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pubmed_646_15364
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OBJECTIVE
The study examines diabetes attitude differences by treatment modality (insulin vs. no insulin), race/ethnicity, and the interaction of these two variables for people with type 2 diabetes.
RESEARCH DESIGN AND METHODS
Data were collected with the Diabetes Care Profile (DCP), an instrument that assesses psychosocial factors related to diabetes. Participants (n = 672) were recruited in the metropolitan Detroit, Michigan, area from 1993 to 1996. A total of 68% of these participants were African-Americans with type 2 diabetes, and 32% were Caucasians with type 2 diabetes. Analyses of covariance were performed to examine the effects of race/ethnicity, treatment, and their interaction for each DCP scale.
RESULTS
The four patient categories (two ethnicities by two treatment modalities) differed by age, years with diabetes, education, and sex distribution. Treatment modality had a significant effect on 6 of the 16 DCP scales (Control, Social and Personal Factors, Positive Attitude, Negative Attitude, Self-Care Ability, and Exercise Barriers). Ethnicity was a significant effect for three scales (Control, Support, and Support Attitudes). The interaction of race/ethnicity and treatment modality was a significant effect for two related attitude scales (Positive Attitude and Negative Attitude).
CONCLUSIONS
The results suggest that attitudes toward diabetes are similar for African-American and Caucasian patients with type 2 diabetes. The results also suggest that treatment modality has a greater effect on attitudes than either race/ethnicity or the interaction effect. However, Caucasian patients using insulin differed from the other patient groups by having the least positive and the most negative attitudes regarding diabetes.
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10.2337/diacare.23.3.313
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pubmed_173_24780
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Microbial activity is one of the most important processes to mediate the flux of organic carbon from the ocean surface to the seafloor. However, little is known about the microorganisms that underpin this key step of the global carbon cycle in the deep oceans. Here we present genomic and transcriptomic evidence that five ubiquitous archaeal groups actively use proteins, carbohydrates, fatty acids and lipids as sources of carbon and energy at depths ranging from 800 to 4,950 m in hydrothermal vent plumes and pelagic background seawater across three different ocean basins. Genome-enabled metabolic reconstructions and gene expression patterns show that these marine archaea are motile heterotrophs with extensive mechanisms for scavenging organic matter. Our results shed light on the ecological and physiological properties of ubiquitous marine archaea and highlight their versatile metabolic strategies in deep oceans that might play a critical role in global carbon cycling.
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10.1038/ncomms9933
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pubmed_419_9930
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Fenofibrate is a widely used anti-hyperlipidemic agonist of peroxisome proliferator-activated receptor alpha (PPARα). As a metabolic blocker, fenofibrate interferes with cancer promotion/progression via its misbalancing effects on cellular metabolism. However, the consequences of its long-term application for patients with diagnosed drug-resistant cancers are unknown. We addressed this point by tracing the phenotypic microevolution of naïve and drug-resistant prostate cancer PC3_DCX20 cells that underwent a long-term exposition to 10 μM and 50 μM fenofibrate. Their resistance to fenofibrate, metabolic profile and invasive phenotype were estimated in the control conditions and under fenofibrate-induced stress. Apparently, drug efflux systems are not effective against the cytostatic FF action. However, wtPC3 and PC3_DCX20 cells that survived the long-term 50 μM fenofibrate treatment gave rise to lineages that displayed an increased proliferation rate, lower motility in the control conditions and enhanced fenofibrate resistance. Attenuated fenofibrate bioavailability modified the pattern of PC3 microevolution, as illustrated by phenotypic differences between wtPC3/PC3_DCX20 lineages propagated in the presence of 50 μM and 10 μM fenofibrate. Collectively, our observations indicate that fenofibrate acts as a selective factor that affects prostate cancer microevolution. We also pinpoint potential consequences of long-term exposition of prostate cancer patients to metabolic blockers.
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10.3390/ph15111320
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pubmed_864_4198
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The incidence of atrial fibrillation (AF) is increased in patients with hypertension and high blood pressure is a well-known risk factor for AF. The target of hypertensive therapy is to reduce the incidence of cardiovascular events. Since AF is associated with increased risks of death, heart failure and stroke, it is desirable if hypertensive therapy is able to reduce the onset of AF. In patients with hypertension or heart failure, anti-hypertensive drug is expected to reduce the onset of AF because of regression of left ventricular hypertrophy or preventing left ventricular remodeling. However, in patients with AF, anti-hypertensive drugs including angiotensin receptor blocker could not reduce the recurrence of AF and cardiovascular events. These results indicated that tight control of blood pressure might be useful for preventing the new-onset of AF in hypertensive patients.
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pubmed_864_4198
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pubmed_73_23285
|
Highly sensitive molecular technologies provide new capacities for cancer biomarker research, but with sensitivity improvements marker specificity is significantly decreased, and too many false-positive results should disqualify the measurement from clinical use. Hence, of the thousands of potential cancer biomarkers only a few have found their way to clinical application. Differentiating false-positive results from true-positive (cancer-specific) results can indeed be difficult, if validation of a marker is performed against inadequate controls. We present examples of accumulating evidence that not only local but also systemic inflammatory reactions are implicated in cancer development and progression and interfere with the molecular image of cancer disease. We analyze several modern strategies of tumor marker discovery, namely, proteomics, metabonomics, studies on circulating tumor cells and circulating free nucleic acids, or their methylation degree, and provide examples of scarce, methodologically correct biomarker studies as opposed to numerous methodologically flawed biomarker studies, that examine cancer patients' samples against those of healthy, inflammation-free persons and present many inflammation-related biomarker alterations in cancer patients as cancer-specific. Inflammation as a cancer-associated condition should always be considered in cancer biomarker studies, and biomarkers should be validated against their expression in inflammatory conditions.
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10.1016/j.bbcan.2010.06.002
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pubmed_1073_19558
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Alternative splicing is a molecular process that contributes greatly to the diversification of proteome and to gene functions. Understanding the mechanisms of stage-specific alternative splicing can provide a better understanding of the development of eukaryotes and the functions of different genes. Schistosoma japonicum is an infectious blood-dwelling trematode with a complex lifecycle that causes the tropical disease schistosomiasis. In this study, we analyzed the transcriptome of Schistosoma japonicum to discover alternative splicing events in this parasite, by applying RNA-seq to cDNA library of adults and schistosomula. Results were validated by RT-PCR and sequencing. We found 11,623 alternative splicing events among 7,099 protein encoding genes and average proportion of alternative splicing events per gene was 42.14%. We showed that exon skip is the most common type of alternative splicing events as found in high eukaryotes, whereas intron retention is the least common alternative splicing type. According to intron boundary analysis, the parasite possesses same intron boundaries as other organisms, namely the classic "GT-AG" rule. And in alternative spliced introns or exons, this rule is less strict. And we have attempted to detect alternative splicing events in genes encoding proteins with signal peptides and transmembrane helices, suggesting that alternative splicing could change subcellular locations of specific gene products. Our results indicate that alternative splicing is prevalent in this parasitic worm, and that the worm is close to its hosts. The revealed secretome involved in alternative splicing implies new perspective into understanding interaction between the parasite and its host.
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10.1371/journal.pone.0138470
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pubmed_45_1563
|
A prothrombin activator, named 'basparin A,' was isolated from the venom of the crotaline snake Bothrops asper, the species responsible for the majority of snakebite cases in Central America. It is an acidic (pI 5.4), 70kDa, single chain P-III metalloproteinase comprising, in addition to the metalloproteinase domain, disintegrin-like, and high-cysteine domains. Basparin A is a glycoprotein displaying immunological cross-reactivity with BaH1, a P-III hemorrhagic metalloproteinase isolated from the same venom. It activates prothrombin through the formation of meizothrombin, without requiring additional cofactors; it is, therefore, a class A snake venom prothrombin activator. In contrast with most venom metalloproteinases, it does not degrade components of the extracellular matrix. Apart from its clotting activity, basparin A inhibits collagen-dependent platelet aggregation in vitro, an effect that does not depend on proteolytic activity. Clotting activity on human plasma is not abrogated by the plasma proteinase inhibitors alpha(2) macroglobulin and murinoglobulin, whereas activity is completely inhibited by Costa Rican polyvalent (Crotalinae) anti-venom. Basparin A does not induce local tissue alterations, such as hemorrhage, myonecrosis, and edema, in mice. Moreover, it does not induce systemic hemorrhage, thrombocytopenia nor prolongation of the bleeding time following intravenous administration. At low doses, the only observed effect induced by basparin A, when injected intravenously or intramuscularly into mice, is defibrin(ogen)ation. At higher doses, intravenous administration resulted in sudden death due to numerous occluding thrombi in pulmonary vessels. Basparin A is likely to play an important role in the coagulopathy associated with B. asper envenoming.
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10.1016/s0003-9861(03)00385-0
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pubmed_358_8418
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Attitude toward drug-free experience is conceptualized as a psychological context for drug use that influences the evaluation of perceived consequences of marijuana use. Two studies examined the moderating effect of attitude toward drug-free experience on relationships between attitudes toward marijuana and drug use. In Study 1 (N = 316), attitude toward drug-free experience emerged as a significant moderator. Participants with positive attitudes toward marijuana use and relatively low attitudes toward drug-free experience used marijuana at the highest rates. Study 2 (N = 308) provided a partial replication and extension. In a second sample, a quadratic relationship emerged between drug-free experience and marijuana use. The interaction between the two attitudes approached significance. Among the 47 participants who had used marijuana more than 100 times in their lifetime, attitude toward drug-free experience moderated the relationship between attitude toward marijuana and marijuana-related problems.
|
10.1016/s0306-4603(99)00016-7
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pubmed_167_809
|
Total contact casts are recognized as the gold standard treatment for neuropathic plantar diabetic foot ulceration, endorsed by all national and international consensus papers. Despite this, research has shown that there is a dichotomy between the existing evidence which supports the use of total contact casts in the management of diabetic foot ulcers and its use in clinical practice. This article aims to highlight the benefits, risks, and barriers associated with total contact cast use in the management of diabetic foot ulcers in the clinical setting, with an emphasis on existing research carried out in this field to encourage change in clinical practice and utilization of this effective treatment modality.
|
10.1016/j.jccw.2018.05.002
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pubmed_1072_16345
|
OBJECTIVE
To study the effect of LSD1 knock-out on human chronic myeloid leukemia cells(K562 cells).
METHODS
The LSD1 gene in K562 cells was knocked-out specifically by using CRISPR/Cas9 system, the single cells were gained by flow cytometric sorting technique, the LSD1+/- and LSD1-/- cell lines were gained after amplificantion and culture, identification of Western blot and sequencing. The MTS assay was used to detect the effect of LSD1 knockout on the proliferation of K562 cells, the flow cytometry was used to examine the expression of K562 cell surface marker after LSD1 knockout.
RESULTS
The LSD1 stable knockout cell line of K562 (LSD1+/- and LSD1-/-)were successfully costructed. It was found that knockout of LSD1 significantly inhibited the proliferation of K562 and the expression of CD235a.
CONCLUSION
LSD1 plays a key role in the regulation of K562 cell proliferation and CD235a expression.
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10.7534/j.issn.1009-2137.2017.05.009
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pubmed_576_4794
|
We undertook two studies to determine the validity and reliability of the revised Perceived Motivational Climate in Sport Questionnaire (PMCSQ-2). In Study 1, 201 female athletes (mean age 16.4 years) were administered the initial version of the PMCSQ-2 and a measure of reported tension and pressure experienced in sport. Exploratory principal component analysis suggested that the PMCSQ-2 contained two higher-order scales (Task-Involving and Ego-Involving climates), each with three subscales (Task: Cooperative Learning, Effort/ Improvement, Important Role; Ego: Intra-Team Member Rivalry, Unequal Recognition, Punishment for Mistakes). In Study 2, 385 female volleyball players (mean age 15.2 years) completed the PMCSQ-2, the Intrinsic Motivation Inventory and a measure of Team Satisfaction. Confirmatory factor analysis was applied to six competing models. The oblique six-factor model and oblique hierarchical model provided comparable fit to the data. Acceptable fit was reached based on model respecification. Across Studies 1 and 2, internal consistency was found to be acceptable for the higher-order scales and subscales (with the exception of the Intra-Team Member Rivalry subscale). We found evidence for the concurrent validity of the instrument.
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10.1080/026404100365018
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pubmed_161_6566
|
A number of single-cell-cloned cell lines have been used to examine the growth-promoting effects of putative mammotrophic agents on the various cell types in normal and neoplastic rat mammary glands. A partially purified novel pituitary-derived growth factor stimulates only cuboidal epithelial cells to divide whereas fibroblast growth factor (FGF) stimulates the growth of stromal and myoepithelial-like cells. Epidermal growth factor (EGF) has a widespread but variable growth-stimulating action, but prolactin and growth hormone are essentially inactive when added alone at a concentration of 5 micrograms/ml. Phosphoethanolamine stimulates the growth of one epithelial cell line and a derivative myoepithelial-like cell line, but is inactive on the other cell lines tested. The use of defined cloned cell lines provides a direct and reproducible assay for the identification and purification of inducers of mammary growth.
|
10.1002/jcp.1041190310
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pubmed_1122_12391
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We have demonstrated a higher nuclear protein content in the hypodiploid fraction of BG-1 human ovarian cancer cells following treatment with one of the ether lipids, ET-18-OCH3. In this study, we have attempted to identify the overexpressed nuclear protein induced in those dying or dead cells in the hypodiploid fraction and its localization before and after ET-18-OCH3 treatment. The pattern of nuclear proteins was analyzed by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) before and after ET-18-OCH3 treatment. The partial amino acid sequence of the most dominantly and consistently up-regulated protein spot after ET-18-OCH3 treatment was determined and it was found to be heat shock protein 27 (HSP27). Immunofluorescence staining disclosed that HSP27 localizes in the cytoplasm of the BG-1 cells before ET-18-OCH3 treatment. Condensation of HSP27 around the nuclei was observed following treatment by ET-18-OCH3. Ultimately, the nuclei of the cells in the hypodiploid fraction were stained by immunofluorescent HSP27. These results indicate that change of the localization of HSP27 may play an important role as a component of the signal transduction pathways affected by ether lipids.
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pubmed_1122_12391
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pubmed_299_20215
|
OBJECTIVES
Information-only interventions for hypertension management have limited effectiveness, particularly among disadvantaged populations. We assessed the impact of viewing African-American patients' stories of successfully controlling hypertension on intention to change hypertension management behaviors and engagement with educational materials.
METHODS
In a three-site randomized trial, 618 African-American Veterans with uncontrolled hypertension viewed an information-only DVD about hypertension (control) or a DVD adding videos of African-American Veterans telling stories about successful hypertension management (intervention). After viewing, patients were asked about their engagement with the DVD, and their intentions to change behavior. Mean scores were compared with two-sided t-tests.
RESULTS
Results favored the Stories intervention, with significantly higher emotional engagement versus control (4.3 vs. 2.2 p<0.0001). Intervention patients reported significantly greater intentions to become more physically active (4.6 vs. 4.4, p=0.018), use salt substitutes (3.9 vs. 3.4, p=0.006), talk openly with their doctor about hypertension (4.6 vs. 4.5, p=0.049), and remember to take hypertension medication (4.8 vs. 4.6, p=0.04).
CONCLUSION
Patients were more emotionally engaged and reported intentions to change behavior when watching real patient hypertension management success stories.
PRACTICE IMPLICATIONS
Stories may be more influential than information alone, and represent a scalable approach to modifying behavioral intention.
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pubmed_299_20215
|
pubmed_586_3724
|
Chemically synthesized yeast tRNA terminal fragments were reconstituted with natural tRNA fragments which were obtained by partial digestion with RNase T1. The synthetic 3'-nonanucleotide (I) accepted alanine (3% with respect to the intact tRNA) when combined with a 4-fold excess of the natural 5'-quarter and the chemically synthesized hexanucleotide (II) stimulated the aminoacylation of the natural 3'-half molecule.
|
10.1111/j.1432-1033.1976.tb10514.x
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pubmed_201_15893
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We developed a metabolomic method to evaluate the effect of pirfenidone on rats with acute paraquat (PQ) poisoning, through the analysis of various tissues (lung, liver, kidney, and heart), by gas chromatography-mass spectrometry (GC-MS). Thirty-eight rats were randomly divided into a control group, an acute PQ (20 mg kg-1) poisoning group, a pirfenidone (20 mg kg-1) treatment group, and a pirfenidone (40 mg kg-1) treatment group. Partial least squares-discriminate analysis (PLS-DA) revealed metabolic alterations in rat tissue samples from the two pirfenidone treatment groups after acute PQ poisoning. The PLS-DA 3D score chart showed that the rats in the acute PQ poisoning group were clearly distinguished from the rats in the control group. Also, the two pirfenidone treatment groups were distinguished from the acute PQ poisoning group and control group. Additionally, the pirfenidone (40 mg kg-1) treatment group was separated farther than the pirfenidone (20 mg kg-1) treatment group from the acute PQ poisoning group. Evaluation of the pathological changes in the rat tissues revealed that treatment with pirfenidone appeared to decrease pulmonary fibrosis in the acute PQ poisoning rats. The results indicate that pirfenidone induced beneficial metabolic alterations in the tissues of rats with acute PQ poisoning. Rats with acute PQ poisoning exhibited a certain reduction in biochemical indicators after treatment with pirfenidone, indicating that pirfenidone could protect liver and kidney function. Accordingly, the developed metabolomic approach proved to be useful to elucidate the effect of pirfenidone in rats of acute PQ poisoning.
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10.1177/0748233717731959
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pubmed_444_20015
|
INTRODUCTION
Community detection, the process of identifying subgroups of highly connected individuals within a network, is an aspect of social network analysis that is relevant but potentially underutilized in prevention research. Guidance on using community detection methods stresses aligning methods with specific research questions but lacks clear operationalization. The Question Alignment approach was developed to help address this gap and promote the high-quality use of community detection methods.
METHODS
A total of 6 community detection methods are discussed: Walktrap, Edge-Betweenness, Infomap, Louvain, Label Propagation, and Spinglass. The Question Alignment approach is described and demonstrated using real-world data collected in 2013. This hypothetical case study was conducted in 2019 and focused on targeting a hand hygiene intervention to high-risk communities to prevent influenza transmission.
RESULTS
Community detection using the Walktrap method best fit the hypothetical case study. The communities derived using the Walktrap method were quite different from communities derived through the other 5 methods in both the number of communities and individuals within communities. There was evidence to support that the Question Alignment approach can help researchers produce more useful community detection results. Compared to other methods of selecting high-risk groups, the Walktrap produced the most communities that met the hypothetical intervention requirements.
CONCLUSIONS
As prevention research incorporating social networks increases, researchers can use the Question Alignment approach to produce more theoretically meaningful results and potentially more useful results for practice. Future research should focus on assessing whether the Question Alignment approach translates into improved intervention results.
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10.1016/j.amepre.2020.04.015
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pubmed_98_5276
|
Food insecurity and food deserts are prominent global health problems, now exacerbated by current COVID-19 pandemic. Some evidence points to the importance of food security, particularly for women in their reproductive age. Women's health and their nutrition status, across the continuum of preconception to pregnancy and postpartum are critical aspects for ensuring positive gestation course and short-/long-term outcomes by affecting essential developmental pathways. Several adverse outcomes (both maternal and neonatal) were reported in scientific literature. Screening programs, new economic policies, implementation of assistance since preconception could be a good strategy to mitigate the negative consequences of food insecurity. Potential strategies could include addressing misconceptions about healthy maternal diet and breast milk adequacy, stress management, promote social support networks, and connecting to supplemental nutrition assistance programs.KEY POINTSFood insecurity (limited food access owing to cost) and desert foods (living in areas with low physical/personal access to nutritious food) are major public health concerns.Large geographical and within-country disparities, multiple socio-economic determinants.Childbearing age and pregnancy are groups at higher vulnerability to develop complications.Food insecurity negatively affects offspring health and development.Peri-conceptional window: an early clinical opportunity to screen and to apply preventive strategies.Help vulnerable groups to have access to more affordable nutritious food, educate and change unhealthy behaviors, adequate stress management, social support networks.
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10.1080/14767058.2021.2016052
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pubmed_542_12138
|
Clostridium difficile has been associated with increased activity of Crohn's disease in some patients, and in them its eradication has proved beneficial. We have seen a patient unresponsive to two courses of vancomycin with persistence of C. difficile colonization and toxin production in whom surgical intervention eliminated the C. difficile cytotoxin and organism.
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10.1097/00004836-198506000-00017
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pubmed_622_10874
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The activity of ornithine decarboxylase (ODC(1)), the first enzyme in polyamine biosynthesis, is induced during carcinogenesis by a variety of oncogenic stimuli. Intracellular levels of ODC and the polyamines are tightly controlled during normal cell growth, and regulation occurs at the levels of transcription, translation and protein degradation. Several known proto-oncogenic pathways appear to control ODC transcription and translation, and dysregulation of pathways downstream of ras and myc result in the constitutive elevation of ODC activity that occurs with oncogenesis. Inhibition of ODC activity reverts the transformation of cells in vitro and reduces tumor growth in several animal models, suggesting high levels of ODC are necessary for the maintenance of the transformed phenotype. The ODC irreversible inactivator DFMO has proven to be not only a valuable tool in the study of ODC in cancer, but also shows promise as a chemopreventive and chemotherapeutic agent in certain types of malignancies.
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10.1007/s00726-007-0531-2
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pubmed_590_14438
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Chemomechanical procedures can be used to eliminate bacteria from root canals. However, detectable bacteria sometimes remain because of the complexity of the root canal system. Endodontic passive ultrasonic irrigation (PUI) with hydrogen peroxide (H2O2) may be a promising option for increasing bactericidal hydroxyl radical (HO•) generation. In this in vitro experiment, we examined the effects of HO• generated using PUI and a low concentration of H2O2. An ultrasonic tip was submerged in 0.45 mol/L (1.5%) H2O2 in a microfuge tube. H2O2 was activated by an ultrasonic unit, the tip of which was kept centered in the tube, to mimic PUI. HO• generation was detected by electron spin resonance spectroscopy. An Enterococcus faecalis suspension in H2O2 was then preparedand activated as described above. Bactericidal effects were assessed by viable counting. Two-way analysis of variance and Tukey's test were used to assess the statistical significance of differences among groups (P < 0.05). HO• generation and bactericidal activity were significantly increased by PUI in H2O2 in a time-dependent manner and were significantly higher than with H2O2 alone or with PUI in a Tris-HCl suspension. These results suggest that PUI in the presence of a low H2O2 concentration is a promising new disinfection strategy.
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10.2334/josnusd.56.35
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pubmed_852_22035
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Myocarditis is a potentially life-threatening disease. Although ventricular thrombus formation in myocarditis is rare, it carries the risk of serious complications. We report on a 10-year-old previously healthy girl presenting with 2 large left ventricular thrombi in acute lymphocytic acute myocarditis. No coagulation disorder was found. Her clinical course and mobile thrombi characteristics prompted us to carry out an urgent surgical thrombectomy rather than primary anticoagulation therapy. The patient has recovered well without clinical signs of thromboembolism.
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10.1542/peds.2012-1185
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pubmed_958_10527
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The effect of carbon tetrachloride administration on liver mitochondrial function and the protective effect of an aqueous extract of Phyllanthus fraternus were studied in rats. The following changes were observed in mitochondria due to the administration of carbon tetrachloride. 1) A decrease in the rate of respiration, respiratory control ratio and P/O ratio using glutamate and malate or succinate as substrates. 2) A decrease in the activities of NADH dehydrogenase (35%), succinate dehydrogenase (76%) and cytochrome c oxidase (51%). The rate of electron transfer through site I, site II and site III was studied independently and found to be significantly decreased. 3) A decrease in the content of cytochrome aa3 (34%). 4) A significant decrease in the levels of phospholipids particularly cardiolipin and a significant increase in the lipid peroxide level was observed. The carbon tetrachloride induced toxicity may be partly due to the lipid peroxidation and partly due to the effect on protein synthesis. Administration of rats with an aqueous extract of P. fraternus prior to carbon tetrachloride administration showed significant protection on the carbon tetrachloride induced mitochondrial dysfunction on all the parameters studied.
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10.1016/s0024-3205(99)00195-2
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pubmed_943_4021
|
OBJECTIVE
To explore the anti-atherogenic mechanism of Huotong Capsule (HTC) on vascular smooth muscle cell (VSMC) apoptosis.
METHODS
VSMC proliferation model of cultured human embryonal thoracic aorta was established by stimulating VSMC with interleukin-1 (IL-1) and HTC was applied to observe the apoptosis inducing effect by transmission electron microscopy, DNA gel electrophoresis and flow cytometry.
RESULTS
Typical apoptotic cellular changes were found after HTC treatment, the VSMC shrinked, the nuclei disappeared after chromatin agglutination, cellular membrane projected and wrapped the organelle to form apoptotic body. DNA gel electrophoresis showed "ladder" strand of DNA, a special phenomenon of cellular apoptosis. And an Ap peak of degraded DNA could be seen by flow cytometry, which widened and heightened when the concentration of HTC increased. The above-mentioned changes were not found in the blank control and untreated model group.
CONCLUSION
HTC could induce apoptosis of human proliferated VSMC.
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pubmed_943_4021
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pubmed_635_4567
|
Nearly 50 years since its potential as a fluorescent base analogue was first recognized, 2-aminopurine (2AP) continues to be the most widely used fluorescent probe of DNA structure and the perturbation of that structure by interaction with enzymes and other molecules. In this review, we begin by considering the origin of the dramatic and intriguing difference in photophysical properties between 2AP and its structural isomer, adenine; although 2AP differs from the natural base only in the position of the exocyclic amine group, its fluorescence intensity is one thousand times greater. We then discuss the mechanism of interbase quenching of 2AP fluorescence in DNA, which is the basis of its use as a conformational probe but remains imperfectly understood. There are hundreds of examples in the literature of the use of changes in the fluorescence intensity of 2AP as the basis of assays of conformational change; however, in this review we will consider in detail only a few intensity-based studies. Our primary aim is to highlight the use of time-resolved fluorescence measurements, and the interpretation of fluorescence decay parameters, to explore the structure and dynamics of DNA. We discuss the salient features of the fluorescence decay of 2AP when incorporated in DNA and review the use of decay measurements in studying duplexes, single strands and other structures. We survey the use of 2AP as a probe of DNA-enzyme interaction and enzyme-induced distortion, focusing particularly on its use to study base flipping and the enhanced mechanistic insights that can be gained by a detailed analysis of the decay parameters, rather than merely monitoring changes in fluorescence intensity. Finally we reflect on the merits and shortcomings of 2AP and the prospects for its wider adoption as a fluorescence-decay-based probe.
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10.1017/S0033583514000158
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pubmed_1045_20827
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The purpose of the present study was to assess the effect of various forms of the surface-bound form of the C1 esterase inhibitor (C1-INH-PI) and decay accelerating factor (DAF) on xenogenic cells. cDNAs of various deletion mutants of the C1-INH-PI, such as delta-1-99 amino acid (AA), delta-108-183AA loop, delta-whole loop, delta-exon5, delta-exon6 + 7, and delta-exon5 + 6 + 7, and that of DAF, the delta-short consensus repeat (SCR) 1-DAF were established. While all deletion mutants of C1-INH-PI except the delta-1-99AA were expressed in the cytoplasm but not on the cell surface, the delta-1-99AA was clearly expressed on the xenogeneic cell surface. Amelioration of complement-mediated xenogeneic cell lysis by delta-1-99AA was next tested, and compared with delta-SCR1 DAF. Both molecules blocked human complement-mediated cell lysis by approximately 57 to 90 and 93 to 98%, respectively, in Chinese hamster ovarian tumor (CHO) cells and pig endothelial cells (PECs). The CHO cell transfectants were incubated with 20% normal human serum, and the amounts of C4 and C3 deposition on the cell surface were analysed by flow cytometry. The DAF transfectant showed a large amount of C4-deposition and much less C3-deposition than the controls (approximately 85% suppression), whereas the delta-1-99AA showed approximately a 40% suppression in both C4- and C3-deposition. Consequently, both the delta-1-99AA C1-INH-PI and delta-SCR1 DAF molecules are quite effective in down-regulating the xenogeneic cell lysis, but accomplished this in different manners.
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10.1034/j.1399-3089.2003.01120.x
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pubmed_1061_19019
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Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a low platelet count and consequent increased risk of bleeding. The etiology underlying this condition remains poorly understood. The aim of this study is to evaluate the association of a single nucleotide polymorphism (SNP) rs4077515 in the caspase recruitment domain-containing protein 9 (CARD9) gene with the pathogenesis and therapy of ITP. Two hundred ninety-four patients with ITP and 324 age-matched healthy participants were recruited in this case-control study. Genotyping of CARD9 rs4077515 polymorphism was performed by Sanger sequencing. Our results revealed that a polymorphism rs4077515 in CARD9 gene is associated with decreased risk of susceptibility to and severity of ITP (susceptibility: codominant, AA vs. GG, OR = 0.175, 95% CI = 0.054-0.776, p = 0.001; recessive, GG + AG vs. AA, OR = 6.183, 95% CI = 2.287-16.715, p < 0.001; severity: allele, A vs. G, OR = 0.685, 95% CI = 0.476-0.985, p = 0.041; codominant, AG vs. GG, OR = 0.571, 95% CI = 0.350-0.931, p = 0.025; dominant, AA + AG vs. GG, OR = 0.558, 95% CI = 0.343-0.907, p = 0.019). The existence of the allele A, the mutant AA genotype and the heterozygous AG genotype of CARD9 rs4077515, plays a protective role in ITP. However, CARD9 rs4077515 polymorphism had no effect on corticosteroid sensitivity or refractoriness of ITP.
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10.1007/s00277-019-03796-7
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pubmed_71_13685
|
The interaction of Candida albicans with the host is of a complex nature involving fungal factors and host's response. In this study, we concentrated on the phenotypic expression of virulence attributes and genotypic characteristics of C. albicans isolates from two distinct clinical entities of candidiasis-blood stream and vaginal infections, and the possible role of these factors. Hence, we conducted a comparative in vitro assessment of virulence characteristics, including adhesion to epithelial cells and HaCat cell line, biofilm formation, aspartic proteinases and phospholipase activity of 20 C. albicans isolates from patients with C. albicans bloodstream infection and 22 isolates from patients with C. albicans vaginitis. Further, we studied the epigenetic phenotypic switching of the strains and their ploidy, by flow cytometry and CHEF techniques. These studies indicated that although no overall differentiation between the isolates of the two groups (bloodstream infection and vaginitis) could be demonstrated, several characteristics were more specific to one of the groups than the other. While the strains from vaginal infection had higher capacity to adhere, the strains from patients with bloodstream infection had higher activity of phospholipase. Differences were also noted in phenotypic switching, with the strains from bloodstream infection revealing primarily the "white" type colonies, known to be more virulent, and had higher DNA content. This study is unique considering the concurrent comparison of isolates from different clinical entities, at the phenotypic and genotypic level.
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10.1111/myc.12623
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pubmed_91_9660
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The lungs of female guinea pigs, either untreated or previously sensitized with aqueous extracts of cotton dust (AECD) were perfused via the pulmonary artery with 0, 10-6, 10-5 or 10-4 g/mL of lyophilized AECD in Tyrodes solution. Pressure changes in the pulmonary artery were monitored during this period. After perfusion, the pulmonary parenchyma was excised, frozen, and later analyzed for c-AMP, c-GMP, histamine, and total protein. Levels of c-AMP and histamine decreased while levels of c-GMP and pulmonary arterial pressure increased with increasing doses of AECD. Correlation coefficients, between the parameters measured, indicate that the ratio of c-AMP to c-GMP (c-AMP/c-GMP) was a better indicator of histamine depletion or change in pulmonary arterial pressure than was the level of either c-AMP or c-GMP alone. Comparisons of the relative changes in c-AMP, c-GMP, c-AMP/c-GMP, histamine, and pulmonary arterial pressure between sensitized and nonsensitized guinea pigs support the hypothesis that the acute changes in pulmonary function that follow breathing of cotton dust are due to the effects of pharmacoactive compounds and not to antigen-antibody response.
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10.1080/15298667991430712
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pubmed_976_4275
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The neural mechanisms that specify target locations for gaze shifts and then convert these into desired patterns of coordinated eye and head movements are complex. Much of this complexity is only revealed when one takes a realistic three-dimensional (3-D) view of these processes, where fundamental computational problems such as kinematic redundancy, reference-frame transformations, and non-commutativity emerge. Here we review the underlying mechanisms and solutions for these problems, starting with a consideration of the kinematics of 3-D gaze shifts in human and non-human primates. We then consider the neural mechanisms, including cortical representation of gaze targets, the nature of the gaze motor command used by the superior colliculus, and how these gaze commands are decomposed into brainstem motor commands for the eyes and head. A general conclusion is that fairly simple coding mechanisms may be used to represent gaze at the cortical and collicular level, but this then necessitates complexity for the spatial updating of these representations and in the brainstem sensorimotor transformations that convert these signals into eye and head movements.
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10.1016/s0079-6123(03)42009-8
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pubmed_321_17097
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RATIONALE
Effective immunomodulatory therapies for children with life-threatening "cytokine storm" triggered by acute influenza infection are lacking. Understanding the immune profiles of children progressing to severe lung injury and/or septic shock could provide insight into pathogenesis.
OBJECTIVES
To compare the endotracheal and serum cytokine profiles of children with influenza-related critical illness and to identify their associations with severe influenza-associated complications.
METHODS
Children with influenza-related critical illness were enrolled across 32 hospitals in development (N = 171) and validation (N = 73) cohorts (December 2008 through May 2016). Concentrations of 42 cytokines were measured in serum and endotracheal samples and clustered into modules of covarying cytokines. Relative concentrations of cytokines and cytokine modules were tested for associations with acute lung injury (ALI), shock requiring vasopressors, and death/ECMO.
MEASUREMENTS AND MAIN RESULTS
Modules of covarying cytokines were more significantly associated with disease severity than individual cytokines. In the development cohort, increased levels of a serum module containing IL6, IL8, IL10, IP10, GCSF, MCP1, and MIP1α [shock odds ratio (OR) = 3.37, family-wise error rate (FWER) p < 10-4], and decreased levels of a module containing EGF, FGF2, SCD40L, and PAI-1 (shock OR = 0.43, FWER p = 0.002), were both associated with ALI, shock, and death-ECMO independent of age and bacterial coinfection. Both of these associations were confirmed in the validation cohort. Endotracheal and serum cytokine associations differed markedly and were differentially associated with clinical outcomes.
CONCLUSION
We identified strong positive and negative associations of cytokine modules with the most severe influenza-related complications in children, providing new insights into the pathogenesis of influenza-related critical illness in children. Effective therapies may need to target mediators of both inflammation and repair.
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10.3389/fimmu.2017.01423
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pubmed_841_8788
|
The effects of prosodic factors on the spectral rate of change of vowel transitions are investigated. Thirty two-syllable English words are placed in carrier phrases and read by a single speaker. Liquid-vowel, diphthong, and vowel-liquid transitions are extracted from different prosodic contexts, corresponding to different levels of stress, pitch accent, word position, and speaking style, following a balanced experimental design. The spectral rate of change in these transitions is measured by fitting linear regression lines to the first three formants and computing the root-mean-square of the slopes. Analysis shows that the spectral rate of change increases with linguistic prominence, i.e., in stressed syllables, in accented words, in sentence-medial words, and in hyperarticulated speech. The results are consistent with a contextual view of vowel reduction, where the extent of reduction depends both on the spectral rate of change and on vowel duration. A numerical model of spectral rate of change is proposed, which can be integrated in a system for concatenative speech synthesis, as discussed in Paper II [J. Wouters and M. Macon, J. Acoust. Soc. Am. 111, 428-438 (2002)].
|
10.1121/1.1428262
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pubmed_319_15095
|
In this work, 2,4-bis[4-(N,N-diisobutylamino)-2,6-dihydroxyphenyl] squaraine (SQ) was systematically studied as an electron donor in solution processed photovoltaic cells, showing power conversion efficiency of >4.0% under AM1.5G 1 sun illumination at room temperature. Low mobilities were found to limit charge transport in the bulk heterojunctions. Efficiency was thus improved to 5.1% at 80 °C mainly due to improvement of photocurrent extraction. We also demonstrated that the SQ compound synthesized via a simple method has high purity, and thus can be used in photovoltaic cells without further purification. Our results suggest the huge potential of SQ and its analogs in organic photovoltaic applications.
|
10.1039/c2cp42445b
|
pubmed_599_8615
|
BACKGROUND
It is important for doctors and patients to know what factors help recovery from depression. Our objectives were to predict the probability of sustained recovery for patients presenting with mild to moderate depression in primary care and to devise a means of estimating this probability on an individual basis.
METHOD
Participants in a randomized controlled trial were identified through general practitioners (GPs) around three academic centres in England. Participants were aged >18 years, with Hamilton Depression Rating Scale (HAMD) scores 12-19 inclusive, and at least one physical symptom on the Bradford Somatic Inventory (BSI). Baseline assessments included demographics, treatment preference, life events and difficulties and health and social care use. The outcome was sustained recovery, defined as HAMD score <8 at both 12 and 26 week follow-up. We produced a predictive model of outcome using logistic regression clustered by GP and created a probability tree to demonstrate estimated probability of recovery at the individual level.
RESULTS
Of 220 participants, 74% provided HAMD scores at 12 and 26 weeks. A total of 39 (24%) achieved sustained recovery, associated with being female, married/cohabiting, having a low BSI score and receiving preferred treatment. A linear predictor gives individual probabilities for sustained recovery given specific characteristics and probability trees illustrate the range of probabilities and their uncertainties for some important combinations of factors.
CONCLUSIONS
Sustained recovery from mild to moderate depression in primary care appears more likely for women, people who are married or cohabiting, have few somatic symptoms and receive their preferred treatment.
|
10.1017/S0033291710000437
|
pubmed_1102_24515
|
Iron sulfur (Fe-S) clusters are important biological cofactors present in proteins with crucial biological functions, from photosynthesis to DNA repair, gene expression, and bioenergetic processes. For the insertion of Fe-S clusters into proteins, A-type carrier proteins have been identified. So far, three of them have been characterized in detail in Escherichia coli, namely, IscA, SufA, and ErpA, which were shown to partially replace each other in their roles in [4Fe-4S] cluster insertion into specific target proteins. To further expand the knowledge of [4Fe-4S] cluster insertion into proteins, we analyzed the complex Fe-S cluster-dependent network for the synthesis of the molybdenum cofactor (Moco) and the expression of genes encoding nitrate reductase in E. coli. Our studies include the identification of the A-type carrier proteins ErpA and IscA, involved in [4Fe-4S] cluster insertion into the radical S-adenosyl-methionine (SAM) enzyme MoaA. We show that ErpA and IscA can partially replace each other in their role to provide [4Fe-4S] clusters for MoaA. Since most genes expressing molybdoenzymes are regulated by the transcriptional regulator for fumarate and nitrate reduction (FNR) under anaerobic conditions, we also identified the proteins that are crucial to obtain an active FNR under conditions of nitrate respiration. We show that ErpA is essential for the FNR-dependent expression of the narGHJI operon, a role that cannot be compensated by IscA under the growth conditions tested. SufA does not appear to have a role in Fe-S cluster insertion into MoaA or FNR under anaerobic growth employing nitrate respiration, based on the low level of gene expression. IMPORTANCE Understanding the assembly of iron-sulfur (Fe-S) proteins is relevant to many fields, including nitrogen fixation, photosynthesis, bioenergetics, and gene regulation. Remaining critical gaps in our knowledge include how Fe-S clusters are transferred to their target proteins and how the specificity in this process is achieved, since different forms of Fe-S clusters need to be delivered to structurally highly diverse target proteins. Numerous Fe-S carrier proteins have been identified in prokaryotes like Escherichia coli, including ErpA, IscA, SufA, and NfuA. In addition, the diverse Fe-S cluster delivery proteins and their target proteins underlie a complex regulatory network of expression, to ensure that both proteins are synthesized under particular growth conditions.
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10.1128/JB.00086-21
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pubmed_575_17644
|
Musculoskeletal pain is an aversive experience that exists within a variety of conditions and can result in significant impairment for individuals. Gaining greater understanding of the factors related to pain vulnerability and resilience to musculoskeletal pain may help target at-risk individuals for early intervention. This analysis builds on our previous work identifying regions where greater gray matter density was associated with lower pain following standardized, exercise induced musculoskeletal injury. Here we sought to examine the relationship between baseline resting state functional connectivity in a priori regions and networks, and delayed onset muscle soreness (DOMS) pain intensity following a single session of eccentric exercise in healthy adults. Participants completed a baseline functional MRI scan and a high intensity trunk exercise protocol in the erector spinae. Pain intensity ratings were collected 48-hours later. Resting state functional connectivity from four seed regions and 3 networks were separately regressed on pain intensity scores. Results revealed that connectivity between left middle frontal gyrus, the left occipital gyrus and cerebellar network seeds and clusters associated with discriminative, emotional, and cognitive aspects of pain were associated with lower post-DOMS pain. Results suggest resilience to clinically relevant pain is associated with aspects of regional and network neural coherence. Investigations of pain modulatory capacity that integrate multimodal neuroimaging metrics are called for. PERSPECTIVE: Our results provide key support for the role of structural and functional coherence in regional and network connectivity in adaptive pain response and represent an important step in clarifying neural mechanisms of resilience to clinically relevant pain.
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10.1016/j.jpain.2021.05.004
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pubmed_359_5090
|
The last century's environmental pollution has created health problems, acidification of ground and lakes, and serious damage to our cultural heritage. Outdoor monuments suffer from this pollution, but so do buried archaeological remains. However, research on the deterioration of archaeological artifacts underground has so far been limited, and it is important to draw attention to this neglected field. This article presents results obtained at the Swedish National Heritage Board on the degradation of archaeological objects of bronze and iron and of bones from prehistoric graves, materials of which seem to be most affected by pollutants. The investigation methods, which were employed, are described. Other relevant studies are briefly reviewed. It is obvious that the deterioration rate of archaeological artifacts, especially of inorganic materials, has accelerated in recent years, and that this increased deterioration to a large part can be attributed to anthropogenic pollution. Regions that might be endangered are exemplified.
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pubmed_359_5090
|
pubmed_64_2178
|
This protocol describes the application of breath testing and ex vivo fermentations to study the association between breath methane and the composition and functionality of the gut microbiome. The protocol provides a useful systems biology approach for studying the gut microbiome in humans, which combines standardized methods in human breath testing and fecal sampling. The model described is accessible and easy to repeat, but its relative simplicity means that it can deviate from human physiological conditions.
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10.1016/j.xpro.2020.100227
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pubmed_1052_21099
|
OBJECTIVE
To examine how race and the diagnostic label of Osteoarthritis (OA) affects older adults' emotions, illness beliefs, and willingness to help a family member.
METHODS
African American and White older adults were randomly assigned to read vignettes describing a sister suffering from chronic pain and disability, either with or without the OA label. Race × diagnostic label ANOVAs were conducted.
RESULTS
Compared to Whites, African Americans were more optimistic that OA could improve with health care, and showed greater willingness to help their sister. The OA label had little impact on emotions, beliefs, or willingness to help. African Americans rated the sister as having more control of their problem than Whites without the OA label, but providing the diagnosis eliminated this difference.
DISCUSSION
The diagnostic label of OA had little effect on these older adults, but racial differences indicate that cultural values regarding family caregiving are important in arthritis care.
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10.1177/0733464812471893
|
pubmed_970_4078
|
OBJECTIVES
We sought to evaluate the incidence and clinical impact of calcified nodule (CN) in patients with heavily calcified lesions requiring rotational atherectomy (RA).
BACKGROUND
It remains unclear whether CN impacts adversely on clinical outcomes in patients with heavily calcified lesions.
METHODS
Between January 2011 and February 2014, 264 patients after second-generation drug-eluting stent (DES) implantation following RA were retrospectively enrolled. CN was defined as a convex shape of the luminal side of calcium as assessed by intravascular ultrasound. The primary endpoint was the cumulative 5-year incidence of major adverse cardiac events (MACE), defined as a composite of cardiac death, clinically driven target lesion revascularization (CDTLR), and definite stent thrombosis (ST).
RESULTS
CN was observed in 128 patients (48.5%) with heavily calcified lesions. Cumulative 5-year incidence of MACE was significantly higher in the CN group than in the non-CN group, mainly driven by a higher rate of CDTLR and ST (35.4% vs. 18.8%, p < .001; 23.2% vs. 7.9%, p < .001; 7.0% vs. 0.93%, p = .009, respectively). Independent risk factors of 5-year MACE included hemodialysis (hazard ratio [HR] = 3.39, 95% confidence intervals [CI]: 2.00-5.73, p < .001), CN (HR = 2.53, 95% CI: 1.49-4.27, p < .001), ostial lesion (HR = 3.02, 95% CI: 1.58-5.78, p = .001), left ventricular ejection fraction ≤40% (HR = 2.17, 95% CI: 1.27-3.70, p = .005), and right coronary artery lesion (HR = 1.82, 95% CI: 1.07-3.11, p = .03).
CONCLUSIONS
CN was observed in 48.5% of heavily calcified lesions, resulting in unfavorable long-term clinical outcomes after second-generation DES implantation following RA.
|
10.1002/ccd.28896
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pubmed_173_12121
|
Chronic obstructive pulmonary disease (COPD) and bronchial asthma often complicate the surgical patients, leading to post-operative morbidity and mortality. Many authors have tried to predict post-operative pulmonary complications but not specifically in COPD. The aim of this review is to provide recent evidence-based guidelines regarding predictors and ventilatory strategies for mechanical ventilation in COPD and bronchial asthma patients. Using Google search for indexing databases, a search for articles published was performed using various combinations of the following search terms: 'Predictors'; 'mechanical ventilation'; COPD'; 'COPD'; 'bronchial asthma'; 'recent strategies'. Additional sources were also identified by exploring the primary reference list.
|
10.4103/0019-5049.165856
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pubmed_92_24077
|
The influence of extremely low frequency electromagnetic fields on net photosynthesis, transpiration, photosynthetic pigment concentration, and gene expression of ribulose 1,5-bisphosphate carboxylase/oxygenase small subunit (RBCS1), during in vitro establishment, in vitro multiplication and acclimatization phases of coffee seedlings were investigated. Untreated coffee plants were considered as control, whereas treated plants were exposed to a 60 Hz sinusoidal magnetic field of 2 mT of magnetic induction during 3 min. This magnetic field was generated by an electromagnet, connected to a wave generator. The results revealed that magnetically treated plants showed a significant increase in net photosynthesis (85.4% and 117.9%, in multiplication and acclimatization phases, respectively), and in photosynthetic pigment concentration (66.6% for establishment phase, 79.9% for multiplication phase, and 43.8% for acclimatization phase). They also showed a differential RBCS1 gene expression (approximately twofold) and a decrease of transpiration rates in regard to their control plants. In conclusion, the findings suggest that the application of 60 Hz magnetic field to in vitro coffee plants may improve the seedlings quality by modifying some photosynthetic physiological and molecular processes, increasing their vigor, and ensuring better plant development in later stages.
|
10.1002/bem.21859
|
pubmed_1051_16094
|
PURPOSE
To compare the 2-year outcome to antivascular endothelial growth factor therapy for myopic choroidal neovascularization (CNV) in the eyes with or without dome-shaped macula (DSM).
METHODS
Data from treatment-naive myopic CNV with a 2-year follow-up were retrospectively collected and divided into two groups according to the presence of DSM. The best-corrected visual acuity was acquired at baseline, 3, 12, and 24 months. The association between visual outcomes and CNV type and area, presence of scleral-derived feeder vessel, macular atrophy, and lacquer cracks at baseline was also evaluated.
RESULTS
Fifty-four eyes of 54 patients were included; 18 eyes (33.4%) had DSM. Choroidal neovascularization was foveal in 10 DSM eyes (55.6%) and in 30 non-DSM eyes (83.9%), P = 0.033. At baseline, the mean best-corrected visual acuity was significantly higher in the DSM group (68.33 ± 12.04 Early Treatment Diabetic Retinopathy Study letters, 20/40 Snellen) compared with the non-DSM group (57.75 ± 13.46 Early Treatment Diabetic Retinopathy Study letters, 20/72 Snellen; P = 0.007). This difference disappeared after 3 months and did not reoccur afterward. All other parameters were not significantly associated with visual outcomes.
CONCLUSION
Overall, DSM does not represent a negative prognostic factor in response to antivascular endothelial growth factor therapy in myopic CNVs after 2 years. However, in DSM eyes, CNVs tend to be extrafoveal, thus ensuring a good visual prognosis from the earliest stage of the disease.
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10.1097/IAE.0000000000003431
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pubmed_590_10901
|
Estrogenic signaling shapes and modifies daily and circadian rhythms, the disruption of which has been implicated in psychiatric, neurologic, cardiovascular, and metabolic disease, among others. However, the activational mechanisms contributing to these effects remain poorly characterized. To determine the activational impact of estrogen on daily behavior patterns and differentiate between the contributions of the estrogen receptors ESR1 and ESR2, ovariectomized adult female mice were administered estradiol, the ESR1 agonist propylpyrazole triol, the ESR2 agonist diarylpropionitrile, or cholesterol (control). Animals were singly housed with running wheels in a 12-hour light, 12-hour dark cycle or total darkness. Estradiol increased total activity and amplitude, consolidated activity to the dark phase, delayed the time of peak activity (acrophase of wheel running), advanced the time of activity onset, and shortened the free running period (τ), but did not alter the duration of activity (α). Importantly, activation of ESR1 or ESR2 differentially impacted daily and circadian rhythms. ESR1 stimulation increased total wheel running and amplitude and reduced the proportion of activity in the light vs the dark. Conversely, ESR2 activation modified the distribution of activity across the day, delayed acrophase of wheel running, and advanced the time of activity onset. Interestingly, τ was shortened by estradiol or either estrogen receptor agonist. Finally, estradiol-treated animals administered a light pulse in the early subjective night, but no other time, had an attenuated response compared with controls. This decreased phase response was mirrored by animals treated with diarylpropionitrile, but not propylpyrazole triol. To conclude, estradiol has strong activational effects on the temporal patterning and expression of daily and circadian behavior, and these effects are due to distinct mechanisms elicited by ESR1 and ESR2 activation.
|
10.1210/en.2014-1101
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pubmed_408_9647
|
The survival rate of women with colorectal carcinoma is higher than that of men. This is true when censored survival rates are compared (P = 0.0008) as well as when relative survival rates are utilized to compensate for the increased life expectancy of females. Women never pregnant (n = 56) or women with no children (n = 66) showed survival rates similar to men, but significantly different to women with one or more children. The actual number of children, however, did not correlate with survival rates.
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10.1016/0021-9681(82)90032-7
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pubmed_36_16391
|
Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule's regularity for a population. We show how to tune an activity's regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. We use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.
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10.1007/s10588-013-9171-0
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pubmed_154_14464
|
PURPOSE
To review our institution's experience in the treatment of craniopharyngioma and assess the merits of initial therapy with limited surgery and irradiation.
METHODS AND MATERIALS
The data of 30 patients (median age 8.6 years) with a diagnosis of craniopharyngioma between April 1984 and September 1997 were reviewed. Their course of treatment, neurologic, endocrine, and cognitive function, and quality of life at last follow-up were compared.
RESULTS
Fifteen patients were initially treated with surgery (8 required irradiation after relapse) and 15 with limited surgery and irradiation (2 required additional treatment for tumor progression). Only 1 patient died of tumor progression. The surgery group lost a mean of 9.8 points in full-scale IQ, and the combined-modality group lost only 1.25 points (p <0.063). Patients in the surgery group who had relapses (n = 9) lost a mean of 13.1 points (p <0.067). A loss of 10 points was considered clinically significant. The surgery group also had more frequent neurologic, ophthalmic, and endocrine complications. The mean Health Utility Index (a functional quality-of-life index) was higher for the combined-modality group (0.85) than for the surgery group (0.71; p <0.063, one-sided t test).
CONCLUSIONS
The acute neurologic, cognitive, and endocrine effects of surgery often affect long-term function and quality of life. Our experience suggests that limited surgery and radiotherapy cause lesser or comparable sequelae. Diabetes insipidus was the only endocrine deficiency that differed substantially in frequency between the two groups. Newer radiation planning and delivery techniques may make a combined-modality approach a good initial option for most patients.
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10.1016/s0360-3016(02)02799-2
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pubmed_159_22306
|
A novel ZnO-CeO2-rGO (ZCG) ternary nanocomposite with varying ZnO/CeO2 weight proportions was synthesized by a hydrothermal process for photoelectrochemical water splitting and photocatalytic application. XRD diffraction peaks of ZCG nanocomposites displayed the patterns of ZnO and CeO2 nanoparticles, and SEM revealed irregular flake-like particles, which were uniformly decorated on the rGO matrix. Increase in the intensity ratio of D and G bands from Raman spectra revealed changes in oxygen bonding in the ZnO-rGO (ZG) and ZCG nanocomposites. The shift in the band edge positions and the decrease in the band gap with increase in the cerium oxide content in ZCG composites were observed from UV-Vis and Mott-Schottky plots. XPS results showed that Ce3+ fraction increased with an increase in the cerium oxide content in ZCG nanocomposites. The ZCG3 (85:15) nanocomposite exhibited decreased electron-hole recombination rate as evidenced from the photoluminescence and electrochemical impedance spectroscopy Nyquist plots. The characteristic frequency in Bode's plot shifted to a lower frequency for the ZCG3 electrode demonstrating low interfacial charge transfer resistance, and ZCG3 photoelectrode displayed a higher photocurrent density of 0.69 mA/cm2 at 1.5 V compared with other photoelectrode. The optimized and highly efficient ZCG3 nanocomposite exhibited improved photocatalytic degradation of methylene blue (MB) with a reaction rate constant of 0.0201 min-1. Combination of defects in the form of Ce3+ ion and surface oxygen vacancies coupled with rGO as the electron acceptor improved the charge carrier density and carrier transport in addition to the formation Schottky-type junction and the presence of an internal electric field.
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10.1007/s11356-020-08990-z
|
pubmed_751_10694
|
It has been proposed that concentrations of nuclear androgen receptor may be predictive of tumor hormone dependence in cases of advanced human prostatic cancer. We have investigated the ability of this receptor population to reflect patient prognosis during endocrine therapy in 12 cases of stage D disease. KCl-extractable, nuclear matrix-bound and total nuclear androgen receptor concentrations showed a significant positive correlation with duration of patient survival (p less than 0.05) while cytosolic and total cellular androgen receptor concentrations were not significantly correlated with survival. However, use of selected threshold concentrations of receptors revealed that only cytosolic, nuclear KCl-extractable and total cellular receptors could significantly differentiate long-term and short-term survivors. Even given the small number of patients studied, the potential use of this androgen receptor assay as an index of both tumor hormone-dependence and patient prognosis was evident. Therefore, in order to make these androgen receptor assays more applicable, we attempted to simplify the methods for use on readily available tissues. Similar amounts of nuclear androgen binding were observed in crude and purified nuclear pellets, in nuclei treated with DNase and KCl in differing orders or in nuclei from tissue homogenized using glass or Polytron homogenization procedures. More importantly, nuclear androgen receptor concentrations in specimens of prostatic cancer or benign hyperplasia taken by needle biopsy or transurethral resection involving electrocautery did not differ from those of parallel specimens taken by Thompson cold punch. Simplified nuclear androgen receptor assays of needle biopsy or electrocautery specimens are accurate and should prove clinically applicable.
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10.1016/s0022-5347(17)45555-8
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pubmed_1047_12281
|
Testicular toxicity and interstitial cell tumours induced by cadmium are prevented by zinc or by low dose cadmium pretreatments. The mechanism of this tolerance is unknown, though metallothionein (MT) is thought to play a role in tissue resistance to cadmium toxicity. Thus, the possible involvement of the testicular MT gene in metal-induced tolerance to cadmium toxicity was studied. Rats were pretreated with zinc (1.0 mmol kg-1, s.c.). Histological examination of the testes indicated such pretreatments prevented the necrotizing effects of subsequent doses of cadmium (20 mumol kg-1, s.c.) administered 24 h later. RNA was extracted from testes or liver 24 h after zinc pretreatment, and analysed by the slot blot technique using the p2A10 cDNA probe to the MT gene. Zinc pretreatment had little effect on MT RNA in the testes, and such pretreatments did not alter testicular cadmium-binding protein capacity. In contrast, RNAs derived from livers of zinc pretreated rats showed marked increases in MT RNA and MT protein. Hence, the testicular MT gene does not appear to play a major role in the induced tolerance to cadmium toxicity and carcinogenesis generated by zinc.
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10.1177/096032719401300110
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pubmed_581_19889
|
We report a case of TNBC treated effectively with a platinum-based regimen after developing resistance to anthracycline and taxane-based neoadjuvant chemotherapy(NAC). A 59-year-old woman with a right breast mass and high fever visited our clinic and was diagnosed as having inflammatory triple negative breast cancer(iTNBC). She was treated with NAC of docetaxel, doxorubicin, and cyclophosphamide(TAC)using pegfilgrastim. After 5 courses of TAC, the therapy failed and the disease progressed. Thus, a combination regimen of gemcitabine and carboplatin(GC)was administered. The treatment was successful, and the patient underwent a curative operation after 6 courses of the GC therapy.
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pubmed_581_19889
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pubmed_315_10933
|
In eukaryotes, genomic DNA is packaged with histone proteins into the cell nucleus as chromatin, condensing the DNA > 10,000-fold. Chromatin is highly dynamic and exerts profound control on gene expression. Localised chromatin decondensation facilitates access of nuclear machinery. Chromatin displays epigenetic inheritance, in that changes in its structure can pass to the next generation independently of the DNA sequence itself. It is now clear that the post-translational modification of histones, for example, acetylation, methylation and phosphorylation, plays a crucial role in the regulation of nuclear function through the 'histone code'. There has been significant progress in identifying and understanding the enzymes that control these complex processes, in particular histone acetyltransferases and histone deacetylases. The exciting discovery that compounds inhibiting histone deacetylase activity also have antitumour properties has focused attention on their use as anticancer drugs. As a consequence, there is ongoing evaluation of several histone deacetylase inhibitor compounds in Phase I and II clinical trials with promising early results. It is likely that many of the enzymes involved in the control of histone modification will provide therapeutic opportunities for the treatment of cancer, including histone methyltransferases and Aurora kinases.
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10.1517/eoed.9.1.135.32947
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pubmed_964_545
|
The contents of panaxadiol and panaxatriol in Shihu Yeguang Pills manufactured by pharmaceutical works in Beijing, Jinan, Guangzhou and other places were determined by TLC-densitometry. A quantitative method has been developed to serve as a reference to quality control of these pills.
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pubmed_964_545
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pubmed_827_1421
|
Respiratory syncytial virus (RSV) is a common cause of virus infection of the human respiratory tract during the first two years of life, with virtually all children experiencing at least one infection within this period. Although this usually leads to mild respiratory illness, some infants develop more severe disease (bronchiolitis, pneumonia, etc.) affecting the lower airways and frequently requiring hospitalisation. There is evidence that bronchiolitis hospitalisations have increased during the last two decades and many of the hospitalised children develop wheezing later in life. The immune response to the virus is probably a major factor in the development or the expression of the pathological phenotype. In particular, a bias towards type-2 cytokine responses seems to be associated with more severe disease, whereas a type-1 response leads to more effective viral clearance and milder illness. Although the virus by itself triggers a type-1 response, a preexisting type-1 deficiency may contribute to the severity of the disease. In that sense, RSV bronchiolitis may serve as a marker, reflecting predisposition of the individual for virus induced wheezing early in life and/or asthma later in life.
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10.1016/s1526-0542(04)90034-6
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pubmed_433_3571
|
PURPOSE
To evaluate the effectiveness of the Genomics ADvISER (www.genomicsadviser.com) decision aid (DA) for selection of secondary findings (SF), compared with genetic counseling alone.
METHODS
A randomized controlled trial (RCT) was conducted to evaluate whether the Genomics ADvISER is superior to genetic counseling when hypothetically selecting SF. Participants were randomized to use the DA followed by discussion with a genetic counselor, or to genetic counseling alone. Surveys were administered at baseline and post-intervention. Primary outcome was decisional conflict. Secondary outcomes were knowledge, preparation for, and satisfaction with decision-making, anxiety, and length of counseling session.
RESULTS
Participants (n = 133) were predominantly White/European (74%), female (90%), and ≥50 years old (60%). Decisional conflict (mean difference 0.05; P = 0.60), preparation for decision-making (0.17; P = 0.95), satisfaction with decision (-2.18; P = 0.06), anxiety (0.72; P = 0.56), and knowledge of sequencing limitations (0.14; P = 0.70) did not significantly differ between groups. However, intervention participants had significantly higher knowledge of SF (0.39; P < 0.001) and sequencing benefits (0.97; P = 0.01), and significantly shorter counseling time (24.40 minutes less; P < 0.001) CONCLUSIONS: The Genomics ADvISER did not decrease decisional conflict but reduced counseling time and improved knowledge. This decision aid could serve as an educational tool, reducing in-clinic time and potentially health care costs.
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10.1038/s41436-019-0702-z
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pubmed_389_6999
|
BACKGROUND
The acute impact of tobacco smoking on the cardiac hemodynamic parameters and its pathological implication in the process of arterial atherosclerosis need further exploration. This investigation was purposed to assess the acute impact of tobacco smoke on blood pressure and cardiac hemodynamic parameters.
METHODS
Using an Ultrasonic Cardiac Output Monitor, and DINAMAP Pro 400 Series V2 blood pressure monitor, several cardiac hemodynamic parameters and the blood pressure were assessed in 14 smokers, 11 females and 3 males, at 2 time points, before and after smoking of one cigarette. Data, in terms of ratio of the means and 95% confidence interval were analyzed using ANOVA.
RESULTS
Single-subject design in which the subject has served as his/her own control has been used. Tobacco smoking led to statistically significant acute increase in the means of all hemodynamic parameters, except for heart rate in female subjects, as compared to the means obtained before smoking.
CONCLUSIONS
Cigarette smoking induces acute non-physiologic alteration in cardiac outflow forces, exposing the aortic valve and arch to mechanical injury that might be implicated in initiating and promoting the process of aortic arch atherosclerosis and associated pathological lesions.
|
10.4021/cr24e
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pubmed_585_22825
|
Treatment of autoreactive inflammatory diseases such as rheumatoid arthritis with anti-inflammatory drugs is associated with an increased rate of reactivation tuberculosis (TB). Interleukin-6 (IL-6) plays a pivotal role in inflammation and protection against various infectious diseases. IL-6 signals by two mechanisms via the ubiquitous transmembrane protein gp130: 'classic' signaling using the membrane-bound IL-6 receptor (IL-6R), which is expressed mainly on hepatocytes and some leukocytes, and trans-signaling using soluble IL-6R (sIL-6R). Trans-signaling by the IL-6/sIL-6R complex is selectively inhibited by natural soluble gp130 (sgp130) and by sgp130 designer proteins. As specific blockade of IL-6 trans-signaling represents a promising approach for the therapy of inflammatory diseases, we evaluated the potential risk of interfering with this alternative pathway and analyzed the outcome of experimental TB after treatment with an IgG1-Fc fusion protein of soluble gp130 (sgp130Fc) and in sgp130Fc-overexpressing transgenic (sgp130Fc(tg)) mice. In contrast to treatment with anti-tumor necrosis factor (TNF) antibodies, administration of sgp130Fc did not interfere with protective immune responses after infection with Mycobacterium tuberculosis (Mtb). Moreover, Mtb-infected sgp130Fc(tg) mice were capable of controlling mycobacterial growth. Our finding that IL-6 trans-signaling plays no role for protective immune responses against Mtb supports the superior safety of therapeutic targeting of IL-6 trans-signaling compared to anti-TNF treatment.
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10.1016/j.imbio.2012.01.015
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pubmed_282_23161
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This paper describes the computationally informed design and experimental validation of a microfluidic chip device with multi-axial stretching capabilities. The device, based on PDMS soft-lithography, consisted of a thin porous membrane, mounted between two fluidic compartments, and tensioned via a set of vacuum-driven actuators. A finite element analysis solver implementing a set of different nonlinear elastic and hyperelastic material models was used to drive the design and optimization of chip geometry and to investigate the resulting deformation patterns under multi-axial loading. Computational results were cross-validated by experimental testing of prototypal devices featuring the in silico optimized geometry. The proposed methodology represents a suite of computationally handy simulation tools that might find application in the design and in silico mechanical characterization of a wide range of stretchable microfluidic devices.
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10.1038/s41598-017-05237-9
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pubmed_163_25891
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Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1-35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivors' HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan-Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 μM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ2=12.1, p=4.9×10-4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.
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pubmed_163_25891
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pubmed_741_13193
|
Diethyl maleate (DEM) is known to produce a rapid depletion of hepatic glutathione (GSH) and to induce an immediate short-term choleresis in experimental animals. The aim of our investigation was to ascertain in rats the effect of DEM on biliary lipid composition during the increment in bile flow. Biochemical and morphological studies of liver tissue were conducted in parallel. In bile fistula rats, a doubling of bile flow occurred immediately after intraperitoneal injection of DEM (0.7 ml/kg body weight) returning to the basal level at 45 min. Choleresis diluted the total bile acid concentration, without modifying the secretion. The phospholipid concentration was not affected by DEM, resulting in increased output (p less than 0.02 vs. controls). Both cholesterol concentration and output were significantly decreased during DEM-induced choleresis. These changes were promptly reversible together with the return of bile flow to control values. Biochemical determinations failed to show a DEM-induced modification of enzymatic activities of the microsomal drug biotransformation pathway. Instead, morphological studies revealed alterations of the Golgi apparatus in hepatocytes with marked distension of the cisternae in coincidence with choleresis. The results demonstrate that the bile acid-independent choleresis induced by DEM is accompanied by an alternation in biliary lipid secretion possibly related to an interaction of the drug with the cellular or subcellular membranes of hepatocytes.
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10.1159/000198956
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pubmed_844_18792
|
The medical community has begun to realize the complexity of aortic pathology in vivo and its often iridescent and ambiguous clinical presentation. Diagnostic modalities such as transesophageal echocardiography, magnetic resonance imaging, and computed tomography have all been shown to be useful to investigate the aorta, both in chronic disease and in acute aortic syndromes. This article focuses on the possibilities and emerging advantages of magnetic resonance imaging with respect to a spectrum of aortic pathologies.
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10.1016/s0733-8651(05)70014-x
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pubmed_99_18827
|
The mitochondrial mutations conferring resistance to antibiotics erythromycin, neomycin, oligomycin and mucidin, have been isolated in a number of strains. An attempt was made to genetically map these markers. The principle of coretention/or loss of two markers in UV induced petite mutants was used for localisation of the mitochondrial markers. The unique order of markers E-O-M-N was established in our experiments. The preferential loss of the Nr marker in petite mutants was observed. No significant differences in the gene order and in gene relative distances were observed between our PG strain and other nonrelated strains of Saccharomyces cerevisiae.
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pubmed_99_18827
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pubmed_176_2676
|
Metastasis remains one of the major challenges before hepatocellular carcinoma (HCC) is finally conquered. Estrogen has recently emerged as a protective factor in the development and progression of HCC, but whether and how it reduces metastasis of HCC remain to be elucidated. We conducted an in vivo highly metastatic rat HCC model in female Sprague-Dawley rats induced by diethylnitrosamine and N-nitrosomorpholine to examine the effects of estrogen on HCC metastasis. Moreover, female rats were randomly distributed into four groups: ovariectomy (OVX), sham operation, ovariectomy followed by 30 μg/kg body weight/day 17α-ethynylestradiol supplementation, and sexually intact control groups. Here, we show that, 60% lung metastasis was observed in the rats of OVX group, whereas 17-25% lung metastasis was found in rats of the other three groups. Furthermore, physiological doses of estrogen, no matter endogenous or exogenous, can suppress metastasis of HCC through decreasing interleukin-6 (IL-6) and hepatocyte growth factor (HGF) expression in the tumor microenvironment. In conclusion, the present study demonstrated that estrogen has the potential to inhibit lung metastasis from rat HCCs in vivo. Its mechanism of action may involve modulation of inflammatory tumor microenvironment by suppression of HGF and IL-6 production.
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10.1007/s10753-011-9299-3
|
pubmed_324_9987
|
OBJECTIVES
Cancer-related fatigue (CRF) is associated with tiredness and sleepiness. It remains unclear, whether such complaints are associated with neurophysiological signs of sleep proneness or a state of neurophysiological hyperarousal in which the patient finds it difficult to relax and to initiate sleep. Therefore the goal of this study is to compare the electroencephalographic (EEG)-vigilance regulation of patients with CRF and healthy controls.
METHODS
A 15-min resting EEG with eyes closed was recorded in 22 patients with CRF and 22 matched healthy controls. Consecutive 1-s segments were classified into seven different vigilance stages ranging from high alertness to relaxed wakefulness (stage 0, A1, A2, A3) and further on to drowsiness (B1, B2/3) and sleep onset (stage C).
RESULTS
Results showed that patients with CRF revealed a higher number of vigilance stages A3 (mean 15.26 vs. 6.67%, P = 0.004) dropped significantly earlier to vigilance levels A3 (drop after 130.8 vs. 533.3 s, P = 0.000) and B2/3&C (407.8 vs. 604.1 s, P = 0.035) and showed significantly more transitions between vigilance stages (46.0 vs. 31.1%, P = 0.003) in comparison to healthy controls.
CONCLUSIONS
These findings suggest an unstable vigilance regulation in patients with CRF and provide a neurophysiological framework for the reported efficacy of psychostimulants in CRF.
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10.3109/15622975.2010.545434
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pubmed_786_11
|
BACKGROUND AND AIMS
We have developed a mouse model of gastric cancer that resembles human intestinal-type adenocarcinoma. The aim of this study was to determine the identity and temporal changes in mediators of IL-6 signaling regulating tumor development.
METHODS
gp130(757F/F) Mice that lack the SHP2-binding site on the IL-6 family receptor gp130 and have increased STAT 3 activity and wild-type littermates were used. Cohorts were assessed by quantitative histology and immunohistochemistry for gastric cell phenotype and proliferation markers from 4 to 40 weeks of tumor development. Northern blotting and in situ hybridization were used to quantify expression of the tumor suppressor TFF1 and the mitogens gastrin and Reg I. Expression of epidermal growth factor receptor (EGFr) and its ligands was measured by RT-PCR analysis. Age-matched differences in gene expression profiles were tested by ANOVA.
RESULTS
Hyperplastic antral tumors with inflammation and ulceration were evident in gp130(757F/F) mice at 4 weeks of age and reached maximum size by 20 weeks. Tumor progression was marked by gastritis, atrophy, intestinal metaplasia, dysplasia, and submucosal invasion after 30 weeks. Both TFF1 and gastrin expression were progressively inhibited during tumorigenesis, whereas Reg I was stimulated. The EGFr and its ligands transforming growth factor (TGF)-alpha and heparin-binding EGF had increased expression corresponding to maximal tumor growth.
CONCLUSIONS
gp130(757F/F) Mice rapidly develop distal stomach tumors, with loss of SHP2/Erk/AP-1 transcriptional regulation exemplified by decreased TFF1 expression and increased STAT1/3 regulated genes such as Reg I. Tumor development occurs in a hypogastrinemic environment. Balanced IL-6 signaling is required for maintaining gastric homeostasis.
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10.1053/j.gastro.2003.10.066
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pubmed_733_6394
|
Activation of the p53 transcription factor in response to a variety of cellular stresses, including DNA damage and oncogene activation, initiates a program of gene expression that blocks the proliferative expansion of damaged cells. While the beneficial impact of the anticancer function of p53 is well established, several recent papers suggest that p53 activation may in some circumstances act in a manner detrimental to the long-term homeostasis of the organism. Here, we discuss the significant participation of p53 in three non-mutually exclusive theories of human aging involving DNA damage, telomere shortening, and oxidative stress. These "good cop/bad cop" functions of p53 appear to place it at the nexus of two opposing forces, cancer and aging. By extension, this relationship implies that therapies aimed to reduce cancer and postpone aging, and thereby increase longevity, will necessarily work either upstream or downstream, but not on the level of, p53.
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10.1016/s0092-8674(02)00818-8
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pubmed_597_20336
|
BACKGROUND
Prostate cancer remains dependent of androgen receptor (AR) signalling, even after emergence of castration resistance. EZN-4176 is a third-generation antisense oligonucleotide that binds to the hinge region (exon 4) of AR mRNA resulting in full-length AR mRNA degradation and decreased AR protein expression. This Phase I study aimed to evaluate EZN-4176 in men with castration-resistant prostate cancer (CRPC).
METHODS
Patients with progressing CRPC were eligible; prior abiraterone and enzalutamide treatment were allowed. EZN-4176 was administered as a weekly (QW) 1-h intravenous infusion. The starting dose was 0.5 mg kg(-1) with a 4-week dose-limiting toxicity (DLT) period and a 3+3 modified Fibonacci dose escalation design. After determination of the DLT for weekly administration, an every 2 weeks schedule was initiated.
RESULTS
A total of 22 patients were treated with EZN-4176. At 10 mg kg(-1) QW, two DLTs were observed due to grade 3-4 ALT or AST elevation. No confirmed biochemical or soft tissue responses were observed. Of eight patients with <5 circulating tumour cells at baseline, a conversion to <5 was observed in three (38%) patients. The most common EZN-4176-related toxicities (all grades) were fatigue (59%), reversible abnormalities in liver function tests ALT (41%) and AST (41%) and infusion-related reactions including chills (36%) and pyrexia (14%).
CONCLUSION
Activity of EZN-4176 at the doses and schedules explored was minimal. The highest dose of 10 mg kg(-1) QW was associated with significant but reversible transaminase elevation.
|
10.1038/bjc.2013.619
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pubmed_410_24889
|
The functional properties of neocortical pyramidal cells (PCs), such as direction and orientation selectivity in visual cortex, predominantly derive from their excitatory and inhibitory inputs. For layer 2/3 (L2/3) PCs, the detailed relationship between their functional properties and how they sample and integrate information across cortical space is not fully understood. Here, we study this relationship by combining functional in vivo two-photon calcium imaging, in vitro functional circuit mapping, and dendritic reconstruction of the same L2/3 PCs in mouse visual cortex. Our work reveals direct correlations between dendritic morphology and functional input connectivity and the orientation as well as direction tuning of L2/3 PCs. First, the apical dendritic tree is elongated along the postsynaptic preferred orientation, considering the representation of visual space in the cortex as determined by its retinotopic organization. Additionally, sharply orientation-tuned cells show a less complex apical tree compared with broadly tuned cells. Second, in direction-selective L2/3 PCs, the spatial distribution of presynaptic partners is offset from the soma opposite to the preferred direction. Importantly, although the presynaptic excitatory and inhibitory input distributions spatially overlap on average, the excitatory input distribution is spatially skewed along the preferred direction, in contrast to the inhibitory distribution. Finally, the degree of asymmetry is positively correlated with the direction selectivity of the postsynaptic L2/3 PC. These results show that the dendritic architecture and the spatial arrangement of excitatory and inhibitory presynaptic cells of L2/3 PCs play important roles in shaping their orientation and direction tuning.
|
10.1016/j.cub.2022.02.048
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pubmed_775_109
|
Subjects conditioned concurrently to two different conditioned stimuli, light and tone, exhibited a significantly higher level of conditioning to the stimulus paired with a strong unconditioned stimulus than to the stimulus paired with a weak one. The findings suggest that habit strength in aversive conditioning varies with the intensity of the unconditioned stimulus.
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10.1126/science.128.3327.774
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pubmed_247_24220
|
Neuromodulation is a new treatment modality for disturbances of bladder function. By stimulation of a sacral nerve the pelvic floor is activated, thus affecting the reflex arcs which control micturition and continence. Along with 2 case histories the methods of the preoperative percutaneous test stimulation and the implantation of stimulator and electrode are described.
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pubmed_247_24220
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pubmed_328_11820
|
The impact of treating astrocytes with the astrocytic toxin l-alpha amino adipic acid (L-AAA) on neuronal outgrowth, complexity and synapse formation was assessed, using a model of astrocyte-neuronal interaction. Treatment of rat primary cortical neurons with conditioned media (CM) derived from astrocytes treated with L-AAA reduced neuronal complexity and synapse formation. L-AAA provoked a reduction in the expression of glial fibrillary acid protein (GFAP) and a reduction in ATP-linked mitochondrial respiration in astrocytic cells. As the NMDA-R/PSD-95/NOS signaling pathway is implicated in regulating the structural plasticity of neurons, treatment of neuronal cultures with the neuronal nitric oxide synthase (nNOS) inhibitor 1-[2-(trifluoromethyl)phenyl] imidazole (TRIM) [100 nM] was assessed and observed to protect against L-AAA-treated astrocytic CM-induced reduction in neuronal complexity and synapse loss. Treatment with the NMDA-R antagonist ketamine protected against the CM-induced loss of synapse formation whereas the novel PSD-95/nNOS inhibitors 2-((1H-benzo[d] [1,2,3]triazol-5-ylamino) methyl)-4,6-dichlorophenol (IC87201) and 4-(3,5-dichloro-2-hydroxy-benzylamino)-2-hydroxybenzoic acid (ZL006) protected against synapse loss with partial protection against reduced neurite outgrowth. Furthermore, L-AAA delivery to the pre-limbic cortex (PLC) of mice was found to increase dendritic spine density and treatment with ZL006 reduced this effect. In summary, L-AAA-induced astrocyte impairment leads to a loss of neuronal complexity and synapse loss in vitro and increased dendritic spine density in vivo that may be reversed by inhibitors of the NMDA-R/PSD-95/NOS pathway. The results have implications for understanding astrocytic-neuronal interaction and the search for drug candidates that may provide therapeutic approaches for brain disorders associated with astrocytic histopathology.
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10.1016/j.neuroscience.2018.09.023
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pubmed_476_19976
|
PURPOSE
Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. As achieving a dry macula is one of the main objectives in AMD management, the purpose of this work was to reach a consensus on the relevance of retinal fluid in function, disease activity control and treatment patterns.
METHODS
Forty-seven Portuguese ophthalmologists specialized in AMD participated in a DELPHI panel. Two rounds of presential meetings were conducted and a cut-off of 80% or more of votes was defined to consider answers consensual.
RESULTS
Consensus was reached for 11 out of 18 questions. These questions focused on the impact of anatomical results on visual acuity, standards exams and parameters to assess disease activity, frequency and factors which influence disease activity assessment, criteria to use non-fixed treatment regimens, usefulness of individualized regimens and conditions for treatment interruption. No consensus was obtained for relevance of the different fluid types in AMD prognosis, frequency of fluid presence assessment, factors commonly associated with progression to geographic atrophy, ideal conditions for a fixed treatment regimen, date of first disease activity assessment and parameters to monitor disease activity.
CONCLUSIONS
Consensus was achieved for over half of the questions assessed through this Delphi study. The questions for which no consensus was reached concerned either subjects that need further investigation or monitoring times which are influenced by resource availability. Raising awareness for these issues will allow the improvement of AMD management and treatment.
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10.1007/s10792-021-02177-2
|
pubmed_1131_24324
|
BACKGROUND
For patients with metastatic renal cell carcinoma (mRCC), targeted therapies have entered the market since 2006. The aims of this study were to evaluate the uptake and use of targeted therapies for mRCC in The Netherlands, examine factors associated with the prescription of targeted therapies in daily clinical practice and study their effectiveness in terms of overall survival (OS).
METHODS
Two cohorts from PERCEPTION, a population-based registry of mRCC patients, were used: a 2008-2010 Cohort (n = 645) and a 2011-2013 Cohort (n = 233). Chi-squared tests for trend were used to study time trends in the use of targeted therapy. Patients were grouped based on the eligibility criteria of the SUTENT trial, the trial that led to sunitinib becoming standard of care, to investigate the use of targeted therapies amongst patients fulfilling those criteria. Multi-level logistic regression was used to identify patient subgroups that are less likely to receive targeted therapies.
RESULTS
Approximately one-third of patients fulfilling SUTENT trial eligibility criteria did not receive any targeted therapy (29 % in the 2008-2010 Cohort; 35 % in the 2011-2013 Cohort). Patients aged 65+ years were less likely to receive targeted therapy in both cohorts and different risk groups (odds ratios range between 0.84-0.92); other factors like number of metastatic sites were of influence in some subgroups. Amongst treated patients, there was a decreasing trend in sunitinib use over time (p = 0.0061), and an increasing trend in pazopanib use (p = 0.0005).
CONCLUSIONS
Targeted therapies have largely replaced interferon-alfa as first-line standard of care. Nevertheless, many eligible patients in Dutch daily practice did not receive targeted therapies despite their ability to improve survival. Reasons for their apparent underutilisation should be examined more carefully.
|
10.1186/s12885-016-2395-x
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pubmed_944_25072
|
The function of the paranasal sinuses has been a controversial subject since the time of Galen, with many different theories advanced about their biological significance. For one, the paranasal sinuses have been regarded as warmers of respiratory air, when in actuality these structures appear to function in cooling the blood. In fact, human paranasal sinuses have been shown to have higher volumes in individuals living in warmer climates, and thus may be considered radiators of the brain. The literature suggests that the transfer of cool venous blood from the paranasal sinuses to the dura mater may provide a mechanism for the convection process of cooling produced by the evaporation of mucus within human sinuses. In turn, the dura mater may transmit these temperature changes, initiated by the cool venous blood from the heat-dissipating surfaces of the sinuses, to the cerebrospinal fluid compartments. Furthermore, it has recently been demonstrated in cadaveric dissections that the thin bony posterior wall of the maxillary sinus serves as an origin for both medial and lateral pterygoid muscle segments, an anatomic finding that had been previously underappreciated in the literature. The present authors hypothesize that the thin posterior wall of the maxillary sinus may flex during yawning, operating like a bellows pump, actively ventilating the sinus system, and thus facilitating brain cooling. Such a powered ventilation system has not previously been described in humans, although an analogous system has been reported in birds.
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10.1016/j.mehy.2011.08.022
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pubmed_0_1517
|
Impotence is one of the common complications after the radical prostatectomy. One of the main reasons of this complication is due to the dysfunction of the veins in corpus cavernosum. Recent studies have shown that the erectile function is improved after the long-term therapy of phosphodiesterase type 5 inhibitor among patients with post-prostatectomy erectile dysfunction. In this study, we evaluated the effects of mirodenafil on the penile erection and corpus cavernosum tissues in the rat model of cavernosal nerve injury. Rats were divided into four groups: (1) control group, (2) bilateral cavernosal nerve injury group, (3) mirodenafil 10 mg therapy group after the nerve injury and (4) mirodenafil 20 mg therapy group after the nerve injury. After we identified the nerve from the pelvic nerve complex on the lateral side of the prostate, the rats in the control group were sutured without causing any nerve injury and in other groups we damaged the nerve by compressing it with a vessel clamp. Then, 10 and 20 mg kg(-1) of mirodenafil were orally administered to two experimental groups. After 8 weeks, the intracavernosal pressure (ICP) was recorded. The immunohistochemical staining and western blot were performed, and the effect of mirodenafil on the expression of cyclic guanosine monophosphate (cGMP) was evaluated through enzyme-linked immunosorbent assay. The ICP of nerve-injured group was decreased compared with the control group; however, the ICP of the mirodenafil-administered groups was improved compared with the nerve-injured group. The Masson's trichrome staining confirmed that the smooth muscle (SM) component was increased in the mirodenafil-administered groups. The nitric oxide synthase expression and cGMP of mirodenafil-administered groups was increased compared with the nerve-injured group. Long-term therapy of mirodenafil may improve the erectile function after the radical prostatectomy by preserving the SM content and inhibiting the fibrosis of the corpus cavernosum.
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10.1038/ijir.2010.19
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pubmed_663_22392
|
OBJECTIVES
We previously found that the polymorphisms of cholesterol 24-hydroxylase (CYP46A1) gene were associated with the risk of Alzheimer's disease (AD) in Chinese. However, its effect in predicting progression of cognitive decline remains unknown.
METHODS
Two hundred and eighty-one Chinese subjects (121 cognitively intact, 101 with mild cognitive impairment and 59 with mildly dementia) were followed-up with a mean (SD) duration of 25.22(5.74) months. Association between the CYP46A1 gene polymorphisms and 2-year cognitive deterioration were evaluated.
RESULTS
At follow-up, 225(80.0%) subjects were reassessed. Sixty-three subjects were diagnosed as AD, 68 were MCI and 94 were cognitively intact. Among them, 158 had improved or remained stable while 67 deteriorated. The 'deteriorated' group was older than 'improved or stable' group (t-test, t = -2.87, p < 0.001). IVS2-150 polymorphism was associated with a higher risk of cognitive deterioration. Subjects with T allele were more likely to deteriorate compared with those without T allele (Pearson chi(2) = 8.98, df 2, p = 0.011). IVS3-128 CC genotype was higher in 'improved or stable' group (Likelihood Ratio = 6.55, df 2, p = 0.038), suggesting a protective role for this allele. The two other polymorphisms, IVS1-192 and IVS4-122, did not show any significant association with cognitive function.
CONCLUSION
CYP46A1 gene may act to modulate the course of cognitive deterioration in late life.
|
10.1002/gps.2196
|
pubmed_844_1190
|
Transplant patients are at risk for developing post-transplant psychiatric problems, most commonly delirium, depression, and anxiety. Transplantation imposes a significant impact on patients, as well as family members. Therefore, the psychological needs of the family unit should be addressed. The advanced practice nurse (APN) functioning as a clinician, educator, consultant, or researcher has the knowledge and clinical skills to provide continuity of care for patients and family members during the transplant process.
|
10.3928/0279-3695-19980501-13
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pubmed_978_8925
|
The indications and results of anterior acromioplasty in patients older than 40 years of age are well documented; however, little is reported concerning this procedure in younger patients because the majority are treated conservatively. Over the last seven years, 26 patients younger than 40 years of age were treated by anterior acromioplasty for subacromial impingement resistant to conservative therapy. The indication for surgery was failed conservative therapy in 17 patients. Six patients had impingement despite previous surgery, such as failed acromioplasty, biceps tenolysis, and biceps tenodesis. Two patients had impingement secondary to greater tuberosity malunion. The average duration of symptoms was 27 months and of conservative therapy, 17 months. All patients had a bursectomy and anterior acromioplasty. In addition, eight had a complete acromioclavicular arthroplasty for concurrent acromioclavicular arthritis, four had a modified acromioclavicular arthroplasty for impingement under the acromioclavicular joint, three had calcium excisions, and one had a rotator cuff repair. The greater tuberosity malunions were advanced in one patient and excised in one. The results were 81% (21) excellent and good, 15% (four) fair, and 4% (one) poor. The average follow-up period was 33 months. The majority of younger patients with subacromial impingement can be successfully treated conservatively. In those patients with persistent symptoms, open acromioplasty can reliably give good results with regard to pain and function.
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pubmed_978_8925
|
pubmed_20_19914
|
BACKGROUND
Prolonged controlled mechanical ventilation depresses diaphragmatic efficiency. Assisted modes of ventilation should improve it. We assessed the impact of pressure support ventilation versus neurally adjusted ventilator assist on diaphragmatic efficiency.
METHOD
Patients previously ventilated with controlled mechanical ventilation for 72 hours or more were randomized to be ventilated for 48 hours with pressure support ventilation (n =12) or neurally adjusted ventilatory assist (n = 13). Neuro-ventilatory efficiency (tidal volume/diaphragmatic electrical activity) and neuro-mechanical efficiency (pressure generated against the occluded airways/diaphragmatic electrical activity) were measured during three spontaneous breathing trials (0, 24 and 48 hours). Breathing pattern, diaphragmatic electrical activity and pressure time product of the diaphragm were assessed every 4 hours.
RESULTS
In patients randomized to neurally adjusted ventilator assist, neuro-ventilatory efficiency increased from 27 ± 19 ml/μV at baseline to 62 ± 30 ml/μV at 48 hours (p <0.0001) and neuro-mechanical efficiency increased from 1 ± 0.6 to 2.6 ± 1.1 cmH2O/μV (p = 0.033). In patients randomized to pressure support ventilation, these did not change. Electrical activity of the diaphragm, neural inspiratory time, pressure time product of the diaphragm and variability of the breathing pattern were significantly higher in patients ventilated with neurally adjusted ventilatory assist. The asynchrony index was 9.48 [6.38- 21.73] in patients ventilated with pressure support ventilation and 5.39 [3.78- 8.36] in patients ventilated with neurally adjusted ventilatory assist (p = 0.04).
CONCLUSION
After prolonged controlled mechanical ventilation, neurally adjusted ventilator assist improves diaphragm efficiency whereas pressure support ventilation does not.
TRIAL REGISTRATION
ClinicalTrials.gov study registration: NCT02473172, 06/11/2015.
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10.1186/s13054-015-1178-0
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pubmed_204_16818
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BACKGROUND
The Shanghai Score System, which weighs electrocardiogram (ECG) findings reflecting repolarization abnormalities, has been proposed for diagnosis of early repolarization syndrome (ERS). However, recent studies have suggested the involvement of depolarization abnormalities in some ERS patients. The aim of this study was to validate the Shanghai Score System in predicting the recurrence of ventricular fibrillation (VF) in ERS patients. The predictive value of fragmented QRS (fQRS) was also investigated.
METHODS
Fifteen consecutive ERS patients (14 males, median age of 47 years) with a history of VF were retrospectively reviewed. The Shanghai Score System points were calculated, and the presence of fQRS was evaluated.
RESULTS
During the median follow-up period of 79.2 months, five patients experienced VF recurrence. In the VF recurrence group, two patients showed augmented amplitude of J waves with horizontal ST-segment, while the other three patients had dynamic changes in J-wave amplitude. The Shanghai Score System points in the VF recurrence group were higher than those in the VF non-recurrence group (6.5 [range: 5.8-6.8] vs. 4.5 [range: 4.0-4.5], p = 0.002). The presence of fQRS on standard 12-lead ECG was more frequently observed in the VF recurrence group compared with the non-recurrence group (100% vs. 10%, p = 0.002).
CONCLUSIONS
The present study demonstrated that the Shanghai Score System could effectively identify ERS patients at high risk for VF recurrence. The results also suggested that the presence of fQRS, a marker of depolarization abnormalities, may be useful for predicting VF recurrence in ERS patients.
|
10.1111/anec.12873
|
pubmed_601_9259
|
A human fibroblast nick translation assay has been applied to an examination of 48 diverse chemical agents to assess their ability to specifically interfere with the DNA excision-repair process following ultraviolet irradiation. Certain inhibitors of DNA polymerase, ribonucleotide reductase and purine and pyrimidine biosynthesis are shown to inhibit the resynthesis step of repair while DNA intercalators and inhibitors of DNA topoisomerases appear to inhibit the incision step. A variety of other agents previously implicated as inhibitors of DNA repair was also examined and found to have no such effect. This type of analysis should prove useful in the rapid identification of new classes of compounds that antagonize normal cellular repair functions and that might, therefore, act as comutagens or cocarcinogens.
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10.1016/0165-7992(86)90024-2
|
pubmed_369_2990
|
BACKGROUND
Dysregulation of WNT signaling has been reported in many malignancies.
OBJECTIVE
This study was conducted to investigate the expression pattern of 14 members of the WNT gene family in different immunophenotypic subtypes of ALL.
METHODS
Semi-quantitative RT-PCR was performed on samples from 71 ALL patients and 36 age-matched healthy individuals. The ALL patients were categorized into B-ALL (76%), T-ALL (22.6%) and mixed lineage (1.4%) and the B-ALL cases were further classified into pro-B, pre-BI, pre-BII and immature/mature-B based on immuno-phenotypic results.
RESULTS
Among the WNT genes, WNT-7B (p=0.026), WNT-9A (p=0.020) and WNT-16B (p=0.023) were significantly over-expressed, whereas WNT-2B (p=0.033), WNT-5A (p=0.016), WNT-7A (p<0.0001) and WNT-10A (p<0.0001) were down-regulated in B-ALL. Among the T-ALL subtype, however, significant down-regulation of WNT-2B, WNT-5B, WNT-7A, WNT-10A and WNT-11 was evident. Comparison between B-ALL subtypes showed significant over-expression of WNT-7B, WNT-9A and WNT-5B in certain subtypes.
CONCLUSION
Our results suggest contribution of the WNT genes in leukemogenesis of ALL.
|
IJIv9i1A6
|
pubmed_575_4289
|
Complications of transoesophageal echocardiography are numerous and may have serious consequences. We present the case of a 31-year-old woman with postoperative airway obstruction secondary to a transesophageal echocardiography probe. The patient had been admitted with acute myocarditis and required temporary mechanical support with a biventricular assist device. She deteriorated on the intensive care unit several hours later with hypoxaemia, high airway pressures and reduced tidal volumes. Sedation was adequate and no external obstruction in the breathing circuit was observed. The tracheal tube was noted to be permanently deformed in the oropharynx, causing airway obstruction. Tracheal tube exchange was required, and the patient recovered from the event. We suspect that the position of the transoesophageal echocardiography probe in the operating theatre had contributed to the deformity, and the presence of airway obstruction was masked by the reduced ventilatory parameters instituted while on mechanical circulatory support. The biventricular assistance devices were explanted subsequently, and the patient was discharged home on day 31. This is the first reported case of a kinked tracheal tube where transoesophageal echocardiography probe placement was suspected to have contributed. A high index of suspicion is required for this complication on the intensive care unit.
|
10.1002/anr3.12122
|
pubmed_877_15191
|
Alkane guest transfer into aqueous dimeric, tetrameric, hexameric, and octameric assemblies of the deep-cavity cavitand TEMOA is examined using molecular simulations. The experimental transitions between aggregation states strongly correlate with calculated alkane transfer free energy minima, demonstrating the guiding role of guest packing on stabilizing multimeric complexes. The predictive simulation approach described affords a salient rationale as to why octameric assemblies have yet to be experimentally observed.
|
10.1039/c8cc00036k
|
pubmed_976_19127
|
Inflammatory bowel diseases (IBD)--ulcerative colitis and Crohn's disease--are associated with increased risk for thrombotic complications both in the arterial and venous system. Cerebral sinus thrombosis is a rare but potentially fatal consequence of these diseases. Modern imaging methods made this uncommon complication of IBD more frequently recognized. The link between IBDs and thrombosis has been extensively studied. Inherited coagulation disorders (APC resistance, antithrombin III and protein-S deficiency), acquired diseases (antiphospholipid syndrome), and the frequent use of corticosteroids were suspected. Two cases of ulcerative colitis associated with cerebral sinus thrombosis successfully treated are reported. The connection between IBD and thrombotic complications and the therapeutic risks are discussed as well.
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pubmed_976_19127
|
pubmed_351_2828
|
Class III antiarrhythmic agents such as E-4031 have demonstrated efficacy in preventing and/or terminating malignant ventricular arrhythmias in experimental models. It has recently been suggested that Class III agents might possess additional antiischemic properties that may translate into a reduction in the frequency or severity of arrhythmia. The potential for the Class III antiarrhythmic agent E-4031 to limit the extent of developing myocardial infarction was assessed in a barbiturate-anesthetized canine model of ischemic-reperfusion injury. Untreated control (n = 13) and E-4031-treated animals (n = 8, 300 micrograms/kg, i.v., immediately preceding myocardial ischemia) were subjected to a 90-min period of left circumflex coronary artery occlusion followed by a 5-h period of reperfusion. The predominant hemodynamic effect displayed by E-4031 was a reduction in heart rate throughout the period of coronary artery occlusion and early reperfusion. Areas at risk of infarction, expressed as percentages of left ventricle, were equivalent in the control and E-4031 treatment groups (38.5 +/- 1.0 and 34.6 +/- 1.9%, respectively). Posterolateral myocardial infarct sizes, expressed either as percentages of risk area or of total left ventricle, were reduced slightly but not significantly in the E-4031 treatment group compared to the control group (35.2 +/- 5.6 and 45.4 +/- 3.0% of risk area, respectively; 12.7 +/- 2.4 and 17.6 +/- 1.4% of left ventricle, respectively). Regional myocardial blood flows in nonischemic and central ischemic zones of myocardium did not differ significantly between the control and E-4031 treatment groups before and during the period of coronary artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1097/00005344-199206000-00008
|
pubmed_756_23374
|
UNLABELLED
This study synthesized multiwall carbon nanotube (MWNT)-titania (TiO2) composites and examined their characteristics and photocatalytic performance for the cleaning of gas-phase benzene, toluene, ethyl benzene, and o-xylene (BTEX) under simulated indoor conditions. Optical and spectral surveys of the as-synthesized composite confirmed that the TiO2 nanoparticles were bound intimately to the MWNT networks. The photocatalytic performance was evaluated using an annular-type reactor inner-coated with MWNT-TiO2 or Degussa P25 TiO2. The composite revealed gas removal ability superior to that of stand-alone TiO2. This composite was also less affected by humidity during toluene decomposition compared to the previous result obtained from a stand-alone TiO2. Unlike another previous result obtained from the TiO2, the performance of the composite was not affected by changes in input concentration (IC) within a simulated indoor air quality range (0.1-1.0 ppm) but it decreased significantly when the IC was increased to 5 and 10 ppm. As the flow rate was decreased from 4.0 to 1.0 L min(-1), the average efficiency for the target compounds increased to 95% or -100%. The MWNT-TiO2 composite could be applied effectively to the decomposition for BTEX under certain simulated indoor conditions.
IMPLICATIONS
Unlike water applications, there are few reports of gas-phase applications of multiwall carbon nanotubes (MWCNT)-TiO2 composites. This study found that MWCNT-TiO2 composites showed performance in the removal of toxic gaseous aromatic superior to that of stand-alone TiO2. In addition, the pollutant degradation efficiency of the composite was less affected by humidity than for a stand-alone TiO2 unit within a simulated indoor relative humidity range. Moreover, unlike the TiO2 unit, the composite's performance was not affected by variations in the input concentrations within the simulated indoor air quality (IAQ) range. In addition, the decomposition efficiencies increased to 100% with decreasing flow rate.
|
10.1080/10962247.2013.801931
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pubmed_891_18813
|
The availability of different wavelengths of lasers has created a surgical panacea in the last decade and laser technology has become the standard of care for many oral and maxillofacial surgical procedures. In this article, based on literature search, we have reviewed the usage of laser in maxillofacial surgery based on the current evidence available on laser-assisted maxillofacial surgery, in PubMed database.
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10.4103/jpbs.JPBS_710_20
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pubmed_249_12284
|
The NPXXY motif (X represents any amino acid) in the seventh transmembrane domain of the chemotactic formyl peptide receptor (FPR) is highly conserved among G protein-coupled receptors. Recent work suggested that this motif contributes to G protein-coupled receptor internalization and signal transduction; however, its role in FPR signaling remains unclear. In this study we replaced Asn(297) and Tyr(301) in the NPXXY motif of the human FPR with Ala (N297A) and Ala/Phe (Y301A/Y301F), respectively, and determined the effects of the substitutions on FPR functions in transfected rat basophilic leukemia cells. Whereas all the mutant receptors were expressed on the cell surface, the N297A receptor exhibited reduced binding affinity and was unable to mediate activation of phospholipase C-beta and the p42/44 mitogen-activated protein kinase (MAP kinase). The Y301F receptor displayed significantly decreased ligand-stimulated internalization and MAP kinase activation, suggesting that the hydrogen bonding at Tyr(301) is critical for these functions. The Y301F receptor showed a chemotactic response similar to that of wild-type FPR, indicating that cell chemotaxis does not require receptor internalization and hydrogen bonding at the Tyr(301) position. In contrast, the Y301A receptor displayed a left-shifted, but overall reduced, chemotaxis response that peaked at 0.1-1 nM. Finally, using a specific MAP kinase kinase inhibitor, we found that activation of MAP kinase is required for efficient FPR internalization, but is not essential for chemotaxis. These findings demonstrate that residues within the NPXXY motif differentially regulate the functions of FPR.
|
10.4049/jimmunol.166.6.4099
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pubmed_912_5141
|
Nerve sheath myxoma (neurothekeoma) are rare benign nerve sheath tumors, usually arising in the skin of the head and neck region and upper extremities in young females. To the best of author's knowledge only two cases of intracranial neurothekeoma have been published in the English literature. These tumors were located in the parasellar area and in middle cranial fossa. This is the first case report of cerebellopontine angle neurothekeoma and third case report of intracranial neurothekeoma. This patient, a 45-year-old female, presented to us with complaints of right side progressive hearing loss for 12 months and swaying during walking for 8 months. Histologically the tumor had lobular appearance with spindle or stellate cells embedded in abundant myxoid background. The tumor cells were diffusely positive for S100. The patient was symptom free at eight month follow up.
|
10.5137/1019-5149.JTN.4255-11.1
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pubmed_445_2654
|
The operative results of 79 patients subjected to posterior fusion of the lumbosacral spine were evaluated on the basis of a follow-up examination performed on average 5.4 years after operation. A method of evaluation was developed which measured the patients' subjective improvement and working capacity. The method proved appropriate for clinical use and gave a more correct picture of the operative result than methods relying on the patients' own opinion or the radiographic assessment as the only criterion. Sixty per cent of the patients were subjectively improved, 40 per cent had returned to their previous or a corresponding occupation and 24 per cent had a good operative result, assessed by the method applied. A statistical analysis was performed in order to find the factors influencing the operative results. Age over 40 years, heavy or moderately heavy preoperative work and over 6 months' preoperative disability had a statistically significant, unfavourable effect on the results. In the case of labourers in heavy occupations, working capacity was seldom restored to a degree sufficient for return to their previous work. The operative technique proved reliable with 91 per cent successful fusions, assessed from functional radiographs. Successful fusion did not imply a good operative result, although it did so more often than non-fusion. On the basis of this study, operative fusion of the lumbosacral spine seems to be of relatively little value in the treatment of patients suffering from low back pain, and factors other than purely medical or surgical have a considerable influence on the operative results.
|
10.3109/17453677908989785
|
pubmed_1082_6033
|
Among the solid tumors of childhood and adolescence, osteosarcoma (OS) represents the most prominent example of efficient aggressive chemotherapy with secondary surgical therapy. A specific subclassification of the tumor is indispensable and must include recent results of cell biology. The co-distribution of different collagen types I-VI reflects the diverse differentiation of osteosarcoma cells, supporting the concept of a pluripotent mesenchymal cell to be the stem cell of the tumor. In contrast, osteonectin (SPARC) may not be considered as a reliable marker for osteosarcoma. The experience of special proteins being secreted by osteosarcoma cells is rather limited. Detailed molecular biological studies are still lacking. A loss of alleles on chromosome 17, particularly in the defined region 17p 13, can be observed in more than 75% of all OS, suggesting the contribution of a tumor suppressor gene, p53, located in that region. It is a 53 kd nucleophosphoprotein binding the major transforming protein, the large T antigen of Simian Virus 40. Immunohistological results showed positive staining with the antibody Pab 240 in 13 of 18 cases. In one osteoblastic OS, a novel splice mutation resulting in a fusing of exon 5 directly to exon 7 was detected. RB1 gene is also of major importance for the tumorigenesis of OS. The multidrug resistance (mdr) is associated with a membrane-bound channel-forming transport protein, the P-glycoprotein. It is a conserved plasma membrane component of about 170 kd. Both the human isoforms mdr 1 and mdr 3 are localised in the long arm of chromosome 7.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1016/S0344-0338(11)80877-0
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pubmed_498_15912
|
Importance
Aesthetic outcomes are key determinants of psychosocial functioning among surgically treated patients with head and neck cancer (HNC); however, long-term aesthetic outcomes after microvascular free tissue transfer (MFTT) are not well described.
Objective
To examine risk factors for impaired long-term aesthetic satisfaction and appearance-related psychosocial functioning after HNC ablation with MFTT.
Design, Setting, and Participants
A cross-sectional, web-based survey was conducted at an academic tertiary care center. A total of 228 individuals who underwent MFTT between January 1, 2015, and December 31, 2019, for treatment of HNC were included. The study was conducted from November 1, 2020, through January 15, 2021.
Exposures
Head and neck cancer ablation with MFTT.
Main Outcomes and Measures
Patient-reported outcomes were assessed via Aesthetic FACE-Q scales. The primary objective was aesthetic satisfaction determined by the Satisfaction With Facial Appearance scale. Secondarily, the Appearance-Related Psychosocial Distress, Psychological Function, and Social Function scales were used to assess appearance-related psychosocial functioning. Patients were stratified by demographic, disease, surgical, and postoperative characteristics. Survey scores on a 100-point scale were compared and subjected to univariable and multivariable linear regression.
Results
A total of 124 of 228 patients (54.4%) completed surveys a median of 34.4 months after MFTT (interquartile range, 22.6-48.8). Most responders (79 [63.7%]) were men with advanced cancer of the oral cavity or skin, reconstructed with anterolateral thigh or osteocutaneous fibula free flaps. Nonresponders had no significant differences in baseline characteristics. The Satisfaction With Facial Appearance score was independently lower among patients who received osteocutaneous flaps (regression coefficient, -10.6 points, 95% CI, -20.4 to -0.8 points) and/or adjuvant (chemo)radiotherapy (regression coefficient, -6.9 points; 95% CI, -13.8 to -0.1 points). Impaired appearance-related psychosocial functioning was independently associated with female sex, a history of anxiety or depression, osteocutaneous flaps, prolonged tube feeding requirements, and any recurrent or persistent disease. After adjustment for covariates, each 1-point increase in the Satisfaction With Facial Appearance score independently estimated improved appearance-related psychosocial functioning as determined by the Appearance-Related Psychosocial Distress scale (regression coefficient, -0.5 points; 95% CI, -0.7 to -0.4 points), Psychological Function scale (regression coefficient, 0.4 points; 95% CI, 0.3 to 0.5 points), and Social Function scale (regression coefficient, 0.4 points; 95% CI, 0.3 to 0.6 points).
Conclusions and Relevance
The findings of this cross-sectional, web-based survey study suggest that osteocutaneous reconstruction and adjuvant therapy independently increase the risk of poor patient-reported long-term aesthetic satisfaction, which correlated with impaired appearance-related psychosocial functioning. Aesthetic outcomes appear to be a priority to address in patients with HNC undergoing MFTT.
|
10.1001/jamaoto.2021.1563
|
pubmed_382_1216
|
Infection with feline immunodeficiency virus (FIV) leads to the development of a disease state similar to AIDS in man. Recent studies have identified the chemokine receptor CXCR4 as the major receptor for cell culture-adapted strains of FIV, suggesting that FIV and human immunodeficiency virus (HIV) share a common mechanism of infection involving an interaction between the virus and a member of the seven transmembrane domain superfamily of molecules. This article reviews the evidence for the involvement of chemokine receptors in FIV infection and contrasts these findings with similar studies on the primate lentiviruses HIV and SIV (simian immunodeficiency virus).
|
10.1080/096876899294779
|
pubmed_177_13927
|
PURPOSE
To compare the diagnostic value of monochromatic and material decomposition (MD) dual- energy computed tomography (DECT) imaging for the evaluation of ischemia.
METHODS
Patients with suspected coronary artery disease underwent rest-stress DECT and SPECT perfusion imaging. DECT images were reconstructed between 40 and 140keV and through MD of iodine/muscle.
RESULTS
MD and monochromatic imaging had a sensitivity, specificity, negative predictive, positive predictive value, and accuracy of 89%, 40%, 67%, 73% and 71%; and 91%, 67%, 67%, 91% and 86%, respectively (p=0.05).
CONCLUSION
DECT using monochromatic energy displayed a non-significantly higher diagnostic accuracy for myocardial ischemia as compared with DECT MD.
|
10.1016/j.clinimag.2017.11.002
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pubmed_600_7496
|
The chemical composition of essential oils obtained from the hydrodistillation of different parts of Amomum maximum Roxb and Amomum muricarpum C. F. Liang & D. Fang (Zingiberaceae) grown in Vietnam are reported. The analysis was performed by means of gas chromatography-flame ionisation detectoorand gas chromatography coupled with mass spectrometry. The major compounds identified in the oils of A. maximum were β-pinene (20.4-40.8%), α-pinene (6.8-15.0%), β-elemene (2.5-12.8%) and β-caryophyllene (2.3-10.3%). Moreover, β-phellandrene (11.6%) was present in the root oil. The main compound identified in all the oil samples of A. muricarpum was α-pinene (24.1-54.7%) and β-pinene (9.2-25.9%). In addition, limonene (7.4%) and δ-3-carene (9.4%) were present in the leaves and stem oils, respectively. However, while β-phellandrene (8.3%) could be seen prominent in the root oil, the fruits contained significant amount of zingiberene (6.3%). The largest amount of τ-muurolol (13.0%) was found in the flower oil.
|
10.1080/14786419.2014.1003064
|
pubmed_723_9066
|
BACKGROUND
The delivery of intravenous medication by continuous infusion is necessary and widespread for treatment of patients with advanced cancer. Few scientific papers have focused on assessment of the chemical compatibility of these therapeutic mixtures. An analytical assessment of the physical and chemical compatibility of these combinations is needed.
OBJECTIVES
To determine the chemical and physical compatibility of binary mixtures of metoclopramide (MET) and midazolam (MID).
METHODS
Mixtures of drugs were prepared under aseptic conditions in 0.9% sodium chloride at concentrations used in our clinical practice for continuous infusion. The samples were stored in polyethylene bags at room temperature in the presence of light for 15 days. Chemical compatibility was evaluated by high-performance liquid chromatography (HPLC). Physical compatibility was tested by visual inspection (for evidence of precipitation and colour change) and by pH determination.
RESULTS
No changes in colour, precipitation of components, measurable losses of volume or notable changes in pH were seen. The combinations tested were compatible for 15 days (retained >95% of their initial concentration).
CONCLUSIONS
This study confirms the analytical compatibility of MET and MID, when mixed in 0.9% sodium chloride at concentrations employed in our clinical practice.
|
10.1136/ejhpharm-2018-001544
|
pubmed_234_2350
|
This study examined changes in folic acid knowledge and use among antenatal women in Dublin maternity hospitals between 1996 and 1997, following a campaign to improve the very low uptake of peri-conceptional folic acid. The results showed significant improvements between the two years. Almost 76% of respondents had heard of folic acid in 1997 compared with 54% in 1996 (p < 0.01), with a shift in the proportion of people hearing of folic acid from hospital doctors to general practitioners (GP). Almost 43% of respondents in 1997 knew that folic acid can prevent spina bifida compared with 21% in 1996 (p < 0.01). A higher proportion was taking folic acid prior to conception in 1997 (16% vs 6%, p < 0.01). We conclude that the improvements may have been in part due to the promotional campaign among health professionals, women's groups and the media. However, less than a fifth of women were taking folic acid peri-conceptionally in 1997 and there is still scope for much improvement.
|
pubmed_234_2350
|
pubmed_386_6400
|
Alzheimer's disease (AD) is characterized by early impairments in memory and progressive neurodegeneration. Disruption of synaptic plasticity processes that underlie learning and memory contribute partly to this pathophysiology. Tripchlorolide (T4 ), an extract from a traditional Chinese herbal Tripterygium wilfordii Hook F, has been shown to be neuroprotective in animal models of Parkinson's disease and to improve cognitive deficits in senescence-accelerated mouse P8. In this study, we investigated the effect of T4 on cognitive decline and synaptic plasticity in five times familial AD (5XFAD) mice co-expressing mutated amyloid precursor protein and presenilin-1. Five-month-old 5XFAD mice and wild type littermates were intraperitoneally injected with T4 , 5 μg/kg or 25 μg/kg, every other day for 60 days. T4 treatment significantly improved spatial learning and memory, alleviated synaptic ultrastructure degradation, up-regulated expression of synapse-related proteins, including synaptophysin, post-synaptic density-95, N-methyl-D-aspartate receptor subunit 1, phosphorylation of calcium/calmodulin dependent protein kinase II α, and phosphorylation of cyclic AMP-response element binding protein, and promoted activation of the phophoinositide-3-kinase-Akt-mammalian target of rapamycin signaling pathway in 5XFAD mice. Accumulation of amyloid β (Aβ) may contribute to synapse dysfunction and memory impairment in AD. We found that T4 treatment significantly reduced cerebral Aβ deposits and lowered Aβ levels in brain homogenates. These effects coincided with a reduction in cleavage of β-carboxyl-terminal amyloid precursor protein (APP) fragment, levels of soluble APPβ, and protein expression of β-site APP cleaving enzyme 1. Taken together, our findings identify T4 as a potent negative regulator of brain Aβ levels and show that it significantly ameliorates synaptic degeneration and cognitive deficits in a mouse model of AD.
|
10.1111/jnc.13056
|
pubmed_528_1462
|
TRNAs from all organisms contain posttranscriptionally modified nucleosides, which are derived from the four canonical nucleosides. In most tRNAs that read codons beginning with U, adenosine in the position 37 adjacent to the 3' position of the anticodon is modified to N(6)-(Delta(2)-isopentenyl) adenosine (i(6)A). In many bacteria, such as Escherichia coli, this residue is typically hypermodified to N(6)-isopentenyl-2-thiomethyladenosine (ms(2)i(6)A). In a few bacteria, such as Salmonella typhimurium, ms(2)i(6)A can be further hydroxylated to N(6)-(cis-4-hydroxyisopentenyl)-2-thiomethyladenosine (ms(2)io(6)A). Although the enzymes that introduce the respective modifications (prenyltransferase MiaA, methylthiotransferase MiaB, and hydroxylase MiaE) have been identified, their structures remain unknown and sequence-function relationships remain obscure. We carried out sequence analysis and structure prediction of MiaA, MiaB, and MiaE, using the protein fold-recognition approach. Three-dimensional models of all three proteins were then built using a new modeling protocol designed to overcome uncertainties in the alignments and divergence between the templates. For MiaA and MiaB, the catalytic core was built based on the templates from the P-loop NTPase and Radical-SAM superfamilies, respectively. For MiaB, we have also modeled the C-terminal TRAM domain and the newly predicted N-terminal flavodoxin-fold domain. For MiaE, we confidently predict that it shares the three-dimensional fold with the ferritin-like four-helix bundle proteins and that it has a similar active site and mechanism of action to diiron carboxylate enzymes, in particular, methane monooxygenase (E.C.1.14.13.25) that catalyses the biological hydroxylation of alkanes. Our models provide the first structural platform for enzymes involved in the biosynthesis of i(6)A, ms(2)i(6)A, and ms(2)io(6)A, explain the data available from the literature and will help to design further experiments and interpret their results.
|
10.1002/prot.21640
|
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