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Retriever1700
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Fibromyalgia as a cause of uncontrolled asthma: a case-control multicenter study.
BACKGROUND
Fibromyalgia can affect the control of asthma when both diseases are present in a single patient.
OBJECTIVES
To characterize asthma in patients with concomitant fibromyalgia to assess whether fibromyalgia is an independent factor of asthma severity that influences poor asthma control. We also evaluated how dyspnea is perceived by patients in order to demonstrate that alterations in the perception of airway obstruction may be responsible for poor asthma control.
METHODS
This was a cross-sectional case-control multicenter study, in which 56 patients in the asthma and fibromyalgia group were matched to 36 asthmatics by sex, approximate age, and asthma severity level. All patients were women. Study variables included the Asthma Control Test (ACT), the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), the Nijmegen hyperventilation syndrome questionnaire, the Hospital Anxiety and Depression Scale, and perception of dyspnea after acute bronchoconstriction.
RESULTS
Although patients in both study groups showed similar asthma severity and use of anti-asthmatic drugs, patients in the asthma and fibromyalgia group showed lower scores on the ACT and MiniAQLQ questionnaires, and higher scores of anxiety and depression as well as hyperventilation compared to asthma patients without fibromyalgia. All these differences were statistically significant.
CONCLUSIONS
Fibromyalgia in patients with asthma influences poor control of the respiratory disease and is associated with altered perception of dyspnea, hyperventilation syndrome, high prevalence of depression and anxiety, and impaired quality of life.
CLINICAL IMPLICATIONS
Fibromyalgia may be considered a risk factor for uncontrolled asthma in patients suffering from asthma and fibromyalgia concomitantly.
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No pos
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No neg
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Retriever1701
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Involvement of p38 mitogen-activated protein kinase in heat shock protein 27 induction in human neutrophils.
We investigated whether tumor necrosis factor-alpha (TNF-alpha) stimulates the induction of heat shock protein 27 (HSP27) in human neutrophils and the mechanism underlying this induction. In intact neutrophils, almost no HSP27 was detected. Stimulation of neutrophils by TNF-alpha increased the levels of HSP27 in the presence, but not in the absence, of cycloheximide. Reverse transcription-polymerase chain reaction (RT-PCR) experiments showed that TNF-alpha also induced HSP27 mRNA in the presence of cycloheximide. TNF-alpha induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. The HSP27 accumulation induced by TNF-alpha was significantly suppressed by 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) or 4-(4-fluorophenyl)-2-(4-nitrophenyl)-5-(4-pyridyl)-1H-imidazole (PD169316); both are specific inhibitors of p38 MAP kinase, but not by 2'-amino-3'-methoxyflavone (PD098059, a specific inhibitor of the upstream kinase that activates p44/p42 MAP kinase). The accumulation of HSP27 induced by TNF-alpha plus cycloheximide was also suppressed by pretreatment with a specific protein kinase C (PKC) inhibitor. Furthermore, phorbol myristate acetate (PMA), a PKC stimulant, but not dibutyryl cyclic AMP, a protein kinase A stimulant, stimulated the accumulation of HSP27. Interestingly, SB203580 did not inhibit PMA-stimulated HSP27 induction. These results strongly suggest that TNF-alpha may act as the regulator of HSP27 induction in neutrophils. p38 MAP kinase (but not p44/p42 MAP kinase) and PKC take part in TNF-alpha-stimulated HSP27 induction in human neutrophils.
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No pos
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No neg
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Retriever1702
|
Simultaneous visualization of Helicobacter pylori and gastric morphology: a new stain.
Although the histopathologic patterns associated with Helicobacter pylori infection have been described, details of the interaction between bacteria, epithelial cells, and inflammatory cells remain elusive. One of the limiting factors has been the lack of a staining technique that allows the simultaneous visualization of H pylori and tissue morphology. By combining three commonly available stains (Steiner, hematoxylin-eosin, and alcian blue at pH 2.5) into a single procedure we have developed a stain that permits the optimal detection of H pylori in tissue sections while simultaneously allowing the histopathologic evaluation of all salient characteristics of the gastric mucosa. This procedure is inexpensive, as easy to perform as any silver stain, and provides consistent results. This stain is as sensitive as the Warthin-Starry stain for the detection of H pylori and significantly more sensitive than hematoxylin-eosin alone (> 99% v 85% when compared with the hematoxylin-eosin stain in a series of 332 positive biopsy specimens; > 99% v 61% in 49 biopsy specimens with rare bacteria). This stain is particularly useful for the visualization of small numbers of bacteria, such as in the evaluation of posttreatment gastric biopsy specimens, in specimens with abundant mucus or debris, and in specimens from the corpus, where H pylori usually does not elicit strong inflammatory responses and, therefore, pathologists' index of suspicion tends to be low.
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No pos
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No neg
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Retriever1703
|
Separation of the Epitopes in a Multi-Epitope Chimera: Helical or Flexible Linkers.
BACKGROUND
The engineered chimeric peptides including functional multi-epitope structures fused by various peptide linkers are widely applied in biotechnological research to improve the expression level and biological activity of chimera.
OBJECTIVE
The aim of our study was to evaluate the effect of helical and flexible linkers on solubility, expression level and folding of multi-epitope chimera containing four epitopes of Human T Lymphotropic Virus Type 1 (HTLV-1).
METHODS
For this purpose, the chimera sequences connected by the helical or flexible linker were inserted into different plasmid vectors and expressed in E. coli strains. The expressed products were analyzed using SDS-PAGE and Western blot techniques. Additionally, the molecular modeling study of the chimera with helical or flexible linker was performed using iterative threading assembly refinement (I-TASSER) to attain their three-dimensional structures.
RESULTS
Comparison of the chimera expression indicated that the insertion of a flexible (GGGGS)3 linker among chimera epitopes could significantly enhance the level of expression, whereas, the low-level of chimera expression was observed for chimera containing the contiguous helical (EAAAK)5 linker. According to the results of sequence alignment and plasmid stability test, the structure and function of a consecutive helical linker among chimera epitopes were similar to porins as the outer-membrane pore-forming proteins. The molecular modeling results confirmed our experimental study.
CONCLUSION
This investigation illustrated the key role of linker design in determining the expression level of multi-epitope chimera and conformational folding.
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No pos
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No neg
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Retriever1704
|
Community standards to facilitate development and address challenges in metabolic modeling.
Standardization of data and models facilitates effective communication, especially in computational systems biology. However, both the development and consistent use of standards and resources remain challenging. As a result, the amount, quality, and format of the information contained within systems biology models are not consistent and therefore present challenges for widespread use and communication. Here, we focused on these standards, resources, and challenges in the field of constraint-based metabolic modeling by conducting a community-wide survey. We used this feedback to (i) outline the major challenges that our field faces and to propose solutions and (ii) identify a set of features that defines what a "gold standard" metabolic network reconstruction looks like concerning content, annotation, and simulation capabilities. We anticipate that this community-driven outline will help the long-term development of community-inspired resources as well as produce high-quality, accessible models within our field. More broadly, we hope that these efforts can serve as blueprints for other computational modeling communities to ensure the continued development of both practical, usable standards and reproducible, knowledge-rich models.
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No pos
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No neg
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Retriever1705
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Novel Neurorights: From Nonsense to Substance.
This paper analyses recent calls for so called "neurorights", suggested novel human rights whose adoption is allegedly required because of advances in neuroscience, exemplified by a proposal of the Neurorights Initiative. Advances in neuroscience and technology are indeed impressive and pose a range of challenges for the law, and some novel applications give grounds for human rights concerns. But whether addressing these concerns requires adopting novel human rights, and whether the proposed neurorights are suitable candidates, are a different matter. This paper argues that the proposed rights, as individuals and a class, should not be adopted and lobbying on their behalf should stop. The proposal tends to promote rights inflationism, is tainted by neuroexceptionalism and neuroessentialism, and lacks grounding in relevant scholarship. None of the proposed individual rights passes quality criteria debated in the field. While understandable from a moral perspective, the proposal is fundamentally flawed from a legal perspective. Rather than conjuring up novel human rights, existing rights should be further developed in face of changing societal circumstances and technological possibilities.
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No pos
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No neg
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Retriever1706
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Glycine-d-tartaric acid (1/1).
In the title co-crystal, C(2)H(5)NO(2)·C(4)H(6)O(6), the gylcine mol-ecule is present in the zwitterion form. In the tartaric acid mol-ecule there is a short intra-molecular O-H⋯O contact. In the crystal, the tartaric acid mol-ecules are linked via pairs of O-H⋯O hydrogen bonds, forming inversion dimers. These dimers are linked via a number of O-H⋯O and N-H⋯O hydrogen bonds involving the two components, forming a three-dimensional network.
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No pos
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No neg
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Retriever1707
|
Clinicopathologic relationships, survival, and therapy in 59 patients with observations on occupation as a new prognostic factor.
Clinicopathologic relationships, survival and therapy were reviewed in 59 patients with mycosis fungoides (MF). An analysis of patient survival disclosed that stage of disease was a significant prognostic variable only if both cutaneous and visceral manifestations were considered in the staging design. The classical three-stage format, based solely on findings of eczema (I), plaques (II), or skin tumors (III), was not a significant factor in predicting survival. However, the inclusion of lymphadenopathy (IV) and organomegaly (V) or circulation Sézary cells (VI) in an expanded model revealed a significant decline in the probability of survival with increasing stage of disease. Regarding cases where the original histopathologic material was available for review, there was no association between the histologic stage of the specimen and the morphology of skin lesions. These data militate against the use of a staging scheme based on histologic criteria. Among 30 different types of treatment employed during the course of this study, highdose electron beam was superior to all other physical and chemotherapeutic modalities. In a case-control study considering occupational factors, patients with MF who were employed in manufacturing or construction industries were at significantly increased risk (relative risk = 4.3). Patient survival was reduced considerably for those with industrial backgrounds, suggesting that this subgroup was inclined to have severe disease. The concept that occupational factors may be implicated in the etiology of mycosis fungoides provides a new dimension to previous pathogenic hypotheses that needs further evaluation.
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No pos
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No neg
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Retriever1708
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Detection and identification of side reactions of halogenated hydrocarbon solvents with amines of pharmaceutical interest by secondary processes to the neutralizations of sulphonphthaleinic dyes with these amines.
The neutralization reactions between amines and diprotic acid dyes in organic solvents generate (dye-, amineH+) and [dye2-, (amineH+)2] ion associates that show two absorption bands in the visible spectrum. An unidentified third absorption band; which appears with a high amine concentration, proves that halogenated hydrocarbon solvents (dichloromethane, chloroform, 1,2-dichloroethane, and carbon tetrachloride) give side reactions with amines (atropine, tropine, quinine, ephedrine, and ajmaline) that generate a quaternary ammonium salt, N-halogenalkylammonium halide ([N(+)-RX,X-]). The molecular weight of the quaternary ammonium salt is the sum of the amine and that of the solvent. The (N(+)-RX,X-) ion associated reacts with [dye2-, (amineH+)2] by substitution reactions, forming (dye2-, amineH+, N(+)-RX) and (dye2-, (N(+)-RX)2] ion associates that justify the third absorption band. The amine-solvent side reactions are of first order with respect to the amine, being very slow processes with rate constant values from 399.4 h-1 (tropine-dichloromethane reaction) to 15.8 h-1 (atropine-1,2- dichloroethane reaction). Rate constants increase with the basicity of the amine measured in the halogenated hydrocarbons employed. Rate constants also increase with a reduction in the number of the halogen atoms present in the halogenated solvent. The new visible absorption band that appears in the amine-dye neutralization gives a quick colorimetric test to bring to light this kind of side reaction in these solvents.
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No pos
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No neg
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Retriever1709
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Associastion of In-hospital Use of Statins, Aspirin, and Renin-Angiotensin-Aldosterone Inhibitors with Mortality and ICU Admission Due to COVID-19.
The exaggerated host response to Sars-CoV-2 plays an important role in COVID-19 pathology but provides a therapeutic opportunity until definitive virus targeted therapies and vaccines become available. Given a central role of endothelial dysfunction and systemic inflammation, repurposing ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, and aspirin has been of interest. In this retrospective, single-center study, we evaluated the primary outcomes of mortality and ICU admission in 587 hospitalized patients with documented COVID-19 with or without ACEIs, ARBs, statins, and aspirin. Atorvastatin was associated with reduced mortality, which persisted after adjusting for age, lockdown status, and other medications (OR: 0.18. 95% CI: 0.06-0.49, P = 0.001). ACEIs were also associated with reduced mortality in the crude model (OR: 0.20, CI: 0.06-0.66, P = 0.008), as ACEIs and ARBs were combined as a single group (OR: 0.35, CI: 0.16-0.75, P = 0.007), although ARBs alone did not reach statistical significance. There was no association between any medications and risk of ICU admission. Aspirin only achieved a significant association of reduced mortality in a subgroup of patients with diabetes in the crude model (OR: 0.17, CI: 0.04-0.80, P = 0.02). The reduced mortality observed with atorvastatin is consistent with other literature, and consideration should be given to atorvastatin as a COVID-19 treatment. While there was suggested benefit of ACEIs and ARBs in the present study, other studies are varied and further studies are warranted to recommend employing these medications as a treatment strategy. Nevertheless, this study combined with others continues to give credibility that ACEIs and ARBs are safe to continue in the setting of COVID-19.
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No pos
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No neg
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Retriever1710
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Antibody-drug conjugates targeting prostate-specific membrane antigen.
Prostate-specific membrane antigen (PSMA) is an integral, non-shed membrane glycoprotein that is a well-characterized and clinically validated marker of prostate cancer. The expression profile and other biological properties of PSMA make it an attractive target for antibody-drug conjugate (ADC) therapy of prostate cancer, as well as a broad range of other tumors in which PSMA is abundantly expressed within the tumor neovasculature. PSMA-targeted ADCs have been developed using auristatin and maytansinoid drugs, and each ADC has undergone extensive preclinical testing and has completed phase 1 testing in men with advanced prostate cancer. The preclinical and clinical findings have largely substantiated the promise of PSMA as an ADC target. This report summarizes the completed studies, current status, and potential future directions for ADCs that target PSMA.
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No pos
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No neg
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Retriever1711
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Activity-dependent changes in GAD and preprotachykinin mRNAs in visual cortex of adult monkeys.
Tachykinin-immunoreactive neurons are a subgroup of the GABA neuronal population in layer IVC of monkey primary visual cortex. Following brief periods of monocular deprivation in adult monkeys, immunoreactivity for both GABA and tachykinins is dramatically reduced in layer IV cells that lie within the deprived ocular dominance columns of this cortical area. The present study shows that these activity-dependent changes are associated with changes in mRNA levels but over different time courses. Radioactive antisense riboprobes derived from monkey-specific cDNAs were used to localize glutamic acid decarboxylase (GAD) and beta-preprotachykinin (beta PPT) mRNAs by in situ hybridization histochemistry. GAD and beta PPT mRNAs decreased in deprived ocular dominance columns of adult monkeys when neural activity was abolished in one eye by intraocular injections of tetrodotoxin (TTX). beta PPT mRNA levels fell within 5 d of deprivation and thus appeared to parallel the fall in immunodetectable tachykinin levels. By contrast, reduced GAD mRNA levels were detectable only after 15 d of deprivation and long after the fall in immunoreactive GAD and GABA levels has maximized. These results suggest that tachykinin gene expression is regulated by transcriptional mechanisms as part of the first response to reduced neural activity whereas the initial downregulation of immunoreactive GAD and GABA depends on posttranscriptional mechanisms. Following a more prolonged period of deprivation, a secondary mechanism for GAD regulation appears to be engaged at the level of gene transcription or possibly by changes in mRNA stability.
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No pos
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No neg
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Retriever1712
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Uptake, depuration, and radiation dose estimation in zebrafish exposed to radionuclides via aqueous or dietary routes.
Understanding uptake and depuration of radionuclides in organisms is necessary to relate exposure to radiation dose and ultimately to biological effects. We investigated uptake and depuration of a mixture of radionuclides to link bioaccumulation with radiation dose in zebrafish, Danio rerio. Adult zebrafish were exposed to radionuclides ((54)Mn, (60)Co, (65)Zn, (75)Se, (109)Cd, (110m)Ag, (134)Cs and (241)Am) at tracer levels (<200 Bq g(-1)) for 14 d, either via water or diet. Radioactivity concentrations were measured in whole body and excised gonads of exposed fish during uptake (14 d) and depuration phases (47 d and 42 d for aqueous and dietary exposures respectively), and dose rates were modelled from activity concentrations in whole body and exposure medium (water or diet). After 14-day aqueous exposure, radionuclides were detected in decreasing activity concentrations: (75)Se>(65)Zn>(109)Cd>(110m)Ag>(54)Mn>(60)Co>(241)Am>(134)Cs (range: 175-8 Bq g(1)). After dietary exposure the order of radionuclide activity concentration in tissues (Bq g(-1)) was: (65)Zn>(60)Co>(75)Se>(109)Cd>(110m)Ag>(241)Am>(54)Mn>(134)Cs (range: 91-1 Bq g(-1)). Aqueous exposure resulted in higher whole body activity concentrations for all radionuclides except (60)Co. Route of exposure did not appear to influence activity concentrations in gonads, except for (54)Mn, (65)Zn, and (75)Se, which had higher activity concentrations in gonads following aqueous exposure. Highest gonad activity concentrations (Bq g(-1)) were for (75)Se (211), (109)Cd (142), and (65)Zn (117), and highest dose rates (μGy h(-1)) were from (241)Am (aqueous, 1050; diet 242). This study links radionuclide bioaccumulation data obtained in laboratory experiments with radiation dose determined by application of a dosimetry modelling tool, an approach that will enable better linkages to be made between exposure, dose, and effects of radionuclides in organisms.
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No pos
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No neg
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Retriever1713
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[General and light microscope observation on histological changes of femoral heads between SANFH rabbit animal models and it were intervened by Osteoking].
OBJECTIVE
To evaluate the histological changes on the femoral heads of the SANFH rabbit animal models and after it were intervened by Osteoking (herbs of the Yi minority in Yunnan province) using general and light microscope observation.
METHOD
A total of 150 New Zealand white rabbits were randomly divided into a non-treatment control group (A group, n = 24), normal rabbits with Osteoking treatment group (B group, n = 24), and the experimental group (n = 102). The experimental group was injected with escherichia coli endotoxin (10 microg x kg(-1)) into auricular vein twice by 24-hour intervals, and prednisolone (20 mg x kg(-1)) was injected into buttock three times by 24-hour intervals to make steroid-induced femoral head necrosis model. At the fifth week, 48 out of 53 rabbits were equally divided into model group (C group, n = 24, models with non-treatment Osteoking) and abnormal rabbits with Osteoking treatment group (D group, n = 24). B group and D group were intragastrically administrated with Osteoking, once every two days. A group and C group were intragastrically administrated with the equal volume of saline. At 8th, 12th and 16th week after model preparation, the femoral head specimens were observed under the general and a light microscope.
RESULT
Macroscopic and light microscopic analysis showed that, clear bone necrosis of femoral head was observed in the C group, and a large number of fat cell proliferation was found in the bone marrow cavity. As compared with C group, the damage level of cells in D group was milder, however, the density of bone trabecula from Osteoking treatment was high, and the ratio of bone lacuna was very low. It is also demonstrated that the surface area of bone necrosis was decreased, and the number of cells from adiposities was reduced significantly. The phenomenon of bone necrosis repaired apparently. The morphology of femoral head from A group and B group is normal.
CONCLUSION
It suggested that Osteoking could effectively help repair steroid-induced femoral head necrosis in the early stage.
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No pos
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No neg
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Retriever1714
|
Computational models to predict blood-brain barrier permeation and CNS activity.
The blood-brain permeation of a structurally diverse set of 281 compounds was modeled using linear regression and a multivariate genetic partial least squares (G/PLS) approach. Key structural features affecting the logarithm of blood-brain partitioning (logBB) were captured through statistically significant quantitative structure-activity relationship (QSAR) models. These relationships reveal the importance of logP, polar surface area, and a variety of electrotopological indices for accurate predictions of logBB. The best models reveal an excellent correlation (r > 0.9) for a training set of 58 compounds. Likewise, the comparison of the average logBB values obtained from an ensemble of QSAR models with experimental values also verifies the statistical quality of the models (r > 0.9). The models provide good agreement (r approximately 0.7) between the predicted logBB values for 34 molecules in the external validation set and the experimental values. To further validate the models for use during the drug discovery process, a prediction set of 181 drugs with reported CNS penetration data was used. A >70% success rate is obtained by using any of the QSAR models in the qualitative prediction for CNS permeable (active) drugs. A lower success rate (approximately 60%) was obtained for the best model for CNS impermeable (inactive) drugs. Combining the predictions obtained from all the models (consensus) did not significantly improve the discrimination of CNS active and CNS inactive molecules. Finally, using the therapeutic classification as a guiding tool, the CNS penetration capability of over 2000 compounds in the Synthline database was estimated. The results were very similar to the smaller set of 181 compounds.
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No pos
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No neg
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Retriever1715
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Using dual-network-analyser for communities detecting in dual networks.
BACKGROUND
Representations of the relationships among data using networks are widely used in several research fields such as computational biology, medical informatics and social network mining. Recently, complex networks have been introduced to better capture the insights of the modelled scenarios. Among others, dual networks (DNs) consist of mapping information as pairs of networks containing the same set of nodes but with different edges: one, called physical network, has unweighted edges, while the other, called conceptual network, has weighted edges.
RESULTS
We focus on DNs and we propose a tool to find common subgraphs (aka communities) in DNs with particular properties. The tool, called Dual-Network-Analyser, is based on the identification of communities that induce optimal modular subgraphs in the conceptual network and connected subgraphs in the physical one. It includes the Louvain algorithm applied to the considered case. The Dual-Network-Analyser can be used to study DNs, to find common modular communities. We report results on using the tool to identify communities on synthetic DNs as well as real cases in social networks and biological data.
CONCLUSION
The proposed method has been tested by using synthetic and biological networks. Results demonstrate that it is well able to detect meaningful information from DNs.
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No pos
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No neg
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Retriever1716
|
Prevalence of COPD in Abu Dhabi, United Arab Emirates.
BACKGROUND
The prevalence of chronic obstructive pulmonary disease (COPD) in Abu Dhabi, United Arab Emirates is unknown.
METHODS
We conducted a cross-sectional survey in a random sample of individuals 40-80 years old in Abu Dhabi, with a particular interest to explore local risk factors other than cigarette smoking. Airflow limitation compatible with COPD was defined as a post-bronchodilator ratio FEV(1)/FVC <0.70.
RESULTS
From 520 participants surveyed (93.7% response rate), 55% male and with a mean age of 52 years, the prevalence of COPD was 3.7% and 95% C.I. (2.0-5.3). There were no differences by gender, and COPD prevalence only significantly increased in those 70 year and older. Among those with COPD, cigarette smoking use was relatively low (12% current- and 12% former-smokers), and it was even lower the use of shisha (5%), pipe (0%), or exposure to passive smoking (5%), while exposure to biomass was higher (33%). Interestingly, bakhour use was very high (78%), but neither bakhour nor any of the above-mentioned exposures were associated with the risk of COPD.
CONCLUSIONS
COPD prevalence in 40-80 years old in Abu Dhabi was 3.7%, and associations with cigarette smoking or with other local inhaled exposures were not observed.
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No pos
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No neg
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Retriever1717
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Factors affecting length of stay in hospital of patients with traumatic spinal cord injury in China.
OBJECTIVE
To investigate factors associated with length of stay in hospital of patients with traumatic spinal cord injury in China, based on recent data spanning a period of 10 years.
METHODS
The study was conducted in the China Rehabilitation Research Center, Beijing, which is the largest rehabilitation hospital in China. Associated variables were statistically analysed, including sex, age, marital status, patient's home address, and payment method as demographic variables, and cause of injury, severity of injury, level of injury, spasticity, osteoporosis, neurogenic bladder, and complications as clinical variables. Univariate analysis and multiple linear regression analysis were used to determine the association between length of stay and these var-iables.
RESULTS
A total of 2,110 participants were included in this study. Median length of stay in hospital was 113.5 days. Longer length of stay correlated significantly with higher age, single status, being struck by an object, motor vehicle collision, complete injury, and complications. Patients whose injury resulted from a fall from a low height, those with neurogenic bladder, and/or patients of older age had shorter lengths of stay.
CONCLUSION
Analysis of data for patients with traumatic spinal cord injury, spanning a recent period of 10 years in China, shows that close attention should be paid to those patients with osteoporosis, spasticity, complete injury, injury caused by object striking or motor vehicle collision, patients with single status, or who are in the age range 15-29 years. Active measures should be taken to reduce length of stay in patients with complications, such as urinary tract infection, respiratory infection, or neuropathic pain.
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No pos
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No neg
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Retriever1718
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I Can't Believe It's Not Toothpaste! Poison Control Center Calls Regarding Dental and Oral-Care Products.
BACKGROUND
A cluster of incidents in which non-tooth-paste products were used to brush teeth prompted a review of all calls to one Poison Control Center (PCC) regarding exposures to dental and oral-care products to determine if any resulted in significant toxicity.
METHODS
Retrospective review of 65,849 calls to one PCC during one calendar year. All inquiries about exposures to substances used as dental or oral-care products were analyzed by a single reviewer for reported adverse effects; including hospital admission or PCC referral for emergent medical evaluation.
RESULTS
798 calls involved exposure to dental or oral-care products, comprising 1.21 % of all calls received. Toothbrushing incidents with non-toothpaste products (122 cases) did not result in any significant recognized toxicity. Twenty-four patients were either referred for emergent medical evaluation (14) or were admitted to the hospital (10). In 23 of these patients (96%), the toxic agent was either an over-the-counter analgesic or a local anesthetic used to treat dental pain.
CONCLUSIONS
Among PCC calls received regarding dental and oral-care products, over-the-counter analgesics and local anesthetics used for dental pain resulted in the most frequent need for emergent medical evaluation or for hospital admission.
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No pos
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No neg
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Retriever1719
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Quantitation of Candida albicans polysaccharide using an enzyme-linked immunosorbent assay.
The enzyme-linked immunosorbent assay (ELISA) for candida polysaccharide antigen in serum was developed by using double antibody sandwich technique. It was found that serum constituents substantially interfered with the assay. The interference was successfully decreased by heating serum in the presence of EDTA which precipitated interfering serum protein. In addition, candida antigen may be liberated from antibody complexes. The candida polysaccharide antigen in the supernatant was precipitated with ethanol and resuspended in the buffer containing gelatin. A maximum sensitivity of 10 ng/ml was found in the assay using this procedure. This procedure of serum treatment may have potential applications for the detection of other polysaccharide antigens in serum.
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No pos
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No neg
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Retriever1720
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[Proposal of an indicator of "social class" based on the occupation].
Socioeconomic level is a variable related with health. In order to obtain an indicator of this variable which is suitable for epidemiological and public health studies, we propose to assign the "social class" on the basis of occupation. Having as a reference the British Classification of Social Class we have used the National Classification of Occupations (CNO) for social classification. Once elaborated, we have used the classification in two population-based studies. More than 96% of individuals studied could be classified. We evaluate the usefulness of this indicator and its limitations. Also, we have indicate the need of validating the proposed classification in the future.
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No pos
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No neg
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Retriever1721
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Quantum chemical calculations of model systems for ascorbic acid adducts with Schiff bases of lysine side chains: possibility of internal charge transfer in proteins.
Ab initio self-consistent field calculations for neutral and cationic ascorbic acid and model compounds have been performed. Furthermore, the bicyclic addition products of alpha-hydroxytetronic acid with methylglyoxal and with the Schiff base formed between methylglyoxal and methylamine have been calculated, again in their neutral and cationic forms, respectively. The results indicate that the investigated cations can act as strong electron acceptors. With the help of space-filling molecular models it has been demonstrated that such conformations of the Schiff base formed between the primary amino group of lysine side chains in proteins and the ascorbic acid methylglyoxal acetal are possible in which the lactone carbonyl group comes near to the N atoms of the peptide groups, so that charge can be transferred between these subunits.
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No pos
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No neg
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Retriever1722
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Product inhibition of carboxypeptidase H.
Carboxypeptidase H is one of several enzymes required for the processing of peptide hormone precursors. In this study, inhibition of carboxypeptidase H by its peptide products was investigated. Carboxypeptidase H activity in bovine adrenal medulla chromaffin granules and rat adrenal medulla homogenate was inhibited by the peptides Met- and Leu-enkephalin, vasopressin, oxytocin, luteinizing hormone-releasing hormone, substance P, and thyrotropin-releasing hormone, with oxytocin and ACTH 1-14 having the least effect, at concentrations of 2-20 mM. Inhibition by amidated peptide products (vasopressin, oxytocin, luteinizing hormone-releasing hormone, substance P, and thyrotropin-releasing hormone) show that the final products of the precursor processing pathway can regulate carboxypeptidase H. These levels of peptides are similar to known intragranular peptide concentrations indicating that product and feedback inhibition of carboxypeptidase H may play a role in the control of neuropeptide synthesis. The proenkephalin-derived peptides Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg6-Gly7-Leu8, and Met-enkephalin-Arg6-Phe7 competitively inhibited bovine and rat carboxypeptidase H with Ki values of 12.0, 6.5, 7.0, and 5.5 mM, respectively. The significantly greater Ki for Met-enkephalin may reflect the effects of higher intragranular concentration of Met-enkephalin, since one proenkephalin molecule contains four copies of Met-enkephalin and only one copy of each of the other enkephalin peptides. Thus, the products from one multivalent precursor molecule may equivalently inhibit carboxypeptidase H activity. Product inhibition of carboxypeptidase H and perhaps other processing enzymes may serve to limit the maximum peptide concentration within the secretory vesicle.
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No pos
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No neg
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Retriever1723
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Synthesis, Molecular Docking and Biological Evaluation of 2-(2-hydrazinyl)thiazoles as Potential Antioxidant, Anti-inflammatory and Anticancer Agent.
BACKGROUND
Recently, the researcher's have worked on development of new methods for the synthesis of bioactive heterocycles using polyethylene glycol as a green solvent. In this context, we are going to report the synthesized 2-(2-hydrazinyl)thiazoles for their in vitro antioxidant, in vitro anti-inflammatory and in vitro anti-cancer activities studies.
OBJECTIVE
The objective of study was to develop novel antioxidant anti-inflammatory and anti-cancer drugs.
METHODS
At the outset, the condensation of substituted acetophenones 1, thiosemicarbazide 2 and α-haloketones 3 carried out using PEG-400 (20 mL) in the presence of 5 mol% glacial acetic acid to afford thiosemicarbazones intermediate. In furthermore, these thiosemicarbazones were reacted with α-haloketones 3 to obtain appropriate 2-(2-hydrazinyl)thiazoles. The synthesized compounds were in vitro tested for their antioxidant, anti-inflammatory, and anti-cancer activity.
RESULTS
In vitro evaluation report showed that nearly all molecules possessed potential antioxidant activity against 2,2-Diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR) and hydrogen peroxide (H2O2) radical scavenging activity. Most of 2-(2-hydrazinyl)thiazoles derivatives have shown significant anti-inflammatory activity as compared to with diclofenac sodium as a reference standard. 2-(2-Hydrazinyl)thiazoles derivatives showed significant anticancer activity for human leukemia cell line K-562 compared to Adriamycin as a reference standard.
CONCLUSION
All tested compounds showed potential 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging activity. Among the tested series, 4b, 4d and 4e exhibited good hydrogen peroxide and 4b, 4e, 4f and 4g showed excellent superoxide radical scavenging activity. In addition, the 4b, 4e and 4g compounds revealed potent in vitro anti-inflammatory activity against standard diclofenac sodium drug. 2-(2-Hydrazinyl)thiazole derivatives such as 4c and 4d showed significant anticancer activity against human leukemia cell line K-562. Thus, these molecules provide an interesting template for design and development new antioxidant, anti-inflammatory and anti-cancer agents.
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No pos
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No neg
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Retriever1724
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Monoclonal Antibodies Specific for STAT3β Reveal Its Contribution to Constitutive STAT3 Phosphorylation in Breast Cancer.
Since its discovery in mice and humans 19 years ago, the contribution of alternatively spliced Stat3, Stat3β, to the overall functions of Stat3 has been controversial. Tyrosine-phosphorylated (p) Stat3β homodimers are more stable, bind DNA more avidly, are less susceptible to dephosphorylation, and exhibit distinct intracellular dynamics, most notably markedly prolonged nuclear retention, compared to pStat3α homodimers. Overexpression of one or the other isoform in cell lines demonstrated that Stat3β acted as a dominant-negative of Stat3α in transformation assays; however, studies with mouse strains deficient in one or the other isoform indicated distinct contributions of Stat3 isoforms to inflammation. Current immunological reagents cannot differentiate Stat3β proteins derived from alternative splicing vs. proteolytic cleavage of Stat3α. We developed monoclonal antibodies that recognize the 7 C-terminal amino acids unique to Stat3β (CT7) and do not cross-react with Stat3α. Immunoblotting studies revealed that levels of Stat3β protein, but not Stat3α, in breast cancer cell lines positively correlated with overall pStat3 levels, suggesting that Stat3β may contribute to constitutive Stat3 activation in this tumor system. The ability to unambiguously discriminate splice alternative Stat3β from proteolytic Stat3β and Stat3α will provide new insights into the contribution of Stat3β vs. Stat3α to oncogenesis, as well as other biological and pathological processes.
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No pos
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No neg
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Retriever1725
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Diagnostic accuracy and additional value of diffusion-weighted imaging for discrimination of malignant cervical lymph nodes in head and neck squamous cell carcinoma.
INTRODUCTION
The aim was to determine the diagnostic accuracy and additional value of diffusion-weighted imaging for detection of malignant lymph nodes in head and neck squamous cell carcinoma.
METHODS
Two hundred nineteen lymph nodes, predominantly smaller than 10 mm (95.4%), in 16 consecutive patients were evaluated at 1.5 T. Lymph nodes were evaluated for maximum short axial diameter, morphological criteria, and apparent diffusion coefficient (ADC) values (b = 0 and b = 1,000 s/mm(2)). Sensitivity, specificity, positive and negative predictive values as well as diagnostic odds ratios (DORs) and areas under the curves (AUCs) of ROC curves were calculated for the various magnetic resonance imaging (MRI) criteria individually and in combination. Histological examination of lymph nodes in the neck dissection specimen was the gold standard to determine malignant involvement.
RESULTS
The optimal ADC threshold was 1.0 x 10(-3) mm(2)/s. Using this cutoff point, sensitivity and specificity were 92.3% and 83.9%, respectively. When used in combination with size and morphological criteria, ADC value <1.0 x 10(-3) mm(2)/s was the strongest predictor of presence of metastasis (DOR = 97.6). A model which added ADC values to the other MRI criteria performed significantly better than a model without ADC values: AUC = 0.98 versus AUC = 0.91 (p = 0.036).
CONCLUSION
In this study, with predominantly small lymph nodes, the ADC criterion is the strongest independent predictor of presence of metastasis. The use of ADC values in combination with the other MRI criteria significantly improves the discrimination between malignant and benign lymph nodes.
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No pos
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No neg
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Retriever1726
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Circulating enterolactone and risk of breast cancer: a prospective study in New York.
It has been proposed that phyto-oestrogens protect against breast cancer. Lignans are the main class of phyto-oestrogens in Western diets. We conducted a case-control study of breast cancer and serum levels of the main human lignan, enterolactone, nested within a prospective cohort study, the New York University Women's Health Study. Serum samples collected at enrollment and stored at -80 degrees C were used. Among 14 275 participants, 417 incident breast cancer cases were diagnosed a median of 5.1 years after enrollment. Cohort members individually matched to the cases on age, menopausal status at enrollment, serum storage duration and, if premenopausal, day of menstrual cycle were selected as controls. No difference in serum enterolactone was observed between postmenopausal cases (median, 14.3 nmol l(-1)) and controls (14.5 nmol l(-1)), whereas premenopausal cases had higher levels (13.9 nmol l(-1)) than their matched controls (10.9 nmol l(-1), P-value=0.01). In the latter group, the odds ratio for the highest vs the lowest quintile of enterolactone was 1.7 (95% confidence interval (CI), 0.8-3.4; P-value for trend=0.05) and after adjustment for known risk factors for breast cancer was 1.6 (95% CI, 0.7-3.4; P-value for trend=0.13). We observed a moderate positive correlation between serum enterolactone and serum sex hormone-binding globulin in postmenopausal women (r=0.29 in controls (P<0.001) and r=0.14 in cases (P=0.04)), but no correlation with oestrogens or androgens. These results do not support a protective role of circulating lignans, in the range of levels observed, in the development of breast cancer.
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No pos
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No neg
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Retriever1727
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Effect of feed-borne pollution with some mycotoxin combinations on broiler chicks.
Broiler chicks were divided into five groups and fed starter mash from the first day after hatching. The first group feed (control) was mycotoxin free, whereas the mycotoxins sterigmatocystin (350 ppb) and aflatoxin B1 (100 ppb) were added to the second group diet, patulin (100 ppb) and aflatoxin B1 (100 ppb) to the third group feed, penicillic acid (850 ppb) and aflatoxin B1 (100 ppb) to the fourth group, and aflatoxins B2a (0.9 ppb) +G2 alpha (25 ppb) +M1 (0.9 ppb) +M2 (1 ppb) to the fifth group. This contaminated feeding lasted for four weeks followed by another four weeks as recovery period during which all groups fed finishing mash without mycotoxins. At the end of the experiment, the chickens of groups two, three, four and five were significantly lower in body weight and feed conversion and reflected higher mortality rates than those of the control group.
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No pos
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No neg
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Retriever1728
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Autoprocessing of neutrophil elastase near its active site reduces the efficiency of natural and synthetic elastase inhibitors.
An imbalance between neutrophil-derived proteases and extracellular inhibitors is widely regarded as an important pathogenic mechanism for lung injury. Despite intense efforts over the last three decades, attempts to develop small-molecule inhibitors for neutrophil elastase have failed in the clinic. Here we discover an intrinsic self-cleaving property of mouse neutrophil elastase that interferes with the action of elastase inhibitors. We show that conversion of the single-chain (sc) into a two-chain (tc) neutrophil elastase by self-cleavage near its S1 pocket altered substrate activity and impaired both inhibition by endogenous α-1-antitrypsin and synthetic small molecules. Our data indicate that autoconversion of neutrophil elastase decreases the inhibitory efficacy of natural α-1-antitrypsin and small-molecule inhibitors, while retaining its pathological potential in an experimental mouse model. The so-far overlooked occurrence and properties of a naturally occurring tc-form of neutrophil elastase necessitates the redesign of small-molecule inhibitors that target the sc-form as well as the tc-form of neutrophil elastase.
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No pos
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No neg
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Retriever1729
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Comparison of long-term fluctuations: laser scanning tomography versus automated perimetry.
BACKGROUND
The aim of our study was to investigate the long-term variability of laser scanning tomography and to compare it with the long-term variability of automated perimetry.
METHOD
We retrospectively reviewed the charts of 199 patients (394 eyes) who underwent both automated perimetry (Octopus) and laser scanning tomography (Heidelberg retina tomograph, HRT) in our hospital since 1994. All patients either had ocular hypertension (OHT) or early stage glaucoma. The mean follow-up time was 5.4 years; the average number of examinations was 7.7. The variability was described by the variance ratio VR.
RESULTS
The HRT parameters showed very similar long-term fluctuations as the Octopus parameters. In detail: VR of HRT parameters ranged from 0.04 (cup area, cup volume, mean cup depth) to 0.35 (contour height variation), whereas VR of Octopus parameters ranged from 0.12 (mean sensitivity) to 0.15 (loss variance).
CONCLUSIONS
The long-term variability of HRT parameters is in the same range as the long-term variability of visual field parameters. Since it is now widely accepted that visual field changes over time should be reproduced at least once or twice before clinical consequences can be drawn, the same should be postulated for HRT changes over time.
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No pos
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No neg
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Retriever1730
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Evolutionary implications of localization of the signaling scaffold protein parafusin to both cilia and the nucleus.
Parafusin (PFUS), a 63 kDa protein first discovered in the eukaryote Paramecium and known for its role in apicomplexan exocytosis, provides a model for the common origin of cellular systems employing scaffold proteins for targeting and signaling. PFUS is closely related to eubacterial rather than archeal phosphoglucomutases (PGM) - as we proved by comparison of their 88 sequences - but has no PGM activity. Immunofluorescence microscopy analysis with a PFUS-specific peptide antibody showed presence of this protein around the base region of primary cilia in a variety of mammalian cell types, including mouse embryonic (MEFs) and human foreskin fibroblasts (hFFs), human carcinoma stem cells (NT-2 cells), and human retinal pigment epithelial (RPE) cells. Further, PFUS localized to the nucleus of fibroblasts, and prominently to nucleoli of MEFs. Localization studies were confirmed by Western blot analysis, showing that the PFUS antibody specifically recognizes a single protein of ca. 63 kDa in both cytoplasmic and nuclear fractions. Finally, immunofluorescence microscopy analysis showed that PFUS localized to nuclei and cilia in Paramecium. These results support the suggestion that PFUS plays a role in signaling between nucleus and cilia, and that the cilium and the nucleus both evolved around the time of eukaryotic emergence. We hypothesize that near the beginnings of eukaryotic cell evolution, scaffold proteins such as PFUS arose as peripheral membrane protein identifiers for cytoplasmic membrane trafficking and were employed similarly during the subsequent evolution of exocytic, nuclear transport, and ciliogenic mechanisms.
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No pos
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No neg
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Retriever1731
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Pre-treatment verification of intensity modulated radiation therapy plans using a commercial electronic portal dosimetry system.
We commissioned a commercially available portal dosimetry system for quality assurance of intensity modulated radiation therapy (IMRT) treatment plans. The system included gamma analysis software to compare the measured and predicted fluence maps from individual IMRT fields. The portal dosimetry system was tested using six head and neck IMRT patient plans, and we demonstrated that the accuracy of the alignment of measured and predicted images improved by retracting and repositioning the electronic portal imaging device (EPID) at each new gantry angle. The mean gamma score (fraction of pixels passing the gamma criteria) for the six test plans (after initial testing and using the EPID retracting and repositioning method) was 0.987 (2SD = 0.018), using gamma criteria of a dose difference of 2% of the maximum field dose and 2 mm distance to agreement. The mean gamma score was 0.989 (2SD = 0.017) for 24 head and neck IMRT patient plans carried out with portal dosimetry. Using gamma criteria of 2% maximum field dose and 2 mm distance to agreement, a gamma score tolerance of 0.980 is a useful way of highlighting only those fields requiring further analysis. Portal dosimetry is a quick way of assessing individual field fluence distributions and can be integrated into an IMRT quality assurance programme.
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No pos
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No neg
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Retriever1732
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Effect of dopamine on carotid chemoreceptor activity in newborn kittens.
In newborn kittens, intravenous bolus injections of dopamine may be inhibitory or excitatory to the carotid chemosensory activity. In order to further identify the role of dopaminergic mechanisms on the chemosensory activity in the kitten, 10 anesthetized, paralyzed and artificially ventilated kittens aged from 1 to 21 days were studied. The activity of a few chemoafferent fibers from one carotid sinus nerve was recorded at three levels of FiO2 in N2, 21, 8 and 100%, before and during a continuous dopamine infusion at a dose of 10 micrograms/kg/min. The immediate effect of dopamine usually was a transient inhibition of carotid chemosensory discharge. After 2 min of infusion, the activity had consistently increased from 4.5 +/- 0.8 to 8.8 +/- 1.4 impulses/s (mean +/- SEM, p < 0.05) in normoxia. Dopamine also significantly increased the steady state chemosensory response to hypoxia from 24.6 +/- 3.7 to 33.4 +/- 5.3 impulses/s. Hence, continuous infusion of dopamine has a dual effect on carotid chemoreceptor activity: early inhibition followed by excitation. The excitatory effect enhances the response to hypoxia. These data suggest that the dual effect of dopamine on carotid chemosensory discharge may be related to dopamine concentration in the carotid body.
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No pos
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No neg
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Retriever1733
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Reply to the 'Comment on "Robust scalable high throughput production of monodisperse drops"' by M. Nakajima, Lab Chip, 2017, 17, DOI: 10.1039/C7LC00181A.
This reply to the comment by Nakajima on our article that appeared in Lab on a Chip (E. Amstad, M. Chemama, M. Eggersdorfer, L. R. Arriaga, M. Brenner and D. A. Weitz, Lab Chip, 2016, 16, 4163-4172) highlights the differences between the microchannel step emulsification devices developed by the Nakajima group and the millipede device reported by us in Lab on a Chip.
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No pos
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No neg
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Retriever1734
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The TonB system in Aeromonas hydrophila NJ-35 is essential for MacA2B2 efflux pump-mediated macrolide resistance.
The TonB system is generally considered as an energy transporting device for the absorption of nutrients. Our recent study showed that deletion of this system caused a significantly increased sensitivity of Aeromonas hydrophila to the macrolides erythromycin and roxithromycin, but had no effect on other classes of antibiotics. In this study, we found the sensitivity of ΔtonB123 to all macrolides tested revealed a 8- to 16-fold increase compared with the wild-type (WT) strain, but this increase was not related with iron deprivation caused by tonB123 deletion. Further study demonstrated that the deletion of tonB123 did not damage the integrity of the bacterial membrane but did hinder the function of macrolide efflux. Compared with the WT strain, deletion of macA2B2, one of two ATP-binding cassette (ABC) types of the macrolide efflux pump, enhanced the sensitivity to the same levels as those of ΔtonB123. Interestingly, the deletion of macA2B2 in the ΔtonB123 mutant did not cause further increase in sensitivity to macrolide resistance, indicating that the macrolide resistance afforded by the MacA2B2 pump was completely abrogated by tonB123 deletion. In addition, macA2B2 expression was not altered in the ΔtonB123 mutant, indicating that any influence of TonB on MacA2B2-mediated macrolide resistance was at the pump activity level. In conclusion, inactivation of the TonB system significantly compromises the resistance of A. hydrophila to macrolides, and the mechanism of action is related to the function of MacA2B2-mediated macrolide efflux.
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No pos
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No neg
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Retriever1735
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H2 generation from steam gasification of swine manure over nickel-loaded perovskite oxides catalysts.
In this study, nickel-loaded perovskite oxides catalysts were synthesized via the impregnation of 10%Ni on XTiO3 (X = Ce, Sr, La, Ba, Ca, and Fe) supports and employed in the catalytic steam gasification of swine manure to produce H2-rich syngas for the first time. The synthesized catalysts were characterized using BET, H2-TPR, XRD, HR-TEM, and EDX analysis. Briefly, using perovskite supports resulted in the production of ultrafine catalyst nanoparticles with a uniform dispersion of Ni particles. According to the catalytic activity test, the gas yield showed the increment as 10% Ni/LaTiO3 < 10% Ni/FeTiO3 < 10% Ni/CeTiO3 < 10% Ni/BaTiO3 < 10% Ni/SrTiO3 < 10% Ni/CaTiO3. Meanwhile, zero coke formation was achieved due to the oxygen mobility of prepared catalysts. Also, the increase in the H2 production for the applied catalysts was in the sequence as 10% Ni/CeTiO3 < 10% Ni/FeTiO3 < 10% Ni/LaTiO3 < 10% Ni/BaTiO3 < 10% Ni/SrTiO3 < 10% Ni/CaTiO3. The maximum H2 selectivity (∼48 vol%) obtained by10% Ni/CaTiO3 was probably due to the synergistic effect of Ni and Ti on enhancing the water-gas shift reaction, and Ca on creating the maximum oxygen mobility compared to other alkaline earth metals doped at the A place of perovskite. Overall, this study provides a suitable solution for enhanced H2 production through steam gasification of swine manure along with suggesting the appropriate supports to prevent Ni deactivation by lowering coke formation at the same time.
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No pos
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No neg
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Retriever1736
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Type I and type II interferons delay human neutrophil apoptosis via activation of STAT3 and up-regulation of cellular inhibitor of apoptosis 2.
We have recently demonstrated that granulocyte-colony stimulating factor (G-CSF) delays human neutrophil apoptosis via up-regulation of cellular inhibitor of apoptosis 2 (cIAP2), which is dependent on activation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Here, we show that type I and type II interferons (IFNs), which bind to the distinct receptors, exert the antiapoptotic effect on human neutrophils through the similar mechanism. IFN-alpha (type I IFN) and IFN-gamma (type II IFN), like G-CSF, delayed human neutrophil apoptosis through the protein synthesis-dependent mechanism. Stimulation of neutrophils with IFN-alpha or IFN-gamma resulted in tyrosine phosphorylation of STAT1 and STAT3 but not phosphorylation of STAT5, Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase. IFN-alpha and IFN-gamma induced the expression of transcripts of cIAP2 and suppressor of cytokine signaling 1 and 3, but not cIAP1, Mcl-1, and A1. IFN-alpha- and IFN-gamma-induced up-regulation of cIAP2 mRNA and protein, phosphorylation of STAT3, and antiapoptotic effect were inhibited significantly by pretreatment of cells with AG490, a specific inhibitor of JAK2. These findings suggest that cIAP2 expression is up-regulated by IFN-alpha and IFN-gamma through, at least in part, activation of the JAK2-STAT3 pathway, and increased expression of the cIAP2 protein may contribute to an IFN-alpha- and IFN-gamma-mediated antiapoptotic effect on human neutrophils.
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No pos
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No neg
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Retriever1737
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Imagery of negative interpersonal experiences influence the neural mechanisms of social interaction.
Negative interpersonal experiences are a key contributor to psychiatric disorders. While previous research has shown that negative interpersonal experiences influence social cognition, less is known about the effects on participation in social interactions and the underlying neurobiology. To address this, we developed a new naturalistic version of a gaze-contingent paradigm using real video sequences of gaze behaviour that respond to the participants' gaze in real-time in order to create a believable and continuous interactive social situation. Additionally, participants listened to two autobiographical audio-scripts that guided them to imagine a recent stressful and a relaxing situation and performed the gaze-based social interaction task before and after the presentation of either the stressful or the relaxing audio-script. Our results demonstrate that the social interaction task robustly recruits brain areas with known involvement in social cognition, namely the medial prefrontal cortex, bilateral temporoparietal junction, superior temporal sulcus as well as the precuneus. Imagery of negative interpersonal experiences compared to relaxing imagery led to a prolonged change in affective state and to increased brain responses during the subsequent social interaction paradigm in the temporoparietal junction, medial prefrontal cortex, anterior cingulate cortex, precuneus and inferior frontal gyrus. Taken together this study presents a new naturalistic social interaction paradigm suitable to study the neural mechanisms of social interaction and the results demonstrate that the imagery of negative interpersonal experiences affects social interaction on neural levels.
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No pos
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No neg
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Retriever1738
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Heparin-Coated Albumin Nanoparticles for Drug Combination in Targeting Inflamed Intestine.
Targeting areas of inflammation offers potential therapeutic and diagnostic benefits by maximizing drug and imaging marker on-target effects while minimizing systemic exposure that can be associated with adverse side effects. This strategy is particularly beneficial in the management of inflammatory bowel disease (IBD). Here an inflammation-targeting (IT) approach based on heparin-coated human serum albumin nanoparticles (HEP-HSA NPs) that utilize the increased intestinal permeability and changes in electrostatic interaction at the site of intestinal inflammation is described. Using small-molecule and biologic drugs as a model for drug combination, the HEP-HSA NPs demonstrate the capacity to load both drugs simultaneously; the dual-drug loaded HEP-HSA NPs exhibit a higher anti-inflammatory effect than both of the single-drug loaded NPs in vitro and selectively bind to inflamed intestine after enema administration in vivo in a murine model of colitis. Importantly, analyses of the physicochemical characteristics and targeting capacities of these NPs indicate that HEP coating modulates NP binding to the inflamed intestine, providing a foundation for future IT-NP formulation development.
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No pos
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No neg
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Retriever1739
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Evaluation of the VITEK 2 system for identification and antimicrobial susceptibility testing of medically relevant gram-positive cocci.
A study was conducted to evaluate the new VITEK 2 system (bioMérieux) for identification and antibiotic susceptibility testing of gram-positive cocci. Clinical isolates of Staphylococcus aureus (n = 100), coagulase-negative staphylococci (CNS) (n = 100), Enterococcus spp. (n = 89), Streptococcus agalactiae (n = 29), and Streptococcus pneumoniae (n = 66) were examined with the ID-GPC identification card and with the AST-P515 (for staphylococci), AST-P516 (for enterococci and S. agalactiae) and AST-P506 (for pneumococci) susceptibility cards. The identification comparison methods were the API Staph for staphylococci and the API 20 Strep for streptococci and enterococci; for antimicrobial susceptibility testing, the agar dilution method according to the procedure of the National Committee for Clinical Laboratory Standards (NCCLS) was used. The VITEK 2 system correctly identified to the species level (only one choice or after simple supplementary tests) 99% of S. aureus, 96.5% of S. agalactiae, 96.9% of S. pneumoniae, 92.7% of Enterococcus faecalis, 91.3% of Staphylococcus haemolyticus, and 88% of Staphylococcus epidermidis but was least able to identify Enterococcus faecium (71.4% correct). More than 90% of gram-positive cocci were identified within 3 h. According to the NCCLS breakpoints, antimicrobial susceptibility testing with the VITEK 2 system gave 96% correct category agreement, 0.82% very major errors, 0.17% major errors, and 2.7% minor errors. Antimicrobial susceptibility testing showed category agreement from 94 to 100% for S. aureus, from 90 to 100% for CNS, from 91 to 100% for enterococci, from 96 to 100% for S. agalactiae, and from 91 to 100% for S. pneumoniae. Microorganism-antibiotic combinations that gave very major errors were CNS-erythromycin, CNS-oxacillin, enterococci-teicoplanin, and enterococci-high-concentration gentamicin. Major errors were observed for CNS-oxacillin and S. agalactiae-tetracycline combinations. In conclusion the results of this study indicate that the VITEK 2 system represents an accurate and acceptable means for performing identification and antibiotic susceptibility tests with medically relevant gram-positive cocci.
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No pos
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No neg
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Retriever1740
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Novel Aspects Targeting Platelets in Atherosclerotic Cardiovascular Disease-A Translational Perspective.
Platelets are important cellular targets in cardiovascular disease. Based on insights from basic science, translational approaches and clinical studies, a distinguished anti-platelet drug treatment regimen for cardiovascular patients could be established. Furthermore, platelets are increasingly considered as cells mediating effects "beyond thrombosis", including vascular inflammation, tissue remodeling and healing of vascular and tissue lesions. This review has its focus on the functions and interactions of platelets with potential translational and clinical relevance. The role of platelets for the development of atherosclerosis and therapeutic modalities for primary and secondary prevention of atherosclerotic disease are addressed. Furthermore, novel therapeutic options for inhibiting platelet function and the use of platelets in regenerative medicine are considered.
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No pos
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No neg
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Retriever1741
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Imperatorin alleviated endometriosis by inhibiting the activation of PI3K/Akt/NF-κB pathway in rats.
AIMS
Most therapeutic drugs of endometriosis have been contraceptives but symptoms recur in up to 75% of cases, which makes it a presses need to try to find novel and safer therapeutic drugs. Imperatorin is a furanocoumarin existing in many plants, possessing multiple activities, including anti-inflammatory. The purpose of this study was to assess the effects and mechanisms of imperatorin in endometriosis.
MAIN METHODS
Ectopic endometrial volume and hematoxylin-eosin staining were used to estimate the effects of imperatorin in experimental endometriosis model rats. Potential mechanisms of imperatorin in endometriosis were systematically analyzed by network pharmacology and molecular docking. Western blotting and enzyme-linked immunosorbent assay were employed to evaluate proteins expression and cytokines levels in PI3K/Akt/NF-κB pathway.
KEY FINDINGS
Imperatorin could significantly inhibit the growth and ameliorate the histopathological features of ectopic endometrium in experimental endometriosis rats. Network pharmacology approaches showed that imperatorin might regulate inflammatory response and cellular function via primarily affecting PI3K-Akt pathway, Endocrine resistance, Th17 cell differentiation in endometriosis. Moreover, 7 core targets (PIK3CA, AKT1, SRC, MAPK8, MAPK14, ERBB2 and CCND1) resulted from the intersection of KEGG and PPI network topological analysis were used to dock with imperatorin, which indicated that imperatorin could preferably fit in the binding pocket of the above target proteins, except for CCND1. Lastly, imperatorin markedly inhibited the activation of PI3K/Akt/NF-κB pathway via suppressing the phosphorylation levels of PI3K, Akt and p65 in the ectopic endometrium tissue.
SIGNIFICANCE
Our findings revealed that imperatorin is a significant multi-target natural active ingredient for treatment endometriosis.
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No pos
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No neg
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Retriever1742
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Analysis and Prediction of Significant Genes in Gastric Cancer Based on TCGA Database.
OBJECTIVE
Use TCGA data to screen the significantly expressed genes in gastric cancer,then analyze the biological functions of characteristic genes.To identify potential targets for the diagnosis, prognosis and therapeutic monitoring of gastric cancer.
METHODS
Download the high-throughput gastric cancer patient tissue mRNA expression data from the TCGA database, and used the edgeR software package to perform gene differences using the Rstudio software according to the |logFC|>1 and p<0.05 standards analysis, then performed enrichment analysis and constructed protein interaction network of the differently expressed genes to find the significant genes.Finally,analyzed the relationship between significant genes and gastric cancer patient prognosis.
RESULTS
The RNA-seq expression data of 375 cases of gastric cancer and 32 adjacent tissues were obtained from the TCGA database. The differential analysis yielded 4320 differential genes, of which 2718 were highly expressed and 1602 were low expressed. Through enrichment analysis, it is found that the differential genes are mainly related to the neural active ligand-receptor interaction, calcium signaling pathway, Protein digestion and absorption, chemical carcinogenesis, and cytochrome P450 metabolism of foreign compounds. Further survival analysis screened out the five significant genes of ALB, AFP, IGFBP1, APOH, and TF are related to the prognosis of gastric cancer.
CONCLUSION
The five significant genes screened by TCGA data may be related to the prognosis of gastric cancer and are expected to become prognostic biomarkers.
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No pos
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No neg
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Retriever1743
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Neonatal resuscitation training for midwives in Uganda: Strengthening skill and knowledge retention.
The objective of this project was to improve birth outcomes for babies in a regional referral hospital in Uganda by strengthening factors that influence the retention and application of neonatal resuscitation skills. Initial training in neonatal resuscitation is not enough on its own. In order to better understand the gap between training and effective practice, an evaluation of a neonatal resuscitation program was carried out. This included practical skill testing of local midwives using a neonatal resuscitation doll pre- and post-training, as well as follow up testing at 1 month and 12 months, followed by focus groups and interviews. Test scores revealed that participants' knowledge grew significantly immediately following the workshop, and remained high after 1 month, but fell by 12 months post-training. Interviews with hospital staff revealed a number of facilitators and barriers to practice, namely knowledge retention and skill application. The most important barrier identified is the lack of refresher training post-workshop. Importantly, the findings demonstrated a need not for refresher training alone, but for improved organizational and administrative support for the newly assigned trainers.
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No pos
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No neg
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Retriever1744
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Magnetic activated cell sorting allows isolation of spermatogonia from adult primate testes and reveals distinct GFRa1-positive subpopulations in men.
BACKGROUND
Isolation of spermatogonial stem cells (SSCs) could enable in vitro approaches for exploration of spermatogonial physiology and therapeutic approaches for fertility preservation. SSC isolation from adult testes is difficult due to low cell numbers and lacking cell surface markers. Glial cell-derived neurotrophic factor family receptor alpha-1 (GFRalpha1) plays a crucial role for the maintenance of SSCs in rodents and is expressed in monkey spermatogonia.
METHODS
Magnetic activated cell sorting was employed for the enrichment of GFRalpha1+ spermatogonia from adult primate testes.
RESULTS
Magnetic activated cell sorting of monkey cells enriched GFRalpha1+ cells threefold. 11.4% of GFRalpha1+ cells were recovered. 42.9% of GFRalpha1+ cells were recovered in sorted fractions of human testicular cells, representing a fivefold enrichment. Interestingly, a high degree of morphological heterogeneity among the GFRalpha1+ cells from human testes was observed.
CONCLUSIONS
Magnetic activated cell sorting using anti-GFRalpha1 antibodies provides an enrichment strategy for spermatogonia from monkey and human testes.
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No pos
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No neg
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Retriever1745
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Controlling the Hydrolysis and Loss of Nitrogen Fertilizer (Urea) by using a Nanocomposite Favors Plant Growth.
Urea tends to be hydrolyzed by urease and then migrate into the environment, which results in a low utilization efficiency and severe environmental contamination. To solve this problem, a network-structured nanocomposite (sodium humate-attapulgite-polyacrylamide) was fabricated and used as an excellent fertilizer synergist (FS) that could effectively inhibit the hydrolysis, reduce the loss, and enhance the utilization efficiency of nitrogen. Additionally, the FS exerted significant positive effects on the expression of several nitrogen-uptake-related genes, ion flux in maize roots, the growth of crops, and the organic matter in soil. The FS could modify the microbial community in the soil and increase the number of bacteria involved in nitrogen metabolism, organic matter degradation, the iron cycle, and photosynthesis. Importantly, this technology displayed a high biosafety and has a great potential to reduce nonpoint agricultural pollution. Therefore, this work provides a promising approach to manage nitrogen and to promote the sustainable development of agriculture and the environment.
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No pos
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No neg
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Retriever1746
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Neurochemical and behavioral alterations in glucocorticoid receptor-impaired transgenic mice after chronic mild stress.
Mice (GR-i) bearing a transgene encoding a glucocorticoid receptor (GR) antisense RNA under the control of a neuron-specific neurofilament promoter were used to investigate the effects of a 4 week chronic mild stress (CMS) on the hypothalamo-pituitary-adrenocortical (HPA) axis and the serotoninergic system in a transgenic model of vulnerability to affective disorders. GR-i mice showed a decrease in both GR-specific binding (hippocampus and cerebral cortex) and GR mRNA levels [hippocampus, cerebral cortex, and dorsal raphe nucleus (DRN)] as well as a deficit in HPA axis feedback control (dexamethasone test) compared with paired wild-type (WT) mice. In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the density of cytosolic GR binding sites in the hippocampus, whereas, in the DRN, GR mRNA levels tended to increase. In contrast, in stressed GR-i mice, both GR mRNA levels and the density of GR binding sites were significantly increased in the hippocampus, cerebral cortex, and DRN. Electrophysiological recordings in brainstem slices and [gamma-35S]GTP-S binding measurements to assess 5-HT1A receptor functioning showed that CMS exposure produced a desensitization of DRN 5-HT1A autoreceptors in WT, but not in GR-i, mice. In addition, CMS was found to facilitate choice behavior of WT, but not GR-i, mice in a decision-making task derived from an alternation paradigm. These results demonstrate that impaired GR functioning affects normal adaptive responses of the HPA axis and 5-HT system to CMS and alters stress-related consequences on decision-making behaviors.
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No pos
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No neg
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Retriever1747
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Rodenticide-humic acid adsorption mechanisms and role of humic acid on their toxicity on human keratinocytes: chromatographic approach to support the biological data.
Humic substances are the most important soil components affecting the behaviour and performances of herbicides in the soil-water-organism system. In this paper, a chromatographic approach was used for analysis of anticoagulant rodenticide-humic acid adsorption mechanisms. Using an equilibrium perturbation method, it was clearly shown that: (i) humic acid can be adsorbed on the C18 stationary phase, and (ii) all the rodenticides can be adsorbed on the humic acid adsorbed on the C18 stationary phase. This approach allowed the determination of the adsorption constant values between the anticoagulant rodenticides and humic acid as well as the corresponding thermodynamic data of this adsorption mechanism. The role of humic acid on the toxicity of these rodenticides on human keratinocytes was also clearly described in relation to these physico-chemical data.
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No pos
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No neg
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Retriever1748
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Development of injectable thermosensitive polypeptide hydrogel as facile radioisotope and radiosensitizer hotspot for synergistic brachytherapy.
Brachytherapy is considered to be an unparalleled form of conformal radiation therapy, which involves the delivery of radiation directly to tumor lesions or the postoperative cavity. With the development of specific applicators, the exploitation of in situ drug-delivery platform introduces opportunities for the synchronous administration of radiosensitizers. In this study, an iodine-131 (I131)-labeled injectable thermosensitive methoxy poly(ethylene glycol)-b-poly(tyrosine) hydrogel (denoted as PETyr-I131) was developed via a facile method. The radioactive source of I131 was immobilized at the subcutaneous injection site and monitored via single-photon emission computed tomography in real time, and hematological and histopathological analyses revealed no obvious side effects. Additionally, the SmacN7 peptide conjugated with cell membrane-permeable oligosarginine (denoted as SmacN7-R9) was used to enhance the radiosensitivity of cancer cells, as confirmed by the results of reactive oxygen species detection, DNA damage assay, cell apoptosis assay, and clonogenic evaluation. Importantly, a synergistic brachytherapy treatment effect on tumor-bearing nude mice was achieved. The proposed thermosensitive supramolecular hydrogel platform, which conformally immobilizes radionuclides and delivers radiosensitizers by virtue of its proximity to the site of the primary tumor or the postoperative cavity, has great potential for achieving synergistic treatment outcomes with reduced radiation-related side effects. STATEMENT OF SIGNIFICANCE: In this work, a kind of radioiodinated thermosensitive supramolecular hydrogel was developed, which was facilely used as the radioactive source for brachytherapy. Meanwhile, SmacN7-R9 peptide was combined as a model radiosensitizer to facilitate the activation of tumor cell apoptosis pathways and promotion of radiation-induced cytotoxicity. Synergistic brachytherapy outcomes were achieved from the in vitro and in vivo evaluations. Therefore, from the practical standpoint, this thermosensitive supramolecular hydrogel platform holds great potential for the 3D-conformally immobilizing radionuclide and delivering radiosensitizer by virtue of its proximity to the site of primary tumor lesions or postoperative cavity, resulting in synergetic treatment outcomes with reduced radiation associated side effects.
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No pos
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No neg
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Retriever1749
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Morphological aspects and biomechanical properties of the vertebroaxial joint (C2-C3).
The C2-C3 intervertebral joint must be regarded as a transitional area situated between the upper cervical spine where most rotation of the neck and little flexion and extension occur and the lower cervical spaces where chiefly motion in the sagittal plane and also somewhat rotation take place. Under normal circumstances the range of flexion-extension reaches 11 degrees, slighter than below (19.5 degrees at C5-C6); on the opposite, the range of rotation attains 7 degrees; less than above but much more than below (0 degrees at C5-C6). The motion in the sagittal and coronal planes is relatively poor because of the location of Penning's motor-axis of C2 which runs far from the vertebral body and the lowness of the intervertebral disc. However, the rotation of C2 with respect to C3 is fair by the peculiar inclination of the articular facets which slope sagittally but also coronally and trace a sphere whereupon C2 may move around its motor-centre in any plane. When C2-C3 is surgically fixed by bone graft, the lack of motion is completed by a "compensatory movement" in the upper cervical spaces and especially at the atlantooccipital joint for flexion-extension. In the same way, C2-C3 may improve its mobility especially in the sagittal plane when the inferior partner is blocked by surgical or arthritic fusion.
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No pos
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No neg
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Retriever1750
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Clara cell secretory protein modulates lung inflammatory and immune responses to respiratory syncytial virus infection.
Clara cell secretory protein (CCSP) has been shown to have anti-inflammatory and immunomodulatory functions in the lung. Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants and young children. RSV usually infects small airways and likely interacts with the Clara cells of bronchioles. To determine a possible role for CCSP during acute RSV infection, CCSP-deficient (CCSP(-/-)) and wild-type (WT) mice were intratracheally infected with RSV and the lung inflammatory and immune responses to RSV infection were assessed. RSV-F gene expression was increased in the lungs of CCSP(-/-) mice as compared with WT mice following RSV infection, consistent with increased viral persistence. Lung inflammation was significantly increased in CCSP(-/-) mice as compared with WT mice after infection. Moreover, although the levels of Th1 cytokines were similar, the levels of Th2 cytokines and neutrophil chemokines were increased in the lungs of CCSP(-/-) mice following infection. Physiologic endpoints of exacerbated lung disease, specifically airway reactivity and mucus production, were increased in CCSP(-/-) mice after RSV infection. Importantly, restoration of CCSP in the airways of CCSP(-/-) mice abrogated the increased viral persistence, lung inflammation, and airway reactivity. These findings suggest a role for CCSP and Clara cells in regulating lung inflammatory and immune responses to RSV infection.
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No pos
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No neg
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Retriever1751
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The stressostat: a novel approach in adaptive laboratory evolution to improve end-product resistance.
End-product inhibition in pH-controlled batch cultures, is the major limiting factor for bacterial biomass formation in the starter culture industry as well as in many other biotechnological processes. Adaptive laboratory evolution (ALE) has emerged over the past decades as a powerful tool for phenotype optimization, but none of the existing ALE methods could select for improved end-product resistance. Therefore, we developed the stressostat (STress Resistance Evolution in Substrate Surplus) as a novel continuous ALE method. Stressostat cultivation applies end-product concentrations as constant evolutionary pressure on microorganisms in the presence of substrate surplus. In this study, we improved the lactate resistance of Lactococcus lactis FM03P in 35 days of stressostat cultivations. The lactate concentrations increased over time from 530 to 675mM, indicating the successful selection for variants with improved lactate resistance. Thirty-four variants were isolated and grouped into four clusters based on their growth rates at high lactate concentrations. In the high-throughput screening without pH control, most isolated variants could grow at high lactate concentrations (870-928mM), while the wild type was completely inhibited. The variants grew slower than wild type at low lactate media indicating possible evolutionary trade-off. However, in pH-controlled batch cultivations, most variants produced more biomass than the wild type. In conclusion, stressostat cultivation is a valuable method to obtain L. lactis variants with improved end-product resistance and further characterization is needed to elucidate underlying resistance mechanisms and potential industrial applications.
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No pos
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No neg
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Retriever1752
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[Cloning, Expression and Immungenicity Analysis of Antigen Eg-01883 Screened from Protoscoleces of Echinococcus granulosus].
Objective
To screen for the Echinococcus granulosus 01883（Eg-01883） specifically expressed at the protoscolex period, clone and express this molecule as well as analyse its immunogenicity.
Methods
Eg-01883, which is highly expressed at the protoscolex period but not in oncosphere， was screened by analysing the published mRNA sequences of E. granuolosus. Total RNA of E. granuolosus was extracted, Eg-01883 was cloned by RT-PCR, and the recombinant plasmid pET28a-Eg-01883 was constructed. Expression of the recombinant protein rEg-01883 was induced by isopropyl-β-D-thiogalactoside （IPTG）. ICR mice were randomized into 3 groups （n=12 in each group）. Mice in the immunization group received subcutaneous injections of 10 μg rEg-01883 in 100 μl PBS emulsified in Freund’s adjuvant at multiple sites, followed by immune enhancement after 2 weeks. Mice in the adjuvant group were injected with PBS and adjuvant. Mice in the control group received no treatment. Blood was obtained through caudal vein before immunization, and at 1, 2, and 4 weeks after the first immunization, and through the eyeball at 6 weeks after immunization. Serum levels of IgG, IFN-γ and IL-4 were determined by ELISA. The immunogenicity of rEg-01883 was identified by Western blotting.
Results
Eg-01883 was screened, cloned, expressed and purified to obtain the recombinant protein rEg-01883, which mainly existed as the inclusion body. ELISA results showed that immunization with rEg-01883 induced production of specific IgG antibody. The serum IgG level in the immunization group increased from 1 week after the first immunization, peaked at 6 weeks（2.344±0.153）, which was significantly higher than those of the adjuvant group（0.206 1±0.006） and the control group （0.241±0.01） （P<0.01）. At 6 weeks after the first immunization, the serum levels of IFN-γ （43.23 pg/ml） and IL-4（24.88 pg/ml） in the immunization group were significantly higher than those in the adjuvant group（21.77 pg/ml, 13.27 pg/ml） and the control group（17.40 pg/ml, 12.25 pg/ml）（P<0.05）. Western blot showed that the recombinant protein rEg-01883 could be recognized by His-Tag antibodies, serum of immunized mice, and serum of mice with secondary infection.
Conclusion
The recombinant protein rEg-01883 shows good immunogenicity in ICR mice.
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No pos
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No neg
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Retriever1753
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Cytoskeletal changes in non-apoptotic cell death.
Dynamic morphology and cytoskeletal changes in Hep-2 cells exhibiting features of non-apoptotic cell death after treatment with zinc were studied using immunofluorescence microscopy and spectrofluorimetry. Among early morphological changes in treated cells was development of vacuolization, surface blebbing, relatively rapid cell detachment from substratum, cell shrinkage and, in some cases, appearance of membrane protrusions. Staining of microfilaments revealed rapid rearrangement and subsequent loss of F-actin accompanied by changes in the amount and localization of G-actin. The use of specific kinase and caspase inhibitors did not prevent surface blebbing as well as other morphological features in dying cells. Dying cells were only weakly positive for phosphatidyl serine and showed only a transient activation of caspase-9 with no signs of activation of caspase-3. These results suggest the existence of nonapoptotic cell death showing morphological features of both apoptosis and necrosis but, biochemically, resembling some other type of cell death.
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No pos
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No neg
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Retriever1754
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'Wait…, let me tell you, if I worked for a boss, I would be on sick leave': A Qualitative Study of Self-Employed Workers in Physically Demanding Jobs in the Netherlands.
PURPOSE
The purpose of this study was to explore the perspectives of self-employed workers with a physically demanding job on work participation.
METHODS
We interviewed self-employed workers with a physically demanding job, using semi-structured interviews, which were audio recorded. The main topic addressed was the workers' health in relation with their work participation, work demands, and preventive measures. The interviews were transcribed verbatim and coded by three team members of the research team in several steps. We used the consolidated criteria for reporting qualitative research (COREQ) checklist to report our findings.
RESULTS
We interviewed 18 self-employed workers: 83% male, 49 years (SD 7), self-employed for 18 years (SD 9) and the majority (n = 14) worked in the construction sector. Thematic analysis revealed facilitators and barriers for work participation across three main themes: personal factors, work factors, and healthcare. Personal factors compassed sub-themes such as health and financial consequences. Work factors included sub-themes related to work demands and adaptations and healthcare encompassed sub-themes associated with work-related care and medication.
CONCLUSION
To our knowledge, this is the first qualitative study that investigated the perspectives of self-employed workers in physically demanding jobs regarding work participation. While most facilitators and barriers were consistent with those described in the literature for employees, certain factors, such as financial consequences of ceasing work, emerged important factors for work participation among self-employed workers.
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No pos
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No neg
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Retriever1755
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The great lockdown, uncertainty and trade: asymmetric impact on imports.
The world economy has recently navigated through the pandemic caused by the coronavirus. Almost all the affected countries have responded with stringency measures to control the pandemic. However, these restrictions appear to have critically impacted the global supply chain and cross-border movement of goods. In this regard, we attempt to investigate the impact of pandemic-related stringency measures on India's import demand. For this purpose, we use bilateral monthly import data of India with its major trading counterparts. Our findings suggest that stringency measures have a positive impact on imports, indicating that the economy relies more on imported items when its domestic production and supply chain are disrupted by the pandemic-related restrictions. Conversely, the import origin countries' restrictions have a negative impact on Indian imports, indicating that these restrictions have adversely affected the production and supply chain in origin countries, thereby reducing the overall flow of imports to India. We also find that economic policy uncertainty of home and product origin countries has a negative impact on Indian imports. Our results also confirm that the pandemic-related restrictions and different types of uncertainty have an asymmetric effect on imports.
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No pos
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No neg
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Retriever1756
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Bonding heterogeneity and lone pair induced anharmonicity resulted in ultralow thermal conductivity and promising thermoelectric properties in n-type AgPbBiSe3.
Efficiency in generation and utilization of energy is highly dependent on materials that have the ability to amplify or hinder thermal conduction processes. A comprehensive understanding of the relationship between chemical bonding and structure impacting lattice waves (phonons) is essential to furnish compounds with ultralow lattice thermal conductivity (κ lat) for important applications such as thermoelectrics. Here, we demonstrate that the n-type rock-salt AgPbBiSe3 exhibits an ultra-low κ lat of 0.5-0.4 W m-1 K-1 in the 290-820 K temperature range. We present detailed analysis to uncover the fundamental origin of such a low κ lat. First-principles calculations augmented with low temperature heat capacity measurements and the experimentally determined synchrotron X-ray pair distribution function (PDF) reveal bonding heterogeneity within the lattice and lone pair induced lattice anharmonicity. Both of these factors enhance the phonon-phonon scattering, and are thereby responsible for the suppressed κ lat. Further optimization of the thermoelectric properties was performed by aliovalent halide doping, and a thermoelectric figure of merit (zT) of 0.8 at 814 K was achieved for AgPbBiSe2.97I0.03 which is remarkable among n-type Te free thermoelectrics.
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No pos
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No neg
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Retriever1757
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Quantitative ultrasound estimates from populations of scatterers with continuous size distributions.
Although quantitative ultrasound imaging based on backscattering coefficients has proven potential for tissue characterization, the scattering models used in most studies assume distributions of identical scatterers. However, actual tissues may exhibit multiple levels of spatial scales. Therefore, the objective of the present study is to analyze the effects of scatterer size distributions when using a fluid-sphere model for estimating values of effective scatterer diameter (ESD) through both simulations and experiments. For simulations, ESD estimates were obtained at several analysis frequencies between 1 and 40 MHz from populations of scatterers with diameters ranging between 25 and 100 μm, 25 and 50 μm, 50 and 100 μm, and 50 and 75 μm. For sufficiently high analysis frequencies, the ESD estimates obtained through simulations were approximately inversely proportional to frequency and mostly independent of the underlying scatterer size distribution. Asymptotic expressions for the expected ESD estimates at low- and high-frequency limits were derived. Experiments were conducted using two gelatin phantoms with contrast agent spheres ranging in diameter from 30 to 140 μm and 70 to 140 μm, and 5-, 7.5-, 10-, and 13-MHz focused transducers. Not only was the asymptotic behavior of ESD versus frequency estimates observed experimentally, but also the experimental ESD estimates using the 10- and 13-MHz transducers were lower than the smallest scatterers present in the second phantom. These results may have a direct impact on how scatterer size estimates corresponding to specimens with different subresolution spatial scales should be interpreted.
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No pos
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No neg
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Retriever1758
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Positional information specifies the site of organ regeneration and not tissue maintenance in planarians.
Most animals undergo homeostatic tissue maintenance, yet those capable of robust regeneration in adulthood use mechanisms significantly overlapping with homeostasis. Here we show in planarians that modulations to body-wide patterning systems shift the target site for eye regeneration while still enabling homeostasis of eyes outside this region. The uncoupling of homeostasis and regeneration, which can occur during normal positional rescaling after axis truncation, is not due to altered injury signaling or stem cell activity, nor specific to eye tissue. Rather, pre-existing tissues, which are misaligned with patterning factor expression domains, compete with properly located organs for incorporation of migratory progenitors. These observations suggest that patterning factors determine sites of organ regeneration but do not solely determine the location of tissue homeostasis. These properties provide candidate explanations for how regeneration integrates pre-existing tissues and how regenerative abilities could be lost in evolution or development without eliminating long-term tissue maintenance and repair.
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No pos
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No neg
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Retriever1759
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Observation of conducting filament growth in nanoscale resistive memories.
Nanoscale resistive switching devices, sometimes termed memristors, have recently generated significant interest for memory, logic and neuromorphic applications. Resistive switching effects in dielectric-based devices are normally assumed to be caused by conducting filament formation across the electrodes, but the nature of the filaments and their growth dynamics remain controversial. Here we report direct transmission electron microscopy imaging, and structural and compositional analysis of the nanoscale conducting filaments. Through systematic ex-situ and in-situ transmission electron microscopy studies on devices under different programming conditions, we found that the filament growth can be dominated by cation transport in the dielectric film. Unexpectedly, two different growth modes were observed for the first time in materials with different microstructures. Regardless of the growth direction, the narrowest region of the filament was found to be near the dielectric/inert-electrode interface in these devices, suggesting that this region deserves particular attention for continued device optimization.
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No pos
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No neg
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Retriever1760
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The intermediate filament protein peripherin is a marker for cerebellar climbing fibres.
Immunocytochemical staining with antibodies to the class III intermediate filament protein peripherin reveals discrete subpopulations of neurons and nerve fibres throughout the rat central nervous system. Some of these fibres enter the cerebellar granular and molecular layers. Here we use light and electron microscopic immunocytochemistry and confocal fluorescence microscopy to identify the peripherin positive fibres in the molecular layer of the cerebella of various mammals. (1) The peripherin positive fibres in the molecular layer have morphological attributes of climbing fibres, and peripherin positive fibres are also detected in the olivo-cerebellar tract. Furthermore peripherin positive neurons can be seen in the inferior olive, from which climbing fibres originate. (2) The peripherin positive molecular layer fibres rapidly degenerate in rats treated with 3-acetylpyridine (3-AP), a reagent which destroys neurons in the inferior olive, and the time course of degeneration of these mirrors that previously described for 3-AP induced destruction of climbing fibres. (3) Cerebella of other mammal species tested (mouse, rabbit, pig, cow and human) revealed a similar peripherin staining pattern in the cerebellum, including fibres in the molecular layer with the morphology of climbing fibres. (4) We also noted peripherin positive spinocerebellar and vestibulocerebellar mossy fibres in the cerebellar granular layer of folia known to receive these inputs. (5) A subset of perivascular nerve fibres are also peripherin positive. These results show that peripherin is a useful marker for mammalian cerebellar climbing fibres, and that a subset of morphologically distinct cerebellar mossy fibres are also peripherin positive.
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No pos
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No neg
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Retriever1761
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Longterm meningeal involvement as the only clinical manifestation of low grade malignant non-Hodgkin's lymphoma.
We present the case of a 56-year-old man who developed-at the age of 46-paraesthesia and numbness in the perianal region, the feet and lower legs accompanied by the presence of B-lymphocytes in the cerebrospinal fluid (CSF). Despite intensive work-up an explanation was not found until he developed hepato-splenomegaly ten years after the initial symptoms. Haematologic evaluation at that time disclosed a low-grade malignant B-cell lymphoma. Repeated CSF examination revealed 31 leukocytes/mm3, of which were mainly lymphocytes. These proved to be B-lymphocytes of monoclonal origin. These findings suggest that a leptomeningeal localisation of a low-grade malignant lymphoma had been present for ten years before systemic manifestation of the disease.
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No pos
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No neg
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Retriever1762
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Progress towards control and elimination of neglected tropical diseases targeted by preventive chemotherapy in São Tomé e Príncipe.
The São Tomé e Príncipe government is committed to achieving neglected tropical disease (NTD) control and elimination as a public health problem by 2025. In 2014, the Ministry of Health led a national survey to determine the prevalence of soil-transmitted helminths (STHs) and schistosomiasis across the country. Following this survey, a preventive chemotherapy (PC) campaign with mebendazole and praziquantel reached 31 501 school-age children in 2015. A follow-up 2017 survey to determine the impact of the intervention showed success in controlling schistosomiasis, as no infections were found, but limited impact on STHs, with prevalence similar to pretreatment levels. The survey also investigated the prevalence of a third NTD, lymphatic filariasis (LF), which was found to be endemic in the country. Since then the Ministry of Health has developed the Strategic Plan for the Fight Against Neglected Tropical Diseases 2019-2025 and identified gaps to be addressed. This narrative review systematises the existing literature reporting on the epidemiology of NTDs for which there are PC programs in São Tomé e Príncipe. PubMed was searched for relevant papers that measured the prevalence of LF, schistosomiasis and STHs. Additionally, data provided by the Ministry of Health surveys were analysed. Finally, we discuss current NTD control, including the impact of the coronavirus disease 2019 pandemic and identify priorities for program strengthening and operational research.
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No pos
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No neg
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Retriever1763
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Tuning the spin state of iron phthalocyanine by ligand adsorption.
The future use of single-molecule magnets in applications will require the ability to control and manipulate the spin state and magnetization of the magnets by external means. There are different approaches to this control, one being the modification of the magnets by adsorption of small ligand molecules. In this paper we use iron phthalocyanine supported by an Au(111) surface as a model compound and demonstrate, using x-ray photoelectron spectroscopy and density functional theory, that the spin state of the molecule can be tuned to different values (S ∼ 0, [Formula: see text], 1) by adsorption of ammonia, pyridine, carbon monoxide or nitric oxide on the iron ion. The interaction also leads to electronic decoupling of the iron phthalocyanine from the Au(111) support.
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No pos
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No neg
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Retriever1764
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Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing.
Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda-sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda-β clamp complex. This complex contains two pairs of Hda dimers sandwiched between two β clamp rings to form an octamer that is stabilized by three discrete interfaces. Two separate surfaces of Hda make contact with the β clamp, which is essential for Hda function in RIDA. The third interface between Hda monomers occludes the active site arginine finger, blocking its access to DnaA. Taken together, our structural and mutational analyses of the Hda-β clamp complex indicate that the interaction of the β clamp with Hda controls the ability of Hda to interact with DnaA. In the octameric Hda-β clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function.
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No pos
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No neg
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Retriever1765
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Diabetes Mellitus and Autoimmune Hepatitis: Demographical and Clinical Description of a Relatively Rare Phenotype.
We studied demographic, metabolic, and clinical characteristics of patients with diabetes and autoimmune hepatitis (AIH) from the German/Austrian DPV registry. A total of 139 patients with diabetes and AIH were analyzed and compared to 437 728 patients with diabetes without AIH. The prevalence of AIH in patients with T1DM (44.8/100 000) seems higher than in the general population, the prevalence of AIH in patients with T2DM (23.6/100 000) does not seem to be increased. Patients with T2DM and AIH had a shorter duration of diabetes (p=0.007) and a higher proportion of females (p<0.001) compared to T2DM without AIH. Patients with diabetes (T1DM or T2DM) and AIH required higher insulin doses (p<0.001 and p=0.03, respectively) and showed increased liver enzymes (aspartate transaminase, alanine transaminase, gamma-glutamyltransferase) compared to diabetes patients without (all p<0.001). We detected a lower percentage of patients treated with oral antidiabetic drugs (p=0.01) and a higher percentage of patients treated by insulin in patients with T2DM and AIH (p<0.001) compared to patients with T2DM alone. We observed a higher incidence of autoimmune thyroid disease (AIT) in patients with diabetes (T1DM or T2DM) and AIH (p<0.001) compared to diabetes patients without AIH. AIH seems more frequent in patients with T1DM. Patients with diabetes and AIH require intensification of antidiabetic therapy and seem to have a higher prevalence of AIT.
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No pos
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No neg
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Retriever1766
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Cocaine seeking and taking: role of hippocampal dopamine D1-like receptors.
Despite the well-documented involvement of dopamine D1-like receptor stimulation in cocaine-induced goal-directed behaviours, little is known about the specific contribution of D1-like receptor populations in the dorsal hippocampus (DH) to drug context-induced cocaine-seeking or drug-reinforced instrumental behaviours. To investigate this question, rats were trained to lever press for un-signalled cocaine infusions in a distinct context followed by extinction training in a different context. Cocaine-seeking behaviour (non-reinforced lever responding) was then assessed in the previously cocaine-paired and extinction contexts. SCH23390-induced D1-like receptor antagonism in the DH, but not the overlying trunk region of the somatosensory cortex, dose-dependently inhibited drug context-induced cocaine-seeking behaviour, without altering cocaine-reinforced instrumental responding, cocaine intake, food-reinforced instrumental responding, or general motor activity, relative to vehicle treatment. These findings suggest that D1-like receptor stimulation in the DH is critical for the incentive motivational effects and/or memory of cocaine-paired contextual stimuli that contribute to drug-seeking behaviour.
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No pos
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No neg
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Retriever1767
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ECG evidence of limited myocardial infarction following coronary occlusion treated by early intravenous rt-PA infusion.
Serial 12-lead surface electrocardiograms (ECGs) were analysed in 110 patients with first evolving myocardial infarction entered in a double-blind placebo-controlled trial of intravenous rt-PA within 2.5 h (mean 1.9 +/- 0.5 (SD)) of pain onset. ECG analysis was performed by two 'blinded' analysts. QRS scoring (by the modified Selvester method) was used as an index of myocardial necrosis. Patient results were analysed according to infarct location. There was no difference between the two treatment groups in ST-segment elevation or QRS score at entry or up to 24 h after symptom onset. However from 24 h, QRS score was lower in patients with anterior infarction given rt-PA than in those given placebo: 5.4 +/- 2.8 vs 7.7 +/- 4.1 (P = 0.02) at 48 h; 4.7 +/- 3.2 vs 8.0 +/- 4.0 (P = 0.01) at 4-10 days; and 4.6 +/- 3.9 vs 7.5 +/- 3.9 (P = 0.01) at 21 days. For patients with inferior infarction, rt-PA treatment also resulted in a lower QRS score although this was not significantly different from the score of the placebo group (P = 0.07). Comparison of QRS scores with ejection fraction measured from the contrast ventriculogram taken at 21 days showed a moderate correlation (r = 0.46) in patients with anterior infarction but a poor correlation in patients with inferior infarction. These ECG results indicate that in evolving anterior myocardial infarction, there is limitation of infarct size from early rt-PA infusion.
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No pos
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No neg
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Retriever1768
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Structural insight into modest binding of a non-PXXP ligand to the signal transducing adaptor molecule-2 Src homology 3 domain.
Although some exceptional motifs have been identified, it is well known that the PXXP motif is the motif of ligand proteins generally recognized by the Src homology 3 (SH3) domain. SH3-ligand interactions are usually weak, with ordinary KD approximately 10 microM. The structural basis for a tight and specific association (KD = 0.24 microm) between Gads SH3 and a novel motif, PX(V/I)(D/N)RXXKP, was revealed in a previous structural analysis of the complex formed between them. In this paper, we report the crystal structure of the signal transducing adaptor molecule-2 (STAM2) SH3 domain in complex with a peptide with a novel motif derived from a ligand protein, UBPY. The derived KD value for this complex is 27 microM. The notable difference in affinity for these parallel complexes may be explained because the STAM2 SH3 structure does not provide a specificity pocket for binding, whereas the Gads SH3 structure does. Instead, the structure of STAM2 SH3 is analogous to that of Grb2 SH3 which, in addition to normal PXXP ligands, has also been shown to moderately recognize the novel motif discussed herein. Thus, the extremely tight interaction observed between Gads SH3 and the novel motif is caused not by an innate ability of the novel motif but rather by an evolutionary change in the Gads SH3 domain. Instead, SH3 domains of STAM2 and Grb2 retain the moderate characteristics of recognizing their ligand proteins like other SH3 domains for appropriate transient interactions between signaling molecules.
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No pos
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No neg
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Retriever1769
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Airborne birch pollen antigens in different particle sizes.
Two particle samplers for ambient air, situated together: a static size-selective bio-aerosol sampler (SSBAS) and a Burkard pollen and spore trap were compared in sampling intact birch pollen grains through one flowering period of Betula (a total of 44 days). The SSBAS trapped pollen grains three times more efficiently than the Burkard trap, but the variations in pollen counts were significantly correlated. In contrast, birch pollen antigenic activity and the pollen count in the Burkard samples were not closely correlated. The antigenic concentration was occasionally high both before and after the pollination period. There was a high birch pollen antigenic activity in particle size classes where intact pollen grains were absent, even on days when the pollen count was very low. Correspondingly, on days with high birch pollen counts in the air, pollen antigenic activity was on several occasions low, indicating that pollen grains were empty of antigenic material. The small particle size classes are especially important to allergic patients because they are able to penetrate immediately into the alveoli and provoke asthmatic reactions. Therefore, aerobiological information systems based on pollen and spore counts should be supplemented with information concerning antigenic activities in the air.
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No pos
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No neg
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Retriever1770
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Role strain in hospice nursing.
This paper utilizes role theory to explore the nursing role at a northern California hospice which is licensed as a home health agency. The writers hypothesize that the special burdens of caring for dying patients, the numerous relationships assumed by the nurse, and the expanded nature of the rapidly developing hospice nursing role may contribute to role strain. Options for managing role strain are presented.
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No pos
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No neg
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Retriever1771
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Pregnancy and neonatal complications in women with polycystic ovary syndrome in relation to second-trimester anti-Müllerian hormone levels.
RESEARCH QUESTION
An association has been found between high anti-Müllerian hormone (AMH) levels during pregnancy and the development of polycystic ovary syndrome (PCOS)-like phenotypic traits in mouse offspring. The aim of this study was to determine whether AMH levels are associated with maternal testosterone levels, and whether high AMH concentration influences the risk of developing PCOS-related adverse pregnancy outcomes.
DESIGN
Maternal serum AMH, testosterone and sex hormone binding globulin levels were measured in blood samples taken in early second-trimester pregnancies from women with PCOS (n = 159) and healthy controls matched for body mass index (n = 320). Possible associations with preeclampsia, gestational hypertension, gestational diabetes, preterm birth and birthweight was explored by logistic and linear regression models.
RESULTS
Women with PCOS had higher AMH, higher total testosterone levels and higher free androgen index than controls (P < 0.001 for all three parameters). Among women with PCOS, high testosterone levels (B = 2.7; β = 0.26; P = 0.001) and low first trimester body mass index (B = -0.5; β = -0.17; P = 0.043) remained independently associated with AMH. High AMH levels were associated with decreased risk of gestational hypertension (adjusted OR 0.55; 95% CI 0.34 to 0.87), but no association was found with other adverse pregnancy outcomes or birthweight.
CONCLUSIONS
Women with PCOS had higher AMH levels during pregnancy compared with controls, but high AMH was not associated with increased risk of adverse pregnancy outcomes or birthweight.
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No pos
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No neg
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Retriever1772
|
Lunar maria: structure and evolution.
The lunar maria are considered to have evolved as homologous, transient, gravity-wave systems from large impact craters on a crustal layer 50 kilometers thick, fluidized from beneath by prompt, shock-induced melting inside an initially hot moon.
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No pos
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No neg
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Retriever1773
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Divergent responses of exposed and naive Pacific tree frog tadpoles to invasive predatory crayfish.
Invasive predators can devastate native species and ecosystems. However, native species may be able to coexist with invasive predators through a variety of mechanisms, such as changes in morphology or behavior due to a plastic response or selection on fixed anti-predator traits. We examined whether exposed and naive populations of Pacific tree frog tadpoles (Pseudacris regilla) display divergent morphological and behavioral traits in response to the invasive predatory red swamp crayfish (Procambarus clarkii). Tadpoles were collected from three study streams with and three without crayfish, in the Santa Monica Mountains of Southern California. We analyzed tadpole morphology and tested anti-predator behavior and survival in the laboratory. Tadpoles from streams with crayfish had shallower, narrower tails than tadpoles from streams without crayfish. Tadpoles from streams with and without crayfish were less active after exposure to crayfish chemical cues. The divergent morphology of naive and exposed tadpoles is consistent with tadpoles exhibiting a plastic response to crayfish or undergoing selection from crayfish predation. In laboratory predation experiments, we found no difference in survival between tadpoles from streams with and without crayfish but tadpoles that survived predation had deeper tail muscles than those that were killed or injured. Our results suggest that deeper tails are advantageous in the presence of crayfish, yet tadpoles from crayfish streams had shallower tails than those from crayfish-free streams. Shallower tails may have an alternative unmeasured advantage or there may be a physiological constraint to developing deeper tails in the wild. These results highlight the ability of a native frog to respond to an invasive predatory crayfish, potentially allowing for coexistence.
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No pos
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No neg
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Retriever1774
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Dominant De Novo Mutations in GJA1 Cause Erythrokeratodermia Variabilis et Progressiva, without Features of Oculodentodigital Dysplasia.
Genetic investigation of inherited skin disorders has informed the understanding of skin self-renewal, differentiation, and barrier function. Erythrokeratodermia variabilis et progressiva (EKVP) is a rare, inherited skin disease that is characterized by transient figurate patches of erythema, localized or generalized scaling, and frequent palmoplantar keratoderma. By using exome sequencing, we show that de novo missense mutations in GJA1 (gap junction protein alpha 1) cause EKVP. The severe, progressive skin disease in EKVP subjects with GJA1 mutations is distinct from limited cutaneous findings rarely found in the systemic disorder oculodentodigital dysplasia, also caused by dominant GJA1 mutations. GJA1 encodes connexin 43 (Cx43), the most widely expressed gap junction protein. We show that the GJA1 mutations in EKVP subjects lead to disruption of Cx43 membrane localization and aggregation within the Golgi. These findings reveal a critical role for Cx43 in epidermal homeostasis, and they provide evidence of organ-specific pathobiology resulting from different mutations within GJA1.
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No pos
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No neg
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Retriever1775
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The renal brush border membrane in man. Protein pattern, inorganic phosphate binding and transport: comparison with other species.
Brush border membranes (BBM) have been prepared from fresh samples of normal human kidney cortex and compared to that from mouse, rat, and rabbit. Human BBM presents a sodium dodecyl sulfate gel electrophoresis protein pattern similar to that of the animal species with 22 proteins having the same molecular weight (MW). Incubation with inorganic 32P reveals a phosphate-binding protein (MW 78,000) common to the animal species. However, the binding capacity is lower in man: 4.3 +/- 2.2 pmol Pi/mg protein compared to 9.9 +/- 2.1, 29.7 +/- 4.3, and 31.1 +/- 5.2 in rabbit, mouse, and rat, respectively. The MW of the binding protein corresponds to that of the monomer of alkaline phosphatase. Alkaline phosphatase activity follows the same increasing order in the four species. The Na gradient-dependent Pi uptake by human BBM vesicles is low: Vmax is 0.90 +/- 0.05 nmol/mg/20 s compared to 1.3 +/- 0.1, 1.5 +/- 0.2, and 5.2 +/- 0.2 in rabbit, mouse, and rat, respectively. However, the Km values are within the same range for the four species.
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No pos
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No neg
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Retriever1776
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GENETIC EVIDENCE FOR A PLEISTOCENE POPULATION EXPLOSION.
Expansions of population size leave characteristic signatures in mitochondrial "mismatch distributions." Consequently, these distributions can inform us about the history of changes in population size. Here, I study a simple model of population history that assumes that, t generations before the present, a population grows (or shrinks) suddenly from female size N0 to female size N1 . Although this model is simple, it often provides an accurate description of data generated by complex population histories. I develop statistical methods that estimate θ0 = 2uN0 , θ1 = 2uN1 , and τ = 2ut (where u is the mutation rate), and place a confidence region around these estimates. These estimators are well behaved, and insensitive to simplifying assumptions. Finally, I apply these methods to published mitochondrial data, and infer that a major expansion of the human population occurred during the late Pleistocene.
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No pos
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No neg
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Retriever1777
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A study of females with deletions of the short arm of the X chromosome.
We have undertaken a clinical and molecular study of 25 females with deletions of the short arm of the X chromosome. We have determined the deletion breakpoints, the parental origin and the activation status of the deleted X chromosomes. Genotype-phenotype correlations suggest that the presence of a single copy of the DFFRX gene, previously postulated as a gene involved in the ovarian failure seen in Turner syndrome, may be compatible with normal ovarian function, and that there may be a gene for Turner-like features located in distal Xp22.3.
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No pos
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No neg
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Retriever1778
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An assessment of the relative contributions of redox and steric issues to laccase specificity towards putative substrates.
Laccases catalyze the one-electron oxidation of a broad range of substrates coupled to the 4 electron reduction of O2 to H2O. Phenols are typical substrates, because their redox potentials (ranging from 0.5 to 1.0 V vs. NHE) are low enough to allow electron abstraction by the T1 Cu(II) that, although a relatively modest oxidant (in the 0.4-0.8 V range), is the electron-acceptor in laccases. The present study comparatively investigated the oxidation performances of Trametes villosa and Myceliophthora thermophila laccases, two enzymes markedly differing in redox potential (0.79 and 0.46 V). The oxidation efficiency and kinetic constants of laccase-catalyzed conversion of putative substrates were determined. Hammett plots related to the oxidation of substituted phenols by the two laccases, in combination with the kinetic isotope effect determination, confirmed a rate-determining electron transfer from the substrate to the enzyme. The efficiency of oxidation was found to increase with the decrease in redox potential of the substrates, and the Marcus reorganisation energy for electron transfer to the T1 copper site was determined. Steric hindrance to substrate docking was inferred because some of the phenols and anilines investigated, despite possessing a redox potential compatible with one-electron abstraction, were scarcely oxidised. A threshold value of steric hindrance of the substrate, allowed for fitting into the active site of T. villosa laccase, was extrapolated from structural information provided by X-ray analysis of T. versicolor lac3B, sharing an identity of 99% at the protein level, thus enabling us to assess the relative contribution of steric and redox properties of a substrate in determining its susceptibility to laccase oxidation. The inferred structural threshold is compatible with the distance between two phenylalanine residues that mark the entrance to the active site. Interaction of the substrate with other residues of the active site is commented on.
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No pos
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No neg
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Retriever1779
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Feelings of parental caring predict health status in midlife: a 35-year follow-up of the Harvard Mastery of Stress Study.
In the early 1950s, multiple-choice scores reflecting feelings of warmth and closeness with parents were obtained from a sample of healthy, undergraduate Harvard men who participated in the Harvard Mastery of Stress Study. Thirty-five years later, detailed medical and psychological histories and medical records were obtained. Ninety-one percent of participants who did not perceive themselves to have had a warm relationship with their mothers (assessed during college) had diagnosed diseases in midlife (including coronary artery disease, hypertension, duodenal ulcer, and alcoholism), as compared to 45% of participants who perceived themselves to have had a warm relationship with their mothers. A similar association between perceived warmth and closeness and future illness was obtained for fathers. Since parents are usually the most meaningful source of social support in early life, the perception of parental love and caring may have important effects on biological and psychological health and illness throughout life.
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No pos
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No neg
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Retriever1780
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Pancreatic digestive function after subtotal gastrectomy--evaluation by an indirect method.
Digestive function of 24 patients with Billroth (BII) subtotal gastrectomy and gastrojejunostomy was investigated using an oral pancreatic function test with fluorescein-dilaurate as substrate (FDL-test). The FDL-test after Bll subtotal gastrectomy revealed maldigestion in 75% of the patients. The mean FDL-ratio (normal when higher than 30%) was 21.6 +/- 4.9% in Bll patients, compared with 62.2 +/- 6.9% in healthy controls (p less than 0.001). No correlation between such digestive complaints as dumping and diarrhoea and the FDL-test results was found. Although FDL-test results were abnormal in all patients with chronic pancreatitis, they were also found to be abnormal in 8 patients who did not have chronic pancreatitis. Consequently, the FDL-test cannot be used as a specific test for chronic pancreatitis after gastric operations. Since free fluorescein is normally absorbed after gastric resection, an abnormal FDL-test result indicates impaired pancreatic digestion, possibly due to delayed enzyme and/or poor intraluminal mixing.
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No pos
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No neg
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Retriever1781
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Identification of a novel prostate tumor target, mindin/RG-1, for antibody-based radiotherapy of prostate cancer.
Gene expression analysis showed that a human mindin homologue, mindin/RG-1, is expressed selectively in prostate tissues and that its expression level is elevated in some prostate tumors. Mindin/RG-1 protein expression is maintained in >80% of prostate cancers metastatic to bone or lymph nodes as well as in locally recurrent tumors in androgen-unresponsive patients. In contrast, mindin/RG-1 expression in other normal tissues is significantly lower than that seen in the prostate. A fully human antibody, 19G9, was generated against mindin/RG-1 protein and was shown to accumulate at high abundance in LNCaP tumor xenografts. Conjugates of this antibody with the chelator CHX-A''-DTPA were generated and radiolabeled with either 111In, 90Y, or 86Y. Small animal positron emission tomography imaging with the 86Y-radiolabeled conjugate showed very specific accumulation of the antibody in LNCaP tumor xenografts with clear tumor delineation apparent at 4 hours. The therapeutic efficacy of [90Y]-CHX-A''-DTPA-19G9 was evaluated in mice bearing LNCaP xenografts. A dose-finding study identified a nontoxic therapeutic dose to be approximately 75 microCi. Significant antitumor effects were seen with a single administration of radiolabeled antibody to animals bearing 200 to 400 mm3 tumors. Inhibition of tumor growth was observed in all treated animals over a 49-day period. At 49 days posttreatment, slow tumor growth recurred but this could be prevented for an additional 40-day period by a second administration of a 75 microCi dose at day 49. We conclude that [90Y]-CHX-A''-DTPA-19G9 is a novel antibody conjugate that has considerable promise for therapy of metastatic prostate cancer in androgen-unresponsive patients.
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No pos
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No neg
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Retriever1782
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A technique for rapid isolation of bone marrow mononuclear cells using Ficoll-Metrizoate and the IBM 2991 blood cell processor.
Marrow from seven normal donors and patients has been layered onto Ficoll-Metrizoate (FM) under pressure in the IBM 2991 blood cell processor to isolate the mononuclear cell (MNC) population prior to allogeneic transplantation or cryopreservation. This separation method, which takes less than 90 min, is a further development since our previous report detailing the use of the IBM 2991 to produce a concentrated marrow 'buffy coat' for infusion (Gilmore & Prentice, 1981). By adding FM to the system, marrow stem cells are further concentrated in a small volume with removal of unwanted granulocytes and red blood cells. This facilitates in in vitro treatment of marrow with monoclonal antibodies (Granger et al. 1982) or drugs, for either the selective elimination of malignant cells prior to autologous bone marrow transplantation (BMT), or T lymphocytes in an attempt to prevent graft versus host disease (GvHD) in allogeneic BMT. Five of the seven marrows processed by this procedure have thus far been infused into lethally irradiated recipients with engraftment (allogeneic); the other two marrows have been cryopreserved.
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No pos
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No neg
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Retriever1783
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Association between toenail selenium and risk of acute myocardial infarction in European men. The EURAMIC Study. European Antioxidant Myocardial Infarction and Breast Cancer.
The association between selenium status and risk of acute myocardial infarction was examined in a multicenter case-control study in 10 centers from Europe and Israel in 1991-1992. Selenium in toenails was assessed for 683 nonfatal male cases with first acute myocardial infarction and 729 controls less than 70 years of age. Median toenail selenium content was 0.553 microgram/g for cases and 0.590 microgram/g for controls. After adjustment for age, center, and smoking, the odds ratio for myocardial infarction in the highest quintile of selenium as compared with the lowest was 0.63 (95 percent confidence interval 0.37-1.07, p for trend = 0.08). The observed inverse trend was somewhat stronger when the authors adjusted for vitamin E status (p = 0.05). Analysis stratified for smoking habits showed an inverse association in former smokers (odds ratio for the 75th-25th percentile contrast = 0.63 (95 percent confidence interval 0.43-0.94)), but not in current smokers (odds ratio = 0.97 (0.71-1.32)) or in those who had never smoked (odds ratio = 1.55 (0.87-2.76)). Analysis stratified by center showed a significant inverse association between selenium levels and risk of myocardial infarction for Germany (Berlin) only (75th to 25th percentile odds ratio = 0.62 (95 percent confidence interval 0.42-0.91)), which was the center with the lowest selenium levels. It appears that the increased risk of acute myocardial infarction at low levels of selenium intake is largely explained by cigarette smoking; selenium status does not appear to be an important determinant of risk of myocardial infarction at the levels observed in a large part of Europe.
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No pos
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No neg
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Retriever1784
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Genome-wide association study of maternal genetic effects and parent-of-origin effects on food allergy.
Previous genetic studies of food allergy (FA) have mainly focused on inherited genotypic effects. The role of parental genotypic effects remains largely unexplored. Leveraging existing genome-wide association study (GWAS) data generated from the Chicago Food Allergy Study, we examined maternal genotypic and parent-of-origin (PO) effects using multinomial likelihood ratio tests in 588 complete and incomplete Caucasian FA trios. We identified 1 single nucleotide polymorphism with significant (P < 5×10) maternal effect on any FA (rs4235235), which is located in a noncoding RNA (LOC101927947) with unknown function. We also identified 3 suggestive (P < 5×10) loci with maternal genetic effects: 1 for any FA (rs976078, in a gene desert region on 13q31.1) and 2 for egg allergy (rs1343795 and rs4572450, in the ZNF652 gene, where genetic variants have been associated with atopic dermatitis). Three suggestive loci with PO effect were observed: 1 for peanut allergy (rs4896888 in the ADGB gene) and 2 for any FA in boys only (rs1036504 and rs2917750 in the IQCE gene). Findings from this family-based GWAS of FA provided some preliminary evidence on maternal genotypic or PO effects on FA. Additional family-based studies are needed to confirm our findings and gain new insight into maternal and paternal genetic contribution to FA.
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No pos
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No neg
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Retriever1785
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Chromulinavorax destructans, a pathogen of microzooplankton that provides a window into the enigmatic candidate phylum Dependentiae.
Members of the major candidate phylum Dependentiae (a.k.a. TM6) are widespread across diverse environments from showerheads to peat bogs; yet, with the exception of two isolates infecting amoebae, they are only known from metagenomic data. The limited knowledge of their biology indicates that they have a long evolutionary history of parasitism. Here, we present Chromulinavorax destructans (Strain SeV1) the first isolate of this phylum to infect a representative from a widespread and ecologically significant group of heterotrophic flagellates, the microzooplankter Spumella elongata (Strain CCAP 955/1). Chromulinavorax destructans has a reduced 1.2 Mb genome that is so specialized for infection that it shows no evidence of complete metabolic pathways, but encodes an extensive transporter system for importing nutrients and energy in the form of ATP from the host. Its replication causes extensive reorganization and expansion of the mitochondrion, effectively surrounding the pathogen, consistent with its dependency on the host for energy. Nearly half (44%) of the inferred proteins contain signal sequences for secretion, including many without recognizable similarity to proteins of known function, as well as 98 copies of proteins with an ankyrin-repeat domain; ankyrin-repeats are known effectors of host modulation, suggesting the presence of an extensive host-manipulation apparatus. These observations help to cement members of this phylum as widespread and diverse parasites infecting a broad range of eukaryotic microbes.
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No pos
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No neg
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Retriever1786
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Enhanced ferroelectric phase content of polyvinylidene difluoride fibers with the addition of magnetic nanoparticles.
Polyvinylidene difluoride (PVDF) fibers with continuously dispersed ferrite (Ni 0.5Zn 0.5Fe 2O 4) nanoparticles were prepared by electrospinning from dimethyl formamide (DMF) solutions. The effects of the electrospinning processing conditions and nanoparticle loading on the formation of the alpha, beta, and gamma phases of PVDF were studied using infrared spectroscopy and differential scanning calorimetry. The amount of the ferroelectric beta and gamma phases present in the fibers was found to increase with increased nanoparticle loading. We have shown that the formation of PVDF phases with extended chain conformations can be enhanced by the addition of a well-dispersed nanoparticle phase. At increased nanoparticle loadings, the alpha phase is completely converted to the more extended beta and gamma phases.
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No pos
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No neg
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Retriever1787
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Polymorphism of 2-(5-benzyl-6-oxo-3-phenyl-1,6-di-hydro-pyridazin-1-yl)acetic acid with two monoclinic modifications: crystal structures and Hirshfeld surface analyses.
Two polymorphs of the title compound, C19H16N2O3, were obtained from ethano-lic (polymorph I) and methano-lic solutions (polymorph II), respectively. Both polymorphs crystallize in the monoclinic system with four formula units per cell and a complete mol-ecule in the asymmetric unit. The main difference between the mol-ecules of (I) and (II) is the reversed position of the hy-droxy group of the carb-oxy-lic function. All other conformational features are found to be similar in the two mol-ecules. The different orientation of the OH group results in different hydrogen-bonding schemes in the crystal structures of (I) and (II). Whereas in (I) inter-molecular O-H⋯O hydrogen bonds with the pyridazinone carbonyl O atom as acceptor generate chains with a C(7) motif extending parallel to the b-axis direction, in the crystal of (II) pairs of inversion-related O-H⋯O hydrogen bonds with an R 2 2(8) ring motif between two carb-oxy-lic functions are found. The inter-molecular inter-actions in both crystal structures were analysed using Hirshfeld surface analysis and two-dimensional fingerprint plots.
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No pos
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No neg
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Retriever1788
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A Tale of 2 Techniques: Preoperative Biliary Drainage and Routine Surgical Drainage with Pancreaticoduodenectomy.
Preoperative drainage of an obstructed biliary tree before pancreaticoduodenal resection (PDR) and placement of intraabdominal drains following pancreatic resection have been suggested to be both unnecessary and associated with a higher complication rate. The evidence for and against that practice is presented and analyzed to highlight its risks and benefits. A selective approach on an individual basis for preoperative biliary decompression is advocated, based on multiple factors. Additionally, the evidence for routine use of surgical drains after PDR is critically reviewed and the rationale for routine drainage is made.
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No pos
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No neg
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Retriever1789
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Bone metabolism: a note on the significance of mouse models.
This minireview briefly surveys the complexity of regulations governing the bone metabolism. The impact of clinical studies devoted to osteoporosis is briefly summarized and the emphasis is put on the significance of experimental mouse models based on an extensive use of genetically modified animals. Despite possible arising drawbacks, the studies in mice are of prime importance for expanding our knowledge on bone metabolism. With respect to human physiology and medicine, one should be always aware of possible limitations as the experimental results may not be, or may be only to some extent, transposed to humans. If applicable to humans, results obtained in mice provide new clues for assessing unforeseen treatment strategies for patients. A recent publication representing in our opinion the important breakthrough in the field of bone metabolism in mice is commented in detail. It provides an evidence that skeleton is endocrine organ that affects energy metabolism and osteocalcin, a protein specifically synthesized and secreted by osteoblasts, is a hormone involved. If confirmed by other groups and applicable to humans, this study provides the awaited connection of long duration between bone disorders on one hand and obesity and diabetes on the other.
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No pos
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No neg
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Retriever1790
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Optimum design and depth resolution of lens-sheet and projection-type three-dimensional displays.
The primary purpose of this paper is to propose a comprehensive optimum-design theory of lenticular-sheet three-dimensional pictures. The proposed theory features the use of depth resolution of a 3-D image as the measure of the 3-D picture quality. The optimum parameters in the picture taking process, the optimum lens pitch and the depth-resolution limitation, are discussed. The obtained results are also applicable to a specific type of integral photography and to the projection-type 3-D display including projection-type holography. It is found that the optimum pitch of the lens sheet or the lens-type direction selective screen ranges between 0.1 mm and 0.5 mm in most cases, whereas it ranges between 0.2 mm and 1 mm for the triple-mirror screen.
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No pos
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No neg
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Retriever1791
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Interplay of bacterial toxins with host defence: molecular mechanisms of immunomodulatory signalling.
Mucosal surfaces are protected by a first line of defence termed the innate immune system, which controls the resident microflora to effectively prevent microbial diseases. Inflammatory processes are activated as a consequence of a complex interplay between microbes and host target cells. Many bacterial pathogens have developed mechanisms to avoid host recognition. Some are even able to exploit the immune response through sophisticated interactions with the host signalling cascades in order to increase their replication and propagation. While in the past major emphasis on bacterial protein toxins was directed towards their cytotoxic role, it is increasingly evident that toxins can also modulate various cellular functions at non-cytolytic concentrations. Here, we review important aspects on the molecular mechanisms of immunomodulatory interference by bacterial toxins, with emphasis on the signalling induced in the intestinal epithelium.
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No pos
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No neg
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Retriever1792
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Efficacy and safety study on a new compound associating low and high molecular weight hyaluronic acid in the treatment of hip osteoarthritis.
The combined use of low and high molecular weight hyaluronic acid (HA) has never been reported in the treatment of osteoarthritis (OA). The aim of this paper was to evaluate the efficacy of a new hybrid association of both preparations in patients suffering from hip OA and to compare the results with those obtained retrospectively from a cohort of patients treated with high molecular weight HA. Twenty patients with moderate-severe hip OA (grade II-IV according to Kellgren-Lawrence score) were enrolled in the study group. After clinical and functional evaluation (Visual Analogue Scale [VAS] for pain, Lequesne Index, Harris Hip Score), each participant received an intra-articular ultrasound-guided injection of the new HA compound at baseline and after 40 days. The measures were repeated at three and six months. The data collected were retrospectively compared with those obtained in a cohort of 20 patients, matched for sex, age, and severity of hip OA, treated with high molecular weight hyaluronic acid. The intra-group comparison showed a significant improvement in clinical and functional outcomes at three and six months in both cohorts, while the infra-group comparison showed better results in the patients treated with the study compound at six months (VAS at rest, P <0.04; VAS during activities, P <0.02; Harris Hip Score, P <0.001). The present study is the first which demonstrates that a combination of low and high molecular weight HA is effective and safe in the management of patients suffering from hip OA and provides better therapeutic results in comparison to high molecular weight HA. We may infer that both HA preparations work synergically, enhancing their positive activities.
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No pos
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No neg
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Retriever1793
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Activation of MMP-2 by human GCT23 giant cell tumour cells induced by osteopontin, bone sialoprotein and GRGDSP peptides is RGD and cell shape change dependent.
We show that osteopontin (OPN), bone sialoprotein (BSP) and GRGDSP peptides, in solution, induce activation of metalloproteinase-2 (MMP-2) secreted by human GCT23 giant cell tumour cells. Activation of MMP-2 is RGD sequence dependent, possibly involves anti-alphaVbeta3 integrins, is preceded by a change from spread to rounded cell morphology and is mimicked by the actin depolymerising agent cytochalasin B. Cells that had spread on OPN, BSP and GRGDSP substrata failed to activate MMP-2, but subsequent addition of soluble GRGDSP induced rounding and MMP-2 activation. Activation induced by GRGDSP and cytochalasin B was cell mediated, inhibited by EDTA, tissue inhibitor of metalloproteinase-2 (TIMP-2) and carboxyl terminal MMP-2 consistent with a role for membrane type (MT)-MMP but did not involve urokinase, plasmin or thrombin activity. Activation induced by GRGDSP and cytochalasin B, but not cell rounding, was inhibited by herbimycin A, cycloheximide and actinomycin D, suggesting a role for tyrosine kinases, protein and RNA synthesis, but was not associated with changes in mRNA for MT-MMP-1, MMP-1, MMP-2, TIMP-1 or TIMP-2. GRGDSP and cytochalasin B enhanced levels of membrane-associated pro- and active form MMP-1 and MMP-2 but not MT-MMP-1, stimulated cell surface MMP-1 staining and induced that of MT-MMP-1, MMP-2 and TIMP-2. This was consistent with the possible relocation of constitutive MT-MMP-1 to the cell surface as a prerequisite for subsequent cell surface MMP-2/TIMP-2/MT-MMP-1 complex formation and to the potential induction of conditions favourable for reciprocal cell surface MMP-1/MMP-2 activation. Our data provide a novel insight into interactions between RGD containing bone matrices, GCT cells and MMPs of potential relevance to GCT pathology.
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No pos
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No neg
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Retriever1794
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The social psychology of perception experiments: hills, backpacks, glucose, and the problem of generalizability.
Experiments take place in a physical environment but also a social environment. Generalizability from experimental manipulations to more typical contexts may be limited by violations of ecological validity with respect to either the physical or the social environment. A replication and extension of a recent study (a blood glucose manipulation) was conducted to investigate the effects of experimental demand (a social artifact) on participant behaviors judging the geographical slant of a large-scale outdoor hill. Three different assessments of experimental demand indicate that even when the physical environment is naturalistic, and the goal of the main experimental manipulation was primarily concealed, artificial aspects of the social environment (such as an explicit requirement to wear a heavy backpack while estimating the slant of a hill) may still be primarily responsible for altered judgments of hill orientation.
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No pos
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No neg
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Retriever1795
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Chitosan grafted low molecular weight polylactic acid for protein encapsulation and burst effect reduction.
Chitosan and chitosan-grafted polylactic acid as a matrix for BSA encapsulation in a nanoparticle structure were prepared through a polyelectrolyte complexation method with dextran sulfate. Polylactic acid was synthetized via a polycondensation reaction using the non-metal-based initiator methanesulfonic acid and grafted to the chitosan backbone by a coupling reaction, with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as the condensing agent. The effect of concentration of the polymer matrix utilized herein on particle diameter, ζ-potential, encapsulation efficiency, and the release kinetic of the model protein bovine serum albumin at differing pH levels was investigated. The influence of pH and ionic strength on the behavior of the nanoparticles prepared was also researched. Results showed that grafting polylactic acid to chitosan chains reduced the initial burst effect in the kinetics of BSA release from the structure of the nanoparticles. Furthermore, a rise in encapsulation efficiency of the bovine serum albumin and diminishment in nanoparticle diameter were observed due to chitosan modification. The results suggest that both polymers actually show appreciable encapsulation efficiency; and release rate of BSA. CS-g-PLA is more suitable than unmodified CS as a carrier for controlled protein delivery.
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No pos
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No neg
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Retriever1796
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Adenocarcinoma of the rete testis.
To date, no studies have evaluated adenocarcinoma of the rete testis statistically, because reports have been limited to single cases or series of 2 cases only. Univariate and multivariate analyses on disease-free survival have been performed after combining all data available in the literature with our own. Information about disease-free survival has been collected in 38 patients. As many as 40% of them died within the first year of diagnosis. Three and 5-year disease-free survival was 49% and 13%, respectively. We have not detected any difference in survival between age groups or side of the lesion. Similarly, statistical difference cannot be proved between survival of tumors with nodular infiltrating or cystic growth pattern, although it has been suggested that these two varieties represent different tumor types from a gross and microscopic morphologic point of view. Univariate analysis reveals that tumor stage, tumor size, and therapy may have an influence on survival. Tumors that are organ-confined and small lesions (testicular mass < 5 cm in maximum diameter) behave definitely better than those disseminated at diagnosis or of a bigger size. Surprisingly, tumor size is not associated with tumor stage or histologic growth pattern (nodular infiltrating versus predominantly cystic). With regard to therapy, cases in which RPLND has been performed as part of the therapy behave better in univariate analysis, while patients who receive radiation do worse. Most probably these facts reflect that patients with clearly advanced disease where local control cannot be achieved by surgery tend to undergo palliative treatment by radiation. On the other hand, RPLND tends to be performed in patients in whom there is no evidence of distant spread. Therefore, it would really be the primary stage that would set the prognosis rather than the consequent treatment, and neither radiation therapy nor RPLND would be true independent variables. Similarly, no significant difference is observed when patients receive chemotherapy. Cox's regression analysis reveals size of the testicular tumor as the only independent predictor of survival. Stage at diagnosis does not have an influence by itself and neither does any form of therapy. In this sense, the negative effect of radiotherapy is eliminated. We are aware that the results drawn from a literature review are far from ideal, but there is not enough evidence to suggest an optimal sequence of treatment for this rare malignancy. To date, no effective chemotherapy has been found. Whenever the tumor is resectable, there appears to be merit in an RPLND.(ABSTRACT TRUNCATED AT 400 WORDS)
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No pos
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No neg
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Retriever1797
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Cervical mucins affect the motility of human spermatozoa in vitro.
OBJECTIVE
To test the hypothesis that human cervical mucins affect the motility and hyperactivated motility of human spermatozoa.
DESIGN
SETTING
University hospital.
PATIENT(S)
Healthy donors.
INTERVENTION(S)
Swim-up sperm fractions of normozoospermic semen samples were incubated in the presence of 0 (control) to 1.3 mg/mL of mucins purified from cervical mucus plugs released during labor. Motility analyses were performed at time 0, and after 0.5, 1, 3, and 7 hours.
MAIN OUTCOME MEASURE(S)
Sperm kinematic variables recorded by computer-aided sperm analysis. Hyperactivation was defined as linearity <30%, amplitude of lateral head displacement >7.0 microm, and curvilinear velocity >70 microm/s.
RESULT(S)
A dose-related effect of cervical mucins on sperm motility was found. Mucins at a concentration of 1.3 mg/mL caused an immediate and significant increase in sperm linearity (27%) and straight-line velocity (16%) compared with control samples. During the first 3 hours of incubation, an approximately 25% increase in linearity and straight-line velocity was found; this increase was statistically significant. Effects on the hyperactivation pattern were found as incubation with mucins for 3 and 7 hours significantly reduced the percentage of hyperactivation from 18% to 9%.
CONCLUSION(S)
Cervical mucins increase the percentage of progressively motile sperm and decrease the percentage of sperm that show hyperactivation.
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No pos
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No neg
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Retriever1798
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[Co-delivery of exogenous protein and DNA into mammalian cells with Lactococcus lactis].
AIM
To develop a co-delivery system of exogenous protein and DNA into mammalian cells using Lactococcus lactis (L. lactis).
METHODS
We constructed E.coli-L.lactis shuttle plasmid, pMG36e-RFP/eGFP, containing a L.lactis expression cassette with the cDNA of red fluorescent protein (RFP) gene and a eukaryotic expression cassette with the cDNA of enhanced green fluorescent protein (eGFP), then electrotransformated it into L.lactis cells, and co-cultured with 293T cells to evaluate the role of the system in the improvement of gene delivering efficiency after L.lactis cells were pretreated with glycine. RFP and GFP expressed in 293T cells was monitored by fluorescence microscopy.
RESULTS
Fluorescence microscopy revealed that the RFP and GFP was expressed in 293T cells.
CONCLUSION
The co-delivery system of protein and DNA into mammalian cells using L.lactis was constructed successfully.
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No pos
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No neg
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Retriever1799
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[A retrospective on behaviorism].
This essay regards the behaviorism as a component of the industrial civilization and the formation of science according to it. The power of the objectivistic "Aussenweg" (Husserl) and man's exteriorization are discovered in Skinner's analysis of human behaviour, in the thought of a psychologist who denies human freedom and follows a perspective of external controls. The behaviorism, the instrumentalization of men and of the human reason are connected with the philosophy of Descartes and Carnap. Finally the deficient truth of the behaviorism becomes distinct in the thoughts of a phenomenological "Selbstvertiefung" and a creative "Phänopraxie".
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No pos
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No neg
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