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pubmed_670_12657
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The complete 129-amino-acid sequences of two rainbow trout lysozymes (I and II) isolated from kidney were established using protein chemistry microtechniques. The two sequences differ only at position 86, I having aspartic acid and II having alanine. A cDNA clone coding for rainbow trout lysozyme was isolated from a cDNA library made from liver mRNA. Sequencing of the cloned cDNA insert, which was 1 kb in length, revealed a 432-bp open reading frame encoding an amino-terminal peptide of 15 amino acids and a mature enzyme of 129 amino acids identical in sequence to II. Forms I and II from kidney and liver were also analyzed using enzymatic amplification via PCR and direct sequencing; both organs contain mRNA encoding the two lysozymes. Evolutionary trees relating DNA sequences coding for lysozymes c and alpha-lactalbumins provide evidence that the gene duplication giving rise to conventional vertebrate lysozymes c and to lactalbumin preceded the divergence of fishes and tetrapods about 400 Myr ago. Evolutionary analysis also suggests that amino acid replacements may have accumulated more slowly on the lineage leading to fish lysozyme than on those leading to mammal and bird lysozymes.
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10.1007/BF02515392
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pubmed_152_5675
|
Protein-protein interactions were measured for ovalbumin and for lysozyme in aqueous salt solutions. Protein-protein interactions are correlated with a proposed potential of mean force equal to the free energy to desolvate the protein surface that is made inaccessible to the solvent due to the protein-protein interaction. This energy is calculated from the surface free energy of the protein that is determined from protein-salt preferential-interaction parameter measurements. In classical salting-out behavior, the protein-salt preferential interaction is unfavorable. Because addition of salt raises the surface free energy of the protein according to the surface-tension increment of the salt, protein-protein attraction increases, leading to a reduction in solubility. When the surface chemistry of proteins is altered by binding of a specific ion, salting-in is observed when the interactions between (kosmotrope) ion-protein complexes are more repulsive than those between the uncomplexed proteins. However, salting-out is observed when interactions between (chaotrope) ion-protein complexes are more attractive than those of the uncomplexed proteins.
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10.1002/bit.10342
|
pubmed_635_3898
|
BACKGROUND
The amyloid precursor protein (APP) is a key molecule in Alzheimer disease. Its localization at the cell surface can trigger downstream signaling and APP cleavages. APP trafficking to the cell surface in neurons is not clearly understood and may be related to the interactions with its partners. In this respect, by having homologies with kinesin light chain domains and because of its capacity to bind APP, PAT1 represents a good candidate.
RESULTS
We observed that PAT1 binds poorly APP at the cell surface of primary cortical neurons contrary to cytoplasmic APP. Using down and up-regulation of PAT1, we observed respectively an increase and decrease of APP at the cell surface. The increase of APP at the cell surface induced by low levels of PAT1 did not trigger cell death signaling.
CONCLUSIONS
These data suggest that PAT1 slows down APP trafficking to the cell surface in primary cortical neurons. Our results contribute to the elucidation of mechanisms involved in APP trafficking in Alzheimer disease.
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10.1186/s12868-015-0152-8
|
pubmed_763_16968
|
Theropod dinosaurs dominated Earth's terrestrial ecosystem as a diverse group of predators for more than 160 million years, yet little is known about their foraging ecology. Maintaining a balanced energy budget presented a major challenge for therapods, which ranged from the chicken-sized Microraptor up to the whale-sized Giganotosaurus, in the face of intense competition and the demands of ontogenetic growth. Facultative scavenging, a behavior present in almost all modern predators, may have been important in supplementing energetically expensive lifestyles. By using agent-based models based on the allometric relationship between size and foraging behaviors, we show that theropods between 27 and 1,044 kg would have gained a significant energetic advantage over individuals at both the small and large extremes of theropod body mass through their scavenging efficiency. These results were robust to rate of competition, primary productivity, and detection distance. Our models demonstrate the potential importance of facultative scavenging in theropods and the role of body size in defining its prevalence in Mesozoic terrestrial systems.
|
10.1086/686094
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pubmed_989_4225
|
A molecularly imprinted polymer (MIP) for the selective solid-phase extraction (SPE) was prepared applying polymerization of pyrrole monomer in the presence of closantel (CLS) as a template molecule. The quantitative measurements were carried out using UV-Vis spectrophotometry. Several important parameters control the performance of polypyrrole sorbent. The influence of seven factors including loading time, polymerization time, amount of sorbent, stirring rate, desorption time, initiator concentration and monomer to template ratio were investigated. The optimization of parameters was performed using Plackett-Burman design (PBD), central composite design (CCD), artificial neural network (ANN) and genetic algorithm (GA). The Pareto plot showed that the effects of loading time, reaction time and amount of sorbent are most important to the process. These significant factors were investigated using CCD and the obtained data were used to train the ANN. The predicted model obtained from the trained ANN was introduced to GA as the fitness function to be optimized. The calibration curve demonstrated linearity over a concentration range of 0.010-10 mM with a correlation coefficient (R2) of 0.9833 under optimal condition. The synthesized MIP sorbent showed a good selectivity and sensitivity toward CLS. The limit of detection (LOD) for CLS was obtained 1.0 μM. The real sample analysis was performed to determine CLS in pharmaceutical and human serum samples.
|
10.1016/j.saa.2020.118779
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pubmed_597_2693
|
The origin of a primary or metastatic carcinoma in the pelvic area is sometimes difficult to establish, in particular the distinction between those originating in the bladder and the prostate. A candidate marker is the HOXB13 gene, essential for prostate development. Some studies have shown expression of HOXB13 protein by immunohistochemistry in the nuclear compartment of benign prostate luminal epithelium and prostate carcinoma. Forty-two cases of biopsies and resection specimens of the prostate and urinary bladder, metastatic lymph nodes, and pelvic masses were retrieved from our databases. In all cases, doubt persisted regarding prostatic versus urothelial origin. All cases were stained for CK7, p63, p504s, PSA, CK20, and HOXB13. Chromogranin A, CD56, and synaptophysin were used when neuroendocrine differentiation was suspected. HOXB13 staining was negative or only weakly positive in all carcinomas of urothelial origin. Three of four carcinomas with neuroendocrine differentiation did not express HOXB13. The fourth carcinoma, in a patient with a history of prostate carcinoma, was positive. In two cases with a synchronous prostatic and urothelial carcinoma, HOXB13 was exclusively expressed in the prostatic carcinoma. Our results demonstrate that HOXB13 expression identifies prostatic origin of a carcinoma with good sensitivity (89 %) and very good specificity (100 %). HOXB13 is a specific and sensitive marker for prostate cells and a valuable diagnostic tool, especially when poorly differentiated or neuroendocrine tumors are encountered. These results justify testing of HOXB13 as a prostate-specific carcinoma marker in larger cohorts for a more thorough evaluation of its sensitivity and specificity.
|
10.1007/s00428-013-1495-0
|
pubmed_1107_9642
|
The antioxidant activity of marchantin H was investigated using various experimental models. Marchantin H inhibited nonenzymatic iron-induced lipid peroxidation in rat brain homogenates with an IC50 value of 0.51 +/- 0.03 microM. It was more potent than desferrioxamine or other classical antioxidants. Marchantin H also suppressed NADPH-dependent microsomal lipid peroxidation with an IC50 value of 0.32 +/- 0.01 microM without affecting microsomal electron transport of NADPH-cytochrome P450 reductase. Marchantin H could scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl and peroxyl radical derived from 2,2 '-azobis(2-amidinopropane) dihydrochloride in aqueous phase, but not the peroxyl radical derived from 2,2 '-azobis(2,4-dimethylvaleronitrile) in hexane. The oxygen consumption during peroxyl radical-induced human erythrocyte ghost oxidation was decreased in a concentration-dependent manner by marchantin H. Furthermore, it was reactive toward superoxide anion generated by the xanthine/xanthine oxidase system. On the other hand, marchantin H inhibited copper-catalyzed oxidation of human low-density lipoprotein, as measured by fluorescence intensity, thiobarbituric acid-reactive substance formation, and electrophoretic mobility in a concentration-dependent manner. Our results indicate that marchantin H is a potentially effective and versatile antioxidant and can be used as a chaperone protecting biomacromolecules against peroxidative damage.
|
10.1006/abbi.1996.0424
|
pubmed_910_2376
|
Amixicile is a promising derivative of nitazoxanide (an antiparasitic therapeutic) developed to treat systemic infections caused by anaerobic bacteria, anaerobic parasites, and members of the Epsilonproteobacteria (Campylobacter and Helicobacter). Amixicile selectively inhibits pyruvate-ferredoxin oxidoreductase (PFOR) and related enzymes by inhibiting the function of the vitamin B1 cofactor (thiamine pyrophosphate) by a novel mechanism. Here, we interrogate the amixicile scaffold, guided by docking simulations, direct PFOR inhibition assays, and MIC tests against Clostridium difficile, Campylobacter jejuni, and Helicobacter pylori Docking simulations revealed that the nitro group present in nitazoxanide interacts with the protonated N4'-aminopyrimidine of thiamine pyrophosphate (TPP). The ortho-propylamine on the benzene ring formed an electrostatic interaction with an aspartic acid moiety (B456) of PFOR that correlated with improved PFOR-inhibitory activity and potency by MIC tests. Aryl substitution with electron-withdrawing groups and substitutions of the propylamine with other alkyl amines or nitrogen-containing heterocycles both improved PFOR inhibition and, in many cases, biological activity against C. difficile Docking simulation results correlate well with mechanistic enzymology and nuclear magnetic resonance (NMR) studies that show members of this class of antimicrobials to be specific inhibitors of vitamin B1 function by proton abstraction, which is both novel and likely to limit mutation-based drug resistance.
|
10.1128/AAC.00670-16
|
pubmed_113_24057
|
In order to reverse tumor immunosuppressive microenvironment and improve antitumor immune effect based on immune checkpoint blocking, a mannose-modified liposome-based CpG ODNs and PD-L1 antagonistic peptides (P) co-delivery system (HA/M-Lipo CpG-P) was constructed, in which hyaluronic acid (HA) coating was supposed to improve the systemic circulation stability and thereby promote its accumulation in tumor tissues. When the HA/M-Lipo CpG-P complexes enter the tumor tissues, HA will be hydrolyzed under the action of hyaluronidase, exposing P peptides. Then, P peptides linked by octapeptides that can be cleaved by matrix metalloproteinases (MMPs) are released into tumor tissues under the action of MMPs, exerting a blocking effect in the PD-1/PD-L1 pathway. The M-Lipo CpG complexes can recognize macrophage surface mannose receptors through its surface modified mannose molecules, and promote the intracellular delivery of CpG ODNs, thereby activating macrophages. The results showed that HA/M-Lipo CpG-P complexes successfully reversed M2-type macrophages in tumor microenvironment (TME) to M1, thereby activating anti-tumor related immune cells and inhibiting tumor growth. Moreover, the HA/M-Lipo CpG-P complexes showed a better tumor inhibitory effect than the HA/M-Lipo CpG or the HA/M-Lipo-P (monotherapy) treatment groups. Overall, HA/M-Lipo CpG-P complexes provide a promising co-delivery strategy for targeting tumors to improve the antitumor effect based on immune checkpoint blockade.
|
10.1016/j.ejps.2021.106044
|
pubmed_481_22176
|
Detection on automated DNA sequencers of polymerase chain reaction (PCR) products of tetra- and penta-nucleotide short tandem repeat (STR) loci frequently reveals one or more extra peaks along with the true, major allele peak. The most frequent extra peak pattern is a single smaller peak which is one repeat unit shorter than the true allele peak. The existence of such artificial peaks is of special importance when the methods are used for forensic investigations because the artificial extra peaks may simulate true alleles when samples containing mixtures of DNA from different individuals are analyzed. We have investigated the relative levels of formation of extra peaks in 14 STR marker systems. We found that not only the parameters of the PCR but also factors determining the stringency during the post-PCR and pre-electrophoresis handling of samples were of importance for the formation of extra peaks. In our hands, the amounts of extra peaks were reduced (i) if the samples were effectively denatured immediately before loading, (ii) if they contained substantial amounts of formamide (i.e. > or = 50%), and (iii) if the temperature of the electrophoresis gel was above a certain level (i.e. > or = 43 degrees C). The results suggest that extra peaks may in part be due to re-annealing of the PCR product under suboptimal conditions. When efforts had been made to reduce the post-PCR formation of extra peaks, the relative peak areas of the extra peaks ranged from 1% to 17% of those of the true alleles. Similar results were obtained when the PCR products were analyzed under native conditions. Low-copy genome analysis excluded that somatic heterogeneity of the STR regions caused the extra peaks. The systems HumVWA31A, HumFibra/FGA, and D21S11 were especially affected by low-stringency conditions, while Hum-TH01, HumCD4, and D12S391 were virtually unaffected by low-stringency conditions. Replacement of the Taq DNA polymerase with DNA polymerases with lower processivity resulted in higher levels of extra peaks. Our results support the hypothesis that extra peaks are produced due to slipped-strand mispairing.
|
10.1002/elps.1150181107
|
pubmed_878_14296
|
BACKGROUND
The whole plant of Momordica charantia Linn (Cucurbitaceae) is used in traditional African medicine in the management of depressive illness.
METHODS
Momordica charantia (MC) (50-400 mg/kg, p.o.) was administered 1 h before behavioural studies using the forced swimming test (FST) and tail suspension test (TST) to investigate antidepressant-like effect while the anxiolytic-like effect was evaluated with elevated plus maze test (EPM), hole-board test (HBT), and light-dark test (LDT).
RESULTS
Acute treatment with MC (50-400 mg/kg) significantly increased swimming time (86.51%) and reduced the duration of immobility (52.35%) in FST and TST with peak effects observed at 200 mg/kg, respectively, in comparison to control. The pretreatment of mice with either sulpiride (dopamine D2 receptor antagonist), or metergoline (5-HT2 receptor antagonist), or cyproheptadine (5-HT2 receptor antagonist), or prazosin (α1-adrenoceptor antagonist), or yohimbine (α2-adrenoceptor antagonist), and atropine (muscarinic cholinergic receptor antagonist) 15 min before oral administration of MC (200 mg/kg) significantly blocked its anti-immobility effect. Similarly, MC (200 mg/kg) significantly reduced anxiety by increasing the open arm exploration (64.27%) in EPM, number of head-dips in HBT (34.38%), and time spent in light compartment (29.38%) in the LDT. However, pretreatment with flumazenil (GABAA receptor antagonist) 15 min before MC (200 mg/kg) significantly blocked (54.76%) its anxiolytic effect.
CONCLUSION
The findings in this study showed that MC possesses antidepressant-like effect that is dependent on the serotonergic (5-HT2 receptor), noradrenergic (α1- and α2-adrenoceptors), dopaminergic (D2 receptor), and muscarinic cholinergic systems and an anxiolytic-like effect that might involve an action on benzodiazepine-type receptor.
|
10.1055/s-0033-1358712
|
pubmed_275_1320
|
Catalytic promiscuity - the ability of a single active site to catalyse more than one chemical transformation - has a natural role in evolution and occasionally in biosynthesis of secondary metabolites. Catalytic promiscuity is more widespread than often recognized. Recent success in adding and enhancing such catalytic activities by protein engineering suggests new potential applications in enzyme-catalyzed organic synthesis.
|
10.1016/j.cbpa.2005.02.008
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pubmed_1070_17367
|
PURPOSE
The mitotic spindle has proven to be an effective therapeutic target in antineoplastic efforts. In this study, we sought to assess the efficacy of ispinesib, a mitotic kinesin spindle protein (KSP) inhibitor in androgen-independent prostate cancer progressing after docetaxel.
PATIENTS AND METHODS
Patients were treated with ispinesib 18 mg/m2 every 21 days and assessed for prostate-specific antigen (PSA) and measurable disease response at regular intervals. Kinesin spindle protein expression in archival tumors, population ispinesib pharmacokinetics, and pharmacodynamic assessments of circulating lymphocytes were included.
RESULTS
The study was terminated after first stage because no responses were seen in the first 21 patients. Median duration of PSA or clinical progression-free survival was 9 weeks. Plasma concentrations of ispinesib were comparable with those observed in previous phase I investigations. Immunohistochemical analysis of archival tumor specimens did not demonstrate significant KSP expression in most of the prostate cancer cases studied. Pharmacodynamic assessments of circulating lymphocytes from patients receiving ispinesib showed an absence of monopolar spindle formation, as would be expected if the drug were having its expected effects.
CONCLUSION
Ispinesib was inactive in this study of patients with androgen-independent, and largely docetaxelresistant, prostate cancer. The lack of efficacy might be explained by the low expression of the drug target seen in prostate cancer, whereas not detecting monopolar spindles in circulating lymphocytes with drug treatment likely reflects the lack of dividing cells in peripheral blood.
|
10.3816/CGC.2008.n.016
|
pubmed_348_19310
|
A novel approach to the introduction of chirality into peptide nucleic acid (PNA) by replacement of the methylene carbonyl linker by an alpha-amino acid derived moiety is described. A monomer compatible with Fmoc-based oligomerization chemistry possessing an L-serine derived linker has been synthesized and incorporated into PNA oligomers. A single, central substitution in a hexathymine PNA strongly destabilized triple helix formation whereas a central substitution in a mixed sequence is much better tolerated. We have investigated the influence of this substitution on the selectivity for strand composition (DNA versus RNA complement) and strand orientation (antiparallel versus parallel) in the context of duplex formation. A PNA 11-mer with a single substitution demonstrates a preference for an antiparallel RNA complement, as judged by thermal denaturation analysis of the complexes.
|
10.1080/15257770701527794
|
pubmed_570_16359
|
Imaginal discs of Drosophila have the remarkable ability to regenerate. After fragmentation wound healing occurs, ectopic wg is induced and a blastema is formed. In some, but not all fragments, the blastema will replace missing structures and a few cells can become more plastic and transdetermine to structures of other discs. A series of systematic cuts through the first leg disc revealed that a cut must transect the dorsal-proximal disc area and that the fragment must also include wg-competent cells. Fragments that fail to both transdetermine and regenerate missing structures will do both when provided with exogenous Wg, demonstrating the necessity of Wg in regenerative processes. In intact leg discs ubiquitously expressed low levels of Wg also leads to blastema formation, regeneration and transdetermination. Two days after exogenous wg induction the endogenous gene is activated, leading to elevated levels of Wg in the dorsal aspect of the leg disc. We identified a wg enhancer that regulates ectopic wg expression. Deletion of this enhancer increases transdetermination, but lowers the amount of ectopic Wg. We speculate that this lessens repression of dpp dorsally, and thus creates a permissive condition under which the balance of ectopic Wg and Dpp is favorable for transdetermination.
|
10.1016/j.ydbio.2010.08.034
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pubmed_446_4751
|
Because billions of cells die every day in their bodies, animals have evolutionarily developed apoptosis to preserve the tissue environment from adverse effects of dead cells, a process achieved via phagocytosis of the cell corpses by professional or amateur phagocytes that are collectively referred to as scavengers. Hence, apoptosis is a merger of two procedures separately occurring inside the dying and the scavenger cells, respectively. The task of apoptosis research is to study how these death procedures occur without hurting the host tissues, and recruitment of in vitro system into the study must be justified for this purpose. Cells in culture have no motivation to preserve the environment, and their death does not involve corpse clearance by scavengers. Therefore, programmed cell death in culture should be redefined, for example as stress-induced cell death, to avoid many sources of confusions, since the word "apoptosis" had already been defined, prior to the era of cell culture, as a silent and beneficial cell suicide with corpse clearance as a distinctive hallmark. We should start over again on apoptosis research by determining whether different physiological apoptotic procedures in animals involve the cytochrome c-caspase pathway, since it has been established from cultured cells as a central mechanism of "apoptosis" but whether it overarches any physiological apoptotic procedure in animals is still unclear. Probably, cells in living animals are programmed to use scavengers to assist their apoptosis but cells in culture have no scavengers to help and thus need to go mainly through the cytochrome c-caspase pathway.
|
10.7150/jca.7577
|
pubmed_195_8300
|
Diabetes induces cardiomyocyte apoptosis and suppresses cardiac autophagy, indicating that the interplay between autophagy and apoptotic cell death pathways is important in the pathogenesis of diabetic cardiomyopathy. The potential mechanism, however, remains unknown. We recently reported that diabetes depresses AMP-activated protein kinase (AMPK) activity, inhibits MAPK8/JNK1-BCL2 signaling, and promotes the interaction between BECN1 and BCL2. Concomitantly, diabetes induces cardiomyocyte apoptosis and suppresses cardiac autophagy. Activation of AMPK directly phosphorylates MAPK8, which mediates BCL2 phosphorylation and subsequent BECN1-BCL2 dissociation, leading to restoration of cardiac autophagy, protection against cardiac apoptosis, and ultimately improvement in cardiac structure and function. We conclude that dissociation of BCL2 from BECN1 through activation of MAPK8-BCL2 signaling may be an important mechanism by which AMPK activation restores autophagy, protects against cardiac apoptosis, and prevents diabetic cardiomyopathy.
|
10.4161/auto.23577
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pubmed_1095_20928
|
The purpose of this study was to describe the epidemic of clinically apparent human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) infection in Nicaragua and to discuss the reasons why the number of HIV patients presenting to the public health care system is increasing compared with other Central American countries. From 1987 to 2004, 1,614 HIV-positive patients were officially reported to the Nicaraguan STI/HIV/AIDS national program. Urban areas along the west-central and eastern part of Nicaragua showed the highest prevalence of AIDS, with a maximum of 54.2/year per 100,000 inhabitants. Most of the infections (91%) were acquired sexually: 65% by heterosexual contacts and 26% by homosexual contacts. The highest rate of infection was found in men aged between 20 to 39 years, with a peak around 35 to 39 years (annual incidence of 125.6 new cases per 100,000 inhabitants), and in women aged 20 to 34 years old, with a peak around 20 to 24 years (annual incidence 46.6 per 100,000 inhabitants). The male to female ratio of infection was 3:1. The death rate was stable until the beginning of 1999, but increased sharply thereafter up to 2004, the year that highly active antiretroviral therapy (HAART) was introduced in Nicaragua. In 2005, we observed a further increase in the mortality. However, our data do not represent the magnitude of the HIV/AIDS epidemic as a whole, due to a lack of systemic surveillance. HIV/AIDS in Nicaragua is in a nascent stage and is concentrated in high-risk populations, such as utility workers, commercial sex workers, men who have sex with men, prisoners, street children, housewives and police and military forces. Education of the population is an urgent need to increase HIV/AIDS-related knowledge, change attitudes, and increase safer sex practice in the community.
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10.1007/s10096-007-0398-x
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pubmed_117_16725
|
BACKGROUND
Acromioclavicular joint (ACJ) injuries are common in ice hockey players and are traditionally evaluated with conventional radiography, which has recognized limitations in the accurate characterization of the spectrum of soft tissue injuries and severity/grade of injury sustained.
PURPOSE
To evaluate the epidemiologic, clinical, and magnetic resonance imaging (MRI) findings in professional ice hockey players who have sustained acute ACJ injuries.
STUDY DESIGN
Case series; Level of evidence, 4.
METHODS
A retrospective review was performed of professional National Hockey League (NHL) players referred for MRI evaluation of acute ACJ injuries. All MRI scans were assessed for status of the ACJ, ligamentous stabilizers, and surrounding musculature. MRI-based overall grade of ACJ injury (modified Rockwood grade 1-6) was assigned to each case. Data regarding mechanism of injury, player handedness, clinical features, and return to play were evaluated.
RESULTS
Overall, 24 MRI examinations of acute ACJ injuries (23 patients; mean age, 24 years) were reviewed. We found that 50% of injuries were sustained during the first period of play, and in 75% of cases, injuries involved the same side as player shooting handedness. Analysis of MRI scans revealed 29% (7/24) grade 1 ACJ injuries, 46% (11/24) grade 2 injuries, 21% (5/24) grade 3 injuries, and 4% (1/24) grade 5 injuries. Trapezius muscle strains were seen in 79% and deltoid muscle strain in 50% of cases. Nonoperative management was used for 23 injuries; 1 patient (grade 5 injury) underwent acute reconstructive surgery. All players successfully returned to professional NHL competition. Excluding cases with additional injuries or surgery (n = 3) or convalescence extending into the offseason (n = 3), we found that the mean return to play was 21.4 days (7.2 games missed). No statistically significant difference was observed in return to play between nonoperatively treated grade 3 injuries (mean, 28.3 days) and grade 1 or 2 injuries (mean, 20.1 days). However, grade 3 injuries were associated with a greater number of NHL scheduled games missed (mean, 12.7) compared with lower grade injuries (mean, 6.1) (P = .027).
CONCLUSION
The spectrum of pathology and grading of acute ACJ injuries sustained in professional ice hockey can be accurately assessed with MRI; the majority of injuries observed in this study were low grade (grades 1 and 2). Although grade 3 injuries were associated with a greater number of games missed, similar return-to-play results were observed between nonoperatively treated grade 3 and grade 1 or 2 ACJ injuries.
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10.1177/2325967120964474
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pubmed_150_2778
|
The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients.
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10.1371/journal.pone.0157510
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pubmed_325_7067
|
A new entropy bound with low computational complexity for differential Shannon entropy estimation with kernel density approach is proposed in this study, which is based on defining a bound for the Kullback-Leibler divergence between two Gaussian mixture models. The proposed entropy bound is derived to provide computational efficiency without decreasing the accuracy in detecting heart sound segments in respiratory sound. It is shown both theoretically and experimentally that using the proposed bound in an adaptive threshold-based detection method gives very similar performance compared to that obtained by a nonparametric kernel based approach, while its computational cost is much lower. The performance of the proposed method is shown and compared with the three methods in the literature by means of experiments utilizing a database of 20 subjects. The results show that the false negative rate values for the proposed method are 1.45±1.50 % and 1.98±1.81 % for low and medium flow rates, respectively. These average values are similar to the results obtained by the alternative methods. Moreover, the average elapsed time of the proposed method for a piece of data with a length of 20 s is 0.05 s, which is significantly lower than that of the other methods.
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10.1109/JBHI.2015.2491500
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pubmed_624_2247
|
Urapidil is a new antihypertensive agent involving both a peripheral and a central mode of action. To evaluate the acute effects of this drug on renal vascular tone and on pressor systems a randomized placebo-controlled crossover study was conducted in 10 patients with uncomplicated essential hypertension. Each subject received, on 2 separate days 1 week apart, an intravenous injection of either placebo or urapidil (25 or, if necessary, 50 mg). Before and after this injection blood pressure and heart rate (Dinamap), renal plasma flow (125I-hippuran), active plasma renin concentration, angiotensin II, aldosterone and catecholamines in plasma were measured. The results show that urapidil, when compared with placebo, greatly reduced blood pressure, while increasing heart rate, renal blood flow, and noradrenaline and adrenaline levels. However, dopamine levels were suppressed. Whereas renin and angiotensin II were only mildly stimulated, aldosterone levels increased significantly. It is concluded that urapidil, given intravenously, has an immediate blood pressure-lowering effect associated with a decrease in renal vascular tone and an increase in renal perfusion. Consequently, both the sympathetic and renin-angiotensin systems are stimulated, although the latter only to a mild degree. The increase in aldosterone may be partially related to the decrease in dopamine levels.
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10.1016/0002-9149(89)90691-7
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pubmed_1006_11388
|
Lowering blood pressure by medical treatment is not enough for correct prevention of the cardiovascular complications of high blood pressure. In this respect, we would like to emphasize the potential value of the non-antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors which may be summarized as follows. In the heart, ACE inhibitors significantly reduce left ventricular hypertrophy. They have no noticeable anti-ischaemic activity and are devoid of antiarrhythmic effects. On the kidneys, ACE inhibitors seem to have a protective effect, still to be determined, in certain cases of diabetes or renal impairment. ACE inhibitors have no deleterious metabolic effects. Other antihypertensive agents share the same properties. Long-term comparative trials are necessary to find out whether some of these drugs are more effective in this field than the others.
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pubmed_1006_11388
|
pubmed_786_20676
|
OBJECTIVE
The main rationale behind the continuous analgesia/sedation currently practiced in the treatment of neonates with severe respiratory failure in intensive care is an attempt at shielding the sick newborn from exogenous stress and pain caused by diagnostic and therapeutic interventions. Until now, however, the factors which influence endogenous, disease-related distress have been largely ignored.
METHOD
We retrospectively studied the daily need for analgesics and sedatives (fentanyl, midazolam, pentobarbital, thiopental) of 40 full-term newborns with severe respiratory failure who had been ventilated for at least 48 h over an observational period of 2-5 days. Dosing of the analgesics and sedatives was based on a neonatal sedation score for ventilated infants. These daily amounts were converted to a normative comparative dose (analgesic/sedative need = ASN) and compared with the oxygenation index (OI) as a measure of the degree of pulmonary insufficiency.
RESULTS
Depending on the duration of ventilation, an increasingly close correlation between the ASN and the OI was detected: the index of correlation (r) was detected to be 0.65 on the second day, but increased up to 0.94 after 5 days. The subgroup of patients who had been ventilated for more than 3 days (n = 8) consistently showed a very high correlation, ranging from r = 0.86 to r = 0.94.
CONCLUSION
Our results indicate a direct relationship between severity of pulmonary failure (expressed as OI) and degree of disease-related distress (reflected by ASN). This supports the hypothesis that in full-term neonates under mandatory intensive care for severe respiratory failure, endogenous distress caused by the primary disease itself, in addition to exogenous distress caused by therapeutic and diagnostic interventions, is key factor for the determination of the required amount of analgesic and sedative drugs.
|
10.1159/000076238
|
pubmed_759_7918
|
Mutagenic activity of N-methyl-N'-nitro-N-nitrosoguanidine with respect to Brucella melitensis was studied. In the course of this study the method of obtaining auxotrophic brucella mutants was elaborated. Numerous assortiment of auxotrophic mutants of different types was obtained. In a number of cases the acquisition of auxotrophy was accompanied by profound changes of the strain, such as the changes in morphology of colonies, in the biochemical activity, in the capacity of agglutination and in the virulence.
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pubmed_759_7918
|
pubmed_167_7585
|
INTRODUCTION
Breast cancer incidence increases from the age of 30 years. As this age range coincides with that in which women usually pursue pregnancy, undergoing medical examinations for conditions such as breast cancer is a concern, especially when pregnancy is uncertain during the first eight weeks. Moreover, in this age range, breast often exhibits a high density, thus compromising diagnosis. For such density, digital breast tomosynthesis (DBT) provides a more accurate diagnosis than 2D mammography given its higher sensitivity and specificity. However, radiation exposure increases during DBT, and it should be determined.
METHODS
We determined the entrance surface dose, scattered radiation dose, and average glandular dose (AGD), which can be mutually compared following an international protocol. Using our proposed method, the distribution of scattered radiation can be easily and quickly obtained with a minor load to the equipment. Then, we can determine the indoor scattered radiation and surface dose on patients during DBT.
RESULTS
We obtained a maximum AGD of 2.32 mGy. The scattered radiation was distributed over both sides with maximum of approximately 40 μGy, whereas the maximum dose around the eye was approximately 10 μGy.
CONCLUSION
By measuring doses using the proposed method, a correct dose information can be provided for patients to mitigate their concerns about radiation exposure. Although the obtained doses were low, their proper management is still required. Overall, the results from this study can help to enhance dose management for patients and safety management regarding indoor radiation.
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10.1016/j.radi.2018.10.006
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pubmed_396_14860
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The mitogen-activated protein (MAP) kinases mediate the response of renal glomerular mesangial cells to a variety of physiologic and pathologic stimuli. This investigation examines the effect of the cyclopentenone prostaglandin 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) on MAP kinases in human mesangial cells. We show that 15d-PGJ2 dose-dependently increases the extracellular signal-regulated kinase (ERK) activity of human mesangial cells, but has no effect on Jun-NH2-terminal kinase or p38 MAP kinase. Despite the fact that 15d-PGJ2 is a peroxisome proliferator-activated receptor (PPAR) ligand, and PPARgamma is shown to be expressed by mesangial cells, the thiazolidinedione PPARgamma agonist ciglitazone does not activate ERK. Additionally, a synthetic PPARgamma antagonist does not attenuate the activation of ERK by 15d-PGJ2. 15d-PGJ2-mediated ERK activation is however blocked by the MEK inhibitor PD 098059, appears to require phosphatidylinositol-3 kinase, but is independent of protein kinase C activation. These results demonstrate a novel effect of 15d-PGJ2 to induce ERK in human mesangial cells independently of PPARgamma.
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10.1006/bbrc.2001.4301
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pubmed_1022_14725
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OBJECTIVE
We examined the effects of learning curve on clinical outcomes and operative time in minimally invasive coronary artery bypass grafting (MICS CABG).
METHODS
We studied 210 consecutive MICS CABG cases performed by the same surgeon, composed of 3 cardiopulmonary bypass (CPB)-assisted single-vessel small thoracotomy (SVST), 87 off-pump SVST, 51 CPB-assisted multivessel small thoracotomy (MVST), and 69 off-pump MVST. For each MICS CABG technique, the frequency of early clinical events (mortality, reopening, stroke, myocardial infarction, and revascularization) was compared between the first 25 cases and the remainder. Logarithmic curve regression analysis and a cumulative summation technique were performed to assess the correlation between operative time and the performed number of each technique.
RESULTS
There was no mortality, and there were 10 conversions to standard sternotomy, all of which were intended as off-pump MVST (P < 0.001, vs other procedures). Experience was otherwise not associated with perioperative outcome. However, experience numbers correlated with operative time in off-pump SVST and off-pump MVST (122 ± 30 minutes, R = 0.18, P < 0.001, and 241 ± 80 minutes, R = 0.38, P < 0.001, respectively) but not in CPB-assisted MVST (258 ± 44 minutes, R = 0.004, P = 0.7). No complications occurred as a result of CPB assistance.
CONCLUSIONS
Minimally invasive coronary artery bypass grafting can be safely initiated, with a very low perioperative risk. Pump assistance is a good strategy to alleviate some of the learning curve and avoid conversions to sternotomy when initiating a multivessel MICS CABG program.
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10.1097/IMI.0000000000000019
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pubmed_344_10586
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Unsatisfactory results of surgery in the late course of pancreatic necrosis made us search for indications and variants of operation in the early phase of the disease. As early surgical intervention, the universal approach was used in 7 patients with necrotizing pancreatitis who had a different prevalence of the inflammatory process in the retroperitoneal space. The drainage proved to be effective and enabled us to always prevent generalized infectious complications in the later phases of the disease in absence of local complications specific for open surgery: bleeding and digestive fistulas. In spite of obvious infected process development in primary open surgery, we noticed a stable decrease in procalcitonin level following the drainage. A surgical intervention has been developed enabling one to reveal in time the volume of damaged retroperitoneal fat tissue and to drain it adequately in compliance with the process prevalence, thus avoiding septic complications in the late phase of the disease. The method's advantage involves refusal from necrosectomy in primary intervention, weekly staged revisions of the retroperitoneal space via formed contrapertures as dictated by evolution of the necrotic process in the gland.
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10.1159/000212991
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pubmed_248_12323
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STUDY DESIGN
Kinematics of the cervical spine during lateral bending were investigated using a novel system of three-dimensional motion analysis.
OBJECTIVES
To demonstrate in vivo intervertebral coupled motions of the cervical spine during lateral bending of the neck.
SUMMARY OF BACKGROUND DATA
No previous studies have successfully documented in vivo three-dimensional intervertebral motions of the cervical spine during lateral bending.
METHODS
Twelve healthy volunteers underwent three-dimensional magnetic resonance imaging (MRI) of the cervical spine in 7 positions with 10 degrees increments of lateral bending. Relative motions of the cervical spine were calculated automatically by superimposing a segmented three-dimensional-MRI of the vertebra in the neutral position over images of each position using volume registration.
RESULTS
Mean maximum lateral bending of the cervical spine to one side was 1.6 degrees to 5.7 degrees at each level. Coupled axial rotation opposite to lateral bending was observed in the upper cervical levels (Oc-C1, 0.2 degrees ; C1-C2, 17.1 degrees ), while in the subaxial cervical levels, it was observed in the same direction as lateral bending except for at C7-T1. Coupled flexion-extension motion was small at all vertebral levels (<1.1 degrees).
CONCLUSIONS
We succeeded in identifying in vivo coupled motions of the cervical spine in lateral bending for the first time.
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10.1097/01.brs.0000195173.47334.1f
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pubmed_915_19724
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In this study, polydopamine (PDA) coated chitosan/calcium pyrophosphate hybrid microflowers (PDA@CS-CaP) were prepared using a facile approach and evaluated as a hemostatic agent. The surface morphology and elements, chemical groups, porous structure, thermostability, zeta potential, as well as surface wettability were systematically characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), N2 adsorption-desorption, thermogravimetry (TGA) and contact angle apparatus. Due to the synergistic effects of the high hydrophilicity (water contact angel nearly 0), chemical activation (the amino and phenol group of PDA), and the flower-like porous hierarchical structure, the prepared PDA@CS-CaP could induce hemocytes and platelets aggregation, promote the blood clotting and achieve bleeding control in vitro and in vivo. Furthermore, the PDA@CS-CaP had no exothermic adverse effects and exhibited better biocompatibility (no cytotoxicity against fibroblasts cells). Thus, the PDA@CS-CaP were expected to be a promising candidate for a safe and promising hemostatic agent because of its porous and hierarchical structures as well as the active PDA coating.
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10.1016/j.carbpol.2019.115175
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pubmed_210_8546
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In this work, we present a multipurpose photonic integrated circuit capable of generating multiheterodyne complex Dual-Combs (DC) THz signals. Our work focuses on translating the functionality of an electro-optic tunable DC system into a photonic chip employing standard building blocks to ensure the scalability and cost efficiency of the integrated device. The architecture we analyze for integration is based on three stages: a seed comb, a mode selection stage and a DC stage. This final DC stage includes a frequency shifter, a key element to improve the final detection of the THz signals and obtain real-time operation. This investigation covers three key aspects: (1) a solution for comb line selection on GHz spaced combs using OIL or OPLL on photonic chips is studied and evaluated, (2) a simple and versatile scheme to produce a frequency shift using the double sideband suppressed carrier modulation technique and an asymmetric Mach Zehnder Interferometer to filter one of the sidebands is proposed, and (3) a multipurpose architecture that can offer a versatile effective device, moving from application-specific PICs to general-purpose PICs. Using the building blocks (BBs) available from an InP-based foundry, we obtained simulations that offer a high-quality Dual-Comb frequency shifted signal with a side mode suppression ratio around 21 dB, and 41 dB after photodetection with an intermediate frequency of 1 MHz. We tested our system to generate a Dual-Comb with 10 kHz of frequency spacing and an OOK modulation with 5 Gbps which can be down-converted to the THz range by a square law detector. It is also important to note that the presented architecture is multipurpose and can also be applied to THz communications. This design is a step to enable a commercial THz photonic chip for multiple applications such as THz spectroscopy, THz multispectral imaging and THz telecommunications and offers the possibility of being fabricated in a multi-project wafer.
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10.3390/s20216089
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pubmed_1030_8989
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In order to better understand the purchase decision-making process of consumers, this paper makes an in-depth study on the precision marketing of e-commerce products on the basis of KNN algorithm. Through data mining, classic KNN algorithm, BPNN algorithm, and other methods, this paper takes the price and purchase intention of e-commerce agricultural products as an example. Based on the classic nearest neighbor algorithm, binomial function is combined with Euclidean distance formula when calculating the nearest neighbor through similarity. The particle swarm optimization algorithm is used to optimize the binomial function coefficient and the K value of the nearest neighbor algorithm, and the results of the best prediction model for the prediction application of e-commerce agricultural product price and purchase intention are established. Both pricing strategies and promotion strategies will weaken the compromise effect of consumers when they choose e-commerce agricultural products. After studying the calculation method of the KNN algorithm, it not only correctly predicts the price of e-commerce agricultural products but also makes a corresponding prediction and analysis of consumers' purchase intention of e-commerce agricultural products, with the highest accuracy of 94.2%. At the same time, in the future precision marketing process, e-commerce agricultural products enterprises use data technology to achieve precision marketing, which effectively changes the shortcomings of traditional marketing and improves the product marketing effect and economic benefits.
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10.1155/2022/4966439
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pubmed_817_13954
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Heterogeneous photocatalysis employing semiconductor oxide photocatalysts is a sustainable and promising method for environmental remediation and clean energy generation. In this context, nanostructured photocatalysts, with at least one dimension in the 1‒100 nm size regime, have attracted ever-growing attention due to their unique and often enhanced size-dependent physicochemical properties. While their reduced size ensures enhanced photocatalytic performance, the same makes it difficult and time/energy-demanding to remove/recover such nanostructured photocatalysts from aqueous media. This fundamental limitation has paved the way towards developing supported nanophotocatalysts where the active photocatalytic nanostructures are coated on the surface of polymeric or inorganic support materials, often in a core@shell conformation. This arrangement solves the problem of photocatalysts' recovery for effective reuse or recycling and leads to improved and desired target properties due to specific photocatalyst-support interactions. While the enhanced physicochemical properties of supported photocatalysts have been widely studied in many target applications, the role of support-photocatalysts interactions in improving these properties remains unexplored. This review article provides an updated viewpoint on the photocatalyst-support interactions and the resulting unique physiochemical properties important for diverse photochemical applications and the design of practical devices. While exploring the properties of supported nanostructured metal oxide/sulfides photocatalysts such as TiO2 and MoS2, we also briefly discuss the common strategies employed to coat the active nanomaterials on the surface of different supports (organic/polymeric, inorganic, active, inert, and magnetic).
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10.1007/s43630-022-00299-9
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pubmed_551_23609
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In the present work, Bacillus subtilis was engineered to produce L-malate. Initially, the study revealed that the slight fumarase activity under anaerobic conditions is extremely favourable for L-malate one-step fermentation accumulation. Subsequently, an efficient heterologous biosynthesis pathway formed by Escherichia coli phosphoenolpyruvate carboxylase and Saccharomyces cerevisiae malate dehydrogenase was introduced into B. subtilis, which led to 6.04 ± 0.19 mM L-malate production. Finally, the L-malate production was increased 1.5-fold to 9.18 ± 0.22 mM by the deletion of lactate dehydrogenase. Under two-stage fermentation conditions, the engineered B. subtilis produced up to 15.65 ± 0.13 mM L-malate, which was 86.3 % higher than that under anaerobic fermentation conditions. Though the L-malate production by the recombinant was low, this is the first attempt to produce L-malate in engineered B. subtilis and paves the way for further improving L-malate production in B. subtilis.
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10.1007/s11274-012-1155-6
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pubmed_1107_23608
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The CD4 receptor contributes to T-cell activation by coligating major histocompatibility complex class II on antigen presenting cells with the T-cell receptor (TCR)/CD3 complex, and triggering a cascade of signaling events including tyrosine phosphorylation of intracellular proteins. Paradoxically, CD3 cross-linking prior to TCR stimulation results in apoptotic cell death, as does injection of anti-CD4 antibodies in vivo of CD4 ligation by HIV glycoprotein (gp) 120. In this report we investigate the mechanism by which CD4 cross-linking induces cell death. We have found that CD4 cross-linking results in a small but rapid increase in levels of cell surface Fas, a member of the tumor necrosis factor receptor family implicated in apoptotic death and maintenance of immune homeostasis. Importantly, CD4 cross-linking triggered the ability of Fas to function as a death molecule. Subsequent to CD4 cross-linking, CD4+ splenocytes cultured overnight became sensitive to Fas-mediated death. Death was Fas-dependent, as demonstrated by cell survival in the absence of plate-bound anti-Fas antibody, and by the lack of CD4-induced death in cells from Fas-defective lymphoproliferative (lpr) mice. We demonstrate here that CD4 regulates the ability of Fas to induce cell death in Cd4+ T cells.
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10.1073/pnas.93.20.11014
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pubmed_167_13006
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Veterinary diagnostic clinicians are increasingly presented with emaciated animals involved in suspected neglect cases. A rise in public awareness and media attention towards animal welfare, combined with changes in legislation and a demand for a higher standard of evidence be presented in animal neglect cases submitted for prosecutions, have created a need for an objective measurement of starvation, particularly given the lack of quantitative assessments at post-mortem examinations. Bone marrow fat (BMF) is the final fat reserve to be mobilised for energy by a calorie-deprived animal during a state of emaciation. Percentage of BMF has been used to study starvation in several species and may provide an objective measure of ante-mortem body condition. This paper reviews the literature on the use of BMF analysis as a post-mortem diagnostic test for ante-mortem starvation. Beginning with a general overview of starvation and usual methods of assessment to describe animals in poor condition, the analysis of BMF is then introduced. Various methods of BMF analysis are discussed, as well as factors that influence the amount of BMF. This review also discusses the limitations of BMF analysis and makes suggestions where future research should be primarily focused.
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10.1016/j.tvjl.2018.11.001
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pubmed_764_11791
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For the last four years there has been a videoconferencing link between the Karlskrona hospital and the university hospital of Lund. Because of a need to transmit angiographic films, its use has been gradually expanded to become an everyday routine, used for both elective and emergency examinations. During 1994 and 1995, 1121 cases were examined over the video link. Apart from 156 normal cases all were discussed with surgeons, most at 96 weekly conferences but approximately 50 at conferences taking place as soon as possible after the examination. Assuming that an average of three doctors attended the conferences before the video link was available, this amounts to a saving of 3 x 8 h in travelling time per videoconference. The average salary was 300 SKr/h and train tickets cost a further 400 SKr per person. The cost of the ISDN connection was approximately 1800 SKr/conference. The net gain was thus about 6500 SKr per videoconference, without taking into account the work that could be done with the doctors still in Karlskrona after the conference.
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10.1258/1357633961929998
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pubmed_616_20790
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Extracellular vesicles (EVs) are key signaling mediators between cancer cells and their supporting stroma, and regulate critical processes such as invasion, metastases, and angiogenesis. We have identified a subset of miRNAs (miR-142-3p, miR-143-3p, miR-145-5p, miR-150-5p, miR-223-3p, miR-451a, miR-486-5p, miR-605-5p) that are enriched in lung adenocarcinoma extracellular vesicles compared to the donor cells from which they were derived. Two well-known tumor suppressors, miR-143-3p and miR-145-5p, were also enriched in serum samples collected during surgery from blood vessels draining directly from lung adenocarcinoma tumor beds. Recently, both miRNAs were found to promote neoangiogenesis in endothelial cells in mouse models of lung adenocarcinoma through targeting of CAMK1D, an inhibitory kinase that can impair angiogenesis when over-expressed. We show that the transfer of miR-143-3p and miR-145-5p within extracellular vesicles from lung adenocarcinoma cells to endothelial cells reduces the levels of CAMK1D and increases tube formation by endothelial cells. This finding suggests that transfer of miRNAs within extracellular vesicles is a method of communication between cancer and endothelial cells which promotes angiogenesis while simultaneously removing tumor suppressive miRNAs within the tumor cells, thus driving tumorigenesis.
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10.18632/oncotarget.19996
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pubmed_1067_9955
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Long term use of immunosuppressants impacts the cardiovascular system and increases the risk of infection and malignancy. To effectively reduce immunosuppression in a transplant recipient a tool is needed to directly monitor the level of immune function. The Cylex(R) Immune Cell Function Assay, approved by the FDA for the assessment of cell-mediated immunity, shows promise as an objective measure of a transplant recipient's immune function. In a blinded retrospective study, the immune function was compared to clinical courses and histological examinations of biopsies of 20 small bowel transplant recipients during periods of immunosuppressant tapering. Eight patients with no major adverse events or changes of immunosuppressive therapy had moderate to low immune function and were categorized as immunologically and clinically stable. Twelve patients displaying strong immune responses were immunologically and clinically volatile requiring addition of steroids and or OKT3. Results validate the clinical utility of the Cylex Immune Cell Function Assay as an objective tool for assessing immune function. By evaluating immune function, physicians now can identify those patients who are candidates for minimization of immunosuppressant therapy, manage the timing and rate of immunosuppressant weaning and be forewarned of increased patient risk.
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10.1016/j.trim.2005.03.019
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pubmed_844_4757
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RATIONALE AND OBJECTIVES
The purpose of this study is to use the relationship between the partial volume effect, count density, matrix size, and reconstruction filter in gated single photon emission computer tomography (SPECT) to recover myocardial thickness, and to validate measurements generated using a computer-assisted automatic contour method with a phantom model and with thickness changes measured by echocardiography.
METHODS
Regional myocardial contour was defined automatically using shape constraints, gray level thresholding, and a gradient method applied to gated technetium-99m (99mTc)-methoxy-isobutyl-isonitile (MIBI) SPECT images. A heart phantom with wall thickness ranging from 0.8 cm to 1.3 cm was constructed. SPECT images were acquired and reconstructed using different matrix sizes, count densities, and filters. Wall thickness determinations derived from the reconstructions made with each combination of matrix size, type of filter, and cutoff frequency were correlated with the measured thicknesses. The best combination was applied to the gated MIBI SPECT images of 55 patients who also had echocardiography and coronary arteriography. Count density measurements were made across each regional myocardial segment to evaluate wall thickness at end-diastole and end-systole. Systolic wall thickening measurements made with this automated computer-assisted contour technique were compared with echocardiographic measurements made from segments with normal perfusion and from regions containing infarcted tissue.
RESULTS
Different reconstruction filters and cutoff frequencies affected the accuracy of measurements of myocardial wall thickness determined from gated myocardial SPECT images. A matrix size of 64 x 64, with a minimum of 10 counts/pixel/frame, and use of a Hanning filter with 0.5 cyc/cm cutoff frequency gave the best combination for myocardial thickness determination and spatial resolution. Application of these factors to the phantom yielded results that correlated very well with the thickness measurements (r = 0.986, P < 0.001). Application of the technique to the clinical SPECT studies yielded measurements of myocardial wall thickening that were not significantly different from that determined by echocardiography.
CONCLUSION
Computer-assisted contour analysis of gated SPECT images enables accurate determination of regional wall thickening using the count density changes within each myocardial segment.
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10.1097/00004424-199805000-00001
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pubmed_482_19452
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Endoscopic stenting with self-expandable metallic stents is widely accepted for the treatment of malignant colorectal obstruction. Generally, stenting is performed as a bridge-to-surgery for primary colorectal cancer (CRC). Furthermore, palliative colonic stenting is performed for extraparenteral malignant tumors (EPMTs). However, predictive factors for improving clinical outcomes after colonic stenting for EPMTs remain unclear. This study is aimed at evaluating patients with EPMTs who underwent colonic stenting and investigating factors influencing clinical improvement after the stenting procedure. Twenty-one patients with colorectal obstruction by EPMTs were treated using self-expandable metallic stents over a period of 8 years. We divided the enrolled patients into the clinically improved and nonimproved groups after colonic stenting. Variables, including age; sex; type of primary cancer; serum albumin level; location of the obstruction; stent type, length, and diameter; prior chemotherapy treatment; ascites; Eastern Cooperative Oncology Group performance status (PS); technical and clinical success rates; stent-related adverse events; and mortality rates, were evaluated. Technical failure was not observed in all cases. Clinical success, defined as the passage of stool and improvement in the colorectal obstruction scoring system (CROSS) without adverse events, was observed in the 14 patients. Univariate analyses revealed no significant differences in factors other than PS before stenting (P = 0.04) between the improved and nonimproved groups. Colonic stenting for EPMTs was effective. PS may be an independent risk factor of clinical outcomes after stenting.
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10.1155/2020/5931341
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pubmed_578_17972
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Ampelomyces quisqualis complex is well known as the most common and widespread hyperparasite of the family Erysiphaceae, the cause of powdery mildew diseases. As commercial biopesticide products it is widely used to control the disease in field and plastic houses. Although genetic diversity within Ampelomyces isolates has been previously recognized, a single name A. quisqualis is still applied to all pycnidial intracellular hyperparasites of powdery mildew fungi. In this study, the phylogenetic relationships among Ampelomyces isolates originating from various powdery mildew fungi in Korea were inferred from Bayesian and maximum parsimony analyses of the sequences of ITS rDNA region and actin gene. In the phylogenetic trees, the Ampelomyces isolates could be divided into four distinct groups with high sequence divergences in both regions. The largest group, Clade 1, mostly accommodated Ampelomyces isolates originating from the mycohost Podosphaera spp. (sect. Sphaerotheca). Clade 2 comprised isolates from several genera of powdery mildews, Golovinomyces, Erysiphe (sect. Erysiphe), Arthrocladiella, and Phyllactinia, and was further divided into two subclades. An isolate obtained from Podosphaera (sect. Sphaerotheca) pannosa was clustered into Clade 3, with those from powdery mildews infecting rosaceous hosts. The mycohosts of Ampelomyces isolates in Clade 4 mostly consisted of species of Erysiphe (sect. Erysiphe, sect. Microsphaera, and sect. Uncinula). The present phylogenetic study demonstrates that Ampelomyces hyperparasite is indeed an assemblage of several distinct lineages rather than a sole species. Although the correlation between Ampelomyces isolates and their mycohosts is not obviously clear, the isolates show not only some degree of host specialization but also adaptation to their mycohosts during the evolution of the hyperparasite.
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10.1016/j.funbio.2010.01.003
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pubmed_51_18009
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BACKGROUND
Previous studies suggest that Dupuytren's disease is caused by fibroblast and myofibroblast contractility. Cell contractility in smooth muscle cells is caused by calcium-dependent and calcium-independent signaling mechanisms. In the calcium-dependent pathway, calcium/calmodulin activates myosin light chain kinase (MLCK). In this study, the effects of calcium/calmodulin inhibition with the FDA-approved drug fluphenazine on Dupuytren's fibroblast contractility and MLCK expression were tested.
METHODS
Fibroblast lines from the palmar fascia of patients with Dupuytren's disease were explanted and used for in vitro study. The effect of fluphenazine on Dupuytren's fibroblast migration was determined using a scratch migration assay, and contractility was determined using fibroblast-populated collagen lattice (FPCL) assays. Immunohistochemical staining of MLCK in different samples of Dupuytren's tissue and normal fascia were compared.
RESULTS
Fluphenazine demonstrated a dose-dependent inhibition of Dupuytren's fibroblast migration, with the maximum inhibition of migration observed at 20 μM (69.8 ± 1.9%). Fluphenazine also inhibited FPCL contraction in a dose-dependent manner. Maximal inhibition was observed at a fluphenazine concentration of 20 μM (52.5 ± 6.1%). Immunohistological staining illustrated that MLCK was predominantly expressed throughout the cytoplasm of select fibroblasts within Dupuytren's nodules, yet was absent in the fibroblasts of Dupuytren's cords and normal palmar fascia.
CONCLUSIONS
Fluphenazine inhibits Dupuytren's fibroblast contractility and migration through inhibition of MLCK in vitro. However, the inconsistent expression of MLCK throughout Dupuytren's tissue suggests that calcium-dependent signaling may not be a primary mode of contracture formation. Fluphenazine inhibition of MLCK is not likely to be a target for the treatment of Dupuytren's disease.
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10.1007/s11552-010-9314-4
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pubmed_282_5357
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This paper identifies a common political struggle behind debates on the validity and permissibility of animal experimentation, through an analysis of two recent European case studies: the Italian implementation of the European Directive 2010/63/EC regulating the use of animals in science, and the recent European Citizens' Initiative (ECI) 'Stop Vivisection'. Drawing from a historical parallel with Victorian antivivisectionism, we highlight important threads in our case studies that mark the often neglected specificities of debates on animal experimentation. From the representation of the sadistic scientist in the XIX century, to his/her claimed capture by vested interests and evasion of public scrutiny in the contemporary cases, we show that animals are not simply the focus of the debate, but also a privileged locus at which much broader issues are being raised about science, its authority, accountability and potential misalignment with public interest. By highlighting this common socio-political conflict underlying public controversies around animal experimentation, our work prompts the exploration of modes of authority and argumentation that, in establishing the usefulness of animals in science, avoid reenacting the traditional divide between epistemic and political fora.
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10.1016/j.shpsc.2017.06.004
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pubmed_1110_8133
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The easy, convenient and high yielding preparation of new thioglycosides incorporating mercaptopyrazolo[1,5-a]pyrimidine moieties from readily accessible starting materials has been reported. The main step of this protocol is the formation of 7-mercaptopyrazolo[1,5-a]pyrimidine-6-carbonitrile derivatives 4a-d by condensation of sodium 2-cyano-3-ethoxy-3-oxoprop-1-ene-1,1-bis(thiolate) 1 with 4-(aryldiazenyl)-1H-pyrazole-3,5-diamines 3a-d to form target compounds 4a-d, which coupled with tetra-O-acetyl-α-D-glycopyranosyl bromides 5a,b in the presence of basic medium to provide the corresponding product purine thioglycoside analogs 6a-h. Ammonolysis of the latter compounds 6a-d at ambient temperature for 10 minutes, led to the free glycoside derivatives 7a-h, which were obtained in approximately quantitative yields. Their structures were created based on the spectroscopic and elemental data.
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10.1080/15257770.2017.1419254
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pubmed_443_13876
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Female Japanese quail (Coturnix coturnix Japonica) placed in 3 equal groups were given 600, 400 or 0 mg furazolidone (Fz)/kg feed for 4 w and then withdrawn for another 4 w. Another (pair-fed) group of same size was given basal feed as much as was consumed by the quail fed 600 mg Fz/kg feed. Fz feeding decreased body weight, feed intake and egg production. Ovaries of the Fz-fed quail decreased in weight and size and were studded with small follicles. Magnum, isthmus and uterus in Fz-fed groups had decreased area, height and number of mucosal folds compared with the control group. Microscopically, in Fz-fed groups, the mucosal glands in magnum and isthmus had decreased cell height with centrally located nuclei and foamy cytoplasm. In the 600 mg Fz-fed group, some birds had atrophy of the glandular tissue in the mucosa and infiltration of mononuclear cells and fibroblasts. Upon cessation of the Fz feeding, all parameters reversed gradually and became non-significantly different from control quail. These observations suggested that Fz-induced changes in mature female quail were reversible.
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pubmed_443_13876
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pubmed_480_4333
|
BACKGROUND
The development of simple approaches to quantitatively estimate functional motor performance in a wide range of ages is crucial for early detection of locomotive syndrome (LS). Sit-to-stand (STS) movements from a chair are important in activities of daily living (ADL), although such tasks are the most mechanically demanding among all ADL. Here, we propose a novel test to score STS abilities to estimate individual functional motor status and investigated age-related changes in STS scores as a method to evaluate reduction in performance.
METHODS
A total of 606 healthy subjects (average age, 48.4 years; age range, 20-87 years) without neuromusculoskeletal disorders participated in the study. We designed a test to score STS abilities, based on STS determinant variables, including seat height, foot positioning, and both-leg- or one-leg-standing tasks. STS scores ranged from 0 to 14 points, depending on the difficulty or mechanical demands of the STS task. We evaluated the STS score of the subjects divided into seven 10-year age groups.
RESULTS
A significant and negative correlation was observed between STS scores and subject age (men: r = -0.65, P < 0.001; women: r = -0.62, P < 0.001). The proportion of subjects able to stand on one leg from a chair seat height of 100% of knee height decreased with age from 100% for both men and women aged 20-29 years to 0.0% and 7.1% for men and women aged 80-87 years, respectively. A large variation in STS scores was observed for subjects aged >60 years. There was a negative linear correlation between mean STS score per age group and mean age (men: R(2) = 0.93, slope = -0.10, intercept = 16.63 points; women: R(2) = 0.92, slope = -0.08, intercept = 14.76 points).
CONCLUSIONS
The ability to perform STS was negatively correlated with age among healthy subjects aged 20-87 years. For subjects aged >60 years, STS abilities decreased, but within-group variability increased. This test was useful to identify the deterioration of functional motor performance and prevent early LS.
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10.1016/j.jos.2016.04.006
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pubmed_1113_21104
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This study investigated the role of neutral, happy, fearful, and angry facial expressions in enhancing orienting to the direction of eye gaze. Photographs of faces with either direct or averted gaze were presented. A target letter (T or L) appeared unpredictably to the left or the right of the face, either 300 ms or 700 ms after gaze direction changed. Response times were faster in congruent conditions (i.e., when the eyes gazed toward the target) relative to incongruent conditions (when the eyes gazed away from the target letter). Facial expression did influence reaction times, but these effects were qualified by individual differences in self-reported anxiety. High trait-anxious participants showed an enhanced orienting to the eye gaze of faces with fearful expressions relative to all other expressions. In contrast, when the eyes stared straight ahead, trait anxiety was associated with slower responding when the facial expressions depicted anger. Thus, in anxiety-prone people attention is more likely to be held by an expression of anger, whereas attention is guided more potently by fearful facial expressions.
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10.1037/1528-3542.7.3.478
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pubmed_238_19426
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Despite the negative impact of social isolation on wellbeing, research has yet to address how organisations may mitigate the effects of workplace isolation and loneliness. The main objective of the study is to explore the mediating role of task interdependence and supportive behaviours of colleagues on the relationship between workplace isolation on workplace wellbeing. A total of 137 volunteers completed a survey assessing workplace isolation, loneliness, task interdependence, supportive behaviours of colleagues and wellbeing at work. SEM analyses supported the negative effects of company isolation on workplace wellbeing. While supportive behaviours had a mediating role, task interdependence did not mediate the relationships between company isolation and loneliness, and wellbeing. The findings show that increased opportunities for interpersonal interactions at work through greater task interdependence are not enough to reverse the negative effects of workplace isolation on wellbeing. In contrast, an investment in a supportive environment may reverse the negative effects of workplace isolation on wellbeing, highlighting the importance of a supportive culture.
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10.1016/j.apergo.2022.103894
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pubmed_111_17104
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This paper presents an autopsy case of primary malignant lymphoma of the urinary bladder. The patient, a 63-year-old man, consulted us because of macroscopic hematuria. Cystoscopy revealed a bladder tumor, which was diagnosed as an anaplastic cell carcinoma by transurethral punch biopsy. The tumor progressively increased in size, despite treatment with preoperative antineoplastic chemotherapy consisting of CDDP. Only ureterocutaneostomy and biopsy were performed at the operation although total cystectomy and ileal conduit had been planned, because the tumor had invaded into the perivesicular tissue. Biopsy revealed B cell lymphoma, which was characterized by specific staining with IgG by the PAP method. Although antineoplastic chemotherapy was performed again after operation, the patient gradually weakened and died 5 months after admission. At autopsy, a hen-egg sized, non-papillary tumor which invading into the perivesicular tissue was found at the anterior wall of the urinary bladder. There were many metastatic nodules in the thraco-lumbar vertebral columns, para-aortic lymphnodes and mesenteric lymphnodes. Lungs and liver were free from metastatic tumors.
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pubmed_111_17104
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pubmed_809_14574
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Microdamage in the form of microcracks has been observed in cortical bone following in vivo and in vitro fatigue loading. It has been suggested that bone has an inherent ability to repair microdamage at physiological activity levels. If the biological remodelling and repair process cannot keep up with the rate of damage accumulation, as in ageing bone and in individuals such as athletes and military recruits, microdamage may accumulate even at physiological activity levels. Such microdamage accumulation is thought to contribute to stress and fragility fractures. It is therefore important to obtain quantitative data on the rate of damage accumulation so as to understand the etiology of skeletal fractures. Sequential labelling of microdamage using fluorochrome stains at different stages of mechanical loading is becoming standard for assessing damage evolution. Although verification of this staining technique is provided in the literature, it has not yet been reported if the stains change the mechanical properties of cortical bone. In this study, monotonic tensile tests were performed to investigate the effect of the staining on the monotonic tensile mechanical properties of cortical bone. Forty-eight specimens were machined from human femora obtained from three male subjects, aged 52-55 years, and all 48 specimens were systematically divided into one control and three treatment groups. Specimens in the first (n = 12) and second treatment groups (n = 12) were stained with alizarin complexone and calcein (0.0005 M), respectively, for 16 h under 50 mmHg vacuum. Specimens in the third treatment group (n = 12) were kept in calcium-supplemented saline solution under the same conditions of the first and second treatment groups. Specimens in the control group (n = 12) were removed from the freezer prior to testing and allowed to thaw at room temperature in saline solution. Differences among the mean values of the mechanical properties for four testing groups were determined by the Mann-Whitney test at a significance level of P < 0.05. The statistical results indicated that the chelating stains and the staining conditions have no significant effect on the mechanical properties of the cortical bone under monotonic tensile loading. This study demonstrated that microcrack labelling with the chelating stains under aforementioned conditions (stain concentration, staining time, etc.) is a reliable method in that staining cortical bone with alizarin complexone and calcein prior to testing does not affect tensile properties.
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10.1111/j.1469-7580.2007.00810.x
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pubmed_137_10161
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Paenibacillus alvei NP75, a Gram-positive bacterium, produces two different antimicrobial peptides, paenibacillin N and P, which has potent antimicrobial activity against many clinical pathogens. The synthesis pattern of these antimicrobial peptides by P. alvei NP75 was studied extensively. The results were outstanding in a way that the paenibacillin N was synthesized irrespective of the growth of bacteria (non-ribosomal mediated), whereas paenibacillin P production was carried out by ribosomal mediated. In addition to the antimicrobial peptides, P. alvei NP75 also produces an immunogenic extracellular protease to defend itself from its own antimicrobial peptide, paenibacillin P. Furthermore, this immunogenic protease production was impaired by the addition of protease inhibitor, phenylmethylsulfonyl fluoride (PMSF). The sodium dodecyl sulfate (SDS) treated strain (mutant) failed to produce paenibacillin P, whereas the production of neither paenibacillin N nor the protease was affected by the plasmid curing. The plasmid curing studies that divulge the genes responsible for the synthesis of paenibacillin N and protease were found to be genome encoded, and paenibacillin P was plasmid encoded. We are reporting, first of its kind, the co-production of two different antimicrobial peptides from P. alvei NP75 through non-ribosomal and ribosomal pathways that could be used as effective antibiotics.
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10.1007/s12602-019-09541-w
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pubmed_637_6253
|
Extracellular signal-regulated kinase 5 (ERK5) has been reported to regulate endothelial integrity and protect from vascular dysfunction under laminar flow. Previously reported research indicates that under laminar flow ERK5 is activated with production of atheroprotective molecules. However, the characterization of ERK5 activation and levels under different flow patterns has not been investigated. Confluent HUVECs were serum-starved then seeded on glass slides. HUVECs incubated in 1% FBS were exposed to continuous laminar flow (CLF), to-and-fro flow (TFF), or pulsatile forward flow (PFF) in a parallel plate flow chamber. At the end of experimentation, cell lysates were immunoblotted with antibodies to phospho-ERK5 and total ERK5. ERK5 activation was assessed by the levels of phosphorylated ERK5. The densitometric mean ± SEM is calculated and analyzed by ANOVA. p < 0.05 is considered significant. Levels of ERK5 decreased with all flow conditions with the largest decrease in TFF flow condition. TFF and CLF exhibited sustained ERK5 phosphorylation in HUVECs stimulated for up to 4 hours. PFF had transient phosphorylation of ERK5 at 2 hours, which then became undetectable at 4 hours of exposure to flow. Also, TFF and CLF both showed decreased levels at 4 hours, suggesting a decrease in activation for these flow conditions. Exposure of HUVEC to different types of shear stress results in varying patterns of activation of ERK5. Activation of ERK5 with TFF suggests a role in the pathogenesis of atherosclerosis and vascular remodeling under disturbed flow conditions.
|
10.1055/s-0037-1599057
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pubmed_1127_19835
|
PURPOSE
The call for clinically relevant outcome criteria has been raised, as assessment of adequate quality of service providers is essential with increasing momentum in the development of palliative care in most European countries. The aim of this study is to investigate important dimensions and indicators for assessment and evaluation of palliative care from the perspective of multi-disciplinary German experts working over years in the field of palliative care.
METHODS
A focus group, using the structured consensus method of the improved nominal group technique (INGT), with nine experts from different disciplines was conducted in Germany.
RESULTS
An abundance of topics (16) were identified, pointing at the complexity of the issue. Main topics were: quality of life, needs assessments of patients and relatives, resource assessment, surveillance of decision-making processes, as well as spiritual well-being. The following properties were claimed as essential for outcome criteria sensitivity, without additional burden on patients, easy applicability, scientific validity, and helpful for communication within the team, ethical discussions as well as for quality management.
CONCLUSIONS
The study identified topics considered important by experts in clinical practise. The discussions exposed the diversity of demands on outcome assessment put up by different stakeholder groups. This and the high number of relevant items show the complexity for the agreement on a unique set of outcome criteria. Further research considering other perspectives is needed.
|
10.1007/s00520-009-0721-4
|
pubmed_467_3036
|
The altanisation strategy, devised to design molecules with large and paratropic perimeter circulations, is applied to the family of [n]annulenes to give, altan-[n]annulenes, i.e. [n,5]coronenes. Analytical expressions are obtained for the eigenvalues of the Hückel Hamiltonian for altan-[n]annulenes, and used in conjunction with selection rules derived from the ipsocentric approach to predict patterns of global ring current in these systems. Density-functional calculations performed on seven altan-[n]annulenes, three neutral and four charged, give current-density maps in essential agreement with the predictions obtained at the unperturbed Hückel level. All but one of the systems show patterns with the tropicities expected for isolated annulenes, in line with the altanisation concept. The apparent exception is altan-[11]annulene-, the only singlet system with a well defined open-shell character in the studied set. The key role of open-shell character can be accommodated by appropriate choice of the occupation numbers of the initial Hückel molecular orbitals, where the anion altan-[11]annulene- is considered as an [11]annulene inside the [22]annulene anion.
|
10.1039/c9cp06835j
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pubmed_571_19353
|
BACKGROUND
To investigate the factor structure, dimensionality and construct validity of the (5-item) PRAFAB questionnaire score in women with stress urinary incontinence (stress UI).
METHODS
A cross validation study design was used in a cohort of 279 patients who were randomly divided into Sample A or B. Sample A was used for preliminary exploratory factor analyses with promax rotation. Sample B provided an independent sample for confirming the premeditated and proposed factor structure and item retention. Internal consistency, item-total and subscale correlations were determined to assess the dimensionality. Construct validity was assessed by comparing factor-based scale means by clinical characteristics based on known relationships.
RESULTS
Factor analyses resulted in a two-factor structure or subscales: items related to 'leakage severity' (protection, amount and frequency) and items related to its 'perceived symptom impact' or consequences of stress UI on the patient's life (adjustment and body (or self) image). The patterns of the factor loadings were fairly identical for both study samples. The two constructed subscales demonstrated adequate internal consistency with Cronbach's alphas in a range of 0.78 and 0.84 respectively. Scale scores differed by clinical characteristics according to the expectations and supported the construct validity of the scales.
CONCLUSION
The findings suggest a two-factorial structure of the PRAFAB questionnaire. Furthermore the results confirmed the internal consistency and construct validity as demonstrated in our previous study. The best description of the factorial structure of the PRAFAB questionnaire was given by a two-factor solution, measuring the stress UI leakage severity items and the perceived symptom impact items. Future research will be necessary to replicate these findings in different settings, type of UI and non-white women and men.
|
10.1186/1471-2490-8-1
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pubmed_134_17398
|
Abstract Ichthyobodo necator (costia) is a common and important flagellate parasite that infests the skin and gills of many freshwater and marine fish. Costia infestations are often fatal and cause significant aquaculture losses worldwide. Recently it has been demonstrated that Ichthyobodo is a multispecies complex with differing host preferences. Knowing if those species have broad or narrow host specificity has important implications for the management of costia. To address the question of host specificity, genomic DNA was isolated from Ichthyobodo trophonts collected from rainbow trout, Oncorhynchus mykiss, koi, Cyprinus carpio, mirror carp, C. carpio, goldfish, Carassius auratus, channel catfish, Ictalurus punctatus, swordtail, Xiphophorus helleri, and Japanese flounder, Paralichthys olivaceus. The small subunit ribosomal RNA (SSU rRNA) gene from each isolate was analysed with previously published Ichthyobodo sequences using Bayesian phylogenetic methods. The internal transcribed spacers (ITS) from six isolates were also PCR-amplified, cloned and sequenced. Both the SSU rRNA phylogenetic analysis and the ITS rRNA sequence data support grouping the 22 Ichthyobodo isolates examined into a complex of nine different species. Many of these species were frequently isolated from multiple hosts, indicating that exchange of infested fish from one region to another has a high potential for spreading the disease. In one instance, the same species was obtained from marine and freshwater fish, further suggesting that certain Ichthyobodo species may not be limited by salinity.
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10.1111/j.1365-2761.2004.00603.x
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pubmed_453_8489
|
In response to low-intensity, low-frequency, phase-locked tonal stimuli with non-alternating polarity, the time-average round window (RW) response of the gerbil is a mixture of the auditory nerve neurophonic (ANN) and cochlear microphonic (CM), with the former often being of equal or greater magnitude than the latter. Forward masking (using a conservative 25% amplitude reduction criterion) can be used to generate ANN tuning curves (TC). Most of these TCs are sharply tuned V-shaped functions. Harmonic distortion is often present in the ANN, especially in response to the lower-frequency (< or = 1 kz) or higher-intensity (> or = 50 dB) stimuli. The TCs created by forward masking of the harmonics are similar in appearance to those generated by masking the fundamental frequency of the ANN. When lower-frequency probe stimuli (< or = approximately equal to 1 kHz) are used, the frequency of the TC tip tends to be higher than that of the probe; with higher probe frequencies, the tip tends to be lower. Regardless of the frequency of the probe, the TC tip threshold occurs at an intensity level lower than that of the probe. The sharpness of these TCs generally increases as a function of the frequency of the probe stimulus and the values of Q10dB are comparable to those of FTCs of cochlear nerve fibers of the gerbil. The amplitude of the ANN is often enhanced in response to a limited intensity range of forward maskers over a restricted range of frequencies that are outside the high-frequency boundary of the forward masker TC. By alternating the polarity of the probe stimulus, the CM can be canceled, allowing the effects of simultaneous maskers to be evaluated.
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10.1016/s0378-5955(96)00195-5
|
pubmed_1118_16756
|
Objectives
This study aimed to determine the minimum inhibitory concentration (MIC) of mouthwashes prepared from neem and mango extracts against Streptococcus mutans (S. mutans) in vitro. Their taste acceptability and effects on plaque index (PI), gingival index (GI) and salivary pH were also evaluated and compared with chlorhexidine (CHX) in children.
Materials and Methods
Dry extracts of neem and mango twigs were prepared and their MIC against S. mutans was determined. The effective MIC was used to prepare mouthwashes from the two extracts. Three parallel groups of children (n=30) used either neem, mango or 0.2% CHX mouthwash for 21 days. The PI and GI were recorded at baseline and at 7 and 21 days. The salivary pH and taste acceptability were also assessed.
Results
The MIC of both extracts was achieved at 25% concentration. There was a significant difference between the GI score of mango group compared with neem and CHX at the three time points (P<0.001). There was no significant difference between the neem and mango groups in PI (P=0.674). There was no significant difference among the three groups in salivary pH either (P=0.817). Intragroup comparison showed significant reductions in PI, GI and salivary pH in all the three groups after 21 days (P<0.001).
Conclusion
Neem and mango mouthwashes can be used as effective alternatives to CHX in children.
|
10.18502/fid.v17i11.4128
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pubmed_12_4513
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A 4-year-old castrated mixed-breed dog had atypical signs of chronic distemper encephalomyelitis. The predominant signs were related to visceral rather than somatic dysfunction. The visceral dysfunction was largely attributable to distemper-associated inflammatory lesions in the spinal cord and resulted in fecal incontinence, urinary incontinence, and priapism. Empirical treatment of the dog resulted in transitory improvement prior to euthanasia performed because of the progressive nature of the encephalomyelitis.
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pubmed_12_4513
|
pubmed_509_1528
|
BACKGROUND
The replacement of caloric beverages such as sugar-sweetened beverages (SSBs) and fruit juices with noncaloric beverages such as plain water has been recommended for diabetes prevention.
OBJECTIVE
We evaluated the relation of plain-water intake and the substitution of plain water for SSBs and fruit juices with incident type 2 diabetes (T2D) in US women.
DESIGN
We prospectively followed 82,902 women in the Nurses' Health Study II who were free of diabetes, cardiovascular disease, or cancer at baseline. Diet, including various beverages, was assessed by using validated food-frequency questionnaires and updated every 4 y. Incident T2D was confirmed by using a validated supplementary questionnaire. We used a 4-y lagged analysis to minimize reverse causation (ie, increased water consumption that was due to early stage of diabetes).
RESULTS
During 1,115,427 person-years of follow-up, we documented 2718 incident T2D cases. Plain-water intake was not associated with T2D risk in the multivariable-adjusted model that included age, BMI, diet, and lifestyle factors; RRs (95% CIs) across categories (<1, 1, 2-3, 4-5, and ≥6 cups/d) were 1.00, 0.93 (0.82, 1.05), 0.93 (0.83, 1.05), 1.09 (0.96, 1.24), and 1.06 (0.91, 1.23), respectively (P-trend = 0.15). We estimated that the replacement of 1 serving SSBs and fruit juices/d by 1 cup plain water/d was associated with 7% (3%, 11%) and 8% (2%, 13%) lower risk of T2D, respectively.
CONCLUSIONS
Plain-water intake, per se, was not significantly associated with risk of T2D. However, substitution of plain water for SSBs or fruit juices was estimated to be associated with modestly lower risk of T2D.
|
10.3945/ajcn.111.032698
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pubmed_718_4728
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Antigenic variation in a major discontinuous site (site D) of foot-and-mouth disease virus (FMDV) of serotype C has been evaluated with neutralizing monoclonal antibodies. Isolates representing the major evolutionary sublines previously defined for serotype C were compared. Extensive variation, comparable to that of continuous epitopes within the hypervariable immunodominant site A (the VP1 G-H loop), was found. The amino acid sequences of the complete capsids of three antigenically highly divergent FMDVs (C1 Haute Loire-Fr/69, C5 Argentina/69, and C3 Argentina/85) have been determined and compared with the corresponding sequences previously determined for seven additional type C viruses. Differences in antigenicity are due to a very limited number of substitutions of surface amino acids accessible to antibodies and located within antigenic sites previously identified on FMDV. A significant number of residues at these positions were also replaced in monoclonal antibody escape mutants. Depending on the variants compared, replacements within site A or at site D, or at both sites, contributed significantly to their antigenic differences. Examples of divergence mediated by a few amino acid replacements were found among FMDVs of Europe and South America. The results suggest that within a serotype of FMDV, antigenically highly divergent viruses can arise in the field by very limited sequence variation at exposed key residues of each of several antigenic sites.
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10.1128/JVI.68.3.1407-1417.1994
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pubmed_1122_15368
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The Association of Directors of Anatomic and Surgical Pathology has developed recommendations for surgical pathologic reporting of common malignant tumors. The recommendations for reporting soft tissue sarcomas are reported here.
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pubmed_1122_15368
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pubmed_646_321
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We describe a healthy 18-month-old child who developed a painful limp, without a history of trauma or fever. The initial laboratory investigations showed normal results but the radiological findings were suggestive of scurvy. Diagnosis was confirmed by blood tests and by a rapid recovery following replacement therapy.
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10.1046/j.1440-1754.2000.00453.x
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pubmed_539_4413
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At small layer separations, the ground state of a nu = 1 bilayer quantum Hall system exhibits spontaneous interlayer phase coherence. The evolution of this state with increasing layer separation d has been a matter of controversy. We report on small system exact diagonalization calculations which suggest that a single-phase transition, likely of first order, separates incompressible states with strong interlayer correlations from compressible states with weak interlayer correlations. We find a dependence of the phase boundary on d and interlayer tunneling amplitude that is in very good agreement with recent experiments.
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10.1103/PhysRevLett.86.1849
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pubmed_465_13550
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A simple and sensitive assay for the cannabinoids is presented using a dabsylation procedure. Dabsyl derivatives of delta 9-tetrahydrocannabinol (delta 9-THC) and cannabinol (CBN) were prepared by reacting with 4-dimethylaminoazobenzene-4'-sulfonyl chloride (dabsyl chloride) in acetone in the presence of sodium carbonate-sodium bicarbonate buffer (pH 10). Crystalline dabsylcannabinoids gave intense absorption in the visible region. With these derivatives, analysis by thin-layer chromatography (TLC) and high performance liquid chromatography (HPLC) were tested. These techniques gave good separation and nanogram detection of dabsyl-THC and -CBN by using n-hexane-ethyl acetate-diethylamine (20:5:1) for TLC and MeOH--H2O (95:5) at 450 nm for HPLC.
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pubmed_465_13550
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pubmed_664_13185
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Ecto-3'-nucleotidase/nuclease (3'NT/NU) is a membrane-bound enzyme that plays a key role in the nutrition of Leishmania sp. protozoan parasites. This enzyme generates nucleosides via hydrolyzes of 3'mononucleotides and nucleic acids, which enter the cell by specific transporters. In this work, we identify and characterize Leishmania amazonensis ecto-3'-nucleotidase activity (La3'-nucleotidase), report ammonium tetrathiomolybdate (TTM) as a novel La3'-nucleotidase inhibitor and approach the possible involvement of ecto-3'-nucleotidase in cellular adhesion. La3'-nucleotidase presented characteristics similar to those reported for the class I single-strand nuclease family; a molecular weight of approximately 40 kDa and optimum activity in an alkaline pH range were observed. Although it is conserved among the genus, La3'-nucleotidase displays different kinetic properties; it can be inhibited by vanadate, molybdate and Cu(2+) ions. Interestingly, ecto-3'-nucleotidase activity is 60-fold higher than that of ecto-5'-nucleotidase in L. amazonensis. Additionally, ecto-3'-nucleotidase activity is two-fold higher in virulent L. amazonensis cells than in avirulent ones. Notably, macrophage-parasite attachment/invasion was increased by 400% in the presence of adenosine 3'-monophosphate (3'AMP); however, this effect was reverted by TTM treatment. We believe that La3'-nucleotidase may play a significant role in the generation of adenosine, which may contribute to mammalian host immune response impairment and establishment of infection.
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10.1016/j.exppara.2011.07.014
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pubmed_114_12947
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A retrospective review of the radiographs of 1215 patients with congenital scoliosis and kyphosis disclosed 298 (25%) to have segmentation defects in the cervical spine. A single level defect was seen in 82 patients, 52 of which were at C2-C3. Of the 298 patients, 235 had scoliosis, (6 cervical, 42 cervicothoracic, 75 thoracic, 4 thoracolumbar, and 1 lumbar), 36 had kyphoscoliosis, 10 lordoscoliosis, and 17 pure kyphosis.
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10.1097/00007632-198405000-00006
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pubmed_613_11523
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Glossina exhibit cyclic ((CYC)GE) or continuous gas exchange ((CON)GE) patterns at rest. However, the factors influencing the transition from one pattern to another are not well understood for these or other insect species. This study examines which factors could aid in predicting the presence or absence of (CYC)GE in adults of three Glossina species: G. palpalis, G. brevipalpis and G. austeni. We report the results of temperature effects on VCO(2), pattern type and the proportion of a population showing (CYC)GE, and the prediction of (CYC)GE versus (CON)GE in Glossina. First, we investigated the influence of temperature on VCO(2) and found significant elevation in resting metabolic rate (RMR) with higher temperature in all three species (P<0.001). Temperature-induced increases in VCO(2) were modulated by increased burst volume and by cycle frequency, except in G. brevipalpis which only appeared to modulate burst volume. These results are largely in keeping with VCO(2) modulation reported for other Glossina species previously. Second, elevating temperature resulted in significantly reduced numbers of individuals showing (CYC)GE (P<0.001 for all three species) contrary to previous reports for other Glossing species. Finally, we examined a range of variables as potential predictors of presence or absence of (CYC)GE in these three species. Using an information theoretic approach (Akaike weights) to select the best explanatory combination of variables which predicts likelihood of (CYC)GE, we found that results varied among species. When species were pooled, the simplest, best-fit model (ΔAIC<2 from the best model, 44.4% probability of being the best model) for predicting pattern type variation was RMR. Overall these results suggest that RMR is a key variable driving pattern type and that elevated temperature reduces the number of individuals showing cyclic patterns through elevation of RMR in these species. This study supports the idea that an interaction between cellular metabolic demand, morphological features of the gas exchange system (e.g. tracheal and spiracular conductances), and CO(2) buffer capacity likely determine gas exchange pattern variation over short time-scales.
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10.1016/j.jinsphys.2011.01.003
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pubmed_641_3866
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The introduction of hematopoietic growth factors during the past five years has changed the scenery of antitumor treatment. Growth factors following high-dose chemotherapy or bone marrow transplantation have become established as part of many treatment protocols. The main benefits are earlier recovery of neutrophils resulting in fewer days with fever, antibiotics and hospitalization. Growth factors were found to reduce the treatment-related morbidity and to improve the practicability of therapeutic regimens. First studies on a prospective chemotherapy dose intensification supported by growth factors are underway. As a further effect of growth factors, an attempted enhancement of antitumor cytotoxicity by recruitment of tumor cells to chemosensitivity or by modulation of antitumor drug metabolism appears realistic based on first data on growth factor priming in AML. New ways to support high-intensity and myeloablative antitumor strategies are opened by the autologous transplantation of peripheral blood progenitor cells mobilized by growth factors and also by the use of new factors like SCF and the synergistic combination of growth factors as part of future strategies against malignant disorders.
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10.1002/stem.5530120301
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pubmed_457_4901
|
A retarding field energy analyzer (RFEA) designed specifically for high energy pulsed electron beam measurements is described in this work. By proper design of the entrance grid, attenuation grid, and beam collector, this RFEA is capable of determining the time-resolved energy distribution of high energy pulsed electron beams normally generated under "soft vacuum" environment. The performance of the RFEA is validated by multiple tests of the leakage current, attenuation coefficient, and response time. The test results show that the retarding potential in the RFEA can go up to the same voltage as the electron beam source, which is 20 kV for the maximum in this work. Additionally, an attenuation coefficient of 4.2 is obtained in the RFEA while the percent difference of the rise time of the electron beam pulse before and after attenuation is lower than 10%. When compared with a reference source, the percent difference of the RFEA response time is less than 10% for fall times greater than 35 ns. Finally, the test results of the 10 kV pseudospark-based pulsed electron beam currents collected under varying retarding potentials are presented in this paper.
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10.1063/1.4973776
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pubmed_669_25414
|
We present a model of circular dichroism for proteins, which is mainly based on both the classical theory of optical activity and a series of effective atomic polarizabilities. Such polarizabilities are extracted from the analysis of a set of synchrotron radiation circular dichroism spectra and their corresponding three-dimensional structures from the Protein Data Bank. Each modeled spectrum is obtained from the protein atomic coordinates and the identification of its secondary structure elements. The resulting spectra are in good agreement with additional experimental data and also with the predictions of some other models. Among them, only our approach is able to describe the effect of d-amino acids. Moreover, our model is also utilized to evaluate protein reconstructions as well as structural changes.
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10.1021/acs.jpcb.1c08183
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pubmed_93_1601
|
We studied the competition between heterogeneous and homogeneous nucleation of an aqueous suspension of charged colloidal spheres close to the container walls. Samples of equilibrium crystalline structure were shear-melted and the metastable melt left to solidify after the cessation of shear. The crystallization kinetics was monitored using time-resolved scattering techniques: at low particle number densities n we applied an improved static light scattering method while at large particle concentrations ultra-small-angle x-ray scattering was applied for the first time. Our results show some unexpected behavior: the heterogeneous nucleation at the container walls is delayed in comparison to the homogeneous bulk nucleation and its rate density appears surprisingly slightly smaller, demonstrating the complexity of the observed crystallization process.
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10.1088/0953-8984/21/46/464115
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pubmed_886_4916
|
BACKGROUND
Patients with Marfan syndrome characteristically have an asthenic body habitus and are considered to be exempt from the obesity epidemic.
OBJECTIVE
To examine the prevalence and clinical impact of obesity in a cohort of adults with Marfan syndrome.
METHODS
Fifty outpatients (30 female) with a mean (+/- SD) age of 38+/-13 years were studied. Demographic variables including previously identified risk factors for aortic dissection were recorded. Body mass index (BMI) was determined and patients were classified as normal (BMI less than 25 kgm2), overweight (BMI 25 kgm2 to 29.9 kgm2) or obese (BMI 30 kgm2 or greater). Other cardiovascular risk factors were examined. An adverse clinical outcome was defined as either the attainment of surgical criteria for aortic root replacement or the presence of aortic dissection.
RESULTS
A family history of aortic dissection was present in 13 (26%) patients. In 23 (46%) patients, there was no known family history of Marfan syndrome. Mean BMI was 25.4+/-7.4 kgm2, with 18 (36%) patients having an elevated BMI. Positive smoking status was present in 15 (30%), hypertension in 13 (26%) and hyperlipidemia in 19 (38%) patients. Adverse clinical outcome was present in 27 (54%) patients. Logistic regression analysis revealed only index case (OR 44; P<0.001) and higher BMI (OR 1.2; P=0.04) to be significantly and independently associated with increased risk of adverse clinical outcome.
CONCLUSIONS
Obesity is common in adults with Marfan syndrome and is associated with an increased risk of aortic complications.
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10.1016/s0828-282x(10)70370-6
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pubmed_467_4175
|
BACKGROUND
There are limited data regarding the impact of final kissing balloon (FKI) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations.
METHODS
All patients undergoing left main or bifurcations percutaneous coronary intervention enrolled in the RAIN registry (Very Thin Stents for Patients With MAIN or BiF in Real Life: The RAIN, a Multicenter Study) evaluating ultrathin stents were included. Major adverse cardiac event (a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis) was the primary end point, while its components, along with target vessel revascularization, were the secondary end points. The main analysis was performed comparing patients with and without FKI after adjustment with inverse probability of treatment weighting. Subgroup analyses were performed according to FKI (short [<3 mm] versus long overlap), strategy (provisional versus 2-stent), routine versus bail-out FKI, and the use of imaging and proximal optimization technique.
RESULTS
Two thousand seven hundred forty-two patients were included. At 16 months (8-20) follow-up, inverse probability of treatment weighting adjusted rates of major adverse cardiac event were similar between FKI and no-FKI group (15.1% versus 15.5%; P=0.967), this result did not change with use of imaging, proximal optimization technique, or routine versus bail-out FKI. In the 2-stent subgroup, FKI was associated with lower rates of target vessel revascularization (7.8% versus 15.9%; P=0.030) and target lesion revascularization (7.3% versus 15.2%; P=0.032). Short overlap FKI was associated with a lower rate of target lesion revascularization compared with no FKI (2.6% versus 5.4%; P=0.034), while long overlap was not (6.8% versus 5.4%; P=0.567).
CONCLUSIONS
In patients with bifurcations or unprotected left main treated with ultrathin stents, short overlap FKI is associated with less restenosis. In a 2-stent strategy, FKI was associated with less target vessel revascularization and restenosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03544294.
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10.1161/CIRCINTERVENTIONS.119.008325
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pubmed_30_1899
|
Van Putten and colleagues have reported an association between akathisia and exacerbations of psychosis in schizophrenic patients treated with neuroleptic drugs. They noted that treatment with an anticholinergic drug, biperiden, led to prompt improvement in both conditions. Recent reports suggest that beta-adrenergic antagonists may be effective in the treatment of akathisia. Based on these observations, we surveyed studies in which beta-adrenergic antagonists were administered as putative antipsychotic agents in order to determine whether reports of improvement may actually have reflected successful treatment of underlying neuroleptic-induced akathisia. Though inferential, the results of this review support this hypothesis. It is possible that the mechanism of action for the anti-akathisia and antipsychotic effects of beta-adrenergic antagonists may be due to enhancement of the firing rate of dopamine neurons in the ventral tegmental area, with subsequent increased release of dopamine and decreased interference with dopaminergic neurotransmission.
|
pubmed_30_1899
|
pubmed_754_1175
|
Although diaphragmatic rupture in children due to blunt trauma is a rare condition we have observed an increasing number of these cases during the last years. Four cases will be reported and compared to the literature. The majority of diaphragmatic ruptures occurred on the left side. One third of all patients, however, had a rupture of the right diaphragm. In contrast to adults rupture of the diaphragm in children is rarely associated with rib fractures. Frequently liver and spleen become injured and two thirds of the patients presented with prolapse of abdominal organs into the pleural cavity. The prognosis of isolated diaphragmatic rupture is good, usually, however, prognosis is limited by the severe injuries sustained by the initial trauma. Only in half of the cases diaphragmatic rupture was diagnosed initially.
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pubmed_754_1175
|
pubmed_904_18326
|
In this chapter we propose a new system that allows reliable acetabular cup placement in total hip arthroplasty (THA) when the surgery is operated in lateral approach. Conceptually it combines the accuracy of computer-generated patient-specific morphology information with an easy-to-use mechanical guide, which effectively uses natural gravity as the angular reference. The former is achieved by using a statistical shape model-based 2D-3D reconstruction technique that can generate a scaled, patient-specific 3D shape model of the pelvis from a single conventional anteroposterior (AP) pelvic X-ray radiograph. The reconstructed 3D shape model facilitates a reliable and accurate co-registration of the mechanical guide with the patient's anatomy in the operating theater. We validated the accuracy of our system by conducting experiments on placing seven cups to four pelvises with different morphologies. Taking the measurements from an image-free navigation system as the ground truth, our system showed an average accuracy of 2. 1 ± 0. 7∘ for inclination and an average accuracy of 1. 2 ± 1. 4∘ for anteversion.
|
10.1007/978-981-13-1396-7_15
|
pubmed_147_25060
|
Our objective was to evaluate the antimicrobial susceptibility of Enterobacteriaceae causing urinary tract infections (UTIs) in adults in Africa. The PubMed database was systematically searched to identify relevant studies published after 2000. Google, World Health Organization, and African Field Epidemiology networks were also searched. Twenty-eight studies, accounting for 381,899 urine isolates from 14 African countries, met the inclusion criteria. Escherichia coli, Klebsiella spp., and Proteus spp. were the most commonly encountered uropathogens. Cefotaxime, imipenem, fosfomycin, and ciprofloxacin were the antibiotics with the highest activity against E. coli isolates from outpatients, with susceptibility being 92 to 99, 100, 100, and 68 to 91%, respectively. The susceptibility among Klebsiella spp. isolates from outpatients varied from 80 to 100% for amikacin and from 53 to 100% for ciprofloxacin, while susceptibility was 74 to 78, 97, and 77% for ciprofloxacin, amikacin, and fosfomycin, respectively, among Klebsiella species isolates from inpatients or patients with hospital-acquired UTIs. With regard to Proteus spp., the highest activity was observed among fluoroquinolones; 71 to 100% of the P. mirabilis isolates were susceptible to ciprofloxacin in four studies, and 74 to 100% of the P. vulgaris isolates were susceptible to ofloxacin in two studies. The currently available evidence suggests that the antimicrobial susceptibility patterns of Enterobacteriaceae uropathogens in African countries were similar to those in countries of southeast Europe. Further original studies are warranted from African countries for which there is limited published data.
|
10.1128/AAC.00359-13
|
pubmed_381_10528
|
Metabolic (dysfunction)-associated fatty liver disease has taken importance during the last two years, given the new criteria for diagnosis compared to the previous criteria used to define non-alcoholic fatty liver disease. Multiple studies have also shown that this definition better adjusts to the pathogenesis and patient characteristics with fatty liver.
|
10.1111/liv.15422
|
pubmed_666_19192
|
INTRODUCTION
Inserts Essure® were used as a definitive sterilization method from 2001 to 2017. They have been used for more than 750,000 procedures. Gynecological or extra gynaecological adverse events have been reported by patients. The objective of the study is to evaluate the resolution of symptoms attributed to Essure® micro-inserts after surgical removal.
METHODS
Monocentric retrospective study. Patients who had surgical removal of Essure® micro-inserts between January 2017 and April 2019 were included. The removal was performed by bilateral salpingectomy with cornuectomy by laparoscopy or vaginal hysterectomy. Symptoms were reported preoperatively, 4-8 weeks after withdrawal (early assessment) and 6-24 months after withdrawal (later assessment).
RESULTS
Ninety patients had a surgical removal of Essure® micro-inserts. Fifty-two vaginal hysterectomies and thirty-five laparoscopic salpingectomies were performed. The main symptoms reported are pelvic pain (70 %), fatigue (66.7 %) and heavy bleeding menstruations (53.3 %). One month after surgery, 46.7 % of patients have a major improvement of symptoms and 51.1 % a partial resolution. The major improvement rate is not significantly different between laparoscopic salpingectomy and vaginal hysterectomy (51.5 % versus 42.3 %) (p = 0.23). At 24 months, results improved with 83.3 % major improvement.
CONCLUSION
Surgical removal may be effective for treating most women with attributed device symptoms. Vaginal hysterectomy and laparoscopic salpingectomy with cornuectomy seem to have an equivalent rate for the resolution of extra-gynecological symptoms.
|
10.1016/j.jogoh.2020.101781
|
pubmed_922_11307
|
We report a case of a 76-year-old male with a history of relapsed and refractory diffuse large B-cell lymphoma (DLBCL).Our patient was initially treated with front line chemotherapy along with central nervous system (CNS) prophylaxis with complete response. He subsequently relapsed, was sensitive to second-line chemotherapy, and underwent autologous stem cell transplantation achieving a complete remission. Only a few months after transplant, the patient suffered his second relapse and was deemed a candidate for Chimeric Antigen Receptor T-Cell Therapy (CAR-T). Given his aggressive disease, combined with the time needed to generate CAR-T cells, a multidisciplinary team recommended to treat our patient with liposomal vincristine in combination with rituximab as a bridge therapy. Durable responses have been seen using liposomal vincristine based on results from a recent phase II trial in heavily pretreated patients with DLBCL1. This therapy was effective in stabilizing and reducing active disease in our patient. This case looks to illustrate the use of liposomal vincristine in combination with immunotherapy in a novel setting bridging highly selected patients with active and refractory lymphoma prior to CAR-T. Moreover, we expanded an additional therapeutic point, highlighting the importance of optimal disease control prior to CAR-T cell harvesting, as recent literature has shown that residual malignant cells in the pheresis product may be inadvertently be transfected with the CAR gene, resulting in resistance and further relapse2.
|
pubmed_922_11307
|
pubmed_154_19815
|
"Kennel cough" in dogs in animal shelters is readily transmissible, reduces adoption rates, and commonly leads to the euthanasia of affected dogs. In cats, tracheobronchitis, conjunctivitis, and pneumonia have been associated with Bordetella bronchiseptica infection-but most cases of upper-respiratory infection (URI) probably are caused by herpesvirus and calicivirus, and many B. bronchiseptica culture-positive cats are clinically normal. Our prospective observational study was undertaken to document the contribution of B. bronchiseptica to disease in cats and dogs from two animal shelters undergoing outbreaks of canine kennel cough, to evaluate whether cross-species transmission might have occurred, and to determine if the presence of infected cats represented a risk to dogs. Clinically defined cases of kennel cough in dogs and URI in cats were investigated in two shelters by calculating clinical-disease incidence, alveolar-lavage cytological examination, bacterial and viral cultures, antibiotic-susceptibility testing, and molecular fingerprinting by pulsed-field gel electrophoresis. In a 40-cat and 40-dog "no-kill" shelter, the prevalences of culture positivity were 47% for B. bronchiseptica and 36% for calicivirus at the same time as two resident dogs demonstrated clinical cough. When no dogs had kennel cough 3 months later, 10% of cats were B. bronchiseptica-culture-positive and 63% calicivirus positive. In a large traditional shelter, the incidence of kennel cough in dogs increased over 12 weeks to a maximum of 19 cases/week/120 dogs, during which time the culture prevalence was 23% for B. bronchiseptica in dogs and 47% in cats. Three to 6 months before the kennel-cough epidemic, no dogs or cats were B. bronchiseptica positive. Very little genetic variability was detected in isolates from these shelters; all isolates except one corresponded to a single strain type which was identical to the pattern in a vaccine used in these shelters. Isolates from other cats, a horse, a llama, and a sea otter were genetically distinct from the shelter isolates. There was widespread resistance to cephalosporins and ampicillin, but low or no resistance to amoxicillin/clavulanate, trimethoprim-sulfamethoxazole, tetracycline, and enrofloxacin. Greater percent resistance was observed in the traditional shelter than in the no-kill shelter and feline isolates were more likely to be resistant than canine isolates.
|
10.1016/s0167-5877(02)00022-3
|
pubmed_41_4116
|
BACKGROUND
Many important geochemical and biogeochemical reactions occur in the mineral/formation water interface of the highly abundant mineral, goethite [α-Fe(OOH)]. Ab initio molecular dynamics (AIMD) simulations of the goethite α-FeOOH (100) surface and the structure, water bond formation and dynamics of water molecules in the mineral/aqueous interface are presented. Several exchange correlation functionals were employed (PBE96, PBE96 + Grimme, and PBE0) in the simulations of a (3 × 2) goethite surface with 65 absorbed water molecules in a 3D-periodic supercell (a = 30 Å, FeOOH slab ~12 Å thick, solvation layer ~18 Å thick).
RESULTS
The lowest energy goethite (100) surface termination model was determined to have an exposed surface Fe3+ that was loosely capped by a water molecule and a shared hydroxide with a neighboring surface Fe3+. The water molecules capping surface Fe3+ ions were found to be loosely bound at all DFT levels with and without Grimme corrections, indicative that each surface Fe3+ was coordinated with only five neighbors. These long bonds were supported by bond valence theory calculations, which showed that the bond valence of the surface Fe3+ was saturated and surface has a neutral charge. The polarization of the water layer adjacent to the surface was found to be small and affected only the nearest water. Analysis by density difference plots and localized Boys orbitals identified three types of water molecules: those loosely bound to the surface Fe3+, those hydrogen bonded to the surface hydroxyl, and bulk water with tetrahedral coordination. Boys orbital analysis showed that the spin down lone pair orbital of the weakly absorbed water interact more strongly with the spin up Fe3+ ion. These weakly bound surface water molecules were found to rapidly exchange with the second water layer (~0.025 exchanges/ps) using a dissociative mechanism.
CONCLUSIONS
Water molecules adjacent to the surface were found to only weakly interact with the surface and as a result were readily able to exchange with the bulk water. To account for the large surface Fe-OH2 distances in the DFT calculations it was proposed that the surface Fe3+ atoms, which already have their bond valence fully satisfied with only five neighbors, are under-coordinated with respect to the bulk coordination. Graphical abstract All first principle calculations, at all practically achievable levels, for the goethite 100 aqueous interface support a long bond and weak interaction between the exposed surface Fe3+ and water molecules capping the surface. This result is supported by bond valence theory calculations and is indicative that each surface Fe3+ is coordinated with only 5 neighbors.
|
10.1186/s12932-017-0040-5
|
pubmed_721_11722
|
The incidence of tuberculosis in the United States appears to be rising, most likely because of the introduction of the human immunodeficiency virus, and other factors such as outbreaks among the homeless and immigration of infected people from other countries. Because diagnosis and treatment of tuberculosis has shifted from specialized centers to the community, it is important that primary care physicians recognize and properly manage early forms of the disease. Several patients are described for whom an early diagnosis was not made, resulting in serious morbidity for the patients and risk of spread of disease to contacts.
|
10.1001/archinte.147.11.2037
|
pubmed_4_6940
|
Recent technological developments regarding wearable soft-robotic devices extend beyond the current application of rehabilitation robotics and enable unobtrusive support of the arms and hands during daily activities. In this light, the HandinMind (HiM) system was developed, comprising a soft-robotic, grip supporting glove with an added computer gaming environment. The present study aims to gain first insight into the feasibility of clinical application of the HiM system and its potential impact. In order to do so, both the direct influence of the HiM system on hand function as assistive device and its therapeutic potential, of either assistive or therapeutic use, were explored. A pilot randomized clinical trial was combined with a cross-sectional measurement (comparing performance with and without glove) at baseline in 5 chronic stroke patients, to investigate both the direct assistive and potential therapeutic effects of the HiM system. Extended use of the soft-robotic glove as assistive device at home or with dedicated gaming exercises in a clinical setting was applicable and feasible. A positive assistive effect of the soft-robotic glove was proposed for pinch strength and functional task performance 'lifting full cans' in most of the five participants. A potential therapeutic impact was suggested with predominantly improved hand strength in both participants with assistive use, and faster functional task performance in both participants with therapeutic application.
|
10.1109/ICORR.2017.8009444
|
pubmed_560_308
|
Macrocyclisation reactions of C(2)-symmetric pseudopeptides containing central pyridine-derived spacers are affected by the presence of different anions. The selection of the proper anion gives excellent results for the preparation of the corresponding macrocyclic structures. Kinetic studies show that the presence of those anions enhances both the yield and the rate of the reaction. Computational studies at the B3LYP/6-31G* level have allowed us to rationalise the experimental results. The obtained transition states (TSs) show that the interaction between the anion and the open-chain pseudopeptidic chain has a stabilising effect. The anion stabilises the two TSs involved: the first one, which involves the formation of the initial bond between the two subunits and leads to an open-chain intermediate, and the second one, which precedes the formation of the cyclic structure. The optimum anion (Br(-) when the central spacer is derived from 2,6-bis(aminomethyl)pyridine, is able to act as a template, in that it forces the two ends of the open-chain intermediate to approach each other by forming hydrogen bonds with the two amino acid subunits present in the intermediate. This stabilises the second TS to a greater extent than the first one, and thus, favours macrocyclisation over the competing oligomerisation reactions. The computational calculations also allowed us to predict the outcome of new experiments. Accordingly, the synthesis of the pseudopeptidic macrocycle derived from 2,6-diaminopyridine was not successful under the optimised conditions previously used. Nevertheless, calculations predicted that in this case Cl(-) should be more efficient than Br(-), and this was subsequently experimentally confirmed. Interestingly, the presence of different substituents on the constituent amino acids seems to play a minor role in the overall process.
|
10.1002/chem.201101416
|
pubmed_968_8669
|
Volt hockey is a team sport developed for persons with physical disabilities, but its influence on well-being is unknown. Elements of well-being have been described as positive emotions, engagement, relationships, meaning, and achievement constituting a theoretical framework referred to as PERMA. The purpose of this study was to describe how well-being according to PERMA is reflected in the experiences of playing volt hockey. Data were collected through focus group and individual interviews including 21 players. A deductive analysis was conducted using the elements in PERMA as preexisting main categories with an additional main category, named resources needed. Findings showed that all five elements constituting well-being according to PERMA were reflected in the experiences of playing volt hockey. In addition, players emphasized the importance of having the resources needed to play volt hockey. In conclusion, having the opportunity to enjoy playing volt hockey enabled the players to flourish and experience feelings of subjective well-being.
|
10.1123/apaq.2021-0035
|
pubmed_1057_11260
|
This communication describes the C-C bond activation of acetonitrile and the trapping of the methyl and cyanide fragments by macrocyclic, dicobalt complexes. Both products display unique structural features as a result of the constraints imposed by the macrocycle. The bridged species [(3PDI2)Co2(μ-CN)(PMe3)2][OTf] ([Co2CN]+) exhibits atypical Co-CN-Co binding, and upon either phosphine dissociation or oxidation, the flexible ligand framework is able to switch between different binding modes of μ-cyanide. Further, the bridging methyl species [(3PDI2)Co2(μ-CH3)(PMe3)][OTf] ([Co2CH3]+) is the first structurally characterized dicobalt complex with a bridging methyl group.
|
10.1039/d0cc03521a
|
pubmed_360_4978
|
Several in vivo preimmunization schedules which are commonly used for induction of in vitro cell-mediated cytotoxicity against weak transplantation antigens have been tested for ability to generate killer cells in congenic anti B6-Lyt1.1 strain combination. Under the conditions studied no cytotoxic cells were generated. Under the same same conditions good cytotoxic response against H-Y antigen was observed.
|
pubmed_360_4978
|
pubmed_450_18285
|
PURPOSE
HER2-positive breast cancer is heterogeneous. Some tumors express mutations, like activating PIK3CA mutations or reduced PTEN expression, that negatively correlate with response to HER2-targeted therapies. In this exploratory analysis, we investigated whether the efficacy of trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprised of the cytotoxic agent DM1 linked to the HER2-targeted antibody trastuzumab, was correlated with the expression of specific biomarkers in the phase III EMILIA study.
EXPERIMENTAL DESIGN
Tumors were evaluated for HER2 (n = 866), EGFR (n = 832), and HER3 (n = 860) mRNA expression by quantitative reverse transcriptase PCR; for PTEN protein expression (n = 271) by IHC; and for PIK3CA mutations (n = 259) using a mutation detection kit. Survival outcomes were analyzed by biomarker subgroups. T-DM1 was also tested on cell lines and in breast cancer xenograft models containing PIK3CA mutations.
RESULTS
Longer progression-free survival (PFS) and overall survival (OS) were observed with T-DM1 compared with capecitabine plus lapatinib in all biomarker subgroups. PIK3CA mutations were associated with shorter median PFS (mutant vs. wild type: 4.3 vs. 6.4 months) and OS (17.3 vs. 27.8 months) in capecitabine plus lapatinib-treated patients, but not in T-DM1-treated patients (PFS, 10.9 vs. 9.8 months; OS, not reached in mutant or wild type). T-DM1 showed potent activity in cell lines and xenograft models with PIK3CA mutations.
CONCLUSIONS
Although other standard HER2-directed therapies are less effective in tumors with PI3KCA mutations, T-DM1 appears to be effective in both PI3KCA-mutated and wild-type tumors. Clin Cancer Res; 22(15); 3755-63. ©2016 AACR.
|
10.1158/1078-0432.CCR-15-2499
|
pubmed_377_23177
|
A microfluidic immunosensor utilizing Mie scattering immunoaggultination assay was developed for rapid and sensitive detection of porcine reproductive and respiratory syndrome virus (PRRSV) from lung tissue samples of domesticated pigs. Antibodies against PRRSV were conjugated to the surface of highly carboxylated polystyrene microparticles (diameter=920nm) and mixed with the diluted PRRSV tissue samples in a Y-shaped microchannel. Antibody-antigen binding induced microparticle immunoagglutination, which was detected by measuring the forward 45° light scattering of 380nm incident beam using microcallipered, proximity fiber optics. For comparison, multi-well experiments were also performed using the same optical detection setup. The detection limit was determined to be 10(-3)TCID(50)ml(-1) for PRRSV dissolved in PBS, while those of previous RT-PCR studies for PRRSV were 10(1)TCID(50)ml(-1) (conventional assays) or <1TCID(50)ml(-1) (quantitative real-time assays). Mie scattering simulations were able to predict the shape of the PRRSV standard curve, indicating that any non-linearity of the standard curve can be interpreted purely as an optical phenomenon. Each assay took less than 5min. A strong correlation could be found between RT-PCR and this method for the lung tissue samples, even though their respective detection mechanisms are different fundamentally (nucleic acids for RT-PCR and virus antigens for light scattering immunoagglutination assay). Several different dilution factors were also tested for tissue samples, and 1/10 and 1/100 were found to be usable. If the microfluidic chips are used only once (i.e. without re-using them), both superior sensitivity and satisfactory specificity can be demonstrated. Specificity studies revealed the presence of Type II PRRSV and non-presence of Type I PRRSV and that the microfluidic chip assay could detect Type II North American strain of PRRSV for the animals tested. This work demonstrates the potential of the Mie scattering immunoassay on a microfluidic chip towards real-time detection system for viral pathogens in domesticated animals.
|
10.1016/j.jviromet.2011.08.008
|
pubmed_943_5944
|
BACKGROUND
Symptoms, a key element in the patient's decision to seek care, are critical to appropriate triage, and influence decisions to pursue further evaluation and initiation of treatment. Although many studies have described symptoms associated with acute coronary syndromes (ACS), few, if any, have examined symptom predictors of ACS and whether they differ by patients' age.
OBJECTIVES
To explore symptom predictors of ACS in younger (< 70 years) and older (> or = 70 years) patients. To test the hypothesis that typical symptoms are predictive of ACS in younger patients, but are less predictive in older patients.
METHOD
Secondary analysis of observational data gathered on 531 patients presenting to the emergency department of a regional cardiac referral center in New England with symptoms suggestive of ACS.
RESULTS
Bivariate analyses revealed no symptoms significantly (p < .01) associated with ACS in older patients. In younger patients presence of chest symptoms and the total number of typical symptoms reported were significantly (p < .01) associated with ACS. After adjustment for age and gender, typical symptoms that were positive predictors of ACS in younger patients included chest symptoms (OR 2.37, 95% CI 1.32-4.27, p = .004) and arm pain (OR 1.78, 95% CI 1.03-3.09, p = .040). Additionally, the total number of typical symptoms reported (OR 1.68, 95% CI 1.31-2.15, p < .001) was a positive predictor of ACS in younger patients. The atypical symptom of fatigue (OR 2.52, 95% CI 1.10-5.81, p = .029) was a significant positive predictor of ACS, whereas dizziness/faintness (OR .50, 95% CI .26-.91, p = .024) was a significant negative predictor of ACS in younger patients. Logistic regression analysis using the entire sample revealed an interaction between age and number of typical symptoms indicating that younger patients had a 36% greater odds for ACS for each additional typical symptom present compared with older patients (OR 1.36, 95% CI 1.02-1.83, p = .038 for interaction between age and number of typical symptoms reported). The model with the interaction between age and chest symptoms revealed a borderline association (p = .10 for the interaction between age and chest symptoms), with younger patients being more likely than older patients to report chest symptoms.
CONCLUSIONS
Typical symptoms are predictive of ACS in younger patients and less predictive in older patients.
|
10.1097/00006199-200107000-00007
|
pubmed_198_5627
|
The Positive and Negative Syndrome Scale (PANSS) was developed out of the need for a well-operationalized method of assessing these syndromes in schizophrenia, including their relationship to one another and to global psychopathology. We surveyed 82 acute and chronic schizophrenics to analyze the psychometric properties of the four PANSS scales. The interrater reliabilities were in the 0.80's, and significant correlations emerged with corresponding criterion measures. The PANSS positive and negative scales were inversely intercorrelated once their shared association with general psychopathology had been partialed out. The results support the scales' reliability, criterion-related validity, and construct validity, while cross-validating some of our previous findings.
|
10.1016/0165-1781(88)90038-8
|
pubmed_666_5275
|
The latest edition of the Japanese Pharmacopoeia (JP) is the second supplement to the 17th edition containing 324 herbal medicines, of which 176 are crude drugs and 35 are Kampo extracts. Although 148 prescription Kampo extracts are covered by national health insurance, only 35 are listed in the latest JP. However, the sales volume of these 35 Kampo extracts accounts for more than 70% of the total sales volume of Kampo products, as Kampo formulas with higher sales volumes are preferentially listed in the JP. The JP officially defines the origin and description of the listed crude drugs and Kampo extracts and elaborates on their limited values and testing methods. As crude drugs and Kampo extracts are derived from natural products and have the characteristics of traditional medicines, some degree of variation has been experienced during their long-term use, which is one of the crucial differences from chemical drugs. The Japanese Pharmacopoeia Committee on Crude Drugs promotes standardization of the JP by reflecting the actual Japanese market situation. This review explains the characteristics of natural and traditional medicines in crude drug-related items, the JP drafting process and points to be noted, and the significance of listing in the JP.
|
10.1248/yakushi.19-00253-6
|
pubmed_424_19650
|
Titanium-oxygen bonds derived from stable nitroxyl radicals are remarkably weak and can be homolyzed at 60 degrees C. The strength of these bonds depends sensitively on the ancillary ligation at titanium. Direct measurements of the rate of Ti-O bond homolysis in Ti-TEMPO complexes Cp2TiCl(TEMPO) (3) and Cp2TiCl(4-MeO-TEMPO) (4) (TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl, 4-MeO-TEMPO = 2,2,6,6-tetramethyl-4-methoxypiperidine-N-oxyl) were conducted by nitroxyl radical exchange experiments. Eyring plots gave the activation parameters, deltaH++ = 27(+/- 1) kcal/mol, deltaS++ = 6.9(+/- 2.3) eu for 3 and deltaH++ = 28(+/- 1) kcal/mol, deltaS++ = 9.0(+/- 3.0) eu for 4, consistent with a process involving the homolysis of a weak Ti-O bond to generate the transient Cp2Ti(III)Cl and the nitroxyl radical. Thermolysis of the titanocene TEMPO complexes in the presence of epoxides leads to the Cp2Ti(III)Cl-mediated ring-opening of the epoxide followed by trapping by the nitroxyl radical. The X-ray crystal structure of the Ti-TEMPO derivative, Cp2TiCl(4-MeO-TEMPO) (4), is reported. DFT (B3LYP/6-31G*) calculations and experimental studies reveal that the strength of the Ti-O bond decreases dramatically with the number of cyclopentadienyl groups on titanium. The calculated Ti-O bond strength of the monocyclopentadienyl complex 2 is 43 kcal/mol, whereas that of the biscyclopentadienyl complex 3 is 17 kcal/mol, a difference of 26 kcal/mol. These studies reveal that the strength of these Ti-O bonds can be tuned over an interesting and experimentally accessible temperature range by appropriate ligation on titanium.
|
10.1021/ja044512f
|
pubmed_559_5613
|
In this study, the authors collected data on the demographic characteristics, phenomenology, and social and economic impact of skin picking. A total of 92 participants completed an anonymous, Internet-based survey through a link to the Trichotillomania Learning Center's home page. Results indicated that skin pickers experienced social, occupational, and academic impairment, a number of medical or mental health concerns, and financial burdens, which they attributed to skin picking. Results also revealed moderate, statistically significant relationships between skin picking severity and symptoms of depression, anxiety, and experiential avoidance. Subsequent mediational analyses demonstrated that the relationship between skin picking severity and symptoms of anxiety and depression was partially mediated by experiential avoidance. Implications, conclusions, and future areas of research are discussed.
|
10.1177/0145445506294083
|
pubmed_1021_13210
|
Hammerhead ribozymes containing 2'-fluoro- or 2'-aminonucleotides were prepared by automated chemical synthesis. Incorporation of 2'-fluorouridines, 2'-fluorocytidines or 2'-aminouridines did not appreciably decrease catalytic activity. The presence of 2'-aminocytidines, however, reduced the activity about 20-fold. No catalytic activity could be measured for ribozymes in which all adenosines were replaced by the 2'-fluoro analogue in presence of MgCl2. No single position could be found responsible for this loss of activity. In an attempt to construct ribozymes to hydrolyse HIV-RNA in the 5'-LTR region several constructs were tested on synthetic substrate as well as on run-off transcripts of about 1000 nucleotides length.
|
pubmed_1021_13210
|
pubmed_58_12508
|
Hominin evolution is characterized by adaptive solutions often rooted in behavioral and cognitive changes. If balancing selection had an important and long-lasting impact on the evolution of these traits, it can be hypothesized that genes associated with them should carry an excess of shared polymorphisms (trans- SNPs) across recent Homo species. In this study, we investigate the role of balancing selection in human evolution using available exomes from modern (Homo sapiens) and archaic humans (H. neanderthalensis and Denisovan) for an excess of trans-SNP in two gene sets: one associated with the immune system (IMMS) and another one with behavioral system (BEHS). We identified a significant excess of trans-SNPs in IMMS (N=547), of which six of these located within genes previously associated with schizophrenia. No excess of trans-SNPs was found in BEHS, but five genes in this system harbor potential signals for balancing selection and are associated with psychiatric or neurodevelopmental disorders. Our approach evidenced recent Homo trans-SNPs that have been previously implicated in psychiatric diseases such as schizophrenia, suggesting that a genetic repertoire common to the immune and behavioral systems could have been maintained by balancing selection starting before the split between archaic and modern humans.
|
10.1590/1678-4685-GMB-2017-0308
|
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