title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Mobile teledermatology is a valid method to estimate prevalence of melanocytic naevi in children. | The prevalence of melanocytic naevi in children correlates with sun exposure and may serve as an objective population risk indicator of future melanoma incidence. The aim was to investigate if mobile teledermatology could offer a valid methodology compared with standard manual, face-to-face counting of naevi on the back of children. Ninety-seven children aged 7-16 years were enrolled. One dermatologist performed manual naevi counting and imaging of the child's back using an iPhone 4S comprising a safe-coded mobile application. Two other dermatologists independently counted naevi from the images. Cohen's weighted kappa (κw) coefficient demonstrated substantial agreement for both dermatologists: κw = 0.69 (0.57-0.81 [95% confidence intervals]) and κw = 0.78 (0.70-0.86), compared with the manual assessment. Inter-rater reliability was also substantial (κw = 0.80 [0.73-0.87]). Use of mobile teledermatology proved valid for estimating naevi prevalence on the back and could provide a more feasible methodology following trends in sun exposure in children. | 25,138,480 | [
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The Equilibrium between Localized and Delocalized States of Thermochromic Semibullvalenes and Barbaralanes-Direct Observation of Transition States of Degenerate Cope Rearrangements. | The UV/Vis spectra of thermochromic semibullvalenes 1 and barbaralanes recorded at various temperatures yield enthalpy differences between the two degenerate classical structures 1 and 1' and the less stable species (1*) that absorb at long wavelengths. The latter species are interpreted in terms of higher, delocalized states that are located just above the flat potential energy barrier between the ground states (ΔH(0) =11 (R=H; in butyronitrile), 1 kJ mol(-1) (R=Ph)). | 25,138,495 | [
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Solvent Effects on the Equilibrium between Localized and Delocalized States of Thermochromic Semibullvalenes and Barbaralanes. | The position of the equilibrium between localized and delocalized states of thermochromic semibullvalenes and barbaralanes (see the Equation) depends strongly on the solvent. Dipolar aprotic solvents, particularly N,N'-dimethylpropylene urea, favor the delocalized, bishomoaromatic state (ΔH(0) =8 kJ mol(-1) (cyclohexane), ΔH(0) <0 kJ mol(-1) (N,N'-dimethylpropylene urea)). | 25,138,496 | [
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An oxidation-labile traceless linker for solid-phase synthesis. | Traceless release of biaryls, acetylenes, alkenes, heterocycles, thioethers, and secondary amines from different solid supports can be achieved under very mild conditions by using a hydrazide group. This group, which is converted into an acyl diazene by oxidation and subsequently cleaved by a nucleophile (see scheme), is thus an attractive new linker for solid-phase synthesis and combinatorial chemistry. | 25,138,498 | [
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Hexasupersilyl-triprismo-hexastannane (tBu3 Si)6 Sn6 -The First Molecular Tin Compound Containing a Sn6 Prism. | Dark violet hexastannane (tBu3 Si)6 Sn6 displays a new framework motif for molecular tin compounds, in which six Sn atoms are located at the corners of a trigonal prism. The compound can be synthesized according to Equation (a). R*=SitBu3 . | 25,138,509 | [
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A spreader-bar approach to molecular architecture: formation of stable artificial chemoreceptors. | The destructive influence of lateral diffusion on nanostructured monolayers can be prevented by using the spreader-bar technique. This approach allows the formation of stable artificial receptors for barbituric acid by lateral structuring of a dodecanethiol monolayer with molecular spreader-bars from thiobarbituric acid without chemical polymerization (see schematic representation). The new technique may have applications in chemosensors, affinity chromatography, stereoselective catalysis, and molecular electronics. | 25,138,511 | [
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A method for the selection of catalytic activity using phage display and proximity coupling. | Phage display has been used extensively for the selection of proteins with binding sites for ligands. Here, as illustrated with the example of DNA polymerase, the use of phage display for selection according to catalytic activity is described. Active enzymes are selected by binding of the reaction product P (see the scheme) cross-linked in the proximity of the enzyme E that catalyzed the reaction with the substrate S. | 25,138,517 | [
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Alkyl migration aptitudes in the vinylidene-acetylene rearrangement and isotope effect in the vinylidene formation process from a deuterium-labeled cyclopropene. | The secret of the mechanism of vinylidene rearrangements has been unlocked by the use of specifically labeled cyclopropenes under mild thermal conditions (see the Equations). (13) C labeling gives the surprising 1,2-alkyl migratory aptitude sequence Et>iPr>Me. Deuterium labeling yields the first measurement of the primary kinetic isotope effect in the ring opening of a cyclopropene to form a vinylidene. | 25,138,518 | [
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Molecular Recognition within a Self-Assembled Cylindrical Host. | A change in geometry is necessary on entry into the capsule: a supramolecular associate approximately 1.8 nm long (see schematic representation), which consists of two halves stabilized by hydrogen bonds, influences the intra- and intermolecular interactions of the guest molecules encapsulated. Thus tertiary amides and anilides such as 1, which exist in solution preferably as E rotamers, are fixed in the Z conformation inside the capsule for steric reasons. | 25,138,521 | [
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Structural abnormalities of corpus callosum and cortical axonal tracts accompanied by decreased anxiety-like behavior and lowered sociability in spock3- mutant mice. | Spock3/Testican-3 is a nervous system-expressed heparan sulfate proteoglycan belonging to a subgroup of the BM-40/SPARC/osteonectin family, the role of which in brain development is unclear. Because Spock1, a member of the Spock family, inhibits their attachment to substrates and the neurite outgrowth of cultured neuronal cells, Spock3 is also thought to be similarly involved in the neuronal development. In the present study, we established a Spock3-mutant mouse harboring a deletion extending from the presumptive upstream regulatory region to exon 4 of the Spock3 locus and performed histological and behavioral studies on these mutant mice. In wild-type (WT) mice, all Spock members were clearly expressed during brain development. In adults, intense Spock1 and Spock2 expressions were observed throughout the entire brain; whereas, Spock3 expression was no longer visible except in the thalamic nuclei. Thus, Spock3 expression is mostly confined to the developmental stage of the brain. In adult mutant mice, the cells of all cortical layers were swollen. The corpus callosum was narrowed around the central region along the rostral-caudal axis and many small spaces were observed without myelin sheaths throughout the entire corpus callosum. In addition, the cortical input and output fibers did not form into thick bundled fibers as well as the WT counterparts did. Moreover, a subpopulation of corticospinal axonal fibers penetrated into the dorsal striatum with moderately altered orientations. Consistent with these modifications of brain structures, the mutant mice exhibited decreased anxiety-like behavior and lowered sociability. Together, these results demonstrate that Spock3 plays an important role in the formation or maintenance of major neuronal structures in the brain. | 25,138,526 | [
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Ubiquitin-activating enzyme is necessary for 17β-estradiol-induced breast cancer cell proliferation and migration. | The sex steroid hormone 17β-estradiol (E2) regulates breast cancer (BC) cell proliferation and migration through the activation of a plethora of signal transduction cascades (e.g., PI3K/AKT activation) starting after E2 binding to the estrogen receptor alpha (ERα). The activity of the ubiquitin (Ub)-system modulates many physiological processes (e.g., cell proliferation and migration), and recently, a specific inhibitor (Pyr-41) of the Ub-activating enzyme (E1), which works as the activator of the Ub-based signaling, has been identified to prevent the functions of the Ub-system. Here, by using Pyr-41, we studied the involvement of the Ub-system in E2-induced signaling to proliferation and migration of BC cells. Our data indicate that E1 activity is involved in the E2:ERα signaling important for cell proliferation and migration through the modulation of the E2-evoked activation of the PI3K/AKT and the p38/MAPK pathways. These discoveries indicate a new molecular circuitry that can be further explored to define new opportunities for BC treatment. | 25,138,535 | [
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Loss of PiT-1 results in abnormal endocytosis in the yolk sac visceral endoderm. | PiT-1 protein is a transmembrane sodium-dependent phosphate (Pi) transporter. PiT-1 knock out (KO) embryos die from largely unknown causes by embryonic day (E) 12.5. We tested the hypothesis that PiT-1 is required for endocytosis in the embryonic yolk sac (YS) visceral endoderm (VE). Here we present data supporting that PiT-1 KO results in a YS remodeling defect and decreased endocytosis in the YS VE. The remodeling defect is not due to an upstream cardiomyocyte requirement for PiT-1, as SM22αCre-specific KO of PiT-1 in the developing heart and the YS mesodermal layer (ME) does not recapitulate the PiT-1 global KO phenotype. Furthermore, we find that high levels of PiT-1 protein localize to the YS VE apical membrane. Together these data support that PiT-1 is likely required in YS VE. During normal development maternal immunoglobulin (IgG) is endocytosed into YS VE and accumulates in the apical side of the VE in a specialized lysosome termed the apical vacuole (AV). We have identified a reduction in PiT-1 KO VE cell height and a striking loss of IgG accumulation in the PiT-1 KO VE. The endocytosis genes Tfeb, Lamtor2 and Snx2 are increased at the RNA level. Lysotracker Red staining reveals a loss of distinct AVs, and yolk sacs incubated ex vivo with phRODO Green Dextran for Endocytosis demonstrate a functional loss of endocytosis. As yolk sac endocytosis is controlled in part by microautophagy, but expression of LC3 had not been examined, we investigated LC3 expression during yolk sac development and found stage-specific LC3 RNA expression that is predominantly from the YS VE layer at E9.5. Normalized LC3-II protein levels are decreased in the PiT-1 KO YS, supporting a requirement for PiT-1 in autophagy in the YS. Therefore, we propose the novel idea that PiT-1 is central to the regulation of endocytosis and autophagy in the YS VE. | 25,138,534 | [
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Successful peripheral neuromodulation for phantom limb pain. | For decades, the heterogeneity of the amputee population and the complex interaction of biopsychosocial factors have confounded researchers' attempts to develop an effective treatment for phantom limb pain. Therefore, it remains difficult to treat, and affected patients often experience decreased quality of life, increased psychological distress, and poorer health outcomes. In the case study, we report a novel strategy for the peripheral placement of neuromodulation leads for the treatment of phantom limb pain in a patient who subsequently described complete and consistent pain relief independent of significant variations in psychosocial stress. | 25,138,543 | [
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Integrating Reiki and community-engaged scholarship: an interdisciplinary educational innovation. | To provide students with a meaningful holistic care experience while integrating community-engaged scholarship, students partnered with a Reiki-prepared faculty member within a nurse-managed community clinic to offer Reiki to the clients and participate in the evaluation of the effectiveness of the modality. This article describes how students and faculty integrated holistic care, scholarship, and community engagement. This experience provided the students with an opportunity to embrace the art and science of holistic nursing while obtaining experience in measuring outcomes. | 25,138,568 | [
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Habitat differences influence genetic impacts of human land use on the American beech (Fagus grandifolia). | Natural reforestation after regional forest clearance is a globally common land-use sequence. The genetic recovery of tree populations in these recolonized forests may depend on the biogeographic setting of the landscape, for instance whether they are in the core or in the marginal part of the species' range. Using data from 501 individuals genotyped across 7 microsatellites, we investigated whether regional differences in habitat quality affected the recovery of genetic variation in a wind-pollinated tree species, American beech (Fagus grandifolia) in Massachusetts. We compared populations in forests that were recolonized following agricultural abandonment to those in remnant forests that have only been logged in both central inland and marginal coastal regions. Across all populations in our entire study region, recolonized forests showed limited reduction of genetic diversity as only observed heterozygosity was significantly reduced in these forests (H(O) = 0.520 and 0.590, respectively). Within inland region, this pattern was observed, whereas in the coast, recolonized populations exhibited no reduction in all genetic diversity estimates. However, genetic differentiation among recolonized populations in marginal coastal habitat increased (F(st) logged = 0.072; F(st) secondary = 0.249), with populations showing strong genetic structure, in contrast to inland region. These results indicate that the magnitude of recovery of genetic variation in recolonized populations can vary at different habitats. | 25,138,571 | [
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Heart failure as a risk factor for diabetes mellitus. | Diabetes mellitus (DM) is a well-recognized risk factor for heart failure (HF). We hypothesized that HF also increases the risk for DM. We explored the hypothesis that HF is a risk factor for DM. The Cardiovascular Health Study was a prospective cohort study of cardiovascular risk in ambulatory older adults. We used a limited-access dataset provided by the National Heart, Lung and Blood Institute. The impact of HF at baseline on DM after 3 or 4 years was examined in a cohort of 3,748 nondiabetic participants aged ≥65 years. The magnitude and significance of the association were evaluated using logistic regression models. Analyses were performed with and without adjustment for confounders and separately among subjects with normal and impaired fasting glucose at baseline. Among subjects with normal fasting glucose at baseline, HF significantly increased the odds of developing impaired fasting glucose after 3 or 4 years [odds ratio (OR) 2.18, 95% confidence interval (CI) 1.03-4.61, p = 0.043] or overt DM (OR 4.78, 95% CI 1.84-12.4, p < 0.001). After adjusting for demographic and biomedical factors, HF remained significantly associated with a worsening DM status (OR 2.43, 95% CI 1.38-4.29, p = 0.002). In the elderly population, the presence of HF more than doubles the incidence of DM within a few years. This association remains significant when adjusting for age, gender and cardiovascular comorbidities. | 25,138,610 | [
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Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate-related osteonecrosis of the jaw: a prospective feasibility study. | Our aim was to assess the feasibility of using leucocyte-rich and platelet-rich fibrin (L-PRF) for the treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a single group study. After treatment with L-PRF, the response of each patient was recorded 1 month and 4 months postoperatively. Further assessments were made of the site, stage, concentration of c-terminal crosslinked telopepide of type 1 collagen, and actinomycosis. Among the total of 34 patients, 26 (77%) showed complete resolution, 6 (18%) had delayed resolution, and 2 (6%) showed no resolution. There was a significant association between the response to treatment and the stage of BRONJ (p=0.002) but no other significant associations were detected. This study has shown that it is feasible to use L-PRF for the treatment of BRONJ, but the effectiveness cannot be judged with this study design. Randomised prospective trials are needed to confirm this. | 25,138,613 | [
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Evaluation of elastic bands for lower extremity resistance training in adults with and without musculo-skeletal pain. | Therapists commonly use elastic bands in resistance exercises during rehabilitation of smaller muscles, such as in the shoulder. However, the effectiveness has not yet been investigated for larger muscle groups. This study investigates muscle activity during lower extremity exercises. Electromyographic (EMG) activity of 10 muscles was measured in 24 women and 18 men during lunges with elastic resistance, lunges with dumbbells, and unilateral leg press in machine using 10 repetition maximum loadings, and normalized to maximal voluntary isometric contraction EMG. Lunges with dumbbells and leg press showed higher activity than lunges with elastic resistance for the vasti and rectus femoris (P < 0.01), whereas lunges with elastic resistance showed higher activity of gluteus maximus, hamstrings, and erector spinae (P < 0.01). Gender, age, and pain in the knees and hip did not influence these findings. However, pain in the lower back decreased muscular activity of the gluteus maximus and vastus medialis (P < 0.01). Lunges with elastic resistance induce high levels of muscle activity in all the large muscle groups at the hip, knee, and back. Importantly, the efficiency of these exercises was equally high regardless of gender, age, and pain in the knees and hip, whereas pain in the lower back led to altered activation strategies. | 25,138,624 | [
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Bone density among infants of gestational diabetic mothers and macrosomic neonates. | Decreased bone density has been found among infants of diabetic mothers and among large-for-gestational-age newborns. To evaluate which etiologies (physical or metabolic effect) have the greatest impact on neonatal bone density. A case-control study was conducted that included two study groups: one comprising 20 appropriate-for-gestational-age (AGA) infants of gestational diabetic mothers (IGDM) and matched controls, and the other comprising 20 macrosomic infants (birth weight > 4 kg) and matched controls. Bone density was examined along the tibia bone using quantitative ultrasound that measured speed of sound. Bone density among the group of macrosomic infants was significantly lower than among the control group (2,976 vs. 3,120 m/s respectively, p < 0.005). No differences in bone density were found between infants of diabetic mothers and their controls (3,005 vs. 3,043 m/s respectively, p = 0.286). Low bone density was predicted only by birth weight (for every increase of 100 g) (OR 1.148 [CI 1.014-1.299], p = 0.003). Bone density was found to be low among macrosomic newborn infants, whereas among AGA-IGDM infants bone density was similar to that of the control group. These findings strengthen the hypothesis that reduced fetal movements secondary to fetal macrosomia constitute the mechanism for reduced bone density. | 25,138,627 | [
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Functional connectivity in frontal-striatal brain networks and cocaine self-administration in female rhesus monkeys. | Cocaine addiction is characterized by alternating cycles of abstinence and relapse and loss of control of drug use despite severe negative life consequences associated with its abuse. The objective of the present study was to elucidate critical neural circuits involved in individual vulnerabilities to resumption of cocaine self-administration following prolonged abstinence. The subjects were three female rhesus monkeys in prolonged abstinence following a long history of cocaine self-administration. Initial experiments examined the effects of acute cocaine administration (0.3 mg/kg, IV) on functional brain connectivity across the whole brain and in specific brain networks related to behavioral control using functional magnetic resonance imaging in fully conscious subjects. Subsequently, these subjects were allowed to resume cocaine self-administration to determine whether loss of basal connectivity within specific brain networks predicted the magnitude of resumption of cocaine intake following prolonged abstinence. Acute cocaine administration robustly decreased global functional connectivity and selectively impaired top-down prefrontal circuits that control behavior, while sparing connectivity of striatal areas within limbic circuits. Importantly, impaired connectivity between prefrontal and striatal areas during abstinence predicted cocaine intake when these subjects were provided renewed access to cocaine. Based on these findings, loss of prefrontal to striatal functional connectivity may be a critical mechanism underlying the negative downward spiral of cycles of abstinence and relapse that characterizes cocaine addiction. | 25,138,647 | [
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Immunoglobulin G4-related paratesticular fibrous pseudotumor and retroperitoneal fibrosis: a case report. | A 46-year-old man with a past history of retroperitoneal fibrosis was admitted with an enlarged, hard right testis. The paratesticular lesion showed heterogeneous hypoechogenicity on ultrasonography, low signal intensity on T1- and T2-weighted magnetic resonance imaging (MRI), and lack of diffusion restriction on diffusion-weighted MRI. Following steroid treatment, the paratesticular mass was decreased in size on follow-up computed tomography. The radiologic and clinical features are recognized as a manifestation of immunoglobulin G4-related sclerosing disease involving the paratesticular region and retroperitoneum. | 25,138,678 | [
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Hormonal regulation of the cytokine microenvironment in the mammary gland. | The mammary gland is a unique organ that undergoes hormone-driven developmental changes over the course of the ovarian cycle during adult life. Macrophages play a role in regulating cellular turnover in the mammary gland and may affect cancer susceptibility. However, the immune microenvironment that regulates macrophage function has not been described. Hormonal regulation of the cytokine microenvironment across the ovarian cycle was explored using microbead multiplex assay for 15 cytokines in mammary glands from C57Bl/6 mice at different stages of the oestrous cycle, and in ovariectomised mice administered oestradiol and progesterone. The cytokines that were found to fluctuate over the course of the oestrous cycle were colony-stimulating factor (CSF)1, CSF2, interferon gamma (IFNG) and tumour necrosis factor alpha (TNFA), all of which were significantly elevated at oestrus compared with other phases. The concentration of serum progesterone during the oestrus phase negatively correlated with the abundance of cytokines CSF3, IL12p40, IFNG and leukaemia inhibitory factor (LIF). In ovariectomised mice, exogenous oestradiol administration increased mammary gland CSF1, CSF2, IFNG and LIF, compared with ovariectomised control mice. Progesterone administration together with oestradiol resulted in reduced CSF1, CSF3 and IFNG compared with oestradiol administration alone. This study suggests that the cytokine microenvironment in the mammary gland at the oestrus phase of the ovarian cycle is relatively pro-inflammatory compared with other stages of the cycle, and that the oestradiol-induced cytokine microenvironment is significantly attenuated by progesterone. A continuously fluctuating cytokine microenvironment in the mammary gland presumably regulates the phenotypes of resident leukocytes and may affect mammary gland cancer susceptibility. | 25,138,705 | [
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Detection of potentially skin sensitizing hydroperoxides of linalool in fragranced products. | On prolonged exposure to air, linalool can form sensitizing hydroperoxides. Positive hydroperoxide patch tests in dermatitis patients have frequently been reported, but their relevance has not been established. Owing to a lack of analytical methods and data, it is unclear from which sources the public might be exposed to sufficient quantities of hydroperoxides for induction of sensitization to occur. To address this knowledge gap, we developed analytical methods and performed stability studies for fine fragrances and deodorants/antiperspirants. In parallel, products recalled from consumers were analysed to investigate exposure to products used in everyday life. Liquid chromatography-mass spectrometry with high mass resolution was found to be optimal for the selective and sensitive detection of the organic hydroperoxide in the complex product matrix. Linalool hydroperoxide was detected in natural linalool, but the amount was not elevated by storage in a perfume formulation exposed to air. No indication of hydroperoxide formation in fine fragrances was found in stability studies. Aged fine fragrances recalled from consumers contained a geometric mean linalool concentration of 1,888 μg/g and, corrected for matrix effects, linalool hydroperoxide at a concentration of around 14 μg/g. In antiperspirants, we detected no oxidation products. In conclusion, very low levels of linalool hydroperoxide in fragranced products may originate from raw materials, but we found no evidence for oxidation during storage of products. The levels detected are orders of magnitude below the levels inducing sensitization in experimental animals, and these results therefore do not substantiate a causal link between potential hydroperoxide formation in cosmetics and positive results of patch tests. | 25,138,721 | [
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Comprehensive three-dimensional analysis of right-sided aortic arch with multiple vascular anomalies. | Right-sided aortic arch is a rare congenital defect usually diagnosed incidentally in adults; it is often asymptomatic unless aneurismal disease develops. In half the cases, an aberrant left subclavian artery arises from a Kommerell's diverticulum; in these cases, congenital heart anomaly is very rarely present. We report a case of incidentally-detected right-sided aortic arch with multiple vascular anomalies including left subclavian artery originating from a Kommerell's diverticulum, supra-sinus origin of coronary arteries and coronary arteriovenous fistula. Through comprehensive 3-dimensional reconstruction of the aortic arch and surrounding structures we defined anatomical relationships, which is useful for follow-up and treatment. | 25,138,741 | [
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Selection considerations when using a 'standard optometrist' to evaluate clinical performance of other eye-care personnel. | Selection of a standard professional is crucial for assessing the clinical performance of other eye-care personnel. This paper describes the selection considerations and the clinical competency assessment of two optometrists required to select a 'standard optometrist' (SO) for evaluating the clinical performance of vision technicians in India. Two optometrists were short-listed from 21 optometrists who responded to an advertisement to be selected as a SO for the assessment of the performance of 24 vision technicians in rural vision centres. Each candidate optometrist performed a routine eye examination on 40 randomly selected, newly registered subjects in a tertiary hospital clinic. Their non-cycloplegic retinoscopic findings were compared with those of an experienced optometrist, while disease diagnoses were compared with the findings of an ophthalmologist. A comparison of retinoscopic findings showed that optometrist A produced retinoscopic values within ±0.50 D agreement for the spherical equivalent (SE) 100 per cent of the time, while optometrist B obtained agreement 91.3 per cent of the time. Similarly, optometrist A's limits of agreement (SE = -0.63 to +0.45 D) and reproducibility limits (SE = 0.78 D) were better than those of optometrist B (SE = -0.98 to +0.70 D and SE =1.18 D, respectively). Optometrist A demonstrated 89.2 per cent sensitivity in detecting ocular pathology compared to 76.3 per cent by optometrist B. Optometrist A achieved consistent and reproducible retinoscopic findings as well as higher sensitivity in detecting ocular pathology and was selected as the SO for a study to assess the clinical performance of one-year trained vision technicians. The concept of a SO calibrated against an ophthalmologist for disease detection and diagnosis and an experienced optometrist for retinoscopy is a useful approach for the evaluation of eye-care personnel. | 25,138,747 | [
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A comparison of methods used to evaluate mobility performance in the visually impaired. | To compare three different approaches to measuring mobility performance when evaluating the visually impaired. 488 participants, including 192 glaucoma, 112 age-related macular degeneration, 91 diabetic retinopathy and 93 healthy volunteers, completed the Assessment of Disability Related to Vision (ADREV) mobility course. The performance of participants on the mobility course was evaluated by noting errors made and time required for completion. Errors noted and time taken were compared using multivariate logistic regression to determine which measurement better differentiated patients with visual disease from healthy volunteers. Multivariate logistic regression was also used to evaluate the combined metric of ADREV errors divided by time to determine its ability to discriminate participants with visual disease from healthy volunteers. Errors noted and time taken while ambulating through the standardised mobility course shared a weak but statistically significant association (Pearson's r=0.36, p<0.05). After controlling for demographic and medical comorbidities, logistic regression analysis revealed that errors noted were better at discriminating individuals with visual disease from healthy volunteers (OR 2.8-4.9, 95% CI 1.5 to 10.3) compared with the time taken for mobility course completion (OR 1.1, 95% CI 1.0 to 1.2). These findings were consistent across all comparisons between healthy volunteers and participants with each type of visual impairment. Finally, the combined metric of ADREV errors divided by time was far more predictive of visual disease compared with either time taken or errors noted during mobility testing (OR 11.0-17.7, 95% CI 3.6 to 77.1). A validated scoring system based on errors is more effective when assessing visual disability during mobility testing than recording the time taken for course completion. The combined metric of ADREV errors noted divided by time taken was most predictive of all the methods used to evaluate visual disability during mobility testing. | 25,138,757 | [
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Comparative role of 20% cord blood serum and 20% autologous serum in dry eye associated with Hansen's disease: a tear proteomic study. | To compare the role of topically applied serum therapy with preservative-free artificial tear (AT) drops in patients with moderate to severe dry eye in Hansen's disease along with change in tear protein profile. 144 consecutive patients were randomly divided into three groups. After a baseline examination of clinical parameters, each of the patients received designated modality of topical therapy six times a day for 6 weeks. Post-treatment documentation of clinical parameters was done at 6 weeks, and then at 12 weeks after discontinuation of topical therapy. Analysis of three tear proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis) was done at baseline, at the first and second post-treatment visits. In the cord blood serum (CBS) group, except for McMonnies score and staining score, all other clinical parameters showed continued improvement in the first and second post-treatment analyses. In the autologous serum (ALS) group, all the clinical parameters except Schirmer's I showed significant improvement in the first post-treatment analysis .This was sustained at a significant level in the second analysis except for tear film break-up time (TBUT) and conjunctival impression cytology grading. In the AT group, all the parameters improved at a non-significant level except for TBUT in the first analysis. In the next analysis, apart from McMonnies score and TBUT, other clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme, lactoferrin levels improved in both post-treatment measurements (statistically insignificant).Total tear protein continued to increase at statistically significant levels in the first and second post-treatment analyses in the CBS group and at a statistically insignificant level in the ALS group. In the AT group, the three tear proteins continued to decrease in both the analyses. In moderate to severe dry eye in Hansen's disease, serum therapy in comparison with AT drops, improves clinical parameters and causes betterment in tear protein profile. CTRI/2013/07/003802. | 25,138,758 | [
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Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomised double-masked open-label clinical trial. | To assess the efficacy and safety of oral azithromycin compared with oral doxycycline in patients with meibomian gland dysfunction (MGD) who had failed to respond to prior conservative management. 110 patients (>12 years old) with MGD were randomly assigned to receive either oral 5-day azithromycin (500 mg on day 1 and then 250 mg/day) or 1-month doxycycline (200 mg/day). They also continued eyelid warming/cleaning and artificial tears. A score comprising five symptoms and seven signs (primary outcome) was recorded prior to treatment and at 1 week, and 1 and 2 months after treatment. Total score was the sum of both scores at each follow-up. Side effects were recorded and overall clinical improvement was categorised as excellent, good, fair or poor based on the percentage of change in the total score. Symptoms and signs improved significantly in both groups (p=0.001). While improvement of symptoms was not different between the groups, bulbar conjunctival redness (p=0.004) and ocular surface staining (p=0.01) were significantly better in the azithromycin group. The azithromycin group showed a significantly better overall clinical response (p=0.01). Mild gastrointestinal side effects were not significantly different between the groups except for the second visit, when the doxycycline group had significantly more side effects (p=0.002). Although both oral azithromycin and doxycycline improved the symptoms of MGD, 5-day oral azithromycin is recommended for its better effect on improving the signs, better overall clinical response and shorter duration of treatment. NCT01783860. | 25,138,765 | [
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Governance practices and performance in US academic medical centers. | Recognition of the complex nature of modern health care delivery has led to interest in investigating the ways in which various factors, including governance structures and practices, influence health care quality. In this study, the chief executive officers (CEOs) of US academic medical centers were surveyed to elicit their perceptions of board structures, activities, and attitudes reflecting 6 widely identified governance best practices; the relationship between use of these practices and organizational performance, based on the University HealthSystem Consortium's Quality & Accountability rankings, was assessed. High-performing hospitals showed greater use of all 6 practices, but the strongest evidence supported a focus on board member education and development, the rigorous use of performance measures to guide quality improvement, and systematic board self-assessment processes. All hospitals, even those with the highest quality ratings, had major gaps in their use of best practices for CEO and board assessments. These findings can serve as the basis for developing sound board improvement plans. | 25,138,782 | [
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Third-wave cognitive therapy versus mentalisation-based treatment for major depressive disorder: a randomised clinical trial. | To compare the benefits and harms of third-wave cognitive therapy versus mentalisation-based therapy in a small sample of depressed participants. The trial was conducted at an outpatient psychiatric clinic for non-psychotic patients in Roskilde, Denmark. 44 consecutive adult participants diagnosed with major depressive disorder. 18 weeks of third-wave cognitive therapy (n=22) versus 18 weeks of mentalisation-based treatment (n=22). The primary outcome was the Hamilton Rating Scale for Depression (HDRS) at end of treatment (18 weeks). Secondary outcomes were: remission (HDRS <8), Beck's Depression Inventory, Symptom Checklist 90 Revised and The WHO-Five Well-being Index 1999. The trial inclusion lasted for about 2 years as planned but only 44 out of the planned 84 participants were randomised. Two mentalisation-based participants were lost to follow-up. The unadjusted analysis showed that third-wave participants compared with mentalisation-based participants did not differ significantly regarding the 18 weeks HDRS score (12.9 vs 17.0; mean difference -4.14; 95% CI -8.30 to 0.03; p=0.051). In the analysis adjusted for baseline HDRS score, the difference was favouring third-wave cognitive therapy (p=0.039). At 18 weeks, five of the third-wave participants (22.7%) were in remission versus none of the mentalisation-based participants (p=0.049). We recorded no suicide attempts or suicides during the intervention period in any of the 44 participants. No significant differences were found between the two intervention groups on the remaining secondary outcomes. Third-wave cognitive therapy may be more effective than mentalisation-based therapy for depressive symptoms measured on the HDRS. However, more randomised clinical trials are needed to assess the effects of third-wave cognitive therapy and mentalisation-based treatment for depression. Registered with Clinical Trials government identifier: NCT01070134. | 25,138,802 | [
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Protocol for the RT Prepare Trial: a multiple-baseline study of radiation therapists delivering education and support to women with breast cancer who are referred for radiotherapy. | There is limited evidence to guide the preparation of patients for radiotherapy. This paper describes the protocol for an evaluation of a radiation therapist led education intervention delivered to patients with breast cancer in order to reduce psychological distress. A multiple-baseline study is being used. Usual care data is being collected prior to the start of the intervention at each of three sites. The intervention is delivered by radiation therapists consulting with patients prior to their treatment planning and on the first day of treatment. The intervention focuses on providing sensory and procedural information to patients and reducing pretreatment anxiety. Recruitment is occurring in three states in Australia. Eligible participants are patients who have been referred for radiotherapy to treat breast cancer. 200 patients will be recruited during a usual care phase and, thereafter, 200 patients in the intervention phase. Measures will be collected on four occasions-after meeting with their radiation oncologist, prior to treatment planning, on the first day of treatment and after treatment completion. The primary hypothesis is that patients who receive the radiotherapy preparatory intervention will report a significantly greater decrease in psychological distress from baseline to prior to radiotherapy treatment planning in comparison with the usual care group. Secondary outcome measures include concerns about radiotherapy, patient knowledge of radiotherapy, patient preparedness and quality of life. Patient health system usage and costs will also be measured. Multilevel mixed effects regression models will be applied to test for intervention effects. Ethics approval has been gained from Curtin University and the three recruiting sites. Results will be reported in international peer reviewed journals. Australian and New Zealand Clinical Trials Registration: ACTRN12611001000998. | 25,138,815 | [
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Medication review saves nurses' time. | A project involving care home nurses that led to a significant reduction in unnecessary prescribing has saved around an hour a day of nursing time. | 25,138,843 | [
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Bariatric surgery. | Essential facts: Type 2 diabetes is linked closely to obesity. Bariatric surgery can lead to dramatic improvements in the management of the condition, according to the National Institute for Health and Care Excellence (NICE). There are two main types of bariatric surgery. A gastric band procedure uses a band to reduce the size of the stomach so a smaller amount of food is required to make the patient feel full. A gastric bypass is where the digestive system is re-routed past most of the stomach so less food is digested. | 25,138,853 | [
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Help for overseas nurses unable to obtain supervised placements. | Nurses from outside the European Economic Area looking to work in the UK will no longer have to complete supervised practice placements (News August 6). | 25,138,869 | [
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It is just a matter of application. | The Camilla Cavendish review of support worker education was clear that improving the quality of healthcare assistant (HCA) learning is central to delivering safe and effective care. Well trained staff should treat patients well, so the point of education and training must be to support HCAs to deliver effective care. But how to guarantee this? | 25,138,890 | [
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Enabling LiTFSI-based electrolytes for safer lithium-ion batteries by using linear fluorinated carbonates as (Co)solvent. | In this Full Paper we show that the use of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) as conducting salt in commercial lithium-ion batteries is made possible by introducing fluorinated linear carbonates as electrolyte (co)solvents. Electrolyte compositions based on LiTFSI and fluorinated carbonates were characterized regarding their ionic conductivity and electrochemical stability towards oxidation and with respect to their ability to form a protective film of aluminum fluoride on the aluminum surface. Moreover, the investigation of the electrochemical performance of standard lithium-ion anodes (graphite) and cathodes (Li[Ni1/3 Mn1/3 Co1/3 ]O2 , NMC) in half-cell configuration showed stable cycle life and good rate capability. Finally, an NMC/graphite full-cell confirmed the suitability of such electrolyte compositions for practical lithium-ion cells, thus enabling the complete replacement of LiPF6 and allowing the realization of substantially safer lithium-ion batteries. | 25,138,922 | [
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[Image-enhanced endoscopy and magnifying endoscopy for esophageal cancer]. | Image diagnoses for esophageal cancer are progressing. With regard to endoscopic examination, chrome endoscopy using iodine have been performed so far to identify the range of lesion and to detect multiple primary cancers. In addition to that, endoscopic ultrasonography is used to diagnose the depth of tumor invasion and to identify lymph node metastasis. Recently, image-enhanced endoscopy (IEE) [e.g. Flexible spectral Imaging Color Enhancement (FICE), i-scan, Narrow Band Imaging (NBI), Autofluorescence imaging (AFI)] has developed. IEE is useful to detect superficial lesion, and is being utilized for diagnosing the tumor depth of invasion by using magnifying endoscopy( ME) together. In this literature, recent progress of endoscopic diagnosis, especially about IEE and ME, is reviewed. In addition to that, a way of endoscopic examination using IEE and ME is introduced. | 25,138,953 | [
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Compressed-sensing-based fluorescence molecular tomographic image reconstruction with grouped sources. | Although the quality of reconstructed results can be improved with the increment of the number of measurements, the scale of the matrices involved in the reconstruction of fluorescence molecular tomography (FMT) will become larger, which leads to the poor efficiency of the process of tomographic image reconstruction. In this paper, we proposed a new method for image reconstruction of FMT based on compressed sensing, in which a scheme of grouped sources is incorporated. The forward equations are implemented using the finite element method (FEM). The reconstruction model is formulated under the framework of compressed sensing theory. The regularization term and the total variation penalty are incorporated in the objective function. During the reconstruction of FMT, the sources are divided into two groups for iteration in turn. One group of sources is employed in the first iteration of inverse problem, and the other group is employed in the next iteration. Simulation results demonstrate that the computation time and mean square error (MSE) of the reconstruction with our algorithm are less than those with the traditional method. The proposed algorithm can reconstruct the target with enhanced contrast and more accurate shape. The proposed algorithm can significantly improve the speed and accuracy of the reconstruction of FMT. Furthermore, our compressed-sensing-based method can reduce the number of measurements. | 25,138,956 | [
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Oxygen uptake at different intensities and sub-techniques predicts sprint performance in elite male cross-country skiers. | To investigate the relationship between sprint-prologue performance (using the classical technique) and the oxygen uptake at the lactate threshold (VO₂obla), maximal oxygen uptake (VO₂max), and mean oxygen uptake during double poling (VO₂dp). Eight elite male cross-country skiers [age 24.8 ± 4.8 years, (mean ± SD)] completed two treadmill roller-skiing tests using the diagonal-stride technique and a 60 s double-poling test on a ski-ergometer to determine their VO₂obla, VO₂max, and VO₂dp. Performance data were generated from a 1.25 km sprint prologue. Power-function modelling was used to predict the skiers' race speeds based on the oxygen-uptake variables and body mass. There were correlations between the race speed and the absolute expression of the VO₂obla (r = 0.79, P = 0.021), VO₂max (r = 0.86, P = 0.0069), and VO₂dp (r = 0.94, P = 0.00062). The following power-function models were established for race-speed prediction: 1.09 · VO₂obla(0.21), 1.05 · VO₂max(0.21), and 1.19 · VO₂dp(0.20); these models explained 60% (P = 0.024), 73% (P = 0.0073), and 87% (P = 0.00073), respectively, of the variance in the race speed. However, body mass did not contribute to any of the models (P = 0.97, 0.88, and 0.21, respectively). Oxygen uptake at different intensities and sub-techniques is an indicator of elite male sprint-prologue performance. The absolute expression of the investigated oxygen-uptake variables should be used when evaluating elite male sprint-prologue performances; if skiers oxygen uptake differs by 1%, their performances will likely differ by 0.2% in favour of the skier with higher oxygen uptake. | 25,138,966 | [
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Epidemiology and outcome of invasive pneumococcal disease among adults in Belgium, 2009-2011. | This epidemiological study examined morbidity and case fatality of invasive pneumococcal disease (IPD) in adults in Belgium as well as distribution and antibiotic susceptibility of Streptococcus pneumoniae serotypes.Adults hospitalised with microbiologically proven IPD were prospectively enrolled. The study started in 2009 with patients aged ≥50 years, whereas in 2010 and 2011, patients aged ≥18 years were included. The clinical presentation, patient profile, treatment, outcome, and mortality were recorded during hospitalisation.Outcome was also assessed one month afterdischarge. Of the 1,875 patients with IPD identified, 1,332 were included in the analysis. Bacteraemic pneumonia, affecting 1,049 of the patients, was the most frequent IPD type (79%), and chronic obstructive pulmonary disease and cancer were the main comorbidities.One-third of patients required admission to intensive care unit. A total of 208 (16%) patients died during hospitalisation and an additional 21 (2%) within one month after discharge. Case fatality rates of ≥20%were observed in patients with chronic heart failure, hepatic disease, and renal insufficiency. Serotypes 7F, 1, 19A, and 3 were the most prevalent and together accounted for 47% (569/1,214) of all IPD cases and 42% (80/189) of mortality. Of the patient isolates, 21% (255/1,204) were resistant to erythromycin and 22% (264/1,204) to tetracycline. Penicillin non-susceptibility was mostly found in serotype 19A isolates. These baseline data are essential when assessing the impact of pneumococcal conjugate vaccination in adults in the future. | 25,138,972 | [
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Early-onset Alzheimer's disease in two Iranian families: a genetic study. | Early-onset Alzheimer's disease (EOAD) represents less than 5% of all AD cases. Autosomal dominant EOAD has been defined as the occurrence of at least three cases in three generations. Mutations in the amyloid precursor protein (APP), presenilin-1 and presenilin-2 genes have been recognized to be the cause of EOAD. We investigated the genotype of EOAD in two generations of two families with EOAD living in an Iranian village. The polymerase chain reaction method was used to study the presenilin-1 and APP genes in 25 subjects of these generations. A guanine-to-adenine transition in exon 17 of the APP gene resulting in a valine-to-isoleucine substitution at codon 717 was detected in 14 subjects including 6 patients with EOAD. This mutation demonstrates the importance of γ-secretase, the necessity of early detection of patients with memory decline in the susceptible population and raising public awareness of consanguinity marriages. | 25,138,979 | [
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PlasmaKinetic™ versus cold knife internal urethrotomy in terms of recurrence rates: a prospective randomized study. | To evaluate the efficacy and outcomes of PlasmaKinetic™ urethrotomy against cold knife direct vision internal urethrotomy in terms of recurrence rates. A total of 136 male patients with urethral strictures were enrolled into the study. The patients were allocated to cold knife or PlasmaKinetic urethrotomy groups sequentially by using computer-generated numbers. Group A (PlasmaKinetic) and group B (cold knife) included 70 and 66 patients, respectively. All patients were reevaluated at the 3rd, 9th and 18th month postoperatively with uroflowmetry. Group A patients had a postoperative 3rd-month maximum flow rate value of 16.09 ml/s, whereas this same parameter was 15.15 ml/s in group B (p < 0.05). The urethral stricture recurrence rate up to the 9-month period was statistically significant for group A (14%) compared with group B (30%). When we compared the recurrence rates of these groups from postoperative day 1 up to the 18th month, the results were 37% for group A and 33% for group B (p > 0.05). PlasmaKinetic urethrotomy provides a better recurrence-free rate during the early period compared with conventional cold knife therapy. Nevertheless, the outcome of the stricture did not change and fibrotic tissue reformed between the 9th and the 18th month. | 25,138,990 | [
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Differential association between metabolic syndrome and coronary artery disease evaluated with cardiac computed tomography according to the presence of diabetes in a symptomatic Korean population. | Metabolic syndrome (MetS) is associated with increased risks of diabetes and coronary artery disease (CAD). Despite the controversial inclusion of established diabetes in MetS, the association between MetS and CAD according to diabetes status has not been elucidated in the Asian population. We evaluated the association between MetS and CAD using the parameters including any plaque, obstructive plaque, and coronary artery calcium score (CACS) >100 according to diabetes status in 2,869 symptomatic Korean subjects who underwent cardiac computed tomographic angiography. The prevalence of MetS was significantly higher in the diabetic subjects than in the non-diabetic subjects (69% vs. 34%, P <0.001). The incidence of any plaque (64% vs. 43%, P <0.001), obstructive plaque (26% vs. 13%, P = 0.006), and CACS >100 (23% vs. 12%, P = 0.012) was significantly higher in diabetic subjects than in non-diabetic subjects. Among the MetS components, decreased high-density lipoprotein level was significantly associated with any plaque (odds ratio [OR] 1.35), obstructive plaque (OR 1.55), and CACS >100 (OR 1.57) in the non-diabetic subjects (P <0.01, respectively). However, none of the MetS components were associated with all the parameters in the diabetic subjects. Multivariate regression analysis revealed that MetS and the number of MetS components (MetSN) were independently associated with any plaque (MetS: OR 1.55, P <0.001; MetSN: OR 1.22, P <0.001), obstructive plaque (MetS: OR 1.52, P = 0.003; MetSN: OR 1.25, P <0.001), and CACS >100 (MetS: OR 1.46, P = 0.015; MetSN: OR 1.21, P = 0.004) only in the non-diabetic subjects, respectively. MetS was independently associated with the presence and severity of CAD only in the non-diabetic subjects among the symptomatic Korean population. | 25,138,993 | [
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Probing of a human proteome microarray with a recombinant pathogen protein reveals a novel mechanism by which hookworms suppress B-cell receptor signaling. | Na-ASP-2 is an efficacious hookworm vaccine antigen. However, despite elucidation of its crystal structure and studies addressing its immunobiology, the function of Na-ASP-2 has remained elusive. We probed a 9000-protein human proteome microarray with Na-ASP-2 and showed binding to CD79A, a component of the B-cell antigen receptor complex. Na-ASP-2 bound to human B lymphocytes ex vivo and downregulated the transcription of approximately 1000 B-cell messenger RNAs (mRNAs), while only approximately 100 mRNAs were upregulated, compared with control-treated cells. The expression of a range of molecules was affected by Na-ASP-2, including factors involved in leukocyte transendothelial migration pathways and the B-cell signaling receptor pathway. Of note was the downregulated transcription of lyn and pi3k, molecules that are known to interact with CD79A and control B-cell receptor signaling processes. Together, these results highlight a previously unknown interaction between a hookworm-secreted protein and B cells, which has implications for helminth-driven immunomodulation and vaccine development. Further, the novel use of human protein microarrays to identify host-pathogen interactions, coupled with ex vivo binding studies and subsequent analyses of global gene expression in human host cells, demonstrates a new pipeline by which to explore the molecular basis of infectious diseases. | 25,139,017 | [
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Basis of virulence in a Panton-Valentine leukocidin-negative community-associated methicillin-resistant Staphylococcus aureus strain. | Community-associated (CA) infections with methicillin-resistant Staphylococcus aureus (MRSA) are on a global rise. However, analysis of virulence characteristics has been limited almost exclusively to the US endemic strain USA300. CA-MRSA strains that do not produce Panton-Valentine leukocidin (PVL) have not been investigated on a molecular level. Therefore, we analyzed virulence determinants in a PVL-negative CA-MRSA strain, ST72, from Korea. Genome-wide analysis identified 3 loci that are unique to that strain, but did not affect virulence. In contrast, phenol-soluble modulins (PSMs) and the global virulence regulator Agr strongly affected lysis of neutrophils and erythrocytes, while α-toxin and Agr had a major impact on in vivo virulence. Our findings substantiate the general key roles these factors play in CA-MRSA virulence. However, our analyses also showed noticeable differences to strain USA300, inasmuch as α-toxin emerged as a much more important factor than PSMs in experimental skin infection caused by ST72. | 25,139,021 | [
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MiR-136 targets E2F1 to reverse cisplatin chemosensitivity in glioma cells. | MicroRNAs (miRNAs) have gained much attention due to their critical roles in diverse biological events, including tumorigenesis. In this study, we demonstrate that miR-136 is down-regulated in two cohorts of patients with glioma. Furthermore, the low-level expression of miR-136 is significantly associated with a more aggressive and/or poor prognostic phenotype of patients with gliomas. Both gain- and loss-of-function experiments showed that miR-136 expression can reverse cisplatin resistance and enhance the response to cisplatin treatment. Furthermore, we identified a novel direct target of miR-136, the E2F transcription factor 1 (E2F1) oncogene. Depletion of E2F1 recapitulated the tumor-suppressive functions of miR-136, whereas re-expression of E2F1 attenuated the function of miR-136 in glioma cells. Finally, we revealed that miR-136 is inversely correlated with E2F1 expression in human glioma samples. The present study provides functional and mechanistic links between the tumor suppressor miR-136 and the oncogene E2F1 for the development of chemoresistance in human glioma. Our results indicate that targeting of the miR-136/E2F1 axis may provide a promising therapeutic approach to treat glioma. | 25,139,024 | [
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Sequencing and de novo assembly of the red cusk-eel (Genypterus chilensis) transcriptome. | The red cusk-eel (Genypterus chilensis) is an endemic fish species distributed along the coasts of the Eastern South Pacific. Biological studies on this fish are scarce, and genomic information for G. chilensis is practically non-existent. Thus, transcriptome information for this species is an essential resource that will greatly enrich molecular information and benefit future studies of red cusk-eel biology. In this work, we obtained transcriptome information of G. chilensis using the Illumina platform. The RNA sequencing generated 66,307,362 and 59,925,554 paired-end reads from skeletal muscle and liver tissues, respectively. De novo assembly using the CLC Genomic Workbench version 7.0.3 produced 48,480 contigs and created a reference transcriptome with a N50 of 846bp and average read coverage of 28.3×. By sequence similarity search for known proteins, a total of 21,272 (43.9%) contigs were annotated for their function. Out of these annotated contigs, 33.5% GO annotation results for biological processes, 32.6% GO annotation results for cellular components and 34.5% GO annotation results for molecular functions. This dataset represents the first transcriptomic resource for the red cusk-eel and for a member of the Ophidiimorpharia taxon. | 25,139,027 | [
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Investigation on bacterial community and diversity in the multilayer aquifer-aquitard system of the Pearl River Delta, China. | Bacteria play an important role in groundwater chemistry. The groundwater resource in the Pearl River Delta (PRD) is responsible for 50 million people's water requirement. High amount of ammonium, arsenic and methane had been reported in groundwater of the PRD, which was considered as the result of intensive bacterial metabolism in the multilayer aquifer-aquitard system. To investigate bacterial community in this system and its relation with groundwater chemistry, sediment and groundwater samples were taken from representative locations in the PRD at different lithological units. Bacterial 16S rRNA gene clone libraries were constructed for microbial identifications and community structures in different strata. Canonical correlation analysis between bacterial linages and environment variables (Cl(-), PO4(3-), SO4(2-), NH4(+)) showed that community structures were significantly modified by geological conditions. Higher bacterial diversity was observed in samples from the Holocene aquitard M1 and aquifer T1, while in the older aquitard M2 and basal aquifer T2, bacterial diversity was much lower. Chloroflexi, γ-proteobacteria and δ-proteobacteria were the dominant phyla in the aquitard sediment. β-proteobacteria was the dominant phylum in sediment which was strongly influenced by fresh water. The results of this study demonstrated that bacterial community contains information of geological events such as sea transgression and deltaic evolution, and microbes in the aquitards have great potential in dominating groundwater quality in aquifers. | 25,139,031 | [
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Detection of insulin granule exocytosis by an electrophysiology method with high temporal resolution reveals enlarged insulin granule pool in BIG3-knockout mice. | We recently identified BIG3 as a negative regulator of insulin granule biogenesis and reported increased insulin secretion in BIG3-knockout (BKO) mice. To pinpoint the site of action for BIG3, we investigated whether BIG3 regulates quantal insulin granule exocytosis. We established an assay to detect insulin granule exocytosis by recording ATP-elicited currents at high temporal resolution by patch clamp. Similarly to insulin, ATP release was increased in BKO β-cells. Although the frequency of insulin granule exocytosis was increased in BKO β-cells, quantal size or release kinetics remained unchanged. Electron microscopy studies showed that the number of insulin granules was increased by >60% in BKO β-cells. However, the number of morphologically docked granules was unaltered. The number of insulin granules having significant distances away from plasma membrane was greatly increased in BKO β-cells. Thus, BIG3 negatively regulates insulin granule exocytosis by restricting insulin granule biogenesis without the release kinetics of individual granules at the final exocytotic steps being affected. Depletion of BIG3 leads to an enlarged releasable pool of insulin granules, which accounts for increased release frequency and consequently increased insulin secretion. | 25,139,048 | [
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Liver resection for colorectal metastases: results and prognostic factors with 10-year follow-up. | Actual 5-year survival rates after resection of colorectal liver metastases (CLM) are 25-45%, whereas 10-year survival rates are extrapolated from survival curves. Few studies have reported long-term survivors with 10 years of actual follow-up. Therefore, no recurrences occurring after 10-plus years have been reported. The aim of our study was to analyze actual 10-year survival rates and prognostic factors. Clinical data of patients with CLM who had undergone first liver resection in our center between January 1990 and December 2000 were retrospectively analyzed. Eighty-nine patients of mean age 64 years were studied. Three patients were excluded from the study: one because of postoperative death, and two from being lost to follow-up. All other subjects had a potential 10-year follow-up. Only 33% patients received perioperative chemotherapy. The actual 10-year overall and disease-free survival rate were 22 and 19%, respectively. Poor prognostic factors were disease-free interval less than 1 year, wedge liver resection, clinical risk score>2, segment 1 CLM location, and peritumoral lymphangitis. Good prognostic factors were tumors having mucinous components in primary tumor and CLM located in the right lobe. With actual long-term follow-up for 10 years, disease-free survival rate is 19% and mainly depends on surgical management. Recurrence continues to occur more than 5 years after liver resection for CLM; cure cannot be assumed at this time. Clinical risk score is a good predictor of cure and should be taken into account when choosing perioperative treatment. | 25,139,067 | [
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Increase of pertussis incidence in 2010 to 2012 after 12 years of low circulation in Spain. | In Spain, whole cell pertussis vaccination started in 1975, with three doses before the age of 6-7 months. Doses at 15-18 months and 4-6 years were introduced in 1996 and 2001, respectively. Spain switched to an acellular vaccine in 2005. From 1998 to 2009, pertussis incidence rates remained ≤1.5 cases/100,000 inhabitants but increased from 2010 to 7.5 cases/100,000 in 2012. Data from 1998 to 2012 were analysed to assess disease trends and susceptible populations. We defined four epidemic periods: 1998-2001 (reference), 2002-05, 2006-09 and 2010-12. In 2002-05, the incidence rate increased in individuals aged 15-49 years (IRR: 1.41 (95% CI: 1.11-1.78)) and ≥50 years (IRR: 2.78 (95% CI: 1.78-4.33)) and in 2006-09 increased also in infants aged <3 months (IRR: 1.83 (95% CI: 1.60-2.09)). In 2010-12, the incidence rate increased notably in all age groups, with IRRs ranging between 2.5 (95% CI: 2.3-2.8) in 5-9 year-olds and 36.0 (95% CI: 19.4-66.8) in 20-29 year-olds. These results, consistent with the country's vaccination history, suggest a progressive accumulation of susceptible individuals due to waning immunity after years of low incidence. Further vaccination strategies should be assessed and implemented to prevent pertussis in pre-vaccinated infants, in whom the disease is more severe. | 25,139,074 | [
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Reduction of α-dystroglycan expression is correlated with poor prognosis in glioma. | Dystroglycan (DG), a multifunctional protein dimer of non-covalently linked α and β subunits, is best known as an adhesion and transduction molecule linking the cytoskeleton and intracellular signaling pathways to extracellular matrix proteins. Loss of DG binding, possibly by degradation or disturbed glycosylation, has been reported in a variety of cancers. DG is abundant at astroglial endfeet forming the blood-brain barrier (BBB) and glia limitans; so, we examined if loss of expression is associated with glioma. Expression levels of α-DG and β-DG were assessed by immunohistochemistry in a series of 78 glioma specimens to determine the relationship with tumor grade and possible prognostic significance. α-DG immunostaining was undetectable in 44 of 49 high-grade specimens (89.8%) compared to 15 of 29 low-grade specimens (51.72%) (P<0.05). Moreover, loss of α-DG expression was an independent predictor of shorter disease-free survival (DFS) (hazards ratio (HR) = 0.142, 95% confidence interval (CI) 0.033-0.611, P=0.0088). Reduced expression of both α-DG and β-DG was also a powerful negative prognostic factor for DFS (HR=2.556, 95% CI 1.403-4.654, P=0.0022) and overall survival (OS) (HR=2.193, 95% CI 1.031-4.666, P=0.0414). Lack of α-DG immunoreactivity is more frequent in high-grade glioma and is an independent predictor of poor clinical outcome. Similarly, lack of both α-DG and β-DG immunoreactivity is a strong independent predictor of clinical outcome. | 25,139,094 | [
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Investigation of the MICs of fidaxomicin and other antibiotics against Hungarian Clostridium difficile isolates. | The aim of this study was to investigate in vitro activities of fidaxomicin and other antibiotics against 188 Clostridium difficile strains collected from different centers of Hungary. C. difficile isolates showed minimum inhibitory concentration (MIC) range for fidaxomicin of ≤0.008-0.5 mg/L, with a MIC90 of 0.125 mg/L. Only four isolates (2.1%) had 0.5 mg/L MIC to fidaxomicin. The obtained MICs showed identical distribution to those found in the EUCAST database for wild-type strains. | 25,139,122 | [
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Ketamine peritonsillar infiltration during tonsillectomy in pediatric patients: An updated meta-analysis. | Peri-operative ketamine peritonsillar infiltration in children can reduce the incidence of postoperative nausea and vomiting (PONV), but its postoperative analgesic time is short. A previous meta-analysis in 2011 was inconclusive due to insufficient data. Consequently, we updated the meta-analysis to verify the role of ketamine peritonsillar infiltration for tonsillectomy in pediatric patients. Ten randomized controlled trials with a total of 522 cases were included. Pain intensity was measured by standard modified CHEOPS score. The pain scores of ketamine group at 30 min and 60 min were significantly lower than placebo group after surgery [weighted mean difference (WMD) -1.20, 95% CI -2.20 to -0.19, P=0.02; WMD -1.71, 95% CI -2.12 to -0.22, P=0.02]. Analgesic requirement in ketamine group were less than placebo group [risk ratio (RR) 0.51, 95% CI 0.26-0.97; P=0.04]. Moreover, the incidence of PONV was lower in ketamine group. (RR 0.73, 95% CI 0.54-0.97; P=0.03). However, there were no differences between these two groups in operation time, anesthesia time, first analgesic time and pain score at 120 min. Compared to placebo, ketamine peritonsillar infiltration can relieve postoperative pain within one hour but not at 120 min and reduces analgesic requirement and incidence of PONV. Moreover, there was no difference in the first analgesic time. | 25,139,134 | [
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Antimicrobial light-activated materials: towards application for food and environmental safety. | To produce light-activated antimicrobial materials composed of the photodynamic dye phloxine B incorporated into paper or cellulose membranes and to investigate ability of these materials to decrease bacterial loads on their surfaces as well as on food surfaces that were in contact with these materials under illumination with regular white light. Antimicrobial cellulose-based materials with incorporated phloxine B were produced using a layer-by-layer deposition method. Antimicrobial properties of the materials were tested in model systems as well as for decontamination of food and food contact surfaces. Pseudomonas aeruginosa, Listeria monocytogenes and Bacillus anthracis were efficiently killed by exposure of the bacterial suspension to the dye-containing material under illumination with white light, but Salmonella Typhimurium and Escherichia coli O157:H7 were only partially affected. Application of the materials for decontamination of food surfaces artificially contaminated with L. monocytogenes was shown to be ineffective, while the self-decontamination of the material surface by exposure to white light resulted in eradication of L. monocytogenes cells from the material surface. The developed materials showed significant self-decontaminating ability when under illumination; however, decontamination of food surfaces in contact with the developed materials was not achieved. The study demonstrates the antibacterial activity of materials with incorporated photodynamic dyes when under illumination with regular-intensity white light. Possible uses of the light-activated antimicrobial materials for food processing, as food contact surfaces, and surfaces in public areas to prevent cross-contamination are discussed. | 25,139,147 | [
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Effect of DOCA/salt hypertension on CRF expression in the amygdala and the autonomic stress response in conscious rats. | The effects of DOCA/salt treatment on amygdala-area CRF gene expression and the autonomic response to air jet stress (AJS) were evaluated in conscious male Sprague Dawley (SD) rats. Fifteen days of DOCA/salt treatment significantly increased resting arterial pressure (AP), decreased resting heart rate (HR) and significantly reduced regional CRF mRNA compared to controls (23±7% vs. 100±26%) independent of changes in regional CRF receptor expression. Twenty min of AJS elicited a rise in AP (~15mmHg) that was similar in both DOCA/salt animals (n=11) and controls (n=6). Alternatively, increases in HR were significantly different in the DOCA/salt animals compared to controls; including one group of DOCA/salt animals (n=5) which responded with an attenuated HR response at the onset of AJS (low-responders) and a second group (n=6) which demonstrated an elevated HR response to AJS (high-responders), specifically during the last 10min of AJS. The divergent HR responses to AJS in the DOCA/salt animals were linked to differences in resting heart rate variability. During recovery HR returned to baseline within 10min in both control and the low responder DOCA group but indicators of spontaneous baroreflex gain only increased significantly in controls. HR in the high-responder DOCA animals did not return to baseline during the same period. These results show that DOCA/salt treatment triggers downregulation of CRF gene expression in the region of the amygdala and significantly alters the HR response to acute stress but does not alter the pressor response to stress compared to normotensive controls. | 25,139,171 | [
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Photoinduced energy transfer from poly(N-vinylcarbazole) to tricarbonylchloro-(2,2'-bipyridyl)rhenium(I). | This work investigates the photoinduced energy transfer from poly(N-vinylcarbazole) (PVK), as a donor material, to fac-(2,2'-bipyridyl)Re(CO)3Cl, as a catalyst acceptor, for its potential application towards CO2 reduction. Photoluminescence quenching experiments reveal dynamic quenching through resonance energy transfer in solid donor/acceptor mixtures and in solid/liquid systems. The bimolecular reaction rate constant at solution-film interfaces for the elementary reaction of the excited state with the quencher material could be determined as 8.8(±1.4)×10(11) L mol(-1) s(-1) by using Stern-Volmer analysis. This work shows that PVK is an effective and cheap absorber material that can act efficiently as a redox photosensitizer in combination with fac-(2,2'-bipyridyl)Re(CO)3Cl as a catalyst acceptor, which might lead to possible applications in photocatalytic CO2 reduction. | 25,139,180 | [
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The effect of protein PEGylation on physical stability in liquid formulation. | The presence of micron aggregates in protein formulations has recently attracted increased interest from regulatory authorities, industry, and academia because of the potential undesired side effects of their presence. In this study, we characterized the micron aggregate formation of hen egg-white lysozyme (Lyz) and its diPEGylated (5 kDa) analog as a result of typical handling stress conditions. Both proteins were subjected to mechanical stress in the absence and presence of silicone oil (SO), elevated temperatures, and freeze-thaw cycles. Flow imaging microscopy showed that PEGylated Lyz formed approximately half as many particles as Lyz, despite its lower apparent thermodynamic stability and more loose protein fold. Further characterization showed that the PEGylation led to a change from attractive to repulsive protein-protein interactions, which may partly explain the reduced particle formation. Surprisingly, the PEGylated Lyz adsorbed an order of magnitude faster onto SO, despite being much larger in size, as determined by small-angle X-ray scattering and dynamic light scattering measurements. Thus, PEGylation may significantly reduce, but not prevent, micron aggregate formation of a protein during typical handling stresses. | 25,139,193 | [
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Ozone and daily mortality rate in 21 cities of East Asia: how does season modify the association? | Previous studies in East Asia have revealed that the short-term associations between tropospheric ozone and daily mortality rate were strongest in winter, which is opposite to the findings in North America and Western Europe. Therefore, we investigated the season-varying association between ozone and daily mortality rate in 21 cities of East Asia from 1979 to 2010. Time-series Poisson regression models were used to analyze the association between ozone and daily nonaccidental mortality rate in each city, testing for different temperature lags. The best-fitting model was obtained after adjustment for temperature in the previous 2 weeks. Bayesian hierarchical models were applied to pool the city-specific estimates. An interquartile-range increase of the moving average concentrations of same-day and previous-day ozone was associated with an increase of 1.44% (95% posterior interval (PI): 1.08%, 1.80%) in daily total mortality rate after adjustment for temperature in the previous 2 weeks. The corresponding increases were 0.62% (95% PI: 0.08%, 1.16%) in winter, 1.46% (95% PI: 0.89%, 2.03%) in spring, 1.60% (95% PI: 1.03%, 2.17%) in summer, and 1.12% (95% PI: 0.73%, 1.51%) in fall. We found significant associations between short-term exposure to ozone and higher mortality rate in East Asia that varied considerably from season to season with a significant trough in winter. | 25,139,207 | [
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Cardiac involvement in chronic progressive external ophthalmoplegia. | Myocardial involvement has not been extensively investigated in mitochondrial myopathies. The aim of the study was to assess the myocardial morpho-functional changes in patients with chronic progressive external ophthalmoplegia (PEO). Twenty patients with PEO and 20 controls underwent standard echocardiography with tissue Doppler imaging (TDI) and integrated backscatter (IBS) analyses. These techniques are capable of providing non-invasively the early, subtle structural and functional changes of the myocardium. TDI myocardial systolic (Sm) and early (Em) and late (Am) diastolic velocities of left ventricular walls were determined. The systo-diastolic variation of IBS was also determined. Patients with PEO exhibited lower Sm, lower Em, and higher Am, and a reduced Em/Am ratio than controls (p<0.001 for all) at interventricular septum and lateral wall levels. In PEO patients, septal and posterior wall cyclic variations of IBS were significantly lower than those in controls (p<0.001). Patients with PEO showed myocardial wall remodeling characterized by increased fibrosis and early left ventricular systo-diastolic function abnormalities. Although cardiac involvement in PEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of these patients. | 25,139,213 | [
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Bacterial role in pine wilt disease development - review and future perspectives. | Mutualistic and beneficial relationships between nematodes and bacteria are highly present in nature, mostly occurring because of nutritional dependence and pathogen protection, and intrinsically related with the environment, the ecological conditions and the nematode life stages. Thirty-four years have passed since the first hypothesis suggesting a bacterial role in pine wilt disease (PWD), associated with the pinewood nematode (PWN), Bursaphelenchus xylophilus. In 1980, researchers reported that bacteria associated with the PWN could produce toxins that lead to PWD development in pine seedlings. It was also suggested a double vector system for PWD, where bacteria were vectored by the PWN and the PWN vectored by an insect from the Monochamus genus. Presently, the specific involvement of bacteria in such complex disease is still controversial, even though the increased number of studies focused on the potential bacteria role has increased considerably. This review is an up-to-date comprehensive perspective and brings new insights on the role of PWN-associated bacteria in PWD. | 25,139,220 | [
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Investigation of age-related differences in an adapted Hayling task. | The Hayling task is traditionally used to assess activation and inhibitory processes efficiency among various populations, such as elderly adults. However, the classical design of the task may also involve the influence of strategy use and efficiency of sentence processing in the possible differences between individuals. Therefore, the present study investigated activation and inhibitory processes in aging with two formats of an adapted Hayling task designed to reduce the involvement of these alternative factors. Thirty young adults (M=20.7 years) and 31 older adults (M=69.6 years) performed an adapted Hayling task including a switching block (i.e., unblocked design) in addition to the classical task (i.e., blocked design), and the selection of the response between two propositions. The results obtained with the classical blocked design showed age-related deficits in the suppression sections of the task but also in the initiation ones. These findings can be explained by a co-impairment of both inhibition and activation processes in aging. The results of the unblocked Hayling task, in which strategy use would be reduced, confirmed this age-related decline in both activation and inhibition processes. Moreover, significant correlations between the unblocked design and the Trail Making Test revealed that flexibility is equally involved in the completion of both sections of this design. Finally, the use of a forced-response choice offers a format that is easy to administer to people with normal or pathological aging. This seems particularly relevant for these populations in whom the production of an unrelated word often poses problems. | 25,139,228 | [
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Pressure mat analysis of naturally occurring lameness in young pigs after weaning. | Lameness is a common problem in modern swine husbandry. It causes welfare problems in affected pigs as well as financial problems for farmers. To minimize these negative consequences of lameness, new treatment and prevention strategies need to be developed and validated using objective and quantitative measurement techniques. An example of such a putative diagnostic tool is the use of a pressure mat. Pressure mats are able to provide both objective loading (kinetic) as well as objective movement (kinematic) information on pig locomotion.In this study, pressure mat analysis was used to assess compensatory force redistribution in lame pigs; in particular a predefined set of four pressure mat parameters was evaluated for its use to objectively distinguish clinically lame from sound pigs. Kinetic data from 10 clinically lame and 10 healthy weaned piglets were collected. These data were analyzed to answer three research questions. Firstly the pattern of compensatory weight distribution in lame animals was studied using the asymmetry indices (ASI) for several combinations of limbs. Secondly, the correlation between total left-right asymmetry index and visual scores of lameness was assessed. Thirdly, by using receiver-operated curve (ROC) analysis, optimal cutoff values for these ASIs were then calculated to objectively detect lame pigs. Lame animals generally showed a shift in loading towards their diagonal and contralateral limbs, resulting in a clear left-right asymmetry. The degree of lameness as graded by visual scoring correlated well with the total left-right ASIs. Lame pigs could be objectively distinguished from sound pigs based on clear cutoff points calculated by ROC analysis for the complete set of four evaluated parameters. The gait of lame pigs is asymmetric, due to the unloading of the affected limb and concomitant weight redistribution towards other limbs. This asymmetry objectively expressed as total left-right asymmetry, correlates well with the subjective visual lameness scoring and can be used to objectively distinguish lame from sound pigs. Pressure mat gait analysis of pigs, therefore, appears to be a promising and useful tool to objectively quantify and possibly early detect lameness in pigs. | 25,139,245 | [
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Comparative evaluation of molar distalization therapy with erupted second molar: Segmented versus Quad Pendulum appliance. | There are controversial opinions about the effect of erupted second molars on distalization of the first molars. Most of the distalizing devices are anchored on the first molars, without including second molars; so, differences between sequentially distalize maxillary molars (second molar followed by the first molar) or distalize second and first molars together are not clear. The aim of the study was to compare sequential versus simultaneous molar distalization therapy with erupted second molar using two different modified Pendulum appliances followed by fixed appliances. The treatment sample consisted of 35 class II malocclusion subjects, divided in two groups: group 1 consisted of 24 patients (13 males and 11 females) with a mean pre-treatment age of 12.9 years, treated with the Segmented Pendulum (SP) and fixed appliances; group 2 consisted of 11 patients (6 males and 5 females) with a mean pre-treatment age of 13.2 years, treated with the Quad Pendulum (QP) and fixed appliances. Lateral cephalograms were obtained before treatment (T1), at the end of distalization (T2), and at the end of orthodontic fixed appliance therapy (T3). A Student t test was used to identify significant between-group differences between T1 to T2, T2 to T3, and T1 to T3. QP and SP were equally effective in distalizing maxillary molars (3.5 and 4 mm, respectively) between T1 and T2; however, the maxillary first molar showed less distal tipping (4.6° vs. 9.6°) and more extrusion (1.1 vs. 0.2 mm) in the QP group than in the SP group, as well as the vertical facial dimension, which increased more in the QP group (1.2°) than in the SP group (0.7°). At T3, the QP group maintained greater increase in lower anterior facial height and molar extrusion and decrease in overbite than the SP group. Quad Pendulum seems to have greater increase in vertical dimension and molar extrusion than the Segmented Pendulum. | 25,139,288 | [
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NK cells kill mycobacteria directly by releasing perforin and granulysin. | Although the mechanisms underlying the cytotoxic effect of NK cells on tumor cells and intracellular bacteria have been studied extensively, it remains unclear how these cells kill extracellular bacterial pathogens. In this study, we examine how human NK cells kill Mycobacterium kansasii and M.tb. The underlying mechanism is contact dependent and requires two cytolytic proteins: perforin and granulysin. Mycobacteria induce enhanced expression of the cytolytic proteins via activation of the NKG2D/NCR cell-surface receptors and intracellular signaling pathways involving ERK, JNK, and p38 MAPKs. These results suggest that NK cells use similar cellular mechanisms to kill both bacterial pathogens and target host cells. This report reveals a novel role for NK cells, perforin, and granulysin in killing mycobacteria and highlights a potential alternative defense mechanism that the immune system can use against mycobacterial infection. | 25,139,289 | [
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Preoperative smoking cessation can reduce postoperative complications in gastric cancer surgery. | Despite the close link between cigarette smoking and the development of gastric cancer, little is known about the effects of cigarette smoking on surgical outcomes after gastric cancer surgery. The aim of this study was to investigate whether preoperative smoking status and the duration of smoking cessation were associated with short-term surgical consequences in gastric cancer surgery. Among 1,489 consecutive patients, 1,335 patients who underwent curative radical gastrectomy at the Samsung Medical Center between January and December 2009 were included in the present study. The smoking status was determined using questionnaires before surgery. Smokers were divided into four groups according to the duration of smoking cessation preoperatively (<2, 2-4, 4-8, and >8 weeks). The primary endpoint was postoperative complications (wound, lung, leakage, and bleeding); secondary endpoints were 3-year recurrence-free survival (RFS) and overall survival (OS). Five hundred twenty-two patients (39.1 %) were smokers. Smokers had a significantly higher overall incidence of postoperative complications than nonsmokers (12.3 vs. 5.2 %, P < 0.001, respectively), especially in impaired wound healing, pulmonary problems, and leakage. Smokers also had more severe complications than nonsmokers. After adjusting for other risk factors, the odds ratio (95 % CI) for the development of postoperative complications in the subgroups who stopped smoking <2 weeks, 2-4, 4-8, and >8 weeks preoperatively were 3.35 (1.92-5.83), 0.99 (0.22-4.38), 2.18 (1.00-4.76), and 1.32 (0.70-2.48), respectively, compared with the nonsmokers. There were no significant differences in 3-year RFS (P = 0.884) and OS (P = 0.258) between smokers and nonsmokers. Preoperative smoking cessation for at least 2 weeks will help to reduce the incidence of postoperative complications in gastric cancer surgery. | 25,139,298 | [
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Canine progenitor epidermal keratinocytes express various inflammatory markers, including interleukin-8 and CD40, which are affected by certain antibiotics. | Bacterial skin infections are common in dogs and humans. Keratinocytes have phenotypic features of nonprofessional antigen-presenting cells and express various cytokines. However, little is known about the effects of antibiotics on inflammatory markers in canine keratinocytes. To investigate inflammatory markers in canine progenitor epidermal keratinocytes (CPEKs) and to determine the effects of selected antibiotics on these markers. The CPEKs were exposed for 2-24 h to three concentrations of amoxicillin, cefalexin, sulfadimethoxine, sulfamethoxazole (or its nitroso metabolite), amikacin or enrofloxacin. Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry were used to detect major histocompatibility complex (MHC) II. CD40 and CXCR1 [interleukin (IL)-8 receptor] were detected using ELISA. Secreted cytokines/chemokines were quantified using a multiplex kit. No MHC II protein was detected. CD40 protein was found at 24 h, with levels being significantly increased by enrofloxacin. The CPEKs secreted no detectable monocyte chemotactic protein-1; undetectable to low (picogram per millilitre range) concentrations of IL-6, IL-7, IL-10, IL-15, tumour necrosis factor-α, interferon-γ and granulocyte-macrophage colony-stimulating factor; and high (nanogram per millilitre range) concentrations of IL-8. Levels of IL-8 increased over 24 h following cell proliferation. They were significantly increased by enrofloxacin after 8 h, and by cefalexin, sulfadimethoxine, sulfamethoxazole, its nitroso metabolite and enrofloxacin after 24 h. The CPEKs expressed CXCR1. Canine progenitor epidermal keratinocytes express various inflammatory proteins, with expression profiles being affected by certain antibiotics. This supports previous work showing keratinocytes to be mediators of inflammation and demonstrates the potential pro-inflammatory effects of certain antibiotics in the skin. | 25,139,312 | [
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Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton. | Following invasion of human red blood cells (RBCs) by the malaria parasite, Plasmodium falciparum, a remarkable process of remodeling occurs in the host cell mediated by trafficking of several hundred effector proteins to the RBC compartment. The exported virulence protein, P falciparum erythrocyte membrane protein 1 (PfEMP1), is responsible for cytoadherence of infected cells to host endothelial receptors. Maurer clefts are organelles essential for protein trafficking, sorting, and assembly of protein complexes. Here we demonstrate that disruption of PfEMP1 trafficking protein 1 (PfPTP1) function leads to severe alterations in the architecture of Maurer's clefts. Furthermore, 2 major surface antigen families, PfEMP1 and STEVOR, are no longer displayed on the host cell surface leading to ablation of cytoadherence to host receptors. PfPTP1 functions in a large complex of proteins and is required for linking of Maurer's clefts to the host actin cytoskeleton. | 25,139,348 | [
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The dynamic impact of repeated stress on the hippocampal spatial map. | Stress alters the function of many physiological processes throughout the body, including in the brain. A neural circuit particularly vulnerable to the effects of stress is the hippocampus, a key component of the episodic and spatial memory system in both humans and rodents. Earlier studies have provided snapshots of morphological, molecular, physiological and behavioral changes in the hippocampus following either acute or repeated stress. However, the cumulative impact of repeated stress on in vivo hippocampal physiology remains unexplored. Here we report the stress-induced modulation of the spatially receptive fields of the hippocampal CA1 'place cells' as mice explore familiar and novel tracks after 5 and 10 days of immobilization stress. We find that similar to what has been observed following acute stress, five days of repeated stress results in decreased excitability of CA1 pyramidal cells. Following ten days of chronic stress, however, this decreased hippocampal excitability is no longer evident, suggesting adaptation may have occurred. In addition to these changes in neuronal excitability, we find deficient context discrimination, wherein both short-term and chronic stress impair the ability of the hippocampus to unambiguously distinguish novel and familiar environments. These results suggest that a loss of network flexibility may underlie some of the behavioral deficits accompanying chronic stress. | 25,139,366 | [
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Burden of carbapenem-resistant organisms in the Frankfurt/Main Metropolitan Area in Germany 2012/2013 - first results and experiences after the introduction of legally mandated reporting. | The federal state of Hesse, Germany, introduced a laboratory-based reporting scheme for carbapenem-resistant organisms (CROs). The results of the first year of mandated reporting of CROs from April 2012 through March 2013 to the Public Health Authority of Frankfurt/Main, responsible for a population of 700,000 inhabitants, are described. Within a period of 12 months 243 CROs were notified to the health authority. Of these 213 isolates had been reported from 16 of the 17 hospitals in Frankfurt/Main, 6 from ambulatory settings and 24 from clinics outside of Frankfurt/Main. Mean incidence rate per 1,000 patient days in hospitals was 0.138 (range 0.02-0.28). In Frankfurt/Main almost all hospitals have reported CROs in the study period though the frequency of isolation varies strongly and many facilities only report CROs sporadically. Molecular data indicate a high diversity of different carbapenemases. Autochthonous transmission must be assumed despite the absence of major outbreaks. Rapid and coordinated efforts by clinicians and health departments are crucial to control the spread of CRO infections. The mandatory reporting scheme provides important data to guide the implementation of preventive measures. | 25,139,410 | [
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PTEN loss-mediated Akt activation increases the properties of cancer stem-like cell populations in prostate cancer. | To demonstrate that the PTEN/PI3K/Akt/NF-κB pathway plays an important role in regulating the prostate cancer stem-like cell population by upregulating ABCG2. Targeted PTEN knockdown in human prostate DU145 and 22Rv1 cells using a small interfering RNA were confirmed by immunoblot analysis using antibodies of PTEN, phospho-Akt, Akt, and α-tubulin. Knockdown PTEN DU145 and 22Rv1 cells were augmented, and the stem cell-like properties were examined by cell viability and tumor sphere formation and treated by Akt IV inhibitor to provide the signal transduction pathway. Luciferase activity assays were performed. The knockdown of PTEN in prostate cancer cell lines increased the stem-like properties of the cells, including their sphere-forming ability, stem cell population number, epithelial-mesenchymal transition-related gene expression, and ABCG2 expression. Additionally, PTEN expression was highly associated with elevated expression of phospho-Akt. Treatment with an Akt inhibitor suppressed the PTEN-mediated effects on the properties of these stem-like cells as well as drug resistance, ABCG2 expression, and the NF-κB pathway. The loss of PTEN in prostate cancer cells resulted in an increased PI3K/Akt pathway. Due to the Akt activation, PTEN loss may play an important role in prostate cancer by promoting cancer stemness through a mechanism that involves enhanced NF-κB signaling. | 25,139,413 | [
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Streptococcus oriloxodontae sp. nov., isolated from the oral cavities of elephants. | Two strains were isolated from oral cavity samples of healthy elephants. The isolates were Gram-positive, catalase-negative, coccus-shaped organisms that were tentatively identified as a streptococcal species based on the results of biochemical tests. Comparative 16S rRNA gene sequence analysis suggested classification of these organisms in the genus Streptococcus with Streptococcus criceti ATCC 19642(T) and Streptococcus orisuis NUM 1001(T) as their closest phylogenetic neighbours with 98.2 and 96.9% gene sequence similarity, respectively. When multi-locus sequence analysis using four housekeeping genes, groEL, rpoB, gyrB and sodA, was carried out, similarity of concatenated sequences of the four housekeeping genes from the new isolates and Streptococcus mutans was 89.7%. DNA-DNA hybridization experiments suggested that the new isolates were distinct from S. criceti and other species of the genus Streptococcus. On the basis of genotypic and phenotypic differences, it is proposed that the novel isolates are classified in the genus Streptococcus as representatives of Streptococcus oriloxodontae sp. nov. The type strain of S. oriloxodontae is NUM 2101(T) ( =JCM 19285(T) =DSM 27377(T)). | 25,139,416 | [
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Taxonomy and phylogeny of two species of the genus Deviata (Protista, Ciliophora) from China, with description of a new soil form, Deviata parabacilliformis sp. nov. | The morphology and morphogenesis of a soil hypotrichous ciliate, Deviata parabacilliformis sp. nov., isolated from northern China, were investigated. D. parabacilliformis measures about 75-210 × 25-60 µm in vivo, with an elongate and flexible body. It possesses one right marginal row, two to four left marginal rows and three dorsal kineties. The main morphogenetic features of D. parabacilliformis are: (i) the oral primordium originates de novo; (ii) anlage IV of the opisthe originates from parental frontoventral row V, anlage V originates de novo, and anlage VI forms from frontoventral row VI; and (iii) anlage I of the proter originates from the anterior portion of the parental paroral, anlage II originates from the buccal cirrus, anlage III originates from the parabuccal cirri, anlage IV originates from parental frontoventral row IV and anlage V forms from the anterior of parental frontoventral row VI. The morphology of an edaphic population of another species of the genus Deviata, Deviata bacilliformis (Gelei 1954) Eigner 1995, was also investigated. This work also provides the first record of SSU rRNA gene sequences for species of the genus Deviata. Molecular phylogenetic analysis suggests that Deviata is not monophyletic, and its position is poorly resolved due to weak phylogenetic signal of the 18S marker in the Stichotrichida. | 25,139,418 | [
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Is the Sequential Laser Technique for Twin-to-Twin Transfusion Syndrome Truly Superior to the Standard Selective Technique? A Meta-Analysis. | To investigate the efficacy of sequential laser coagulation in the treatment of twin-to-twin transfusion syndrome (TTTS). MEDLINE, EMBASE and the Cochrane Library were systematically searched for comparative studies on the efficacy of sequential versus standard selective laser coagulation for TTTS. The primary outcome measure in these studies was survival of at least one twin, both twins and fetal demise. Three cohort studies comparing the selective laser treatment technique (n = 120) versus the sequential technique (n = 224) in 344 monochorionic twin pregnancies were included. Mean survival of at least one twin was 88% in the selective group versus 92% (p = 0.22) in the sequential group. Mean survival of both twins was lower in the selective group (52%) than in the sequential group (75%) (p = 0.002). Donor fetal demise decreased from 34% in the selective to 10% in the sequential group (p < 0.01), and recipient fetal demise decreased from 16 to 7% (p = 0.02). Limited evidence suggests improved double neonatal survival as well as decreased donor and recipient fetal demise with the use of the sequential technique. However, these results are based on small non-randomized studies with evident forms of bias and methodological limitations. A randomized controlled trial to assess the efficacy of sequential laser technique is therefore required. | 25,139,419 | [
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Ophthalmic imaging. | The last two decades have seen a revolution in ophthalmic imaging. In this review we present an overview of the breadth of ophthalmic imaging modalities in use today and describe how the role of ophthalmic imaging has changed from documenting abnormalities visible on clinical examination to the detection of clinically silent abnormalities which can lead to an earlier and more precise diagnosis. This review is based on published literature in the fields of ophthalmic imaging and with focus on most commonly used imaging modalities. New imaging techniques enable non-invasive evaluation of ocular structures at a resolution of a few micrometres. This has led to a re-evaluation of diagnostic criteria for ocular disease, which were previously defined by clinical findings without significant reference to imaging. Lack of formal training and clinical guidelines regarding use of new imaging techniques in diagnosing and monitoring various ocular conditions. Lack of large normative databases and interchangeability issues between different commercial machines can hinder the detection of disease progression. Imaging devices are being constantly refined with improved image capture and image analysis tools. Clinical applications of new techniques and devices have yet to be determined using systematic scientific research methods. | 25,139,430 | [
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Total synthesis and biological studies of cryptocin and derivatives of equisetin and fusarisetin A. | Total synthesis of cryptocin, a fungus metabolite, was achieved based on the biosynthetic hypothesis. A variety of derivatives of cryptocin, equisetin and fusarisetin A were prepared, wherein the racemization of C-3 and diastereoselectivity of C-5 were investigated. We further examined their inhibitory effects on breast cancer cell survival and metastasis, and summarized the structure-activity relationship. | 25,139,438 | [
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Boron-double-ring sheet, fullerene, and nanotubes: potential hydrogen storage materials. | Similar to carbon-based graphene, fullerenes and carbon nanotubes, boron atoms can form sheets, fullerenes, and nanotubes. Here we investigate several of these novel boron structures all based on the boron double ring within the framework of density functional theory. The boron sheet is found to be metallic and flat in its ground state. The spherical boron cage containing 180 atoms is also stable and has I symmetry. Stable nanotubes are obtained by rolling up the boron sheet, and all are metallic. The hydrogen storage capacity of boron nanostructures is also explored, and it is found that Li-decorated boron sheets and nanotubes are potential candidates for hydrogen storage. For Li-decorated boron sheets, each Li atom can adsorb a maximum of 4 H2 molecules with g(d) =7.892 wt %. The hydrogen gravimetric density increases to g(d) =12.309 wt % for the Li-decorated (0,6) boron nanotube. | 25,139,442 | [
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Prognostic value of midregional pro-A-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide in patients with stable coronary heart disease followed over 8 years. | Pathophysiological studies suggest that A-type natriuretic peptides (ANPs) might provide valuable information beyond B-type natriuretic peptides (BNPs) about cardiac dysfunction in patients with coronary heart disease (CHD). We aimed to assess the predictive value of midregional pro-A-type natriuretic peptide (MR-proANP) for recurrent cardiovascular disease (CVD) events in stable CHD patients for whom information on N-terminal proBNP (NT-proBNP) was already available. Plasma concentrations of MR-proANP and NT-proBNP were measured at baseline in a cohort of 1048 patients aged 30-70 years with CHD who were participating in an in-hospital rehabilitation program. Main outcome measures were cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. During a median follow-up of 8.1 years, 150 patients (incidence 21.1 per 1000 patient-years) experienced a secondary CVD event. MR-proANP was associated with a hazard ratio (HR) of 1.89 (95% CI, 1.01-3.57) when the top quartile was compared to the bottom quartile in the fully adjusted model (P for trend = 0.011). For NT-proBNP the respective HR was 2.22 (95% CI, 1.19-4.14) with a P for trend = 0.001. Finally, MR-proANP improved various model performance measures, including c-statistics and reclassification metrics, but without being superior to NT-proBNP. Although we found an independent association of MR-proANP as well as NT-proBNP when used as single markers with recurrent CVD events after adjustment for established risk factors, the results of a simultaneous assessment of both markers indicated that MR-proANP fails to provide additional prognostic information to NT-proBNP in the population studied. | 25,139,456 | [
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Utilization of Zwitterion-based solutions to dissect the relative effects of solution pH and ionic strength on the aggregation behavior and conformational stability of a fusion protein. | Solution pH and ionic strength (I) have complex effects on protein stability. We developed an experimental approach based on exploitation of the zwitterionic characteristic of amino acid molecules to probe the relative contribution from each. A variety of types of amino acid solutions were adopted to investigate the effects of pH and I in a manner that allows independent evaluation of each factor. The same effect could not be achieved using conventional buffer solutions. Size-exclusion chromatography, capillary differential scanning calorimetry, and fluorescence spectroscopy were utilized to probe the protein aggregation and conformation. The results suggested that, in addition to pH, solution ionic strength as a function of ionization state of the amino acid molecules and the ions introduced by pH adjustment played an important role in the aggregation and conformation of the protein studied. This experimental approach offers a useful tool to aid fundamental understanding of the relative effects of solution pH and ionic strength on protein stability. | 25,139,470 | [
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The strong relation between post-hemodialysis blood methylglyoxal levels and post-hemodialysis blood glucose concentration rise. | Hemodialysis is known to decrease blood glucose concentration (BGC), insulin, and methylglyoxal levels. However, the effects of decreases in these factors on the increase in post-hemodialysis BGC remain unknown. This study identifies the effects of hemodialysis-induced changes in concentrations of these elements on post-hemodialysis BGC. Study subjects included seventeen insulin-treated diabetes patients receiving hemodialysis. The fluctuations in BGC on hemodialysis-treatment days and non-hemodialysis-treatment days were evaluated using a continuous glucose monitoring system. BGC was evaluated before breakfast, before starting hemodialysis, at the end of hemodialysis, 1 h post-hemodialysis (lunch), and 6 h post-hemodialysis (dinner). BGC, insulin, and methylglyoxal levels were measured at the start and end of hemodialysis. This study also evaluated the changes in the concentrations of glucose and insulin in the arterial line and the venous line during hemodialysis. Hemodialysis decreases BGC, insulin, and methylglyoxal levels. Concentrations of glucose and insulin in the arterial line gradually decreased during dialysis, while concentrations in the venous line approached their original concentrations in the dialysis solution. BGC rose sharply after eating lunch 1 h post-hemodialysis. The blood glucose, insulin, and methylglyoxal concentrations at the end of hemodialysis were associated with the M values and the mean amplitude of glycemic excursion values between before lunch and dinner. In particular, methylglyoxal concentration at the end of hemodialysis was strongly related to the post-hemodialysis increase in BGC. Hemodialysis-induced decreases in methylglyoxal concentrations and methylglyoxal concentration at the end of hemodialysis influence post-hemodialysis fluctuations in BGC. | 25,139,482 | [
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1,25-Vitamin D3 promotes cardiac differentiation through modulation of the WNT signaling pathway. | Cardiovascular disease (CVD) remains the leading cause of death worldwide. Low levels of vitamin D are associated with high risk of myocardial infarction, even after controlling for factors associated with coronary artery disease. A growing body of evidence indicates that vitamin D plays an important role in CVD-related signaling pathways. However, little is known about the molecular mechanism by which vitamin D modulates heart development. The WNT signaling pathway plays a pivotal role in tissue development by controlling stem cell renewal, lineage selection and, even more importantly, heart development. In this study, we examined the role of 1,25-D3 (the active form of vitamin D) on cardiomyocyte proliferation, apoptosis, cell phenotype, cell cycle progression and differentiation into cardiomyotubes. We determined that the addition of 1,25-D3 to cardiomyocytes cells: i) inhibits cell proliferation without promoting apoptosis; ii) decreases expression of genes related to the regulation of the cell cycle; iii) promotes formation of cardiomyotubes; iv) induces the expression of casein kinase-1-α1, a negative regulator of the canonical WNT signaling pathway; and v) increases the expression of the noncanonical WNT11, which it has been demonstrated to induce cardiac differentiation during embryonic development and in adult cells. In conclusion, we postulate that vitamin D promotes cardiac differentiation through a negative modulation of the canonical WNT signaling pathway and by upregulating the expression of WNT11. These results indicate that vitamin D repletion to prevent and/or improve cardiovascular disorders that are linked with abnormal cardiac differentiation, such as post infarction cardiac remodeling, deserve further study. | 25,139,490 | [
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What forgetting tells us about remembering: the influence of top-down control on hemispheric asymmetries in verbal memory. | It has been suggested that left hemisphere (LH) advantages in verbal processing is due to superior top-down control of verbal information. It is not clear how top-down mechanisms affect the encoding and retrieval of verbal information from hemispheric memory and whether they only influence activation or also encompass the inhibition of verbal information. The directed forgetting method, in conjunction with divided visual field presentation, was used to examine the influence of top-down control mechanisms on hemispheric asymmetries in verbal memory. Participants were cued to remember or forget words. Cues were presented either simultaneously with targets or after a short delay. A recognition memory test using divided visual field presentation was then given. Response times (RTs) revealed effects of cue timing in the LH. With simultaneous cues, RTs were faster to "Remember" words compared to "Forget" words. With delayed cues, RTs for "Remember" and "Forget" words were equivalent. In the right hemisphere (RH), "Remember" words were consistently faster than "Forget" words, regardless of cue timing. These data provide evidence that top-down mechanisms influenced LH verbal memory retrieval more than RH verbal memory retrieval. Finally, there was little evidence to suggest the hemispheres differ in inhibitory processing. | 25,139,497 | [
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Unexpected roles for ancient proteins: flavone 8-hydroxylase in sweet basil trichomes is a Rieske-type, PAO-family oxygenase. | Most elucidated hydroxylations in plant secondary metabolism are catalyzed by oxoglutarate- or cytochrome P450-dependent oxygenases. Numerous hydroxylations still evade clarification, suggesting that they might be performed by alternative enzyme types. Here, we report the identification of the flavone 8-hydroxylase (F8H) in sweet basil (Ocimum basilicum L.) trichomes as a Rieske-type oxygenase. Several features of the F8H activity in trichome protein extracts helped to differentiate it from a cytochrome P450-catalyzed reaction and identify candidate genes in the basil trichome EST database. The encoded ObF8H proteins share approximately 50% identity with Rieske-type protochlorophyllide a oxygenases (PTC52) from higher plants. Homology cloning and DNA blotting revealed the presence of several PTC52-like genes in the basil genome. The transcripts of the candidate gene designated ObF8H-1 are strongly enriched in trichomes compared to whole young leaves, indicating trichome-specific expression. The full-length ObF8H-1 protein possesses a predicted N-terminal transit peptide, which directs green fluorescent protein at least in part to chloroplasts. The F8H activity in crude trichome protein extracts correlates well with the abundance of ObF8H peptides. The purified recombinant ObF8H-1 displays high affinity for salvigenin and is inactive with other tested flavones except cirsimaritin, which is 8-hydroxylated with less than 0.2% relative activity. The efficiency of in vivo 8-hydroxylation by engineered yeast was improved by manipulation of protein subcellular targeting. blast searches showed that occurrence of several PTC52-like genes is rather common in sequenced plant genomes. The discovery of ObF8H suggests that Rieske-type oxygenases may represent overlooked candidate catalysts for oxygenations in specialized plant metabolism. | 25,139,498 | [
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Antihypertensive medication exposure and cardiovascular outcomes in hemodialysis patients. | Our understanding of the effectiveness of cardioprotective medications in maintenance dialysis patients is based upon drug exposures assessed at a single point in time. We employed a novel, time-dependent approach to modeling medication use over time to examine outcomes in a large national cohort. We linked Medicaid prescription claims with United States Renal Data System registry data and Medicare claims for 52,922 hypertensive maintenance dialysis patients. All-cause mortality and a combined cardiovascular disease (CVD)-endpoint were modeled as functions of exposure to cardioprotective antihypertensive medications (renin angiotensin system antagonists, β-adrenergic blockers, and calcium channel blockers) measured with three time-dependent covariates (weekly exposure status, proportion of prior weeks with exposure, and number of switches in exposure status) and with propensity adjustment. Current cardioprotective medication exposure status as compared to not exposed was associated with lower adjusted hazard ratios (AHRs) for mortality, though the magnitude depended upon the proportion of prior weeks with medication (duration) and the number of switches between active and non-active use (switches) (AHR range 0.54-0.90). Combined CVD-endpoints depended upon the proportion of weeks on medication: AHR = 1.18 for 10% and AHR = 0.90 for 90% of weeks. Combined CVD-endpoint was also lower for patients with fewer switches. Effectiveness depends not only on having a drug available but is tempered by duration and stability of use, likely reflecting variation in clinical stability and patient behavior. | 25,139,551 | [
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Synthesis, biological evaluation and molecular modeling study of 2-(1,3,4-thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class of DHFR inhibitors. | A new series of 2-(1,3,4-thiadiazolyl- or 4-methyl-thiazolyl)thio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 29, 34, and 39 proved to be the most active DHFR inhibitors with IC50 values range of 0.1-0.6 μM. Compounds 28, 31 and 33 showed remarkable broad-spectrum antimicrobial activity comparable to the known antibiotic Gentamicin. Compounds 26, 33, 39, 43, 44, 50, 55 and 63 showed broad spectrum antitumor activity with GI values range of 10.1-100%. Molecular modeling study concluded that recognition with key amino acid Glu30, Phe31 and Phe34 is essential for binding. ADMET properties prediction of the active compounds suggested that compounds 29 and 34 could be orally absorbed with diminished toxicity. | 25,139,568 | [
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Synthesis, biological evaluation and SAR analysis of O-alkylated analogs of quercetin for anticancer. | O-Alkylated quercetin analogs were synthesized and their anticancer activities were assessed by a high-throughout screening (HTS) method. The structure-activity relationships (SAR) showed that introduction of long alkyl chain such as propyl group at the C-3 OH position or short alkyl chain such as ethyl group at the C-4' OH position were very important for keeping inhibitory activities against the 16 cancer cell lines. Furthermore, when the two n-butyl groups were introduced into the C-3, C-7 or C-4', C-7 positions, the anticancer activity was enhanced. | 25,139,569 | [
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Longitudinal resting state fMRI analysis in healthy controls and premanifest Huntington's disease gene carriers: a three-year follow-up study. | We previously demonstrated that in the premanifest stage of Huntington's disease (preHD), a reduced functional connectivity exists compared to healthy controls. In the current study, we look at possible changes in functional connectivity occurring longitudinally over a period of 3 years, with the aim of assessing the potential usefulness of this technique as a biomarker for disease progression in preHD. Twenty-two preHD and 17 healthy control subjects completed resting state functional magnetic resonance imaging (fMRI) scans in two visits with 3 years in between. Differences in resting state connectivity were examined for eight networks of interest using FSL with three different analysis types: a dual regression method, region of interest approach, and an independent component analysis. To evaluate a possible combined effect of gray matter volume change and the change in blood oxygenation level dependent signal, the analysis was performed with and without voxel-wise correction for gray matter volume. To evaluate possible correlations between functional connectivity change and the predicted time to disease onset, the preHD group was classed as preHD-A if ≥10.9 years and preHD-B if <10.9 years from predicted disease onset. Possible correlations between burden of pathology score and functional connectivity change in preHD were also assessed. Finally, longitudinal change in whole brain and striatal volumetric measures was assessed in the studied cohort. Longitudinal analysis of the resting state-fMRI (RS-fMRI) data revealed no differences in the degree of connectivity change between the groups over a period of 3 years, though a significantly higher rate of striatal atrophy was found in the preHD group compared to controls in the same period. Based on the results found in this study, the provisional conclusion is that RS-fMRI lacks sensitivity in detecting changes in functional connectivity in HD gene carriers prior to disease manifestation over a 3-year follow-up period. | 25,139,578 | [
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Evidence for efficacy of acute treatment of episodic tension-type headache: methodological critique of randomised trials for oral treatments. | The International Headache Society (IHS) provides guidance on the conduct of trials for acute treatment of episodic tension-type headache (TTH), a common disorder with considerable disability. Electronic and other searches identified randomised, double-blind trials of oral drugs treating episodic TTH with moderate or severe pain at baseline, or that tested drugs at first pain onset. The aims were to review methods, quality, and outcomes reported (in particular the IHS-recommended primary efficacy parameter pain-free after 2 hours), and to assess efficacy by meta-analysis. We identified 58 reports: 55 from previous reviews and searches, 2 unpublished reports, and 1 clinical trial report with results. We included 40 reports of 55 randomised trials involving 12,143 patients. Reporting quality was generally good, with potential risk of bias from incomplete outcome reporting and small size; the 23 largest trials involved 82% of patients. Few trials reported IHS outcomes. The number needed to treat values for being pain-free at 2 hours compared with placebo were 8.7 (95% confidence interval [CI] 6.2 to 15) for paracetamol 1000 mg, 8.9 (95% CI 5.9 to 18) for ibuprofen 400mg, and 9.8 (95% CI 5.1 to 146) for ketoprofen 25mg. Lower (better) number needed to treat values were calculated for outcomes of mild or no pain at 2 hours, and patient global assessment. These were similar to values for these drugs in migraine. No other drugs had evaluable results for these patient-centred outcomes. There was no evidence that any one outcome was better than others. The evidence available for treatment efficacy is small in comparison to the size of the clinical problem. | 25,139,586 | [
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Nox2-dependent signaling between macrophages and sensory neurons contributes to neuropathic pain hypersensitivity. | Emerging lines of evidence indicate that production of reactive oxygen species (ROS) at distinct sites of the nociceptive system contributes to the processing of neuropathic pain. However, the mechanisms underlying ROS production during neuropathic pain processing are not fully understood. We here detected the ROS-generating nicotinamide adenine dinucleotide phosphate oxidase isoform Nox2 in macrophages of dorsal root ganglia (DRG) in mice. In response to peripheral nerve injury, Nox2-positive macrophages were recruited to DRG, and ROS production was increased in a Nox2-dependent manner. Nox2-deficient mice displayed reduced neuropathic pain behavior after peripheral nerve injury, whereas their immediate responses to noxious stimuli were normal. Moreover, injury-induced upregulation of tumor necrosis factor α was absent, and activating transcription factor 3 induction was reduced in DRG of Nox2-deficient mice, suggesting an attenuated macrophage-neuron signaling. These data suggest that Nox2-dependent ROS production in macrophages recruited to DRG contributes to neuropathic pain hypersensitivity, underlining the observation that Nox-derived ROS exert specific functions during the processing of pain. | 25,139,590 | [
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Downregulation of endogenous STAT3 augments tumoricidal activity of interleukin 15 activated dendritic cell against lymphoma and leukemia via TRAIL. | Effector functions in tumor resistance by dendritic cells (DCs) are less well characterized. In this study, we describe that the murine DCs upon stimulation with recombinant IL-15 in vitro or in vivo, expresses TNF superfamily member TRAIL which mediates cytotoxicity and growth inhibition against a murine lymphoma called Dalton lymphoma (DL) via apoptosis. Presence of tumor lysate or intact tumor cells significantly reduces the DC mediated tumoricidal effect, possibly via masking and down-regulating TRAIL in DCs. The antitumor effect of DC derived TRAIL was further augmented by deactivation of STAT3 in tumor cells by cucurbitacin I, which makes it more susceptible to DC derived TRAIL Treatment of tumor cells with cucurbitacin I upregulates TRAIL receptor expression in addition to activation of caspases. Compared to naïve DCs, DCs from tumor bearing mice are significantly impaired in TRAIL expression and consequent antitumor functions against DL which was partially restored by activation with IL-15 or LPS. Priming with recombinant IL-15 prolongs the survival of tumor bearing mice treated with cucurbitacin I. Naïve peripheral blood DCs derived from chronic myeloid leukemia (CML) patients have significant impairment in expression of TRAIL and consequent tumoricidal properties against TRAIL sensitive lymphoma cell lines and primary tumor cells compared to normal control. | 25,139,620 | [
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Cerebellar control of gait and interlimb coordination. | Synaptic and intrinsic processing in Purkinje cells, interneurons and granule cells of the cerebellar cortex have been shown to underlie various relatively simple, single-joint, reflex types of motor learning, including eyeblink conditioning and adaptation of the vestibulo-ocular reflex. However, to what extent these processes contribute to more complex, multi-joint motor behaviors, such as locomotion performance and adaptation during obstacle crossing, is not well understood. Here, we investigated these functions using the Erasmus Ladder in cell-specific mouse mutant lines that suffer from impaired Purkinje cell output (Pcd), Purkinje cell potentiation (L7-Pp2b), molecular layer interneuron output (L7-Δγ2), and granule cell output (α6-Cacna1a). We found that locomotion performance was severely impaired with small steps and long step times in Pcd and L7-Pp2b mice, whereas it was mildly altered in L7-Δγ2 and not significantly affected in α6-Cacna1a mice. Locomotion adaptation triggered by pairing obstacle appearances with preceding tones at fixed time intervals was impaired in all four mouse lines, in that they all showed inaccurate and inconsistent adaptive walking patterns. Furthermore, all mutants exhibited altered front-hind and left-right interlimb coordination during both performance and adaptation, and inconsistent walking stepping patterns while crossing obstacles. Instead, motivation and avoidance behavior were not compromised in any of the mutants during the Erasmus Ladder task. Our findings indicate that cell type-specific abnormalities in cerebellar microcircuitry can translate into pronounced impairments in locomotion performance and adaptation as well as interlimb coordination, highlighting the general role of the cerebellar cortex in spatiotemporal control of complex multi-joint movements. | 25,139,623 | [
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Standard of care and future pharmacological treatment options for malignant glioma: an urgent need for screening and identification of novel tumor-specific antigens. | Malignant gliomas (MGs) represent the most common primary brain tumors in adults, the most deadly of which is grade IV glioblastoma. Patients with glioblastoma undergoing current standard-of-care therapy have a median survival of 12 - 15 months. Over the past 25 years, there have been modest advancements in the treatment of MGs. Assessment of therapeutic responses has continued to evolve to account for the increasing number of agents being tested in the clinic. Currently approved therapies for primary tumors have been extended for use in the setting of recurrent disease with modest efficacy. Agents initially approved for recurrent gliomas have begun to demonstrate efficacy against de novo tumors but will ultimately need to be evaluated in future studies for scheduling, timing and dosing relative to chemotherapy. Screening and identification of tumor-specific mutations is critical for the advancement of effective therapy that is both safe and precise for the patient. Two unique antigens found in glioblastoma are currently being employed as targets for immunotherapeutic vaccines, one of which has advanced to Phase III testing. Whole genome sequencing of MGs has yielded two other novel mutations that offer great promise for the development of molecular inhibitors. | 25,139,628 | [
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Outcomes in acute heart failure: 30-day readmission versus death. | For patients hospitalized with acute heart failure, health policy initiatives in the USA have drawn attention to 30-day mortality and readmission. Confusion around definitions, populations, and thus reported rates for these two outcomes is common. Among Medicare fee-for-service patients hospitalized with heart failure, all-cause mortality 30 days from the time of admission is 11.7 % and all-cause unplanned readmission 30 days from discharge is 23.0 %. Rates for Medicaid and commercially insured patients are lower. Mortality rates have been relatively stable, while readmission rates increased under the Diagnosis Related Group payment system then began decreasing under the Hospital Readmission Reductions Program. Risk models are reasonable at predicting mortality, whereas readmission has been harder to anticipate. The use of risk-standardized hospital rates as performance measures has generated considerable debate. Future work should clarify the interaction between the two measures, the optimal time window and factors influencing rates and trends-including socioeconomic status. | 25,139,630 | [
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Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia. | To identify risk factors and clinical biomarkers of prevalent diabetes foot complications, including foot ulcers, gangrene and amputations among patients with diabetes in Jeddah, Saudi Arabia. 598 diabetes patients from Jeddah participated in the current study. Patients were considered to have diabetes foot complications if they reported diagnosis of foot ulcers or gangrene or amputations in a questionnaire administered by a physician and confirmed by clinical exams. Information on socio-demographic and lifestyle variables was self-reported by patients, and several clinical markers were assessed following standard procedures. The prevalence of diabetes foot complications in this population was 11.4%. In the multivariable model without adjustment for PAD (peripheral artery disease) and DPN (diabetes peripheral neuropathy), non-Saudi nationality, longer diabetes duration and insulin use was significantly associated with higher diabetes foot complications prevalence. Each 1g/L increase of hemoglobin was associated with 2.8% lower prevalence of diabetes foot complications. In the multivariable model adjusting for PAD and DPN, the previously observed associations except for nationality were no longer significant. Patients with both DPN and PAD had 9.73 times the odds of diabetes foot complications compared to the patients with neither condition. In this population, longer diabetes duration, insulin use, lower hemoglobin levels and non-Saudi nationality were associated with higher prevalence of foot complications. These associations were largely explained by the presence of DPN and PAD except for non-Saudi nationality. Diabetes patients with both DPN and PAD had nearly 10-fold increased risk of foot complications than those with neither condition. | 25,139,632 | [
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A review of the economic tools for assessing new medical devices. | Whereas the economic evaluation of pharmaceuticals is an established practice within international health technology assessment (HTA) and is often produced with the support of comprehensive methodological guidance, the equivalent procedure for medical devices is less developed. Medical devices, including diagnostic products, are a rapidly growing market in healthcare, with over 10,000 medical technology patent applications filed in Europe in 2012-nearly double the number filed for pharmaceuticals. This increase in the market place, in combination with the limited, or constricting, budgets that healthcare decision makers face, has led to a greater level of examination with respect to the economic evaluation of medical devices. However, methodological questions that arise due to the unique characteristics of medical devices have yet to be addressed fully. This review of journal publications and HTA guidance identified these characteristics and the challenges they may subsequently pose from an economic evaluation perspective. These unique features of devices can be grouped into four categories: (1) data quality issues; (2) learning curve; (3) measuring long-term outcomes from diagnostic devices; and (4) wider impact from organisational change. We review the current evaluation toolbox available to researchers and explore potential future approaches to improve the economic evaluation of medical devices. | 25,139,635 | [
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Characterization of a mutant glucose isomerase from Thermoanaerobacterium saccharolyticum. | A series of site-directed mutant glucose isomerase at tryptophan 139 from Thermoanaerobacterium saccharolyticum strain B6A were purified to gel electrophoretic homogeneity, and the biochemical properties were determined. W139F mutation is the most efficient mutant derivative with a tenfold increase in its catalytic efficiency toward glucose compared with the native GI. With a maximal activity at 80 °C of 59.58 U/mg on glucose, this mutant derivative is the most active type ever reported. The enzyme activity was maximal at 90 °C and like other glucose isomerase, this mutant enzyme required Co(2+) or Mg(2+) for enzyme activity and thermal stability (stable for 20 h at 80 °C in the absence of substrate). Its optimum pH was around 7.0, and it had 86 % of its maximum activity at pH 6.0 incubated for 12 h at 60 °C. This enzyme was determined as thermostable and weak-acid stable. These findings indicated that the mutant GI W139F from T. saccharolyticum strain B6A is appropriate for use as a potential candidate for high-fructose corn syrup producing enzyme. | 25,139,657 | [
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Beneficial effect of cilostazol-mediated neuronal repair following trimethyltin-induced neuronal loss in the dentate gyrus. | Cilostazol acts as an antiplatelet agent and has other pleiotropic effects based on phosphodiesterase-3-dependent mechanisms. We evaluated whether cilostazol would have a beneficial effect on neuronal repair following hippocampal neuronal damage by using a mouse model of trimethyltin (TMT)-induced neuronal loss/self-repair in the hippocampal dentate gyrus [Ogita et al. (2005) J Neurosci Res 82:609-621]; these mice will hereafter be referred to as impaired animals. A single treatment with cilostazol (10 mg/kg, i.p.) produced no significant change in the number of 5-bromo-2'-deoxyuridine (BrdU)-incorporating cells in the dentate granule cell layer (GCL) or subgranular zone on day 3 after TMT treatment. However, chronic treatment with cilostazol on days 3-15 posttreatment resulted in an increase in the number of BrdU-incorporating cells in the dentate GCL of the impaired animals, and these cells were positive for neuronal nuclear antigen or doublecortin. Cilostazol was effective in elevating the level of phosphorylated cyclic adrenosine monophosphate response element-binding protein (pCREB) in the dentate gyrus of impaired animals. The results of a forced swimming test revealed that the chronic treatment with cilostazol improved the depression-like behavior seen in the impaired animals. In the cultures of hippocampal neural stem/progenitor cells, exposure to cilostazol produced not only enhancement of proliferation activity but also elevation of pCREB levels. Taken together, our data suggest that cilostazol has a beneficial effect on neuronal repair following neuronal loss in the dentate gyrus through promotion of proliferation and/or neuronal differentiation of neural progenitor cells in the subgranular zone. | 25,139,675 | [
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Understanding the polar mechanism of the ene reaction. A DFT study. | The molecular mechanism of ene reactions has been characterised by DFT methods at the MPWB1K/6-311G(d,p) level of theory. Most reactions take place along a two-stage one-step mechanism in which the C-C bond formation takes place before the hydrogen transfer process. A very good correlation between the polar character of the reaction measured by the global electron density transfer at the transition state and the activation energy has been found. This behaviour allows establishing a useful classification of ene reactions in N-ene having a very high activation energy, P-ene reactions having activation energies between 35 and 20 kcal mol(-1), and H-ene reactions having activation energies below 20 kcal mol(-1). ELF topological analysis allows the characterisation of the two-stage one-step mechanism associated with a two-centre nucleophilic/electrophilic interaction. Formation of the C-C single bond is achieved by the C-to-C coupling of two pseudoradical centres formed at the two interacting carbon atoms in the first stage of the reaction. This topological analysis establishes that bonding changes are non-concerted. Finally, a DFT reactivity analysis makes it possible to characterise the electrophilic/nucleophilic behaviour of the reagents involved in ene reactions, and consequently, to predict the feasibility of ene reactions. | 25,139,695 | [
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Prospective randomized trial comparing open reduction and internal fixation with minimally invasive reduction and percutaneous fixation in managing displaced intra-articular calcaneal fractures. | Managing displaced intra-articular calcaneal fractures remains controversial. A prospective randomised trial was undertaken to compare open reduction and internal fixation (ORIF) with minimally invasive reduction and percutaneous fixation (MIRPF). Forty-five displaced intra-articular calcaneal fractures were randomised to undergo either ORIF (n = 23) or MIRPF (n = 22). Patients were followed up clinically and radiologically for a minimum of one year postoperatively. The primary outcome measure was wound-healing complication. Functional outcome was assessed using Creighton Nebraska Health Foundation (CNF) scale, and radiological outcome was assessed using plain radiographs and computed tomography (CT) scans. Of the 23 heels in the ORIF group, seven (30%) had wound-healing problems, compared with none in the MIRPF group (p = 0.005). There was no statistically significant difference in radiological outcomes between groups, as measured by Böhler's angle, Gissane's angle and Score Analysis of Verona (SAVE). Median time to return to work was two weeks earlier (p = 0.004), and the functional outcome score (CNF scale) at one year of follow-up was better (p = 0.013) following MIRPF compared with ORIF. MIRPF is associated with fewer wound-healing problems, better functional outcome and earlier return to work compared with ORIF. | 25,139,716 | [
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Rationale and design of REWARD (revving-up exercise for sustained weight loss by altering neurological reward and drive): a randomized trial in obese endometrial cancer survivors. | Obesity is a leading risk factor for endometrial cancer (EC), particularly Type I forms, which are increasing in the U.S. Although death rates from most cancers have been decreasing, overall mortality in EC is increasing in the U.S. EC survivors' poor fitness combined with their surgical treatments may make weight loss particularly challenging. High intensity exercise increases neurotrophins and neurological reward via altered striatal dopamine in animals, and, in humans, chronic high intensity exercise enhances meal-induced satiety and may reduce hedonic eating. "Assisted" exercise, a mode of exercise whereby a patient's voluntary exercise rate is augmented mechanically, may modulate brain dopamine levels in Parkinson's Disease patients but has not been previously evaluated as a treatment for obesity. We describe the rationale and design of the REWARD trial, which has the overarching goal of randomizing 120 obese EC survivors to "assisted" or voluntary rate cycling to evaluate the efficacy of "assisted" exercise in enhancing and sustaining weight loss. Patients in both arms will receive 3 days/week of supervised exercise and 1 day/week of a group dietary behavioral intervention for 16 weeks and, then, will be followed for 6 months. The primary outcome is weight loss. Secondary outcomes include measures for body composition, fitness, eating behavior, exercise motivation and, quality of life as well as cognition and food reward and motivation as assessed by functional magnetic resonance imaging (fMRI) tasks. If successful, the REWARD program could be extended to help sustain weight loss in obese cancer and non-cancer patients. | 25,139,726 | [
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0.1970655,
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