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pubmed_1042_2526
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Objective To explore the mechanism of obstructive sleep apnea(OSA) by assessing the association between human TWIK-related acid-sensitive K + channel-1(TASK-1) gene and OSA. Methods A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region,China,from April to December 2016.Two single nucleotide polymorphisms(rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a Kompetitive Allele Specific PCR genotyping system. Results In patients with blood potassium <3.95 mmol/L,the distribution of rs1275988 alleles(G vs.A)(χ =4.474,P=0.034) and recessive model(GG+GA vs.AA)(χ =4.327,P=0.038) showed significant differences between severe and non-OSA groups.The distribution of rs2586886 alleles(G vs.A)(χ =6.345,P=0.012) and dominant model(AA+GA vs.GA)(χ =4.431,P=0.035) showed significant differences between severe and non-OSA groups.The Logistic regression analysis showed that the GG genotype was a risk factor for OSA patients with blood potassium <3.95 mmol/L(OR=7.854,95% CI:1.710-36.000,P=0.008;OR=8.849,95% CI:1.816-43.117,P=0.007). Conclusions Both the GG genotypes of rs1275988 and rs2586886 in the TASK-1 gene may be potential risk factors in severe OSA patients with blood potassium <3.95 mmol/L.Serum potassium>3.95 mmol/L in patients with TASK-1 GG genotype may be conducive to reducing the incidence of severe OSA.
|
10.3881/j.issn.1000-503X.11246
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pubmed_372_9254
|
Dispersing metal nanoclusters on the oxide supports is attracting close attention in heterogeneous catalysis, but great challenges still lie in controlling the size and dispersion of nanoclusters due to the inevitable agglomeration. Here, we propose a sequential photochemical deposition strategy named "first store, and then release" to uniformly fabricate the size-controlling noble metal nanoclusters on semiconductor oxides. Using the typical semiconductor TiO2, the photoexcited electrons can be first stored as reduced species (e.g. Ti3+) under irradiation and the Ti3+ species can optimize both the nucleation and growth processes in dark reaction, resulting in a uniform dispersing of various noble metals (Au, Pt, Ag etc.) with size diameters of ∼1 nm. The nanoclusters catalysts exhibited superior performance in catalytic oxidation of HCHO compared with that of nanoparticles. This work brings a new and useful strategy to construct size-controlling noble metals on the oxide supports for heterogeneous catalysis and the related fields.
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10.1016/j.isci.2021.103572
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pubmed_471_20474
|
BACKGROUND
Chinese traditional herbal medicine Fuzhengkangai (FZKA) formulation combination with gefitinib can overcome drug resistance and improve the prognosis of lung adenocarcinoma patients. However, the pharmacological and molecular mechanisms underlying the active ingredients, potential targets, and overcome drug resistance of the drug are still unclear. Therefore, it is necessary to explore the molecular mechanism of FZKA.
METHODS
A systems pharmacology and bioinformatics-based approach was employed to investigate the molecular pathogenesis of EGFR-TKI resistance with clinically effective herb formula. The differential gene expressions between EGFR-TKI sensitive and resistance cell lines were calculated and used to find overlap from targets as core targets. The prognosis of core targets was validated from the cancer genome atlas (TCGA) database by Cox regression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment is applied to analysis core targets for revealing mechanism in biology.
RESULTS
The results showed that 35 active compounds of FZKA can interact with eight core targets proteins (ADRB2, BCL2, CDKN1A, HTR2C, KCNMA1, PLA2G4A, PRKCA and LYZ). The risk score of them were associated with overall survival and relapse free time (HR = 6.604, 95% CI: 2.314-18.850; HR = 5.132, 95% CI: 1.531-17.220). The pathway enrichment suggested that they involved in EGFR-TKI resistance and non-small cell lung cancer pathways, which directly affect EGFR-TKI resistance. The molecular docking showed that licochalcone a and beta-sitosterol can closely bind two targets (BCL2 and PRKCA) that involved in EGFR-TKI resistance pathway.
CONCLUSIONS
This study provided a workflow for understanding mechanism of CHM for against drug resistance.
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10.1186/s12906-018-2347-x
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pubmed_92_11962
|
Purpose: To evaluate the anti-neovascularization effects and investigate the possible mechanisms of SERPINA3K, a member of serine proteinase inhibitor family, using a specific rat model of suture-induced corneal neovascularization. Methods: A rat corneal suture model was set up and SERPINA3K was topically administered three times daily for 7 days. The clinical indications were evaluated on day 2, 5 and 7, including area of neovascularization and inflammation index. The eyeballs were collected after day 7 and the following examinations were performed: histological investigation, immunostaining, western blot and quantitative real-time polymerase chain reaction (PCR) assay. Wnt3a, a Wnt pathway ligand, was added to cultured Human Umbilical Vein Endothelial Cells (HUVEC), followed by detecting cell migration and western blot. Meanwhile, an in vitro VEGF165-stimulated HUVEC model was applied and the following measurements were conducted: cell proliferation, cell migration and tube formation. Results: SERPINA3K significantly suppressed corneal neovascularization and inhibited corneal inflammation. SERPINA3K downregulated the levels of β-catenin, non-pi-β-catenin and transcription factor 4 (TCF4), but upregulated the level of pi-β-catenin of the corneas induced by suture. SERPINA3K also decreased the gene expression and protein level of VEGF. Meanwhile, induction of Wnt3a increased the cell migration, activated the Wnt signaling and upregulated VEGF in cultured HUVEC, which were antagonized by SERPINA3K. In addition, SERPINA3K significantly inhibited VEGF165-induced cell proliferation and migration of HUVEC, SERPINA3K also specifically suppressed the VEGF165-induced tube formation of HUVEC. Conclusions: SERPINA3K has therapeutic potential for corneal neovascularization. The underlying mechanism may be through inhibiting Wnt signaling pathway and VEGF.
|
10.1167/iovs.14-14023
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pubmed_910_12060
|
The potent and selective anti-tumor agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), localizes in lysosomes and forms cytotoxic copper complexes that generate reactive oxygen species (ROS), resulting in lysosomal membrane permeabilization (LMP) and cell death. Herein, the role of lysosomal membrane stability in the anti-tumor activity of Dp44mT was investigated. Studies were performed using molecules that protect lysosomal membranes against Dp44mT-induced LMP, namely heat shock protein 70 (HSP70) and cholesterol. Up-regulation or silencing of HSP70 expression did not affect Dp44mT-induced LMP in MCF7 cells. In contrast, cholesterol accumulation in lysosomes induced by the well characterized cholesterol transport inhibitor, 3-β-[2-(diethyl-amino)ethoxy]androst-5-en-17-one (U18666A), inhibited Dp44mT-induced LMP and markedly and significantly (p<0.001) reduced the ability of Dp44mT to inhibit cancer cell proliferation (i.e., increased the IC(50)) by 140-fold. On the other hand, cholesterol extraction using methyl-β-cyclodextrin enhanced Dp44mT-induced LMP and significantly (p<0.01) increased its anti-proliferative activity. The protective effect of U18666A in increasing lysosomal cholesterol and preventing the cytotoxic activity of Dp44mT was not due to induced autophagy. Instead, U18666A was found to decrease lysosomal turnover, resulting in autophagosome accumulation. Moreover, preincubation with U18666A did not prevent the ability of Dp44mT to induce autophagosome synthesis, indicating that autophagic initiation via Dp44mT occurs independently of LMP. These studies demonstrate the significance of lysosomal membrane stability in relation to the ability of Dp44mT to execute tumor cell death and overcome pro-survival autophagy. Hence, lysosomal-dependent cell death induced by Dp44mT serves as an important anti-tumor strategy. These results are important for comprehensively understanding the mechanism of action of Dp44mT.
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pubmed_910_12060
|
pubmed_793_13884
|
1 Rats and mice given tributyl S,S,S,-phosphorotrithioate (DEF) showed large dose-related falls in body temperature which lasted several hours to several days at environmental temperatures below thermoneutrality (30 to 31 degrees C). 2 DEF produced only mild sedation and a remarkable degree of motor control was retained even when body temperatures fell below 30 degrees C. At the dose producing maximal hypothermia only 2% of rats died within the first 24 h, although prolonged hypothermia was usually lethal. 3 Hypothermia was associated with a complete block of cold-induced thermogenesis, with relatively little effect on basal metabolism at thermoneutrality. 4 Heat conservation mechanisms (peripheral vasoconstriction and piloerection) appeared to be unaffected by DEF and retained their usual temperature thresholds. 5 Adrenal catecholamine secretion in response to handling or acute cold exposure was normal in DEF-treated rats but the fall in body temperature could be markedly reduced by large intraperitoneal injections of noradrenaline, although not atropine. The increase in oxygen consumption produced by injected catecholamines was also unaffected by DEF treatment. 6 It is concluded that the block of cold-induced thermogenesis probably results from a lack of catecholamine release at the tissue level. That this is likely to be mediated at a peripheral site is suggested by the lack of effect of intracerebroventricular DEF.
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10.1111/j.1476-5381.1980.tb07898.x
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pubmed_1119_11000
|
Thirty cases of mandibular defects were reconstructed with a free iliac flap vascularised by the deep circumflex iliac vessels. Twenty five of these cases involved soft tissue damage with a defect of the mandible. The surgical procedure described by I. Taylor was used. Three anatomical variations of the pedicle were found. The features of the iliac bone are particularly suitable for mandibular reconstruction. The natural shape of the iliac bone does not require complex osteotomies and its healing capacity allows simple osteosynthesis. The thickness of the muscular pedicle, and thus the flap, is determined by the position of the lower edge of the skin components with respect to the iliac crest. This type of flap currently remains very useful in reconstruction of major mandibular and adjacent soft tissue destruction because of the very low incidence of failure (2 cases) and complications.
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pubmed_1119_11000
|
pubmed_94_8289
|
OBJECTIVE
To investigate the clinical effect of electroacupuncture at Baihui (GV20) and Shuigou (GV26) points in the treatment of brain injury in patients with sepsis-associated encephalopathy(SAE).
METHODS
A total of 70 patients with SAE were randomly divided into control group and treatment group, with 35 patients in each group. The patients in the control group were given routine western medicine treatment, including anti-infective therapy, nerve nutrition, and mechanical ventilation, and those in the treatment group were given electroacupuncture at GV20 and GV26 in addition to the treatment in the control group. The course of treatment was 1 week for both groups. Serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and neuron-specific enolase (NSE) were measured for both groups, the Montreal Cognitive Assessment (MoCA) scale was used to assess the change in cognitive function, and Glasgow Coma Scale (GCS) score was determined before and after treatment and was used to evaluate treatment outcome after treatment.
RESULTS
Both groups had significant reductions in the serum levels of CRP, IL-6, and NSE after 24 h and one week of treatment (P<0.05), and compared with the control group, the treatment group had significant reductions in the levels of CRP, IL-6 and NSE after treatment (P<0.05). The treatment group had significant increases in the total score of MoCA and the scores of all dimensions except attention after one week of treatment (P<0.05), and the treatment group had significantly higher scores than the control group after treatment (P<0.05). Both groups had a significant increase in GCS score after one week of treatment (P<0.05), and the treatment group had a significantly higher GCS score than the control group after treatment (P<0.05). The treatment group had a significantly higher total effective rate than the control group ［88.6% (31/35) vs 57.1% (20/35), P<0.05］.
CONCLUSION
Electroacupuncture at GV20 and GV26 can effectively improve brain injury and effective rate in SAE patients.
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10.13702/j.1000-0607.190781
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pubmed_63_6107
|
The bed bug, Cimex lectularius, aggregates under filter paper disks previously stained by adults. A multiple choice assay was used to determine differences in aggregation behavior among two strains, multiple lifestages, and levels of starvation. There were no differences in level of aggregation between established and recently derived strains, or among adults and nymphs of different instars. Propensity to aggregate decreased with time since feeding, but preference for stained disks remained high. We also examined which sensory structures mediate aggregation, and whether antennectomy affected movement, orientation, and arrestment under stained disks. Bed bugs that were left intact, blinded, or surgically altered by the removal of probosci or the distal antennal segments exhibited high levels of aggregation under stained disks. However, the removal of the pedicel significantly reduced aggregation compared to intact bugs. Video recordings of movement and orientation by bugs with intact, partial and complete antennectomies demonstrated that neither partial nor complete antennectomies affected walking speed, path straightness, direction of movement or frequency of encounters with either stained or clean disks. However, complete removal of both antennae significantly reduced the percentage of encounters with stained disks that resulted in arrestment. These findings suggest aggregation by bed bugs is a result of arrestment mediated by direct, close-range contact between sensilla on the pedicel and stained disks.
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10.1016/j.jinsphys.2009.03.001
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pubmed_411_19056
|
We conducted a two-sample Mendelian randomization study to determine the association of smoking initiation with seven psychiatric disorders. We used 353 independent single-nucleotide polymorphisms associated with cigarette smoking initiation as instrumental variables at genome-wide significance threshold (p < 5 × 10-8) from a recent genome-wide association study in 1,232,091 European-origin participants. Summary-level data for seven psychiatric disorders, including anxiety, bipolar disorder, insomnia, major depressive disorder, posttraumatic stress disorder, suicide attempts, and schizophrenia, was obtained from large genetic consortia and genome-wide association studies. The odds ratios of genetically predicted smoking initiation were 1.96 for suicide attempts (95% CI 1.70, 2.27; p = 4.5 × 10-20), 1.69 for post-traumatic stress disorder (95% CI 1.32, 2.16; p = 2.5 × 10-5), 1.54 for schizophrenia (95% CI 1.35, 1.75; p = 1.6 × 10-10), 1.41 for bipolar disorder (95% CI 1.25, 1.59; p = 1.8 × 10-8), 1.38 for major depressive disorder (95% CI 1.31, 1.45; p = 2.3 × 10-38), 1.20 for insomnia (95% CI 1.14, 1.25; p = 6.0 × 10-14) and 1.17 for anxiety (95% CI 0.98, 1.40; p = 0.086). Results of sensitivity analyses were consistent and no horizontal pleiotropy was detected in MR-Egger analysis. However, the associations with suicide attempts, schizophrenia, bipolar disorder, and anxiety might be related to possible reverse causality or weak instrument bias. This study found that cigarette smoking was causally associated with increased risks of a number of psychiatric disorders. The causal effects of smoking on suicide attempts, schizophrenia, bipolar disorder and anxiety needs further research.
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10.1038/s41598-020-70458-4
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pubmed_281_17147
|
Fourier Transform Infrared (FTIR) microspectroscopy is well known for its effectiveness in spectral and biochemical analyses of various materials. It enables to determine the sample biochemical composition by assigning detected frequencies, characteristic for functional groups of main biological macromolecules. In analysis of tissue sections one of two measurement modes, namely transmission and transflection, is usually applied. The first one has relatively straightforward geometry, hence it is considered to be more precise and accurate. However, IR-transparent media are very fragile and expensive. Transflection does not require expensive substrates, but is more prone to disruptive influence of Mie scattering as well as electric field standing wave effect. The excessive comparison of spectra' characteristics, obtained via both measurement modes, was performed in this paper. By the means of Mann-Whitney non-parametrical U test and PCA, the comparison of results obtained with both modes and assessment of usefulness of IR spectra obtained with transmission and transflection modes to differentiate between healthy and GBM-affected tissue, were performed. The main objective of the presented research is to compare the results of FTIR analysis of unfixed biological samples performed with transflection and transmission mode. In frame of the study we demonstrated the discrepancies between results of biochemical analysis performed based on data obtained with transmission and transflection. Such observation suggests that caution should be taken in drawing conclusions from the results obtained with transflection geometry, as its more prone to disruptive effects. Despite that, IR spectra developed with both modes allowed to distinguish GBM area from healthy tissue, which proves their diagnostic potential. Especially, application of the ME-EMSC correction of spectra before PCA enhances the performance of both methods to distinguish the analysed tissue areas.
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10.1016/j.saa.2022.122086
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pubmed_99_15415
|
This report documents the experience of the authors with two patients who had received thoracic radiation for disseminated teratocarcinomas of the testis, survived their malignancies, and subsequently developed squamous cell carcinomas of the esophagus. To the authors' knowledge, only 11 other cases of esophageal malignancies arising in patients who had received previous mediastinal irradiation have been reported in the world literature. With increasingly successful mediastinal radiation for malignant disease resulting in prolonged patient survival, an increasing number of such patients with subsequent esophageal malignancies can be anticipated. Close follow-up of patients receiving radiation therapy to periesophageal tissues is recommended, and prompt evaluation of any symptoms of esophageal dysfunction is indicated.
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10.1002/1097-0142(1984)54:4<726::aid-cncr2820540422>3.0.co;2-x
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pubmed_962_6829
|
The amphibian urea transporter (fUT) shares many properties with the mammalian urea transporters (UT) derived from UT-A and UT-B genes. The transport of urea by fUT is inhibited by the mercurial agent p-chloromercuribenzenesulfonic acid (pCMBS). We found that in oocytes expressing cRNA encoding fUT, a 5-min preincubation in 0.5 mM mercury chloride (HgCl2) also significantly reduced urea uptake. The transport of urea by fUT was rendered mercury (Hg2+) insensitive by mutating either of the residues C185 or H187, both of which lie within the M-I region (close to the hypothetical UT pore). In oocytes expressing a mixture of the C185 and H187 mutants, Hg2+ sensitivity was reestablished. The transport of urea by the mouse UTs mUT-A2 and mUT-A3 was not sensitive to Hg2+. Introducing cysteine residues analogous to that mutated in fUT into mUT-A2 or mUT-A3 did not induce Hg2+ sensitivity. Additionally, introducing the double cysteine, histidine mutations into mUT-A2 or mUT-A3 still did not induce Hg2+ sensitivity, indicating that a region outside of the M-I region also contributes to the Hg2+-induced block of fUT. Using a series of chimeras formed between UT-A3 and fUT, we found that as well as C185 and H187, residues within the COOH terminal of fUT determine Hg2+ sensitivity, and we propose that differences in the folding of this region between fUT and mUT-A2/mUT-A3 allow access of Hg2+ to the fUT channel pore.
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10.1152/ajprenal.00449.2005
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pubmed_822_17541
|
PURPOSE
Uterine clear-cell carcinoma (UCCC) is a rare subset of type II endometrial carcinoma with a poor prognosis relative to the most common type of endometrioid carcinoma. Due to its rarity, there has been limited direct evidence of the efficacy of specific adjuvant therapy posthysterectomy in women with UCCC. We present a review of current literature regarding adjuvant therapy of uterine clear cell carcinoma.
METHODS
We searched for English-language publications through Pubmed using a combination of the following key words: endometrial carcinoma, clear cell carcinoma, recurrence, prognosis, adjuvant therapy, radiation treatment and chemotherapy. Due to the rarity of UCCC, studies were not limited by design or number of patients.
RESULTS
There is a paucity of randomized prospective controlled studies focusing on UCCC adjuvant therapy. Findings have largely been derived from retrospective studies of type II endometrial carcinomas or all endometrial cancers as a group. Very few retrospective studies were found to focus on UCCC adjuvant therapy, although certain larger studies did have subset analyses of UCCC patients.
CONCLUSIONS
For early stage disease, locoregional radiotherapy, especially vaginal brachytherapy, has evidence of efficacy. The therapeutic gain of radiotherapy may be further improved with the addition of systemic chemotherapy. Evidence for combined radiation therapy with systemic chemotherapy in women with advanced stage UCCC has remained debatable. UCCC-specific studies are needed to determine the best adjuvant therapy for UCCC without the confounding effects of USC and other endometrial cancers.
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10.1007/s00404-015-3973-x
|
pubmed_762_1746
|
This study introduces a direct method of assessing cerebral lateralization for language based on fMRI activation. The method, derived from a voxel-based morphometry study by C. H. Salmond et al. (2000, Hum. Brain Mapping 11, 223-232), bases lateralization on the direct statistical comparison of the magnitude of task-induced activation in homotopic regions of the two hemispheres. Lateralization results obtained with this direct method were compared to those obtained with a widely used method which involves the calculation of a laterality index (LI) based on the number of significantly activated voxels in the inferior frontal gyrus of each hemisphere. In order to compare the validity of the two methods, a covert verb-generation task was performed by eight children with epilepsy whose language lateralization was examined using invasive techniques. Lateralization results derived from fMRI activation showed that the calculation of a LI presented some limitations. Importantly, the LI value was dependent on the activation threshold chosen to calculate that LI. As a consequence, the correlation between the LI and the invasive methods could vary with the chosen threshold. By contrast, the proposed direct method gave some indication of the reliability of the lateralization and provided results that, in all eight children, were consistent with those obtained using invasive techniques. It is suggested that the direct method could be used in future fMRI studies to establish hemispheric lateralization for cognitive functions.
|
10.1006/nimg.2002.1327
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pubmed_495_7892
|
Nafadotride (N[(n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyano naphtalene-2-carboxamide) is a novel compound, which inhibits potently and stereoselectively [125I]iodosulpride binding at recombinant human dopamine D3 receptors. the levoisomer displays an apparent Ki value of 0.3 nM at the dopamine D3 receptor, but is 10 times less potent at the human recombinant dopamine D2 receptor. In comparison, the dextroisomer displays 20-fold less apparent affinity at the dopamine D3 receptor and reduced (2-fold) selectivity. l-Nafadotride displays iow, micromolar affinity at dopamine D1 and D4 receptors and negligible apparent affinity at various other receptors. In dopamine D3 receptor-transfected NG-108 15 cells, in which dopamine agonists increase mitogenesis, l-nafadotride has no intrinsic activity, but competitively antagonizes the quinpirole-induced mitogenetic response, monitored by [3H]thymidine incorporation with a pA2 of 9.6. In dopamine D2 receptor-transfected Chinese Hamster Ovary cells, l-nafadotride also behaves as a competitive antagonist of quinpirole-induced mitogenesis with an 11-fold lower potency. These studies establish nafadotride as a pure, extremely potent, competitive and preferential dopamine D3 receptor antagonist in vitro. l-Nafadotride displaces in vivo N-[3H]propylnorapomorphine accumulation at lower dosage and for longer periods in limbic structures, containing both dopamine D2 and D3 receptors than in the stratum, containing dopamine D2 receptor only. At low dosage (0.1-1 mg/kg), nafadotride, unlike haloperidol, a dopamine D2 receptor-preferring antagonist, increases spontaneous locomotion of habituated rats and climbing behavior of mice, at doses that do not modify striatal homovanillic acid levels. At high dosage (1-100 mg/kg), nafadotride, like haloperidol, produces catalepsy and antagonizes apomorphine-induced climbing.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed_495_7892
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pubmed_532_19776
|
Despite a conceptually simple mechanism of signaling, the JAK-STAT pathway exhibits considerable behavioral complexity. Computational pathway models are tools to investigate in detail signaling process. They integrate well with experimental studies, helping to explain molecular dynamics and to state new hypotheses, most often about the structure of interactions. A relatively small amount of experimental data is available for a JAK1/2-STAT1 variant of the pathway, hence, only several computational models were developed. Here we review a dominant approach of kinetic modeling of the JAK1/2-STAT1 pathway, based on ordinary differential equations. We also give a brief overview of attempts to computationally infer topology of this pathway.
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10.4161/jkst.24672
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pubmed_380_7728
|
Cell attachment and the assembly of cytoskeletal and signaling complexes downstream of integrins are intimately linked and coordinated. Although many intracellular proteins have been implicated in these processes, a new paradigm is emerging from biochemical and genetic studies that implicates integrin-linked kinase (ILK) and its interacting proteins, such as CH-ILKBP (alpha-parvin), paxillin, and PINCH in coupling integrins to the actin cytoskeleton and signaling complexes. Genetic studies in Drosophila, Caenorhabditis elegans, and mice point to an essential role of ILK as an adaptor protein in mediating integrin-dependent cell attachment and cytoskeletal organization. Here we demonstrate, using several different approaches, that inhibiting ILK kinase activity, or expression, results in the inhibition of cell attachment, cell migration, F-actin organization, and the specific cytoskeletal localization of CH-ILKBP and paxillin in human cells. We also demonstrate that the kinase activity of ILK is elevated in the cytoskeletal fraction and that the interaction of CH-ILKBP with ILK within the cytoskeleton stimulates ILK activity and downstream signaling to PKB/Akt and GSK-3. Interestingly, the interaction of CH-ILKBP with ILK is regulated by the Pi3 kinase pathway, because inhibition of Pi3 kinase activity by pharmacological inhibitors, or by the tumor suppressor PTEN, inhibits this interaction as well as cell attachment and signaling. These data demonstrate that the kinase and adaptor properties of ILK function together, in a Pi3 kinase-dependent manner, to regulate integrin-mediated cell attachment and signal transduction.
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10.1091/mbc.e03-05-0308
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pubmed_984_13476
|
BACKGROUND AND AIMS
The pathogenetic link between ulcerative colitis and sclerosing cholangitis (SC) is unclear. We hypothesized that colitis induces changes in bile composition via inflammation-induced reduction of hepatobiliary transporter gene expression, ultimately resulting in cholestasis and bile duct injury.
METHODS
Alterations in transporter expression and bile secretion in acute dextran sulphate sodium (DSS)-induced colitis were compared with lipopolysaccharide (LPS)-treated mice serving as positive control. Whether chronic DSS-colitis elicits cholangitis in genetically predisposed animals was studied in heterozygous multidrug resistance gene 2 knockout mice (Mdr2(+/-)).
RESULTS
LPS but not DSS-colitis changed major hepatobiliary transporters (Ntcp, Bsep, Mrp2-4, Ostalpha/beta, Abcg5/8, Oatp1-4, Mdr1b and Mdr2), enzymes (Cyp3a11 and Cyp7a1), nuclear receptors (RXRalpha, FXR, CAR and PXR) and proinflammatory mediators (tumour necrosis factor alpha and inducible nitric oxide synthase). Formation of toxic bile reflected by an increased bile acid/phospholipid ratio was observed neither in acute nor in chronic colitis, although heterozygous Mdr2(+/-) mice developed mild portal inflammation after chronic colitis.
CONCLUSIONS
In contrast to LPS, DSS-colitis has a minor impact on hepatobiliary gene expression and bile secretion. Therefore, intestinal inflammation-associated changes of hepatobiliary transporter expression do not play a pathogenetic role in SC.
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10.1111/j.1478-3231.2009.02044.x
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pubmed_978_20053
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We present a case of narcolepsy mimicking suicidal carbon monoxide poisoning. The signs and symptoms of narcolepsy in this previously undiagnosed man were initially missed, which emphasizes the importance of extracting a detailed history of a decedent's behavior prior to his or her death. Narcoleptics are often involved in motor vehicle accidents. This report again demonstrates that narcolepsy and driving don't mix, even when the vehicle is stationary. We also briefly review the various sleep disorders.
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10.1097/00000433-198909000-00011
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pubmed_560_21394
|
Osteoblast and osteoclast activity is disrupted in post-menopausal osteoporosis. Thus, to fully address this imbalance, therapies should reduce bone resorption and promote bone formation. Dietary factors such as phyto-oestrogens and Zn have beneficial effects on osteoblast and osteoclast activity. However, the effect of combinations of these factors has not been widely studied. We therefore examined the effect of coumestrol, daidzein and genistein in the presence or absence of zinc sulphate (Zn) on osteoclast and osteoblast activity. Osteoclast differentiation and bone resorption were significantly reduced by coumestrol (10- 7 m), daidzein (10- 5 m) and genistein (10- 7 m); and this direct anti-osteoclastic action was unaffected by Zn (10- 5 m). In addition, Zn augmented the inhibitory effect of phyto-oestrogens on the osteoblast-derived stimulus for osteoclast formation, significantly reducing the ratio of receptor activator of NF-κB ligand (RANKL)-to-osteoprotegerin mRNA expression in human osteoblast. We then examined the effect of these compounds on osteoblast activity. Mineralisation was enhanced by coumestrol (10- 5 to 10- 7 m), daidzein (10- 5 to 10- 6 m) and genistein (10- 5 m); and Zn significantly augmented this response. Zn and phyto-oestrogens also significantly enhanced alkaline phosphatase activity and Runt-related transcription factor 2 (Runx2) mRNA expression. On the other hand, Zn blunted phyto-oestrogen-induced type I collagen and osteocalcin expression and suppressed coumestrol and daidzein-stimulated osterix expression. Zn may therefore modify the anabolic action of phyto-oestrogens, promoting characteristics associated with early rather than late stages of osteoblast differentiation. Our data suggest that while Zn enhances the anti-osteoclastic effect of phyto-oestrogens, it may limit aspects of their anabolic action on bone matrix formation.
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10.1017/S0007114511007355
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pubmed_424_22166
|
Three Gram-positive, moderately halophilic, heterotrophic bacterial strains were isolated from a neutral saline lake in the Xin-Jiang area of China. The strains, designated 8-2(T), W11-1 and 25-7(T), were motile, spore-forming, aerobic rods and contained meso-diaminopimelic acid in their cell walls. Their DNA G+C contents were 37.4, 37.2 and 39.9 mol%, respectively. The main fatty acids in the cellular membranes of these novel strains were C(15) and C(17) methyl-branched. No species with validly published names showed 16S rRNA gene sequence similarity of more than 95 % with respect to these novel isolates; the most closely related species was a halophilic denitrifier, Bacillus halodenitrificans (94.6 %). Polyphasic taxonomic studies revealed that these strains belong to the Bacillaceae and are distantly related to other genera of the family. It is proposed that a new genus, Salinibacillus, should be created, with Salinibacillus aidingensis (type strain, 25-7(T)=AS 1.3565(T)=JCM 12389(T)) as the type species. Another species, Salinibacillus kushneri, is also proposed, with 8-2(T) (=AS 1.3566(T)=JCM 12390(T)) as the type strain.
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10.1099/ijs.0.63287-0
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pubmed_697_3568
|
In forensic DNA casework, the interpretation of an evidentiary profile may be dependent upon the assumption on the number of individuals from whom the evidence arose. Three methods of inferring the number of contributors-NOCIt, maximum likelihood estimator, and maximum allele count, were evaluated using 100 test samples consisting of one to five contributors and 0.5-0.016 ng template DNA amplified with Identifiler® Plus and PowerPlex® 16 HS. Results indicate that NOCIt was the most accurate method of the three, requiring 0.07 ng template DNA from any one contributor to consistently estimate the true number of contributors. Additionally, NOCIt returned repeatable results for 91% of samples analyzed in quintuplicate, while 50 single-source standards proved sufficient to calibrate the software. The data indicate that computational methods that employ a quantitative, probabilistic approach provide improved accuracy and additional pertinent information such as the uncertainty associated with the inferred number of contributors.
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10.1111/1556-4029.13284
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pubmed_304_8387
|
The beta-range synchronization between cortical motor and muscular activity as revealed by EEG/MEG-EMG coherence has been extensively investigated for steady-state motor output. However, there is a lack of information on the modulation of the corticomuscular coherence in conjunction with dynamic force output. We addressed this question comparing the EEG-EMG coherence and the cortical motor spectral power in eight healthy subjects in a visuomotor task, in which the subjects exerted a steady-state or periodically modulated dynamic isometric force output with their right-index finger to keep a visual cursor within a target zone. In the static condition, significant coherence was confined to the beta-range. In the dynamic condition, the most distinct coherence occurred in the gamma-range and the significant beta-range coherence was strikingly reduced. The cortical motor power in the beta-range during dynamic force output was decreased, whereas the power in the gamma-range remained without significant change. We conclude that during dynamic force the corticospinal oscillation mode of the sensorimotor system shifts towards higher (principally gamma) frequencies for the rapid integration of the visual and somatosensory information required to produce the appropriate motor command.
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10.1016/j.neuroimage.2006.10.018
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pubmed_83_20016
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The importance of ovarian teratoma as a cause of opsoclonus myoclonus ataxia syndrome (OMAS) and other paraneoplastic syndromes continues to be underestimated. A strong suspicion and appropriate diagnosis remain keys to successful outcome of paraneoplastic OMAS with ovarian teratoma. We report a 14-year-old girl with paraneoplastic OMAS in association with an ovarian teratoma who improved completely following resection of tumour as well as immunotherapy and review the literature briefly.
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10.1080/01658107.2019.1573374
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pubmed_234_17683
|
A 44-year-old woman presenting with headache and decreased visual acuity was found to have bilateral papilloedema. Radiograph showed an enlarged pituitary fossa. MR scans demonstrated a large solid tumor with central necrosis, and both suprasellar and infrasellar extension. The invasive pituitary macroadenoma was surgically debulked, followed by radiotherapy. The clinical and imaging features of pituitary macroadenomas are discussed.
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pubmed_234_17683
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pubmed_589_17496
|
Mucin1 (MUC1) is a transmembrane oncogenic protein that plays a central role in malignant transformation and disease evolution, including cell proliferation, survival, self-renewal, and metastatic invasion. MUC1 has been shown to interact with diverse effectors such as β-catenin, receptor tyrosine kinases, and c-Abl, which are of importance in the pathogenesis of various hematological malignancies. In myeloid leukemia, MUC1 has been shown to have an essential role in leukemia stem-cell function, the induction of reactive oxygen species (ROS), and the promotion of terminal myeloid differentiation. As such, MUC1 is an attractive therapeutic target in hematologic malignancies. Targeting MUC1 has been shown to be an effective approach for inducing cell death in tumor in in vivo and in vitro models. Furthermore, MUC1 inhibition is synergistic with other therapeutic agents in the treatment of hematologic disorders. This review will explore the role of MUC1 in hematological malignancies, and strategies for targeting this oncoprotein.
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10.1080/10428194.2016.1195500
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pubmed_630_24774
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Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22-/-) ± infection. Interleukin-22-/- mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22-/- mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22-/- mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22-/- mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22-/- mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.
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10.1371/journal.ppat.1005481
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pubmed_713_14854
|
Inadequate trophoblast proliferation, shallow invasion and exaggerated rate of trophoblast apoptosis are implicated in early recurrent miscarriage (ERM). However, the mechanistic bases of this association have not been fully established. We aimed at investigating the involvement of fascin, an actin-bundling protein, in trophoblast activities and ERM. We found that fascin was downregulated in the cytotrophoblasts (CTBs) and distal cytotrophoblasts (DCTs) of ERM placentae. Knockdown of fascin altered cellular and nucleolar morphology, and inhibited the proliferation but increased apoptosis of trophoblastic HTR8/SVneo cells. Furthermore, fascin knockdown decreased the expression of transcription factors such as Snail1/2, Twist and Zeb1/2, mesenchymal molecules such as Vimentin and N-cadherin, and the protein expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylates signal transducer and activator of transcript 3 (STAT3). Exposure of HTR-8/SVneo cells to hypoxia reoxygenation (H/R) decreased fascin expression to affect the cells' invasion. Our results indicate for the first time that the downregulation of fascin is involved in the pathogenesis of early recurrent miscarriage; and hence a potential therapeutic target against the disease.
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10.1016/j.yexcr.2021.112597
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pubmed_87_17445
|
The aim of this study was to develop a method based on ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) for lipid profiling in human placental choriocarcinoma (JEG-3) cells. Lipids were solid-liquid extracted from JEG-3 cells using a solution of chloroform/methanol (2:1, v/v) in a simple procedure requiring minimal sample alteration. Simultaneous separation of complex lipid mixtures in their major classes was achieved with a reversed-phase (C8) UHPLC column and a mobile phase containing methanol with 1 mM ammonium formate and 0.2 % formic acid (A)/water with 2 mM ammonium formate and 0.2 % formic acid (B). Lipids were characterized using time-of-flight (TOF) and Orbitrap under full scan and positive electrospray ionization mode with both analyzers. A total of 178 species of lipids, including 37 phosphatidylcholines (PC), 32 plasmalogen PC, 9 lyso PC, 4 lyso plasmalogen PC, 30 triacylglycerols, 22 diacylglycerols, 7 cholesterol esters, 25 phosphatidylethanolamines, and 12 sphingomyelins, were identified using TOF and Orbitrap. The identification of all lipid classes was based on exact mass characterization with an error < 5 ppm. The developed methodology was applied to study lipid alterations in human placental cells against the exposure to perfluorinated chemicals (PFCs) and tributyltin (TBT).
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10.1007/s11356-014-3172-5
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pubmed_229_9628
|
Claudins, the major transmembrane proteins of tight junctions, are members of the tetraspanin superfamily of proteins that mediate cellular adhesion and migration. Their functional importance is demonstrated by mutations in claudin genes that eliminate tight junctions in myelin and the testis, abolish Mg(2+) resorption in the kidney, and cause autosomal recessive deafness. Here we report that two paralogs among 15 claudin genes in the zebrafish, Danio rerio, are expressed in the otic and lateral-line placodes at their earliest stages of development. Related claudins in amphibians and mammals are expressed in a similar manner in vertebrate primordia such as sensory placodes, branchial arches, and limb buds. We also show that the claudin gene family may have expanded along the chordate stem lineage from urochordates to gnathostomes, in parallel with the elaboration of vertebrate characters. We propose that tight junctions not only form barriers in mature epithelia, but also participate in vertebrate morphogenesis.
|
10.1073/pnas.171325898
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pubmed_389_7197
|
DNA uptake sequences are widespread throughout the Neisseria gonorrhoeae genome. These short, conserved sequences facilitate the exchange of endogenous DNA between members of the genus Neisseria. Often the DNA uptake sequences are present as inverted repeats that are able to form hairpin structures. It has been suggested previously that DNA uptake sequence inverted repeats present 3' of genes play a role in rho-independent termination and attenuation. However, there is conflicting experimental evidence to support this role. The aim of this study was to determine the role of DNA uptake sequences in transcriptional termination. Both bioinformatics predictions, conducted using TransTermHP, and experimental evidence, from RNA-seq data, were used to determine which inverted repeat DNA uptake sequences are transcriptional terminators and in which direction. Here we show that DNA uptake sequences in the inverted repeat configuration occur in N. gonorrhoeae both where the DNA uptake sequence precedes the inverted version of the sequence and also, albeit less frequently, in reverse order. Due to their symmetrical configuration, inverted repeat DNA uptake sequences can potentially act as bi-directional terminators, therefore affecting transcription on both DNA strands. This work also provides evidence that gaps in DNA uptake sequence density in the gonococcal genome coincide with areas of DNA that are foreign in origin, such as prophage. This study differentiates for the first time, to our knowledge, between DNA uptake sequences that form intrinsic transcriptional terminators and those that do not, providing characteristic features within the flanking inverted repeat that can be identified.
|
10.1099/mgen.0.000069
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pubmed_1141_21649
|
A gelatin sponge model of concomitant tumor immunity was employed in order to examine the clonality of T cells associated with progressing and rejected tumor sites. Here we show that freshly isolated T cells bearing TCR V(beta)1, CDR3 RPGTGN, J(beta)1.1 and TCR V(beta)8, CDR3 GD, J(beta)1.6 predominated progressing and rejected tumor sites. Despite the similarity in T cell populations, the T cells from rejected tumor sites were capable of killing the autologous tumor cells, whereas T cells from progressing tumor sites were not able to do so. The differing cytolytic ability could not be attributed to a difference in TCR zeta chain protein expression levels between both T cell populations. After a 5 day mixed lymphocyte tumor culture the T cells from the progressing tumor site were capable of killing autologous tumor cells, which suggested changes took place within the cell population during in vitro culture. Further TCR analysis revealed T cells bearing TCR V(beta)1, CDR3 RPGTGN, J(beta)1.1 and TCR V(beta)8, CDR3 GD, J(beta)1.6 were not expanded following the in vitro culture. These data suggest that the lack of cytotoxicity of freshly isolated tumor-infiltrating lymphocytes (TIL) was not due to abnormal TCR zeta chain expression or major differences in the TCR V(beta) usage. Additionally, the gain of TIL effector function did not correlate with an expansion of the TCR bearing T cells found to predominate the in vivo response. These data suggest that the predominant TCR V(beta) used by lymphocytes infiltrating regressing or rejected tumors may not represent the tumor reactive T cells that grow in culture or respond to the autologous tumor in vitro.
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10.1093/intimm/12.5.639
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pubmed_241_21142
|
OBJECTIVE
To report the diagnostic, clinical, and histopathologic features of a patient with coccidioidomycosis endophthalmitis without concomitant systemic involvement diagnosed by vitreous biopsy.
DESIGN
Interventional case report.
PARTICIPANTS
One patient.
INTERVENTION
Diagnostic pars plana vitrectomy, systemic and intravitreal antifungal treatment, and enucleation.
MAIN OUTCOME MEASURES
Diagnostic, clinical, and histopathologic features of chronic coccidioidomycosis endophthalmitis.
RESULTS
A 64-year-old white man from Southern California presented with chronic intraocular inflammation in the right eye that had lasted 18 months. He had been unsuccessfully treated with topical and subtenon steroids. At presentation, best-corrected visual acuity was 20/400 in the right eye and 20/20 in the left eye. Ophthalmoscopy of the right eye revealed significant vitritis and multiple yellowish chorioretinal lesions. Evaluation by an internist showed no underlying inflammatory, infectious, or neoplastic systemic illnesses. A vitreous biopsy followed by histopathologic examination showed the presence of multiple Coccidioides sp. microorganisms. The patient was then treated with intravitreal amphotericin B and oral fluconazole. Best-corrected visual acuity initially improved to 20/80, but inflammation progressed and did not respond to 2 subsequent injections of antifungals, 2 additional pars plana vitrectomies, and oral fluconazole. The eye eventually became blind and painful and was enucleated. Histopathologic examination disclosed intraocular granulomas displaying multiple Coccidioides sp. microorganisms.
CONCLUSIONS
Coccidioides sp. endophthalmitis may present with no concomitant systemic involvement. Histopathologic examination of the vitreous is helpful in the diagnosis. A high index of suspicion is important, especially in areas where the incidence of coccidioidomycosis is rising.
|
10.1016/j.ophtha.2010.01.033
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pubmed_306_25236
|
The recovery test in the "surrogate" mode is often exploited for trueness assessment when appropriate certified reference materials are not available or to support reference material studies. The species effect occurs when chemical forms of native and surrogate analytes are different. It usually results in obtaining incomparable analytical signals for both forms. Influence of the species effect on the results obtained by "surrogate" recovery test was examined. The examination was performed theoretically on the basis of a extended mathematical model and the results predicted by the model were checked experimentally. Experiments were carried out with the use of synthetic samples containing selenite ions and l-selenomethionine acting as inorganic and organic form of selenium, respectively. Moreover, real samples of thermal spring water and vitamin drink were analysed with the use of flow injection system. The system was dedicated to perform not only spiking but also UV digestion of the synthetic and real samples in order to study the species effect. The system was coupled to hydride generation atomic fluorescence spectrometer (HG-AFS) enabling to determine total amount of selenium.
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pubmed_306_25236
|
pubmed_1110_11396
|
We examined the relationship between viruses and co-occurring bacterial communities across spatiotemporal scale in two contrasting freshwater lakes, namely meromictic Lake Pavin and dimictic Lake Aydat (Central France). Next-generation sequencing of 16S rRNA genes suggested distinct patterns in bacterioplankton community composition (BCC) between the lakes over depths and seasons. BCC were generally dominated by members of Actinobacteria, Proteobacteria, and Bacteroidetes covering about 95% of all sequences. Oxygen depletion at the bottom waters in Aydat and existence of permanent anoxia in the monimolimnion of Pavin resulted in the occurrence and dominance of lesser known members of lake communities such as Methylotenera, Methylobacter, Gallionella, Sulfurimonas, and Syntrophus in Pavin and Methylotenera and Sulfuritalea in Aydat. Differences in BCC appeared strongly related to dissolved oxygen concentration, temperature, viral infection, and virus-to-bacteria ratio. UniFrac analysis indicated a clear distinction in BCC when the percentage of viral infected bacterial cells and virus-to-bacteria ratio exceeded a threshold level of 10% and 5, respectively, suggesting a link between viruses and their potential bacterial host communities. Our study revealed that in both the lakes, the prevailing environmental factors across time and space structured and influenced the adaptation of bacterial communities to specific ecological niches.
|
10.1007/s00248-018-1143-y
|
pubmed_762_23266
|
OBJECTIVE
To study the changes in the variables in patients with gynecological malignancies after operation.
METHOD
Platelet alphagranule membrane protein (GMP-140), von Willebrand Factor (vWF), antithrombin III activity (AT-III), protein C-dependent partial thromboplastin activation time, plasminogen activity (PLG), the activity of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI), D-Dimer were examined in 20 normal non-pregnant women and 38 patients after operation with gynecological malignancies.
RESULTS
vWF, GMP-140, PLG, D-Dimer, and PAI of patients with malignancies before operation were obviously higher than those of the healthy women (P<0.01). After operation the parameters were obviously elevated in the patients (P<0.01). AT-III and partial thromboplastin activation time were significantly reduced in comparison with the healthy subjects (P<0.01). t-PA showed no significant difference between the groups (P>0.05).
CONCLUSIONS
Obvious prethrombotic state characterizes the patients with gynecological malignancies after operation.
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pubmed_762_23266
|
pubmed_417_4167
|
Given current computational environments, it is worthwhile to establish amino acid residue-level functions which approximate protein folds quite well. Such functions must be the interim steps toward protein three-dimensional structure prediction. I have shown that an empirical hydrophobic penalty function of protein, derived from the number of residues in a sphere around each residue, could be utilized to distinguish the correctly folded structure from the incorrect ones. In order to assess the predictive power of the penalty function, I have generated conformations by randomly changing main chain dihedral angles, and applied the penalty function to them. If only a local region was allowed to change its conformation, native-like structures could be generated within a reasonable computational time. In global simulations, however, a considerable number of nonnative conformations, which gave as small a penalty value as that of the native protein, were found. Although some of the conformations were compact and globular, they were quite different from the native structure in that they lacked most of the secondary structures. This result shows that the penalty function alone cannot define the native structure, and that substructure information may help the penalty function to reach the correctly folded structure.
|
10.1016/0263-7855(93)80002-9
|
pubmed_656_24348
|
A set of three new Ru(ii) polypyridyl complexes decorated with 5-aryl tetrazolato ligands (R-CN4)-, (D series, namely D1, D3 and D4), is presented herein. Whereas complex D1 represents the pyrazinyl tetrazolato analogue of a previously reported Ru(ii) complex (D2) with the general formula cis-[(dcbpy)2Ru(N^N)]+, in which dcbpy is 2,2'-bipyridine-4,4'-dicarboxylic acid and N^N is the chelating 2-pyridyl tetrazolato anion, the design of the unprecedented Ru(ii) species D3 and D4 relied upon a completely different architecture. More specifically, the molecular structure of thiocyanate-based species cis-[(dcbpy)2Ru(NCS)2], that is typically found in benchmark Ru(ii) dyes for dye sensitized solar cell (DSSCs), was modified with the replacement of two of the -NCS ligands in favour of the introduction of 5-aryl tetrazolato anions, such as the deprotonated form of 5-(4-bromophenyl)-1H-tetrazole, for complex D3 and 5-(4-cyanophenyl)-1H-tetrazole in the case of complex D4. To streamline the behavior of the D series of Ru(ii) complexes as photosensitizers for DSSCs, an in-depth analysis of the excited state properties of D1, D3 and D4 was performed through TDDFT calculations and TDAS (nanosecond transient difference absorption spectroscopy). The obtained results highlight a trend that was confirmed once D1, D3 and D4 were tested as photosensitizers for DSSC under different conditions. Along the series of the Ru(ii) complexes, the neutrally charged species D3 and D4 displayed the best photovoltaic performances.
|
10.1039/d0dt02621b
|
pubmed_438_15656
|
RB plays dual roles in the regulation of cell proliferation and differentiation. The nervous tissue-specific gene Rig-1, a member of the roundabout (Robo) guidance receptor family, was identified as an RB-regulated gene in the mouse embryo. Herein, we report that a 2.3kb genomic DNA fragment, which contains the first 129 bases of the 5'-untranslated region and 2.2kb of the 5'-flanking region of Rig-1, has a cell type-specific promoter activity. Rig-1 promoter activity is downregulated by RB and upregulated by Pax-2. Furthermore, Rig-1 and Pax-2 mRNAs are coexpressed in the hindbrain and spinal cord of the E11.5 mouse embryo, suggesting that Pax-2 may regulate Rig-1 expression during the embryonic stage. Pax-2 interacts with RB and reverses its transcriptional suppression on the Rig-1 promoter. In summary, the ubiquitous tumor suppressor RB and the neuron-enriched transcription factor Pax-2 may play a role in the regulation of Rig-1 expression during embryogenesis.
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10.1016/s0006-291x(02)02032-6
|
pubmed_882_11676
|
INTRODUCTION
Opportunistic screening is an effective means of identifying subjects with Atrial Fibrillation (AF). Previous studies of opportunistic screening have been performed areas with high population density and before the development of novel oral anticoagulant drugs. We performed a study to determine feasibility of AF screening in a predominantly rural, low population density area.
METHODS
Over 6 months, subjects 65 years and older were screened by local General Practitioners using radial pulse palpation confirmed by 12 lead Electrocardiogram. Data were recorded electronically and those with newly identified AF were followed up to examine management post diagnosis.
RESULTS
In total, 7262 subjects were screened and an irregular pulse was found in 916 (12.6%) of whom 735 (10.1%) had known AF and 55 (0.76%) had newly detected AF. Of these 55 patients with newly documented AF, 28 (50.9%) were women, 38 (69.1%) had hypertension and eight (14.5%) had a smoking history. Mean body mass index in subjects with newly documented AF was 28.9 kg/m(2)(SD 5.6) There was no significant difference in gender mix (P = 0.4), smoking history (P = 0.8) or alcohol history (P = 0.8) with the overall population. Fifty-one (92.7%) subjects had a CHA2DS2VaSC score ≥ 2 of whom 33 (64.7%) were eventually anticoagulated and nine (17.6%) commenced on Aspirin. The rate of newly identified patients in AF was lower than in previous reported key studies because of a higher rate of subjects with known AF.
CONCLUSION
Opportunistic AF screening in a rural environment identified a substantial number of new cases, although less than in previous screening studies.
|
10.1093/qjmed/hcw011
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pubmed_740_8162
|
The π-cation interaction that differs from the cation-π interaction is a valuable concept in molecular design of pharmaceuticals and pesticides. In this Perspective we present an up-to-date review (from 1995 to 2017) on bioactive molecules involving π-cation interactions with the recognition site, and categorize into systems of inhibitor-enzyme, ligand-receptor, ligand-transporter, and hapten-antibody. The concept of π-cation interactions offers use of π systems in a small molecule to enhance the binding affinity, specificity, selectivity, lipophilicity, bioavailability, and metabolic stability, which are physiochemical features desired for drugs and pesticides.
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10.1021/acs.jafc.8b00758
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pubmed_1080_1405
|
Information on a total of 119 patients with echocardiographically detected right heart thrombi was collected by questionnaire. Two major thrombus types with different morphology, etiology and clinical significance were identified: (1) 48 patients had long, thin, extremely mobile thrombi which resembled a worm or a snake (type A); (2) 57 patients had more or less immobile, non-specific clots resembling left heart thrombi (type B). Type A patients had a high incidence of deep venous thrombosis and a low incidence of potentially thrombogenetic cardiac abnormalities. The reverse was true for group B. These observations and the peculiar worm-shape of type A thrombi suggest that most type A thrombi originate in peripheral veins, while most type B thrombi develop within the right heart chambers. Clinically, type A patients were a high-risk group; pulmonary embolism was the rule and was usually severe. Early (less than or equal to 8 days) thrombus-related mortality was excessively high (42%), including 13 deaths from pulmonary embolism, one from paradoxical peripheral embolism and six perioperative deaths. Type B thrombi were much more benign; pulmonary embolism was not uncommon (40%) but never fatal. Early thrombus-related mortality was only 4% (two peri-operative deaths). Fourteen cases could not be classified as A or B because their thrombi were highly mobile (= not B) but not worm-shaped (= not A). This small group was intermediate between groups A and B in all respects. An analysis of the relationship between therapy and outcome revealed that type B thrombi had a good prognosis irrespective of the treatment. In type A cases early thrombus-related mortality was much lower with surgery (27%) than with conservative treatment (54%). However, the selection of surgical cases was certainly very biased and it is not clear to what extent the better results of surgery are caused by patient selection. Thus the optimal management of these cases remains to be determined.
|
10.1093/oxfordjournals.eurheartj.a059427
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pubmed_651_11251
|
Serial computer assisted quantitative sacroiliac scintiscanning (SI joint/sacrum ratios) 3 hours after low dosage (5 mCi) 99mTc methylene diphosphonate has been used as an objective index of sacroiliitis in a single blind 14-day cross-over comparison of azapropazone 600 mg b.d. and naproxen 500 mg b.d. in 18 patients with active sacroiliitis. Clinical assessments included visual analogue scales for measurement of pain and early morning stiffness, chest expansion, a modified Schober test, and goniometric measurement of thoracolumbar spinal flexion by means of an inclinometer. Statistically significant decreases in pain (p less than 0.001) and early morning stiffness (p less than 0.001) followed treatment with each NSAID, but there was no significant difference in the fall in these parameters, although 15 out of 18 patients expressed a preference for naproxen. Chest expansion and thoracolumbar flexion were not significantly affected by either drug. Serial quantitative scintigraphy showed a mean fall in joint sacrum ratios following each treatment which was statistically significant (p less than 0.02) only after naproxen. Serial quantitative scintigraphy can be used as an objective method of assessing sacroiliitis and was sufficiently sensitive to reflect the patients' subjective preference in a short-term comparison of 2 NSAID.
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10.1136/ard.43.2.157
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pubmed_794_10736
|
Therapeutic education aims to help patients acquire skills and knowledge, and to improve psychosocial aspects to manage chronic disease. After anterior cruciate ligament reconstruction (ACLR), only 35 to 60% of the patients are able to go back to their previous sport. Return to sport depends on the motivation of the patient. No therapeutic education has already been proposed. We aimed to evaluate the effect of therapeutic education sessions on knowledge improvement during inpatient rehabilitation after ACLR, compared to patients operated with the same surgical technic, but who had no therapeutic education because of outpatient rehabilitation. Sessions were performed by a multidisciplinary team. The evaluation of the knowledge was performed with a true or false 12-items self-report questionnaire. Fifty-four patients were studied and compared to 54 patients with no therapeutic education. The educated and the non-educated groups were comparable. The number of correct answers increased from 73% before therapeutic education to 95% at the end of the hospitalization (p < 0.001). This improvement persisted over time with 91.5% of correct answers at four months (p = 0.94). The non-educated group had 70% of correct answers. This was significantly lower than the results obtained from the educated group at four months (p < 0.001). It was comparable to the result obtained before therapeutic education (p = 0.91). Therapeutic patient education performed during hospitalization for rehabilitation enables patients to have a better knowledge of the stages from rehabilitation to return to sport and the risks of complication after ACLR.
|
10.3390/healthcare10050934
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pubmed_600_4028
|
It has been suggested that oral and maxillofacial surgery (OMFS) is better established in dental schools than in medical schools, and as a result, dental students have a greater insight into the scope of the specialty. We explore how much time is allocated to OMFS in the undergraduate curriculum in medical schools in the UK, and the students' perceptions of the specialty. A total of 186 final year students from 5 medical schools were recruited in a questionnaire-based survey. Of them, 141 (76%) reported no exposure to OMFS, and 37 of the 45 students (82%) who had had some exposure reported that it was not part of their timetabled curriculum. The 2 aspects considered most important by students were the long training pathway (n=38, 20%) and the requirement for dual qualification (n=33, 18%). Our results suggest that UK medical schools provide limited exposure to OMFS. We think it is important that the specialty is included in the compulsory undergraduate curriculum to ensure that medical students gain some awareness. This will not only allow junior doctors to make better informed decisions about their chosen careers, but may also help to reduce the number of inappropriate referrals from doctors in other specialties.
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pubmed_600_4028
|
pubmed_795_9981
|
This paper describes a compilation and further analysis of three qualitative studies, conducted independently, on women's health care decisions. Key areas regarding women's health, which span the life cycle, were examined including prenatal genetic screening, hormone replacement therapy and the use of complementary/alternative medicine in the treatment of breast cancer. Common themes were evident across all the focus groups in each of the three studies including: women's information seeking behavior; reliance on trusted information sources; the desire for information sharing; active involvement in the decision-making process; and accepting the consequences of the final decision. The findings have important implications for health care professionals as they engage women in the decision-making process about health concerns.
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10.1016/s0738-3991(02)00175-1
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pubmed_143_16225
|
BACKGROUND
Seasonal influenza is responsible for excess mortality and morbidity all over the northern hemisphere. To the authors' knowledge there are no comprehensive data available about morbidity and mortality of hospitalized influenza patients in Austria. The aim of this study was to assess the intrahospital mortality of hospitalized patients with influenza in this tertiary care hospital.
METHODS
During the 2017-2018 influenza season all patients presenting to the emergency department with influenza-like illness as well as hospitalized patients developing symptoms suggestive of influenza were tested with a rapid real-time PCR influenza test. In total 751 patients were tested at this tertiary care hospital and 330 showed a positive Influenza test result positive and were therefore included in the present study. The primary outcome was intrahospital mortality.
RESULTS
Of the 330 positively tested patients n = 110 (33%) were type A influenza and n = 220 (67%) were type B influenza. The hospitalization rate of patients presenting to the emergency department with a positive influenza test was 59% with a mean length stay of 8.6 days in this hospital and an intrahospital mortality of 8.3% (n = 16). Pneumonia was diagnosed in 30% of hospitalized patients with influenza and antibiotics were used in 65.8% of all hospitalized patients with influenza. Patients aged 80 years and older reached an intrahospital mortality of 16.4%.
CONCLUSION
The results of the present study show a high hospitalization and intrahospital mortality rate of influenza patients in a tertiary care hospital during the 2017-2018 influenza season in Austria.
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10.1007/s00508-019-01578-9
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pubmed_323_8180
|
Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer-associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. We conducted a hospital-based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs) in the interleukin 17A (IL17A) gene on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan Kit. IL17A rs4711998 A>G polymorphism was associated with the decreased risk of ESCC. When the IL17A rs4711998 AA homozygote genotype was used as the reference group, the AG genotype was associated with a significantly decreased risk for ESCC (AG vs. AA: adjusted odds ratio 0.72, 95% confidential interval 0.53-0.98, P = 0.039). However, there was no significant association between the other five SNPs and ESCC risk. Stratified analyses indicated that a significantly decreased risk of ESCC associated with the IL17A rs4711998 A>G polymorphism was evident among younger patients and patients who never smoking or drinking. These findings indicated that functional polymorphism IL17A rs4711998 A>G might contribute to ESCC susceptibility. However, our results were obtained with a limited sample size; the power of our analysis was low. Future larger studies with more rigorous study designs of other ethnic populations are required to confirm current findings.
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10.1111/dote.12045
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pubmed_485_15135
|
A linkage relationship has been detected between the bovine plasma protease inhibitor 2 (Pi-2) and S blood group loci by linkage study within a single pedigree. Using the sequential lodscore test, the recombination fraction (theta) with maximum likelihood has been estimated at 0.200 +/- 0.043, with a maximum lodscore value of 3.466 at theta = 0.200.
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10.1111/j.1365-2052.1987.tb00774.x
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pubmed_484_2120
|
Aeromonas hydrophila strains recovered from clinical samples and ambient sources were phenotypically and genetically identified. In addition, the distribution of putative virulence factors was assayed. To determine the genetic diversity of these strains, random amplification of polymorphic DNA (RAPD) and enterobacterial repetitive intergenic consensus (ERIC)-PCR markers were used. The discriminatory ability of the techniques, using Simpson's index, was 0.96 for both methods. The most consistent dendrogram was obtained when RAPD and ERIC data were combined. The genetic diversity revealed a high intra-specific genetic diversity (h=0.364+/-0.024 and I=0.538+/-0.030). The strains showed a tendency to cluster according to their origin of isolation (best-cut test 0.80 and bootstrap values >50%). The present study demonstrates and quantifies the high intra-specific diversity within this species and reveals a clear differentiation of strains according to their ecological origin. The distribution of virulence-related genes confirm that A. hydrophila is a genetically heterogeneous species that harbour ecotypes which have different pathogenic potential to human and other animals.
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10.1016/j.femsle.2004.11.011
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pubmed_250_17083
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In the search for new potentially anticancer drugs, series of angucyclinone aza-analogues containing pyridine and pyridopyridazine rings have been designed and synthesized by a highly efficient sequence involving a one-pot step for the synthesis of tricyclic quinone intermediate and highly regiocontrolled cycloaddition reactions with polarized 1,3-dienes. The new N-heterocyclic angular quinones were evaluated in vitro on normal human fibroblasts and on a panel of four distinct human cancer cell lines. All tested compounds showed high to moderate antitumor activity. Among the compounds, those with one and two pyridine moieties fused to the quinone system have shown the best effect. Structure-activity relationships established the main structural requirement for the activity of the new potential anticancer drugs.
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10.1016/j.bmc.2008.10.064
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pubmed_886_20573
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Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation. Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 muM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 muM, and three were moderately sensitive with IC50 values between 1 and 10 muM. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity.
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10.1186/1479-5876-8-39
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pubmed_229_1566
|
Hydrogen uptake in the presence of various terminal electron acceptors was examined in Escherichia coli mutants synthesizing either hydrogenase 1 or hydrogenase 2. Both hydrogenases mediated nitrate-dependent H2 consumption but neither of them was coupled with nitrite. Unlike hydrogenase 2, hydrogenase 1 demonstrated poor activity with electron acceptors of low midpoint redox potential. Oxygen-linked H2 uptake via hydrogenase 1 was observed over a wide range of air concentrations. Hydrogenase 2 catalyzed this reaction only at low air concentrations. Thus, hydrogenase 1 works in cells at higher redox potential, being more tolerant to oxygen than hydrogenase 2.
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10.1111/j.1574-6968.2001.tb10790.x
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pubmed_601_7905
|
The authors report on 15 unselected consecutive children and adolescents treated for hypothalamo-pituitary Cushing's disease by transsphenoidal sella exploration and microadenomectomy. The diagnosis was established by dynamic endocrine testing. Peri- and post-operative measurements of ACTH levels were used to monitor the effectivity of the surgical procedure. In one patient no microadenoma was found. Hypercortisolism was corrected in 13 of the 15 patients. Although transient secondary adrenocortical insufficiency occurred in all of the successfully operated patients, no permanent damage of the anterior or posterior pituitary was found by postoperative endocrinological follow-up testing. One patient died of pneumonia as a direct consequence of surgery.
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10.1007/978-3-7091-8813-2_17
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pubmed_861_17947
|
BACKGROUND
Associations between several persistent organic pollutants (POPs) and type 2 diabetes have been found in humans, but the relationship has rarely been investigated in the general population. The current nested case-control study examined internal exposure to polychlorinated biphenyls (PCB) and pesticides and the incidence of type 2 diabetes among participants of two population-based German cohort studies.
METHODS
We retrospectively selected 132 incident cases of type 2 diabetes and 264 age- and sex-matched controls from the CARdiovascular Living and Aging in Halle (CARLA) study (2002-2006, East Germany) and the Cooperative Health Research in the Region of Augsburg (KORA) study (1999-2001, South Germany) based on diabetes status at follow-up examinations in 2007-2010 and 2006-08, respectively (60% male, mean age 63 and 54 years). We assessed the association between baseline POP concentrations and incident diabetes by conditional logistic regression adjusted for cohort, BMI, cholesterol, alcohol, smoking, physical activity, and parental diabetes. Additionally, we examined effect modification by sex, obesity, parental diabetes and cohort.
RESULTS
In both cohorts, diabetes cases showed a higher BMI, a higher frequency of parental diabetes, and higher levels of POPs. We observed an increased chance for incident diabetes for PCB-138 and PCB-153 with an odds ratio (OR) of 1.50 (95%CI: 1.07-2.11) and 1.53 (1.15-2.04) per interquartile range increase in the respective POP. In addition, explorative results suggested higher OR for women and non-obese participants.
CONCLUSIONS
Our results add to the evidence on diabetogenic effects of POPs in the general population, and warrant both policies to prevent human exposure to POPs and additional research on the adverse effects of more complex chemical mixtures.
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10.1016/j.envint.2019.05.030
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pubmed_124_7864
|
The elevated blood pressure of spontaneously hypertensive rats (SHR) was further exacerbated by subjecting these animals to surgically induced adrenal-regeneration hypertension (ARH). When chronic abnormally high blood pressure had been in effect for 12 weeks, the animals were subjected to an acute and massive myocardial infarction with isoprenaline. Hypertensive but intact SHR survived better than ARH-treated animals. Circulating enzyme (CPK, SGOT, SGPT and LDH), lipid and glucose levels and BUN manifested much greater excursions commensurate with more extensive myocardial infarction in ARH-treated than in intact SHR. ARH-treated SHR displayed a high incidence of atrial and ventricular thrombi associated with frequent left ventricular aneurysm formation. It is suggested that the more extensive myocardial connective tissue and ground-substance degeneration in ARH-treated SHR is due to the impoverished steroidogenic capacity of their regenerated adrenal glands.
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pubmed_124_7864
|
pubmed_1057_2050
|
Correction for 'Fullerene C76 as a novel electrocatalyst for VO2+/VO2+ and chlorine evolution inhibitor in all-vanadium redox flow batteries' by Farah A. El Diwany et al., Chem. Commun., 2020, 56, 7569-7572, DOI: 10.1039/D0CC03544K.
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10.1039/d0cc90303e
|
pubmed_266_20030
|
WHAT IS KNOWN AND OBJECTIVE
This article summarizes the effects of sivelestat on acute lung injury/acute respiratory distress syndrome (ALI/ARDS) or ARDS with coagulopathy, both of which are frequently seen in patients with COVID-19.
COMMENT
COVID-19 patients are more susceptible to thromboembolic events, including disseminated intravascular coagulation (DIC). Various studies have emphasized the role of neutrophil elastase (NE) in the development of DIC in patients with ARDS and sepsis. It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of injuries in alveolar epithelium and vascular endothelium, as well as reversing the neutrophil-mediated increased vascular permeability.
WHAT IS NEW AND CONCLUSIONS
Sivelestat, a selective NE inhibitor, has not been evaluated for its possible therapeutic effects against SARS-CoV-2 infection. Based on its promising beneficial effects in underlying complications of COVID-19, sivelestat could be considered as a promising modality for better management of COVID-19-induced ALI/ARDS or coagulopathy.
|
10.1111/jcpt.13251
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pubmed_140_9661
|
Toxicity of reduced graphene oxide (rGO) has been a topic of multiple studies and was shown to depend on a variety of characteristics of rGO and biological objects of interest. In this paper, we demonstrate that when studying the same dispersions of rGO and fluorescent Escherichia coli (E. coli) bacteria, the outcome of nanotoxicity experiments also depends on the type of culture medium. We show that rGO inhibits the growth of bacteria in a nutrition medium but shows little effect on the behavior of E. coli in a physiological saline solution. The observed effects of rGO on E. coli in different media could be at least partially rationalized through the adsorption of bacteria and nutrients on the dispersed rGO sheets, which is likely mediated via hydrogen bonding. We also found that the interaction between rGO and E. coli is medium-dependent, and in physiological saline solutions they form stable flocculate structures that were not observed in nutrition media. Furthermore, the aggregation of rGO and E. coli in saline media was observed regardless of whether the bacteria were alive or dead. Filtration of the aggregate suspensions led to nearly complete removal of bacteria from filtered liquids, which highlights the potential of rGO for the filtration and separation of biological contaminants, regardless of whether they include live or dead microorganisms.
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10.3390/nano9101454
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pubmed_949_214
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The relative contribution of the scaphoid, lunate, triquetrum, and capitate to wrist motion was examined in 6 fresh cadaver forearms. A wrist-joint motion simulator was used to dynamically move each wrist through planar and nonplanar motions. During wrist flexion-extension, the motion of the capitate closely followed the motion of the third metacarpal, while the lunate motion was approximately 50% of the total motion; the triquetrum, 65%, and the scaphoid, 90%. Similar differences in motion for these carpal bones occurred during radioulnar deviation and circumduction and dart-throw motions. This suggests that the scaphoid, lunate, and triquetrum do not normally function as a single unit, but that each bone has an unique arc of motion during global wrist motion.
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10.1016/S0363-5023(97)80133-5
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pubmed_262_7744
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In 2003, the ISO 15189 international standardization program on the quality and competence of the clinical reference laboratory was introduced. To date, 46 facilities have committed themselves to providing a higher level of medical service by incorporating a quality management system (QMS) and acquiring accreditation. QMS is defined as "setting up a policy and goals pertaining to quality, and adopting an appropriate system," and is a scheme that includes all managerial and technical factors that can affect test results. Regarding the Health Sciences Research Institute Group, 4 facilities have previously received the accreditation described above, but in the process of implementing the QMS, a number of problems have been identified. Here, we report on the effectiveness of adopting such a QMS based on the results of employee questionnaires, internal audits, customer complaint analyses, and external audits by the Japan Accreditation Board for Conformity Assessment (JAB), the official inspection body for accreditation.
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pubmed_262_7744
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pubmed_582_15397
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Ab initio calculations, at the level of second order Møller-Plesset perturbation theory, and using a triple-zeta Gaussian basis set with polarization and diffuse functions on all atoms, have been carried out on the donor-acceptor complexes of boron trifluoride with ammonia and its mono-, di- and trimethyl derivatives. The structures, interaction energies and vibrational spectra of the complexes have been determined. An eclipsed and a staggered conformer have been examined for each complex, and the preferred conformer was found to be the staggered species in each case. The computed data have been compared with those for some similar complexes containing boron trifluoride and a series of oxygen and sulphur electron donors (water, hydrogen sulphide, methanol, methanethiol, dimethyl ether and dimethyl sulphide) and the effect of successive methyl substitution in all three series has been investigated.
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10.1016/j.saa.2008.01.014
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pubmed_373_2840
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Magnetoencephalographic (MEG) brain mapping was performed in 90 patients with lesions associated with eloquent sensorimotor cortex. The MEG-derived sensorimotor mapping information was utilised for risk analysis and planning. Subsequently, these patients underwent either stereotactic volumetric resection, stereotactic biopsy or non-surgical management of their lesions. In seventeen patients, the MEG sensorimotor localization was integrated into an operative stereotactic database (consisting of CT, MRI and digital angiography) to be used in an interactive fashion during computer-assisted stereotactic volumetric resection procedures. The spatial relationship between the MEG derived functional anatomy, the structural/radiological anatomy and the pathology could then be viewed simultaneously, thereby affording a safer trajectory and approach. In addition, the real-time availability of functional mapping information in an interactive fashion helped reduce surgical risk and minimise functional morbidity. All of these patients had resection of their lesions with no change in their neurological status. In conclusion, MEG is a non-invasive, accurate, and reproducible method for pre-operative assessment of patients with lesions associated with eloquent sensory and motor cortex. The interactive use of MEG functional mapping in the operating room can allow for a safer approach and resection of these eloquent cortex lesions.
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10.1007/978-3-7091-6513-3_16
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pubmed_768_19464
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Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its clinical significance in human prostate cancer have not been reported. In the present study, we analyzed the expression pattern of Rsf-1 in human prostate cancer tissues and found that Rsf-1 was overexpressed in 45 % of prostate cancer specimens. There was a significant association between Rsf-1 overexpression and tumor stage (p=0.0039) and preoperative PSA level (p=0.015). Furthermore, Rsf-1 overexpression correlated with poor biomedical recurrence-free survival in prostate cancer patients (p<0.001). Rsf-1 overexpression could serve as an independent predictor for poor recurrence-free survival (p=0.012). In addition, small interfering RNA (siRNA) knockdown in DU145 cells with high endogenous Rsf-1 expression decrease cell proliferation, colony formation, and invasion. In conclusion, Rsf-1 is overexpressed in human prostate cancers and serves as a novel prognostic marker. Rsf-1 contributes to prostate cancer cell growth and invasion, which makes it a candidate therapeutic target.
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10.1007/s13277-014-1766-7
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pubmed_445_10840
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The synthesis of inorganic pyrophosphate by the mitochondria of Endomyces magnusii was found to be coupled with respiration. The mitochondria of E. magnusii can utilize the energy of the phosphoanhydride bond of inorganic pyrophosphate for the synthesis of ATP. The study with inhibitors suggests the participation of inorganic pyrophosphatase and ATPase in this process.
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pubmed_445_10840
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pubmed_428_4572
|
BACKGROUND
The fat mass and obesity-associated (FTO) gene harbors the strongest common genetic variant associated with obesity. Recently, rs1421085-T to -C substitution mapped in FTO was shown to induce a developmental shift of human adipocytes from an energy-combusting beige to an energy-storing white phenotype in vitro. As browning of adipocytes selectively enhances fat oxidation (FatOx), we hypothesized that rs1421085-C in FTO is associated with deceased FatOx compared with carbohydrate oxidation (CarbOx) and an increased respiratory quotient (RQ).
METHODS
In the Netherlands Epidemiology of Obesity study, a population-based cohort study of middle-aged individuals (45-65 years), anthropometry and genotyping was performed (n=5744), in addition to indirect calorimetry (n=1246). With linear regression analyses, we examined associations of rs1421085 genotype with FatOx, CarbOx and RQ.
RESULTS
In the total study population, 36.7% carried the rs1421085-TT genotype, 47.6% rs1421085-CT and 15.7% rs1421085-CC. Mean (s.d.) age was 56 (6) years, mean (s.d.), body mass index (BMI) was 26.3 (4.4) kg m-2 and 56% of the total population were women. Measures of adiposity (difference, 95% confidence interval) were higher in CC carriers compared with that in rs1421085-TT carriers: BMI +0.56 (0.15, 0.98) kg m-2, waist circumference +1.25 (0.02, 2.49) cm and total body fat mass +1.21 (0.28, 2.14) kg. However, no differences in mean FatOx (+2.5 (-2.4, 7.4) mg min-1), CarbOx (-6.1 (-17.4, 5.2) mg min-1) or RQ (-0.01 (-0.02, 0.01)) were observed between the two genotypes.
CONCLUSIONS
We observed no evidence for associations of rs1421085 in FTO with FatOx and RQ. This indicates that the rs1421085-C allele in FTO induces obesity likely via other pathways than via reduced FatOx.
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10.1038/ijo.2017.146
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pubmed_82_6345
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A model of medical examinations useful in general evaluation of the nervous system was proposed. It is designed for doctors of occupational health services who perform prophylactic examinations but they are not neurologists. Technically simple elements of routine neurological examinations are selected. They are easy to perform and provide most observations which can be interpreted by a doctor who is not specialised in neurology.
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pubmed_82_6345
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pubmed_1043_2741
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It was demonstrated using the indirect immunofluorescent technique that normal human and rabbit sera, and IgG isolated from them intensively reacted with fibroblasts of human and bovine heart valves. The results obtained with Fab and Fc fragments of IgG sugges that this reaction is due to the Fc region of the IgG molecule and related to the presence of the Fc receptor on fibroblasts of heart valves.
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pubmed_1043_2741
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pubmed_835_5029
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Autistic young people experience higher levels of anxiety than neurotypical young people. Having worries is part of feeling anxious. This makes it surprising that very little research has looked at the kind of worries autistic young people have. Leaving school, in particular, can be a worrying time for young people. Twenty-two autistic young people and 22 neurotypical young people who were at mainstream secondary schools agreed to take part in the study. They were between 16 and 18 years of age. They were asked to sort through a series of pictures, showing the different types of worries that young people might experience. They were then asked to pick out their four main worries and say how much they thought about each worry and how upset the worry made them. They also completed a questionnaire about their level of anxiety. There were similarities and differences between the autistic and neurotypical young people's worries. Both groups worried about failing and how they might get on in further education. The autistic young people were more worried about change and friendships. Work and money were particular concerns for the neurotypical young people. The autistic young people said that they found their worries more upsetting than the neurotypical young people. Having a better understanding of autistic young people's worries at important points in their lives might mean that more timely help and support can be given to them. Simply knowing what to ask young autistic school leavers about may help them to express unspoken concerns.
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10.1177/13623613221111313
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pubmed_649_4860
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A protein-tyrosine kinase has been isolated from a soluble extract of bovine thymus based on its ability to phosphorylate the tyrosine-containing peptide angiotensin I. The purification procedure employs sequential chromatography on columns of DEAE-cellulose, heparin-agarose, casein-agarose, butyl-agarose, and Sephadex G-75. The purified enzyme (p40) is a monomer of Mr = 40,000. The p40 kinase contains an ATP-binding site as determined by photoaffinity labeling experiments and catalyzes an intramolecular autophosphorylation reaction that leads to its modification on tyrosine. Of several proteins tested only the cytoplasmic domain of the erythrocyte band 3 protein serves as a good substrate for p40 (Km = 12 microM). Increasing concentrations of NaCl stimulate the phosphorylation of angiotensin I, inhibit the phosphorylation of band 3, and have no effect on the autophosphorylation of p40. At low concentrations of NaCl, Mn2+ is the preferred divalent cation. Peptide mapping experiments indicate that p40 is distinct from pp60src and from the major phosphotyrosine containing proteins of T and B lymphocyte membranes.
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pubmed_649_4860
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pubmed_581_9942
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This study aimed to determine the parental correlates of body weight status among adolescents in Tehran. The participants were 465 high school students and their parents who resided in Tehran. Body weight and height of the students were measured, and body mass index (BMI)-for-age and body weight status of the students were determined according to the world health organization growth reference (2007). Parents of the students completed a self-administered questionnaire including socio-demographic information, self-reported parental body weight and height, and parental perception of student's body weight status. About half of the parents had an incorrect perception about body weight status of their children with higher rates of underestimation than overestimation. The percentage of parents who correctly perceived body weight status of the students decreased from 100.0% in severe thinness group to 14.0% in obese group. There were no significant associations between marital status, occupation, and education of parents and BMI-for-age of the students. While, both BMI of mother and BMI of father were significantly associated with students' BMI-for-age (r = 0.29 and r = 0.27, respectively; P < 0.05). A great number of parents had incorrect perception regarding body weight status of their offspring; this was true specifically for parents of overweight and obese students. Both parental BMI and parental perception regarding students' body weight status were associated with students' BMI-for-age, indicating the need for parental involvement in weight management programs targeting adolescents.
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10.5812/ijem.42701
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pubmed_1044_18241
|
AIM
To validate a reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) assay to detect SARS-CoV-2 in saliva in two independent Aotearoa New Zealand laboratories.
METHODS
An RT-qPCR assay developed at University of Illinois Urbana-Champaign, USA, was validated in two New Zealand laboratories. Analytical measures, such as limit of detection (LOD) and cross-reactivity, were performed. One hundred and forty-seven saliva samples, each paired with a contemporaneously collected nasal swab, mainly of nasopharyngeal origin, were received. Positive (N=33) and negative (N=114) samples were tested blindly in each laboratory. Diagnostic sensitivity and specificity were then calculated.
RESULTS
The LOD was <0.75 copy per µL and no cross-reactivity with MERS-CoV was detected. There was complete concordance between laboratories for all saliva samples with the quantification cycle values for all three genes in close agreement. Saliva had 98.7% concordance with paired nasal samples: and a sensitivity, specificity and accuracy of 97.0%, 99.1% and 99.1%, respectively.
CONCLUSION
This saliva RT-qPCR assay produces reproducible results with a low LOD. High sensitivity and specificity make it a reliable option for SARS-CoV-2 testing, including for asymptomatic people requiring regular screening.
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pubmed_1044_18241
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pubmed_540_17174
|
Some of the SARS-CoV-2 variants are said to be more infectious than the previous others and are causing panic around the globe. Cases related to Delta plus (δ+) and omicron (ο) variants are on the rise worldwide. This sudden surge warrants an investigation into the reasons for its binding with ACE-2. The present study attempts to find out the structural basis of binding interactions of SARS-CoV-2 mutants based on computational modeling and comparative analysis. In silico strategies including protein-protein docking, mutation analysis, molecular dynamics, and binding energy calculations were used to study the binding of the 'receptor binding domain' (RBD) of the seven 'variants of concern' which include Alpha (α), Beta (β), Gamma (γ), Kappa (κ), Delta (δ), Delta plus (δ+) and omicron (ο) with ACE-2 (human angiotensin-converting enzyme-2) and with antibodies. Among all the variants dealt with in this study, Delta plus and omicron were found to be binding more strongly to ACE-2 than others due to inherent mutations and the consequent change in the hydrophilic and hydrophobic environment of the binding site. Furthermore, molecular dynamic (MD) simulations and subsequent MM/PBSA calculations provided useful structural insights into key residues participating in the interaction. Infectivity of a virus could be dependent on the interplay of evading antibodies and simultaneously attaching strongly with the host receptor. A cross-correlation between mutant spike proteins' binding with ACE-2 and antibodies provides a holistic assessment of the binding nature of these mutants vis-à-vis native virus and offers opportunities for designing potential therapeutics against these new mutants.
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10.1080/07391102.2022.2108901
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pubmed_551_7029
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In this report, we present a hybrid structure involving a small quantity of Co element uniformly deposited on porous SnO(2) spheres as stable and high capacity anode materials for lithium-ion batteries. Specifically, Co element deposited on SnO(2) nanomaterials exhibited an exceptional reversible capacity of 810 mA h g(-1) after 50 cycles which is higher than the pure SnO(2) electrode. Based on the experiments results, a possible mechanism for the change of this structure during lithium ion insertion/extraction was proposed. The minute quantity of Co element uniformly deposited on SnO(2) spherical structure could prevent Sn aggregation during charging-discharging, and high porosity of the spherical structure allowed the volume expansion during lithium ion alloying/dealloying. The SnO(2) deposited with small quantities of Co element as electrode facilitated improved performance of lithium ion batteries with higher energy densities.
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10.1039/c2nr31307c
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pubmed_893_3595
|
We studied the effect of moderate heat stress (30oC) and muscarinic cholinergic receptor agonists arecoline and pilocarpine on sensitivity of the behavior of the nematode Caenorhabditis elegans of N2 line to the action of the agonist of nicotinic cholinergic receptor agonist levamisole. Heat stress and muscarinic cholinergic receptor agonists increased the sensitivity of swimming induced by mechanical stimulation to levamisole (32-64 μM), which manifested in dyscoordination of locomotor muscles during swimming and complete loss of ability to swim. Combined exposure to heat stress and muscarinic cholinergic receptor agonists revealed their synergism in the influence on sensitivity of swimming behavior to levamisole: heating to 30oC potentiated the effect of arecoline and arecoline potentiated the effect of heat stress. It is assumed, that the effect of heat stress on the sensitivity of nicotinic receptors is mediated by its effect on muscarinic receptors.
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10.1007/s10517-017-3944-2
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pubmed_19_14188
|
The goal of this study was to determine whether intensive training can ameliorate cognitive skills in children. Children aged 7 to 9 from low socioeconomic backgrounds participated in one of two cognitive training programs for 60 minutes/day and 2 days/week, for a total of 8 weeks. Both training programs consisted of commercially available computerized and non-computerized games. Reasoning training emphasized planning and relational integration; speed training emphasized rapid visual detection and rapid motor responses. Standard assessments of reasoning ability - the Test of Non-Verbal Intelligence (TONI-3) and cognitive speed (Coding B from WISC IV) - were administered to all children before and after training. Neither group was exposed to these standardized tests during training. Children in the reasoning group improved substantially on TONI (Cohen's d = 1.51), exhibiting an average increase of 10 points in Performance IQ, but did not improve on Coding. By contrast, children in the speed group improved substantially on Coding (d = 1.15), but did not improve on TONI. Counter to widespread belief, these results indicate that both fluid reasoning and processing speed are modifiable by training.
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10.1111/j.1467-7687.2010.01005.x
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pubmed_120_8355
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Porphyromonas gingivalis is one of the major causative organisms of periodontitis and has been shown to be susceptible to toluidine blue-mediated photosensitization in vitro. The aims of the present study were to determine whether this technique could be used to kill the organism in the oral cavities of rats and whether this would result in a reduction in the alveolar bone loss characteristic of periodontitis. The maxillary molars of rats were inoculated with P. gingivalis and exposed to up to 48 J of 630-nm laser light in the presence of toluidine blue. The number of surviving bacteria was then determined, and the periodontal structures were examined for evidence of any damage. When toluidine blue was used together with laser light there was a significant reduction in the number of viable P. gingivalis organisms. No viable bacteria could be detected when 1 mg of toluidine blue per ml was used in conjunction with all light doses used. On histological examination, no adverse effect of photosensitization on the adjacent tissues was observed. In a further group of animals, after time was allowed for the disease to develop in controls, the rats were killed and the level of maxillary molar alveolar bone was assessed. The bone loss in the animals treated with light and toluidine blue was found to be significantly less than that in the control groups. The results of this study show that toluidine blue-mediated lethal photosensitization of P. gingivalis is possible in vivo and that this results in decreased bone loss. These findings suggest that photodynamic therapy may be useful as an alternative approach for the antimicrobial treatment of periodontitis.
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10.1128/AAC.47.3.932-940.2003
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pubmed_5_18137
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Blockers of CFTR with well-characterized kinetics and mechanism of action will be useful as probes of pore structure. We have studied the mechanism of block of CFTR by the arylaminobenzoates NPPB and DPC. Block of macroscopic currents by NPPB and DPC exhibited similar voltage-dependence, suggestive of an overlapping binding region. Kinetic analysis of single-channel currents in the presence of NPPB indicate drug-induced closed time constants averaging 2.2 msec at -100 mV. The affinity for NPPB calculated from single-channel block, K(D) = 35 microm, exceeds that for other arylaminobenzoates studied thus far. These drugs do not affect the rate of activation of wild-type (WT) channels expressed in oocytes, consistent with a simple mechanism of block by pore occlusion, and appear to have a single binding site in the pore. Block by NPPB and DPC were affected by pore-domain mutations in different ways. In contrast to its effects on block by DPC, mutation T1134F-CFTR decreased the affinity and reduced the voltage-dependence for block by NPPB. We also show that the alteration of macroscopic block by NPPB and DPC upon changes in bath pH is due to both direct effects (i.e., alteration of voltage-dependence) and indirect effects (alteration of cytoplasmic drug loading). These results indicate that both NPPB and DPC block CFTR by entering the pore from the cytoplasmic side and that the structural requirements for binding are not the same, although the binding regions within the pore are similar. The two drugs may be useful as probes for overlapping regions in the pore.
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10.1007/s002320001053
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pubmed_855_7345
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Homologous recombination (HR) occurs in all organisms, and is important for repair of DNA damage, chromosome segregation during meiosis, and genetic diversification. Genes critical for recombinational DNA repair and meiotic recombination include members of the RecA/RAD51 family, of which seven have been identified in mammals. Here, we describe the disruption of Rad51d (recently designated Rad51l3) in mice and its phenotypic consequences. Rad51d-deficient mice die between 8.5 and 11.5 dpc. The affected embryos are smaller than littermates, posteriorly truncated, and developmentally delayed. Embryonic fibroblasts from mutant embryos could not be propagated more than one generation in culture. Rad51d-deficient blastocysts were not sensitive to gamma radiation or methylmethanesulfonate (MMS) in blastocyst outgrowth experiments. The variable and generalized developmental progression defects in Rad51d-deficient embryos suggests that mutant cells may undergo delayed or suboptimal repair of DNA damage, resulting in accumulated degrees of mutation and/or cell cycle perturbation that are incompatible with normal embryonic development. genesis 26:167-173, 2000.
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10.1002/(sici)1526-968x(200003)26:3<167::aid-gene1>3.0.co;2-m
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pubmed_179_17804
|
OBJECTIVE
The aim: To identify admission variables associated with Functional Ambulation Classif i cation (FAC) 1 to 4 (unable to walk without assistance) at time of discharge (dFAC<5) from a comprehensive stroke unit (CSU).
PATIENTS AND METHODS
Materials and methods: Patients admitted to CSU at Oberig Clinic, Kyiv, Ukraine, August 01, 2012 to July 31, 2018, were screened for study selection criteria. Association of qualifying patients' data with FAC score at CSU discharge was retrospectively assessed by univariate and multivariate logistic regression, odds ratios (OR) and 95% conf i dence intervals (95% CI) using MedCalc v. 19.1.
RESULTS
Results: The study cohort (442 of 492 admitted patients) had median age: 65.8 years, gender: 43% female, stroke-type: 84% ischemic strokes, median baseline NIHSS total score: 10. Estimated time from stroke onset to CSU admission was from less-than-24-hours to over-180-days. The univariate logistic regression analysis, revealed 28 variables signif i cantly (p<0.05) related to dFAC<5; while in multivariate analysis only 4 admission variables were signif i cantly (p<0.05) associated with dFAC<5: age (OR= 1.07; 95% CI 1.03-1.10, on average, for each additional year, p<0.001), baseline NIHSS score (OR= 1.15; 95% CI 1.08-1.22, on average, with a 1-point increase in the total score, p<0.001), initial FAC score (OR= 0.40; 95% CI 0.31-0.52, on average, with a 1-point decrease in the score, p<0.001), and very late CSU admission (over 180 days; OR= 5.7; 95% CI 1.9-17.1, p=0.002).
CONCLUSION
Conclusions: Four admission variables may be independently associated with dFAC<5 and provide opportunity for improving CSU outcomes and mitigating risk for inability to ambulate without assistance after CSU discharge.
|
pubmed_179_17804
|
pubmed_497_7771
|
The differences between maximum-likelihood (ML) and regression (REG) interval mapping in the analysis of quantitative trait loci (QTL) are investigated analytically and numerically by simulation. The analytical investigation is based on the comparison of the solution sets of the ML and REG methods in the estimation of QTL parameters. Their differences are found to relate to the similarity between the conditional posterior and conditional probabilities of QTL genotypes and depend on several factors, such as the proportion of variance explained by QTL, relative QTL position in an interval, interval size, difference between the sizes of QTL, epistasis, and linkage between QTL. The differences in mean squared error (MSE) of the estimates, likelihood-ratio test (LRT) statistics in testing parameters, and power of QTL detection between the two methods become larger as (1) the proportion of variance explained by QTL becomes higher, (2) the QTL locations are positioned toward the middle of intervals, (3) the QTL are located in wider marker intervals, (4) epistasis between QTL is stronger, (5) the difference between QTL effects becomes larger, and (6) the positions of QTL get closer in QTL mapping. The REG method is biased in the estimation of the proportion of variance explained by QTL, and it may have a serious problem in detecting closely linked QTL when compared to the ML method. In general, the differences between the two methods may be minor, but can be significant when QTL interact or are closely linked. The ML method tends to be more powerful and to give estimates with smaller MSEs and larger LRT statistics. This implies that ML interval mapping can be more accurate, precise, and powerful than REG interval mapping. The REG method is faster in computation, especially when the number of QTL considered in the model is large. Recognizing the factors affecting the differences between REG and ML interval mapping can help an efficient strategy, using both methods in QTL mapping to be outlined.
|
10.1093/genetics/156.2.855
|
pubmed_748_10551
|
BACKGROUND
We investigated whether increased collagen type I synthesis and deposition contribute to enhancement of myocardial fibrosis and deterioration of cardiac function in patients with hypertensive heart disease (HHD).
METHODS AND RESULTS
We studied 65 hypertensives with left ventricular hypertrophy subdivided into 2 groups: 34 patients without heart failure (HF) and 31 patients with HF. Transvenous endomyocardial biopsies of the interventricular septum were performed to quantify the amount of fibrotic tissue and the extent of collagen type I deposition. The carboxy-terminal propeptide of procollagen type I (PIP), an index of collagen type I synthesis, was measured by radioimmunoassay in serum samples from the coronary sinus and the antecubital vein. Compared with normotensives, the amount of collagen tissue, the extent of collagen type I deposition, and coronary and peripheral PIP were increased (P<0.01) in the 2 groups of hypertensives. These parameters were also increased (P<0.01) in HF hypertensives compared with non-HF hypertensives. Coronary PIP was higher (P<0.01) than peripheral PIP in hypertensives but not in normotensives. The amount of collagen tissue was inversely correlated with the ejection fraction and directly correlated with both coronary and peripheral PIP in all hypertensives.
CONCLUSIONS
These findings suggest that an excess of cardiac collagen type I synthesis and deposition may be involved in the enhancement of myocardial fibrosis that accompanies the development of HF in HHD. In addition, our data show that the heart secretes PIP via the coronary sinus into the peripheral circulation in patients with HHD. Thus, PIP determined in peripheral blood can be a useful marker of myocardial fibrosis in these patients.
|
10.1161/01.CIR.0000140973.60992.9A
|
pubmed_686_14888
|
Estrogen-dependent transcriptional activation by estrogen receptor alpha (ERalpha) depends on the conformation of helices 3 and 12 in the ligand-binding domain. To better understand the function of helix 3 in ERalpha, we examined the role of charged residues, which are conserved in most steroid receptors in helix 3, in estrogen-dependent transactivation. The replacement of Asp-351 with lysine (D351K) or leucine (D351 L) completely abolished estrogen-dependent transactivation without affecting estrogen-binding, DNA-binding and homodimerization activities in ERalpha. The mutations dramatically reduced the ligand-dependent activation function 2 activity and impaired the ability of ERalpha to bind p160 coactivators. In addition, the D351K mutant effectively inhibited the transcriptional activation activity of wild-type ERalpha. Furthermore Asp-351 was required not only for the estrogen-dependent conformational change of wild-type ERalpha but also for the constitutive transcriptional activity and ligand-independent active conformation of ERalpha mutant Y537N. Similarly, in the orphan nuclear receptor called estrogen-related receptor 3 (ERR3), the replacement of Asp-273 (the corresponding amino acid to Asp-351 in ERalpha) with lysine abolished constitutive transcriptional activity of ERR3 without affecting DNA-binding activity and impaired the ability of the receptor to interact with p160 coactivators. These data suggest a role of Asp-351 in inducing and stabilizing the active conformation of ERalpha, and our results experimentally confirm the concept that Asp-351 in helix 3 interacts with the amide hydrogen of L540 in helix 12 to form a transcriptionally competent surface for binding p160 coactivators.
|
10.1677/jme.1.01846
|
pubmed_361_5962
|
Two patients with acute myelomonocytic leukemia (AMMoL) were tested to determine whether or not their cells produced granulocyte colony-stimulating factor (G-CSF). Using the NFS-60 bioassay method, relatively high levels of G-CSF were demonstrated in the serum pre-treated with acid-dialysis and in the media conditioned by leukemia cells. Northern blot analysis for G-CSF using cDNA as a probe revealed that G-CSF production was increased at the mRNA level in the cells. No rearrangement at the DNA level, however, was observed by genomic Southern analysis. Our data indicate that the leukemic cells in AMMoL probably have the capacity to synthesize and secrete G-CSF.
|
10.1016/0145-2126(88)90007-0
|
pubmed_223_7542
|
The MIRACUM consortium is developing a Clinical Trials Recruitment Support System to support the data-driven recruitment of patients for clinical trials. The design of the prototype includes both open source solutions (OMOP CDM, Atlas) and open standards for interoperability (FHIR). The aim of the prototype is to create a patient screening list of potential participants for a clinical study. The paper shows the modular structure and functionality of the prototype building the foundation for the practical implementation of the CTRSS and, at the same time, demonstrating the use of open source solutions and standards for the development of clinical support systems.
|
10.3233/SHTI200142
|
pubmed_1032_6960
|
SCOPE
Dietary polyphenols may protect against breast cancer. However, it is unknown whether polyphenols reach human malignant breast tumors in molecular forms and(or) at concentrations likely to act against cancer.
METHODS AND RESULTS
Ninteen breast cancer patients consumed three capsules daily from biopsy-confirmed diagnosis to surgery (6 ± 2 days). The capsules contained pomegranate, orange, lemon, olive, cocoa, and grapeseed extracts plus resveratrol, providing 37 different phenolics (473.7 mg), theobromine and caffeine (19.7 mg). A total of 101 metabolites are identified in urine, 69 in plasma, 39 in normal (NT), and 33 in malignant (MT) tissues by UPLC-ESI-QTOF-MS. Eight control patients did not consume extracts. Phenolic-derived metabolites in MT and NT are mainly glucuronidated and(or) sulfated. Some representative metabolites detected in MT (median and range, pmol g-1 ) are urolithin-A-3-O-glucuronide (26.2; 3.2-66.5), 2,5-dihydroxybenzoic acid (40.2; 27.7-52.2), resveratrol-3-O-sulfate (86.4; 7.8-224.4), dihydroresveratrol-3-O-glucuronide (109.9; 10.3-229.4), and theobromine (715.0; 153.9-3,216). Metabolites, as detected in breast tissues, do not exert antiproliferative or estrogenic/antiestrogenic activities in MCF-7 breast cancer cells.
CONCLUSION
This is the first study that describes the metabolic profiling of dietary phenolics and methylxanthines in MT and NT comprehensively. Although phase-II conjugation might hamper a direct anticancer activity, long-term tumor-senescent chemoprevention cannot be discarded.
|
10.1002/mnfr.201801239
|
pubmed_1115_20228
|
AIM
To study the expression of myeloid-related proteins(MRP)8 and myeloid-related proteins(MRP)14 in human esophageal squamous cell carcinoma and to investigate if there was any correlation between MRP8 and MRP14 expression level and histopathological grade in these tumors.
METHODS
In this study, 65 cases of advanced esophageal squamous cell carcinoma were assessed for MRP8 and MRP14 expression using immunohistochemistry. Statistical analysis was performed for the comparison of MRP8 and MRP14 expression in normal and tumor tissues, and their relationship with clinicopathological features.
RESULTS
Reduced or absent expression of MRP8 and MRP14 was observed in esophageal squamous cell carcinoma, with a significant difference between tumor tissues and normal tissues (P<0.01 and P<0.01 for MRP8 and MRP14, respectively). Poorly differentiated tumors presented a greater decrease than well and moderately differentiated tumors, with a correlation between their protein level and histopathological grading (P<0.001 and P<0.001, respectively). However, no significant association was found between MRP8 and MRP14 expression and age or gender (P>0.05).
CONCLUSION
These findings suggest that the decreased expression of MRP8 and MRP14 might play an important role in the pathogenesis of human esophageal squamous cell carcinoma, being particularly associated with poor differentiation of tumor cells.
|
10.3748/wjg.v10.i8.1093
|
pubmed_1086_11393
|
Blood-cerebrospinal fluid (CSF) barrier function and expansion of the ventricular system were investigated in embryonic rats (E12-18). Permeability markers (sucrose and inulin) were injected intraperitoneally and concentrations measured in plasma and CSF at two sites (lateral and 4th ventricles) after 1 h. Total protein concentrations were also measured. CSF/plasma concentration ratios for endogenous protein were stable at approximately 20% at E14-18 and subsequently declined. In contrast, ratios for sucrose (100%) and inulin (40%) were highest at the earliest ages studied (E13-14) and then decreased substantially. Between E13 and E16 the volume of the lateral ventricles increased over three-fold. Decreasing CSF/plasma concentration ratios for small, passively diffusing molecules during embryonic development may not reflect changes in permeability. Instead, increasing volume of distribution appears to be important in this decline. The intracellular presence of a small marker (3000 Da biotin-dextranamine) in plexus epithelial cells following intraperitoneal injection indicates a transcellular route of transfer. Ultrastructural evidence confirmed that choroid plexus tight junctions are impermeable to small molecules at least as early as E15, indicating the blood-CSF barrier is morphologically and functionally mature early in embryonic development. Comparison of two albumins (human and bovine) showed that transfer of human albumin (surrogate for endogenous protein) was 4-5 times greater than bovine, indicating selective blood-to-CSF transfer. The number of plexus epithelial cells immunopositive for endogenous plasma protein increased in parallel with increases in total protein content of the expanding ventricular system. Results suggest that different transcellular mechanisms for protein and small molecule transfer are operating across the embryonic blood-CSF interface.
|
10.1111/j.1460-9568.2006.04904.x
|
pubmed_105_15342
|
Background: The incidence of Type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD) has risen over the years. This comorbid condition significantly increases the probability of cirrhosis, liver cancer, and mortality compared to the disease alone. The multi-targeted, holistic treatment efficacy of traditional Chinese medicine (TCM) plays a vital role in the treatment of T2DM and NAFLD. Jiedu Tongluo Tiaogan Formula (JTTF), based on TCM theory, is widely used in clinical treatment, and its effectiveness in lowering glucose, regulating lipids, improving insulin resistance, and its pathways of action have been demonstrated in previous studies. However, the mechanism of this formula has not been investigated from a metabolomics perspective. Moreover, high-quality clinical studies on T2DM combined with NAFLD are lacking. Therefore, we aim to conduct a clinical trial to investigate the clinical efficacy, safety, and possible pathways of JTTF in the treatment of T2DM combined with NAFLD using metabolomics techniques. Methods: A total of 98 participants will be recruited to this clinical trial and randomly assigned to either a treatment group (JTTF + conventional basic treatment) or control group (conventional basic treatment) in a 1:1 ratio. Both groups will have received the same lifestyle interventions in the preceding 12 weeks. The primary outcome will be change in visceral fat area and total score on the TCM syndromes efficacy score scale. The secondary outcome will include changes in ultrasound steatosis grade, fibrosis 4 score (FIB-4), metabolic parameters, anthropometric parameters, visceral fat area. In addition, serum and urine samples collected at baseline and at the end of 12 weeks of treatment will be sequentially tested for untargeted and targeted metabolomics. Discussion: This study will evaluate the efficacy and safety of JTTF, as well as investigate the differential metabolites and possible mechanisms of JTTF treatment in T2DM combined with NAFLD. We hypothesize that patients will benefit from JTTF, which may provide strong evidence for the clinical use of JTTF in the treatment of T2DM and NAFLD, leading to the possibility of further mechanistic exploration. Clinical Trial Registration: This clinical trial has been registered in China Clinical Trial Registry (ChiCTR 2100051174).
|
10.3389/fphar.2022.924021
|
pubmed_282_7700
|
Intermolecular features like hydrogen bonding and π-type interactions play pivotal roles in stabilizing molecular structures in ionic liquids with planar rings and hydrogen-bond donors and acceptors. However, the delicate interplay among these interactions is complicated and depends on specific ion types. In this work, ab initio molecular dynamics simulations were performed to reveal competitive and cooperative characteristics among hydrogen bonding and π-type interactions in a typical imidazolium-oxalatoborate ionic liquid. Imidazolium rings take preferential on-top parallel orientations, leading to their particular π-π stacking distributions at short distances. Intermolecular interactions between imidazolium and oxalato rings are manifested by short-range on-top parallel orientations and in-plane hydrogen bonding interactions, promoting their parallel displaced offset stacking arrangements. However, on an intermediate distance scale, attractive Coulombic interactions between imidazolium and oxalato rings dominate and contribute to their perpendicular orientations. Spatial coordination patterns between intermolecular oxalato rings are balanced by repulsive electrostatic interactions and steric hindrance effects, leading to their tilted orientations in local environments.
|
10.1021/acs.jpcb.7b05564
|
pubmed_1_4596
|
From a biological perspective aging (senescence) appears to be a form of complex disease syndrome, though this is not the traditional view. This essay aims to foster a realistic understanding of aging by scrutinizing ideas old and new. The conceptual division between aging-related diseases and an underlying, non-pathological aging process underpins various erroneous traditional ideas about aging. Among biogerontologists, another likely error involves the aspiration to treat the entire aging process, which recent advances suggest is somewhat utopian. It also risks neglecting a more modest but realizable goal: to develop preventative treatments that partially protect against aging.
|
10.3389/fgene.2015.00212
|
pubmed_520_7736
|
PROBLEM/CONDITION
Sickle cell disease (SCD), an inherited blood disorder affecting an estimated 100,000 persons in the United States, is associated with multiple complications and reduced life expectancy. Complications of SCD can include anemia, debilitating acute and chronic pain, infection, acute chest syndrome, stroke, and progressive organ damage, including decreased cognitive function and renal failure. Early diagnosis, screenings and preventive interventions, and access to specialist health care can decrease illness and death. Population-based public health surveillance is critical to understanding the course and outcomes of SCD as well as the health care use, unmet health care needs, and gaps in essential services of the population affected by SCD.
PERIOD COVERED
2004-2018.
DESCRIPTION OF THE PROGRAM
In 2015, CDC established the Sickle Cell Data Collection (SCDC) program to characterize the epidemiology of SCD in two states (California and Georgia). Previously, surveillance for SCD was conducted by two short-term projects: Registry and Surveillance System for Hemoglobinopathies (RuSH), which was conducted during 2010-2012 and included 2004-2008 data, and Public Health Research, Epidemiology, and Surveillance for Hemoglobinopathies (PHRESH), which was conducted during 2012-2014 and included 2004-2008 data. Both California and Georgia participated in RuSH and PHRESH, which guided the development of the SCDC methods and case definitions. SCDC is a population-based tracking system that uses comprehensive data linkages in state health systems. These linkages serve to synthesize and disseminate population-based, longitudinal data for persons identified with SCD from multiple sources using selected International Classification of Diseases, Ninth Revision, Clinical Modification, and Tenth Revision codes and laboratory results confirmed through state newborn screening (NBS) programs or clinic case reporting. Administrative and clinical data sources include state Medicaid and Children's Health Insurance Program databases, death certificates, NBS programs, hospital discharge and emergency department records, and clinical records or case reports. Data from multiple sources and years are linked and deduplicated so that states can analyze and report on SCD population prevalence, demographic characteristics, health care access and use, and health outcomes. The SCD case definition is based on an algorithm that classifies cases with laboratory confirmation as confirmed cases and those with a reported clinical diagnosis or three or more diagnostic codes over a 5-year period from an administrative data source as probable cases. In 2019, nine states (Alabama, California, Georgia, Indiana, Michigan, Minnesota, North Carolina, Tennessee, and Virginia) were funded as part of an SCDC capacity-building initiative. The newly funded states developed strategies for SCD case identification and data linkage similar to those used by California and Georgia. As of 2021, the SCDC program had expanded to 11 states with the addition of Colorado and Wisconsin.
RESULTS
During 2004-2018, the cumulative prevalence of confirmed and probable SCD cases identified in California and Georgia was 9,875 and 14,777 cases, respectively. The 2018 annual prevalence count was 6,027 cases for California and 9,141 for Georgia. Examination of prevalence counts by contributing data source during 2014-2018 revealed that each data source captured 16%-71% of cases in California and 17%-87% in Georgia; therefore, no individual source is sufficient to estimate statewide population prevalence. The proportion of pediatric SCD patients (children aged 0-18 years) was 27% in California and 40% in Georgia. The percentage of females with SCD in California and Georgia was 58% and 57%, respectively. Of the cases with SCD genotyping data available (n = 5,856), 63% of patients had sickle cell anemia. SCDC data have been used to directly apprise health care providers and policymakers about health care needs and gaps for patients with SCD. For example, an SCDC Georgia assessment indicated that 10% of babies born during 2004-2016 with SCD lived more than a 1-hour drive from any SCD specialty care option, and another 14% lived within a 1-hour drive of a periodic SCD specialty clinic only. Likewise, an SCDC California assessment indicated that during 2016-2018, most patients with SCD in Los Angeles County lived approximately 15-60 miles from hematologists experienced in SCD care. A surveillance capacity and performance assessment of all 11 SCDC states during 2020-2021 indicated that states differed in the availability of data sources used for SCD surveillance and the time frames for accessing each state data source. Nonetheless, methods for standardizing reporting were developed across all participating states.
INTERPRETATION
This report is the first comprehensive description of CDC's efforts in collaboration with participating states to establish, maintain, and expand SCD surveillance through the SCDC program to improve health outcomes for persons living with SCD. Findings from California and Georgia analyses highlighted a need for additional SCD specialty clinics. Despite different approaches, expansion of SCDC to multiple states was possible using standardized, rigorous methods developed across all participating states for reporting on disease prevalence, health care needs and use, and deaths.
PUBLIC HEALTH ACTION
Findings from surveillance can be used to improve and monitor care and outcomes for persons with SCD. These and other SCDC analyses have had a role in opening new SCD clinics, educating health care providers, developing state health care policies, and guiding new research initiatives. Public health officials can use this report as a guiding framework to plan or implement surveillance programs for persons with SCD. Both data-related activities (data sources; patient identifiers; and obtaining, transferring, and linking data) and the administrative considerations (stakeholder engagement, costs and resources, and long-term sustainability) are crucial to the success of these programs.
|
10.15585/mmwr.ss7109a1
|
pubmed_266_638
|
The design of supply chain networks (SCNs) aims at determining the number, location, and capacity of production facilities, as well as the allocation of markets (customers) and suppliers to one or more of these facilities. This paper reviews the existing literature on the use of simulation-optimization methods in the design of resilient SCNs. From this review, we classify some of the many works in the topic according to factors such as their methodology, the approach they use to deal with uncertainty and risk, etc. The paper also identifies several research opportunities, such as the inclusion of multiple criteria (e.g., monetary, environmental, and social dimensions) during the design-optimization process and the convenience of considering hybrid approaches combining metaheuristic algorithms, simulation, and machine learning methods to account for uncertainty and dynamic conditions, respectively.
|
10.1016/j.simpat.2020.102166
|
pubmed_830_10770
|
Mammalian CST (CTC1-STN1-TEN1) associates with telomeres and depletion of CTC1 or STN1 causes telomere defects. However, the function of mammalian CST remains poorly understood. We show here that depletion of CST subunits leads to both telomeric and non-telomeric phenotypes associated with DNA replication defects. Stable knockdown of CTC1 or STN1 increases the incidence of anaphase bridges and multi-telomeric signals, indicating genomic and telomeric instability. STN1 knockdown also delays replication through the telomere indicating a role in replication fork passage through this natural barrier. Furthermore, we find that STN1 plays a novel role in genome-wide replication restart after hydroxyurea (HU)-induced replication fork stalling. STN1 depletion leads to reduced EdU incorporation after HU release. However, most forks rapidly resume replication, indicating replisome integrity is largely intact and STN1 depletion has little effect on fork restart. Instead, STN1 depletion leads to a decrease in new origin firing. Our findings suggest that CST rescues stalled replication forks during conditions of replication stress, such as those found at natural replication barriers, likely by facilitating dormant origin firing.
|
10.1038/emboj.2012.215
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pubmed_1015_10461
|
The basilar pontine gray in adult rats was subjected to electron microscopic examination in order to characterize: 1) certain general cytologic features, 2) the principle categories of presynaptic profiles, and 3) the postsynaptic targets of the various categories of presynaptic boutons. General cytologic features included the presence of neuronal somata exhibiting either a smooth contoured nucleus and central nucleolus or an irregularly contoured nucleus with numerous invaginations and an eccentric nucleolus. In addition, dendritic protrusions with variable morphology were apparent as well as a class of dendrites and somata with a curious dense, granular matrix. Four general types of presynaptic profiles were distinguished and were classified as: round vesicle boutons, elongate vesicle, pleomorphic vesicle, and dense core vesicle boutons. The category of round vesicle boutons formed asymmetric synaptic contacts and included three subtypes. One group contained vesicles with diameters of 25-35 nm, a second group contained larger (40-60 nm) round vesicles, and a third group of much larger boutons (2.5-6.8 microns) exhibited the smaller round vesicles. Another general category of presynaptic profile contained distinctly elongated synaptic vesicles, formed symmetrical active sites, and ranged in size from 0.4-1.7 microns. A third category of synaptic end-structures was distinguished by the presence of pleomorphic synaptic vesicles and microtubules and exhibited a distinctive pale or lucent matrix, while the fourth type was characterized by a mixed population of clear and dense core vesicles. Analysis of the distribution of such bouton types over the surface of pontine neurons revealed that: somata and proximal dendrites were contacted by round, elongate, and dense core vesicle boutons; intermediate and distal dendrites received synapses from all categories of boutons including the large endings with smaller round vesicles, while dendritic spines were contacted by round vesicle boutons (large and small), the large boutons, and elongate vesicle boutons. Synapses were also observed to occur between two vesicle-containing profiles. In such situations, pleomorphic vesicle boutons were found to be postsynaptic to either elongate vesicle boutons or small boutons with round vesicles and at the same time were presynaptic to a dendritic profile.
|
10.1002/cne.901950203
|
pubmed_927_17168
|
Six healthy volunteers and 17 diabetics (6 insulin-dependent and 11 diet- and tablet-treated) were treated with a special processed, palatable guar gum (10 g b.i.d. immediately before meals) for periods of one or three weeks or, in some cases, up to 13 weeks. A standardized test meal was given to study the effect of the fiber on postprandial glucose levels. Ten g guar was stirred in water and taken immediately before the test meal. The postprandial blood glucose levels were similar in the healthy volunteers but significantly lower in the diabetics following treatment with guar for one and three weeks, respectively. Furthermore, the fasting blood glucose levels were significantly lower in the diabetics after three, but not one, weeks of treatment. The lower postprandial glucose levels were coupled with attenuated and delayed insulin levels in accordance with an effect of guar gum on the rate of carbohydrate absorption. The cholesterol levels were on average reduced with 14% in the diabetics following three weeks' treatment with guar. The higher the initial cholesterol level, the greater the reduction in cholesterol; 26% reduction was achieved in four patients with initial levels above 7 mM. The alpha-lipoprotein cholesterol levels were not significantly changed, thus an increase in the alpha-lipoprotein cholesterol/total serum cholesterol ratio was obtained. Neither plasma triglycerides nor body weights altered during treatment. The reported side-effects were as expected and were usually mild and transient (e.g. increased flatulence). The data show that guar gum also reduces postprandial glucose levels on a long-term basis and may improve the diabetic control. Additionally, treatment with this fiber leads to a concentration-dependent decrease in cholesterol levels.
|
10.1016/0021-9150(82)90166-6
|
pubmed_409_5822
|
A case of primary histiocytic lymphoma in the uterine cervix of a 22-year-old nulligravid woman is reported. To avoid surgical or radiological castration she received six courses of combination chemotherapy (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 2 mg all iv on Day 1 and then together with oral prednisone 50 mg twice daily on Days 1-5). Approximately 20 months after therapy she delivered a healthy child. Six years have passed since primary treatment was initiated. No evidence of recurrent lymphoma has been observed.
|
10.1016/0090-8258(90)90024-f
|
pubmed_1102_10999
|
Older people are particularly susceptible to acute kidney injury (AKI) for a variety of reasons. Because of this, medication changes during admission and transitions of care follow-up are often necessary to ensure the safety of these patients. The American Geriatrics Society's Beers Criteria provide guidance for select medications that are potentially inappropriate in the older adult population. However, other medications, particularly those for cardiovascular disease and diabetes that are not included in the kidney function-specific section of the Beers Criteria (Table 6), can sometimes be overlooked. This manuscript will provide insight to both pharmacists and student pharmacists on the importance of being vigilant for medications that may need dosage adjustment during episodes of AKI. As interns in the outpatient setting, pharmacy students can provide education to patients and their families in order to ensure these medications are being taken correctly and are properly restarted if their discontinuation was intended for only a short time.
|
10.4140/TCP.n.2021.187
|
pubmed_576_7457
|
Hepatocytes and hepatic stellate cells play important roles in retinoid storage and metabolism. Hepatocytes process postprandial retinyl esters and are responsible for secretion of retinol bound to retinol-binding protein (RBP) to maintain plasma retinol levels. Stellate cells are the body's major cellular storage sites for retinoid. We have characterized and utilized an immortalized rat stellate cell line, HSC-T6 cells, to facilitate study of the cellular aspects of hepatic retinoid processing. For comparison, we also carried out parallel studies in Hepa-1 hepatocytes. Like activated primary stellate cells, HSC-T6 express myogenic and neural crest cytoskeletal filaments. HSC-T6 cells take up and esterify retinol in a time- and concentration-dependent manner. Supplementation of HSC-T6 culture medium with free fatty acids (up to 300 micrometer) does not affect retinol uptake but does enhance retinol esterification up to 10-fold. RT-PCR analysis indicates that HSC-T6 cells express all 6 retinoid nuclear receptors (RARalpha, -beta, -gamma, and RXRalpha, -beta, -gamma) and like primary stellate cells, HSC-T6 stellate cells express cellular retinol-binding protein, type I (CRBP) but fail to express either retinol-binding protein (RBP) or transthyretin (TTR). Addition of retinol (10(-8)-10(-5) m) or all-trans-retinoic acid (10(-10)-10(-6) m) rapidly up-regulates CRBP expression. Using RAR-specific agonists and antagonists and an RXR-specific agonist, we show that members of the RAR-receptor family modulate HSC-T6 CRBP expression.Thus, HSC-T6 cells display the same retinoid-related phenotype as primary stellate cells in culture and will be a useful tool for study of hepatic retinoid storage and metabolism.
|
pubmed_576_7457
|
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