title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Taste characteristics based quantitative and qualitative evaluation of ginseng adulteration. | Adulteration of American ginseng with Asian ginseng is common and has caused much damage to customers. Panel evaluation is commonly used to determine their differences, but it is subjective. Chemical instruments are used to identify critical compounds but they are time-consuming and expensive. Therefore, a fast, accurate and convenient method is required. A taste sensing system, combining both advantages of the above two technologies, provides a novel potential technology for determining ginseng adulteration. The aim is to build appropriate models to distinguish and predict ginseng adulteration by using taste characteristics. It was found that ginsenoside contents decreased linearly (R(2) = 0.92) with mixed ratios. A bioplot of principal component analysis showed a good performance in classing samples with the first two principal components reaching 89.7%, and it was noted that it was the bitterness, astringency, aftertaste of bitterness and astringency, and saltiness leading the successful determination. After factor screening, bitterness, astringency, aftertaste of bitterness and saltiness were employed to build latent models. Tastes of bitterness, astringency and aftertaste bitterness were demonstrated to be most effective in predicting adulteration ratio, mean while, bitterness and aftertaste bitterness turned out to be most effective in ginsenoside content prediction. Taste characteristics of adulterated ginsengs, considered as taste fingerprint, can provide novel guidance for determining the adulteration of American and Asian ginseng. | 25,087,639 | [
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Rapid reconstitution of biosynthetic machinery for fungal metabolites in Aspergillus oryzae: total biosynthesis of aflatrem. | Reconstitution of the biosynthetic machinery for fungal secondary metabolites in Aspergillus oryzae provides an opportunity both for stepwise determination of the biosynthetic pathways and the total biosynthesis of fungal natural products. However, to maximize the utility of the reconstitution system, a simple and rapid strategy for the introduction of heterologous genes into A. oryzae is required. In this study, we demonstrated an effective method for introducing multiple genes involved in the biosynthesis of fungal metabolites by using the expression vectors pUARA2 and pUSA2, each of which contains two cloning sites. The successful introduction of all the aflatrem biosynthetic genes (seven genes in total) after two rounds of transformation enabled the total biosynthesis of aflatrem. This rapid reconstitution strategy will facilitate the functional analysis of the biosynthetic machinery of fungal metabolites. | 25,087,641 | [
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Effect of Er,Cr:YSGG laser irradiation on apical sealing ability of calcium silicatecontaining endodontic materials in root-end cavities. | The aim of this research was to evaluate the apical sealing abilities of 60 root-end cavities filled with mineral trioxide aggregate (MTA) and iRoot BP cements after treated with either 17% EDTA solution or Er,Cr:YSGG laser irradiation. After the filling procedure, apical leakage quantity was measured at 4 weeks using a fluid filtration method. One root from each group was processed for scanning electron microscopy and energy dispersive X-ray spectroscopy analyses. Both EDTA/MTA and laser irradiation/MTA combinations showed significantly lower microleakage than EDTA/iRoot BP and laser irradiation/iRoot BP combinations (p<0.05). Between groups of the same filling material, there were no significant differences among specimens treated with EDTA or laser (p>0.05). Both MTA and iRoot-BP demonstrated tag-like structures within the dentinal tubules when used in conjunction with EDTA. | 25,087,664 | [
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Contraception for women with medical disorders. | Many women in the reproductive years have chronic medical conditions that are affected by pregnancy or in which the fetus is placed at increased risk. In most of these women, ongoing medical management of their conditions is greatly improved, even compared with a decade or two ago. However, their condition may still be seriously exacerbated by the physiological changes of pregnancy, and close monitoring of a carefully planned pregnancy is optimal. This requires effective and safe contraceptive use until pregnancy is desired and the medical condition is stabilised. Many contraceptives will also have adverse effects on some medical conditions, and there is now a considerable awareness of the complexities of some of these interactions. For this reason the World Health Organization has developed an excellent, simple and pragmatic programme of guidelines on a four point scale (the WHO "Medical Eligibility Criteria": WHO-MEC), summarising risk of specific contraceptive methods in women with specified chronic medical conditions. The general approach to contraceptive management of many of these conditions is addressed in this article. | 25,087,667 | [
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Commentary on "Intermittent versus continuous androgen deprivation in prostate cancer." Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, Dawson NA, Donnelly BJ, Venner PM, Vaishampayan UN, Schellhammer PF, Quinn DI, Raghavan D, Ely B, Moinpour CM, Vogelzang NJ, Thompson IM Jr, University of Michigan, Division of Hematology/Oncology, Ann Arbor, MI. N Engl J Med 2013; 368(14):1314-25. doi: 10.1056/NEJMoa1212299. | Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization. A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events. Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.). | 25,087,673 | [
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Commentary on "African American men with very low-risk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: should active surveillance still be an option for them?" Sundi D, Ross AE, Humphreys EB, Han M, Partin AW, Carter HB, Schaeffer EM, Johns Hopkins University, Baltimore, MD. J Clin Oncol 2013; 31(24):2991-7. [Epub 2013 Jun 17]. doi: 10.1200/JCO.2012.47.0302. | Active surveillance (AS) is a treatment option for men with very low-risk prostate cancer (PCa); however, favorable outcomes achieved for men in AS are based on cohorts that under-represent African American (AA) men. To explore whether race-based health disparities exist among men with very low-risk PCa, we evaluated oncologic outcomes of AA men with very low-risk PCa who were candidates for AS but elected to undergo radical prostatectomy (RP). We studied 1,801 men (256 AA, 1,473 white men, and 72 others) who met National Comprehensive Cancer Network criteria for very low-risk PCa and underwent RP. Presenting characteristics, pathologic data, and cancer recurrence were compared among the groups. Multivariable modeling was performed to assess the association of race with upgrading and adverse pathologic features. AA men with very low-risk PCa had more adverse pathologic features at RP and poorer oncologic outcomes. AA men were more likely to experience disease upgrading at prostatectomy (27.3% v 14.4%; P <.001), positive surgical margins (9.8% v 5.9%; P =.02), and higher Cancer of the Prostate Risk Assessment Post-Surgical scoring system (CAPRA-S) scores. On multivariable analysis, AA race was an independent predictor of adverse pathologic features (odds ratio, [OR], 3.23; P =.03) and pathologic upgrading (OR, 2.26; P =.03). AA men with very low-risk PCa who meet criteria for AS but undergo immediate surgery experience significantly higher rates of upgrading and adverse pathology than do white men and men of other races. AA men with very low-risk PCa should be counseled about increased oncologic risk when deciding among their disease management options. | 25,087,674 | [
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[Hepatitis B infection transmission by anti-HBc-positive grafts]. | In Spain, the rate of anti-HBc positive, HBsAg-negative carriers is approximately 10% of adults between the ages of 26 and 65 years. It is therefore impossible to exclude these donors without increasing the mortality of recipients on waiting lists. The incidence of de novo hepatitis B infection in HBsAg-negative recipients of anti-HBc-positive donors is high without prophylaxis and is related to the serological state of the recipient against HBV. Anti-HBc and anti-HBs-positive recipients have low risk, with or without prophylaxis. This patient group therefore does not require prophylaxis but rather periodic posttransplantation checkups. For the other recipient groups (naïve, anti-Hbc and anti-HBs isolates), prophylaxis with IgG HB, lamivudine or combined therapy decreases the incidence of infection. These patients should be treated with prophylaxis immediately after transplantation. Depending on the risk, cost and benefit, patients should currently be treated with lamivudine 100mg/d indefinitely or for longer periods (>10 years). Periodic checkups of HBsAg should be conducted, and if there is graft dysfunction then HBV DNA should be checked. IF HBV DNA is discovered in the donor and found to be positive in serum or in the biopsy, the prophylaxis should be an analogue with a high barrier to resistance from the start. Grafts from anti-HBc-positive donors are not considered at-risk grafts and are used according to donor severity, without being determined by the recipient's serological profile. | 25,087,711 | [
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Are endothelial outgrowth cells a potential source for future re-vascularization therapy? | Endothelial progenitor cells (EPCs) represent a heterogeneous cell population that is believed to be involved in vasculogenesis after ischemic diseases. EPCs could have a potential for future therapies with the purpose of enhancing endothelial repair. However, due to the low amount of these cells in circulation they have to be expanded in vitro before administration into recipients. The purpose of this study was to analyse and evaluate possible changes in morphology and functionality as a result of in vitro ageing of a subtype of EPCs called endothelial outgrowth cells (EOCs), since such changes might compromise the cells' ability to participate in vasculogenesis. EOCs were isolated and grown from human umbilical cord blood using two methodologies with varying degree of cell purification. The changes between the two culture setups and the changes occurring in EOCs over time were traced by flow cytometry and assays for growth, tube formation, and beta-galactosidase production. The cells showed to be indistinguishable from each other during the first weeks of culture. The cells showed a changed morphology with bigger and more granular cells and the growth rate decreased with time. The cells also showed an increased Beta-galactosidase expression and decreased tube formation ability in late passage EOCs. Our data indicates that EOCs undergo senescence during long-term expansion and therefore time for cell harvest has to be validated in order to achieve functional cells still maintaining a therapeutic potential. A possible application in large animal or humans could be local injection of EOCs into affected areas and thereby reducing the need for long-term expansion of the cells. | 25,087,725 | [
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Bioresorbable scaffolds for the treatment of coronary artery disease: current status and future perspective. | Bioresorbable scaffolds represent a novel approach in the treatment of coronary artery disease which allows for vessel wall support without leaving a permanent foreign body in the coronary artery. This technology has the potential to reduce some of the shortcomings of current standard treatment with metallic drug-eluting stents, such as late in-stent restenosis, impaired vasomotion of the stented segment and hindrance of surgical revascularizations. Currently, several bioresorbable scaffolds are available and undergoing clinical or preclinical evaluation. This review will present the current status of development of bioresorbable scaffolds, describe the degradation/resorption process of each device and the clinical data available to date. | 25,087,771 | [
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Direct reimplantation as an alternative approach for treatment of anomalous aortic origin of the right coronary artery. | Anomalous aortic origin of the coronary artery (AAOCA) is a rare cardiac anomaly associated with myocardial ischemia, infarction, and even sudden death. We report 2 patients presenting with AAOCA of the right coronary artery originating from the left coronary sinus with an initial intramural course. In both patients, we performed uncomplicated direct reimplantation of the right coronary artery into the right coronary sinus. For this purpose, the right coronary artery was dissected from the transmural emersion point out of the aortic wall, subsequently as proximal as possible transected and directly reimplanted into the right coronary sinus. In both cases, the postoperative course was uneventful, and cardiac computed tomography confirmed excellent postoperative results after 1 year of follow-up. This technique is a convenient and easily performable approach, characterized by short cross-clamp times and avoidance of aortotomy, and thus is an excellent alternative strategy. | 25,087,812 | [
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Minimal important difference in field walking tests in non-cystic fibrosis bronchiectasis following exercise training. | The 6-min walk distance (6MWD) and incremental shuttle walk distance (ISWD) are clinically meaningful measures of exercise capacity in people with non-cystic fibrosis (CF) bronchiectasis, but the change in walking distance which constitutes clinical benefit is undefined. This study aimed to determine the minimal important difference for the 6MWD and ISWD in non-CF bronchiectasis. Thirty-seven participants with mean FEV1 70% predicted completed both field walking tests before and after an 8-week exercise program. The minimal important difference was calculated using a distribution-based and anchor-based method, with the global rating of change scale used. The mean change in 6MWD in participants who reported themselves to be unchanged was 10 m, compared to 36 m (small change) and 45 m (substantial change) (p = 0.01). For the ISWD, the mean change in participants who reported themselves to be unchanged was 33 m, compared to 54 m (small change) and 73 m (substantial change) (p = 0.04). The anchor-based method defined the minimal important difference for 6MWD as 24.5 m (AUC 0.76, 95% CI 0.61-0.91) and for ISWD as 35 m (AUC 0.88, 95% CI 0.73-0.99), based on participant's global rating of change. The distribution-based method indicated a value of 22.3 m for the 6MWD and 37 m for the ISWD. There was excellent agreement between the two methods for the 6MWD (kappa = 0.91) and the ISWD (kappa = 0.92). Small changes in 6MWD and ISWD may represent clinically important benefits in people with non-CF bronchiectasis. These data are likely to assist in the interpretation of change in exercise capacity following intervention. | 25,087,836 | [
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Tuning gelation kinetics and mechanical rigidity of β-hairpin peptide hydrogels via hydrophobic amino acid substitutions. | Self-assembling peptide hydrogels with faster gelation kinetics and higher mechanical rigidity are favorable for their practical applications. A design strategy to control the folding, self-assembly, and hydrogelation of β-hairpin peptides via hydrophobic amino acid substitutions has been explored in this study. Isoleucine has higher hydrophobicity and stronger propensity for β-sheet hydrogen bonding than valine. After the valine residues of MAX1 (VKVKVKVKV(D)PPTKVKVKVKV-NH2) were replaced with isoleucines, oscillatory rheometry and circular dichroism (CD) spectroscopy characterizations indicated that the variants had clearly faster self-assembly and hydrogelation rates and that the resulting gels displayed higher mechanical stiffness. Transmission electron microscopy (TEM) indicated the parent MAX1 and its variants all formed networks of long and entangled fibrils with the similar diameters of ∼3 nm, suggesting little effect of hydrophobic substitutions on the self-assembled morphology. The MAX1I8 (IKIKIKIKV(D)PPTKIKIKIKI-NH2) hydrogel showed the fastest gelation rate (within 5 min) and the highest gel rigidity with the series, supporting the homogeneous cell distribution within its 3D scaffold. In addition, the MAX1I8 hydrogel showed quick shear-thinning and rapid recovery upon cessation of shear strain, and the MTT and immunological assays indicated its low cytotoxicity and good biocompatibility. These features are highly attractive for its widespread use in 3D cell culturing and regenerative medical treatments. | 25,087,842 | [
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Highly stable layered double hydroxide colloids: a direct aqueous synthesis route from hybrid polyion complex micelles. | Aqueous suspensions of highly stable Mg/Al layered double hydroxide (LDH) nanoparticles were obtained via a direct and fully colloidal route using asymmetric poly(acrylic acid)-b-poly(acrylamide) (PAA-b-PAM) double hydrophilic block copolymers (DHBCs) as growth and stabilizing agents. We showed that hybrid polyion complex (HPIC) micelles constituted of almost only Al(3+) were first formed when mixing solutions of Mg(2+) and Al(3+) cations and PAA3000-b-PAM10000 due to the preferential complexation of the trivalent cations. Then mineralization performed by progressive hydroxylation with NaOH transformed the simple DHBC/Al(3+) HPIC micelles into DHBC/aluminum hydroxide colloids, in which Mg(2+) ions were progressively introduced upon further hydroxylation leading to the Mg-Al LDH phase. The whole process of LDH formation occurred then within the confined environment of the aqueous complex colloids. The hydrodynamic diameter of the DHBC/LDH colloids could be controlled: it decreased from 530 nm down to 60 nm when the metal complexing ratio R (R = AA/(Mg + Al)) increased from 0.27 to 1. This was accompanied by a decrease of the average size of individual LDH particles as R increased (for example from 35 nm at R = 0.27 down to 17 nm at R = 0.33), together with a progressive favored intercalation of polyacrylate rather than chloride ions in the interlayer space of the LDH phase. The DHBC/LDH colloids have interesting properties for biomedical applications, that is, high colloidal stability as a function of time, stability in phosphate buffered saline solution, as well as the required size distribution for sterilization by filtration. Therefore, they could be used as colloidal drug delivery systems, especially for hydrosoluble negatively charged drugs. | 25,087,853 | [
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A robust and accurate center-frequency estimation (RACE) algorithm for improving motion estimation performance of SinMod on tagged cardiac MR images without known tagging parameters. | A robust and accurate center-frequency (CF) estimation (RACE) algorithm for improving the performance of the local sine-wave modeling (SinMod) method, which is a good motion estimation method for tagged cardiac magnetic resonance (MR) images, is proposed in this study. The RACE algorithm can automatically, effectively and efficiently produce a very appropriate CF estimate for the SinMod method, under the circumstance that the specified tagging parameters are unknown, on account of the following two key techniques: (1) the well-known mean-shift algorithm, which can provide accurate and rapid CF estimation; and (2) an original two-direction-combination strategy, which can further enhance the accuracy and robustness of CF estimation. Some other available CF estimation algorithms are brought out for comparison. Several validation approaches that can work on the real data without ground truths are specially designed. Experimental results on human body in vivo cardiac data demonstrate the significance of accurate CF estimation for SinMod, and validate the effectiveness of RACE in facilitating the motion estimation performance of SinMod. | 25,087,857 | [
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Involvement of cerebral nervous system areas and cytokines on antihyperalgesic and anti-inflammatory activities of Kielmeyera rugosa Choisy (Calophyllaceae) in rodents. | Kielmeyera rugosa is a medicinal plant known in Northeastern Brazil as 'pau-santo', and it is used in the treatment of several tropical diseases such as malaria, schistosomiasis, and leishmaniasis. We evaluated antihyperalgesic and anti-inflammatory activities of methanol stem extract of K. rugosa (MEKR) in mice. The mechanical hyperalgesia induced by carrageenan and tumor necrosis factor-alpha (TNF-α), prostaglandin E2 , and dopamine were assessed. We also investigated the anti-inflammatory effect of MEKR on carrageenan-induced pleurisy and paw edema. Ninety minutes after the treatment, the animals were submitted to an imunofluorescence for Fos protein. MEKR (100, 200, and 400 mg/kg; p.o.) inhibited the development of mechanical hypernociception and edema. MEKR significantly decreased TNF-α and interleukin 1β levels in pleural lavage and suppressed the recruitment of leukocytes. MEKR (1, 10, and 100 mg/mL) did not produce cytotoxicity, determined using the methyl-thiazolyl-tetrazolium assay in vitro. The locomotor activity was not affected. MEKR activated significantly the bulb olfactory, piriform cortex, and periaqueductal gray of the central nervous system. Our results provide first time evidence to propose that MEKR attenuates mechanical hyperalgesia and inflammation, in part, through an activation of central nervous system areas, mainly the periaqueductal gray and piriform cortex areas. | 25,087,858 | [
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A visuomotor disorder in the absence of movement: does optic ataxia generalize to learned isometric hand action? | Visuomotor deficits in parietal patients suffering from Optic Ataxia (OA) have been so far studied during natural reaching movements. We aimed at understanding if these disorders are also present when more abstract visuomotor transformations are involved. A patient with unilateral OA was tested during both standard reaches and isometric actions, therefore in the absence of hand displacement. Isometric action was affected similarly to standard reaches, with endpoint errors to visual targets that were found in both central and peripheral vision. The dissociation of perceptual and motor components of errors highlighted the existence of field, hand and hemispace effects, which depended on the type of error investigated. A generalization of the reaching disorder to learned isometric conditions would suggest that lesions of posterior parietal cortex (PPC) affect sensory-motor transformations not only for standard reaches, but also when visual signals need to be aligned with information from hand force receptors, therefore regardless of the specific remapping required to generate the directional motor output. The isometric impairment emerged with high and similar severity regardless of whether targets were in central or peripheral vision. Since under all isometric conditions gaze and hand position were decoupled, the spatial correspondence between the hand and the gaze seems to play a critical role in this syndrome. This indicates that regardless of the action to be performed and the specific remapping required, there exists in PPC an abstract representation of the directional motor output, where the computation of eye-hand alignment by parietal neurons plays a crucial role. | 25,087,860 | [
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Origin licensing requires ATP binding and hydrolysis by the MCM replicative helicase. | Loading of the six related Minichromosome Maintenance (MCM) proteins as head-to-head double hexamers during DNA replication origin licensing is crucial for ensuring once-per-cell-cycle DNA replication in eukaryotic cells. Assembly of these prereplicative complexes (pre-RCs) requires the Origin Recognition Complex (ORC), Cdc6, and Cdt1. ORC, Cdc6, and MCM are members of the AAA+ family of ATPases, and pre-RC assembly requires ATP hydrolysis. Here we show that ORC and Cdc6 mutants defective in ATP hydrolysis are competent for origin licensing. However, ATP hydrolysis by Cdc6 is required to release nonproductive licensing intermediates. We show that ATP binding stabilizes the wild-type MCM hexamer. Moreover, by analyzing MCM containing mutant subunits, we show that ATP binding and hydrolysis by MCM are required for Cdt1 release and double hexamer formation. This work alters our view of how ATP is used by licensing factors to assemble pre-RCs. | 25,087,873 | [
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High dengue NS1 antigenemia in febrile patients in Ibadan, Nigeria. | We conducted a dengue seroprevalence survey among febrile patients positive or negative for malaria in Ibadan, Nigeria. Dengue IgG and NS1 seroprevalence of 73% and 35%, respectively, was observed, and 43% of those with malaria had acute dengue infection (NS1 determination). On the other hand, all participants with malaria were IgG dengue seropositive consistent with the endemicity of both arthropod-borne infections in the region. These data indicate that dengue is emerging as a major and neglected cause of fever in Nigeria. | 25,087,878 | [
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Disruption of the baculovirus core gene ac78 results in decreased production of multiple nucleocapsid-enveloped occlusion-derived virions and the failure of primary infection in vivo. | The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac78 gene is one of the baculovirus core genes. Recent studies showed that ac78 is essential for budded virion (BV) production and the embedding of occlusion-derived virion (ODV) into occlusion body during the AcMNPV life cycle. Here, we report that an ac78-knockout AcMNPV (vAc78KO) constructed in this study had different phenotypes than those described in the previous studies. A few infectious BVs were detected using titer assays, immunoblot analyses and plaque assays, indicating that ac78 is not essential for BV formation. Electron microscopy confirmed that the ac78 deletion did not affect nucleocapsid assembly and ODV formation. However, the numbers of multiple nucleocapsid-enveloped ODVs and ODV-embedded occlusion bodies were significantly decreased. Subsequently, the highly conserved amino acid residues 2-25 and 64-88 of Ac78, which are homologous to an oxidoreductase and cytochrome c oxidase, respectively, were demonstrated to play a crucial role in the morphogenesis of multiple nucleocapsid-enveloped ODV. Immunoblot analysis found that Ac78 was an ODV envelope-associated protein. Consistently, amino acid residues 56-93 of Ac78 were identified as an inner nuclear membrane sorting motif, which may direct the localization of Ac78 to the ODV envelope. In vivo infectivity assays showed that the occlusion bodies of vAc78KO were unable to establish primary infection in the midgut of Trichoplusia ni larvae. Taken together, our results suggest that ac78 plays an important role in BV production and proper multiple nucleocapsid-enveloped ODV formation, as well as AcMNPV primary infection in vivo. | 25,087,880 | [
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Characterization of antithrombin levels in pregnancy. | To characterize antithrombin (AT) levels in normal pregnancy. We performed secondary analyses with data from 3 studies. Using a single measurement from each subject in the first analysis (cross-sectional), we correlated AT levels with gestational age from the middle of the second trimester throughout the third trimester of pregnancy. Using serial measurements in a second analysis (cohort), we compared AT levels between the late first and second trimesters of pregnancy and baseline (the level at 6 weeks postpartum). Using serial measurements in a third analysis (cohort), we analyzed the pattern of change in AT levels in the immediate postpartum period. Assays of AT activity were performed using the Dade Behring (Siemens) Berichrom Antithrombin III Chromogenic Assay. AT levels were correlated with gestational age using the Pearson correlation coefficient and compared between the different time points using one-way ANOVA. Overall, AT levels were 20% lower than baseline during pregnancy (p<0.01). There was no significant difference between AT levels obtained between late first trimester and late second trimester. From midtrimester to term, however, AT levels were negatively correlated with gestational age with a 13% drop during this period of time (r=-0.26 [-0.39, -0.11]; p<0.01). Immediately after childbirth, AT levels fell precipitously to 30% below baseline (p<0.05) and reached a nadir 12 hours postpartum before rising and returning to baseline by 72 hours postpartum. It appears that antithrombin (AT) is consumed at the time of delivery. Our findings have implications for AT replacement or even anticoagulation at the time of delivery. | 25,087,890 | [
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Hira-mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote. | Extensive chromatin reprogramming occurs at fertilization and is thought to be under the control of maternal factors, but the underlying mechanisms remain poorly understood. We report that maternal Hira, a chaperone for the histone variant H3.3, is required for mouse development past the zygote stage. Male pronucleus formation is inhibited upon deletion of Hira due to a lack of nucleosome assembly in the sperm genome. Hira mutant oocytes are incapable of developing parthenogenetically, indicative of a role for Hira in the female genome. Both parental genomes show highly reduced levels of DNA replication and transcription in the mutants. It has long been thought that transcription is not required for zygote development. Surprisingly, we found that Hira/H3.3-dependent transcription of ribosomal RNA is required for first cleavage. Our results demonstrate that Hira-mediated H3.3 incorporation is essential for parental genome reprogramming and reveal an unexpected role for rRNA transcription in the mouse zygote. | 25,087,892 | [
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Pediatric nasal valve surgery: short-term outcomes and complications. | To examine the short-term outcomes and complications of open nasal valve surgery in children under 16 years of age. case series and chart review study setting: an urban, tertiary, pediatric otolaryngology practice. Children under 16 years of age who had undergone nasal valve surgery with cartilage grafting for functional indications were identified. Patients with cleft-related nasal deformities were excluded. Charts were reviewed for indications and short-term outcomes (patient satisfaction and postoperative complications within the first 90 days). A literature review assessed prior outcomes in adult nasal valve patients. Fifteen pediatric patients, 15 years old or younger, were identified as having undergone open nasal valve repair utilizing septal or auricular cartilage grafts. Patient age ranged from 6 to 15 years. Surgical indications were nasal obstruction with nasal valve stenosis related to either previous trauma (n=10), congenital deformity (n=3), iatrogenic injury (n=1) or hemangioma of infancy (n=1). All patients noted improvement of symptoms at the 90 day interval or later. There was one episode of self-limited epistaxis, which occurred on postoperative day 7 following splint removal. In children, an obstructive nasal breathing pattern may be caused by nasal valve collapse, which can be addressed with nasal valve surgery. This small series suggests that short-term results in children may be similar to those observed in the adult population. Pediatric nasal valve surgery outcomes have not been described previously; studies focused on long-term outcomes following pediatric nasal valve surgery are needed. 4. | 25,087,897 | [
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The level of specialist assessment of adult asthma is influenced by patient age. | Late onset asthma is associated with more severe disease and higher morbidity than in younger asthma patients. This may in part relate to under recognition of asthma in older adults, but evidence on the impact of patient age on diagnostic assessment of asthma in a specialist setting is sparse. To examine the impact of patient age on the type and proportion of diagnostic tests performed in patients undergoing specialist assessment for asthma. Data from a clinical population consisting of all patients consecutively referred over a 12 months period to a specialist clinic for assessment of asthma were analysed. A total of 224 patients with asthma or suspected asthma were referred during the 12 month period; 86 adults aged <35 years, 95 aged 35-55 years and 43 aged >55 years. Symptom characteristics were similar, but adults >35 years had a lower lung function than younger adults, and were more frequently smokers. However, a regression analysis showed that older age was associated with a lower likelihood of diagnostic assessment with a reversibility test, a bronchial challenge test, or measurement of exhaled NO, independently of a known diagnosis of asthma, smoking habits and lung function at referral. A lower level of diagnostic assessment was observed already after the age of 35 years, indicating a risk for under diagnosis of asthma at an earlier patient age than previously thought. | 25,087,903 | [
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Practice-oriented research: what it takes to do collaborative research in private practice. | The goal of this paper is to describe the authors' experience conducting research in and for private practice. Based on two distinct research programs (one guided by a scientist practitioner leading various groups of clinicians and another from a network of practitioners and researchers), a number of practice-oriented studies are presented. Lessons learned from these collaborative projects are discussed in terms of challenges and strategies to deal with them, as well as benefits that can be earned from conducting empirical studies within clinical routine. General recommendations are then offered to foster the engagement of clinicians in their own working environment and to facilitate partnerships between researchers and practitioners in developing and implementing valid, feasible, and informative clinical studies. | 25,087,919 | [
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Birth trends and factors affecting childbearing among thoracic surgeons. | As more women enter the thoracic surgery profession, issues affecting childbearing become increasingly important. We set out to assess birth trends and factors affecting childbearing among thoracic surgeons. A 33-question anonymous survey was sent to women diplomats of American Board of Thoracic Surgery, residents in Thoracic Surgery Residents Association, and members of Women in Thoracic Surgery. Findings were compared with national norms. There were a total of 113 respondents (88 women, 25 men). Of 69% (61 of 88) of women and 88% (22 of 25) of men who desired children, 98% (60 of 61) of women versus 50% (11 of 22) of men delayed pregnancy (p < 0.0001). Eighty-two percent (72 of 88) of women versus 60% (15 of 25) of men felt their career would be adversely affected, with 6% (54 of 88) of women versus 16% (4 of 25) of men reporting that pregnancy would be viewed unfavorably among peers (p < 0.03 and p < 0.0001, respectively). Of women of childbearing age, 28% (15 of 54) utilized assisted reproductive technology (national average 12%, p < 0.0002). The total fertility rate was 0.6 ± 0.2 children per woman whereas the national rate was 1.9. The average age at first-childbirth was 34.3 ± 0.7 years, while the national norm was 25.4. Women thoracic surgeons begin their family later in life and have fewer children compared with the national average. These findings are likely related to the perception that their career would be adversely affected and to advanced maternal age. Residency programs and practice groups should strive to develop policies that support childbearing earlier in training as the number of women thoracic surgeons grows. | 25,087,932 | [
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Prevalence and genotypic characterization of human parvovirus B19 in children with hemato-oncological disorders in North India. | Human parvovirus B19 (B19V) has been associated with chronic anemia in immuno-compromised patients. In the present study, the prevalence and genotype distribution of B19V in children from North India, suffering with hemato-oncological disorders is reported. Children with aplastic anemia/leukemia/chronic hematological disorders, and healthy blood donors were enrolled in the study. Blood samples from cases and blood donors were analyzed for anti-B19V IgM and anti-B19V IgG antibodies by ELISA and for B19V-DNA by PCR. B19V-DNA positive samples were studied further for determination of viral load in samples and for B19V-DNA sequence (VP1/VP2 overlapping region) analysis. Total 238 cases (103 leukemia, 77 aplastic anemia and 58 chronic hematological disorders) and 350 blood donors were enrolled in the study. Anti-B19V IgM was positive in 16 (6.7%) cases, B19V-DNA was detected in 13 (5.5%) cases and anti-B19V IgG was positive in 127 (53.4%) cases. Total 223 (63.5%) blood donors were positive for anti-B19V IgG, however, anti-B19V IgM and B19V-DNA was not detected in any blood donor. The prevalence of anti-B19V IgG was significantly higher in children > 10 years of age. Viral load of B19V decreased with appearance of specific antibodies. Phylogenetic analysis of the VP1/VP2 overlapping region revealed that genotype 1 predominated in these patients (11/13, 84.6%), followed by genotype 3 (2/13, 15.4%). No genotype 2 was detected. All the genotype 1strains were sub-typed as 1a, except four strains, which matched neither 1a nor 1b and formed a separate cluster. Both the genotype 3 strains were sub-typed as 3b. | 25,087,946 | [
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Anti-allergic effect of bee venom in an allergic rhinitis mouse model. | Bee venom (BV) has been used as an anti-inflammatory and immune modulating agent in Oriental medicine. This study used a mouse model to investigate the anti-allergic effect of BV, which is used in the treatment of various inflammatory diseases in traditional medicine. BV was obtained from the National Institute of Agricultural Science and Technology of Korea. Female BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA). BV was administered nasally prior to the intranasal instillation of OVA. Allergic behavior, serum OVA-specific immunoglobulin E (IgE), interleukin (IL)-4, IL-10, and interferon-gamma (INF-γ) levels in nasal lavage fluid were measured. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate histological change. BV attenuated nasal symptoms and inhibited the production of OVA-specific IgE and IL-4 in sensitized mice. The degree of inflammatory cell infiltration and goblet cell hyperplasia was attenuated by BV. Thus, BV effectively reduced allergic inflammation in a mouse model of allergic rhinitis, suggesting its potential as a useful therapeutic agent to treat allergic rhinitis. | 25,087,951 | [
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Eugenol ameliorates hepatic steatosis and fibrosis by down-regulating SREBP1 gene expression via AMPK-mTOR-p70S6K signaling pathway. | Beneficial effect of eugenol on fatty liver was examined in hepatocytes and liver tissue of high fat diet (HFD)-fed C57BL/6J mice. To induce a fatty liver, palmitic acid or isolated hepatocytes from HFD-fed Sprague-Dawley (SD) rats were used in vitro studies, and C57BL/6J mice were fed HFD for 10 weeks. Lipid contents were markedly decreased when hepatocytes were treated with eugenol for up to 24 h. Gene expressions of sterol regulatory element binding protein 1 (SREBP1) and its target enzymes were suppressed but those of lipolysis-related proteins were increased. As a regulatory kinase for lipogenic transcriptional factors, the AMP-activated protein kinase (AMPK) signaling pathway was examined. Protein expressions of phosphorylated Ca(2+)-calmodulin dependent protein kinase kinase (CAMKK), AMPK and acetyl-CoA carboxylase (ACC) were significantly increased and those of phosphorylated mammalian target of rapamycin (mTOR) and p70S6K were suppressed when the hepatocytes were treated with eugenol at up to 100 µM. These effects were all reversed in the presence of specific inhibitors of CAMKK, AMPK or mTOR. In vivo studies, hepatic triglyceride (TG) levels and steatosis score were decreased by 45% and 72%, respectively, in eugenol-treated mice. Gene expressions of fibrosis marker protein such as α-smooth muscle actin (α-SMA), collagen type I (Col-I) and plasminogen activator inhibitor-1 (PAI-1) were also significantly reduced by 36%, 63% and 40% in eugenol-treated mice. In summary, eugenol may represent a potential intervention in populations at high risk for fatty liver. | 25,087,956 | [
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Validity of trunk extensor and flexor torque measurements using isokinetic dynamometry. | This study aimed to evaluate the validity and test-retest reliability of trunk muscle strength testing performed with a latest-generation isokinetic dynamometer. Eccentric, isometric, and concentric peak torque of the trunk flexor and extensor muscles was measured in 15 healthy subjects. Muscle cross sectional area (CSA) and surface electromyographic (EMG) activity were respectively correlated to peak torque and submaximal isometric torque for erector spinae and rectus abdominis muscles. Reliability of peak torque measurements was determined during test and retest sessions. Significant correlations were consistently observed between muscle CSA and peak torque for all contraction types (r=0.74-0.85; P<0.001) and between EMG activity and submaximal isometric torque (r ⩾ 0.99; P<0.05), for both extensor and flexor muscles. Intraclass correlation coefficients were comprised between 0.87 and 0.95, and standard errors of measurement were lower than 9% for all contraction modes. The mean difference in peak torque between test and retest ranged from -3.7% to 3.7% with no significant mean directional bias. Overall, our findings establish the validity of torque measurements using the tested trunk module. Also considering the excellent test-retest reliability of peak torque measurements, we conclude that this latest-generation isokinetic dynamometer could be used with confidence to evaluate trunk muscle function for clinical or athletic purposes. | 25,087,981 | [
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Quercetin attenuates renal ischemia/reperfusion injury via an activation of AMP-activated protein kinase-regulated autophagy pathway. | Renal ischemia/reperfusion (I/R) is a major cause of acute renal failure. Quercetin, a flavonoid antioxidant, presents in many kinds of food. The molecular mechanism of quercetin on renal protection during I/R is still unclear. Here, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renal protection by quercetin. To investigate whether quercetin protects renal cells from I/R-induced cell injury, an in vitro model of I/R and an in vivo I/R model were used. Cell apoptosis was determined by propidium iodide/annexin V staining. Western blotting and immunofluorescence were used to determine the autophagy. AMPK expression was inhibited with appropriate short hairpin RNA (shRNA). In cultured renal tubular cell I/R model, quercetin decreased the cell injury, up-regulated the AMPK phosphorylation, down-regulated the mammalian target of rapamycin (mTOR) phosphorylation and activated autophagy during I/R. Knockdown of AMPK by shRNA transfection decreased the quercetin-induced autophagy but did not affect the mTOR phosphorylation. In I/R mouse model, quercetin decreased the increased serum creatinine level and altered renal histological score. Quercetin also increased AMPK phosphorylation, inhibited the mTOR phosphorylation and activated autophagy in the kidneys of I/R mice. These results suggest that quercetin activates an AMPK-regulated autophagy signaling pathway, which offers a protective effect in renal I/R injury. | 25,087,994 | [
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Ursolic acid ameliorates autoimmune arthritis via suppression of Th17 and B cell differentiation. | Ursolic acid (UA) is a pentacyclic triterpenoid found in most plant species, which has been shown anti-inflammatory and anti-oxidative activities. In this study, we examined the effects of UA on collagen-induced arthritis (CIA) in mice, and to identify the mechanisms underlying the effects. CIA was induced in mice. Two weeks later, the mice were treated with UA (150 mg/kg, ip, 3 times per week) for 4 weeks. The expression of cytokines and oxidative stress markers in joint tissues was measured with immunohistochemistry. The numbers of CD4+IL-17+, CD4+CD25+Foxp3+ and pSTAT3 cells in spleens were determined using confocal immunostaining or flowcytometric analyses. Serum antibody levels and B cell-associated marker mRNAs were analyzed with ELISAs and qRT-PCR, respectively. CD4+ T cells and CD19+ B cells were purified from mice spleens for in vitro studies. UA treatment significantly reduced the incidence and severity of CIA-induced arthritis, accompanied by decreased expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6, IL-21 and IL-17) and oxidative stress markers (nitrotyrosine and iNOS) in arthritic joints. In CIA mice, UA treatment significantly decreased the number of Th17 cells, while increased the number of Treg cells in the spleens, which was consistent with decreased expression of pSTAT3, along with IL-17 and RORγt in the splenocytes. In addition, UA treatment significantly reduced the serum CII-specific IgG levels in CIA mice. The inhibitory effects of UA on Th17 cells were confirmed in an in vitro model of Th17 differentiation. Furthermore, UA dose-dependently suppressed the expression of B cell-associated markers Bcl-6, Blimp1 and AID mRNAs in purified CD19+ B cells pretreated with IL-21 or LPS in vitro. UA treatment significantly ameliorates CIA in mice via suppression of Th17 and differentiation. By targeting pathogenic Th17 cells and autoantibody production, UA may be useful for the treatment of autoimmune arthritis and other Th17-related diseases. | 25,087,995 | [
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Alzheimer's disease progression model based on integrated biomarkers and clinical measures. | Biomarkers and image markers of Alzheimer's disease (AD), such as cerebrospinal fluid Aβ42 and p-tau, are effective predictors of cognitive decline or dementia. The aim of this study was to integrate these markers with a disease progression model and to identify their abnormal ranges. The data of 395 participants, including 86 normal subjects, 108 early mild cognitive impairment (EMCI) subjects, 120 late mild cognitive impairment (LMCI) subjects, and 81 AD subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For the participants, baseline and long-term data on cerebrospinal fluid Aβ42 and p-tau, hippocampal volume, and ADAS-cog were available. Various linear and nonlinear models were tested to determine the associations among the ratio of Aβ42 to p-tau (the Ratio), hippocampal volume and ADAS-cog. The most likely models for the Ratio, hippocampal volume, and ADAS-cog (logistic, Emax, and linear models, respectively) were used to construct the final model. Baseline disease state had an impact on all the 3 endpoints (the Ratio, hippocampal volume, and ADAS-cog), while APOEε4 genotype and age only influence the Ratio and hippocampal volume. The Ratio can be used to identify the disease stage for an individual, and clinical measures integrated with the Ratio improve the accuracy of mild cognitive impairment (MCI) to AD conversion forecasting. | 25,088,003 | [
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Prediction of spontaneous HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients during the immune clearance phase. | Spontaneous hepatitis B virus (HBV) e antigen (HBeAg) seroconversion is associated with reduced risk of liver-related complications, but is poorly understood. In this study, 113 chronic hepatitis B patients in the immune active HBeAg-positive phase were followed up for 76 weeks. Based on the outcome of liver function, HBeAg, hepatitis B viral e antibody (anti-HBe) and HBV DNA at week 76, 18 patients were classified as spontaneous HBeAg seroconversion group (group A) and 95 patients were classified as non-spontaneous HBeAg seroconversion group (group B). In multivariate logistic regression analysis, only week 28 HBV DNA levels were used for the logistic regression equation, and the odds ratio was 0.505 (95% confidence interval (CI): 0.366-0.697). The areas under the receiver operating characteristic curve for HBV DNA and HBeAg levels at week 28 were 0.824 (P < 0.001, 95% CI: 0.720-0.927) and 0.832 (P < 0.001, 95% CI: 0.744-0.921), respectively. Based on the maximization of Youden's index, the optimal cutoff values of HBV DNA and HBeAg levels at week 28 were 3.84 log10 IU/ml and 1.53 log10 PEI-U/ml, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HBV DNA levels at week 28 were 50.0%, 97.9%, 81.8%, and 91.2%, respectively. The sensitivity, specificity, PPV, and NPV of HBeAg levels at week 28 were 94.4%, 60.0%, 30.9%, and 98.3%, respectively. In conclusion, the dynamic monitoring of HBV DNA and HBeAg levels predicted accurately determines spontaneous HBeAg seroconversion over the duration of 1 year. | 25,088,043 | [
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Aquastella gen. nov.: a new genus of saprolegniaceous oomycete rotifer parasites related to Aphanomyces, with unique sporangial outgrowths. | The oomycete genus Aquastella is described to accommodate two new species of parasites of rotifers observed in Brooktrout Lake, New York State, USA. Three rotifer species--Keratella taurocephala, Polyarthra vulgaris, and Ploesoma truncatum--were infected, and this is the first report of oomycete infection in these species. Aquastella attenuata was specific to K. taurocephala and Aquastella acicularis was specific to P. vulgaris and P. truncatum. The occurrence of infections correlated with peak host population densities and rotifers were infected in the upper layers of the water column. Sequencing of 18S rRNA and phylogenetic analysis of both species placed them within the order Saprolegniales, in a clade closely related to Aphanomyces. The Aquastella species were morphologically distinct from other rotifer parasites as the developing sporangia penetrated out through the host body following its death to produce unique tapered outgrowths. Aquastella attenuata produced long, narrow, tapering, finger-like outgrowths, whilst A. acicularis produced shorter, spike-like outgrowths. We hypothesize that the outgrowths serve to deter predation and slow descent in the water column. Spore cleavage was intrasporangial with spore release through exit tubes. Aquastella attenuata produced primary zoospores, whereas A. acicularis released spherical primary aplanospores, more typical of other genera in the Aphanomyces clade. | 25,088,070 | [
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Complex Regional Pain Syndrome type I with atypical scintigraphic pattern--diagnosis and evaluation of the entity with three phase bone scintigraphy. A case report. | Complex Regional Pain Syndrome (CRPS) is a neurological disorder of unknown etiology which may lead to severe disability. Its diagnosis is very difficult and based on diagnostic criteria which have been changing over last years. Still, there is no golden standard in diagnosis of this entity. Three-phase bone scan is a widely used diagnostic modality which has been proved useful in CRPS evaluation. The syndrome may present various scintigraphic patterns. Different diagnostic modalities can also be helpful when CRPS is suspected including plain film radiography, magnetic resonance imaging and ultrasonography. Multidisciplinary approach is necessary for proper and quick diagnosis. We present a case of CRPS in 12-year-old girl in whom the diagnosis was based on the bone scan. | 25,088,114 | [
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Nestin expression in mesenchymal stromal cells: regulation by hypoxia and osteogenesis. | The intermediate filament protein nestin is used as a marker for neural stem cells, and its expression is inversely correlated with cellular differentiation. More recently, nestin expression has also been described in other cell types including multipotential mesenchymal stromal cells (MSCs). In this study, we examined the expression of nestin in equine, canine and human bone marrow-derived MSCs undergoing osteogenic differentiation, to determine whether nestin levels were attenuated as the cells acquired a more mature phenotype. In addition, the expression of nestin may be under the influence of cellular hypoxia, as nestin expression is known to increase in areas of ischemic tissue damage. Therefore, we also examined the effects of hypoxia on expression of nestin in human MSCs and examined a role for hypoxia inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in the response. Additionally, we quantified the temporal expression of nestin in the fracture callus during bone regeneration, a site that has been characterized as hypoxic. There were no significant changes in nestin expression in MSCs during osteogenic differentiation. There was a significant increase in expression of nestin mRNA and protein in human MSCs in response to hypoxia (1% O2) or the chemical hypoxia mimetic desferroxamine. This may be due to upregulation of VEGF under hypoxia, as treatment of cells with the VEGF receptor antagonist CPO-P11 attenuated hypoxia-induced nestin expression. A significant increase in nestin mRNA expression was observed in the fracture callus of mice three and seven days post fracture. Nestin was not a selective marker for MSCs, as its expression was maintained during osteogenic differentiation, in all species examined. Furthermore our data suggest that nestin expression can be induced by hypoxia, and that this increase in nestin is partially regulated by HIF-1α and VEGF. Interestingly, nestin levels were significantly upregulated at the fracture site. Further studies are required to understand the role of nestin in bone cell biology and ultimately bone regeneration. | 25,088,159 | [
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Cardiac arrhythmias in hypokalemic periodic paralysis: Hypokalemia as only cause? | It is unknown how often cardiac arrhythmias occur in hypokalemic periodic paralysis (HypoPP) and if they are caused by hypokalemia alone or other factors. This systematic review shows that cardiac arrhythmias were reported in 27 HypoPP patients. Cases were confirmed genetically (13 with an R528H mutation in CACNA1S, 1 an R669H mutation in SCN4A) or had a convincing clinical diagnosis of HypoPP (13 genetically undetermined) if reported prior to the availability of genetic testing. Arrhythmias occurred during severe hypokalemia (11 patients), between attacks at normokalemia (4 patients), were treatment-dependent (2 patients), or unspecified (10 patients). Nine patients died from arrhythmia. Convincing evidence for a pro-arrhythmogenic factor other than hypokalemia is still lacking. The role of cardiac expression of defective skeletal muscle channels in the heart of HypoPP patients remains unclear. Clinicians should be aware of and prevent treatment-induced cardiac arrhythmia in HypoPP. | 25,088,161 | [
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Thrombolysis in recurrent stroke-beyond guidelines: a case report. | Intravenous (IV) thrombolysis is approved and proven treatment for acute ischemic stroke in the window period of 4.5 hours. The therapeutic benefit is not extended to many patients with prior stroke and recurrent stroke as they are excluded in the protocol for thrombolysis. We report a case of successful IV thrombolysis in a young patient with recent prior stroke and recurrent stroke. A 35-year-old male presented in our emergency with recurrent stroke had a history of acute onset vertigo, headache, and vomiting. He was diagnosed to have posterior circulation stroke before 5 days on the basis of clinical history and neuroimaging. On the day of presentation to our hospital, he had developed new symptom of acute onset right hemiparesis with dysarthria. IV tissue plasminogen activator administered within 2 hours of onset of new symptoms resulted in significant improvement in spite of the recent prior stroke. | 25,088,167 | [
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Clinical characteristics of cardioembolic transient ischemic attack: comparison with noncardioembolic transient ischemic attack. | Previous studies show that 6%-31% of transient ischemic attacks (TIA) were caused by cardiogenic cerebral embolism (cardioembolic TIA). As prompt initiation of therapy is essential in TIA to prevent subsequent strokes, determining their cause is important. In this study, we aim to determine the features of cardioembolic TIA and to compare them with those of noncardioembolic etiology. We retrospectively reviewed patients with a tissue-defined TIA who were admitted to our hospital from April 2007 to August 2013. The etiology was categorized according to Trial of Org 10172 in Acute Stroke Treatment, and TIA of cardioembolic origin and cervicocerebrovascular etiology (noncardioembolic TIA) were included in this study. Those with 2 or more possible causes or undetermined etiologies were excluded. Age, sex, comorbidities, ABCD2 score, and CHADS2 score were assessed and compared between the 2 groups. There were no significant differences in the neurologic symptoms and their duration, morbidities of hypertension, diabetes, and dyslipidemia between the 2 groups. Coronary and peripheral artery diseases were more common in the cardioembolic TIA group (18.4% vs. 6.9%). Incidences of prior stroke and cerebral infarction determined by MRI were similar between the 2 groups. The ABCD2 score showed a similar distribution, but the CHADS2 score was significantly different; the cardioembolic TIA group showed a higher score (P = .005). Clinical features are similar in tissue-defined TIA of cardioembolic and noncardioembolic etiologies. The CHADS2 score can be useful in assessing the probability of cardioembolic TIA. | 25,088,173 | [
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Fetal cardiac interventions. | The present article aims to highlight fetal cardiac interventions (FCIs) in terms of indications, strategies, and fetal prognoses. FCIs of the early years were predominantly pharmacological therapies for fetal arrhythmia or heart block. A transplacental transmission of therapeutic agents has now become the main route of pharmacological FCIs. There have been various FCI strategies, which can be categorized into three types: pharmacological, open FCIs, and closed FCIs. Rather than as a routine management for materno-fetal cardiac disorders, however, FCIs are only applied in those fetal cardiac disorders that are at an increased risk of mortality and morbidity and warrant an interventional therapy. Pharmacological FCIs have been well applied in fetal arrhythmias but require further investigations for novel therapeutic agents. The development of open FCI in humans is an issue for the long run. Closed FCIs may largely rely on advanced imaging techniques. Hybrid FCIs might be the future goal in the treatment of fetal heart diseases. | 25,088,192 | [
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Involvement of neurons and retinoic acid in lymphatic development: new insights in increased nuchal translucency. | Increased nuchal translucency originates from disturbed lymphatic development. Abnormal neural crest cell (NCC) migration may be involved in lymphatic development. Because both neuronal and lymphatic development share retinoic acid (RA) as a common factor, this study investigated the involvement of NCCs and RA in specific steps in lymphatic endothelial cell (LEC) differentiation and nuchal edema, which is the morphological equivalent of increased nuchal translucency. Mouse embryos in which all NCCs were fluorescently labeled (Wnt1-Cre;Rosa26(eYfp) ), reporter embryos for in vivo RA activity (DR5-luciferase) and embryos with absent (Raldh2(-/-) ) or in utero inhibition of RA signaling (BMS493) were investigated. Immunofluorescence using markers for blood vessels, lymphatic endothelium and neurons was applied. Flow cytometry was performed to measure specific LEC populations. Cranial nerves were consistently close to the jugular lymph sac (JLS), in which NCCs were identified. In the absence of RA synthesis, enlarged JLS and nuchal edema were observed. Inhibiting RA signaling in utero resulted in a significantly higher amount of precursor-LECs at the expense of mature LECs and caused nuchal edema. Neural crest cells are involved in lymphatic development. RA is required for differentiation into mature LECs. Blocking RA signaling in mouse embryos results in abnormal lymphatic development and nuchal edema. | 25,088,217 | [
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IL-21 acts as a promising therapeutic target in systemic lupus erythematosus by regulating plasma cell differentiation. | Plasma cells, which secrete auto-antibodies, are considered to be the arch-criminal of autoimmune diseases such as systemic lupus erythematosus, but there are many cytokines involved in inducing the differentiation of B-cell subsets into plasma cells. Here, we emphasize IL-21, which has emerged as the most potent inducer of plasma cell differentiation. In this review, we focused on the promoting effects of IL-21 on plasma cell differentiation and discuss how these effects contribute to B cell-mediated autoimmune disease. | 25,088,225 | [
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International neurosurgical volunteerism: a temporal, geographic, and thematic analysis of foundation for international education in neurological surgery volunteer reports. | To examine the experiences of volunteers of the Foundation for International Education in Neurological Surgery. A qualitative analysis of >150 volunteer reports from 2004-2013 was performed using grounded theory. Various themes were explored based on their occurrence in the reports. Volunteer reports of extended trips appeared to peak in 2009, with a heavy emphasis on activity in Africa. Prominent themes in the reports included volunteer contributions, successful strategies, challenges, and future directions. Volunteers demonstrated wide-ranging contributions. Successful strategies included continuity and collaboration with other organizations. Challenges were overwhelmingly related to equipment or infrastructure. Common suggestions for future directions included institutional collaboration and subspecialty development. | 25,088,231 | [
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Prevalence of breast masses and barriers to care: results from a population-based survey in Rwanda and Sierra Leone. | Breast cancer incidence may be increasing in low- and middle-income countries (LMIC). This study estimates the prevalence of breast masses in Rwanda (RW) and Sierra Leone (SL) and identifies barriers to care for women with breast masses. only. Data were collected from households in RW and SL using Surgeons Overseas Assessment of Surgical Need (SOSAS), a cross-sectional, randomized, cluster-based population survey designed to identify surgical conditions. Data regarding breast masses and barriers to care in women with breast masses were analyzed. 3,469 households (1,626 RW; 1,843 SL) were surveyed and 6,820 persons (3,175 RW; 3,645 SL) interviewed. Breast mass prevalence was 3.3% (SL) and 4.6% (RW). Overall, 93.8% of masses were in women, with 49.1% (SL) and 86.1% (RW) in women >30 years. 73.7% (SL) and 92.4% (RW) of women reported no disability; this was their primary reason for not seeking medical attention. Overall, 36.8% of women who reported masses consulted traditional healers only. For women in RW and SL, minimal education, poverty, and reliance on traditional healers are barriers to medical care for breast masses. Public health programs to increase awareness and decrease barriers are necessary to lower breast cancer mortality rates in low- and middle-income countries (LMIC). | 25,088,235 | [
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Maternal obesity influences the relationship between location of neonate fat mass and total fat mass. | It is suggested that maternal obesity perpetuates offspring obesity to future generations. To determine whether location of neonate fat mass (FM: central vs. peripheral) is related to total neonate FM and whether maternal obesity influences this relationship. Neonate body composition and skin-fold thicknesses were assessed in healthy neonates (n = 371; 1-3 days old). Linear regression models examined the relationship between total FM and location of FM (central vs. peripheral). Location of FM was calculated by skin-folds: peripheral was the sum of (biceps and triceps)/2 and central was represented by the subscapular skin-fold. A significant interaction was found for location of FM and maternal obesity. Holding all predictors constant, in offspring born to non-obese mothers, a 0.5 mm increase in central FM predicted a 15 g greater total FM, whereas a 0.5 mm increase in peripheral FM predicted a 66 g greater total FM. However, in offspring born to obese mothers, a 0.5 mm increase in central FM predicted a 56 g total FM, whereas a 0.5 mm increase in peripheral FM predicted a 14 g greater total FM. The relationship between total FM and location of FM is influenced by maternal obesity. | 25,088,238 | [
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Characterization of rock bream (Oplegnathus fasciatus) cytosolic Cu/Zn superoxide dismutase in terms of molecular structure, genomic arrangement, stress-induced mRNA expression and antioxidant function. | Superoxide dismutases (SODs) are dedicated to scavenge and dismutate the superoxide anions in order to protect the cells from oxidative stress by establishing the redox homeostasis. In this study, we describe a cytosolic Cu/ZnSOD, the second SOD member from rock bream Oplegnathus fasciatus (Of-cCu/ZnSOD) at molecular, genomic structural-, transcriptional- and functional-levels. The determination of genomic arrangement of Of-cCu/ZnSOD by means of a BAC library revealed that its primary transcript is represented by five exons and encoded a peptide of 154 amino acids. In silico investigation of Of-cCu/ZnSOD indicated the presence of several family characteristics including two Cu/ZnSOD signatures, seven metal liganding residues and eight β-sheets forming a β-barrel topology. Alignment and modeling studies confirmed the conservation of Cu/ZnSOD at primary and tertiary levels. While invertebrate Cu/ZnSOD members mainly demonstrate a tetraexonic structure, the vertebrate members have acquired an additional intron in the third exon resulting in a quinquepartite arrangement with class-specific exon lengths. Although, teleost Cu/ZnSOD members resembled the mammalian orthologs in their genomic organization, they shared a proximal position with molluscan members in the phylogeny. The antioxidant (AO) activity of Of-cCu/ZnSOD was affirmed by a recombinant protein which was also used to examine the biophysical and biochemical properties. The pronounced activity was detected when the rOf-cCu/ZnSOD was expressed with the Cu(2+) and Zn(2+) supplementation. The optimum activities were observed at pH10 and 25°C, and KCN strongly inhibited the activity of the rOf-cCu/ZnSOD. Furthermore, a constitutive mRNA expression of Of-cCu/ZnSOD with higher levels in blood>liver>heart and brain was observed, which was consistent with the transcriptional profile of Of-mMnSOD, suggesting important physiological role(s). This idea was further strengthened by the temporal assessment of Of-cCu/ZnSOD transcripts in animals under pathological (bacteria- or viral-induced) and physiological (H2O2-induced oxidative) stress conditions using qPCR, in which it exhibited significantly up-regulated levels. Screening of Of-cCu/ZnSOD 5'-flanking region revealed the presence of several important transcription factor binding sites that potentially govern the Cu/ZnSOD expression. These findings conjointly contribute to expand our understanding regarding the piscine Cu/ZnSODs and; in particular, the AO enzyme network of rock bream. | 25,088,251 | [
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Direct observation of α-actinin tension and recruitment at focal adhesions during contact growth. | Adherent cells interact with extracellular matrix via cell-substrate contacts at focal adhesions. The dynamic assembly and disassembly of focal adhesions enables cell attachment, migration and growth. While the influence of mechanical forces on the formation and growth of focal adhesions has been widely observed, the force loading on specific proteins at focal adhesion complex is not clear. By co-expressing force sensitive α-actinin FRET probes and fluorescence labeled paxillin in MDCK cells, we have simultaneously observed the time-dependent changes in tension in α-actinin and the dynamics of focal adhesion during cell migration. We show that increase in tension in α-actinin at the focal adhesion coincides with elongation of the adhesion in its growth phase. The enlargement of focal adhesion is through a force sensitive recruitment of α-actinin and paxillin to the adhesion sites. Changes in α-actinin tension and correlated relocation of α-actinin in an active adhesion also guide the growth direction of the adhesion. The results support the model that cytoskeletal tension is coupled to focal adhesion via the linking protein, α-actinin at the adhesion complex. Lysophosphatidic acid caused an immediate increase in α-actinin tension followed by drastic focal adhesion formation and elongation. Application of Rho-ROCK inhibitor, Y27632, resulted in reversible reduction in tension in α-actinin and disassociation of focal adhesion, suggesting the involvement of myosin-II mediated contractile force in the focal adhesion dynamics. These findings suggest that α-actinin not only serves as a physical linker between cytoskeleton and integrin, but also participates in force transmission at adhesion sites to facilitate adhesion׳s growth. | 25,088,253 | [
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Renal and urological diseases of the newborn neonatal acute kidney injury. | Survival of critically ill neonates in the intensive care unit has improved over the past decades reflecting improvements in obstetric, delivery room and neonatal intensive care, however, morbidity remains significant. Acute kidney injury is a common occurrence in these neonates and despite improved understanding of the pathophysiology and management of acute kidney injury in full term and preterm infants, the mortality remains as high as 61%. Furthermore, there is growing evidence that despite recovery from the acute injury, these infants are at risk for developing hypertension and chronic kidney disease later in life. Emphasis on improving our capability to detect renal insult and injury early, before renal failure occurs, and identification of novel therapeutic agents to prevent and treat acute kidney injury may impact mortality and morbidity. This review focuses on our current knowledge of acute kidney injury in the newborn, approaches to investigating and managing this complication and what future trends in this field may bring. | 25,088,261 | [
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Renal venous thrombosis in neonates. | Neonatal renal vein thrombosis (RVT) is associated with potentially serious morbidities. Almost 80% of cases of RVT present within the first postnatal month. The most common risk factors for RVT are birth asphyxia/ in utero fetal distress, being the infant of a diabetic mother, volume contraction and coagulation abnormalities. Thrombus formation may be initiated by vascular injury, diminished vascular flow, increased blood viscosity, hyperosmolality or underlying thrombophilia. The classic triad of RVT includes gross hematuria, flank mass (unilateral or bilateral enlargement of kidneys) and thrombocytopenia. Laboratory tests may reveal hematuria, proteinuria, polycythemia, hemolytic anemia, thrombocytopenia and possibly acute kidney injury. The etiology for a hypercoagulable state should be investigated. Renal ultrasound with Doppler may show increased size of the affected kidney, increased echogenicity and loss of corticomedullary differentiation. Renal venography remains the gold standard for the diagnosis of RVT. Other causes of renal enlargement must be considered. Supportive treatment includes correction of fluid and electrolyte disturbances and treatment of infection and underlying pathophysiologic abnormalities. Use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) should be considered if there is evidence of disseminated intravascular coagulation. Conventional anticoagulants may attenuate hypercoagulability and decrease the risk for thrombus progression and embolism. Surgery is rarely indicated unless there is bilateral involvement with involvement of the IVC. RVT carries the risk of hypertension and chronic kidney disease. | 25,088,263 | [
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Fluid and electrolyte disorders in the newborn: sodium and potassium. | Tubular development continues after birth in full and pre-term infants. As the survival of premature infants increases, serious imbalances in water and electrolytes in this group have become more prevalent. A diminished ability of the immature kidney to reabsorb water and respond to mineralocorticoids, a high excretion of filtered sodium, perinatal complications affecting tubular function, and the use of medications such as diuretics, indomethacin and amphotericin B, are common factors leading to sodium and potassium imbalances in this age group. Appropriate diagnosis and treatment should be guided by a careful assessment of volume status, urine electrolytes and osmolality. | 25,088,265 | [
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Ageing in people with Prader-Willi syndrome: mortality in the UK population cohort and morbidity in an older sample of adults. | The past two decades have seen a great improvement in the care of people with Prader-Willi syndrome (PWS), particularly with regard to control of diet and behaviour management. Has this affected mortality rates or thrown up new issues regarding premature ageing or dementia? We investigated two aspects of ageing in people with PWS: (1) an estimate of mortality over 9 years in a cohort of people with PWS, originally recruited in 1998-2000; and (2) premature ageing or dementia in people aged ⩾40 years. (1) A follow-up of the population-based 1998-2000 cohort to investigate the subsequent mortality rate; and (2) the recruitment and structured assessment of all members of the Prader-Willi Syndrome Association UK (PWSA-UK) aged ⩾40 years who agreed to participate. Follow-up of the population-based 1998-2000 cohort gave a mortality rate of at least 7/62 over 9 years (1.25% per annum; 20 untraced), age at death was between 13 and 59 years. Twenty-six members of the PWSA-UK aged ⩾40 years were recruited, 18 of whom had a genetic diagnosis (gd) of PWS. Twenty-two (14 gd) showed no evidence of dementia. Four, with possible symptoms, are described in more detail; all are female, of maternal uniparental disomy (mUPD) genetic subtype, or have a disomic region, and all have a long history of psychotic illness. The mortality rate in people with PWS seems to be declining. The subgroup of people with PWS due to UPD or disomic region with female gender and a history of psychosis may be at risk of early onset dementia. | 25,088,280 | [
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Mechanism of curcumin resistance to human cytomegalovirus in HELF cells. | We have previously shown that curcumin exhibited an outstanding anti-HCMV effect in vitro and in vivo. However, the underlying mechanism for the anti-HCMV effect remains unclear. Levels of IL-6 and TNF-α cytokine secretions in HELF cells were determined by enzyme-linked immunosorbent assay (ELISA); cell cycles were assessed by flow cytometry; ie and ul83 gene expressions were evaluated using reverse transcriptase real-time quantitative PCR; HCMV IE and UL83 antigen expressions were studied using immunofluorescence staining assay and western blot. Curcumin reduced HCMV immediate early antigen (IEA) and UL83A expressions and IL-6, and TNF-α secretions and recovered cell proliferation to normal level in HCMV infected HELF cells. Curcumin anti-HCMV effect may possibly be that curcumin concurrently alters host cell microenviroment and inhibits the HCMV antigen expressions. These findings may provide a basic understanding of the curcumin anti-HCMV effect and a novel strategy for further development of curcumin anti-HCMV treatment. | 25,088,288 | [
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Reaching Out To Women Who Are Victims of Intimate Partner Violence. | To evaluate if disclosure of abuse among female university students and among women at an emergency department varied based on three different types of data collection method used; and to explore women's development of symptoms of post-traumatic stress disorder (PTSD) and the outcome on health. Cross-sectional research design was used (N = 306 women). The women who experienced intimate partner violence (IPV) in their current relationship, and had symptoms of PTSD, reported significantly lower physical and mental health. In addition, the women who experienced three types of abuse (physical, mental, and sexual) reported significantly more symptoms of PTSD. Detecting IPV and screening for PTSD in clinical settings might benefit women who suffer from violence in their intimate relationships. | 25,088,306 | [
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[Universality of amino acid signaling between diverse plasma cells]. | Both glutamic (Glu) and gamma-aminobutyric (GABA) acids are believed to play roles as neurotransmitters released from particular neurons into synaptic clefts in the mammalian central nervous system. Although GABA has been shown to act as an extracellular signal outside the brain, little attention has been paid to the possible expression of machineries required for neuronal glutamatergic signaling in cells other than central neurons. We first demonstrated the presence of Glu receptors in peripheral tissues such as the adrenal and pituitary glands three decades ago. In this review, I will outline our experimental findings accumulated since then on the physiological and pathological significance of neuronal amino acids as an extracellular signal for the maintenance of homeostasis in a variety of plasma cells. For example, Glu is released upon stimulation in a Ca2+-dependent manner for signal output in osteoblasts, where Glu is essential for the expression of the master regulator of osteoblastogenesis through a particular inotropic receptor subtype. In contrast, GABA plays a role in mechanisms underlying the suppression of cellular differentiation and maturation through a particular metabotropic receptor subtype in osteoblasts. Taken together, osteoblastic maturation proceeds as a delicate balancing between excitatory glutamatergic and inhibitory GABAergic signals, as seen in the brain. Re-evaluation of drugs currently used could be beneficial for the efficient discovery and development of innovative drugs useful for the prophylaxis and/or therapy of a variety of diseases relevant to the disturbance of glutamatergic and GABAergic signaling in diverse plasma cells. | 25,088,319 | [
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[Function of glycochains in virus infection]. | Influenza A virus (IAV) has two envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). HA binds to sialic acids at the terminals of glycochains on the host cell surface as virus receptors. NA shows sialidase activity, which cleaves sialic acids from the terminals of glycochains. A new subtype (antigenicities of HA and NA) of IAV for humans has pandemic potential. We investigated the functions of HA and NA in IAV replication and pandemic potential in terms of glycoscience. We found that the sialidase activity of pandemic IAV had low pH stability, which enhanced IAV replication. It is thought that the low pH stability contributed to the pandemics in 1968 and 2009. HA also binds to sulfatide not containing sialic acid, and we found that sulfatide enhanced IAV replication. Binding of HA to sulfatide on the host cell surface enhanced progeny IAV formation in infected cells through the induction of the nuclear export of viral ribonucleoproteins by apoptosis. Sialic acid species are divided into N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). The HAs of some human IAVs bind not only to Neu5Ac but also to Neu5Gc, which may facilitate the occurrence of a human IAV-based pandemic by genetic reassortment among IAV genomes in pig tracheas expressing Neu5Gc. We identified the amino acid residues of human IAV HA responsible for Neu5Gc binding and developed new techniques for the sensitive detection of IAV receptor specificities and infected cells. Our "glycovirology" research will provide new insights into the mechanisms of IAV replication and pandemic potential. | 25,088,320 | [
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[Degrading anticancer drugs in the medical environment using a visible light-driven photocatalyst]. | Occupational exposure to anticancer drugs is recognized as a risk for healthcare workers. Reducing anticancer drugs in the environment is important to prevent the exposure of individuals to anticancer drugs. However, there are currently no effective degrading agents for all anticancer drugs used in clinical settings. We previously reported the resolution of an anticancer drug with the use of a photocatalyst (TiO2), which acts by absorbing ultraviolet light to degrade organic compounds. In this study, we evaluated anticancer drug degradation using a visible light-driven photocatalyst (Cu/WO3). Anticancer drugs [cyclophosphamide (CPA), paclitaxel (PTX), methotrexate (MTX), irinotecan (CPT-11), cytarabine (Ara-C), and 5-fluorouracil (5-FU)], were experimentally deposited on a stainless steel plate. The visible light-driven photocatalytic agent (0.075% Cu/WO3 solution) was sprayed onto the plate, and the plate was then left under a fluorescent lamp for 12 h. The anticancer drugs remaining on the plate were assayed by high-performance liquid chromatography (HPLC). CPA, PTX, MTX, CPT-11, Ara-C, and 5-FU were found to be degraded by up to 37.7%, >99.0%, 57.1%, 54.6%, 69.5%, and 36.3%, respectively. The visible light-driven photocatalyst was therefore confirmed to degrade anticancer drugs under a fluorescent lamp. The ability of the visible light-driven photocatalyst to degrade multiple chemotherapeutic agents without the need for altering the light source could make it a useful tool for reducing anticancer drug pollution in clinical settings. | 25,088,322 | [
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Cardiorespiratory Response to Exercise before and after Pulmonary Valve Replacement in Patients with Repaired Tetralogy of Fallot: A Retrospective Study and Systematic Review of the Literature. | To describe and analyze the cardiopulmonary responses to exercise for patients with repaired tetralogy of Fallot (TOF) before and after pulmonary valve replacement (PVR) and compare our results with those in the literature. Between 1973 and 2012, 278 patients had a first-time PVR after TOF repair. During their evaluations, 76 patients (27%) had exercise testing before PVR, and 63 (23%) had at least one test after PVR. There were 17 patients (average age at surgery 40 ± 14 years, 65% female) with both pre- and postoperative testing within 36 months of surgery. We then combined our results with previously reported studies for meta-analysis. Patients who had exercise testing before PVR were older compared with those who did not have testing performed (37 ± 13 vs. 30 ± 17 years, P < .001). Preoperatively, patients achieved a peak heart rate of 153 ± 28 bpm and a peak VO2 of 21.5 ± 7.2 mL/kg/min (61 ± 15% of expected). Postoperatively, they achieved a peak heart rate of 156 ± 25 bpm and a peak VO2 of 23.3 ± 6.5 mL/kg/min (67 ± 15% of expected). Paired analysis demonstrated a significant increase in peak VO2 percentage (P = .04) but not for absolute VO2 measurements (mL/kg/min). We identified six published studies with similar usable data. Combining all seven data sets for meta-analysis, there was no significant change in peak VO2 following PVR (P = .2). Patients with repaired TOF have an abnormally low aerobic capacity at the time of PVR. We appreciated a modest improvement in percentage of predicted peak VO2 after PVR; however, meta-analysis of the available literature did not demonstrate an appreciable difference in aerobic capacity following PVR. | 25,088,332 | [
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Muscle magnetic resonance imaging and histopathology in ACTA1-related congenital nemaline myopathy. | Muscle biopsy is usually diagnostic in nemaline myopathy (NM), but some patients may show nonspecific findings, leading to pitfalls in diagnosis. Muscle MRI is a helpful complementary tool. We assessed the clinical, histopathological, MRI, and molecular findings in a 19-year-old patient with NM in whom 2 muscle biopsies with ultrastructural examination showed no nemaline bodies. We analyzed the degree and pattern of muscle MRI involvement of the entire body, including the tongue and pectoral muscles. Muscle MRI abnormalities in sartorius, adductor magnus, and anterior compartment muscles of the leg suggested NM. A previously unreported fatty infiltration of the tongue was found. A third biopsy after the muscle MRI showed scant nemaline bodies. A novel heterozygous de novo ACTA1 c.611C>T/p.Thr204Ile mutation was detected. We highlight the contribution of muscle imaging in addressing the genetic diagnosis of ACTA1-related NM. | 25,088,345 | [
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Multiscale optical Ca2+ imaging of tonal organization in mouse auditory cortex. | Spatial patterns of functional organization, resolved by microelectrode mapping, comprise a core principle of sensory cortices. In auditory cortex, however, recent two-photon Ca2+ imaging challenges this precept, as the traditional tonotopic arrangement appears weakly organized at the level of individual neurons. To resolve this fundamental ambiguity about the organization of auditory cortex, we developed multiscale optical Ca2+ imaging of unanesthetized GCaMP transgenic mice. Single-neuron activity monitored by two-photon imaging was precisely registered to large-scale cortical maps provided by transcranial widefield imaging. Neurons in the primary field responded well to tones; neighboring neurons were appreciably cotuned, and preferred frequencies adhered tightly to a tonotopic axis. By contrast, nearby secondary-field neurons exhibited heterogeneous tuning. The multiscale imaging approach also readily localized vocalization regions and neurons. Altogether, these findings cohere electrode and two-photon perspectives, resolve new features of auditory cortex, and offer a promising approach generalizable to any cortical area. | 25,088,366 | [
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Evaluation of tertiary pyridine resin for the separation of lanthanides by simulated moving-bed chromatography. | Lanthanide separation by simulated moving-bed chromatography was studied as a model system for separating lanthanide fission products and minor actinides from used nuclear fuels. The simulated moving-bed system was modeled for a tertiary pyridine anion-exchange resin supported on silica particles as the stationary phase and a mixture of methanol and 1 M nitric acid as the mobile phase. Pulse injection tests using a single packed column were used to obtain chromatographic parameters for mathematical modeling of the simulated moving-bed system. Higher concentrations of methanol improved the separation, but the chromatograms showed evidence of nonlinearity of the isotherms. The mathematical model of the simulated moving-bed process predicted a production rate of purified samarium and neodymium at 118 g solute/L resin/day and a purity of 99.5%. The optimal methanol ratio for the production rate for various product purities was determined from the model. The excellent separation of Nd and Sm suggests that the simulated moving-bed system could be applied to the separation of minor actinides such as americium and curium. | 25,088,396 | [
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A GAL4 driver resource for developmental and behavioral studies on the larval CNS of Drosophila. | We report the larval CNS expression patterns for 6,650 GAL4 lines based on cis-regulatory regions (CRMs) from the Drosophila genome. Adult CNS expression patterns were previously reported for this collection, thereby providing a unique resource for determining the origins of adult cells. An illustrative example reveals the origin of the astrocyte-like glia of the ventral CNS. Besides larval neurons and glia, the larval CNS contains scattered lineages of immature, adult-specific neurons. Comparison of lineage expression within this large collection of CRMs provides insight into the codes used for designating neuronal types. The CRMs encode both dense and sparse patterns of lineage expression. There is little correlation between brain and thoracic lineages in patterns of sparse expression, but expression in the two regions is highly correlated in the dense mode. The optic lobes, by comparison, appear to use a different set of genetic instructions in their development. | 25,088,417 | [
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Control of outer radial glial stem cell mitosis in the human brain. | Evolutionary expansion of the human neocortex is partially attributed to a relative abundance of neural stem cells in the fetal brain called outer radial glia (oRG). oRG cells display a characteristic division mode, mitotic somal translocation (MST), in which the soma rapidly translocates toward the cortical plate immediately prior to cytokinesis. MST may be essential for progenitor zone expansion, but the mechanism of MST is unknown, hindering exploration of its function in development and disease. Here, we show that MST requires activation of the Rho effector ROCK and nonmuscle myosin II, but not intact microtubules, centrosomal translocation into the leading process, or calcium influx. MST is independent of mitosis and distinct from interkinetic nuclear migration and saltatory migration. Our findings suggest that disrupted MST may underlie neurodevelopmental diseases affecting the Rho-ROCK-myosin pathway and provide a foundation for future exploration of the role of MST in neocortical development, evolution, and disease. | 25,088,420 | [
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The sex-determining factors SRY and SOX9 regulate similar target genes and promote testis cord formation during testicular differentiation. | Male sex determination is mediated sequentially by sex-determining region Y (SRY) and related SRY-box 9 (SOX9) transcription factors. To understand the gene regulatory hierarchy for SRY and SOX9, a series of chromatin immunoprecipitation and whole-genome promoter tiling microarray (ChIP-Chip) experiments were conducted with mouse gonadal cells at the time of sex determination. SRY and SOX9 bind to the promoters of many common targets involved in testis differentiation and regulate their expression in Sertoli cells. SRY binds to various ovarian differentiation genes and represses their activation through WNT/β-catenin signaling. Sertoli cell-Sertoli cell junction signaling, important for testis cord formation, is the top canonical pathway among the SRY and SOX9 targets. Hence, SRY determines Sertoli cell fate by repressing ovarian and activating testicular differentiation genes, promotes early Sertoli cells to form testis cord, and then passes on its functions to SOX9, which regulates common targets and activates its own gene regulatory program, beyond SRY actions, in sex determination. | 25,088,423 | [
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One-pot aldol condensation and hydrodeoxygenation of biomass-derived carbonyl compounds for biodiesel synthesis. | Integrating reaction steps is of key interest in the development of processes for transforming lignocellulosic materials into drop-in fuels. We propose a procedure for performing the aldol condensation (reaction between furfural and acetone is taken as model reaction) and the total hydrodeoxygenation of the resulting condensation adducts in one step, yielding n-alkanes. Different combinations of catalysts (bifunctional catalysts or mechanical mixtures), reaction conditions, and solvents (aqueous and organic) have been tested for performing these reactions in an isothermal batch reactor. The results suggest that the use of bifunctional catalysts and aqueous phase lead to an effective integration of both reactions. Therefore, selectivities to n-alkanes higher than 50% were obtained using this catalyst at typical hydrogenation conditions (T=493 K, P=4.5 MPa, 24 h reaction time). The use of organic solvent, carbonaceous supports, or mechanical mixtures of monofunctional catalysts leads to poorer results owing to side effects; mainly, hydrogenation of reactants and adsorption processes. | 25,088,473 | [
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Renal cell carcinoma to haemangioblastoma metastasis: a rare manifestation of Von Hippel-Lindau syndrome. | Brain metastases are the most common intracranial malignancy in adults and may occasionally deposit within a pre-existing primary brain neoplasm. We describe, in two directly related family members, the rare occurrence of renal cell carcinoma (RCC) metastasis to haemangioblastoma (HB) in the context of Von Hippel-Lindau syndrome. Detection of this phenomenon can be marred by histological overlap between RCC and HB and therefore careful histological examination, and consideration of supportive immunohistochemistry, is required when examining all HB resections. Metastatic RCC to HB upstages a primary RCC and is clinically diagnostic of Von Hippel-Lindau syndrome. | 25,088,480 | [
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The international spread of Academic Health Science Centres: a scoping review and the case of policy transfer to England. | Academic Health Science Centres (AHSCs) have been a key feature of the North American healthcare landscape for many years, and the term is becoming more widely used internationally. The defining feature of these complex organisations is a tripartite mission of delivering high quality research, medical education and clinical care. The biomedical innovations developed in AHSCs are often well documented, but less is known about the policy and organisational processes which enable the translation of research into patient care. This paper has two linked purposes. Firstly, we present a scoping review of the literature which explores the managerial, political and cultural perspectives of AHSCs. The literature is largely normative with little social science theory underpinning commentary and descriptive case studies. Secondly, we contribute to addressing this gap by applying a policy transfer framework to the English case to examine how AHSC policy has spread internationally. We conclude by suggesting a research agenda on AHSCs using the relevant literatures of policy transfer, professional/managerial relations and boundary theory, and highlighting three key messages for policy makers: (1) competing policy incentives for AHSCs should be minimised; (2) no single AHSC model will fit all settings; (3) AHSC networks operate internationally and this should be encouraged. | 25,088,488 | [
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Laparoscopic sleeve gastrectomy in patients over 60 years: impact of age on weight loss and co-morbidity improvement. | Advanced age has traditionally been considered a relative contraindication to bariatric surgery due to increased perioperative risk and less weight loss. However, it is now being reconsidered in older patients after encouraging results in recent series and the increasing life expectancy. We compared operative and postoperative outcomes of laparoscopic sleeve gastrectomy in patients over 60 years with outcomes in younger patients. We also, analyzed the effect of bariatric surgery on improvement and resolution of co-morbidities in the older group. From November 2008 to November 2013, 130 patients underwent laparoscopic sleeve gastrectomy. Of these, 28 patients (21.5%) were 60 years or older. Outcomes in terms of perioperative complications, short-term and medium-term weight loss, remission or improvement of co-morbidities and medication requirements were extracted from our prospective database. Short-term mortality was 0% and 30-day complication rate was similar in both groups (17.9% versus 17.6% according to Clavien-Dindo classification). At 12 months postsurgery, older patients had lost 49% percent of excess weight compared to 60% in the younger group (P = 0.012). At 2 years, the results were 45% versus 60%, respectively, with P = 0.015. At least 1 major co-morbidity improved in 65.2% of older patients. Before surgery, the older group took an average of 4.3 medications compared to 2.7 at 1 year after surgery (P<0.001). Laparoscopic sleeve gastrectomy is a safe and effective treatment for morbid obesity in people over 60 years, although younger patients show greater weight loss. Daily medication requirements and co-morbidities decrease significantly in older patients after this procedure. | 25,088,486 | [
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Comparison of clinical characteristics of familial and sporadic obsessive-compulsive disorder. | Obsessive-compulsive disorder (OCD) is a heterogeneous condition with evidence of familiality in a considerable proportion of patients. A classification into familial and sporadic forms has been proposed to explain the heterogeneity. The current study aims to compare the demographic, clinical and comorbidity patterns of patients with and without a family history of OCD in first-degree relatives. 802 consecutive patients who consulted a specialty OCD Clinic at a tertiary care psychiatric hospital in India were evaluated with the Mini-International Neuropsychiatric Interview, the Yale-Brown Obsessive-Compulsive Scale, and the Clinical Global Impression Scale. Family history was assessed by interviewing patients and at least one first-degree relative. Family history of OCD was seen in 152 patients (19%). Family history was associated with juvenile onset (Χ(2)=19.472, p<0.001), obsessions of contamination (Χ(2)=6.658, p=0.01), hoarding (Χ(2)=4.062, p=0.032), need for symmetry (Χ(2)=3.95, p=0.047), washing compulsion (Χ(2)=7.923, p=0.005), ordering compulsions (Χ(2)=6.808, p=0.009), repeating compulsions (Χ(2)=4.950, p=0.026) and compulsions by proxy (Χ(2)=7.963, p=0.005). Family history was also associated with greater severity of OCD (t=-2.31, p=0.022) and compulsions (t=-3.09, p=0.002) and longer duration of illness at presentation (t=-2.93, p=0.004). Our findings suggest that familial OCD may have distinctive clinical features. Studying familial forms of OCD may offer unique insight in to understanding the genetic basis of OCD. | 25,088,515 | [
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Marine legislation--the ultimate 'horrendogram': international law, European directives & national implementation. | The EU is a pre-eminent player in sustainable development, adopting more than 200 pieces of legislation that have direct repercussions for marine environmental policy and management. Over five decades, measures have aimed to protect the marine environment by tackling the impact of human activities, but maritime affairs have been dealt with by separate sectoral policies without fully integrating all relevant sectors. Such compartmentalisation has resulted in a patchwork of EU legislation and resultant national legislation leading to a piecemeal approach to marine protection. These are superimposed on international obligations emanating from UN and other bodies and are presented here as complex 'horrendograms' showing the complexity across vertical governance. These horrendograms have surprised marine experts despite them acknowledging the many uses and users of the marine environment. Encouragingly since 2000, the evolution in EU policy has progressed to more holistic directives and here we give an overview of this change. | 25,088,540 | [
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Proton-coupled sugar transport in the prototypical major facilitator superfamily protein XylE. | The major facilitator superfamily (MFS) is the largest collection of structurally related membrane proteins that transport a wide array of substrates. The proton-coupled sugar transporter XylE is the first member of the MFS that has been structurally characterized in multiple transporting conformations, including both the outward and inward-facing states. Here we report the crystal structure of XylE in a new inward-facing open conformation, allowing us to visualize the rocker-switch movement of the N-domain against the C-domain during the transport cycle. Using molecular dynamics simulation, and functional transport assays, we describe the movement of XylE that facilitates sugar translocation across a lipid membrane and identify the likely candidate proton-coupling residues as the conserved Asp27 and Arg133. This study addresses the structural basis for proton-coupled substrate transport and release mechanism for the sugar porter family of proteins. | 25,088,546 | [
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Cytoprotective pyridinol antioxidants as potential therapeutic agents for neurodegenerative and mitochondrial diseases. | As part of our ongoing efforts to identify compounds having potential utility in treating neurodegenerative and mitochondrial disorders, a series of pyridinol analogues have been prepared. The synthetic route employed for the preparation of the new analogues is different, and considerably more efficient, than that used in previously reported studies. The new route yields a pair of pyridinol regioisomers that can be readily separated and evaluated. Their ability to quench lipid peroxidation and reactive oxygen species (ROS), and to preserve mitochondrial membrane potential (Δψm) and support ATP synthesis is reported. The optimal side chain length was found to be 16 carbon atoms. The metabolic stability of those compounds having optimal biological activities was evaluated in vitro using bovine liver microsomes. The omission of any side chain hydroxyl group and introduction of an azetidine moiety at position 6 of the pyridinol redox core (8 and 9) increased their microsomal stability as compared to the exocyclic dimethylamino group. The favorable metabolic stability conferred by the azetidine moiety in compounds 8 and 9 makes these compounds excellent candidates for further evaluation. | 25,088,548 | [
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Standing and flowing: the complex origins of adaptive variation. | A population faced with a new selection pressure can only adapt if appropriate genetic variation is available. This genetic variation might come from new mutations or from gene exchange with other populations or species, or it might already segregate in the population as standing genetic variation (which might itself have arisen from either mutation or gene flow). Understanding the relative importance of these sources of adaptive variation is a fundamental issue in evolutionary genetics (Orr & Betancourt ; Barrett & Schluter ; Gladyshev et al. ) and has practical implications for conservation, plant and animal breeding, biological control and infectious disease prevention (e.g. Robertson ; Soulé & Wilcox ; Prentis et al. ; Pennings ). In this issue of Molecular Ecology, Roesti et al. () make an important contribution to this longstanding debate. | 25,088,550 | [
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[Acceptability of HIV testing provided to infants in pediatric services in Cote d'Ivoire, meanings for pediatric diagnostic coverage]. | HIV testing in children had rarely been a central concern for researchers. When pediatric tracking retained the attention, it was more to inform on the diagnosis tools' performances rather than the fact the pediatric test can be accepted or refused. This article highlights the parents' reasons which explain why pediatric HIV test is accepted or refused. To study among parents, the explanatory factors of the acceptability of pediatric HIV testing among infant less than six months. Semi-structured interview with repeated passages in the parents of infants less than six months attending in health care facilities for the pediatric weighing/vaccination and consultations. We highlight that the parents' acceptance of the pediatric HIV screening is based on three elements. Firstly, the health care workers by his speech (which indicates its own knowledge and perceptions on the infection) directed towards mothers' influences their acceptance or not of the HIV test. Secondly, the mother who by her knowledge and perceptions on HIV, whose particular status, give an impression of her own wellbeing for her and her child influences any acceptance of the pediatric HIV test. Thirdly, the marital environment of the mother, particularly characterized by the ease of communication within the couple, to speak about the HIV test and its realization for the parents or the mother only are many factors which influence the effective realization of the pediatric HIV testing. The preventive principle of HIV transmission and the desire to realize the test in the newborn are not enough alone to lead to its effective realization, according to certain mothers confronted with the father's refusal. On the other hand, the other mothers refusing the realization of the pediatric test told to be opposed to it; of course, even if their partner would accept it. The mothers are the principal facing the pediatric HIV question and fear the reprimands and stigma. The father, the partner could be an obstacle, when he is opposed to the infant HIV testing, or also the facilitator with his realization if he is convinced. The father position thus remains essential face to the question of pediatric HIV testing acceptability. The mothers are aware of this and predict the difficulties of achieving their infant to be tested without the preliminary opinion of their partner at the same time father, and head of the family. The issue of pediatric HIV testing, at the end of our analysis, highlights three elements which require a comprehensive management to improve the coverage of pediatric HIV test. These three elements would not exist without being influenced; therefore they are constantly in interaction and prevent or support the realization or not pediatric test. Also, with the aim to improve the pediatric HIV test coverage, it is necessary to take into account the harmonious management of these elements. Firstly, the mother alone (with her knowledge, and perceptions), its marital environment (with the proposal of the HIV test integrating (1) the partner and/or father with his perceptions and knowledge on HIV infection and (2) facility of speaking about the test and its realization at both or one about the parents, the mother) and of the knowledge, attitudes and practices about the infection of health care workers of the sanitary institution. Our recommendations proposed taking into account a redefinition of the HIV/AIDS approach towards the families exposed to HIV and a more accentuated integration of the father facilitating their own HIV test acceptation and that of his child. | 25,088,574 | [
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Circulating TGF-β1-related biomarkers in patients with hepatocellular carcinoma and their association with HCC staging scores. | TGF-β1 was inversely correlated with E-cadherin but significantly correlated with VEGF. VEGF and AFP had a low coefficient value but statistically significant. A significant correlation was found between E-cadherin and MMP2. In conclusion, TGF-β and E-cadherin are inversely correlated in HCC patients' sera and not related to the BCLC classification nor survival but rather to the biological properties of the tumor. | 25,088,578 | [
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Development and characterization of an ascorbate oxidase-based sensor-biosensor system for telemetric detection of AA and antioxidant capacity in fresh orange juice. | A new carbon ascorbate oxidase-based sensor-biosensor system (SB) was coupled to a dual-channel telemetric device for online simultaneous electrochemical detection of ascorbic acid (AA) and antioxidant capacity in Hamlin, Sanguinello, and Moro orange varieties. The electrocatalytic performances of the SB were investigated by cyclic voltammetry and amperometric techniques. The phenol composition of orange juice of each variety, and the cyclic voltammetries of the most represented phenols, were provided. The in vitro calibrations were performed in PBS (pH 5.6), applying a constant potential of +500 mV. A standard mixture of phenols, based on orange juice composition, was used as reference material for studying SB behavior. SB works at an applied potential of +500 mV, in a concentration range comprised between the LOD 0.26 μM and 20 μM. In this concentration range, limiting the data acquisition time to 2 min, the problems of electrode passivation due to phenols polymerization were overcome. AA calibration showed that the biosensor registered statistically lower currents than the sensor since the enzyme oxidized AA before it reached the electrode surface. Standard mixture calibration showed that currents registered by sensor and biosensor did not statistically differ. The difference between sensor and biosensor AA registered currents was used to calculate an AA selectivity index and, consequently, to determine the AA content and the antioxidant capacity in the juices. The novelty of the SB is its ability to distinguish between AA and phenols contribution to antioxidant capacity. The obtained results were in accordance with reference methods. | 25,088,601 | [
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Identification of Chinese herbal medicines by fluorescence microscopy: fluorescent characteristics of medicinal bark. | Medicinal bark refers to structures outside the vascular cambium of stems, branches and roots of gymnospermous and dicotyledonous plants that are used as medicinal materials; bark is an important type of Chinese herbal medicine. However, identification of the species from which the bark comes can be very difficult, especially when the bark is dried and sliced. In our previous studies, we have found that fluorescence microscopy is a powerful tool for the identification of easily confused Chinese herbal medicines, powdered Chinese herbal medicines and decoction dregs. To establish the fluorescent characteristics by which medicinal barks can be identified, for ensuring their safe and effective use, a systematic microscopic investigation by normal light and fluorescence microscope was carried out on transverse section samples of 11 medicinal barks commonly used in China. Specifically, the fluorescent characteristics of mechanical tissues, including stone cells and fibres as well as secretory tissues, have been observed. The microscopic features of medicinal bark are here systematically and comparatively described and illustrated. Under the fluorescence microscope, various tissues emitted fluorescence of different colours, and we found that both the colours and the intensity can be used to distinguish and identify these barks. | 25,088,607 | [
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Physicians' influence on veterans' decision to use acupuncture. | To compare patients' acupuncture use with physician's attitudes toward and history of referral for acupuncture. A questionnaire was administered to patients of the Atlanta Veterans Affairs Medical Center and the physicians whom they identified as most influencing their healthcare decisions. A total of 114 patients were matched with 33 physicians. Physicians' history of referral was not significantly related to patients' acupuncture use. Physicians' belief that acupuncture would increase patient satisfaction, however, was associated with higher rates of patient acupuncture use (p=0.01). Qualitative analysis of an open-ended question that probed further into physicians' attitudes regarding acupuncture revealed three key themes: lack of knowledge about the treatment; misperceptions regarding availability of acupuncture at VA; and lack of VA providers to meet demand. These results indicate that physicians' referral patterns are not associated with patients' acupuncture use. However, some evidence shows a link between patients' acupuncture use and physicians' beliefs that the treatment will increase patient satisfaction, showing that physician attitudes may have some influence on patients' acupuncture use. In order to cultivate shared-decision making between patients and their physicians it will be important to address gaps in provider knowledge about acupuncture and its availability. | 25,088,615 | [
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Hydrodissection-free phacoemulsification surgery: mechanical cortical cleaving dissection. | We describe hydrodissection-free phacoemulsification surgery (hydro-free phaco), which eliminates conventional cortical-cleaving hydrodissection during cataract surgery. To replace hydrodissection, we devised a mechanical cortical-cleaving dissection technique that is performed during phacoemulsification. The new technique prevents the high pressure within the endocapsular space or the posterior chamber-anterior hyaloid membrane barrier area that is common with hydrodissection. This reduces hydrodissection-related complications such as posterior capsule rupture, anterior hyaloid membrane tear, extension of zonule fracture, and pseudoexpulsive hemorrhage. Using this technique, phacoemulsification was performed effectively without complications in 547 of 550 cataract eyes. We propose this technique to prevent hydrodissection-related complications in eyes with a high risk for complications. Neither author has a financial or proprietary interest in any material or method mentioned. | 25,088,632 | [
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Endoilluminator-assisted transcorneal illumination for Descemet membrane endothelial keratoplasty: enhanced intraoperative visualization of the graft in corneal decompensation secondary to pseudophakic bullous keratopathy. | Compromised visibility is problematic with Descemet membrane endothelial keratoplasty (DMEK), especially in the presence of corneal edema. Visibility may be enhanced by dehydrating the cornea preoperatively and by debriding the epithelium, staining the graft, and using a handheld slitlamp during surgery. Because the DMEK graft is transparent, thin, and flimsy, it is difficult to confirm the position, orientation, and morphology even with a clearer cornea. We describe a technique (endoilluminator-assisted DMEK) for identifying graft orientation and enhancing 3-dimensional depth perception within the anterior chamber of the graft. The technique uses oblique light from the endoilluminator for better visualization. Light reflexes from graft folds and edges aid further. This technique has the advantages of being able to visualize the entire graft even through hazy cornea, providing the surgeon with better comprehension of graft dynamics, morphology, orientation, and positioning. This leads to easier and faster surgery, potentially decreasing graft damage due to excessive fluidics and unnecessary manipulation. No author has a financial or proprietary interest in any material or method mentioned. | 25,088,633 | [
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Intraindividual aqueous flare comparison after implantation of hydrophobic intraocular lenses with or without a heparin-coated surface. | To assess the efficacy of a heparin-surface-modified (HSM) hydrophobic acrylic intraocular lens (IOL) (EC-1YH PAL) and the same IOL without heparin coating (EC-1Y-PAL) by the flare and cell intensity in the anterior chamber after uneventful cataract surgery. Department of Ophthalmology, Paracelsus Medical University Salzburg, Austria. Comparative case series. Routine phacoemulsification with randomized implantation of an HSM IOL in 1 eye (HSM IOL group) and an uncoated IOL (uncoated IOL group) in the fellow eye was performed. Postoperative inflammation was assessed objectively using a laser flare-cell meter (FM-600) preoperatively as well as 1 day and 1 and 3 months postoperatively. Aqueous cells in the anterior chamber, distance visual acuities, and subjective manifest refraction were also evaluated at each visit. One hundred eyes (50 patients) were enrolled. In both groups, the mean flare values increased significantly from preoperatively to 1 day postoperatively (P<.001) and nearly reached preoperative values by 3 months postoperatively. One day postoperatively, the mean flare value was statistically significantly lower in the HSM IOL group (14.92 photons per millisecond [ph/ms] ± 7.47 [SD]) than in the uncoated IOL group (mean 16.73 ± 7.81 ph/ms) (P=.04); there was no statistically significant difference between groups 1 and 3 months postoperatively (both P>.58). The HSM IOL group had a greater and quicker decrease in aqueous cells, reaching statistical significance 1 month postoperatively (P=.01). The HSM IOL showed a significant lower inflammatory reaction in the early postoperative stage with a faster disappearance of inflammatory signs. No author has a financial or proprietary interest in any material or method mentioned. | 25,088,637 | [
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Targeted elimination of activated hepatic stellate cells by an anti-epidermal growth factor-receptor single chain fragment variable antibody-tumor necrosis factor-related apoptosis-inducing ligand (scFv425-sTRAIL). | Progressive liver fibrosis is the result of chronic liver injury and is characterized by the excessive accumulation of extracellular matrix that may result in liver failure. Activated hepatic stellate cells are known to play a central role in this process and their elimination is a crucial step towards the resolution and reversion of liver fibrosis. In the present study, we investigated the potential application of an anti-epidermal growth factor receptor single chain fragment variable antibody-tumor necrosis factor-related apoptosis-inducing ligand (scFv425-sTRAIL) fusion protein in the targeted elimination of activated hepatic stellate cells. Activated hepatic stellate cells (LX2 cells) were treated by adenovirus-derived scFv425-sTRAIL to evaluate its effect on the viability and extracellular matrix production of this type of cells. In vitro treatment of activated hepatic stellate cells with scFv425-sTRAIL induced a significant reduction in viability (up to 100% reduction) and extracellular matrix production (60% reduction), yet no significant effect was observed on hepatic parenchymal cells. Blockage of the epidermal growth factor receptor (EGFR) by a monoclonal antibody significantly reduced the effectiveness of scFv425-sTRAIL in activated hepatic stellate cells, whereas a reduced effectivity was also observed after inhibition of the caspase pathway. Evidence is presented for the successful application of the scFv425-sTRAIL fusion protein in the targeted elimination of activated hepatic stellate cells via EGFR and simultaneous activation of the caspase pathway. scFv425-sTRAIL may thus represent a new therapeutic compound against liver fibrosis. | 25,088,657 | [
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Factors predicting future ACS episodes in children with sickle cell anemia. | While a doctor-diagnosis of asthma is associated with an increased risk of pain and acute chest syndrome (ACS) in children with sickle cell anemia (SCA), little is known about the relationship between specific asthma characteristics and clinical factors and future morbidity in children with SCA. We evaluated the relationship between (i) asthma risk factors at the time of a clinical visit (respiratory symptoms, maternal history of asthma, allergy skin tests, spirometry results) and (ii) the known risk factor of ACS early in life, on prospective pain and ACS episodes in a cohort of 159 children with SCA followed from birth to a median of 14.7 years. An ACS episode prior to 4 years of age, (incidence rate ratio [IRR] = 2.84; P < 0.001], female gender (IRR = 1.80; P = 0.009), and wheezing causing shortness of breath (IRR = 1.68; P = 0.042) were associated with future ACS rates. We subsequently added spirometry results (obstruction defined as FEV1 /FVC less than the lower limits of normal; and bronchodilator response, FEV1 ≥ 12%) and prick skin test responses to the model. Only ≥ 2 positive skin tests had a significant effect (IRR 1.87; P = 0.01). Thus, early in life ACS events, wheezing causing shortness of breath, and ≥ 2 positive skin tests predict future ACS events. | 25,088,663 | [
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Immune-protected xenogeneic bioartificial livers with liver-specific microarchitecture and hydrogel-encapsulated cells. | Development of a xenogeneic biological liver support is important in providing a bridge to transplantation or liver regeneration, thus helping to overcome the chronic shortage of liver donors. Among the critical factors in developing biological liver support are the creation of in vivo mimetic micro liver tissue (mLT), especially mLTs containing liver-specific ultrastructure, and an encapsulation method that can package massive numbers of cells while providing immune-protection from the host immune system. We describe here the development of mLTs that include liver microarchitecture and their in situ encapsulation in hydrogel composites. Concave microwells and the tri-culture of three types of primary liver cells were applied for the construction of mLTs showing excellent liver functions and long-term (>1 month) viability in vitro. Large quantities of rat mLTs were encapsulated in collagen-alginate composites, implanted into hepatic failure mice and sustained their survival during regeneration of the remaining liver. The proposed liver support system offers xenogeneic hepatic assistance by mimicking native liver microarchitecture and providing immune-protection without the need for complicated devices or processes, and as such represents a promising system for recovery of organ function. | 25,088,727 | [
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Greater clinical and cognitive improvement with clozapine and risperidone associated with a thinner cortex at baseline in first-episode schizophrenia. | Cortical thickness may be useful as a treatment response predictor in first-episode (FE) patients with schizophrenia, although this possibility has been scarcely assessed. In this study we assessed the possible relation between cortical thickness in regions of interest selected because of previously reported structural alterations in schizophrenia and clinical and cognitive changes after two years of treatment with risperidone or clozapine in 31 neuroleptic-naïve FE patients with schizophrenia (16 of them treated with clozapine and 15 with risperidone). Using the last-observation-carried-forward (LOCF), a larger improvement in positive, negative and total symptoms was predicted by the amount of baseline cortical thinning in the right prefrontal cortex (pars orbitalis). After two years of treatment, cognitive status was reassessed in the 17 patients (11 on clozapine) who had not dropped out. Working memory improvement after reassessment was associated with a greater baseline cortical thinning in the left prefrontal cortex (pars orbitalis), and verbal memory improvement with a greater baseline cortical thinning in the left pars triangularis. Significant but weak cortical thickness decrease from baseline to follow-up was observed in patients in comparison to controls (left pars triangularis and opercularis, and left caudal middle frontal areas). These results may support a positive predictive role for cortical thinning in the frontal region with regard to clinical and cognitive improvement with clozapine and risperidone in FE patients with schizophrenia. | 25,088,730 | [
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Twist expression in dentigerous cyst, odontogenic keratocyst, and ameloblastoma. | Epithelial-mesenchymal transition (EMT) is a process which is associated with a loss of intercellular adhesion, acquired mesenchymal shape, and increased motility by epithelial cells. Twist is one of the key regulators of EMT.In view of the distinct clinical behavior of odontogenic lesions, the objective of the present study was to investigate the immunohistochemical expression of Twist in these lesions. In this study, 70 formalin-fixed, paraffin-embedded tissue blocks of odontogenic lesion consisting of 16 unicystic ameloblastomas (UA), 17 solid ameloblastomas (SA), 18 odontogenic keratocysts (OKC), and 19 dentigerous cysts (DC) were reviewed using immunohistochemistry for Twist staining. In this study, Twist immunostaining was evident in all groups of the specimens except the dentigerous cyst group. Twist expression was seen in 58.8 % (10/17) of SA, 50 % (8/16) of UA, and 44.4 % (8/18) of OKCs. 23.5 % of SA, 18.8 % of UA, and 16.7 % of OKCs showed Twist expression in more than 50 % of cells. Statistical analysis showed that Twist expression levels were significantly higher in ameloblastomas (SA and UA) and OKCs than dentigerous cysts (P = 0.002). There were no significant differences between Twist expression in SAs, UAs, and OKCs (P > 0.05). The results of this study propose that the high expression rate of Twist plays a role in the pathogenesis of ameloblastomas and OKCs and might be one of the reasons for the aggressive behavior of ameloblastomas and high recurrence of OKCs and could reinforce the classification of OKC as an odontogenic tumor. | 25,088,731 | [
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Effects and after-effects of voluntary intermittent light finger touch on body sway. | Effects of light touch on body sway have usually been investigated with some form of constant contact. Only two studies investigated transient sway dynamics following the addition or withdrawal of light touch. This study adopted a paradigm of intermittent touch and assessed body sway during as well as following short periods of touch of varying durations to investigate whether effects and after-effects of touch differ as a function of touch duration. In a modified heel-to-toe posture, 15 blindfolded participants alternated their index finger position between no-touching and touching on a strain gauge in response to low- and high-pitched auditory cues. Five trials of 46 s duration were segmented into 11 sections: a 6-s no-touching period was followed by five pseudo-randomly ordered touching periods of 0.5-, 1-, 1.5-, 2-, and 5-s duration, each of which was followed by another 6-s no-touching interval. Consistent with previous research, compared to no-touching intervals sway was reduced during touch periods with touch durations greater than 2 s. Progressive reductions in sway were evident after touch onset. After touch withdrawal in the 2-s touch condition, postural sway increased and returned to baseline level nearly immediately. Interestingly, in the 5-s touch condition, reductions in sway persisted even after touch withdrawal in the medio-lateral and antero-posterior plane for around 2.5 s and 5.5 s, respectively. Our intermittent touch paradigm resulted in duration-dependent touch effects and after-effects; the latter is a novel finding and may result from a more persistent postural set involved in proactive sway control. | 25,088,757 | [
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Selfish punishment with avoiding mechanism can alleviate both first-order and second-order social dilemma. | Punishment, especially selfish punishment, has recently been identified as a potent promoter in sustaining or even enhancing the cooperation among unrelated individuals. However, without other key mechanisms, the first-order social dilemma and second-order social dilemma are still two enduring conundrums in biology and the social sciences even with the presence of punishment. In the present study, we investigate a spatial evolutionary four-strategy prisoner׳s dilemma game model with avoiding mechanism, where the four strategies are cooperation, defection, altruistic and selfish punishment. By introducing the low level of random mutation of strategies, we demonstrate that the presence of selfish punishment with avoiding mechanism can alleviate the two kinds of social dilemmas for various parametrizations. In addition, we propose an extended pair approximation method, whose solutions can essentially estimate the dynamical behaviors and final evolutionary frequencies of the four strategies. At last, considering the analogy between our model and the classical Lotka-Volterra system, we introduce interaction webs based on the spatial replicator dynamics and the transformed payoff matrix to qualitatively characterize the emergent co-exist strategy phases, and its validity are supported by extensive simulations. | 25,088,776 | [
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An evaluation of the quality of evidence underpinning diabetes management models: a review of the literature. | There is a paucity of research on the quality of evidence relating to primary care workforce models. Thus, the aim of the present study was to evaluate the quality of evidence on diabetes primary care workforce models in Australia. The National Health and Medical Research Council of Australia's (National Health and Medical Reseach Council; 2000, 2001) frameworks for evaluating scientific evidence and economic evaluations were used to assess the quality of studies involving primary care workforce models for diabetes care involving Australian adults. A search of medical databases (MEDLINE, AMED, RURAL, Australian Indigenous HealthInfoNet and The Cochrane Institute), journals for diabetes care (Diabetes Research and Clinical Practice, Diabetes Care, Diabetic Medicine, Population Health Management, Rural and Remote Health, Australian Journal of Primary Health, PLoS Medicine, Medical Journal of Australia, BMC Health Services Research, BMC Public Health, BMC Family Practice) and Commonwealth and state government health websites was undertaken to acquire Australian studies of diabetes workforce models published 2005-13. Various diabetes workforce models were examined, including 'one-stop shops', pharmacy care, Aboriginal services and telephone-delivered interventions. The quality of evidence was evaluated against several criteria, including relevance and replication, strength of evidence, effect size, transferability and representativeness, and value for money. Of the 14 studies found, four were randomised controlled trials and one was a systematic review (i.e. Level II and I (best) evidence). Only three provided a replicable protocol or detailed intervention delivery. Eleven lacked a theoretical framework. Twelve reported significant improvements in clinical (patient) outcomes, commonly HbA1c, cholesterol and blood pressure; only four reported changes in short- and long-term outcomes (e.g. quality of life). Most studies used a small or targeted population. Only two studies assessed both benefits and costs of their intervention compared with usual care and cost effectiveness. More rigorous studies of diabetes workforce models are needed to determine whether these interventions improve patient outcomes and, if they do, represent value for money. WHAT IS KNOWN ABOUT THE TOPIC?: Although health systems with strong primary care orientations have been associated with enhanced access, equity and population health, the primary care workforce is facing several challenges. These include a mal-distribution of resources (supply side) and health outcomes (demand side), inconsistent support for teamwork care models, and a lack of enhanced clinical inter-professional education and/or training opportunities. These challenges are exacerbated by an ageing health workforce and general population, as well as a population that has increased prevalence of chronic conditions and multi-morbidity. Although several policy directions have been advocated to address these challenges, there is a lack of high-quality evidence about which primary care workforce models are best (and which models represent better value for money than current practice) and what the health effects are for patients. WHAT DOES THIS PAPER ADD?: This study demonstrated several strengths and weaknesses of Australian diabetes models of care studies. In particular, only five of the 14 studies assessed were designed in a way that enabled them to achieve a Level II or I rating (and hence the 'best' level of evidence), based on the NHMRC's (2000, 2001) frameworks for assessing scientific evidence. The majority of studies risked the introduction of bias and thus may have incorrect conclusions. Only a few studies described clearly what the intervention and the comparator were and thus could be easily replicated. Only two studies included cost-effectiveness studies of their interventions compared with usual care. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS?: Although there has been an increase in the number of primary care workforce models implemented in Australia, there is a need for more rigorous research to assess whether these interventions are effective in producing improved health outcomes and represent better value for money than current practice. Researchers and policymakers need to make decisions based on high-quality evidence; it is not obvious what effect the evidence is having on primary care workforce reform. | 25,088,795 | [
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Anal Pap smears and anal cancer: what dermatologists should know. | Squamous epithelial cells are susceptible to infection by the human papillomavirus. Infection of squamous epithelium with oncogenic human papillomavirus types is associated with development of dysplasia and potential malignant transformation. Historically, cervical cancer has been the most prevalent human papillomavirus-induced squamous neoplasia. However, because of widespread screening via Pap smear testing, rates of cervical cancer in the United States have decreased dramatically during the past 50 years. Rates of anal cancer, in contrast, have doubled during the past 30 years. The groups at highest risk for development of anal cancer are men who have sex with men, HIV-positive patients, and patients immunosuppressed as a result of solid-organ transplantation. By detecting dysplasia before it develops into invasive cancer, anal Pap smears may be a potentially useful screening tool for anal cancer, particularly in individuals known to be at increased risk. However, at this time, sufficient data supporting the benefit of anal Pap smear screening are lacking. With insufficient evidence, no national health care organizations currently recommend the use of anal Pap smears as a routine screening test, even among high-risk groups. | 25,088,812 | [
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Catalytic borylation of SCF₃-functionalized arenes by rhodium(I) boryl complexes: regioselective C-H activation at the ortho-position. | An unprecedented reaction pathway for the borylation of SCF3-containing arenes using [Rh(Bpin)(PEt3)3] (pin=pinacolato) is reported. Catalytic processes were developed and the functionalizations proceed under mild reaction conditions. The C-H activations occur with a unique regioselectivity for the position ortho to the SCF3 group, which apparently serves as directing group. Borylated SCF3 compounds can serve as versatile building blocks. | 25,088,814 | [
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Initial experience of ArcCHECK and 3DVH software for RapidArc treatment plan verification. | The purpose of this study was to perform delivery quality assurance with ArcCHECK and 3DVH system (Sun Nuclear, FL) and to evaluate the suitability of this system for volumetric-modulated arc therapy (VMAT) (RapidArc [RA]) verification. This software calculates the delivered dose distributions in patients by perturbing the calculated dose using errors detected in fluence or planar dose measurements. The device is tested to correlate the gamma passing rate (%GP) and the composite dose predicted by 3DVH software. A total of 28 patients with prostate cancer who were treated with RA were analyzed. RA treatments were delivered to a diode array phantom (ArcCHECK), which was used to create a planned dose perturbation (PDP) file. The 3DVH analysis used the dose differences derived from comparing the measured dose with the treatment planning system (TPS)-calculated doses to perturb the initial TPS-calculated dose. The 3DVH then overlays the resultant dose on the patient's structures using the resultant "PDP" beams. Measured dose distributions were compared with the calculated ones using the gamma index (GI) method by applying the global (Van Dyk) normalization and acceptance criteria, i.e., 3%/3mm. Paired differences tests were used to estimate statistical significance of the differences between the composite dose calculated using 3DVH and %GP. Also, statistical correlation by means of logistic regression analysis has been analyzed. Dose-volume histogram (DVH) analysis for patient plans revealed small differences between treatment plan calculations and 3DVH results for organ at risk (OAR), whereas planning target volume (PTV) of the measured plan was systematically higher than that predicted by the TPS. The t-test results between the planned and the estimated DVH values showed that mean values were incomparable (p < 0.05). The quality assurance (QA) gamma analysis 3%/3mm showed that in all cases there were only weak-to-moderate correlations (Pearson r: 0.12 to 0.74). Moreover, clinically relevant differences increased with increasing QA passing rate, indicating that some of the largest dose differences occurred in the cases of high QA passing rates, which may be called "false negatives." The clinical importance of any disagreement between the measured and the calculated dose is often difficult to interpret; however, beam errors (either in delivery or in TPS calculation) can affect the effectiveness of the patient dose. Further research is needed to determinate the role of a PDP-type algorithm to accurately estimate patient dose effect. | 25,088,815 | [
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Controllable Nd₂Fe₁₄B/α-Fe nanocomposites: chemical synthesis and magnetic properties. | It is extremely desirable but challenging to develop exchange-coupled magnets with well-dispersed hard/soft phase and confined size to meet the high energy requirements of advanced magnets in modern industry and information technology. Here, we report a novel bottom-up strategy with two-step thermal decomposition and reductive annealing process to synthesize Nd₂Fe₁₄B/α-Fe nanocomposites, in which effective control of the hard/soft magnetic phase size and proportion was achieved. It is worth noting that the composition, as well as phase distribution, can be readily tuned by changing the ratio between Nd-Fe-B-oxide and α-Fe. This work provides an effective approach to adjust the phase size and distribution for exchange-coupled, rare-earth nanomagnets, which can be fundamental for high energy magnets. | 25,088,826 | [
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... |
Diagnostic accuracy of ultrasonic histogram features to evaluate radiation toxicity of the parotid glands: a clinical study of xerostomia following head-and-neck cancer radiotherapy. | To investigate the diagnostic accuracy of ultrasound histogram features in the quantitative assessment of radiation-induced parotid gland injury and to identify potential imaging biomarkers for radiation-induced xerostomia (dry mouth)-the most common and debilitating side effect after head-and-neck radiotherapy (RT). Thirty-four patients, who have developed xerostomia after RT for head-and-neck cancer, were enrolled. Radiation-induced xerostomia was defined by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity scale. Ultrasound scans were performed on each patient's parotids bilaterally. The 34 patients were stratified into the acute-toxicity groups (16 patients, ≤ 3 months after treatment) and the late-toxicity group (18 patients, > 3 months after treatment). A separate control group of 13 healthy volunteers underwent similar ultrasound scans of their parotid glands. Six sonographic features were derived from the echo-intensity histograms to assess acute and late toxicity of the parotid glands. The quantitative assessments were compared to a radiologist's clinical evaluations. The diagnostic accuracy of these ultrasonic histogram features was evaluated with the receiver operating characteristic (ROC) curve. With an area under the ROC curve greater than 0.90, several histogram features demonstrated excellent diagnostic accuracy for evaluation of acute and late toxicity of parotid glands. Significant differences (P < .05) in all six sonographic features were demonstrated between the control, acute-toxicity, and late-toxicity groups. However, subjective radiologic evaluation cannot distinguish between acute and late toxicity of parotid glands. We demonstrated that ultrasound histogram features could be used to measure acute and late toxicity of the parotid glands after head-and-neck cancer RT, which may be developed into a low-cost imaging method for xerostomia monitoring and assessment. | 25,088,832 | [
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... |
Retrograde transplantar arch angioplasty of below-the-knee arterial occlusions: outcomes compared to anterograde recanalization. | To compare the clinical outcomes of retrograde transplantar arch angioplasty and conventional below-the-knee (BTK) anterograde recanalization. One hundred twelve limbs in 96 patients underwent attempt at antegrade tibial angioplasty. Among 27 technical failures, retrograde trans-dorsal or -planter percutaneous transluminal angioplasty was attempted in 22 limbs. Ankle-brachial index (ABI), thrombolysis in myocardial infarction (TIMI) flow grade, and dorsal/plantar arterial pulse score improvement were compared immediately after the procedures between patients received successful anterograde angioplasty (anterograde angioplasty group [AAG], 85 limbs in 71 patients) and retrograde angioplasty (retrograde angioplasty group [RAG], 22 limbs in 20 patients). Target vessel restenosis and limb salvage were observed during follow-up. Primary technical success rate was 75.9% in the RAG (vs. 74.0% AAG, P > .05). ABI improved from 0.55 ± 0.21 to 0.93 ± 0.19 in the RAG (vs. 0.56 ± 0.14 to 0.89 ± 0.18 AAG, P > .05). TIMI flow grade demonstrated greater reperfusion of distal foot tissue in the RAG (2.3 ± 0.8 vs. 1.0 ± 0.8, P < .05). Primary patency rates at 12 and 24 months were 63.6% (14 of 22) and 45.5% (10 of 22) in the RAG and 52.9% (45 of 85) and 37.6% (32 of 85) in the AAG, respectively (P > .05). Kaplan-Meier analysis after 24 months found limb salvage rates of 93.8% in the RAG and 96.5% in the AAG (P > .05). Retrograde transplantar arch angioplasty achieved better immediate blood flow and similar ABI improvement, primary patency rate, and limb salvage rate compared to conventional transtibial angioplasty for BTK occlusions. This could become a supplementary technique when anterograde angioplasty fails. | 25,088,835 | [
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0.003002... |
Tissue-engineered nerve constructs under a microgravity system for peripheral nerve regeneration. | Mesenchymal stem cells (MSCs) seeded in a 3D scaffold often present characteristics of low proliferation and migration, which affect the microstructure of tissue-engineered nerves (TENs) and impair the therapeutic effects of nerve defects. By promoting MSC differentiation and mass/nutrient transport, rotary cell culture systems (RCCSs) display potential for advancing the construction of MSC-based TENs. Thus, in this study, we attempted to construct a TEN composed of adipose-derived mesenchymal stem cells (ADSCs) and acellular nerve graft (ANG) utilizing an RCCS. Compared to TENs prepared in a static 3D approach, MTT and cell count results displayed an increased number of ADSCs for TENs in an RCCS. The similarity in cell cycle states and high rates of apoptosis in the static 3D culture demonstrated that the higher proliferation in the RCCS was not due to microgravity regulation but a result of preferential mass/nutrient transport. Quantitative PCR and ELISA indicated that the RCCS promoted the expression of ADSC neural differentiation-associated genes compared to the static 3D culture. Furthermore, this difference was eliminated by adding the Notch1 signaling pathway inhibitor DAPT to the 3D static culture. TEM, axon immunostaining, and retrograde labeling analysis after sciatic nerve transplantation indicated that the TENs prepared in the RCCS exhibited more regenerative characteristics for repairing peripheral nerves than those prepared in a static 3D approach. Therefore, these findings suggest that the RCCS can modulate the construction, morphology, and function of engineered nerves as a promising alternative for nerve regeneration. | 25,088,840 | [
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0.1178384,... |
Switching from insulin to liraglutide improved glycemic control and the quality of life scores in a case of type 2 diabetes and active Crohn's disease. | A 44-year-old man with type 2 diabetes of five years' duration was admitted for the management of poor glycemic control despite the administration of insulin therapy. On admission, he received vigorous treatment for a 28-year history of Crohn's disease and a 14-year history of a psychiatric disorder. His glycosylated hemoglobin A1c (HbA1c) level was 11.3%, his fasting blood glucose level was 567 mg/dL and his C-peptide level was 1.0 ng/mL. His quality of life (QOL) was severely impaired as a result of frequent episodes of hyperglycemia and hypoglycemia. Treatment with liraglutide was commenced in place of insulin, which improved the patient's glycemic control to an HbA1c level of 5.5% and markedly increased his QOL score with no hypoglycemia. | 25,088,877 | [
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Liver abscess caused by CTX-M-55-type extended-spectrum β-lactamase (ESBL)-producing Salmonella enteritidis. | Liver abscesses secondary to Salmonella species are rarely described in the general population. We herein describe a case of a liver abscess caused by CTX-M-55-type extended-spectrum β-lactamase (ESBL)-producing Salmonella enteritidis, which has not been reported in the literature. A 54-year-old male was admitted due to a high fever and was clinically diagnosed with a liver abscess. Culture of the fluid from the liver abscess revealed CTX-M-55-type ESBL-producing S. enteritidis. Although the patient underwent percutaneous transhepatic abscess drainage and antibiotic therapy, he died one month later. It should be noted that liver abscesses are potentially fatal depending on the causative pathogen. | 25,088,889 | [
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0.007351979,
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Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice. | Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity. | 25,088,904 | [
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0.... |
Novel retinoblastoma mutation abrogating the interaction to E2F2/3, but not E2F1, led to selective suppression of thyroid tumors. | Mutant mouse models are indispensable tools for clarifying gene functions and elucidating the pathogenic mechanisms of human diseases. Here, we describe novel cancer models bearing point mutations in the retinoblastoma gene (Rb1) generated by N-ethyl-N-nitrosourea mutagenesis. Two mutations in splice sites reduced Rb1 expression and led to a tumor spectrum and incidence similar to those observed in the conventional Rb1 knockout mice. The missense mutant, Rb1(D326V/+) , developed pituitary tumors, but thyroid tumors were completely suppressed. Immunohistochemical analyses of thyroid tissue revealed that E2F1, but not E2F2/3, was selectively inactivated, indicating that the mutant Rb protein (pRb) suppressed thyroid tumors by inactivating E2F1. Interestingly, Rb1(D326V/+) mice developed pituitary tumors that originated from the intermediate lobe of the pituitary, despite selective inactivation of E2F1. Furthermore, in the anterior lobe of the pituitary, other E2F were also inactivated. These observations show that pRb mediates the inactivation of E2F function and its contribution to tumorigenesis is highly dependent on the cell type. Last, by using a reconstitution assay of synthesized proteins, we showed that the D326V missense pRb bound to E2F1 but failed to interact with E2F2/3. These results reveal the effect of the pRb N-terminal domain on E2F function and the impact of the protein on tumorigenesis. Thus, this mutant mouse model can be used to investigate human Rb family-bearing mutations at the N-terminal region. | 25,088,905 | [
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0.218371,
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-0.072... |
Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. | Data regarding the incidence and severity of post-ERCP pancreatitis (PEP) are primarily from nonrandomized studies. To determine the incidence, severity, and mortality of PEP from a systematic review of the placebo or no-stent arms of randomized, controlled trials (RCTs). MEDLINE, EMBASE, and Cochrane databases were searched to identify RCTs evaluating the efficacy of drugs and/or pancreatic stents to prevent PEP. Systematic review of patients enrolled in RCTs evaluating agents for PEP prophylaxis. Patients in the placebo or no-stent arms of the RCTs ERCP. Incidence, severity, and mortality of PEP. There were 108 RCTs with 13,296 patients in the placebo or no-stent arms. Overall, the PEP incidence was 9.7% and the mortality rate was 0.7%. Severity of PEP was reported for 8857 patients: 5.7%, 2.6%, and 0.5% of cases were mild, moderate, and severe, respectively. The incidence of PEP in 2345 high-risk patients was 14.7% and the severity of PEP was mild, moderate, and severe in 8.6%, 3.9%, and 0.8%, respectively, with a 0.2% mortality rate. The incidence of PEP was 13% in North American RCTs compared with 8.4% in European and 9.9% in Asian RCTs. ERCPs conducted before and after 2000 had a PEP incidence of 7.7% and 10%, respectively. Difference in PEP risk among patients in the included RCTs. The incidence of PEP and severe PEP is similar in high-risk patients and the overall cohort. Discrepancies in the incidence of PEP across geographic regions require further study. | 25,088,919 | [
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0.2511738,
-0.115214... |
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