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23594348
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Stabilization of cytokinin levels enhances Arabidopsis resistance against Verticillium longisporum.
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Verticillium longisporum is a vascular pathogen that infects the Brassicaceae host plants Arabidopsis thaliana and Brassica napus. The soilborne fungus enters the plant via the roots and colonizes the xylem of roots, stems, and leaves. During late stages of infections, Verticillium spp. spread into senescing tissue and switch from biotrophic to a necrotrophic life style. Typical symptoms of V. longisporum-induced disease are stunted growth and leaf chlorosis. Expression analyses of the senescence marker genes SENESCENCE-ASSOCIATED GENE12, SENESCENCE-ASSOCIATED GENE13, and WRKY53 revealed that the observed chlorosis is a consequence of premature senescence triggered by Verticillium infection. Our analyses show that, concomitant with the development of chlorosis, levels of trans-zeatin decrease in infected plants. Potentially, induction of cytokinin oxidase/dehydrogenase expression by Verticillium infection contributes to the observed decreases in cytokinin levels. Stabilization of Arabidopsis cytokinin levels by both pharmacological and genetic approaches inhibits Verticillium proliferation and coincides with reduced disease symptom development. In summary, our results indicate that V. longisporum triggers premature plant senescence for efficient host plant colonization.
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10.1094/MPMI-12-12-0287-R
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10670311
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Nocturia, nocturnal polyuria and secondary nocturnal voiding.
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Getting up once to the toilet at night is normal. Getting up more than once may be abnormal. Potential causes include: nocturia, which is bladder related; nocturnal polyuria, which is cardiac in origin; and being awake for a variety of reasons that are not linked to the bladder. Bladder problems, therefore, are not always the reason for frequency in micturition at night and treatment will only be effective if the correct cause and/or causes are identified. The most useful investigation to help with diagnosis is a frequency volume chart linked to an assessment identifying causes of secondary nocturnal voiding and nocturnal polyuria. Getting up to the toilet at night will not always be successfully treated by anticholinergics. Charting is the key to diagnosis, appropriate interventions and successful outcomes. This article will focus on working definitions, prevalence, causes, investigations and treatment options for nocturia, nocturnal polyuria and secondary nocturnal voiding.
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10.12968/bjon.1999.8.13.6561
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21098280
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Tailor-made RNAi knockdown against triplet repeat disease-causing alleles.
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Nucleotide variations, including SNPs, in the coding regions of disease genes are important targets for RNAi treatment, which is a promising medical treatment for intractable diseases such as triplet repeat diseases. However, the identification of such nucleotide variations and the design of siRNAs conferring disease allele-specific RNAi are quite difficult. In this study we developed a pull-down method to rapidly identify coding SNP (cSNP) haplotypes of triple repeat, disease-causing alleles, and we demonstrated disease allele-specific RNAi that targeted cSNP sites in mutant Huntingtin alleles, each of which possessed a different cSNP haplotype. Therefore, the methods presented here allow for allele-specific RNAi knockdown against disease-causing alleles by using siRNAs specific to disease-linked cSNP haplotypes, and advanced progress toward tailor-made RNAi treatments for triplet repeat diseases.
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10.1073/pnas.1012153107
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33346289
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Permanent and reversibly programmable shapes in liquid crystal elastomer microparticles capable of shape switching.
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Reversibly programmable liquid crystal elastomer microparticles (LCEMPs), formed as a covalent adaptable network (CAN), with an average diameter of 7 μm ± 2 μm, were synthesized via a thiol-Michael dispersion polymerization. The particles were programmed to a prolate shape via a photoinitiated addition-fragmentation chain-transfer (AFT) exchange reaction by activating the AFT after undergoing compression. Due to the thermotropic nature of the AFT-LCEMPs, shape switching was driven by heating the particles above their nematic-isotropic phase transition temperature (T NI ). The programmed particles subsequently displayed cyclable two-way shape switching from prolate to spherical when at low or high temperatures, respectively. Furthermore, the shape programming is reversible, and a second programming step was done to erase the prolate shape by initiating AFT at high temperature while the particles were in their spherical shape. Upon cooling, the particles remained spherical until additional programming steps were taken. Particles were also programmed to maintain a permanent oblate shape. Additionally, the particle surface was programmed with a diffraction grating, demonstrating programmable complex surface topography via AFT activation.
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10.1039/d0sm01836h
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8303940
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Primary in vitro sensitization of human T-helper lymphocytes by peptides derived from the V3 loop of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein.
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To generate CD4+ T-helper cell lines, lymphocytes from HIV-seronegative subjects were primed in vitro with peptides derived from the V3 loop of HIV-1 gp120. Antigen-specific reactivity was inhibited by an anti-DR monoclonal antibody, indicating HLA-class II dependency, but peptides could be recognized in different HLA-class II contexts. Three sites on V3LAI and two on V3MN were identified as targets of the respective V3LAI- and V3MN-specific lines. Recognition of V3 peptides was isolate-specific. The lines did not react against whole gp160, which suggests that V3 may be differently presented when used as such rather than as part of the entire glycoprotein. Similar results were obtained in chimpanzees immunized in vivo against V3LAI.
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10.1016/0264-410x(94)90010-8
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24150545
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Primary amyloid goiter mimicking rapid growing thyroid malignancy.
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Amyloid accumulation in the thyroid gland leading to a clinically detectable mass, known as amyloid goiter, is a rare condition associated with primary amyloidosis. Moreover, a localized primary amyloid goiter involving only the thyroid gland is rarer still. Here, we report a patient with a localized primary amyloid goiter that had grown rapidly, causing dysphagia and dyspnea on exercise, and confused us with malignancy such as anaplastic carcinoma. After surgery, no further symptoms occurred. A diagnosis of amyloid goiter was established on microscopic examination. In patients with a rapidly enlarging thyroid gland presenting with dysphagia, dyspnea, or hoarseness, amyloid goiter and malignancy should both be suspected, even when systemic amyloidosis is not suspected.
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10.1007/s00405-013-2777-5
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31047784
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Detection of Pneumocystis jirovecii by quantitative real-time PCR in oral rinses from Pneumocystis pneumonia asymptomatic human immunodeficiency virus patients.
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Pneumocystis pneumonia (PCP) is a potentially life-threatening fungal infection usually seen in immunocompromised patients. Pneumocystis jirovecii can be easily detected from oral rinse samples in HIV patients with suspected PCP. In this study, a quantitative real-time PCR assay was used to establish the frequency of detection of P. jirovecii in oral rinses from HIV patients without respiratory symptoms or suspicion of PCP. Two saline oral rinses were collected from 100 ambulant HIV patients and from 60 COPD patients (comparator group). Four HIV patients were positive for P. jirovecii. In three patients, the first sample was positive and in one the second one was positive. One of these patients was on PCP prophylaxis and had a CD4 + count of 76 cells/mm 3. The mean CD4 + count for all patients was 527 cells/mm 3. All qRT-PCR test results for the COPD patients were negative. No patient developed PCP at six months follow-up. The qRT-PCR assay can be used to detect P. jirovecii DNA in oral rinse samples from HIV patients without evident clinical symptoms, however the oral carriage of this fungus was rare in our cohort of patients. In conclusion, although rare, a positive oral rinse P. jirovecii result may reflect colonisation, in particular in patients with HIV. This needs to be kept in mind when using oral rinses and qRT-PCR in the diagnosis of P. jirovecii infection. Copyright © 2019. Published by Elsevier Masson SAS.
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10.1016/j.mycmed.2019.04.001
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34266459
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Knock-in models related to Alzheimer's disease: synaptic transmission, plaques and the role of microglia.
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Microglia are active modulators of Alzheimer's disease but their role in relation to amyloid plaques and synaptic changes due to rising amyloid beta is unclear. We add novel findings concerning these relationships and investigate which of our previously reported results from transgenic mice can be validated in knock-in mice, in which overexpression and other artefacts of transgenic technology are avoided. App NL-F and App NL-G-F knock-in mice expressing humanised amyloid beta with mutations in App that cause familial Alzheimer's disease were compared to wild type mice throughout life. In vitro approaches were used to understand microglial alterations at the genetic and protein levels and synaptic function and plasticity in CA1 hippocampal neurones, each in relationship to both age and stage of amyloid beta pathology. The contribution of microglia to neuronal function was further investigated by ablating microglia with CSF1R inhibitor PLX5622. Both App knock-in lines showed increased glutamate release probability prior to detection of plaques. Consistent with results in transgenic mice, this persisted throughout life in App NL-F mice but was not evident in App NL-G-F with sparse plaques. Unlike transgenic mice, loss of spontaneous excitatory activity only occurred at the latest stages, while no change could be detected in spontaneous inhibitory synaptic transmission or magnitude of long-term potentiation. Also, in contrast to transgenic mice, the microglial response in both App knock-in lines was delayed until a moderate plaque load developed. Surviving PLX5266-depleted microglia tended to be CD68-positive. Partial microglial ablation led to aged but not young wild type animals mimicking the increased glutamate release probability in App knock-ins and exacerbated the App knock-in phenotype. Complete ablation was less effective in altering synaptic function, while neither treatment altered plaque load. Increased glutamate release probability is similar across knock-in and transgenic mouse models of Alzheimer's disease, likely reflecting acute physiological effects of soluble amyloid beta. Microglia respond later to increased amyloid beta levels by proliferating and upregulating Cd68 and Trem2. Partial depletion of microglia suggests that, in wild type mice, alteration of surviving phagocytic microglia, rather than microglial loss, drives age-dependent effects on glutamate release that become exacerbated in Alzheimer's disease. © 2021. The Author(s).
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10.1186/s13024-021-00457-0
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34379807
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The genome of a nonphotosynthetic diatom provides insights into the metabolic shift to heterotrophy and constraints on the loss of photosynthesis.
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Although most of the tens of thousands of diatom species are photoautotrophs, a small number of heterotrophic species no longer photosynthesize. We sequenced the genome of a nonphotosynthetic diatom, Nitzschia Nitz4, to determine how carbon metabolism was altered in the wake of this trophic shift. Nitzschia Nitz4 has retained its plastid and plastid genome, but changes associated with the transition to heterotrophy were cellular-wide and included losses of photosynthesis-related genes from the nuclear and plastid genomes, elimination of isoprenoid biosynthesis in the plastid, and remodeling of mitochondrial glycolysis to maximize adenosine triphosphte (ATP) yield. The genome contains a β-ketoadipate pathway that may allow Nitzschia Nitz4 to metabolize lignin-derived compounds. Diatom plastids lack an oxidative pentose phosphate pathway (oPPP), leaving photosynthesis as the primary source of NADPH to support essential biosynthetic pathways in the plastid and, by extension, limiting available sources of NADPH in nonphotosynthetic plastids. The genome revealed similarities between nonphotosynthetic diatoms and apicomplexan parasites for provisioning NADPH in their plastids and highlighted the ancestral absence of a plastid oPPP as a potentially important constraint on loss of photosynthesis, a hypothesis supported by the higher frequency of transitions to parasitism or heterotrophy in lineages that have a plastid oPPP. © 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.
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10.1111/nph.17673
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20161651
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Frontal Atrophy and Attention Deficits in Older Adults with a History of Elevated Depressive Symptoms.
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Studies of older adults with depressive disorders indicate greater cognitive deficits and brain alterations than would be expected for their age. There is some evidence that these findings are present after a single episode of depression, but this work has been cross-sectional in nature. We investigated both cross-sectional and longitudinal associations between a history of elevated depressive symptoms (HDS), frontal lobe volumes, and cognitive performance within the context of normal age-related changes over time in the Baltimore Longitudinal Study of Aging. After controlling for age, HDS was associated with smaller total frontal gray matter volumes and with smaller regional volumes in the cingulate gyrus and orbitofrontal cortex. Men, but not women, with HDS showed deficits in auditory attention span at older ages. Results confirm previous reports that even a single episode of depression is associated with adverse outcomes in older adults but suggest that HDS does not affect longitudinal trajectories of cognitive and brain volume change.
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10.1007/s11682-009-9078-z
|
1235939
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Distribution of Gm and Inv factors in two samples of the Greek population.
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Gm and Inv polymorphism has been investigated on a sample of the general Greek population (N = 256) and on a sample of the Achaia population of Northwestern Peloponnusus (N = 150). The estimated frequencies were, respectively in the two groups: Gm1, 0.156 vs. 0.180; Gm1,2,0.010 vs. 0.017; Gm4,12, 0.834 vs. 0.803; Inv (+1), 0.125 vs. 0.140.
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10.1017/s0001566000010503
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12675368
|
Reproductive skew and the origin of sterile castes.
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Reproductive skew theory has not heretofore formally addressed one of the most important questions in evolutionary biology: How can whole-life sterile castes evolve? We construct a transactional skew model investigating under what conditions a subordinate in a multimember group is favored to develop into a morphologically specialized worker caste. Our model demonstrates that, contrary to former expectations, the ecological and genetic conditions favoring caste differentiation are far more restrictive than those favoring high skew. Caste differentiation cannot be selected in saturated, symmetrical relatedness groups unless the genetic relatedness among group members is extremely high. In contrast, it can be selected in the saturated, asymmetrical relatedness (parent-offspring) groups with complete skew. If we also consider the future reproduction of subordinates, caste differentiation is possible only after the group size reaches a certain critical point. Most importantly, caste differentiation in a parent-offspring group increases its saturated group size. The positive feedback between group size and the degree of caste differentiation can continue in principle until completely sterile worker castes emerge. Thus, at least in the case of parent-offspring groups, group size but not the degree of reproductive skew may be a better index of the level of social complexity. A scheme for the evolution of sterile worker castes that integrates the role of group size into the framework of reproductive skew theory is proposed.
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10.1086/346099
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36320850
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Lattice dynamic stability and electronic structures of ternary hydrides La 1- x Y x H 3 via first-principles cluster expansion.
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Lanthanum hydride compounds LaH 3 become stabilized by yttrium substitution under the influence of moderate pressure. Novel materials with a wide range of changes in the structural properties as a function of hydrogen are investigated by means of the first-principles cluster expansion technique. Herein, the new compounds La 1- x Y x H 3, where 0 ≤ x ≤ 1, are determined to adopt tetragonal structures under high-pressure with the compositions La 0.8 Y 0.2 H 3, La 0.75 Y 0.25 H 3, and La 0.5 Y 0.5 H 3. The corresponding thermodynamic and dynamical stabilities of the predicted phases are confirmed by a series of calculations including, for example, phonon dispersion, electronic band structure, and other electronic characteristics. According to the band characteristics, all hydrides except that of I 4 1 / amd symmetry are semiconductors. The tetragonal La 0.5 Y 0.5 H 3 phase is found to become semi-metallic, as confirmed by adopting the modified Becke-Johnson exchange potential. The physical origins of the semiconductor properties in these stable hydrides are discussed in detail. Our findings provide a deeper insight into this class of rare-earth ternary hydrides. This journal is © The Royal Society of Chemistry.
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10.1039/d2ra03194a
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9595530
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Effects of endothelin-1 on inflammatory incapacitation of the rat knee joint.
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This study assessed the possible local nociceptive and hyperalgesic properties of endothelin-1 (ET-1) in the rat knee-joint incapacitation test, in which animals are placed for 1 min/h on a revolving (3 rpm) metal cylinder and nociception is measured as the time the hindpaw of the injected limb was off the cylinder (i. e., paw elevation time, PET). Carrageenan (Cg; 150 micrograms/joint), E. coli LPS (1 microgram/joint), and ET-1 (120 or 240 pmol/joint) each increased PET persistently, unlike sarafotoxin S6c (120-240 pmol/joint) or PBS. ET-1 (15 and 30 pmol/joint, 30 min before) did not cause incapacitation per se but potentiated PET induced by Cg, increasing the area under the curve (AUC in arbitrary units, 0-6 h) from 105 +/- 9 to 165 +/- 10 and 169 +/- 25, respectively. Prior Cg injection (300 micrograms/joint, 72 h before) sensitized the joint to incapacitation triggered by restimulation with either Cg (300 micrograms/joint), LPS (1 microgram/joint), or ET-1 (30 pmol/joint). Treatment with bosentan (10 mg/kg i. v., 15 min before joint stimulation) did not affect PET values in naive animals to Cg or LPS, but significantly reduced the upregulated response evoked by restimulation with LPS (but not Cg), from 465 +/- 24 to 290 +/- 49 (AUC 0-12 h). Therefore, ET-1 triggers nociception and hyperalgesia in the naive knee joint of the rat, perhaps via ETA receptors. Although local endogenous ETs may not have a role in inflammatory nociception in the naive joint, they may participate in articular incapacitation induced by restimulation with LPS. This latter finding could be relevant to the etiology of pain associated with chronic arthritic diseases.
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10.1097/00005344-199800001-00149
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24382676
|
Assessment of clinical and nonclinical characteristics associated with health-related quality of life in patients with high-grade gliomas: a feasibility study.
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Results from several studies suggest that there is value in evaluating the association between nonclinical characteristics of patients and quality of life (QoL), but few studies have focused on brain cancer. The primary goal of this feasibility study was to explore the relationship between clinical factors and nonclinical factors and QoL in brain cancer patients. Participants in this cross-sectional study were drawn from two hospital sites. Eligible patients were 18-75 years old with a pathologically confirmed diagnosis of a brain cancer histology and stable disease after treatment. Data were obtained from medical chart review and a self-administered survey consisting of main study variables and two QoL standardized measures. Independent sample t test was used to determine differences between patient factors and QoL measures. The sample population was comprised of 26 patients with a median age at survey of 57.5 years (range 33-72). Quality of life was adversely associated with younger age, having underage children and living alone. Patients' meaning of QoL differed by gender, however most patients viewed it as affecting multiple aspects of their lives. Nonclinical characteristics were significantly associated with QoL more often than clinical characteristics. Identifying these factors may help improve the quality of care for these patients. This effort demonstrates the relevancy and feasibility of conducting a larger scale study to confirm or refute these findings.
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10.1007/s00520-013-2093-z
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39451878
|
The First Comprehensive Evaluation of Immuno-Inflammatory Markers for Prognosis in Esophageal Cancer Patients: A South Asian Perspective.
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Esophageal cancer (EC) remains a significant health challenge in South Asia, with poor prognosis despite advancements in diagnostics and treatment. Identifying and validating prognostic factors is essential for improving patient outcomes. Methods: A prospective study was conducted with 146 biopsy-confirmed EC patients at the Dr. Ruth K. M. Pfau Civil Hospital, Karachi, Pakistan. Clinical and laboratory data were collected and analyzed using descriptive statistics, receiver operating characteristic (ROC) analysis, and the Chi-square test. Survival outcomes were assessed using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models for univariate and multivariate regression analyses, with statistical significance set at p ≤ 0.05. Results: Bivariate analysis showed significant associations of the neutrophil lymphocyte ratio (NLR) ( p = 0.017), C-reactive protein to albumin ratio (CAR) ( p = 0.033), red cell distribution width to platelet ratio (RPR) ( p = 0.020), and systemic immune-Inflammation index (SII) ( p = 0.009) with patient survival. Univariate analysis identified tumor length >10 cm ( p = 0.016), T4 stage ( p = 0.015), metastasis ( p < 0.001), surgery not performed ( p < 0.001), and SII ( p = 0.022) as significant factors for survival, with higher SII linked to poorer overall survival ( p = 0.020). Interestingly, in the multivariate model, only metastasis ( p < 0.001) and surgery not performed ( p = 0.011) remained significant. Conclusions: Immuno-inflammatory markers may be less pertinent prognostic factors for EC in the South Asian population.
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10.3390/clinpract14050163
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9046024
|
Free fatty acid metabolism during myocardial ischemia and reperfusion.
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Long chain free fatty acids (FFA) are the preferred metabolic substrates of myocardium under aerobic conditions. However, under ischemic conditions long chain FFA have been shown to be harmful both clinically and experimentally. Serum levels of free fatty acids frequently are elevated in patients with myocardial ischemia. The proposed mechanisms of the detrimental effects of free fatty acids include: (1) accumulation of toxic intermediates of fatty acid metabolism, such as long chain acyl-CoA thioesters and long chain acylcarnitines, (2) inhibition of glucose utilization, particularly glycolysis, during ischemia and/or reperfusion, and (3) uncoupling of oxidative metabolism from electron transfer. The relative importance of these mechanisms remains controversial. The primary site of FFA-induced injury appears to be the sarcolemmal and intracellular membranes and their associated enzymes. Inhibitors of free fatty acid metabolism have been shown experimentally to decrease the size of myocardial infarction and lessen postischemic cardiac dysfunction in animal models of regional and global ischemia. The mechanism by which FFA inhibitors improve cardiac function in the postischemic heart is controversial. Whether the effects are dependent on decreased levels of long chain intermediates and/or enhancement of glucose utilization is under investigation. Manipulation of myocardial fatty acid metabolism may prove beneficial in the treatment of myocardial ischemia, particularly during situations of controlled ischemia and reperfusion, such as percutaneous transluminal coronary angioplasty and coronary artery bypass grafting.
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10.1023/a:1006886601825
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22622108
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Impact of hypertension on ventricular-arterial coupling and regional myocardial work at rest and during isometric exercise.
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To understand better the mechanism of left ventricular (LV) remodeling related to hypertension, it is important to evaluate LV function in relation to the changes in loading conditions. The aim of this study was to investigate changes in conventional ventricular-arterial coupling indexes, LV strain, and a new index reflecting regional myocardial work assessed noninvasively at rest and during isometric exercise in a random sample including participants with normal blood pressure and those with hypertension. A total of 148 participants (53.4% women; mean age, 52.0 years; 39.2% with hypertension) underwent simultaneous echocardiographic and arterial data acquisition at rest and during increased afterload (handgrip exercise). End-systolic pressure was determined from the carotid pulse wave. Arterial elastance (Ea) and LV elastance (Ees) were calculated as end-systolic pressure/stroke volume and end-systolic pressure/end-systolic volume. Doppler tissue imaging and two-dimensional speckle tracking were used to derive LV longitudinal strain. Regional myocardial work (ejection work density [EWD]) was the area of the pressure-strain loop during ejection. At rest, with adjustments applied, Ees (3.06 vs 3.71 mm Hg/mL, P =.0003), Ea/Ees (0.54 vs 0.47, P =.002) and EWD (670 vs 802 Pa/m(2), P =.0001) differed significantly between participants with normal blood pressure and those with hypertension. During handgrip exercise, Ea and Ea/Ees significantly increased (P <.0001) in both groups. Doppler tissue imaging and two-dimensional LV strain decreased in participants with hypertension (P ≤.008). Only in subjects with normal blood pressure EWD significantly increased (+14.7%, P =.0009). Although patients with hypertension compared with those with normal blood pressure have increased LV systolic stiffness and regional myocardial work to match arterial load at rest, they might have diminished cardiac reserve to increase myocardial performance, as estimated by EWD during isometric exercise. Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.
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10.1016/j.echo.2012.04.018
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9920816
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Manganese dipyridoxyl diphosphate: MRI contrast agent with antioxidative and cardioprotective properties?
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Manganese dipyridoxyl diphosphate (MnDPDP) is a contrast agent for magnetic resonance imaging (MRI) of the liver. Aims of the study were to examine if MnDPDP possesses superoxide dismutase (SOD) mimetic activity in vitro, and if antioxidant protection can be demonstrated in an ex vivo rat heart model. Superoxide (*O-2) and hydroxyl radicals (*OH-) were generated in xanthine oxidase and Fenton reactions. Spin adducts with 5,5-dimethyl-1-pyrroline-N-oxide were detected by electron spin resonance spectroscopy. Contractile function and enzyme release were monitored in rat hearts during hypoxia-reoxygenation. Low microM concentrations of MnDPDP and its metabolite Mn dipyridoxyl ethylene-diamine (MnPLED) dismutated *O-2, but showed no activity in Fenton or catalase reactions. MnDPDP 30 microM improved contractile function and reduced enzyme release in rat hearts during reoxygenation. It is concluded that MnDPDP and MnPLED possess SOD mimetic activities and may thereby protect the heart in oxidative stress. Copyright 1999 Academic Press.
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10.1006/bbrc.1998.0131
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10627602
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AMPA-kainate subtypes of glutamate receptor in rat cerebral microglia.
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Microglial cells were isolated from rat cerebral cortex, and kainate (KA)-induced inward current was measured at a holding potential of -40 or -60 mV. 6-Cyano-7-nitroquinoxaline-2, 3-dione-sensitive KA-induced currents increased with increasing KA concentration. The half-activation concentration and Hill coefficient were 3.3 x 10(-4) M and 1.4, respectively. Although glutamate (Glu) and AMPA-induced currents were much smaller than that induced by KA, all KA-, Glu-, and AMPA-induced currents were greatly and consistently enhanced in the presence of cyclothiazide (CTZ). On the other hand, KA-induced currents were much less sensitive to potentiation by concanavain A, suggesting that the KA-induced response in rat microglia is predominantly mediated by AMPA-preferring receptors (subunits GluR1-GluR4). The current-voltage relationships of KA- and AMPA-CTZ-induced currents were almost linear or slightly outward rectifying. The reversal potential of KA-induced current shifted to negative potentials (from +4 to -40 mV) on switching from high Na(+) to high Ca(2+) external solution, indicating the low Ca(2+) permeability through the AMPA-KA receptor channel complexes. AMPA-KA receptor expression was studied with immunohistochemistry and reverse transcription-PCR, from which GluR2, GluR3, GluR4, and GluR5 were identified. Lower levels of mRNAs for GluR7 and KA-1-KA-2 were also indicated. Finally, activation of these receptors with KA or Glu significantly enhanced the production of tumor necrosis factor-alpha. These results suggest that primary cultured rat microglia possesses functional Glu receptor, which may mediate neuron to microglia communication in the physiological and pathological states.
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38891956
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Specific Mutations Reverse Regulatory Effects of Adenosine Phosphates and Increase Their Binding Stoichiometry in CBS Domain-Containing Pyrophosphatase.
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Regulatory cystathionine β-synthase (CBS) domains are widespread in proteins; however, difficulty in structure determination prevents a comprehensive understanding of the underlying regulation mechanism. Tetrameric microbial inorganic pyrophosphatase containing such domains (CBS-PPase) is allosterically inhibited by AMP and ADP and activated by ATP and cell alarmones diadenosine polyphosphates. Each CBS-PPase subunit contains a pair of CBS domains but binds cooperatively to only one molecule of the mono-adenosine derivatives. We used site-directed mutagenesis of Desulfitobacterium hafniense CBS-PPase to identify the key elements determining the direction of the effect (activation or inhibition) and the "half-of-the-sites" ligand binding stoichiometry. Seven amino acid residues were selected in the CBS1 domain, based on the available X-ray structure of the regulatory domains, and substituted by alanine and other residues. The interaction of 11 CBS-PPase variants with the regulating ligands was characterized by activity measurements and isothermal titration calorimetry. Lys100 replacement reversed the effect of ADP from inhibition to activation, whereas Lys95 and Gly118 replacements made ADP an activator at low concentrations but an inhibitor at high concentrations. Replacement of these residues for alanine increased the stoichiometry of mono-adenosine phosphate binding by twofold. These findings identified several key protein residues and suggested a "two non-interacting pairs of interacting regulatory sites" concept in CBS-PPase regulation.
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10.3390/ijms25115768
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1301166
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A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes.
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The gene loci for adrenal hypoplasia congenita (AHC) and glycerol kinase deficiency (GK) map in Xp21 distal to Duchenne muscular dystrophy (DMD), and proximal to DXS28 (C7), by analysis of patient deletions. We have constructed a yeast artificial chromosome (YAC) contig encompassing a 1.2 Mb region extending distally from DMD, and containing DXS708 (JC-1), the distal junction clone of a patient with GK and DMD. A pulsed-field gel electrophoresis map of the YAC contig identified 3 potential CpG islands. Whole YAC hybridization identified cosmids both for construction of cosmid contigs, and isolation of single copy probes. Thirteen new single copy probes and DXS28 and DXS708 were hybridized on a panel of patients; the deletion mapping indicates that the YAC contig contains both GK and at least part of AHC, and together with the physical map defines a GK critical region of 50-250 kb. In one AHC patient with a cytogenetically detectable deletion we used the new probes to characterize a complex double deletion. Non-overlapping deletions observed in other unrelated AHC patients indicate that the AHC gene is large, extending over at least 200-500 kb. This mapping provides the basis for the identification of the AHC and GK genes.
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10.1093/hmg/1.8.579
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20006500
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Tetrasubstituted pyridines as potent and selective AKT inhibitors: Reduced CYP450 and hERG inhibition of aminopyridines.
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The synthesis and evaluation of tetrasubstituted aminopyridines, bearing novel azaindazole hinge binders, as potent AKT inhibitors are described. Compound 14c was identified as a potent AKT inhibitor that demonstrated reduced CYP450 inhibition and an improved developability profile compared to those of previously described trisubstituted pyridines. It also displayed dose-dependent inhibition of both phosphorylation of GSK3beta and tumor growth in a BT474 tumor xenograft model in mice. Copyright 2009 Elsevier Ltd. All rights reserved.
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10.1016/j.bmcl.2009.11.061
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1710
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Effects of cyanide and doxapram during panting.
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The ventilatory responses, blood gases and acid-base status to intravenous injections of KCN and doxapram hydrochloride were studied in anesthetized dogs during normothermia and thermally induced panting. In the normothermic animal, KCN evoked elevation of VE (154.7%), VT (70.1%), f (48.3%, PaO2 (12.1%) and pH (0.098 units), while PaCO2 diminished by 9.7 mm Hg. During panting, KCN infusions resulted in increases of VE (24.5%), VT (46.6%), PaO2 (3.9%) and pH (0.034 units), while f decreased (10.1%). Bolus injections of doxapram during normothermia increased VE (32.6%), VT (18.8%) and f (17.1%). During panting VE, VT and f increased by 18.0%, 18.2% and 1.5%, respectively. These results demonstrate that the peripheral (arterial) chemoreceptors preserve the capacity to react to acute chemical stimuli in animals in which the thermal stimuli override the normal chemical control of respiration in order to control body temperature, and that this reaction contributes to the integrated respiratory drive.
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10.1007/BF00587344
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31417996
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Algorithms for immunochromatographic assay: review and impact on future application.
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Lateral flow immunoassay (LFIA) is a critical choice for applications of point-of-care testing (POCT) in clinical and laboratory environments because of its excellent features and versatility. To obtain authentic values of analyte concentrations and reliable detection results, the relevant research has featured the application of a diversity of methods of mathematical analysis to technical analysis to allow for use with a small quantity of data. Accordingly, a number of signal and image processing strategies have also emerged for the application of gold immunochromatographic and fluorescent strips to improve sensitivity and overcome the limitations of correlative hardware systems. Instead of traditional methods to solve the problem, researchers nowadays are interested in machine learning and its more powerful variant, deep learning technology, for LFIA detection. This review emphasizes different models for the POCT of accurate labels as well as signal processing strategies that use artificial intelligence and machine learning. We focus on the analytical mechanism, procedural flow, and the results of the assay, and conclude by summarizing the advantages and limitations of each algorithm. We also discuss the potential for application of and directions of future research on LFIA technology when combined with Artificial Intelligence and deep learning.
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10.1039/c9an00964g
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14973071
|
Enhanced efficacy of tumor cell vaccines transfected with secretable hsp70.
|
Tumor immunotherapy has exploited the ability of heat shock proteins to chaperone precursors of antigenic peptides to antigen-presenting cells and to activate efficiently an immune response against tumor-associated antigens. The most common strategy is based on the purification of heat shock protein-peptide complexes from tumor cell lines or from tumor surgical samples for in vivo administration. In this article, we have modified the murine-inducible hsp70 into a secreted protein and engineered tumor cells to secrete constitutively their antigenic repertoire associated with the hsp70 protein. In vitro studies showed that the relocalization of hsp70 from the cytoplasm to the secretory pathway did not modify the ability of hsp70 to interact with peptides derived either from natural tumor-associated antigens or model antigens, and that antigen-presenting cells specifically took up the secreted hsp70 and presented the chaperoned epitopes to T cells. In vivo studies showed that tumors secreting hsp70 displayed increased immunogenicity, with induction of a strong and specific CTL response. Mice injected with hsp70-secreting tumors showed increased survival and impaired tumor take compared with mice bearing parental tumors. More than 70% of mice rejected tumor cells secreting hsp70 through mechanisms that involve T lymphocytes and natural killer cells, with the induction of a memory response in the case of T lymphocytes. Moreover, hsp70 secretion increased the immunogenic potential of tumor cell vaccines.
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10.1158/0008-5472.can-03-2936
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3567144
|
Two high-affinity ligand binding states of uterine estrogen receptor distinguished by modulation of hydrophobic environment.
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The steroid binding function of soluble (cytosolic) estrogen receptors from calf uteri was evaluated under conditions known to modify the extent of hydrophobic interaction with receptor-associated proteins. Receptor preparations were equilibrated into 6 M urea (+/- 0.4 M KCl) buffers and control buffers (+/- 0.4 M KCl) by chromatography through small columns of Sephadex G-25 or by dialysis at 0-6 degrees C. Equilibrium dissociation constants (Kd) and binding capacities (n) of experimental and control receptor preparations were determined by 13-point Scatchard analyses using concentrations of 17 beta-[3H]estradiol from 0.05 to 10 nM. Nonspecific binding was determined at each concentration by parallel incubations with a 200-fold molar excess of the receptor-specific competitor diethylstilbestrol. The control receptor population was consistently found to be a single class of binding sites with a high affinity for estradiol (Kd = 0.36 +/- 0.09 nM, n = 14) which was unaffected by G-25 chromatography, by dialysis, by dilution, or by the presence of 0.4 M KCl. However, equilibration into 6 M urea induced a discrete (10-fold) reduction in receptor affinity (Kd = 3.45 +/- 0.86 nM, n = 6) to reveal a second, thermodynamically stable, high-affinity binding state. The presence of 0.4 M KCl did not significantly influence the discrete change in receptor affinity induced by urea. However, KCl did help prevent the reduction in binding capacity induced by urea. The effects of urea on both receptor affinity and binding capacity were reversible, suggesting a lack of covalent modification.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1021/bi00377a010
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26218653
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Design, synthesis, in-vitro antiproliferative activity and kinase profile of new picolinamide based 2-amido and ureido quinoline derivatives.
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New 2-amido and ureido quinoline derivatives substituted with 2-N-methylamido-pyridin-4-yloxy group at the 5-position of quinoline (18 final compounds) have been designed and synthesized as anticancer sorafenib congeners. Among the synthesized derivatives, fourteen compounds were selected for evaluation of their antiproliferative activity over a panel of 60 cancer cell lines at a single dose concentration of 10 μM at National Cancer Institute (NCI, USA). Four compounds, 9b-d and 9f showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC50 values. The data revealed that 2,4-difluorophenyl (9b) and 4-chloro-3-trifluoromethylphenyl (9d) urea compounds are the most active derivatives with significant efficacies and superior potencies than sorafenib in 36 and 12 cancer cell lines, respectively, belonging particularly to renal carcinoma cell (RCC), ovarian, and non small cell lung cancer (NSCL). Compound 9b and 9d were found to be six and two times more potent than sorafenib against A498 RCC line, with IC50 values of 0.42 μM and 1.36 μM, respectively. Accordingly, compound 9d was screened over a panel of 41 oncogenic kinases at a single dose concentration of 10 μM to profile its kinase inhibitory activity. Interestingly, the compound showed highly selective inhibitory activities ( 81.8% and 96.3%) against BRAF(V600E) and C-RAF kinases with IC50 values of 316 nM and 61 nM, respectively. In addition, molecular docking, cell cycle analysis, compliance to Lipinski's rule of five, and in silico toxicity assessment have been reported. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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10.1016/j.ejmech.2015.07.025
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2419900
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Expression of apolipoprotein E during nerve degeneration and regeneration.
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A 37-kDa glycoprotein has been described recently, whose synthesis is dramatically increased after injury of the rat sciatic and optic nerves. Cells in the nerve sheath, distal to the site of injury, produce and secrete large amounts of this protein, so that by 3 weeks after injury, it represents 2-5% of the total soluble extracellular protein in the regenerating sciatic nerve sheath, although it fails to accumulate in damaged optic nerve. Results presented here reveal extensive homology between the 37-kDa nerve injury-induced protein and a well-studied serum protein, apolipoprotein E (apoE), that is involved in lipid and cholesterol metabolism and that has been shown recently to be present in adult and developing rat astroglia. Both proteins have identical isoelectric focusing points and similar molecular masses. Antibodies raised against the 37-kDa protein recognize apoE and anti-apoE serum crossreacts with the 37-kDa protein. Sequence data for two 14 amino acid stretches of the 37-kDa protein match identical regions of apoE. These data suggest that the 37-kDa protein is identical to serum apoE and that it could have similar functions to the latter. In the nervous system, for example, it may be involved in the mobilization and reutilization of lipid in the repair, growth, and maintenance of myelin and axonal membranes, both during development and after injury.
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10.1073/pnas.83.4.1125
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2029627
|
The role of the olfactory tubercle in the effects of cocaine, morphine and brain-stimulation reward.
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Using the quantitative 2-[14C]deoxyglucose autoradiographic method, local rates of glucose utilization were measured in rats after the administration of morphine or cocaine in the presence or absence of rewarding brain stimulation to the medial forebrain bundle. In animals that did not receive brain stimulation, cocaine significantly increased glucose utilization in the olfactory tubercle, medial prefrontal cortex and substantia nigra pars reticulata, whereas morphine significantly increased glucose metabolism in the olfactory tubercle only. Stimulation itself increased metabolic rates in a number of sites, such as the olfactory tubercle, nucleus accumbens, medial prefrontal cortex, ventral tegmental area and others. However, in self-stimulating animals both morphine and cocaine caused further increases in activity in the olfactory tubercle. Since the olfactory tubercle was the only structure to cause a significant increase in metabolic rate following each treatment, the results implicate this limbic structure in the rewarding effects of morphine, cocaine and brain-stimulation reward.
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10.1016/0006-8993(91)91076-d
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19423310
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NF-kappaB inhibitory activity of cyclitols isolated from Hancornia speciosa.
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Hancornia speciosa Gomes (Apocynaceae) is a Brazilian plant traditionally employed to treat inflammatory conditions, among other uses. The chemopreventive effect of an ethanol extract from H. speciosa leaves (EHS) was evaluated in a battery of in vitro tests [inhibition of aromatase, NF-kappaB and ornithine decarboxylase (ODC), antioxidant response elements (ARE) induction and cell proliferation assays]. Bioassay-directed fractionation of EHS following by inhibition of 12-O-tetradecanoyl-13-acetate (TPA)-mediated NF-kB activation led to the isolation of the cyclitols quinic acid (1) (85.0+/-12.3 microM) and l-(+)-bornesitol (2) (IC(50)=27.5+/-3.8 microM), along with rutin (26.8+/-6.3 microM). Based on these lead compounds, the cyclitols per-O-acetyl-1l-(+)-bornesitol (3) (IC(50)=38.4+/-6.2 microM), myo-inositol (4) (>180.2 microM), scyllo-inositol (5) (83.0+/-13.7 microM) and beta-d-galactoside-myo-inositol (6) (52.4+/-8.4 microM) were evaluated in the assay, but found to be somewhat less active than 1 and 2. None of the compounds was active in the ARE, aromatase or ODC assays and did not inhibit proliferation of MCF-7, LNCaP, HepG2 or LU-1 cell lines at a final concentration of 20 microg/ml (equivalent to 104.07-32.76 microM). This work identifies l-(+)-bornesitol, quinic acid and rutin as NF-kappaB inhibitors of H. speciosa and suggests cyclitols, in addition to myo-inositol, are potentially useful as chemopreventive agents.
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10.1016/j.phymed.2009.03.022
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31946423
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Sleep Apnea and Hypopnea Events Detection Based on Airflow Signals Using LSTM Network.
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Sleep Apnea-Hypopnea Syndrome (SAHS) is a sleep-related breathing disorder which involves the reduction in breathing airway when patiens sleep. However, a large proportion of patients are usually undiagnosed and untreated which may lead to the risk of life. In this paper, we propose an automatic SAHS event detection method based on Long Short-Term Memory (LSTM) network via nasal airway pressure and temperature signals from clinical polysomnography (PSG) dataset. Focusing on time location of the events, we firstly segment the two channels of signals into a series of sequences by feature extraction. Secondly, a LSTM network is established and these sequences are subsequently fed into this LSTM network for SAHS event classification. The experimental results on both our clinical PSG dataset and public MIT-BIH PSG database show that our method is promising in terms of recall.
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10.1109/EMBC.2019.8857558
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36276969
|
Signals of adaptation to agricultural stress in the genomes of two European bumblebees.
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Human-induced environmental impacts on wildlife are widespread, causing major biodiversity losses. One major threat is agricultural intensification, typically characterised by large areas of monoculture, mechanical tillage, and the use of agrochemicals. Intensification leads to the fragmentation and loss of natural habitats, native vegetation, and nesting and breeding sites. Understanding the adaptability of insects to these changing environmental conditions is critical to predicting their survival. Bumblebees, key pollinators of wild and cultivated plants, are used as model species to assess insect adaptation to anthropogenic stressors. We investigated the effects of agricultural pressures on two common European bumblebees, Bombus pascuorum and B. lapidarius. Restriction-site Associated DNA Sequencing was used to identify loci under selective pressure across agricultural-natural gradients over 97 locations in Europe. 191 unique loci in B. pascuorum and 260 in B. lapidarius were identified as under selective pressure, and associated with agricultural stressors. Further investigation suggested several candidate proteins including several neurodevelopment, muscle, and detoxification proteins, but these have yet to be validated. These results provide insights into agriculture as a stressor for bumblebees, and signal for conservation action in light of ongoing anthropogenic changes. Copyright © 2022 Hart, Verbeeck, Ariza, Cejas, Ghisbain, Honchar, Radchenko, Straka, Ljubomirov, Lecocq, Dániel-Ferreira, Flaminio, Bortolotti, Karise, Meeus, Smagghe, Vereecken, Vandamme, Michez and Maebe.
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10.3389/fgene.2022.993416
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1002813
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Binding of progesterone by human uterine cytosol.
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Progesterone binding by 100,000 X g cytosols of human myometria from patients undergoing hysterectomy for various reasons was assayed using equilibrium dialysis or DEAE-cellulose filtration. The estimates of high-affinity porgesterone binding obtained by both techniques showed a significant correlation. Dialysis and filtration assays with cortisol competing with [3H]progesterone for binding indicated that the specific progesterone binding by the cytosols was the result of progesterone interaction with two high-affinity constitutents. Myometrial cytosols from tissues under progestin stimulation (secretory endometrium or pregnancy) had low concentrations of progestin binders. Cytosols from uteri with atrophic endometrium showed consistently high concentrations of progestin binders and those tissues under estrogen stimulation (proliferative endometrium or hyperplasia) and variable binder concentrations. No differences were detected between grouped observtions classified into 10 clinical categories. The DEAE-cellulose filtration is an effective method for evaluating progesterone binding which uses well-established statistical techniques and requires less tissue, less time for incubations, and fewer points for reliable analysis than does equilibrium dialysis.
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10.1210/jcem-43-6-1211
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12198875
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[Peptic stenosis, motility disorder or carcinoma. What is ate the bottom of dysphagia?].
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Dysphagia is the characteristic cardinal symptom of diseases of the esophagus. Etiologically, consideration must first be given to carcinoma of the esophagus. Among the cancers affecting this organ, adenocarcinoma of the distal part of the esophagus is the most common. The most important differential diagnosis in patients who have difficulty swallowing is peptic stricture of the distal esophagus arising from long-standing reflux disease. Further possible causes are motility disorders of the esophagus including, in particular, achalasia and--more rarely--diverticula, foreign bodies, membranes or rings, benign tumors or extraluminal processes.
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16516374
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Follicular sterol composition in gonadotrophin stimulated women with polycystic ovarian syndrome.
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This is the first study evaluating whether oocyte development and fertilization competence are related to intrafollicular concentration of cholesterol, meiosis-activating sterols and progesterone, after human chorionic gonadotrophin (HCG) administration of women with polycystic ovarian syndrome (PCOS). The concentration of follicular fluid meiosis-activating sterol (FF-MAS) significantly increased in the periovulatory period from 10-14 to 34-38 h after HCG administration, while the concentration of testis meiosis-activating sterol (T-MAS) decreased, suggesting a HCG-dependent inhibition of sterol Delta14-reductase. There was no correlation between follicular lanosterol, FF-MAS, T-MAS, and progesterone concentrations and the presence or absence of MII oocytes. Interestingly, free cholesterol level was significantly lower and FF-MAS/cholesterol and progesterone/cholesterol ratios significantly higher in follicles containing MII oocytes compared to follicles from which oocytes were not retrieved. Yet, fertilization and embryo quality did not correlate with follicular sterols. This knowledge should be beneficial for the implementation of protocols for in vitro maturation process, usually used in PCOS patients.
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10.1016/j.mce.2006.01.013
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38651177
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Effectiveness and infectious complications of BCMA T-cell engagers in treating multiple myeloma: Real-world evidence from Sweden.
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Multiple myeloma (MM), an incurable disease characterized by frequent relapses and a need for multiple treatments, often progresses to a relapse/refractory status resistant to all available drugs and drug classes. Bispecific antibodies, specifically BCMA T-cell engagers, have emerged as effective treatments for MM, demonstrating impressive efficacy. However, these treatments can adversely affect the immune system, increasing vulnerability to infections. This study evaluated the efficacy and safety of BCMA T-cell engagers in 58 Swedish patients with poor MM prognosis. The patients exhibited a 69% overall response rate, with 69% survival and 60% progression-free survival at 15 months. Despite the risk of infectious complications, the prognosis of MM patients can be significantly improved with vigilant monitoring and proactive management of infections. This real-world data highlight the potential of BCMA T-cell engagers in treating MM, emphasizing the need for careful patient monitoring to mitigate infection risks. © 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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10.1002/cam4.7048
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37954727
|
The Calm Before the Storm: A Pheochromocytoma Case Report.
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Pheochromocytomas are rare tumors that arise from the sympathetic ganglia or adrenal medulla and secrete catecholamines that are known for the classic triad of headaches, profuse sweating, and paroxysmal hypertension. However, there have been instances of asymptomatic patients found to have a pheochromocytoma. Adrenal incidentalomas are accidentally discovered through radiologic imaging, and subsequent testing can confirm a pheochromocytoma. Here, we present a case of a 67-year-old female found to have an adrenal incidentaloma on kidney ultrasound (US) after presenting to the emergency room (ER) due to nausea. She had minimally elevated creatinine at the ER. At her follow-up with her primary care provider (PCP), a kidney US was ordered and showed a probable right suprarenal mass. Further abdominal computed tomography (CT) and abdominal magnetic resonance imaging (MRI) showed that the mass was indeed adrenal, but its etiology is considered indeterminant. Although asymptomatic, further biochemical tests showed elevated serum and urine metanephrines and normetanephrines. Together, these findings revealed that the adrenal mass was likely a silent pheochromocytoma. She underwent a successful right adrenalectomy with pathology confirming pheochromocytoma. This case adds to the literature on the existence of silent pheochromocytomas and highlights the importance of following up on any abnormal findings with a PCP. This patient, although asymptomatic from her pheochromocytoma, needed surgery to prevent possible pheochromocytoma crises, which could cause cardiovascular complications and even death. Copyright © 2023, Trinh et al.
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10.7759/cureus.46915
|
11749137
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Virus neutralising antibodies against 22 bovine viral diarrhoea virus isolates in vaccinated calves.
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Seven of nine colostrum deprived calves, free from bovine viral diarrhoea virus (BVDV), were vaccinated with a commercially available vaccine containing two inactivated strains of BVDV, an inactivated strain of bovine herpesvirus-1 and modified-live strains of bovine respiratory syncytial virus and para-influenza-3 virus. The two other calves were kept as controls. The virus neutralising (VN) antibodies induced by vaccination were tested against 22 antigenically diverse BVDV isolates, including reference strains and field isolates, both cytopathic and non-cytopathic, as well as genotypes I and II. The strains were isolated in Belgium, France, Germany, the United Kingdom and the USA. While there were variations in the VN titres of the individual calves against all the strains, serum from the seven animals neutralised 20 or more of the strains tested. From the results, it can be concluded that the vaccine can stimulate the production of VN antibodies capable of neutralising a wide range of European and American isolates of BVDV, including genotypes I and II. Copyright 2002 Harcourt Publishers Ltd.
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10.1053/tvjl.2001.0638
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24016639
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[End of life in neonatology: palliative care integration].
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Today the limitation of therapeutic effort and the neonatal palliative care are extremely important and had been increasingly done by several countries. Nevertheless, in Portugal, studies and guidelines regarding end of life attitudes are still a shortage. We analyzed 49 files in a retrospective review of neonatal deaths between 2010 and 2012; the results were compared with those from a previous study made in the same NICU that included the neonatal deaths of 1992-1995 and 2002-2005. The results show that congenital anomalies were the cause of death for 57.1% newborns, extreme prematurity for 18.4% and 16.3% died with infection. Regarding to the mode of death, 57.1% of newborns died after cardiopulmonary resuscitation failure, 20.4% after withholding treatment and 22.4% of deaths followed therapy withdrawal. Differences were found between the three groups classified according to the 'mode of death', length of stay and parental presence during death. Therapeutic limitation practices and palliative care were reported in 28.6% of the files and a Do-Not-Resuscitate Order was included in 16.3%. The former two increased during the three periods analyzed. The use of a neonatal pain scale, opioids and sedatives administration, parental presence during death, clinical meetings with neonatologists, interdisciplinary meetings and psychological support for parents also increased. This study shows a trend towards an increase in therapeutic limitation practices and palliative care in this NICU in the last three decades. However, there is still a lot to do regarding the clinical research, medical education and ethical discussion.
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30833964
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Control of a Humanoid NAO Robot by an Adaptive Bioinspired Cerebellar Module in 3D Motion Tasks.
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A bioinspired adaptive model, developed by means of a spiking neural network made of thousands of artificial neurons, has been leveraged to control a humanoid NAO robot in real time. The learning properties of the system have been challenged in a classic cerebellum-driven paradigm, a perturbed upper limb reaching protocol. The neurophysiological principles used to develop the model succeeded in driving an adaptive motor control protocol with baseline, acquisition, and extinction phases. The spiking neural network model showed learning behaviours similar to the ones experimentally measured with human subjects in the same task in the acquisition phase, while resorted to other strategies in the extinction phase. The model processed in real-time external inputs, encoded as spikes, and the generated spiking activity of its output neurons was decoded, in order to provide the proper correction on the motor actuators. Three bidirectional long-term plasticity rules have been embedded for different connections and with different time scales. The plasticities shaped the firing activity of the output layer neurons of the network. In the perturbed upper limb reaching protocol, the neurorobot successfully learned how to compensate for the external perturbation generating an appropriate correction. Therefore, the spiking cerebellar model was able to reproduce in the robotic platform how biological systems deal with external sources of error, in both ideal and real (noisy) environments.
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10.1155/2019/4862157
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23112469
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Lymphoma of the cervix: A diagnostic pitfall on cervicovaginal smear.
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Malignant lymphoma that secondarily involves the cervix is a rare condition and may be difficult to distinguish from follicular cervicitis and small cell carcinoma. Cervical lymphoma is sometimes misdiagnosed on cervicovaginal cytology due to its rarity. We report a case of a cervical lymphoma in a 65-year-old woman, which was diagnosed as a squamous cell carcinoma on cervicovaginal cytology.
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10.4103/0970-9371.101184
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39565905
|
7-Year outcomes after surgical aortic valve replacement with a stented bovine pericardial bioprosthesis in over 1100 patients: a prospective multicenter analysis.
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Safety, efficacy, and durability are important considerations when selecting a bioprosthesis for aortic valve replacement (AVR). This study assessed 7-year clinical outcomes and haemodynamic performance of the Avalus bioprosthesis. Patients indicated for surgical AVR were enrolled in this prospective, nonrandomized trial, conducted across 39 sites globally. The primary end-point of this analysis was freedom from surgical explant or percutaneous valve-in-valve reintervention due to structural valve deterioration (SVD) at 7 years of follow-up, determined using Kaplan-Meier (KM) analysis. We also evaluated a composite end-point of SVD or severe haemodynamic dysfunction (SHD) requiring reintervention. Survival, valve-related safety events, and haemodynamic performance were assessed. Deaths and safety events were adjudicated by an independent clinical events committee. A total of 1132 patients underwent surgical AVR. Mean age was 70 years; 854 patients (75%) were men. Mean STS risk of mortality was 2.0 ± 1.4%, and 659 patients (58%) had a NYHA classification of I/II. One or more concomitant procedures were performed in 577 patients (51%). At 7 years, the Kaplan-Meier rate of freedom from SVD/SHD requiring reintervention was 1.2% (0.5-2.5%) with no cases adjudicated as SVD. The survival rate was 82.6% (79.5-85.0%). The KM event rate was 5.7% (4.3-7.7%) for reintervention, 6.3% (4.9-8.3%) for endocarditis, and 0.4% (0.1-1.1%) for valve thrombosis. Mean aortic gradient, dimensionless velocity index, and effective orifice area were 13.8 ± 5.9 mmHg, 0.42 ± 0.09, and 1.99 ± 0.53 cm2, respectively. This analysis demonstrated excellent durability of the Avalus valve with good clinical outcomes and stable haemodynamic performance through 7 years of follow-up. www. clinicaltrials. gov ID: NCT02088554. © The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.
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10.1093/ejcts/ezae414
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8781599
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Lymphocytic infundibulohypophysitis presenting in the postpartum period: case report.
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Lymphocytic adenohypophysitis is a well-known autoimmune disorder affecting the anterior pituitary gland. Posterior pituitary gland function can be impaired by a similar autoimmune disorder called lymphocytic infundibulohypophysitis. Only very few cases have been reported. We present a patient with central diabetes insipidus in the postpartum period. On radiologic and endocrine evidence lymphocytic involvement of the pituitary stalk and infundibulum was suspected. A diagnostic pterional craniotomy was performed. The diagnosis of lymphocytic infundibulohypophysitis was confirmed by biopsy. We present a case of lymphocytic infundibulohypophysitis. In view of its autoimmune pathophysiology the occurrence of this disorder in the postpartum period is not surprising, even though it has not been reported before. This rare disorder should be distinguished from the more common lymphocytic adenohypophysitis.
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10.1016/0090-3019(96)00215-7
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27433371
|
Spectroscopic Characteristics of Dissolved Organic Matter in Afforestation Forest Soil of Miyun District, Beijing.
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In this study, soil samples collected from different plain afforestation time (1 year, 4 years, 10 years, 15 years, and 20 years) in Miyun were characterized, including total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), available K (K(+)), microbial biomass carbon (MBC), and dissolved organic carbon (DOC). The DOM in the soil samples with different afforestation time was further characterized via DOC, UV-Visible spectroscopy, excitation-emission matrix (EEM) fluorescence spectroscopy, and (1)H NMR spectroscopy. The results suggested that the texture of soil sample was sandy. The extracted DOM from soil consisted mainly of aliphatic chains and only a minor aromatic component. It can be included that afforestation can improve the soil quality to some extent, which can be partly reflected from the indexes like TOC, TN, TP, K(+), MBC, and DOC. And the characterization of DOM implied that UV humic-like substances were the major fluorophores components in the DOM of the soil samples, which consisted of aliphatic chains and aromatic components with carbonyl, carboxyl, and hydroxyl groups.
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10.1155/2016/1480857
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12861329
|
Improving cancer screening among lesbians over 50: results of a pilot study.
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To explore the impact of two one-hour lesbian-specific educational interventions by a lesbian physician on the cancer screening behaviors of lesbians. A pilot pre- and post-test intervention study. Two lesbian, gay, bisexual, and transgendered senior organizations in the San Francisco Bay Area (one urban, one suburban). 36 participants aged 50-81 (meanX = 60.2, SD = 6.48). The majority were Caucasian (86%), single (61%), living in urban areas (67%), employed (56%), and educated beyond high school (meanX = 15.47 years, SD = 2.90, range 9-21). Eleven percent (n = 4) did not have any health insurance and were not on Medicaid or Medicare. A lesbian physician led a one-hour, didactic, lesbian- specific educational program on cancer screening, including a review of current research findings with regard to lesbians' risk for cancer and 45 minutes of information on recommended cancer screening, followed by a 15-minute question-and-answer period. Participants completed a pre- and postintervention survey. Follow-up data were available for 22 women. Of the six women (27%) who had not focused their attention on breast screening behaviors for two years or more, one-third had obtained mammograms and half began performing monthly breast self-examinations. Of the four women (18%) who had not undergone a pelvic examination for three years or more, one obtained a pelvic examination. The women reported no changes in colorectal cancer screening behaviors. Some of these difficult-to-reach women changed their behavior in a very short period of time, supporting the need for a larger study to confirm these findings. A need exists to develop appropriate interventions for the underserved population of lesbians older than 50.
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10.1188/03.ONF.E71-E79
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22100862
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[Endocavitary surgical procedures, an alternative to myomectomy in patients with symptomatic fibroids].
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Endometrial ablation can be used in heavy menstrual bleeding due to symptomatic submucosal myomas in women without desire of pregnancy. Those methods used alone, lead to an improvement on bleeding but results are not as good as in women without myomas. They can be associated with hysteroscopic myomectomy and, then, the results on bleeding are better than myomectomy alone. Second generation endometrial ablation methods must be used preferentially as they present less surgical complications than first generation methods. As the pregnancies that may occur after endometrial ablation have high risk of complications, a contraceptive mean is highly recommended after surgery. Transcervical sterilisation by intratubal insert (Essure) can also be proposed, but for women with Essure placed before endometrial ablation, only Thermachoice and bipolar resection have proven their safety. Finally, economical outcomes of endometrial ablation in myomas haven't been assessed yet. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
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10.1016/j.jgyn.2011.09.028
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17628718
|
Apelin effects in human splanchnic arteries. Role of nitric oxide and prostanoids.
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Apelin effects were examined in human splanchnic arteries from liver donors (normal arteries) and from liver recipients. Segments 3 mm long were obtained from mesenteric arteries taken from liver donors (normal arteries), and from hepatic arteries taken from cirrhotic patients undergoing liver transplantation (liver recipients), and the segments were mounted in organ baths for isometric tension recording. In arteries under resting conditions, apelin (10(-10)-10(-6) M) caused no effect in any of the arteries tested. In arteries precontracted with the thromboxane A(2) analogue U46619 (10(-7)-10(-6) M), apelin (10(-10)-10(-6) M) produced concentration-dependent relaxation that was lower in hepatic than in mesenteric arteries, whereas sodium nitroprusside (10(-8)-10(-4) M) produced a similar relaxation in both types of arteries. The inhibitor of nitric oxide synthesis N(w)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) diminished the relaxation to apelin in mesenteric but not in hepatic arteries. The inhibitor of cyclooxygenase meclofenamate (10(-5) M) did not affect the relaxation provoked by apelin in both types of arteries. Therefore, apelin may produce relaxation in normal human splanchnic arteries, and this relaxation may be mediated in part by nitric oxide without involvement of prostanoids. This relaxation as well as the role of nitric oxide may be decreased in splanchnic arteries from cirrhotic patients.
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10.1016/j.regpep.2007.06.005
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31859924
|
MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY (MRCP) VERSUS ENDOSONOGRAPHY-GUIDED FINE NEEDLE ASPIRATION (EUS-FNA) FOR DIAGNOSIS AND FOLLOW-UP OF PANCREATIC INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS.
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Intraductal papillary mucinous tumor (IPMN) are being diagnosed with increasing frequency. Computerized tomography scanning is commonly used as the primary imaging modality before surgery nonetheless magnetic resonance cholangiopancreatography (MRCP) provides better characterization. Endosonography-guided fine needle aspiration (EUS-FNA) has emerged as a way to reach pathological diagnose. To compare results of both methods with surgical pathology findings for classification of IPMN. Thirty-six patients submitted to surgical resection with preoperative suspect of IPMN were submitted preoperatively to MRCP and EUS-FNA. Images obtained were analyzed according to a classification determined for each method. ROC curve was used for statistical analysis, that compared the images tests with the purpose of finding the best method for diagnosis and classification of IPMN. Sixteen patients underwent pancreatoduodenectomy, 16 to subtotal pancreatectomy and only four laparotomy. Pathological diagnosis was IPMN (n=33) and pancreatic intraepithelial neoplasia type 2 (n=3). Twenty-nine revealed non-invasive neoplasia and invasive form in four patients. MRCP and EUS-FNA have correctly diagnosed and classified (type of IPMN), in 62.5% and 83.3% (p=0.811), the affected segment location in 69% and 92% (p=0.638) and identification of nodules and/or vegetation presence in 45% and 90% (p=0.5). Regarding to histopathological diagnosis by EUS-FNA the sensitivity was 83.3%; specificity was 100%; positive predictive value was 100%; negative predictive value was 33.3% and accuracy was 91.7%. There was no significant difference in the diagnosis of IPMN. However, EUS-FNA showed better absolute results than MRCP to identify nodule and/or vegetation.
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10.1590/0102-672020190001e1471
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1557125
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Normal dystrophin transcripts detected in Duchenne muscular dystrophy patients after myoblast transplantation.
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Gene delivery by transplantation of normal myoblasts has been proposed as a treatment of the primary defect, lack of the muscle protein dystrophin, that causes Duchenne muscular dystrophy (DMD), a lethal human muscle degenerative disorder. To test this possibility, we transplanted normal myoblasts from a father or an unaffected sibling into the muscle of eight boys with DMD, and assessed their production of dystrophin. Three patients with deletions in the dystrophin gene expressed normal dystrophin transcripts in muscle biopsy specimens taken from the transplant site one month after myoblast injection. Using the polymerase chain reaction we established that the dystrophin in these biopsies derived from donor myoblast DNA. These results show that transplanted myoblasts persist and produce dystrophin in muscle fibres of DMD patients.
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10.1038/356435a0
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32716230
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Why the mask? The effectiveness of face masks in preventing the spread of respiratory infections such as COVID-19 - a home testing protocol.
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Since the start of the COVID-19 pandemic there has been much debate in the media on whether masks should be worn to stop the spread of the virus. There are two ways in which they could work. Firstly, to protect the person wearing the mask, and secondly, to reduce the likelihood of the person wearing the mask passing the disease on to anyone else. This is not an easy issue to address and many factors come into play such as droplet size, aerosol transmission and the viral load, as well as the specific properties of any given mask. The method used in this study was to measure the change in relative humidity when wearing a mask, compared to no mask, in various scenarios, based on the assumption that as the virus is air-borne the smaller the increase in humidity the less the spread of the virus. The results above show that the use of a mask, excluding some simple home-made ones, significantly reduces the spread of humidity. However, their effectiveness is device specific and needs to be considered in greater detail for each type of mask, especially the direction of escaping air when forward flow is blocked.
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10.1080/03091902.2020.1797198
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6803245
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Arachidonic acid metabolism in glutathione-deficient macrophages.
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Mouse resident peritoneal macrophages were treated with the glutathione (GSH) synthesis inhibitor buthionine sulfoximine to deplete intracellular GSH. The arachidonic acid metabolites released by the GSH-depleted macrophages in response to a zymosan challenge were analyzed by HPLC. Buthionine sulfoximine treatment resulted in inhibition of both prostaglandin E2 and leukotriene C synthesis that was directly related to the degree of GSH depletion. Macrophages in which GSH levels were reduced to 3% of normal exhibited reductions to 4% and 1%, respectively, in PGE2 and LTC formation. The total quantity of cyclooxygenase metabolites secreted by GSH-deficient macrophages was identical to that of control cells as a result of increased synthesis of prostacyclin and, to a lesser extent, 12-L-hydroxy-5,8,10-heptadecatrienoic acid. Total lipoxygenase products were decreased, however; increased formation of hydroxyicosatetraenoic acids only partially compensated for the deficit in leukotriene C production. These findings extent our earlier observations on the inhibition of leukotriene C synthesis in GSH-depleted macrophages and confirm with intact cells the previously suggested role of GSH in prostaglandin E2 formation.
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10.1073/pnas.79.5.1621
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7418845
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Effects of propafenone on TEA-induced action potentials in vascular smooth muscle of canine coronary arteries.
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The Ca++-dependent, TEA-induced action potential is blocked by propafenone in a dose-dependent manner. Such results suggests that in coronary arterial smooth muscle one mechanism of action of propafenone is to inhibit Ca++ inward current.
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10.1007/BF01965982
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35570398
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Matched linac stereotactic radiotherapy: An assessment of delivery similarity and distributive patient-specific quality assurance feasibility.
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Matching multiple linacs to common baseline data allows patients to be treated, and patient-specific quality assurance (PSQA) to be completed on any linac. Stereotactic body radiotherapy (SBRT) requires higher levels of accuracy and quality assurance than routine radiotherapy. The achieved linac matching must therefore be evaluated before distributive treatment or PSQA models can be implemented safely. This investigation aimed to propose metrics for defining linacs to be matched for SBRT deliveries, assess 12 linacs against these criteria, and determine if a distributive PSQA model could be implemented by reviewing the rates of false PSQA results. Ten SBRT spine plans were delivered by 12 matched Elekta linacs and measured using one of seven SRS MapCHECK devices. For gamma criteria of (3%, 2 mm), 96.9% of equivalent location detectors, showed a range of gamma ≤ 1.0 and 99.9% showed a standard deviation of ≤ 0.5. For criteria of (3%,1 mm) and (2%,1 mm), these ranges decreased to 92.1% and 80.2% while the standard deviations decreased to 99.3% and 95.7%, respectively. The dose differences showed that 43.6%, 82.7%, and 91.4% of detectors had a dose range of ≤ 3.0%, ≤ 5.0%, and ≤ 6.0%, respectively. Standard deviations of dose differences were 1.5%, 2.5%, and 3.0% for 94.1%, 98.3%, and 99.5% of detectors, respectively. For the fleet of linacs, distributive PSQA yielded false results for 0.0%, 17.7%, and 33.0% of plans, equivalent to 1.2%, 3.5%, and 9.4% of detectors when using gamma criteria of (3%,2 mm), (3%,1 mm), or (2%,1 mm), respectively. These linacs could be considered matched for SBRT treatments and implement a distributive PSQA model when gamma analysis was completed with a criterion of (3%, 2 mm). For stricter criterion of (3%,1 mm) or (2%,1 mm), they did not meet the proposed metrics. © 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.
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10.1002/acm2.13652
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32166487
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Radiomics analysis of lung CT image for the early detection of metastases in patients with breast cancer: preliminary findings from a retrospective cohort study.
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To investigate whether subtle changes in radiomics features are present in lung CT images prior to the development of CT-detectable lung metastases in patients with breast cancer. Thirty-three radiomics features were measured in the metastasis region (MR) and in matched contralateral tissues (non-metastasis region, NMR) of 29 breast cancer patients at the last CT scan, as well as in the corresponding regions of the patients' pre-metastasis scan (pre-MR and pre-NMR). We also compared them with normal lung tissues (control group, CG) from 29 healthy volunteers. Then, 8 patients from the 29 patients with lung metastases and 8 patients who did not develop lung metastases were chosen for further study of the correlation between radiomics parameters and tumor growth. In the MR vs. NMR and MR vs. CG groups, almost all radiomics features were significantly different. Twenty-six parameters showed significant differences between the pre-MRs and pre-NMRs. Linear fitting demonstrated a significant correlation between 5 features and tumor growth in the metastasis group, but not in the non-metastasis group. Among them, run percentage was the most representative feature. The calculated area under curves (AUCs), based on run percentage for the classification of metastasis and pre-metastasis, were 0.954 and 0.852, respectively. Radiomics features may allow early detection of lung metastases before they become visually detectable, and the feature run percentage may be a promising image surrogate marker for the microinvasion of tumor cells into the lung tissue. • The significant differences in radiomics features between pre-MR and pre-NMR are critical for the early detection of lung metastases. • Five radiomics features show a correlation with tumor growth. • The radiomics feature run percentage may be a potential imaging biomarker for the early detection of lung metastases.
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10.1007/s00330-020-06745-5
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29856100
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Neither self-reported atopy nor IgE-mediated allergy are linked to gastrointestinal symptoms in patients with irritable bowel syndrome.
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Among patients with irritable bowel syndrome (IBS), atopic disease has been proposed as a common comorbidity increasing the IBS symptom burden. We therefore assessed the prevalence of self-reported atopy among patients with IBS as compared to non-IBS controls, and whether atopy and higher serum IgE levels were associated with increased IBS symptom severity. Levels of total and specific IgE in serum were measured and questionnaires assessing the presence of atopic disease (ie, eczema, asthma, rhinoconjunctivitis, and pollen allergy), gastrointestinal symptom burden, food intolerance, somatic, and psychological symptoms were completed. In total, 223 patients with IBS and 47 controls participated. Presence of atopic disease was reported in 55% of patients with IBS compared to 40% of controls (P =.07). IBS patients with atopic manifestations (N = 123) had higher total serum IgE levels (median 31 vs 16 kU A /L, P <.001) and higher prevalence of self-reported food intolerance (28% vs 9%, P =.002) than non-atopic IBS patients (N = 100), respectively, but no major difference in gastrointestinal or psychological symptom burden was noted. However, severe somatic symptoms were more common among atopic than non-atopic patients with IBS (38% vs 27%, P =.028). We found no associations between self-reported atopy and IBS symptom severity using linear regression models. Atopic disease is common in patients with IBS, but that is also true for subjects without IBS. The presence of atopic disease in IBS is associated with self-reported food intolerance and somatic symptom severity, but unrelated to IBS symptom severity. © 2018 John Wiley & Sons Ltd.
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10.1111/nmo.13379
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29515303
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Dense Deposit Disease Involving C3 and C4d Deposits.
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Dense deposit disease (DDD), earlier called Type II membranoproliferative glomerulonephritis is distinct disease having frequent relapses reaching end-stage kidney disease by 10-year in up to 50%-60% of cases and high recurrence rate in the allograft. The term DDD is derived from its distinctive ribbon-like osmiophilic deposits in the lamina densa of glomerular basement membrane by electron microscopy. Pathogenetically, alternate pathway dysfunction leads to this disease, which is diagnosed by ultrastructure. Herein, we describe our observation of C4d positivity in an adolescent boy with DDD.
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10.4103/ijn.IJN_164_16
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26314864
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Distinct transcriptional responses elicited by unfolded nuclear or cytoplasmic protein in mammalian cells.
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Eukaryotic cells possess a variety of signaling pathways that prevent accumulation of unfolded and misfolded proteins. Chief among these is the heat shock response (HSR), which is assumed to respond to unfolded proteins in the cytosol and nucleus alike. In this study, we probe this axiom further using engineered proteins called 'destabilizing domains', whose folding state we control with a small molecule. The sudden appearance of unfolded protein in mammalian cells elicits a robust transcriptional response, which is distinct from the HSR and other known pathways that respond to unfolded proteins. The cellular response to unfolded protein is strikingly different in the nucleus and the cytosol, although unfolded protein in either compartment engages the p53 network. This response provides cross-protection during subsequent proteotoxic stress, suggesting that it is a central component of protein quality control networks, and like the HSR, is likely to influence the initiation and progression of human pathologies.
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10.7554/eLife.07687
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28806619
|
A long-term recurrence-free survival of a patient with the mixed adeno-neuroendocrine bile duct carcinoma: A case report and review of the literature.
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Neuroendocrine tumors arising primarily in the bile duct are rare. And among these tumors, mixed adeno-neuroendocrine carcinoma (MANEC) is quite uncommon. We report a patient with MANEC who achieved long-term recurrence-free survival. And our case report includes analysis previous case reports. A 66-year-old man underwent investigation for persistent anorexia and fatigue. Laboratory tests showed that the values of hepatobiliary enzymes were increased. On CT, a 10mm×8mm hypervascular tumor was observed in the distal bile duct and the proximal bile duct was markedly dilated. Endoscopic retrograde cholangiography (ERC) also showed a stenosis with a long diameter of 10mm. Examination of a biopsy specimen obtained from the narrow site of the bile duct at the time of ERC revealed tubular adenocarcinoma. Therefore, pylorus-preserving pancreaticoduodenectomy was performed under a preoperative diagnosis of distal bile duct carcinoma. Postoperative pathologic examination revealed alveolar structures and a mixture of moderately differentiated adenocarcinoma with synaptophysin-positive and chromogranin-A-positive neuroendocrine carcinoma. Therefore, the final diagnosis was MANEC, pT3, pN1, M0, pStage II B (TNM classification of the UICC). Curative resection was achieved and there has been no recurrence after 30 months. In the previous reports, only five patients (14.7%) survived for 24 months or longer. Median survival was longer (14 months) in the curative resection group and shorter (6 months) in the non-curative resection group. Curative resection is essential to achieve long-term survival in patients with bile duct MANEC, even if these patients have lymph node metastasis. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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10.1016/j.ijscr.2017.07.052
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24119439
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Public health systems analysis--where the River Kabul meets the River Indus.
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In this paper we review two recent paradigmatic shifts and consider how a two-way flow in innovation has been critical to the emergence of new thinking and new practices. The first area relates to our understanding of the nature of public health systems and the shift from a medical paradigm to a more holistic paradigm which emphasises the social, economic and environmental origins of ill-health and looks to these as key arenas in which to tackle persistent inequalities in populations' health experiences. In respect of this paradigmatic shift, it is argued, developing countries were in advance of their more developed counterparts. Specifically, the Alma Ata Declaration and the Primary Health Care Approach which was central to its implementation pre-figured elements of what was to be called in developed countries The New Public Health such as the need for greater community involvement and recognition of the importance of other sectors in determining health outcomes. But this paradigmatic shift added a new complexity to our understanding which made the identification of appropriate policy responses increasingly difficult. However, a parallel shift was taking place in the cognate field of operational research/systems analysis (OR/SA) which was adding greatly to our ability to analyse and to identify key points of intervention in complex systems. This led to the emergence of new techniques for problem structuring which overcame many of the limitations of formal mathematical models which characterised the old paradigm. In this paradigmatic shift developed countries have led the way, specifically in the new fields of Community Operational Research and Operational Research for Development, but only by drawing strongly on the experience and philosophies to be found in developing countries.
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10.1186/1744-8603-9-39
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31961285
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Hymenobacter sediminis sp. nov., isolated from lake sediment.
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A Gram-stain-negative, facultatively aerobic, rod-shaped, motile by gliding and pink-pigmented bacterial strain, designated ELS1360 T, was isolated from a lake sediment sample collected in Inner Mongolia, PR China. Strain ELS1360 T grew optimally at 33 °C, at pH 6.5-7.0 and without NaCl. Strain ELS1360 T exhibited 97.3, 97.1 and 96.9 % 16S rRNA gene sequence similarities to Hymenobacter aquatilis HMF3095 T, Hymenobacter luteus JCM 30328 T and Hymenobacter latericoloratus JCM 30327 T, respectively, and 90.4-96.9 % to other members of the genus Hymenobacter. Results of phylogenetic analysis based on 16S rRNA gene sequences showed that strain ELS1360 T belonged to the genus Hymenobacter and clustered with H. luteus JCM 30328 T and H. latericoloratus JCM 30327 T. The predominant cellular fatty acids were iso-C 15:0, summed feature 3 and C 16:1 ω5 c. Strain ELS1360 T contained MK-7 as the sole menaquinone. The major polar lipids contained phosphatidylethanolamine and two unidentified lipids. The genomic DNA G+C content of strain ELS1360 T was 57.1 mol%. Based on the results of our phylogenetic, phenotypic, genotypic and chemotaxonomic analyses, it is concluded that strain ELS1360 T represents a novel species within the genus Hymenobacter, for which the name Hymenobacter sediminis sp. nov. is proposed. The type strain is ELS1360 T (=KCTC 62449 T =MCCC 1H00319 T ).
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10.1099/ijsem.0.003990
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25797371
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T11TS inhibits Angiopoietin-1/Tie-2 signaling, EGFR activation and Raf/MEK/ERK pathway in brain endothelial cells restraining angiogenesis in glioma model.
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Malignant gliomas represent one of the most aggressive and hypervascular primary brain tumors. Angiopoietin-1, the peptide growth factor activates endothelial Tie-2 receptor promoting vessel maturation and vascular stabilization steps of angiogenesis in glioma. Epidermal growth factor receptor (EGFR) and Tie-2 receptor on endothelial cells once activated transmits signals through downstream Raf/MEK/ERK pathway promoting endothelial cell proliferation and migration which are essential for angiogenesis induction. The in vivo effect of sheep erythrocyte membrane glycopeptide T11-target structure (T11TS) on angiopoietin-1/Tie-2 axis, EGFR signaling and Raf/MEK/ERK pathway in glioma associated endothelial cells has not been investigated previously. The present study performed with rodent glioma model aims to investigate the effect of T11TS treatment on angiopoietin-1/Tie-2 signaling, EGFR activity and Raf/MEK/ERK pathway in glioma associated endothelial cells within glioma milieu. T11TS administration in rodent glioma model inhibited angiopoietin-1 expression and attenuated Tie-2 expression and activation in glioma associated brain endothelial cells. T11TS treatment also downregulated total and phosphorylated EGFR expression in glioma associated endothelial cells. Additionally T11TS treatment inhibited Raf-1 expression, MEK-1 and ERK-1/2 expression and phosphorylation in glioma associated brain endothelial cells. Thus T11TS therapy remarkably inhibits endothelial angiopoietin-1/Tie-2 signaling associated with vessel maturation and simultaneously antagonizes endothelial cell proliferation signaling by blocking EGFR activation and components of Raf/MEK/ERK pathway. Collectively, the findings demonstrate a multi-targeted anti-angiogenic activity of T11TS which augments the potential for clinical translation of T11TS as an effective angiogenesis inhibitor for glioma treatment. Copyright © 2015 Elsevier Inc. All rights reserved.
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10.1016/j.yexmp.2015.03.026
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31200834
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MCL1 inhibition enhances the therapeutic effect of MEK inhibitors in KRAS-mutant lung adenocarcinoma cells.
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MCL1 is an anti-apoptotic BCL2 family member that is highly expressed in various malignant tumors. However, little is known about the role of MCL1 in KRAS-mutant lung adenocarcinomas. In this study, we aimed to clarify whether MCL1 could be a therapeutic target in KRAS-mutant lung adenocarcinomas for which no effective molecular targeted drugs are available. We examined to what extent MCL1 knockdown either alone or in combination with MEK inhibitor trametinib suppressed growth or induced apoptosis in the KRAS-mutant lung adenocarcinoma cell line H441 and EGFR-mutant lung adenocarcinoma cell line H1975. Furthermore, we investigated the therapeutic effects of dual inhibition of MCL1 and Bcl-xL, another anti-apoptotic BCL2 family member, in these two cell lines. MCL1 knockdown alone did not induce apoptosis in H441 or H1975 cells. However, MCL1-depleted H441 and H1975 cells underwent apoptosis and decreased in number in the presence of trametinib. We also confirmed that combined therapy by MCL1 knockdown and trametinib almost completely suppressed the growth of H441 cells in vivo. Moreover, dual knockdown of MCL1 and Bcl-xL induced extensive apoptosis in H441 and H1975 cells. These findings suggest that combined treatments of MCL1 knockdown and trametinib or dual inhibition of MCL1 and Bcl-xL would be effective therapies for lung adenocarcinomas including the KRAS-mutant subtype. Copyright © 2019 Elsevier B. V. All rights reserved.
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10.1016/j.lungcan.2019.05.014
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12687627
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Engineering a chemical implementation device and an imaging device for detecting chemiluminescence with a Polaroid high-speed detector film: application to influenza diagnostics with the ZstatFlu-II test.
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We describe the engineering and product development of the chemiluminescent ZstatFlu-II Test kit for influenza diagnostics. The reaction vessel is a chemical implementation device with a polystyrene bottom chamber and a polypropylene top chamber that screw together. The patient's specimen is dispersed in a proprietary diluent and mixed inside the bottom chamber with the influenza viral neuraminidase-specific substrate, 1,2-dioxetane-4,7-dimethoxy-Neu5Ac. Neuraminidase catalysis releases the dioxetane. The top chamber contains 40% NaOH and is sealed at the top with an ABS plastic plug-crush pin assembly. The top chamber floor is 85% thinner at the centre, forming a frangible flap. An automated imaging device serves as an incubator for the chemical implementation devices and also facilitates the piercing of the flap by the crush pin. This action results in NaOH flushing into the bottom chamber, initiating chemiluminescence. The imaging device also exposes the Polaroid high-speed detector film to chemiluminescence. At the end of exposure, the film is automatically processed and ejected. Chemiluminescence from an influenza virus-positive specimen produces a "+"-shaped white image, archiving the diagnostic outcome. The modular ZstatFlu-II test kit components are easily adaptable for the chemiluminescent detection of a wide range of analytes. Copyright 2003 John Wiley & Sons, Ltd.
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10.1002/bio.709
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34443018
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Anisotropic to Isotropic Transition in Monolayer Group-IV Tellurides.
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Monolayer group-IV tellurides with phosphorene-derived structures are attracting increasing research interest because of their unique properties. Here, we systematically studied the quasiparticle electronic and optical properties of two-dimensional group-IV tellurides (SiTe, GeTe, SnTe, PbTe) using the GW and Bethe-Salpeter equation method. The calculations revealed that all group-IV tellurides are indirect bandgap semiconductors except for monolayer PbTe with a direct gap of 1.742 eV, while all of them are predicted to have prominent carrier transport ability. We further found that the excitonic effect has a significant impact on the optical properties for monolayer group-IV tellurides, and the predicted exciton binding energy is up to 0.598 eV for SiTe. Interestingly, the physical properties of monolayer group-IV tellurides were subject to an increasingly isotropic trend: from SiTe to PbTe, the differences of the calculated quasiparticle band gap, optical gap, and further exciton binding energy along different directions tended to decrease. We demonstrated that these anisotropic electronic and optical properties originate from the structural anisotropy, which in turn is the result of Coulomb repulsion between non-bonding electron pairs. Our theoretical results provide a deeper understanding of the anisotropic properties of group-IV telluride monolayers.
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10.3390/ma14164495
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12465463
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HIV-2 and SIV vector systems.
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Lentiviral vectors have received much attention in recent years due to their ability to efficiently transduce non-dividing cells. Of the lentiviruses HIV-2 and SIV offer several unique benefits as the basis for lentiviral vector design. HIV-1, HIV-2 and SIV remain the only known primate lentiviruses, and consequently are among the most extensively studied viruses known. Substantial effort has been devoted towards identifying the pathogenic determinants of the primate lentiviruses and towards understanding their replication within primates. Of the primate lentiviruses, the pathogenicity and rates of transmission of HIV-2 and SIV fall far below that of HIV-1, potentially providing vectors based upon HIV-2/SIV with a greater degree of biosafety. Last, and perhaps most importantly, HIV-2 and SIV are viruses which may be studied within non-human primate models susceptible to AIDS-like disease, making vectors based upon these viruses accessible to substantial preclinical evaluation. We approach this Chapter presenting information regarding the basic biology of HIV-2 and SIV and conclude by pointing to how unique features of HIV-2 and SIV are well suited to vector design, hoping to leave the reader with a greater appreciation of the potential these viruses offer within the field of gene transfer applications.
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10.1023/a:1021026730034
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24795675
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Storybooks aren't just for fun: narrative and non-narrative picture books foster equal amounts of generic language during mother-toddler book sharing.
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Parents and children encounter a variety of animals and objects in the early picture books they share, but little is known about how the context in which these entities are presented influences talk about them. The present study investigated how the presence or absence of a visual narrative context influences mothers' tendency to refer to animals as individual characters or as members of a kind when sharing picture books with their toddlers (mean age 21.3 months). Mother-child dyads shared both a narrative and a non-narrative book, each featuring six animals and matched in terms of length and quantity of text. Mothers made more specific (individual-referring) statements about animals in the narrative books, whereas they provided more labels for animals in the non-narrative books. But, of most interest, the frequency and proportion of mothers' use of generic (kind-referring) utterances did not differ across the two different types of books. Further coding of the content of the utterances revealed that mothers provided more story-specific descriptions of states and actions of the animals when sharing narrative books and more physical descriptions of animals when sharing non-narrative books. However, the two books did not differ in terms of their elicitation of natural facts about the animals. Overall, although the two types of books encouraged different types of talk from mothers, they stimulated generic language and talk about natural facts to an equal degree. Implications for learning from picture storybooks and book genre selection in classrooms and home reading are discussed.
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10.3389/fpsyg.2014.00325
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11370340
|
Early teenage marriage and subsequent pregnancy outcome.
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The relationship between marriage before 16 years and pregnancy outcome throughout the childbearing period was examined. Participants included all married women attending six randomly selected primary health care units in Jeddah with at least one infant and complete medical files. Early teenage marriage was found for 27.2% of women. Most of these were illiterate (57.1%), housewives (92.4%) and grand multiparae (66.7%). They were at twice the risk of spontaneous abortion, four times the risk of combined fetal death and infant mortality, and twice the risk of losing pregnancies any time during their childbearing years. They remained at high risk of poor pregnancy outcome throughout their reproductive lives. Despite tradition, marriage should be discouraged before 16 years.
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36723397
|
Diagnostic Value of Artificial Intelligence-Assistant Diagnostic System Combined With Contrast-Enhanced Ultrasound in Thyroid TI-RADS 4 Nodules.
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This study evaluated the diagnostic value of artificial intelligence-assistant diagnostic system combined with contrast-enhanced ultrasound in The American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) 4 category thyroid nodules. Thyroid nodules that were evaluated as ACR TI-RADS 4 by conventional ultrasound were selected, all of which had pathological or fine needle aspiration (FNA) results. All nodules were examined by contrast-enhanced ultrasound (CEUS) and artificial intelligence (AI) analysis. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of AI, CEUS and their combined diagnosis were compared; Analyzed and compared the diagnostic efficiency of AI, CEUS and their combined diagnosis. A total of 148 thyroid nodules were included in 140 patients, including 58 malignant nodules and 89 benign nodules. The sensitivity of combined diagnosis was significantly higher than that of AI or CEUS alone (P.05), but there was a significant difference in NPV between AI and combined diagnosis (P <.05). The AUC of the combined diagnosis was 0.859, which was higher than that of AI, CEUS alone. AI has a high diagnostic efficiency, which was helpful for radiologists to make rapid assessment. AI combined CEUS can significantly improve the diagnostic sensitivity and NPV, which was beneficial for the early detection of malignant nodules. © 2023 American Institute of Ultrasound in Medicine.
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10.1002/jum.16170
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8840134
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Different characteristics of AMPA receptor agonists acting at AMPA receptors expressed in Xenopus oocytes.
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A series of (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) analogues were evaluated for activity at homo-oligomeric glutamate1-flop (Glu1-flop) receptors expressed in Xenopus oocytes, using the two-electrode voltage clamp technique. (RS)-2-Amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) (EC50, 2.4 microM), a homologue of AMPA having a carboxyl group as the terminal acidic functionality, was five times more potent than AMPA (EC50, 12 microM) and 20 times more potent than kainate (EC50, 46 microM). (RS)-2-Amino-3(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid (Tri-F-AMPA), in which an electronegative trifluoromethyl group is substituted for the methyl group on the isoxazole ring in the AMPA structure, was three times more potent than AMPA, whereas (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-5-carboxylic acid (5-HPCA), a bicyclic analogue of AMPA with highly restricted conformational flexibility was 10 times less potent than AMPA. The limiting slope of log-log plots of Glu1-flop receptor currents versus low agonist concentrations had a value of 1.7 for ACPA and kainate compared to 1.5 for Tri-F-AMPA and 1.3 for 5-HPCA and AMPA. The amplitude of responses evoked by near saturating concentrations of the agonists varied more than 7-fold. The sequence of efficacy was ACPA = kainate > Tri-F-AMPA > AMPA > 5-HPCA. Moreover, when saturating concentrations of Tri-F-AMPA and kainate were co-applied, the response was significantly greater than when each of the agonists was applied separately. The potency of the antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX) (estimated KB, approximately 200 nM), to block currents mediated by Glu1-flop receptors was similar for all of the agonists tested in this study. These results indicate that relatively minor changes in the molecular structure of AMPA are associated with marked effects on potency and efficacy. In particular, it is suggested that the acidity of the terminal group plays a major role in determining the degree of receptor activation in the steady state.
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10.1016/0014-2999(96)00292-0
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21743838
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FHIT gene expression is repressed by mitogenic signaling through the PI3K/AKT/FOXO pathway.
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The Fragile Histidine Triad gene or FHIT functions as tumor suppressor in many epithelial cell types. Although its tumor suppressive mechanism is the subject of intense study, less is known about how FHIT gene expression itself is regulated. Here we show that PI3 kinase and its downstream target AKT suppress FHIT gene expression in response to growth factor stimulation in actively cycling cells. Upon removal of mitogens from the culture environment, FHIT mRNA and protein levels are observed to increase as a result of derepression from these protooncogenic kinases. AKT signaling through the FOXO transcription factors appears to be the basis for FHIT gene regulation. Increases in FHIT gene expression are directly dependent on endogenous FOXO3a in MCF7 breast carcinoma cells as evidenced by experiments with RNAi targeting FOXO transcription factor family members. Thus, this is the first report demonstrating that FHIT gene expression is normally repressed in actively cycling cells through the PI3K/AKT/FOXO3a axis.
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25337109
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(1)H magnetic resonance spectroscopy and diffusion weighted imaging findings of medulloblastoma in 3.0T MRI: A retrospective analysis of 17 cases.
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(1)H magnetic resonance spectroscopy and diffusion weighted imaging features of the cerebellar vermis in 17 medulloblastoma patients were retrospectively analyzed, and 17 healthy volunteers were selected as controls. (1)H magnetic resonance spectroscopy showed that in all 17 medulloblastoma patients, N-acetyl aspartate and creatine peaks were significantly decreased, the choline peak was significantly increased, and there was evidence of a myo-inositol peak. Further, 11 patients showed a low taurine peak at 3.4 ppm, five patients showed a lipid peak at 0.9-1.3 ppm, and three patients showed a negative lactic acid peak at 1.33 ppm. Compared with the control group, the ratios of N-acetyl aspartate/choline and N-acetyl aspartate/creatine were significantly decreased, and the ratio of choline/creatine was increased, in medulloblastoma patients. Diffusion weighted imaging displayed hyperintensity and decreased apparent diffusion coefficient in medulloblastoma patients. These findings indicate that (1)H magnetic resonance spectroscopy and diffusion weighted imaging are useful for qualitative diagnosis of medulloblastoma.
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10.3969/j.issn.1673-5374.2012.32.011
|
2378654
|
[Coincidence of chronic inflammatory paranasal sinus disorders and cochleo-vestibular disorders].
|
In the course of initial examination the authors frequently observed a coincidence of labyrinthine symptoms with radiologic signs of chronic sinusitis. Of 72 patients who were hospitalized for acute labyrinthine symptoms, 72% presented with these signs. On the other hand, 49% of the patients admitted to sinus surgery manifested labyrinthine symptoms. A well-pneumatized mastoid was found in both groups. In the control group, consisting of patients whose consultation was unconnected to ear or nose complaints, chronic sinusitis was found in 28% and labyrinthine symptoms in 24%, but the two together were only found in 11%. It was shown by means of the chi2 test that the two symptom complexes are interdependent (p less than 0.01). Histologic examination of the mucosa of paranasal sinuses and peri-labyrinthine cells does not at the moment provide a satisfactory explanation. Pathologic autonomic nerve connections between the two systems may lead to higher vulnerability of the labyrinths of patients with chronic sinusitis. Other possible explanations, i. e., relating to certain neuropeptides and a well-pneumatized mastoid, are discussed. The authors wish to emphasize that their study is based on clinical data. At the moment a satisfactory pathophysiological explanation is lacking. In addition to antiphlogistic and rheologic medication, long-term planning of sinus surgery should be recommended for all patients in whom the two symptoms occur simultaneously. Whether this can help prevent recurrences, or put an end to progressive processes, can only be determined after a longer observation period.
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10.1055/s-2007-998194
|
30122851
|
Choroidal Melanoma Resection.
|
Uveal melanoma is the most common intraocular malignant tumor, with the choroid being the most common site. Management of choroidal melanoma has evolved greatly over the past years. In the past, the conventional method of treatment was enucleation of the affected eye with a debate regarding the effect of enucleation to promote or prevent metastasis. However, nowadays, there are many therapeutic options available including plaque radiotherapy, proton beam radiotherapy, argon laser photocoagulation, transpupillary thermotherapy, stereotactic radiotherapy using gamma knife, enucleation, and surgical resection of the tumor whether through transscleral approach "Exoresection" or less commonly through internal resection approach "Endoresection." The indications and complications of each technique are reviewed. Although radiotherapy is the primary treatment of choroidal melanoma in most ocular oncology centers, it is used as an adjuvant therapy in combination with surgical resection. Preoperative stereotactic radiotherapy before endoresection and brachytherapy to the surgical bed in both exo and endoresection can effectively decrease the recurrence rate. In this article, we will focus on surgical resection of choroidal melanoma whether endoresection or exoresection. We collected data published in indexed journals and related books.
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10.4103/meajo.MEAJO_73_18
|
29446017
|
Transformation of heavy metal fractionation under changing environments: a case study of a drainage system in an e-waste dismantling community.
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The change in environmental conditions during the transportation of contaminated soil and sediment was expected to affect the transformation of heavy metal fractionation. This study disclosed the serious contamination of copper (Cu), lead (Pb), and zinc (Zn) in the sewer sediment of an e-waste dismantling community in Thailand which may be caused by flushed contaminated soil and e-waste fragments. Two environmental conditions were simulated to observe the transformation of heavy metal fractionation. The anoxic sewer condition was induced using high substrate and sulfate in a closed container. The aeration of anoxic contaminated sediment was applied to simulate the transformation to an oxidative environment. The BCR sequential extraction was applied for heavy metal fractionation in this study. The study results exhibited that when heavy metal contaminated soil was transferred into this induced anoxic condition, fractionation was redistributed based on the chemical change of system that tends to be associated into F3 (oxidizable fraction) > F2 (reducible fraction) > F1 (acid soluble/exchangeable fraction). Cu exhibited the outstanding capability association to F3. The iron sulfide was not observed as usual due to its lower capability than Cu, Pb, and Zn. When contaminated sediment was transported to a more oxidative environment, the heavy metals fractionation would be redistributed again among those new environment media. It is noteworthy that F3 of Cu was stable even in oxic conditions. F2 of Fe was not developed by this oxic condition, possibly because its dehydration process was limited. The redistribution under an oxic environment became F1 > F2 > F3 indicating their more available form. This transformation was imperative and should be taken into account in heavy metal contaminated site management and control.
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10.1007/s11356-018-1495-3
|
23487367
|
Markers of intestinal inflammation, not bacterial burden, correlate with clinical outcomes in Clostridium difficile infection.
|
Clostridium difficile is a leading hospital-acquired infection. Many patients remain symptomatic for several days on appropriate antibiotic therapy. To assess the contribution of ongoing infection vs persistent inflammation, we examined the correlation between fecal cytokine levels, fecal C. difficile burden, and disease outcomes in C. difficile infection (CDI). We conducted a prospective cohort study in Barnes Jewish Hospital between June 2011 and May 2012 of hospitalized adults with CDI. We determined fecal interleukin 8 (IL-8) and lactoferrin protein concentrations by enzyme immunoassay. We used real-time polymerase chain reaction (PCR) to measure relative fecal IL-8 and CXCL-5 RNA transcript abundances, and quantitative PCR to enumerate C. difficile burden. Of 120 study subjects, 101 (84%) were started on metronidazole, and 33 of those (33%) were subsequently given vancomycin. Sixty-two (52%) patients had diarrhea persistent for 5 or more days after starting CDI therapy. Initial fecal CXCL-5 messenger RNA (mRNA), IL-8 mRNA, and IL-8 protein correlated with persistent diarrhea and use of vancomycin. Time to diarrhea resolution was longer in patients with elevated fecal cytokines at diagnosis. Fecal cytokines were more sensitive than clinical severity scores in identifying patients at risk of treatment failure. Clostridium difficile burden did not correlate with any measure of illness or outcome at any point, and decreased equally with metronidazole and vancomycin. Persistent diarrhea in CDI correlates with intestinal inflammation and not fecal pathogen burden. These findings suggest that modulation of host response, rather than adjustments to antimicrobial regimens, might be a more effective approach to patients with unremitting disease.
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10.1093/cid/cit147
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36158156
|
Personalizing treatment in end-stage kidney disease: deciding between haemodiafiltration and haemodialysis based on individualized treatment effect prediction.
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Previous studies suggest that haemodiafiltration reduces mortality compared with haemodialysis in patients with end-stage kidney disease (ESKD), but the controversy surrounding its benefits remains and it is unclear to what extent individual patients benefit from haemodiafiltration. This study is aimed to develop and validate a treatment effect prediction model to determine which patients would benefit most from haemodiafiltration compared with haemodialysis in terms of all-cause mortality. Individual participant data from four randomized controlled trials comparing haemodiafiltration with haemodialysis on mortality were used to derive a Royston-Parmar model for the prediction of absolute treatment effect of haemodiafiltration based on pre-specified patient and disease characteristics. Validation of the model was performed using internal-external cross validation. The median predicted survival benefit was 44 (Q1-Q3: 44-46) days for every year of treatment with haemodiafiltration compared with haemodialysis. The median survival benefit with haemodiafiltration ranged from 2 to 48 months. Patients who benefitted most from haemodiafiltration were younger, less likely to have diabetes or a cardiovascular history and had higher serum creatinine and albumin levels. Internal-external cross validation showed adequate discrimination and calibration. Although overall mortality is reduced by haemodiafiltration compared with haemodialysis in ESKD patients, the absolute survival benefit can vary greatly between individuals. Our results indicate that the effects of haemodiafiltration on survival can be predicted using a combination of readily available patient and disease characteristics, which could guide shared decision-making. © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.
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10.1093/ckj/sfac153
|
36328966
|
Edge Detection Method Based on Nonlinear Spiking Neural Systems.
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Nonlinear spiking neural P (NSNP) systems are a class of neural-like computational models inspired from the nonlinear mechanism of spiking neurons. NSNP systems have a distinguishing feature: nonlinear spiking mechanism. To handle edge detection of images, this paper proposes a variant, nonlinear spiking neural P (NSNP) systems with two outputs (TO), termed as NSNP-TO systems. Based on NSNP-TO system, an edge detection framework is developed, termed as ED-NSNP detector. The detection ability of ED-NSNP detector relies on two convolutional kernels. To obtain good detection performance, particle swarm optimization (PSO) is used to optimize the parameters of the two convolutional kernels. The proposed ED-NSNP detector is evaluated on several open benchmark images and compared with seven baseline edge detection methods. The comparison results indicate the availability and effectiveness of the proposed ED-NSNP detector.
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10.1142/S0129065722500605
|
22031784
|
Dietary supplementation with vitamin E and C attenuates dexamethasone-induced glucose intolerance in rats.
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Glucocorticoid excess induces marked insulin resistance and glucose intolerance. A recent study has shown that antioxidants prevent dexamethasone (DEX)-induced insulin resistance in cultured adipocytes. The purpose of this investigation was to examine the effects of dietary vitamin E and C (Vit E/C) supplementation on DEX-induced glucose intolerance in rats. We hypothesized that feeding rats a diet supplemented with Vit E/C would improve glucose tolerance and restore insulin signaling in skeletal muscle, adipose, and liver and prevent alterations in AMPK signaling in these tissues. Male Wistar rats received either a control or Vit E/C-supplemented diet (0.5 g/kg diet each of L-ascorbate and DL-all rac-alpha-tocopherol) for 9 days prior to, and during, 5 days of daily DEX treatment (subcutaneous injections 0.8 mg/g body wt). DEX treatment resulted in increases in the glucose and insulin area under the curve (AUC) during an intraperitoneal glucose tolerance test. The glucose, but not insulin, AUC was lowered with Vit E/C supplementation. Improvements in glucose tolerance occurred independent of a restoration of PKB phosphorylation in tissues of rats stimulated with an intraperitoneal injection of insulin but were associated with increases in AMPK signaling in muscle and reductions in AMPK signaling and the expression of fatty acid oxidation enzymes in liver. There were no differences in mitochondrial enzymes in triceps muscles between groups. This study is the first to report that dietary Vit E/C supplementation can partially prevent DEX-induced glucose intolerance in rats.
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10.1152/ajpregu.00304.2011
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23964768
|
Ernest L. Mazzaferri, MD, MACP (1936-2013).
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Professor and physician Dr. Ernest L. Mazzaferri Sr. passed away on May 14, 2013, at 76 years of age ( 1, 2 ). Ernie is remembered as a caring and talented physician, an accomplished scholar and educator, as well as a loving husband, father, and grandfather. He was a luminary figure, and few people have had a greater impact in thyroidology in recent decades. Here we include reflections from a few of us that knew him, as well as commentaries from people who did not. Ernie's passion was caring for patients and how to improve their care. Our goal is to pay tribute and memorialize the person we knew and the impact that he had on patients around the world through his dedication to research, lecturing, and writing that achieved remarkable global influence.
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10.1089/thy.2013.2308.ob
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36301973
|
Medical student wellness assessment beyond anxiety and depression: A scoping review.
|
A significant increase in distress and mental health illnesses has been identified in medical students during their training. As a result, medical schools have attempted to understand factors linked to well-being. Wellness questionnaires present a useful approach to identifying students with risk factors for mental health to provide appropriate resources for support and referrals. This study aims to identify validated questionnaires in the literature that measure medical student wellness. A scoping review methodology was selected and an exhaustive search of MEDLINE, Embase, CINAHL, APA PsycInfo, EPIC, and Education Source, was performed from 1999 to May 27, 2021. A compilation of validated wellness evaluation tools, surveys and questionnaires assessing wellness beyond depression and anxiety was reviewed. All validated methods of wellness assessment for medical students were included. 5,001 studies were identified once duplicate records were removed. After applying inclusion and exclusion criteria, 23 articles were included in a qualitative synthesis and explored in detail. The following six validated questionnaires measuring the wellness of medical school students are reported and discussed: the Medical Student Stress Profile (MSSP), the Medical Student Stress Questionnaire (MSSQ), the Medical Student Well-Being Index (MSWBI), the Perceived Medical School Stress (PMSS), the Perceived Stress Scale for Medical Students (PSSMS), and the Oldenburg Burnout Inventory-Medical Student Version (OLBI-MS). These validated questionnaires provide various aspects to the assessment of wellbeing. Wellbeing evaluations are reliable in identifying medical students who are at risk for mental health illnesses but must be chosen carefully based on contexts, academic environment and student population. A direct comparison between validated questionnaires for student wellbeing is not possible and individual medical schools must determine the appropriateness and validity of such tools based on population-specific characteristics and demands.
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10.1371/journal.pone.0276894
|
33137324
|
P-glycoprotein deficiency enhances metabolic activation of and platelet response to clopidogrel through marked up-regulation of Cyp3a11 in mice: Direct evidence for the interplay between P-glycoprotein and Cyp3a.
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Variability in P-glycoprotein (P-gp) efflux transporting activity was supposed to be involved in altered intestinal absorption and bioavailability of clopidogrel in patients; however, reliable evidence is still lacking. In this study, we sought to determine whether P-gp could play an important role in the metabolic activation of and platelet response to clopidogrel in mice. Abcb1a/1b knock-out (KO) and wild-type (WT) mice were used to evaluate differences in the intracellular accumulation of clopidogrel in the intestine, liver, and brain tissues and in systemic exposure of clopidogrel and its main metabolites as well as the mechanisms involved. Results indicated that, compared with WT mice, KO mice exhibited an 84% increase in systemic exposure of clopidogrel active thiol metabolite H4 and a 14.5% rise of suppression of ADP-induced platelet integrin αIIbβ3 activation, paralleled by a 41% decrease in systemic exposure of clopidogrel due to enhanced systemic clearance. Furthermore, KO mice displayed a 45% increase in Cyp3a11 but a 23% decrease in Ces1 at their protein levels compared with WT mice. Concurrently, intracellular clopidogrel concentrations in the tissues examined did not differ significantly between KO and WT mice. We conclude that although P-gp does not transport clopidogrel and its major metabolites in mice, P-gp-deficient mice exhibit elevated formation of the active metabolite H4 and enhanced antiplatelet effect of clopidogrel through up-regulation of Cyp3a11 and down-regulation of Ces1, suggesting that P-gp activity may correlate inversely with the formation of H4 and antiplatelet efficacy of clopidogrel in clinical settings due to P-gp and CYP3A4 interplay. Copyright © 2020 Elsevier Inc. All rights reserved.
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10.1016/j.bcp.2020.114313
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8271038
|
Magnetically enhanced radionuclide therapy.
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Radiopharmaceutical therapy is an increasingly common treatment for cancer. This therapy involves the injection of radiolabeled tumor-specific agents into the patient with subsequent preferential accumulation in the tumor sites. Particulate radiation (usually beta particles) emitted by the radioisotope kill or damage the tumor cells. The effectiveness of radiopharmaceutical therapy, however, is limited by the size of the tumor treated. Energetic particles can easily exist small tumors before they are able to deposit their energy and inflict significant damage. We propose the use of a static magnetic field to be applied after the radiopharmaceutical has localized in the tumors, constraining these particles to helical paths. This application would result in substantially confining the emitted particles within the tumor's boundaries, thus increasing radiation dose to the tumor. Computer simulations of radionuclide treatments using 131I, 186Re and 90Y show that a magnetic field of 10 Tesla can increase the radiation dose achieved by conventional radionuclide therapy by up to 71%. In addition, total radiation dose to surrounding normal tissues is substantially reduced. Magnetically enhanced radionuclide therapy (MERiT) therefore shows promise as an effective treatment of cancer and warrants further study.
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27416439
|
Unions asked to take co-operative approach.
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A call for unions to take a co-operative and constructive approach towards competitive tendering has been made by Scottish Health Minister Michael Forsyth.
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10.7748/ns.2.34.43.s70
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27853648
|
Endothelial progenitor cell number and ERK phosphorylation serve as predictive and prognostic biomarkers in advanced hepatocellular carcinoma patients treated with sorafenib.
|
Sorafenib is an oral anti-angiogenic multi-kinase inhibitor used for systemic therapy in patients with advanced hepatocellular carcinoma (HCC) who are not suitable candidates for surgery or liver transplantation. An earlier study conducted with HCC tumor tissue suggested that ERK phosphorylation (pERK), a downstream target of sorafenib, may serve as a potential biomarker for therapeutic efficacy of sorafenib. However, no study thus far has utilized a minimal invasive procedure to predict HCC patient responsiveness to sorafenib. We evaluated the biomarker utility of circulating endothelial progenitor cells (EPCs) frequency and intracellular pERK levels in EPCs in peripheral blood obtained pre- and post-sorafenib therapy or after transarterial chemoembolistaion (TACE). A statistically significant reduction in the level of ERK phosphorylation and in the absolute number of EPCs was detected following in vivo sorafenib treatment ( p < 0.01 for both). In contrast, the decrease in the level of ERK phosphorylation and EPC number was either marginally significant or insignificant in patients treated with TACE ( p = 0.05 and 0.06, respectively). In vitro sorafenib treatment of pre- and post-samples from the same patient cohort inhibited ERK phosphorylation levels in EPCs and decreased the number of EPCs at all doses tested ( p = 0.01). Our findings support that the evaluation of both the circulating EPC frequency and the level of ERK phosphorylation in EPCs may serve as potential non-invasive biomarkers of sorafenib efficacy, both as predictor of treatment outcome and efficacy during drug treatment.
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10.1080/2162402X.2016.1226718
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8917816
|
Facilitation of luminance grating detection by induced gratings.
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Grating induction causes a homogeneous test field surrounded by sinewave gratings to possess an induced counterphase grating [McCourt M. E. (1982). Vision Research, 22, 119]. There is currently no consensus about the stage of visual processing at which illusory phenomena such as simultaneous brightness contrast are signaled. We measured the masking efficacy of induced gratings by measuring contrast detection thresholds for targets (sinewave luminance gratings) added in phase to both real and induced gratings which were matched in apparent contrast. At spatial frequencies below c. 0.5 c/deg, target detection and discrimination were comparably facilitated by both real and induced low-contrast pedestals (0.5-2%). At higher spatial frequencies (above 1.0 c/deg) facilitation continued to be observed for targets added in-phase to real grating pedestals, but occurred only for targets added out-of-phase with induced pedestal gratings. Higher inducing frequencies by themselves were not responsible for the observed phase shift of facilitation, however, since both real and induced pedestals produced similar target contrast discrimination functions when inducing frequency was varied by manipulating viewing distance (which holds the ratio of inducing grating period and test field height constant). The results imply the existence of at least two types of lateral interactive processes: one producing in-phase facilitation, and a second producing out-of-phase facilitation. The relative contribution of each process depends upon the ratio of inducing grating period and test field height.
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10.1016/0042-6989(95)00244-8
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33142655
|
Textile dyes loaded chitosan nanoparticles: Characterization, biocompatibility and staining capacity.
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Textile dyeing is a hazardous and toxic process. While traditionally it has been managed through effluent treatment, new approaches focused upon improving the dyeing process are gaining relevance. In this work, we sought to obtain, for the first time, an eco-friendly chitosan-nanoparticle based textile dyeing method. To that end, yellow everzol and navy blue itosperse loaded chitosan nanoparticles were produced and their capacity to dye textiles and cytotoxicity towards human skin cells were evaluated. The results obtained showed that it was possible to obtain nanoencapsulated dyes through ionic gelation with an average entrapment efficacy above 90 %. Nanoparticles presented a positive surface charge and sizes between 190 and 800 nm with yellow everzol NPs occurring via ionic interactions while navy blue itosperse NPs were formed through hydrogen bonds. Furthermore, the produced dye NPs presented no cytotoxicity towards HaCat cells and presented staining percentages reaching 17.60 % for a viscose/wool blend. Copyright © 2020 Elsevier Ltd. All rights reserved.
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10.1016/j.carbpol.2020.117120
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35148575
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Intralesional Epidermal Growth Factor for Diabetic Foot Ulcers.
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To determine the role of the intralesional recombinant epidermal growth factor (rEGF) in the healing and prevention of extremity amputation in advanced diabetic foot ulcer patients. Observational study. Department of Cardiovascular Surgery, Duzce State Hospital, Duzce, Turkey, between November 2018 and September 2019. A total of 58 patients with diabetic foot ulcers that were treated at the study place were enrolled. The lesions were graded with Wagner Classification System. EGF (75 microg of Heberprot-P) vials were stored at +4°C and cold-chain requirements were followed. EGF 5 mL was dissolved with 0.09% saline solution; and 0.5-1 ml of the solution was injected into the tissues and edge of the lesions regularly. The data was evaluated at the end of two years of the treatment period. The primary objective was wound healing, formation of granulation tissue; and the secondary objective was the prevention of lower extremity amputation. Diabetic foot ulcers wound healing was achieved in 93.1% (n=54) of patients with the formation of granulation tissue. The complete recovery was observed in 94.1% (n=32) of the patients who had Grade III and IV lesions. Lower extremity amputation was performed in two (3.4%) subjects. The lesions of two patients required flap surgery. The most common adverse events were tremor and syncope. Recombinant epidermal growth factor is highly effective for the treatment of diabetic foot ulcers and prevention of extremity amputation. Intralesional rEGf provides efficient and safe wound healing/closure in patients with diabetic foot ulcers. Key Words: Amputation, Epidermal growth factor, Diabetic foot, Wound healing.
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10.29271/jcpsp.2022.03.278
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17137905
|
Pioglitazone as adjunctive therapy in adolescents with type 1 diabetes.
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To determine whether the addition of the thiazoladinedione, pioglitazone, to standard therapy improves metabolic control in adolescents with type 1 diabetes (T1D) and clinical evidence of insulin resistance. Randomized, placebo-controlled 6-month 2-site trial of pioglitazone therapy in 35 adolescents with T1D, high insulin requirements (>0.9 U/kg/d), and suboptimal metabolic control (A1c 7.5%-11%), with the primary outcome of change in A1c. Secondary outcomes include change in insulin dose, body mass index (BMI), lipids, and waist and hip circumference. Metabolic control (A1c) was improved at 6 months in all subjects (P =.02). There was no significant difference between the pioglitazone and placebo treatment groups at 6 months in either change in A1c (-0.4% +/- 0.9% and -0.5% +/- 1.2%, respectively) or insulin dose. BMI SDS increased by 0.3 +/- 0.3 (kg/m(2)) in the pioglitazone group and remained unchanged in the placebo group (P =.01). There was no significant difference in change in any lipid parameters between the pioglitazone and placebo groups at 6 months. Adjunctive pioglitazone therapy was not effective in improving glycemic control in adolescents with T1D. Pioglitazone was associated with increased BMI.
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10.1016/j.jpeds.2006.08.049
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1911678
|
Plasma-cell tumours of the condyle.
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Plasma cell tumours are a group of disorders which are characterized by neoplastic proliferation of atypical plasma cells involved in the production of monoclonal immunoglobulins. Bone pain, renal insufficiency and normocytic-normochromic anaemia are suggestive data for diagnosis. In 12-15% of cases of multiple myeloma, the first manifestation of the disease appears in the jaw bones and oral cavity. Two cases of multiple myeloma affecting the mandibular condyle are presented, and the incidence of oral and maxillofacial lesions is briefly reviewed.
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10.1016/0266-4356(91)90197-d
|
30978237
|
Dental pulp exposure, periapical inflammation and suppurative osteomyelitis of the jaws in juvenile Baltic grey seals (Halichoerus grypus grypus) from the late 19th century.
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The systematic analysis of museum collections can provide important insights into the dental and skeletal pathology of wild mammals. Here we present a previously unreported type of dental defect and related skull pathology in five juvenile Baltic grey seals that had been collected in the course of a seal culling program along the Danish coast in 1889 and 1890. All five skulls exhibited openings into the pulp cavities at the crown tips of all (four animals) or two (one animal) canines as well as several incisors and (in one animal) also some anterior premolars. The affected teeth showed wide pulp cavities and thin dentin. Pulp exposure had caused infection, inflammation, and finally necrosis of the pulp. As was evidenced by the extensive radiolucency around the roots of the affected teeth, the inflammation had extended from the pulp into the periapical space, leading to apical periodontitis with extensive bone resorption. Further spreading of the inflammation into the surrounding bone regions had then caused suppurative osteomyelitis of the jaws. The postcanine teeth of the pathological individuals typically had dentin of normal thickness and, except for one specimen, did not exhibit pulp exposure. The condition may have been caused by a late onset of secondary and tertiary dentin formation that led to pulp exposure in anterior teeth exposed to intense wear. Future investigations could address a possible genetic causation of the condition in the studied grey seals.
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10.1371/journal.pone.0215401
|
32884098
|
Meta-analysis of controlled trials testing horticultural therapy for the improvement of cognitive function.
|
Improving cognitive function is one of the most challenging global issues in cognitive impairment population. Horticultural therapy involves the expertise of a horticultural therapist who establishes a treatment plan for horticultural activities that aim to achieve cognitive changes, and thereby improve health-related quality of life. However, more convincing evidence demonstrating the effect of horticultural therapy on cognitive function is essential. The purpose of this study was to conduct a meta-analysis of controlled trials testing the effect of horticultural therapy on cognitive function and the findings indicate that horticultural therapy programs significantly improved cognitive function. The effect size of the horticultural therapy program was large. Findings of this meta-analysis have important implications for practice and policies. Contemporary healthcare systems should consider horticultural therapy as an important intervention for improving patients' cognitive function. Governments and policy-makers should consider horticultural therapy as an important tool to prevent the decline of cognitive function in cognitive impairment population.
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10.1038/s41598-020-71621-7
|
29177718
|
Unprecedented homotopy perturbation method for solving nonlinear equations in the enzymatic reaction of glucose in a spherical matrix.
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The theory of glucose-responsive composite membranes for the planar diffusion and reaction process is extended to a microsphere membrane. The theoretical model of glucose oxidation and hydrogen peroxide production in the chitosan-aliginate microsphere has been discussed in this manuscript for the first time. We have successfully reported an analytical derived methodology utilizing homotopy perturbation to perform the numerical simulation. The influence and sensitive analysis of various parameters on the concentrations of gluconic acid and hydrogen peroxide are also discussed. The theoretical results enable to predict and optimize the performance of enzyme kinetics.
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10.1007/s00449-017-1865-0
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28553395
|
Retrograde Partial Migration of Ventriculoperitoneal Shunt with Chamber: Review of Causative Factors and Its Prevention.
|
Distal migration of shunt is a very common occurrence. Proximal migration of shunt is rare and possible pathophysiological mechanisms to explain this unusual complication is rarely attempted. A 5-month-old child shunted for posttraumatic hydrocephalus presented 1.5 years later with raised intracranial pressure and seizures. Imaging showed subdural hygroma, partial intracranial migration of shunt/chamber. On endoscopy, choroid plexus was adherent to shunt tip and some pericranial tissue was found in the anchoring suture (intraventricularly displaced). Shunt was retrieved endoscopically and diversion established by endoscopic third ventriculostomy with symptoms free follow-up. Host-related and surgical factors have been postulated. Tug-of-war effect on the anchoring suture and collapsing cortex are the possible mechanisms that explain proximal migration in our case. Three-point fixation of the chamber to pericranium, small burr hole with a smaller durotomy, can prevent shunt migration. Proximal shunt migrations should be dealt with endoscopy so as to avoid complications.
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10.4103/1817-1745.205654
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7441568
|
[Conversion of erucic acid in subcellular fractions from liver, kidneys and heart of rat, 8 min after intravenous injection (author's transl)].
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Rats were intravenously injected with albumin-bound [14 14C] erucic acid, and after 8 min the 14C radioactivity (RA) of the fatty acids were studied in mitochondria, microsomes and other fractions of liver, kidneys and heart cells. 1. In liver, which contained 15% of the injected RA, oleic acid (18: 1) was the main fatty acid (FA) formed (26% of the 14C recovered) whereas in kidneys (0,53% of the injected RA) the proportion of nervonic acid (24: 1) was higher (20%) than that of 18: 1 (14%). No appreciable transformation was encountered in heart, which contained 0,53% of the injected RA. 2. In liver, the microsomes showed the higher converted 14C RA (45%), mainly as 18: 1 (33%), much higher than in mitochondria (11%), whereas the amount of total 14C FA was a little higher in the latter fraction. 3. In kidneys, the mitochondrial and microsomal fractions contained the same percentage of 14C oleic acid (15%), whereas nervonic acid was recovered in higher proportion, 29 and 20%, in microsomes and in mitochondria respectively. 4. Results show that the same kind of metabolic activity, i. e., shortening or elongation, was observed in the whole cell as that previously shown with isolated fractions. However, mitochondrial oxidation and exchanges of transformed fatty acids between organelles can modify the extent of the phenomenon.
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21284832
|
Detection of dengue-4 virus in pune, western india after an absence of 30 years--its association with two severe cases.
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Difference in severity of dengue outbreaks has been related to virus serotype, genotype and clades within genotypes. Till the 1980 s, India and Sri Lanka reported low number of dengue hemorrhagic fever (DHF) cases despite circulation of all four serotypes of dengue virus (DENV). Since the 1990 s the occurrence of DHF has increased. The increase has been attributed to changes in virus lineage especially with regard to DENV-2 and DENV-3. DENV-1 has been associated with dengue fever (DF) outbreaks and DENV-4 reports have been rare. The emergence of DENV-4 was reported recently in 2003 in Delhi and in 2007 in Hyderabad. The last report of DENV-4 from Maharashtra was in 1975 from Amalner. We report on the detection of DENV-4 in Pune, Maharashtra after an absence of almost 30 years. Two cases were detected in 2009-10, serotyped by multiplex reverse transcriptase polymerase chain reaction (RT-PCR). Both the cases were recorded as severe dengue (Category 3) requiring intensive care unit (ICU) level of treatment. Depending on the hemagglutination inhibiting (HI) antibody titres the 2009 case was characterized as a primary infection and the 2010 case as a secondary infection. Both the cases presented plasma leakage and neither showed any kind of haemorrhage. The 2009 case survived while the 2010 case was fatal. An isolate was obtained from the 2009 case. Based on envelope (E) gene sequence analysis, the virus belonged to genotype I of DENV-4, and clustered with isolates from India and Sri Lanka and was distant from the isolates from Thailand. The nucleotide and amino acid diversity of the E gene of the Indian isolates increased from 1996 to 2007 to 2009 in context of the E gene sequences of other isolates belonging to genotype I. The increasing diversity in the circulating DENV-4 calls for close monitoring of the DENV-4 serotype.
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10.1186/1743-422X-8-46
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2332502
|
CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity.
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CAP37, an antimicrobial protein of human neutrophil granules, is a specific chemoattractant for monocytes. Purified to homogeneity by sequential chromatography over carboxymethyl Sephadex, G-75 Sephadex, and hydrophobic interaction HPLC, demonstratively endotoxin-free CAP37 was maximally chemotactic over a range of 1.3 X 10(-9)-10(-8) M. Thus it was active in the same molar concentrations as formyl-methionyl-leucyl-phenylalanine. CAP37 lacked chemotactic activity for neutrophils and lymphocytes. In checkerboard assays CAP37 had some chemokinetic activity as well. It was also chemotactic for rabbit mononuclear cells. Higher concentrations (2.7 X 10(-8) M) were required for activity with rabbit cells than with human. Sequence analysis of the first 42 NH2-terminal amino acid residues of CAP37 showed strong homologies with known serine proteases that mediate various functions in inflammation. However, a critical substitution of a serine for a histidine at position 41 suggested that CAP37 lacked serine protease action. This impression was supported by the failure of CAP37 to bind tritiated diisopropyl fluorophosphate. 89% of total CAP37 was released extracellularly from human neutrophils while they phagocytized Staphylococcus aureus. We propose that CAP37 released from neutrophils during phagocytosis and degranulation may mediate recruitment of monocytes in the second wave of inflammation.
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10.1172/JCI114593
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1845689
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[Effect of isradipine on urinary excretion of catecholamines and their metabolites in patients with pheochromocytoma].
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An effect of calcium antagonist-isradipine-on catecholamines and their metabolites excretion with the urine in 4 patients with pheochromocytoma has been analysed. It was found that the excretion of OFFnoradrenaline and vanilaminomandelic acid is reduced. It may indicate inhibitory effect of calcium antagonists on catecholamines secretion in patients with pheochromocytoma.
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10689943
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[A case of non-Hodgkin lymphoma in the central nervous system, developing during treatment of galactorrhea amenorrhea syndrome].
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We report a 27-year-old woman with a non-Hodgkin lymphoma in the central nervous system (CNS), showing monoparesis of the right upper extremity during treatment for the galactorrhea amenorrhea syndrome. The MRI demonstrated an infiltrative lesion with an obvious gadolinium-enhancement effect, extending from the pituitary stalk and hypothalamus through the 4th ventricle to the dorsal part of the medulla and upper cervical spinal cord. Because no tumors were detected in any other organ in either a physical examination or radiological investigations, including CT for the chest and abdomen, she was diagnosed as having primary CNS non-Hodgkin lymphoma (B cell origin) on the basis of an open brain biopsy. After the irradiation of the whole brain, followed by chemotherapy (methotrexate + CHOP), the infiltrative tumor disappeared on the MRI with a slight improvement for monoparesis of the right upper extremity. In this patient, primary CNS lymphoma might originate around the hypothalamus and infiltrate the medulla, inducing not only monoparesis of the right upper extremity but the galactorrhea amenorrhea syndrome.
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20830245
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Primary lung seminoma in a 76-year-old man: a case report.
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Seminoma is a rare event in old male population. In this report, we present a rare case of primary seminoma in the lung of a 76-years-old man. The patient was a 76-year-old man admitted with respiratory tract symptom and hemoptysis. The Chest Routine Scan and CT showed there was a consolidation area in the basal segments at the lower lobe of left lung. Bronchoscope also exhibited a neoplasm in left lung. During left lower lobectomy, we found that adherence occurred widely in left thoracic wall, and the pleural membrane was shrinkage. No chemotherapy or radiotherapy was given. Patient was died at 140 days after the surgery mainly due to the dyscrasia and secondary seminoma in left 7th to 9th ribs. Placental alkaline phosphatase (PLAP) and CD117 were found to be positive with immunohistochemical studies. Along with other evidences, this case was identified as the manifestations of seminoma. Although primary seminoma of the lung is rare in old male population, the diagnosis should be taken into serious consideration in order to improve the treatment. And in this case, primary lung seminoma is associated with high degree of malignancy and metastasis.
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