohol use-specific parenting were associated with adolescent drinking trajectories. Three waves of data from a longitudinal study investigating adolescent substance use were used. The community sample (N=378) was aged 10-13 at the first wave of assessment. Our findings show that over time, parents are less likely to discipline their adolescents' drinking, more likely to grant their adolescent permission to drink, and less likely to communicate the consequences of alcohol use. Moreover, these changes are associated with escalation in adolescent alcohol use. Parental efficacy at preventing alcohol use declined, but did not relate to changes in adolescent drinking. | 25,117,845 | [
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The emerging trend of work beyond retirement age in Germany. Increasing social inequality? | Population ageing, demographic change and the financial crisis has put the financial sustainability of the German pension system at risk. In reaction to these challenges, Germany recently abandoned generous early retirement policies and moved towards policies encouraging higher employment among the elderly. In this article we evaluate how these labour market and pension policies affected the retirement decisions of older workers in Germany over the last three decades. Complementing previous research on early retirement, we focus in particular on those working past the mandatory retirement age of 65 years and examine whether the composition of this group of postretirement-age workers has changed over time. We analyse pooled cross-sectional data from three rounds of the German Ageing Survey which allow us to cover the last three decades from 1980 to 2008. Estimating multinomial logit models we distinguish explanatory factors on the individual, organizational and institutional level that frame the decision to leave the labour market before the age of 65, to stop working at 65 or to work past 65. Over the last three decades, the share of German workers leaving the labour market after the mandatory retirement age of 65 has increased markedly. This trend towards working longer has changed particularly among the low educated workforce which in previous decades traditionally has exhibited a tendency to retire early. In contrast to high-skilled workers, the decision to work longer among low-educated workers is mainly driven by financial need (and is usually not in line with their desire or their ability to work for longer). Our findings suggest an increase in social inequality in retirement decisions as a result of the policy shift towards activation. We conclude by arguing for a more fine-grained understanding of the reasons why people work longer. Such research would provide valuable insights into how to design future labour market and pension reforms preventing a rise in social inequalities. | 25,117,859 | [
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Effect of electrohydraulic shockwave treatment on tenderness, muscle cathepsin and peptidase activities and microstructure of beef loin steaks from Holstein young bulls. | Hydrodynamic pressure processing (HDP) or shockwave treatment improved tenderness (18% reduction in Warner-Bratzler shear force (WBSF) of beef loin steaks. Endogenous muscle proteolyic activities (cathepsins and peptidases) and protein fragmentation of sarcoplasmic and myofibrillar proteins detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were not influenced by HDP. However, microstructure changes were clearly detected using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Specifically a disruption of the structure at the muscle fiber bundles and an increased endomysium space were observed. The present paper supports the evidence of physical disruption of the muscle fibers as a cause behind the tenderness improvement. The paper discusses the possible mechanisms responsible for the meat tenderisation induced by HDP treatment. | 25,117,876 | [
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School-level factors associated with increased fruit and vegetable consumption among students in California middle and high schools. | This study assessed associations between selective school-level factors and students' consumption of fruits and vegetables at school. Better understanding of school factors associated with increased produce consumption is especially important, as students are served more produce items at school. This cross-sectional study included 5439 seventh- and ninth-grade students from 31 schools in California in 2010. Multilevel regression models estimated whether the odds of consuming fruits or vegetables at school among students eating the school lunch were associated with the length of the lunch period, quality/variety of produce options, or other factors. A longer lunch period was associated with increased odds of a student eating fruits (odds ratio [OR] = 1.40) and vegetables (OR = 1.54) at school. Better fruit quality increased the odds of a student consuming fruit (OR = 1.44). Including a salad bar and involving students in food service decisions increased a student's odds of consuming vegetables (OR = 1.48 and OR = 1.34, respectively). This study suggests that institutional factors in schools are positively associated with middle and high school students' consumption of produce items at school. Additional efforts to structure school meal environments to enhance students' consumption of produce items can benefit students' nutrition and health. | 25,117,889 | [
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The placebo effect in early-phase glaucoma clinical trials. | To analyze the extent and prevalence of the placebo effect in prior early-phase glaucoma clinical studies. Articles were evaluated on phase I and II trials of glaucoma medicines that became commercially available after 1977 with a placebo arm that involved glaucoma patients. We included 23 studies with 23 treatment arms with a total of 1703 patients in articles evaluating 10 different glaucoma medications. This study showed that at 8 AM (n = 18), the average decrease in placebo from untreated baseline was 2.3 ± 1.6 mm Hg (9%), while for the diurnal curve (n = 17), the mean decrease was 1.4 ± 1.1 mm Hg (6%). At 8 AM, 8/18 treatment arms had greater than 2 mm Hg intraocular pressure (IOP) decrease, and all had at least some reduction in IOP. For the diurnal curve, 4 of 17 studies had reduced IOP greater than 2 mm Hg. One treatment arm had no placebo effect. This study suggests that a placebo effect is common in glaucoma clinical trials and potentially could limit the ability to evaluate the efficacy of a new medicine. | 25,117,918 | [
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Can trained volunteers make a difference at mealtimes for older people in hospital? A qualitative study of the views and experience of nurses, patients, relatives and volunteers in the Southampton Mealtime Assistance Study. | Malnutrition is common amongst hospitalised older patients and associated with increased morbidity and mortality. Poor dietary intake results from factors including acute illness and cognitive impairment but additionally patients may have difficulty managing at mealtimes. Use of volunteers to help at mealtimes is rarely evaluated. To obtain multiple perspectives on nutritional care of older inpatients, acceptability of trained volunteers and identify important elements of their assistance. A qualitative study 1 year before and after introduction of volunteer mealtime assistants on one ward and parallel comparison with a control ward in a Medicine for Older People department at a UK university hospital. Semi-structured interviews and focus groups, in baseline and intervention years, with purposively sampled nursing staff at different levels of seniority; patients or close relatives; and volunteers. At baseline staff felt under pressure with insufficient people assisting at mealtimes. Introducing trained volunteers was perceived by staff and patients to improve quality of mealtime care by preparing patients for mealtimes, assisting patients who needed help, and releasing nursing time to assist dysphagic or drowsy patients. There was synergy with other initiatives, notably protected mealtimes. Interviews highlighted the perceived contribution of chronic poor appetite and changes in eating patterns to risk of malnutrition. Improved quality of mealtime care attributed to volunteers' input has potential to enhance staff morale and patients'/relatives' confidence. A volunteer mealtime assistance scheme may work best when introduced in context of other changes reflecting commitment to improving nutrition. (i) A mealtime assistance scheme should incorporate training, supervision and support for volunteers; (ii) Good relationships and a sense of teamwork can develop between wards staff and volunteers; (iii) Impact may be maximised in the context of 'protected mealtimes'. | 25,117,920 | [
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HIV and noncommunicable diseases (NCDs) in Latin America: a call for an integrated and comprehensive response. | The life expectancy of people living with HIV has dramatically improved with the much increased access to antiretroviral therapy. Consequently, a larger number of people living with HIV are living longer and facing the increased burden of noncommunicable diseases (NCDs). NCDs and HIV infection share common epidemiologic and sociodemographic characteristics that influence their outcomes, which may be difficult to address in the relatively weak health systems of the region. Data on the prevalence and interactions of NCDs and HIV in Latin American countries remain very limited, which hinders their governments' ability to make informed decisions about health care policies. Therefore, there is an urgent need to develop a research agenda that will be the basis for an integrated and comprehensive health care approach to HIV and NCD comorbidities in Latin America. | 25,117,966 | [
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Bacteriocins: Recent Trends and Potential Applications. | In the modern era, there is great need for food preservation in both developing and developed countries due to increasing demand for extending shelf life and prevention of spoilage of food material. With the emergence of new pathogens and ability of micro-organisms to undergo changes, exploration of new avenues for the food preservation has gained importance. Moreover, awareness among consumers regarding harmful effects of chemical preservatives has been increased. Globally, altogether there is increasing demand by consumers for chemical-free and minimal processed food products. Potential of bacteriocin and its application in reducing the microbiological spoilages and in the preservation of food is long been recognized. Bacteriocins are normally specific to closely related species without disrupting the growth of other microbial populations. A number of applications of bacteriocin have been reported for humans, live stock, aquaculture etc. This review is focused on recent trends and applications of bacteriocins in different areas in addition to their biopreservative potential. | 25,117,970 | [
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Enteral nutrition within 72 h after onset of acute pancreatitis vs delayed initiation. | To explore early (within 72 h) vs delayed enteral nutrition (EN) therapy for patients with acute pancreatitis (AP). A total of 93 patients were allocated to two groups: early enteral nutrition (EEN) group (started within 72 h after onset) and delayed enteral nutrition (DEN) group (started beyond 72 h but within 7 days after onset). Baseline parameters and scores were recorded on admission and on day 3 after the initiation of EN therapy, as were the clinical outcome variables. Hospital mortality, length of stay, number of patients requiring mechanical ventilation and incidence of pancreatic infection in the EEN group were significantly lower than those in the DEN group; all six reported deaths were in the DEN group. In the DEN group, more patients suffered from sepsis, shock or acute kidney injury, and more patients required surgical intervention or continuous renal replacement therapy. On day 3 after EN therapy was initiated, the acute physiology and chronic health evaluation II scores, sequential organ failure assessment scores, C-reactive protein levels and the incidence of bowel wall thickening were lower in the EEN group than in the DEN group. The time when EN therapy was initiated was a prognostic variable for pancreatic infection (odds ratio, 24.08; P=0.014). Compared with the DEN therapy, EEN therapy can accelerate the recovery of disturbed homeostasis, reduce the incidence of pancreatic infection and improve the clinical outcomes of AP patients. For AP patients, EN therapy should be initiated within 72 h after onset. | 25,117,988 | [
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Associations of sugar-containing beverages with asthma prevalence in 11-year-old children: the PIAMA birth cohort. | Recently, a few studies have linked soft drink consumption to increased asthma risk, but the contribution of different types of soft drinks is unknown. We investigated cross-sectional associations between six different types of soft drinks and asthma in 11-year-old children. We analyzed data of 2406 children participating in the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort. At age 11, children self-reported consumption of sugar-added drinks, diet drinks, sweetened milk drinks, 100% fruit juice, energy drinks and sport drinks. The definition of asthma was based on parental reports of wheezing, prescription of inhaled corticosteroids and doctor's diagnosis of asthma. The prevalence of asthma in this study was 5.8%. In adjusted logistic regression analyses, asthma risk was increased for high (⩾10 glasses/week (gl/wk) versus low (<4 gl/wk) consumption of 100% fruit juice (odds ratio (OR): 2.09, 95% confidence interval (CI): 1.21-3.60), sugar-added drinks (OR: 1.56, 95%CI: 0.95-2.56) and for very high (>21.5 gl/wk) versus low (<12.5 gl/wk) total sugar-containing beverage (SCB) consumption (OR: 1.91, 95%CI: 1.04-3.48). Consumption of other beverages and consumption of fruit were not associated with increased asthma risk. No evidence for mediation of the observed associations by body mass index was found. This study indicates that high consumption of 100% fruit juice and total SCBs is associated with increased asthma risk in children. The positive association between consumption of 100% fruit juice and asthma is an unexpected finding that needs confirmation in future studies. | 25,117,998 | [
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In vitro anticancer activity of loquat tea by inducing apoptosis in human leukemia cells. | Fresh loquat leaves have been used as folk health herb in Asian countries for long time, although the evidence supporting their functions is still minimal. This study aimed to clarify the chemopreventive effect of loquat tea extract (LTE) by investigating the inhibition on proliferation, and underlying mechanisms in human promyelocytic leukemia cells (HL-60). LTE inhibited proliferation of HL-60 in a dose-dependent manner. Molecular data showed that the isolated fraction of LTE induced apoptosis of HL-60 as characterized by DNA fragmentation; activation of caspase-3, -8, and -9; and inactivation of poly(ADP)ribose polymerase. Moreover, LTE fraction increased the ratio of pro-apoptotic Bcl-2-associated X protein (Bax)/anti-apoptotic myeloid cell leukemia 1 (Mcl-1) that caused mitochondrial membrane potential loss and cytochrome c released to cytosol. Thus, our data indicate that LTE might induce apoptosis in HL-60 cells through a mitochondrial dysfunction pathway. These findings enhance our understanding for chemopreventive function of loquat tea. | 25,118,018 | [
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Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain. | The analgesic potency of opioids is reduced in neuropathic pain. However, the molecular mechanism is not well understood. The present study demonstrated that increased methylation of the Mu opioid receptor (MOR) gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and intraplantar (i.pl.), not intracerebroventricular (i.c.v.) injection of morphine, the potency of morphine analgesia was significantly reduced in nerve-injured mice compared with control sham-operated mice. After peripheral nerve injury, we observed a decreased expression of MOR protein and mRNA, accompanied by an increased methylation status of MOR gene PP, in DRG. However, peripheral nerve injury could not induce a decreased expression of MOR mRNA in the spinal cord. Treatment with 5-aza-2'-deoxycytidine (5-aza-dC), inhibited the increased methylation of MOR gene PP and prevented the decreased expression of MOR in DRG, thereby improved systemic, spinal and periphery morphine analgesia. Altogether, our results demonstrate that increased methylation of the MOR gene PP in DRG is required for the decreased morphine analgesia in neuropathic pain. | 25,118,039 | [
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Of early animals, anaerobic mitochondria, and a modern sponge. | The origin and early evolution of animals marks an important event in life's history. This event is historically associated with an important variable in Earth history - oxygen. One view has it that an increase in oceanic oxygen levels at the end of the Neoproterozoic Era (roughly 600 million years ago) allowed animals to become large and leave fossils. How important was oxygen for the process of early animal evolution? New data show that some modern sponges can survive for several weeks at low oxygen levels. Many groups of animals have mechanisms to cope with low oxygen or anoxia, and very often, mitochondria - organelles usually associated with oxygen - are involved in anaerobic energy metabolism in animals. It is a good time to refresh our memory about the anaerobic capacities of mitochondria in modern animals and how that might relate to the ecology of early metazoans. | 25,118,050 | [
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Fitness for entering a simple exercise program and mortality: a study corollary to the exercise introduction to enhance performance in dialysis (EXCITE) trial. | In this corollary analysis of the EXCITE study, we looked at possible differences in baseline risk factors and mortality between subjects excluded from the trial because non-eligible (n=216) or because eligible but refusing to participate (n=116). Baseline characteristics and mortality data were recorded. Survival and independent predictors of mortality were assessed by Kaplan-Meier and Cox regression analyses. The incidence rate of mortality was higher in non-eligible vs. eligible non-randomized patients (21.0 vs. 10.9 deaths/100 persons-year; P<0.001). The crude excess risk of death in non-eligible patients (HR 1.96; 95% CI 1.36 to 2.77; P<0.001) was reduced after adjustment for risk factors which differed in the two cohorts including age, blood pressure, phosphate, CRP, smoking, diabetes, triglycerides, cardiovascular comorbidities and history of neoplasia (HR 1.60; 95% CI 1.10 to 2.35; P=0.017) and almost nullified after including in the same model also information on deambulation impairment (HR 1.16; 95% CI 0.75 to 1.80; P=0.513). Deambulation ability mostly explains the difference in survival rate in non-eligible and eligible non-randomized patients in the EXCITE trial. Extending data analyses and outcome reporting also to subjects not taking part in a trial may be helpful to assess the representability of the study population. | 25,118,055 | [
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Synchronous tRNA movements during translocation on the ribosome are orchestrated by elongation factor G and GTP hydrolysis. | The translocation of tRNAs through the ribosome proceeds through numerous small steps in which tRNAs gradually shift their positions on the small and large ribosomal subunits. The most urgent questions are: (i) whether these intermediates are important; (ii) how the ribosomal translocase, the GTPase elongation factor G (EF-G), promotes directed movement; and (iii) how the energy of GTP hydrolysis is coupled to movement. In the light of recent advances in biophysical and structural studies, we argue that intermediate states of translocation are snapshots of dynamic fluctuations that guide the movement. In contrast to current models of stepwise translocation, kinetic evidence shows that the tRNAs move synchronously on the two ribosomal subunits in a rapid reaction orchestrated by EF-G and GTP hydrolysis. EF-G combines the energy regimes of a GTPase and a motor protein and facilitates tRNA movement by a combination of directed Brownian ratchet and power stroke mechanisms. | 25,118,068 | [
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Viunalikeviruses are environmentally common agents of horizontal gene transfer in pathogens and biocontrol bacteria. | Bacteriophages have been used as natural biocontrol and therapeutic agents, but also as biotechnological tools for bacterial engineering. We showed recently that the transducing bacteriophage ϕMAM1 is a ViI-like phage and a member of the new genus, 'Viunalikevirus'. Here, we show that four additional ViI-like phages and three new environmentally isolated viunalikeviruses, all infecting plant and human pathogens, are very efficient generalised transducers capable of transducing chromosomal markers at frequencies of up to 10(-4) transductants per plaque-forming unit. We also demonstrate the interstrain transduction of plasmids and chromosomal markers, including genes involved in anabolism, genes for virulence and genes encoding secondary metabolites involved in biocontrol. We propose that all viunalikeviruses are likely to perform efficient horizontal gene transfer. Viunalikeviruses therefore represent useful agents for functional genomics and bacterial engineering, and for chemical and synthetic biology studies, but could be viewed as inappropriate choices for phage therapy. | 25,118,075 | [
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The quantified patient: a patient participatory culture. | The Quantified Self Movement, which aims to improve various aspects of life and health through recording and reviewing daily activities and biometrics, is a new and upcoming practice of self monitoring that holds much promise. Now, the most underutilized resource in ambulatory health care, the patient, can participate like never before, and the patient's Quantified Self can be directly monitored and remotely accessed by health care professionals. | 25,118,077 | [
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Reboxetine adjuvant therapy in patients with schizophrenia showing a suboptimal response to clozapine: a 12-week, open-label, pilot study. | The present 12-week open-label uncontrolled trial was aimed to explore the efficacy of reboxetine add-on pharmacotherapy on clinical symptoms and cognitive functioning in 15 patients with schizophrenia with suboptimal response (mean [SD] Brief Psychiatric Rating Scale baseline total score, 32.2 [5.4]) despite receiving clozapine monotherapy at the highest tolerated dosage. The results obtained evidenced that reboxetine at a dosage of 4 mg/d mildly reduced only depressive symptoms (Calgary Depression Scale for Schizophrenia: P = 0.035, Cohen d = 0.7), whereas worsening of performances on phonemic fluency (P = 0.012, Cohen d = 0.5) was observed. After Bonferroni correction, changes at the Calgary Depression Scale for Schizophrenia and at the Verbal Fluency Task were not further confirmed.The results obtained indicate that reboxetine seemed to be scarcely effective for reducing clinical symptoms in patients with schizophrenia who have had an incomplete clinical response to clozapine. Regarding cognitive functioning, in our sample, a trend to experience cognitive impairment in the examined domains was observed, as confirmed by a mild worsening of performances on cognitive tasks.Schizophrenia is a heterogeneous disorder with regard to pathophysiology; therefore, data reflecting the mean response of a sample of patients may fail to reveal therapeutic effects. More research is needed to better identify subgroups of patients with peculiar features, which may account for responsivity to experimental medications and augmentation strategies. | 25,118,083 | [
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The rise of mortality from mental and neurological diseases in Europe, 1979-2009: observational study. | We studied recent trends in mortality from seven mental and neurological conditions and their determinants in 41 European countries. Age-standardized mortality rates were analysed using standard methods of descriptive epidemiology, and were related to cultural, economic and health care indicators using regression analysis. Rising mortality from mental and neurological conditions is seen in most European countries, and is mainly due to rising mortality from dementias. Mortality from psychoactive substance use and Parkinson's disease has also risen in several countries. Mortality from dementias has risen particularly strongly in Finland, Iceland, Malta, Netherlands, Spain, Sweden and the United Kingdom, and is positively associated with self-expression values, average income, health care expenditure and life expectancy, but only the first has an independent effect. Although trends in mortality from dementias have probably been affected by changes in cause-of-death classification, the high level of mortality from these conditions in a number of vanguard countries suggests that it is now among the most frequent causes of death in high-income countries. Recognition of dementias as a cause of death, and/or refraining from life-saving treatment for patients with dementia, appear to be strongly dependent on cultural values. | 25,118,099 | [
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Bipolar disorder and its relation to major psychiatric disorders: a family-based study in the Swedish population. | Bipolar disorder (BPD) shares genetic components with other psychiatric disorders; however, uncertainty remains about where in the psychiatric spectra BPD falls. To understand the etiology of BPD, we studied the familial aggregation of BPD and co-aggregation between BPD and schizophrenia, depression, anxiety disorders, attention-deficit hyperactivity disorder, drug abuse, personality disorders, and autism spectrum disorders. A population-based cohort was created by linking several Swedish national registers. A total of 54,723 individuals with BPD were identified among 8,141,033 offspring from 4,149,748 nuclear families. The relative risk of BPD in relatives and the co-occurrence of other psychiatric disorders in patients with BPD and their relatives were compared to those of matched-population controls. Structural equation modeling was used to estimate the heritability and tetrachoric correlation. The familial risks for relatives of BPD probands were 5.8-7.9 in first-degree relatives, and decreased with genetic distance. Co-occurrence risks for other psychiatric disorders were 9.7-22.9 in individuals with BPD and 1.7-2.8 in full siblings of BPD probands. Heritability for BPD was estimated at 58%. The correlations between BPD and other psychiatric disorders were considerable (0.37-0.62) and primarily due to genetic effects. The correlation with depression was the highest (0.62), and was 0.44 for schizophrenia. The high familial risks provide evidence that genetic factors play an important role in the etiology of BPD, and the shared genetic determinants suggest pleiotropic effects across different psychiatric disorders. Results also indicate that BPD is in both the mood and psychotic spectra, but possibly more closely related to mood disorders. | 25,118,125 | [
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Use of psychotherapy in a representative adult community sample in São Paulo, Brazil. | Little is known about the use of psychotherapy to treat common mental disorders in a major city in a middle-income country. Our data come from in-home interviews with a stratified random sample of 2000 community residents aged 18 to 65 years in the city of São Paulo, Brazil. The information obtained included sociodemographic characteristics; psychotropic drugs; mental status; and lifetime, previous 12 months, and current use of psychotherapy. Logistic regression was used to examine determinants of use of psychotherapy. Of the sample, 22.7% met General Health Questionnaire-12 criteria for common mental disorders. Lifetime, previous 12 months, and current use of psychotherapy were reported by 14.6%, 4.6%, and 2.3% of the sample, respectively. Users typically were women, were more educated, had higher income, were not married, were unemployed, and had common mental disorders. Further analysis found that 47% (with higher education and income) paid out-of-pocket, and 53% used psychotropic medication. Psychotherapy does not seem to be the preferred treatment of common mental disorders. | 25,118,139 | [
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Effects of earthworms on physicochemical properties and microbial profiles during vermicomposting of fresh fruit and vegetable wastes. | This study aimed to investigate the effect of earthworms on physicochemical and microbial properties during vermicomposting of fresh fruit and vegetable wastes (FVW) by contrasting two decomposing systems of FVW with and without earthworms for 5weeks. Compared to control treatment (without earthworms), vermicomposting treatment resulted in a rapid decrease of electrical conductivity and losses of total carbon and nitrogen from the 2nd week. Quantitative PCR displayed that earthworms markedly enhanced bacterial and fungal densities, showing the higher values than control, during the whole decomposition process. In addition, denaturing gradient gel electrophoresis combined with sequencing analysis revealed that earthworms pronouncedly modified bacterial and fungal community structures, through broadening the community diversities of Actinobacteria, Bacteroidetes, Proteobacteria, and Ascomycotina. These results suggest that the presence of earthworms promoted the activity and population of bacteria and fungi, and modified their communities, thus altering the decomposition pathway of fresh FVW. | 25,118,152 | [
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Co-inheritance of α-thalassaemia and β-thalassaemia in a prenatal screening population in mainland China. | To determine the prevalence of α-thalassaemia in β-thalassaemia individuals in a Chinese population. The standard diagnostic marker for β-thalassaemia was elevation of the Hb A2 level (>3.5%) with low mean corpuscular volume. The common α-thalassaemia mutations were studied by molecular analysis in all identified β-thalassaemia carriers. A prevalence rate of 3.3% for β-thalassaemia was found in our population; α- and β-thalassaemia interactions were found to co-exist in 17.8% of the β-thalassaemia carriers. The -SEA deletion was the most common α-thalassaemia mutation co-inherited with β-thalassaemia, followed by the -α3.7 deletion, the -α4.2 deletion, Hb Quong Sze, and Hb Constant Spring. Our results suggest that it could be valuable to study co-existing α-globin mutations in subjects with β-thalassaemia trait in a prenatal screening programme, especially in populations with a high prevalence of haemoglobinopathies. | 25,118,159 | [
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Type II cytokines impair host defense against an intracellular fungal pathogen by amplifying macrophage generation of IL-33. | Interleukin (IL)-4 subverts protective immunity to multiple intracellular pathogens, including the fungus Histoplasma capsulatum. Previously, we reported that H. capsulatum-challenged CCR2(-/-) mice manifest elevated pulmonary fungal burden owing to exaggerated IL-4. Paradoxical to our anticipation in IL-33 driving IL-4, we discovered that the latter prompted IL-33 in mutant mice. In infected CCR2(-/-) animals, amplified IL-33 succeeded the heightened IL-4 response and inhibition of IL-4 signaling decreased IL-33. Moreover, macrophages, but not epithelial cells or dendritic cells, from these mice expressed higher IL-33 in comparison with controls. Dissection of mechanisms that promulgated IL-33 revealed type-II cytokines and H. capsulatum synergistically elicited an IL-33 response in macrophages via signal transducer and activator of transcription factor 6/interferon-regulatory factor-4 and Dectin-1 pathways, respectively. Neutralizing IL-33 in CCR2(-/-) animals, but not controls, enhanced their resistance to histoplasmosis. Thus we describe a previously unrecognized role for IL-4 in instigating IL-33 in macrophages. Furthermore, in the presence of intracellular fungal pathogens, the type-II cytokine-driven IL-33 response impairs immunity. | 25,118,166 | [
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A high-density genetic map for soybean based on specific length amplified fragment sequencing. | Soybean is an important oil seed crop, but very few high-density genetic maps have been published for this species. Specific length amplified fragment sequencing (SLAF-seq) is a recently developed high-resolution strategy for large scale de novo discovery and genotyping of single nucleotide polymorphisms. SLAF-seq was employed in this study to obtain sufficient markers to construct a high-density genetic map for soybean. In total, 33.10 Gb of data containing 171,001,333 paired-end reads were obtained after preprocessing. The average sequencing depth was 42.29 in the Dongnong594, 56.63 in the Charleston, and 3.92 in each progeny. In total, 164,197 high-quality SLAFs were detected, of which 12,577 SLAFs were polymorphic, and 5,308 of the polymorphic markers met the requirements for use in constructing a genetic map. The final map included 5,308 markers on 20 linkage groups and was 2,655.68 cM in length, with an average distance of 0.5 cM between adjacent markers. To our knowledge, this map has the shortest average distance of adjacent markers for soybean. We report here a high-density genetic map for soybean. The map was constructed using a recombinant inbred line population and the SLAF-seq approach, which allowed the efficient development of a large number of polymorphic markers in a short time. Results of this study will not only provide a platform for gene/quantitative trait loci fine mapping, but will also serve as a reference for molecular breeding of soybean. | 25,118,194 | [
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20 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors. | The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin-responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B, and dynorphin and these could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that agouti-related protein/neuropeptide Y neurons project onto GnRH and kisspeptin neurons, allowing for a crosstalk between food intake and reproduction. Finally, while puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. The mechanisms underlying leptin resistance in pregnancy have lagged; however, the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the following decade to shed new light on these complex and essential pathways. | 25,118,207 | [
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Proteome-wide light/dark modulation of thiol oxidation in cyanobacteria revealed by quantitative site-specific redox proteomics. | Reversible protein thiol oxidation is an essential regulatory mechanism of photosynthesis, metabolism, and gene expression in photosynthetic organisms. Herein, we present proteome-wide quantitative and site-specific profiling of in vivo thiol oxidation modulated by light/dark in the cyanobacterium Synechocystis sp. PCC 6803, an oxygenic photosynthetic prokaryote, using a resin-assisted thiol enrichment approach. Our proteomic approach integrates resin-assisted enrichment with isobaric tandem mass tag labeling to enable site-specific and quantitative measurements of reversibly oxidized thiols. The redox dynamics of ∼2,100 Cys-sites from 1,060 proteins under light, dark, and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (a photosystem II inhibitor) conditions were quantified. In addition to relative quantification, the stoichiometry or percentage of oxidation (reversibly oxidized/total thiols) for ∼1,350 Cys-sites was also quantified. The overall results revealed broad changes in thiol oxidation in many key biological processes, including photosynthetic electron transport, carbon fixation, and glycolysis. Moreover, the redox sensitivity along with the stoichiometric data enabled prediction of potential functional Cys-sites for proteins of interest. The functional significance of redox-sensitive Cys-sites in NADP-dependent glyceraldehyde-3-phosphate dehydrogenase, peroxiredoxin (AhpC/TSA family protein Sll1621), and glucose 6-phosphate dehydrogenase was further confirmed with site-specific mutagenesis and biochemical studies. Together, our findings provide significant insights into the broad redox regulation of photosynthetic organisms. | 25,118,246 | [
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RESTORE: REcovery after Serious Trauma--Outcomes, Resource use and patient Experiences study protocol. | Traumatic injury is a leading contributor to the overall global burden of disease. However, there is a worldwide shortage of population data to inform understanding of non-fatal injury burden. An improved understanding of the pattern of recovery following trauma is needed to better estimate the burden of injury, guide provision of rehabilitation services and care to injured people, and inform guidelines for the monitoring and evaluation of disability outcomes. To provide a comprehensive overview of patient outcomes and experiences in the first 5 years after serious injury. This is a population-based, nested prospective cohort study using quantitative data methods, supplemented by a qualitative study of a seriously injured participant sample. All 2547 paediatric and adult major trauma patients captured by the Victorian State Trauma Registry with a date of injury from 1 July 2011 to 30 June 2012 who survived to hospital discharge and did not opt-off from the registry. To analyse the quantitative data and identify factors that predict poor or good outcome, whether there is change over time, differences in rates of recovery and change between key participant subgroups, multilevel mixed effects regression models will be fitted. To analyse the qualitative data, thematic analysis will be used to identify important themes and the relationships between themes. The results of this project have the potential to inform clinical decisions and public health policy, which can reduce the burden of non-fatal injury and improve the lives of people living with the consequences of severe injury. | 25,118,259 | [
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A critical role of the C-terminal segment for allosteric inhibitor-induced aberrant multimerization of HIV-1 integrase. | Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are a promising class of antiretroviral agents for clinical development. Although ALLINIs promote aberrant IN multimerization and inhibit IN interaction with its cellular cofactor LEDGF/p75 with comparable potencies in vitro, their primary mechanism of action in infected cells is through inducing aberrant multimerization of IN. Crystal structures have shown that ALLINIs bind at the IN catalytic core domain dimer interface and bridge two interacting subunits. However, how these interactions promote higher-order protein multimerization is not clear. Here, we used mass spectrometry-based protein footprinting to monitor surface topology changes in full-length WT and the drug-resistant A128T mutant INs in the presence of ALLINI-2. These experiments have identified protein-protein interactions that extend beyond the direct inhibitor binding site and which lead to aberrant multimerization of WT but not A128T IN. Specifically, we demonstrate that C-terminal residues Lys-264 and Lys-266 play an important role in the inhibitor induced aberrant multimerization of the WT protein. Our findings provide structural clues for exploiting IN multimerization as a new, attractive therapeutic target and are expected to facilitate development of improved inhibitors. | 25,118,283 | [
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Predictive markers of radiotherapy-induced rectal cancer regression. | Patients with locally advanced rectal cancer receive preoperative radiotherapy to reduce the probability of recurrence and to possibly improve overall survival. However, this appears dependent on the extent of histological tumour regression seen in the resected bowel, which can be highly variable between individuals. No predictive marker that can stratify patient management in this regard is currently available. Experimental data implicates a variety of factors that are involved in the DNA damage response following radiation injury, tumour tissue oxygenation, autoimmune antitumour response triggered by radiotherapy and in the pathogenesis of colorectal cancer, as potential indicators of radiation sensitivity. These details are presented in this review, which may serve as targets for clinical validation studies aiming to find predictors of radiotherapy response in rectal cancer. | 25,118,294 | [
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Effects of different levels of pressure support on intra-individual breath-to-breath variability. | Evidence exists that during pressure support ventilation (PSV), the addition of an extrinsic (ie, ventilator-generated) breath-to-breath variability (BBV) of breathing pattern improves respiratory function. If BBV is beneficial per se, choosing the PS level that maximizes it could be considered a valid strategy for conventional PSV. In this study, we evaluated the effect of different PS levels on intrinsic BBV in acutely ill, mechanically ventilated subjects to determine whether a significant relationship exists between PS level and BBV magnitude. Fourteen invasively mechanically ventilated subjects were prospectively studied. PS was adjusted at 20 cm H2O and sequentially reduced to 15, 10, and 5 cm H2O. Arterial blood gas analysis and pressure at 0.1 s after the onset of inspiration (P0.1) were measured at each PS level. Airway and esophageal pressure and air flow were continuously recorded. Peak inspiratory flow, tidal volume (VT), breathing frequency, and pressure-time product (PTP) were calculated on a breath-by-breath basis. The breathing pattern variability was assessed by the coefficient of variation of the time series of VT, peak inspiratory flow, and breathing frequency from ∼ 60 consecutive breath cycles at each PS level. A general linear model for repeated measures was applied, with PS as an independent factor. A significance level of .05 was considered. Despite a large inter-individual difference in all measured variables (P < .001), the coefficient of variation was as low as 30%, and no significant differences in the coefficient of variation of peak inspiratory flow, breathing frequency, and VT between PS levels were observed (P > .15). Additionally, a significant increase in P0.1, PTP, and breathing frequency (P < .01) and a reduction in VT (P < .001) were observed with PS reduction. Despite a significant increase in spontaneous activity with PS reduction, BBV was not influenced by the PS level and was as low as 30% for all evaluated parameters. | 25,118,312 | [
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Low-dose CT for patients with clinically suspected acute appendicitis: optimal strength of sinogram affirmed iterative reconstruction for image quality and diagnostic performance. | As there is increased concern over the radiation exposure particularly in adolescents and young adults, computed tomography (CT) dose reduction is needed in the diagnosis of acute appendicitis. To evaluate the optimal strength of sinogram affirmed iterative reconstruction (SAFIRE) to obtain the best image quality on a 30-mAs applied low-dose CT (LDCT 30mAs) and to compare the diagnostic performances of the LDCT 30mAs with different SAFIRE strengths with that of the 100-mAs applied LDCT (LDCT 100mAs) for the diagnosis of acute appendicitis. A total of 102 consecutive patients (47 men, 55 women; mean age, 41.2 years; range, 15-82 years) with right lower quadrant pain underwent abdominal-pelvic CT, consisting of arterial phase LDCT 100mAs and portal venous phase LDCT30mAs under a fixed 120 kV. LDCT 30mAs images were reconstructed separately with five strength levels (S1-S5). Two blinded radiologists recorded scores for the subjective image quality of the LDCT 30mAs dataset (S0-S5) and confidence scores for the diagnosis of acute appendicitis on each dataset and LDCT 100mAs. CT image noise was measured for each set. The study population consisted of 58 patients with confirmed appendicitis and 44 without appendicitis. There was no significant difference in diagnostic performance between LDCT 100mAs and LDCT 30mAs with any strength for both readers (AUC for reader 1, LDCT 30mAs with S0-S5 = 0.97, LDCT 100mAs = 0.93, P = 0.0936; for reader 2, LDCT 30mAs with S0-S5 = 0.96, LDCT 100mAs = 0.97, P = 0.128). The measured noise decreased as the strength increased from S0 to S5 (mean, 20.8 > 17.7 > 15.6 > 13.5 > 11.5 > 9.5, P < 0.0001). However, overall subjective image quality on S3 was better than the other strengths for both readers (S0 < S1 < S2 < S3 > S4 > S5, P < 0.0001). Although measured noise declined as SAFIRE strength increased, S3 seems optimal for the best subjective image quality on LDCT 30mAs. The diagnostic performance of LDCT 30mAs with any strength is comparable to that of LDCT 100mAs for the diagnosis of acute appendicitis. | 25,118,330 | [
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[Genetic characteristics of influenza A/H3N2 virus neuraminidase gene: a survey from 2010 to 2012 in Qinghai Province, China]. | This study aims to perform a survey of genetic variation in neuraminidase (NA) gene of influenza A/H3N2 virus, as well as related resistance to NA inhibitors, in Qinghai Province of China, 2010 to 2012. Strains of influenza A/H3N2 isolated during an influenza survey from 2010 to 2012 in Qinghai were enrolled by random sampling. Viral RNA was extracted and amplified by RT-PCR. Purified PCR products were sequenced thereafter. Genetic analysis of nucleic acid and the derived amino acid sequences was performed by MEGA 4.0. Phylogenetic trees were also constructed. Strains isolated during 2010-2011 in this study clustered closely with World Health Organization (WHO) 2010-2012 reference vaccine strain A/Perth/16/2009 and 2008-2010 reference vaccine strain A/Brisbane/10/2007 on the phylogenetic tree, while the 2012 isolates were located on another branch. In analysis of derived amino acid sequences, the 2010 isolates mutated at K81T, the 2011 isolates mutated at I26V and D127N, while the 2012 isolates mutated at E41K, P46A, I58V, T71N, L81P, D93G, D127N, D151N, and I307M. The D151N mutation added a glycosylation site to the activity center of NA. No significant variation was discovered in H3N2 NA gene of 2010-2011 isolates in Qinghai, China. Isolates of 2012 were found with significant mutation, which has the potential of inducing minor resistance to NA inhibitors like zanamivir and oseltamivir. | 25,118,381 | [
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