title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
|---|---|---|---|
Modeling companion diagnostics in economic evaluations of targeted oncology therapies: systematic review and methodological checklist. | The successful use of a targeted therapy is intrinsically linked to the ability of a companion diagnostic to correctly identify patients most likely to benefit from treatment. The aim of this study was to review the characteristics of companion diagnostics that are of importance for inclusion in an economic evaluation. Approaches for including these characteristics in model-based economic evaluations are compared with the intent to describe best practice methods. Five databases and government agency websites were searched to identify model-based economic evaluations comparing a companion diagnostic and subsequent treatment strategy to another alternative treatment strategy with model parameters for the sensitivity and specificity of the companion diagnostic (primary synthesis). Economic evaluations that limited model parameters for the companion diagnostic to only its cost were also identified (secondary synthesis). Quality was assessed using the Quality of Health Economic Studies instrument. 30 studies were included in the review (primary synthesis n = 12; secondary synthesis n = 18). Incremental cost-effectiveness ratios may be lower when the only parameter for the companion diagnostic included in a model is the cost of testing. Incorporating the test's accuracy in addition to its cost may be a more appropriate methodological approach. Altering the prevalence of the genetic biomarker, specific population tested, type of test, test accuracy and timing/sequence of multiple tests can all impact overall model results. The impact of altering a test's threshold for positivity is unknown as it was not addressed in any of the included studies. Additional quality criteria as outlined in our methodological checklist should be considered due to the shortcomings of standard quality assessment tools in differentiating studies that incorporate important test-related characteristics and those that do not. There is a need to refine methods for incorporating the characteristics of companion diagnostics into model-based economic evaluations to ensure consistent and transparent reimbursement decisions are made. | 25,142,227 | [
-0.06200324,
0.09997495,
-0.04387657,
-0.3664812,
0.008187071,
-0.1279574,
0.02916006,
0.1720399,
0.32606,
-0.02713419,
-0.09548227,
0.1822135,
0.1048367,
-0.1561824,
-0.172032,
0.03865827,
-0.3972587,
0.07354331,
-0.06352514,
0.1363288,
0.13771,
0.1057737,
-0.1052304,
... |
Immunization with a novel chimeric peptide representing B and T cell epitopes from HER2 extracellular domain (HER2 ECD) for breast cancer. | Because of direct stimulating immune system against disease, vaccination or active immunotherapy is preferable compared to passive immunotherapy. For this purpose, a newly designed chimeric peptide containing epitopes for both B and T cells from HER2 ECD subdomain III was proposed. To evaluate the effects of the active immunization, a discontinuous B cell epitope peptide was selected based on average antigenicity by bioinformatics analysis. The selected peptide was collinearly synthesized as a chimera with a T helper epitope from the protein sequence of measles virus fusion (208-302) using the GPSL linker. Three mice were immunized with the chimeric peptide. Reactive antibodies with HER2 protein in ELISA and immunofluorescence assays with no cross-reactivity were generated. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay indicated that the anti-peptide sera had inhibitory effects on proliferation of SK-BR-3 cells. Hence, the newly designed, discontinuous chimeric peptide representing B and T cell epitopes from subdomain III of HER2-ECD can form the basis for future vaccines design, where these data can be applied for monoclonal antibody production targeting the distinct epitope of HER2 receptor compared to the two broadly used anti-HER2 monoclonal antibodies, Herceptin and pertuzumab. | 25,142,233 | [
0.007496058,
-0.3991554,
-0.05538836,
-0.01252954,
0.009347019,
-0.08557432,
0.04456139,
0.4450471,
-0.04302648,
0.1737829,
-0.1901638,
0.4307424,
0.06563419,
0.341558,
-0.2735942,
-0.1232596,
-0.4222812,
0.1250451,
-0.2060486,
0.1246874,
0.3929248,
0.01219065,
-0.0717221... |
Tacrolimus pharmacodynamics and pharmacogenetics along the calcineurin pathway in human lymphocytes. | Although therapeutic drug monitoring has improved the clinical use of immunosuppressive drugs, there is still interpatient variability in efficacy and toxicity that pharmacodynamic monitoring may help to reduce. To select the best biomarkers of tacrolimus pharmacodynamics, we explored the strength and variability of signal transduction and the influence of polymorphisms along the calcineurin pathway. Peripheral blood mononuclear cells from 35 healthy volunteers were incubated with tacrolimus (0.1-50 ng/mL) and stimulated ex vivo. Inhibition of NFAT1 (nuclear factor of activated T cells 1) translocation to the nucleus and intracellular expression of interleukin-2 in CD4(+) and CD8(+) T cells and the surface activation marker CD25 in CD3(+) cells were measured by flow cytometry. We sequenced the promoter regions of immunophilins and calcineurin subunits and characterized selected single nucleotide polymorphisms in the genes of the calcineurin pathway with allelic discrimination assays. All responses closely fitted an I/Imax sigmoid model. Large interindividual variability (n = 30) in I0 and IC50 was found for all biomarkers. Moreover, strong and statistically significant associations were found between tacrolimus pharmacodynamic parameters and polymorphisms in the genes coding cyclophilin A, the calcineurin catalytic subunit α isoenzyme, and CD25. This study demonstrates the consistency and large interindividual variability of signal transduction along the calcineurin pathway, as well as the strong influence of pharmacogenetic polymorphisms in the calcineurin cascade on both the physiological activity of this route and tacrolimus pharmacodynamics. | 25,142,246 | [
-0.07272296,
-0.1972215,
-0.2554529,
-0.1939289,
0.1147167,
-0.1891181,
-0.2094663,
0.1959052,
0.0593168,
-0.1172022,
0.08361938,
-0.533844,
0.01021198,
-0.07403202,
-0.3988131,
-0.1187738,
-0.4842945,
-0.2398479,
-0.05065969,
0.4385019,
0.3841958,
0.4648403,
0.1202798,
... |
College Students: Mental Health Problems and Treatment Considerations. | Attending college can be a stressful time for many students. In addition to coping with academic pressure, some students have to deal with the stressful tasks of separation and individuation from their family of origin while some may have to attend to numerous work and family responsibilities. In this context, many college students experience the first onset of mental health and substance use problems or an exacerbation of their symptoms. Given the uniqueness of college students, there is a need to outline critical issues to consider when working with this population. In this commentary, first, the prevalence of psychiatric and substance use problems in college students and the significance of assessing age of onset of current psychopathology are described. Then, the concerning persistent nature of mental health problems among college students and its implications are summarized. Finally, important aspects of treatment to consider when treating college students with mental health problems are outlined, such as the importance of including parents in the treatment, communicating with other providers, and employing of technology to increase adherence. It is concluded that, by becoming familiar with the unique problems characteristic of the developmental stage and environment college students are in, practitioners will be able to better serve them. | 25,142,250 | [
-0.2085339,
0.2618532,
0.04693804,
0.03358497,
0.006413808,
-0.1903816,
-0.2432349,
-0.06971503,
-0.08051773,
0.1324498,
0.141597,
-0.2871762,
-0.235377,
-0.01378213,
-0.3554228,
-0.01555097,
0.1195639,
0.2918305,
-0.0685158,
-0.1410816,
0.0145586,
0.2629934,
-0.1714316,
... |
Distal femoral osteotomy. | Osteotomies around the knee are well-recognized treatments for unloading the affected compartment in cases of lower limb malalignment. There are few papers in the literature describing the outcomes of distal femoral osteotomy (DFO), as compared with the studies reporting on high tibial osteotomy (HTO), probably because valgus malalignment is less common than the varus one. There is still debate as to what the correct indication is and which surgical techniques lead to the best outcomes in performing a DFO. Besides, it is still controversial whether patellofemoral arthritis should be considered as a contraindication to performing a DFO, as well as in HTO. In this article, we will summarize the indications for DFO, the surgical techniques reported in the literature, and their outcomes. | 25,142,271 | [
-0.01585233,
0.06984363,
0.2529275,
-0.2518048,
-0.09910028,
-0.1557494,
-0.01007956,
0.2363475,
-0.4394253,
0.06072646,
0.255518,
-0.2385621,
-0.1132907,
-0.114341,
-0.2529247,
-0.5235671,
-0.07697351,
0.5244608,
-0.2787141,
-0.2772821,
-0.3216852,
0.04416196,
-0.0840197... |
Distribution of ether lipids and composition of the archaeal community in terrestrial geothermal springs: impact of environmental variables. | Archaea can respond to changes in the environment by altering the composition of their membrane lipids, for example, by modification of the abundance and composition of glycerol dialkyl glycerol tetraethers (GDGTs). Here, we investigated the abundance and proportions of polar GDGTs (P-GDGTs) and core GDGTs (C-GDGTs) sampled in different seasons from Tengchong hot springs (Yunnan, China), which encompassed a pH range of 2.5-10.1 and a temperature range of 43.7-93.6°C. The phylogenetic composition of the archaeal community (reanalysed from published work) divided the Archaea in spring sediment samples into three major groups that corresponded with spring pH: acidic, circumneutral and alkaline. Cluster analysis showed correlation between spring pH and the composition of P- and C-GDGTs and archaeal 16S rRNA genes, indicating an intimate link between resident Archaea and the distribution of P- and C-GDGTs in Tengchong hot springs. The distribution of GDGTs in Tengchong springs was also significantly affected by temperature; however, the relationship was weaker than with pH. Analysis of published datasets including samples from Tibet, Yellowstone and the US Great Basin hot springs revealed a similar relationship between pH and GDGT content. Specifically, low pH springs had higher concentrations of GDGTs with high numbers of cyclopentyl rings than neutral and alkaline springs, which is consistent with the predominance of high cyclopentyl ring-characterized Sulfolobales and Thermoplasmatales present in some of the low pH springs. Our study suggests that the resident Archaea in these hot springs are acclimated if not adapted to low pH by their genetic capacity to effect the packing density of their membranes by increasing cyclopentyl rings in GDGTs at the rank of community. | 25,142,282 | [
0.3026552,
0.3645363,
-0.1473254,
0.1849995,
-0.4128346,
-0.1058931,
-0.3723434,
0.1974571,
0.08511724,
-0.1753786,
-0.1402472,
-0.4282294,
-0.224496,
0.1489724,
-0.4592457,
-0.09591955,
-0.0457205,
0.1140325,
0.1532223,
0.203899,
0.1541995,
0.4629955,
-0.392314,
0.1172... |
IL-15-dependent CD8+ CD122+ T cells ameliorate experimental autoimmune encephalomyelitis by modulating IL-17 production by CD4+ T cells. | Interleukin-15 (IL-15) is an inflammatory cytokine whose role in autoimmune diseases has not been fully elucidated. Th17 cells have been shown to play critical roles in experimental autoimmune encephalomyelitis (EAE) models. In this study, we demonstrate that blockade of IL-15 signaling by TMβ-1 mAb treatment aggravated EAE severity. The key mechanism was not NK-cell depletion but depletion of CD8+ CD122+ T cells. Adoptive transfer of exogenous CD8+ CD122+ T cells to TMβ-1-treated mice rescued animals from severe disease. Moreover, transfer of preactivated CD8+ CD122+ T cells prevented EAE development and significantly reduced IL-17 secretion. Naïve effector CD4+ CD25- T cells cultured with either CD8+ CD122+ T cells from wild-type mice or IL-15 transgenic mice displayed lower frequencies of IL-17A production with lower amounts of IL-17 in the supernatants when compared with production by effector CD4+ CD25- T cells cultured alone. Addition of a neutralizing antibody to IL-10 led to recovery of IL-17A production in Th17 cultures. Furthermore, coculture of CD8+ CD122+ T cells with effector CD4+ T cells inhibited their proliferation significantly, suggesting a regulatory function for IL-15 dependent CD8+ CD122+ T cells. Taken together, these observations suggest that IL-15, acting through CD8+ CD122+ T cells, has a negative regulatory role in reducing IL-17 production and Th17-mediated EAE inflammation. | 25,142,300 | [
-0.3497988,
-0.537148,
-0.1942234,
-0.2598445,
-0.004599874,
-0.1157652,
0.06477206,
0.2752803,
-0.2430046,
-0.3013204,
-0.1725583,
0.2437018,
-0.01584356,
-0.1645484,
-0.1845579,
0.07226951,
-0.4647051,
0.06026926,
-0.3764485,
0.1380106,
-0.01872126,
0.2968442,
-0.006370... |
Potential anticancer agents. I. Synthesis of isoxazole moiety containing quinazoline derivatives and preliminarily in vitro anticancer activity. | 14 new structures of isoxazole-moiety-containing quinazoline derivatives(3a~3n) were synthesized for the first time and characterized by IR, (1)H NMR, (13)C NMR, ESI-MS. Subsequently, their in vitro anticancer activity against A549, HCT116 and MCF-7 cell lines was preliminarily evaluated using the MTT method. Among them, most compounds showed good to excellent anticancer activity, especially 3d, 3i, 3k and 3m exhibited the more potent anticancer activity against A549, HCT116 and MCF-7 cell lines, which can be regarded as the promising drug candidates for development of anticancer drugs. | 25,142,319 | [
-0.2960079,
0.06597556,
-0.1118621,
0.09492179,
0.004762595,
0.3464405,
-0.1165709,
0.4779111,
0.1283309,
-0.01959217,
0.1116662,
0.1552926,
-0.06533024,
-0.02234044,
-0.457339,
-0.05398495,
-0.5412595,
0.2237375,
-0.1102669,
0.3327645,
0.3896481,
0.1780184,
-0.01403831,
... |
The place of four-dimensional ultrasound in evaluating fetal anomalies. | To analyze the capability of four-dimensional surface rendering mode ultrasound (4D SRM USG) in the detection of fetal abnormalities, and also compare it with 2D USG. A total of 1,379 pregnant women were enrolled in the study, and they all underwent 2D USG screening. In the same session, they were all subsequently screened using 4D USG. The findings of both methods were compared. A total of 194 fetal anomalies were detected in 176 of 1,379 pregnant women by 2D USG. When all cases, including superficial and non-superficial anomalies, were evaluated together, we found that 2D USG was significantly better than 4D SRM USG in detecting anomalies (p < 0.001). However, 4D SRM USG was superior to 2D USG in terms of image quality, clarity, the distinction between the surrounding structures, and intelligibility among the cases with a superficial anomaly (p < 0.005). 4D USG is superior to 2D USG in detecting malformations related to fetus face, spine, extremities, abdominal wall, and the body surface. However, 4D SRM USG detected only approximately half of the cases with anomalies, and showed a better quality of image in only 15 % of all cases. Therefore, 4D SRM USG may only be suitable for use as a complementary tool in the evaluation of fetal anomalies, especially those of the face, spine, extremity, and abdominal wall. | 25,142,340 | [
0.1139611,
0.2636815,
0.1521757,
-0.2381717,
0.2172306,
-0.0911037,
-0.1788113,
-0.270951,
0.3959709,
-0.2778448,
0.1548789,
-0.1836779,
-0.2969393,
-0.07746126,
-0.02892812,
0.106198,
-0.4833494,
-0.2159894,
-0.2607886,
-0.6094272,
0.3341433,
0.2316945,
-0.1494053,
0.2... |
Polycyclic aromatic hydrocarbons (PAHs) in Crassostrea rhizophorae and Cathorops spixii from the Caroni Swamp, Trinidad, West Indies. | Dietary exposure to polycyclic aromatic hydrocarbons (PAHs) may pose serious threats to human health. However, within the Caribbean, quantitative assessments regarding the risks associated with dietary PAH exposure remain sparse. This study investigated PAH presence in edible biota from the Caroni Swamp and quantitatively assessed the potential health threat to human consumers. Mangrove oysters (Crassostrea rhizophorae) and Madamango sea catfish (Cathorops spixii) collected from seven sites in the Caroni Swamp were analysed for 16 priority PAHs. Total PAH levels ranged from 109 ± 18.4 to 362 ± 63.0 ng/g dry wt. in Crassostrea rhizophorae and 7.5 ± 0.9 to 43.5 ± 25.5 ng/g dry wt. in Cathorops spixii (average ± standard deviation). Benzo[a]pyrene levels in Crassostrea rhizophorae at all sites exceeded international guidelines from British Colombia (Canada) and the European Union (EU). Incremental lifetime cancer risk (ILCR) values based on the ingestion of Crassostrea rhizophorae ranged from 8.4 × 10(-6) to 1.6 × 10(-5) and slightly exceeded the commonly used 1 × 10(-6) acceptable level of risk. Information from this study is important in understanding the potential health risks posed by PAHs, it is critical towards the protection of public health, and it serves as a useful baseline for comparison with future work. | 25,142,345 | [
-0.3045315,
-0.2191298,
0.1353007,
-0.2943518,
-0.02716827,
0.008019094,
-0.1583876,
0.09981897,
0.3391028,
-0.007661534,
-0.02182596,
-0.1004387,
-0.1704489,
-0.4042714,
-0.4436257,
-0.2871654,
-0.7309232,
0.2664814,
0.04388169,
-0.01768728,
-0.1301661,
0.458888,
0.11724... |
Response of growth and superoxide dismutase to enhanced arsenic in two Bacillus species. | Species differences in inorganic arsenic tolerance were investigated by comparing the responses of Bacillus subtilis (B. subtilis) and Bacillus thuringiensis (B. thuringiensis) to elevated concentrations of As(III) and As(V). The cell densities in treatments were always lower during the experiment compared to controls, with the exception of exposure to 1.0 mg As(V) l(-1) on the first day. It was also found that relative growth rate (RGR) of B. thuringiensis was lower than that of B. subtilis. Furthermore, RGR of each Bacillus species was negative correlation with toxicity of inorganic arsenic. However, total cell number still increased in each treatment according to cell density and RGR assays. Superoxide dismutase (SOD) activity of both Bacillus species was promoted by As(III) and As(V), especially under high arsenic concentration condition. In addition, SOD activity of B. thuringiensis was higher than that of B. subtilis during the same exposure time. In lipid peroxidation assay, thiobarbituric acid-reactive substances (TBARS) content of each Bacillus species had a significant increase with increment of arsenic concentration. Moreover, significant difference was observed between the two Bacillus species under high arsenic concentration. TBARS content of B. thuringiensis was higher than that of B. subtilis, indicating that effect of arsenic on cell membranes of B. thuringiensis was much more than that of B. subtilis. These results suggest that the two Bacillus species could adapt and live in high arsenic aquifers, although their growth and cell membranes were affected by As treatment in a way. | 25,142,350 | [
0.2304294,
-0.2295176,
-0.07059654,
0.02712172,
-0.2366266,
-0.1735296,
-0.0973548,
0.218928,
-0.04322386,
-0.1150571,
0.0008439699,
0.2853531,
-0.3895011,
0.3299007,
-0.4098072,
-0.07513718,
0.01480662,
0.3642312,
0.2379487,
0.05144043,
0.5309843,
0.4760204,
-0.1071167,
... |
Surgical management of multilevel cervical spinal stenosis and spinal cord injury complicated by cervical spine fracture. | There are few reports regarding surgical management of multilevel cervical spinal stenosis with spinal cord injury. Our purpose is to evaluate the safety and feasibility of open-door expansive laminoplasty in combination with transpedicular screw fixation for the treatment of multilevel cervical spinal stenosis and spinal cord injury in the trauma population. This was a retrospective study of 21 patients who had multilevel cervical spinal stenosis and spinal cord injury with unstable fracture. An open-door expansive posterior laminoplasty combined with transpedicular screw fixation was performed under persistent intraoperative skull traction. Outcome measures included postoperative improvement in Japanese Orthopedic Association (JOA) score and incidence of complications. The average operation time was 190 min, with an average blood loss of 437 ml. A total of 120 transpedicular screws were implanted into the cervical vertebrae between vertebral C3 and C7, including 20 into C3, 34 into C4, 36 into C5, 20 into C6, and 10 into C7. The mean preoperative JOA score was 3.67 ± 0.53. The patients were followed for an average of 17.5 months, and the average JOA score improved to 8.17 ± 1.59, significantly higher than the preoperative score (t = 1.798, P < 0.05), with an average improvement of 44.7 ± 11.7%. Postoperative complications in four patients included cerebrospinal fluid leakage, delayed wound healing, pulmonary infection, and urinary system infection. All four patients were responsive to antibiotic treatment; one died from respiratory failure 3 months postoperatively. The open-door expansive laminoplasty combined with posterior transpedicular screw fixation is feasible for treating multilevel cervical spinal stenosis and spinal cord injury complicated by unstable fracture. Its advantages include minimum surgical trauma, less intraoperative blood loss, and satisfactory stable supportive effect for reduction of fracture. | 25,142,353 | [
0.1031598,
-0.08136138,
0.2110003,
0.03424671,
-0.174434,
-0.4801401,
-0.2961823,
-0.02407667,
0.1935636,
0.1713071,
-0.03568367,
-0.06267571,
-0.04756758,
0.03623688,
-0.2599788,
-0.08097773,
-0.2467985,
0.09897694,
-0.1072858,
-0.1774453,
0.02871531,
0.134474,
-0.065270... |
Spatial and temporal control of fungal natural product synthesis. | Despite their oftentimes-elusive ecological role, fungal natural products have, for better or worse, impacted our daily lives tremendously owing to their diverse and potent bioactive properties. This Janus-faced nature of fungal natural products inevitably ushered in a field of research dedicated towards understanding the ecology, organisms, genes, enzymes, and biosynthetic pathways that give rise to this arsenal of diverse and complex chemistry. Ongoing research in fungal secondary metabolism has not only increased our appreciation for fungal natural products as an asset but also sheds light on the pivotal role that these once-regarded "metabolic wastes" play in fungal biology, defense, and stress response in addition to their potential contributions towards human mycoses. Full orchestration of secondary metabolism requires not only the seamless coordination between temporal and spatial control of SM-associated machineries (e.g. enzymes, cofactors, intermediates, and end-products) but also integration of these machineries into primary metabolic processes and established cellular mechanisms. An intriguing, but little known aspect of microbial natural product synthesis lies in the spatial organization of both pathway intermediates and enzymes responsible for the production of these compounds. In this highlight, we summarize some major breakthroughs in understanding the genes and regulation of fungal natural product synthesis and introduce the current state of knowledge on the spatial and temporal control of fungal natural product synthesis. | 25,142,354 | [
-0.04410503,
-0.0552423,
-0.01756013,
-0.0971944,
-0.07194589,
-0.06106265,
-0.05819698,
0.08908588,
0.1023596,
-0.04480727,
-0.05784055,
-0.3403156,
-0.05956347,
-0.06506661,
-0.5959581,
0.1730519,
-0.4066841,
0.190089,
0.2333793,
-0.0656448,
0.2351666,
0.3570084,
-0.475... |
Factors associated with effects of 90Y-ibritumomab tiuxetan in patients with relapsed or refractory low-grade B cell non-Hodgkin lymphoma: single-institution experience with 94 Japanese patients in rituximab era. | This retrospective study analyzes the results of radioimmunotherapy (RIT) with (90)Y-ibritumomab tiuxetan in 94 Japanese patients with relapsed or refractory low-grade B cell non-Hodgkin lymphoma at a single institution. All patients had previously been administered with 1-8 (median 1) regimens of rituximab alone or combined with other chemotherapeutic regimens at a mean age of 64 years. The overall response rate was 90 % and the complete response (CR) rate was 69 %. The median overall survival was not reached and progression-free survival (PFS) was 26 months, respectively, for the early phase 50 patients during a median follow-up period of 46.5 months. In this cohort, the PFS rates for the 50 early phase patients who had undergone ≤2 and ≥3 previous regimens, and for those who achieved CR compared with those who did not (partial response, PR; stable disease, SD; progressive disease, PD) were 38 and 11 months, respectively. Multivariate analysis showed that these two factors were statistically significant (p = 0.0011 and p <0.0001, respectively). The overall incidence of grade ≥3 non-hematological toxicity was 9 %. Two patients died of treatment-related deteriorating hepatitis C. A second malignancy developed in two patients at 10.5 and 3.5 months after treatment. We recommend administering (90)Y-ibritumomab tiuxetan as early in the disease course as possible, and at the latest as a third-line therapy to maximize the benefits of RIT, which should improve the quality of life for patients. | 25,142,378 | [
-0.2207267,
-0.3309238,
0.1257053,
-0.2040506,
-0.1961644,
-0.2494486,
0.211578,
0.09610948,
-0.0776948,
0.2382246,
0.02768169,
0.09580467,
-0.0940185,
0.1138059,
-0.2192351,
-0.4598119,
0.09977686,
0.333278,
0.177509,
0.03587162,
0.03018535,
0.3398226,
-0.09613482,
0.0... |
Association between bipolar episodes and fluid and electrolyte homeostasis: a retrospective longitudinal study. | Imbalance of fluid and electrolyte homeostasis has been suggested to be associated with the neuropathological processes underlying bipolar disorder. However, longitudinal data regarding the association of bipolar episodes with fluid balance are still lacking. We hypothesized that mania may be associated with a relative fluid retention and hemodilution, and depression with a relative hemoconcentration. Patients with bipolar disorder (n = 43) admitted to a mental health center, both with depressive and manic episodes, were retrospectively followed between 2005 and 2013. Fluid balance and electrolyte serum indices were compared between their manic and depressive episodes. We adjusted for physical and psychiatric comorbidities and for psychotropic treatment, using two-way analysis of variance with repeated measures. There was a significant reduction in serum fluid balance indices during mania compared to depression: mean hemoglobin concentration 13.9 ± 1.4 g/dL versus 14.5 ± 1.4 g/dL, paired t = -4.2, p < 0.0005; mean hematocrit 41.1 ± 4.1% versus 42.3 ± 3.7%, paired t = -3.0, p < 0.005; mean albumin concentration 4.2 ± 0.3 g/dL versus 4.5 ± 0.3 g/dL, paired t = -4.5, p < 0.0001; and mean sodium concentration 140.3 ± 2.0 mEq/L versus 141.0 ± 2.0 mEq/L, paired t = -2.1, p = 0.04, respectively. Controlling for physical and psychiatric comorbidities and psychotropic treatment did not alter these associations. Our results support the notion of an imbalance of fluid and electrolyte homeostasis among bipolar episodes, which is suggestive for relative hemoconcentration during depressive episodes and relative hemodilution during manic episodes. These findings may eventually lead to novel therapeutic targets. | 25,142,404 | [
-0.2046665,
-0.0880145,
-0.2438882,
-0.3851941,
-0.02596868,
-0.3381156,
-0.2049379,
-0.1652033,
-0.2688772,
-0.195829,
0.2366977,
0.4899451,
-0.2935148,
-0.1581167,
-0.0566483,
-0.04162143,
0.1850018,
-0.02947299,
-0.05704793,
-0.1734038,
-0.1770277,
-0.01007722,
-0.2053... |
National and state patterns of teen births in the United States, 1940-2013. | This report presents trends from 1940 through 2013 in national birth rates for teenagers, with particular focus on the period since 1991. The percent changes in rates for 1991-2012 and for 2007-2012 are presented for the United States and for states. Preliminary data for 2013 are shown where available. Tabular and graphical descriptions of the trends in teen birth rates for the United States and each state, by age group, race, and Hispanic origin, are presented and discussed. Data are shown for the U.S. territories. Birth rates for U.S. teenagers have generally fallen in the United States since peaking in 1957. The rate fell 57% between 1991 and 2013. The 2013 preliminary rate (26.6 per 1,000 aged 15-19) is less than one-third of the historically highest rate (96.3 in 1957). During 1991-2012, rates fell for all race and Hispanic ethnicity groups, with the largest declines measured for non-Hispanic black teenagers. In the more recent period, 2007-2012, the declines have been steepest for Hispanic teenagers. Birth rates declined significantly for teenagers in all states during 1991-2012; during 2007-2012, rates fell for all but two states. The drop in teen birth rates translates into an estimated 4 million fewer births to teenagers from 1992 through 2012. The declines in teen birth rates reflect a number of behavioral changes, including decreased sexual activity, increases in the use of contraception at first sex and at most recent sex, and the adoption and increased use of hormonal contraception, injectables, and intrauterine devices. | 25,142,408 | [
-0.4208957,
0.1184445,
-0.1651847,
-0.0670744,
0.05542312,
-0.09011286,
-0.3339512,
-0.06628986,
0.1314173,
0.005282072,
0.2016998,
-0.1235963,
-0.184004,
-0.09768466,
-0.09081884,
-0.01575632,
0.2238203,
0.1843104,
0.199232,
-0.1554047,
0.3261754,
0.4009159,
0.02794453,
... |
Standard individual cognitive behaviour therapy for paediatric obsessive-compulsive disorder: a systematic review of effect estimates across comparisons. | Previous meta-analyses of paediatric obsessive-compulsive disorder (OCD) have shown much higher effect size for standard individual cognitive behaviour therapy (SI-CBT) compared with control conditions than for serotonin reuptake inhibitors (SRIs) compared with placebo. Other factors, such as systematic differences in the provided care or exposure to factors other than the interventions of interest (performance bias) may be stronger confounders in psychotherapy research than in pharmacological research. These facts led us to review SI-CBT studies of paediatric OCD with the aim to compare the effect estimates across different comparisons, including active treatments. We included only randomized controlled trials (RCTs) or cluster RCTs with treatment periods of 12-16 weeks. Outcome was post-test score on the Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS). Thirteen papers reporting from 13 RCTs with 17 comparison conditions were included. SI-CBT was superior to wait-list and placebo therapy but not active treatments. Effect estimates for SI-CBT in wait-list comparison studies were significantly larger than in placebo-therapy comparison studies. In addition, the SI-CBT effect estimate was not significantly different when compared with SRIs alone or combined SRIs and CBT. Performance bias may have inflated previous effect estimates for SI-CBT when comparison contingencies included wait-list. However, the calculated SI-CBT effect estimate was lower but significant when compared with placebo therapy. The effects of SI-CBT and active treatments were not significantly different. In conclusion, our data support the current clinical guidelines, although better comparisons between SI-CBT and SRIs are needed. | 25,142,430 | [
0.008110682,
0.2249072,
-0.3032162,
-0.1347589,
0.2533329,
-0.3598111,
-0.200045,
-0.1322446,
-0.02665025,
-0.1746582,
-0.05806768,
0.5205575,
-0.2193918,
0.0622235,
-0.3567051,
-0.1391193,
-0.2585662,
0.4129915,
-0.2955234,
0.3337158,
0.05826812,
0.1985797,
-0.1580207,
... |
Pharyngeal transit in patients with chronic progressive external ophthalmoplegia. | A common presentation of mitochondrial myopathies is chronic progressive external ophthalmoplegia (CPEO). Dysphagia is a complaint in about 50% of cases. This investigation evaluated pharyngeal transit in patients with CPEO. Videofluoroscopic swallowing evaluation was performed with paste, liquid and solid boluses in 14 patients with CPEO and in 16 normal volunteers. There was no difference between patients and volunteers in the duration of pharyngeal swallowing events with the liquid bolus. Compared to control participants, patients with CPEO had significantly shorter duration of pharyngeal transit for paste and solid boluses, of pharyngeal clearance for paste bolus, and of upper oesophageal sphincter transit for paste and solid boluses. Spontaneous multiple swallows and effortful swallows were performed by patients but not by the volunteers. It was concluded that patients with CPEO have shorter pharyngeal transit duration of paste and solid boluses than normal volunteers, which may be a consequence of a spontaneous smaller bolus volume in each swallow and/or effortful swallows. | 25,142,449 | [
-0.367668,
-0.1619078,
-0.1039293,
-0.1081482,
0.008992629,
-0.3220564,
0.05163614,
-0.1434591,
0.1272641,
-0.04844461,
0.3015614,
0.3469789,
-0.09455667,
-0.03293163,
-0.09938139,
0.1763949,
-0.6762892,
0.1003719,
-0.5304167,
-0.06934568,
0.1839368,
0.1993117,
0.2287571,... |
Adipokines: a link between obesity and dementia? | Being overweight or obese, as measured with body-mass index or central adiposity (waist circumference), and the trajectory of body-mass index over the life course have been associated with brain atrophy, white matter changes, disturbances of blood-brain barrier integrity, and risk of all-cause late-onset dementia and Alzheimer's disease. This observation leads us to question what it is about body-mass index that is associated with health of the brain and dementia risk. If high body-mass index and central adiposity represent an increase in adipose tissue, then the endocrine function of adipose tissue, mediated by adipose tissue hormones and adipokines, could be a clue to mechanisms that underlie the association with dementia and Alzheimer's disease. Hundreds of adipokines have been identified, creating a complexity that is a challenge to simplify. Nonetheless, adipokines are being investigated in association with clinical dementia outcomes, and with imaging-based measures of brain volume, structure, and function in human beings and in preclinical models of clinical dementia. | 25,142,458 | [
-0.1297351,
-0.07415582,
0.07965798,
-0.244251,
0.2981612,
-0.2001174,
-0.09530604,
0.1343099,
0.01880315,
0.2383287,
-0.1772873,
-0.04725524,
0.1237007,
-0.1763053,
-0.4866605,
0.0644777,
-0.1648168,
0.2667907,
0.03903016,
0.03227457,
-0.1367271,
0.1363541,
-0.1482835,
... |
Mechanisms of exercise intolerance in global initiative for chronic obstructive lung disease grade 1 COPD. | The purpose of this study was to determine if a dissociation existed between respiratory drive, as estimated by diaphragmatic electromyography (EMGdi), and its pressure-generating capacity during exercise in mild chronic obstructive pulmonary disease (COPD) and whether this, if present, had negative sensory consequences. Subjects meeting spirometric criteria for mild COPD (n=16) and age and sex-matched controls (n=16) underwent detailed pulmonary function testing and a symptom limited cycle test while detailed ventilatory, sensory and respiratory mechanical responses were measured. Compared with controls, subjects with mild COPD had greater ventilatory requirements throughout submaximal exercise. At the highest equivalent work rate of 60 W, they had a significantly higher: total work of breathing (32±17 versus 16±7 J·min(-1); p<0.01); EMGdi (37.3±17.3 versus 17.9±11.7% of maximum; p<0.001); and EMGdi to transdiaphragmatic pressure ratio (0.87±0.38 versus 0.52±0.27; p<0.01). Dyspnoea-ventilation slopes were significantly higher in mild COPD than controls (0.17±0.12 versus 0.10±0.05; p<0.05). However, absolute dyspnoea ratings reached significant levels only at high levels of ventilation. Increased respiratory effort and work of breathing, and a wider dissociation between diaphragmatic activation and pressure-generating capacity were found at standardised work rates in subjects with mild COPD compared with controls. Despite these mechanical and neuromuscular abnormalities, significant dyspnoea was only experienced at higher work rates. | 25,142,487 | [
-0.2243425,
-0.1216986,
0.04243593,
0.08096179,
-0.005317924,
-0.3093714,
-0.2099287,
-0.4537228,
-0.06003483,
-0.3653257,
-0.2019707,
-0.4210974,
-0.317211,
-0.2323298,
-0.05555602,
-0.242193,
-0.6021635,
0.4148442,
-0.2492905,
-0.2428809,
-0.5028853,
-0.01079474,
0.1720... |
De novo use of generic tacrolimus in liver transplantation - a single center experience with one-yr follow-up. | Use of generic tacrolimus in liver transplantation (LT) could result in cost savings. Generic tacrolimus has been shown to be bioequivalent to innovator tacrolimus in healthy volunteers and renal transplant patients. There are limited data on the de novo use of generic tacrolimus in LT. This study aimed to determine whether the de novo use of generic tacrolimus (Adoport, Sandoz,UK) was associated with differences in outcomes, safety, and cost compared with innovator tacrolimus (Prograf, Astellas, Japan). Patients were studied before and after a programmatic change from de novo IS with Prograf to Adoport. Outcomes, tacrolimus levels, doses, and costs were compared for the first-yr post-LT. Ninety-four patients were studied, 46 Prograf, 48 Adoport. No significant differences in rejection, cytomegalovirus infection, acute kidney injury, sepsis, or graft loss were observed between groups. Tacrolimus costs were significantly reduced with the de novo use of Adoport. Day 14 dose normalized levels in Adoport patients showed significant variation but at the day 30 and one yr, there were no significant differences in the doses or levels of tacrolimus between groups. Adoport is safe and effective compared to Prograf when used de novo in LT patients. Tacrolimus costs were significantly reduced by the use of Adoport. | 25,142,496 | [
-0.2581845,
0.02878836,
-0.1135019,
0.219465,
0.09255646,
-0.1772228,
-0.01606193,
-0.142648,
-0.1176577,
0.052618,
-0.004233003,
-0.3594475,
0.0385178,
0.4614449,
-0.737663,
-0.2187303,
-0.0681519,
-0.3488822,
-0.2529331,
0.07519925,
0.003429172,
0.1852549,
-0.3574831,
... |
Why do satellite imageries show exceptionally high chlorophyll in the Gulf of Mannar and the Palk Bay during the Norteast Monsoon? | The Gulf of Mannar (GoM) and the Palk Bay (PB) are two least studied marine environments located between India and Sri Lanka. Exceptionally high chlorophyll a concentration in the GoM and the PB during the Northeast Monsoon (November-February) is a consistent feature in satellite imageries, which has been attributed to the intrusion of the Bay of Bengal (BoB) waters. The analyses of the Moderate Resolution Imaging Spectroradiometer (MODIS) and field chlorophyll data collected from 30 locations in the Indian sector of the GoM and the PB in January 2011 showed significant overestimations in the satellite data. This error was much higher in the PB (60-80 %) as compared to the GoM (18-28 %). The multivariate analyses evidenced that the exceptionally high satellite chlorophyll in the PB is contributed largely by turbidity, colored dissolved organic matter (CDOM), and bottom reflectance. The paper cautions that though MODIS is superior in estimating chlorophyll a in optically complex waters, there are still chances of overestimations in regions like the PB. | 25,142,503 | [
-0.126989,
-0.08482061,
0.2687891,
-0.1702983,
-0.2167733,
-0.159359,
-0.3748019,
0.01407239,
-0.001946446,
-0.08400323,
-0.03717471,
0.1017839,
0.3503583,
0.2544845,
-0.3429265,
-0.05508689,
-0.5114614,
0.2463011,
0.009179275,
-0.02822338,
0.3013337,
0.2737075,
-0.116750... |
Determination of organochlorine pesticide concentrations in flathead mullet (Mugil cephalus) caught from the western Black Sea coast of Turkey. | The objective of this study was to determine the levels of 14 organochlorine pesticides (OCPs) in flathead mullet (Mugil cephalus) caught from the western Black Sea coast of Turkey. The fish samples were caught from five different locations of the western Black Sea coast of Turkey in August 2009. Organochlorine pesticides were extracted from the liver tissues, and then the levels of OCPs were measured using gas chromatography with an electron capture detector. Organochlorine pesticides were detected in all locations. The levels of total OCPs in fish samples ranged between 0.224 and 1.103 μg g(-1) dry weight in the western Black Sea coast of Turkey. DDT, beta-HCH, and endosulfan I were the dominant OCPs in the fish samples. The levels of DDT in fish samples ranged between 0.081 and 0.186 μg g(-1) dry weight. The levels of total HCH in fish samples ranged between 0.007 and 0.376 μg g(-1) dry weight in the western Black Sea coast of Turkey. Although the usage of OCPs was banned in Turkey, the results of this study clearly indicated the presence of OCPs in the western Black Sea coast of Turkey and exposure of living organisms to these chemicals. | 25,142,504 | [
-0.09799948,
0.25726,
0.1107007,
-0.0424048,
0.1524722,
-0.06597473,
-0.3652606,
0.06371953,
-0.1147319,
0.3212785,
0.2325999,
0.1122755,
-0.01499128,
0.07366304,
-0.2753426,
-0.2022377,
-0.4391145,
0.4481636,
0.2305694,
0.1995199,
-0.04830614,
0.3558844,
0.1175576,
-0.... |
The life and times of Ferruccio Ritossa. | Ferruccio Ritossa wrote these lines only a few months before he died, as a preface to a book he wanted to write and that, unfortunately, we will never be able to read. It was to be the story of his life, an amazing story indeed. With this article, we want to take a picture of Ferruccio's life, a mosaic of events, facts, ideas, hopes, and memories linked in a way that they will not go away, even after "a stroll in our brain." | 25,142,515 | [
-0.07732356,
-0.1390776,
-0.07892697,
-0.0661793,
0.1878269,
-0.2303818,
-0.3198813,
-0.2319022,
-0.1759475,
-0.133868,
-0.1030129,
0.3583133,
0.115157,
-0.03710318,
-0.5931718,
-0.2532424,
0.1149029,
-0.1061101,
-0.1345255,
0.03255409,
0.1113566,
0.04518658,
-0.08461528,... |
Progressive promoter element combinations classify conserved orthogonal plant circadian gene expression modules. | We aimed to test the proposal that progressive combinations of multiple promoter elements acting in concert may be responsible for the full range of phases observed in plant circadian output genes. In order to allow reliable selection of informative phase groupings of genes for our purpose, intrinsic cyclic patterns of expression were identified using a novel, non-biased method for the identification of circadian genes. Our non-biased approach identified two dominant, inherent orthogonal circadian trends underlying publicly available microarray data from plants maintained under constant conditions. Furthermore, these trends were highly conserved across several plant species. Four phase-specific modules of circadian genes were generated by projection onto these trends and, in order to identify potential combinatorial promoter elements that might classify genes into these groups, we used a Random Forest pipeline which merged data from multiple decision trees to look for the presence of element combinations. We identified a number of regulatory motifs which aggregated into coherent clusters capable of predicting the inclusion of genes within each phase module with very high fidelity and these motif combinations changed in a consistent, progressive manner from one phase module group to the next, providing strong support for our hypothesis. | 25,142,519 | [
-0.08275748,
0.3630598,
-0.01213966,
-0.06016919,
0.04862036,
-0.2813382,
-0.2012425,
-0.1931992,
0.2079215,
-0.1463778,
-0.08480443,
-0.075781,
0.1085533,
0.0657146,
-0.3689959,
0.2066907,
-0.2413357,
0.1574093,
0.01447943,
-0.0258465,
0.4317679,
0.2636897,
-0.0668022,
... |
Counterintuitive properties of the fixation time in network-structured populations. | Evolutionary dynamics on graphs can lead to many interesting and counterintuitive findings. We study the Moran process, a discrete time birth-death process, that describes the invasion of a mutant type into a population of wild-type individuals. Remarkably, the fixation probability of a single mutant is the same on all regular networks. But non-regular networks can increase or decrease the fixation probability. While the time until fixation formally depends on the same transition probabilities as the fixation probabilities, there is no obvious relation between them. For example, an amplifier of selection, which increases the fixation probability and thus decreases the number of mutations needed until one of them is successful, can at the same time slow down the process of fixation. Based on small networks, we show analytically that (i) the time to fixation can decrease when links are removed from the network and (ii) the node providing the best starting conditions in terms of the shortest fixation time depends on the fitness of the mutant. Our results are obtained analytically on small networks, but numerical simulations show that they are qualitatively valid even in much larger populations. | 25,142,521 | [
-0.03047589,
-0.2629828,
-0.1111973,
0.2058696,
0.3343962,
-0.3016495,
-0.1825994,
0.07958617,
0.1778695,
-0.1673398,
-0.1232919,
0.08411187,
-0.00124197,
0.130432,
-0.2827655,
-0.2504679,
-0.2598797,
-0.008355781,
-0.08504263,
0.1996361,
0.5353679,
0.3896659,
-0.08063444... |
The effect of glass-forming sugars on vesicle morphology and water distribution during drying. | Cryopreservation requires that stored materials be kept at extremely low temperatures and uses cryoprotectants that are toxic to cells at high concentrations. Lyopreservation is a potential alternative where stored materials can remain at room temperatures. That storage process involves desiccating cells filled with special glass-forming sugars. However, current desiccation techniques fail to produce viable cells, and researchers suspect that incomplete vitrification of the cells is to blame. To explore this hypothesis, a cell is modelled as a lipid vesicle to monitor the water content and membrane deformation during desiccation. The vesicle is represented as a moving, bending-resistant, inextensible interface and is tracked by a level set method. The vesicle is placed in a fluid containing a spatially varying sugar concentration field. The glass-forming nature is modelled through a concentration-dependent diffusivity and viscosity. It is found that there are optimal regimes for the values of the osmotic flow parameter and of the concentration dependence of the diffusivity to limit water trapping in the vesicle. Furthermore, it is found that the concentration dependencies of the diffusivity and viscosity can have profound effects on membrane deformations, which may have significant implications for vesicle damage during the desiccation process. | 25,142,522 | [
-0.3559061,
-0.01565775,
-0.4247055,
-0.1466629,
-0.05903683,
-0.1763474,
-0.04191603,
0.1861985,
0.1920161,
0.1561869,
0.1684832,
0.00124675,
-0.4698739,
-0.05687871,
-0.1391743,
-0.1672048,
-0.2139309,
0.08522113,
-0.02583688,
0.02630579,
0.3348575,
0.3686487,
-0.185824... |
[Hypothermia and memory disturbance as initial manifestations associated with lesions of the diencephalon in a patient with anti-aquaporin 4 antibody-associated disorder: a case report]. | A 69-year-old woman was admitted due to gradual progression of daytime sleepiness and forgetfulness over a period of approximately 1 month. Bradycardia and hypothermia were observed on admission, and neurological examination revealed memory disturbance, mild dysarthria, and bradykinesia. Fluid-attenuated inversion recovery (FLAIR) images of the brain magnetic resonance imaging (MRI) indicated signal hyperintensity in the region bordering the lateral and third ventricles. Serum anti-aquaporin 4 (AQP4) antibody was detected. The patient had no history or findings of optic neuritis or myelitis, and she was diagnosed as anti-AQP4 antibody-associated disorder. Diencephalon lesion and/or symptoms are rarely observed at the onset of neuromyelitis optica. Differential diagnosis of this disorder is necessary in cases manifesting diencephalon symptoms or involving lesions bordering the third ventricle without evidence of previous optic neuritis or myelitis. | 25,142,537 | [
-0.1661534,
-0.06682426,
0.01191152,
-0.241628,
-0.03350991,
-0.3639832,
-0.2305908,
-0.3194203,
-0.03164846,
-0.03945846,
0.3917629,
0.5866053,
0.1881979,
-0.07809314,
0.1250233,
-0.2774672,
-0.2109206,
0.1527233,
-0.0007025678,
-0.1475533,
0.0386749,
0.04715978,
-0.2891... |
Periodic leg movements during sleep are associated with polymorphisms in BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD. | To examine association between periodic leg movements (PLM) and 13 single nucleotide polymorphisms (SNPs) in 6 loci known to increase risk of restless legs syndrome (RLS). Stanford Center for Sleep Sciences and Medicine and Clinical Research Unit of University of Wisconsin Institute for Clinical and Translational Research. Adult participants (n = 1,090, mean age = 59.7 years) from the Wisconsin Sleep Cohort (2,394 observations, 2000-2012). A previously validated automatic detector was used to measure PLMI. Thirteen SNPs within BTBD9, TOX3/BC034767, MEIS1 (2 unlinked loci), MAP2K5/SKOR1, and PTPRD were tested. Analyses were performed using a linear model and by PLM category using a 15 PLM/h cutoff. Statistical significance for loci was Bonferroni corrected for 6 loci (P < 8.3 × 10(-3)). RLS symptoms were categorized into four groups: likely, possible, no symptoms, and unknown based on a mailed survey response. Prevalence of PLMI ≥ 15 was 33%. Subjects with PLMs were older, more likely to be male, and had more frequent RLS symptoms, a shorter total sleep time, and higher wake after sleep onset. Strong associations were found at all loci except one. Highest associations for PLMI > 15/h were obtained using a multivariate model including age, sex, sleep disturbances, and the best SNPs for each loci, yielding the following odds ratios (OR) and P values: BTBD9 rs3923809(A) OR = 1.65, P = 1.5×10(-8); TOX3/BC034767 rs3104788(T) OR = 1.35, P = 9.0 × 10(-5); MEIS1 rs12469063(G) OR = 1.38, P = 2.0 × 10(-4); MAP2K5/SKOR1 rs6494696(G) OR = 1.24, P = 1.3×10(-2); and PTPRD(A) rs1975197 OR = 1.31, P = 6.3×10(-3). Linear regression models also revealed significant PLM effects for BTBD9, TOX3/BC034767, and MEIS1. Co-varying for RLS symptoms only modestly reduced the genetic associations. Single nucleotide polymorphisms demonstrated to increase risk of RLS are strongly linked to increased PLM as well, although some loci may have more effects on one versus the other phenotype. | 25,142,570 | [
0.01863542,
-0.1782774,
0.03619892,
-0.2634235,
-0.2005584,
-0.2310714,
0.02137608,
0.1952216,
0.1061909,
-0.2460561,
0.2798885,
0.3219975,
0.0456855,
0.1009871,
-0.2975675,
-0.1817411,
-0.4956473,
-0.2433171,
0.3783621,
-0.06371301,
-0.1592181,
0.3126684,
-0.01132834,
... |
Which adenomas are detected by fecal occult blood testing? A state-wide analysis from Bavaria, Germany. | Guaiac-based fecal occult blood tests (gFOBTs) are the most widely used noninvasive tests for colorectal cancer screening. While it is well known that they detect only a minority of colorectal adenomas, evidence for the characteristics of adenomas associated with detection is sparse. We derived estimates of the positive likelihood ratio (LR+), a summary measure of diagnostic performance, according to adenoma characteristics by comparing findings at colonoscopy among 19,208 and 181,128 participants who underwent colonoscopy to follow-up a positive gFOBT and as a primary screening examination, respectively, in Bavaria, Germany, in 2007-2009. Age and sex-adjusted estimates of LR+ (95% confidence intervals, 95% CI) ranged from 1.09 (1.05-1.13) for adenomas <1 cm to 2.52 (2.30-2.75) for adenomas >2 cm, and were much higher for pedunculated adenomas (1.96, 95% CI 1.85-2.08) than for flat or sessile adenomas (1.11, 95% CI 1.02-1.21 and 1.12, 95% CI 1.08-1.16, respectively). Villous or tubulovillous structure and dysplasia were likewise associated with a higher chance to be detected by gFOBT. Diagnostic performance was worse for proximal than for distal adenomas (age and sex adjusted LR+:1.16, 95% CI 1.09-1.23 and 1.35, 95% CI 1.29-1.41, respectively) which was explained by the lower proportions of large, pedunculated and nontubular adenomas in the proximal colon. Size, pedunculated shape, and nontubular histology are the key determinants of detection which also explain lower detection rates of adenomas located in the proximal colon. | 25,142,576 | [
0.1663485,
-0.06910233,
-0.2219471,
-0.3038191,
0.2051405,
-0.2830188,
-0.02129055,
0.1363595,
0.01572055,
-0.04640367,
-0.05393365,
0.2965939,
-0.06990952,
-0.25793,
-0.1601852,
0.1717901,
-0.4436278,
0.296021,
0.2229197,
0.00147313,
0.2390007,
0.3126525,
-0.2888718,
0... |
Comprehensive analysis of herpes simplex virus 1 (HSV-1) entry mediated by zebrafish 3-O-Sulfotransferase isoforms: implications for the development of a zebrafish model of HSV-1 infection. | Binding of herpes simplex virus 1 (HSV-1) envelope glycoprotein D (gD) to the receptor 3-O-sulfated heparan sulfate (3-OS HS) mediates viral entry. 3-O-Sulfation of HS is catalyzed by the 3-O-sulfotransferase (3-OST) enzyme. Multiple isoforms of 3-OST are differentially expressed in tissues of zebrafish (ZF) embryos. Here, we performed a comprehensive analysis of the role of ZF 3-OST isoforms (3-OST-1, 3-OST-5, 3-OST-6, and 3-OST-7) in HSV-1 entry. We found that a group of 3-OST gene family isoforms (3-OST-2, -3, -4, and -6) with conserved catalytic and substrate-binding residues of the enzyme mediates HSV-1 entry and spread, while the other group (3-OST-1, -5, and -7) lacks these properties. These results demonstrate that HSV-1 entry can be recapitulated by certain ZF 3-OST enzymes, a significant step toward the establishment of a ZF model of HSV-1 infection and tissue-specific tropism. | 25,142,596 | [
0.1857183,
-0.213765,
-0.1136432,
0.1378096,
-0.1580513,
-0.2978404,
0.1935562,
-0.007447795,
-0.1277498,
-0.09365112,
0.1060088,
-0.1196898,
-0.3205891,
-0.09338038,
-0.3906291,
0.3076406,
-0.400218,
0.286353,
0.2801974,
0.09297473,
-0.0275792,
0.1907647,
-0.2048841,
0... |
Immunodeficient mouse models with different disease profiles by in vivo infection with the same clinical isolate of enterovirus 71. | Like poliovirus infection, severe infection with enterovirus 71 (EV71) can cause neuropathology. Unlike poliovirus, EV71 is often associated with hand-foot-and-mouth disease (HFMD). Here we established three mouse models for experimental infection with the same clinical isolate of EV71. The NOD/SCID mouse model is unique for the development of skin rash, an HFMD-like symptom. While the NOD/SCID mice developed limb paralysis and death at near-100% efficiency, the gamma interferon receptor knockout (ifngr KO) and stat-1 knockout mice exhibited paralysis and death rates near 78% and 30%, respectively. Productive infection with EV71 depends on the viral dose, host age, and inoculation route. Levels of infectious EV71, and levels of VP1-specific RNA and protein in muscle, brain, and spinal cord, were compared side by side between the NOD/SCID and stat-1 knockout models before, during, and after disease onset. Spleen fibrosis and muscle degeneration are common in the NOD/SCID and stat-1 knockout models. The main differences between these two models include their disease manifestations and cytokine/chemokine profiles. The pathology of the NOD/SCID model includes (i) inflammation and expression of viral VP1 antigen in muscle, (ii) increased neutrophil levels and decreased eosinophil and lymphocyte levels, and (iii) hair loss and skin rash. The characteristic pathology of the stat-1 knockout model includes (i) a strong tropism of EV71 for the central nervous system, (ii) detection of VP1 protein in the Purkinje layer of cerebellar cortex, pons, brain stem, and spinal cord, (iii) amplification of microglial cells, and (iv) dystrophy of intestinal villi. Our comparative studies on these new models with oral or intraperitoneal (i.p.) infection underscored the contribution of host immunity, including the gamma interferon receptor, to EV71 pathogenesis. In the past decade, enterovirus 71 (EV71) has emerged as a major threat to public health in the Asia-Pacific region. Disease manifestations include subclinical infection, common-cold-like syndromes, hand-foot-and-mouth disease (HFMD), uncomplicated brain stem encephalitis, severe dysregulation of the autonomic nerve system, fatal pulmonary edema, and cardiopulmonary collapse. To date, no effective vaccine or treatment is available. A user-friendly and widely accessible animal model for researching EV71 infection and pathogenesis is urgently needed by the global community, both in academia and in industry. | 25,142,603 | [
0.04414255,
-0.4506933,
-0.08006287,
-0.2199862,
0.152656,
-0.09334861,
-0.03423766,
0.09054783,
-0.2146485,
-0.1482284,
-0.08984101,
-0.09499879,
0.3469827,
0.187834,
-0.1390925,
-0.2955983,
-0.06994983,
-0.2833905,
-0.1490815,
0.1860663,
-0.109347,
0.4472981,
-0.1629625... |
Intrabronchial infection of rhesus macaques with simian varicella virus results in a robust immune response in the lungs. | Varicella-zoster virus (VZV) is the etiological agent of varicella (chickenpox) and herpes zoster (shingles). Primary VZV infection is believed to occur via the inhalation of virus either in respiratory droplets or from shedding varicella lesions or by direct contact with infectious vesicular fluid. However, the ensuing immune response in the lungs remains incompletely understood. We have shown that intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of acute and latent VZV infection in humans. In this study, we performed an in-depth analysis of the host immune response to acute SVV infection in the lungs and peripheral blood. We report that acute SVV infection results in a robust innate immune response in the lungs, characterized by the production of inflammatory cytokines, chemokines, and growth factors as well as an increased frequency of plasmacytoid dendritic cells (DCs) that corresponded with alpha interferon (IFN-α) production and a rapid decrease in viral loads in the lungs. This is followed by T and B cell proliferation, antibody production, T cell differentiation, and cytokine production, which correlate with the complete cessation of viral replication. Although terminally differentiated CD8 T cells became the predominant T cell population in bronchoalveolar lavage cells, a higher percentage of CD4 T cells were SVV specific, which suggests a critical role for these cells in the resolution of primary SVV infection in the lungs. Given the homology between SVV and VZV, our data provide insight into the immune response to VZV within the lung. Although primary VZV infection occurs primarily via the respiratory route, the host response in the lungs and its contribution to the cessation of viral replication and establishment of latency remain poorly understood. The difficulty in accessing lung tissue and washes from individuals infected with VZV has hampered efforts to address this knowledge gap. SVV infection of rhesus macaques is an important model of VZV infection of humans; therefore, we utilized this animal model to gain a comprehensive view of the kinetics of the immune response to SVV in the lung and its relationship to the resolution of acute infection in respiratory tissues. These data not only advance our understanding of host immunity to VZV, a critical step in developing new vaccines, but also provide additional insight into immunity to respiratory pathogens. | 25,142,604 | [
0.02474484,
-0.1979906,
-0.5446283,
-0.3013322,
0.0454996,
-0.4003396,
-0.3974961,
-0.0984474,
-0.1733272,
0.01349234,
0.1542289,
-0.2129386,
-0.1922029,
0.1429081,
-0.41249,
-0.1163175,
-0.1963086,
-0.2367726,
0.3030792,
0.2044474,
0.3946768,
0.3556378,
-0.1850518,
-0.... |
Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. | Over the past 5 years, a new generation of highly potent and broadly neutralizing HIV-1 antibodies has been identified. These antibodies can protect against lentiviral infection in nonhuman primates (NHPs), suggesting that passive antibody transfer would prevent HIV-1 transmission in humans. To increase the protective efficacy of such monoclonal antibodies, we employed next-generation sequencing, computational bioinformatics, and structure-guided design to enhance the neutralization potency and breadth of VRC01, an antibody that targets the CD4 binding site of the HIV-1 envelope. One variant, VRC07-523, was 5- to 8-fold more potent than VRC01, neutralized 96% of viruses tested, and displayed minimal autoreactivity. To compare its protective efficacy to that of VRC01 in vivo, we performed a series of simian-human immunodeficiency virus (SHIV) challenge experiments in nonhuman primates and calculated the doses of VRC07-523 and VRC01 that provide 50% protection (EC50). VRC07-523 prevented infection in NHPs at a 5-fold lower concentration than VRC01. These results suggest that increased neutralization potency in vitro correlates with improved protection against infection in vivo, documenting the improved functional efficacy of VRC07-523 and its potential clinical relevance for protecting against HIV-1 infection in humans. In the absence of an effective HIV-1 vaccine, alternative strategies are needed to block HIV-1 transmission. Direct administration of HIV-1-neutralizing antibodies may be able to prevent HIV-1 infections in humans. This approach could be especially useful in individuals at high risk for contracting HIV-1 and could be used together with antiretroviral drugs to prevent infection. To optimize the chance of success, such antibodies can be modified to improve their potency, breadth, and in vivo half-life. Here, knowledge of the structure of a potent neutralizing antibody, VRC01, that targets the CD4-binding site of the HIV-1 envelope protein was used to engineer a next-generation antibody with 5- to 8-fold increased potency in vitro. When administered to nonhuman primates, this antibody conferred protection at a 5-fold lower concentration than the original antibody. Our studies demonstrate an important correlation between in vitro assays used to evaluate the therapeutic potential of antibodies and their in vivo effectiveness. | 25,142,607 | [
-0.01988109,
-0.05331563,
-0.3531394,
-0.07749492,
0.1867427,
0.1652044,
0.02809392,
0.1501883,
0.1234865,
-0.04585833,
0.2743846,
0.02037952,
0.234359,
0.133574,
-0.2394823,
-0.2672293,
-0.3679777,
-0.1227916,
-0.2350652,
0.1996672,
-0.003707828,
0.3917169,
-0.0192702,
... |
Systematic review of the multidimensional fatigue symptom inventory-short form. | Fatigue is a subjective complaint that is believed to be multifactorial in its etiology and multidimensional in its expression. Fatigue may be experienced by individuals in different dimensions as physical, mental, and emotional tiredness. The purposes of this study were to review and characterize the use of the 30-item Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) in published studies and to evaluate the available evidence for its psychometric properties. A systematic review was conducted to identify published articles reporting results for the MFSI-SF. Data were analyzed to characterize internal consistency reliability of multi-item MFSI-SF scales and test-retest reliability. Correlation coefficients were summarized to characterize concurrent, convergent, and divergent validity. Standardized effect sizes were calculated to characterize the discriminative validity of the MFSI-SF and its sensitivity to change. Seventy articles were identified. Sample sizes reported ranged from 10 to 529 and nearly half consisted exclusively of females. More than half the samples were composed of cancer patients; of those, 59% were breast cancer patients. Mean alpha coefficients for MFSI-SF fatigue subscales ranged from 0.84 for physical fatigue to 0.93 for general fatigue. The MFSI-SF demonstrated moderate test-retest reliability in a small number of studies. Correlations with other fatigue and vitality measures were moderate to large in size and in the expected direction. The MFSI-SF fatigue subscales were positively correlated with measures of distress, depressive, and anxious symptoms. Effect sizes for discriminative validity ranged from medium to large, while effect sizes for sensitivity to change ranged from small to large. Findings demonstrate the positive psychometric properties of the MFSI-SF, provide evidence for its usefulness in medically ill and nonmedically ill individuals, and support its use in future studies. | 25,142,703 | [
-0.1927862,
-0.002660641,
0.05342983,
-0.3375309,
-0.1069394,
-0.2837897,
-0.05765326,
0.1859345,
-0.1273168,
-0.2986232,
0.2189239,
-0.002595824,
-0.1257185,
-0.03652947,
-0.07843043,
-0.4626677,
-0.1945197,
0.05029149,
-0.02846887,
0.1055073,
-0.3361423,
-0.01576904,
-0... |
Effects of ventilation rate per person and per floor area on perceived air quality, sick building syndrome symptoms, and decision-making. | Ventilation rates (VRs) in buildings must adequately control indoor levels of pollutants; however, VRs are constrained by the energy costs. Experiments in a simulated office assessed the effects of VR per occupant on perceived air quality (PAQ), Sick Building Syndrome (SBS) symptoms, and decision-making performance. A parallel set of experiments assessed the effects of VR per unit floor area on the same outcomes. Sixteen blinded healthy young adult subjects participated in each study. Each exposure lasted four hours and each subject experienced two conditions in a within-subject study design. The order of presentation of test conditions, day of testing, and gender were balanced. Temperature, relative humidity, VRs, and concentrations of pollutants were monitored. Online surveys assessed PAQ and SBS symptoms and a validated computer-based tool measured decision-making performance. Neither changing the VR per person nor changing the VR per floor area, had consistent statistically significant effects on PAQ or SBS symptoms. However, reductions in either occupant-based VR or floor-area-based VR had a significant and independent negative impact on most decision-making measures. These results indicate that the changes in VR employed in the study influence performance of healthy young adults even when PAQ and SBS symptoms are unaffected. The study results indicate the importance of avoiding low VRs per person and low VRs per floor area to minimize decrements in cognitive performance. | 25,142,723 | [
-0.1127784,
-0.05358573,
-0.01762055,
0.1587979,
-0.01067095,
0.04205918,
0.03254811,
0.08277535,
0.09462968,
-0.4368614,
0.3207268,
-0.1457802,
-0.1853926,
0.1921593,
0.02149776,
-0.2453865,
-0.5155933,
0.1137925,
-0.0697908,
0.08994006,
-0.372369,
0.6876101,
-0.1757247,... |
Metabolites in safety testing assessment in early clinical development: a case study with a glucokinase activator. | The present article summarizes Metabolites in Safety Testing (MIST) studies on a glucokinase activator, N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (PF-04937319), which is under development for the treatment of type 2 diametes mellitus. Metabolic profiling in rat, dog, and human hepatocytes revealed that PF-04937319 is metabolized via oxidative (major) and hydrolytic pathways (minor). N-Demethylation to metabolite M1 [N-methyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide] was the major metabolic fate of PF-04937319 in human (but not rat or dog) hepatocytes, and was catalyzed by CYP3A and CYP2C isoforms. Qualitative examination of circulating metabolites in humans at the 100- and 300-mg doses from a 14-day multiple dose study revealed unchanged parent drug and M1 as principal components. Because M1 accounted for 65% of the drug-related material at steady state, an authentic standard was synthesized and used for comparison of steady-state exposures in humans and the 3-month safety studies in rats and dogs at the no-observed-adverse-effect level. Although circulating levels of M1 were very low in beagle dogs and female rats, adequate coverage was obtained in terms of total maximal plasma concentration (∼7.7× and 1.8×) and area under the plasma concentration-time curve (AUC; 3.6× and 0.8× AUC) relative to the 100- and 300-mg doses, respectively, in male rats. Examination of primary pharmacology revealed M1 was less potent as a glucokinase activator than the parent drug (compound PF-04937319: EC50 = 0.17 μM; M1: EC50 = 4.69 μM). Furthermore, M1 did not inhibit major human P450 enzymes (IC50 > 30 μM), and was negative in the Salmonella Ames assay, with minimal off-target pharmacology, based on CEREP broad ligand profiling. Insights gained from this analysis should lead to a more efficient and focused development plan for fulfilling MIST requirements with PF-04937319. | 25,142,735 | [
-0.3224467,
0.2330418,
-0.2268096,
-0.3051907,
0.08335944,
-0.2563322,
-0.2571467,
0.10289,
0.2734832,
-0.1648789,
0.1869193,
-0.02317053,
0.04385744,
0.2361544,
-0.3370452,
0.2355488,
-0.8750765,
0.1176061,
0.1354401,
0.09424798,
0.3676174,
0.2450433,
0.04220397,
0.052... |
Dual cases of type 1 narcolepsy with schizophrenia and other psychotic disorders. | Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia. Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens. Ten cases were identified, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested first in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable. Narcolepsy can occur in association with schizophrenia, with significant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted. | 25,142,772 | [
0.0728286,
-0.2739489,
-0.1814787,
-0.09808286,
0.1262642,
-0.5246019,
-0.2749549,
0.03765059,
0.09727973,
0.07349236,
0.1337318,
0.2009125,
0.146231,
0.1251722,
0.248903,
-0.06029747,
-0.3708309,
0.06650912,
0.1295911,
-0.09717517,
-0.01366452,
0.4416302,
-0.3877276,
-... |
Comprehensive screening for mutations associated with colorectal cancer in unselected cases reveals penetrant and nonpenetrant mutations. | Germline mutation testing in patients with colorectal cancer (CRC) is offered only to a subset of patients with a clinical presentation or tumor histology suggestive of familial CRC syndromes, probably underestimating familial CRC predisposition. The aim of our study was to determine whether unbiased screening of newly diagnosed CRC cases with next generation sequencing (NGS) increases the overall detection rate of germline mutations. We analyzed 152 consecutive CRC patients for germline mutations in 18 CRC-associated genes using NGS. All patients were also evaluated for Bethesda criteria and all tumors were investigated for microsatellite instability, immunohistochemistry for mismatch repair proteins and the BRAF*V600E somatic mutation. NGS based sequencing identified 27 variants in 9 genes in 23 out of 152 patients studied (18%). Three of them were already reported as pathogenic and 12 were class 3 germline variants with an uncertain prediction of pathogenicity. Only 1 of these patients fulfilled Bethesda criteria and had a microsatellite instable tumor and an MLH1 germline mutation. The others would have been missed with current approaches: 2 with a MSH6 premature termination mutation and 12 uncertain, potentially pathogenic class 3 variants in APC, MLH1, MSH2, MSH6, MSH3 and MLH3. The higher NGS mutation detection rate compared with current testing strategies based on clinicopathological criteria is probably due to the large genetic heterogeneity and overlapping clinical presentation of the various CRC syndromes. It can also identify apparently nonpenetrant germline mutations complicating the clinical management of the patients and their families. | 25,142,776 | [
-0.1514885,
-0.06906875,
0.1851467,
-0.3131262,
0.1597624,
-0.3612017,
0.2385816,
0.1890406,
-0.04137838,
-0.01687419,
0.1443701,
0.3807665,
0.138466,
-0.1057254,
-0.04799742,
-0.2240053,
-0.2899555,
-0.1538314,
0.1810128,
-0.007608667,
0.3418987,
0.2130826,
0.01662551,
... |
Adamts1 mediates ethanol-induced alterations in collagen and elastin via a FoxO1-sestrin3-AMPK signaling cascade in myocytes. | A variety of stressors including alcohol (EtOH) are known to induce collagen production and fibrotic diseases. Matrix metalloproteinases (MMP) play an important role in regulating fibrosis, but little is known regarding the relationship between EtOH and MMPs. In addition, the signaling cascades involved in this process have not been elucidated. We have identified the MMP Adamts1 as a target of EtOH regulation. To characterize the function of Adamts1, we examined EtOH-induced alterations in collagen I and elastin protein levels in C2C12 myocytes. Incubation of myocytes with 100 mM EtOH decreased elastin and increased collagen content, respectively, and these changes were associated with increased O-GLcNAc modification of Adamts1. Conversely, silencing of Adamts1 by siRNA blocked the adverse effects of EtOH on collagen and elastin levels. Similar results were obtained after treatment with a pharmacological inhibitor of MMP. Changes in collagen were due, at least in part, to a decreased interaction of Adamts1 with its endogenous inhibitor TIMP3. The AMPK inhibitor compound C blocked the EtOH-induced stimulation of collagen and O-GLcNAc Adamts1 protein. Changes in AMPK appear linked to FoxO1, since inhibition of FoxO1 blocked the effects of EtOH on AMPK phosphorylation and O-GLcNAc levels. These FoxO-dependent modifications were associated with an upregulation of the FoxO1 transcription target sestrin 3, as well as increased binding of sestrin 3 with AMPK. Collectively, these data indicate that EtOH regulates the collagen I and elastin content in an Adamts1-dependent manner in myocytes. Furthermore, Adamts1 appears to be controlled by the FoxO1-sestrin 3-AMPK signaling cascade. | 25,142,777 | [
-0.05109206,
0.358804,
0.07222385,
0.1382831,
-0.1758371,
-0.03382139,
-0.008138597,
0.195444,
0.2041344,
0.279368,
0.0589407,
0.1061049,
-0.222722,
-0.1851355,
-0.1627073,
0.4117652,
-0.2191639,
0.1338944,
-0.3578124,
0.115588,
0.08255184,
0.119969,
-0.403873,
-0.30531... |
[Organ and kidney function preservation in renal cell carcinoma]. | The organ-preserving partial nephrectomy has increasingly established itself in small unilateral renal tumours (<4 cm) with contralateral healthy kidney and counter gained in recent years in importance. There was found a significantly increased cardiovascular mortality rate and deteriorated quality of life, the more intact kidney tissue has been removed. In the present study, the influence of pre- and perioperative factors on direct postoperative course was examined, including 5-year survival rate and relapse behaviour after open organ-preserving partial nephrectomy in our own collective. In this retrospective study of 1657 patients were collected, who underwent surgery between 2007 and 2013 in the Department of Urology at the University Hospital Essen because of a renal tumour. 38 % of these operations (n = 636) were performed organ-preserving. In this trial there are factors identified that have an impact on need of blood transfusion and length of hospitalization in organ-preserving operation method. No independent parameter can be determined for the need of blood transfusion. Tumour size and thus time of resection procedure does not affect the need of erythrocytes administration. In addition, the tumour size influences neither the postoperative serum-haemoglobin nor serum-creatinine. Increased patient age and female gender are identified as non-modifiable factors, which cause a longer hospitalisation. Postoperative pain therapy can be considered as a variable size, which does not affect the length of hospital stay. Modifiable factors that increase the overall length of stay, however, are the type of direct postoperative monitoring (ICU vs. anaesthetic recovery room) and the administration of blood transfusions. There are constant factors, which can be associated with a longer residence time in the framework of an organ-preserving partial nephrectomy. Further there is shown evidence of the independence of the tumour size - in addition to proven good oncological results - of an extension of indication of organ-preserving nephrectomy of tumours > 4 cm. | 25,142,788 | [
0.03250803,
0.09536428,
-0.4967889,
-0.2168631,
-0.00009738894,
-0.5951863,
0.3430359,
0.2946171,
-0.0237529,
-0.02281781,
-0.03583746,
-0.008973383,
0.08219905,
-0.2380883,
-0.3315578,
-0.198001,
-0.1427235,
0.1281863,
0.1761441,
0.2690665,
0.01932939,
0.1290606,
-0.4068... |
Robust meta-analysis shows that glioma transcriptional subtyping complements traditional approaches. | Gliomas traditionally have been sub-classified based on histopathological observations. However, this approach is subject to inter-observer variability, and histopathological features may not reflect the biological mechanisms that drive tumor growth. High-throughput transcriptional profiling has shown promise in objectively and reproducibly identifying glioma subtypes. Most prior studies have typically used only modest sample sizes and have sometimes overlooked important data-processing steps to ensure sample quality and to evaluate the robustness of quantitative findings. The purpose of our study was to define robust glioma subtypes by applying rigorous preprocessing and validation steps to 1,952 microarray samples aggregated from 16 prior studies. This data set is the most comprehensive collection of glioma microarray samples compiled to date. We evaluated each sample for quality-control issues, corrected for probe-composition biases, and adjusted for intra- and inter-study batch effects. Using a training/testing validation design that simulates a "bench-to-bedside process," we identified six transcriptional subtypes that contained a heterogeneous mix of histopathological subtypes and tumor grades. Similar to prior studies, age, survival and treatment patterns differed significantly across the transcriptional subtypes. However, due to our large sample size, we also observed that within a given histopathological subtype, our transcriptional subtypes provided additional prognostic value. Lastly, we used a pathway-based approach to elucidate the biological mechanisms associated with each subtype. Our findings provide clinical and biological insights that may not be apparent with alternative approaches or smaller data sets, and our approach serves as an example for meta-analyses that can be applied to other complex diseases. | 25,142,794 | [
-0.1231103,
0.1701787,
-0.1832207,
-0.3645845,
-0.07972427,
-0.4049901,
-0.3197309,
0.04260221,
0.2182767,
-0.1436353,
-0.1121128,
0.00336965,
0.06865387,
-0.04062266,
-0.2189022,
-0.01756546,
-0.006224993,
0.1916461,
-0.2476617,
0.1849086,
0.1421976,
0.1940447,
-0.126959... |
High levels of CD4⁺ CTLA-4⁺ Treg cells and CCR5 density in HIV-1-infected patients with visceral leishmaniasis. | Visceral leishmaniasis (VL) in HIV-1-infected patients has been associated with poor immunological recovery and frequent disease relapses. The aim of this study was to analyse the role of T cell populations, Treg cells and CCR5 density in patients with VL compared to HIV-1-infected patients without leishmaniasis. A cross-sectional study of nine Leishmania-HIV-1-coinfected (LH) patients with VL receiving suppressive cART for at least 1 year were compared to 16 HIV-1-infected patients with non-immunological response (NIR, CD4 count below 250 cells/mm(3)) and 26 HIV-1-infected patients with immunological response (IR, CD4 count above 500 cells/mm(3)) without leishmaniasis. LH patients had a deep depletion of naïve T cells (p = 0.002), despite similar levels of effector T cells compared to NIR patients. CD4 Treg cells were similar compared to NIR patients, but higher compared to IR patients (p < 0.001). Interestingly, CD4 Treg CTLA-4(+) cells were higher in LH patients compared to either NIR or IR patients (p = 0.022 and p < 0.001, respectively), and the CD4 Treg/TEM ratio was similar to NIR patients, but higher compared to IR patients (p = 0.017). CCR5(+) T cell levels were higher compared to IR patients (p < 0.001), while CCR5 density on T cells were higher compared to both NIR and IR patients (p < 0.005 in both cases). Higher levels of CD4(+) CTLA-4(+) Treg cells and CCR5 density on CD8(+) T cells are strongly associated with VL in HIV-1-infected patients. Also, these patients have a poor immunological profile that might explain the persistence and relapse of the pathogen. | 25,142,804 | [
0.2961199,
-0.1158046,
-0.05417595,
0.04655694,
-0.408357,
-0.3353978,
-0.04391462,
-0.13183,
-0.08074737,
-0.005071006,
-0.1576767,
-0.08458754,
-0.001384589,
-0.05898829,
-0.6842816,
-0.3698349,
-0.326495,
0.2091399,
0.07899383,
0.09760737,
-0.1417696,
0.4802332,
0.0352... |
Intranasal drug delivery of olanzapine-loaded chitosan nanoparticles. | The aim of this study was to investigate olanzapine (OZ) systemic absolute bioavailability after intranasal (i.n.) administration in vivo to conscious rabbits. Furthermore, the study investigated the potential use of chitosan nanoparticles as a delivery system to enhance the systemic bioavailability of olanzapine following intranasal administration. Olanzapine-loaded chitosan nanoparticles were prepared through ionotropic gelation of chitosan with tripolyphosphate anions and studied in terms of their size, drug loading, and in vitro release. The OZ nanoparticles were administered i.n. to rabbits, and OZ plasma concentration at predetermined time points was compared to i.n. administration of OZ in solution. The concentrations of OZ in plasma were analyzed by ultra performance liquid chromatography mass spectroscopy (UPLC/MS). OZ-loaded chitosan nanoparticles significantly (p < 0.05) enhanced systemic absorption with 51 ± 11.2% absolute bioavailability as compared to 28 ± 6.7% after i.n. administration of OZ solution. The results of the present study suggest that intranasal administration of OZ-loaded chitosan nanoparticles formulation could be an attractive modality for delivery of OZ systemically. | 25,142,821 | [
0.1331347,
-0.2511385,
-0.1573565,
-0.106259,
-0.01895635,
-0.0714691,
-0.2415423,
0.004422298,
-0.2286433,
-0.3694779,
0.1556318,
-0.1360387,
0.1600639,
0.1145726,
-0.4432532,
-0.02434329,
-0.8627921,
-0.04482181,
0.2739694,
-0.1270999,
0.03705881,
-0.08506614,
-0.000712... |
Improvement in estimated glomerular filtration rate in patients with chronic kidney disease undergoing catheter ablation for atrial fibrillation. | Chronic kidney disease (CKD) and atrial fibrillation (AF) often coexist. We studied the association of CKD with atrial fibrosis and the effect of AF ablation on kidney function. AF patients who had a pre- and postablation serum creatinine and who completed a late gadolinium enhancement cardiac magnetic resonance imaging (MRI; LGE-MRI) prior to ablation were included. Estimated glomerular filtration rate (eGFR) was calculated and CKD was staged using the National Kidney Foundation guidelines. Patients with eGFR <30 mL/min/1.73 m(2) were excluded. LGE-MRI was used to quantify atrial fibrosis. Patients were followed for recurrence and change in eGFR. A total of 392 patients were included in the study. A total of 118 (30.2%) had CKD stage 1, 198 (50.4%) CKD stage 2, 56 (14.3%) CKD stage 3A, and 20 (5.1%) CKD stage 3B. Patients with advanced CKD were more likely to be male and to have cardiovascular disease. Atrial fibrosis was not significant different between included CKD stages: 15.8 ± 8.8%, 16.6 ± 12.1%, 17.1 ± 10.4%, and 16.5 ± 8.4% for CKD stage 1, 2, 3A, and 3B, respectively (P = 0.476). At a median of 115 days following ablation, eGFR increased significantly in CKD stage 2 (74 ± 9 to 80 ± 23; P = 0.04), 3A (53 ± 5 to 69 ± 24; P < 0.001), and 3B (40 ± 4 to 71 ± 28; P < 0.01) and decreased in CKD stage 1 (109 ± 18 to 82 ± 28; P < 0.001). Arrhythmia recurrence was associated with atrial fibrosis (hazard ratio [HR] = 1.04, P < 0.01) and persistent AF (HR = 1.5; P = 0.04) but not with CKD stage (HR = 0.98; P = 0.89). Restoring sinus rhythm with ablation leads to significant improvement of renal function in patients with chronic kidney disease. | 25,142,836 | [
0.04709088,
0.1922071,
-0.5549957,
-0.212146,
-0.02251414,
-0.2817745,
0.02301274,
-0.06651729,
-0.3193425,
-0.01419262,
-0.2442672,
0.3440599,
-0.07098353,
0.1502351,
-0.01043157,
-0.3460056,
0.008849451,
0.05840287,
0.06435528,
-0.2075118,
-0.3570036,
-0.03108702,
-0.26... |
Age-specific changes in intrinsic breast cancer subtypes: a focus on older women. | Breast cancer (BC) is a disease of aging and the number of older BC patients in the U.S. is rising. Immunohistochemical data show that with increasing age, the incidence of hormone receptor-positive tumors increases, whereas the incidence of triple-negative tumors decreases. Few data exist on the frequency of molecular subtypes in older women. Here, we characterize the incidence and outcomes of BC patients by molecular subtypes and age. Data from 3,947 patients were pooled from publicly available clinical and gene expression microarray data sets. The PAM50 algorithm was used to classify tumors into five BC intrinsic subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like. The association of age and subtype with recurrence-free survival (RFS), overall survival, and disease-specific survival (DSS) was assessed. The incidence of luminal (A, B, and A+B) tumors increased with age (p < .01, p < .0001, and p < .0001, respectively), whereas the percentage of basal-like tumors decreased (p < .0001). Among patients 70 years and older, luminal B, HER2-enriched, and basal-like tumors were found at a frequency of 32%, 11%, and 9%, respectively. In older women, luminal subtypes had better outcomes than basal-like and HER2-enriched subtypes. After controlling for subtype, treatment, tumor size, nodal status, and grade, increasing age had no impact on RFS or DSS. More favorable BC subtypes increase with age, but older patients still have a substantial percentage of high-risk tumor subtypes. After accounting for tumor subtypes, age at diagnosis is not an independent prognostic factor for outcome. | 25,142,841 | [
0.3355711,
-0.07964328,
-0.1232008,
-0.09052735,
-0.3003081,
-0.09135153,
0.271672,
-0.024622,
0.1543477,
0.06349964,
-0.05297341,
0.3270912,
0.02854064,
-0.09660728,
-0.2567065,
-0.2716488,
0.2620106,
0.03919404,
0.0814613,
-0.08771361,
0.302906,
0.2159939,
-0.1881612,
... |
[Ecological executive function characteristics and effects of executive function on quality of life in young adult epileptics]. | To explore the characteristics of ecological executive function in young adults with idiopathic or probably symptomatic epilepsy and examine the effects of executive function on quality of life. Fifty-five epileptics (EP) and 39 matched healthy controls (HC) aged 18-44 years at our hospital were selected. The differences in ecological executive function and quality of life were compared between two groups with the Behavior Rating Inventory of Executive Function-adult version (BRIEF-A) and QOLIE-31. Comparing with controls, the epileptics yielded higher scores significantly on most subscales of BRIEF-A (P < 0.05), including total score [(55 ± 9) vs (48 ± 7)], inhibition [(54 ± 7) vs (48 ± 7)], emotion control [(56 ± 8) vs (49 ± 7)], self-monitor [(54 ± 10) vs (47 ± 7)], initiation [(51 ± 10) vs (46 ± 9)], working memory [(56 ± 10) vs (50 ± 9)], planning [(53 ± 10) vs (47 ± 7)], behavioral regulation index (BRI) and metacognition index (MI). Pearson's correlation test showed that the total score of QOLIE-31 had significantly negative correlations with the scores of BRIEF-A, such as global executive composite (GEC), behavioral regulation index (BRI), metacogniton index (MI), inhibition, emotional control, monitoring, initiation and working memory (r = -0.284- -0.457, P < 0.05). Moreover, seizure control and seizure type were also related with the total score of QOLIE-31(r = -0.302, r = 0.268, P < 0.05). Multiple stepwise regression analysis showed that emotional control in BRIEF-A was related with seizure worry and cognitive function in QOLIE-31(t = -2.137, t = -2.427, P < 0.05) . Behavioral regulation index (BRI) was closely related with emotional well-being in QOLIE-31(t = -2.148, P < 0.05). Also, working memory was related with cognitive function, overall quality of life and total score in QOLIE-31(t = -3.138, -3.564, -2.948, P < 0.05). And inhibition was related with energy, social function and total score in QOLIE-31(t = -3.007, -3.580, -2.191, P < 0.05). Young adults with idiopathic or probably symptomatic epilepsy may have significant executive function impairment. The aspects of emotional control, BRI, working memory and inhibition in ecological executive function are significantly related with quality of life in epilepsy. | 25,142,848 | [
0.2224877,
0.3458816,
0.1334224,
-0.2228287,
0.01706032,
-0.4440641,
-0.5035707,
-0.2760969,
-0.2940607,
-0.1837974,
-0.09910669,
0.6040017,
0.03084679,
0.0372126,
-0.1401254,
-0.1801789,
-0.01315071,
0.378768,
0.08487204,
0.04637748,
-0.4642023,
0.294936,
0.2403715,
-0... |
[Surgical correction of congenital vertical talus by one-stage comprehensive soft-tissue release and peritalar reduction incorporating tibialis anterior transfer]. | To evaluate the surgical efficacies of one-stage comprehensive soft-tissue release and peritalar reduction incorporating tibialis anterior transfer (CSTR-PTR-TAT) in patients with congenital vertical talus (CVT) before the age of 4 years. Thirty-five feet of 21 children with true congenital vertical talus were underwent one-stage CSTR-PTR-TAT. The male-to-female ratio was 2.5: 1. Twenty-three percent (5 patients with 8 feet) belonged to isolated CVT and the remainder CVT associated with other congenital or neuromuscular abnormalities. The mean operative age was 30.1 (12-48) months. All patients were available for clinical and radiological follow-ups for a mean period of 3.5 (1.5-7) years.Kodros scoring system was utilized for assessment of final outcomes. The outcomes of 3 feet (9%) were excellent, 27 (77%) good and 5 (14%) fair. All patients wore normal shoes and were satisfied by their functional results and appearance. The patients with fair results were associated with arthrogryposis. No talar avascular necrosis was encountered.None required further operation.Radiologically there was a statistically significant postoperative improvement of measured angles compared to preoperative values (P < 0.05). All radiological parameters were within normal ranges. There was no difference of post operative angles compared to those at the final follow-up (P > 0.05). As a complex deformity usually associated with other congenital or neuromuscular abnormalities, CVT may be satisfactorily managed with one-stage correction by CSTR-PTR-TAT before the age of 4 years. | 25,142,853 | [
0.09934135,
0.09318895,
0.262202,
-0.3139582,
-0.0848698,
-0.3269099,
0.00803633,
0.3469015,
0.2002653,
0.1607509,
0.09286083,
0.1590533,
0.07594483,
0.2169634,
-0.5161334,
-0.5031657,
-0.3215728,
-0.2064206,
0.1587672,
-0.08926442,
-0.04937384,
0.2671698,
-0.233912,
-0... |
[Analysis of prognostic factors for patients with traumatic acute subdural hematomas treated by surgery]. | To analyze the factors correlated with the surgical prognosis of patients with traumatic acute subdural hematoma (ASDH). A total of 117 surgical patients for traumatic ASDH between January 2007 and August 2012 were retrospectively reviewed. The clinical factors correlated with prognosis were statistically analyzed.Glasgow outcome score (GOS) was used for prognostic evaluations and favorable prognosis was defined as 4-5 points. The percentage of patients with favorable prognosis was 43.59% and the mortality 39.32%. The factors correlated with favorable prognosis included age <40 years, pre-operative GCS >8, no pre-operative herniation, duration between injury and surgical depression ≤ 4 h, without injury of drainage vein, mild brain edema and good brain palpation; the factors correlated with mortality included age >60 years, pre-operative GCS ≤ 8, pre-operative herniation, duration between injury and surgical depression >4 h, injury of drainage vein, serious brain edema and weak brain palpation Logistic regression confirmed preoperative GCS >8, no preoperative herniation, injury of drainage vein and postoperative good brain palpation were independent factors associated with favorable prognosis. Patients with age <40 years, preoperative GCS>8, no preoperative herniation, injury of drainage vein and postoperative good brain palpation tend to have favorable prognoses. | 25,142,860 | [
0.2062396,
-0.0436662,
-0.2799521,
-0.2805028,
-0.1656286,
-0.1417099,
-0.365617,
0.07226013,
-0.3523615,
-0.02861163,
0.007356936,
-0.04523597,
-0.4476738,
-0.2180512,
-0.1914669,
0.1209292,
-0.2064654,
0.3604381,
0.1575745,
0.1420536,
0.1137124,
-0.02486304,
0.02130252,... |
Simultaneous monitoring of cerebral metal accumulation in an experimental model of Wilson's disease by laser ablation inductively coupled plasma mass spectrometry. | Neuropsychiatric affection involving extrapyramidal symptoms is a frequent component of Wilson's disease (WD). WD is caused by a genetic defect of the copper (Cu) efflux pump ATPase7B. Mouse strains with natural or engineered transgenic defects of the Atp7b gene have served as model of WD. These show a gradual accumulation and concentration of Cu in liver, kidneys, and brain. However, still little is known about the regional distribution of Cu inside the brain, its influence on other metals and subsequent pathophysiological mechanisms. We have applied laser ablation inductively coupled plasma mass spectrometry and performed comparative metal bio-imaging in brain sections of wild type and Atp7b null mice in the age range of 11-24 months. Messenger RNA and protein expression of a panel of inflammatory markers were assessed using RT-PCR and Western blots of brain homogenates. We could confirm Cu accumulation in brain parenchyma by a factor of two in WD (5.5 μg g(-1) in the cortex) vs. controls (2.7 μg g(-1)) that was already fully established at 11 months. In the periventricular regions (PVR) known as structures of prominent Cu content, Cu was reduced in turn by a factor of 3. This corroborates the view of the PVR as efflux compartments with active transport of Cu into the cerebrospinal fluid. Furthermore, the gradient of Cu increasing downstream the PVR was relieved. Otherwise the architecture of Cu distribution was essentially maintained. Zinc (Zn) was increased by up to 40% especially in regions of high Cu but not in typical Zn accumulator regions, a side effect due to the fact that Zn is to some degree a substrate of Cu-ATPases. The concentrations of iron (Fe) and manganese (Mn) were constant throughout all regions assessed. Inflammatory markers TNF-α, TIMP-1 and the capillary proliferation marker α-SMA were increased by a factor of 2-3 in WD. This study confirmed stable cerebral Cu accumulation in parenchyma and discovered reduced Cu in cerebrospinal fluid in Atp7b null mice underlining the diagnostic value of micro-local analytical techniques. | 25,142,911 | [
-0.1989189,
-0.0916669,
-0.5729738,
-0.2098463,
0.3124854,
-0.4113866,
0.01498168,
-0.05466564,
-0.1540022,
0.2647377,
-0.0436993,
0.2142265,
0.2544277,
-0.1243742,
-0.6044703,
0.1388523,
0.2417794,
0.07792268,
-0.168042,
0.363317,
0.408134,
0.2988642,
-0.13188,
0.01377... |
Monocyte-derived dendritic cells from HLA-B27+ axial spondyloarthritis (SpA) patients display altered functional capacity and deregulated gene expression. | This study aimed to compare the functional capacity and gene expression profile of monocyte-derived dendritic cells (MD-DCs) in HLA-B27+ axial spondyloarthritis (SpA) patients and healthy controls. MD-DCs were differentiated with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for seven days, starting from purified CD14+ monocytes and stimulated with lipopolysaccharide (LPS) for six and twenty four hours. Their capacity to stimulate allogeneic CD4+ T cells from unrelated healthy donor was tested. Transcriptomic study was performed with Affymetrix HuGene 1.0 ST microarrays. Gene expression levels were compared between patients and controls using a multivariate design under a linear model (LIMMA). Real-time quantitative PCR (qRT-PCR) was performed for validation of the most striking gene expression differences. The stimulatory capacity of allogeneic CD4+ T cells by MD-DCs from SpA patients was decreased. Transcriptomic analysis revealed 81 genes differentially expressed in MD-DCs between SpA patients and controls (P <0.01 and fold-change <0.66 or >1.5). Four selected genes were validated by q ADAMTS15, CITED2, F13A1 and SELL. Expression levels of ADAMTS15 and CITED2, encoding a metallopeptidase and a transcription factor, respectively, were inversely correlated with each other (R = 0.75, P = 0.0003). Furthermore, in silico analysis identified several genes of the Wnt signaling pathway having expression co-regulated with CITED2. This study revealed altered function and gene expression pattern in MD-DCs from HLA-B27+ axial SpA. Co-expression study showed an inverse correlation between ADAMTS15 and CITED2. Moreover, the Wnt signaling pathway appeared as deregulated in SpA MD-DCs, a finding which may be connected to Th17-driven inflammatory responses. | 25,142,923 | [
-0.1272941,
0.2641737,
-0.02035453,
0.3090937,
-0.009121547,
-0.5538474,
-0.3702213,
0.2735379,
-0.2880004,
0.05418969,
0.2102313,
0.07339901,
0.102497,
-0.291158,
-0.6652097,
0.3366014,
-0.1973578,
-0.1073186,
-0.5959899,
0.411111,
0.8396974,
0.3731636,
-0.2746465,
0.0... |
Fate of xylem-transported 11C- and 13C-labeled CO2 in leaves of poplar. | In recent studies, assimilation of xylem-transported CO2 has gained considerable attention as a means of recycling respired CO2 in trees. However, we still lack a clear and detailed picture on the magnitude of xylem-transported CO2 assimilation, in particular within leaf tissues. To this end, detached poplar leaves (Populus × canadensis Moench 'Robusta') were allowed to take up a dissolved (13)CO2 label serving as a proxy of xylem-transported CO2 entering the leaf from the branch. The uptake rate of the (13)C was manipulated by altering the vapor pressure deficit (VPD) (0.84, 1.29 and 1.83 kPa). Highest tissue enrichments were observed under the highest VPD. Among tissues, highest enrichment was observed in the petiole and the veins, regardless of the VPD treatment. Analysis of non-labeled leaves showed that some (13)C diffused from the labeled leaves and was fixed in the mesophyll of the non-labeled leaves. However, (13)C leaf tissue enrichment analysis with elemental analysis coupled to isotope ratio mass spectrometry was limited in spatial resolution at the leaf tissue level. Therefore, (11)C-based CO2 labeling combined with positron autoradiography was used and showed a more detailed spatial distribution within a single tissue, in particular in secondary veins. Therefore, in addition to (13)C, (11) C-based autoradiography can be used to study the fate of xylem-transported CO2 at leaf level, allowing the acquisition of data at a yet unprecedented resolution. | 25,142,926 | [
-0.05696845,
0.1525138,
-0.0319333,
0.3268925,
0.2629538,
-0.1057876,
-0.3439672,
-0.0708498,
-0.1125428,
-0.03277647,
0.09515846,
-0.1705081,
0.05872341,
-0.01561317,
-0.5496024,
-0.07096145,
-0.06100692,
0.08920019,
0.2281954,
0.3524739,
0.3324783,
0.7282614,
-0.0278448... |
The economic cost of a poor start to life. | A primary challenge for nutrition policy in low-income settings is to position nutrition as an investment rather than simply as a form of social spending that governments grant poor people to the degree that governments prioritize equity. Various economic models have produced estimates of the economic costs of malnutrition as a combination of the impact of malnutrition on mortality, on health care costs for the survivors, including those that manifest in adult years, and on the lost productivity attributable to malnutrition. However, these estimates often center on the costs of early mortality and are sensitive to assumptions on how to place a dollar cost on mortality. This study argues that even when focusing only on the productivity impact of malnutrition - clearly a lower bound of the full costs - the economic consequences of malnutrition are substantial. Stating this somewhat differently, the economic returns to preventing malnutrition are on a par with those investments generally considered at the heart of economic development strategies. Moreover, the body of evidence that has been accumulated to indicate these productivity gains is both substantial and robust. | 25,142,929 | [
-0.3317104,
0.02377051,
-0.1516993,
-0.1624573,
0.2133367,
0.1576528,
-0.08003931,
0.09855766,
0.06328148,
-0.03397268,
-0.03204381,
0.08744274,
-0.2445155,
0.0660444,
-0.4306917,
-0.2628649,
-0.0246044,
0.06341124,
-0.3002983,
-0.03463349,
-0.02954334,
0.5729022,
-0.1134... |
The effect of late gestation foetal hypoglycaemia on cardiovascular and endocrine function in sheep. | An appropriate foetal cardiovascular (CV) response to reduced substrate supply (e.g. oxygen or other nutrients) is vital for growth and development, and may impact on CV control. The prevailing nutritional environment and associated CV changes may influence subsequent CV responses to challenges during late gestation, for example, umbilical cord occlusion (UCO). We investigated the effect of low-circulating glucose on foetal CV control mechanisms and response to UCO. Under general anaesthesia, late gestation foetal sheep (n = 7, 119 days gestational age (dGA), term ∼147 days) were implanted with vascular catheters, a bladder catheter, electrocardiogram electrodes and an umbilical cord occluder. Mean arterial pressure (MAP), heart rate (HR) and kidney function were monitored during maternal saline (MSAL, 125dGA) and insulin (MINS, 126dGA) infusion, and foetal CV responses were assessed during incremental doses of angiotensin II, a 90-s total UCO, and administration of phenylephrine to assess baroreflex function. During MINS infusion, the decrease in maternal and foetal blood glucose was associated with a small but significant decrease in foetal HR and reduced foetal baroreflex sensitivity (P < 0.05). The increase in foetal MAP during a 90-s UCO was greater during hypoglycaemia (P < 0.05). The MAP response to angiotensin II was not affected by hypoglycaemia. Decreased foetal HR and baroreflex sensitivity and increased CV responsiveness to UCO during hypoglycaemia indicates altered CV homoestatic mechanisms. The combination of altered nutrition and a CV challenge, such as UCO, during late gestation may have a cumulative effect on foetal CV function. | 25,142,930 | [
0.1724294,
-0.098067,
-0.2900927,
-0.1817621,
0.2021036,
-0.1756191,
-0.3254865,
-0.005056418,
0.03080215,
-0.05385783,
-0.01841255,
0.1727307,
0.05084357,
-0.1356072,
-0.4153075,
-0.1703041,
-0.1545211,
0.397787,
-0.2306744,
0.2015284,
0.03046927,
0.08986266,
-0.1034727,... |
Five new anthraquinones from the seed of Cassia obtusifolia. | A phytochemical investigation on the seeds of Cassia obtusifolia led to the isolation of five new anthraquinones, including one aglycon and four glycosides. The structures were elucidated by analysis of extensive spectroscopic data and the results of acid hydrolysis. All these isolates were evaluated for their inhibitory effects against α-glucosidase, and 1 showed potent activity with IC50 value of 185 ± 15 µM. | 25,142,941 | [
-0.2889726,
0.1711969,
-0.2790251,
0.07155517,
0.193209,
0.3559963,
-0.4024152,
-0.002607147,
0.2776732,
-0.06507358,
0.1300076,
0.02064929,
-0.0189578,
-0.3542157,
-0.1423533,
0.3859965,
-0.5406392,
0.4186852,
0.05198281,
0.07373454,
0.4381469,
0.1501495,
-0.2257072,
-... |
[Renal arteriovenous fistula with a vein aneurysm: a case report]. | A 54-year-old woman presented with abdominal distension. Her medical history was unremarkable. Contrast-enhanced computed tomography (CT) revealed a left renal arteriovenous fistula and a large vein aneurysm, and she was diagnosed with aneurismal-type renal arteriovenous fistula. She was successfully treated with transcatheter arterial embolization using steel coils. Although she had pulmonary embolism as a serious post-operative complication, she recovered with anticoagulant therapy using heparin and warfarin. A contrast-enhanced CT scan performed 6 months after transcatheter arterial embolization did not show recanalization. | 25,142,960 | [
-0.1384548,
0.3807006,
-0.2582244,
0.2666096,
0.2351079,
-0.03188265,
-0.4872453,
-0.1604174,
-0.0596658,
-0.03896483,
0.2587897,
0.3310078,
-0.1862776,
-0.2330416,
-0.3266315,
-0.1065363,
-0.1136176,
0.5305152,
0.4087747,
-0.4527628,
-0.04497546,
0.113664,
-0.4479106,
... |
Serological versus molecular typing of surface-associated immune evading polysaccharide antigens-based phenotypes of Staphylococcus aureus. | The aim of this study was to compare the performance of serological versus molecular typing methods to detect capsular polysaccharide (CP) and surface-associated polysaccharide antigen 336 phenotypes of Staphylococcus aureus isolates. Molecular typing of CP types 1, 5 and 8 was carried out using PCR, whereas serological typing of CP1, 2, 5, 8 and antigen 336 was carried out by slide agglutination using specific antisera. By genotyping, 14/31 strains were CP8 positive, 12/31 strains were CP5 and the remaining 6/31 isolates were non-typable (NT). One isolate was positive for both CP5 and CP8 by PCR, but was confirmed as CP8 type serologically. Detection of CP2 and type 336 by PCR was not possible because specific primers were either not available or non-specific. Using serotyping, 14/31 strains were CP8 positive, 11/31 CP5 positive and 2/31 positive for antigen 336. The remaining four S. aureus isolates were serologically NT. However, three of four NT and two 336-positive S. aureus isolates were encapsulated as determined by light microscopy after capsular staining. This discovery was surprising and warrants further investigations on the identification and characterization of additional capsular phenotypes prevalent among S. aureus clinical isolates. It was concluded that serological typing was a better method than molecular typing for use in epidemiological investigations based upon the distribution of surface-associated polysaccharide antigens-based phenotypes. | 25,142,964 | [
0.07265481,
-0.003635971,
0.04695373,
-0.3135227,
-0.2019265,
-0.2035775,
-0.2392209,
0.1444959,
0.06342686,
0.1119842,
-0.05464324,
0.2403312,
0.06290781,
-0.1656078,
0.06500603,
-0.1927935,
-0.01281172,
0.2960625,
0.1036565,
-0.004576069,
0.2268969,
0.2553197,
-0.252906... |
Novel treatment strategies for schizophrenia from improved understanding of genetic risk. | Recent years have seen significant advances in our understanding of the genetic basis of schizophrenia. In particular, genome-wide approaches have suggested the involvement of many common genetic variants of small effect, together with a few rare variants exerting relatively large effects. While unequivocal identification of the relevant genes has, for the most part, remained elusive, the genes revealed as potential candidates can in many cases be clustered into functionally related groups which are potentially open to therapeutic intervention. In this review, we summarise this information, focusing on the accumulating evidence that genetic dysfunction at glutamatergic synapses and post-synaptic signalling complexes contributes to the aetiology of the disease. In particular, there is converging support for involvement of post-synaptic JNK pathways in disease aetiology. An expansion of our neurobiological knowledge of the basis of schizophrenia is urgently needed, yet some promising novel pharmacological targets can already be discerned. | 25,142,969 | [
0.08535912,
0.0833805,
0.2053322,
-0.4431138,
0.05776853,
-0.2260536,
-0.09104393,
-0.1239318,
-0.04319263,
0.1431634,
0.04768574,
0.07361995,
0.0372345,
0.02889436,
-0.3148214,
0.02189745,
-0.3615255,
0.2049321,
0.03753887,
0.04873396,
-0.07503261,
0.3399827,
-0.1088084,... |
[Relationship between cyclooxygenase-2 in nasopharyngeal carcinoma and cervical lymph node metastasis]. | To explore the expression of cyclooxygenase-2 (COX-2) in lowly differentiated nasopharyngeal carcinoma and examine its relationship with cervical lymph node metastasis. On the basis of COX expression, a total of 104 patients with lowly differentiated squamous cell carcinoma NPC were divided into 2 groups of COX-2 high-expression and COX-2 low-expression. The influence on prognosis was assessed by retrospective analysis. The overall positive rate for COX-2 staining was 78.8% (82/104) . The rate of patients with lymph node metastasis was significantly higher than that in those without (84.5% vs 55.0%, χ(2) = 6.765, P = 0.009). Further comparison showed that patients with age <45 years and neck lymph node metastasis had higher rate of COX-2 high expression than those with age >45 years and no cervical lymph node metastasis (58.7% vs 37.7%, χ(2) = 4.439, P = 0.035; 52.4% vs 25.0%, χ(2) = 4.861, P = 0.027). At the end of follow-up, the recurrence rate with inter-group statistical differences (χ(2) = 4.786, P = 0.029) was 32.7% (16/49) and 14.6% (8/55) respectively. Meanwhile, as compared with COX-2 high-expression group, the transferring rate in COX-2 low-expression group significantly decreased (17.7% vs 28.6%, χ(2) = 4.037, P = 0.045). Multiple logistic regression analysis showed that COX-2 high expression was a risk factor of nasopharyngeal carcinoma recurrence [OR = 2.039, 95%CI (1.042-5.875)]. COX-2 expression is up-regulated in lowly differentiated nasopharyngeal carcinoma tissues. And it may be risk factor influencing the prognosis of NPC. | 25,142,993 | [
0.1069808,
-0.1201053,
-0.2723601,
0.03768438,
-0.09909971,
-0.3511716,
-0.08423567,
0.09364384,
0.08029387,
0.009875945,
0.1283266,
0.04587396,
0.1067749,
-0.1888011,
-0.3945306,
-0.2990394,
0.04268729,
0.1276509,
0.05711199,
0.3032499,
0.06426481,
0.2263428,
-0.3717072,... |
[Expressions of Dab2 and ERK1 in esophageal carcinoma tissues and their clinical significance]. | To explore the expressions of protein and mRNA of disabled-2 (Dab2) and extracellular signal-regulated kinase1 (ERK1) in esophageal squamous cell carcinoma tissue (ESCC) and their clinical significance. The expressions of protein and mRNA of Dab2 and ERK1 were detected in ESCC (n = 59), atypical hyperplasia (n = 27) and normal esophageal mucosa (n = 36) tissues by immunohistochemistry, in situ hybridization and reverse transcription polymerase chain reaction (RT-PCR). The expressions of protein and mRNA of Dab2 were lesser in ESCC than those in atypical hyperplasia and normal esophageal mucosa tissues (23.7% vs 94.4%, 44.4% and 18.6% vs 97.2%, 33.3%). And the expressions of protein and mRNA ERK1 were higher in ESCC than those in atypical hyperplasia and normal esophageal mucosa tissues (81.4% vs 44.4%, 63.0% and 78.0% vs 30.6%, 51.9%) (all P < 0.05). Additionally, the expressions of protein and mRNA of Dab2 and ERK1 were closely related with lymph node metastasis in ESCC tissue and the expressions of protein and mRNA of ERK1 closely related with the depth of tumor invasion in ESCC tissue (all P < 0.05). Furthermore, the results of correlation analysis revealed that expressions of protein and mRNA of Dab2 and ERK1 in ESCC had a negative correlation (all P < 0.05). The expressions of protein and mRNA of Dab2 and ERK1 play important roles in the infiltration, metastasis and carcinogenesis of ESCC and their effects may be antagonistic to each other. | 25,142,995 | [
-0.1743895,
-0.2061781,
-0.319873,
-0.1592553,
0.08300326,
-0.4110848,
-0.01955885,
0.3782556,
-0.05197433,
0.3270371,
0.2871129,
0.1164409,
0.211067,
-0.3057721,
0.03690883,
-0.3479832,
-0.4818985,
-0.001534439,
0.1452031,
-0.2228783,
0.4821901,
0.1168557,
-0.2070326,
... |
Effects of herbicide-treated host plants on the development of Mamestra brassicae L. caterpillars. | Herbicides are widely used pesticides that affect plants by changing their chemistry. In doing so, herbicides might also influence the quality of plants as food for herbivores. To study the effects of herbicides on host plant quality, 3 plant species (Plantago lanceolata L., P. major L., and Ranunculus acris L.) were treated with sublethal rates of either a sulfonylurea (Atlantis WG, Bayer CropScience) or a glyphosate (Roundup LB Plus, Monsanto) herbicide, and the development of caterpillars of the cabbage moth Mamestra brassicae L. that fed on these plants was observed. Of the 6 tested plant-herbicide combinations, 1 combination (R. acris + sulfonylurea herbicide) resulted in significantly lower caterpillar weight, increased time to pupation, and increased overall development time compared with larvae that were fed unsprayed plants. These results might be caused by a lower nutritional value of these host plants or increased concentrations of secondary metabolites that are involved in plant defense. The results of the present and other studies suggest potential risks to herbivores that feed on host plants treated with sublethal rates of herbicides. However, as the effects of herbicides on host plant quality appear to be species-specific and as there are numerous plant-herbicide-herbivore relationships in agricultural landscapes, a general reduction in herbicide contamination of nontarget habitats (e.g., field margins) might mitigate the negative effects of herbicides on host plant quality. | 25,143,001 | [
0.08068792,
0.422399,
-0.09364075,
-0.3063326,
0.03726767,
-0.02225645,
-0.3182539,
0.08254431,
0.09790961,
-0.09026805,
0.03033572,
-0.08706156,
0.1858351,
0.1218279,
-0.3516336,
0.08547579,
-0.2592978,
0.4732929,
0.1072162,
-0.1682543,
-0.03783703,
0.5393089,
-0.288693,... |
Liver enzyme elevation during darunavir-based antiretroviral treatment in HIV-1-infected patients with or without hepatitis C coinfection: data from the ICONA foundation cohort. | To investigate differences in liver enzyme elevation (LEE) between HIV-infected patients with and without HCV coinfection who start a darunavir/ritonavir-containing regimen. HIV-infected patients enrolled in the Italian Cohort of Naïve to Antiretrovirals (ICONA) Foundation Study were included if they started darunavir/ritonavir for the first time. Patients were classified as not HCV coinfected, HCV active coinfected (HCV RNA positive), and HCV nonactive coinfected (HCV-Ab positive/HCV RNA negative). Time to LEE endpoint was defined using the ACTG toxicity scale, based on changes relative to baseline. Kaplan-Meier was used to estimate 1-year and 2-year probability of LEE. The incidence rate ratios (IRRs) of LEEs were estimated until the last follow-up (intention-to-treat analysis [ITT]) and up to darunavir/ritonavir discontinuation (on-treatment analysis [OT]). Overall, 703 patients were included. Ninety-one were HCV-Ab positive; of those, 68 (9.7%) had active HCV coinfection. In 879 person-years of follow-up, 101 LEEs occurred (ITT). No severe hepatotoxicity event was registered in active HCV coinfected patients. HCV active coinfection was predictive of LEE in the overall population (OT: adjusted incidence rate ratio (IRR), 2.25; 95% CI, 0.70-7.24; P = .17; ITT: adjusted IRR, 3.62; 95% CI, 1.67-7.83; P < .001) and in naïve patients (OT: adjusted IRR, 6.29; 95% CI, 2.54-15.55; P = .00; ITT: adjusted IRR, 3.87; 95% CI, 0.99-15.16; P = .05). No grade 3-4 LEEs occurred in HCV active coinfected patients. HCV active coinfected patients experienced low grade LEEs more frequently than HCV-Ab negative patients. Darunavir/ritonavir seems to be safe whatever the HCV status, when liver enzymes are carefully monitored. | 25,143,024 | [
0.04558407,
0.2065588,
0.05847763,
0.155357,
0.008539545,
-0.2556077,
-0.1164149,
0.1922153,
0.1753342,
-0.07651076,
-0.07093251,
0.09919915,
0.2621955,
0.2311153,
-0.3143691,
-0.3471333,
-0.3270651,
0.1238549,
0.3252524,
0.3166448,
0.2554365,
0.1589123,
-0.3724535,
0.2... |
Time flies: Time of day and social environment affect cuticular hydrocarbon sexual displays in Drosophila serrata. | Recent work on Drosophila cuticular hydrocarbons (CHCs) challenges a historical assumption that CHCs in flies are largely invariant. Here, we examine the effect of time of day and social environment on a suite of sexually selected CHCs in Drosophila serrata. We demonstrate that males become more attractive to females during the time of day that flies are most active and when most matings occur, but females become less attractive to males during the same time of day. These opposing temporal changes may reflect differences in selection among the sexes. To evaluate the effect of social environment on male CHC attractiveness, we manipulated male opportunity for mating: male flies were housed either alone, with five females, with five males or with five males and five females. We found that males had the most attractive CHCs when with females, and less attractive CHCs when with competitor males. Social environment mediated how male CHC attractiveness cycled: males housed with females and/or other males showed temporal changes in CHC attractiveness, whereas males housed alone did not. In total, our results demonstrate temporal patterning of male CHCs that is dependent on social environment, and suggest that such changes may be beneficial to males. | 25,143,030 | [
0.1885262,
0.05220752,
-0.1986215,
0.08547972,
0.124576,
-0.02185216,
-0.09797045,
0.03866033,
0.2007641,
-0.09199417,
-0.004734208,
0.02660154,
-0.04403468,
-0.3770785,
-0.2391406,
-0.1454885,
-0.284412,
0.1691193,
0.2906585,
-0.1516312,
-0.2664719,
0.564439,
-0.1904148,... |
Foster carers influence brood pathogen resistance in ants. | Social organisms face a high risk of epidemics, and respond to this threat by combining efficient individual and collective defences against pathogens. An intriguing and little studied feature of social animals is that individual pathogen resistance may depend not only on genetic or maternal factors, but also on the social environment during development. Here, we used a cross-fostering experiment to investigate whether the pathogen resistance of individual ant workers was shaped by their own colony of origin or by the colony of origin of their carers. The origin of care-giving workers significantly influenced the ability of newly eclosed cross-fostered Formica selysi workers to resist the fungal entomopathogen Beauveria bassiana. In particular, carers that were more resistant to the fungal entomopathogen reared more resistant workers. This effect occurred in the absence of post-infection social interactions, such as trophallaxis and allogrooming. The colony of origin of eggs significantly influenced the survival of the resulting individuals in both control and pathogen treatments. There was no significant effect of the social organization (i.e. whether colonies contain a single or multiple queens) of the colony of origin of either carers or eggs. Our experiment reveals that social interactions during development play a central role in moulding the resistance of emerging workers. | 25,143,036 | [
0.2391237,
0.02486592,
-0.1475028,
-0.2823439,
0.172055,
-0.1471332,
-0.1175391,
-0.2886595,
-0.06127492,
-0.3976634,
0.03223742,
-0.4513498,
0.1377418,
-0.1963767,
0.03109573,
-0.03238861,
-0.459047,
0.09871082,
-0.1152718,
0.2646445,
-0.2082934,
0.5104339,
-0.1989836,
... |
Tissue cell assisted fabrication of tubular catalytic platinum microengines. | We report a facile platform for mass production of robust self-propelled tubular microengines. Tissue cells extracted from fruits of banana and apple, Musa acuminata and Malus domestica, are used as the support on which a thin platinum film is deposited by means of physical vapor deposition. Upon sonication of the cells/Pt-coated substrate in water, microscrolls of highly uniform sizes are spontaneously formed. Tubular microengines fabricated with the fruit cell assisted method exhibit a fast motion of ∼100 bodylengths per s (∼1 mm s(-1)). An extremely simple and affordable platform for mass production of the micromotors is crucial for the envisioned swarms of thousands and millions of autonomous micromotors performing biomedical and environmental remediation tasks. | 25,143,056 | [
-0.1134491,
-0.09055313,
-0.1779645,
0.1522863,
0.1031475,
-0.01955234,
-0.4937135,
0.09851839,
0.1336662,
0.07450645,
0.08796286,
-0.2131663,
0.01010935,
-0.00167237,
-0.6192783,
0.1825462,
-0.2883535,
0.03936862,
-0.03774309,
-0.1900856,
0.3042753,
0.04515718,
-0.349865... |
Size at birth is associated with blood pressure but not insulin resistance in 6-8 year old children in rural Nepal. | Earlier, we reported that antenatal micronutrient supplementation reduced the risk of metabolic syndrome and microalbuminuria among offspring at 6-8 years of age in rural Nepal. In the same birth cohort, we examined associations of size at birth (weight, length and ponderal index), and gestational age, with cardiometabolic risk factors in childhood across all antenatal micronutrient interventions. There was an inverse association between birth weight and systolic blood pressure (SBP, β = -1.20 mm Hg/kg; 95% confidence interval (CI): -1.93, -0.46) and diastolic blood pressure (DBP, β = -1.24 mm Hg/kg; 95% CI: -2.00, -0.49). Current child body mass index was positively associated with SBP but not with DBP. Birth weight was unassociated with insulin resistance, but each kilogram of increase was associated with a reduced risk of high triglycerides (odds ratio (OR) = 0.64/kg; 95% CI: 0.41, 0.97) and an increased risk of high waist circumference (OR = 3.16/kg; 95% CI: 2.47, 4.41). In this rural Nepalese population of children 6-8 years of age with a high prevalence of undernutrition, size at birth was inversely associated with blood pressure and triglycerides and positively associated with waist circumference. | 25,143,065 | [
-0.07842663,
-0.09893677,
-0.09501418,
-0.03930445,
0.06960522,
-0.1083098,
-0.2932922,
0.003588623,
0.09651067,
0.1150724,
0.1413326,
-0.08078337,
-0.008360727,
0.04871607,
-0.3094161,
-0.07577935,
-0.1233631,
0.4456606,
-0.01460376,
0.1198665,
-0.5366442,
0.1510546,
-0.... |
Childhood obesity and autonomic dysfunction: risk for cardiac morbidity and mortality. | The epidemic of childhood obesity is becoming a major predictor for risk of cardiovascular diseases (CVD) and mortality during adulthood. Alterations in the morphology of the heart due to obesity could be a predictor for the dysfunction of cardiac autonomic modulation (CAM). A number of epidemiologic studies have evaluated the effect of obesity and CAM in children, finding that obesity impaired the balance of CAM toward a sympathetic overflow and reduced parasympathetic modulation, a significant predictor of CVD morbidity and mortality in adults. Lifestyle modifications, for example long-term exercise programs, have been shown to improve CAM in the obese. This review discusses the recent evidence on childhood and adolescent obesity and its impact on CAM, as well as how early lifestyle changes could help improve CAM, which may in turn reduce the burden of CVD in adults. | 25,143,120 | [
-0.2075712,
0.04617599,
-0.1750715,
-0.004816485,
-0.05800134,
-0.2696427,
-0.0005996678,
0.07086173,
-0.2729932,
-0.06459825,
0.05026127,
0.1588843,
0.0550769,
-0.1818444,
-0.4639135,
0.005101657,
-0.3009933,
0.3715559,
0.02556979,
0.1183616,
-0.07735679,
0.3559985,
-0.4... |
Prognostic significance of immunophenotypes and a nodular pattern in primary mediastinal large B-cell lymphoma. | To investigate the clinicopathological and prognostic significance of a nodular pattern and immunophenotypes in primary mediastinal large B-cell lymphoma (PMBL), histopathological features, including a nodular pattern and immunophenotypes, were analyzed in 58 Japanese PMBL patients. The patients were 23 men and 35 women with a median age of 31 years. The 4-year progression free survival (PFS) rate was 78%, and the 4-year overall survival (OS) rate was 89%. Among the histopathological and immunohistochemical features, Bcl6(+) (P = 0.013), MUM1(+) (P = 0.091), and pale cytoplasm (P = 0.064) were favorable prognostic indicators of PFS, and Bcl6(+) (P = 0.051) and MUM1(+) (P = 0.07) were favorable prognostic indicators of OS. Patients with Bcl2 negativity (n = 11) had 4-year PFS and OS rates of 100%. Histologically, a nodular pattern, resembling nodular sclerosis classical Hodgkin lymphoma (CHL), was observed in 22 patients (38%). However, this was not a significant prognostic indicator. In conclusion, Bcl6(+) , MUM1(+) , Bcl2(-) , and pale cytoplasm are candidate favorable prognostic indicators for PMBL and should be further examined in larger studies. We suggest that PMBL with a nodular pattern may belong to the same histological spectrum as nodular sclerosis CHL. | 25,143,126 | [
-0.07371633,
-0.04815759,
-0.006497633,
-0.566012,
-0.3673792,
-0.3174329,
0.1639284,
-0.1627788,
-0.06817751,
0.09551121,
0.1081749,
0.3917317,
0.2605005,
0.2180964,
-0.03849255,
-0.007291401,
-0.1424678,
0.3339402,
0.2027605,
0.2073816,
0.5756307,
0.4163598,
-0.00782094... |
Proteome analysis of early lineage specification in bovine embryos. | During mammalian embryo development, the zygote undergoes embryonic cleavage in the oviduct and reaches the uterus at the morula stage, when compaction and early lineage specification take place. To increase knowledge about the associated changes of the embryonic protein repertoire, we performed a comprehensive proteomic analysis of in vitro produced bovine morulae and blastocysts (six biological replicates), using an iTRAQ-based approach. A total of 560 proteins were identified of which 502 were quantified. The abundance of 140 proteins was significantly different between morulae and blastocysts, among them nucleophosmin (NPM1), eukaryotic translation initiation factor 5A-1 (EIF5A), receptor of activated protein kinase C 1 (GNB2L1/RACK1), and annexin A6 (ANXA6) with increased, and glutathione S-transferase mu 3 (GSTM3), peroxiredoxin 2 (PRDX2), and aldo-keto reductase family 1 member B1 (AKR1B1) with decreased abundance in blastocysts. Seventy-three percent of abundance altered proteins increased, reflecting an increase of translation activity in this period. This is further supported by an increase in the abundance of proteins involved in the translation machinery and the synthesis of ATP. Additionally, a complementary 2D saturation DIGE analysis led to the detection of protein isoforms, e.g. of GSTM3 and PRDX2, relevant for this period of mammalian development, and exemplarily verified the results of the iTRAQ approach. In summary, our systematic differential proteome analysis of bovine morulae and blastocysts revealed new molecular correlates of early lineage specification and differentiation events during bovine embryogenesis. | 25,143,135 | [
0.08460671,
-0.08720586,
-0.1760301,
-0.09883621,
-0.07251652,
-0.04995695,
0.1236615,
-0.02500319,
0.2552082,
-0.1741508,
0.1164388,
-0.1064563,
-0.001127229,
0.01193838,
0.08984485,
0.09561728,
-0.6629362,
0.0304041,
0.1928245,
-0.2377286,
0.5614862,
0.3925098,
-0.08061... |
Naming game on networks: let everyone be both speaker and hearer. | To investigate how consensus is reached on a large self-organized peer-to-peer network, we extended the naming game model commonly used in language and communication to Naming Game in Groups (NGG). Differing from other existing naming game models, in NGG everyone in the population (network) can be both speaker and hearer simultaneously, which resembles in a closer manner to real-life scenarios. Moreover, NGG allows the transmission (communication) of multiple words (opinions) for multiple intra-group consensuses. The communications among indirectly-connected nodes are also enabled in NGG. We simulated and analyzed the consensus process in some typical network topologies, including random-graph networks, small-world networks and scale-free networks, to better understand how global convergence (consensus) could be reached on one common word. The results are interpreted on group negotiation of a peer-to-peer network, which shows that global consensus in the population can be reached more rapidly when more opinions are permitted within each group or when the negotiating groups in the population are larger in size. The novel features and properties introduced by our model have demonstrated its applicability in better investigating general consensus problems on peer-to-peer networks. | 25,143,140 | [
-0.1481107,
0.4922917,
0.1575223,
-0.006409273,
0.3501342,
-0.1561381,
-0.4629273,
0.01439856,
0.04721786,
-0.3168905,
0.1543365,
-0.04179397,
-0.09736551,
-0.127964,
-0.4040026,
0.08453323,
0.04703168,
0.2926591,
0.001055532,
-0.2422297,
0.2464058,
0.3388718,
-0.1438318,... |
Extraordinarily high pseudocapacitance of metal organic framework derived nanostructured cerium oxide. | MOF derived CeO2 showed a pseudocapacitance of 1204 F g(-1) at 0.2 A g(-1), far exceeding its theoretical capacitance (560 F g(-1)). The present study demonstrates that combination of a two-way strategy, controlled nano-architecture and redox active electrolyte additive, could potentially alleviate both low energy density and capacitance fading issues plaguing the current metal oxide pseudocapacitors. | 25,143,153 | [
-0.2194591,
0.3222527,
-0.0742844,
0.1175627,
-0.09390476,
0.1019023,
-0.2726237,
0.002168773,
-0.07722122,
-0.1486201,
-0.1130519,
0.2661395,
0.03132847,
0.1360003,
-0.4574882,
-0.07440829,
-0.1376394,
0.06253847,
-0.1219755,
0.04277439,
-0.1510286,
0.1013658,
-0.0473020... |
[Clinical classification and surgical management of cervicothoracic intraspinal lipomas]. | To explore the clinical classification and surgical management of cervicothoracic intraspinal lipomas. A total of 22 patients with cervicothoracic intraspinal lipomas were analyzed retrospectively with regards to clinical manifestations, radiographic features, intraoperative findings, surgical techniques and follow-ups. Total (n = 4), subtotal (n = 7) and partial (n = 11) resection was performed. Long-term neurological outcomes were evaluated by modified McCormick classification scheme. Their symptoms improved (n = 15), unchanged (n = 3) and deteriorated (n = 4). And cervicothoracic intraspinal lipomas could be classified into extradural, transitional, chaotic and secondary intramedullary groups. Different groups of cervicothoracic intraspinal lipomas vary in the degree of resection and surgical efficacy. Total resection may be performed on most extradural lipomas. The surgical objective of transitional lipomas is decompression. Chaotic and secondary intramedullary lipomas should target effective resection to avoid neurological function injury. Intraoperative use of laser facilitates tumor resection. Intraoperative electrophysiological monitoring protects spinal cord. | 25,143,160 | [
-0.007722415,
0.08423796,
0.1436699,
-0.3915676,
-0.01457609,
-0.3590775,
-0.3037821,
0.02420552,
0.2984507,
0.3128023,
-0.0001453512,
0.03860829,
0.08627795,
-0.421901,
-0.07787402,
0.06384631,
-0.4877727,
-0.297491,
0.1457325,
-0.09344231,
-0.1238748,
0.3594862,
0.01716... |
[Clinical features and microsurgical treatment of spinal intramedullary cavernoma]. | To explore the clinical features and microsurgical treatment of spinal intramedullary cavernomas (SICs). A total of 21 patients with pathologically confirmed SIC undergoing microsurgical resection of cavernomas at Beijing Tiantan Hospital and Taian Central Hospital from June 2005 to December 2012 were reviewed retrospectively. The postoperative neurological status improved (n = 13) and remained unchanged (n = 6) and aggravated (n = 2). The clinical features of SICs are related with their different pathological processes. Magnetic resonance imaging (MRI) is specific for the diagnosis of SICs. Appropriate strategies and refined microsurgical techniques are essential for improving the clinical efficacies of SICs. | 25,143,163 | [
0.04451781,
0.39875,
0.1802104,
-0.3465223,
-0.08040313,
-0.04805863,
-0.03882504,
-0.03218687,
0.1555049,
0.2739742,
0.1753251,
0.06149443,
-0.09174978,
-0.394443,
-0.2566812,
-0.1411461,
-0.3065355,
-0.1705995,
0.08804377,
0.3422951,
-0.09016523,
0.2543038,
0.1050668,
... |
Effect of minimally invasive surgery on the risk for surgical site infections: results from the National Surgical Quality Improvement Program (NSQIP) Database. | Surgical site infection (SSI) represents the second most common cause of hospital-acquired infection and the most common type of infection in patients undergoing surgery. However, evidence is scarce regarding the effect of the surgical approach (open surgery vs minimally invasive surgery [MIS]) on the risk for SSIs. To evaluate the role of the surgical approach on the risk for SSIs in a large contemporary cohort of patients undergoing surgery across different specialties. The American College of Surgeons National Surgical Quality Improvement Program database is a national, prospective perioperative database specifically developed to assess quality of surgical care. We queried the database from January 1, 2005, through December 31, 2011, for patients undergoing appendectomy (n = 97,780), colectomy (n = 118,407), hysterectomy (n = 26,639), or radical prostatectomy (n = 11,183). Thirty-day SSIs. We abstracted the data on 30-day SSIs and compared patients undergoing open procedures and MIS using propensity score matching. Logistic regression analyses of the matched cohorts tested the association between the surgical approach and risk for SSIs. The overall 30-day rates of SSIs were 5.4% for appendectomy, 12.1% for colectomy, 2.8% for hysterectomy, and 1.7% for prostatectomy. After propensity score matching, MIS was associated with lower rates of postoperative SSIs in patients undergoing MIS vs open procedures for appendectomy (3.8% vs 7.0%; P < .001), colectomy (9.3% vs 15.0%; P < .001), hysterectomy (1.8% vs 3.9%; P < .001), and radical prostatectomy (1.0% vs 2.4%; P < .001). In logistic regression analyses, MIS was associated with lower odds of SSIs in patients treated with appendectomy (odds ratio [OR], 0.52 [95% CI, 0.48-0.58]; P < .001), colectomy (OR, 0.58 [95% CI, 0.55-0.61]; P < .001), hysterectomy (OR, 0.44 [95% CI, 0.37-0.53]; P < .001), and radical prostatectomy (OR, 0.39 [95% CI, 0.25-0.61]; P < .001). The proportion of patients developing SSIs within 30 days after surgery can be substantial and depends on the type of surgery. Minimally invasive surgery is significantly associated with reduced odds of SSIs. This advantage should be considered when assessing the overall benefits of minimally invasive techniques. | 25,143,176 | [
-0.1187956,
0.008081823,
-0.5905552,
-0.2759774,
-0.3891306,
-0.1511233,
-0.1289932,
-0.03800077,
0.0346749,
-0.03379497,
0.2289948,
0.1942539,
0.05419188,
-0.4249281,
-0.1668718,
-0.234855,
-0.05322081,
0.04944417,
0.1291109,
-0.4026456,
-0.1241282,
-0.09174693,
-0.13920... |
Identification of Belgian mosquito species (Diptera: Culicidae) by DNA barcoding. | Since its introduction in 2003, DNA barcoding has proven to be a promising method for the identification of many taxa, including mosquitoes (Diptera: Culicidae). Many mosquito species are potential vectors of pathogens, and correct identification in all life stages is essential for effective mosquito monitoring and control. To use DNA barcoding for species identification, a reliable and comprehensive reference database of verified DNA sequences is required. Hence, DNA sequence diversity of mosquitoes in Belgium was assessed using a 658 bp fragment of the mitochondrial cytochrome oxidase I (COI) gene, and a reference data set was established. Most species appeared as well-supported clusters. Intraspecific Kimura 2-parameter (K2P) distances averaged 0.7%, and the maximum observed K2P distance was 6.2% for Aedes koreicus. A small overlap between intra- and interspecific K2P distances for congeneric sequences was observed. Overall, the identification success using best match and the best close match criteria were high, that is above 98%. No clear genetic division was found between the closely related species Aedes annulipes and Aedes cantans, which can be confused using morphological identification only. The members of the Anopheles maculipennis complex, that is Anopheles maculipennis s.s. and An. messeae, were weakly supported as monophyletic taxa. This study showed that DNA barcoding offers a reliable framework for mosquito species identification in Belgium except for some closely related species. | 25,143,182 | [
-0.0482755,
0.1572438,
0.1424768,
-0.2168174,
0.02302748,
-0.138366,
0.05265497,
-0.009160942,
0.2566303,
-0.3043755,
-0.1752504,
-0.4191812,
0.1394655,
-0.2984997,
-0.9930931,
-0.2043276,
-0.01295894,
0.3315214,
0.5050189,
-0.01997901,
0.2513451,
-0.0749654,
0.1076653,
... |
The electron is a catalyst. | The electron is an efficient catalyst for conducting various types of radical cascade reaction that proceed by way of radical and radical ion intermediates. But because electrons are omnipresent, catalysis by electrons often passes unnoticed. In this Review, a simple analogy between acid/base catalysis and redox catalysis is presented. Conceptually, the electron is a catalyst in much the same way that a proton is a catalyst. The 'electron is a catalyst' paradigm unifies mechanistically an assortment of synthetic transformations that otherwise have little or no apparent relationship. Diverse radical cascades, including unimolecular radical substitution reactions (SRN1-type chemistry), base-promoted homolytic aromatic substitutions (BHAS), radical Heck-type reactions, radical cross-dehydrogenative couplings (CDC), direct arene trifluoromethylations and radical alkoxycarbonylations, can all be viewed as electron-catalysed reactions. | 25,143,210 | [
-0.1681191,
-0.005973335,
-0.1200857,
0.07361322,
0.04468099,
-0.2849089,
-0.4167517,
-0.1157125,
0.1702299,
-0.001377329,
0.001248136,
0.1756699,
0.2703429,
0.3060364,
-0.6563176,
-0.2826777,
-0.5888558,
0.00729482,
0.1220814,
-0.07962698,
-0.04748783,
0.08508921,
-0.124... |
A nanoporous two-dimensional polymer by single-crystal-to-single-crystal photopolymerization. | In contrast to the wide number and variety of available synthetic routes to conventional linear polymers, the synthesis of two-dimensional polymers and unambiguous proof of their structure remains a challenge. Two-dimensional polymers-single-layered polymers that form a tiling network in exactly two dimensions-have potential for use in nanoporous membranes and other applications. Here, we report the preparation of a fluorinated hydrocarbon two-dimensional polymer that can be exfoliated into single sheets, and its characterization by high-resolution single-crystal X-ray diffraction analysis. The procedure involves three steps: preorganization in a lamellar crystal of a rigid monomer bearing three photoreactive arms, photopolymerization of the crystalline monomers by [4 + 4] cycloaddition, and isolation of individual two-dimensional polymer sheets. This polymer is a molecularly thin (~1 nm) material that combines precisely defined monodisperse pores of ~9 Å with a high pore density of 3.3 × 10(13) pores cm(-2). Atomic-resolution single-crystal X-ray structures of the monomer, an intermediate dimer and the final crystalline two-dimensional polymer were obtained and prove the single-crystal-to-single-crystal nature and molecular precision of the two-dimensional photopolymerization. | 25,143,211 | [
-0.1412567,
0.1544876,
0.1423785,
-0.137643,
0.2160864,
-0.1059808,
-0.5247229,
-0.07836415,
0.4130848,
0.06924144,
-0.10126,
-0.5235614,
-0.01734184,
0.1000026,
-0.1852084,
-0.1126331,
-0.4959761,
0.2461026,
0.02997702,
0.05990031,
0.347097,
0.1853389,
-0.2651046,
-0.0... |
γδ T-cell-rich variants of pityriasis lichenoides and lymphomatoid papulosis: benign cutaneous disorders to be distinguished from aggressive cutaneous γδ T-cell lymphomas. | T cells with a γδ phenotype have been associated with aggressive lymphomas. Yet, inflammatory skin disorders and low-grade lymphoproliferative disorders have rarely been described with a predominant γδ T-cell infiltrate. To review our experience and determine the clinical relevance of the γδ T-cell phenotype in lymphomatoid papulosis (LyP) and pityriasis lichenoides (PL). A retrospective dermatopathology file review looking for LyP and PL characterized by a γδ T-cell phenotype was performed. Clinical manifestations and course, histological features and molecular data were analyzed. Six of 16 cases of LyP and four of 23 cases diagnosed as PL during a 5-year period (2009-14) were identified. The median follow-up for the whole group was 16 months (range 3-64), showing an indolent clinical course in all cases. The detection of a predominantly γδ T-cell phenotype in papular lymphoid-rich infiltrates in the absence of other lesions is not associated with a clinically aggressive course. γδ T-cell-rich variants of LyP and PL may reflect a spectrum of related conditions. This is a single academic centre retrospective chart review of a relatively small sample. | 25,143,223 | [
-0.1320877,
-0.4301881,
-0.4750327,
-0.3896156,
-0.06814508,
-0.4573154,
-0.1818348,
-0.09147695,
-0.03592934,
0.3324449,
0.1615254,
0.307532,
0.07394497,
-0.05994732,
-0.05802318,
-0.1751486,
-0.1596788,
-0.03580249,
0.4166991,
-0.1621653,
0.3352551,
0.4589952,
-0.207980... |
Long-term quality of life after radical prostatectomy: 8-year longitudinal study in Japan. | To assess long-term health-related quality of life in patients undergoing radical prostatectomy. A total of 120 patients with at least 5 years of follow up after radical prostatectomy were included in the present study. Health-related quality of life outcomes were assessed using three questionnaires, the Short Form 36-Item Health Survey, the University of California, Los Angeles Prostate Cancer Index and the International Prostate Symptom Score. A total of 91 patients (73%) responded at a median follow-up time of 102 months (range 85-123 months). Among general health-related quality of life domains, mental and role composite summary score remained stable throughout the follow-up period. At the final survey, no significant differences were observed in any of the domains compared with the age-matched average score of the Japanese population. Although the slight decrease in urinary function scores and International Prostate Symptom Score beyond 5 years postoperatively compared with 5 years, the differences were not significant. The sexual function summary score showed a substantially lower score just after radical prostatectomy and remained at a deteriorated level (P < 0.001). Responders at the final survey were more likely to report favorable general, urinary and sexual outcomes at 60 months compared with non-responders. When taking age-related changes into account, general health-related quality of life seems to remain stable in the long term after radical prostatectomy: patients with favorable health-related quality of life outcomes during the first 5 years after radical prostatectomy maintain favorable outcomes thereafter. | 25,143,229 | [
0.02790335,
-0.1930967,
-0.1308921,
-0.3506809,
-0.2885662,
-0.2587156,
0.1804904,
0.4123301,
-0.1235727,
-0.1209763,
0.2491664,
-0.000684941,
-0.06449969,
-0.133318,
-0.3296098,
-0.2730664,
0.3250177,
0.367545,
0.3660099,
-0.2132897,
0.2480724,
0.3495155,
-0.07593136,
... |
Dimerization of 30Kc19 protein in the presence of amphiphilic moiety and importance of Cys-57 during cell penetration. | Recently, the recombinant 30Kc19 protein, originating from silkworm hemolymph of Bombyx mori has attracted attention due to its cell-penetrating property and potential application as a protein delivery system. However, this observation of penetration across cell membrane has raised questions concerning the interaction of the protein-lipid bilayer. Here, we report a dimerization propensity of the 30Kc19 protein in the presence of amphiphilic moieties; sodium dodecyl sulfate (SDS) or phospholipid. Native PAGE showed that the 30Kc19 monomer formed a dimer when SDS or phospholipid was present. In the glutathione-S-transferase (GST) pull-down assay, supplementation of the 30Kc19 protein to mammalian cell culture medium showed dimerization and penetration; due to phospholipids at the cell membrane, the main components of the lipid bilayer. Mutagenesis was performed, and penetration was observed by 30Kc19 C76A and not 30Kc19 C57A, which meant that the presence of cysteine at position 57 (Cys-57) is involved in dimerization of the 30Kc19 at the cell membrane during penetration. We anticipate application of the native 30Kc19 protein with high cell-penetrating efficiency for delivery of cargos to various cell types. The intracellular cargo delivery using the 30Kc19 protein is a non-virus derived (e.g. TAT) delivery method, which can open up new approaches for the delivery of therapeutics in bioindustries, such as pharma- and cosmeceuticals. | 25,143,246 | [
-0.04761374,
-0.2406921,
-0.2375849,
-0.07131508,
-0.06000575,
0.1083333,
-0.2506877,
0.2531391,
0.1856395,
-0.1975924,
0.1427038,
-0.1453295,
-0.001594896,
0.03511894,
-0.4419951,
0.1538711,
-0.2979929,
-0.06265979,
-0.05213377,
-0.00541449,
0.01201329,
0.2396353,
-0.014... |
Collapse of the native structure caused by a single amino acid exchange in human NAD(P)H:quinone oxidoreductase(1.). | Human quinone oxidoreductase 1 (NQO1) is essential for the antioxidant defense system, stabilization of tumor suppressors (e.g. p53, p33, and p73), and activation of quinone-based chemotherapeutics. Overexpression of NQO1 in many solid tumors, coupled with its ability to convert quinone-based chemotherapeutics into potent cytotoxic compounds, have made it a very attractive target for anticancer drugs. A naturally occurring single-nucleotide polymorphism (C609T) leading to an amino acid exchange (P187S) has been implicated in the development of various cancers and poor survival rates following anthracyclin-based adjuvant chemotherapy. Despite its importance for cancer prediction and therapy, the exact molecular basis for the loss of function in NQO1 P187S is currently unknown. Therefore, we solved the crystal structure of NQO1 P187S. Surprisingly, this structure is almost identical to NQO1. Employing a combination of NMR spectroscopy and limited proteolysis experiments, we demonstrated that the single amino acid exchange destabilized interactions between the core and C-terminus, leading to depopulation of the native structure in solution. This collapse of the native structure diminished cofactor affinity and led to a less competent FAD-binding pocket, thus severely compromising the catalytic capacity of the variant protein. Hence, our findings provide a rationale for the loss of function in NQO1 P187S with a frequently occurring single-nucleotide polymorphism. Structural data are available in the Protein Data Bank under the accession numbers 4cet (P187S variant with dicoumarol) and 4cf6 (P187S variant with Cibacron blue). NQO1 P187S and NQO1 P187S bind by nuclear magnetic resonance (View interaction) NQO1 P187S and NQO1 P187S bind by x-ray crystallography (1, 2) NQO1 and NQO1 bind by molecular sieving (1, 2). | 25,143,260 | [
-0.03448439,
0.2593495,
0.09590722,
-0.2522848,
0.1489601,
-0.3320432,
0.1182146,
0.1469814,
0.2050933,
-0.03616922,
0.08560783,
0.07132085,
0.06225355,
-0.1720175,
-0.4706233,
0.07878284,
-0.4586907,
-0.03255013,
0.1743768,
0.1968741,
0.3078681,
0.1128562,
-0.3474967,
... |
The prognosis of diabetic retinopathy in patients with type 2 diabetes since 1996-1998: the Skaraborg Diabetes Register. | Diabetes mellitus is the main reason for visual impairment among patients of working ages. The aim of this paper was to investigate the prognosis of eye complications in patients with diabetes during 10 years of follow-up and contributing risk factors. Data from ophthalmological records (occurrence of retinopathy and laser treatment and visual acuity), and clinical data (blood pressure, glycosylated hemoglobin (HbA1c), body mass index (BMI), and antihypertensive treatment) from the Skaraborg Diabetes Register were retrieved in the Skaraborg Screening Program of 1,258 patients diagnosed during 1996-1998. Kaplan Meyer survival analysis and Log Rank test were used to analyze eye complications in 773 patients with type 2 diabetes and ≤70 years at diagnosis. Visual acuity was above the limit for driving license in 96 % of 548 patients and only nineteen patients were treated by laser. At diagnosis of diabetes, mean HbA1c was 6.7 ± 1.7 % (59 ± 7.1 mmol/mol), and systolic blood pressure was 142.9 ± 0.7 mmHg; neither changed significantly during follow-up. Retinopathy appeared about 1 year, and maculopathy 2 years earlier, if HbA1c ≥ 7 % (63 mmol/mol) at diagnosis (p < 0.001 and p < 0.006). Antihypertensive treatment, higher BMI, and higher age at diagnosis were associated with less retinopathy during follow-up. Most patients with diabetes develop little retinopathy for the first 10 years after diagnosis. High HbA1c at baseline was associated with retinopathy and maculopathy during follow-up. Antihypertensive treatment, probably a proxy for regular controls and early detection of diabetes, was associated with less retinopathy. | 25,143,261 | [
0.1773856,
-0.2279886,
-0.6147047,
-0.2855013,
0.232962,
-0.4235399,
0.2455058,
0.0455621,
0.1376803,
-0.2879366,
0.1704526,
0.1044934,
-0.01061449,
-0.2864032,
-0.1506084,
0.09542109,
0.009382448,
0.5055481,
0.2816305,
0.1181837,
-0.04321886,
0.4619516,
-0.2297132,
-0.... |
[Recent advances in understanding the innate immune mechanisms and developing new disease resistance breeding strategies against the rice blast fungus Magnaporthe oryzae in rice]. | Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most destructive diseases in rice. Utilization of resistant cultivars is the most effective and economic strategy against the disease. Recently, rice blast has become an advanced model system for elucidating the molecular mechanisms of plant-fungal interactions. Significant progress has been made in the molecular biology, genomics and proteomics of the rice-M. oryzae interaction and host resistance in the last few years. In this review, we summarize the recent advances in understanding the molecular basis of PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI) in rice against M. oryzae, and propose the new strategies for blast resistance molecular breeding. We also discuss the new challenges for future investigations. | 25,143,273 | [
-0.06858147,
-0.182311,
0.3936256,
-0.2122523,
-0.1949443,
-0.1928742,
0.1336043,
0.1126045,
-0.04818687,
0.06357368,
0.1799026,
0.4436661,
-0.2559552,
-0.06330784,
-0.4282068,
-0.2838595,
-0.5070481,
0.1137406,
0.1141827,
-0.1613126,
0.06284393,
0.3353955,
-0.4192936,
... |
Retinal vasculitis: a novel paradoxical effect of anti-TNFα? | Retinal vasculitis (RV) is extremely rare in spondyloarthritis associated with Crohn's disease. Infliximab, a chimeric monoclonal antibody to tumour necrosis factor (TNF) α, is efficient in spondyloarthritis, Crohn's disease and RV. We present the case of a 41-year-old man with a known history of spondyloarthritis associated with Crohn's disease. He was under treatment with infliximab. Four days after his 12th infusion of infliximab, he presented with sudden blurred vision. Although his disease was in remission, ophthalmological examination revealed bilateral peripheral retinal occlusive vasculitis. The patient responded positively to the treatment by laser photocoagulation and peribulbar corticosteroid injection. Infliximab was not stopped. There was improvement in his eye disease. To the best of our knowledge, this is the first case of new onset of RV occurring under infliximab in a patient with Crohn's related spondyloarthritis. This case illustrates the possibility of a paradoxical effect of this kind of therapy. | 25,143,312 | [
-0.006261643,
-0.3170637,
-0.3909715,
0.1121243,
0.2081314,
-0.2271001,
-0.04876405,
0.1035836,
-0.2873293,
-0.2264491,
0.01603618,
0.1969254,
-0.05272903,
-0.1169068,
0.1071234,
-0.1839964,
-0.4966948,
-0.1243553,
0.3105109,
-0.09497903,
0.1553084,
0.4441223,
-0.240062,
... |
Sigmoid volvulus in an adolescent girl: staged management with emergency colonoscopic reduction and decompression followed by elective sigmoid colectomy. | A case of acute sigmoid volvulus in a 14-year-old adolescent girl presenting with acute low large bowel obstruction with a background of chronic constipation has been presented. Abdominal radiograph and CT scan helped in diagnosis. She underwent emergency colonoscopic detorsion and decompression uneventfully. Lower gastrointestinal contrast study showed very redundant sigmoid colonic loop without any transition zone and she subsequently underwent elective sigmoid colectomy with good outcome. The sigmoid volvulus should be considered in the differential diagnosis of paediatric acute abdomen presenting with marked abdominal distention, absolute constipation and pain but without vomiting. Plain abdominal radiograph and the CT scan are helpful to confirm the diagnosis. Early colonoscopic detorsion and decompression allows direct visualisation of the vascular compromise, assessment of band width of the volvulus and can reduce complications and mortality. Associated Hirschsprung's disease should be suspected if clinical and radiological features are suggestive in which case a rectal biopsy before definitive surgery should be considered. | 25,143,313 | [
-0.04527022,
-0.1442226,
0.1231114,
-0.3937875,
0.08369329,
-0.4081305,
-0.1211703,
-0.2977262,
-0.07895198,
-0.09011304,
-0.08285301,
0.05663814,
-0.4825033,
0.1672626,
-0.1521459,
-0.3047202,
-0.464005,
0.07051522,
-0.02276188,
-0.4757084,
0.07170324,
0.1056291,
-0.2540... |
ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation. | The objective of this article is to test the effects of angiotensin-converting enzyme (ACE)-inhibition on glomerular epithelial cell number in an inducible experimental model of focal segmental glomerulosclerosis (FSGS). Although ACE-inhibition has been shown to limit podocyte loss by enhancing survival, little is known about its effect on podocyte number following an abrupt decline in disease. Experimental FSGS was induced with cytotoxic antipodocyte antibody. Following induction, groups were randomized to receive the ACE-inhibitor enalapril, the smooth muscle relaxant hydralazine (blood pressure control) or drinking water. Blood pressure, kidney function and histology were measured seven and 14 days following disease induction. Both glomerulosclerosis and urinary albumin-to-creatinine ratio were less in the ACE-inhibition arm at day 14. At day 7 of disease, mean podocyte numbers were 26% and 29% lower in the enalapril and hydralazine arms, respectively, compared to normal mice in which no antibody was injected. At day 14, the mean podocyte number was only 18% lower in the enalapril arm, but was 39% lower in the hydralazine arm compared to normal mice. Podocyte proliferation did not occur at any time in any group. Compared to water- or hydralazine-treated mice with FSGS, the enalapril arm had a higher mean number of glomerular parietal epithelial cells that co-expressed the podocyte proteins WT-1 and synaptopodin, as well as phospho-ERK. The results show following an abrupt decline in podocyte number, the initiation of ACE-inhibition but not hydralazine, was accompanied by higher podocyte number in the absence of proliferation. This was accompanied by a higher number of parietal epithelial cells that co-express podocyte proteins. Increasing podocyte number appears to be accompanied by reduced glomerulosclerosis. | 25,143,333 | [
-0.1587586,
-0.1790996,
-0.3771272,
-0.3393458,
0.1552248,
-0.1055163,
0.01696674,
0.3419845,
0.06752611,
-0.09069116,
-0.1040968,
0.3195201,
-0.2226088,
-0.2213599,
-0.5008259,
-0.02026115,
-0.2528952,
0.321827,
0.0182991,
0.4787973,
-0.3899769,
-0.01958029,
-0.2275608,
... |
A highly potent agonist to protease-activated receptor-2 reveals apical activation of the airway epithelium resulting in Ca2+-regulated ion conductance. | The airway epithelium provides a barrier that separates inhaled air and its various particulates from the underlying tissues. It provides key physiological functions in both sensing the environment and initiating appropriate innate immune defenses to protect the lung. Protease-activated receptor-2 (PAR2) is expressed both apically and basolaterally throughout the airway epithelium. One consequence of basolateral PAR2 activation is the rapid, Ca(2+)-dependent ion flux that favors secretion in the normally absorptive airway epithelium. However, roles for apically expressed PAR2 activation have not been demonstrated, in part due to the lack of specific, high-potency PAR2 ligands. In the present study, we used the newly developed PAR2 ligand 2at-LIGRLO(PEG3-Pam)-NH2 in combination with well-differentiated, primary cultured airway epithelial cells from wild-type and PAR2 (-/-) mice to examine the physiological role of PAR2 in the conducting airway after apical activation. Using digital imaging microscopy of intracellular Ca(2+) concentration changes, we verified ligand potency on PAR2 in primary cultured airway cells. Examination of airway epithelial tissue in an Ussing chamber showed that apical activation of PAR2 by 2at-LIGRLO(PEG3-Pam)-NH2 resulted in a transient decrease in transepithelial resistance that was due to increased apical ion efflux. We determined pharmacologically that this increase in ion conductance was through Ca(2+)-activated Cl(-) and large-conductance K(+) channels that were blocked with a Ca(2+)-activated Cl(-) channel inhibitor and clotrimazole, respectively. Stimulation of Cl(-) efflux via PAR2 activation at the airway epithelial surface can increase airway surface liquid that would aid in clearing the airway of noxious inhaled agents. | 25,143,347 | [
0.2991951,
-0.4985619,
-0.2852309,
-0.1116933,
0.02857182,
0.06038241,
0.1288838,
0.09719201,
0.3346025,
0.2137041,
-0.00438252,
0.3441316,
-0.1021727,
0.1359212,
-0.4975209,
-0.05437209,
-0.3797253,
0.1440706,
-0.170748,
0.0240309,
0.2979881,
0.1486131,
-0.04316127,
0.... |
Pericyte contractility controls endothelial cell cycle progression and sprouting: insights into angiogenic switch mechanics. | Microvascular stability and regulation of capillary tonus are regulated by pericytes and their interactions with endothelial cells (EC). While the RhoA/Rho kinase (ROCK) pathway has been implicated in modulation of pericyte contractility, in part via regulation of the myosin light chain phosphatase (MLCP), the mechanisms linking Rho GTPase activity with actomyosin-based contraction and the cytoskeleton are equivocal. Recently, the myosin phosphatase-RhoA-interacting protein (MRIP) was shown to mediate the RhoA/ROCK-directed MLCP inactivation in vascular smooth muscle. Here we report that MRIP directly interacts with the β-actin-specific capping protein βcap73. Furthermore, manipulation of MRIP expression influences pericyte contractility, with MRIP silencing inducing cytoskeletal remodeling and cellular hypertrophy. MRIP knockdown induces a repositioning of βcap73 from the leading edge to stress fibers; thus MRIP-silenced pericytes increase F-actin-driven cell spreading twofold. These hypertrophied and cytoskeleton-enriched pericytes demonstrate a 2.2-fold increase in contractility upon MRIP knockdown when cells are plated on a deformable substrate. In turn, silencing pericyte MRIP significantly affects EC cycle progression and angiogenic activation. When MRIP-silenced pericytes are cocultured with capillary EC, there is a 2.0-fold increase in EC cycle entry. Furthermore, in three-dimensional models of injury and repair, silencing pericyte MRIP results in a 1.6-fold elevation of total tube area due to EC network formation and increased angiogenic sprouting. The pivotal role of MRIP expression in governing pericyte contractile phenotype and endothelial growth should lend important new insights into how chemomechanical signaling pathways control the "angiogenic switch" and pathological angiogenic induction. | 25,143,350 | [
-0.2578269,
0.09398107,
-0.1108542,
-0.3449247,
-0.01001434,
0.0262273,
-0.0862507,
0.1950871,
0.2160623,
0.257767,
-0.004530342,
0.3358529,
-0.4981913,
-0.1569072,
-0.7769663,
0.2741384,
-0.3548452,
-0.002491256,
-0.1844694,
0.219406,
0.1457917,
0.2892861,
0.2012603,
-... |
Proteasome inhibition in skeletal muscle cells unmasks metabolic derangements in type 2 diabetes. | Two-dimensional difference gel electrophoresis (2-D DIGE)-based proteome analysis has revealed intrinsic insulin resistance in myotubes derived from type 2 diabetic patients. Using 2-D DIGE-based proteome analysis, we identified a subset of insulin-resistant proteins involved in protein turnover in skeletal muscle of type 2 diabetic patients, suggesting aberrant regulation of the protein homeostasis maintenance system underlying metabolic disease. We then validated the role of the ubiquitin-proteasome system (UPS) in myotubes to investigate whether impaired proteasome function may lead to metabolic arrest or insulin resistance. Myotubes derived from muscle biopsies obtained from people with normal glucose tolerance (NGT) or type 2 diabetes were exposed to the proteasome inhibitor bortezomib (BZ; Velcade) without or with insulin. BZ exposure increased protein carbonylation and lactate production yet impaired protein synthesis and UPS function in myotubes from type 2 diabetic patients, marking the existence of an insulin-resistant signature that was retained in cultured myotubes. In conclusion, BZ treatment further exacerbates insulin resistance and unmasks intrinsic features of metabolic disease in myotubes derived from type 2 diabetic patients. Our results highlight the existence of a confounding inherent abnormality in cellular protein dynamics in metabolic disease, which is uncovered through concurrent inhibition of the proteasome system. | 25,143,351 | [
0.004961779,
-0.1154394,
0.1033662,
-0.112003,
0.1303135,
-0.1103203,
0.1509358,
0.1604874,
0.4301691,
0.1655331,
0.1160735,
0.03109013,
-0.1593331,
0.06714173,
-0.363168,
0.2765216,
-0.5262195,
0.0608065,
-0.1477646,
0.0462252,
0.01589993,
0.3617018,
-0.1786909,
-0.074... |
Joint analysis of differential gene expression in multiple studies using correlation motifs. | The standard methods for detecting differential gene expression are mostly designed for analyzing a single gene expression experiment. When data from multiple related gene expression studies are available, separately analyzing each study is not ideal as it may fail to detect important genes with consistent but relatively weak differential signals in multiple studies. Jointly modeling all data allows one to borrow information across studies to improve the analysis. However, a simple concordance model, in which each gene is assumed to be differential in either all studies or none of the studies, is incapable of handling genes with study-specific differential expression. In contrast, a model that naively enumerates and analyzes all possible differential patterns across studies can deal with study-specificity and allow information pooling, but the complexity of its parameter space grows exponentially as the number of studies increases. Here, we propose a correlation motif approach to address this dilemma. This approach searches for a small number of latent probability vectors called correlation motifs to capture the major correlation patterns among multiple studies. The motifs provide the basis for sharing information among studies and genes. The approach has flexibility to handle all possible study-specific differential patterns. It improves detection of differential expression and overcomes the barrier of exponential model complexity. | 25,143,368 | [
0.1214944,
-0.02110645,
-0.05982854,
0.01861213,
0.0828664,
-0.4226889,
-0.310719,
0.02030029,
0.1431998,
-0.2948607,
-0.02567895,
-0.2379882,
0.2484415,
0.1892283,
-0.4472288,
0.1433171,
-0.1010136,
-0.08805087,
-0.2930946,
0.2234003,
0.2195411,
0.01154051,
0.02023002,
... |
Program impact pathway analysis of a social franchise model shows potential to improve infant and young child feeding practices in Vietnam. | By mapping the mechanisms through which interventions are expected to achieve impact, program impact pathway (PIP) analysis lays out the theoretical causal links between program activities, outcomes, and impacts. This study examines the pathways through which the Alive & Thrive (A&T) social franchise model is intended to improve infant and young child feeding (IYCF) practices in Vietnam. Mixed methods were used, including qualitative interviews with franchise management board members (n = 12), surveys with health providers (n = 120), counseling observations (n = 160), and household surveys (n = 2045). Six PIP components were assessed: 1) franchise management, 2) training and IYCF knowledge of health providers, 3) service delivery, 4) program exposure and utilization, 5) maternal behavioral determinants (knowledge, beliefs, and intentions) toward optimal IYCF practices, and 6) IYCF practices. Data were collected from A&T-intensive areas (A&T-I; mass media + social franchise) and A&T-nonintensive areas (A&T-NI; mass media only) by using a cluster-randomized controlled trial design. Data from 2013 were compared with baseline where similar measures were available. Results indicate that mechanisms are in place for effective management of the franchise system, despite challenges to routine monitoring. A&T training was associated with increased capacity of providers, resulting in higher-quality IYCF counseling (greater technical knowledge and communication skills during counseling) in A&T-I areas. Franchise utilization increased from 10% in 2012 to 45% in 2013 but fell below the expected frequency of 9-15 contacts per mother-child dyad. Improvements in breastfeeding knowledge, beliefs, intentions, and practices were greater among mothers in A&T-I areas than among those in A&T-NI areas. In conclusion, there are many positive changes along the impact pathway of the franchise services, but challenges in utilization and demand creation should be addressed to achieve the full intended impact. | 25,143,372 | [
-0.1773728,
0.02316499,
0.145725,
-0.2500306,
0.2364427,
-0.2176519,
-0.03749092,
-0.1984061,
0.1161766,
-0.2045725,
-0.2078156,
0.03900856,
-0.5769579,
-0.1773405,
-0.3884402,
-0.197891,
-0.7195818,
0.07320417,
-0.1358543,
0.01611311,
0.4712234,
0.4521643,
-0.1687956,
... |
Fbxo45 inhibits calcium-sensitive proteolysis of N-cadherin and promotes neuronal differentiation. | Fbxo45 is an atypical E3 ubiquitin ligase, which specifically targets proteins for ubiquitin-mediated degradation. Fbxo45 ablation results in defective neuronal differentiation and abnormal formation of neural connections; however, the mechanisms underlying these defects are poorly understood. Using an unbiased mass spectrometry-based proteomic screen, we show here that N-cadherin is a novel interactor of Fbxo45. N-cadherin specifically interacts with Fbxo45 through two consensus motifs overlapping the site of calcium-binding and dimerization of the cadherin molecule. N-cadherin interaction with Fbxo45 is significantly abrogated by calcium treatment. Surprisingly, Fbxo45 depletion by RNAi-mediated silencing results in enhanced proteolysis of N-cadherin. Conversely, ectopic expression of Fbxo45 results in decreased proteolysis of N-cadherin. Fbxo45 depletion results in dramatic reduction in N-cadherin expression, impaired neuronal differentiation, and diminished formation of neuronal processes. Our studies reveal an unanticipated role for an F-box protein that inhibits proteolysis in the regulation of a critical biological process. | 25,143,387 | [
-0.2405873,
0.03151424,
0.05015574,
-0.2740275,
-0.04863305,
-0.1422152,
-0.1722328,
0.2142679,
0.2298014,
0.2949499,
0.1106112,
0.5837367,
-0.1665639,
-0.1733838,
-0.1500686,
0.06961551,
-0.5881426,
0.05792287,
-0.3184022,
-0.1279465,
-0.0337263,
0.3388506,
0.0462039,
... |
The actin regulators Enabled and Diaphanous direct distinct protrusive behaviors in different tissues during Drosophila development. | Actin-based protrusions are important for signaling and migration during development and homeostasis. Defining how different tissues in vivo craft diverse protrusive behaviors using the same genomic toolkit of actin regulators is a current challenge. The actin elongation factors Diaphanous and Enabled both promote barbed-end actin polymerization and can stimulate filopodia in cultured cells. However, redundancy in mammals and Diaphanous' role in cytokinesis limited analysis of whether and how they regulate protrusions during development. We used two tissues driving Drosophila dorsal closure--migratory leading-edge (LE) and nonmigratory amnioserosal (AS) cells--as models to define how cells shape distinct protrusions during morphogenesis. We found that nonmigratory AS cells produce filopodia that are morphologically and dynamically distinct from those of LE cells. We hypothesized that differing Enabled and/or Diaphanous activity drives these differences. Combining gain- and loss-of-function with quantitative approaches revealed that Diaphanous and Enabled each regulate filopodial behavior in vivo and defined a quantitative "fingerprint"--the protrusive profile--which our data suggest is characteristic of each actin regulator. Our data suggest that LE protrusiveness is primarily Enabled driven, whereas Diaphanous plays the primary role in the AS, and reveal each has roles in dorsal closure, but its robustness ensures timely completion in their absence. | 25,143,400 | [
0.02485522,
-0.006684639,
-0.373425,
-0.04503107,
0.154092,
-0.1476769,
-0.08144382,
0.03560235,
0.2127881,
-0.1062774,
-0.06502728,
-0.1514984,
-0.1434819,
-0.2740319,
-0.6366677,
0.3282928,
-0.5675653,
0.0496456,
-0.1436391,
-0.009612131,
0.5409896,
0.1078382,
-0.142065... |
Regulation of microtubule-based transport by MAP4. | Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores as an experimental system. In these cells, pigment granules (melanosomes) move along MTs to the cell center (aggregation) or to the periphery (dispersion) by means of cytoplasmic dynein and kinesin-2, respectively. We found that aggregation signals induced phosphorylation of threonine residues in the MT-binding domain of the Xenopus MAP4 (XMAP4), thus decreasing binding of this protein to MTs. Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs of melanosomes, whereas removal of XMAP4 from MTs reduced the length of kinesin-2-dependent runs and suppressed pigment dispersion. We hypothesize that binding of XMAP4 to MTs negatively regulates dynein-dependent movement of melanosomes and positively regulates kinesin-2-based movement. Phosphorylation during pigment aggregation reduces binding of XMAP4 to MTs, thus increasing dynein-dependent and decreasing kinesin-2-dependent motility of melanosomes, which stimulates their accumulation in the cell center, whereas dephosphorylation of XMAP4 during dispersion has an opposite effect. | 25,143,402 | [
0.06439061,
-0.1084438,
-0.2899123,
-0.2631882,
-0.04896085,
-0.3642794,
0.01566262,
0.3525097,
-0.09099233,
-0.04751977,
0.08797194,
0.05338589,
-0.2595958,
0.01751316,
-0.3174267,
0.2050817,
-0.3818597,
-0.02070875,
0.2977033,
-0.4069487,
0.453113,
-0.04096503,
-0.05522... |
Two Dictyostelium tyrosine kinase-like kinases function in parallel, stress-induced STAT activation pathways. | When Dictyostelium cells are hyperosmotically stressed, STATc is activated by tyrosine phosphorylation. Unusually, activation is regulated by serine phosphorylation and consequent inhibition of a tyrosine phosphatase: PTP3. The identity of the cognate tyrosine kinase is unknown, and we show that two tyrosine kinase-like (TKL) enzymes, Pyk2 and Pyk3, share this function; thus, for stress-induced STATc activation, single null mutants are only marginally impaired, but the double mutant is nonactivatable. When cells are stressed, Pyk2 and Pyk3 undergo increased autocatalytic tyrosine phosphorylation. The site(s) that are generated bind the SH2 domain of STATc, and then STATc becomes the target of further kinase action. The signaling pathways that activate Pyk2 and Pyk3 are only partially overlapping, and there may be a structural basis for this difference because Pyk3 contains both a TKL domain and a pseudokinase domain. The latter functions, like the JH2 domain of metazoan JAKs, as a negative regulator of the kinase domain. The fact that two differently regulated kinases catalyze the same phosphorylation event may facilitate specific targeting because under stress, Pyk3 and Pyk2 accumulate in different parts of the cell; Pyk3 moves from the cytosol to the cortex, whereas Pyk2 accumulates in cytosolic granules that colocalize with PTP3. | 25,143,406 | [
0.2221465,
0.09800565,
0.0979171,
-0.3318953,
-0.274086,
0.1163032,
0.1944045,
0.1623303,
0.007112397,
0.08744963,
0.08131618,
-0.03335139,
-0.5863897,
0.09801418,
-0.3067866,
-0.361764,
0.1563824,
-0.03541593,
-0.01425045,
0.06795141,
0.5074776,
0.2209154,
-0.03830082,
... |
Systematic lipidomic analysis of yeast protein kinase and phosphatase mutants reveals novel insights into regulation of lipid homeostasis. | The regulatory pathways required to maintain eukaryotic lipid homeostasis are largely unknown. We developed a systematic approach to uncover new players in the regulation of lipid homeostasis. Through an unbiased mass spectrometry-based lipidomic screening, we quantified hundreds of lipid species, including glycerophospholipids, sphingolipids, and sterols, from a collection of 129 mutants in protein kinase and phosphatase genes of Saccharomyces cerevisiae. Our approach successfully identified known kinases involved in lipid homeostasis and uncovered new ones. By clustering analysis, we found connections between nutrient-sensing pathways and regulation of glycerophospholipids. Deletion of members of glucose- and nitrogen-sensing pathways showed reciprocal changes in glycerophospholipid acyl chain lengths. We also found several new candidates for the regulation of sphingolipid homeostasis, including a connection between inositol pyrophosphate metabolism and complex sphingolipid homeostasis through transcriptional regulation of AUR1 and SUR1. This robust, systematic lipidomic approach constitutes a rich, new source of biological information and can be used to identify novel gene associations and function. | 25,143,408 | [
0.06823207,
-0.1352773,
0.09079045,
-0.203752,
-0.04163306,
-0.04836708,
0.04441606,
0.2876924,
0.1274324,
-0.1938308,
0.1629815,
-0.2583048,
-0.2855194,
0.1021748,
-0.5563617,
0.2272517,
-0.4390434,
-0.1064317,
-0.001240769,
-0.03195919,
0.09290686,
0.3557014,
-0.0921665... |
A current understanding of vascular calcification in CKD. | Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have significant cardiovascular morbidity and mortality that is in part due to the development of vascular calcification. Vascular calcification is an active, highly regulated process that shares many similarities with normal bone formation. New discoveries related to extracellular vesicles, microRNAs, and calciprotein particles continue to reveal the mechanisms that are involved in the initiation and progression of vascular calcification in CKD. Further innovations in these fields are critical for the development of biomarkers and therapeutic options for patients with CKD and ESRD. | 25,143,458 | [
-0.365317,
0.1862685,
0.001732936,
-0.0622819,
-0.1276877,
-0.2032636,
-0.02611177,
0.4335215,
0.2337957,
0.1472934,
-0.03223974,
0.2251002,
-0.2059759,
-0.07462523,
-0.4251005,
-0.3784009,
-0.1187189,
-0.05254272,
0.1037387,
0.1722668,
-0.1524989,
0.2777705,
-0.3026045,
... |
High-resolution imaging of dietary lipids in cells and tissues by NanoSIMS analysis. | Nanoscale secondary ion MS (NanoSIMS) imaging makes it possible to visualize stable isotope-labeled lipids in cells and tissues at 50 nm lateral resolution. Here we report the use of NanoSIMS imaging to visualize lipids in mouse cells and tissues. After administering stable isotope-labeled fatty acids to mice by gavage, NanoSIMS imaging allowed us to visualize neutral lipids in cytosolic lipid droplets in intestinal enterocytes, chylomicrons at the basolateral surface of enterocytes, and lipid droplets in cardiomyocytes and adipocytes. After an injection of stable isotope-enriched triglyceride-rich lipoproteins (TRLs), NanoSIMS imaging documented delivery of lipids to cytosolic lipid droplets in parenchymal cells. Using a combination of backscattered electron (BSE) and NanoSIMS imaging, it was possible to correlate the chemical data provided by NanoSIMS with high-resolution BSE images of cell morphology. This combined imaging approach allowed us to visualize stable isotope-enriched TRLs along the luminal face of heart capillaries and the lipids within heart capillary endothelial cells. We also observed examples of TRLs within the subendothelial spaces of heart capillaries. NanoSIMS imaging provided evidence of defective transport of lipids from the plasma LPs to adipocytes and cardiomyocytes in mice deficient in glycosylphosphatidylinositol-anchored HDL binding protein 1. | 25,143,463 | [
-0.01823034,
-0.1033724,
-0.3737527,
-0.1953374,
0.2947547,
0.01323993,
0.03860186,
0.1905273,
-0.07411151,
-0.04196965,
-0.1041909,
-0.112425,
-0.002128548,
-0.1239395,
-0.3830846,
-0.01963077,
-0.8940967,
-0.309427,
0.1680401,
0.04670506,
-0.03226851,
0.2850453,
0.11244... |
Fodinomyces uranophilus gen. nov. sp. nov. and Coniochaeta fodinicola sp. nov., two uranium mine-inhabiting Ascomycota fungi from northern Australia. | Seven acidophilic/acidotolerant fungal strains were characterized from samples of process waters (raffinate) at one of Australia's largest uranium mines, the Ranger Mine in Northern Territory. They were isolated from raffinate, which typically were very acidic (pH 1.7-1.8) and contained high concentrations of total dissolved/colloidal salts (> 100 g/L). Five of the isolates correspond to two new acidotolerant Ascomycota fungi. The first is a member of a new genus, here described as Fodinomyces (Teratosphaeriaceae, Capnodiales, Dothideomycetes) and does not show clear close affiliation with any other described fungus in the scientific literature. The second belongs to the genus Coniochaeta (Coniochaetaceae, Coniochaetales, Sordariomycetes) and is closely related to Coniochaeta hansenii. | 25,143,478 | [
-0.1388603,
-0.3100806,
0.2694609,
0.1881596,
0.006635453,
-0.04208023,
-0.238816,
0.03466265,
-0.04309114,
0.04000027,
0.1429702,
-0.2621524,
0.2576265,
0.02789867,
-0.01517349,
-0.2784123,
-0.2378884,
0.1856439,
0.4618082,
-0.2817344,
-0.0198015,
0.2355154,
-0.1781506,
... |
A comparison of concentric and eccentric glenospheres in reverse shoulder arthroplasty: a randomized controlled trial. | Inferior scapular notching following reverse shoulder arthroplasty is due to mechanical impingement and, in some studies, has been associated with poorer functional scores, lower patient satisfaction, and more limited shoulder motion. We aimed to test the hypothesis that inferior positioning of the center of rotation with eccentric glenosphere designs decreases the adduction deficit before impingement occurs and improves clinical outcome. A randomized, controlled, double-blinded trial was performed. According to the results of a power analysis, fifty patients undergoing reverse shoulder arthroplasty for the diagnosis of cuff tear arthropathy were randomized intraoperatively to receive either a concentric or eccentric glenosphere. The glenoid baseplate was positioned flush to the inferior border of the glenoid before the glenosphere was then attached. Notching was assessed using an anteroposterior radiograph, and clinical outcome was assessed using the visual analog pain scale score, shoulder function rating, American Shoulder and Elbow Surgeons score, and Oxford shoulder score. Active forward elevation and external rotation were assessed. The outcome assessor was blinded to the treatment group. The mean follow-up period for the groups was forty-three and forty-seven months. Patient demographics and preoperative scores were similar between the groups. At the time of the final follow-up, four patients (14.8%) in the concentric group had developed inferior scapular notching (two with Nerot grade I and two with Nerot grade II), ranging in size from 1.1 to 7.4 mm, compared with one patient (4.3%; Nerot grade I) in the eccentric group (p = 0.36). No notching occurred in any patient with glenoid overhang of >3.5 mm. No significant difference between the groups was seen with respect to functional outcome scores, patient satisfaction, or shoulder motion. There were no differences in notching rates or clinical outcomes between concentric and eccentric glenospheres following reverse shoulder arthroplasty. Inferior glenosphere overhang of >3.5 mm, however, prevented notching. This may be achieved with a modified surgical technique, but eccentric glenospheres provide an additional option. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. | 25,143,506 | [
-0.3319417,
0.630576,
-0.07544953,
-0.3578034,
-0.1860624,
-0.5171598,
-0.361888,
0.0862304,
0.1849514,
0.1050091,
0.1346593,
-0.3005077,
-0.2050693,
-0.4527108,
0.09601229,
0.09824041,
-0.2326359,
0.2404523,
-0.1172872,
-0.2971348,
-0.06505491,
-0.01064194,
0.1402459,
... |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.