title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Comparative study of cost of care of outpatients with bipolar disorder and schizophrenia. | To assess and compare the average annual the cost of illness of outpatients with bipolar disorder and schizophrenia. Cost of illness in 75 out-patients with bipolar disorder and 53 out-patients with schizophrenia was assessed over a 9-month period by using bottom-up approach. The cost of 9 months was annualized by dividing the 9 months cost by 3 and then multiplying the obtained figure with 4. Total average annual costs of care of bipolar disorder was Indian rupees 32,759 (US $ 655.18) and that of schizophrenia was Indian rupees 48,059 (US $ 961.18) and there was no significant difference between the two groups. In both the groups, indirect costs (bipolar disorder-64.0%; Schizophrenia-77.6%) were higher than direct costs (bipolar disorder-36%; Schizophrenia-22.4%). Cost of medications was high. Patient and their families bore the main brunt of financial burden (95.4-96% of the total cost). In Bipolar disorder total treatment costs were significantly higher in those who had lower level of functioning. In bipolar disorder group number of visits to the hospital correlated with total cost, indirect cost and provider's cost, whereas in schizophrenia group total number of visits correlated with provider's cost only. Only a small proportion (13.7%) of the total cost of bipolar disorder was predicted by presence or absence of alcohol dependence and number of visits. In the schizophrenia group, only positive symptom score as per the rating on PANSS appeared as a significant predictor of total cost, explaining 15.6% of the total cost. Costs for outpatients with bipolar disorder are similar to the cost of outpatients with schizophrenia. Costs are higher in patients of bipolar disorder with lower level of functioning. Findings of the study suggests that reducing the number of visits to the hospital by providing care at the doorsteps, focusing on reduction of substance use and improving the level of functioning of the patients can reduce the cost of care of bipolar disorder. | 25,246,322 | [
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Preliminary study of Huai Qi Huang granules delay the development of primary glomerular diseases in human. | To evaluate the effects of Huai Qi Huang (HQH) granules on primary glomerulonephritis patients, and to discuss its possible mechanisms. Sixteen patients diagnosed with primary glomerular disease between December 2011 and December 2012 were enrolled. Their blood and urine samples were collected at day 0 (the baseline levels), 30, and 90 of receiving HQH granules orally. Levels of creatinine and cystatin C (Cys-C) in serum and urine, and total protein and albumin in urine were measured by automatic biochemical analyzer. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine was tested by ELISA; serum malondialdehyde (MDA) was measured by thiobarbituric acid method, the erythrocyte count in urine was calculated under light microscope. Serum levels of creatinine, MDA, Cys-C and NGAL at day 30 and 90 were significantly lower than the baseline levels. Urinary levels of Cys-C, NGAL, total protein, albumin and erythrocyte counts were also decreased; level of estimated glomerular filtration (eGFR) was increased. HQH granules have certain effect on delaying the development of primary glomerular disease with mild proteinuria and hematuresis in patients. This study may supply a new treatment for primary glomerular diseases. | 25,246,341 | [
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Seasonal immune modulation in humans: observed patterns and potential environmental drivers. | Cyclical fluctuations in host immunity have been proposed as a driver of respiratory infection seasonality, however few studies have attempted to directly assess whether or not seasonal immune modulation occurs in humans. We reviewed studies assessing immune status at different times of the year, restricting our review to studies assessing any of the following three biomarkers: antibody responses following vaccination, delayed-type hypersensitivity responses following skin testing, and clinical responses following experimental infection. After systematic review and critical appraisal of the literature, six separate studies were available for final discussion. These results indicate that human immunity does vary by season. In the tropical setting of West Africa, both cell mediated and humoral immune responses appear to be reduced in children during the rainy season. In the tropical setting of Bangladesh, cell mediated immune responses also appear to be reduced in children during the rainy season. In the temperate setting of Russia, resistance to influenza infection appears to be reduced in young adults during winter. Seasonal variation in immunity appears to occur in humans, and it is plausible that this variation may contribute to the seasonality of respiratory infections. Further research to assess the extent of seasonal immune modulation is required. We outline a number of recommendations to minimise bias in future studies. | 25,246,360 | [
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Locking plate fixation provides superior fixation of humerus split type greater tuberosity fractures than tension bands and double row suture bridges. | This paper aims to determine the strongest fixation method for split type greater tuberosity fractures of the proximal humerus by testing and comparing three fixation methods: a tension band with No. 2 wire suture, a double-row suture bridge with suture anchors, and a manually contoured calcaneal locking plate. Each method was tested on eight porcine humeri. A osteotomy of the greater tuberosity was performed 50° to the humeral shaft and then fixed according to one of three methods. The humeri were then placed in a testing apparatus and tension was applied along the supraspinatus tendon using a thermoelectric cooling clamp. The load required to produce 3mm and 5mm of displacement, as well as complete failure, was recorded using an axial load cell. The average load required to produce 3mm and 5mm of displacement was 658N and 1112N for the locking plate, 199N and 247N for the double row, and 75N and 105N for the tension band. The difference between the three groups was significant (P<0.01). The average load to failure of the locking plate (810N) was significantly stronger than double row (456N) and tension band (279N) (P<0.05). The stiffness of the locking plate (404N/mm) was significantly greater than double row (71N/mm) and tension band (33N/mm) (P<0.01). Locking plate fixation provides the strongest and stiffest biomechanical fixation for split type greater tuberosity fractures. | 25,246,375 | [
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Epigenetic modifiers of islet function and mass. | Type 2 diabetes (T2D) is associated with insulin resistance in target tissues including the β-cell, leading to significant β-cell loss and secretory dysfunction. T2D is also associated with aging, and the underlying mechanisms that increase susceptibility of an individual to develop the disease implicate epigenetics: interactions between susceptible loci and the environment. In this review, we discuss the effects of aging on β-cell function and adaptation, besides the significance of mitochondria in islet bioenergetics and epigenome. We highlight three important modulators of the islet epigenome, namely: metabolites, hormones, and the nutritional state. Unraveling the signaling pathways that regulate the islet epigenome during aging will help to better understand the development of disease progression and to design novel therapies for diabetes prevention. | 25,246,382 | [
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Pantothenate and pantetheine antagonize the antitubercular activity of pyrazinamide. | Pyrazinamide (PZA) is a first-line tuberculosis drug that inhibits the growth of Mycobacterium tuberculosis via an as yet undefined mechanism. An M. tuberculosis laboratory strain that was auxotrophic for pantothenate was found to be insensitive to PZA and to the active form, pyrazinoic acid (POA). To determine whether this phenotype was strain or condition specific, the effect of pantothenate supplementation on PZA activity was assessed using prototrophic strains of M. tuberculosis. It was found that pantothenate and other β-alanine-containing metabolites abolished PZA and POA susceptibility, suggesting that POA might selectively target pantothenate synthesis. However, when the pantothenate-auxotrophic strain was cultivated using a subantagonistic concentration of pantetheine in lieu of pantothenate, susceptibility to PZA and POA was restored. In addition, we found that β-alanine could not antagonize PZA and POA activity against the pantothenate-auxotrophic strain, indicating that the antagonism is specific to pantothenate. Moreover, pantothenate-mediated antagonism was observed for structurally related compounds, including n-propyl pyrazinoate, 5-chloropyrazinamide, and nicotinamide, but not for nicotinic acid or isoniazid. Taken together, these data demonstrate that while pantothenate can interfere with the action of PZA, pantothenate synthesis is not directly targeted by PZA. Our findings suggest that targeting of pantothenate synthesis has the potential to enhance PZA efficacy and possibly to restore PZA susceptibility in isolates with panD-linked resistance. | 25,246,400 | [
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Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus. | Small cross-sectional studies have suggested that metformin, a first-line oral hypoglycemic agent, may lower thyroid-stimulating hormone (TSH) levels. Our objective was to determine whether the use of metformin monotherapy, when compared with sulfonylurea monotherapy, is associated with an increased risk of low TSH levels (<0.4 mIU/L) in patients with type 2 diabetes mellitus. Using the Clinical Practice Research Datalink, we identified patients who began receiving metformin or sulfonylurea monotherapy between Jan. 1, 1988, and Dec. 31, 2012. We assembled 2 subcohorts of patients with treated hypothyroidism or euthyroidism, and followed them until Mar. 31, 2013. We used Cox proportional hazards models to evaluate the association of low TSH levels with metformin monotherapy, compared with sulfonylurea monotherapy, in each subcohort. A total of 5689 patients with treated hypothyroidism and 59,937 euthyroid patients were included in the subcohorts. Among patients with treated hypothyroidism, 495 events of low TSH levels were observed during follow-up (incidence rate 119.7/1000 person-years). In the euthyroid group, 322 events of low TSH levels were observed (incidence rate 4.5/1000 person-years). Compared with sulfonylurea monotherapy, metformin monotherapy was associated with a 55% increased risk of low TSH levels in patients with treated hypothyroidism (incidence rate 79.5/1000 person-years v. 125.2/1000 person-years, adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.09-2.20), with the highest risk in the 90-180 days after initiation (adjusted HR 2.30, 95% CI 1.00-5.29). No association was observed in euthyroid patients (adjusted HR 0.97, 95% CI 0.69-1.36). In this longitudinal population-based study, metformin use was associated with an increased incidence of low TSH levels in patients with treated hypothyroidism, but not in euthyroid patients. The clinical consequences of this need further investigation. | 25,246,411 | [
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Comparing histological activity indexes in UC. | Assessment of disease activity in UC is important for designing an optimal therapeutic strategy. No single histology score is considered optimum. The aim of this study was to compare intraobserver reproducibility and the interobserver agreement of available histological UC activity indexes. One hundred and two biopsy specimens (collected between 2003 and 2014) were scored blindly by three pathologists by determining Geboes, Riley, Gramlich and Gupta indexes and global visual evaluation (GVE). Intraobserver reproducibility and interobserver agreements for index and items of index were studied by intraclass correlation coefficient for quantitative parameter and by κ values and Krippendorff index for qualitative parameters. Relationship between indexes was studied by computation of Pearson's and Spearman's correlation coefficients. Geboes, Riley, Gramlich and Gupta indexes and GVE showed good intraobserver reproducibility and a good interobserver agreement. Histological items that showed the best interobserver agreement were 'erosion/ulceration or surface epithelial integrity' and 'acute inflammatory cells infiltrate/neutrophils in lamina propria'. The five scores were strongly correlated. Correlation between indexes is strong. Intraobserver reproducibility and interobserver agreement for all indexes is very good. Histological items that showed the best interobserver agreement are 'erosion/ulceration' and 'acute inflammatory cells infiltrate/neutrophils in lamina propria'. | 25,246,423 | [
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Wnt pathway in atypical teratoid rhabdoid tumors. | Atypical teratoid rhabdoid tumor (ATRT) is an aggressive pediatric brain tumor with limited therapeutic options. The hypothesis for this study was that the Wnt pathway triggered by the Wnt5B ligand plays an important role in ATRT biology. To address this hypothesis, the role of WNT5B and other Wnt pathway genes was analyzed in ATRT tissues and ATRT primary cell lines. Transcriptome-sequencing analyses were performed using nanoString platforms, immunohistochemistry, Western blotting, quantitative reverse transcriptase PCR, immunoprecipitation, short interference RNA studies, cell viability studies, and drug dose response (DDR) assays. Our transcriptome-sequencing results of Wnt pathway genes from ATRT tissues and cell lines indicated that the WNT5B gene is significantly upregulated in ATRT samples compared with nontumor brain samples. These results also indicated a differential expression of both canonical and noncanonical Wnt genes. Imunoprecipitation studies indicated that Wnt5B binds to Frizzled1 and Ryk receptors. Inhibition of WNT5B by short interference RNA decreased the expression of FRIZZLED1 and RYK. Cell viability studies a indicated significant decrease in cell viability by inhibiting Frizzled1 receptor. DDR assays showed promising results with some inhibitors. These promising therapeutic options will be studied further before starting a translational clinical trial. The success of these options will improve care for these patients. | 25,246,426 | [
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PhaseTank: genome-wide computational identification of phasiRNAs and their regulatory cascades. | Emerging evidence has revealed phased siRNAs (phasiRNAs) as important endogenous regulators in plants. However, the integrated prediction tools for phasiRNAs are still limited. In this article, we introduce a stand-alone package PhaseTank for systematically characterizing phasiRNAs and their regulatory networks. (i) It can identify phasiRNAs/tasiRNAs functional cascades (miRNA/phasiRNA → PHAS loci → phasiRNA → target) with high sensitivity and specificity. (ii) By one command analysis, it generates comprehensive annotation and quantification of the predicted PHAS genes from any given sequences. (iii) PhaseTank has no restriction with regards to prior information of sequence homology of unrestricted organism origins. PhaseTank is a free and open-source tool. The package is available at http://phasetank.sourceforge.net/. Supplementary data are available at Bioinformatics online. | 25,246,430 | [
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Reverse intestinal rotation: a rare case of volvulus around a vitelline duct remnant. | We present a rare case of reverse intestinal rotation with volvulus around a Meckel's diverticulum attached to a vitelline duct remnant. The diagnosis was established by CT. The patient was treated with exploratory laparotomy and small bowel resection. The patient made a full recovery and was discharged home on the seventh postoperative day. | 25,246,458 | [
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Fatal recurrence of fulminant giant cell myocarditis and recovery after initialisation of an alternative immunosuppressive regime. | We report on a challenging case of a 34-year-old male patient with giant cell myocarditis (GCM) and fulminant relapse after discontinuing immunomodulatory therapy 2 years after the initial event. Specific combined immunosuppressive therapy with antithymocyte globulin (ATG), cyclosporine and high-dose glucocorticoids combined with guideline-based heart failure medication led to the recovery of GCM, improvement of systolic left ventricular function and clinical remission. This case report emphasises the importance of an immunosuppressive therapy for the prognosis and outcome and the risk of discontinuation. Most importantly, ATG seems to be one new possible potential treatment option for patients with acute GCM. | 25,246,472 | [
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Midlife blood pressure change and left ventricular mass and remodelling in older age in the 1946 British Birth Cohort Study. | Antecedent blood pressure (BP) may contribute to cardiovascular disease (CVD) independent of current BP. Blood pressure is associated with left ventricular mass index (LVMI) which independently predicts CVD. We investigated the relationship between midlife BP from age 36 to 64 and LVMI at 60-64 years. A total of 1653 participants in the British 1946 Birth Cohort underwent BP measurement and echocardiography aged 60-64. Blood pressure had previously been measured at 36, 43, and 53 years. We investigated associations between BP at each age and rate of change in systolic blood pressure (SBP) between 36-43, 43-53, and 53-60/64 years on LVMI at 60-64 years. Blood pressure from 36 years was positively associated with LVMI. Association with SBP at 53 years was independent of SBP at 60-64 years and other potential confounders (fully adjusted β at 53 years = 0.19 g/m(2); 95% CI: 0.11, 0.27; P < 0.001). Faster rates of increase in SBP from 43 to 53 years and 53 to 60/64 years were associated with increased LVMI. Similar relationships were seen for diastolic, pulse, and mean pressure. Rate of increase in SBP between 43-53 years was associated with largest change in LVMI (β at 43-53 years = 3.12 g/m(2); 95% CI: 1.53, 4.72; P < 0.001). People on antihypertensive medication (43 years onwards) had greater LVMI even after adjustment for current BP (β at 43 years = 12.36 g/m(2); 95% CI: 3.19, 21.53; P = 0.008). Higher BP in midlife and rapid rise of SBP in 5th decade is associated with higher LVMI in later life, independent of current BP. People with treated hypertension have higher LVMI than untreated individuals, even accounting for their higher BP. Our findings emphasize importance of midlife BP as risk factor for future CVD. | 25,246,483 | [
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The NF-κB regulator Bcl-3 governs dendritic cell antigen presentation functions in adaptive immunity. | Bcl-3 is an atypical member of the IκB family and modulates gene expression via interaction with p50/NF-κB1 or p52/NF-κB2 homodimers. We report in the present study that Bcl-3 is required in dendritic cells (DCs) to assure effective priming of CD4 and CD8 T cells. Lack of Bcl-3 in bone marrow-derived DCs blunted their ability to expand and promote effector functions of T cells upon Ag/adjuvant challenge in vitro and after adoptive transfers in vivo. Importantly, the critical role of Bcl-3 for priming of T cells was exposed upon Ag/adjuvant challenge of mice specifically ablated of Bcl-3 in DCs. Furthermore, Bcl-3 in endogenous DCs was necessary for contact hypersensitivity responses. Bcl-3 modestly aided maturation of DCs, but most consequentially, Bcl-3 promoted their survival, partially inhibiting expression of several antiapoptotic genes. Loss of Bcl-3 accelerated apoptosis of bone marrow-derived DCs during Ag presentation to T cells, and DC survival was markedly impaired in the context of inflammatory conditions in mice specifically lacking Bcl-3 in these cells. Conversely, selective overexpression of Bcl-3 in DCs extended their lifespan in vitro and in vivo, correlating with increased capacity to prime T cells. These results expose a previously unidentified function for Bcl-3 in DC survival and the generation of adaptive immunity. | 25,246,497 | [
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Functional avidity-driven activation-induced cell death shapes CTL immunodominance. | Immunodominance is a complex phenomenon that relies on a mere numerical concept, while being potentially influenced at every step of the immune response. We investigated the mechanisms leading to the establishment of CTL immunodominance in a retroviral model and found that the previously defined subdominant Env-specific CD8(+) T cells are endowed with an unexpectedly higher functional avidity than is the immunodominant Gag-recognizing counterpart. This high avidity, along with the Env Ag overload, results in a supraoptimal TCR engagement. The overstimulation makes Env-specific T lymphocytes more susceptible to apoptosis, thus hampering their expansion and leading to an unintentional "immune kamikazing." Therefore, Ag-dependent, hyperactivation-induced cell death can be regarded as a novel mechanism in the establishment of the immunodominance that restrains and opposes the expansion of high-avidity T cells in favor of lower-affinity populations. | 25,246,498 | [
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Brief experimental analysis of reading deficits for children with attention-deficit/hyperactivity disorder. | Reading difficulties are especially high among children with attention-deficit/hyperactivity disorder (ADHD). Although there are a number of empirically supported reading interventions for children with ADHD, there is little data to guide the selection of the most efficacious reading intervention for a specific child. Brief experimental analysis (BEA) is a procedure that directly compares the efficacy of various academic interventions with the goal of guiding the selection of the intervention that results in optimal efficacy. The current proof of concept study examined the efficacy of the BEA methodology for determining the relative effectiveness of seven reading interventions for children with ADHD. The seven interventions included empirically supported ADHD interventions as well as traditional interventions found in the BEA literature. Six children diagnosed with ADHD completed the proof of concept study. Results indicated that the BEA successfully determined an efficacious intervention for each participant. The efficacy of the interventions and the optimal intervention based on BEA procedures varied for each child, suggesting the importance of a BEA approach when comparing various interventions for reading in children with ADHD. Implications and future directions for selecting effective reading interventions for children with ADHD are discussed. | 25,246,507 | [
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Reconstitution of actin-based motility by vasodilator-stimulated phosphoprotein (VASP) depends on the recruitment of F-actin seeds from the solution produced by cofilin. | Vasodilator-stimulated phosphoprotein (VASP) is active in many filopodium-based and cytoskeleton reorganization processes. It is not fully understood how VASP directly functions in actin-based motility and how regulatory proteins affect its function. Here, we combine bead motility assay and single filament experiments. In the presence of a bundling component, actin bundles that grow from the surface of WT-VASP-coated beads induced movement of the beads. VASP promotes actin-based movement alone, in the absence of other actin nucleators. We propose that at physiological salt conditions VASP nucleation activity is too weak to promote motility and bundle formation. Rather, VASP recruits F-actin seeds from the solution and promotes their elongation. Cofilin has a crucial role in the nucleation of these F-actin seeds, notably under conditions of unfavorable spontaneous actin nucleation. We explored the role of multiple VASP variants. We found that the VASP-F-actin binding domain is required for the recruitment of F-actin seeds from the solution. We also found that the interaction of profilin-actin complexes with the VASP-proline-rich domain and the binding of the VASP-F-actin binding domain to the side of growing filaments is critical for transforming actin polymerization into motion. At the single filament level, profilin mediates both filament elongation rate and VASP anti-capping activity. Binding of profilin-actin complexes increases the polymerization efficiency by VASP but decreases its efficiency as an anti-capper; binding of free profilin creates the opposite effect. Finally, we found that an additional component such as methylcellulose or fascin is required for actin bundle formation and motility mediated by VASP. | 25,246,528 | [
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Antifibrotic therapy in simian immunodeficiency virus infection preserves CD4+ T-cell populations and improves immune reconstitution with antiretroviral therapy. | Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4(+) T cells/µL, and CD4(+) T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4(+) T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4(+) T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4(+) T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. | 25,246,534 | [
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Dynamical traps lead to the slowing down of intramolecular vibrational energy flow. | The phenomenon of intramolecular vibrational energy redistribution (IVR) is at the heart of chemical reaction dynamics. Statistical rate theories, assuming instantaneous IVR, predict exponential decay of the population with the properties of the transition state essentially determining the mechanism. However, there is growing evidence that IVR competes with the reaction timescales, resulting in deviations from the exponential rate law. Dynamics cannot be ignored in such cases for understanding the reaction mechanisms. Significant insights in this context have come from the state space model of IVR, which predicts power law behavior for the rates with the power law exponent, an effective state space dimensionality, being a measure of the nature and extent of the IVR dynamics. However, whether the effective IVR dimensionality can vary with time and whether the mechanism for the variation is of purely quantum or classical origins are issues that remain unresolved. Such multiple power law scalings can lead to surprising mode specificity in the system, even above the threshold for facile IVR. In this work, choosing the well-studied thiophosgene molecule as an example, we establish the anisotropic and anomalous nature of the quantum IVR dynamics and show that multiple power law scalings do manifest in the system. More importantly, we show that the mechanism of the observed multiple power law scaling has classical origins due to a combination of trapping near resonance junctions in the network of classical nonlinear resonances at short to intermediate times and the influence of weak higher-order resonances at relatively longer times. | 25,246,538 | [
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Complementary symbiont contributions to plant decomposition in a fungus-farming termite. | Termites normally rely on gut symbionts to decompose organic matter but the Macrotermitinae domesticated Termitomyces fungi to produce their own food. This transition was accompanied by a shift in the composition of the gut microbiota, but the complementary roles of these bacteria in the symbiosis have remained enigmatic. We obtained high-quality annotated draft genomes of the termite Macrotermes natalensis, its Termitomyces symbiont, and gut metagenomes from workers, soldiers, and a queen. We show that members from 111 of the 128 known glycoside hydrolase families are represented in the symbiosis, that Termitomyces has the genomic capacity to handle complex carbohydrates, and that worker gut microbes primarily contribute enzymes for final digestion of oligosaccharides. This apparent division of labor is consistent with the Macrotermes gut microbes being most important during the second passage of comb material through the termite gut, after a first gut passage where the crude plant substrate is inoculated with Termitomyces asexual spores so that initial fungal growth and polysaccharide decomposition can proceed with high efficiency. Complex conversion of biomass in termite mounds thus appears to be mainly accomplished by complementary cooperation between a domesticated fungal monoculture and a specialized bacterial community. In sharp contrast, the gut microbiota of the queen had highly reduced plant decomposition potential, suggesting that mature reproductives digest fungal material provided by workers rather than plant substrate. | 25,246,537 | [
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Emergence of long-range order in sheets of magnetic dimers. | Quantum spins placed on the corners of a square lattice can dimerize and form singlets, which then can be transformed into a magnetic state as the interactions between dimers increase beyond threshold. This is a strictly 2D transition in theory, but real-world materials often need the third dimension to stabilize long-range order. We use high pressures to convert sheets of Cu(2+) spin 1/2 dimers from local singlets to global antiferromagnet in the model system SrCu2(BO3)2. Single-crystal neutron diffraction measurements at pressures above 5 GPa provide a direct signature of the antiferromagnetic ordered state, whereas high-resolution neutron powder and X-ray diffraction at commensurate pressures reveal a tilting of the Cu spins out of the plane with a critical exponent characteristic of 3D transitions. The addition of anisotropic, interplane, spin-orbit terms in the venerable Shastry-Sutherland Hamiltonian accounts for the influence of the third dimension. | 25,246,541 | [
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Insulin and insulin-like growth factor 1 receptors are required for normal expression of imprinted genes. | In addition to signaling through the classical tyrosine kinase pathway, recent studies indicate that insulin receptors (IRs) and insulin-like growth factor 1 (IGF1) receptors (IGF1Rs) can emit signals in the unoccupied state through some yet-to-be-defined noncanonical pathways. Here we show that cells lacking both IRs and IGF1Rs exhibit a major decrease in expression of multiple imprinted genes and microRNAs, which is partially mimicked by inactivation of IR alone in mouse embryonic fibroblasts or in vivo in brown fat in mice. This down-regulation is accompanied by changes in DNA methylation of differentially methylated regions related to these loci. Different from a loss of imprinting pattern, loss of IR and IGF1R causes down-regulated expression of both maternally and paternally expressed imprinted genes and microRNAs, including neighboring reciprocally imprinted genes. Thus, the unoccupied IR and IGF1R generate previously unidentified signals that control expression of imprinted genes and miRNAs through transcriptional mechanisms that are distinct from classical imprinting control. | 25,246,545 | [
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Bimodal activation of BubR1 by Bub3 sustains mitotic checkpoint signaling. | The mitotic checkpoint (also known as the spindle assembly checkpoint) prevents premature anaphase onset through generation of an inhibitor of the E3 ubiquitin ligase APC/C, whose ubiquitination of cyclin B and securin targets them for degradation. Combining in vitro reconstitution and cell-based assays, we now identify dual mechanisms through which Bub3 promotes mitotic checkpoint signaling. Bub3 enhances signaling at unattached kinetochores not only by facilitating binding of BubR1 but also by enhancing Cdc20 recruitment to kinetochores mediated by BubR1's internal Cdc20 binding site. Downstream of kinetochore-produced complexes, Bub3 promotes binding of BubR1's conserved, amino terminal Cdc20 binding domain to a site in Cdc20 that becomes exposed by initial Mad2 binding. This latter Bub3-stimulated event generates the final mitotic checkpoint complex of Bub3-BubR1-Cdc20 that selectively inhibits ubiquitination of securin and cyclin B by APC/C(Cdc20). Thus, Bub3 promotes two distinct BubR1-Cdc20 interactions, involving each of the two Cdc20 binding sites of BubR1 and acting at unattached kinetochores or cytoplasmically, respectively, to facilitate production of the mitotic checkpoint inhibitor. | 25,246,557 | [
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Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium-activated kinase pathway. | Imbalances between proinflammatory and proresolving mediators can lead to chronic inflammatory diseases. The balance of arachidonic acid-derived mediators in leukocytes is thought to be achieved through intracellular localization of 5-lipoxygenase (5-LOX): nuclear 5-LOX favors the biosynthesis of proinflammatory leukotriene B4 (LTB4), whereas, in theory, cytoplasmic 5-LOX could favor the biosynthesis of proresolving lipoxin A4 (LXA4). This balance is shifted in favor of LXA4 by resolvin D1 (RvD1), a specialized proresolving mediator derived from docosahexaenoic acid, but the mechanism is not known. Here we report a new pathway through which RvD1 promotes nuclear exclusion of 5-LOX and thereby suppresses LTB4 and enhances LXA4 in macrophages. RvD1, by activating its receptor formyl peptide receptor2/lipoxin A4 receptor, suppresses cytosolic calcium and decreases activation of the calcium-sensitive kinase calcium-calmodulin-dependent protein kinase II (CaMKII). CaMKII inhibition suppresses activation P38 and mitogen-activated protein kinase-activated protein kinase 2 kinases, which reduces Ser271 phosphorylation of 5-LOX and shifts 5-LOX from the nucleus to the cytoplasm. As such, RvD1's ability to decrease nuclear 5-LOX and the LTB4:LXA4 ratio in vitro and in vivo was mimicked by macrophages lacking CaMKII or expressing S271A-5-LOX. These findings provide mechanistic insight into how a specialized proresolving mediator from the docosahexaenoic acid pathway shifts the balance toward resolution in the arachidonic acid pathway. Knowledge of this mechanism may provide new strategies for promoting inflammation resolution in chronic inflammatory diseases. | 25,246,560 | [
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Left-right dissociation of hippocampal memory processes in mice. | Left-right asymmetries have likely evolved to make optimal use of bilaterian nervous systems; however, little is known about the synaptic and circuit mechanisms that support divergence of function between equivalent structures in each hemisphere. Here we examined whether lateralized hippocampal memory processing is present in mice, where hemispheric asymmetry at the CA3-CA1 pyramidal neuron synapse has recently been demonstrated, with different spine morphology, glutamate receptor content, and synaptic plasticity, depending on whether afferents originate in the left or right CA3. To address this question, we used optogenetics to acutely silence CA3 pyramidal neurons in either the left or right dorsal hippocampus while mice performed hippocampus-dependent memory tasks. We found that unilateral silencing of either the left or right CA3 was sufficient to impair short-term memory. However, a striking asymmetry emerged in long-term memory, wherein only left CA3 silencing impaired performance on an associative spatial long-term memory task, whereas right CA3 silencing had no effect. To explore whether synaptic properties intrinsic to the hippocampus might contribute to this left-right behavioral asymmetry, we investigated the expression of hippocampal long-term potentiation. Following the induction of long-term potentiation by high-frequency electrical stimulation, synapses between CA3 and CA1 pyramidal neurons were strengthened only when presynaptic input originated in the left CA3, confirming an asymmetry in synaptic properties. The dissociation of hippocampal long-term memory function between hemispheres suggests that memory is routed via distinct left-right pathways within the mouse hippocampus, and provides a promising approach to help elucidate the synaptic basis of long-term memory. | 25,246,561 | [
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The cardiac-specific N-terminal region of troponin I positions the regulatory domain of troponin C. | The cardiac isoform of troponin I (cTnI) has a unique 31-residue N-terminal region that binds cardiac troponin C (cTnC) to increase the calcium sensitivity of the sarcomere. The interaction can be abolished by cTnI phosphorylation at Ser22 and Ser23, an important mechanism for regulating cardiac contractility. cTnC contains two EF-hand domains (the N and C domain of cTnC, cNTnC and cCTnC) connected by a flexible linker. Calcium binding to either domain favors an "open" conformation, exposing a large hydrophobic surface that is stabilized by target binding, cTnI[148-158] for cNTnC and cTnI[39-60] for cCTnC. We used multinuclear multidimensional solution NMR spectroscopy to study cTnI[1-73] in complex with cTnC. cTnI[39-60] binds to the hydrophobic face of cCTnC, stabilizing an alpha helix in cTnI[41-67] and a type VIII turn in cTnI[38-41]. In contrast, cTnI[1-37] remains disordered, although cTnI[19-37] is electrostatically tethered to the negatively charged surface of cNTnC (opposite its hydrophobic surface). The interaction does not directly affect the calcium binding affinity of cNTnC. However, it does fix the positioning of cNTnC relative to the rest of the troponin complex, similar to what was previously observed in an X-ray structure [Takeda S, et al. (2003) Nature 424(6944):35-41]. Domain positioning impacts the effective concentration of cTnI[148-158] presented to cNTnC, and this is how cTnI[19-37] indirectly modulates the calcium affinity of cNTnC within the context of the cardiac thin filament. Phosphorylation of cTnI at Ser22/23 disrupts domain positioning, explaining how it impacts many other cardiac regulatory mechanisms, like the Frank-Starling law of the heart. | 25,246,568 | [
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α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation. | Physiologically, α-synuclein chaperones soluble NSF attachment protein receptor (SNARE) complex assembly and may also perform other functions; pathologically, in contrast, α-synuclein misfolds into neurotoxic aggregates that mediate neurodegeneration and propagate between neurons. In neurons, α-synuclein exists in an equilibrium between cytosolic and membrane-bound states. Cytosolic α-synuclein appears to be natively unfolded, whereas membrane-bound α-synuclein adopts an α-helical conformation. Although the majority of studies showed that cytosolic α-synuclein is monomeric, it is unknown whether membrane-bound α-synuclein is also monomeric, and whether chaperoning of SNARE complex assembly by α-synuclein involves its cytosolic or membrane-bound state. Here, we show using chemical cross-linking and fluorescence resonance energy transfer (FRET) that α-synuclein multimerizes into large homomeric complexes upon membrane binding. The FRET experiments indicated that the multimers of membrane-bound α-synuclein exhibit defined intermolecular contacts, suggesting an ordered array. Moreover, we demonstrate that α-synuclein promotes SNARE complex assembly at the presynaptic plasma membrane in its multimeric membrane-bound state, but not in its monomeric cytosolic state. Our data delineate a folding pathway for α-synuclein that ranges from a monomeric, natively unfolded form in cytosol to a physiologically functional, multimeric form upon membrane binding, and show that only the latter but not the former acts as a SNARE complex chaperone at the presynaptic terminal, and may protect against neurodegeneration. | 25,246,573 | [
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Epigenetic dysregulation by nickel through repressive chromatin domain disruption. | Investigations into the genomic landscape of histone modifications in heterochromatic regions have revealed histone H3 lysine 9 dimethylation (H3K9me2) to be important for differentiation and maintaining cell identity. H3K9me2 is associated with gene silencing and is organized into large repressive domains that exist in close proximity to active genes, indicating the importance of maintenance of proper domain structure. Here we show that nickel, a nonmutagenic environmental carcinogen, disrupted H3K9me2 domains, resulting in the spreading of H3K9me2 into active regions, which was associated with gene silencing. We found weak CCCTC-binding factor (CTCF)-binding sites and reduced CTCF binding at the Ni-disrupted H3K9me2 domain boundaries, suggesting a loss of CTCF-mediated insulation function as a potential reason for domain disruption and spreading. We furthermore show that euchromatin islands, local regions of active chromatin within large H3K9me2 domains, can protect genes from H3K9me2-spreading-associated gene silencing. These results have major implications in understanding H3K9me2 dynamics and the consequences of chromatin domain disruption during pathogenesis. | 25,246,589 | [
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Basis for substrate recognition and distinction by matrix metalloproteinases. | Genomic sequencing and structural genomics produced a vast amount of sequence and structural data, creating an opportunity for structure-function analysis in silico [Radivojac P, et al. (2013) Nat Methods 10(3):221-227]. Unfortunately, only a few large experimental datasets exist to serve as benchmarks for function-related predictions. Furthermore, currently there are no reliable means to predict the extent of functional similarity among proteins. Here, we quantify structure-function relationships among three phylogenetic branches of the matrix metalloproteinase (MMP) family by comparing their cleavage efficiencies toward an extended set of phage peptide substrates that were selected from ∼ 64 million peptide sequences (i.e., a large unbiased representation of substrate space). The observed second-order rate constants [k(obs)] across the substrate space provide a distance measure of functional similarity among the MMPs. These functional distances directly correlate with MMP phylogenetic distance. There is also a remarkable and near-perfect correlation between the MMP substrate preference and sequence identity of 50-57 discontinuous residues surrounding the catalytic groove. We conclude that these residues represent the specificity-determining positions (SDPs) that allowed for the expansion of MMP proteolytic function during evolution. A transmutation of only a few selected SDPs proximal to the bound substrate peptide, and contributing the most to selectivity among the MMPs, is sufficient to enact a global change in the substrate preference of one MMP to that of another, indicating the potential for the rational and focused redesign of cleavage specificity in MMPs. | 25,246,591 | [
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Extraction of the deciduous canine as an interceptive treatment in children with palatal displaced canines - part I: shall we extract the deciduous canine or not? | To analyse whether extraction of the deciduous canines facilitates eruption of the palatal displaced canines (PDCs), and to analyse root resorption in adjacent teeth caused by the PDCs. Eligibility criteria for participants were as follows: children at age 10-13 years with either maxillary unilateral or bilateral PDC, persisting deciduous canine and no previous experience of orthodontic treatment. Sixty-seven patients (40 girls and 27 boys; age: mean ± standard deviation: 11.4±1.0) with unilateral (45) or bilateral (22) PDCs were consecutively recruited and randomly allocated using permuted block randomization method to extraction or non-extraction. No patients dropped out after the randomization or during the study. Patients underwent a clinical examination and cone beam computed tomography at baseline (T0), after 6 (T1) and 12 months (T2). The total observation time was 24 months. Outcome measures were eruption, positional changes, length of time until eruption, and root resorption of adjacent teeth. The baseline images were measured blinded while the 6- and 12-month control images were not, since it was not possible to blind the extracted canine. Significantly more spontaneous eruptions of the PDCs were seen in the extraction group (EG) than in the control group (CG), with rates of 69 and 39 per cent, respectively, with a mean eruption time of 15.6±5.6 months in the EG and 18.8±5.8 months in the CG. Significant differences in changes between the groups, in favour of the EG, were found for all variables except for the sagittal angle. In the EG, the changes in the distances of the canine cusp-tip were larger during the first 6 months, while the change of apex was larger between 6 and 12 months. There were no significant differences in resorption of adjacent teeth between the groups. Imputation values were used for the PDCs who had erupted at T2, since no x-rays were taken for ethical reasons, which might have given uncertainty in the positional changes between T1 and T2. Extraction of the deciduous canine is an effective treatment in patients with PDCs. Significantly more positional changes and shorter mean eruption time were seen in the EG. Resorptions of lateral incisors were seen in both groups, but none exceeded grade 2 (resorption up to half of the dentine thickness to the pulp). This trial was registered in "FoU i Sverige" (http://www.fou.nu/is/sverige), registration number: 40921. The protocol was not published before trial commencement. | 25,246,604 | [
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Early neonatal bilirubin, hematocrit, and glucose-6-phosphate dehydrogenase status. | To document the patterns of bilirubin and hematocrit values among glucose-6-phosphate dehydrogenase (G6PD)-deficient and G6PD-normal Nigerian neonates in the first week of life, in the absence of exposure to known icterogenic agents. The G6PD status of consecutive term and near-term neonates was determined, and their bilirubin levels and hematocrits were monitored during the first week of life. Infants were stratified into G6PD deficient, intermediate, and normal on the basis of the modified Beutler's fluorescent spot test. Means of total serum bilirubin (TSB) and hematocrits of the 3 groups of infants were compared. The 644 neonates studied comprised 353 (54.8%) boys and 291 (45.2%) girls and 540 (83.9%) term and 104 (16.1%) near-term infants. They consisted of 129 (20.0%) G6PD-deficient, 69 (10.7%) G6PD-intermediate, and 446 (69.3%) G6PD-normal neonates. The G6PD-deficient and G6PD-intermediate infants had higher mean TSB than their G6PD-normal counterparts at birth and throughout the first week of life (P < .001). Mean peak TSB levels were 14.1 (9.48), 10.2 (3.8), and 6.9 (3.3) mg/dL for G6PD-deficient, G6PD-intermediate, and G6PD-normal neonates, respectively. Peak TSB was attained on approximately day 4 in all 3 groups, and trends in TSB were similar. Mean hematocrits at birth were similar in the 3 G6PD groups. However, G6PD-deficient and -intermediate infants had higher declines in hematocrit, bilirubin levels, and need for phototherapy than G6PD-normal infants (P < .001). The G6PD-deficient and G6PD-intermediate neonates had a higher risk of neonatal hyperbilirubinemia and would therefore need greater monitoring in the first week of life, even without exposure to known icterogenic agents. | 25,246,627 | [
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Binding of WIP to actin is essential for T cell actin cytoskeleton integrity and tissue homing. | The Wiskott-Aldrich syndrome protein (WASp) is important for actin polymerization in T cells and for their migration. WASp-interacting protein (WIP) binds to and stabilizes WASp and also interacts with actin. Cytoskeletal and functional defects are more severe in WIP(-/-) T cells, which lack WASp, than in WASp(-/-) T cells, suggesting that WIP interaction with actin may be important for T cell cytoskeletal integrity and function. We constructed mice that lack the actin-binding domain of WIP (WIPΔABD mice). WIPΔABD associated normally with WASp but not F-actin. T cells from WIPΔABD mice had normal WASp levels but decreased cellular F-actin content, a disorganized actin cytoskeleton, impaired chemotaxis, and defective homing to lymph nodes. WIPΔABD mice exhibited a T cell intrinsic defect in contact hypersensitivity and impaired responses to cutaneous challenge with protein antigen. Adoptively transferred antigen-specific CD4(+) T cells from WIPΔABD mice had decreased homing to antigen-challenged skin of wild-type recipients. These findings show that WIP binding to actin, independently of its binding to WASp, is critical for the integrity of the actin cytoskeleton in T cells and for their migration into tissues. Disruption of WIP binding to actin could be of therapeutic value in T cell-driven inflammatory diseases. | 25,246,631 | [
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ERBB2 deficiency alters an E2F-1-dependent adaptive stress response and leads to cardiac dysfunction. | The tyrosine kinase receptor ERBB2 is required for normal development of the heart and is a potent oncogene in breast epithelium. Trastuzumab, a monoclonal antibody targeting ERBB2, improves the survival of breast cancer patients, but cardiac dysfunction is a major side effect of the drug. The molecular mechanisms underlying how ERBB2 regulates cardiac function and why trastuzumab is cardiotoxic remain poorly understood. We show here that ERBB2 hypomorphic mice develop cardiac dysfunction that mimics the side effects observed in patients treated with trastuzumab. We demonstrate that this phenotype is related to the critical role played by ERBB2 in cardiac homeostasis and physiological hypertrophy. Importantly, genetic and therapeutic reduction of ERBB2 activity in mice, as well as ablation of ERBB2 signaling by trastuzumab or siRNAs in human cardiomyocytes, led to the identification of an impaired E2F-1-dependent genetic program critical for the cardiac adaptive stress response. These findings demonstrate the existence of a previously unknown mechanistic link between ERBB2 and E2F-1 transcriptional activity in heart physiology and trastuzumab-induced cardiac dysfunction. | 25,246,633 | [
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Evidence for distorted mental representation of the hand in osteoarthritis. | Some chronic pain states are associated with a distortion of the perceived size or shape of the painful area, and multisensory illusions that disrupt these dimensions can modulate pain in healthy controls and people with painful disorders. Illusory hand resizing has recently been found to relieve pain in hand OA, raising the possibility that the illusion corrects some underlying perceptual disturbance. We evaluated this possibility by measuring perceived hand size in healthy controls and those with painful hand OA before and after illusory hand resizing. The aim was to investigate whether people with painful hand OA have distorted representations of hand size and whether these representations are malleable. We hypothesized that hand OA is associated with a distorted mental representation of the painful hand and that perceived hand size can be modulated via multisensory illusion. Twelve volunteers with painful hand OA and 12 healthy age-matched controls performed three tasks (hand stretch, hand shrink and no illusion) in a randomized order then estimated the size of their hand using an adjustable photographic image. Our hypotheses were supported: under normal conditions, perceived hand size was smaller for the OA group than for healthy controls, consistent with a distorted mental representation of the painful hand. Furthermore, illusory stretching increased perceived hand size in both groups, while illusory shrinking decreased perceived hand size in healthy controls but not in the OA group. These results suggest that hand OA is associated with a distorted mental representation of the painful hand and are consistent with the idea that the pain relief offered by multisensory illusions may work via normalization of this distortion. | 25,246,638 | [
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Frequency and time to relapse after discontinuing 6-month therapy with IVIg or pulsed methylprednisolone in CIDP. | We reported that 6-month therapy with intravenous immunoglobulin (IVIg) was more frequently effective or tolerated than intravenous methylprednisolone (IVMP) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now retrospectively compared the proportion of patients who eventually worsened after discontinuing therapy and the median time to clinical worsening. By March 2013, data were available from 41 of the 45 patients completing the trial with a median follow-up after therapy discontinuation of 42 months (range 1-60). Three patients withdrew during the original study and one failed to respond to either of the therapies. No patient received a diagnosis alternative to CIDP during the follow-up. Twenty-eight of the 32 patients treated with IVIg (as primary or secondary therapy after failing to respond to IVMP) improved after therapy (87.5%) as compared with 13 of the 24 patients treated with IVMP as primary or secondary therapy (54.2%). After a median follow-up of 42 months (range 1-57), 24 out of 28 patients responsive to IVIg (85.7%) worsened after therapy discontinuation. The same occurred in 10 out of 13 patients (76.9%) responsive to IVMP (p=0.659) after a median follow-up of 43 months (range 7-60). Worsening occurred 1-24 months (median 4.5) after IVIg discontinuation and 1-31 months (median 14) after IVMP discontinuation (p=0.0126). A similarly high proportion of patients treated with IVIg or IVMP eventually relapse after therapy discontinuation but the median time to relapse was significantly longer after IVMP than IVIg. This difference may help to balance the more frequent response to IVIg than to IVMP in patients with CIDP. | 25,246,645 | [
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Deletion of L4 domains reveals insights into the importance of ribosomal protein extensions in eukaryotic ribosome assembly. | Numerous ribosomal proteins have a striking bipartite architecture: a globular body positioned on the ribosomal exterior and an internal loop buried deep into the rRNA core. In eukaryotes, a significant number of conserved r-proteins have evolved extra amino- or carboxy-terminal tail sequences, which thread across the solvent-exposed surface. The biological importance of these extended domains remains to be established. In this study, we have investigated the universally conserved internal loop and the eukaryote-specific extensions of yeast L4. We show that in contrast to findings with bacterial L4, deleting the internal loop of yeast L4 causes severely impaired growth and reduced levels of large ribosomal subunits. We further report that while depleting the entire L4 protein blocks early assembly steps in yeast, deletion of only its extended internal loop affects later steps in assembly, revealing a second role for L4 during ribosome biogenesis. Surprisingly, deletion of the entire eukaryote-specific carboxy-terminal tail of L4 has no effect on viability, production of 60S subunits, or translation. These unexpected observations provide impetus to further investigate the functions of ribosomal protein extensions, especially eukaryote-specific examples, in ribosome assembly and function. | 25,246,649 | [
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Metabolic impact of an NADH-producing glucose-6-phosphate dehydrogenase in Escherichia coli. | In Escherichia coli, the oxidative branch of the pentose phosphate pathway (oxPPP) is one of the major sources of NADPH when glucose is the sole carbon nutrient. However, unbalanced NADPH production causes growth impairment as observed in a strain lacking phosphoglucoisomerase (Δpgi). In this work, we studied the metabolic response of this bacterium to the replacement of its glucose-6-phosphate dehydrogenase (G6PDH) by an NADH-producing variant. The homologous enzyme from Leuconostoc mesenteroides was studied by molecular dynamics and site-directed mutagenesis to obtain the NAD-preferring LmG6PDH(R46E,Q47E). Through homologous recombination, the zwf loci (encoding G6PDH) in the chromosomes of WT and Δpgi E. coli strains were replaced by DNA encoding LmG6PDH(R46E,Q47E). Contrary to some predictions performed with flux balance analysis, the replacements caused a substantial effect on the growth rates, increasing 59 % in the Δpgi strain, while falling 44 % in the WT. Quantitative PCR (qPCR) analysis of the zwf locus showed that the expression level of the mutant enzyme was similar to the native enzyme and the expression of genes encoding key enzymes of the central pathways also showed moderate changes among the studied strains. The phenotypic and qPCR data were integrated into in silico modelling, showing an operative G6PDH flux contributing to the NADH pool. Our results indicated that, in vivo, the generation of NADH by G6PDH is beneficial or disadvantageous for growth depending on the operation of the upper Embden-Meyerhof pathway. Interestingly, a genomic database search suggested that in bacteria lacking phosphofructokinase, the G6PDHs tend to have similar preferences for NAD and NADP. The importance of the generation of NADPH in a pathway such as the oxPPP is discussed. | 25,246,670 | [
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Global health research in narrative: a qualitative look at the FICRS-F experience. | For American professional and graduate health sciences trainees, a mentored fellowship in a low- or middle-income country (LMIC) can be a transformative experience of personal growth and scientific discovery. We invited 86 American trainees in the Fogarty International Clinical Research Scholars and Fellows Program and Fulbright-Fogarty Fellowship 2011-2012 cohorts to contribute personal essays about formative experiences from their fellowships. Nine trainees contributed essays that were analyzed using an inductive approach. The most frequently addressed themes were the strong continuity of research and infrastructure at Fogarty fellowship sites, the time-limited nature of this international fellowship experience, and the ways in which this fellowship period was important for shaping future career planning. Trainees also addressed interaction with host communities vis-à-vis engagement in project implementation. These qualitative essays have contributed insights on how a 1-year mentored LMIC-based research training experience can influence professional development, complementing conventional evaluations. Full text of the essays is available at http://fogartyscholars.org/. | 25,246,694 | [
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Neural changes associated with emotion processing in children experiencing peer rejection: a functional MRI study. | This study was performed to investigate differences between children who did and did not experience peer rejection in psychological state through surveys and in emotion processing during an interpersonal stress challenge task to reflect naturalistic interpersonal face-to-face relationships. A total of 20 right-handed children, 10 to 12 yr of age, completed self-rating questionnaires inquiring about peer rejection in school, depression, and anxiety. They then underwent an interpersonal stress challenge task simulating conditions of emotional stress, in reaction to positive, negative and neutral facial expression stimuli, using interpersonal feedbacks, and functional magnetic resonance imaging (FMRI) for an analysis of neural correlates during the task. Ten were the peer-rejection group, whereas the remainder were the control group. Based on the behavioral results, the peer-rejection group exhibited elevated levels of depression, state anxiety, trait anxiety and social anxiety as compared to the control group. The FMRI results revealed that the peer-rejection group exhibited greater and remarkably more extensive activation of brain regions encompassing the amygdala, orbitofrontal cortex and ventrolateral prefrontal cortex in response to negative feedback stimuli of emotional faces. The different brain reactivities characterizing emotion processing during interpersonal relationships may be present between children who do and do not experience peer rejection. | 25,246,750 | [
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Extremely elevated international normalized ratio of warfarin in a patient with CYP2C9*1/*3 and thyrotoxicosis. | A 73-yr-old Korean man with permanent atrial fibrillation visited outpatient clinic with severely increased International Normalized Ratio (INR) values after taking a usual starting dosage of warfarin to prevent thromboembolism. We found out later from his blood tests that he had hyperthyroidism at the time of treatment initiation. His genetic analysis showed CYP2C9*1/*3 and VKORC1+1173TT genotypes. We suspect that both hyperthyroidism and genetic variant would have contributed to his extremely increased INR at the beginning of warfarin therapy. From this case, we learned that pharmacogenetic and thyroid function test might be useful when deciding the starting dosage of warfarin in patients with atrial fibrillation. | 25,246,753 | [
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Unexpected and permanent central visual loss after removal of intraocular silicone oil. | Here we report a case of unexplained sudden visual loss after removal of silicone oil for rhegmatogenous retinal detachment repair. A patient with visual loss in one eye after removal of silicone oil was investigated with best-corrected Snellen visual acuity assessment, fundus biomicroscopy, optical coherence tomography, color fundus photograph, fluorescein angiography, electrophysiologic examination, automated perimetry, and visual evoked potentials. Best-corrected Snellen visual acuity was 20/30 while the silicone oil was in place. Visual acuity dropped dramatically to 20/200 after silicone oil removal. No other complications associated with oil removal were noted. The retina remained attached. Visual evoked potentials revealed decreased amplitude due to a damaged optic nerve, while the earliest central visual field defects disappeared unexpectedly almost 2 years after the last surgical procedure. No other abnormalities were demonstrated. Vision loss is a possible complication of silicone oil and removal. This case was distinguished by the permanent decrease of visual acuity despite the unexplained and quite complete recovery of the foveal threshold with no other relevant visual field defects. | 25,246,762 | [
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Superior rejection profile during the first 24 months after heart transplantation under tacrolimus as baseline immunosuppressive regimen. | The use of tacrolimus (TAC) in patients after heart transplantation (HTX) has increased over the last few years. In this retrospective study, we evaluated the effects of a TAC (conventional and extended-release TAC)-based immunosuppressive therapy regarding rejection profile in comparison to a cyclosporine A (CSA)-based regimen in patients after HTX. The data of 233 patients who underwent HTX at the Heidelberg Heart Transplantation Center from May 1998 until November 2010 were retrospectively analyzed. Primary immunosuppressive therapy was changed from a CSA (n=114) to a TAC (n=119)-based regimen in February 2006 according to center routine. Follow-up period was 2 years post-HTX. Primary endpoint was time to first biopsy-proven rejection requiring therapy. In all patients, routine follow-up at the Heidelberg Heart Transplantation Center was mandatory. Multivariate risk factor analysis regarding time to first rejection episode showed no statistically significant differences regarding recipient age, donor age, recipient sex, donor sex, sex mismatch, ischemic time, and diagnosis leading to HTX between the two groups (all P= not statistically significant). Time to first biopsy-proven rejection was significantly longer in the TAC group (intention-to-treat analysis, n=233, log-rank test P<0.0001; per-protocol analysis, n=150, log-rank test P=0.0003). In patients who underwent a change of primary immunosuppression (n=49), a significantly longer time to first biopsy-proven rejection was also found in the primary TAC subgroup (log-rank test P=0.0297). Further subgroup analysis in the TAC subgroups showed no statistically significant differences in time to biopsy-proven rejection under extended-release TAC compared to conventional TAC (intention-to-treat analysis, log-rank test P=0.1736). Our study demonstrated that a TAC-based primary immunosuppressive therapy is superior to a CSA-based immunosuppressive regimen in patients after HTX regarding time to first biopsy-proven rejection. | 25,246,772 | [
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Exploring motivations to seek and undergo prosthodontic care: an empirical approach using the Theory of Planned Behavior construct. | Motivations for seeking and undergoing prosthodontic care are poorly understood and are not often explored for clinical purposes when determining treatment need and understanding the factors related to the demand for health care and effective use. This article uses the Theory of Planned Behavior construct to identify factors related to the motivations of edentulous subjects to seek and undergo prosthodontic treatment. The conceptual framework of the Theory of Planned Behavior includes attitude toward behavior, an individual's positive or negative evaluation of self-performance of the particular behavior; the subjective norm, an individual's perception of social normative pressures or relevant others' beliefs that he or she should or should not perform such behavior; and perceived behavioral control, or an individual's perceived ease or difficulty in performing the particular behavior, determined by the total set of accessible control beliefs. These components mediate a subject's intention and behavior toward an object and may also explain health-related behaviors, providing strong predictions across a range of health behaviors. This study suggests categories for each component of the Theory of Planned Behavior, based on clinical evidence and practical reasoning. Attitudes toward behavior include perceived consequences of no treatment, perceived potential benefits and risks of treatment, dental anxiety, previous experiences, and interpersonal abilities of the health care providers. The subjective norm includes the opinions of relevant others, advertisement, professionally defined normative need, perceived professional skills, and technical quality of care. Perceived behavioral control includes subject's time, availability and opportunity, treatment costs, subject's perceived need, and accessibility to dental care. This conceptual model represents a theoretical multidimensional model that may help clinicians better understand the patient's treatment behaviors and provide additional information for clinical research on patient's adherence to interventions in prosthodontics. | 25,246,777 | [
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Carboxyl-modified single-wall carbon nanotubes improve bone tissue formation in vitro and repair in an in vivo rat model. | The clinical management of bone defects caused by trauma or nonunion fractures remains a challenge in orthopedic practice due to the poor integration and biocompatibility properties of the scaffold or implant material. In the current work, the osteogenic properties of carboxyl-modified single-walled carbon nanotubes (COOH-SWCNTs) were investigated in vivo and in vitro. When human preosteoblasts and murine embryonic stem cells were cultured on coverslips sprayed with COOH-SWCNTs, accelerated osteogenic differentiation was manifested by increased expression of classical bone marker genes and an increase in the secretion of osteocalcin, in addition to prior mineralization of the extracellular matrix. These results predicated COOH-SWCNTs' use to further promote osteogenic differentiation in vivo. In contrast, both cell lines had difficulties adhering to multi-walled carbon nanotube-based scaffolds, as shown by scanning electron microscopy. While a suspension of SWCNTs caused cytotoxicity in both cell lines at levels >20 μg/mL, these levels were never achieved by release from sprayed SWCNTs, warranting the approach taken. In vivo, human allografts formed by the combination of demineralized bone matrix or cartilage particles with SWCNTs were implanted into nude rats, and ectopic bone formation was analyzed. Histological analysis of both types of implants showed high permeability and pore connectivity of the carbon nanotube-soaked implants. Numerous vascularization channels appeared in the formed tissue, additional progenitor cells were recruited, and areas of de novo ossification were found 4 weeks post-implantation. Induction of the expression of bone-related genes and the presence of secreted osteopontin protein were also confirmed by quantitative polymerase chain reaction analysis and immunofluorescence, respectively. In summary, these results are in line with prior contributions that highlight the suitability of SWCNTs as scaffolds with high bone-inducing capabilities both in vitro and in vivo, confirming them as alternatives to current bone-repair therapies. | 25,246,785 | [
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Nanostructured lipid carrier surface modified with Eudragit RS 100 and its potential ophthalmic functions. | This study was carried out to evaluate the ocular performance of a cationic Eudragit (EDU) RS 100-coated nanostructured lipid carrier (NLC). The genistein encapsulated NLC (GEN-NLC) was produced using the melt-emulsification technique followed by surface absorption of EDU RS 100. The EDU RS 100 increased the surface zeta potential from -7.46 mV to +13.60 mV, by uniformly forming a spherical coating outside the NLC surface, as shown by transmission electron microscopy images. The EDU RS 100 on the NLC surface effectively improved the NLC stability by inhibiting particle size growth. The obtained EDU RS 100-GEN-NLC showed extended precorneal clearance and a 1.22-fold increase in AUC (area under the curve) compared with the bare NLC in a Gamma scintigraphic evaluation. The EDU RS 100 modification also significantly increased corneal penetration producing a 3.3-fold increase in apparent permeability coefficients (Papp) compared with references. Draize and cytotoxicity testing confirmed that the developed EDU RS 100-GEN-NLC was nonirritant to ocular tissues and nontoxic to corneal cells. These results indicate that the NLC surface modified by EDU RS 100 significantly improves the NLC properties and exhibits many advantages for ocular use. | 25,246,787 | [
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Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies. | We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. | 25,246,790 | [
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Association between smoking and cognitive impairment in multiple sclerosis. | Although smoking is known to cause various symptoms in multiple sclerosis (MS) patients, there have been no reports regarding the relationship between smoking and cognitive impairment in MS. Studying the effects of cigarette smoking in MS patients is imperative as there is a high prevalence of cognitive impairment in MS patients. In this study we examined the potentially deleterious effects of heavy smoking on mentation of patients with MS. MS patients receiving care at the Neurology Clinic at Bezmialem Vakıf University, between the ages of 18-65 years who have at least graduated elementary school were included in the study. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) is a commonly used method to assess cognitive function in MS patients and was utilized in our study. Patients that smoked for at least 10 pack-years were considered heavy smokers. ALL THE PATIENTS WERE STRATIFIED INTO TWO GROUPS: heavy smokers (n=20) and nonsmokers (n=24). For heavy smokers, their cognitive functioning was more impaired than that of nonsmokers (P=0.04, χ (2)=4.227). For patients with cognitive impairment, 78.9% of the Paced Auditory Serial Addition Test and 63.2% of the Symbol Digit Modalities Test scores were found to be lower. Previous reports have suggested that smoking increases the frequency of relapse among individuals with relapsing-remitting MS and accelerates disease progression in patients with progressive MS. According to the results of our study, heavy smokers had increased cognitive impairment when compared to nonsmokers. Extensive studies are necessary to further elucidate the relationship between smoking and cognitive impairment in MS patients. | 25,246,792 | [
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Cognitive assessments for the early diagnosis of dementia after stroke. | The early detection of poststroke dementia (PSD) is important for medical practitioners to customize patient treatment programs based on cognitive consequences and disease severity progression. The aim is to diagnose and detect brain degenerative disorders as early as possible to help stroke survivors obtain early treatment benefits before significant mental impairment occurs. Neuropsychological assessments are widely used to assess cognitive decline following a stroke diagnosis. This study reviews the function of the available neuropsychological assessments in the early detection of PSD, particularly vascular dementia (VaD). The review starts from cognitive impairment and dementia prevalence, followed by PSD types and the cognitive spectrum. Finally, the most usable neuropsychological assessments to detect VaD were identified. This study was performed through a PubMed and ScienceDirect database search spanning the last 10 years with the following keywords: "post-stroke"; "dementia"; "neuro-psychological"; and "assessments". This study focuses on assessing VaD patients on the basis of their stroke risk factors and cognitive function within the first 3 months after stroke onset. The search strategy yielded 535 articles. After application of inclusion and exclusion criteria, only five articles were considered. A manual search was performed and yielded 14 articles. Twelve articles were included in the study design and seven articles were associated with early dementia detection. This review may provide a means to identify the role of neuropsychological assessments as early PSD detection tests. | 25,246,795 | [
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Effect of delayed intrathecal administration of capsaicin on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats. | The current study was designed to examine the antinociceptive effect of intrathecally administered capsaicin, a transient receptor potential vanilloid 1 receptor agonist, in a rat model of neuropathic pain induced by unilateral sciatic nerve chronic constriction injury. Male adult Sprague Dawley rats were randomly assigned to six groups, and all rats underwent unilateral sciatic nerve chronic constriction injury. Two weeks after injury, five groups received intrathecal administration of either capsaicin in three different dosing regimens or equal volumes of vehicle. The other group received intrathecal capsaicin on the third day after nerve injury. The antinociceptive effect of capsaicin was assessed by measuring the capsaicin-induced change in thermal and mechanical response thresholds. Capsaicin (150-300 μg/100-200 μL), when administered by fast infusion or chronic infusions at 8 μL/hour or 1 μL/hour, attenuated thermal hyperalgesia as indicated by significantly prolonging paw withdrawal latency to noxious thermal stimulation. The antinociceptive effect of capsaicin was more profound in the injured limb compared to that in the uninjured limb. When capsaicin was administered on the third day after nerve injury, it failed to attenuate thermal hyperalgesia. No significant effect on the mechanical response threshold was observed with intrathecally administered capsaicin. Our data suggest that intrathecal capsaicin could significantly attenuate thermal hyperalgesia, depending on the time when the drug is given after nerve injury, and that the antinociceptive efficacy of intrathecal capsaicin positively correlates with the previously reported dynamic profile of spinal transient receptor potential vanilloid 1 activity after nerve injury. | 25,246,806 | [
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Cowden syndrome presenting as breast cancer: imaging and clinical features. | Cowden syndrome is an uncommon, autosomal dominant disease which is characterized by multiple hamartomas of the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. The diagnosis of Cowden syndrome implicates an increased risk of developing breast cancer. We report a case of a 22-year-old woman with Cowden syndrome that presented as breast cancer with concomitant bilateral exuberant benign masses in both breasts. | 25,246,819 | [
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Internal iliac artery embolization during an endovascular aneurysm repair with detachable interlock microcoils. | The purpose of this study was to evaluate the effectiveness of detachable interlock microcoils for an embolization of the internal iliac artery during an endovascular aneurysm repair (EVAR). A retrospective review was conducted on 40 patients with aortic aneurysms, who had undergone an EVAR between January 2010 and March 2012. Among them, 16 patients were referred for embolization of the internal iliac artery for the prevention of type II endoleaks. Among 16 patients, 13 patients underwent embolization using detachable interlock microcoils during an EVAR. Computed tomographic angiographies and clinical examinations were performed during the follow-up period. Technical success, clinical outcome, and complications were reviewed. Internal iliac artery embolizations using detachable interlock microcoils were technically successful in all 13 patients, with no occurrence of procedure-related complications. Follow-up imaging was accomplished in the 13 cases. In all cases, type II endoleak was not observed with computed tomographic angiography during the median follow-up of 3 months (range, 1-27 months) and the median clinical follow-up of 12 months (range, 1-27 months). Two of 13 (15%) patients had symptoms of buttock pain, and one patient died due to underlying stomach cancer. No significant clinical symptoms such as bowel ischemia were observed. Internal iliac artery embolization during an EVAR using detachable interlock microcoils to prevent type II endoleaks appears safe and effective, although this should be further proven in a larger population. | 25,246,822 | [
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Breaking into the International Arena: Malaysian Journal of Medical Sciences publishing Report 2013. | The most recent Malaysian Journal of Medical Sciences (MJMS)-MyCite report has shown that it has achieved a level becoming of a leading national medical science journal. This editorial reports on submission and acceptance rates of MJMS throughout the year 2013 and their geographical contributors. Our rejection rate of 29.76% with a 21.95% withdrawal rate because of poor quality of content and data as well as plagiarism indicates the seriousness of this journal to maintain the integrity and quality of it's scientific data. | 25,246,830 | [
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Mycobacterium szulgai pulmonary infection: case report of an uncommon pathogen in Korea. | Mycobacterium szulgai (M. szulgai) is an unusual pathogen in a human non-tuberculous mycobacterial infection. Pulmonary infection due to M. szulgai may be clinically and radiologically confused with active pulmonary tuberculosis. In contrast to other non-tuberculous mycobacteria, M. szulgai infection is well controlled by combination antimycobacterial therapy. Most of the previously reported cases of M. szulgai pulmonary infection showed cavitary upper lobe infiltrates. We herein describe a case of pulmonary M. szulgai infection that shows clinical and radiological presentations similar to active pulmonary tuberculosis. | 25,246,828 | [
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Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis. | Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis. The hsIgA was purified from human colostrum and administered to Balb/c mice by the intranasal route prior to infection with M. tuberculosis or in a pre-incubated formulation with mycobacteria, with the principal aim to study its effect on qualitative pulmonary histopathology. The intranasal administration of hsIgA and the pre-incubation of mycobacteria with this preparation was associated with the presence of organised granulomas with signs of immune activation and histological features related to efficient disease control. This effect was highly evident during the late stage of infection (60 days), as demonstrated by numerous organised granulomas with numerous activated macrophages in the lungs of treated mice. The administration of hsIgA to mice before intratracheal infection with M. tuberculosis or the pre-incubation of the bacteria with the antibody formulation induced the formation of well-organised granulomas and inflammatory lesions in lungs compared with non-treated animals which correlates with the protective effect already demonstrated by these antibody formulations. | 25,246,833 | [
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Analysis of mechanical strength to fixing the femoral neck fracture in synthetic bone type Asnis. | To analyze the results of biomechanical assays of fixation of Pauwels type III femoral neck fracture in synthetic bone, using 7.5mm cannulated screws in inverted triangle formation, in relation to the control group. TEN SYNTHETIC BONES WERE USED, FROM A DOMESTIC BRAND, DIVIDED INTO TWO GROUPS: test and control. In the test group, a 70° tilt osteotomy of the femoral neck was fixated using three cannulated screws in inverted triangle formation. The resistance of this fixation and its rotational deviation were analyzed at 5mm displacement (phase 1) and 10mm displacement (phase 2). The control group was tested in its integrity until the fracture of the femoral neck occurred. The Mann-Whitney test was used for group analysis and comparison. The values in the test group in phase 1, in samples 1-5, showed a mean of 579N and SD =77N. Rotational deviations showed a mean of 3.33°, SD = 2.63°. In phase 2, the mean was 696N and SD =106N. The values of the maximum load in the control group had a mean of 1329N and SD=177N. The analysis of mechanical strength between the groups determined a statistically significant lower value in the test group. Level of Evidence III, Control Case. | 25,246,851 | [
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Clinical and demographic study on open fractures caused by motorcycle traffic accidents. | To assess socio-demographic characteristics of individuals that suffered open fractures caused by motorcycle traffic accident and evaluate infection rate in search of associated risk factors. A retrospective study comprising 81 patients with open fractures caused by motorcycle accidents was carried out. Clinic and socio-demographic features were collected from patients' records. Comparison between infected and non-infected patients was performed to find out which variables were possibly associated to this complication. Patients were mostly young adults (mean 32.9 years old), of the masculine gender (83.9%), single (60.5%), from the country side (40.7%), mostly presenting tibial open fractures (48.2%). Fractures type IIIA and type IIIB were the most prevalent lesions (68,8%), and soft tissue damage graded as I and II were the most frequent (64.62%). Infection was present in 23.7% of the patients and it was associated to age higher than 40 years old (p=0.011), to time delay from trauma to first surgical procedure longer than 24 hours (p=0,012), and also to soft tissue damage extent (p=0.001). Patients with open fractures caused by motorcycle traffic accident were mostly young single men, coming from the state capital and presented severe tibial open fractures, which 23.7% of the cases progressed to infection. Level of Evidence III, Retrospective Comparative Study. | 25,246,853 | [
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Simultaneous Computation of Dynamical and Equilibrium Information Using a Weighted Ensemble of Trajectories. | Equilibrium formally can be represented as an ensemble of uncoupled systems undergoing unbiased dynamics in which detailed balance is maintained. Many nonequilibrium processes can be described by suitable subsets of the equilibrium ensemble. Here, we employ the "weighted ensemble" (WE) simulation protocol [Huber and Kim, <iBiophys. J.</i<b1996</b, <i70</i, 97-110] to generate equilibrium trajectory ensembles and extract nonequilibrium subsets for computing kinetic quantities. States do not need to be chosen in advance. The procedure formally allows estimation of kinetic rates between arbitrary states chosen after the simulation, along with their equilibrium populations. We also describe a related history-dependent matrix procedure for estimating equilibrium and nonequilibrium observables when phase space has been divided into arbitrary non-Markovian regions, whether in WE or ordinary simulation. In this proof-of-principle study, these methods are successfully applied and validated on two molecular systems: explicitly solvated methane association and the implicitly solvated Ala4 peptide. We comment on challenges remaining in WE calculations. | 25,246,856 | [
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Effects of starting powder and thermal treatment on the aerosol deposited BaTiO3 thin films toward less leakage currents. | To prepare high-density integrated capacitors with low leakage currents, 0.2-μm-thick BaTiO3 thin films were successfully deposited on integrated semiconductor substrates at room temperature by the aerosol deposition (AD) method. In this study, the effects of starting powder size were considered in an effort to remove macroscopic defects. A surface morphology of 25.3 nm and an interface roughness of less than 50 nm were obtained using BT-03B starting powder. The nano-crystalline thin films achieved after deposition were annealed at various temperatures to promote crystallization and densification. Moreover, the influence of rapid thermal annealing process on the surface morphology and crystal growth was evaluated. As the annealing temperature increased from room temperature to 650°C, the root mean square (RMS) roughness decreased from 25.3 to 14.3 nm. However, the surface was transformed into rough performance at 750°C, which agreed well with the surface microstructure trend. Moreover, the crystal growth also reveals the changes in surface morphology via surface energy analysis. | 25,246,860 | [
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Sex hormone levels and sexual dysfunction in men after coronary artery bypass graft. | Sexual dysfunction is one of the most common problems in men after coronary artery bypass graft (CABG). Etiology of sexual dysfunction in these patients may be psychological or organic due to hormonal changes. The purpose was to evaluate the incidence and type of sexual dysfunction and changes in serum concentration of sex hormones in male patients undergoing on-pump CABG. In this before and after study we enrolled 40 men aged less than 70 years who were candidate for on-pump CABG. Interviews were done by a physician before and 12 weeks after the operation in regard to the impact of surgery on their sexual activities. The serum levels of 6 sex hormones were also determined. The statistical tests used for data analysis included analysis of variance, McNemar's test and chi-square analysis. The mean±SD age of the patients was 51.27±7.86 years. Incidence of sexual dysfunction was 22.5% (9 cases) before and 47.7% (19 cases) after operation. Types of sexual dysfunction were premature ejaculation (5% before, 2.5% after), impotence (7.5% before, 12.5% after) and loss of libido (10% before, 32% after). The level of sex hormones were generally decreased after operation but it was statistically significant only for estrogen (p-value=0.02). Sexual dysfunction and reduction in serum level of sex hormones are common in patients before on-pump CABG and mostly get worse after surgery. Complementary studies are suggested for prevention and treatment of sexual dysfunction. | 25,246,907 | [
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Effect of combined density gradient centrifugation on X- and Y- sperm separation and chromatin integrity. | It has been claimed that by using different washing methods, the sperms can be separated according to size, motility, density, chromosomal content and surface markings and charge. These methods also reduce sperm chromatin deficiencies and screen the sperms before applying in assisted reproduction techniques. This study compared simple density gradient methods and a combined method with albumin density gradient and PureSperm separation (alb/PureSperm) for sex preselection by double fluorescence in situ hybridization (FISH) versus chromomycin A3 staining to determine chromatin integrity. 30 normal semen samples were prepared with PureSperm, albumin gradients and alb/PureSperm. All samples were then stained by FISH and chromomycin A3. The results were compared with SPSS 11.5 and the Kruskal-Wallis test. The proportion of X-bearing spermatozoa by PureSperm separation (47.58±5.67) and Y-bearing spermatozoa by albumin gradient (46.13±3.83) methods were slightly higher than in putative normal sperm samples (1:1), but there were no significant differences in the X- or Y- bearing spermatozoa counts among the three methods. Albumin gradient separation tended to underestimate abnormal spermatozoa compared to PureSperm and combined alb/PureSperm. Routine separation methods slightly enriched X- or Y- bearing spermatozoa, but the differences were not significant for clinical purposes. The combined alb/PureSperm method had no advantages for assessing sex ratio or chromatin integrity compared to simpler gradient methods. | 25,246,909 | [
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Recommended foods for male infertility in Iranian traditional medicine. | Male infertility accounts for 30-50% of all infertilities among couples. Iranian traditional medicine (ITM) stressed the importance of nutrition in the prevention and treatment of male infertility. Many Iranian traditional physicians have described the traits of specific foods for prevention and treatment of male infertility. To explore the principles and roles of foods recommended by ITM scientists in prevention and treatment of male infertility as well as enlisting all the recommended foods for treating this problem addressed through the ITM original resources written between 815 and 1901. In this review study specific data related to the subject among all referral ITM texts was extracted firstly, and then the collected data were analyzed using inductive content analysis. The analysis of data revealed that foods that enhance sexual performance must have 3 properties; they should be warm in nature, very nutritious, and flatulent. Foods that are warm in nature and nutritious affect the quality and quantity of semen. A food having the third trait of being flatulent is required to complete sexual performance by creating an erection. Foods with only one of these traits must be consumed with another food that has the other trait. This study also provided a list of foods that can enhance the quality and increase the quantity of semen. Foods that can enhance sexual performance and the quality and quantity of semen can be recommended to male patients who suffer from infertility in medical centers. | 25,246,919 | [
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Evaluation of two DNA extraction methods from maternal plasma for using in non-invasive bovine fetus gender determination. | Fetal DNA in maternal plasma and serum has been shown to be a useful material for prenatal fetal sex determination during early gestational ages. Non-invasive prenatal diagnosis is now possible at 8(th) week of pregnancy, by maternal blood sample testing. The purpose of this study was to evaluate two DNA extraction methods from mother plasma and its routine clinical application in bovine fetus gender determination with non-invasive method. Maternal blood samples were taken from 40 pregnant cows during the 8(th)-38(th) weeks of gestation. DNA was extracted from 350 µl of maternal plasma with two salting-out and phenol-chloroform methods. The absorption in A260 and purity (A260/A280) of extracted DNA were detected by ultraviolet spectrophotometer. Three µl of the extracted DNA with phenol-chloroform method was used as a template. The PCR reaction was carried out to amplify the fragments of X and Y chromosomes of amelogenin, TSPY and BC1.2 genes. The difference between the mean absorption of DNA extracted by phenol-chloroform method and salting-out method was not significant in A260 (p>0.05, p=0.3549), but the difference between mean purity (A260/A280) of DNA extracted by phenol-chloroform method and salting-out method was significant (p<0.001). X chromosome fragment was detected in all 40 samples and Y chromosome fragments were detected in 25 plasma samples which were delivered a male calf. The sensitivity and specificity of test was 100% with no false negative and false positive results. The results showed that phenol-chloroform method is a simple and sensitive method for isolation of fetal DNA in maternal plasma. | 25,246,921 | [
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Investigation of the prevalence of female genital tract tuberculosis and its relation to female infertility:An observational analytical study. | Genital tuberculosis is a common entity in gynecological practice particularly among infertile patients. It is rare in developed countries but is an important cause of infertility in developing countries. The present study has investigated the prevalence of female genital tract tuberculosis (FGT) among infertile patients, which was conducted at the Obstetrics and Gynecology Unit-I, Allied Hospital, affiliated with Punjab Medical College, Faisalabad, Pakistan. 150 infertile women who were referred to infertility clinic were selected randomly and enrolled in our study. Patients were scanned for possible presence of FGT by examination and relevant investigation. We evaluated various aspects (age, symptoms, signs, and socio-economic factors) of the patients having tuberculosis. Very high frequency of FGT (20%) was found among infertile patients. While, a total of 25 patients out of 30 (83.33%) showed primary infertility and the remaining 5 cases (16.67%) had secondary infertility. Among secondary infertility patients, the parity ranged between 1 and 2. A total of 40% of patients (12 cases) were asymptomatic but infertile. Evidence of family history was found in 4 out of a total of 30 patients (13.3%), respectively. According to histopathological and bacteriological examination of endometrial biopsy and laparotomy, tuberculous endometritis was found in 20 out of a total of 25 (80%) cases, while tuberculous salpingitis and tuberculous oophoritis were found both in 2 (8%) of the cases, respectively. Only one case (4%) of tuberculosis cervicitis was found in the present study. Although infertility is not a disease in classical sense, but it is an extremely important personal concern for many couples and a significant health problem for our profession. So, it is worthwhile to identify and evaluate the factors contributing to infertility. | 25,246,930 | [
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Role of PPAR γ in the Differentiation and Function of Neurons. | Neuronal processes (neurites and axons) have an important role in brain cells communication and, generally, they are damaged in neurodegenerative diseases. Recent evidence has showed that the activation of PPARγ pathway promoted neuronal differentiation and axon polarity. In addition, activation of PPARγ using thiazolidinediones (TZDs) prevented neurodegeneration by reducing neuronal death, improving mitochondrial function, and decreasing neuroinflammation in neuropathic pain. In this review, we will discuss important evidence that supports a possible role of PPARγ in neuronal development, improvement of neuronal health, and pain signaling. Therefore, activation of PPARγ is a potential target with therapeutic applications against neurodegenerative disorders, brain injury, and pain regulation. | 25,246,934 | [
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Supercritical carbon dioxide: a solvent like no other. | Supercritical carbon dioxide (scCO2) could be one aspect of a significant and necessary movement towards green chemistry, being a potential replacement for volatile organic compounds (VOCs). Unfortunately, carbon dioxide has a notoriously poor solubilising power and is famously difficult to handle. This review examines attempts and breakthroughs in enhancing the physicochemical properties of carbon dioxide, focusing primarily on factors that impact solubility of polar and ionic species and attempts to enhance scCO2 viscosity. | 25,246,947 | [
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Relay cross metathesis reactions of vinylphosphonates. | Dimethyl (β-substituted) vinylphosphonates do not readily undergo cross metathesis reactions with Grubbs catalyst and terminal alkenes. However, the corresponding mono- or diallyl vinylphosphonate esters undergo facile cross metathesis reactions. The improved reactivity is attributed to a relay step in the cross metathesis reaction mechanism. | 25,246,952 | [
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Lateral ordering of PTCDA on the clean and the oxygen pre-covered Cu(100) surface investigated by scanning tunneling microscopy and low energy electron diffraction. | We have investigated the adsorption of perylene-3,4,9,10-tetracarboxylic acid dianhydride (PTCDA) on the clean and on the oxygen pre-covered Cu(100) surface [referred to as (√2 × 2√2)R45° - 2O/Cu(100)] by scanning tunneling microscopy (STM) and low energy electron diffraction (LEED). Our results confirm the (4√2 × 5√2)R45° superstructure of PTCDA/Cu(100) reported by A. Schmidt et al. [J. Phys. Chem. 1995, 99,11770-11779]. However, contrary to Schmidt et al., we have no indication for a dissociation of the PTCDA upon adsorption, and we propose a detailed structure model with two intact PTCDA molecules within the unit cell. Domains of high lateral order are obtained, if the deposition is performed at 400 K. For deposition at room temperature, a significant density of nucleation defects is found pointing to a strong interaction of PTCDA with Cu(100). Quite differently, after preadsorption of oxygen and formation of the (√2 × 2√2)R45° - 2O/Cu(100) superstructure on Cu(100), PTCDA forms an incommensurate monolayer with a structure that corresponds well to that of PTCDA bulk lattice planes. | 25,246,964 | [
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Second generation silver(I)-mediated imidazole base pairs. | The imidazole-Ag(I)-imidazole base pair is one of the best-investigated artificial metal-mediated base pairs. We show here that its stability can be further improved by formally replacing the imidazole moiety by a 2-methylimidazole or 4-methylimidazole moiety. A comparison of the thermal stability of several double helices shows that the addition of one equivalent of Ag(I) leads to a 50% larger increase in the melting temperature when a DNA duplex with methylated imidazole nucleosides is applied. This significant effect can likely be attributed to a better steric shielding of the metal ion within the metal-mediated base pair. | 25,246,972 | [
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Visible light photoredox-catalyzed deoxygenation of alcohols. | Carbon-oxygen single bonds are ubiquitous in natural products whereas efficient methods for their reductive defunctionalization are rare. In this work an environmentally benign protocol for the activation of carbon-oxygen single bonds of alcohols towards a reductive bond cleavage under visible light photocatalysis was developed. Alcohols were activated as 3,5-bis(trifluoromethyl)-substituted benzoates and irradiation with blue light in the presence of [Ir(ppy)2(dtb-bpy)](PF6) as visible light photocatalyst and Hünig's base as sacrificial electron donor in an acetonitrile/water mixture generally gave good to excellent yields of the desired defunctionalized compounds. Functional group tolerance is high but the protocol developed is limited to benzylic, α-carbonyl, and α-cyanoalcohols; with other alcohols a slow partial C-F bond reduction in the 3,5-bis(trifluoromethyl)benzoate moiety occurs. | 25,246,974 | [
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Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label. | DNA or its analogues with an environment-sensitive fluorescent label are potentially useful as a probe for studying the structure and dynamics of nucleic acids. In this work, pyrrolidinyl peptide nucleic acid (acpcPNA) was labeled at its backbone with Nile red, a solvatochromic benzophenoxazine dye, by means of click chemistry. The optical properties of the Nile red-labeled acpcPNA were investigated by UV-vis and fluorescence spectroscopy in the absence and in the presence of DNA. In contrast to the usual quenching observed in Nile red-labeled DNA, the hybridization with DNA resulted in blue shifting and an enhanced fluorescence regardless of the neighboring bases. More pronounced blue shifts and fluorescence enhancements were observed when the DNA target carried a base insertion in close proximity to the Nile red label. The results indicate that the Nile red label is located in a more hydrophobic environment in acpcPNA-DNA duplexes than in the single-stranded acpcPNA. The different fluorescence properties of the acpcPNA hybrids of complementary DNA and DNA carrying a base insertion are suggestive of different interactions between the Nile red label and the duplexes. | 25,246,975 | [
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Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)-adenine derivatives. | An investigation of the interactions of two novel and several known DBTAA-adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is in contrast to the majority of previously studied DBTAA analogues (DNA/RNA intercalators). Only DBTAA-propyladenine conjugates revealed the molecular recognition of AT-DNA by an ICD band pattern > 300 nm, whereas significant ICD bands did not appear for other ds-DNA/RNA. A structure-activity relation for the studied series of compounds showed that the essential structural features for the ICD recognition are a) the presence of DNA-binding appendages (adenine side chain and positively charged side chain) on both DBTAA side chains, and b) the presence of a short propyl linker, which does not support intramolecular aromatic stacking between DBTAA and adenine. The observed AT-DNA-ICD pattern differs from previously reported ss-DNA (poly dT) ICD recognition by a strong negative ICD band at 350 nm, which allows for the dynamic differentiation between ss-DNA (poly dT) and coupled ds-AT-DNA. | 25,246,976 | [
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A case of vasculitis, retinitis and macular neurosensory detachment presenting post typhoid fever. | Ocular and extraocular immune-mediated phenomena are known to occur following febrile illness. Vasculitis, retinitis and neurosensory detachment are not well-recognized sequelae of typhoid fever. We report a case of vasculitis, retinitis and macular neurosensory detachment presenting post typhoid fever. A 27-year-old female presented with decreased vision in right eye with history of typhoid fever (treated adequately 6 weeks prior). Her best corrected visual acuity in right eye was 20/125, N36. Fundus showed a patch of vasculitis and retinitis superior to the disc associated with macular neurosensory detachment and disc pallor. With oral steroids, the inflammation resolved and visual acuity improved to 20/20 at 6 weeks. Immune-mediated vasculitis and retinitis following typhoid fever may respond well to systemic steroids. | 25,246,983 | [
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Reducing the use of benzodiazepines and cyclopyrrolones in clinical practice. | Recently, the use of benzodiazepines (BZD) and cyclopyrrolones (CP) has drawn a great deal of attention. About 100,000 patients - approximately 2% of the Danish population - are believed to be addicted to BZD. This article describes a simple and effective method of reducing the use of dependency-producing drugs in clinical practice. Local rules were implemented according to Danish directive CIR nr 12 13/01/2003 regarding addictive drugs. Prescriptions for BZD and CP were only issued on a monthly basis, and only following personal consultation. This monthly requirement forced the physician as well as the patient to evaluate whether the existing prescription pattern was indicated, or whether a drug-reducing regime should be introduced. The prescription pattern was monitored using the Ordiprax System (Institute for Rational Pharmacotherapy, IRF), which records pharmacy's sales of prescription drugs as prescribed by clinical practices. Two individual clinics in Thyborøn - Harboøre Community, covering some 2300 patients, were surveyed. All patients using BZD or CP were included in this study, with the exception of patients suffering from serious psychiatric or physical disorders. After 15 months, the use of BZD and CP was reduced by 50% and 75%, respectively. The process of changing prescription habits was far easier than expected. A whole group of patients, initially invisible to the physician, was exposed. During the first three months, as few as 4-5 additional consultations for every 1000 patients was required. There was essentially no need for assistance from our usual partners, including psychiatrists, hospitals, specialist units for addictive treatment. We strongly recommend that these simple procedures be incorporated into daily routine when prescribing either a BD or a CP. | 25,247,003 | [
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Skeletal malocclusion: a developmental disorder with a life-long morbidity. | The likelihood of birth defects in orofacial tissues is high due to the structural and developmental complexity of the face and the susceptibility to intrinsic and extrinsic perturbations. Skeletal malocclusion is caused by the distortion of the proper mandibular and/or maxillary growth during fetal development. Patients with skeletal malocclusion may suffer from dental deformities, bruxism, teeth crowding, trismus, mastication difficulties, breathing obstruction and digestion disturbance if the problem is left untreated. In this review, we focused on skeletal malocclusion that affects 27.9% of the US population with different severity levels. We summarized the prevalence of class I, II and III of malocclusion in different ethnic groups and discussed the most frequent medical disorders associated with skeletal malocclusion. Dental anomalies that lead to malocclusion such as tooth agenesis, crowding, missing teeth and abnormal tooth size are not addressed in this review. We propose a modified version of malocclusion classification for research purposes to exhibit a clear distinction between skeletal vs. dental malocclusion in comparison to Angle's classification. In addition, we performed a cross-sectional analysis on orthodontic (malocclusion) data through the BigMouth Dental Data Repository to calculate potential association between malocclusion with other medical conditions. In conclusion, this review emphasizes the need to identify genetic and environmental factors that cause or contribute risk to skeletal malocclusion and the possible association with other medical conditions to improve assessment, prognosis and therapeutic approaches. | 25,247,012 | [
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BE-SAFE: Bedside sonography for assessment of the fetus in emergencies: educational intervention for late-pregnancy obstetric ultrasound. | Late obstetric emergencies are time critical presentations in the emergency department. Evaluation to ensure the safety of mother and child includes rapid assessment of fetal viability, fetal heart rate (FHR), fetal lie, and estimated gestational age (EGA). Point-of-care (POC) obstetric ultrasound (OBUS) offers the advantage of being able to provide all these measurements. We studied the impact of POC OBUS training on emergency physician (EP) confidence, knowledge, and OBUS skill performance on a live model. This is a prospective observational study evaluating an educational intervention we designed, called the BE-SAFE curriculum (BEdside Sonography for the Assessment of the Fetus in Emergencies). Subjects were a convenience sample of EP attendings (N=17) and residents (N=14). Prior to the educational intervention, participants completed a self-assessment survey on their confidence regarding OBUS, and took a pre-test to assess their baseline knowledge of OBUS. They then completed a 3-hour training session consisting of didactic and hands-on education in OBUS. After training, each subject's time and accuracy of performance of FHR, EGA, and fetal lie was recorded. Post-intervention knowledge tests and confidence surveys were administered. Results were compared with non-parametric t-tests. Pre- and post-test knowledge assessment scores for previously untrained EPs improved from 65.7% [SD=20.8] to 90% [SD=8.2] (p<0.0007). Self-confidence on a scale of 1-6 improved significantly for identification of FHR, fetal lie, and EGA. After training, the average times for completion of OBUS critical skills were as follows: cardiac activity (9s), FHR (68.6s), fetal lie (28.1s), and EGA (158.1 sec). EGA estimates averaged 28w0d (25w0d-30w6d) for the model's true gestational age of 27w0d. After a focused POC OBUS training intervention, the BE-SAFE educational intervention, EPs can accurately and rapidly use ultrasound to determine FHR, fetal lie, and estimate gestational age in mid-late pregnancy. | 25,247,032 | [
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Impact of post-intubation interventions on mortality in patients boarding in the emergency department. | Emergency physicians frequently perform endotracheal intubation and mechanical ventilation. The impact of instituting early post-intubation interventions on patients boarding in the emergency department (ED) is not well studied. We sought to determine the impact of post-intubation interventions (arterial blood gas sampling, obtaining a chest x-ray (CXR), gastric decompression, early sedation, appropriate initial tidal volume, and quantitative capnography) on outcomes of mortality, ventilator-associated pneumonia (VAP), ventilator days, and intensive care unit (ICU) length-of-stay (LOS). This was an observational, retrospective study of patients intubated in the ED at a large tertiary-care teaching hospital and included patients in the ED for greater than two hours post-intubation. We excluded them if they had incomplete data, were designated "do not resuscitate," were managed primarily by the trauma team, or had surgery within six hours after intubation. Of 169 patients meeting criteria, 15 died and 10 developed VAP. The mortality odds ratio (OR) in patients receiving CXR was 0.10 (95% CI 0.01 to 0.98), and 0.11 (95% CI 0.03 to 0.46) in patients receiving early sedation. The mortality OR for patients with 3 or fewer interventions was 4.25 (95% CI 1.15 to 15.75) when compared to patients with 5 or more interventions. There was no significant relationship between VAP rate, ventilator days, or ICU LOS and any of the intervention groups. The performance of a CXR and early sedation as well as performing five or more vs. three or fewer post-intubation interventions in boarding adult ED patients was associated with decreased mortality. | 25,247,049 | [
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Ultrasound detection of superior vena cava thrombus. | Superior vena cava (SVC) syndrome is most commonly the insidious result of decreased vascular flow through the SVC due to malignancy, spontaneous thrombus, infections, and iatrogenic etiologies. Clinical suspicion usually leads to computed tomography to confirm the diagnosis. However, when a patient in respiratory distress requires emergent airway management, travel outside the emergency department is not ideal. With the growing implementation of point-of-care ultrasound (POCUS), clinicians may make critical diagnoses rapidly and safely. We present a case of SVC syndrome due to extensive thrombosis of the deep venous system cephalad to the SVC diagnosed by POCUS. | 25,247,051 | [
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Mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes. | Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. | 25,247,053 | [
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Socioeconomic status does not predict cocaine use among ischemic stroke patients: A nested case-control study. | Previous studies of cocaine use and stroke have focused on acute effects of cocaine in perceived high-risk populations. We characterized mechanisms and risk factors for cocaine use among ischemic stroke patients from a broad range of socioeconomic backgrounds to inform medical management decisions and prevention efforts. We studied consecutive adults admitted with acute ischemic stroke to our institution between January 2007 and December 2010 with a history or laboratory confirmation of cocaine use. Age, sex, and race-matched cocaine-negative controls were derived from the same study population. Demographics, risk factors, clinical and imaging data were compared between groups. Among 4073 acute ischemic stroke patients, 91 (2.2%) had a history of cocaine use and/or a positive toxicology screen (cases). Cocaine abusers did not differ from controls by occupation, income, or educational level (P > 0.5). Active tobacco use independently increased the odds of cocaine use among stroke patients (odds ratio 3.9, 95% confidence interval 2.0-7.5), as did the history of migraine (odds ratio 2.5, 95% confidence interval 1.1-5.9). Stroke subtype also predicted cocaine use among stroke patients (odds ratio 0.73, 95% confidence interval 0.58-0.93). Stroke patients with current or past cocaine use could not be distinguished from non-users by socioeconomic factors. Liberal use of toxicology screening among a much broader population of patients is needed for proper identification and management. Further study of causal mechanisms for cardioembolism in cocaine-associated stroke is warranted. | 25,247,073 | [
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Gasless minimum incision access used for extracorporeal orthotopic bladder substitution after laparoscopic radical cystectomy. | Radical cystectomy is the gold standard for treating invasive bladder cancer. We report our outcomes of gasless minimum incision access (GMIA) for extracorporeal orthotopic bladder substitution (ECOBS) after laparoscopic radical cystectomy. Radical surgery was performed in patients in the same hospital suffering from bladder cancer in T2N0M0 G1-2 stage. Group 1 included 11 patients aged 56.6 (42-72) years, which underwent laparoscopic radical cystectomy and ECOBS using GMIA. Group 2 included 18 patients aged 56.7 (41-76) years, which were operated by open radical cystectomy and orthotopic bladder substitution. The average duration of operation was 492.0 ±85.7 minutes in Group 1 and 318.0 ±58.0 in Group 2 (p = 0.001). Estimated blood loss was 290.0 ±120.0 and 613.2 ±359.0 ml in groups respectively. In the postoperative period, narcotic analgesics were used in the amount of 166.0 ±28.0 mg and 264.0 ±112.0 mg (p = 0.05), intestinal function recovery was observed on 3.5 ±0.9 and 6.0 ±2.9 days after the operation (p = 0.05) in the groups respectively. Minor postoperative complications were observed in 36.4% and 56.0%, major complications - in 9.1% and 11.2% in groups respectively. Median hospitalization time was 19.0 ±2.0 days in Group 1 and 24.9 ±6.5 in Group 2 (p = 0.01). GMIA in ECOBS can be used as an effective surgical approach after laparoscopic radical cystectomy; this method requires further observation. | 25,247,092 | [
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Nano-rings with a handle - Synthesis of substituted cycloparaphenylenes. | The research of cycloparaphenylenes (CPPs), the smallest armchair carbon nanotube, has been a quest for the past decades which experienced a revival in 2008 when the first synthesis was achieved. Since then CPPs with various ring sizes have been realized. The incorporation of substituents and the synthesis of CPPs with building blocks different from phenyl rings bear challenges of their own. Such structures, however, are highly interesting, as they allow for an incorporation of CPPs as defined nano-objects for other applications. Therefore, this review provides a status report about the current efforts in synthesizing CPPs beyond the parent unsubstituted oligo-phenylene structure. | 25,247,115 | [
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Liquid fuel cells. | The advantages of liquid fuel cells (LFCs) over conventional hydrogen-oxygen fuel cells include a higher theoretical energy density and efficiency, a more convenient handling of the streams, and enhanced safety. This review focuses on the use of different types of organic fuels as an anode material for LFCs. An overview of the current state of the art and recent trends in the development of LFC and the challenges of their practical implementation are presented. | 25,247,123 | [
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The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver. | Semiconductor quantum dots (QD) and superparamagnetic iron oxide nanocrystals (SPIO) have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an important entry route into the human body. Therefore, it is crucial to investigate biological responses of the body to nanocrystals to avoid harmful side effects. In recent years, we established a system to embed nanocrystals with a hydrophobic oleic acid shell either by lipid micelles or by the amphiphilic polymer poly(maleic anhydride-alt-1-octadecene) (PMAOD). The goal of the current study is to investigate the uptake processes as well as pro-inflammatory responses in the liver after the injection of these encapsulated nanocrystals. By immunofluorescence and electron microscopy studies using wild type mice, we show that 30 min after injection polymer-coated nanocrystals are primarily taken up by liver sinusoidal endothelial cells. In contrast, by using wild type, Ldlr (-/-) as well as Apoe (-/-) mice we show that nanocrystals embedded within lipid micelles are internalized by Kupffer cells and, in a process that is dependent on the LDL receptor and apolipoprotein E, by hepatocytes. Gene expression analysis of pro-inflammatory markers such as tumor necrosis factor alpha (TNFα) or chemokine (C-X-C motif) ligand 10 (Cxcl10) indicated that 48 h after injection internalized nanocrystals did not provoke pro-inflammatory pathways. In conclusion, internalized nanocrystals at least in mouse liver cells, namely endothelial cells, Kupffer cells and hepatocytes are at least not acutely associated with potential adverse side effects, underlining their potential for biomedical applications. | 25,247,125 | [
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Near-field photochemical and radiation-induced chemical fabrication of nanopatterns of a self-assembled silane monolayer. | A general concept for parallel near-field photochemical and radiation-induced chemical processes for the fabrication of nanopatterns of a self-assembled monolayer (SAM) of (3-aminopropyl)triethoxysilane (APTES) is explored with three different processes: 1) a near-field photochemical process by photochemical bleaching of a monomolecular layer of dye molecules chemically bound to an APTES SAM, 2) a chemical process induced by oxygen plasma etching as well as 3) a combined near-field UV-photochemical and ozone-induced chemical process, which is applied directly to an APTES SAM. All approaches employ a sandwich configuration of the surface-supported SAM, and a lithographic mask in form of gold nanostructures fabricated through colloidal sphere lithography (CL), which is either exposed to visible light, oxygen plasma or an UV-ozone atmosphere. The gold mask has the function to inhibit the photochemical reactions by highly localized near-field interactions between metal mask and SAM and to inhibit the radiation-induced chemical reactions by casting a highly localized shadow. The removal of the gold mask reveals the SAM nanopattern. | 25,247,126 | [
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Microarray Analysis of Gene Expression Reveals that Cyclo-oxygenase-2 Gene Therapy Up-regulates Hematopoiesis and Down-regulates Inflammation During Endochondral Bone Fracture Healing. | Cyclo-oxygenase-2 (Cox-2) is an inflammatory mediator that is necessary for the tissue repair, including bone fracture healing. Although the application of Cox-2 gene therapy to a murine closed femoral fracture has accelerated bony union, but the beneficial effect was not observed until the endochondral stage of bone repair that is well after the inflammatory stage normally subsides. To identify the molecular pathways through which Cox-2 regulates fracture healing, we examined gene expression profile in fracture tissues in response to Cox-2 gene therapy during the endochondral bone repair phase. Cox-2 gene therapy was applied to the closed murine femur fracture model. Microarray analysis was performed at 10 days post-fracture to examine global gene expression profile in the fracture tissues during the endochondral bone repair phase. The entire repertoire of significantly expressed genes was examined by gene set enrichment analysis, and the most up-regulated individual genes were evaluated further. The genes that normally promote inflammation were under-represented in the microarray analysis, and the expression of several inflammatory chemokines was significantly down-regulated. There was an up-regulation of two key transcription factor genes that regulate hematopoiesis and erythropoiesis. More surprisingly, there was no significant up-regulation in the genes that are normally involved in angiogenesis or bone formation. However, the expression of two tissue remodeling genes was up-regulated. The down-regulation of the inflammatory genes in response to Cox-2 gene therapy was unexpected, given the pro-inflammatory role of prostaglandins. Cox-2 gene therapy could promote bony union through hematopoietic precursor proliferation during endochondral bone repair and thereby enhances subsequently fracture callus remodeling that leads to bony union of the fracture gap. | 25,247,155 | [
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Efficacy of Dual Energy X-ray Absorptiometry for Evaluation of Biomechanical Properties: Bone Mineral Density and Actual Bone Strength. | Bone mineral density (BMD) is an important index in diagnosis of osteoporosis and other metabolic bone diseases, prediction of fractures, and monitoring treatment. This study was to find a more feasible technique for prediction of osteoporotic fracture between dual energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and to reveal the actual change of bone strength when BMD was changed. Ten of these 20 specimens were used as the demineralized group and the other 10 as the control. Each specimen was immersed in HCl solution at for a period of at least 10 minutes, up to 100 minutes, at an interval of 10 minutes for different levels of demineralization. BMD was measured using DXA and QCT. Uniaxial compression tests were conducted to measure biomechanical parameters. Pearson correlation analysis was used respectively between BMD and biomechanical parameters and between DXA and QCT. Elastic modulus (r=0.87) and yield stress (r=0.84) showed a statistically significant correlation with DXA BMD. Through correlation analysis with QCT BMD and elastic modulus, correlation coefficient showed hemi-vertebra (r=0.80) and trabecular (r=0.68). In yield stress, there was a statistically significant correlation in hemi-vertebra (r=0.87) and trabecular bone (r=0.84). DXA is a current standard technique not only for diagnosis of osteoporosis but also for prediction of fracture risk compared to QCT. Actual decrease of bone strength was much greater than that of BMD by both DXA and QCT. | 25,247,158 | [
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Study of the polycarbonate-urethane/metal contact in different positions during gait cycle. | Nowadays, a growing number of young and more active patients receive hip replacement. More strenuous activities in such patients involve higher friction and wear rates, with friction on the bearing surface being crucial to ensure arthroplasty survival in the long term. Over the last years, the polycarbonate-urethane has offered a feasible alternative to conventional bearings. A finite element model of a healthy hip joint was developed and adjusted to three gait phases (heel strike, mid-stance, and toe-off), serving as a benchmark for the assessment of the results of joint replacement model. Three equivalent models were made with the polycarbonate-urethane Tribofit system implanted, one for each of the three gait phases, after reproducing a virtual surgery over the respective healthy models. Standard body-weight loads were considered: 230% body-weight toe-off, 275% body-weight mid-stance, and 350% body-weight heel strike. Contact pressures were obtained for the different models. When comparing the results corresponding to the healthy model to polycarbonate-urethane joint, contact areas are similar and so contact pressures are within a narrower value range. In conclusion, polycarbonate-urethane characteristics are similar to those of the joint cartilage. So, it is a favorable alternative to traditional bearing surfaces in total hip arthroplasty, especially in young patients. | 25,247,180 | [
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Clinical correlates of Hachinski ischemic score and vascular factors in cognitive function of elderly. | The aim of this study is to investigate the relationship between Hachinski ischemic score (HIS) and vascular factors as well as between HIS and the cognitive function in elderly community. Demographic characteristics, such as sex, age, education, history of drinking and smoking, family history of dementia and stroke, diabetes mellitus, hypertension, hyperlipidemia, cardiovascular disease, stroke, and dementia, were surveyed. Neurological examination was administered to every subject and HIS was checked by a neurologist. From a total of 392 participants aged 65 and over in a rural community, 348 completed the survey and were finally enrolled. Among the vascular factors, history of hypertension (P = 0.008), history of stroke (P < 0.001), family history of dementia (P = 0.01), and history of cardiac diseases (P = 0.012) showed a significant relationship with HIS. In the cognitive function tests, both Korean version of the Mini-Mental State Examination and the Clinical Dementia Rating (Global and Sum of Boxes) had a significant relationship with HIS. Our study suggested HIS may have an association with some vascular factors and cognitive scales in community dwelling elderly. In this study, the HIS seemed to contribute to the evaluation of the quantity of vascular factors and to the prediction of status of cognitive function. | 25,247,189 | [
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One adaptive synchronization approach for fractional-order chaotic system with fractional-order 1 < q < 2. | Based on a new stability result of equilibrium point in nonlinear fractional-order systems for fractional-order lying in 1 < q < 2, one adaptive synchronization approach is established. The adaptive synchronization for the fractional-order Lorenz chaotic system with fractional-order 1 < q < 2 is considered. Numerical simulations show the validity and feasibility of the proposed scheme. | 25,247,207 | [
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Anticipatory looks reveal expectations about discourse relations. | Previous research provides evidence for expectation-driven processing within sentences at phonological, lexical, and syntactic levels of linguistic structure. Less well-established is whether comprehenders also anticipate pragmatic relationships between sentences. To address this, we evaluate a unit of discourse structure that comprehenders must infer to hold between sentences in order for a discourse to make sense-the intersentential coherence relation. In a novel eyetracking paradigm, we trained participants to associate particular spatial locations with particular coherence relations. Experiment 1 shows that the subset of listeners who successfully acquired the location∼relation mappings during training subsequently looked to these locations during testing in response to a coherence-signaling intersentential connective. Experiment 2 finds that listeners' looks during sentences containing coherence-biasing verbs reveal expectations about upcoming sentence types. This work extends existing research on prediction beyond sentence-internal structure and provides a new methodology for examining the cues that comprehenders use to establish relationships at the discourse level. | 25,247,235 | [
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Zinc-specific intramolecular excimer formation in TQEN derivatives: fluorescence and zinc binding properties of TPEN-based hexadentate ligands. | Zn(2+)-induced fluorescence enhancement of the TPEN (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine)-based ligand, N,N-bis(1-isoquinolylmethyl)-N',N'-bis(pyridylmethyl)ethylenediamine (N,N-1-isoBQBPEN, 1b), has been investigated. Upon Zn(2+) binding, 1b shows a fluorescence increase (ϕZn = 0.028) at 353 and 475 nm. The fluorescence enhancement at longer wavelengths is due to intramolecular excimer formation of two isoquinolines and is specific for Zn(2+); Cd(2+) induces very small fluorescence at 475 nm (ICd/IZn = 10%). The excimer formation of the [Zn(1b)](2+) complex in the excited state is supported by the time-dependent DFT calculation. Neither long-wavelength fluorescence nor excimer formation is observed in the Zn(2+) complex of N,N'-1-isoBQBPEN (2b). The quinoline analog N,N-BQBPEN (1a) exhibits similar but significantly smaller excimer formation. Thermodynamic and kinetic comparisons of Zn(2+) binding properties of ethylenediamine-based hexadentate ligands with pyridines and (iso)quinolines are comprehensively discussed. | 25,247,241 | [
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Long-term outcomes after revision neural decompression and fusion for same-level recurrent lumbar stenosis: defining the effectiveness of surgery. | Single-cohort study of patients undergoing revision neural decompression and fusion for same-level recurrent lumbar stenosis. To assess the long-term outcomes of revision surgery using validated patient-reported outcomes measures. Recurrent lumbar stenosis may occur after lumbar spine surgery, leading to significant discomfort and radicular pain. Although numerous studies have reported clinical outcomes after primary lumbar surgery, there remains a paucity of data on the outcomes after revision surgery for recurrent same-level stenosis. Fifty-three patients undergoing revision neural decompression and instrumented fusion for same-level recurrent stenosis-associated back and leg pain were included in this study. Baseline and 2-year visual analog scale for leg pain (LP-VAS), visual analog scale for low back pain (BP-VAS), Oswestry Disability Index (ODI), Zung self-reported depression score (ZDS), time to narcotic independence, time to return to work, health-state utility [EuroQol (EQ-5D)], and physical and mental quality of life [SF-12 physical and mental component scores (PCS and MCS)] were assessed. Mean±SD duration of time between index surgery and revision surgery was 4.00±4.19 years. A significant improvement from baseline was observed in BP-VAS (9.28±1.01 vs. 5.00±2.94, P=0.001), LP-VAS (9.55±0.93 vs. 3.45±2.95, P=0.001), and ODI (36.02±6.01 vs. 21.75±12.08, P=0.001). Mean±SD SF-12 PCS (7.17±11.22, P=0.001), SF-12 MCS (12.57±13.03, P=0.001), ZDS (12.37±16.80, P=0.001), and EQ-5D (0.42±0.34, P=0.001) were also significantly improved. The mean cumulative 2-year gain in health-utility state was 0.84 QALY. Median (interquartile range) duration of postoperative narcotic use was 6 (1.4-12.2) months and time of missed work was 6 (4.0-10.0) months. Our study suggests that revision neural decompression and instrumented fusion for recurrent same-level stenosis provides significant improvement in all patient-assessed outcome metrics and should be offered as a viable treatment option. | 25,247,253 | [
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The adsorption of ochratoxin a by lactobacillus species. | The objective of this study was to examine ochratoxin A (OTA) binding by three lactic acid bacteria (LAB) species: Lactobacillus plantarum, L. brevis, and L. sanfranciscensis. Experiments were conducted using MRS medium and PBS buffer contaminated with 1000 ng/mL OTA and inoculated with live or thermally inactivated bacterial biomass at a concentration of 1 or 5 mg dry weight/mL. It was found that, depending on the strain and biomass density, live bacterial cells reduced OTA content by 16.9% to 35% in MRS medium and by 14.8% to 26.4% in PBS after 24 h of contact. OTA binding was higher in the case of thermally inactivated bacterial biomass (46.2% to 59.8%). The process is very rapid: OTA was removed from PBS as early as after 30 min of contact. The binding of the toxin by cells was partially reversible under the treatment by water and 1 M HCl. The results show that OTA is adsorbed to the surface structures of the cell wall, which is promoted not only by the hydrophobic properties of the cell wall, but also by electron donor-acceptor and Lewis acid-base interactions. | 25,247,265 | [
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FDG PET/CT images demonstrating epididymo-orchitis in a patient with HIV, acute kidney injury and known epididymo-orchitis on scrotal ultrasound. | A 52-year-old man with HIV was referred for an F-FDG PET/CT scan for the cause of kidney injury. FDG PET/CT scan revealed increased renal cortical FDG activity, which can be seen in HIV nephropathy or acute interstitial nephritis. Diffuse increased FDG uptake was demonstrated within the right testicle and epididymis, consistent with the patient's known right epididymo-orchitis, as diagnosed on ultrasound 1 week before admission. Multiple enlarged lymph nodes with increased FDG activity were also found within the right inguinal and external iliac nodal chains, which were presumed to be reactive. The patient was treated with ciprofloxacin with symptomatic improvement. | 25,247,269 | [
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High systemic levels of the cytokine-inducing HMGB1 isoform secreted in severe macrophage activation syndrome. | Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic inflammation. High mobility group box 1 (HMGB1) is a nuclear protein extensively leaked extracellularly during necrotic cell death or actively secreted by natural killer (NK) cells, macrophages and additional cells during infection or sterile injury. Extracellular HMGB1 orchestrates key events in inflammation as a prototypic alarmin. The redox states of its three cysteines render the molecule mutually exclusive functions: fully reduced "all-thiol HMGB1" exerts chemotactic activity; "disulfide HMGB1" has cytokine-inducing, toll-like receptor 4 (TLR4)-mediated effects—while terminally oxidized "sulfonyl HMGB1" lacks inflammatory activity. This study examines the kinetic pattern of systemic HMGB1 isoform expression during therapy in four children with severe MAS. Three of the four patients with underlying systemic rheumatic diseases were treated with biologics and two suffered from triggering herpes virus infections at the onset of MAS. All patients required intensive care unit therapy due to life-threatening illness. Tandem mass-spectrometric analysis revealed dramatically increased systemic levels of the cytokine-inducing HMGB1 isoform during early MAS. Disease control coincided with supplementary etoposide therapy initiated to boost apoptotic cell death, when systemic HMGB1 levels drastically declined and the molecule emerged mainly in its oxidized, noninflammatory isoform. Systemic interferon (IFN)-γ and ferritin peaked concomitantly with HMGB1, whereas interleukin (IL)-18 and monocyte chemotactic protein (MCP)-1 levels developed differently. In conclusion, this work provides new insights in HMGB1 biology, suggesting that the molecule is not merely a biomarker of inflammation, but most likely also contributes to the pathogenesis of MAS. These observations encourage further studies of disulfide HMGB1 antagonists to improve outcome of MAS. | 25,247,290 | [
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Benchmarking undedicated cloud computing providers for analysis of genomic datasets. | A major bottleneck in biological discovery is now emerging at the computational level. Cloud computing offers a dynamic means whereby small and medium-sized laboratories can rapidly adjust their computational capacity. We benchmarked two established cloud computing services, Amazon Web Services Elastic MapReduce (EMR) on Amazon EC2 instances and Google Compute Engine (GCE), using publicly available genomic datasets (E.coli CC102 strain and a Han Chinese male genome) and a standard bioinformatic pipeline on a Hadoop-based platform. Wall-clock time for complete assembly differed by 52.9% (95% CI: 27.5-78.2) for E.coli and 53.5% (95% CI: 34.4-72.6) for human genome, with GCE being more efficient than EMR. The cost of running this experiment on EMR and GCE differed significantly, with the costs on EMR being 257.3% (95% CI: 211.5-303.1) and 173.9% (95% CI: 134.6-213.1) more expensive for E.coli and human assemblies respectively. Thus, GCE was found to outperform EMR both in terms of cost and wall-clock time. Our findings confirm that cloud computing is an efficient and potentially cost-effective alternative for analysis of large genomic datasets. In addition to releasing our cost-effectiveness comparison, we present available ready-to-use scripts for establishing Hadoop instances with Ganglia monitoring on EC2 or GCE. | 25,247,298 | [
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Genetic diversity and levels of expression of factor H binding protein among carriage isolates of Neisseria meningitidis. | The prevention of meningococcal disease may be improved by recombinant vaccines such as 4CMenB and rLP2086 that target the factor H binding protein (fHbp), an immunogenic surface component of Neisseria meningitidis present as one of three variants. Whether such vaccines decrease carriage of invasive isolates and thus induce herd immunity is unknown. We analyzed the genetic diversity and levels of expression of fHbp among 268 carriage strains and compare them to those of 467 invasive strains. fhbp gene sequencing showed higher proportions of variants 2 and 3 among carriage isolates (p<0.0001). Carriage isolates expressed lower levels of fHbp (p<0.01) but that remain high enough to predict targeting by antibodies against fHbp particularly in group B isolates belonging to the frequent hypervirulent clonal complexes in Europe and North America (cc32, cc41/44, cc269). This suggests that fHbp targeting meningococcal vaccines might reduce, at least in part, the acquisition of some hyperinvasive isolates. | 25,247,300 | [
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Fluorescent bilayer nanocoils assembled from an asymmetric perylene diimide molecule with ultrasensitivity for amine vapors. | Highly fluorescent bilayer nanocoils assembled from an asymmetric perylene diimide molecule exhibit unprecedented sensitivity to trace amines, that is, three orders of magnitude greater than our previously reported solid nanofibers. The coiled nanostructure design for new sensing materials offers a novel option for optimizing the sensitivities of fluorescence sensors based on organic nanomaterials. | 25,247,350 | [
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Human evolution: genomic gifts from archaic hominins. | The dispersal of humans throughout the world was accompanied by adaptations to local environments. New research shows that a previously identified haplotype of the EPAS1 gene, which allows Tibetans to live at high altitude, was inherited from archaic hominin ancestors. | 25,247,359 | [
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It's all about the constraints. | Our ever-growing knowledge about the human brain and human behavior is opening doors to increasingly impressive technological achievements. This neurobiological inspiration has a significant history and involves almost equal parts neuroscience, computation and art. With a focus on the sense of vision, this essay presents a selective and highly condensed snapshot of the history of how neurobiology has inspired technological developments, pointing the way to where new inspirations may lead. | 25,247,361 | [
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... |
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