title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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The impact of parental diagnosis of borderline personality disorder on offspring: learning from clinical practice. | The aim of this study was to explore mental health clinicians' opinions regarding the impact of a parental diagnosis of borderline personality disorder (BPD) on offspring and factors that may protect these children from developing emotional and/or behavioural difficulties. Expert opinions from 64 clinicians were collected through a voluntary and anonymous online qualitative survey. Thematic analysis of the data revealed five main themes relating to the impact of parental BPD symptoms on offspring. Children in these families were observed to develop behavioural, emotional and interpersonal difficulties, disturbances to cognitive processes and self dysfunction. A number of protective factors for offspring were also identified, such as supportive social networks, therapeutic intervention and child and parent characteristics. A model for the potential transgenerational transmission of emotional dysregulation from parent to child was proposed. | 25,200,499 | [
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Hematopoietic stem cell transplantation for sickle cell disease: state of the science. | Sickle cell disease (SCD) is an inherited disorder secondary to a point mutation at the sixth position of the beta chain of human hemoglobin resulting in the replacement of valine for glutamic acid. This recessive genetic abnormality precipitates the polymerization of the deoxygenated form of hemoglobin S inducing a major distortion of red blood cells (S-RBC), which decreases S-RBC deformability leading to chronic hemolysis and vaso-occlusion. These processes can result in severe complications including chronic pain, end-organ dysfunction, stroke, and early mortality. The only proven curative therapy for patients with SCD is myeloablative conditioning and allogeneic stem cell transplantation from HLA-matched sibling donors. In this review, we discuss the most recent advances in allogeneic stem cell transplantation in patients with SCD including more novel approaches such as reduced toxicity conditioning and the use of alternative allogeneic donors, including matched unrelated donors (MUDs), unrelated cord blood donors (UCBT), and familial haploidentical (FHI) donors. The results to date are very encouraging regarding allogeneic stem cell transplantation for patients with SCD including high survival rates and enabling a greater number of patients suffering from this chronic and debilitating condition to receive curative allogeneic stem cell therapies. However, we still have several areas to investigate and barriers to overcome to successfully cure the majority of patients with severe SCD through allogeneic stem cell therapies. | 25,200,500 | [
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Alternate deacylating specificities of the archaeal sirtuins Sir2Af1 and Sir2Af2. | Sirtuins were originally shown to regulate a wide array of biological processes such as transcription, genomic stability, and metabolism by catalyzing the NAD(+) -dependent deacetylation of lysine residues. Recent proteomic studies have revealed a much wider array of lysine acyl modifications in vivo than was previously known, which has prompted a reevaluation of sirtuin substrate specificity. Several sirtuins have now been shown to preferentially remove propionyl, succinyl, and long-chain fatty acyl groups from lysines, which has changed our understanding of sirtuin biology. In light of these developments, we revisited the acyl specificity of several well-studied archaeal and bacterial sirtuins. We find that the Archaeoglobus fulgidus sirtuins, Sir2Af1 and Sir2Af2, preferentially remove succinyl and myristoyl groups, respectively. Crystal structures of Sir2Af1 bound to a succinylated peptide and Sir2Af2 bound to a myristoylated peptide show how the active site of each enzyme accommodates a noncanonical acyl chain. As compared to its structure in complex with an acetylated peptide, Sir2Af2 undergoes a conformational change that expands the active site to accommodate the myristoyl group. These findings point to both structural and biochemical plasticity in sirtuin active sites and provide further evidence that sirtuins from all three domains of life catalyze noncanonical deacylation. | 25,200,501 | [
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The effect of aggression management training programmes for nursing staff and students working in an acute hospital setting. A narrative review of current literature. | Patient aggression is a longstanding problem in general hospital nursing. Staff training is recommended to tackle workplace aggression originating from patients or visitors, yet evidence on training effects is scarce. To review and collate current research evidence on the effect of aggression management training for nurses and nursing students working in general hospitals, and to derive recommendations for further research. Systematic, narrative review. Embase, MEDLINE, the Cochrane library, CINAHL, PsycINFO, pubmed, psycArticles, Psychology and Behavioural Sciences Collection were searched for articles evaluating training programs for staff and students in acute hospital adult nursing in a 'before/after' design. Studies published between January 2000 and September 2011 in English, French or German were eligible of inclusion. The methodological quality of included studies was assessed with the 'Quality Assessment Tool for Quantitative Studies'. Main outcomes i.e. attitudes, confidence, skills and knowledge were collated. Nine studies were included. Two had a weak, six a moderate, and one a strong study design. All studies reported increased confidence, improved attitude, skills, and knowledge about risk factors post training. There was no significant change in incidence of patient aggression. Our findings corroborate findings of reviews on training in mental health care, which point to a lack of high quality research. Training does not reduce the incidence of aggressive acts. Aggression needs to be tackled at an organizational level. | 25,200,511 | [
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Subgroup-dependent effects of voluntary alcohol intake on behavioral profiles in outbred Wistar rats. | Experimental animal models are critical for understanding the genetic, environmental and neurobiological underpinnings of alcohol use disorders. Limited studies investigate alcohol-induced effects on behavior using free-choice paradigms. The aims of the present experiment were to study voluntary alcohol intake using a modified intermittent access paradigm, investigate the effects of voluntary alcohol intake on behavioral profiles in water- and alcohol-drinking rats, and select extreme low- and high-drinking animals for a more detailed behavioral characterization. Sixty outbred male Wistar rats were randomized into water and alcohol groups. Behavioral profiles in the multivariate concentric square field™ (MCSF) test were assessed prior to and after voluntary alcohol intake. The animals had intermittent access to 20% alcohol and water for three consecutive days per week for seven weeks. The results revealed increased alcohol intake over time. No major alcohol-induced differences on behavior profiles were found when comparing water- and alcohol-drinking animals. The high-drinking animals displayed an alcohol deprivation effect, which was not found in the low-drinking animals. High-drinking rats had lower risk-taking behavior prior to alcohol access and lower anxiety-like behavior after voluntary alcohol intake compared to low-drinking rats. In conclusion, the modified intermittent access paradigm may be useful for pharmacological manipulation of alcohol intake. With regard to behavior, the present findings highlights the importance of studying subgroup-dependent differences and add to the complexity of individual differences in behavioral traits of relevance to the vulnerability for excessive alcohol intake. | 25,200,519 | [
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[Pathophysiology of spasticity]. | Spasticity is characterized by abnormal increase in phasic and velocity-dependent response to muscle stretching, such as exaggerated tendon jerks and clonus. Clasp-knife phenomenon is often observed in the affected muscles. Spasticity is caused by either an excess input to the spinal cord or a disordered descending control of the spinal motor system including the myotatic reflex arc. The increased input due to hyperactivity of γ motor neurons has not been demonstrated in human subjects. The hyperactivity of excitatory interneurons and decreased function of the inhibitory system interneurons in the spinal cord as well as the uncoupling of the inhibitory system from the central system are believed to be involved in spasticity; however, the underlying pathology may differ based on the lesion site and the time elapsed since loss of reciprocal inhibition. | 25,200,573 | [
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A sesquiterpene lactone from a medicinal herb inhibits proinflammatory activity of TNF-α by inhibiting ubiquitin-conjugating enzyme UbcH5. | UbcH5 is the key ubiquitin-conjugating enzyme catalyzing ubiquitination during TNF-α-triggered NF-κB activation. Here, we identified an herb-derived sesquiterpene lactone compound IJ-5 as a preferential inhibitor of UbcH5 and explored its therapeutic value in inflammatory and autoimmune disease models. IJ-5 suppresses TNF-α-induced NF-κB activation and inflammatory gene transcription by inhibiting the ubiquitination of receptor-interacting protein 1 and NF-κB essential modifier, which is essential to IκB kinase activation. Mechanistic investigations revealed that IJ-5 preferentially binds to and inactivates UbcH5 by forming a covalent adduct with its active site cysteine and thereby preventing ubiquitin conjugation to UbcH5. In preclinical models, pretreatment of IJ-5 exhibited potent anti-inflammatory activity against TNF-α- and D-galactosamine-induced hepatitis and collagen-induced arthritis. These findings highlight the potential of UbcH5 as a therapeutic target for anti-TNF-α interventions and provide an interesting lead compound for the development of new anti-inflammation agents. | 25,200,604 | [
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Cellular level robotic surgery: Nanodissection of intermediate filaments in live keratinocytes. | We present the nanosurgery on the cytoskeleton of live cells using AFM based nanorobotics to achieve adhesiolysis and mimic the effect of pathophysiological modulation of intercellular adhesion. Nanosurgery successfully severs the intermediate filament bundles and disrupts cell-cell adhesion similar to the desmosomal protein disassembly in autoimmune disease, or the cationic modulation of desmosome formation. Our nanomechanical analysis revealed that adhesion loss results in a decrease in cellular stiffness in both cases of biochemical modulation of the desmosome junctions and mechanical disruption of intercellular adhesion, supporting the notion that intercellular adhesion through intermediate filaments anchors the cell structure as focal adhesion does and that intermediate filaments are integral components in cell mechanical integrity. The surgical process could potentially help reveal the mechanism of autoimmune pathology-induced cell-cell adhesion loss as well as its related pathways that lead to cell apoptosis. | 25,200,612 | [
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Preliminary studies of the ICD-11 classification of personality disorder in practice. | This study aims to compare ICD-10 and putative ICD-11 classifications of personality disorder in different clinical populations. Prospective recording of ICD-10 and ICD-11 personality disorder classifications was carried out in (1) an anxious medical population, (2) an acute psychiatric in-patient population and (3) a retrospective recording of a mixed anxiety depression cohort in which all baseline data were scored from baseline information using the ICD-11 classification and compared with the original ICD-10 assessments. Comparison of ICD-10 and ICD-11 prevalence of personality disorder in each population was carried out. Data from 722 patients were recorded. Using the ICD-10 criteria, the prevalence of generic personality disorder was 33.8% compared with 40.4% using the ICD-11 ones (χ2 = 6.7; P < 0.01), with 103 (14.3%) discordant assessments. Using the severity definitions in ICD-11, 34.3% of patients had personality difficulty. Severity level varied greatly by population; severe personality disorder was five times more common in the inpatient group. The four domain traits originally denoted as qualifying severity in ICD-11, negative affective, dissocial, anankastic and detached, were linked to anxious, borderline, dissocial, anankastic and schizoid personality disorders in ICD-10. Many patients had pathology in two or more domains. The ICD-11 classification of personality disorder yields somewhat higher levels of personality dysfunction than ICD-10, possibly because the age range for the onset of diagnosis is now flexible. The range of severity levels make the classification more useful than ICD-10 in clinical practice as it identifies the greater pathology necessary for intervention. | 25,200,623 | [
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Self-assessment of alcohol consumption as a health-education strategy in nursing students. | In the field of preventive activities, early identification of excessive alcohol consumption is essential. The simplicity of existing instruments for detecting hazardous drinking makes for ready assimilation in university students. To ascertain nursing students' level of knowledge about alcohol prevention activities and assess their skills, acquired through self-assessment of their own alcohol consumption, in managing tools designed to detect hazardous drinkers. Before and after intervention study. We assessed 1060 nursing students and ascertained their level of knowledge about excessive alcohol consumption. Following an educational intervention in which students were taught to use the recommended screening instruments in clinical practice through self-assessment of their own consumption (Systematic Interview of Alcohol Consumption and Alcohol Use Disorders Inventory Test), we tested the skills acquired in detecting hazardous drinkers and their knowledge of alcohol prevention activities. Initially, the concept of hazardous drinker was known by only 24.1% of students and the method of quantifying alcohol consumption by only 3.1%. The prevalence of hazardous drinkers was 17.9% (95% CI: 15.5-20.3). After the educational intervention, 95.8% of students stated that they understood the concept of hazardous drinker and 92.5% stated that they understood how to quantify alcohol consumption, with these proportions being significantly higher than those obtained at baseline (p<0.001). When asked about the intervention's usefulness, 91.3% viewed it favourably. By using a simple educational intervention, nursing students can improve their knowledge and skill detection of hazardous drinkers and quantification of alcohol consumption. These concepts allow for students to be satisfactorily introduced into the prevention activities during their university education. After assessing their own consumption, a considerable proportion of students realise that they are indulging in excessive alcohol consumption, which could in turn make for greater awareness of the problem among future health professionals. | 25,200,633 | [
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Linking form to function: Biophysical aspects of artificial antigen presenting cell design. | Artificial antigen presenting cells (aAPCs) are engineered platforms for T cell activation and expansion, synthesized by coupling T cell activating proteins to the surface of cell lines or biocompatible particles. They can serve both as model systems to study the basic aspects of T cell signaling and translationally as novel approaches for either active or adoptive immunotherapy. Historically, these reductionist systems have not been designed to mimic the temporally and spatially complex interactions observed during endogenous T cell-APC contact, which include receptor organization at both micro- and nanoscales and dynamic changes in cell and membrane morphologies. Here, we review how particle size and shape, as well as heterogenous distribution of T cell activating proteins on the particle surface, are critical aspects of aAPC design. In doing so, we demonstrate how insights derived from endogenous T cell activation can be applied to optimize aAPC, and in turn how aAPC platforms can be used to better understand endogenous T cell stimulation. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling. | 25,200,637 | [
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Reduced-FOV excitation decreases susceptibility artifact in diffusion-weighted MRI with endorectal coil for prostate cancer detection. | The purposes of this study were to determine if image distortion is less in prostate MR apparent diffusion coefficient (ADC) maps generated from a reduced-field-of-view (rFOV) diffusion-weighted-imaging (DWI) technique than from a conventional DWI sequence (CONV), and to determine if the rFOV ADC tumor contrast is as high as or better than that of the CONV sequence. Fifty patients underwent a 3T MRI exam. CONV and rFOV (utilizing a 2D, echo-planar, rectangularly-selective RF pulse) sequences were acquired using b=600, 0s/mm(2). Distortion was visually scored 0-4 by three independent observers and quantitatively measured using the difference in rectal wall curvature between the ADC maps and T2-weighted images. Distortion scores were lower with the rFOV sequence (p<0.012, Wilcoxon Signed-Rank Test, n=50), and difference in distortion scores did not differ significantly among observers (p=0.99, Kruskal-Wallis Rank Sum Test). The difference in rectal curvature was less with rFOV ADC maps (26%±10%) than CONV ADC maps (34%±13%) (p<0.011, Student's t-test). In seventeen patients with untreated, biopsy confirmed prostate cancer, the rFOV sequence afforded significantly higher ADC tumor contrast (44.0%) than the CONV sequence (35.9%), (p<0.0012, Student's t-test). The rFOV sequence yielded significantly decreased susceptibility artifact and significantly higher contrast between tumor and healthy tissue. | 25,200,645 | [
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Roles of SATB2 in site-specific stemness, autophagy and senescence of bone marrow mesenchymal stem cells. | Craniofacial bone marrow mesenchymal stem cells (BMSCs) display some site-specific properties that differ from those of BMSCs derived from the trunk and appendicular skeleton, but the characteristics of craniofacial BMSCs and the mechanisms that underlie their properties are not completely understood. Previous studies indicated that special AT-rich binding protein 2 (SATB2) may be a potential regulator of craniofacial skeletal patterning and site-specific osteogenic capacity. Here, we investigated the stemness, autophagy, and anti-aging capacity of mandible-derived BMSCs (M-BMSCs) and tibia-derived BMSCs (T-BMSCs) and explored the role of SATB2 in regulating these properties. M-BMSCs not only possessed stronger expression of SATB2 and stemness markers (pluripotency genes, such as Nanog, OCT-4, Sox2, and Nestin) but also exhibited stronger autophagy and anti-aging capacities under normal or hypoxia/serum deprivation conditions compared to T-BMSCs. Exogenous expression of SATB2 in T-BMSCs significantly enhanced the expression of pluripotency genes as well as autophagy and anti-aging capacity. Moreover, SATB2 markedly enhanced osteogenic differentiation of BMSCs in vitro, and promoted bone defect regeneration and the survival of BMSCs that were transplanted into mandibles with critical size defects. Mechanistically, SATB2 upregulates pluripotency genes and autophagy-related genes, which in turn activate the mechanistic target of rapamycin signaling pathway. Collectively, our results provide novel evidence that site-specific BMSCs have distinct biological properties and suggest that SATB2 plays a potential role in regulating the stemness, autophagy, and anti-aging properties of craniofacial BMSCs. The application of SATB2 to manipulate stem cells for the reconstruction of bone defects might represent a new approach. | 25,200,657 | [
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Ventricular septal rupture, right ventricular dissection, and tricuspid chordae rupture--A rare complication after inferior and right ventricular infarction. | A 76-year-old man under stable hemodynamic condition was admitted to our hospital for delayed percutaneous coronary intervention following a diagnosis of acute inferior myocardial infarction. Bedside echocardiography revealed ventricular septal rupture at the basal posteroinferior wall with a large left-to-right shunt. Right ventricular free-wall intramyocardial dissection and tricuspid chordae rupture were noted. Coronary angiography demonstrated occlusion of the proximal right coronary artery, which was treated by balloon angioplasty and stenting. While preparing for surgical repair, the patient's overall cardiac and renal function deteriorated and surgery was contraindicated. The patient died 16 days after discharge. | 25,200,667 | [
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Investigating evolutionary lag using the species-pairs evolutionary lag test (SPELT). | For traits showing correlated evolution, one trait may evolve more slowly than the other, producing evolutionary lag. The species-pairs evolutionary lag test (SPELT) uses an independent contrasts based approach to detect evolutionary lag on a phylogeny. We investigated the statistical performance of SPELT in relation to degree of lag, sample size (species pairs), and strength of association between traits. We simulated trait evolution under two models: one in which trait X changes during speciation and the lagging trait Y catches up as a function of time since speciation; and another in which trait X evolves in a random walk and the lagging trait Y is a function of X at a previous time period. Type I error rates under "no lag" were close to the expected level of 5%, indicating that the method is not prone to false-positives. Simulation results suggest that reasonable statistical power (80%) is reached with around 140 species pairs, although the degree of lag and trait associations had additional influences on power. We applied the method to two datasets and discuss how estimation of a branch length scaling parameter (κ) can be used with SPELT to detect lag. | 25,200,679 | [
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Enforcement of a high-spin ground state for the first 3d heterometallic 12-metallacrown-4 complex. | Cu(II)(DMF)2Cl2[12-MC(Fe(III)N(Shi))-4](DMF)4·2DMF was synthesized as the first heterometallic transition metal 12-MC-4 complex. The purposeful placement of specific metal ions in the different sites of the metallacrown attains the establishment of a high-spin ground state. Inducing the anticipated superior exchange interactions, the central Cu(II) guest ion averts the common mutual cancellation of the spins, as is observed in the corresponding homometallic compounds. | 25,200,695 | [
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Quantitative simulation of ultrasonic time of flight diffraction technique in 2D geometries using Huygens-Fresnel diffraction model: theory and experimental comparison. | This article presents an analytical approach for simulation of ultrasonic diffracted wave signals from cracks in two-dimensional geometries based on a novel Huygens-Fresnel Diffraction Model (HFDM). The model employs the frequency domain far-field displacement expressions derived by Miller and Pursey in 2D for a line source located on the free surface boundary of a semi-infinite elastic medium. At each frequency in the bandwidth of a pulsed excitation, the complex diffracted field is obtained by summation of displacements due to the unblocked virtual sources located in the section containing a vertical crack. The time-domain diffracted wave signal amplitudes in a general isotropic solid are obtained by standard Fast Fourier Transform (FFT) procedures. The wedge based finite aperture transducer refracted beam profiles were modelled by treating the finite dimension transducer as an array of line sources. The proposed model is able to evaluate back-wall signal amplitude and lateral wave signal amplitude, quantitatively. The model predicted range-dependent diffracted amplitudes from the edge of a bottom surface-breaking crack in the isotropic steel specimen were compared with Geometrical Theory of Diffraction (GTD) results. The good agreement confirms the validity of the HFDM method. The simulated ultrasonic time-of-flight diffraction (TOFD) A-scan signals for surface-breaking crack lengths 2 mm and 4 mm in a 10 mm thick aluminium specimen were compared quantitatively with the experimental results. Finally, important applications of HFDM method to the ultrasonic quantitative non-destructive evaluation are discussed. | 25,200,698 | [
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Seasonal variation in night blindness incidence among Union soldiers in the US Civil War. | During the US Civil War, medical officers typically attributed night blindness among soldiers to malingering. A dietary basis was not generally suspected or appreciated. Incident cases of night blindness, scurvy, and diarrheal diseases, as well as mean troop strength among Union troops, were abstracted by month and race from tabulations of the US Surgeon General for the period from July 1861 through June 1866. Monthly incidence rates and annual incidence rates are presented as time series by race. Night blindness incidence was seasonal. Seasonal patterns of night blindness incidence were similar for white and black soldiers, although the peak incidence rates were approximately 2-3 times higher in black soldiers. The seasonal effect for white Union soldiers increased progressively to 1864. The seasonal pattern for night blindness roughly parallels that for scurvy and for diarrheal diseases. The peak season for night blindness incidence was summer, and the next highest season was spring. The mode of monthly incidence rates for diarrheal diseases slightly anticipated that for night blindness and scurvy. In addition, there was greater relative variation in monthly incidence for night blindness and scurvy than for diarrheal diseases. Nutritional night blindness occurred in a seasonal pattern among soldiers forced to subsist on nutritionally inadequate diets. The seasonal pattern is consistent with seasonal variations in the availability of foodstuffs with high vitamin A or provitamin A content, superimposed on marginal vitamin A reserves, and possibly exacerbated by co-occurring seasonal patterns of diarrheal disease. | 25,200,714 | [
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Strong conservation of rhoptry-associated-protein-1 (RAP-1) locus organization and sequence among Babesia isolates infecting sheep from China (Babesia motasi-like phylogenetic group). | Rhoptry-associated-protein 1 (RAP-1) is considered as a potential vaccine candidate due to its involvement in red blood cell invasion by parasites in the genus Babesia. We examined its value as a vaccine candidate by studying RAP-1 conservation in isolates of Babesia sp. BQ1 Ningxian, Babesia sp. Tianzhu and Babesia sp. Hebei, responsible for ovine babesiosis in different regions of China. The rap-1 locus in these isolates has very similar features to those described for Babesia sp. BQ1 Lintan, another Chinese isolate also in the B. motasi-like phylogenetic group, namely the presence of three types of rap-1 genes (rap-1a, rap-1b and rap-1c), multiple conserved rap-1b copies (5) interspaced with more or less variable rap-1a copies (6), and the 3' localization of one rap-1c. The isolates Babesia sp. Tianzhu, Babesia sp. BQ1 Lintan and Ningxian were almost identical (average nucleotide identity of 99.9%) over a putative locus of about 31 Kb, including the intergenic regions. Babesia sp. Hebei showed a similar locus organization but differed in the rap-1 locus sequence, for each gene and intergenic region, with an average nucleotide identity of 78%. Our results are in agreement with 18S rDNA phylogenetic studies performed on these isolates. However, in extremely closely related isolates the rap-1 locus seems more conserved (99.9%) than the 18S rDNA (98.7%), whereas in still closely related isolates the identities are much lower (78%) compared with the 18S rDNA (97.7%). The particularities of the rap-1 locus in terms of evolution, phylogeny, diagnosis and vaccine development are discussed. | 25,200,723 | [
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Increasing phosphorus supply is not the mechanism by which arbuscular mycorrhiza increase attractiveness of bean (Vicia faba) to aphids. | Arbuscular mycorrhizal (AM) fungi, important plant mutualists, provide plants with nutrients such as phosphorus (P) in return for carbon. AM fungi also enhance the attractiveness of plants to aphids via effects on emissions of plant volatiles used in aphid host location. We tested whether increased P uptake by plants is the mechanism through which AM fungi alter the volatile profile of plants and aphid behavioural responses by manipulating the availability of P and AM fungi to broad beans (Vicia faba L.) in a multi-factorial design. If AM fungi affect plant volatiles only via increased P acquisition, we predicted that the emission of volatiles and the attractiveness of mycorrhizal beans to aphids would be similar to those of non-mycorrhizal beans supplied with additional P. AM fungi and P addition increased leaf P concentrations by 40 and 24%, respectively. The production of naphthalene was less in mycorrhizal plants, regardless of P addition. By contrast, production of (S)-linalool, (E)-caryophyllene and (R)-germacrene D was less in plants colonized by AM fungi but only in the absence of P additions. The attractiveness of plants to pea aphids (Acyrthosiphon pisum Harris) was positively affected by AM fungi and correlated with the extent of root colonization; however, attractiveness was neither affected by P treatment nor correlated with leaf P concentration. These findings suggest that increased P uptake is not the main mechanism by which mycorrhiza increase the attractiveness of plants to aphids. Instead, the mechanism is likely to operate via AM fungi-induced plant systemic signalling. | 25,200,735 | [
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Two Enzyme Cooperatively Catalyzed Tandem Polymerization for the Synthesis of Polyester Containing Chiral (R)- or (S)-Ibuprofen Pendants. | An interesting cooperation between Candida antarctica Lipase B (CAL-B) and alkaline protease from Bacillus subtilis (BSP) in the copolymerization of bulky ibuprofen-containing hydroxyacid methyl ester (HAEP) and ε-caprolactone (ε-CL) is observed. This cooperation improved the M¯n of the polymers from 3130 (CAL-B) to 9200 g mol<sup-1</sup (CAL-B/BSP). Experimental results clearly indicate that CAL-B mainly catalyzes the ring-opening polymerization (ROP) of ε-CL under the initiation of HAEP to form the homopolymer of ε-CL, while BSP catalyzes the subsequent polycondensation of the ROP product to yield the copolymer with increased molecular weight. Furthermore, using suitable chemo-enzymatic methods, valuable polyesters with chiral (R)- or (S)-ibuprofen pendants can be tailor-made. | 25,200,738 | [
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The HIV-1 accessory protein Vpr induces the degradation of the anti-HIV-1 agent APOBEC3G through a VprBP-mediated proteasomal pathway. | The host anti-HIV-1 factor APOBEC3G (A3G) plays a potential role in restricting HIV-1 replication, although this antagonist can be encountered and disarmed by the Vif protein. In this paper, we report that another HIV-1 accessory protein, viral protein R (Vpr), can interact with A3G and intervene in its antiviral behavior. The interaction of Vpr and A3G was predicted by computer-based screen and confirmed by a co-immunoprecipitation (Co-IP) approach. We found that Vpr could reduce the virion encapsidation of A3G to enhance viral replication. Subsequent experiments showed that Vpr downregulated A3G through Vpr-binding protein (VprBP)-mediated proteasomal degradation, and further confirmed that the reduction of A3G encapsidation associated with Vpr was due to Vpr's degradation-inducing activity. Our findings highlight the versatility of Vpr by unveiling the hostile relationship between Vpr and A3G. In addition, the observation that A3G is targeted to the proteasomal degradation pathway by Vpr in addition to Vif implicates the existence of crosstalk between different HIV-1-host ubiquitin ligase complex systems. | 25,200,749 | [
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Short communication: Amino trap column improves the separation of methylimidazoles, 5-hydroxymethyl-2-furaldehyde, and sugars in Maillard reaction. | A simultaneous analysis of methylimidazoles, reducing sugars, and 5-hydroxymethyl-2-furaldehyde in the Maillard reaction was improved by use of an amino trap column. Analysis was carried out by using high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) coupled with an amino trap column. The amino trap column was a useful tool to improve the separation of methylimidazoles, reducing sugars, and 5-hydroxymethyl-2-furaldehyde. This technique is useful for simultaneous analysis of methylimidazoles, reducing sugars, and 5-hydroxymethyl-2-furaldehyde in risk assessment for dairy products. | 25,200,783 | [
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Intravesical bacillus Calmette-Guérin efficiently reduces p70S6K1 but not 4E-BP1 phosphorylation in nonmuscle invasive bladder cancer. | We characterized the functional consequences of intravesical bacillus Calmette-Guérin on the molecular mechanism of the AKT/mTOR signaling pathway in nonmuscle invasive bladder cancer. To our knowledge this has not been reported previously. At age 7 weeks female Fischer 344 rats received 1.5 mg/kg MNU intravesically every other week for 6 weeks. They were randomized at 10 per group to MNU (0.2 ml vehicle), bacillus Calmette-Guérin (10(6) cfu Connaught strain), rapamycin (15 μg/ml) and bacillus Calmette-Guérin plus simultaneous rapamycin, each intravesically for 6 weeks. At week 15 the bladders were collected for histopathology, immunohistochemistry and immunoblot to determine p-AKT, Rictor, Raptor, p-4E-BP1, p-p70S6K1, p-AMPK-α, p-mTOR and p-p53. Papillary carcinoma (pTa) and high grade intraepithelial neoplasia (pTis) predominated in the MNU group while normal urothelium, papillary and flat hyperplasia were more common in treated groups. Nonmuscle invasive bladder cancer treated with bacillus Calmette-Guérin showed suppression of p70S6K1 but not 4E-BP1 phosphorylation. This suggests that 4E-BP1 is regulated differently than p70S6K1, escaping the bacillus Calmette-Guérin action that occurs in a mTOR independent manner. The association of bacillus Calmette-Guérin with rapamycin but not rapamycin monotherapy affected p70S6K1 and 4E-BP1 phosphorylation with no features of in situ carcinoma (pTis). The activation status of p70S6K1 and 4E-BP1 might be used to stratify patients who could benefit from targeting such molecular elements with multitarget/multidrug intravesical therapy. In the future 4E-BP1 might be a worthwhile new target for bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer. | 25,200,808 | [
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Free-breathing, zero-TE MR lung imaging. | The investigation of three-dimensional radial, zero-echo time (TE) imaging for high-resolution, free-breathing magnetic resonance (MR) lung imaging using prospective and retrospective motion correction. Zero-TE was implemented similarly to the rotating-ultra-fast-imaging-sequence, providing 3D, isotropic, radial imaging with proton density contrast. Respiratory motion was addressed using prospective triggering (PT), prospective gating (PG) and retrospective gating (RG) with physiological signals obtained from a respiratory belt and interleaved pencil beam and DC navigators. The methods were demonstrated on four healthy volunteers at 3T. 3D, radial zero-TE imaging with high imaging bandwidth and nominally zero echo-time enables efficient capture of short-lived signals from the lung parenchyma and the vessels. Compared to Cartesian encoding, unaccounted for free-breathing respiration resulted in only benign blurring artifacts confined to the origin of motion. Breath holding froze respiration but achieved only limited image resolution (~1.8 mm, 30 s). PT and PG obtained similar quality expiratory-phase images at 1.2 mm resolution in ~6 min scan time. RG allowed multi-phase imaging in ~15 min, derived from eight individually stored averages. Zero-TE appears to be an attractive pulse sequence for 3D isotropic lung imaging. Prospective and retrospective approaches provide high-quality, free-breathing MR lung imaging within reasonable scan time. | 25,200,814 | [
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Diagnostic and remedial capability of transcervical falloposcopy in conjunction with laparoscopy. | Tubal factor accounts for 25-30% of cases of female infertility. Laparoscopy "Gold Standard" for tubal evaluation. However, it is known that during the initial infection of the fallopian tube mucosal damage occurs, a condition which plays a decisive role in reproduction. In this prospective randomized study, 468 infertile women with evidence of fallopian tube disease were included. In this, for 256 patients (group 1) after laparoscopic salpingolysis, salpingostomy we performed an additional step operation transcervical falloposcopy tubal dilatation (TFTD). 212 patients (group 2) produced only laparoscopic salpingolysis, salpingostomy. As a result, TFTD patency of the fallopian tubes for coaxial catheter was restored in 50 (78%) of 64 tubes with bilateral total occlusion, in 238 (93%) of 254 with partial occlusion of the bilateral, in 14 (58%) of 24 total unilateral occlusion and 26 (92%) of 28 with partial unilateral occlusion. Total number of pregnancies for one year in the first group of patients was 152 (59.3%), in the second 57 (27.1%), of which in the first group 147 -intrauterine pregnancies (57.4%) and in the second - 46 (21.7%). Falloposcopy surgeon provides good opportunities for the diagnosis and treatment of intralumen lesions. Significant increase in the frequency of uterine pregnancy in the case of an additional step - TFTD during salpingolysis, salpingostomy in patients with tubal factor infertility. | 25,200,821 | [
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Immunological and hemostasiological disorders in women with ovarian hyperstimulation syndrome. | To assess the markers of destabilization of homeostasis in women with ovarian hyperstimulation syndrome (OHSS), the investigation of the levels of cortisol, markers of renin-angiotensin-aldosterone system, endothelin, proinflammatory cytokines, acute phase proteins, and parameters of hemostasis was performed. Our survey involved 105 women who became pregnant after IVF: 21 women with symptoms of the early moderate and severe OHSS, 28 women with the late moderate and severe OHSS, and 56 pregnant women undergoing IVF without symptoms of OHSS. It was found significant increase of levels of cortisol, interleukins, the number of leucocytes, concentration of fibrinogen and D-dimers in patients with early and late OHSS. The development of late OHSS is associated with the lower level of IL-8 and ceruloplasmin. The OHSS is characterized by leukocytosis, higher level of IL-6, TNF-α, fibrinogen, D-dimers, thus reflecting the homeostasis imbalance. The determination of the level of fibrinogen, D-dimers, leukocytes can be an important screening test of the intensity of the inflammatory process in patients with OHSS. | 25,200,828 | [
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Promoter methylation and expression of the VANGL2 gene in the myocardium of pediatric patients with tetralogy of fallot. | Tetralogy of Fallot (ToF) is the most common form of cyanotic congenital heart disease and is a major cause of significant morbidity and mortality. VANGL2 is a critical gene in the planar cell polarity pathway that plays an important role in the development of the heart. This study investigates the methylation status of the promoter region of VANGL2 and the expression pattern of VANGL2 in cardiac tissue. The promoter region of VANGL2 was sequenced in 200 ToF patients and 400 control subjects. Methylation levels were measured in four regions of the VANGL2 promoter (B1-1: -282 bp ∼ -117 bp, B1-2: -117 bp ∼ 41 bp, B2: 8 bp ∼ 157 bp, B3: 132 bp ∼ 401 bp) by bisulfite sequencing PCR in the right ventricular outflow tract of the myocardium. Quantitative real-time PCR and immunohistochemistry were used to detect the mRNA and protein expression levels, respectively. No mutations were found in the promoter region, but two SNPs (rs11582932 T>G, rs11265385 T>G) were found in ToF patients and controls with similar frequencies (p>0.05). The overall methylation status of the VANGL2 promoter was significantly higher in ToF patients than in controls (p=0.0234). Specifically, the methylation levels of regions B1-1 and B3 were significantly higher in ToF patients (p=0.0042, p=0.0418). Both the VANGL2 mRNA and protein levels were significantly lower in ToF patients than in controls (p<0.05). The aberrant VANGL2 promoter methylation and the decreased gene expression in ToF patients may provide important clues for the development of ToF. | 25,200,836 | [
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Fat-free mass loss generated with weight loss in overweight and obese adults: What may we expect? | There is concern that intentional weight loss may generate excessive loss of fat-free mass (FFM). Idealists target minimal loss of FFM, while others consider that FFM loss of up to 25% of weight loss is acceptable. In a cross-sectional study of 275 weight-stable, overweight or obese adults, we used whole-body dual-energy X-ray absorptiometry to measure FFM. A range of models was used to estimate the expected ΔFFM/Δweight ratio required to attain the body composition of a weight-stable individual at a lower body mass index (BMI). Higher BMI was associated linearly with higher FFM in men and women. Proportional ΔFFM/Δweight was influenced by sex, BMI and age. Direct scatter plot analysis, quadratic curve fit modelling and linear FFM-BMI modelling provided similar estimates for each model of ΔFFM/Δweight ratio, with 40% for men and 33% for women. These results show that the 25% rule is inappropriate and our estimates are higher than those generally reported after intentional weight loss indicating favourable preservation of FFM. | 25,200,854 | [
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USA300 methicillin-resistant Staphylococcus aureus in Zurich, Switzerland between 2001 and 2013. | USA300 methicillin-resistant Staphylococcus aureus (MRSA) is the most prevalent MRSA in the United States of America (USA) and a global epidemic threat. We investigated the prevalence of USA300 at a tertiary care hospital in Zurich, Switzerland, where all MRSA strains have been collected and PFGE typed since 1992. These strains were retrospectively compared to the PFGE pattern of USA300 strain JE2. Isolates with a respective PFGE pattern were spa-typed and tested for the presence of the arginine catabolic mobile element (ACME) arc gene cluster and Panton-Valentine Leucocidin (PVL) genes. The first MRSA strain with a USA300 PFGE pattern was isolated in 2001 from a patient visiting from the USA. USA300 strains represented between 0% (in 2002) and 9.2% (in 2012) of all MRSA isolates in our hospital. We identified various USA300 subtypes based on either the PFGE pattern, the spa-type or absence of either the PVL genes or ACME arc gene cluster. All the USA300 strains including the variants (n=47) accounted for 5.6% of all MRSA isolates typed between 2001 and 2013 and reached a maximum of 14.5% in 2009. They predominantly caused skin and soft tissue infections (74.4%). In conclusion, even though USA300 has been present in our hospital for over twelve years it has not become the predominant MRSA clone like in the USA. However, in light of the global burden of USA300, care must be taken to further contain the spread of this lineage and of MRSA in general in our hospital. | 25,200,859 | [
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An evaluation of eye tracking technology in the assessment of 12 lead electrocardiography interpretation. | This study investigated eye tracking technology for 12 lead electrocardiography interpretation to Healthcare Scientist students. Participants (n=33) interpreted ten 12 lead ECG recordings and randomized to receive objective individual appraisal on their efforts either by traditional didactic format or by eye tracker software. One hundred percent of participants reported the experience positively at improving their ECG interpretation competency. ECG analysis time ranged between 13.2 and 59.5s. The rhythm strip was the most common lead studied and fixated on for the longest duration (mean 9.9s). Lead I was studied for the shortest duration (mean 0.25s). Feedback using eye tracking data during ECG interpretation did not produce any significant variation between the assessment marks of the study and the control groups (p=0.32). Although the hypothesis of this study was rejected active teaching and early feedback practices are recommended within this discipline. | 25,200,901 | [
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Timelines in the management of adrenal crisis - targets, limits and reality. | To evaluate current management timelines in adrenal crisis (AC) and to establish time targets and time limits for emergency treatment. Patients from a prospective study who had reported an AC (n = 46) were contacted and asked about management of their AC. A survey among 24 European endocrinologists collected expert recommendations concerning time targets and time limits for contact-arrival time of emergency health professionals and presentation of emergency card-glucocorticoid (GC) injection time. Median time targets and time limits regarded by experts as adequate for contact-arrival time were 45 and 90 min, respectively, and for card-injection time 15 and 30 min, respectively. Thirty-seven of 46 patients could be interviewed. All patients were equipped with an emergency card but only 23 (62%) with an emergency kit. Seven patients (19%) were trained in GC self-injection. The median time interval between contacting a health professional and arrival was 20 min (range 2-2880 min); ≤45 min: n = 32 (86%), <90 min: n = 34 (92%). The median time interval between arrival and administration of GC was 30 min (range 2-2400 min); ≤15 min: n = 17 (46%), ≤30 min: n = 20 (54%). While the time between contacting health professionals and their arrival was within the limits set by experts, initiation of GC administration was delayed in 46% of patients. Thus, improved management of AC needs to focus on shortening the presentation of card-injection time. Given the current reality in the management of AC, promotion of self-injection of GC (s.c. or i.m.) is warranted. | 25,200,922 | [
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Upconverting nanoparticles with a mesoporous TiO₂ shell for near-infrared-triggered drug delivery and synergistic targeted cancer therapy. | Malignant tumors remain a major health burden throughout the world and effective therapeutic strategies are urgently needed. Herein, we report the synthesis of upconverting nanoparticles with a mesoporous TiO2 (mTiO2) shell for near-infrared (NIR)-triggered drug delivery and synergistic targeted cancer therapy. The NaGdF4:Yb,Tm could convert NIR light to UV light, which activated the mTiO2 to produce reactive oxygen species for photodynamic therapy (PDT). Due to the large surface area and porous structure, the mTiO2 shell endowed the nanoplatform with another functionality of anticancer drug loading for chemotherapy. The hyaluronic acid modified on the surface not only promised controlled drug release but also conferred targeted ability of the system toward cluster determinant 44 overexpressed cancer cells. More importantly, cytotoxicity experiments demonstrated that combined therapy mediated the highest rate of death of breast carcinoma cells compared with that of single chemotherapy or PDT. | 25,200,923 | [
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Differential expression of THELPER 1 cytokines upon antigen stimulation predicts ex vivo proliferative potential and cytokine production of virus-specific T cells following re-stimulation. | Cytomegalovirus (CMV) and human adenovirus (ADV) infections are causes of morbidity after stem cell transplantation. Antigen (Ag)-specific T cells are essential for the control of viral infections. However, in vivo expansion potential of T-cell subpopulations is hardly predictable in humans. Furthermore, ex vivo identification of human T cells with repopulating capacity for adoptive T-cell transfer has been difficult. We analyzed Ag-specific T-cell populations, subdivided according to the expression of different THELPER- 1 (Th1) cytokines. Isolation by flow cytometry was based on interferon-gamma (IFN)-γ, interleukin (IL)-2, or tumor necrosis factor-alpha (TNF-α) secretion of T cells after ex vivo stimulation with the Ags hexon (for ADV) and pp65 (for CMV). Isolated T cells were expanded and examined for functional characteristics, expansion/differentiation potential, and naïve, effector memory, central memory, and late effector phenotypes. Isolation based on IFN-γ production provides a T-cell population with a mixture of early, central memory, and effector memory T cells, high expansion potential, and effective cytokine production. Selection of T cells with Ag-specific expression of IL-2 or TNF-α, however, results in a T-cell population with reduced proliferation and lower effector potential after expansion. We conclude that the exclusive secretion of IFN-γ in the human antiviral T-cell responses preferentially leads to higher repopulation capacities of antiviral T cells, compared to IL-2 or TNF-α secreting T-cell populations. | 25,200,928 | [
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Consensus guidelines for glycemic monitoring in type 1/type 2 & GDM. | Stringent monitoring of blood glucose in diabetes plays an important role as the treatment of the disease itself. Blood glucose monitoring (BGM) strategies such as measurement of Hb1Ac, Self-Monitoring of Blood Glucose (SMBG) and Continuous Glucose Monitoring (CGM) plays a vital role in achieving the important goal of preventing long term complications of diabetes. Although the use of BGM is recommended by various international guidelines in T1DM and T2DM, there is no consensus on the utility of BGM in India. So, there is a need to develop a guidance for uniform monitoring mechanism among the care givers taking into account the variations and challenges that are unique to Indian population. A committee was established that comprised of physicians, researchers and other healthcare professionals having expertise in diabetes treatment to oversee the formulation of guidelines on different monitoring and treatment aspects of diabetes. Extensive literature searches were conducted to identify and analyze the evidence available on BGM. An initial draft of BGM guidelines was presented to core members who discussed the subject matter and presented their opinion. This was then taken to wider expert audience to invite their comments that were incorporated in the initial draft. The first compilation was presented at a conference attended by nearly 200 experts. Again, their opinion was sought and the next version was prepared which was sent to core committee members for the final inputs. The Indian consensus guideline on BGM using Hb1Ac, SMBG and CGM as the primary tools was then finalized. | 25,200,925 | [
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Metabolomics of AS-5 RBC supernatants following routine storage. | The safety and efficacy of stored red blood cells (RBCs) transfusion has been long debated due to retrospective clinical evidence and laboratory results, indicating a potential correlation between increased morbidity and mortality following transfusion of RBC units stored longer than 14 days. We hypothesize that storage in Optisol additive solution-5 leads to a unique metabolomics profile in the supernatant of stored RBCs. Whole blood was drawn from five healthy donors, RBC units were manufactured, and prestorage leucoreduced by filtration. Samples were taken on days 1 and 42, the cells removed, and mass spectrometry-based metabolomics was performed. The results confirmed the progressive impairment of RBC energy metabolism by day 42 with indirect markers of a parallel alteration of glutathione and NADPH homeostasis. Moreover, oxidized pro-inflammatory lipids accumulated by the end of storage. The supernatants from stored RBCs may represent a burden to the transfused recipients from a metabolomics standpoint. | 25,200,932 | [
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Tunnel communication and increased graft signal intensity on magnetic resonance imaging of double-bundle anterior cruciate ligament reconstruction. | This study aimed to evaluate the association between magnetic resonance imaging (MRI) findings of tunnel communication and increased graft signal intensity (SI) and clinical evaluation of knee stability and outcome after double-bundle (DB) anterior cruciate ligament (ACL) reconstruction. Fifty-nine patients were evaluated with 1.5 T MRI and with clinical evaluation 2 years after DB ACL reconstruction. The MRI finding of tunnel communication was defined as the absence of a bony bridge between the anteromedial (AM) and posterolateral (PL) tunnels. The SI of the intra-articular portion of both grafts was analyzed on proton-density (PD)-weighted and T2-weighted images and graded on a scale, with I being a normal SI similar to that of the posterior cruciate ligament, II being > 50% of the graft having a normal SI, and III being < 50% of the graft having a normal SI. The clinical evaluation of knee stability and function included KT-1,000 arthrometric side-to-side difference, pivot shift test, and International Knee Documentation Committee (IKDC) and Lysholm knee evaluation scores. The association between the MRI findings and the clinical findings was calculated using the Fisher exact test and the 2-tailed t test. Tunnel communication was seen in the femur in 10% of patients and in the tibia in 27% of patients. Increased graft SI was seen in 15% of the AM grafts and 59% of the PL grafts. No statistically significant association (P < .05) between the MRI findings of tunnel communication or increased graft SI and knee laxity was found. The MRI findings of tunnel communication or increased graft SI were not associated with knee laxity 2 years after DB ACL reconstruction. Tibial tunnel communication was associated with increased range of movement with flexion, and increased AM graft SI was associated with reduced range of flexion in the knee. Level IV, therapeutic case series. | 25,200,943 | [
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Mothers' perceptions of family centred care in neonatal intensive care units. | To explore mothers' perceptions of family centred care (FCC) in neonatal intensive care units (NICUs) in England. The qualitative experiences of 12 mothers from three NICUs in the UK were elicited using individual interviews. A thematic network analysis was conducted on the transcribed interviews A central global theme supported by a number of organizing themes were developed reflecting the views of the mothers and their experiences of FCC. A global theme of "Finding My Place" was identified, supported by six organizing themes: Mothering in Limbo; Deference to the Experts; Anxious Surveillance; Muted Relations, Power Struggles and Consistently Inconsistent. Mothers experienced a state of liminality and were acutely sensitive to power struggles, awkward relationships and inconsistencies in care. To try to maintain their equilibrium and protect their baby they formed deferential relationships with health professionals and remained in a state of anxious surveillance. This study illustrates that despite the rhetoric around the practice of FCC in NICUs, there was little in the mother's narratives to support this. It is of the utmost importance to minimize the consequences of the liminal experience, to improve staff-mother interactions and to facilitate mothers' opportunities to be primary caregivers. | 25,200,972 | [
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Fathers' perception of information received during their infants' stay at a neonatal intensive care unit. | To explore fathers' perception of information received during their infants' care at a neonatal intensive care unit (NICU). An inductive, qualitative and descriptive study. Eight fathers in two units were interviewed. The infants' gestational age at birth ranged between 23 and 36 weeks. Data were collected through semi-structured, individual interviews and were analyzed by qualitative content analysis. Three categories were identified: perception of information, perception of the source of information, and circumstances influencing the perception of information. Information had an important impact; comprehensible and adequate information increased the fathers' knowledge, which generated a sense of control. Early information about the infant's care was particularly important and positively affected father and infant bonding. Ensuring a high quality of information is an important task for NICU staff. Fathers' perception of the quality of information depended on the contents of the information and how it was conveyed. Comprehensible information at the onset of the infant's hospital stay increased the fathers' sense of security, and made them feel in control. It is important that the staff strive to identify what information the father requires, and prevent situations when fathers feel uncertainty about what the staff expect from them. | 25,200,974 | [
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Folate, vitamin B-6, and vitamin B-12 intake and mild cognitive impairment and probable dementia in the Women's Health Initiative Memory Study. | Whether higher B vitamin intake (ie, B-6, B-12, and folate) is protective against cognitive decline in later life remains uncertain. Several prospective, observational studies find higher B vitamin intake to be associated with lower risk of dementia; other studies, including most trials of B vitamin supplementation, have observed no effect on cognition. We examined this question in a large population of older women carefully monitored for development of mild cognitive impairment (MCI) and probable dementia. To determine whether baseline folate, vitamin B-6, and/or vitamin B-12 intake, alone or in combination, are associated with incident MCI/probable dementia among older women. Prospective, longitudinal cohort study. Participants were enrolled between 1993 and 1998, and B vitamin intake was self-reported using a food frequency questionnaire administered at baseline. Postmenopausal women (N=7,030) free of MCI/probable dementia at baseline in the Women's Health Initiative Memory Study. Over a mean follow-up of 5.0 years, 238 cases of incident MCI and 69 cases of probable dementia were identified through rigorous screening and expert adjudication. Cox proportional hazard models adjusting for sociodemographic and lifestyle factors examined the association of B vitamin intake above and below the Recommended Daily Allowance and incident MCI/probable dementia. Folate intake below the Recommended Daily Allowance at study baseline was associated with increased risk of incident MCI/probable dementia (hazard ratio 2.0, 95% CI 1.3 to 2.9), after controlling for multiple confounders. There were no significant associations between vitamins B-6 or B-12 and MCI/probable dementia, nor any evidence of an interaction between these vitamins and folate intake. Folate intake below the Recommended Daily Allowance may increase risk for MCI/probable dementia in later life. Future research should include long-term trials of folic acid supplementation to examine whether folate may impart a protective effect on cognition in later life. | 25,201,007 | [
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Test-retest reliability of (11)C-ORM-13070 in PET imaging of α2C-adrenoceptors in vivo in the human brain. | α2C-Adrenoceptors share inhibitory presynaptic functions with the more abundant α2A-adrenoceptor subtype, but they also have widespread postsynaptic modulatory functions in the brain. Research on the noradrenergic system of the human brain has been hampered by the lack of suitable PET tracers targeted to the α2-adrenoceptor subtypes. PET imaging with the specific α2C-adrenoceptor antagonist tracer [(11)C]ORM-13070 was performed twice in six healthy male subjects to investigate the test-retest reliability of tracer binding. The bound/free ratio of tracer uptake relative to nonspecific uptake into the cerebellum during the time interval of 5 - 30 min was most prominent in the dorsal striatum: 0.77 in the putamen and 0.58 in the caudate nucleus. Absolute test-retest variability in bound/free ratios of tracer ranged from 4.3 % in the putamen to 29 % in the hippocampus. Variability was also <10 % in the caudate nucleus and thalamus. Intraclass correlation coefficients (ICC) ranged from 0.50 in the hippocampus to 0.89 in the thalamus (ICC >0.70 was also reached in the caudate nucleus, putamen, lateral frontal cortex and parietal cortex). The pattern of [(11)C]ORM-13070 binding, as determined by PET, was in good agreement with receptor density results previously derived from post-mortem autoradiography. PET data analysis results obtained with a compartmental model fit, the simplified reference tissue model and a graphical reference tissue analysis method were convergent with the tissue ratio method. The results of this study support the use of [(11)C]ORM-13070 PET in the quantitative assessment of α2C-adrenoceptors in the human brain in vivo. Reliable assessment of specific tracer binding in the dorsal striatum is possible with the help of reference tissue ratios. | 25,201,008 | [
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Lactic acidosis treatment by nanomole level of spermidine in an animal model. | Lactic acidosis occurs in a number of clinical conditions, e.g. in surgeries, orthotopic liver transplant, and anesthetic agent administration, which has deleterious effects on the patient's survival. The most rational therapy for these patients, the sodium bicarbonate administration, cannot prevent those accompanying deficiencies and may actually be harmful. In addition, tromethamine adjusts the blood pH, it does not affect the lactate accumulation. Therefore, discovery of a therapeutic agent is still a major unsolved problem. In this study, the rats were divided into different groups and lactic acidosis type B was induced in them. Then, the effect of different injection doses of spermidine (0-20nmol) on lactic acidosis was analyzed by measuring the lactate level and pH in the rat blood samples. The results showed that spermidine effectively and simultaneously inhibited the lactate and pyruvate accumulations, and also adjusted the pH of bloodstream. On the other hand, it has been shown (Damuni et al., 1984; Rahmatullah and Roche, 1988) that spermidine increases the activity of phosphatase, leading to prevention of lactate accumulation. The results indicate that administration of only nanomole level of spermidine may be the best treatment in the liver transplant and other patients suffering from lactic acidosis type B. | 25,201,010 | [
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Renewed impact of lidocaine on refractory ventricular arrhythmias in the amiodarone era. | Recent guidelines for treating ventricular fibrillation (VF) and ventricular tachycardia (VT) stress class III antiarrhythmic drugs, but some malignant arrhythmias refractory to these agents still occur in clinical practice. The possibility of a new treatment strategy involving lidocaine and amiodarone combination therapy was evaluated. From September 2008 to September 2013, 62 patients were treated at our hospital with lidocaine. The medical records were retrospectively reviewed. Twenty inappropriate patients were excluded. The remaining 42 patients were analyzed. Patients were divided into two groups according to the effectiveness of lidocaine in terminating refractory ventricular arrhythmias: the effective group. LVEF was significantly higher in the lidocaine effective (E) group compared to the ineffective (I) group (44±16% vs. 32±10%, p=0.027). There were more patients already on amiodarone at the start of lidocaine therapy in the E group compared to the I group (11/26 vs. 1/16, p=0.012). Furthermore, patients receiving lidocaine without amiodarone were re-analyzed to estimate the actual effect of lidocaine. Of the 30 patients not receiving amiodarone, 15 were in the effective without amiodarone (E w/o A) group and 15 were in the ineffective without amiodarone (I w/o A) group. LVEF was significantly higher in the E w/o A group than in the I w/o A group (51±16% vs. 32±9%, p=0.001). This retrospective study suggests that combination therapy with lidocaine and amiodarone can terminate most refractory ventricular arrhythmias. Even in patients with a sufficient LVEF not receiving amiodarone, it is possible that lidocaine can contribute to a favorable outcome. | 25,201,023 | [
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Quercetin alleviates myocyte toxic and sensitizes anti-leukemic effect of adriamycin. | Objectives Derived from plants, flavonoids have been proven to possess anti-cancer activities. Adriamycin (ADM), an anthracycline antibiotic, is widely applied in the chemotherapy for leukemia; however, it has a side effect of heart damage. This study aims to explore potential anti-leukemia effects of quercetin (Que) and the underlying mechanism. Methods The P388 xenograft mice models were first established and then treated with Que alone or in combination with ADM. Subsequently, we evaluated their effects on cell proliferation and apoptosis by observing the cell cycle and detecting the Caspase-3 level, respectively. The underlying pro-apoptotic mechanism was further investigated by detecting the expression levels of NF-κB, Bcl-2, and Bax. The cardiomyocyte ultrastructural changes of P388 leukemic mice after drug treatment were also observed. The protective effect of Que on cardiomyocyte was evaluated by detecting enzymatic activity changes of glutathione peroxidase, superoxide dismutase, and malondialdehyde. Results Compared with ADM group, the combination of ADM and Que showed prolonged survival time and less peripheral white blood cells. Que could sensitize the anti-leukemic effect of ADM by inhibiting the proliferation of white blood cells through trapping the cells at the S phase; caspase-3 was activated via the expressional regulation of Bcl-2, Bax, and NF-κB. When applied in combination with ADM, Que could attenuate heart damage by cleaning the reactive oxygen species. Conclusion Our study may provide informative evidences for the underlying mechanism of anti-cancer effects of Que and sheds light on the clinical application of Que in leukemia treatment. | 25,201,038 | [
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IBD: Faecal calprotectin testing--the need for better standardization. | Measurement of faecal calprotectin concentration is increasingly used to assess disease activity in patients with IBD. Lasson et al. have now demonstrated that calprotectin concentrations in faeces of patients with mild or moderate left-sided or extensive ulcerative colitis vary considerably and have questioned the long-term stability of calprotectin when stored at room temperature. | 25,201,042 | [
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Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness-eveningness preference and circadian rhythm sleep disorder. | A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep-wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness-eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes. | 25,201,053 | [
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Chronic kidney disease status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation. | There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients with dual antiplatelet therapy. Chronic kidney disease (CKD) is associated with increased risk of cardiovascular event, but the association between the possession of CYP2C19 loss-of-function (LOF) alleles and clinical outcome according to the presence of CKD is poorly understood. The aim of this study was to investigate whether CKD status modifies the association of CYP2C19 polymorphism in predicting outcomes in a prospective cohort study. We enrolled 331 patients following coronary stent implantation. Patients were divided into two groups: CKD (n=154) and non-CKD (n=177). Platelet reactivity and CYP2C19 polymorphism were examined. The subjects were further divided into two groups according to the possession of CYP2C19 LOF alleles: carriers and non-carriers. Patients were followed up and clinical events were evaluated according to CKD and carrier status. The proportion of high platelet reactivity was significantly higher in carriers than in non-carriers in both CKD (42.4% versus 21.7%; P=0.016) and non-CKD groups (34.3% versus 3.7%; P<0.001). In the non-CKD group alone, the incidence of cardiovascular events was significantly higher in carriers than in non-carriers (13.7% versus 1.7%; P=0.013). Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers than in non-carriers in the non-CKD group (log-rank test: P=0.013) and there was no significant difference in the CKD group (log-rank test: P=0.591). Multivariate analysis identified carriers as an independent predictor of cardiovascular events only in the non-CKD group alone (hazard ratio: 8.048; 95% confidence interval: 1.066 to 60.757; P=0.043). CYP2C19 polymorphism significantly correlates with clinical outcome in non-CKD patients, and CKD status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation. | 25,201,060 | [
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Proteomics of apheresis platelet supernatants during routine storage: Gender-related differences. | Proteomics has identified potential pathways involved in platelet storage lesions, which correlate with untoward effects in the recipient, including febrile non-haemolytic reactions. We hypothesize that an additional pathway involves protein mediators that accumulate in the platelet supernatants during routine storage in a donor gender-specific fashion. Apheresis platelet concentrates were collected from 5 healthy males and 5 females and routinely stored. The 14 most abundant plasma proteins were removed and the supernatant proteins from days 1 and 5 were analyzed via 1D-SDS-PAGE/nanoLC-MS/MS, before label-free quantitative proteomics analyses. Findings from a subset of 18 proteins were validated via LC-SRM analyses against stable isotope labeled standards. A total of 503 distinct proteins were detected in the platelet supernatants from the 4 sample groups: female or male donor platelets, either at storage day 1 or 5. Proteomics suggested a storage and gender-dependent impairment of blood coagulation mediators, pro-inflammatory complement components and cytokines, energy and redox metabolic enzymes. The supernatants from female donors demonstrated increased deregulation of structural proteins, extracellular matrix proteins and focal adhesion proteins, possibly indicating storage-dependent platelet activation. Routine storage of platelet concentrates induces changes in the supernatant proteome, which may have effects on the transfused patient, some of which are related to donor gender. The rationale behind this study is that protein components in platelet releasates have been increasingly observed to play a key role in adverse events and impaired homeostasis in transfused recipients. In this view, proteomics has recently emerged as a functional tool to address the issue of protein composition of platelet releasates from buffy coat-derived platelet concentrates in the blood bank. Despite early encouraging studies on buffy coat-derived platelet concentrates, platelet releasates from apheresis platelets have not been hitherto addressed by means of extensive proteomics technologies. Indeed, apheresis platelets are resuspended in donors' plasma, which hampers detection of less abundant proteins, owing to the overwhelming abundance of albumin (and a handful of other proteins), and the dynamic range of protein concentrations of plasma proteins. In order to cope with these issues, we hereby performed an immuno-affinity column-based depletion of the 14 most abundant plasma proteins. Samples were thus assayed via GeLC-MS, a workflow that allowed us to cover an unprecedented portion of the platelet supernatant proteome, in comparison to previous transfusion medicine-oriented studies in the literature. Finally, we hereby address the issue of biological variability, by considering the donor gender as a key factor influencing the composition of apheresis platelet supernatants. As a result, we could conclude that platelet supernatants from male and female donors are not only different in the first place, but they also store differently. This conclusion has been so far only suggested by classic transfusion medicine studies, but has been hitherto unsupported by actual biochemistry/proteomics investigations. In our opinion, the main strengths of this study are related to the analytical workflow (immunodepletion and GeLC-MS) and proteome coverage, the translational validity of the results (from a transfusion medicine standpoint) and the biological conclusion about the intrinsic (and storage-dependent) gender-related differences of platelet supernatants. | 25,201,077 | [
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Relationship between the adsorption species of cesium and radiocesium interception potential in soils and minerals: an EXAFS study. | This study examined the radiocesium (RCs) interception potential (RIP), cation exchange capacity (CEC), total organic carbon (TOC) content, and adsorption species in soils and minerals by using extended X-ray absorption fine structure (EXAFS) spectroscopy. The RIP related to Cs(+) adsorption by frayed-edge site (FES) has often been used to measure the mobility and bioavailability of RCs in the environment. This study found that the presence of organic matter (OM) can reduce RIP to a certain extent. The adsorption amount (=Q(T)) in soil was obviously correlated to RIP at a small [Cs(+)] region, whereas a linear relationship between Q(T) and CEC was observed at a large [Cs(+)] region. Both the inner-sphere (IS) and outer-sphere (OS) complexes of Cs(+) were observed through EXAFS at a molecular scale. The linear correlation between log (RIP/CEC) and the ratio of the coordination number (CN) of IS (=CNIS) and OS (=CNOS) complexes noted as CNIS/(CNIS + CNOS) suggested that the ratio of CN is very sensitive to Cs(+) adsorption species with variable RIP and CEC. The adsorption species of Cs(+) in soil was mainly dependent on the clay mineral content of soil. RIP was affected not only by FES but also by other strong adsorption sites, such as the interlayers and cavities identified as the IS complex in EXAFS analysis. Findings indicated that the EXAFS approach is a powerful and efficient tool to explore the behavior of Cs(+) in a given environment. | 25,201,086 | [
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Manipulation of RNA using engineered proteins with customized specificity. | A large number of RNA-binding proteins play critical roles in controlling eukaryotic gene expression at multiple RNA-processing steps. Many of these proteins have modular configuration, containing a RNA binding domain to recognize their target and functional module to affect RNA metabolism. This simple configuration motivated the design of artificial factors that specifically manipulate RNA. While significant progress has been made since 1990s to engineer DNA binding proteins with designed specificity, design of analogous RNA binding factors was not practical until recently. With the increasing complexity of biological pathways involving RNA regulation, engineering RNA binding factors with customized specificity and function has become an emerging field of research. Such factors can serve as novel method to manipulate RNA metabolism and thus are very useful in basic biological and medical research. Here we discuss the current advances in engineering RNA binding proteins, with emphasis on the design principles and their potential applications as new therapeutic reagents and basic biological tools. | 25,201,107 | [
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Mid-regional pro-adrenomedullin: an indicator of the failing Fontan circuit in patients with univentricular hearts? | In patients after the Fontan procedure, assessment of a failing Fontan circuit is difficult. Natriuretic peptides failed to be reliable markers of functional status or systemic ventricular function in this patient cohort. The aim of the study was to assess the clinical utility of mid-regional pro-adrenomedullin (MR-proADM) in patients after the Fontan procedure. Plasma MR-proADM levels were measured in 53 patients after the Fontan procedure and compared with clinical status, echocardiographic, and laboratory parameters including NT-proBNP. Median MR-proADM levels were 0.668 nmol/L in patients with a failing Fontan circuit as compared with 0.357 nmol/L in those without Fontan failure (P = 0.001). Levels of MR-proADM were significantly related to the presence of Fontan failure (r = 0.444, P = 0.001), NYHA class (r = 0.434, P < 0.001), and γ-glutamyltransferase levels (r = 0.554, P < 0.001). According to receiver operating characteristic (ROC) curve analysis, Fontan failure was best predicted by MR-proADM [area under the curve (AUC) 0.985, P = 0.001], NT-proBNP (AUC 0.947, P = 0.003), NYHA class (AUC 0.962, P = 0.002), and the inspiratory/expiratory ratio of the inferior vena cava diameter (AUC 0.973, P = 0.007). The optimal cut-off of MR-proADM for the prediction of Fontan failure was 0.520 nmol/L with a sensitivity of 100%, specificity of 93.9%, positive predictive value of 57.1%, negative predictive value of 100%, and overall accuracy of 94.3%. However, the data should also be validated in a larger cohort of patients. Serial measurements of MR-proADM levels may help identify patients at risk for a failing Fontan circulation especially when exceeding 0.520 nmol/L. In these patients, intensified medical care should be considered to prevent further clinical deterioration. | 25,201,135 | [
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Food allergy in South African children with atopic dermatitis. | The prevalence of food allergy in South Africa is unknown, but previously thought to be rare in black South Africans. This study aimed to determine the prevalence of, and risk factors for, IgE-mediated food allergy in South African children with atopic dermatitis (AD). This was a prospective, observational study in a paediatric university hospital in Cape Town. Children with AD, aged 6 months to 10 yrs, were randomly recruited from the dermatology clinic. They were assessed for sensitization and allergy by questionnaire, skin prick tests, Immuno Solid Phase Allergen Chip (ISAC) test and incremental food challenges. 100 participants (59 black Africans and 41 of mixed race) were enrolled, median age 42 months. There were high overall rates of food sensitization (66%) and food allergy (40%). Egg (25%) and peanut (24%) were the most common allergies. Black participants had comparable sensitization (69% vs. 61%) but lower allergy rates (34% vs. 46%) than mixed race participants. This was especially evident for peanut allergy (15% Blacks vs. 37% mixed race allergic to peanut, p = 0.01). Early-onset AD (<6 months), severe eczema, and young age <2 yrs were significant risk factors for food allergy. The prevalence of food allergy is unexpectedly high in South African children with AD, and comparable with food allergy rates in patients with AD in developed countries. There are ethnic differences, with significantly lower peanut allergy rates in Blacks compared to mixed race patients. These results are not generalizable to an unselected South African population, which requires further study. | 25,201,137 | [
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Further validation of the Health Promoting Activities Scale with mothers of typically developing children. | The Health Promoting Activities Scale (HPAS) measures the frequency that mothers participate in self-selected leisure activities that promote health and wellbeing. The scale was originally validated on mothers of school-aged children with disabilities, and the current article extends this research using a comparative sample of mothers of typically developing school-aged children. Australian mothers (N = 263) completed a questionnaire containing the HPAS, a measure of depression, anxiety and stress (DASS-21) and questions concerning their weight, height, sleep quality and demographics. Statistical analysis assessed the underlying structure, internal consistency and construct validity of the HPAS. Inferential statistics were utilised to investigate the construct validity. Exploratory factor analysis supported the unidimensionality of the HPAS. It showed good internal consistency (Cronbach's alpha = 0.78). Significantly lower HPAS scores were recorded for women who were obese; had elevated levels of depression, anxiety and stress; had poor quality sleep or had heavy caring commitments. The mean HPAS score in this sample (M = 32.2) was significantly higher than was previously reported for women of children with a disability (M = 21.6: P < 0.001). Further psychometric evaluation of the HPAS continues to support the HPAS as a sound instrument that measures the frequency that women participate in meaningful occupation that is associated with differences in mental health and wellbeing and other health indicators. | 25,201,148 | [
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Measuring social support in patients with advanced medical illnesses: An analysis of the Duke-UNC Functional Social Support Questionnaire. | To date, no measure of social support has been developed specifically for either palliative care or oncology settings. The present study examined the psychometric properties of the Duke-University of North Carolina Functional Social Support Questionnaire (DUFSS) in order to (1) assess the adequacy of the scale in the context of severe medical illness and (2) evaluate whether a brief subset of items might generate roughly comparable utility. The 14-item DUFSS was administered to 1,362 individuals with advanced cancer or AIDS. Classical test theory (CTT) and item response theory (IRT) analyses were utilized to develop an abbreviated version of the DUFSS that maintained adequate reliability and validity and might increase the feasibility of its administration in a palliative care setting. The reliability and concurrent validity of the DUFSS-5 were evaluated in a separate validation sample of patients with advanced cancer. Analyses generated a five-item version of the DUFSS (the DUFSS-5) that collapsed response levels into only three options, instead of five. Correlations between the DUFSS-5 and measures of depression, quality of life, and desire for hastened death, as well as regression models testing the main-effect and buffering models of social support, provided support for the utility of the DUFSS-5. Both the DUFSS and the abbreviated DUFSS-5 appear to have adequate reliability and validity in this setting. Moreover, the DUFSS-5 represents a potentially important option for healthcare researchers, particularly for those working in palliative care settings where issues of patient burden are paramount. Such analyses are critical for advancing the development and refinement of psychosocial measures, but have often been neglected. | 25,201,170 | [
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Egr-1 participates in abnormally high gdnf gene transcription mediated by histone hyperacetylation in glioma cells. | Abnormally high transcription of the glial cell-line derived neurotrophic factor (gdnf) gene in glioma cells is related to the hyperacetylation of histone H3 lysine 9 (H3K9) in its promoter region II, but the mechanism remains unclear. There are three consecutive putative binding sites for the transcription factor early growth response protein 1(Egr-1) in promoter region II of the gdnf gene, and Egr-1 participates in gdnf gene transcription activation. Here we show that the acetylation level of H3K9 at Egr-1 binding sites in gdnf gene promoter region II in rat C6 astroglioma cells was significantly higher than that in normal astrocytes, and the binding capacity was also significantly higher. In C6 astroglioma cells, gdnf gene transcription significantly decreased after Egr-1 knock-down. In addition, the deletion or mutation of the Egr-1 binding site also significantly down-regulated the activity of promoter region II of this gene in vitro. When curcumin decreased the acetylation level of H3K9 at the Egr-1 binding site, the binding of Egr-1 to promoter region II and GDNF mRNA levels significantly decreased. In contrast, trichostatin A treatment significantly increased H3K9 acetylation at the Egr-1 binding site, which significantly increased both the binding of Egr-1 with promoter region II and GDNF mRNA levels. In this context, knocking down Egr-1 significantly reduced the elevation in gdnf gene transcription. Collectively, our results demonstrate that the hyperacetylation of H3K9 at Egr-1 binding sites in promoter region II of the gdnf gene can up-regulate the binding of Egr-1 to increase gdnf gene transcription in glioma cells. | 25,201,174 | [
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Transcriptional regulation by mutant p53 and oncogenesis. | More than half of all human cancers carry p53 gene mutations whose resulting proteins are mostly full-length with a single amino acid change, abundantly present in cancer cells and unable to exert oncosuppressor activities. Frequently, mutant p53 proteins gain oncogenic functions through which they actively contribute to the establishment, the maintenance and the spreading of a given cancer cell. Intense research effort has been devoted to the deciphering of the molecular mechanisms underlying the gain of function of mutant p53 proteins. Here we mainly review the oncogenic transcriptional activity of mutant p53 proteins that mainly occurs through the aberrant cooperation with bona-fide transcription factors and leads to either aberrant up-regulation or down-regulation of selected target genes. Thus, mutant p53 proteins are critical components of oncogenic transcriptional networks that have a profound impact in human cancers. | 25,201,190 | [
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Prediction of occult hepatitis B virus infection in liver transplant donors through hepatitis B virus blood markers. | Occult hepatitis B virus infection is defined as detectable HBV-DNA in liver of HBsAg-negative individuals, with or without detectable serum HBV-DNA. In deceased liver donors, results of tissue analysis cannot be obtained prior to allocation for liver transplantation. we investigated prevalence and predictability of occult hepatitis B using blood markers of viral exposure/infection in deceased liver donors. In 50 consecutive HBsAg-negative/anti-HBc-positive and 20 age-matched HBsAg-negative/anti-HBc-negative donors, a nested-PCR assay was employed in liver biopsies for diagnosis of occult hepatitis B according to Taormina criteria. All donors were characterized for plasma HBV-DNA and serum anti-HBs/anti-HBe. In liver tissue, occult hepatitis B was present in 30/50 anti-HBc-positive (60%) and in 0/20 anti-HBc-negative donors (p<0.0001). All anti-HBc-positive donors with detectable HBV-DNA in plasma (n=5) or anti-HBs>1,000 mIU/mL (n=5) eventually showed occult infection, i.e, 10/30 occult hepatitis B-positive donors which could have been identified prior to transplantation. In the remaining 40 anti-HBc-positive donors, probability of occult infection was 62% for anti-HBe-positive and/or anti-HBs ≥ 58 mIU/mL; 29% for anti-HBe-negative and anti-HBs<58 mIU/mL. In deceased donors, combining anti-HBc with other blood markers of hepatitis B exposure/infection allows to predict occult hepatitis B with certainty and speed in one third of cases. These findings might help refine the allocation of livers from anti-HBc-positive donors. | 25,201,211 | [
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Comparison of outcomes of ambulance users and nonusers in ST elevation myocardial infarction. | In a systematic province-wide evaluation of care and outcomes of ST elevation myocardial infarction (STEMI), we sought to examine whether a previously documented association between ambulance use and outcome remains after control for clinical risk factors. All 82 acute care hospitals in Quebec (Canada) that treated at least 30 acute myocardial infarctions annually participated in a 6-month evaluation in 2008 to 2009. Medical record librarians abstracted hospital chart data for consecutive patients with a discharge diagnosis of myocardial infarction who presented with characteristic symptoms and met a priori study criteria for STEMI. Linkage to administrative databases provided outcome data (to 1 year) and co-morbidities. Of 1,956 patients, 1,222 (62.5%) arrived by ambulance. Compared with nonusers of an ambulance, users were older, more often women, and more likely to have co-morbidities, low systolic pressure, abnormal heart rate, and a higher Thrombolysis In Myocardial Infarction risk index at presentation. Ambulance users were less likely to receive fibrinolysis or to be sent for primary angioplasty (78.5% vs 83.2% for nonusers, p = 0.01), although if they did, treatment delays were shorter (p <0.001). The 1-year mortality rate was 18.7% versus 7.1% for nonusers (p <0.001). Greater mortality persisted after adjusting for presenting risk factors, co-morbidities, reperfusion treatment, and symptom duration (hazard ratio 1.56, 95% confidence interval 1.30 to 1.87). In conclusion, ambulance users with STEMI were older and sicker than nonusers. Mortality of users was substantially greater after adjustment for clinical risk factors, although they received faster reperfusion treatment overall. | 25,201,215 | [
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Animal models of chronic obstructive pulmonary disease. | Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time, the association of other inducers or inhibitors, exacerbations or the use of transgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers' questions on disease identification or treatment responses. | 25,201,221 | [
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Costeff syndrome: clinical features and natural history. | Costeff syndrome (CS) is a rare autosomal-recessive neurological disorder, which is known almost exclusively in patients of Iraqi Jewish descent, manifesting in childhood with optic atrophy, ataxia, chorea and spastic paraparesis. Our aim was to study the clinical spectrum of CS and natural history using a cross-sectional study design. Consecutive patients with CS were recruited to the study. Patients were diagnosed based on clinical features, along with elevated urinary levels of methylglutaconic and methylglutaric acid, and by identification of the disease-causing mutation in the OPA3 gene in most. All patients were examined by a neurologist and signs and symptoms were rated. 28 patients with CS (16 males, 21 families, age at last observation 28.6 ± 16.1 years, range 0.5-68 years) were included. First signs of neurological deficit appeared in infancy or early childhood, with delayed motor milestones, choreiform movements, ataxia and visual disturbances. Ataxia and chorea were the dominant motor features in childhood, but varied in severity among patients and did not seem to worsen with age. Pyramidal dysfunction appeared later and progressed with age (r = 0.71, p < 0.001) leading to spastic paraparesis and marked gait impairment. The course of neurological deterioration was slow and the majority of patients could still walk beyond the fifth decade. While visual acuity seemed to deteriorate, it did not correlate with age. CS is a rare neurogenetic disorder that causes serious disability and worsens with age. Spasticity significantly increases over the years and is the most crucial determinant of neurological dysfunction. | 25,201,222 | [
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Long-term outcomes of 3 surgical adjuvants used for internal limiting membrane peeling in idiopathic macular hole surgery. | Indocyanine green (ICG), an adjuvant used for peeling of the internal limiting membrane (ILM) during vitreous surgery for idiopathic macular hole (MH), has been reported to be toxic, possibly affecting postoperative visual acuity. We compared the long-term outcomes (within 2 years) of brilliant blue G (BBG), ICG, and triamcinolone acetonide (TA). This study involved 97 eyes of 94 patients who underwent vitreous surgery for MH at the Yamagata University Hospital between June 2002 and November 2010. The surgical adjuvants used were BBG for 15 eyes, ICG for 61 eyes, and TA for 21 eyes. We compared the postoperative visual acuities, initial closure rates, final closure rates, and complications of the 3 groups. In all 3 groups, the visual acuity significantly improved after surgery. The magnitude of the improvement at 2 years after surgery was significantly better in the BBG group than in the ICG group (Mann-Whitney test, P = 0.020). The postoperative visual acuity did not significantly differ between the BBG and TA groups (P = 0.627) or between the ICG and TA groups (P =0 .137). Thus, the surgery using BBG resulted in a significantly better outcome in visual acuity than did the surgery using ICG. The 3 groups did not differ in initial or final closure rates or in incidence of complications. Analysis of the long-term outcomes of vitreous surgeries provided evidence that BBG is a useful adjuvant for ILM peeling. | 25,201,225 | [
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Use of urinary metabolomics to evaluate the effect of hyperuricemia on the kidney. | Clinical studies show that hyperuricemia is a risk factor in the progression and development of cardiovascular and metabolic disease. Elevated serum levels of uric acid induce renal injury via an inflammation response, but the detailed mechanism is still under study. To better understand the effect of hyperuricemia on the kidney, we used gas chromatography-mass spectrometry-based metabolomics to investigate the role of uric acid in the mouse kidney. Partial least-squares discriminant analysis revealed significant differences between control and hyperuricemia groups in urine metabolic profiles. We identified 33 metabolites from 76 highly reproducible peaks and found abnormal uric acid levels related to comprehensive kidney injury, including excretive function and energy metabolism. Additionally, inflammation induced by the interleukin 6/signal transducer and activator of transcription 3 signaling pathway participated in hyperuricemia-induced kidney injury. This study helps understand the relationship between hyperuricemia and kidney injury. Metabolomics may be a useful strategy for early diagnosis of kidney damage. | 25,201,228 | [
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Haemodynamic interactions of medetomidine and the peripheral alpha-2 antagonist MK-467 during step infusions in isoflurane-anaesthetised dogs. | The haemodynamic interactions of a step infusion with medetomidine (MED) and the peripherally acting alpha-2 antagonist MK-467 (MK) were compared with MED infused alone in isoflurane-anaesthetised dogs. Eight purposely-bred Beagles were used in a randomised crossover study. Anaesthesia was induced with propofol intravenously (IV) and maintained with isoflurane in oxygen. Dogs received 1.25 µg/kg MED as a 1 min loading dose IV, along with a step-down MED infusion at rates of 8.0 µg/kg/h (step 1: 0-20 min), 5.5 µg/kg/h (step 2: 20-40 min) and 4.0 µg/kg/h (step 3: 40-95 min). Five minutes after starting the MED infusion, the dogs received MK-467 in a step-up infusion at rates of 100 µg/kg/h (step 1: 5-35 min), 200 µg/kg/h (step 2: 35-65 min) and 500 µg/kg/h (step 3: 65-95 min). Heart rate (HR), systolic (SAP) and mean arterial (MAP) blood pressures and arteriovenous oxygen content differences (a-vO2 diff) were calculated. Plasma drug concentrations were analysed. Repeated-measures general linear mixed models with Bonferroni correction were used for statistical analyses. MED infusion alone increased SAP maximally by 24.9%, MAP by 34.7% and a-vO2 diff by 222.5%, and reduced HR by 32.3%, but these changes were significantly attenuated by MK-467. Most MED effects returned to baseline during step 2 of MK-467 infusion and step 3 of MED infusion (MED/MK-467 ratio 1:18 to 1:50). Plasma concentrations of MED tended to be lower with the addition of MK-467. The use of step infusions helped to narrow down the therapeutic range for the MED/MK-467 infusion dose ratio during isoflurane anaesthesia in dogs. | 25,201,249 | [
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Proximal migration of fibular malleolus during tibial lengthening despite syndesmotic screw fixation: a series of 22 cases. | During tibial lengthening procedures, it is recommended to prevent fibular malleolus proximal migration using a distal tibiofibular syndesmotic screw, which is removed at 6 months. We have observed proximal migrations of the fibular malleolus despite placement of this syndesmotic screw. The objective of this study was to demonstrate this migration and to study the influence of two factors that may favor its occurrence: positioning of the syndesmotic screw and union of the fibula at the time of removal. An unhealed fibula at the time the distal tibiofibular syndesmotic screw is removed and its tricortical position promote the proximal migration of the fibular malleolus. This was a retrospective, single-center, analytical study that included 22 lengthening procedures in 18 patients from 5 to 17 years of age who had undergone tibial lengthening and presented a preoperative continuous fibula. The position of the fibular malleolus, union of the fibula, and the tri- or quadricortical position of the screw were assessed based on four successive x-rays. Tricortical positioning of the syndesmotic screw was significantly associated with proximal migration of the fibular malleolus during lengthening (P=0.0248<0.05). However, there was no significant relation between an unhealed fibula and proximal migration of the fibular malleolus when the screw was removed (P=0.164>0.05). Proximal migration of the fibular malleolus during lengthening is promoted by placing a non-quadricortical syndesmotic screw. Quadricortical positioning of the screw should be recommended. Migration of the fibular malleolus after ablation of the syndesmotic screw seems to be related to absence of fibular union but this series was too small to demonstrate this clearly. Level IV: Retrospective study. | 25,201,280 | [
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Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones. | The antiphospholipid syndrome (APS) is an autoimmune disease characterized by high titres of auto-antibodies (aPL) leading to thrombosis and consequent infarcts. However, many affected patients develop neurological symptoms in the absence of stroke. Similarly, in a mouse model of this disease (eAPS), animals consistently develop behavioural abnormalities despite lack of ischemic brain injury. Therefore, the present study was designed to identify structural alterations of hippocampal neurones underlying the neurological symptoms in eAPS. Adult female Balb/C mice were subjected to either induction of eAPS by immunization with β2-Glycoprotein 1 or to a control group. After sixteen weeks animals underwent behavioural and cognitive testing using Staircase test (experiment 1 and 2) and Y-maze alternation test (experiment 1) and were tested for serum aPL levels (both experiments). Animals of experiment 1 (n = 7/group) were used for hippocampal neurone analysis using Golgi-Cox staining. Animals of experiment 2 (n = 7/group) were used to analyse molecular markers of total dendritic integrity (MAP2), presynaptic plasticity (synaptobrevin 2/VAMP2) and dendritic spines (synaptopodin) using immunohistochemistry. eAPS mice developed increased aPL titres and presented with abnormal behaviour and impaired short term memory. Further, they revealed a reduction of dendritic complexity of hippocampal CA1 neurones as reflected by decreased dendritic length, arborization and spine density, respectively. Additional decrease of the spine-associated protein expression of Synaptopodin points to dendritic spines as major targets in the pathological process. Reduction of hippocampal dendritic complexity may represent the structural basis for the behavioural and cognitive abnormalities of eAPS mice. | 25,201,289 | [
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Technological innovation and developmental strategies for sustainable management of aquatic resources in developing countries. | Sustainable use and allocation of aquatic resources including water resources require implementation of ecologically appropriate technologies, efficient and relevant to local needs. Despite the numerous international agreements and provisions on transfer of technology, this has not been successfully achieved in developing countries. While reviewing some challenges to technological innovations and developments (TID), this paper analyzes five TID strategic approaches centered on grassroots technology development and provision of localized capacity for sustainable aquatic resources management. Three case studies provide examples of successful implementation of these strategies. Success requires the provision of localized capacity to manage technology through knowledge empowerment in rural communities situated within a framework of clear national priorities for technology development. | 25,201,321 | [
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Assessing toxicity of copper, cadmium and chromium levels relevant to discharge limits of industrial effluents into inland surface waters using common onion, Allium cepa bioassay. | Toxicity of copper, cadmium and chromium relevant to established tolerance limits for the discharge of industrial effluents into inland surface waters was evaluated by Allium cepa bioassay. The roots of A. cepa bulbs exposed to Cu(2+) (3 mg L(-1)) individually or in mixtures with Cd(2+) (0.1 mg L(-1)) or/and Cr(6+) (0.1 mg L(-1)) exhibited the highest growth inhibition, mitotic index depression and nuclear abnormalities. Root tip cells exposed to Cr(6+) or Cd(2+) alone or in mixture displayed significant chromosomal aberrations in comparison to the controls. EC50s for root growth inhibition followed the order Cu(2+) < Cd(2+) < Cr(6+) indicating greater toxicity of copper. The results show that the industrial effluent discharge regulatory limits for these metals need to be reviewed considering potential cyto-genotoxicity to biological systems. | 25,201,323 | [
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Long-term follow-up of mobile bearing total ankle arthroplasty in the United States. | The published long-term follow-up of modern total ankle arthroplasty is limited. We report results after a minimum of 10-year follow-up in a cohort of patients who underwent the Scandinavian Total Ankle Replacement (STAR™) in the United States. Between 1998 and 2003, 18 patients underwent total ankle arthroplasty for end-stage ankle degeneration and were available for follow-up at a minimum of 10 years postoperatively out of a consecutive series of 41 patients. All surgeries were performed by a single surgeon at a single institution. Clinical, radiographic, and functional examinations were performed. Revision was defined as failure of either the tibial or the talar metallic component. The mean length of follow-up was 12.6 years (range, 10.2 to 14.6). Overall implant survival was 94.4% (17/18). A total of 39% (7/18) required additional surgical procedures, most of which were performed greater than 9 years postoperatively, and 1 required a revision of the prosthesis. Preoperative VAS pain scale scores improved from 8.1 to 2.1 out of 10 at latest follow-up. Mean Buechel-Pappas Scale scores improved from 32.8 to 82.1 and mean AOFAS Ankle-Hindfoot Scale scores improved from 32.8 to 78.1 at latest follow-up. All patients reported their outcome as good or excellent. In the current cohort of STAR ankle patients, implant survival, patient satisfaction, pain relief, and function were high. However, the rate of additional procedures was also high, which highlights the need for patient follow-up and additional long-term outcome studies on total ankle arthroplasty. Level IV, cohort study. | 25,201,330 | [
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Forward osmosis niches in seawater desalination and wastewater reuse. | This review focuses on the present status of forward osmosis (FO) niches in two main areas: seawater desalination and wastewater reuse. Specific applications for desalination and impaired-quality water treatment and reuse are described, as well as the benefits, advantages, challenges, costs and knowledge gaps on FO hybrid systems are discussed. FO can play a role as a bridge to integrate upstream and downstream water treatment processes, to reduce the energy consumption of the entire desalination or water recovery and reuse processes, thus achieving a sustainable solution for the water-energy nexus. FO hybrid membrane systems showed to have advantages over traditional membrane process like high pressure reverse osmosis and nanofiltration for desalination and wastewater treatment: (i) chemical storage and feed water systems may be reduced for capital, operational and maintenance cost, (ii) water quality is improved, (iii) reduced process piping costs, (iv) more flexible treatment units, and (v) higher overall sustainability of the desalination and wastewater treatment process. Nevertheless, major challenges make FO systems not yet a commercially viable technology, the most critical being the development of a high flux membrane, capable of maintaining an elevated salt rejection and a reduced internal concentration polarization effect, and the availability of appropriate draw solutions (cost effective and non-toxic), which can be recirculated via an efficient recovery process. This review article highlights the features of hybrid FO systems and specifically provides the state-of-the-art applications in the water industry in a novel classification and based on the latest developments toward scaling up these systems. | 25,201,336 | [
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Bimetallic nickel-iron nanoparticles for groundwater decontamination: effect of groundwater constituents on surface deactivation. | The incorporation of catalytic metals on iron nanoparticles to form bimetallic nanoparticles (BNPs) generates a class of highly reactive materials for degrading chlorinated hydrocarbons (e.g., trichloroethylene, TCE) in groundwater. Successful implementation of BNPs to groundwater decontamination relies critically on the stability of surface reactive sites of BNPs in groundwater matrices. This study investigated the effect of common groundwater solutes on TCE reduction with Ni-Fe (with Ni at 2 wt.%) bimetallic nanoparticles (herein denoted as Ni-Fe BNPs). Batch experiments involving pre-exposing the nanoparticles to various groundwater solutions for 24 h followed by reactions with TCE solutions were conducted. The results suggest that the deactivation behavior of Ni-Fe BNPs differs significantly from that of the well-studied Pd-Fe BNPs. Specifically, Ni-Fe BNPs were chemically stable in pure water. Mild reduction in TCE reaction rates were observed for Ni-Fe BNPs pre-exposed to chloride (Cl(-)), bicarbonate (HCO3(-)), sulfite (SO3(2-)) and humic acid solutions. Nitrate (NO3(-)), sulfate (SO4(2-)) and phosphate (HPO4(2-)) may cause moderate to severe deactivation at elevated concentrations (>1 mM). Product analysis and surface chemistry investigations using high-resolution X-ray photoelectron spectroscopy (HR-XPS) reveal that NO3(-) decreased particle reactivity mainly due to progressive formation of passivating oxides, whereas SO4(2-) and phosphate elicited rapid deactivation as a result of specific poisoning of the surface nickel sites. At similar levels, phosphate is the most potent deactivation agent among the solutes examined in this study. While our findings point out the desirable quality of Ni-Fe nanoparticles, particularly their greater electrochemical stability compared to Pd-Fe BNPs, its susceptibility to chemical poisoning at high levels of complexing ligands is also noted. Groundwater chemistry is therefore an important factor to consider when choosing appropriate material(s) for decontaminating the complex environmental media. | 25,201,338 | [
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Acute coagulopathy in children with multiple trauma: a retrospective study. | Acute coagulopathy associated with trauma has been recognized for decades and is a constituent of the "triad of death" together with hypothermia and acidosis. The aim of this study was to determine to what extent coagulopathy is already established upon emergency department (ED) admission and the association with the severity of injury, impaired outcome, and mortality. Ninety-one injured children were admitted to the ED in our hospital. Pediatric Trauma Score (PTS), Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were used to estimate injury severity, and organ function was assessed by the Sequential Organ Failure Assessment (SOFA) score. Coagulopathy upon pediatric intensive care unit admission was present in 33 children (39.3%): 21 males and 12 females. PTS ranged from 1 to 12 (mean 8.2) in 51 children without coagulopathy and from -1 to +11 (mean 6.8) in 33 children with coagulopathy (p = 0.087). ISS and GCS ranged from 4 to 57 (mean 28) and from 3 to 11 (mean 7.3), respectively, in the coagulopathy group, whereas in the group without coagulopathy, ISS score ranged from 4 to 41 (mean 20.5; p = 0.08) and GCS from 8 to 15 (mean 12.8; p = 0.01). SOFA ranged from 0 to 10 (mean 3.4) in children without coagulopathy and from 0 to 15 (mean 5.4) in the coagulopathy group (p = 0.002). Among 33 children with coagulopathy, 7 did not survive (21%), all with parenchymal brain damage, whereas all trauma patients without coagulopathy survived (p < 0.001). Acute coagulopathy is present on admission to the ED and is associated with injury severity and significantly higher mortality. | 25,201,343 | [
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Differential effects of experimental ulcerative colitis on P2X7 receptor expression in enteric neurons. | The digestive tracts of ulcerative colitis and Crohn's disease patients present with pathophysiological processes and intestinal necrosis. This study examined the P2X7 receptor and changes in the distal colon in enteric neurons of rats with experimental ulcerative colitis. The analysis was performed in the distal colons of rats with ulcerative colitis induced by the administration of 2,4,6-trinitrobenzene sulfonic acid (colitis group). The survival time after colitis induction was 24 h. The treated animals were compared to sham rats injected with phosphate-buffered saline and to animals with no intervention (control group). Tissues were prepared for immunohistochemical double-staining methods to examine P2X7 receptor, choline acetyltransferase (ChAT), calbindin, calretinin, anti-HuC/D (pan-neuronal) and S100β (pan-glial). The colocalization of the P2X7 receptor-immunoreactive (IR) cells was observed in the myenteric plexus with nitric oxide synthase (NOS)-, ChAT-,calbindin-, calretinin- and HuC/D-IR neurons and S100β-IR cells in the control, sham and colitis groups. The neuronal density (cell bodies/cm(2)) decreased in the myenteric plexus by 11, 18, 34, 22 and 60% in the P2X7 receptor, NOS-, ChAT-, calbindin- and calretinin-IR neurons, respectively. In addition, the densities (cell bodies/cm(2)) of HuC/D-IR neurons and S100β-IR enteric glial cells decreased by 33 and 29%, respectively. The profile areas were reduced by 6.8 and 21% in NOS- and ChAT-IR neurons, respectively. There was also a 20% increase of calbindin-IR neurons. Morphological changes were observed, such as increased neutrophils, disintegration of the intestinal epithelium and goblet cells and decreased collagen. This study demonstrated that colitis differentially affects P2X7 receptor-expressing enteric neurons based on their chemical codes and may cause changes in morphology and motility. | 25,201,348 | [
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Higher sensitivity to cadmium induced cell death of basal forebrain cholinergic neurons: a cholinesterase dependent mechanism. | Cadmium is an environmental pollutant, which is a cause of concern because it can be greatly concentrated in the organism causing severe damage to a variety of organs including the nervous system which is one of the most affected. Cadmium has been reported to produce learning and memory dysfunctions and Alzheimer like symptoms, though the mechanism is unknown. On the other hand, cholinergic system in central nervous system (CNS) is implicated on learning and memory regulation, and it has been reported that cadmium can affect cholinergic transmission and it can also induce selective toxicity on cholinergic system at peripheral level, producing cholinergic neurons loss, which may explain cadmium effects on learning and memory processes if produced on central level. The present study is aimed at researching the selective neurotoxicity induced by cadmium on cholinergic system in CNS. For this purpose we evaluated, in basal forebrain region, the cadmium toxic effects on neuronal viability and the cholinergic mechanisms related to it on NS56 cholinergic mourine septal cell line. This study proves that cadmium induces a more pronounced, but not selective, cell death on acetylcholinesterase (AChE) on cholinergic neurons. Moreover, MTT and LDH assays showed a dose dependent decrease of cell viability in NS56 cells. The ACh treatment of SN56 cells did not revert cell viability reduction induced by cadmium, but siRNA transfection against AChE partially reduced it. Our present results provide new understanding of the mechanisms contributing to the harmful effects of cadmium on the function and viability of neurons, and the possible relevance of cadmium in the pathogenesis of neurodegenerative diseases. | 25,201,352 | [
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Rationale for unequal randomization in clinical trials is rarely reported: a systematic review. | To assess the reporting of the unequal randomization ratio in reports of trials with this design and to identify the justification for the design. Systematic review of reports of trials with unequal randomization. We selected all original reports of two parallel-group randomized controlled trials with unequal randomization, which were published in 2009 and 2010 in core clinical journals in MEDLINE on the basis of the abstract (and full text, if necessary). Additional information was collected by an author survey. We retrieved 106 reports (prevalence, 4.7%). The randomization ratio was not stated in 8.5% of reports and 51.9% of abstracts. Sample size calculation was reported in 70 reports, with unequal randomization not taken into account in 25.7% (n = 18). Justification for unequal randomization was not reported in 77.4% (n = 82) of reports. Combining information from reports and author surveys, we had justification for 41 trials. The main justification was safety issues for 20 trials. In 11 of those latter 20 reports, adverse events were not fully reported. A better reporting of the randomization ratio, sample size calculation, and justification to unequal randomization could help readers appraise the quality and risk of bias of such trials. | 25,201,357 | [
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[Reconstruction of the superior vena cava for invasive thymoma under monitoring of regional cerebral saturation of oxygen]. | A 63-year-old man was referred to our department for surgical resection of invasive thymoma (type B3)after 2 courses of chemo-therapy resulted in stable disease. Resection of the tumor was done through a median sternotomy under monitoring of regional cerebral saturation of oxygen (rSo2) using near-infrared spectroscopy (NIRS). The tumor invaded to the right upper lobe (S3), the right phrenic nerve, the superior vena cava (SVC), and the bilateral brachiocephalic vein (BCV). Although bilateral clamping of the BCVs induced significant decrease in rSo2, unilateral clamping of the BCV did not. Therefore, reconstruction of the SVC by sequential reconstruction of BCVs was carried out, and the tumor was successfully and safely excised with the SVC and a part of the right upper lobe. | 25,201,361 | [
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[Radical nephrectomy and caval tumor thrombectomy with cardiopulmonary bypass combined with right anterior minithoracotomy;report of a case]. | Renal cell carcinoma is a tumor with a distinct feature that it can invade the renal vein and grow intravascularly extending to the inferior vena cava (IVC). We herein report a case of a 71-year-old female who presented with a neoplasm that involved the right kidney and an intra-IVC tumor thrombus. We performed radical nephrectomy and tumor thrombectomy under cardiopulmonary bypass through a right anterior mini thoracotomy. The patient was discharged on the 13th day after the surgery without any complication, and is currently in good health at 7 months after the operation. | 25,201,372 | [
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[Primary malignant peripheral nerve sheath tumor of the lung; report of a case]. | We report a patient with primary malignant peripheral nerve sheath tumor (MPNST) of the lung. A 84-year-old man was referred to our hospital because of an abnormal shadow on chest X-ray. The computed tomography( CT) of the chest revealed a 6 cm tumor close to the posterior chest wall in the left thorax. He was followed-up because a benign tumor from posterior mediastinum was suspected. But the CT after 17 months showed the tumor enlargement. We performed complete resection under video-assisted thoracic surgery. It arose from the left lower lobe and was diagnosed as primary MPNST of the lung by immuno-histopathological examination. MPNSTs have a poor prognosis with tendency to recur. Although there is no sign of recurrence a year after surgery, we should follow-up carefully. | 25,201,374 | [
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Juvenile idiopathic arthritis in relation to maternal prenatal smoking. | Cigarette smoking increases the risk of seropositive adult rheumatoid arthritis. The relationship of smoking with juvenile idiopathic arthritis (JIA), a heterogeneous group of 7 mutually exclusive categories of chronic childhood inflammatory arthritides, is unknown. Our objective was to evaluate the association between JIA and its categories with maternal prenatal smoking. This case-control study used International Classification of Diseases, Ninth Revision codes from hospital records to identify 1,196 JIA cases born in Washington state and diagnosed at a quaternary pediatric center from 1997-2010. Controls (n = 5,618) were randomly selected from birth records of children without JIA, frequency matched on birth year. Prenatal smoking exposure was assessed from subjects' birth certificates. Chart review categorized JIA into International League of Associations for Rheumatology categories. Adjusted odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated using logistic regression. We did not observe an increased risk of JIA in relation to maternal prenatal smoking. Prenatal smoking was reported less often among mothers of JIA cases (11%), than among control mothers (17%; OR 0.71 [95% CI 0.58-0.87]), a relationship somewhat more marked for oligoarticular/extended oligoarticular JIA. Although this relationship persisted after adjustment, we cannot rule out that the effect may have been due to residual confounding by socioeconomic status. We did not observe an increased risk of JIA or its individual categories with maternal prenatal smoking. | 25,201,389 | [
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Hierarchical porous carbon aerogel derived from bagasse for high performance supercapacitor electrode. | Renewable, cost-effective and eco-friendly electrode materials have attracted much attention in the energy conversion and storage fields. Bagasse, the waste product from sugarcane that mainly contains cellulose derivatives, can be a promising candidate to manufacture supercapacitor electrode materials. This study demonstrates the fabrication and characterization of highly porous carbon aerogels by using bagasse as a raw material. Macro and mesoporous carbon was first prepared by carbonizing the freeze-dried bagasse aerogel; consequently, microporous structure was created on the walls of the mesoporous carbon by chemical activation. Interestingly, it was observed that the specific surface area, the pore size and distribution of the hierarchical porous carbon were affected by the activation temperature. In order to evaluate the ability of the hierarchical porous carbon towards the supercapacitor electrode performance, solid state symmetric supercapacitors were assembled, and a comparable high specific capacitance of 142.1 F g(-1) at a discharge current density of 0.5 A g(-1) was demonstrated. The fabricated solid state supercapacitor displayed excellent capacitance retention of 93.9% over 5000 cycles. The high energy storage ability of the hierarchical porous carbon was attributed to the specially designed pore structures, i.e., co-existence of the micropores and mesopores. This research has demonstrated that utilization of sustainable biopolymers as the raw materials for high performance supercapacitor electrode materials is an effective way to fabricate low-cost energy storage devices. | 25,201,446 | [
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Collaborative care for depression in European countries: a systematic review and meta-analysis. | This is a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the effectiveness of collaborative care compared to Primary Care Physician's (PCP's) usual care in the treatment of depression, focusing on European countries. A systematic review of English and non-English articles, from inception to March 2014, was performed using database PubMed, British Nursing Index and Archive, Ovid Medline (R), PsychINFO, Books@Ovid, PsycARTICLES Full Text, EMBASE Classic+Embase, DARE (Database of Abstract of Reviews of Effectiveness) and the Cochrane Library electronic database. Search term included depression, collaborative care, physician family and allied health professional. RCTs comparing collaborative care to usual care for depression in primary care were included. Titles and abstracts were independently examined by two reviewers, who extracted from the included trials information on participants' characteristics, type of intervention, features of collaborative care and type of outcome measure. The 17 papers included, regarding 15 RCTs, involved 3240 participants. Primary analyses showed that collaborative care models were associated with greater improvement in depression outcomes in the short term, within 3 months (standardized mean difference (SMD) -0.19, 95% CI=-0.33; -0.05; p=0.006), medium term, between 4 and 11 months (SMD -0.24, 95% CI=-0.39; -0.09; p=0.001) and medium-long term, from 12 months and over (SMD -0.21, 95% CI=-0.37; -0.04; p=0.01), compared to usual care. The present review, specifically focusing on European countries, shows that collaborative care is more effective than treatment as usual in improving depression outcomes. | 25,201,482 | [
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Oxidative degradation study on antimicrobial agent ciprofloxacin by electro-Fenton process: kinetics and oxidation products. | Oxidative degradation of the antimicrobial agent ciprofloxacin hydrochloride (CIP) has been investigated using electro-Fenton (EF) treatment with a constant current in the range 60-500 mA. The process generates highly oxidant species OH in situ via electrochemically monitored Fenton reaction. The EF experiments were performed using cells with a carbon felt cathode and Pt anode. Effect of applied current and catalyst concentration on the kinetics of oxidative degradation and mineralization efficiency have been investigated. Degradation of CIP followed pseudo-first order reaction kinetics. The rate constant of the oxidation of CIP by OH has been determined to be (1.01 ± 0.14) × 10(10) M(-1) s(-1) by using competitive kinetics method. An optimum current of 400 mA and a catalyst concentration of Fe(2+) at 0.1mM are found to be optimal for an effective degradation of CIP under our operating conditions. A remarkably high degree of mineralization (>94%) was obtained at 6h of treatment under these conditions. A number of stable intermediate products have been identified using HPLC and LC-MS/MS analyses. Based on the identified reaction intermediates, a plausible reaction pathway was proposed for the mineralization process. The high degree of mineralization obtained in this work highlights the potential application of EF process in the efficient removal of fluoroquinolone based drugs in aqueous medium. | 25,201,488 | [
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Reoperations for persistent or recurrent primary hyperparathyroidism: results of a retrospective cohort study at a tertiary referral center. | Parathyroid reoperations are challenging and achieving a cure requires multidisciplinary treatment team cooperation. The aims of this study were to summarize our experience in revision surgery for persistent (pHPT) or recurrent primary hyperparathyroidism (rHPT) and to explore factors underlying failure to cure at initial surgery. This was a retrospective cohort study of patients who underwent reoperations for pHPT or rHPT at a tertiary referral center. The database of parathyroid surgery was searched for eligible patients (treated in the years 2000-2012). The primary outcome was the cure rate. All the patients were followed-up for at least 12 months postoperatively. Factors underlying failure to cure at initial surgery were reviewed based on hospital records. The study group comprised 88 patients (69 women, 19 men) operated on for persistent (n=57) or recurrent disease (n=31), who underwent 98 reoperations, including 26 (2.4%) patients first operated on at our institution, and 72 (81.8%) patients operated on elsewhere, but referred for revision surgery. A long-term cure was achieved in 83/88 patients (94.3%). The mean post-reoperation follow-up was 91.7 (12-176) months. Missed hyperfunctioning parathyroid gland was found on reoperation in eutopic position in 49 (55.5%) patients, and in ectopic position in 39 (44.3%) patients, including 20 (22.7%) cases of cervical ectopy and 19 (21.6%) cases of mediastinal ectopy. Multidisciplinary treatment team cooperation at a tertiary referral center, consisting of an accurate preoperative localization, expertise in parathyroid re-explorations, and correct use of intraoperative adjuncts, contribute to the high success rate of parathyroid reoperations. | 25,201,515 | [
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Short-term variation in plasma mitotane levels confirms the importance of trough level monitoring. | Mitotane is the drug of choice in patients with adrenocortical carcinoma. The anti-neoplastic effect is correlated with mitotane plasma levels, which render it crucial to reach and maintain the concentration above 14 mg/l. However, mitotane pharmacokinetics is poorly understood. The aim of this study was to investigate the variation in plasma mitotane levels during the day and the influence of a single morning dose. A prospective case-control study was conducted to investigate the variation in plasma mitotane levels. Patients who had been treated for at least 24 weeks and had reached the therapeutic plasma level (14 mg/l) at least once were eligible. In the first group, mitotane levels were determined hourly for the duration of 8 h after administration of a single morning dose. In the second group, mitotane levels were assessed similarly without administration of a morning dose. Ten patients were included in this study, and three patients participated in both groups. Median plasma level at baseline was 16.2 mg/l (range 11.3-23.3 mg/l) in the first group (n=7) and 17.0 mg/l (13.7-23.8) in the second group (n=6). Plasma levels displayed a median increase compared with baseline of 24% (range 6-42%) at t=4 after morning dose and a change of 13% (range -14 to 33%) at t=4 without morning dose (P=0.02). A substantial increase in mitotane plasma levels was observed in steady-state patients within a period of 8 h after morning dosing. Without morning dose, mitotane curves showed a variable profile throughout the day. This implies that random sampling could yield incidentally high levels. For this reason, we recommend early-morning trough sampling as standard management in monitoring mitotane treatment. | 25,201,518 | [
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Binswanger's disease: toward a diagnosis agreement and therapeutic approach. | Binswanger's disease (BD) is a progressive form of cerebral small vessel disease affecting the white matter and other subcortical structures. Clinical and imaging characteristics, neuropsychological profile and cerebrospinal fluid analysis aid in making the diagnosis. BD shares features of other small vessel diseases and degenerative neurological conditions, which makes diagnosis difficult. However, with recent developments in MRI methods and serum/cerebrospinal fluid biomarkers, we have gained a greater understanding of the complex pathophysiology of the disease that will guide us to a more certain diagnosis. There is growing evidence that the white matter injury in BD is related to endothelial dysfunction with a secondary inflammatory response leading to breakdown of the neurovascular unit. This review summarizes current and future research directions, including pathophysiological mechanisms and potential therapeutic approaches. | 25,201,523 | [
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Developmental relations between vocabulary knowledge and reading comprehension: a latent change score modeling study. | The present study followed a sample of first-grade (N = 316, Mage = 7.05 at first test) through fourth-grade students to evaluate dynamic developmental relations between vocabulary knowledge and reading comprehension. Using latent change score modeling, competing models were fit to the repeated measurements of vocabulary knowledge and reading comprehension to test for the presence of leading and lagging influences. Univariate models indicated growth in vocabulary knowledge, and reading comprehension was determined by two parts: constant yearly change and change proportional to the previous level of the variable. Bivariate models indicated previous levels of vocabulary knowledge acted as leading indicators of reading comprehension growth, but the reverse relation was not found. Implications for theories of developmental relations between vocabulary and reading comprehension are discussed. | 25,201,552 | [
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Host immune modulation by antimicrobial drugs: current knowledge and implications for antimicrobial chemotherapy. | It is known that antimicrobial agents possess several, beneficial, secondary properties which complement their primary antimicrobial activity like the immunomodulatory capacity that enforces host defense mechanisms or reduces host inflammatory response. In this review the current state of our recent research about the interaction between some antimicrobial agents and the immune system as complex pyramid of redundant cellular factors, humoral effectors and mediators against various microbial pathogens, will be presented and compared with recent literature data. The nature of such interactions is diverse and depends on the drug, the host immunological status and the microorganism. A more complete understanding of the host immune modulation by antimicrobial drugs may guide the selection of appropriate regimens for given clinical situations. | 25,201,570 | [
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Haemophilus influenzae oral vaccination for preventing acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease. | Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. COPD is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis. To assess the effectiveness of an oral, whole-cell, non-typeable H. influenzae (NTHi) vaccine in protecting against recurrent episodes of acute exacerbations of chronic bronchitis and COPD in adults. To assess the effectiveness of NTHi vaccine in reducing NTHi colonising the respiratory tract during recurrent episodes of acute exacerbations of COPD. We searched the following databases: CENTRAL (2014, Issue 6), MEDLINE (1946 to July week 3, 2014), EMBASE (1974 to July 2014), CINAHL (1981 to July 2014), LILACS (1982 to July 2014) and Web of Science (1955 to July 2014). We also searched trials registries and contacted authors of trials requesting unpublished data. We included randomised controlled trials comparing the effects of an oral monobacterial NTHi vaccine in adults with recurrent acute exacerbations of chronic bronchitis or COPD when there was overt matching of the vaccine and placebo groups on clinical grounds. The selection criteria considered populations aged less than 65 years and those older than 65 years. Two authors independently assessed trial quality and extracted data from original records and publications for incidence and severity of bronchitis episodes and carriage rate of NTHi measured in the upper respiratory tract, as well as data relevant to other primary and secondary outcomes. We identified six placebo-controlled randomised controlled trials with a total of 557 participants. They investigated the efficacy of enteric-coated, killed preparations of H. influenzae in populations prone to recurrent acute exacerbations of chronic bronchitis or COPD. The vaccine preparation and immunisation regime in all trials consisted of at least three courses of formalin-killed H. influenzae in enteric-coated tablets taken at intervals (for example, days 0, 28 and 56). Each course generally consisted of two tablets taken after breakfast over three consecutive days. In all cases the placebo groups took enteric-coated tablets containing glucose. Risk of bias was moderate across the studies, namely due to the lack of information provided about methods and inadequate presentation of results.Meta-analysis of the oral NTHi vaccine showed a small, non-statistically significant reduction in the incidence of acute exacerbations of chronic bronchitis or COPD by 2.048% (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.84 to 1.12, P value = 0.68). There was no significant difference in mortality rate between the vaccine and placebo groups (odds ratio (OR) 1.62, 95% CI 0.63 to 4.12, P value = 0.31).We were unable to meta-analyse the carriage levels of NTHi in participants as each trial reported this result using different units and tools of measurement. Four trials showed no significant difference in carriage levels, while two trials showed a significant decrease in carriage levels in the vaccinated group compared with placebo.Four trials assessed severity of exacerbations measured by requirement for antibiotics. Three of these trials were comparable and when meta-analysed showed a statistically significant 80% increase in antibiotic courses per person in the placebo group (RR 1.81, 95% CI 1.35 to 2.44, P value < 0.0001). There was no significant difference between the groups with regards to hospital admission rates (OR 0.96, 95% CI 0.13 to 7.04, P value = 0.97). Adverse events were reported in all six trials with a point estimate suggestive that they occurred more frequently in the vaccine group, however, this result was not statistically significant (RR 1.43, 95% CI 0.70 to 2.92, P value = 0.87). Quality of life was not meta-analysed but was reported in two trials, with results at six months showing an improvement in quality of life in the vaccinated group (scoring at least two points better than placebo). Analyses demonstrate that NTHi oral vaccination of patients with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations. Evidence is mixed and the individual trials that show a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD. | 25,201,571 | [
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The community-based delivery of an innovative neonatal kit to save newborn lives in rural Pakistan: design of a cluster randomized trial. | Worldwide, an estimated 2.9 million neonatal deaths occurred in 2012, accounting for 44% of all under-five deaths. In Pakistan, more than 200,000 newborns die annually and neonatal mortality rates are higher than in any other South Asian country and haven't changed over the last three decades. The high number of neonatal deaths highlights the urgent need for effective and sustainable interventions that target newborn mortality in Pakistan. This cluster randomized trial aims at evaluating the impact of delivering an integrated neonatal kit to pregnant women during the third trimester of pregnancy and providing education on how to use the contents (intervention arm) compared to the current standard of care (control arm) in the district of Rahimyar Khan, Punjab province, Pakistan. The kit, which will be distributed through the national Lady Health Worker program, comprises a clean delivery kit (sterile blade, cord clamp, clean plastic sheet, surgical gloves and hand soap), sunflower oil emollient, chlorhexidine, ThermoSpot™, Mylar infant sleeve, and a reusable instant heat pack. Lady health workers will be provided with a standard portable hand-held electric weighing scale. The primary outcome measure is neonatal mortality (death in the first 28 days of life). While many cost-effective, evidence-based interventions to save newborn lives exist, they are not always accessible nor have they been integrated into a portable kit designed for home-based implementation entirely by caregivers. The implementation of cost-effective, portable, and easy-to-use interventions has tremendous potential for sustainably reducing neonatal mortality and long-term improvements in population health. The bundling of interventions and commodities together also has much potential for cost-effective delivery and maximizing gains from points of contact. This study will provide empirical evidence on the feasibility and effectiveness of the delivery of an innovative neonatal kit to pregnant women in Pakistan. Together, these findings will help inform policy on the most appropriate interventions to improve newborn survival. ClinicalTrial.gov NCT02130856. Registered May 1, 2014. | 25,201,572 | [
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Association between a functional polymorphism rs712 within let-7-binding site and risk of papillary thyroid cancer. | KRAS mutation is frequently detected in a series of cancers, including papillary thyroid cancer (PTC). Recently, a genetic variant of rs712 in the 3' untranslated region of the KRAS gene has been reported to be functional in the regulation of KRAS by disrupting complementary site of let-7 and miR-181. We aimed to investigate whether the polymorphism is a risk factor for PTC. We conducted an association study, including 252 PTC patients and 290 healthy controls. The KRAS rs712 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Although no significant difference of the KRAS rs712 distribution was observed between cases and controls in overall analysis, stratification analysis showed that patients carrying the KRAS rs712TT genotype were less likely to develop stages T3 and T4 under a recessive genetic model (OR 0.26, 95% CI 0.08-0.82). These results supported the role of the KRAS rs712 polymorphism as a potential genetic biomarker for the extension of PTC. Further population-based association studies are of great value to confirm the results in diverse ethnicities. | 25,201,577 | [
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Doing fence sitting: a discursive analysis of clinical psychologists' constructions of mental health. | A growing body of research indicates that the way health care professionals conceptualize mental health might have important clinical implications. We adopted a discursive psychology approach to explore clinical psychologists' accounts of mental health and its effects. Semistructured interviews were conducted with 11 clinical psychologists in the East Midlands region of the United Kingdom. The participants constructed mental health through building up biological factors and psychosocial aspects as opposite ends of the same spectrum, and then positioned themselves as distant from these extremes to manage issues of stake and accountability. A discourse of moral concern for service users was used to negotiate the implications of having different views of mental health from service users, enabling clinicians to manage issues of accountability and demonstrate their ability to be helpful. This suggests that clinicians should be mindful of the effects of their use of language and make the contingent nature of their knowledge explicit. | 25,201,580 | [
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Prediction of the influences of missense mutations on cholesteryl ester transfer protein structure. | The structure of human plasma cholesteryl ester transfer protein (CETP) was mapped in silico by a search of the structural effects of missense mutations in the CETP gene. Sixteen deleterious substitutions were chosen among 54 known missense mutations and further ranked by stability change score into six structural and ten functional mutations with large and small stability changes, respectively. A cluster of eight mutations in a central region spanning residues 184-296 with exclusively destabilizing effects was evident. Moreover, the mutations were differently distributed between ordered and highly fluctuating regions. Putative cholesterol-binding regions, mostly unique for CETP in a whole CETP-including protein family, were identified. Three of six structural mutations influence cholesteryl ester and phosphatidylcholine binding by CETP. The local partially disordered structure of some putative cholesterol-binding regions is suggested to be differently influenced by cholesterol binding. This may underlie the impairment of the local ordering effect of cholesterol by the L261R substitution. Also, cholesterol may competitively inhibit cholesteryl ester binding to the CETP molecule, with triglyceride binding being largely undisturbed. This analysis may contribute to the ongoing design and mechanistic studies of new CETP inhibitors. | 25,201,589 | [
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[JNC 8 is released… but this is not the JNC 8! New US guidelines for the management of hypertension]. | During year 2013, several recommendations for the management of hypertension were published: recommendations of the French and European Societies of Hypertension and two recommendations from the USA, those from the ACC/AHA/CDC groups and those from the JNC 8. The recommendations of the JNC 8 are not, strictly speaking, the recommendations of JNC 8, since they are neither endorsed by their sponsor: the National Heart, Lung and Blood Institute (NHLBI), nor by any other supervisor. They only commit their authors. Just before the publication of the JNC 8, "competing" recommendations, jointly produced by the AHA, ACC and CDC, were jointly published in Hypertension and in the Journal of American College of Cardiology, with different preferred treatment choices and significantly different algorithms. The authors of the JNC 8 have only included in their literature review randomized controlled trials of sufficient power. Randomized controlled trials are clearly the gold standard of comparative trials in medicine, but can they summarize all the knowledge? The authors of the JNC 8 propose in subjects over 60, a therapeutic threshold and target blood pressure of 150/90mmHg. This original threshold is poorly supported by the evidence and possibly increases the risk of physicians' inertia. The issue of experts' conflicts of interest has greatly changed the rules of drafting guidelines for clinical practice. Knowing that the vast majority of clinical trials is promoted by drug industry, could guidelines be strictly without any conflict of interest? Finally, recommendations for practice should have as primary, if not unique, objective to improve the practice. | 25,201,593 | [
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Predictors of early care withdrawal following out-of-hospital cardiac arrest. | To identify factors that associated with early care withdrawal in out-of-hospital cardiac arrest patients. Data was collected from 189 survivors to hospital admission. Patients were classified by survival status upon hospital discharge, and those who died were categorized into withdrawal vs. no withdrawal of care. Those who had care withdrawn were further subdivided into early care withdrawal i.e. ≤72 h vs. late withdrawal >72 h. Multivariable adjusted odds ratios were used to assess factors associated with early care withdrawal. Of 189 patients with cardiac arrest, only 36 had advanced directives (19%) and 99 (52%) had care withdrawn. Most patients whose care was withdrawn died in hospital (94/99, 95%), and the remainder died in hospice. Care was withdrawn early ≤72 h in the majority of patients (59/94, 63%). Median time to early care withdrawal was 2 days IQR (1-3). Factors associated with early care withdrawal were age ≥75 years, poor initial neurologic exam, multiple co morbidities, multi-organ failure, lactic acid ≥10 mmolL(-1), Caucasian race and absence of bystander CPR. Advance directives did not appear to determine early care withdrawal. Although most cardiac arrest patients do not have advance directives, care is often withdrawn in more than 50% and in many before the accepted time for neurological awakening (72h). The decision to withdraw care is influenced by older age, race, preexisting co morbidities, multi-organ failure, and a poor initial neurological exam. Further studies are needed to better understand this phenomenon and other sociological factors that guide such decisions. | 25,201,612 | [
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Why evidence-based medicine is a good approach in physical and rehabilitation medicine. Thesis. | According to a good definition, evidence-based medicine (EBM) is: "The explicit, conscientious, and judicious use of the current best evidence in making decisions about the care of individual patients (and populations)". More appropriate in a clinical context like that of physical and rehabilitation medicine (PRM) is looking at evidence based clinical practice (EBCP), whose definition is: "The integration of best research evidence with clinical expertise and patient values". In the past the term evidence-based physical and rehabilitation medicine (EBPRM) was also proposed. In this thesis, after some historical notes on EBM and on PRM, we will discuss why in our view EBPRM must be the real foundation of our everyday PRM clinical practice. | 25,201,616 | [
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A comparison of hospital administrative costs in eight nations: US costs exceed all others by far. | A few studies have noted the outsize administrative costs of US hospitals, but no research has compared these costs across multiple nations with various types of health care systems. We assembled a team of international health policy experts to conduct just such a challenging analysis of hospital administrative costs across eight nations: Canada, England, Scotland, Wales, France, Germany, the Netherlands, and the United States. We found that administrative costs accounted for 25.3 percent of total US hospital expenditures--a percentage that is increasing. Next highest were the Netherlands (19.8 percent) and England (15.5 percent), both of which are transitioning to market-oriented payment systems. Scotland and Canada, whose single-payer systems pay hospitals global operating budgets, with separate grants for capital, had the lowest administrative costs. Costs were intermediate in France and Germany (which bill per patient but pay separately for capital projects) and in Wales. Reducing US per capita spending for hospital administration to Scottish or Canadian levels would have saved more than $150 billion in 2011. This study suggests that the reduction of US administrative costs would best be accomplished through the use of a simpler and less market-oriented payment scheme. | 25,201,663 | [
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Improving access to malaria medicine through private-sector subsidies in seven African countries. | Improving access to quality-assured artemisinin combination therapies (ACTs) is an important component of malaria control in low- and middle-income countries. In 2010 the Global Fund to Fight AIDS, Tuberculosis, and Malaria launched the Affordable Medicines Facility--malaria (AMFm) program in seven African countries. The goal of the program was to decrease malaria morbidity and delay drug resistance by increasing the use of ACTs, primarily through subsidies intended to reduce costs. We collected data on price and retail markups on antimalarial medicines from 19,625 private for-profit retail outlets before and 6-15 months after the program's implementation. We found that in six of the AMFm pilot programs, prices for quality-assured ACTs decreased by US$1.28-$4.34, and absolute retail markups on these therapies decreased by US$0.31-$1.03. Prices and markups on other classes of antimalarials also changed during the evaluation period, but not to the same extent. In all but two of the pilot programs, we found evidence that prices could fall further without suppliers' losing money. Thus, concerns may be warranted that wholesalers and retailers are capturing subsidies instead of passing them on to consumers. These findings demonstrate that supranational subsidies can dramatically reduce retail prices of health commodities and that recommended retail prices communicated to a wide audience may be an effective mechanism for controlling the market power of private-sector antimalarial retailers and wholesalers. | 25,201,662 | [
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Higher-order conditioning is impaired by hippocampal lesions. | Behavior in the real world is rarely motivated by primary conditioned stimuli that have been directly associated with potent unconditioned reinforcers. Instead, motivation and choice behavior are driven by complex chains of higher-order associations that are only indirectly linked to intrinsic reward and often exert their influence outside awareness. Second-order conditioning (SOC) [1] is a basic associative-learning mechanism whereby stimuli acquire motivational salience by proxy, in the absence of primary incentives [2, 3]. Memory-systems theories consider first-order conditioning (FOC) and SOC to be prime examples of hippocampal-independent nondeclarative memory [4, 5]. Accordingly, neurobiological models of SOC focus almost exclusively on nondeclarative neural systems that support motivational salience and reward value. Transfer of value from a conditioned stimulus to a neutral stimulus is thought to require the basolateral amygdala [6, 7] and the ventral striatum [2, 3], but not the hippocampus. We developed a new paradigm to measure appetitive SOC of tones in rats. Hippocampal lesions severely impaired both acquisition and expression of SOC despite normal FOC. Unlike controls, rats with hippocampal lesions could not discriminate between positive and negative secondary conditioned tones, although they exhibited general familiarity with previously presented tones compared with new tones. Importantly, normal rats' behavior, in contrast to that of hippocampal groups, also revealed different confidence levels as indexed by effort, a central characteristic of hippocampal relational memory. The results indicate, contrary to current systems models, that representations of intrinsic relationships between reward value, stimulus identity, and motivation require hippocampal mediation when these relationships are of a higher order. | 25,201,688 | [
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Changes in antioxidant enzymes and lipid peroxidation in extensor digitorum longus muscles of streptozotocin-diabetic rats may contribute to muscle atrophy. | We investigated muscle atrophy, major antioxidant enzymes and lipid peroxidation in the extensor digitorum longus (EDL, predominantly fast fibers) and soleus (predominantly slow fibers) muscle of streptozotocin-diabetic rats. Female Wistar rats were divided into a control (n = 5) and streptozotocin-induced diabetic group (n = 5). Eight weeks after diabetes induction the EDL and soleus muscles were removed and catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase activity (SOD), and thiobarbituric acid reactive substances (TBARS) levels measured. The CAT activity increased in both the EDL and soleus muscles of the diabetic rats (p < 0.01), whereas the GPX and SOD activities were increased only in the EDL muscle (p < 0.01 and p < 0.05). The TBARS levels were only increased in the EDL muscle of the diabetic rats (p < 0.01). Both muscles showed significant atrophy but the EDL muscle elicited the greatest atrophy. In conclusion, it appears that adaptive responses to oxidative stress were adequate in the soleus muscle, but not in the EDL muscle, of diabetic rats. Thus fast twitch muscle fibers may be more susceptible to oxidative stress than slow twitch muscle fibers and this may contribute to muscle atrophy under diabetic conditions. | 25,201,710 | [
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Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: a systematic review and meta-analysis. | Epidermal growth factor receptor (EGFR) mutation is a reliable and sensitive biomarker for EGFR-TKI therapy in non-small-cell lung cancer (NSCLC). However, detection of EGFR mutation in tissues has obvious limitations. Circulating free DNA (cfDNA) has been reported as an alternative approach for the detection of EGFR mutations. This systematic review and meta-analysis was designed to assess the diagnostic performance of cfDNA, compared with tissues. True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted or calculated for each study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance. 20 eligible studies involving 2012 cases were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.674 (95%CI: 0.517-0.800), 0.935 (95%CI: 0.888-0.963), 10.307 (95%CI: 6.167-17.227), 0.348 (95%CI: 0.226-0.537), and 29.582 (95%CI: 4.582-60.012), respectively. The AUC was 0.93 (95% CI: 0.90-0.95). The meta-analysis suggests that detection of EGFR mutation by cfDNA is of adequate diagnostic accuracy and cfDNA analysis could be a promising screening test for NSCLC. | 25,201,768 | [
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Effects crude protein levels on female Nile tilapia (Oreochromis niloticus) reproductive performance parameters. | The goal of the present work was to study the reproductive performance of Nile Tilapia (Oreochromis niloticus) female broodstock fed diets containing different levels of crude protein (CP). Two hundred and forty Nile tilapia (O. niloticus) were used at an average age of 30 months, with 180 females and 60 males. The broodstock were lodged separately in masonry tanks with continuous water flow. The females were stocked in thirty tanks with dimensions of 8 m(3) in a completely randomized design consisting of five treatments and six replications. The treatments consisted of five diets with different levels of CP (32, 34, 36, 38 and 40%) and with digestible energy per gram of protein of 9.5 kg of feed. The crude protein (CP) levels positively influenced (p<0.05) reproductive parameters (female relative and absolute fecundity, egg diameter, fasting larvae survival capacity), the somatic indexes (gonadosomatic (GSI), hepatosomatic (HIS), viscerosomatic (VSI)), total plasma protein, albumin and triglycerides. There were no significant differences (p>0.05) observed with regard to spawning weight and female weight. The reproductive parameters studied in the present research indicate that diets formulated with 38% CP with digestible energy per gram of CP of 9.5 were the best diets for tilapia females during the reproductive period. | 25,201,770 | [
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