title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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[Effect of Pi transportation, dampness resolving and phlegm expelling herbs on the obesity degree, fat hormones, and leptin resistance in diet-induced obesity rats]. | To observe the effect of Pi transportation, dampness resolving and phlegm expelling herbs (PTDRPEH) on the obesity degree, fat hormones, and leptin resistance in diet-induced obesity (DIO) rats. Among the 120 Wister rats, 10 were recruited as the blank control group (fed with basal forage), and the remaining 110 were administered with high-fat high-nutrition forage for 17 weeks. According to weight, we obtained 40 DIO rats and 10 diet-induced obesity resistance (DIO-R) rats. DIO rats were further divided into four groups, i.e., the DIO model group (normal saline, at the daily dose of 2 mL), the sibutramine group (at the daily dose of 1.6 mg/kg), the dampness resolving and phlegm expelling group (DRPE, at the daily dose of 3.2 g/kg), and the Pi transportation group (PT, at the daily dose of 3.2 g/kg). All were given by gastrogavage. Normal saline (2 mL) was given by gastrogavage to rats in the blank control group and the DIO-R group. The basal forage was administered to rats in the blank control group, while high fat forage was continually given to rats in the remaining five groups. Their body weights and body lengths were measured after 16 weeks of gastrogavage. All intra-abdominal fat was taken out to measure the degree of obesity and fat contents. Insulin resistance index (IRI), blood glucose, triglycerides, cholesterol, leptin, neuropeptide Y (NPY), tumor necrosis factor alpha (TNF-alpha), and adiponectin were detected after blood withdrawing. Leptin, TNF-alpha, adiponectin, suppressors of cytokine signaling-3 (SOCS-3), and other relevant adipose hormones and inflammatory cytokines were examined in the fat homogenate. Compared with the blank control group, DIO model rats' body weight, body mass index (BMI), fat factor, IRI, serum leptin, TNF-alpha, and SOCS-3 significantly increased (P < 0.05, P < 0.01); serum NPY, serum leptin, and adiponectin decreased (P < 0.05). Leptin increased and NPY decreased in DIO-R model rats. Compared with the DIO group, DIO-R model rats' body weight, BMI, fat factor, IRI, serum NPY, TNF-alpha, and SOCS-3 all decreased (P < 0.05, P < 0.01); leptin and adiponectin in serum and the fat homogenate all increased (P < 0.05, P < 0.01). After intervention with Sibutramine, rats' body weight, BMI, fat factor, and TNF-alpha in the fat homogenate obviously decreased (P < 0.05, P < 0.01). Serum TNF-alpha decreased, leptin and adiponectin increased in rats of the DRPE group (P < 0.05, P < 0.01). BMI, fat factor, IRI, leptin, and SOCS-3 showed a decreasing tendency, but with no statistical difference (P > 0.05). The body weight, BMI, fat factor, IRI, TNF-alpha, and SOCS-3 all decreased in the PT group (P < 0.05, P < 0.01); leptin and adiponectin in the serum and the fat homogenate increased (P < 0.05, P < 0.01). Sibutramine could reduce body weight and TNF-alpha in the adipose tissue. Herbs of PT could inhibit fat diet-induced obesity and insulin resistance (IR), with superior effect to herbs of DRPE. Its mechanism might be closely related to promoting leptin and adiponectin secreted by fat, reducing leptin resistance, and elevating serum levels of leptin and adiponectin. | 25,223,188 | [
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[Benefit of ocular draping on bacterial contamination after intravitreal injection using a plate-type eyelid speculum]. | To evaluate the effect of ocular draping on rates of bacterial contamination of the ocular surface immediately after intravitreal injection using a plate-type eyelid speculum. Twelve institutions participated in this prospective randomized study. Patients from each institution undergoing intravitreal injections were randomly assigned to 2 groups, with and without ocular draping. Following each institution's standard protocol for aseptic preparation, intravitreal injection was performed using a plate-type eyelid speculum designed for intravitreal injections with or without draping. Immediately after the intravitreal injection, a cotton swab was used to obtain a sample at the injection site and sent for bacterial culture. Of 262 eyes involved in the study, cultures were positive in five eyes (1.9%) using standard methods and positive in an additional 25 eyes (9.5%) using methods to increase culture sensitivity. There was no significant difference in the combined rate of bacterial contamination between the 2 groups (p = 0.561, Fisher's exact test). Ocular draping did not decrease the rate of bacterial contamination immediately after intravitreal injection performed using a plate-type eyelid speculum. | 25,223,208 | [
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[Investigation of clinical characteristics and surgical treatment for conjunctival epithelial inclusion cyst]. | To investigate the clinical characteristics and surgical treatment in eyes with conjunctival epithelial inclusion cysts (CEIC). This study involved the retrospective, medical-record-based investigation of 37 eyes of 34 patients diagnosed with CEIC by slit-lamp biomicroscopy and anterior segment optical coherence tomography (AS-OCT). CEIC were found most commonly in the nasal area of the conjunctiva (64.9%). Thirteen eyes (35.1%) had more than 1 cyst, and 10 eyes (27.0%) had a past history of punctures. Adhesion (9 eyes) between cyst and surrounding connective tissues was found to be significantly more in eyes with a puncture history (5 eyes; p = 0.0234, Fisher's exact test). Complete excision of cysts through a small conjunctival incision could be performed significantly more often among the 28 eyes without adhesion than in the 9 eyes with adhesion (p = 0.002). Pathological examination of the cysts indicated that they involved goblet cells in 16 eyes and mild inflammation in 4 eyes, consistent with the findings in previous reports. CEIC are predominantly found in the nasal area of the conjunctiva. In eyes without puncture history, adhesion of cysts to the surrounding tissues was rarely observed and cysts were successfully excised "en bloc" via minimally invasive surgery. | 25,223,210 | [
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[Effects of physics on development of optometry in the United States from the late 19th to the mid 20th century]. | In this paper, it was studied how physics affected development of optometry in the United States, from aspects of formation and academization of optometry. It was also revealed that history of optometry was analogous to history of engineering. Optics in the 19th century was divided into electromagnetic study of light and visual optics. Development of the visual optics promoted professionalization of ophthalmology that had already started in the 18th century. The visual optics also stimulated formation of optometry and optometrists body in the late 19th century of the United States. The American optometrists body were originated from opticians who had studied visual optics. Publication of several English academic textbooks on visual optics induced appearance of educated opticians (and jewelers). They acquired a right to do the eye examination in the early 20th century after C. F. Prentice's trial in 1897, evolving into optometrists. The opticians could be considered as craftsmen, and they were divided into (dispensing) opticians and optometrists. Such history of American optometrists body is analogous to that of engineers body in the viewpoints of craftsmen origin and separation from craftsmen. Engineers were also originated from educated craftsmen, but were separated from craftsmen when engineering was built up. Education system and academization of optometry was strongly influenced by physics, too. When college education of optometry started at American universities, it was not belonged to medical school but to physics department. Physics and optics were of great importance in curriculum, and early faculty members were mostly physicists. Optometry was academized in the 1920s by the college education, standardization of curriculum, and formation of the American Academy of Optometry. This is also analogous to history of engineering, which was academized by natural sciences, especially by mathematics and physics. The reason why optometry was academized not by medicine but by physics is because ophthalmologists did not have conciliatory attitudes to optometry education. Optometry became independent of physics from the 1930s to the 1940s. Optometric researches concentrated on binocular vision that is not included to discipline of physics, and faculty members who majored in optometry increased, so that optometry departments and graduate schools were established around 1940. Such independence from natural sciences after academization also resembles history of engineering. On the contrary, history of optometry was different from history of ophthalmology in several aspects. Ophthalmology had already been formed in the 18th century before development of visual optics, and was not academized by visual optics. Ophthalmologists body were not originated from craftsmen, and were not separated from craftsmen. History of optometry in the United States from the late 19th to the mid 20th century is analogous to history of engineering rather than history of medicine, though optometry is a medical discipline. | 25,223,224 | [
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Atomically resolved imaging of highly ordered alternating fluorinated graphene. | One of the most desirable goals of graphene research is to produce ordered two-dimensional (2D) chemical derivatives of suitable quality for monolayer device fabrication. Here we reveal, by focal series exit wave reconstruction (EWR), that C2F chair is a stable graphene derivative and demonstrates pristine long-range order limited only by the size of a functionalized domain. Focal series of images of graphene and C2F chair formed by reaction with XeF2 were obtained at 80 kV in an aberration-corrected transmission electron microscope. EWR images reveal that single carbon atoms and carbon-fluorine pairs in C2F chair alternate strictly over domain sizes of at least 150 nm(2) with electron diffraction indicating ordered domains ≥ 0.16 μm(2). Our results also indicate that, within an ordered domain, functionalization occurs on one side only as theory predicts. In addition, we show that electron diffraction provides a quick and easy method for distinguishing between graphene, C2F chair and fully fluorinated stoichiometric CF 2D phases. | 25,223,226 | [
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Asymmetric reduction of α-amino ketones with a KBH4 solution catalyzed by chiral Lewis acids. | An efficient enantioselective reduction of α-amino ketones with potassium borohydride solution catalyzed by chiral N,N'-dioxide-metal complex catalysts was accomplished under mild reaction conditions for the first time. It provided a simple, convenient, and practical approaches for obtaining synthetically important chiral β-amino alcohols in good to excellent yields (up to 98%) and enantioselectivities (up to 97% ee). | 25,223,259 | [
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Identification of oxidative stress and responsive genes of HepG2 cells exposed to quinocetone, and compared with its metabolites. | Quinocetone, a new quinoxaline 1,4-dioxide derivative used in food-producing animals in China, exerts genotoxic effects on HepG2 cells. It triggers significant cytotoxicity and genotoxicity in vitro, but the detailed mechanism by which quinocetone induces adverse biological effects is not yet known. We analyzed the mechanisms behind quinocetone intoxication by investigating oxidative stress based on non-enzymatic and enzymatic antioxidant activities, and by identifying differentially regulated genes of HepG2 cells exposed to quinocetone using polymerase chain reaction (PCR)-based suppression subtractive hybridization to illustrate the toxicity mechanism of quinocetone. Meanwhile, the characteristics of oxidative stress and differentially regulated genes induced by quinocetone metabolites, 1,4-bisdesoxyquinocetone and 3-methylquinoxaline-2-carboxylic acid, were investigated too. Results showed that quinocetone damaged the antioxidant defense abilities of HepG2 cells by reducing the activities of endogenous antioxidant enzymes, lowering glutathione concentration, and elevating malondialdehyde level. We identified 160 quinocetone-responsive genes that were associated with cell proliferation, glucose metabolism, oxidative stress, and apoptosis, such as NAD(P)H dehydrogenase, quinone 1; and prolyl 4-hydroxylase, beta polypeptide. The expressions of some differentially regulated genes were confirmed by real-time reverse transcription-polymerase chain reaction. However, quinocetone metabolites showed little effects on HepG2 cells. These results showed that reactive oxygen species were the key mediators of quinocetone cytotoxicity in HepG2 cells and that c-MYC-dependent activation of the mitochondrial apoptotic pathway may be associated with quinocetone-induced toxicity. | 25,223,261 | [
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Vaccination recommendations for patients with neuromuscular disease. | Neuromuscular diseases (NMDs) encompass a broad spectrum of conditions. Because infections may be relevant to the final prognosis of most NMDs, vaccination appears to be the simplest and most effective solution for protecting NMD patients from vaccine-preventable infections. However, very few studies have evaluated the immunogenicity, safety, tolerability, and efficacy of different vaccines in NMD patients; therefore, detailed vaccination recommendations for NMD patients are not available. Here, we present vaccination recommendations from a group of Italian Scientific Societies for optimal disease prevention in NMD patients that maintain high safety levels. We found that NMD patients can be classified into two groups according to immune function: patients with normal immunity and patients who are immunocompromised, including those who intermittently or continuously take immunosuppressive therapy. Patients with normal immunity and do not take immunosuppressive therapy can be vaccinated as healthy subjects. In contrast, immunocompromised patients, including those who take immunosuppressive therapy, should receive all inactivated vaccines as well as influenza and pneumococcal vaccines; these patients should not be administered live attenuated vaccines. In all cases, the efficacy and long-term persistence of immunity from vaccination in NMD patients can be lower than in normal subjects. Household contacts of immunocompromised NMD patients should also be vaccinated appropriately. | 25,223,270 | [
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Using aqueous ammonia in hydroaminomethylation reactions: ruthenium-catalyzed synthesis of tertiary amines. | The direct synthesis of tertiary amines from ammonia and olefins is presented. Using a combination of Ru3 (CO)12 and 2-phosphino-substituted imidazole ligand as catalyst system allows for hydroaminomethylation reactions of bulk aliphatic and functionalized olefins. Tertiary amines are obtained in an atom-efficient domino process in moderate to good isolated yields (45-76%) with excellent regioselectivities (n/iso up to 99:1). | 25,223,274 | [
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Cholesterol in brain disease: sometimes determinant and frequently implicated. | Cholesterol is essential for neuronal physiology, both during development and in the adult life: as a major component of cell membranes and precursor of steroid hormones, it contributes to the regulation of ion permeability, cell shape, cell-cell interaction, and transmembrane signaling. Consistently, hereditary diseases with mutations in cholesterol-related genes result in impaired brain function during early life. In addition, defects in brain cholesterol metabolism may contribute to neurological syndromes, such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), and even to the cognitive deficits typical of the old age. In these cases, brain cholesterol defects may be secondary to disease-causing elements and contribute to the functional deficits by altering synaptic functions. In the first part of this review, we will describe hereditary and non-hereditary causes of cholesterol dyshomeostasis and the relationship to brain diseases. In the second part, we will focus on the mechanisms by which perturbation of cholesterol metabolism can affect synaptic function. | 25,223,281 | [
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Impact of VANA academic-practice partnership participation on educational mobility decisions and teaching aspirations of nurses. | This study reports findings assessing the influence of the Department of Veterans Affairs Nursing Academy (VANA) academic-practice partnership program on nurse decision making regarding educational mobility and teaching aspirations. We conducted national surveys with nursing faculty from VANA partnership sites in 2011 (N = 133) and 2012 (N = 74). Faculty who spent more hours per week in the VANA role and who reported an increase in satisfaction with their participation in VANA were more likely to have been influenced by their VANA experience in choosing to pursue a higher degree (p < .05). Sixty-nine percent of VANA faculty reported that they would be very interested in staying on as a VANA faculty member if the program should continue. Six measures were positively associated with VANA's influence on the desire to continue as faculty beyond the VANA pilot; support from VANA colleagues, quality of VANA students, amount of guidance with curriculum development, availability of administrative support, support for improving teaching methods, and overall satisfaction with VANA experience (p < .05). As the popularity of academic-practice partnerships grows and their list of benefits is further enumerated, motivating nurses to pursue both higher degrees and faculty roles should be listed among them based on results reported here. | 25,223,286 | [
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From suicide survivor to peer counselor: breaking the silence of suicide bereavement. | This study sought to explore the phenomenon of peer counseling in suicide bereavement by addressing the question, what are the lived experiences of suicide survivors who become peer counselors? Participants were 15 individuals bereaved through suicide who had been volunteering with others bereaved in the same manner. This research employed the interpretative phenomenological analysis (IPA) approach to provide a detailed description of participants' journeys that went from experiencing the suicide of a loved one, to the decision to become a peer counselor, to, finally, providing support to other survivors. The findings suggest that participants understand the provision of peer counseling as a transformative process. Being a peer counselor means actively challenging the silence around suicide by speaking out about suicide-related issues and offering other survivors a safe space to share their stories. The broader implications of these findings for suicide postvention research and clinical practice are addressed. | 25,223,311 | [
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Function of global regulator CodY in Bacillus thuringiensis BMB171 by comparative proteomic analysis. | CodY is a highly conserved protein in low G+C gram-positive bacteria that regulates genes involved in sporulation and stationary-phase adaptation. Bacillus thuringiensis is a grampositive bacterium that forms spores and parasporal crystals during the stationary phase. To our knowledge, the regulatory mechanism of CodY in B. thuringiensis is unknown. To study the function of CodY protein in B. thuringiensis, BMB171codY(-) was constructed in a BMB171 strain. A shuttle vector containing the ORF of cry1Ac10 was transformed into BMB171 and BMB171codY(-), named BMB171cry1Ac and BMB171codY(-)cry1Ac, respectively. Some morphological and physiological changes of codY mutant BMB171codY(-)cry1Ac were observed. A comparative proteomic analysis was conducted for both BMB171codY(-)cry1Ac and BMB171cry1Ac through two-dimensional gel electrophoresis and MALDI-TOF-MS/MS analysis. The results showed that the proteins regulated by CodY are involved in microbial metabolism, including branched-chain amino acid metabolism, carbohydrate metabolism, fatty acid metabolism, and energy metabolism. Furthermore, we found CodY to be involved in sporulation, biosynthesis of poly-β-hydroxybutyrate, growth, genetic competence, and translation. According to the analysis of differentially expressed proteins, and physiological characterization of the codY mutant, we performed bacterial one-hybrid and electrophoretic mobility shift assay experiments and confirmed the direct regulation of genes by CodY, specifically those involved in metabolism of branched-chain amino acids, ribosomal recycling factor FRR, and the late competence protein ComER. Our data establish the foundation for in-depth study of the regulation of CodY in B. thuringiensis, and also offer a potential biocatalyst for functions of CodY in other bacteria. | 25,223,328 | [
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Genetic and physiological responses of three freshwater diatoms to realistic diuron exposures. | This study examined the effects of diuron on strains of three major freshwater diatom species, Eolimna minima, Nitzschia palea and Planothidium lanceolatum. These species are frequently recorded in the Morcille River, where diuron runs off during phytosanitary treatments of the vineyards around. Here, there were three diatom exposure groups for each species: 0, 1 and 10 μg/L diuron during a 14-day laboratory assessment. Diuron water concentration, cell number, photosynthetic activity and gene expression were assessed at 6 h and 2, 7 and 14 days after contamination. Diuron exposure altered photosynthetic activity in that the optimal quantum yield of photosystem II (PSII) decreased between 40 and 50% and, for P. lanceolatum at 10 μg/L, there was complete inhibition. Genetic responses indicated diuron effects on both photosystem II and mitochondrial metabolism in all three species at both diuron exposure levels. Thus, analysis of the expression of psaA, d1, cox1, nad5 and 12s could be an early biomarker to detect pesticide pollution. Overall, this study revealed differences in diuron sensitivity among the three species: E. minima and N. palea appeared to be more tolerant than P. lanceolatum. These results suggest that the development of molecular tools, and more precisely of biomarkers, will aid in early assessment of contamination and water quality. | 25,223,354 | [
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"Ilizarov" external fixation: what the radiologist needs to know. | Circular external fixation, including the Ilizarov method, is a complex and often long-term treatment used for various orthopedic conditions. Due to the complexity of the hardware, frequent postoperative complications, and the potential for significant radiographic changes between visits, it is important for the radiologist to have a basic understanding of ring fixators. This publication reviews indications for external fixation versus internal fixation and whether to use a circular or uniplanar construct if external fixation is elected. Indications for and characteristics of static circular frames, intercalary and non-intercalary transport frames, and deformity circular frames will also be discussed. While general similarities exist between frame types, each has unique components of which the radiologist must be aware. An emphasis is placed on the important features and complications that arise during treatment. | 25,223,361 | [
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Effect of folic acid on bone metabolism: a randomized double blind clinical trial in postmenopausal osteoporotic women. | In spite of several studies, the impact of homocysteine level and folic acid supplementation on bone metabolism is yet to be recognized. In this registered clinical trial (IRCT2014042217385N1), we aimed to find out the power of 6-month folic acid supplementation on homocysteine level and bone metabolism. Forty postmenopausal osteoporotic women (50 to 87 years) were enrolled in the study. All participants were randomized to receive folic acid 1 mg (n = 17) or placebo (n = 14). At baseline, 3 months, and finally 6 months post intervention, the level of homocysteine, vitamin B12, and bone biomarkers were measured. Both groups were similar at baseline. The homocysteine decreased in both groups but statistically non-significant (P > 0.05). The changes of the serum level of vitamin B12, osteocalcin, and β cross laps were significant between groups after 6 months (P ≤ 0.05). The trend of changes of bone biomarkers after 6 months folic acid supplementation shows that homocysteine concentration and/or folic acid supplementation have impact on the rate of bone metabolism. However, further investigations by larger sample size and differentiating age and gender are still needed to clarify the exact role of folate, homocysteine and vitamin B12. | 25,223,378 | [
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Organic-inorganic azafullerene-gold C(59)N-Au nanohybrid: synthesis, characterization, and properties. | Azafullerene (C59 N) was functionalized using a Mannich-type reaction and then subsequently condensed with lipoic acid to yield dithiolane-modified C59 N. In the following step, the extended dithiolane moiety from the C59 N core was utilized to decorate the azafullerene sphere with gold nanoparticles (Au NPs). The latter were initially stabilized with dodecanothiol (DT⋅Au) and then integrated on azafullerene through a ligand exchange reaction with the dithiolane-functionalized C59 N to produce the C59 N/DT⋅Au nanohybrid. The nanohybrid was fully characterized by spectroscopy and microscopy, revealing the formation of spherical nanoparticles with a diameter in the range of 2-5 nm, as imaged by HR-TEM. In the electronic absorption spectrum of C59 N/DT⋅Au nanohybrid, the characteristic surface plasmon band (SPB) of Au NPs was observed, however, it was redshifted compared with that of DT⋅Au. The redshift of the SPB is indicative of closer interparticle proximity of Au NPs, in accordance with the formation of aggregated NPs as observed by TEM, in C59 N/DT⋅Au nanohybrid. Excited-state interactions in C59 N/DT⋅Au were probed by photoluminescence assays. It was found that the weak emission of C59 N at 819 nm was blueshifted by 14 nm in C59 N/DT⋅Au, but was stronger in intensity, thus suggesting energy transfer to C59 N, within the organic-inorganic C59 N/DT⋅Au nanohybrid. Finally, with the aid of pump-probe measurements and transient absorption spectroscopy, the formation of the singlet excited state of C59 N was identified. | 25,223,388 | [
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Two new diterpenoids from Leonotis leonurus R. Br. | Two new diterpenoids, 14α-hydroxy-9α,13α-epoxylabd-5(6)-en-7-on-16,15-olide (1) and 13ξ-hydroxylabd-5(6),8(9)-dien-7-on-16,15-olide (2) along with six known diterpenoids were isolated from the aerial parts of Leonotis leonurus R. Br. These structures were determined on the basis of spectroscopic analyses. Some of the isolated compounds showed weak to moderate estrogen sulfotransferase inhibitory activity. | 25,223,430 | [
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The effect of local policy actions on mortality among homeless people: a before-after study. | Homeless people have a 3-5-fold increased risk of mortality compared with general populations. After 2005, policy actions being implemented in Rotterdam, the Netherlands, have improved the living conditions of this group. This study examines the effect of policies aimed at improving living conditions on mortality risks of the homeless. Register-based 10-year follow-up study of homeless in Rotterdam, the Netherlands. The participants are homeless adults (aged 18+ years) who visited one or more services for homeless people in Rotterdam in 2001. The intervention of local policies after 2005 was to get homeless people into housing, increase their participation in employment and other regular daytime activities, and controlling drug and alcohol addictions. The main outcome measure is mortality rate ratios calculated using Poisson regression. Differences in mortality between the periods 2001-05 vs. 2006-10 were assessed. The cohort of homeless adults in 2001 consisted of 1870 men and 260 women, with a mean age of 40.3 years. During the 10 years of follow-up, 265 persons (232 male and 33 female) died. Adjusted for age and sex, no significant difference in mortality was observed between the periods 2001-05 and 2006-10 (P = 0.9683). A different splitting in periods did not change the results. Five years of local policy efforts improved their living conditions, but left the mortality rate of a homeless cohort unchanged. Incomplete reach of the program and long previous histories of homelessness ask for additional policies beyond the provision of housing and other services. Attention to the prevention of homelessness seems needed. | 25,223,433 | [
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Simultaneous variable selection for joint models of longitudinal and survival outcomes. | Joint models of longitudinal and survival outcomes have been used with increasing frequency in clinical investigations. Correct specification of fixed and random effects is essential for practical data analysis. Simultaneous selection of variables in both longitudinal and survival components functions as a necessary safeguard against model misspecification. However, variable selection in such models has not been studied. No existing computational tools, to the best of our knowledge, have been made available to practitioners. In this article, we describe a penalized likelihood method with adaptive least absolute shrinkage and selection operator (ALASSO) penalty functions for simultaneous selection of fixed and random effects in joint models. To perform selection in variance components of random effects, we reparameterize the variance components using a Cholesky decomposition; in doing so, a penalty function of group shrinkage is introduced. To reduce the estimation bias resulted from penalization, we propose a two-stage selection procedure in which the magnitude of the bias is ameliorated in the second stage. The penalized likelihood is approximated by Gaussian quadrature and optimized by an EM algorithm. Simulation study showed excellent selection results in the first stage and small estimation biases in the second stage. To illustrate, we analyzed a longitudinally observed clinical marker and patient survival in a cohort of patients with heart failure. | 25,223,432 | [
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Real time ligand-induced motion mappings of AChBP and nAChR using X-ray single molecule tracking. | We observed the dynamic three-dimensional (3D) single molecule behaviour of acetylcholine-binding protein (AChBP) and nicotinic acetylcholine receptor (nAChR) using a single molecule tracking technique, diffracted X-ray tracking (DXT) with atomic scale and 100 μs time resolution. We found that the combined tilting and twisting motions of the proteins were enhanced upon acetylcholine (ACh) binding. We present the internal motion maps of AChBP and nAChR in the presence of either ACh or α-bungarotoxin (αBtx), with views from two rotational axes. Our findings indicate that specific motion patterns represented as biaxial angular motion maps are associated with channel function in real time and on an atomic scale. | 25,223,459 | [
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Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: a subgroup analysis of the EACH study. | The EACH study assessed the efficacy of oxaliplatin, 5-fluorouracil, and leucovorin (the FOLFOX4 regimen) compared with doxorubicin alone in terms of overall survival (OS), progression-free survival (PFS), and safety in patients with advanced hepatocellular carcinoma (HCC). We present the results of this study in Chinese patients. In a multicenter, open-label, randomized, phase III study (NCT00471965), 371 patients (279 patients from the People's Republic of China) were randomized 1:1 to receive either FOLFOX4 or doxorubicin until disease progression, intolerable toxicity, death, or surgical resection. Baseline characteristics of the Chinese patients enrolled in the study were similar for the 2 treatment groups and in comparison with the whole EACH cohort. Median OS at the prespecified time point of treatment was 5.7 months with FOLFOX4 and 4.3 months with doxorubicin (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.55-0.98; p = .03). At the end of the follow-up period, median OS was 5.9 months with FOLFOX4 and 4.3 months with doxorubicin (HR: 0.75; 95% CI: 0.58-0.98; p = .03). Median PFS was 2.4 months and 1.7 months in the FOLFOX4 and doxorubicin groups, respectively (HR: 0.55; 95% CI: 0.45-0.78; p = .0002). The response rate (RR) and disease control rate (DCR) were significantly higher in the FOLFOX4 group than in the doxorubicin group (RR: 8.6% vs. 1.4%, p = .006; DCR: 47.1% vs. 26.6%, p = .0004). Hematological toxicity was more frequently reported in the FOLFOX4 group. For Chinese HCC patients enrolled in the EACH study, FOLFOX4 significantly improved the RR and DCR and prolonged survival compared with doxorubicin. Systemic chemotherapy with oxaliplatin-based regimens may play an important role in the treatment of Chinese patients with advanced HCC. | 25,223,462 | [
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TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy. | Tanshinone IIA (TAN) has few clinical applications for anti-cancer therapy mainly due to its high lipophicity, low cellular uptake, and poor bioavailability. To improve the anti-cancer effect and bioavailability of TAN, we developed a mixed micelle system constituted with D-α-tocopheryl polyethylene glycol succinate-graft-poly(D,L-lactide-co-glycolide) (TPGS-g-PLGA) copolymer and Pluronic F68. TAN was encapsulated in the TPGS-g-PLGA/Pluronic F68 mixed micelles by using the thin film hydration technology optimized by the central composite design/response surface method (CCD/RSM). TAN-loaded mixed micelles were highly stable in the presence or absence of bovine serum albumin (BSA) and achieved sustained drug release in vitro. Compared with free TAN, TAN mixed micelles had higher cytotoxicity and pro-apoptotic effects against human hepatocellular carcinoma HepG2 cells. The significant enhancement on pro-apoptosis by TAN micelles was evidenced by increased chromosome condensation, mitochondria membrane potential loss, cell apoptosis, and cleavages of caspase-3 and PARP. Furthermore, pharmacokinetic studies revealed that TAN mixed micelles significantly prolonged the circulation time and improved bioavailability of TAN in rats. These results demonstrated that TAN-loaded TPGS-g-PLGA/F68 mixed micelles are an effective strategy to deliver TAN for cancer therapy. | 25,223,472 | [
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Dance for people with Parkinson disease: what is the evidence telling us? | (1) To appraise and synthesize the literature on dance interventions for individuals with Parkinson disease (PD); (2) to provide information regarding the frequency, intensity, duration, and type of dance used in these programs; and (3) to inform the development of future studies evaluating dance interventions in this population. Eight databases (MEDLINE, Cumulative Index to Nursing and Allied Health Literature [CINAHL], the Allied and Complementary Medicine Database [AMED], SPORTDiscus, PubMed, PubMed Central, Sage, and ScienceDirect) were electronically searched in April 2014. The references lists from the included articles were also searched. Studies retrieved during the literature search were reviewed by 2 reviewers independently. Suitable articles were identified by applying inclusion criteria. Data regarding participants and the frequency, intensity, duration, and type of dance form used were extracted. The effect that each dance program had on defined outcomes and the feasibility of each program were also reviewed. Thirteen articles were identified. The quality of studies varied, and methodological limitations were evident in some. The evidence evaluated suggests that two 1-hour dance classes per week over 10 to 13 weeks may have beneficial effects on endurance, motor impairment, and balance. Dance may be helpful for some people with PD. This article provides preliminary information to aid clinicians when implementing dance programs for people with PD. Higher-quality multicenter studies are needed to determine the effect of other dance genres and the optimal therapy volume and intensity. | 25,223,491 | [
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Development and characterization of co-loaded curcumin/triazole-halloysite systems and evaluation of their potential anticancer activity. | Positively charged halloysite nanotubes functionalized with triazolium salts (f-HNT) were employed as a carrier for curcumin molecules delivery. The synthesis of these f-HNT new materials is described. Their interaction with curcumin was evaluated by means dynamic light scattering (DLS) and UV-vis spectroscopy in comparison with pristine unmodified HNT (p-HNT). The curcumin load into HNT was estimated by thermogravimetric analysis (TGA) measurements, while the morphology was investigated by scanning electron microscopy (SEM) techniques. Release of curcumin from f-HNT, at three different pH values, by means of UV-vis spectroscopy was also studied. Furthermore, different cancer cell lines were used to evaluate the potential cytotoxic effect of HNT at different concentrations and culture times. The results indicated that the f-HNT drug carrier system improves the solubility of curcumin in water, and that the drug-loaded f-HNT exerted cytotoxic effects against different cell lines. | 25,223,492 | [
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P3HT-based nanoarchitectural Fano solar cells. | The finite difference time domain simulation shows the existence of an asymmetric quadrupole of Fano resonance on the surface of a gold-silica core-shell (Au@silica) nanoparticle (NP) as being incorporated into the metal oxide nanoarchitecture/P3HT hybrid. Compared to the metal oxide nanoarchitecture/P3HT hybrid solar cell, a 30% enrichment of the short-circuit current density (Jsc) is attained in the P3HT-based nanoarchitectural Fano solar cell with the Au@silica NPs. The enhancement of charge separation in the cell by the electric field of the Fano resonance is directly evidenced by time-resolved photoluminescence measurements. The increase of the degree of P3HT order in the hybrid by the incorporation of Au@silica NPs into the hybrid active layer may also contribute to the enhancement in the Jsc. Charge carrier dynamic measurements show that an electron collection efficiency of ∼97% can be maintained in the P3HT-based nanoarchitectural Fano solar cell. Significant improvement of the efficiency of the inverted metal oxide/P3HT hybrid solar cell is therefore achieved. | 25,223,500 | [
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Silicon particles as trojan horses for potential cancer therapy. | Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells. We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents. In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular. | 25,223,512 | [
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High-speed separation and detection of amino acids in laver using a short capillary electrophoresis system. | A high-speed separation method of capillary MEKC with LIF detection had been developed for separation and determination of amino acids in laver. The CE system comprised a manual slotted-vial array (SVA) for sample introduction that could improve the separation efficiency by reducing injection volume. Using a capillary with 80 mm effective separation length, the separation conditions for amino acids were optimized. Applied with the separation electric field strength of 300 V/cm, the ten amino acids could be completely separated within 2.5 min with 10 mol/L Na2HPO4-NaOH buffer (pH = 11.5) including 30 mmol/L SDS. Theoretical plates for amino acids ranged from 72,000 to 40,000 (corresponding to 1.1-2.0 μm plate heights) and the detection limits were between 25 and 80 nmol/L. Finally, this method was applied to analyze the composition of amino acids in laver and eight known amino acids could be found in the sample. The contents of five amino acids, tyrosine, glutamic acid, glycine, lysine, and aspartic acid that could be completely separated in real sample were determined. The recoveries ranged from 82.3% to 123% that indicated the good reliability for this method in laver sample analysis. | 25,223,519 | [
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Inter- and intra-individual comparative study of two gadolinium-based agents: A pilot study. | The aim of the study was to evaluate the acute adverse events rate and enhancement properties of gadoterate meglumine (Dotarem(®)) and gadobenate dimeglumine (MultiHance(®)) in a small-scale controlled double-blinded study, using inter- and intra-individual comparisons. Forty-one randomly selected patients were scanned with Dotarem(®). The rate of adverse reactions, qualitative and quantitative image evaluation was performed vs. a control group of 46 patients who underwent MultiHance(®) over the same 1-month time period (population 1), and 27 patients who underwent both Dotarem(®) and MultiHance(®)-enhanced body MRI studies within an 18-month period (population 2). Data were subjected to statistical analysis. Only 1 mild acute adverse event (vomiting) was observed in population 1 (with Dotarem(®)). Blinded assessment of image quality was good for both agents in all patients. Population 1 showed significantly higher liver percentage enhancement with MultiHance(®) (p < 0.0001). There was a trend to higher pancreas-to-liver enhancement with Dotarem(®), significant in population 2 (p = 0.0333). This small-scale multi-blinded study characterizes a strategy to objectively assess intravenous contrast agents, which may be an ideal method to evaluate whether a new contrast agent should be introduced for clinical use at any institution, and to re-evaluate the agent in standard use. Whenever available, intra-individual assessment may be ideal. | 25,223,524 | [
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Case-base methods for studying vaccination safety. | Pooling of controls under nested-case control settings can produce substantial efficiency gains compared to standard time-matched analysis using the Mantel-Haenszel method or conditional logistic regression. In the context of possible adverse effects of early childhood vaccinations, we propose pooling of the information from the controls to estimate the population exposure prevalence as a parametric or nonparametric function of time, and possibly other factors. This function in turn may be used as a plug-in estimate to control for confounding in the subsequent estimation of rate ratios. We derive standard errors for the resulting two-step estimators, demonstrate through simulations the efficiency gains compared to standard matched analysis, and propose a novel graphical presentation of the vaccination and adverse event time data. We formulate the methods in the general framework of case-base sampling, which subsumes the different case-control and case-only methods. | 25,223,544 | [
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An FDA overview of rodent carcinogenicity studies of angiotensin II AT-1 receptor blockers: pulmonary adenomas and carcinomas. | Sipahi et al. (2010) performed a meta-analysis of 5 clinical trials (n=68,402) of 3 Angiotensin II (AngII) receptor subtype AT-1 blockers (ARBs) in cardiovascular disease. It revealed excess new lung cancer diagnoses in the cohorts treated with an ARB and background therapy (0.9% vs. 0.7% in non-ARB control; RR: 1.25; CI: 1.05-1.49; p=0.01). The FDA responded with a larger meta-analysis of 31 clinical trials (n=155,816) of ARBs that found no evidence of any excess of site-specific cancer (lung, breast, prostate), solid/skin cancer or cancer death (FDA safety communication, 3 June 2011). The FDA then re-visited the 19 rodent carcinogenicity assays of 9 ARBs, starting with those for Losartan in 1994, for any evidence of dosage-related lung tumorigenicity in this class. Assays were performed in 5 strains of rats and 5 strains of wild-type and transgenic mice per protocols and dosages sanctioned by FDA's executive carcinogenicity assessment committee (eCAC). Duration was lifetime except for 26-week assays of azilsartan and olmesartan in transgenic Tg rasH2 mice, and an assay of olmesartan in p53(+/-) transgenic mice. The dosages provided exposures approximating, and in most cases up to 20-300times greater than, that in patients. Depending on strain, up to 35% of untreated mice spontaneously developed lung tumors. Regression analysis of placebo-corrected mouse lung tumor incidence collapsed across strains, gender, and ARBs vs. multiples of human exposure revealed no excess lung neoplasia. The R(2) of <0.001 reflected the virtually identical number of treated cohorts with more tumors than its control cohort vs. those with less. Regardless of strain, both control and medicated rats were essentially devoid of lung tumors in the lifetime trials. Accordingly, there was neither promotion of background lung tumors in the mouse, nor initiation of de novo lung tumors in the rat. The negative lung findings in the mouse Tg rasH2 strain are also noteworthy given that, historically, the most prevalent spontaneous tumors in 26week trials in that model are lung adenomas and carcinomas. The negative results of the 19, mostly lifetime, assays for cancer viewed en masse add to the results of the meta-analysis of the shorter clinical trials of ARBs that were benign regardless of statistical method used (random vs. fixed effect), comparator arm (with or without ACE-inhibitors) and major co-factors (smoking or cancer history). | 25,223,563 | [
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RhoGTPases, actomyosin signaling and regulation of the epithelial Apical Junctional Complex. | Epithelial cells form regulated and selective barriers between distinct tissue compartments. The Apical Junctional Complex (AJC) consisting of the tight junction (TJ) and adherens junction (AJ) control epithelial homeostasis, paracellular permeability and barrier properties. The AJC is composed of mutliprotein complexes consisting of transmembrane proteins that affiliate with an underlying perijunctional F-actin myosin ring through cytoplasmic scaffold proteins. AJC protein associations with the apical actin-myosin cytoskeleton are tightly controlled by a number of signaling proteins including the Rho family of GTPases that orchestrate junctional biology, epithelial homeostasis and barrier function. This review highlights the vital relationship of Rho GTPases and AJCs in controlling the epithelial barrier. The pathophysiologic relationship of Rho GTPases, AJC, apical actomyosin cytoskeleton and epithelial barrier function is discussed. | 25,223,584 | [
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Investigating inhibitory control in children with epilepsy: an fMRI study. | Deficits in executive function are noted increasingly in children with epilepsy and have been associated with poor academic and psychosocial outcomes. Impaired inhibitory control contributes to executive dysfunction in children with epilepsy; however, its neuroanatomic basis has not yet been investigated. We used functional magnetic resonance imaging (fMRI) to probe the integrity of activation in brain regions underlying inhibitory control in children with epilepsy. This cross-sectional study consisted of 34 children aged 8-17 years: 17 with well-controlled epilepsy and 17 age- and sex-matched controls. Participants performed the antisaccade (AS) task, representative of inhibitory control, during fMRI scanning. We compared AS performance during neutral and reward task conditions and evaluated task-related blood oxygen level-dependent (BOLD) activation. Children with epilepsy demonstrated impaired AS performance compared to controls during both neutral (nonreward) and reward trials, but exhibited significant task improvement during reward trials. Post hoc analysis revealed that younger patients made more errors than older patients and all controls. fMRI results showed preserved activation in task-relevant regions in patients and controls, with the exception of increased activation in the left posterior cingulate gyrus in patients specifically with generalized epilepsy across neutral and reward trials. Despite impaired inhibitory control, children with epilepsy accessed typical neural pathways as did their peers without epilepsy. Children with epilepsy showed improved behavioral performance in response to the reward condition, suggesting potential benefits of the use of incentives in cognitive remediation. | 25,223,606 | [
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Intraoperative fine-needle aspiration biopsy (FNA) for lung cancer: diagnostic value and risk of pleural dissemination. | Intraoperative fine-needle aspiration biopsy (FNA) is one of the most important diagnostic tools for undiagnosed lung nodules suspected of being lung cancer; however, the sensitivity and safety of FNA, including the risk of intrapleural dissemination of cancer cells, have not been established. Between 2006 and 2008, 324 patients underwent lung resection for cancers located in the lung periphery. Intraoperative FNA for definite diagnosis was performed immediately after thoracotomy in 147 (45.4%) of these patients, but not in the other 177. A diagnosis of lung cancer was obtained by the intraoperative FNA in 124 (84.4%) of the 147 patients. During a median follow-up of 55 months, pleural dissemination or malignant effusion ipsilateral to the operated side as the first recurrent site occurred in 11 (7.4%) of the 147 patients who underwent the needle biopsy and 10 (5.6%) of the 177 patients who did not. This difference was not significant (P = 0.5046). Intraoperative FNA was safe and useful for the diagnosis of peripheral lung cancer and did not increase the risk of pleural dissemination in this series. | 25,223,625 | [
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X-ray spectroscopic study of solvent effects on the ferrous and ferric hexacyanide anions. | We present an Fe Kα resonant inelastic X-ray scattering (RIXS) and X-ray emission (XES) study of ferrous and ferric hexacyanide dissolved in water and ethylene glycol. We observe that transitions below the absorption edge show that the solvent has a distinct effect on the valence electronic structure. In addition, both the RIXS and XES spectra show a stabilization of the 2p levels when dissolved in water. Using molecular dynamics simulations, we propose that this effect arises from the hydrogen-bonding interactions between the complex and nearby solvent molecules. This withdraws electron density from the ligands, stabilizing the complex but also causing a slight increase in π-backbonding. | 25,223,627 | [
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Glutaryl-coenzyme A dehydrogenase from Geobacter metallireducens - interaction with electron transferring flavoprotein and kinetic basis of unidirectional catalysis. | Glutaryl-CoA dehydrogenases (GDHs) are FAD containing acyl-CoA dehydrogenases that usually catalyze the dehydrogenation and decarboxylation of glutaryl-CoA to crotonyl-CoA with an electron transferring flavoprotein (ETF) acting as natural electron acceptor. In anaerobic bacteria, GDHs play an important role in the benzoyl-CoA degradation pathway of monocyclic aromatic compounds. In the present study, we identified, purified and characterized the benzoate-induced BamOP as the electron accepting ETF of GDH (BamM) from the Fe(III)-respiring Geobacter metallireducens. The BamOP heterodimer contained FAD and AMP as cofactors. In the absence of an artificial electron acceptor, at pH values above 8, the BamMOP-components catalyzed the expected glutaryl-CoA oxidation to crotonyl-CoA and CO2 ; however, at pH values below 7, the redox-neutral glutaryl-CoA conversion to butyryl-CoA and CO2 became the dominant reaction. This previously unknown, strictly ETF-dependent coupled glutaryl-CoA oxidation/crotonyl-CoA reduction activity was facilitated by an unexpected two-electron transfer between FAD(BamM) and FAD(BamOP) , as well as by the similar redox potentials of the two FAD cofactors in the substrate-bound state. The strict order of electron/proton transfer and C-C-cleavage events including transient charge-transfer complexes did not allow an energetic coupling of electron transfer and decarboxylation. This explains why it was difficult to release the glutaconyl-CoA intermediate from reduced GDH. Moreover, it provides a kinetic rational for the apparent inability of BamM to catalyze the reverse reductive crotonyl-CoA carboxylation, even under thermodynamically favourable conditions. For this reason reductive crotonyl-CoA carboxylation, a key reaction in C2-assimilation via the ethylmalonyl-CoA pathway, is accomplished by a different crotonyl-CoA carboxylase/reductase via a covalent NADPH/ene-adduct. | 25,223,645 | [
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Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolimod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation. | Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1mg/kg) or siponimod (0.001 and 0.01mg/kg) was intravenously infused over 10min to the halothane-anaesthetized guinea pigs (n=4), whereas the effects of fingolimod (1μmol/L) and siponimod (1μmol/L) on hERG current were examined (n=3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct IKr inhibition may play a key role in fingolimod-induced QT-interval prolongation. | 25,223,691 | [
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Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats. | We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. | 25,223,692 | [
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The National Library of Medicine's (NLM) Hazardous Substances Data Bank (HSDB): background, recent enhancements and future plans. | The National Library of Medicine's (NLM) Division of Specialized Information Services (SIS) Toxicology and Environmental Health Information Program is responsible for the management of the online Hazardous Substances Data Bank (HSDB). HSDB, a part of NLM's Toxicology Data Network (TOXNET(®)), is a file of chemical/substance information with one record for each specific chemical or substance, or for a category of chemicals or substances. Like the rest of TOXNET's databases and other resources, HSDB is available online at no cost to global users. HSDB has approximately 5600 chemicals and substances, with a focus on toxicology information and also on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, and related areas of likely interest to HSDB users. All data are from a core set of books, government documents, technical reports, selected primary journal literature, and other online sources of information, with a goal of linking the HSDB content to as much publicly available information as possible. HSDB's content is peer-reviewed by the Scientific Review Panel, a group of experts in the areas covering the scope of HSDB content. Recent enhancements include the addition of chemical structures to HSDB records, the addition of new subfields such as age groups for human data, more occupational exposure standards, and the addition of information on numerous nanomaterials. Examples of future plans include providing more exposure-related information, e.g., uses of a chemical or substance in consumer products; the addition of information summaries aimed towards consumers and other members of the public wanting to learn about a chemical or substance; more visual content such as diagrams (images) of the pathways of metabolism of a substance; and enhanced search features and navigation. | 25,223,694 | [
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Single- and Bi-component T2* analysis of tendon before and during tensile loading, using UTE sequences. | To determine if the application of tensile force alters the single- or bi-component T2* values of human tendons as measured on a clinical MRI scanner with ultrashort echo time (UTE sequences and if single- or bi-component T2* values differ when measured with 2D-UTE, 3D-UTE, or 3D-UTE-Cones sequences. Ten tendons were imaged before and during the application of tension using various UTE sequences at 3 Tesla. Single and bi-component T2* analysis was performed pre- and posttension and compared with Bonferroni-corrected paired Wilcoxon tests. Range of mean pre- and posttension T2* analysis values were: short T2* fraction (78.6-79.7% and 77.3-79.7%, respectively; P = 1.0 for all sequences), long T2* fraction (20.3-21.4% and 20.3-22.7%, respectively; P = 1.0 for all sequences), short T2* (0.9-1.0 ms and 0.9 ms, respectively; P = 1.0 for all sequences), long T2* (19.9-20.4 ms and 21.9-24.0 ms, respectively; P = 0.9 for 2D-UTE and P = 1.0 for 3D-UTE and 3D-UTE-Cones), and single-component T2* (2.3-2.5 ms and 2.5-3.2 ms, respectively; P = 1.0 for all sequences). No significant difference in single- or bi-component results was found after the application of tension to tendons. Results are similar regardless of UTE sequence used for acquisition. | 25,223,714 | [
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Sacral nerve stimulation changes rectal sensitivity and biomechanical properties in patients with irritable bowel syndrome. | Sacral nerve stimulation (SNS) has been demonstrated to alleviate symptoms and improve quality of life in selected patients with irritable bowel syndrome (IBS). The mechanisms of action, however, remain unknown. The aim of the study was to evaluate the effects of SNS on rectal sensitivity and biomechanical properties in patients with IBS. Twenty patients with diarrhea-predominant (n = 11) or mixed (n = 9) IBS were treated with SNS in a controlled, randomized crossover trial. They were randomized to either 1 month of SNS (ON) or placebo (OFF) with the opposite setting for the next month. Sensory and biomechanical parameters were assessed by multimodal rectal stimulation at the end of each period. IBS-specific symptoms were evaluated at baseline and at the end of each treatment period. Cold stimuli were better tolerated in the ON period (19.9 °C[± 0.6]) compared to the OFF period (21.8 °C[± 0.6]; p = 0.03). Significantly lower cross-sectional areas were needed to elicit sensory responses in the ON period (1545 mm(2) [± 95]) compared to the OFF period (1869 mm(2) [± 92]; p = 0.015). The association between reduced sensory threshold and improvement of constipation was of borderline significance (p = 0.05). Wall stiffness was significantly lower in the ON period (192 mmHg[± 10]) compared to the OFF period (234 mmHg[± 10]; p = 0.004). Reduced wall stiffness was significantly associated with improved overall GSRS-IBS symptom score (p = 0.01). Reduced sensory threshold to stretch (p = 0.02) and reduced wall stiffness (p < 0.001) were predictors of the GSRS-IBS symptom score. SNS for diarrhea-predominant and mixed IBS relaxes the rectal wall, while making it more sensitive to stretch and less sensitive to cold. Reduced wall stiffness and increased sensitivity to stretch are associated with improved GSRS-IBS symptom score. | 25,223,743 | [
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Size misperception among overweight and obese families. | Perception of body size is a key factor driving health behavior. Mothers directly influence children's nutritional and exercise behaviors. Mothers of ethnic minority groups and lower socioeconomic status are less likely to correctly identify young children as overweight or obese. Little evaluation has been done of the inverse--the child's perception of the mother's weight. To determine awareness of weight status among mother-child dyads (n = 506). Cross-sectional study conducted in an outpatient pediatric dental clinic of Columbia University Medical Center, New York, NY. Primarily Hispanic (82.2 %) mothers (n = 253), 38.8 ± 7.5 years of age, and children (n = 253), 10.5 ± 1.4 years of age, responding to a questionnaire adapted from the validated Behavioral Risk Factor Surveillance System. Anthropometric measures-including height, weight, and waist circumference-and awareness of self-size and size of other generation were obtained. 71.4 % of obese adults and 35.1 % of overweight adults underestimated size, vs. 8.6 % of normal-weight (NW) adults (both p < 0.001). Among overweight and obese children, 86.3 % and 62.3 % underestimated their size, vs. 14.9 % NW children (both p < 0.001). Among mothers with overweight children, 80.0 % underestimated their child's weight, vs. 7.1 % of mothers with NW children (p < 0.001); 23.1 % of mothers with obese children also underestimated their child's weight (p < 0.01). Among children with obese mothers, only 13.0 % correctly classified the adult's size, vs. 76.5 % with NW mothers (p < 0.001). Among obese mothers, 20.8 % classified overweight body size as ideal, vs. 1.2 % among NW mothers (p < 0.001). Overweight/obese adults and children frequently underestimate their size. Adults misjudge overweight/obese children as being of normal weight, and children of obese mothers often underestimate the adult's size. Failure to recognize overweight/obesity status among adults and children can lead to prolonged exposure to obesity-related comorbidities. | 25,223,750 | [
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'Learning disabilities' as a 'black box': on the different conceptions and constructions of a popular clinical entity in Israel. | This article aims to stimulate new thinking about learning disabilities than is customary in local literature. Previous educational and psychological studies concerning learning disabilities regarded them as if they were objective categories with formal definitions and criteria accepted in scholarly literature. Contrary to that, this article explores the various conceptions, constructions, and meanings of learning disabilities that comprise the narrative descriptions and explanations of didactic diagnosticians. For this purpose, 50 in-depth interviews were conducted. There are four sections. Part One lays out the theoretical and methodological background of the sociological and discursive debate about learning disabilities. Part Two explores the various main thematic aspects and narrative strategies that were used by the diagnosticians in their construction of their purportedly 'objective', 'a-historical', 'a-political' experts' narrative. The third part reveals the polyphonic multifaceted nature of the learning disabilities construct. The experts' narrative undermines the objective and homogeneous definitions in the literature by uncovering learning disabilities' heterogeneous meaning repertoire. This repertoire consists, among others, of conceptualizing disability as a 'disease', a 'symptom', a 'genetic defect', a 'disorder', an 'educational difficulty', a 'variance', and even a 'gift'. This part also reveals the experts' narrative reaction strategies to the aforementioned polyphonic spectacle. It is revealed that the interviewees' narrative deconstructs the 'scientific factual nature' of the clinical categories. The fourth part highlights a central paradox in the expert narrative: The tension between the narrative stigmatic-labeling aspects and the destigmatic-'liberating' aspects. The claim is made that this tension can partly explain the current popularity of the LD diagnosis. This article is the third in a series of papers that seeks to contribute to the creation of a more nuanced disability discourse by exposing its shaky scientific foundations. | 25,223,763 | [
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BRCA1 modulates the autophosphorylation status of DNA-PKcs in S phase of the cell cycle. | Non-homologous end-joining (NHEJ) and homologous recombination (HR) are the two prominent pathways responsible for the repair of DNA double-strand breaks (DSBs). NHEJ is not restricted to a cell-cycle stage, whereas HR is active primarily in the S/G2 phases suggesting there are cell cycle-specific mechanisms that play a role in the choice between NHEJ and HR. Here we show NHEJ is attenuated in S phase via modulation of the autophosphorylation status of the NHEJ factor DNA-PKcs at serine 2056 by the pro-HR factor BRCA1. BRCA1 interacts with DNA-PKcs in a cell cycle-regulated manner and this interaction is mediated by the tandem BRCT domain of BRCA1, but surprisingly in a phospho-independent manner. BRCA1 attenuates DNA-PKcs autophosphorylation via directly blocking the ability of DNA-PKcs to autophosphorylate. Subsequently, blocking autophosphorylation of DNA-PKcs at the serine 2056 phosphorylation cluster promotes HR-required DNA end processing and loading of HR factors to DSBs and is a possible mechanism by which BRCA1 promotes HR. | 25,223,785 | [
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Conjoint propagation and differentiation of human embryonic stem cells to cardiomyocytes in a defined microcarrier spinner culture. | Myocardial infarction is accompanied by a significant loss of cardiomyocytes (CMs). Functional CMs, differentiated from human embryonic stem cells (hESCs), offer a potentially unlimited cell source for cardiac disease therapies and regenerative cardiovascular medicine. However, conventional production methods on monolayer culture surfaces cannot adequately supply the large numbers of cells required for such treatments. To this end, an integrated microcarrier (MC) bioprocessing system for hESC propagation and subsequent CM differentiation was developed. Production of hESC-derived CMs was initially established in monolayer cultures. This control condition was compared against hESC expansion on laminin-coated MC with cationic surface charge, in a stirred serum-free defined culture. Following expansion, the hESC/MC aggregates were placed in a CM differentiation medium, using Wnt signalling modulators in four different culture conditions. This process eliminated the need for manual colony cutting. The final optimized protocol was tested in stirred spinner flasks, combining expansion and differentiation on the same MC, with only media changes during the culture process. In the propagation phase, a 15-fold expansion of viable pluripotent HES-3 was achieved, with homogeneous sized aggregates of 316 ± 11 μm. Of the four differentiation conditions, stirred spinner flask cultures (MC-Sp) provided the best controlled aggregate sizes and yielded 1.9 × 10⁶ CM/ml, as compared to 0.5 × 10⁶ CM/ml using the monolayer cultures method: a four-fold increase in CM/ml. Similar results (1.3 × 10⁶ CM/ml) were obtained with an alternative hESC H7 line. The hESC/MC-derived CM expressed cardiac-specific transcription factors, structural, ion channel genes, and exhibited cross-striations of sarcomeric proteins, thus confirming their cardiac ontogeny. Moreover, E-4031 (0.3 μM) prolonged the QT-interval duration by 40% and verapamil (3 μM) reduced it by 45%, illustrating the suitability of these CM for pharmacological assays. We have demonstrated a robust and scalable microcarrier system for generating hESC-derived CM. This platform is enabled by defined microcarrier matrices and it integrates cell propagation and differentiation within a continuous process, in serum-free culture media. It can generate significant numbers of CM, which are potentially suitable for future clinical therapies. | 25,223,792 | [
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Trade-off of ovarian lipids and total body lipids for fecundity and starvation resistance in tropical populations of Drosophila melanogaster. | In Drosophila melanogaster, clines of starvation resistance along a latitudinal gradient (south to north) have been reported in India, which matched with their cline for total body lipids (TL ). Nevertheless, producing too many reserves is likely to be costly and a trade-off might exist with life-history traits. Previous studies on starvation resistance and life-history traits of D. melanogaster have mainly focused on quantification of total body lipids, instead of separating ovarian lipids from total body lipids. In the present study, we have quantified absolute ovarian lipids (OL ) versus absolute body lipids excluding ovarian lipids (BL ) and examined associations with fecundity as well as starvation resistance in two latitudinal populations (8.34 vs. 32.43°N) of D. melanogaster. Firstly, we observed a trade-off between BL and OL that matched the trade-off of starvation resistance, longevity versus fecundity and development time in latitudinal populations of D. melanogaster. Southern populations had higher starvation resistance, more BL and lesser OL, whereas northern populations had enhanced fecundity, OL and lesser BL . Secondly, within population, starvation resistance also correlated with BL , and fecundity with OL . However, there was no correlation between starvation resistance and OL . Moreover, there was utilization of BL and nonutilization of OL under starvation stress. Therefore, resources invested for fecundity in the form of OL were independent of evolved starvation resistance in D. melanogaster. Our results suggest that a common pool of energy storage compounds (lipids) are allocated differentially between fecundity and starvation resistance and are consistent with Y-model of resource allocation. | 25,223,796 | [
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Urotensin II increases foam cell formation by repressing ABCA1 expression through the ERK/NF-κB pathway in THP-1 macrophages. | Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages. Cultured THP-1 macrophages were treated with U II, followed by measuring the intracellular lipid contents, cholesterol efflux and ABCA1 levels. The results showed that U II dramatically decreased ABCA1 levels and impaired cholesterol efflux. However, the effects of U II on ABCA1 protein expression and cellular cholesterol efflux were partially reversed by inhibition of extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF-κB) activity, suggesting the potential roles of ERK1/2 and NF-κB in ABCA1 expression, respectively. Our current data indicate that U II may have promoting effects on the progression of atherosclerosis, likely through suppressing ABCA1 expression via activation of the ERK/NF-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation. | 25,223,800 | [
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[Instent rupture of a saphenous vein graft during percutaneous intervention successfully treated with a covered stent]. | Percutaneous coronary interventions of saphenous vein grafts are associated with an increased risk of periprocedural complications; among these, the rupture of the vein graft is probably the less common and the most dangerous; it is even more exceptional when it occurs on a stented portion of the graft. We report the case of a 75-year-old man who presented during a balloon angioplasty of intent restenosis of a saphenous vein graft a spectacular graft rupture at the level of the previously stented site and who was ultimately successfully treated with a covered stent. | 25,223,830 | [
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Anti-metastatic immunotherapy based on mucosal administration of flagellin and immunomodulatory P10. | Current therapies against malignant melanoma generally fail to increase survival in most patients, and immunotherapy is a promising approach as it could reduce the dosage of toxic therapeutic drugs. In the present study, we show that an immunotherapeutic approach based on the use of the Toll-like receptor (TLR)-5 ligand flagellin (Salmonella Typhimurium FliCi) combined with the major histocompatibility complex class II-restricted P10 peptide, derived from the Paracoccidioides brasiliensis gp43 major surface protein, reduced the number of lung metastasis in a murine melanoma model. Compounds were administered intranasally into C57Bl/6 mice intravenously challenged with syngeneic B16F10-Nex2 melanoma cells, aiming at the local (pulmonary) immune response modulation. Along with a marked reduction in the number of lung nodules, a significant increase in survival was observed. The immunization regimen induced both local and systemic proinflammatory responses. Lung macrophages were polarized towards a M1 phenotype, lymph node cells, and splenocytes secreted higher interleukin-12p40 and interferon (IFN)-γ levels when re-stimulated with tumor antigens. The protective effect of the FliCi+P10 formulation required TLR-5, myeloid differentiation primary response gene 88 and IFN-γ expression, but caspase-1 knockout mice were only partially protected, suggesting that intracellular flagellin receptors are not involved with the anti-tumor effect. The immune therapy resulted in the activation of tumor-specific CD4(+) T lymphocytes, which conferred protection to metastatic melanoma growth after adoptive transfer. Taken together, our results report a new immunotherapeutic approach based on TLR-5 activation and IFN-γ production capable to control the metastatic growth of B16F10-Nex2 melanoma, being a promising alternative to be associated with chemotherapeutic drugs for an effective anti-tumor responses. | 25,223,833 | [
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Fixed-dose enoxaparin after bariatric surgery: the influence of body weight on peak anti-Xa levels. | There is lack of data on the pharmacodynamics of low-molecular-weight heparins in obese patients. The aims of this study are to investigate the correlation between anti-factor Xa (anti-Xa) levels and body weight with fixed-dose enoxaparin after bariatric surgery and to investigate the percentage of patients that reach the desired prophylactic range for anti-Xa levels. Blood for anti-Xa peak levels measurement was drawn 3-5 h after administration of enoxaparin at the planned visit 8-16 days after surgery. Patients were included in three categories: <110 kg (group 1), 110-150 kg (group 2), and >150 kg (group 3). Fifty-one patients were included (43.9 ± 9.9 years, 75% women). Mean anti-Xa level was 0.37 ± 0.14 IU/ml. This level was the highest in group 1 (0.47 ± 0.13 IU/ml) and lowest in group 3 (0.23 ± 0.07). No subprophylactic (<0.2 IU/ml) anti-Xa levels were detected in group 1, whereas this was observed in 38% in patients in group 3. Supraprophylactic levels (>0.5 IU/ml) were most often present in group 1 (36%). With multivariable regression analysis, body weight (β -0.720 (95 % confidence interval -.717; -.993), p < 0.001) was an independent predictor of anti-Xa levels, whereas lean body was not independently associated. This was confirmed in a non-linear mixed effects analysis of the data. Patients with excessive body weight may not be adequately treated with fixed-dose enoxaparin thromboprophylaxis while patients with lower body weight may have an increased bleeding risk. Body weight is a better predictor of anti-Xa levels compared to lean body weight. | 25,223,871 | [
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Castleman disease of the neck: CT and MR imaging findings. | To characterize the computed tomography (CT) and magnetic resonance imaging (MRI) findings of Castleman disease of the neck. The imaging findings of 21 patients with Castleman disease of the neck were reviewed retrospectively. Of the 21 patients, 16 underwent unenhanced and contrast-enhanced CT scans; 5 underwent unenhanced and contrast-enhanced MRI scans. The unenhanced CT images showed isolated or multiple well-defined homogenous mild hypodensity lesions in fifteen cases, and a heterogeneous nodule with central areas of mild hypodensity in one case. Calcification was not observed in any of the patients. In five patients, MR T1-weighted images revealed well-defined, homogeneous isointense or mild hyperintense lesions to the muscle; T2-weighted images showed these as intermediate hyperintense. Sixteen cases showed intermediate to marked homogeneous enhancement on contrast-enhanced CT or MR T1-weighted images. Of the other five cases that underwent double-phase CT scans, four showed mild or intermediate heterogeneous enhancement at the arterial phase, and homogeneous intermediate or marked enhancement at the venous phase; the remaining case showed mild and intermediate ring-enhancement with a central non-enhanced area at the arterial and venous phases, respectively. Castleman disease of the neck can be characterized as solitary or multiple well-defined, mild hypodensity or homogeneous intense lesions on plain CT/MR scans, and demonstrates intermediate and marked enhancement on contrast-enhanced CT/MR scans. On double-phase CT scans, Castleman disease often demonstrates mild enhancement at the arterial phase, and gradually uniform enhancement at venous phase. Double-phase enhanced CT or MRI may help to differentiate Castleman disease from other diseases. | 25,223,886 | [
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Do poor-responder patients benefit from increasing the daily gonadotropin dose during controlled ovarian hyperstimulation for IVF? | We aim to assess the in vitro fertilization-embryo transfer (IVF-ET) outcome in patients receiving an extremely high 450 daily dose (IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF. Moreover, in those who failed to conceive while using 450 daily dose (IU) of gonadotropins, we aim to evaluate whether increasing the daily dose gonadotropins to 600 IU will improve IVF outcome. All consecutive women, admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. Nine-hundred one consecutive IVF cycles were evaluated. While there was no between-group difference in the duration of COH, patients who conceived were significantly younger, yielded higher number of oocytes retrieved and embryos transferred and had significantly lower cancellations. In a sub-analysis, including only those patients who failed to conceive while using 450 daily dose (IU) of gonadotropins, and who underwent a subsequent IVF cycle attempt with the used of 600 IU daily dose of gonadotropins, no improvements in COH characteristics or cancellation rates were observed with increasing the daily gonadotropin dose to 600 IU. To conclude, in poor responders undergoing COH with an extremely high daily gonadotropin dose (450 IU), the most important factors that predict IVF success are female age and the number of oocytes retrieved. Moreover, patients who failed to conceive on a daily gonadotropin dose of 450 IU will not benefit from increasing the dose to 600 IU and should therefore consider the options of egg donation or adoption. | 25,223,892 | [
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Biogeographical distribution of denitrifying anaerobic methane oxidizing bacteria in Chinese wetland ecosystems. | The discovery of denitrifying anaerobic methane oxidation with nitrite as electron acceptor mediated by 'Candidatus Methylomirabilis oxyfera' connected the biogeochemical carbon and nitrogen cycle in a new way. However, it is important to have a comprehensive understanding about the distribution of M. oxyfera-like bacteria in the terrestrial realm, especially the wetland ecosystems that are known as the largest natural source of atmospheric methane. Here, our molecular evidence demonstrated that a wide geographical distribution of M. oxyfera-like bacteria at oxic/anoxic interfaces of various wetlands (n = 91) over the Chinese territory. Intriguingly, the M. oxyfera-like bacteria were detected in some extreme environments, indicating that M. oxyfera-like bacteria occupied a wide range of habitats. Quantitative polymerase chain reaction estimated that the abundance of M. oxyfera-like bacteria ranged from 2.2 × 10(3) to 2.3 × 10(7) copies g(-1) dry soil, and up to around 0.62% of the total number of bacteria. Moreover, the M. oxyfera-like bacteria showed high biodiversity in wetland ecosystems based on the analysis of 462 pmoA and 287 16S rRNA gene sequences. The current study revealed the widespread distribution and biogeography of M. oxyfera-like bacteria in the terrestrial system. | 25,223,900 | [
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Age differences in self-referencing: Evidence for common and distinct encoding strategies. | Although engagement of medial prefrontal cortex (MPFC) underlies self-referencing of information for younger and older adults, the region has not consistently been implicated across age groups for the encoding of self-referenced information. We sought to determine whether making judgments about others as well as the self influenced findings in the previous study. During an fMRI session, younger and older adults encoded adjectives using only a self-reference task. For items later remembered compared to those later forgotten, both age groups robustly recruited medial prefrontal cortex, indicating common neural regions support encoding across younger and older adults when participants make only self-reference judgments. Focal age differences emerged in regions related to emotional processing and cognitive control, though these differences are more limited than in tasks in which judgments also are made about others. We conclude that making judgments about another person differently affects the ways that younger and older adults make judgments about the self, with results of a follow-up behavioral study supporting this interpretation. This article is part of a Special Issue entitled Memory and Aging. | 25,223,905 | [
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Hormones and venous thromboembolism among postmenopausal women. | Abstract Venous thromboembolism (VTE) is a common and potentially fatal disease in postmenopausal women. VTE has emerged as the most prevalent adverse effect of oral estrogens in 50-60-year-old women. Obesity and VTE history can be easily used to identify women at high risk but genetic screening is not cost-effective. Based on consistent biological and epidemiological findings, transdermal estrogen is the safest option with respect to VTE, especially in women at high risk. There is strong evidence that VTE risk is greater in women using medroxyprogesterone acetate compared with those receiving other progestins. Based on observational data, progesterone appears safe with respect to VTE. More research and action are needed to avert the hepatic first-pass effect of oral estrogens and to increase awareness of hormone-related VTE. Improving individual risk stratification and a personalized approach to hormone therapy are major challenges for future work. | 25,223,916 | [
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Noroviruses associated with outbreaks of acute gastroenteritis in the State of Rio Grande do Sul, Brazil, 2004-2011. | Acute gastroenteritis norovirus (NoV) in a country of continental dimensions like Brazil has resulted in under-reporting of the number of outbreaks, as well as the genotypes associated. To demonstrate the role of NoV in outbreaks occurring in the State of Rio Grande do Sul, Southern Brazil, we determined its prevalence, as well as the genotypes associated, and evaluated clinical and epidemiological aspects. NoV investigation was carried out in rotavirus group A negative stool samples from 2265 patients from 741 outbreaks that occurred in the State of Rio Grande do Sul, Brazil, during a period of eight years (2004-2011). NoV detection and nucleotide sequencing for genotype characterization was carried by using sets of primers targeting a conservative Rd-Rp polymerase genome region and the viral capsid gene, respectively. NoVs were detected in 817 stool samples (36.1%) and associated with 327 outbreaks (44.1%). NoV GII.2, GII.3, GII.4, GII.6, GII.12, GII.13, GII.14, GII.15, GII.17, GII.21; and GI.1 and GI.3 were characterized. GII.4 was the most frequently detected (72.3%), with five variants identified (Asia_2003, Hunter_2004, Yerseke_2006a, Den_Haag_2006b, New Orleans_2009). This study describes the first detection of GI.1 and GII.13 and GII.15 in Brazil and demonstrates NoV winter-spring seasonality in this region of the country. NoVs were responsible for almost 50% of outbreaks, with about 70% of them resulting from genotype GII.4 and its variants. The seasonality observed could help health authorities to establish a system of active surveillance in order to reduce NoV impact especially in congregate settings. | 25,223,919 | [
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Surgical management of bone metastases: quality of evidence and systematic review. | Surgical management of metastatic bone disease (MBD) is typically reserved for lesions with the highest risk of fracture. However, the high risk of perioperative complications associated with surgery may outweigh the benefits of improved pain and/or function. The goal of this study was to (1) assess the quality of current evidence in this domain; (2) confirm that surgical management of metastases to the long bones and pelvis/acetabulum provides pain relief and improved function; and (3) assess perioperative morbidity and mortality rates. We conducted a systematic review of the literature for clinical studies that reported pain relief and function outcomes, as well as perioperative complications and mortality, in patients with MBD to the long bones and/or pelvis/acetabulum treated surgically. Multiple databases were searched up to January 2012. Pooled weighted proportions are reported. Forty-five studies were included in the final analysis, with 807 patients. All included studies were level IV with 'moderate' overall quality of evidence using the Methodological Index for Non-Randomized Studies scale. Pain relief following surgical management of metastases was 93, 91, and 93 % in the humerus, femur, and pelvis/acetabulum, respectively. Maintained or improved function after surgery was seen in 94, 89, and 94 % in the humerus, femur, and pelvis/acetabulum, respectively. Perioperative complications and mortality were 17 and 4 %, respectively. Despite the inherent limitations of the current evidence, a benefit for the surgical management of bone metastases to the long bones and pelvis/acetabulum is evident; however, there is still substantial risk of perioperative morbidity and mortality that should be considered. | 25,223,925 | [
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Human fecal microbiome-based biomarkers for colorectal cancer. | Colorectal cancer may develop slowly over years from precursor lesions, and thus screening combined with early diagnosis is the key to disease prevention. Recent studies have elucidated specific traits in the gut microbiome associated with colorectal cancer and suggested that the microbiome may be useful in screening for colorectal cancer purposes but failed to provide protocols that can be applied in a practical situation. A recent study by Zackular and colleagues, presented on page 1112, provides an important way forward here in showing that specific analysis of multiple aspects of the microbiome composition in toto provides reliable detection of both precancerous and cancerous lesions. This important achievement when combined with other noninvasive techniques promises to provide highly effective tools for early colorectal cancer diagnosis and its prevention. | 25,223,933 | [
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Occurrence of multidrug resistance to oral antibiotics among Escherichia coli urine isolates from outpatient departments in Germany: extended-spectrum β-lactamases and the role of fosfomycin. | The in vitro activities of fosfomycin and seven other antibiotics commonly used for oral treatment of urinary tract infections (UTIs) were evaluated for 499 Escherichia coli isolated from urine samples during a nationwide laboratory-based surveillance study in 2010. Overall, the highest resistance rates were found for amoxicillin (42.9%), followed by amoxicillin/clavulanic acid (32.7%), trimethoprim/sulfamethoxazole (SXT) (30.9%), ciprofloxacin (19.8%), cefuroxime (10.0%), cefpodoxime (8.6%) and cefixime (8.2%). One-half of the isolates (n=252; 50.5%) were fully susceptible to the eight drugs, whilst only 6 strains (1.2%) were resistant to fosfomycin. Combined resistance to amoxicillin, cefuroxime, ciprofloxacin and SXT was detected in 29 isolates (5.8%). Moreover, 40 isolates (8.0%) produced an extended-spectrum β-lactamase (ESBL), including CTX-M-type ESBLs detected in 39/40 isolates (97.5%) and a TEM-52 ESBL in 1 strain (2.5%). The predominant CTX-M-type ESBL was CTX-M-15 (27/39; 69.2%). Of the 27 CTX-M-15 producers, 19 (70.4%) belonged to the clonal lineage E. coli O25b-ST131. All but one ESBL-producing strains were fosfomycin-susceptible. In view of the emergence of multidrug resistance to standard oral antibiotics, these data support that oral fosfomycin (trometamol salt) may represent a valuable option in the treatment of uncomplicated UTIs. | 25,223,936 | [
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Filarial antigenemia and Loa loa night blood microfilaremia in an area without bancroftian filariasis in the Democratic Republic of Congo. | Implementation of mass drug administration for lymphatic filariasis (LF) has been delayed in central Africa because of incomplete mapping and coendemic loiasis. We mapped two regions in eastern Democratic Republic of Congo that were suspected to have LF. Night blood samples were collected from 2,724 subjects in 30 villages. Filarial antigenemia rates by card test exceeded 1% in 28 villages (range = 0-14%). Prevalence rates for large sheathed microfilariae (Mf) ranged from 4% to 40%; Mansonella perstans rates ranged from 22% to 98%. Large Mf were exclusively Loa loa by microscopy, and only 1 of 337 samples tested by quantitative polymerase chain reaction (qPCR) was positive for Wuchereria bancrofti DNA. Filarial antigen positivity was strongly associated with high L. loa Mf counts. Periodicity studies revealed atypical patterns, with no significant diurnal periodicity in some individuals. Thus, methods routinely used for LF mapping may not be reliable in areas in central Africa that are highly endemic for loiasis. | 25,223,938 | [
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Usefulness of 11C-methionine-positron emission tomography for the diagnosis of progressive multifocal leukoencephalopathy. | Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating disease of the brain caused by the JC virus that occurs mainly in immunocompromised patients. The prognosis is very poor. As the lesion looks like non- specific leukoencephalopathy, making a diagnosis at the early stage is very difficult. We report three PML cases in which there was a mismatch between (11)C-methionine-positron emission tomography (MET-PET) uptake and (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake. All three cases demonstrated the hyper-uptake of MET around the white matter lesions and hypo-uptake of FDG inside the lesions. We speculate that the infection had ended inside the white matter lesions of these patients, while JC virus infection was ongoing around the lesions, resulting in the increase of methionine metabolism, and the glucose metabolism was reduced or intermediate because inflammatory cells infiltrate PML lesions rarely. Two patients who were diagnosed and treated with mefloquine while the JC virus was at a low level in the cerebrospinal fluid are still alive. We suggest the usefulness of MET-PET for the early diagnosis of PML and early treatment with mefloquine. | 25,223,960 | [
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Peripherally cross-linking the shell of core-shell polymer micelles decreases premature release of physically loaded combretastatin A4 in whole blood and increases its mean residence time and subsequent potency against primary murine breast tumors after IV administration. | Determine the feasibility and potential benefit of peripherally cross-linking the shell of core-shell polymer micelles on the premature release of physically loaded hydrophobic drug in whole blood and subsequent potency against solid tumors. Individual Pluronic F127 polymer micelles (F127 PM) peripherally cross-linked with ethylenediamine at 76% of total PEO blocks (X-F127 PM) were physically loaded with combretastatin A4 (CA4) by the solid dispersion method and compared to CA4 physically loaded in uncross-linked F127 PM, CA4 in DMSO in vitro, or water-soluble CA4 phosphate (CA4P) in vivo. X-F127 PM had similar CA4 loading and aqueous solubility as F127 PM up to 10 mg CA4 / mL at 22.9 wt% and did not aggregate in PBS or 90% (v/v) human serum at 37°C for at least 24 h. In contrast, X-F127 PM decreased the unbound fraction of CA4 in whole blood (fu) and increased the mean plasma residence time and subsequent potency of CA4 against the vascular function and growth of primary murine 4T1 breast tumors over CA4 in F127 PM and water-soluble CA4P after IV administration. Given that decreasing the fu is an indication of decreased drug release, peripherally cross-linking the shell of core-shell polymer micelles may be a simple approach to decrease premature release of physically loaded hydrophobic drug in the blood and increase subsequent potency in solid tumors. | 25,223,962 | [
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Molecular-based isothermal tests for field diagnosis of malaria and their potential contribution to malaria elimination. | In countries where malaria transmission has decreased substantially, thanks to the scale-up of control interventions, malaria elimination may be feasible. Nevertheless, this goal requires new strategies such as the active detection and treatment of infected individuals. As the detection threshold for the currently used diagnostic methods is 100 parasites/μL, most low-density, asymptomatic infections able to maintain transmission cannot be detected. Identifying them by molecular methods such as PCR is a possible option but the field deployment of these tests is problematic. Isothermal amplification of nucleic acids (at a constant temperature) offers the opportunity of addressing some of the challenges related to the field deployment of molecular diagnostic methods. One of the novel isothermal amplification methods for which a substantial amount of work has been done is the loop-mediated isothermal amplification (LAMP) assay. The present review describes LAMP and several other isothermal nucleic acid amplification methods, such as thermophilic helicase-dependent amplification, strand displacement amplification, recombinase polymerase amplification and nucleic acid sequence-based amplification, and explores their potential use as high-throughput, field-based molecular tests for malaria diagnosis. | 25,223,973 | [
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Ganciclovir inhibits human adenovirus replication and pathogenicity in permissive immunosuppressed Syrian hamsters. | Adenovirus infections of immunocompromised patients can develop into deadly multiorgan or systemic disease. The virus is especially threatening for pediatric allogeneic hematopoietic stem cell transplant recipients; according to some studies, 10% or more of these patients succumb to disease resulting from adenovirus infection. At present, there is no drug approved for the treatment or prevention of adenovirus infections. Compounds that are approved to treat other virus infections are used off-label to combat adenovirus, but only anecdotal evidence of the efficacy of these drugs exists. Ganciclovir, a drug approved for the treatment of herpesvirus infection, was previously reported to be effective against human adenoviruses in vitro. To model adenovirus infections in immunocompromised humans, we examined ganciclovir's efficacy in immunosuppressed Syrian hamsters intravenously infected with type 5 human adenovirus (Ad5). This animal model is permissive for Ad5 replication, and the animals develop symptoms similar to those seen in humans. We demonstrate that ganciclovir suppresses Ad5 replication in the liver of infected hamsters and that it mitigates the consequences of Ad5 infections in these animals when administered prophylactically or therapeutically. We show that ganciclovir inhibits Ad5 DNA synthesis and late gene expression. The mechanism of action for the drug is not clear; preliminary data suggest that it exerts its antiadenoviral effect by directly inhibiting the adenoviral DNA polymerase. While more extensive studies are required, we believe that ganciclovir is a promising drug candidate to treat adenovirus infections. Brincidofovir, a drug with proven activity against Ad5, was used as a positive control in the prophylactic experiment. | 25,224,011 | [
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A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. | Venous leg ulcers produce significant clinical and economic burdens on society and often require advanced wound therapy. The purpose of this multicenter, randomized, controlled study is to evaluate the safety and efficacy of one or two applications of dehydrated human amnion/chorion membrane allograft and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. The primary study outcome was the proportion of patients achieving 40% wound closure at 4 weeks. Of the 84 participants enrolled, 53 were randomized to receive allograft and 31 were randomized to the control group of multilayer compression therapy alone. At 4 weeks, 62% in the allograft group and 32% in the control group showed a greater than 40% wound closure (p = 0.005), thus showing a significant difference between the allograft-treated groups and the multilayer compression therapy alone group at the 4-week surrogate endpoint. After 4 weeks, wounds treated with allograft had reduced in size a mean of 48.1% compared with 19.0% for controls. Venous leg ulcers treated with allograft had a significant improvement in healing at 4 weeks compared with multilayer compression therapy alone. | 25,224,019 | [
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Evaluation of prognostic scale Thrombolysis In Myocardial Infarction and Killip. An ST-elevation myocardial infarction new scale. | Prognostic systems are complex. So it is necessary to find tools, which are easy to use and have good calibration and discrimination. The objective of this study is to evaluate the usefulness of Killip, Thrombolysis In Myocardial Infarction (TIMI), and age to develop a new prognostic scale for patients with ST-elevation myocardial infarction (STEMI). The study population included all patients with STEMI consecutively admitted to the Intensive Care Unit of Carlos Haya Hospital, Malaga, Spain. Top variables included are Killip and TIMI, hospital mortality, intensive care unit stay, treatment received, and care times intervals. The results are 806 patients; 75.6% men; age 63.11 ± 12.83 years old; TIMI, 3.57 ± 2.38; Killip I, 81.4%; and hospital mortality, 11.3%. Mortality increased in relation to age, TIMI, and Killip (P < .001). Receiver operating characteristic (ROC) area for TIMI is 0.832 (0.786-0.878) and Killip, 0.757 (0.698-0.822). Thrombolysis In Myocardial Infarction classification was associated with Killip and age by multiple linear regression. Patients were stratified into 5 groups according to Killip and age: Killip I and younger than 65 years (n = 369; mortality, 1.4%; odds ratio [OR], 1), Killip I and 65 to 75 years old (n = 173; mortality, 6.9%; OR, 5.43 [1.88-15.66]), Killip I and older than 75 years (n = 112; mortality, 18.9%; OR, 13.03 [4.69-36.21]), Killip II to III (n = 129; mortality, 31%; OR, 22.72 [12.55-85.29]), Killip IV (n = 20; mortality, 80%; OR, 291.2 [71.32-1189]). ROC area is 0.84 (0.798-0.883). We created a scale with scores based on the β coefficient of logistical regression. The TIMI scale discriminated hospital mortality correctly for STEMI. It performed better than Killip alone and similar to a simple model that included age and Killip. The 2-variable model consists of a simple scale with 5 categories. | 25,224,025 | [
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Antiarrhythmic effect of lithium in rats after myocardial infarction by activation of Nrf2/HO-1 signaling. | Glycogen synthase kinase-3 (GSK-3) signaling has been shown to play a role in the regulation of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of antioxidant genes, including heme oxygenase-1 (HO-1). We assessed whether lithium, a GSK-3 inhibitor, attenuates cardiac sympathetic reinnervation after myocardial infarction, a status of high reactive oxygen species (ROS), by attenuating nerve growth factor (NGF) expression and whether Nrf2/HO-1 signaling is involved in the protection. Twenty-four hours after ligation of the left anterior descending artery, male Wistar rats were treated for 4 weeks. The postinfarction period was associated with increased oxidative-nitrosative stress, as measured by myocardial superoxide, nitrotyrosine, and dihydroethidium fluorescent staining. In concert, myocardial norepinephrine levels and immunohistochemical analysis of sympathetic nerve revealed a significant increase in innervation in vehicle-treated rats compared with sham-operated rats. Arrhythmic scores during programmed stimulation in the vehicle-treated rats were significantly higher than those in sham. This was paralleled by a significant upregulation of NGF protein and mRNA in the vehicle-treated rats, which was reduced after administration of LiCl. LiCl stimulated the nuclear translocation of Nrf2 and the transactivation of the Nrf2 target gene HO-1. Inhibition of phosphoinositide 3-kinase by wortmannin reduced the increase in Nrf2 nucleus translocation and HO-1 expression compared with lithium alone. In addition, the lithium-attenuated NGF levels were reversed in the presence of the Nrf2 inhibitor trigonelline, HO-1 inhibitor SnPP, and peroxynitrite generator SIN-1, indicating the role of Nrf2/HO-1/ROS. In conclusion, lithium protects against ventricular arrhythmias by attenuating NGF-induced sympathetic innervation via antioxidant activation of the Nrf2/HO-1 axis. | 25,224,036 | [
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Nuclear Nrf2 induction by protein transduction attenuates osteoclastogenesis. | It has been reported that reactive oxygen species (ROS) play a role as intracellular signaling molecules in RANKL stimulation. Previously we demonstrated that induction of cytoprotective enzyme expression by Nrf2-gene transfer successfully ameliorated RANKL-dependent osteoclastogenesis. In the present study, we hypothesized that Nrf2 activation by inhibiting ubiquitination and degradation of Nrf2 by ETGE-peptide would induce Nrf2-dependent cytoprotective enzyme expression, attenuate ROS signaling, and thereby inhibit RANKL-dependent osteoclastogenesis. ETGE-peptide containing a cell-permeable sequence (seven consecutive arginine; 7R-ETGE) was applied to a mouse macrophage cell-line RAW 264.7 cell or a primary macrophage culture. ETGE-peptide prevents Keap1 from binding to Nrf2. Nrf2 nuclear translocation and Nrf2-dependent cytoprotective enzyme induction was observed. The effects of 7R-ETGE on RANKL-dependent induction of intracellular ROS levels and osteoclastogenesis were examined. Finally, the protective effect of 7R-ETGE on RANKL-mediated bone destruction was investigated in mice. 7R-ETGE dose-dependently induced nuclear Nrf2, followed by the induction of cytoprotective enzyme expression at both the gene and protein level. 7R-ETGE inhibited upregulation of intracellular ROS levels by RANKL stimulation, and osteoclastogenesis was attenuated. Of particular interest was that local injection of 7R-ETGE ameliorated RANKL-mediated bone destruction. Local induction of nuclear Nrf2 by protein transduction is a potential novel therapeutic target for bone destruction diseases such as periodontitis and rheumatoid arthritis. | 25,224,039 | [
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Noncardiac surgery in patients with aortic stenosis: a contemporary study on outcomes in a matched sample from the Danish health care system. | Past research has identified aortic stenosis (AS) as a major risk factor for adverse outcomes in noncardiac surgery; however, more contemporary studies have questioned the grave prognosis. To further our understanding of this, the risks of a 30-day major adverse cardiovascular event (MACE) and all-cause mortality were investigated in a contemporary Danish cohort. AS is not an independent risk factor for adverse outcomes in noncardiac surgery. All patients with and without diagnosed AS who underwent noncardiac surgery in 2005 to 2011 were identified through nationwide administrative registers. AS patients (n = 2823; mean age, 75.5 years, 53% female) were matched with patients without AS (n = 2823) on propensity score for AS and surgery type. In elective surgery, MACE (ie, nonfatal myocardial infarction, ischemic stroke, or cardiovascular death) occurred in 66/1772 (3.7%) of patients with AS and 52/1772 (2.9%) of controls (P = 0.19), whereas mortality occurred in 67/1772 (3.8%) AS patients and 51/1772 (2.9%) controls (P = 0.13). In emergency surgery, 163/1051 (15.5%) AS patients and 120/1051 (11.4%) controls had a MACE (P = 0.006), whereas 225/1051 (21.4%) vs 179/1051 (17.0%) AS patients and controls died, respectively (P = 0.01). Event rates were higher for those with symptoms (defined as use of nitrates, congestive heart failure, or use of loop diuretics), compared with those without symptoms (P < 0.0001). AS is associated with high perioperative rates of MACE and mortality, but perhaps prognosis is, in practice, not much worse for patients with AS than for matched controls. Symptomatic patients and patients undergoing emergency surgery are at considerable risks of a MACE and mortality. | 25,224,044 | [
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HLA-DRA variants predict penicillin allergy in genome-wide fine-mapping genotyping. | Immediate reactions to β-lactams are the most common causes of anaphylactic reactions and can be life-threatening. The few known genetic factors influencing these reactions suggest a link with atopy and inflammation. We performed a fine-mapping genome-wide association study of the genetic predictors of β-lactam allergy to better understand the underlying mechanisms. We studied 387 patients with immediate allergic reactions to β-lactams and 1124 paired control subjects from Spain. We replicated the results in 299 patients and 362 paired control subjects from Italy. We found significant associations with the single nucleotide polymorphisms rs4958427 of ZNF300 (c.64-471G>A, P = 9.9 × 10(-9)), rs17612 of C5 (c.4311A>C [p.Glu1437Asp], P = 7.5 × 10(-7)), rs7754768 and rs9268832 of the HLA-DRA | HLA-DRB5 interregion (P = 1.6 × 10(-6) and 4.9 × 10(-6)), and rs7192 of HLA-DRA (c.724T>G [p.Leu242Val], P = 7.4 × 10(-6)) in an allelic model, with similar results in an additive model. Single nucleotide polymorphisms of HLA-DRA and ZNF300 predicted skin test positivity to amoxicillin and other penicillins but not to cephalosporins. A haplotype block in HLA-DRA and the HLA-DRA | HLA-DRB5 interregion encompassed a motif involved in balanced expression of the α- and β-chains of MHC class II, whereas rs7192 was predicted to influence α-chain conformation. HLA-DRA rs7192 and rs8084 were significantly associated with allergy to penicillins and amoxicillin (P = 6.0 × 10(-4) and P = 4.0 × 10(-4), respectively) but not to cephalosporins in the replication study. Gene variants of HLA-DRA and the HLA-DRA | HLA-DRB5 interregion were significant predictors of allergy to penicillins but not to cephalosporins. These data suggest complex gene-environment interactions in which genetic susceptibility of HLA type 2 antigen presentation plays a central role. | 25,224,099 | [
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The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: a systematic review and meta-analysis. | Circadian- and sleep disturbances may be central for understanding the pathophysiology and treatment of depression. The effect of melatonin on depression/depressive symptoms has been investigated previously. This systematic review assesses the current evidence of a therapeutic- and prophylactic effect of melatonin in adult patients against depression or depressive symptoms. A search was performed in The Cochrane Library, PubMed, EMBASE and PsycINFO for published trials on November 14th 2013. Inclusion criteria were English language, RCTs or crossover trials. Our outcome was measurement of depression/depressive symptoms with a validated clinician-administered or self-rating questionnaire. PRISMA recommendations were followed and the Cochrane risk-of-bias tool used. Ten studies in 486 patients were included in the final qualitative synthesis and four studies, 148 patients, were included in two meta-analyses. Melatonin doses varied from 0.5-6 mg daily and the length of follow-up varied from 2 weeks to 3.5 years. Three studies were done on patients without depression at inclusion, two studies in patients with depression and five studies included a mixture. Six studies showed an improvement in depression scores in both the melatonin and placebo groups but there was no significant difference. One study showed a significant prophylactic effect and another found a significant treatment effect on depression with melatonin compared to placebo. The two meta-analyses did not show any significant effect of melatonin. No serious adverse events were reported. Although some studies were positive, there was no clear evidence of a therapeutic- or prophylactic effect of melatonin against depression or depressive symptoms. | 25,224,106 | [
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Predictors of poor sleep quality and excessive daytime sleepiness in peritoneal dialysis patients. | To explore the possible impact factors on daytime sleepiness among peritoneal patients from a single center in China. A cross-sectional study was conducted in 98 prevalent peritoneal dialysis (PD) patients using both the Pittsburgh Sleep Quality Index (PSQI) questionnaire of sleep quality and the Epworth Sleepiness Scale (ESS) questionnaire of excessive daytime sleepiness (EDS). Biochemical differences between daytime sleepiness and non-daytime sleepiness population were evaluated, following univariate and multivariable analysis to find the risk factors on sleep disturbance. The prevalence of "poor sleep quality" (PSQI > 5) was 74.49%, while daytime sleepiness (ESS ≥ 9) occurred in 22.45%. Mean PSQI was 9.06 ± 4.60 and EES was 6.31 ± 4.98. Compared to non-EDS cases, patients with ESS ≥ 9 had worse residual renal function (RRF), higher serum creatinine, higher serum magnesium and elevated serum ferritin. In univariate analysis, ESS correlated with serum albumin (r = 0.346, p = 0.015), phosphate (r = 0.313, p = 0.029), magnesium (r = 0.376, p = 0.008) and urinary Kt/V (r = -0.341, p = 0.029). Finally, multivariable linear regression indicated that urinary Kt/V, PSQI and magnesium were independent predictors of ESS score. EDS does exist in PD patients and is associated both with poor nighttime sleep quality and lower RRF. Hypermagnesemia may be a treatable risk factor to improve daytime tiredness. | 25,224,151 | [
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Different strategies underlying uncertain decision making: higher executive performance is associated with enhanced feedback-related negativity. | The aim of the present study was to investigate the role of executive functions (EFs) in different strategies underlying risky decision making. Adult participants from a nonclinical sample were assigned to low or high EF groups based on their performance on EF tasks measuring shifting, updating, and inhibition. ERPs were recorded while participants performed the Balloon Analogue Risk Task (BART). In this task, each balloon pump was associated with either a reward or a balloon pop with unknown probability. The BART behavioral measures did not show between-group differences. However, the feedback-related negativity (FRN) associated with undesirable outcomes was larger in the high EF group than in the low EF group. Since the FRN represents salience prediction error, our results suggest that the high EF group formed internal models that were violated by the outcomes. Thus, we provided ERP evidence for EFs influencing risky decision-making processes. | 25,224,177 | [
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Review of global rotavirus strain prevalence data from six years post vaccine licensure surveillance: is there evidence of strain selection from vaccine pressure? | Comprehensive reviews of pre licensure rotavirus strain prevalence data indicated the global importance of six rotavirus genotypes, G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] and G12P[8]. Since 2006, two vaccines, the monovalent Rotarix (RV1) and the pentavalent RotaTeq (RV5) have been available in over 100 countries worldwide. Of these, 60 countries have already introduced either RV1 or RV5 in their national immunization programs. Post licensure vaccine effectiveness is closely monitored worldwide. This review aimed at describing the global changes in rotavirus strain prevalence over time. The genotype distribution of the nearly 47,000 strains that were characterized during 2007-2012 showed similar picture to that seen in the preceding period. An intriguing finding was the transient predominance of heterotypic strains, mainly in countries using RV1. Unusual and novel antigen combinations continue to emerge, including some causing local outbreaks, even in vaccinated populations. In addition, vaccine strains have been found in both vaccinated infants and their contacts and there is evidence for genetic interaction between vaccine and wild-type strains. In conclusion, the post-vaccine introduction strain prevalence data do not show any consistent pattern indicative of selection pressure resulting from vaccine use, although the increased detection rate of heterotypic G2P[4] strains in some countries following RV1 vaccination is unusual and this issue requires further monitoring. | 25,224,179 | [
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Effective treatment of congestive heart failure using adaptive servo-ventilation in an end-stage renal disease patient on hemodialysis. | A 61-year-old man who was being treated with hemodialysis (HD) for end-stage renal disease presented with symptoms of severe congestive heart failure (CHF). Removing excess intravascular fluid during HD was difficult due to the patient's chronic hypotension induced by severe left ventricular (LV) dysfunction. The application of adaptive servo-ventilation (ASV) increased the patient's cardiac output and blood pressure during HD, thus resulting in the effective removal of excess intravascular fluid. Therefore, ASV may be effective for treating CHF in HD patients with LV dysfunction and chronic hypotension. | 25,224,193 | [
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Lung Nocardia elegans infection diagnosed on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). | A 73-year-old man with adultonset Still's disease developed a high fever, coughing, dyspnea and bloody sputum and was therefore admitted to our hospital. Thoracic X-ray and CT scans revealed oval lesions in the bilateral lungs. A bacterial isolate from the sputum was identified to be Nocardia elegans (N. elegans) on comparative 16S rRNA gene sequencing and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). The patient recovered following treatment with imipenem/cilastatin and amikacin. To the best of our knowledge, this is the first case of nocardiosis caused by N. elegans identified on MALDI-TOF MS. | 25,224,198 | [
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A fatal case of acute myocardial infarction following the improvement of influenza A(H1N1)pdm2009-related acute myocarditis. | A 52-year-old Indian man was hospitalized due to dyspnea and a high fever caused by influenza A(H1N1)pdm2009. Elevated cardiac enzymes, a chest X-ray showing bilateral infiltrative shadows, cardiomegaly and pleural effusion and echocardiography indicating diffuse hypokinesis of the left ventricle suggested cardiac failure due to acute myocarditis. Owing to the administration of combined modality therapy, including steroids and intravenous γ-globulin, the patient's clinical symptoms of influenza completely resolved. However, he suddenly complained of epigastric pain due to acute myocardial infarction and died. This report is an educational case, the results of which suggest that greater attention should be paid to the potential for myocardial infarction even after an influenza virus infection is found to improve. | 25,224,206 | [
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Self-regulated left-right asymmetric expression of Pitx2c in the developing mouse limb. | The transcription factor Pitx2c is expressed in primordial visceral organs in a left-right (L-R) asymmetric manner and executes situs-specific morphogenesis. Here we show that Pitx2c is also L-R asymmetrically expressed in the developing mouse limb. Human PITX2c exhibits the same transcriptional activity in the mouse limb. The asymmetric expression of Pitx2c in the limb also exhibits dorsal-ventral and anterior-posterior polarities, being confined to the posterior-dorsal region of the left limb. Left-sided Pitx2c expression in the limb is regulated by Nodal signaling through a Nodal-responsive enhancer. Pitx2c is expressed in lateral plate mesoderm (LPM)-derived cells in the left limb that contribute to various limb connective tissues. The number of Pitx2c(+) cells in the left limb was found to be negatively regulated by Pitx2c itself. Although obvious defects were not apparent in the limb of mice lacking asymmetric Pitx2c expression, Pitx2c may regulate functional L-R asymmetry of the limb. | 25,224,222 | [
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Effects of van der Waals interaction and electric field on the electronic structure of bilayer MoS2. | The modification of the electronic structure of bilayer MoS2 by an external electric field can have potential applications in optoelectronics and valleytronics. Nevertheless, the underlying physical mechanism is not clearly understood, especially the effects of the van der Waals interaction. In this study, the spin orbit-coupled electronic structure of bilayer MoS2 has been investigated using the first-principle density functional theory. We find that the van der Waals interaction as well as the interlayer distance has significant effects on the band structure. When the interlayer distance of bilayer MoS2 increases from 0.614 nm to 0.71 nm, the indirect gap between the Γ and Λ points increases from 1.25 eV to 1.70 eV. Meanwhile, the energy gap of bilayer MoS2 transforms from an indirect one to a direct one. An external electric field can shift down (up) the energy bands of the bottom (top) MoS2 layer and also breaks the inversion symmetry of bilayer MoS2. As a result, the electric field can affect the band gaps, the spin-orbit interaction and splits the valance bands into two groups. The present study can help us understand more about the electronic structures of MoS2 materials for potential applications in electronics and optoelectronics. | 25,224,268 | [
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Tumor-suppressive miR148a is silenced by CpG island hypermethylation in IDH1-mutant gliomas. | IDH1/2-mutant gliomas harbor a distinct glioma-CpG island methylation phenotype (G-CIMP) that may promote the initiation and progression of secondary pathway gliomas by silencing tumor-suppressive genes. The potential role of tumor-suppressive microRNAs (miRNA; miR) in this process is not understood. To identify potential tumor-suppressive miRNA hypermethylated in glioma, the methylation profiles of IDH1/2(WT) gliomas (n = 11) and IDH1(MUT) glioma (n = 20) were compared by using massively parallel reduced representation bisulfite sequencing (RRBS). The methylation status of selected miRNA was validated by using targeted bisulfite sequencing (BiSEQ) in a large cohort of glioma tissue samples including 219 IDH1(WT) and 72 IDH1/2(MUT) samples. The expression of selected miRNAs was determined by using the TaqMan qPCR. Functional analyses of miR148a were conducted and target genes were identified. We identify miR148a as a novel, G-CIMP-associated miRNA whose methylation is tightly correlated with IDH1 mutation and associated with improved survival in patients with malignant glioma. We confirm that downregulation of miR148a can occur via DNA methylation. We demonstrate that IDH1 mutation provides a mechanism of miR148a methylation and downregulation, and that restoration of miR148a reduced tumorigenic properties of glioma cells, possibly by targeting DNMT1. We identify miR148a as a novel G-CIMP-associated miRNA, and provide results suggesting that miR148a restoration may have therapeutic implications. | 25,224,277 | [
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Starch-g-Poly-(N, N-dimethyl acrylamide-co-acrylic acid): an efficient Cr (VI) ion binder. | Synthesis of Starch-g-(Poly N, N-dimethylacrylamide-co-acrylic acid) was carried out by solution polymerization technique using potassium perdisulfate (K(2)S(2)O(8)) as the initiator. The graft copolymer was characterized by measuring molecular weight, using size exclusion chromatography (SEC), FTIR spectroscopy and X-ray diffraction (XRD) studies. The synthetic graft copolymer was used for removal of hexavalent chromium ion [Cr (VI)] from its aqueous solution. Various operating variables affecting the metal sorption such as, the amount of adsorbent, solution pH, contact time, temperature and the Cr (VI) solution concentration were extensively investigated. FTIR and UV-VIS spectroscopy, cyclic voltammetry (CV) were employed to study the metal complexation. The adsorption data could be well described by the pseudo-second-order and Langmuir isotherm model which indicate a chemisorption process. Calculation of the various thermodynamic parameters for the adsorption was also done. The negative value of free energy change (ΔG°) indicates the spontaneous nature of the adsorption. | 25,224,290 | [
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Uncertain diagnosis of fabry disease in patients with neuropathic pain, angiokeratoma or cornea verticillata: consensus on the approach to diagnosis and follow-up. | Individuals with neuropathic pain, angiokeratoma (AK) and/or cornea verticillata (CV) may be tested for Fabry disease (FD). Classical FD is characterised by a specific pattern of these features. When a patient presents with a non-specific pattern, the pathogenicity of a variant in the α-galactosidase A (GLA) gene may be unclear. This uncertainty often leads to considerable distress and inappropriate counselling and treatment. We developed a clinical approach for these individuals with an uncertain diagnosis of FD. A document was presented to an FD expert panel with background information based on clinical experience and the literature, followed by an online survey and a written recommendation. The 13 experts agreed that the recommendation is intended for individuals with neuropathic pain, AK and/or CV only, i.e. without kidney, heart or brain disease, with an uncertain diagnosis of FD. Only in the presence of FD-specific neuropathic pain (small fibre neuropathy with FD-specific pattern), AK (FD-specific localisations) or CV (without CV inducing medication), FD is confirmed. When these features have a non-specific pattern, there is insufficient evidence for FD. If no alternative diagnosis is found, follow-up is recommended. In individuals with an uncertain diagnosis of FD, the presence of an FD-specific pattern of CV, AK or neuropathic pain is sufficient to confirm the diagnosis of FD. When these features are non-specific, a definite diagnosis cannot (yet) be established and follow-up is indicated. ERT should be considered only in those patients with a confirmed diagnosis of FD. | 25,224,312 | [
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Chemical reaction-induced multi-molecular polarization (CRIMP). | Here we present a novel hyperpolarization method, Chemical Reaction-Induced Multi-molecular Polarization (CRIMP), which could be applied to the study of several in vivo processes simultaneously including glycolysis, TCA cycle, fatty acid synthesis and pH mapping. Through the use of non-enzymatic decarboxylation, we generate four hyperpolarized imaging agents from hyperpolarized 1,2-(13)C pyruvic acid. | 25,224,323 | [
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Alternating current cloud point extraction on a microchip: the effect of electrode geometry. | We report on the effect of electrode geometry on alternating current cloud point extraction (ACPE). ACPE is a technique utilized to extract membrane-associated biomolecules in an electrode-integrated microfluidic channel. In this study, we investigated the effect of gap size (4∼22 μm) between microband electrodes on ACPE. A decrease in gap size resulted in efficient and rapid concentration of fluorescent-labeled phospholipids, a model of membrane-associated biomolecules. We also investigated the effect of applied voltage amplitude on ACPE using devices with decreased electrode gap size. When the gap was small, ACPE was achieved with low applied voltages. ACPE of membrane proteins extracted from HeLa cells was also studied to demonstrate the applicability of the ACPE to real samples. The results provide a guideline to improve the performance of ACPE and facilitate application of the ACPE technique as part of an overall analytical process. | 25,224,325 | [
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Occupational exposure to N,N-dimethylformamide in the summer and winter. | We evaluated total body burden of N,N-dimethylformamide (DMF) taken through the lung and skin by personal exposure of workers to DMF and urinalysis of N-methylformamide (NMF) and N-acetyl-S(N-methylcarbamoyl)-cysteine (AMCC). A total of 270 workers were engaged in four different jobs in a workplace distant from main production lines emanating high levels of DMF. They were not required to wear any personal protective equipment including respirators or gloves. We found that log-transformed urinary levels of NMF and AMCC increased with an increase in log-transformed concentrations of exposure to DMF. Urinary levels of NMF and AMCC were significantly higher in the summer than the winter, although there was no significant seasonal difference in the concentrations of exposure to DMF. Our findings suggested that the increased urinary levels of NMF and AMCC in the summer resulted in increased skin absorption of DMF due to an increased amount of DMF absorbed by the moisturized skin under humid and hot conditions. Seasonal changes in the relative internal exposure index confirmed the present finding of enhanced summertime skin absorption of DMF. AMCC is thought to be a useful biomarker for assessments of cumulative exposure to DMF over a workweek and for evaluations of workers' health effects. | 25,224,331 | [
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Serum miRNA profiling identifies miR-150/30a as potential biomarker for workers with damaged nerve fibers from carbon disulfide. | As crucial small regulatory molecules, serum microRNAs (miRNAs) have been widely identified as potential noninvasive biomarkers. To survey and identify serum miRNAs associated with workers who had experienced injury to their nerve system from carbon disulfide (CS2), we profiled abnormally expressed miRNAs using the microarray technique and further performed qRT-PCR validation in case and control samples (n=20). Microarray profiling in pooled RNA samples showed that many miRNAs in workers exposed to CS2 were aberrantly expressed. Based on control samples exposed to CS2, a great amount of abnormal miRNAs, including some miRNA gene clusters and families, were obtained from microarray datasets. Most of deregulated miRNAs were up-regulated, and almost all miRNAs showed consistent expression patterns between workers with different numbers of damaged nerve fibers. Functional enrichment analysis suggested that these abnormal miRNAs showed versatile roles by contributing to multiple biological processes. Some aberrantly expressed miRNAs were characterized as miRNA gene clusters or families, and they always showed consistent expression patterns. miR-150 and miR-30a were selected to be further validated by qRT-PCR as up-regulated species, and they could discern case samples from control samples. miR-150 and miR-30a may be potential noninvasive biomarkers for a damaged nervous system. | 25,224,332 | [
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PET and NIR optical imaging using self-illuminating (64)Cu-doped chelator-free gold nanoclusters. | Self-illuminating fluorescence imaging without autofluorescence background interference has recently aroused more research interests in molecular imaging. Currently, only a few self-illuminating probes were developed, based mainly on toxic quantum dots such as CdSe, CdTe. Herein, we report a novel design of nontoxic self-illuminating gold nanocluster ((64)Cu-doped AuNCs) for dual-modality positron emission tomography (PET) and near-infrared (NIR) fluorescence imaging based on Cerenkov resonance energy transfer (CRET). PET radionuclide (64)Cu was introduced by a chelator-free doping method, which played dual roles as the energy donor and the PET imaging source. Meanwhile, AuNCs acted as the energy acceptor for NIR fluorescence imaging. (64)Cu-doped AuNCs exhibited efficient CRET-NIR and PET imaging both in vitro and in vivo. In a U87MG glioblastoma xenograft model, (64)Cu-doped AuNCs showed high tumor uptake (14.9 %ID/g at 18 h) and produced satisfactory tumor self-illuminating NIR images in the absence of external excitation. This self-illuminating nanocluster with non-toxicity and good biocompatibility can be employed as a novel imaging contrast agent for biomedical applications, especially for molecular imaging. | 25,224,367 | [
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Long-lasting uveitis remission and hearing loss recovery after rituximab in Vogt-Koyanagi-Harada disease. | Vogt-Koyanagi-Harada disease (VKHD) is a multisystemic disorder characterized by granulomatous panuveitis variably combined with T cell-mediated neurologic and cutaneous manifestations. Early and aggressive treatment with systemic corticosteroids is the mainstay of treatment for VKHD. Additional use of immunosuppressants, intravenous immunoglobulins, and tumor necrosis factor-alpha inhibitors can help the most severely affected patients and work as corticosteroid-sparing agents. We report the case of a young woman with relapsing and multiresistant VKHD who demonstrated a stable remission of both uveitis and high-frequency hearing loss following rituximab intravenous administration (1 g. twice, 2 weeks apart, and 6 months later). A complete clinical response was observed 1 month since the first infusion, and no ocular relapses were recorded during the following year; in addition, audiometry showed a high-frequency hearing recovery in the right ear. Further observational studies are required to define the role of CD20 inhibition in the management of VKHD. | 25,224,382 | [
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Thioester-containing proteins of the tick Ixodes ricinus: gene expression, response to microbial challenge and their role in phagocytosis of the yeast Candida albicans. | The ability of ticks to act as vectors for a wide range of serious human and animal infectious diseases is apparently linked to the insufficiency of the tick immune system to effectively eliminate pathogens they transmit. At the tick-pathogen interface, an important role is presumably played by components of an ancient complement system that includes a repertoire of thioester-containing proteins (TEPs), which in Ixodes sp. comprises three α2-macroglobulins (A2M), three C3 complement component-related molecules (C3), two macroglobulin complement-related (Mcr) and one insect-type TEPs (Tep). In order to assess the function of TEPs in tick immunity, a quantitative real-time PCR expression analysis of tick TEPs was performed at various developmental stages of Ixodes ricinus, and in tissues dissected from adult females. Expression of TEP genes was mostly tissue specific; IrA2M1, IrC3-1, IrC3-3 were found to be expressed in cells of tick fat body adjacent to the tracheal trunks, IrA2M2 in hemocytes, IrTep in ovaries, IrMcr1 in salivary glands and only IrA2M3, IrC3-2 and IrMcr2 mRNAs were present in multiple organs. Expression of tick TEPs was further examined in response to injection of model microbes representing Gram-negative, Gram-positive bacteria and yeast. The greatest expression induction was observed for IrA2M1 and IrC3-1 after challenge with the yeast Candida albicans. Phagocytosis of the yeast was strongly dependent on an active thioester bond and the subsequent silencing of individual tick TEPs by RNA interference demonstrated the involvement of IrC3-1 and IrMcr2. This result suggests the existence of a distinct complement-like pathway, different from that leading to phagocytosis of Gram-negative bacteria. Understanding of the tick immune response against model microbes should provide new concepts for investigating interactions between ticks and relevant tick-borne pathogens. | 25,224,405 | [
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Brain-derived neurotrophic factor in urinary continence and incontinence. | Urinary incontinence adversely affects quality of life and results in an increased financial burden for the elderly. Accumulating evidence suggests a connection between neurotrophins, such as brain-derived neurotrophic factor (BDNF), and lower urinary tract function, particularly with regard to normal physiological function and the pathophysiological mechanisms of stress urinary incontinence (SUI) and bladder pain syndrome/interstitial cystitis (BPS/IC). The interaction between BDNF and glutamate receptors affects both bladder and external urethral sphincter function during micturition. Clinical findings indicate reduced BDNF levels in antepartum and postpartum women, potentially correlating with postpartum SUI. Experiments with animal models demonstrate that BDNF is decreased after simulated childbirth injury, thereby impeding the recovery of injured nerves and the restoration of continence. Treatment with exogenous BDNF facilitates neural recovery and the restoration of continence. Serotonin and noradrenaline reuptake inhibitors, used to treat both depression and SUI, result in enhanced BDNF levels. Understanding the neurophysiological roles of BDNF in maintaining normal urinary function and in the pathogenesis of SUI and BPS/IC could lead to future therapies based on these mechanisms. | 25,224,451 | [
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The expression pattern of systemically injected AAV9 in the developing mouse retina is determined by age. | Systemic delivery of AAV9 offers the potential for widespread and efficient gene delivery to the retina, and may thus be a useful approach for treatment of disease where intraocular injections are not possible, for syndromes affecting multiple organs, or where early intervention is required. The expression resulting from intravenous injection of AAV9 is more efficient in neonates than adults, and here we characterize the effect of age on retinal transduction of AAV9 in the mouse retina. We find that the pattern of expression in neonatal mice is correlated to the development of the retinal vasculature, and that the area of the retinal transduction as well as the cell types infected vary depending on the age at injection. Furthermore, we demonstrate that sequential injections of AAV9 vectors carrying two different transgenes infect adjacent areas of the retina, providing a larger area of coverage. Lastly, we show that the retina's endogenous spatiotemporal expression pattern of Mfsd2a, a protein associated with the maturation of a functional blood-brain barrier, coincides with suppression of retinal transduction by intravenously-delivered AAV9, suggesting that AAV9 crosses the blood-retina barrier through transcytosis. | 25,224,467 | [
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0.2749429,
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Potential roles of noncoding RNAs in environmental epigenetic transgenerational inheritance. | "Epigenetic transgenerational inheritance" (ETI) has been defined as germline (sperm or egg) transmission of epigenetic information between generations in the absence of direct exposures or genetic manipulations. Among reported cases of ETI in mammals, the majority are induced by environmental factors, including environmental toxicants [e.g. agricultural fungicide vinclozolin, plastic additive bisphenol A, pesticide methoxychlor, dioxin, di-(2-ethylhexyl) phthalate, dichlorodiphenyltrichloroethane, and hydrocarbons] and poor nutritional conditions. Although the ETI phenomenon is well established, the underlying mechanism remains elusive. Putative epimutations, including changes in DNA methylation and histone modification patterns, have been reported, but it remains unclear how these epimutations are formed in the first place, and how they are memorized in the germline and then get transmitted to subsequent generations. Based on recent advances in our understanding of regulatory noncoding RNAs (ncRNAs), I propose that ncRNAs are involved in ETI, during both the initial epimutation formation and the subsequent germline transmission of epimutations. ncRNAs can function at epigenetic levels by affecting DNA methylation and histone modifications, thereby changing gene transcriptional activities, which can lead to an altered mRNA transcriptome associated with a disease phenotype. Alternatively, novel or altered ncRNA expression can cause dysregulated post-transcriptional regulation, thus directly affecting the mRNA transcriptome and inducing a disease phenotype. Sperm-borne ncRNAs are potential mediators for epigenetic memory across generations, but they alone may not be sufficient for stable transmission of epimutations across generations. Overall, research on ncRNAs in the context of ETI is urgently needed to shed light on the underlying mechanism of ETI. | 25,224,488 | [
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Phosphorylation regulates mycobacterial proteasome. | Mycobacterium tuberculosis possesses a proteasome system that is required for the microbe to resist elimination by the host immune system. Despite the importance of the proteasome in the pathogenesis of tuberculosis, the molecular mechanisms by which proteasome activity is controlled remain largely unknown. Here, we demonstrate that the α-subunit (PrcA) of the M. tuberculosis proteasome is phosphorylated by the PknB kinase at three threonine residues (T84, T202, and T178) in a sequential manner. Furthermore, the proteasome with phosphorylated PrcA enhances the degradation of Ino1, a known proteasomal substrate, suggesting that PknB regulates the proteolytic activity of the proteasome. Previous studies showed that depletion of the proteasome and the proteasome-associated proteins decreases resistance to reactive nitrogen intermediates (RNIs) but increases resistance to hydrogen peroxide (H2O2). Here we show that PknA phosphorylation of unprocessed proteasome β-subunit (pre-PrcB) and α-subunit reduces the assembly of the proteasome complex and thereby enhances the mycobacterial resistance to H2O2 and that H2O2 stress diminishes the formation of the proteasome complex in a PknA-dependent manner. These findings indicate that phosphorylation of the M. tuberculosis proteasome not only modulates proteolytic activity of the proteasome, but also affects the proteasome complex formation contributing to the survival of M. tuberculosis under oxidative stress conditions. | 25,224,505 | [
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Gender issues in the neurobiology of epilepsy: a clinical perspective. | A patient's hormonal milieu contributes to the timing of emergence of several epilepsy syndromes that are known to begin at puberty and recede with the end of reproductive potential. One's hormonal balance at any particular moment contributes to seizure occurrence in both men and women. The best studied condition, catamenial epilepsy, refers to seizure clusters occurring in a cyclical pattern related to menses. Treatment of epilepsy using hormones complements standard antiepileptic therapy and its use will be reviewed, along with some other medications unique to catamenial epilepsy, such as diuretics.Seizures and “silent” epileptiform discharges in turn affect the hypothalamic pituitary axis and can cause release of hormones at inappropriate times leading to sexual dysfunction, menstrual irregularity, infertility and premature termination of reproductive states. Combined with psychological consequences of epilepsy, this sexual dysfunction has deleterious effects on the quality of life in patients and their partners. | 25,224,522 | [
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Increased common atrioventricular valve tenting is a risk factor for progression to severe regurgitation in patients with a single ventricle with unbalanced atrioventricular septal defect. | Significant atrioventricular valve regurgitation (AVVR) increases mortality in patients with unbalanced atrioventricular septal defects (uAVSDs) and a single ventricle. We tested the hypothesis that abnormal leaflet tethering is associated with progressive AVVR in patients with a single ventricle with uAVSD. We retrospectively reviewed the initial presentation and prebidirectional cavopulmonary anastamosis echocardiograms of 46 consecutive patients with uAVSD with single ventricle palliation. AVVR was graded as moderate to severe if the sum of vena contracta width to dominant valve annulus ratio was ≥ 0.33. We measured tenting height, annular to leaflet angle and annular diameter, indexed to patient size where appropriate. Multivariate analysis of variables to predict progressive AVVR was performed. At follow-up of 3.3 ± 2.4 years, 24 patients had mild AVVR (Group A) and 22 had moderate to severe AVVR. Overall mortality was 6%, whereas 10 had valve repair/replacement surgery. Of 22 patients with severe AVVR at follow-up, 9 had severe AVVR at initial presentation (Group B), whereas 13 had mild AVVR at presentation but developed severe AVVR at their prebidirectional cavopulmonary anastamosis echocardiogram (Group C). Group A patients had a smaller tenting height at initial presentation compared with patients in Group B and Group C, and also had early progressive reduction of indexed tenting height (P < .01). An absolute tenting height >6 mm (odds ratio, 6.6; 95% confidence interval, 1.1-39.0; P = .03) at the initial echocardiogram was identified as an independent predictor of subsequent severe AVVR. Early leaflet tethering is predictive of subsequent AVVR in patients with a single ventricle with uAVSD. Patients with competent AVV had progressive reduction in the degree of leaflet tethering, whereas patients with AVVR did not. This may represent an important adaptive process to maintain valve competency in uAVSD. | 25,224,553 | [
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Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT₂A receptors, in mice. | 2-([2-(4-cyano-2,5-dimethoxyphenyl)ethylamino]methyl)phenol (25CN-NBOH) is structurally similar to N-benzyl substituted phenethylamine hallucinogens currently emerging as drugs of abuse. 25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro, but has not been behaviorally characterized. 25CN-NBOH was compared to the traditional phenethylamine hallucinogen R(-)-2,5-dimethoxy-4-iodoamphetamine (DOI) using mouse models of drug-elicited head twitch behavior and drug discrimination. Drug-elicited head twitches were quantified for 10 min following administration of various doses of either DOI or 25CN-NBOH, with and without pretreatments of 0.01 mg/kg 5-HT2A antagonist M100907 or 3.0 mg/kg 5-HT2C antagonist RS102221. The capacity of 25CN-NBOH to attenuate DOI-elicited head twitch was also investigated. Mice were trained to discriminate DOI or M100907 from saline, and 25CN-NBOH was tested for generalization. 25CN-NBOH induced a head twitch response in the mouse that was lower in magnitude than that of DOI, blocked by M100907, but not altered by RS102221. DOI-elicited head twitch was dose-dependently attenuated by 25CN-NBOH pretreatment. 25CN-NBOH produced an intermediate degree of generalization (55 %) for the DOI training dose, and these interoceptive effects were attenuated by M100907. Finally, 25CN-NBOH did not generalize to M100907 at any dose, but ketanserin fully substituted in these animals. 25CN-NBOH was behaviorally active, but less effective than DOI in two mouse models of hallucinogenic effects. The effectiveness with which M100907 antagonized the behavioral actions of 25CN-NBOH strongly suggests that the 5-HT2A receptor is an important site of agonist action for this compound in vivo. | 25,224,567 | [
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Evaluation of the 5 and 8 pH point titration methods for monitoring anaerobic digesters treating solid waste. | Simple titration methods certainly deserve consideration for on-site routine monitoring of volatile fatty acid (VFA) concentration and alkalinity during anaerobic digestion (AD), because of their simplicity, speed and cost-effectiveness. In this study, the 5 and 8 pH point titration methods for measuring the VFA concentration and carbonate system alkalinity (H2CO3*-alkalinity) were assessed and compared. For this purpose, synthetic solutions with known H2CO3*-alkalinity and VFA concentration as well as samples from anaerobic digesters treating three different kind of solid wastes were analysed. The results of these two related titration methods were verified with photometric and high-pressure liquid chromatography measurements. It was shown that photometric measurements lead to overestimations of the VFA concentration in the case of coloured samples. In contrast, the 5 pH point titration method provides an accurate estimation of the VFA concentration, clearly corresponding with the true value. Concerning the H2CO3*-alkalinity, the most accurate and precise estimations, showing very similar results for repeated measurements, were obtained using the 8 pH point titration. Overall, it was concluded that the 5 pH point titration method is the preferred method for the practical monitoring of AD of solid wastes due to its robustness, cost efficiency and user-friendliness. | 25,224,566 | [
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Current approaches for RNA labeling in vitro and in cells based on click reactions. | Over recent years, click reactions have become recognized as valuable and flexible tools to label biomacromolecules such as proteins, nucleic acids, and glycans. Some of the developed strategies can be performed not only in aqueous solution but also in the presence of cellular components, as well as on (or even in) living cells. These labeling strategies require the initial, specific modification of the target molecule with a small, reactive moiety. In the second step, a click reaction is used to covalently couple a reporter molecule to the biomolecule. Depending on the type of reporter, labeling by the click reaction can be used in many different applications, ranging from isolation to functional studies of biomacromolecules. In this minireview, we focus on labeling strategies for RNA that rely on the click reaction. We first highlight click reactions that have been used successfully to label modified RNA, and then describe different strategies to introduce the required reactive groups into target RNA. The benefits and potential limitations of the strategies are critically discussed with regard to possible future developments. | 25,224,574 | [
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Maternal directiveness in childhood survivors of acute lymphoblastic leukemia. | Parental intrusiveness is associated with internalizing problems in healthy children. Given the unique demands that childhood cancer places on parents, it is important to determine whether intrusiveness operates differently in survivors of childhood cancer. The current study tested whether cancer survivorship moderates the relation between maternal directiveness-one aspect of intrusiveness-and children's internalizing problems. Survivors (7-12 years old) of acute lymphoblastic leukemia (ALL) (n = 25) and their mothers, and healthy controls (n = 22) and their mothers engaged in parent-child interactions. Mothers completed a measure of children's psychosocial adjustment, and observations of 10-min parent-child interactions were obtained. Cancer survivorship moderated the relation between directiveness and children's withdrawn/depressed symptoms. Maternal directiveness was associated with increased withdrawn/depressed symptoms for children in the control group. This association was not significant for survivors of ALL. Findings suggest that childhood cancer may alter the context in which children experience maternal directiveness. | 25,224,583 | [
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Retrospective analysis of spinal trauma in patients with ankylosing spondylitis: a descriptive study in Indian population. | This study aims to understand the demographics, mode of trauma, hospital stay, complications, neurological improvement, mortality and expenditure incurred by Indian patients with spinal trauma and ankylosing spondylitis (AS). Retrospective analysis of the patient data admitted to a tertiary referral hospital from 2008 to 2013 with the diagnosis of AS and spinal trauma was carried out. The variables studied were demographics, mode of trauma, neurological status, neurological improvement, involved vertebral level, duration of hospital stay, comorbid factors, expenditure and complications during the stay. Forty-six patients with diagnosis of AS with spine trauma were admitted over the last 5 years with a total of 52 fractures. All were male patients; 58.6% had injury because of trivial trauma and 78.2% patients presented with neurological injury. C5 C6, C6 C7, C7 D1 and D12 were the most common injured level. Fractures through intervertebral disc were most common in cervical spine. Of the patients, 52.7% had shown neurological improvement of at least grade 1(AIS). Mean expenditure of patient admitted with spinal cord injury (SCI) with AS is 7957 USD (United States dollar), which is around five times the per capita income in India (as per year 2013). Males with AS are much more prone to spinal fractures than females and its incidence may be higher than previously reported. Domestic falls are the most common mechanism of spinal trauma in this population. High velocity injuries are associated with complete SCI. The study reinforces the need for development of subsidized spinal care services for SCI management. | 25,224,600 | [
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0.1001215,
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