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Ancestral Protein Reconstruction and Circular Permutation for Improving the Stability and Dynamic Range of FRET Sensors.
Small molecule biosensors based on Förster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors. Here, we show how these problems can be overcome using ancestral protein reconstruction and circular permutation. Ancestral protein reconstruction, used as a protein engineering strategy, leverages phylogenetic information to improve the thermostability of proteins, while circular permutation enables the termini of an SBP to be repositioned to maximize the dynamic range of the resulting FRET sensor. We also provide a protocol for cloning the engineered SBPs into FRET sensor constructs using Golden Gate assembly and discuss considerations for in situ characterization of the FRET sensors. | {
"pile_set_name": "PubMed Abstracts"
} |
The influence of gender of the surgeon on surgical procedure preference for breast cancer.
There are few data in the literature with regard to the influence of surgeon gender and the treatment of breast cancer. In this retrospective review we propose to test the hypothesis that male surgeons are just as likely as female surgeons to provide breast-conservative treatment. From 1990 through 1997 2271 women with breast cancer in Cincinnati, Ohio were operated on by surgeons within the TriHealth Corporation. We compared the performance rate of breast conservation therapy (BCT) with the rate of mastectomy in early-stage breast cancer patients between male and female surgeons. Male surgeons were significantly more likely to provide their patients with breast-conserving treatment than their female colleagues for stages 0 and IIb (P < 0.05). Although male surgeons performed more BCT than female surgeons for stages I and IIa the difference was not statistically significant. For the three stages combined there was a 30 per cent greater chance of a patient receiving breast-conserving treatment if she went to a male surgeon (P < 0.05). We conclude that in our institution male surgeons are no more likely to select mastectomy than their female colleagues and there appears to be an increased use of BCT by male surgeons. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis of [111]- and {010}-faceted anatase TiO2 nanocrystals from tri-titanate nanosheets and their photocatalytic and DSSC performances.
[111]- and {010}-faceted anatase nanocrystals with controllable crystal size and morphology were synthesized from tri-titanate H2Ti3O7 nanosheets by hydrothermal reaction. The nanostructures and the formation reaction mechanism of the obtained TiO2 nanocrystals were investigated using XRD, FE-SEM, and TEM. Furthermore, the photocatalytic and dye-sensitized solar cell (DSSC) performances of the synthesized anatase nanocrystals were also characterized. Two types of reactions occur in the formation process of the anatase nanocrystals. One is an in situ topochemical conversion reaction of the layered titanate structure to an anatase structure, and another is the dissolution-deposition reaction on the particle surface, which splits the formed nanosheet-like particles into small TiO2 nanocrystals. The surface photocatalytic activity and the DSSC performance of the anatase nanocrystals are dependent on the crystal facet exposed on the particle surface, which increases in the order of non-facet < [111]-facet < {010}-facet. The increasing order corresponds to the increasing order of the bandgap and energy level of the lowest valence band of the anatase nanocrystals. Furthermore, the facet of the anatase also affects the DSSC performance, which is enhanced in the order of non-facet < [111]-facet < {010}-facet. | {
"pile_set_name": "PubMed Abstracts"
} |
Representative input load of antibiotics to WWTPs: Predictive accuracy and determination of a required sampling quantity.
Predicting the input loads of antibiotics to wastewater treatment plants (WWTP) using certain input data (e.g. prescriptions) is a reasonable method if no analytical data is available. Besides the spatiotemporal uncertainties of the projection itself, only a few studies exist to confirm the suitability of required excretion data from literature. Prescription data with a comparatively high resolution and a sampling campaign covering 15 months were used to answer the question of applicability of the prediction approach. As a result, macrolides, sulfamethoxazole and trimethoprim were almost fully recovered close to 100% of the expected input loads. Nearly all substances of the beta-lactam family exhibit high elimination rates during the wastewater transport in the sewer system with a low recovery rate at the WWTP. The measured input loads of cefuroxime, ciprofloxacin and levofloxacin fluctuated greatly through the year which was not obvious from relatively constant prescribed amounts. The latter substances are an example that available data are not per se sufficient to monitor the actual release into the environment. Furthermore, the extensive data pool of this study was used to calculate the necessary number of samples to determine a representative annual mean load to the WWTP. For antibiotics with low seasonality and low input scattering a minimum of about 10 samples is required. In the case of antibiotics exhibiting fluctuating input loads 30 to 40 evenly distributed samples are necessary for a representative input determination. As a high level estimate, a minimum number of 20-40 samples per year is proposed to reasonably estimate a representative annual input load of antibiotics and other micropollutants. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of different stimulators and a blocker of insulin release on islet Na+, K+-ATPase activity.
The effect of several insulin secretagogues and a blocker upon islet Na+, K+-ATPase activity was studied using rat islet homogenates. None of the agents tested modified the enzyme activity when added directly to the enzyme assay. Activity of Na+, K+-ATPase measured in islets preincubated during 3 min with glucose 3.3, 8 or 16.6 mM, as well as with 15 mM KIC or 1.2 microM somatostatin, did not significantly change. The presence of glucagon (1.4 microM) plus theophylline (10 mM) in the preincubation medium significantly enhanced activity while tolbutamide (1.48 mM) or gliclazide (76 microM) significantly decreased such activity. These results suggest that Na+, K+-ATPase activity would not be a main common step involved in the mechanism by which glucose, KIC, glucagon + theophylline and somatostatin exert their effect on insulin secretion. Conversely, the enzyme might contribute to the stimulatory effect of gliclazide and tolbutamide on insulin release. Such effect would be secondary to the release of some cellular mediator rather than a direct action of these compounds on the enzyme. Such effect would later favor a rise in the cytosolic concentration of calcium which might trigger the release of insulin. | {
"pile_set_name": "PubMed Abstracts"
} |
Minimizing the Number of Edges via Edge Concentration in Dense Layered Graphs.
Edge concentration in dense bipartite graphs is a technique for reducing the numbers of edges and edge crossings in graph drawings. The conventional method proposed by Newbery is designed to reduce the number of edge crossings; however, it does not always reduce the number of edges. Reducing the number of edges is also an important factor for improving the readability of graphs. However, no edge concentration method with the explicit purpose of minimizing the number of edges has previously been studied. In this study, we propose a novel, efficient heuristic method for minimizing the number of edges during edge concentration. We demonstrate the efficiency of the proposed method via a comparison using randomly generated graphs. We find that Newbery's method fails to reduce the number of edges when the number of vertices is large. By contrast, the proposed method achieves an average compression ratio of 47 to 82 percent for all generated graph groups. We also present a real-world application of the proposed method using a causality network of biological data. | {
"pile_set_name": "PubMed Abstracts"
} |
Analysis of clinical misdiagnoses in children treated with enucleation.
To evaluate discordant clinical and pathological diagnoses leading to pediatric enucleations over time. All pathology reports of pediatric enucleation specimens (subjects aged 0 to 18 years) from 1960 to 2008 were reviewed. Specimens with discordant clinical and pathologic diagnoses were further analyzed. Formalin-fixed, paraffin-embedded sections of enucleated eyes of any misdiagnosed cases were reevaluated. Of 729 pediatric patients (746 eyes) who had enucleation from 1960 to 2008, 29 patients (4.0%) and 30 eyes (4.0%) had discordant clinical and pathological diagnoses. The misdiagnosis enucleation rate decreased with each respective decade studied, with the highest rate of 6.5% (18 of 276 eyes) in the 1960s and no misdiagnoses from 1990 to 2008. Of the 369 eyes enucleated for the clinical indication of malignancy, 22 eyes (6.0%) were misdiagnosed in that no evidence of malignancy was found on histopathological examination. Of the 377 eyes enucleated for benign clinical indications, 7 cases (1.9%) were found to be malignant by histopathology. Misdiagnoses leading to pediatric enucleation have decreased during the past 5 decades, likely owing to improved diagnostic techniques. Benign and malignant intraocular conditions can simulate each other, especially retinoblastoma, Coats disease, nematode and bacterial endophthalmitis, panuveitis, and persistent hyperplastic primary vitreous. | {
"pile_set_name": "PubMed Abstracts"
} |
Abnormalities of thyroid function and glucose control in subjects with Rett syndrome.
We have identified subtle abnormalities of thyroid function and glucose control in patients with Rett syndrome. The mean serum total thyroxine (T4) concentration was significantly lower in a group of subjects with Rett syndrome (6.9 +/- 1.5 microgram/dl, n = 34; p < 0.001) than the adult reference range (8.5 +/- 1.75 microgram/dl, n = 200). This differences remained significant even for the 17 subjects not taking anticonvulsants (7.6 +/- 1.5 microgram/dl; p < 0.05 vs. adult reference). The difference was more marked when compared to age-adjusted normals, with 10 subjects having a serum total T4 concentration below normal for age including 3 of 17 of the subjects not taking anticonvulsants. This decrease in serum total T4 concentration was not due to changes in binding proteins as measured by 3,5,3'-triiodothyronine resin uptake, and was associated with a decreased concentration of thyroid-stimulating hormone (1.7 +/- 1.6 mU/l, n = 23 vs. 2.5 +/- 1.0 mU/l, n = 200; p < 0.01). Oral glucose tolerance tests were performed in 10 of the subjects with Rett syndrome. They had a delay in the peak glucose and insulin concentrations. Glucose levels were elevated at 1 and 2 hours (p < 0.05), and insulin levels were elevated at 1, 2, and 3 hours (p < 0.05). Two subjects fulfilled criteria for impaired glucose tolerance. | {
"pile_set_name": "PubMed Abstracts"
} |
Preferences for policy options for cannabis in an Australian general population: A discrete choice experiment.
Policy choices for illicit drugs such as cannabis entail consideration of competing factors such as individual health, societal views about pleasure, and criminal justice impacts. Society must weigh up these factors in determining the preferred cannabis policy; although often cast as a contest between legalisation of cannabis or full prohibition the actual policy choices are not so black and white. This study assessed societal preferences for different cannabis policies and multiple consequences. A discrete choice experiment (DCE) quantified value-based preferences for alternative cannabis policies described by the five key attributes legal status, health harms, criminal justice service costs, rates of cannabis use and purchase location. An online survey was conducted on a population sample of 1020 Australians. The analytical model was based on stated choices for Policy A, B or Current Policy. The results revealed a strong general preference for either civil penalties or legalisation compared to cannabis cautioning (Current Policy) and a strong dislike of criminalising possession and use of cannabis. Results also demonstrate difference in preferences among those with different demographics and beliefs. Understanding these nuances help to quantify the range of preferences held within the population and can be used to inform policy. This is the first known DCE survey applied to the area of illicit drugs policy. It demonstrates the public hold disparate views on the most appropriate status for cannabis offences and they are able to make trade-offs between policy choices and outcomes in complex areas of social policy. | {
"pile_set_name": "PubMed Abstracts"
} |
Higher profile for migraine management spurs boom in DM offerings.
With more employers taking an interest in DM, the economic case has been broadened to include such factors as absenteeism and worker productivity. This trend has prompted many organizations to take a new look at managing migraines. Surveys suggest these debilitating headaches arc responsible for millions in lost productivity, and yet there are several effective treatment strategies. Further, developers believe even modest migraine DM programs can deliver an ROI. | {
"pile_set_name": "PubMed Abstracts"
} |
The thermal grill illusion and what is painful about it.
The 'thermal grill illusion' refers to paradoxical sensations of heat and pain, resulting from simultaneous application of interlaced warm and cold stimuli to the skin. It provides an interesting model of integrative mechanisms in the nervous system, supposed to be relevant in explaining the hypersensitivity found in chronic pain of unclear etiology. The aim of this study is to investigate the perceptual qualities elicited by a reconstruction of the original grill stimulator and to compare these qualities with those elicited by a single temperature thermode of identical dimensions. Healthy participants performed these comparisons by choosing adjectives describing the perceived sensory qualities. We hypothesized that the thermal grill would be perceived as different from a single temperature hot stimulus near pain threshold because of varying sensory qualities. Moreover, the qualities elicited by the grill were expected to be different from the qualities elicited by its single component temperatures. The thermal grill elicited a complex percept, which was distinguished almost perfect from a hot stimulus. The pattern of perceived qualities of the thermal grill differed from single temperature warm and hot stimuli. Pain-related sensations were less present in the grill percept than in a single hot stimulus near pain threshold. The spectrum of qualities of the grill stimulus changed marginally with stimulus duration by decrease of a cold component and concurrent increase of a heat component. In conclusion, the percept of the thermal grill is not simply pain--it can be understood as a metaesthetic percept at the transition from heat to pain. | {
"pile_set_name": "PubMed Abstracts"
} |
[Mechanism of the formation of DNA-protein cross-links during the gamma irradiation of chromatin in aqueous solutions].
The method of gel electrophoresis was used to study DNA-protein cross-link formation in fragmentized chromatin gamma-irradiated in water solutions (0.03%). By introducing changes into irradiation conditions (for instance, the use of different gases saturating the solution and the administration of radical acceptors) and by the subsequent electrophoretic analysis (treatment of the exposed chromatin by dissociating mixtures and enzymes) the authors showed a covalent nature of the cross-links in a radiation-induced DNA-protein complex and found the value of G (a cross-link) to be 0.02. | {
"pile_set_name": "PubMed Abstracts"
} |
Lorazepam.
The nurse administering any BZD--especially lorazepam--to a neonate must be knowledgeable about the drug's effects and risks and must remember that BZDs do not provide analgesia. The sedative effects of lorazepam will increase with concomitant use of opioids. The nurse must be alert for adverse reactions (Table 1). Close monitoring of the neonate's respiratory effort and blood pressure is important. Because of the various reported cases of myoclonus in neonates after lorazepam administration, close observation for seizure activity is imperative. Although lorazepam use may be beneficial in specific instances, administration should be approached with caution in the neonate (especially in the preterm neonate) and other agents considered. | {
"pile_set_name": "PubMed Abstracts"
} |
Cross-reactivity of organs in allograft rejection. Comparison of effect of thyroid allografts on established islet allografts.
The effect of allotransplantation of thyroid or islet allografts into rats with established islet allografts was studied to determine the cross-reactivity of the thyroid and islets in allograft rejection. Islets obtained from cultured neonatal rat (F344) pancreas explants were transplanted bilaterally underneath the kidney capsule of Wistar-Furth rats. After 21 days these allografts did not exhibit signs of rejection. Thyroid (half lobe) from either F344 or Brown Norway rats was transplanted underneath the capsule of the remaining kidney. Transplant of the thyroid from F344 rats resulted in immediate rejection of the islet transplant, whereas transplant of the thyroid from Brown Norway rats was without effect on the islet allograft. This indicates that the thyroid contains immunocompetent cells (cells that present antigen or induce recognition of antigen) that are capable of initiating rejection of established islet allografts. The cytotoxic T-lymphocytes that result are specific for the organ bearing the immunocompetent cells at time of transplantation. | {
"pile_set_name": "PubMed Abstracts"
} |
Quantitative image reconstruction of GaN quantum dots from oversampled diffraction intensities alone.
The missing data problem, i.e., the intensities at the center of diffraction patterns cannot be experimentally measured, is currently a major limitation for wider applications of coherent diffraction microscopy. We report here that, when the missing data are confined within the centrospeckle, the missing data problem can be reliably solved. With an improved instrument, we recorded 27 oversampled diffraction patterns at various orientations from a GaN quantum dot nanoparticle and performed quantitative image reconstruction from the diffraction intensities alone. This work in principle clears the way for single-shot imaging experiments using x-ray free electron lasers. | {
"pile_set_name": "PubMed Abstracts"
} |
'Template-switching': a supramolecular strategy for the quantitative, gram-scale construction of a molecular target in the solid state.
A template-switching strategy based on the modularity of template-directed solid-state synthesis has been successfully utilised to achieve a quantitative, stereospecific solid-state synthesis of a p-[2.2]-cyclophane target in gram quantities. | {
"pile_set_name": "PubMed Abstracts"
} |
The crystal structures of psoralen cross-linked DNAs: drug-dependent formation of Holliday junctions.
The single-crystal structures are presented for two DNA sequences with the thymine bases covalently cross-linked across the complementary strands by 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT). The HMT-adduct of d(CCGCTAGCGG) forms a psoralen-induced Holliday junction, showing for the first time the effect of this important class of chemotheraputics on the structure of the recombination intermediate. In contrast, HMT-d(CCGGTACCGG) forms a sequence-dependent junction. In both structures, the DNA duplex is highly distorted at the thymine base linked to the six-member pyrone ring of the drug. The psoralen cross-link defines the intramolecular interactions of the drug-induced junction, while the sequence-dependent structure is nearly identical to the native Holliday junction of d(CCGGTACCGG) alone. The two structures contrast the effects of drug- and sequence-dependent interactions on the structure of a Holliday junction, suggesting a role for psoralen in the mechanism to initiate repair of psoralen-lesions in mammalian DNA. | {
"pile_set_name": "PubMed Abstracts"
} |
Polysaccharides for vascular cell targeting.
Carbohydrate structures are involved in numerous biological activities such as inflammation, and cell adhesion/migration/proliferation. This gives the rationale for the design of vascular targeted drug delivery systems bearing sugar moieties. For the imaging and treatment of vascular diseases, an overview is presented with polysaccharides targeting vascular components. After a general description of the vasculature and the main blood components, a special emphasis is placed on carbohydrate-based molecules, such as heparin/heparan sulfate, and carbohydrate-binding proteins, such as selectins found in the vascular system. The methods using heparin and heparin analogs in delivery systems applied to vascular components are then described. | {
"pile_set_name": "PubMed Abstracts"
} |
Safety-II and resilience: the way ahead in patient safety in anaesthesiology.
Anaesthesiology is a specialty with a remarkable track record regarding improvements in safety. Nevertheless, modern healthcare poses increasing demands on quality and outcome: more complexity, more patients with increasing risk-factors, more regulation from society concerning quality and outcome and finally more demand of the stakeholders for efficiency. This leads us to ask the question if our traditional way of handling 'risk' and 'safety' will stand the challenges of the future? Most of the success of modern anaesthesiology results from improved technology, pharmacology, training and education, improved systems, focus on human performance as well as standardization and development of guiding information. All of these aspects are crucial and have their relevance for well tolerated and modern practice. But despite all of these achievements, we must face the fact that we still cannot control complex processes by application of linear thinking (standardization). Modern risk-management concepts in other ultra-safe systems such as civil aviation or air traffic control introduced the concept of 'resilience' as well as 'safety-II' in order to deal with the challenges of increasing complex conditions. We are well advised to consider adapting these modern concepts of 'resilience' and 'safety-II' thinking when we want to substantially improve patient safety in anaesthesiology. | {
"pile_set_name": "PubMed Abstracts"
} |
[Antitumor activity of gamma delta T lymphocytes].
Increasing knowledge about the role played by gamma delta T lymphocytes in antitumor immunity is of importance to both the fundamental and clinical sciences. gamma delta T cells are also characterized with reference to theirself neoplastic transformation and development of leukemias or lymphomas with gamma delta fenotype. | {
"pile_set_name": "PubMed Abstracts"
} |
Discrete spacers for photometric characterization of humic acids separated by capillary isotachophoresis.
A group of twenty discrete spacers suitable for photometric characterization of humic acids (HAs) after their isotachophoretic (ITP) separation at pH 10 was found. The spacers, inorganic and organic acids and amino acids of suitable acid-base and migration properties exhibiting no light absorption in the UV region of the light spectrum, made possible to perform this characterization in a sensitive spike mode of the ITP analysis. Using this approach a complex mixture of humic constituents present in a test HA preparation was separated into 22 fractions migrating in the interzonal boundary layers formed by the zones of discrete spacers and 21 fractions mixed with the zones of the spacers. A photometric monitoring of the fractions in the ITP stack at a 405 nm detection wavelength provided an adequate selectivity and sensitivity into the characterization. Relative sizes of the detected fractions of the test HA preparation ranged from 0.2-0.3 to 27.5% (based on the response of the phototometric detector at 405 nm). The fractions representing ca. 0.2-0.3% of the total peak area could be still quantified when 800 ng of the test preparation was loaded onto the ITP column. A typical repeatability of the total area of the detection signal corresponding to humic constituents in the ITP stack was ca. 2.5%. Repeatabilities of the peak areas of the fractions of the humic constituents defined by the spacers ranged from 2 to 6% for the fractions representing 1% or more of the total area and from 8 to 12% for those representing less than 1%. No marks of aggregations of the humic constituents were detected and reproducible ITP profiles (fingerprints) of the studied humic preparation were achieved under the developed working conditions. | {
"pile_set_name": "PubMed Abstracts"
} |
[Effect of an intervention based on virtual reality on motor development and postural control in children with Down Syndrome].
There are few studies on the effect of a virtual reality-based intervention on motor development and postural control in children with Down Syndrome (DS). To determine the effect of a virtual reality-based intervention on motor development and postural control in children with DS. Study with a quantitative approach, with a quasi-experimental design, which included 16 children with DS randomly assigned to an experimental group (GWBB, n = 9) and con trol group (GC, n = 7). Postural control was evaluated by the center of pressure displacement and motor development with TGMD-2. The intervention program was carried out for five weeks, two times per week. The data were subjected to statistical analysis, the Shapiro Wilk test for the sample distribution, and the Student's T-test for the comparison of group means. Significant chan ges were observed in the TGMD-2 Test and its manipulation subtest (p <0.01) respectively. In the rest of the tests, there was an improvement, but no significant differences were observed. A virtual reality-based intervention was effective in GWBB, providing low-impact exercises to improve postural control and thus leading to improved motor skills in children with DS. | {
"pile_set_name": "PubMed Abstracts"
} |
A comparison of three standard methods of identifying mast cells in endobronchial biopsies in normal and asthmatic subjects.
Reported mast-cell counts in endobronchial biopsies from asthmatic subjects are conflicting, with different methodologies often being used. This study compared three standard methods of counting mast cells in endobronchial biopsies from asthmatic and normal subjects. Endobronchial biopsies were obtained from atopic asthmatic subjects (n = 17), atopic nonasthmatic subjects (n = 6), and nonatopic nonasthmatic control subjects (n = 5). After overnight fixation in Carnoy's fixative, mast cells were stained by the short and long toluidine blue methods and antitryptase immunohistochemistry and were counted by light microscopy. Method comparison was made according to Bland & Altman. The limits of agreement were unacceptable for each of the comparisons, suggesting that the methods are not interchangeable. Coefficients of repeatability were excellent, and not different for the individual techniques. These results suggest that some of the reported differences in mast-cell numbers in endobronchial biopsies in asthma may be due to the staining method used, making direct comparisons between studies invalid. Agreement on a standard method is required for counting mast cells in bronchial biopsies, and we recommend the immunohistochemical method, since fixation is less critical and the resultant tissue sections facilitate clear, accurate, and rapid counts. | {
"pile_set_name": "PubMed Abstracts"
} |
Economic burden of hypoglycemia in patients with Type 2 diabetes.
Hypoglycemia is an acute complication of diabetes that increases morbidity, mortality and economic costs of diabetes. It presents major clinical problems for the management of Type 2 diabetes as this disease represents the great majority of all diabetes cases. Hypoglycemia makes it difficult for some individuals to achieve good glycemic control, reduces quality of life and increases the burden of diabetes to healthcare systems. Understanding hypoglycemia risk factors can help patients with Type 2 diabetes to correct and avoid hypoglycemia. Recently, an increased risk of hypoglycemia with intensive glycemic control has been identified as an important problem in optimally controlling blood glucose levels in patients with Type 2 diabetes. | {
"pile_set_name": "PubMed Abstracts"
} |
Structural characterization of the tunnels of Mycobacterium tuberculosis truncated hemoglobin N from molecular dynamics simulations.
The structure of oxygenated trHbN from Mycobacterium tuberculosis shows an extended heme distal hydrogen-bond network that includes Tyr33(B10), Gln58(E11), and the bound O(2). In addition, trHbN structure shows a network of hydrophobic cavities organized in two orthogonal branches. In the present work, the structure and the dynamics of oxygenated and deoxygenated trHbN in explicit water was investigated from 100 ns molecular dynamics (MD) simulations. Results show that, depending on the presence or the absence of a coordinated O(2), the Tyr33(B10) and Gln58(E11) side chains adopt two different configurations in concert with hydrogen bond network rearrangement. In addition, our data indicate that Tyr33(B10) and Gln58(E11) control the dynamics of Phe62(E15). In deoxy-trHbN, Phe62(E15) is restricted to one conformation. Upon O(2) binding, the conformation of Gln58(E11) changes and residue Phe62(E15) fluctuates between two conformations. We also conducted a systematic study of trHbN tunnels by analyzing thousands of MD snapshots with CAVER. The results show that tunnel formation is the result of the dynamic reshaping of short-lived hydrophobic cavities. The analyses indicate that the presence of these cavities is likely linked to the rigid structure of trHbN and also reveal two tunnels, EH and BE, that link the protein surface to the buried distal heme pocket and not present in the crystallographic structure. The cavities are sufficiently large to accomodate and store ligands. Tunnel dynamics in trHbN was found to be controlled by the side-chain conformation of the Tyr33(B10), Gln58(E11), and Phe62(E15) residues. Importantly, in contrast to recently published works, our extensive systematic studies show that the presence or absence of a coordinated dioxygen does not control the opening of the long tunnel but rather the opening of the EH tunnel. In addition, the data lead to new and distinctly different conclusion on the impact of the Phe62(E15) residue on trHbN tunnels. We propose that the EH and the long tunnels are used for apolar ligands storage. The trajectories bring important new structural insights related to trHbN function and to ligand diffusion in proteins. | {
"pile_set_name": "PubMed Abstracts"
} |
Dynamics of the hypoxia-inducible factor-1-vascular endothelial growth factor promoter complex.
Some transactivator-promoter complexes are highly dynamic due to active disruption of the complex by proteolytic or nonproteolytic mechanisms, and this appears to be an important mechanism by which their activity is governed tightly and eventually terminated. However, the generality of these mechanisms is unclear. In this report, we address the dynamics of hypoxia-inducible factor-1 (HIF-1) binding to the vascular endothelial growth factor promoter. HIF-1 is a heterodimeric transcription factor whose activity is triggered by an increase in HIF-1alpha levels in hypoxic cells. A "competition ChIP" assay is employed to demonstrate that HIF-1alpha forms a kinetically stable complex with the native vascular endothelial growth factor promoter that has a half-life in excess of 1 h. Thus, HIF-1 activity does not require rapid proteolytic turnover of the promoter-bound transactivator, nor is the activator-promoter complex constantly disassembled by chaperones. However, we do find that after cessation of the inducing signal, HIF-1 activity is slowly returned to basal levels by proteasome-mediated proteolysis of the promoter-bound HIF-1alpha protein. | {
"pile_set_name": "PubMed Abstracts"
} |
The major surface glycoprotein of simian rotavirus (SA11) contains distinct epitopes.
The polypeptide specificities on monoclonal antibodies previously derived against the SA11 simian, NIC bovine, and Wa human strains of rotavirus were determined by radioimmunoprecipitation of infected cell lysates. All the monoclonal antibodies derived using NIC and Wa were found to be directed against the major component of the inner capsid, while most of the SA11 monoclones were directed against the major outer capsid glycoprotein. When several SA11 glycoprotein-specific monoclonal antibodies were used in competitive binding studies, four distinct epitopes, which correlated with the functional activities of the antibodies, were defined. One epitope appeared most critical for virus neutralization, another was involved to a lesser extent, and the remaining two epitopes seemed to have no role. A possible topographical arrangement of these epitopes is suggested. | {
"pile_set_name": "PubMed Abstracts"
} |
Activity of a newly identified serine protease in CNS demyelination.
We have identified a novel serine protease, myelencephalon-specific protease (MSP), which is preferentially expressed in the adult CNS, and therein, is abundant in both neurones and oligodendroglia. To determine the potential activity of MSP in CNS demyelination, we examined its expression in multiple sclerosis lesions and in two animal models of multiple sclerosis: Theiler's murine encephalomyelitis virus (TMEV) and myelin oligodendrocyte glycoprotein (MOG)-induced experimental allergic encephalomyelitis (EAE) in marmosets. High levels of MSP were present within infiltrating mononuclear cells, including macrophages and T cells, which characteristically fill sites of demyelination, both in multiple sclerosis lesions and in animal models of this disease. The functional consequence of excess MSP on oligodendroglia was determined in vitro by evaluating the effects of recombinant MSP (r-MSP) on oligodendrocyte survival and process number. Application of excess r-MSP resulted in a dramatic loss of processes from differentiated oligodendrocytes, and a parallel decrease in process outgrowth from immature cells. Transfection of oligodendrocyte progenitors with an MSP-green fluorescent protein construct produced similar changes in oligodendrocyte process number. Importantly, r-MSP did not affect oligodendrocyte survival or differentiation towards the sulphatide-positive lineage. We further demonstrate that myelin basic protein, and to a lesser extent myelin oligodendrocyte glycoprotein, can serve as MSP substrates. These studies support the hypothesis that excess MSP, as is present in inflammatory CNS lesions, promotes demyelination. | {
"pile_set_name": "PubMed Abstracts"
} |
[Intracranial aneurysm and coronary ectasia].
Coronary aneurysms are uncommon and can exceptionally be associated with other aneurysmal localizations. A 34 year-old man with a history of aneurysm of the coronary arteries revealed by myocardial infarction without a wave six months earlier, presented cerebral hemorrhage secondary to an aneurysmal rupture of the anterior communicating artery. Other aneurysmal localizations such as the abdominal artery, pulmonary artery, hepatic artery, popliteal artery, coronary venous system or the left ventricle have been associated with coronary artery aneurysm. Only one case of coronary and cerebral aneurysm has been previously reported in the literature in an 8-year-old child with X-linked lymphoproliferative syndrome and EBV-induced infectious mononucleosis. Our case suggests that systemic aneurysmal disease may be a clinical entity and that cerebral angiogram should be discussed in patients with a coronary artery aneurysm. | {
"pile_set_name": "PubMed Abstracts"
} |
Use of temporalis fascia for exposed hydroxyapatite orbital implants.
The hydroxyapatite implant (Bio-Eye, Intergrated Orbital Implant, Inc., San Diego, CA, U.S.A.) has gained increasing popularity as an orbital implant in recent years. Several complications may occur, including infection, exposure, extrusion, and various peg problems. Exposure of the implant appears to be the most common complication, ranging up to 21.6%. Many techniques, including nonsurgical and surgical approaches, have been described to manage these exposures. When surgery is indicated, a patch graft may be required to cover the defect. We report our experience and technique with autogenous temporalis fascia as a patch graft. Autografts such as temporalis fascia are easily obtained, bring about no immunological reaction, and have no risk of infectious transmission. | {
"pile_set_name": "PubMed Abstracts"
} |
Total synthesis and biological evaluation of viscolin, a 1,3-diphenylpropane as a novel potent anti-inflammatory agent.
Total synthesis of viscolin, an anti-inflammatory 1,3-diphenylpropane isolated from Viscum coloratum, employing the Wittig reaction is reported. Key steps in the synthesis of viscolin depend on the selection of protecting groups to maintain the para hydroxyl group that is the most critical chemical structure influencing the biological activity of viscolin and the utilization of microwave-assisted Wittig olefination reaction. Anti-inflammatory potency of the synthetic viscolin, its precursor product 16, and its analogue 17, through their effects on reactive oxygen species (ROS), nitric oxide (NO), and pro-inflammatory cytokine production in leukocytes and microglial cells were evaluated. Excellent inhibition of ROS and NO production in inflammatory cells could confer the synthetic viscolin to be a potent anti-inflammatory agent for the treatment of oxidative stress-induced diseases. | {
"pile_set_name": "PubMed Abstracts"
} |
Mitochondrial DNA mutations and oxidative damage in skeletal muscle of patients with chronic uremia.
Abundant evidence has been gathered to suggest that mitochondrial DNA (mtDNA) sustains many more mutations and greater oxidative damage than does nuclear DNA in human tissues. Uremic patients are subject to a state of enhanced oxidative stress due to excess production of oxidants and a defective antioxidant defense system. This study was conducted to investigate mtDNA mutations and oxidative damage in skeletal muscle of patients with chronic uremia. Results showed that large-scale deletions between nucleotide position (np) 7,900 and 16,300 of mtDNA occurred at a high frequency in muscle of uremic patients. Among them, the 4,977-bp deletion (mtDNA(4977)) was the most frequent and most abundant large-scale mtDNA deletion in uremic skeletal muscle. The proportion of mtDNA(4977) was found to correlate positively with the level of 8-hydroxy 2'-deoxyguanosine (8-OHdG) in the total DNA of skeletal muscle (r = 0.62, p < 0.05). Using long-range PCR and DNA sequencing, we identified and characterized multiple deletions of mtDNA in skeletal muscle of 16 of 19 uremic patients examined. The 8,041-bp deletion, which occurred between np 8035 and 16,075, was flanked by a 5-bp direct repeat of 5'-CCCAT-3'. Some of the deletions were found in more than 1 patient. On the other hand, we found that the mean 8-OHdG/10(5 )dG ratio in the total cellular DNA of muscle of uremic patients was significantly higher than that of the controls (182.7 +/- 63.6 vs. 50.9 +/- 21.5, p = 0.05). In addition, the mean 8-OHdG/10(5 )dG ratio in muscle mtDNA of uremic patients was significantly higher than that in nuclear DNA (344.0 +/- 56.9 vs. 146.3 +/- 95.8, p = 0.001). Moreover, we found that the average content of lipid peroxides in mitochondrial membranes of skeletal muscle of uremic patients was significantly higher than that of age-matched healthy subjects (23.76 +/- 6.06 vs. 7.67 +/- 0.95 nmol/mg protein; p < 0.05). The average content of protein carbonyls in the mitochondrial membranes prepared from uremic skeletal muscles was significantly higher than that in normal controls (24.90 +/- 4.00 vs. 14.48 +/- 1.13 nmol/mg protein; p < 0.05). Taken together, these findings suggest that chronic uremia leads to mtDNA mutations together with enhanced oxidative damage to DNA, lipids, and proteins of mitochondria in skeletal muscle, which may contribute to the impairment of mitochondrial bioenergetic function and to skeletal myopathy commonly seen in uremic patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Water sorption properties of extruded zein films.
Water interactions in extruded zein films were investigated through moisture sorption isotherms. Sorption isotherms of zein products were affected by composition and structure morphology. Zein powder showed moisture sorption hysteresis, which was not observed in extruded samples. Extruded samples held less moisture than zein powder, while films containing oleic acid showed further reduction in moisture uptake. Brunauer, Emmett, and Teller (BET) and Guggenheim, Anderson, and De Boer (GAB) models fitted well the moisture sorption isotherms of zein products. Monolayer values estimated by BET and GAB models were consistent with predictions based on zein structural models. Water vapor permeability (WVP) of zein films was affected by the relative humidity of testing environment. Higher relative humidity resulted in higher WVP. | {
"pile_set_name": "PubMed Abstracts"
} |
Somatic alterations of the NF1 gene in an NF1 individual with multiple benign tumours (internal and external) and malignant tumour types.
Neurofibromatosis type 1 is a common familial cancer syndrome, affecting about 1 in every 4,000 individuals worldwide. We have carried out NF1 gene mutation analysis on DNA isolated from 25 tumours (dermal and plexiform neurofibromas, malignant peripheral nerve sheath tumour, MPNST), obtained at post-mortem from an NF1 patient. Macro and micro sequence alterations of the NF1 gene were studied by dHPLC, microsatellite, RFLP markers and multiplex ligation probe amplification (MLPA). The underlying germline mutation involves a deletion of exons 2 and 3. Of the 25 tumours studied from this patient, characterised somatic mutations were identified in 9 tumours, these were six small deletions (748del T, 2534-2557 del 24bp, 2843delA, 3047-3048 del GT, 4743del G, 7720-7721 delAA), an insertion 649 ins 73 bp, a non-sense mutation R1513X and a single splice site mutation, IVS4C-1 G>A, eight of these represent novel sequence changes in the gene. Evidence for loss of heterozygosity (LOH) was identified in DNA from 7 of the tumours. Each of the tumours analysed contained a different somatic NF1 mutation, indicating that each tumour is the result of an independent somatic event. The somatic mutation detection rate in this study is 64% (16/25), is one of the highest rates in genomic DNA reported so far in a single NF1 patient. Only 68 characterised NF1 somatic mutations have so far been reported and so our data will contribute to NF1 somatic mutational spectrum of the NF1 gene and will be important for understanding the molecular basis of NF1 tumorigenesis. | {
"pile_set_name": "PubMed Abstracts"
} |
Inhibition of HIV-1 protease by short peptides derived from the terminal segments of the protease.
The active HIV-1 protease is a homodimeric enzyme. A beta-sheet consisting of N- and C-terminal segments provides the main driving force for dimerization of the inactive protomers. Several short peptides with sequences derived from the N- and C-termini of the protease were tested for inhibition of protease activity and for inhibition of HIV-1 replication in lymphocytes. Medium inhibitory activity was found with each of the peptides in the enzyme test and no inhibition of the lymphocytes was found up to 200 micrograms/ml. The enzyme tests indicate that HIV-1 protease is the target of the inhibitory action. Synergistic action could not be found with pairs of the peptides derived from the two different termini. Prolonged incubation with one of the peptides increased inhibition indicating a slow dissociation of the protease dimers. No cytotoxic effect of the inhibitors could be found below 200 micrograms/ml. | {
"pile_set_name": "PubMed Abstracts"
} |
Hypertensive pancreatic duct sphincter as a cause of pancreatitis. Successful treatment with hydrostatic balloon dilatation.
Four patients with recurrent episodes of acute pancreatitis, despite surgical sphincteroplasty in three and duodenoscopic sphincterotomy in one, are described. All patients were diagnosed by endoscopic pancreatic sphincter manometry confirming the diagnosis of a hypertensive pancreatic sphincter. Hydrostatic balloon dilation of the pancreatic sphincter was successfully employed as a single therapeutic modality. It is likely that more widespread use of these techniques will lead to an increase in the reported incidence and to a nonsurgical treatment in a condition previously thought to be rare. | {
"pile_set_name": "PubMed Abstracts"
} |
Cellular cholesterol trafficking and compartmentalization.
Cholesterol is an essential structural component in the cell membranes of most vertebrates. The biophysical properties of cholesterol and the enzymology of cholesterol metabolism provide the basis for how cells handle cholesterol and exchange it with one another. A tightly controlled--but only partially characterized--network of cellular signalling and lipid transfer systems orchestrates the functional compartmentalization of this lipid within and between organellar membranes. This largely dictates the exchange of cholesterol between tissues at the whole body level. Increased understanding of these processes and their integration at the organ systems level provides fundamental insights into the physiology of cholesterol trafficking. | {
"pile_set_name": "PubMed Abstracts"
} |
Cortical encoding of timbre changes in cochlear implant users.
Most cochlear implant (CI) users describe music as a noise-like and unpleasant sound. Using behavioral tests, most prior studies have shown that perception of pitch-based melody and timbre is poor in CI users. This article will focus on cortical encoding of timbre changes in CI users, which may allow us to find solutions to further improve CI benefits. Furthermore, the value of using objective measures to reveal neural encoding of timbre changes may be reflected in this study. A case-control study of the mismatch negativity (MMN) using electrophysiological technique was conducted. To derive MMNs, three randomly arranged oddball paradigms consisting of standard/deviant instrumental pairs: saxophone/piano, cello/trombone, and flute/French horn, respectively, were presented. Ten CI users and ten normal-hearing (NH) listeners participated in this study. After filtering, epoching, and baseline correction, independent component analysis (ICA) was performed to remove artifacts. The averaged waveforms in response to the standard stimuli (STANDARD waveform) and the deviant stimuli (DEVIANT waveform) in each condition were separately derived. The responses from nine electrodes in the fronto-central area were averaged to form one waveform. The STANDARD waveform was subtracted from the DEVIANT waveform to derive the difference waveform, for which the MMN was judged to be present or absent. The measures used to evaluate the MMN included the MMN peak latency and amplitude as well as MMN duration. The MMN, which reflects the ability to automatically detect acoustic changes, was present in all NH listeners but only approximately half of CI users. In CI users with present MMNs, the MMN peak amplitude and duration were significantly smaller and shorter compared to those in NH listeners. Our electrophysiological results were consistent with prior behavioral results that CI users' performance in timbre perception was significantly poorer than that in NH listeners. Our results may suggest that timbre information is poorly registered in the auditory cortex of CI users and the capability of automatic detection of timbre changes is degraded in CI users. Although there are some limitations of the MMN in CI users, along with other objective auditory evoked potential tools, the MMN may be a useful objective tool to indicate the extent of sound registration in auditory cortex in the future efforts of improving CI design and speech strategy. | {
"pile_set_name": "PubMed Abstracts"
} |
Gene expression profiling in the liver and lung of perfluorooctane sulfonate-exposed mouse fetuses: comparison to changes induced by exposure to perfluorooctanoic acid.
Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are environmental contaminants found in the tissues of humans and wildlife. They are activators of peroxisome proliferator-activated receptor-alpha (PPAR alpha) and exhibit hepatocarcinogenic potential in rats. PFOS and PFOA are also developmental toxicants in rodents and PFOS has been shown to induce pulmonary deficits in rat offspring. Pregnant CD-1 mice were dosed with 0, 5, or 10mg/kg PFOS from gestation days 1-17. Transcript profiling was conducted on the fetal liver and lung. Results were contrasted to data derived from a previous PFOA study. PFOS-dependent changes were primarily related to activation of PPAR alpha. No remarkable differences were found between PFOS and PFOA. Given that PPAR alpha signaling is required for neonatal mortality in PFOA-treated mice but not those exposed to PFOS, the neonatal mortality observed for PFOS may reflect functional deficits related to the physical properties of the chemical rather than to transcript alterations. | {
"pile_set_name": "PubMed Abstracts"
} |
Adult patients with Prader-Willi syndrome: clinical characteristics, life circumstances and growth hormone secretion.
Prader-Willi syndrome is characterized by a typical clinical phenotype and by a complex genetic basis that includes large deletions, uniparental disomy and imprinting mutations of chromosome region 15q11-q13. This report delineates the clinical characteristics, morbidity and growth hormone secretory status of 19 adults with Prader-Willi syndrome. The patients were 18-34 years of age. Morbidity included marked obesity with body mass index in excess of 30 kg/m2 (grade 1-3 according to WHO), metabolic diseases, sleep apnoea and lipolymphoedema. Severe growth hormone deficiency (GHD) was seen in 38% of the patients, and levels of insulin-like growth factor I were decreased in 87%. Thus, GHD is seen, not only in children with Prader-Willi syndrome, but also in adults with the syndrome. | {
"pile_set_name": "PubMed Abstracts"
} |
Klf10 Gene, a Secondary Modifier and a Pharmacogenomic Biomarker of Hydroxyurea Treatment Among Patients With Hemoglobinopathies.
The klf10 gene could indirectly modify γ-globin chain production and hence the level of fetal hemoglobin (HbF) ameliorating the phenotype of β-hemoglobinopathies and the response to hydroxycarbamide (hydroxyurea [HU]) therapy. In this study, we aimed to evaluate the frequency of different genotypes for the klf10 gene in β-thalassemia major (B-TM), β-thalassemia intermedia (B-TI), and sickle cell disease (SCD) patients by polymerase chain reaction and to assess its relation to disease phenotypes and HU response. This cross-sectional study included 75 patients: 50 B-TM, 12 SCD, and 13 B-TI patients (on stable HU dose). The relation of the klf10 gene polymorphism (TIEG, TIEG1, EGRα) (rs3191333: c*0.141C>T) to phenotype was studied through baseline mean corpuscular volume, HbF, and transfusion history, whereas evaluation of response to HU therapy was carried out clinically and laboratory. The frequency of the mutant klf10 genotype (TT) and that of the mutant allele (T) was significantly higher among B-TM patients compared with those with B-TI and SCD patients. Only homozygous SCD patients for the wild-type allele within the klf10 gene had a significantly lower transfusion frequency. The percentage of HU responders and nonresponders between different klf10 polymorphic genotypes among B-TI or SCD patients was comparable. Although the klf10 gene does not play a standalone role as an HbF modifier, our data support its importance in ameliorating phenotype among β-hemoglobinopathies. | {
"pile_set_name": "PubMed Abstracts"
} |
Second primary malignancies among patients with soft tissue tumors in Sweden.
Survival from soft tissue tumors (STTs) has been improved because of the successful treatment. One of the late sequelae in STT survivors is the development of a second malignancy. The present study aimed at quantifying risks for second malignancies in patients with STTs, and risks for second STTs after other primary malignancies. Adjusted standardized incidence ratios (SIRs), calculated from the Swedish Family-Cancer Database, were used as a measure of risk. Among 6,671 primary STT patients, a total of 650 second malignancies occurred. Besides second STTs, other cancer sites with an increased SIR were the nervous system, endocrine glands, skin (melanoma and squamous cell carcinoma) and prostate; the risk for non-Hodgkin lymphoma (NHL) was also increased. The overall risk of second malignancies decreased in the following order: fibrosarocma (1.63) > myxosarcoma (1.48) > leiomyosarcoma (1.44) > liposarcoma (1.21). An increased risk of second STTs after primary cancers of the bone, ovary, nervous system, cervix, thyroid gland, skin, endometrium, breast, upper aerodigestive tract, and after Hodgkin disease, NHL and leukemia was also noted. This study showed that the incidence of second primary malignancies in patients with STTs was increased, but the SIRs varied among specific cancer sites. Besides therapeutic effects, the associations between STTs and bone and nervous system tumors suggested that cancer syndromes, such as neurofibromatosis type 1 and Li-Fraumeni syndrome, may partly explain the excesses. The associations of STTs with cancers of the skin (squamous cell carcinoma and melanoma) and with NHL may be related to immunodeficiency. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparison of three methods of DNA extraction from cold-smoked salmon and impact of physical treatments.
To compare three bacterial DNA extraction procedures on cold-smoked salmon (CSS) and assess the impact on their efficiency of two physical treatments of the food matrix, ionizing irradiation and freezing. As molecular methods for bacterial detection have become an important analytical tool, we compared bacterial DNA extraction procedures on CSS. Working with frozen and irradiated CSS, we obtained negative responses from samples known to be highly contaminated. Thus, we decided to study the impact of these two physical treatments on bacterial DNA extraction procedures. The efficiency of bacterial DNA extraction directly from the fish matrix suspension was measured by an rpoB PCR-based reaction. The results demonstrated that the DNeasy tissue extraction kit (Qiagen, Courtaboeuf, France) was the most efficient and reproducible method. We also showed that freezing and ionizing irradiation have a negative impact on DNA extraction. This was found probably not to be due to inhibition as the PCR reaction remained negative after adding BSA to the PCR mix reaction. The extraction kit was the most efficient method. Physical treatments were shown to hamper bacterial DNA extraction. Attention must be paid to molecular bacterial detection on food products subject to freezing or to ionizing irradiation. | {
"pile_set_name": "PubMed Abstracts"
} |
Unmyelinated primary afferent fibers in dorsal funiculi of cat sacral spinal cord.
The present study tests the hypothesis that there are numerous unmyelinated primary afferent fibers in cat posterior funiculi. The animals have unilateral dorsal rhizotomies from L6 to Ca3. One week later the axons of both S2 dorsal funiculi are counted. The data indicate that there are approximately 22,500 myelinated and 8,500 unmyelinated axons on the unoperated side and 11,000 myelinated and 3,900 unmyelinated axons on the operated side. On this basis, we suggest that 51% of the myelinated and 54% of the unmyelinated axons in cat dorsal funiculi arise from dorsal root ganglion cells and thus are primary afferent axons. If this is correct, then 71% of the primary afferent axons in the cat dorsal funiculus are myelinated and 29% are unmyelinated. The function of this large group of previously unsuspected fine sensory axons remains to be determined. | {
"pile_set_name": "PubMed Abstracts"
} |
[Diabetes and pregnancy].
Diabetes mellitus during pregnancy could result in severe or fatal complications to mother or the unborn product, like polyhydramnios, preeclampsia, abortion, neonatal asphyxia, macrosomia, stillbirth, and others, therefore is very important the early detection and treatment of diabetes. Gestacional Diabetes Mellitus (GDM) is the carbohydrate intolerance of variable severity first recognized during pregnancy. The screening test consist of 50 g of oral glucose and a plasma glucose measurement at one hour, regardless of the time of the last meal, and this may do in all pregnancies between 24 and 28 weeks of gestation. If plasma glucose level above 140 mg/dl results, a oral glucose tolerance test with 100 g must be done. This is the GDM diagnostic test. The risk factors for gestacional diabetes (older than 30 years of age, obesity, arterial hypertension, glucosury, previous GDM, family history of diabetes, family history of macrosomia) identify only 50% of pregnancies with gestacional diabetes, therefore, is necessary to screen all pregnancies who become pregnant, a strict control before pregnant is indispensable, with aim to slow congenital malformations probability and another complications. Gestacional diabetes prevalence in hispanic women in the U.S.A. is 12.3 percent. Diabetes mellitus prevalence in Mexico is about 2-6 percent. The goal of management of diabetes during pregnancy is the maintainance of fasting plasma glucose 105 mg/dl and 120 mg/dl two hours after meals. Treatment consist in diabetes education, diet with caloric needs calculation, exercise, and occasionally insulin. Is necessary the prenatal monitoring, the supervision of delivery or cesarean metabolic changes, and the postnatal monitoring of the mother and product. | {
"pile_set_name": "PubMed Abstracts"
} |
Venous insufficiency in male workers with a standing profession. Part 1: epidemiology.
Chronic venous insufficiency (CVI) in the occupational population is often poorly recognized. The dimensions of this problem have never been thoroughly investigated in the Netherlands. To study the epidemiology and risk factors of CVI in males with a standing position at work. To develop a simple diagnostic instrument for screening an (occupational) population for CVI. 387 male workers with a standing profession were examined by means of a questionnaire, physical examination, Doppler ultrasound investigation, light reflection rheography and optical leg volume measurements. CVI was present in 29% of the subjects and correlated with age, weight and duration of standing work. Complaints of the legs were reported by 81% of the individuals with CVI but also by 63% of the persons without CVI. The questionnaire had a predictive value of 80% in detecting CVI. CVI was a major problem because of the quantity (29%) and the accompanying complaints. Neither the questionnaire nor other investigative measures proved to be as efficient in diagnosing CVI as physical examination in combination with Doppler ultrasound investigation. | {
"pile_set_name": "PubMed Abstracts"
} |
The value of Bilicheck as a screening tool for neonatal jaundice in term and near-term babies.
To determine the accuracy of Bilicheck in assessing serum bilirubin. To evaluate the effectiveness of Bilicheck as a screening device in a population of jaundiced term and near-term babies. Prospective evaluation of paired Bilicheck measurements and serum bilirubin in 300 babies. There was a strong correlation between Bilicheck and serum bilirubin. The mean difference between Bilicheck and serum bilirubin was -10.7 micromol/l, but the 95% limits of agreement were wide at -80 micromol/l to +60 micromol/l. Bilicheck identified significant jaundice (serum bilirubin above 250 micromol/l) with a sensitivity (95% confidence interval) of 91% (88% to 94%) and specificity of 66% (60% to 71%). The area under the receiver operator characteristic curve was 0.85. There were five false negatives, all of whom had a serum bilirubin below 300 micromol/l. If Bilicheck had been used as a screening device, there would have been a 55% decrease in blood samples taken in these babies. Bilicheck cannot be used to measure serum bilirubin in term and near-term babies with jaundice, but is an effective screening method, which can be used to safely reduce the number of blood tests in these babies. | {
"pile_set_name": "PubMed Abstracts"
} |
Impacts of anti-EGFR monoclonal antibody in prostate cancer PC3 cells.
Epidermal growth factor receptor (EGFR) network appears to be a rich target for prostate cancer. Thus, in this current investigation, to pursue our newly developed anti-EGFR monoclonal antibody (mAb) in prostate cancer, its inhibitory effect was investigated in PC3 cells. The binding specificity of antibody was examined by flow cytometry and immunofluorescence staining. The cultivated cells were treated with various doses of the anti-EGFR mAb at different time points and the cellular and/or molecular impacts were assessed. MTT assay was utilized to examine the cytotoxic effects. Semi-quantitative RT-PCR was used to evaluate the expression of EGFR and some important apoptosis signaling molecules (e.g., MAPK-1, STAT-5, Akt-1 kinase). Flow cytometric and immunofluorescence staining analyses showed that the anti-EGFR mAb can bind to EGFR with high specificity. The results revealed that the anti-EGFR mAb can inhibit cell growth in a dose and time dependent manner. RT-PCR analysis revealed that the binding of anti-EGFR mAb to its receptors can eventually result in downregulation of Akt-1 kinase gene, but not MAPK-1, STAT-5 and EGFR genes. Based on our findings, it can be concluded that Akt-1 is the most important downstream signaling molecules affected by anti-EGFR mAbs. | {
"pile_set_name": "PubMed Abstracts"
} |
Differential calcineurin/NFATc3 activity contributes to the Ito transmural gradient in the mouse heart.
Kv4 channels are differentially expressed across the mouse left ventricular free wall. Accordingly, the transient outward K+ current (Ito), which is produced by Kv4 channels, is greater in left ventricular epicardial (EPI) than in endocardial (ENDO) cells. However, the mechanisms underlying heterogeneous Kv4 expression in the heart are unclear. Here, we tested the hypothesis that differential [Ca2+]i and calcineurin/NFATc3 signaling in EPI and ENDO cells contributes to the gradient of Ito function in the mouse left ventricle. In support of this hypothesis, we found that [Ca2+]i, calcineurin, and NFAT activity were greater in ENDO than in EPI myocytes. However, the amplitude of Ito was the same in ENDO and EPI cells when [Ca2+]i, calcineurin, and NFAT activity were equalized. Consistent with this, we observed complete loss of Ito and Kv4 heterogeneity in NFATc3-null mice. Interestingly, Kv4.3, Kv4.2, and KChIP2 genes had different apparent thresholds for NFATc3-dependent suppression and were ordered as Kv4.3 approximately KChIP2>Kv4.2. Based on these data, we conclude that calcineurin and NFATc3 constitute a Ca(2+)-driven signaling module that contributes to the nonuniform distribution of Kv4 expression, and hence Ito function, in the mouse left ventricle. | {
"pile_set_name": "PubMed Abstracts"
} |
Colocalisation of c-Fos and glucocorticoid receptor as well as of 5-HT(1A) and glucocorticoid receptor immunoreactivity-expressing cells in the brain structures of low and high anxiety rats.
We sought to determine the colocalisation of c-Fos (a marker of neuronal activation) and glucocorticoid receptors (GRs) as well as of 5-HT(1A) and glucocorticoid receptor immunoreactivity-expressing cells (ir) in the dorsomedial prefrontal cortex (M2), dentate gyrus of the hippocampus (DG), and basolateral nucleus of the amygdala (BLA) in low and high anxiety rats (i.e., rats with duration of a freezing response in the conditioned fear test one standard error or more below or above the mean value: low responders (LR) and high responders (HR), respectively). It was found that 1.5 h after a testing session of the conditioned fear test, the LR animals had a higher activity of the cortical M2 area and DG (c-Fos), a higher expression of GRs-ir, as well as an increased number of cells co-expressing c-Fos and GRs-ir in the same brain areas. In the case of HR rats, they had similar expression of c-Fos in the BLA, but a significantly higher concentration of GRs-ir and c-Fos/GR colocalised neurons in the same amygdala nucleus. The pattern of distribution of 5-HT(1A) and GR receptor-ir in LR and HR animals was similar to the c-Fos and GRs-ir expression. LR animals showed a higher density of 5-HT(1A) and GRs-ir in the cortical M2 area and DG as well as an increased number of cells co-expressing 5-HT(1A) and GR-ir in the same brain areas. HR rats had a significantly higher concentration of 5-HT(1A) and GR-ir as well as a greater number of c-Fos/GR protein colocalised neurons in the BLA. The present data add to the arguments for the neurobiological background of differences in individual responses to aversive conditioned stimuli. | {
"pile_set_name": "PubMed Abstracts"
} |
Studies on scavenger receptors under experimental hypercholesterolemia: modulation on selenium supplementation.
Scavenger receptors (SR) are the cell surface proteins that can bind and internalize modified lipoproteins. Because ox-LDL seems to play a key role in foam cell formation during atherogenesis, SR may be critical for pathogenesis of atherosclerosis. The present study was aimed to study the effect of selenium (Se) supplementation on SR, i.e., SRB1 and CD36 under experimental hypercholesterolemia. Male Sprague Dawley rats were divided into three groups and fed on the control diet, high cholesterol diet (HCD), and HCD + Se, respectively, for a period of 4 months. Selenium and reactive oxygen species (ROS) levels were estimated in serum and liver respectively. mRNA expression using RT-PCR and protein expression using ELISA were analyzed for SRB1 and CD36 receptors. Selenium levels decreased whereas ROS levels increased under experimental hypercholesterolemic state. Selenium supplementation (1 ppm), however, diminished the HCD-induced ROS levels. Furthermore, the protein expression of SRB1 was significantly reduced in HCD group in comparison to the control group. On the other hand, HCD-induced increase in CD36 mRNA and protein expression decreased significantly on Se supplementation. In conclusion, CD36 receptors seem to play a pro-atherogenic role under hypercholesterolemic state. Selenium supplementation, in addition, might prove to be a therapeutically valuable approach in near future to limit the adverse effect of hypercholesterolemia. | {
"pile_set_name": "PubMed Abstracts"
} |
The prevalence of long bone fractures in pediatric inflammatory bowel disease.
The association of inflammatory bowel disease (IBD) with decreased bone mineral density is well recognized. In the adult population, up to 50% of IBD patients are reported to have osteopenia, correlating with an increase in the incidence of fractures as compared with controls. The aim of this study was to determine the prevalence of fractures in a pediatric population with IBD as compared with healthy sibling controls (SC). The families of 209 patients with IBD were sent a questionnaire asking them to compare their children with IBD to a healthy sibling (non-IBD). Surveys were returned by 132 of the 209 families (63%). The sample characteristics of this sample closely resembled the overall clinic population for age (mean 14.3 vs 14.7 years), gender (53% vs 59% male) and diagnosis (58.1 vs 57.8 Crohn disease). Completed surveys described 263 children. Of the 132 with IBD 73 (55%) had Crohn disease, 52 (39%) had ulcerative colitis and 7 (6%) had indeterminate colitis. There were 76/132 males (age range, 4-18 years) with IBD and 64/131 males (age range, 1-26 years) in the sibling controls. Mean ages of the IBD sample 14.3 +/-.3 was compared with 13.9 +/- in SC. Of the total group, 73/263 (28%) reported ever having a fracture, 44 (60%) were siblings (SC), and 29 (40%) had IBD. Of the 29 children with IBD, 17 (59%) reported having a fracture after diagnosis including 2 who had fractures both before and after diagnosis. The total number of fractures reported was 96 (55 SC:41 IBD). In this survey, we found no statistically significant difference in the prevalence of fracture in IBD patients compared with their normal siblings. | {
"pile_set_name": "PubMed Abstracts"
} |
Neural functions of bisecting GlcNAc.
Bisecting GlcNAc, a branch structure in N-glycan, has unique functions and is involved in several diseases including Alzheimer's disease (AD). In this review, we provide an overview of the biosynthesis of bisecting GlcNAc and its physiological and pathological functions, particularly in the nervous system where bisecting GlcNAc is most highly expressed. The biosynthetic enzyme of bisecting GlcNAc is N-acetylglucosaminyltransferase-III (GnT-III). Overexpression, knockdown, and knockout of GnT-III have so far revealed various functions of bisecting GlcNAc, which are mediated by regulating the functions of key carrier proteins. GnT-III-deficient AD model mice showed reduced amyloid-β (Aβ) accumulation in the brain by suppressing the function of a key Aβ-generating enzyme, β-site APP-cleaving enzyme-1 (BACE1), and greatly improved AD pathology. Altered BACE1 subcellular localization in GnT-III-deficient cells, from early endosomes to lysosomes, suggests that bisecting GlcNAc serves as a trafficking tag for the movement of modified proteins to an endosomal compartment. For therapeutic application, we have employed high-throughput screening to search for GnT-III inhibitors. These findings highlight the importance of bisecting GlcNAc modification in the nervous system. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors affecting the rate of metmyoglobin accumulation in pre-packaged beef.
Factors affecting the rate of discoloration of pre-packaged beef have been compared quantitatively in a number of experimental animals. Inter-muscular variability is the most important single factor and ranges from the stable M. longissimus dorsi to the unstable M. psoas major, the degree of discoloration of the latter muscle being almost eight times greater after 96 h storage at 0°C. Among other intrinsic factors studied, age post mortem has a slight accelerating effect while pH, within the narrow range exhibited by experimental animals, has no effect. Inter-animal variability also has an effect, but only a slight one. Of the extrinsic factors studied, temperature is most important from a practical standpoint, the degree of discoloration after 96 h storage at 10°C ranging from two to five times that at 0°C, depending on the muscle. Light produces only a minor accelerating effect but UV produces serious discoloration in all muscles within hours, even at 0°C. Slight differences exist between packaging films but these are not commercially significant. | {
"pile_set_name": "PubMed Abstracts"
} |
A study of thirty autosomal single nucleotide polymorphism markers in Hungarian population.
Testing of thirty autosomal single nucleotide polymorphisms were performed in 218 independent Hungarian male and female samples. We applied this system to 24 paternity testing cases including 14 inclusions and 10 exclusions. | {
"pile_set_name": "PubMed Abstracts"
} |
New n-type organic semiconductors: synthesis, single crystal structures, cyclic voltammetry, photophysics, electron transport, and electroluminescence of a series of diphenylanthrazolines.
The synthesis, properties, and electroluminescent device applications of a series of five new diphenylanthrazoline molecules 1a-1e are reported. Compounds 1b, 1c, and 1d crystallized in the monoclinic system with the space groups P2(1)/c, C2/c, and P2(1)/c, respectively, revealing highly planar molecules. Diphenylanthrazolines 1a-1e have a formal reduction potential in the range -1.39 to -1.58 V (versus SCE) and estimated electron affinities (LUMO levels) of 2.90-3.10 eV. Compounds 1a-1e emit blue light with fluorescence quantum yields of 58-76% in dilute solution, whereas they emit yellow-green light as thin films. The diphenylanthrazoline molecules as the emissive layers in light-emitting diodes gave yellow light with a maximum brightness of 133 cd/m(2) and an external quantum efficiency of up to 0.07% in ambient air. Bilayer light-emitting diodes using compounds 1a-1e as the electron-transport layer and poly(2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene) as the emissive layer had a maximum external efficiency of 3.1% and 2.0 lm/W and a brightness of up to 965 cd/m(2) in ambient air. These results represent enhancements of up to 50 times in external quantum efficiency and 17 times in brightness when using 1a-1e as the electron-transport materials in polymer light-emitting diodes. These results demonstrate that the new diphenylanthrazolines are promising n-type semiconductors for organic electronics. | {
"pile_set_name": "PubMed Abstracts"
} |
Bridging the intention-behavior gap for cardiac rehabilitation participation: the role of perceived barriers.
Patients referred to cardiac rehabilitation after an acute coronary syndrome event commonly report strong intention to attend, but at least one-third do not participate. This study explored whether well-documented cardiac rehabilitation barriers (e.g., comorbidities, logistical/time constraints, and low social support) moderate the association between intention to participate and actual program enrollment and attendance. Following referral but prior to commencing a 12-week outpatient cardiac rehabilitation program, 100 patients with acute coronary syndrome completed measures of intention to attend cardiac rehabilitation, perceived cardiac rehabilitation barriers, and social support. Program enrollment and attendance were determined by chart review. Despite high reported intention to attend (M = 6.08/7.00, SD = 1.80), nearly one-in-five did not enroll. Weaker intention to attend (b = 0.46, SE = 0.16, p = 0.004) and greater cardiac rehabilitation barriers (b= -1.67, SE = 0.70, p = 0.017) corresponded to lower program enrollment. Similarly, weaker intention (b = 2.29, SE = 0.50, p < 0.001) and greater barriers (b =-6.19, SE = 1.55, p < 0.001) predicted poorer attendance. Barriers moderated the association between intention to participate and cardiac rehabilitation enrollment (b=-0.60, SE = 0.29, p = 0.037) and attendance (b = -3.12, SE = 1.02, p = 0.003). Perceived cardiac rehabilitation barriers influence whether patients successfully translate their intention to attend into actual program participation. Enhancing self-efficacy to overcome barriers may represent an important intervention target among prospective cardiac rehabilitation patients. Implications for Rehabilitation Patients with acute coronary syndrome report strong intention to attend cardiac rehabilitation upon referral, yet cardiac rehabilitation programs remain underutilized. Assessing and addressing perceived barriers during the transition to cardiac rehabilitation, even when patients present as highly motivated to attend, may be critical to promoting program uptake. Rehabilitation professionals should ask patients about specific barriers to attending cardiac rehabilitation (e.g., financial constraints, transportation problems) and provide individualized solutions (e.g., fee subsidization, home- or web-based programs) to increase participation. | {
"pile_set_name": "PubMed Abstracts"
} |
Variability in electromyographic surface recordings of the human masseter muscle.
Serial registrations of integrated unilateral surface masseter EMG were performed in eight healthy subjects in the rest position, during controlled gentle biting and during maximal clenching at five different sessions in order to analyse the variability. The recording conditions were standardised. The EMG activity for the group did not differ significantly between the sessions at any level but individual variations were great in the rest position both within and between days. Good consistency was found at controlled force levels. Temporally stable measurements of masseter activity which permit quantitative comparisons thus seem possible. | {
"pile_set_name": "PubMed Abstracts"
} |
M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 1. Sensory adaptation to weightlessness and readaptation to one-g: an overview.
Experiments on human spatial orientation were conducted on four crewmembers of Space Shuttle Spacelab Mission 1. This introductory paper presents the conceptual background of the project, the relationship among the experiments and their relevance to a "sensory reinterpretation hypothesis". Detailed experiment procedures and results are presented in the accompanying papers in this series. The overall findings are discussed in this article as they pertain to the following aspects of hypothesized sensory reinterpretation in weightlessness: utricular otolith afferent signals are reinterpreted as indicating head translation rather than tilt, sensitivity of reflex responses to footward acceleration is reduced, and increased weighting is given to visual and tactile cues in orientation perception and posture control. Three subjects developed space motion sickness symptoms, which abated after several days. Head movements, as well as visual and tactile cues to orientation influenced symptoms in a manner consistent with the sensory-motor conflict theory of space motion sickness. Six short duration tests of motion sickness susceptibility, conducted pre-flight, failed to predict sickness intensity in weightlessness. An early otolith-spinal reflex, measured by electromyography from the gastrocnemius-soleus muscles during sudden footward acceleration, was inhibited immediately upon entering weightlessness and declined further during the flight, but was unchanged from pre-flight when measured shortly after return to earth. Dynamic visual-vestibular interaction was studied by measuring subjective roll self-motion created by looking into a spinning drum. Results suggest increased weighting of visual cues and reduced weighting of graviceptor signals in weightlessness. Following the 10 day flight, erect posture with eyes closed was disturbed for several days.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Depression and cardiovascular disease: the end of simple models.
In this editorial, we propose that the association between depression and cardiovascular disease may be conceptualised as a continuous, bidirectional process that originates in youth. The paper byÅberg and colleagues in this issue adds to this literature showing that low cardiovascular fitness at adolescence increases the risk of future depression. | {
"pile_set_name": "PubMed Abstracts"
} |
Concerted action of Smad and CREB-binding protein regulates bone morphogenetic protein-2-stimulated osteoblastic colony-stimulating factor-1 expression.
Bone remodeling depends upon proper osteoblast and osteoclast function. Bone morphogenetic protein-2 (BMP-2) stimulates differentiation of osteoblasts from pluripotent precursors. Osteoclast formation depends on the concerted action of osteoblast-derived receptor activator of NF-kappaB ligand and colony-stimulating factor-1 (CSF-1). BMP-2 stimulates receptor activator of NF-kappaB ligand expression. However, the effect of BMP-2 on CSF-1 expression has not been studied. We investigated the role of BMP-2 in CSF-1 expression in osteogenic C2C12 cells. Incubation of C2C12 cells with BMP-2 supported osteoclastogenesis of spleen cells with a concomitant increase in expression of CSF-1 mRNA and protein. To determine the mechanism, we identified a BMP-responsive element between -627 bp and -509 bp in the CSF-1 promoter. DNase I footprint analysis revealed the presence of consensus Smad binding motif in this region. Electrophoretic mobility shift assay showed BMP-2-stimulated binding of proteins to this motif. Mutation of core sequence as well as its 5'- and 3'-flanking sequences abolished the DNA-protein interaction resulting in inhibition of CSF-1 transcription. Supershift analysis detects the presence of Smads 1, 5, and 4 and the transcriptional coactivator CREB-binding protein in the BMP-responsive element-protein complex. In addition, Smads 1 and 5 alone or in combination with Smad 4 increased CSF-1 transcription. Furthermore, CREB-binding protein markedly increased transcription of CSF-1. These data represent the first evidence that BMP-2 increases the osteoclastogenic CSF-1 expression by a transcriptional mechanism using the canonical Smad pathway and provide a mechanism for BMP-2-induced osteoclast differentiation. | {
"pile_set_name": "PubMed Abstracts"
} |
Arylsulfatase A pseudodeficiency in healthy Brazilian individuals.
Molecular alterations associated with arylsulfatase A pseudodeficiency (ASA-PD) were characterized by PCR and restriction endonuclease analysis in a sample of healthy individuals from Brazil. ASA activity was also assayed in all subjects. Two individuals homozygous for the N350S and 1524+95A<--G mutations were detected, corresponding to a frequency of 1.17% (4 of 324 alleles). The individual frequency of the N350S mutation was 20.7% (71 of 342 alleles) and 7.9% (27 of 342 alleles) for the 1524+95A<--G mutation. The frequency of the ASA-PD allele in our population was estimated to be 7.9%. This is the first report of ASA-PD allele frequency in a South American population. In addition, the methods used are effective and suitable for application in countries with limited resources. All patients with low ASA activity should be screened for ASA-PD as part of the diagnostic protocol for metachromatic leukodystrophy. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of tibial plateau leveling osteotomy on patellar tendon angle: a radiographic cadaveric study.
To determine the effect of tibial plateau leveling osteotomy (TPLO) on patellar tendon angle (PTA) in dogs. Cadaveric radiographic study. Pelvic limb pairs (n=5) obtained from skeletally mature dogs, weighing 22-36 kg. TPLO was performed using a radiolucent jig that allowed for plateau segment rotation to a tibial plateau angle (TPA) of 15 degrees, 6 degrees, and 0 degrees. Before, and at each of the prescribed rotations, PTA was measured by the tibial plateau (PTA(TP)) and common tangent (PTA(CT)) methods with the stifle positioned at 135 degrees of flexion. Linear regression analysis was performed to evaluate the correlation between TPA and PTA. At a mean (+/-SD) TPA of 5.9+/-0.7 degrees, mean+/-SD PTA(TP) and PTA(CT) were 94.1+/-1.6 degrees and 86.8+/-2.5 degrees, respectively. A linear correlation was observed between TPA and PTA(TP) (r=0.85) and between TPA and PTA(CT) (r=0.61). Based on the regression equation of TPA and PTA(CT), a TPA of 12 degrees corresponded to a PTA(CT) of approximately 90 degrees. TPLO to a TPA of 6 degrees reduces PTA to values similar to those recommended when performing tibial tuberosity advancement in dogs with cranial cruciate ligament insufficiency. TPLO may neutralize tibial thrust by modifying PTA as well as decreasing TPA. TPLO to a TPA of 6 degrees may not be necessary to neutralize the cranial tibial thrust according to the plateau rotation based on PTA(CT) measurement. | {
"pile_set_name": "PubMed Abstracts"
} |
Influence of Cotton Root System Size on Tolerance to Rotylenchulus reniformis.
The factors that influence the ability of cotton to minimize yield loss despite parasitism by Rotylenchulus reniformis (i.e., tolerance) were evaluated for 12 cotton genotypes. Reproduction of R. reniformis and total length of the root system were measured under greenhouse conditions, and the relationship of those variables to yield loss caused by R. reniformis in infested fields was evaluated. Values for nematodes per gram of root and root length were standardized by setting the genotype with greatest value as 100% and then calculating a percentage for each genotype. There was significant variability among genotypes in yield loss, resistance, and root length. Average yield loss for the genotypes ranged from 10.4% for IAC 26RMD to 43.2% for IMACD 5675B2RF. The least nematode reproduction was on IAC 26RMD, which had 49.6% of the reproduction on the susceptible check, Deltapine 16. The genotype with the shortest total root length was 34% less than the genotype with the greatest length. There was a significant linear relationship between percentage yield loss caused by R. reniformis and root length and nematodes per gram of root, both expressed as a percentage of the maximum, represented by the following equation: Yield loss (%) = 16.1258 - 0.1918*(% maximum root length) + 0.3728*(% maximum eggs + vermiform/g of roots). We conclude that tolerance to R. reniformis in cotton is influenced by the size of the root system and the parasitic load on the plant (nematodes per gram of root). Management approaches that increase root growth may lower the parasitic load, thereby reducing losses in cotton to R. reniformis. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolated exercise-induced rhabdomyolysis of brachialis and brachioradialis muscles: an atypical clinical case.
OBJECTIVE AND PATIENT: To report an atypical case of exercise-induced bilateral brachialis and brachioradialis rhabdomyolysis in a 25-year-old woman. Persistent focal muscle pain, atypical by its duration and intensity, even after moderate exercise, should prompt the search for rhabdomyolysis and discuss the possibility of acute compartment syndrome. MRI images can validate the muscle edema. Progressive and adapted training as well as respecting individual limits are necessary measures to prevent rhabdomyolysis. | {
"pile_set_name": "PubMed Abstracts"
} |
Modalities for treatment of antisperm antibody mediated infertility: novel perspectives.
Immunoinfertility because of antisperm antibodies (ASA) is an important cause of infertility in humans. The incidence of ASA in infertile couples is 9-36% depending on the reporting center. Early claims regarding the incidence and involvement of ASA in involuntary infertility were probably overemphasized, which has resulted in subsequent confusion, doubt, and underestimation of their clinical significance. No immunoglobulin that binds to sperm should be called an antisperm antibody in a strict sense unless it is directed against a sperm antigen that plays a role in fertilization and fertility. ASA directed against the fertilization-related antigens are more relevant to infertility than the immunoglobulins that bind to sperm associated antigens. Several methods have been reported for treatment of immunoinfertility. These include: immunosuppressive therapies using corticosteroids or cyclosporine; assisted reproductive technologies such as intrauterine insemination, gamete intrafallopian transfer, in vitro fertilization, and intracytoplasmic sperm injection; laboratory techniques such as sperm washing, immunomagnetic sperm separation, proteolytic enzyme treatment, and use of immunobeads. Most of the available techniques have side effects, are invasive and expensive, have low efficacy, or provide conflicting results. Recent findings using defined sperm antigens that have a role in fertilization/fertility have provided animal models and innovative novel perspectives for studying the mechanism of immunoinfertility and possible modalities for treatment. The better understanding of local immunity and latest advances in hybridoma and recombinant technologies, proteomics and genomics leading to characterization of sperm antigens relevant to fertility will help to clarify the controversy and to establish the significance of ASA in infertility. | {
"pile_set_name": "PubMed Abstracts"
} |
Fabrication of hollow metal oxide nanocrystals by etching cuprous oxide with metal(II) ions: approach to the essential driving force.
Hollow metal oxide nanocrystals were prepared by etching cuprous oxide with metal ions and were applied as photoelectrodes. As a hard template, polyvinylpyrrolidone stabilized cuprous oxide (PVP-Cu2O) and non-stabilized cuprous oxide (nPVP-Cu2O) were synthesized by a precipitation method. Hollow iron oxide and cobalt oxide nanocrystals with a truncated octahedral morphology were fabricated by an etching reaction with transition metal(II) ions (Fe(2+) or Co(2+)). In the etching reaction process, a cationic exchange reaction occurs between the divalent metal ion and Cu(+) due to the higher Lewis acidity. Facet selective etching of cuprous oxide has been observed during the ionic exchange reaction of Cu(+) and O(2-) ions in PVP-Cu2O complexes with transition metal(II) ions (Fe(2+) or Co(2+)) at the surface of a (110) facet. Amorphous states of hollow metal oxide products were annealed to form α-Fe2O3 (hematite) and Co3O4 and their crystal structure was examined with X-ray diffraction and HR-TEM. The optical absorption behavior of semiconductor nanocrystals was measured with UV-vis spectroscopy to define band gap energy. The hollow hematite structure has a 2.08 eV band gap and Co3O4 (Co(II,III) oxide) has a 1.80 eV indirect band gap. Using these hollow nanocrystals, a metal oxide monolayer film was fabricated with a secondary growth approach and was studied for its photocatalytic properties. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparison of the binding and functional actions of angiotensin agonists in clone 9 cells: additional evidence for angiotensin II receptor heterogeneity.
The effects of the angiotensin-II (AII) agonists and antagonists on both 125I-SARILE binding and phosphoinositol (PI) accumulation in clone 9 cells were examined. Clone 9 cells, which are derived from rat liver, have been shown to respond to AII agonists with an increase in PI accumulation which is inhibitable by Sar1,Ile8-AII (SARILE) and DUP-753 but not PD-123319, suggesting that they possess the AT1 subtype of AII receptor. The present results confirmed these properties. The order of potency of AII agonists was AII > AIII > AI. Clone 9 cells also possessed binding sites for 125I-SARILE. The majority of these were AT1 type receptors, although a small number of AT2 receptors may also have been present. The order of potency of AII agonists in inhibiting 125I-SARILE binding was AII >> AIII = AI. The difference in rank order of potency between the functional and binding assay was due to AIII being much less potent in the binding assay than the functional assay. Since the potency of AIII relative to AII was lower than that at either AT1 or AT2 subtypes of AII receptor, these data suggest that an additional subtype, with selectively low affinity for AIII, exists. | {
"pile_set_name": "PubMed Abstracts"
} |
Contributions to the basic problems of complexometry-XXV Determination of rare earths and phosphate without separation.
A new method for coraplexometric determination of rare earths (RE) and phosphate without prior separation is described. It is based on indirect determination of RE by back-titration of an excess of DTPA with zinc solution, with Xylenol Orange as indicator. After the titration an excess of La-EDTA complex solution is added and the solution is titrated again with zinc at 40-50 degrees . During this titration lanthanum is displaced from its complex and precipitated as phosphate: LaY(-) + Zn(2+)+ PO(4)(3-) = LaPO(4) + ZnY(2-). The consumption of zinc solution corresponds to the amount of phosphate. | {
"pile_set_name": "PubMed Abstracts"
} |
Use of the ARG7 gene as an insertional mutagen to clone PHON24, a gene required for derepressible neutral phosphatase activity in Chlamydomonas reinhardtii.
In Chlamydomonas reinhardtii, transforming DNA apparently integrates at random locations in the nuclear genome and generates a high number of mutants by gene inactivation. Twenty-four phoN mutants lacking the derepressible neutral (DN) phosphatase activity were isolated following transformation of the cw15arg7 strain with plasmid pASL harbouring the ARG7 gene encoding argininosuccinate lyase. In all mutants resulting from the transformation with linearised pASL, a functional ARG7 copy was found to be closely linked to a phoN mutation but additional ARG7 copies were present elsewhere in the genome. Of the 13 mutants submitted to allelism analysis, four were allelic or tightly linked to the previously isolated MNNG-induced phoN mutants (phoN2, phoN3, phoN24), the remaining mutants were distributed among seven additional loci. To learn more about the function of the genes involved in DN phosphatase production, we cloned PHON24 by plasmid rescue and screening of a wild-type genomic library. One clone complemented the phoN24 mutation in cotransformation experiments, as did several subcloned fragments. In all phoN24+ transformants, the DN phosphatase activity was 2-3 times lower than in the wild-type strain but about 10 times higher than in the untransformed control. In wild-type, PHON24 transcript accumulation was independent of inorganic phosphate deficiency. The transcripts were present in the MNNG-induced phoN24 mutant but were lacking in the two insertional phoN24 mutants. Insertional mutagenesis has thus permitted the isolation of novel mutants which were missing after induction with a chemical mutagen and the cloning of a gene which is probably involved in the regulation of the DN phosphatase. | {
"pile_set_name": "PubMed Abstracts"
} |
alpha-1 Adrenergic receptors stimulation induces the proliferation of neural progenitor cells in vitro.
The proliferation of neural progenitor cells (NPCs) is regulated by classical neurotransmitters such as dopamine, serotonin and acetylcholine, via its own receptors. Previous studies have reported that the depletion of L-norepinephrine decreases the proliferation of NPCs in the adult rat hippocampus and it has been suggested that L-norepinephrine regulates the proliferation of NPCs. However, it remains unknown whether or not adrenergic receptors are involved in the increased proliferation of NPCs. In the present study, an MTT cell proliferation assay was carried out in order to investigate the roles played by adrenergic receptors in the proliferation of NPCs. We demonstrated that L-epinephrine enhanced the proliferation of embryonic NPCs in vitro. In addition, the alpha-1 adrenergic receptor agonist L-phenylephrine was found to enhance the proliferation of NPCs, whereas an alpha-adrenergic antagonist and selective alpha-1 antagonists significantly inhibited cell proliferation increases induced by L-epinephrine and L-phenylephrine. These results suggest that stimulation with alpha-1 adrenergic receptors induces the proliferation of embryonic NPCs. | {
"pile_set_name": "PubMed Abstracts"
} |
Urinary Biomarkers in Overactive Bladder: Revisiting the Evidence in 2019.
In overactive bladder (OAB), after an initial outbreak of research, it is more consensual that biomarkers may be better used to phenotype patients. Herein, we revisit this topic, including some of the most promising biomarkers. To provide a comprehensive analysis of the actual role of biomarkers in OAB. A PubMed-based literature search was conducted, including the most relevant articles published in the last 15 yr, on nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), adenosine triphosphate (ATP), genomics, and microbiota as OAB biomarkers. Articles with no full text available or not written in English were excluded. Additional reviews were included. Urinary NGF, BDNF, and ATP are increased in many OAB patients. These biomarkers can help identify OAB phenotypes and select the ideal candidates for new therapies directed to neurotrophic and purinergic pathways. Circulating urinary miRNA may be useful for establishing the ideal moment for bladder outlet obstruction relief and will eventually lead to the development of therapeutic agents that inhibit or reverse fibrotic pathways in the bladder. Urinary microbiota seems to be related to OAB symptoms, in particular urgency urinary incontinence, and may have strong implications in the prevention, diagnosis, and treatment of OAB. In the future, physicians may consider the use of biomarkers to identify distinct OAB phenotypes, with distinct causal mechanisms, selecting patients for specific target therapies with expected better outcomes. Overactive bladder biomarkers can be useful for phenotype patients and for selecting more effective target therapies. | {
"pile_set_name": "PubMed Abstracts"
} |
Risk factors for infection with plasmid-mediated high-level tetracycline resistant Neisseria gonorrhoeae.
This study was done to determine whether the increase in high-level tetracycline resistant Neisseria gonorrhoeae (TRNG) was associated with increased tetracycline use. From 547 persons with positive cultures seen consecutively at a sexually transmitted disease (STD) clinic, 51 (9%) isolates were resistant to tetracycline. Of these 51 isolates, 37 (73%) had high-level resistance (TRNG) which was mediated by the tetM determinant located on a 25.2-megadalton plasmid. Women were twice as likely as men to have TRNG. Previous visits to an STD clinic and oral antibiotic use for a sexually transmitted disease within a one to five month period were used as surrogates for prior tetracycline use. Patients who had been to an STD clinic were almost twice as likely to have TRNG (RR = 1.9, 95% CI: 1.01, 3.46), and those who took an oral antibiotic had a relative risk of 1.8. The authors postulate that previous tetracycline use selects for tetM-containing microorganisms in the genitourinary tract that, at the time of gonococcal infection, have the ability to transfer the determinant to N. gonorrhoeae. The above findings might have implications for modifying the current Centers for Disease Control (CDC) recommendation to prescribe tetracycline for suspected Chlamydia infection among patients with gonorrhea. | {
"pile_set_name": "PubMed Abstracts"
} |
The patent ductus arteriosus as a source of recurrent peripheral embolisations.
A patient with a multiple peripheral embolisation of unknown origin is presented. Because of her extreme obesity, some diagnostic procedures could not be performed (CAT), and some were performed with great difficulty (conventional ECHO, DSA of the aorta). Transesophageal echocardiography was the key procedure in the diagnosis of the floating thrombotic mass in the descending aorta. A surgical operation was performed, and a thrombus was found in the aortic orifice of the hemodynamically insignificant patent ductus arteriosus. The patient has now been 18 months in good condition and free of thromboembolic events. | {
"pile_set_name": "PubMed Abstracts"
} |
Pathogenesis of angiopathy in diabetes.
Hyperglycaemia as a common feature of diabetes mellitus is a cause of different pathogenic mechanisms influencing endothelial function. Oxidative stress is one of the main causative factors inducing endothelial dysfunction and changes in plasma protein or platelet function. In type 2 diabetes mellitus, a combination of hyperglycaemia together with dyslipidaemia, obesity and other factors may accelerate the process of glycoxidation and lipid oxidation, causing an early impairment of the vessel wall or properties of circulating blood. This induces hypercoagulability characterised by impaired fibrinolysis and hyperaggregability. The initial functional changes are later substituted by morphologically impaired structure of the blood capillaries (microangiopathy) or arteries (macroangiopathy). The latter represent advanced atherosclerosis when typical plaques are formed. Failure of protective scavenger mechanisms is one possible explanation of vessel wall pathology in diabetes. | {
"pile_set_name": "PubMed Abstracts"
} |
A structural study of self-assembled chitosan-based sponge materials.
Uncontrolled dissolution in solvent media is a key challenge related to the utility of chitosan composite materials. Thermal annealing offers a solution to address this problem. However, conventional characterization methods pose limitations regarding key structural features, especially for carbohydrate materials that possess similar biopolymer components. Herein, self-assembled chitosan-based sponges were prepared with and without annealing to compare their structural and physicochemical properties. The utility of Raman micro-imaging is reported with dye probe etching as an effective and facile method to reveal structural features for chitosan-based composite materials, before and after thermal annealing. We proposed that such composites undergo a structural change from a loosely packed to a more densely packed structure. As well, the multi-functional role of polyethylene oxide in the composites and the potential role of solvent etching was evaluated. The improved stability of the treated composites reveals their potential utility for applications in aqueous media. | {
"pile_set_name": "PubMed Abstracts"
} |
[FGF2 signaling pathway components in tissues of the posterior eye sector in the adult newt Pleurodeles waltl].
The FGF2 signaling pathway components in tissues of the posterior wall in the normal and regenerating eye of the adult Pleurodeles waltl newt were detected for the first time. The fgf2 gene expression was found in the retina, retinal pigment epithelium, and choroid using polymerase chain reaction (PCR). A high homology of the mRNA nucleotide sequence of the most conservative fgf2 gene region in the P. waltl with the fgf2 orthologs in other vertebrates was proved. The Fgf2 protein aminoacid sequence of the P. waltl newt demonstrates even more homology with this growth factor in other vertebrates. The Fgf2 protein with a molecular weight 35 kDa was found in the studied eye tissues using Western blot hybridization. Localization of the Fgf2 protein and its Fgfr receptors was immunohistochemically studied in the pigment epithelium, choroid, central and growth retina regions of the newt native eye, and in the connective cilium of photoreceptors. Using real-time PCR and immunohistochemistry methods, it was found that the fgf2 gene down-regulation and a decrease in the intensity of the immunochemical reaction of its protein product (Fgf2) occur in the early period after the retina removal (in 4-8 days) (as compared with those in the same department of the unoperated eye). | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of motion sickness susceptibility by motion sickness susceptibility questionnaire in adolescents with idiopathic scoliosis: a case-control study.
Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine, with unknown origin. Some studies have noted impaired postural balance in AIS, in particular, difficulty to manage situations with sensory conflict. The motion sickness susceptibility can be secondary to a sensory conflict, for example, between visual and vestibular information. Our hypothesis is: patients with AIS have difficulty in managing situations with sensory conflict and therefore have increased motion sickness susceptibility. The purpose of this study was to evaluate in AIS subjects by evaluating their susceptibility to motion sickness, as compared to a control group. We conducted an analysis of data on motion sickness susceptibility collected prospectively from 2012, with the B score of motion sickness susceptibility questionnaire. This evaluation was completed for 65 adolescents (age 14.5 ± 1.6 year) with major right thoracic AIS (Cobb = 40.7° ± 13.1°) and 71 matched controls (14.6 ± 1.6 year). Adolescents with major right thoracic AIS were more susceptible to motion sickness (B score = 5.3 ± 5.8) than controls (B score = 3.4 ± 3.7) with significant difference (p = 0.025). We interpret our results suggesting there is difficulty for patients with AIS to manage situations with sensory conflict. Previous studies focusing on situations with sensory conflict in AIS have required sophisticated technology. They are not accessible for routine patient management. Our research shows the same result with simple, non invasive, low-cost and quick method: B score of motion sickness susceptibility questionnaire. | {
"pile_set_name": "PubMed Abstracts"
} |
Novel influenza A (H1N1)-associated encephalopathy/encephalitis with severe neurological sequelae and unique image features--a case report.
Since the outbreak of novel influenza A (H1N1) in 2009, various neurological complications have been cited. We described a male patient with H1N1-associated encephalopathy/encephalitis presenting with severe neurological symptoms and signs. Residual neurological sequelae were dominant. This is the first report of extensive cortical-subcortical necroses over the bilateral frontal-parietal areas based on an MRI study. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparative evaluation of laboratory developed real-time PCR assays and RealStar(®) BKV PCR Kit for quantitative detection of BK polyomavirus.
Quantitative, viral load monitoring for BK virus (BKV) by real-time PCR is an important tool in the management of polyomavirus associated nephropathy in renal transplant patients. However, variability in PCR results has been reported because of polymorphisms in viral genes among different subtypes of BKV, and lack of standardization of the PCR assays among different laboratories. In this study we have compared the performance of several laboratory developed PCR assays that target highly conserved regions of BKV genome with a commercially available, RealStar(®) BKV PCR Kit. Three real-time PCR assays (i) VP1 assay: selected from the literature that targets the major capsid protein (VP1) gene (ii) VP1MOD assay: VP1 assay with a modified probe, and (iii) BKLTA assay: newly designed assay that targets the large T antigen gene were assessed in parallel, using controls and clinical specimens that were previously tested using RealStar(®) BKV PCR Kit (Altona Diagnostics GmbH, Hamburg, Germany). Nucleic acid from all samples were extracted using the QIA symphony virus/bacteria kit on an automated DNA extraction platform QIA symphony SP (Qiagen). Primer and probe concentration, and reaction conditions for laboratory developed assays were optimized and the limit of detection of different assays was determined. Positive control for laboratory developed BK assays was prepared through construction of a plasmid carrying respective amplicon sequences. The 95% detection limit of VP1, VP1MOD and BKLTA assays were 1.8×10(2), 3×10(3) and 3.5×10(2) genomic copies/ml, respectively, as determined by Probit regression analysis of data obtained by testing a dilution series of a titered patient specimen, using RealStar(®) BKV PCR Kit. The inter-assay and intra-assay, coefficient of variations of these assays using calibrated, plasmid standards were <1%. All assays, including the RealStar(®) BKV PCR assay, were highly specific when tested against a panel of external proficiency specimens containing both BK and JC viruses. All assays, except the VP1MOD assay determined BK viral load in proficiency specimens within the same log values. With reference to results obtained by RealStar(®) BKV PCR assay, the sensitivity and specificity of different assays tested in 116 serum specimens submitted for BK viral load assay were 91% and 97% for VP1 assay, 88% and 97% for VP1MOD assay, and 97% and 98% for BKLTA assay, respectively. BK Viral load in positive specimens determined by various assays was highly correlated (R(2)>0.97), based on linear regression analysis. The performance characteristics of the newly designed, BKLTA assay were highly comparable to RealStar(®) BKV PCR assay, and can be used for routine detection and viral load monitoring of BKV in a cost-effective manner. | {
"pile_set_name": "PubMed Abstracts"
} |
Basal and infection-induced levels of heat shock proteins in human aging.
Heat shock proteins (Hsp) are ubiquitously expressed proteins, which are highly inducible by a variety of stressful stimuli. As organisms age, various denatured proteins such as proteins modified by oxidation have been detected. Such abnormal proteins might serve as stress signals for the induction of Hsp, which plays indispensable roles in protecting proteins from denaturation. Although it is well known that the heat shock induced expression of Hsp decreases with age, little attention has been given to the unstimulated, basal levels of Hsp. Therefore, a study was performed to examine the expression pattern of various Hsp with aging, under normal physiological conditions in human peripheral blood cells. The basal levels of Hsp32, Hsp70 and Hsp90 increased significantly with age in controls but not patients. Moreover, the levels of Hsp32, Hsp70, Hsp90, but not Hsp27 correlated positively among each other, indicating both common and different regulatory mechanisms. Higher levels of Hsp32, Hsp70 and Hsp90 were noticed in patients with inflammation, a commonly occurring natural stimulant of Hsp production, compared to control subjects. The production of Hsp appeared to be related to the circulating levels of C-reactive protein and cytokines. | {
"pile_set_name": "PubMed Abstracts"
} |
Delayed treatment of bladder outlet obstruction after sling surgery: association with irreversible bladder dysfunction.
Our urethrolysis cohort demonstrated an unusual delay time to surgical treatment of bladder outlet obstruction. We determined whether urethrolysis outcomes, ie persistent bladder symptoms, were associated with time between sling and urethrolysis surgeries. Retrospective analysis of all patients who underwent urethrolysis for post-sling voiding dysfunction between June 1997 and June 2002 was performed. We excluded from study 6 patients with a known history of overactive bladder symptoms, neurogenic bladder dysfunction and use of anticholinergic pharmacotherapy before stress incontinence surgery. The remaining 15 patients were stratified into 2 outcomes groups based upon the absence or presence of post-urethrolysis bladder storage symptoms. Patients (7) in group 1 have no current bladder symptoms. Patients (8) in group 2 still require anticholinergic drug therapy for significant bladder symptoms of frequency and urgency. Data collected for the 2 groups included mean age, existence of urinary retention before urethrolysis, mean time to urethrolysis in months, urethrolysis outcome based upon subjective bladder symptoms and followup duration. For comparison of mean age between groups the standard t test was used. Fisher's exact test was used to compare frequency of urinary retention before urethrolysis between groups. Lastly the Mann-Whitney U test was conducted to compare time to urethrolysis between groups. All statistical analyses were conducted using the SPSS software package (SPSS, Inc., Chicago, Illinois). There was no statistically significant difference between the groups with respect to age or frequency of urinary retention before urethrolysis. Time to urethrolysis for the whole cohort ranged from 2 to 66 months. Mean followup after urethrolysis was 17.3 +/- 22.9 months. Comparison of mean time between incontinence and urethrolysis surgeries between group 1 (9.0 +/- 10.1 months) and group 2 (31.25 +/- 21.9 months) demonstrated a statistically significant difference (p = 0.01). This urethrolysis population demonstrated an unusual delay time to surgical treatment of bladder outlet obstruction. We categorized the cohort according to absence or presence of persistent bladder storage symptoms, and found a strong association between persistent bladder symptoms and greater delay to urethrolysis. | {
"pile_set_name": "PubMed Abstracts"
} |
Why are suspected cases of child maltreatment referred by educators so often unsubstantiated?
School professionals have a unique vantage point for identifying child maltreatment and they are a frequent source of referral to child protective services. Disturbingly, past studies have found that maltreatment concerns reported by educators go unsubstantiated by child protective services at much higher rates than suspected maltreatment reported by other professionals. This study explores whether there are systematic differences in the characteristics of cases reported by educators as compared to other professionals and examines whether such variation might account for differences in investigation outcome. Analyses were based on 7,725 cases of suspected maltreatment referred by professionals to child protective services from the Canadian Incidence Study of Reported Child Abuse and Neglect - 2003 a national database on the characteristics of children and families investigated by child protective services. School professionals were responsible for 35.8% of professional referrals. Reports by educators were much more likely to be unsubstantiated (45.3%) than those by other professionals (28.4%) in subsequent child protective investigation. Cases reported by educators were found to contain significantly more child risk factors (e.g., child emotional and behavioural problems) and fewer caregiver and family risk factors (e.g., caregiver mental health problem, single parent family) than cases reported by other professionals. Even controlling for these differences, educator-reported concerns were still 1.84, 95% CI [1.41, 2.40] times as likely to be unsubstantiated as reports from other professionals. Contrary to the notion that educators are mostly reporting non-severe cases, suspected/substantiated cases reported by school professionals were more likely to be judged as chronic and more likely to involve families with a previous child protection history. Results are concerning for the capacity of the education and child protection systems to work together to meet their shared goal of promoting healthy child development. Additional research is needed on the way in which child risks and problems influence child protective service, particularly in the context of chronic abuse and neglect and lack of availability of child and family mental health interventions. Potential problems with credibility of school professionals as reporters of child maltreatment concerns also warrant further investigation. | {
"pile_set_name": "PubMed Abstracts"
} |
Expression of transforming growth factor-beta s and their receptors by human retinal glial cells.
To help test the hypothesis that transforming growth factor beta (TGF-beta) may serve an autocrine function in the retina, we asked whether human Müller (glial) cells in culture express TGF-beta receptors, contain transcripts for various isoforms of this cytokine, and release TGF-beta s into the medium. Using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique with specific primers for TGF-beta 1, -beta 2 and -beta 3 precursors and for TGF-beta type I and type II receptors, we searched for mRNA transcripts expressed by cultured human Müller cells. Also, an ELISA assay allowed quantification of the levels of various TGF-beta s in medium exposed to these glial cells. Human Müller cells in culture express transcripts for both type I and type II TGF-beta receptors and also for TGF-beta 1 and TGF-beta 2. In conditioned medium, the concentration of TGF-beta 1 in the mature form was below detectable levels, and the total TGF-beta 1 was relatively low (mean = 252 pg/ml in confluent cultures). In contrast, the mean levels of mature (55 pg/ml) and total (2530 pg/ml) TGF-beta 2 were markedly higher. Our observations that cultured Müller cells contain mRNA coding for the TGF-beta 2 precursor, release TGF-beta 2 into the medium and express transcripts for both type I and type II TGF-beta receptors are consistent with the idea that this cytokine serves an autocrine function for these glia in the retina. | {
"pile_set_name": "PubMed Abstracts"
} |
[Substitution in psychogeriatrics. A comparative study in nursing homes and substitution projects in Drenthe].
Due to a strong increase of the ageing population in the Netherlands there is a growing need for care for psychogeriatric patients. The shortage of beds in psychogeriatric nursing homes has led to the development of substitute care in residential homes for the elderly and in community centers. If substitution is realized in these substitute care projects in the sense that alternative services are delivered for patients who would otherwise have been admitted to nursing homes, the level of impairment and disruptive behaviour should be of the same level in nursing homes and substitute care projects. Groups of patients of three nursing homes, three day-treatment facilities, eight day-care-projects in residential homes for the elderly and seven centers for day-care in the community were compared. Sociodemographic characteristics, behaviour and care-patterns of all 670 patients who were in care on the first of October of 1992 in these services were investigated. An assessment-scale for elderly patients, based on the Stockton Geriatric Rating Scale, was used to investigate behaviour. Substitute care appears to be possible for a limited and specific group of patients. Substitution for the severely disturbed patients (over 40% of the nursing home patients) does not seem to be possible. Due to the development of substitute care for psychogeriatric patients in residential homes for the elderly and centers for day-care in the community, services seem to develop towards more specific and specialized care. We recommend the foundation of a psychogeriatric case register, which allows the study of the transfer of patients across facilities.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Fungal Endophytes: an Alternative Source for Production of Volatile Compounds from Agarwood Oil of Aquilaria subintegra.
Fungal endophytes are microorganisms that are well-known for producing a diverse array of secondary metabolites. Recent studies have uncovered the bioprospecting potential of several plant endophytic fungi. Here, we demonstrate the presence of highly bioactive fungal endophytic species in Aquilaria subintegra, a fragrant wood plant collected from Thailand. Thirty-three fungal endophytic strains were isolated and further identified to genus level based on morphological characteristics. These genera included Colletotrichum, Pestalotiopsis, Fusarium, Russula, Arthrinium, Diaporthe and Cladosporium. All strains were cultured on potato dextrose broth for 30 days prior to partitioning with ethyl acetate. The volatile compounds of all extracts were investigated by gas chromatography-mass spectrometry (GC-MS). Four strains-Arthrinium sp. MFLUCC16-0042, Colletotrichum sp. MFLUCC16-0047, Colletotrichum sp. MFLUCC16-0048 and Diaporthe sp. MFLUCC16-0051-produced a broad spectrum of volatile compounds, including β-agarofuran, α-agarofuran, δ-eudesmol, oxo-agarospirol, and β-dihydro agarofuran. These compounds are especially important, because they greatly resemble those originating from the host-produced agarwood oil. Our findings demonstrate the potential of endophytic fungi to produce bioactive compounds with applications in perfumery and cosmetic industries. Antioxidant activity of all extracts was also evaluated by using 2,2-diphenyl-2-picrylhydrazyl radical scavenging assays. The ethyl acetate extract of Diaporthe sp. MFLUCC16-0051 demonstrated superior antioxidant capacity, which was comparable to that of the gallic acid standard. Our results indicate that the MFLUCC16-0051 strain is a resource of natural antioxidant with potential medicinal applications. | {
"pile_set_name": "PubMed Abstracts"
} |
Meeting diagnostic related group goals for elderly patients.
Strong economic incentives for prompt discharge under the diagnostic related group (DRG) system challenge hospital social workers to balance the needs of individual patients and the needs of their employing institution. A sample of 219 elderly patients at a large, urban teaching hospital were assigned to regular or early intervention groups. The relationships among timing, type, and amount of social work intervention; ability of patients to care for themselves; availability of social support; and other variables were examined. Early and adequate social work diagnosis and intervention tended to limit excessive hospital stays and facilitate the institution's ability to adhere to DRG guidelines. | {
"pile_set_name": "PubMed Abstracts"
} |
Towards multifunctional antioxidants: synthesis, electrochemistry, in vitro and cell culture evaluation of compounds with ligand/catalytic properties.
Numerous human diseases are linked to a biochemical condition known as oxidative stress (OS). Antioxidants are therefore becoming increasingly important as potential disease prevention and therapeutic agents. Since OS is a multi-stressor event, agents combining a range of different antioxidant properties, such as redox catalysis and metal binding, might be more effective and selective than mono-functional agents. Selenium derivatives of aniline and pyridine combine redox activity with metal binding properties. These multifunctional agents have a distinct electrochemical profile, and exhibit good catalytic activity in the glutathione peroxidase mimic and metallothionein assays. They also show antioxidant activity in a skin cell model of UVA-induced stress. These compounds might therefore provide the basis for novel agents combining two or more distinct antioxidant properties. | {
"pile_set_name": "PubMed Abstracts"
} |
Erythrocyte invasion: vocabulary and grammar of the Plasmodium rhoptry.
Malaria is a dangerous infectious disease caused by obligate intracellular protozoan Plasmodium parasites. In the vertebrate host, erythrocyte recognition and establishment of a nascent parasitophorous vacuole are essential processes, and are largely achieved using molecules located in the microorganelles of the invasive-stage parasites. Recent proteome analyses of the phylogenetically related Toxoplasma parasite have provided protein catalogs for these microorganelles, which can now be used to identify orthologous proteins in the Plasmodium genome. Of importance is the formation of a complex between the proteins secreted from the rhoptry neck portion (RONs) and micronemes (AMA1), which localize at the moving junction during parasite invagination into the host cell. In this article I review the largely unexplored paradigm of the malaria merozoite rhoptry, focusing on the high molecular weight rhoptry protein complex (the RhopH complex), and speculate on its grammar during invasion. | {
"pile_set_name": "PubMed Abstracts"
} |
A practical approach to umbilical artery pH and blood gas determinations.
The use of the Apgar score as a means of identifying birth asphyxia has been challenged. Routine umbilical cord blood pH has been recommended as a more objective measure of the condition of the newborn. The purposes of this study were to evaluate a simplified and selective method of umbilical artery pH blood sampling and to determine the effect of delay in sampling upon umbilical artery pH, carbon dioxide pressure (PCO2), and oxygen pressure (PO2). Umbilical arterial blood of 25 patients was sampled from clamped umbilical cord segments every 15 minutes for 1 hour after delivery. The clamped umbilical cord segments were left at room temperature with no special care given. The blood samples were collected in non-heparinized and non-iced plastic syringes and processed promptly after sampling. During the 60 minutes after delivery, there were no statistically significant changes in pH, PCO2, or PO2 of umbilical arterial blood. Our results indicate that umbilical arterial blood may be obtained simply and reliably from clamped umbilical cord segments for pH and gas determinations for up to an hour after delivery. | {
"pile_set_name": "PubMed Abstracts"
} |
Complex phosphorus thermochemistry. Volume-based thermodynamics and the estimation of standard enthalpies of formation of gas phase ions: Delta(f)H(o) (PCl4+, g) and Delta(f)H(o) (PCl6-, g).
Energy-resolved collision-induced dissociation in a flowing afterglow-guided ion beam tandem mass spectrometer has recently enabled the accurate determination of the standard enthalpy of formation of the gaseous phosphorus pentachloride cation, Delta(f)H(o) ([PCl4(+)], g), found to be 414 +/- 17 kJ mol(-1) (giving a value of 378 +/- 18 kJ mol(-1) at 0 K). Such experimental values for the standard enthalpy of formation of gas phase complex are now being incorporated into the NIST standard reference data program. Such results, can, inter alia, provide a benchmark by which to test earlier computationally based methods which were made to estimate such quantities in the absence of any experimental data. The establishment of this value experimentally also affords us with the opportunity to explore the likely success of newer, simpler approaches. Previous large-scale direct minimization computations to estimate this (and other) standard enthalpies of formation match very well these new experimental results. This paper raises the question as to whether the much simpler volume-based thermodynamics (VBT) approach could yield equally satisfactory results and so circumvent, completely, the need for detailed modeling of the lattices involved. The conclusion is that the VBT approach portrays the extremely complex thermodynamics quite adequately. Thus for the purposes of obtaining basic thermodynamic data, complex modeling of the underlying structures involved may no longer be necessary. At least this should be the case for highly symmetrical ions, like PCl4(+), where detailed packing with counterions is possibly less important than in other cases and where covalent interactions (less easily modeled) with neighboring ions is unlikely to be strongly featured. Other gaseous complex ion enthalpies of formation are also predicted here. | {
"pile_set_name": "PubMed Abstracts"
} |
Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline.
The effectiveness of the 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementias in achieving clinically relevant improvements is unclear. To review the evidence for the effectiveness of cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and the neuropeptide-modifying agent memantine in achieving clinically relevant improvements, primarily in cognition, global function, behavior, and quality of life, for patients with dementia. Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE, EMBASE, Allied and Complementary Medicine Database, CINAHL, AgeLine, and PsycINFO from January 1986 through November 2006. English-language randomized, controlled trials were included in the review if they evaluated pharmacologic agents for adults with a diagnosis of dementia, did not use a crossover design, and had a quality score of at least 3 on the Jadad scale. Data were extracted on study characteristics and outcomes, including adverse events. Effect sizes were calculated and data were combined when appropriate. 96 publications representing 59 unique studies were eligible for this review. Both cholinesterase inhibitors and memantine had consistent effects in the domains of cognition and global assessment, but summary estimates showed small effect sizes. Outcomes in the domains of behavior and quality of life were evaluated less frequently and showed less consistent effects. Most studies were of short duration (6 months), which limited their ability to detect delay in onset or progression of dementia. Three studies directly compared different cholinesterase inhibitors and found no differences in cognition and behavior. Limitations of available studies included short duration, inclusion of only patients with mild to moderate Alzheimer disease, poor reporting of adverse events, lack of clear definitions for statistical significance, limited evaluation of behavior and quality-of-life outcomes, and limited direct comparison of different treatments. Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia. | {
"pile_set_name": "PubMed Abstracts"
} |
The stereoselective disposition of disopyramide in the dog.
The disposition of d-, 1-, and d,1-disopyramide was studied in 5 conscious dogs after intravenous administration (15 mg/kg) of each compound using a balanced crossover design. The clearance of d-disopyramide (15.4 +/- 5.10 ml/min/kg) was significantly greater than that of the l-isomer (9.45 +/- 2.52 ml/min/kg) (p < 0.001). The clearance of the d,1-mixture was intermediate between that obtained for the d- and l-isomers. The steady-state volume of distribution of the three compounds was similar (approximately 1.4 liters/kg). The elimination half-life reflected differences in clearance, being 76.4 +/- 7.30 min for d-disopyramide, 112 +/- 23.4 min for 1-disopyramide, and 97.2 +/- 15.1 min for d,1-disopyramide. The effect of general anesthesia with urethane and chloralose on the disposition of the compounds was also examined. General anesthesia decreased the clearance and increased the half-life of all three compounds. No consistent differences in the volume of distribution were observed with anesthesia as compared to control. Thus, there is stereoselective elimination of the optical isomers of disopyramide in the dog, and general anesthesia decreases the clearance of d-, 1-, and d,1-disopyramide. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of linguistic interference on sentence identification.
This study was designed to investigate the extent to which continuous speech competition, in sentence identification paradigm, produces linguistic interference over and above acoustic masking. We evaluated performance on the Synthetic Sentence Identification (SSI) test in 24 bilingual speakers of English and Spanish under four experimental conditions: (1) target and competition both in English, (2) target and competition both in Spanish, (3) target in English, competition in Spanish, and (4) target in Spanish, competition in English. After controlling for the effects of acoustic masking, results showed significantly better performance in conditions when target and competition were in different languages (interlingual interference) than when target and competition were in the same language (intralingual interference). The difference in performance is attributed to the effects of greater linguistic interference when target and competition were in the same language. | {
"pile_set_name": "PubMed Abstracts"
} |
Mutation of tryptophan-21 in mouse nerve growth factor (NGF) affects binding to the fast NGF receptor but not induction of neurites on PC12 cells.
By using in vitro DNA mutagenesis, we replaced the tryptophan residue at position 21 in mouse nerve growth factor (NGF) with either phenylalanine, leucine or serine. Yield, biological activity, immunological reactivity and receptor binding of the recombinant proteins were determined. All three mutants were produced at considerably lower yields than wild-type NGF, with the serine mutant being undetectable. The results of competitive binding assays show that tryptophan-21 is involved in recognition of the fast NGF receptor of PC12 cells. However, specific biological activity of NGF is not altered by the replacement of tryptophan-21. Our results therefore suggest that biological activity of NGF is not directly coupled to binding to the fast NGF receptor. | {
"pile_set_name": "PubMed Abstracts"
} |
Action of the lateral hypothalamic area on subfornical organ neurons projecting to the supraoptic nucleus in the rat.
The activity of all subfornical organ neurons (N = 20) that were antidromically identified by electrical stimulation of the rat hypothalamic supraoptic nucleus region was excited by microiontophoretically applied angiotensin II. Electrical stimulation of the lateral hypothalamic area produced either an excitatory response (N = 12) or no effect (N = 8) in the activity of identified subfornical organ neurons. The excitatory responses to iontophoretically applied angiotensin II or stimulation of the lateral hypothalamic area were blocked by iontophoretically applied saralasin, an antagonist of angiotensin II. | {
"pile_set_name": "PubMed Abstracts"
} |
Stable reduction product of misonidazole.
The predominant stable product (greater than 80%) of the anaerobic radiation chemical reduction (pH 7, formate, N2O) of misonidazole (MISO) has been identified as the cyclic guanidinium ion MISO-DDI, a 4,5-dihydro-4,5-dihydroxyimidazolium ion. This cation was prepared as its sulfate salt by the reaction of glyoxal and the appropriate N-substituted guanidinium sulfate. Its formation during MISO reduction was established by NMR spectral comparison and by derivatization as glyoxal bis-oxime, which was formed in 86% yield in fully reduced systems. The toxicity of pure MISO-DDI X sulfate was examined in vivo (C3H mice) and in vitro (CHO cells). This product is less toxic than the parent MISO and free glyoxal. A reactive, short-lived, intermediate is suggested as the agent responsible for the toxicity of MISO under hypoxic conditions. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of hydrocortisone on the pituitary response to growth hormone releasing hormone.
In depression, the growth hormone (GH) response to clonidine and L-tryptophan (L-TRP) is reduced, suggesting reduced alpha2-adrenergic and serotonin (5-HT)1A receptor function. Pretreatment with hydrocortisone (100 mg, orally 11 h before) also blunts the GH response to L-TRP. This effect may be mediated at the hypothalamic level via reduced 5-HT1A receptor function or at the pituitary level, either by a direct effect on somatotrope cells or via enhanced insulin-like growth factor-1 (IGF-1) or somatostatin (SS) release. To examine the effects of acute and chronic exposure to hydrocortisone on baseline and stimulated GH release from the pituitary. Twelve healthy male volunteers received pretreatment with acute hydrocortisone (100 mg, 11 h before), chronic hydrocortisone (20 mg twice a day for 1 week) and placebo in a double blind, balanced order, crossover design. Serial measurements of plasma GH, IGF-1 and thyroid stimulating hormone (TSH) levels were made at baseline and following intravenous administration of 1 mcg/kg GHRH. The GH response to growth hormone releasing hormone (GHRH) was significantly blunted by pretreatment with both acute and chronic hydrocortisone. Baseline IGF-1 levels were significantly lower at baseline after chronic hydrocortisone compared with placebo. Baseline TSH levels were significantly lower after acute hydrocortisone compared with placebo, suggesting an increase in somatostatin levels. These data suggest that hydrocortisone acts at the pituitary level to reduce GH release. The TSH and IGF-1 data support the hypothesis that hydrocortisone reduces GH release by enhancing somatostatin and IGF-1 release. | {
"pile_set_name": "PubMed Abstracts"
} |
Cognitive bias modification in problem and pathological gambling using a web-based approach-avoidance task: A pilot trial.
There is evidence that training addicted participants to implicitly avoid disorder-related stimuli by using a training version of the Approach-Avoidance Task (AAT) results in reduced substance consumption (i.e., Approach Bias Modification [AppBM]). The aim of the present web-based study was to investigate the feasibility and effectiveness of AppBM in reducing gambling-related symptoms. A self-selected sample of participants with problem/pathological slot-machine gambling completed an online survey and received either AppBM or Sham training (final N = 131). Attrition during study participation was high (66%). In both conditions slot-machine related and neutral pictures were presented. Within the AppBM condition all slot-machine related pictures had to be pushed and all neutral pictures had to be pulled, whereas in the Sham condition the contingency was 50:50. Eight weeks after baseline, participants were re-assessed. Both groups showed a similar reduction in gambling-related symptoms. Findings are at odds with the hypothesis claiming that only contingency trainings yield beneficial effects. However, it cannot be ruled out that effects result from other factors unrelated to training such as expectancy effects. We think this study holds valuable information how to conduct larger trials in the future and may prove helpful to improve training and its delivery. | {
"pile_set_name": "PubMed Abstracts"
} |
AZD2171 shows potent antitumor activity against gastric cancer over-expressing fibroblast growth factor receptor 2/keratinocyte growth factor receptor.
AZD2171 is an oral, highly potent, and selective vascular endothelial growth factor signaling inhibitor that inhibits all vascular endothelial growth factor receptor tyrosine kinases. The purpose of this study was to investigate the activity of AZD2171 in gastric cancer. We examined the antitumor effect of AZD2171 on the eight gastric cancer cell lines in vitro and in vivo. AZD2171 directly inhibited the growth of two gastric cancer cell lines (KATO-III and OCUM2M), with an IC(50) of 0.15 and 0.37 micromol/L, respectively, more potently than the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib. Reverse transcription-PCR experiments and immunoblotting revealed that sensitive cell lines dominantly expressed COOH terminus-truncated fibroblast growth factor receptor 2 (FGFR2) splicing variants that were constitutively phosphorylated and spontaneously dimerized. AZD2171 completely inhibited the phosphorylation of FGFR2 and downstream signaling proteins (FRS2, AKT, and mitogen-activated protein kinase) in sensitive cell lines at a 10-fold lower concentration (0.1 micromol/L) than in the other cell lines. An in vitro kinase assay showed that AZD2171 inhibited kinase activity of immunoprecipitated FGFR2 with submicromolar K(i) values ( approximately 0.05 micromol/L). Finally, we assessed the antitumor activity of AZD2171 in human gastric tumor xenograft models in mice. Oral administration of AZD2171 (1.5 or 6 mg/kg/d) significantly and dose-dependently inhibited tumor growth in mice bearing KATO-III and OCUM2M tumor xenografts. AZD2171 exerted potent antitumor activity against gastric cancer xenografts overexpressing FGFR2. The results of these preclinical studies indicate that AZD2171 may provide clinical benefit in patients with certain types of gastric cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
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