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Molecular identification of monomeric aspartate racemase from Bifidobacterium bifidum.
Bifidobacterium bifidum is a useful probiotic agent exhibiting health-promoting properties and contains d-aspartate as an essential component of the cross-linker moiety in the peptidoglycan. To help understand D-aspartate biosynthesis in B. bifidum NBRC 14252, aspartate racemase, which catalyzes the racemization of D- and L-aspartate, was purified to homogeneity and characterized. The enzyme was a monomer with a molecular mass of 27 kDa. This is the first report showing the presence of a monomeric aspartate racemase. Its enzymologic properties, such as its lack of cofactor requirement and susceptibility to thiol-modifying reagents in catalysis, were similar to those of the dimeric aspartate racemase from Streptococcus thermophilus. The monomeric enzyme, however, showed a novel characteristic, namely, that its thermal stability significantly increased in the presence of aspartate, especially the D-enantiomer. The gene encoding the monomeric aspartate racemase was cloned and overexpressed in Escherichia coli cells. The nucleotide sequence of the aspartate racemase gene encoded a peptide containing 241 amino acids with a calculated molecular mass of 26 784 Da. The recombinant enzyme was purified to homogeneity and its properties were almost the same as those of the B. bifidum enzyme.
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{
"pile_set_name": "PubMed Abstracts"
}
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Eosinophilic angiocentric fibrosis: an unusual entity producing complete lacrimal duct obstruction.
Eosinophilic angiocentric fibrosis is an unusual fibrotic condition of unknown aetiology that tends to affect the upper respiratory tract. Twenty-one cases have been reported in the literature and only three have had ocular adnexal involvement. Despite characteristic histopathological and clinical findings, the diagnosis remains a challenge. Furthermore, its progressive nature with potential to invade adjacent structures and the lack of response to current treatment modalities make management difficult. We describe a case of sinonasal eosinophilic angiocentric fibrosis that presented with bilateral nasolacrimal duct obstruction.
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{
"pile_set_name": "PubMed Abstracts"
}
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Comparative immunohistochemical demonstration of peptide F- and other enkephalin-containing neurons in the enteric nervous system of the rat.
The immunohistochemical localization of peptide F and the related enkephalins met5-enkephalin (met-enk), leu5-enkephalin (leu-enk), met5-enkephalin-arg6-phe7 (met-enk-arg-phe), and met5-enkephalin-arg6-gly7-leu8 (met-enk-arg-gly-leu) was investigated by means of the indirect immunofluorescence technique in the enteric nervous system of the rat. Peptide F-like immunoreactivity was widely distributed within neuronal structures throughout the gastrointestinal (GI) tract of the rat. Peptide F-containing nerve cell bodies were mainly located in the myenteric plexus, and only rarely were seen in the submucosal plexus. Peptide F-immunoreactive nerve fibers were principally present in the myenteric plexus and circular muscle layer; few were found in the submucosal plexus, longitudinal muscle layer, muscularis mucosa, and mucosa. No peptide F-containing fibers were found associated with blood vessels in the gut. By comparing the distribution of immunoreactive peptide F with other related enkephalins met-enk, leu-enk, met-enk-arg-phe, and met-enk-arg-gly-leu, we observed that there was a remarkable similarity in the distribution of peptide F and other enkephalins in the GI tract. These data, combined with our previous studies, indicate that peptide F may coexist with other related enkephalins in the same neurons of the enteric nervous system. The results suggest that peptide F, a product of the proenkephalin A gene, may play a physiological role within the enteric nervous system.
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{
"pile_set_name": "PubMed Abstracts"
}
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Paradoxical embolism with thrombus stuck in a patent foramen ovale: a review of treatment strategies.
Paradoxical embolism represents a rare condition occurring when a thrombus originating from venous system produces pulmonary embolism and systemic embolization through an intracardiac or pulmonary shunt. The evidence of a thrombus entrapped in a patent foramen ovale (PFO) is an even more rare condition. There is uncertainty about the optimal treatment strategy. A 58-year-old male patient was admitted to our Internal Medicine Unit with the diagnosis of bilateral bronchopneumonia. During hospitalization, the co-occurrence of chest pain and amaurosis led us to hypothesize a paradoxical embolism. Transthoracic echocardiography showed the presence of a thrombus stuck over the interatrial septum. A contrast-enhanced chest CT scan showed multiple pulmonary embolisms and brain CT scan documented a hypodense area, of ischemic significance, in the left occipital lobe near tentorium. In order to prevent further embolization, emergency cardiac surgery (right atriotomy, removal of thrombus and closure of the PFO, pulmonary thrombectomy) was performed without complications. Although rare, the evidence of a thrombus stuck in a patent foramen ovale represents a clinical emergency. The optimal therapeutic approach is still debated. The surgical correction seems to be a safe and effective option for these patients.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Beeckman's medical learning by reading].
Isaac Beeckman (1588-1637) is a self-learning man. He learned medicine by his reading medical books (contemporary and classic). In this paper I study how Beeckman read and understood them. He did not merely memorize them. But he gave some supplementary explanations to their (he thought) insufficient passages, sometimes criticized them and gave mechanical explanation that was based on atomism with hydrostatics. We can find similar ways of reading in the works of Lucretius and Cardano which young Beeckman read repeatedly. Beeckman learned the way of explaining natural phenomena with atomism from Lucretius' De rerum natura, and the way of explaining mechanics with natural philosophy and of demonstrating the principles of natural philosophy with machines from Cardano's De subtilitate. Beeckman's interactive reading is a good style of self-learning, but to avoid some bad effects of self-learning, he had to talk actually to a good respondent such as young Descartes.
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{
"pile_set_name": "PubMed Abstracts"
}
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Impact of static pressure on transmembrane fluid exchange in high molecular weight cut off microdialysis.
With the interest of studying larger biomolecules by microdialysis (MD), this sampling technique has reached into the ultrafiltration region of fluid exchange, where fluid recovery (FR) has a strong dependence on pressure. Hence in this study, we focus on the fluid exchange across the high molecular weight cut off MD membrane under the influence of the static pressure in the sampling environment. A theoretical model is presented for MD with such membranes, where FR has a linear dependence upon the static pressure of the sample. Transmembrane (TM) osmotic pressure difference and MD perfusion rate decide how fast FR increases with increased static pressure. A test chamber for in vitro MD under static pressure was constructed and validated. It can hold four MD probes under controlled pressurized conditions. Comparison showed good agreement between experiment and theory. Moreover, test results showed that the fluid recovery of the test chamber MD can be set accurately via the chamber pressure, which is controlled by sample injection into the chamber at precise rate. This in vitro system is designed for modelling in vivo MD in cerebrospinal fluid and studies with biological samples in this system may be good models for in vivo MD.
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{
"pile_set_name": "PubMed Abstracts"
}
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Predictive value of IL-35 and IL-17 in diagnosis of childhood asthma.
This study aimed to evaluate the correlation between serum levels of IL-17 and IL-35 and the presence and severity of childhood asthma. The study was performed on 60 diagnosed asthmatic children, who were further classified into four groups according to the Global Initiative for Asthma Guidelines for Asthma Severity and Control (GINA) 2016, plus 30 age- and sex-matched apparently healthy children. All participants were subjected to full medical history, clinical examination, pulmonary function tests and laboratory evaluation in the form of complete blood count (CBC), serum total IgE, IL-17 and IL-35 by ELISA. Our results revealed that eosinophils count, IgE and IL-17 were significantly higher in the asthmatic group than the control group (p < .001), while IL-35 levels were significantly lower in asthmatics than control (p < .001). A strong negative correlation was found between serum IL-17 and serum IL-35; a positive correlation was found between serum IL-17 and both of serum total IgE and eosinophils counts in atopic asthmatic patients, and serum IL-35 showed significant negative correlations with both. ROC analysis of the data showed that the cut-off value of IL-35 level was <189.5 pg/mL and for IL-17 level, it was >13.1 pg/mL; this value could predict childhood asthma with sensitivity of 81.7% and 83.3%, and specificity of 76.7% and 70%, respectively. A combination of both cytokines yielded an increase in sensitivity to 95%. In conclusion, in the current study, IL-17 is upregulated while IL-35 is downregulated in childhood asthma with a significant negative correlation between both. These results suggest that both may play an important role in the pathogenesis of childhood asthma.
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{
"pile_set_name": "PubMed Abstracts"
}
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Genotoxicity, acute oral and dermal toxicity, eye and dermal irritation and corrosion and skin sensitisation evaluation of silver nanoparticles.
To clarify the health risks related to silver nanoparticles (Ag-NPs), we evaluated the genotoxicity, acute oral and dermal toxicity, eye irritation, dermal irritation and corrosion and skin sensitisation of commercially manufactured Ag-NPs according to the OECD test guidelines and GLP. The Ag-NPs were not found to induce genotoxicity in a bacterial reverse mutation test and chromosomal aberration test, although some cytotoxicity was observed. In acute oral and dermal toxicity tests using rats, none of the rats showed any abnormal signs or mortality at a dose level of ∼ 2000 mg/kg. Similarly, acute eye and dermal irritation and corrosion tests using rabbits revealed no significant clinical signs or mortality and no acute irritation or corrosion reaction for the eyes and skin. In a skin sensitisation test using guinea pigs, one animal (1/20) showed discrete or patchy erythema, thus Ag-NPs can be classified as a weak skin sensitiser.
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{
"pile_set_name": "PubMed Abstracts"
}
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Anticipated changes in reimbursements for US outpatient emergency department encounters after health reform.
We study how reimbursements to emergency departments (EDs) for outpatient visits may be affected by the insurance coverage expansion of the Patient Protection and Affordable Care Act as previously uninsured patients gain coverage either through the Medicaid expansion or through health insurance exchanges. We conducted a secondary analysis of data (2005 to 2010) from the Medical Expenditure Panel Survey. We specified multiple linear regression models to examine differences in the payments, charges, and reimbursement ratios by insurance category. Comparisons were made between 2 groups to reflect likely movements in insurance status after the Patient Protection and Affordable Care Act implementation: (1) the uninsured who will be Medicaid eligible afterward versus Medicaid insured, and (2) the uninsured who will be Medicaid ineligible afterward versus the privately insured. From 2005 to 2010, as a percentage of total ED charges, outpatient ED encounters for Medicaid beneficiaries reimbursed 17% more than for uninsured individuals who will become Medicaid eligible after Patient Protection and Affordable Care Act implementation: 40.0% versus 34.0%, mean absolute difference=5.9%, 95% confidence interval 5.7% to 6.2%. During the same period, the privately insured reimbursed 39% more than for uninsured individuals who will not be Medicaid eligible after Patient Protection and Affordable Care Act implementation: 54.0% versus 38.8%, mean absolute difference=15.2%, 95% confidence interval 12.8% to 17.6%. Assuming historical reimbursement patterns remain after Patient Protection and Affordable Care Act implementation, outpatient ED encounters could reimburse considerably more for both the previously uninsured patients who will obtain Medicaid insurance and for those who move into private insurance products through health insurance exchanges. Although our study does provide insight into the future, multiple factors will ultimately influence reimbursements after implementation of the act.
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{
"pile_set_name": "PubMed Abstracts"
}
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Relevance of nuclear localization and functions of RNA helicase A.
RNA helicase A (RHA) regulates gene expression at transcriptional and post-transcriptional levels. It is also known that RHA shuttles between the nucleus and the cytoplasm. RHA possesses nuclear transport domain which functions as a nuclear localization signal (NLS) and nuclear export signal (NES), and predominantly localizes in the nucleus. Here, we identified regions that influence cellular localization of RHA. We showed that double-stranded RNA binding domain I and II (dsRBD I and II) positively localized to the cytoplasm. Mutational analysis revealed that RNA-binding ability was important to localization of dsRBD to the cytoplasm. RHA mutants lacking association with Pol II complexes were partially spilled from the nucleus. Furthermore, a minimal transactivation domain (MTAD), which is minimal region to interact with Pol II complexes, mainly localized to the nucleus in comparison with GFP. Our results indicated that the intracellular localization of RHA might be regulated by not only NLS and NES but also functional domains.
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{
"pile_set_name": "PubMed Abstracts"
}
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Calcification of different designs of silicone intraocular lenses in eyes with asteroid hyalosis.
To describe the association between calcification of older and newer designs of silicone intraocular lenses (IOLs) and asteroid hyalosis. Case series with clinicopathologic correlation. Sixteen silicone IOLs explanted because of decreased visual acuity associated with opacifying deposits on the posterior optic surface. All 16 lenses underwent gross and light microscopic analyses. Selected lenses underwent alizarin red staining or scanning electron microscopy coupled with energy dispersive x-ray spectroscopy for elemental composition. Clinical data in each case were obtained by a questionnaire sent to the explanting surgeons. Clinical data in relation to 111 hydrophilic acrylic lenses explanted because of calcification also were assessed for comparison. Deposit morphologic features and location were evaluated under gross and light microscopy. The calcified nature of the deposits was assessed by histochemical staining and surface analyses. Clinical data obtained included age at IOL implantation, gender, implantation and explantation dates, as well as history of neodymium:yttrium-aluminum-garnet laser treatment. The presence of asteroid hyalosis in the affected eye was investigated for the explanted silicone and hydrophilic acrylic lenses. The 16 lenses were of 8 designs manufactured from different silicone materials, which were explanted 9.21+/-3.66 years after implantation. Neodymium:yttrium-aluminum-garnet laser applications performed in 12 cases partially removed deposits from the lens, followed by a gradual increase in their density after the procedures. The presence of asteroid hyalosis was confirmed in 13 cases; no notes regarding this condition were found in patient charts in the other 3 cases. The deposits were only on the posterior optic surface of the silicone lenses and were composed of calcium and phosphate. A history of asteroid hyalosis was not found in relation to any of the 111 cases of postoperative calcification of hydrophilic acrylic lenses. Including this current series, there are 22 cases of calcification of silicone lenses involving 8 designs manufactured from different silicone materials described in the literature. The presence of asteroid hyalosis was confirmed in 86.4% of cases. These findings may be added to the list of pros and cons surgeons consider when selecting or recommending an IOL.
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{
"pile_set_name": "PubMed Abstracts"
}
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Chitosan-DNA complexes: charge inversion and DNA condensation.
The design of biocompatible polyelectrolyte complexes is a promising strategy for in vivo delivery of biologically active macromolecules. Particularly, the condensation of DNA by polycations received considerable attention for its potential in gene delivery applications, where the development of safe and effective non-viral vectors remains a central challenge. Among polymeric polycations, Chitosan has recently emerged as a very interesting material for these applications. In this study, we compare the observed aggregation behavior of Chitosan-DNA complexes with the predictions of existing models for the complexation of oppositely charged polyelectrolytes. By using different and complementary microscopy approaches (AFM, FESEM and TEM), light scattering and electrophoretic mobility techniques, we characterized the structures of the complexes formed at different charge ratios and Chitosan molecular weight. In good agreement with theoretical predictions, a reentrant condensation, accompanied by charge inversion, is clearly observed as the polycation/DNA charge ratio is increased. In fact, the aggregates reach their maximum size in correspondence of a value of the charge ratio where their measured net charge inverts its sign. This value does not correspond to the stoichiometric 1:1 charge ratio, but is inversely correlated with the polycation length. Distinctive "tadpole-like" aggregates are observed in excess polycation, while only globular aggregates are found in excess DNA. Close to the isoelectric point, elongated fiber-like structures appear. Within the framework of the models discussed, different apparently uncorrelated observations reported in the literature find a systematic interpretation. These results suggest that these models are useful tools to guide the design of new and more efficient polycation-based vectors for a more effective delivery of genetic material.
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{
"pile_set_name": "PubMed Abstracts"
}
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Pharmacological evidence for calcium channel inhibition by danshen (Salvia miltiorrhiza) on rat isolated femoral artery.
This study investigated the relaxant actions of danshen (Salvia miltiorrhiza) and its lipid-soluble- and water-soluble-fractions on endothelium-denuded rat isolated femoral artery rings. Danshen, its water-soluble fraction and its lipid-soluble fraction produced relaxation of the phenylephrine-precontracted artery rings with IC50 values of 149 +/- 20 microg/mL, 160 +/- 25 microg/mL, and 23 +/- 6 microg/mL, respectively. Pretreatment of the artery rings with a non-selective potassium channel inhibitor tetraethylammonium (TEA, 10 mM) produced a significant two-fold rightward shift of the concentration-response curve to danshen and a four-fold shift to its water-soluble fraction, but had no effect on the lipid-soluble fraction. A 3.3-fold shift was produced on the concentration-response curve of danshen when the artery rings were pretreated with a mixture of 10 mM TEA, 1 mM 4-aminopyridine (K(V) blocker), 1 microM glibenclamide (K(ATP) blocker), 100 nM iberiotoxin (BK(Ca) blocker), and 100 microM barium chloride (K(IR) blocker). Involvement of Ca2+ channels was investigated in endothelium-denuded artery rings incubated with Ca2+-free buffer and primed with 1 microM phenylephrine or 60 mM KCl for 5 minutes prior to adding CaCl2 to elicit contraction. In artery rings primed with phenylephrine, pretreatment with 1 mg/mL danshen, 1 mg/mL water-soluble fraction of danshen, 0.1 mg/mL lipid-soluble fraction of danshen, and 100 nM nifedipine abrogated the CaCl2-induced contraction. On the other hand, in artery rings primed with KCl, these agents produced 40%, 25%, 53%, and 92% inhibition on the maximum contraction induced by CaCl2, respectively. Increasing the concentrations of danshen and its water-soluble fraction to 3 mg/mL, and the lipid-soluble fraction to 0.3 mg/mL further reduced the maximum contraction to 92%, 93%, and 83%, respectively. Taken together, these findings suggested the vasorelaxant actions of danshen and its fractions were produced primarily by inhibition of Ca2+ influx in the vascular smooth muscle cells and a small component was mediated by the opening of K+ channels.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effect of leptin gene polymorphism on the breeding value of milk production traits in Iranian Holstein.
New molecular techniques focused on genome analysis, open new possibilities for more accurate evaluation of economiclly important traits in farm animals. Milk production traits are typical quantitative characteristics controlled by a number of genes. Mutations in their sequences may alter animal performance as well as their breeding values. In this study, we investigated the effect of Kpn2I restriction fragment length polymorphisms in the leptin gene, on bull breeding values for milk yield, fat, and protein yield, and their percentage. In order to test for an association between the leptin single-nucleotide polymorphism in exon 2 and milk productivity, we genotyped 134 Iranian Holstein bulls. Breeding values for milk-related traits (milk yield, fat, and protein yield and percentage) were estimated using the BLUP based on an animal model. The effect of the genotypes of Kpn2I polymorphism on the breeding values for milk-related traits was examined using least square methods. The T allele frequency was 0.425. Genotypes were distributed according to the Hardy-Weinberg equilibrium. Bulls with TT genotype had higher milk, fat and protein yield compared with TC and CC bulls (P < 0.05). Bulls with CC genotype had higher protein percentage compared with TT and TC bulls (P < 0.05). The association between leptin polymorphism with milk production traits suggests that this marker may be useful for selection based on molecular information.
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{
"pile_set_name": "PubMed Abstracts"
}
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Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology.
We present ultra-high resolution optical coherence tomography (OCT) structural intensity and optical Doppler tomography (ODT) flow velocity images of the human retina in vivo. The ultra-high speed OCT system is based on Spectral Domain or Fourier Domain technology, which provides a sensitivity advantage over conventional OCT of more than 2 orders of magnitude. This sensitivity improvement allows video rate OCT and ODT cross sectional imaging of retinal structures. Images will be presented with axial resolutions of 6 and 3.5 microns. We observed small features in the inner and outer plexiform layers, which are believed to be small blood vessels. Flow velocity images will be presented showing pulsatile flow in retinal arteries and veins.
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{
"pile_set_name": "PubMed Abstracts"
}
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Data management and analysis systems for bluetongue virus zoning in Australia.
Bluetongue virus (BTV) monitoring data in Australia is managed using a secure web-enabled centralised database. Scientists across the country submit virological and entomological data from sentinel and other sites using the Internet. Automated reporting and mapping systems make this data immediately available to all users. This system underpins the process used for defining zone boundaries. Immediate access to monitoring results allows the zones to be redefined as soon as any evidence of expansion of the area of BTV activity is detected. The method used to define zone boundaries, incorporating detailed information on vector and virus activity, property boundaries and subdivision boundaries, geography and climate, is described.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Application of acute extreme hypervolemic hemodilution in spine surgery].
To evaluate the security and validity of the acute extreme hypervolemic hemodilution (AEHH) in spine surgery. Thirteen patients (8 males, 5 females; age, 16-65 years; weight, 50-75 kg) who had undergone major spine operations were enrolled in this study. Eleven of them had undergone anterior decompression, who were given the grafting and the internal fixation for their thoraco-lumber spinal burst fractures; the other 2 patients were given the correction operation for their scoliosis. The baselines of the haematocrit (Hct) were 0.363-0.481 before operation. The patients had no cardiac, pulmonary, hepatic or renal dysfunction or coagulation abnormality. The hemodynamic status and the haematocrit were observed during operation. The parameters of thromboelastography (TEG), arterial blood gas, and electrolytes were measured and observed at the following time points: before AEHH, after AEHH, 60 minutes after AEHH, 120 minutes after AEHH, and the end of the operation. The total fluid volume was recorded. The autologous blood volume was 1 050-1 575 ml (average, 1 419 +/- 198 ml), plasma substitute 2 100-3 150 ml (average, 2 838 +/- 397 ml), blood loss 1 000-3 130 ml (average, 1 747 +/- 743 ml), urine 450-1 270 ml (average, 871 +/- 374 ml), and the net blood transfusion 1 206-2 661 ml (1 863 +/- 598 ml). The homogenous blood of 400 ml was transfused in 1 patient for making up the blood loss of 3 130 ml. There were no statistically significant differences in the hemodynamic measurements, arterial blood gas, and electrolyte variables when compared with the baseline values before the hemodilution (P > 0.05). The reaction time of TEG was longer 60 minutes after AEHH than before AEHH (P < 0.05); the other parameters of TEG had no differences when compared with the baseline values (P > 0.05). The AEHH is safe and efficient in reduction of the perioperative homogenous blood transfusion in spine surgery.
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{
"pile_set_name": "PubMed Abstracts"
}
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Calculating singlet excited states: Comparison with fast time-resolved infrared spectroscopy of coumarins.
In contrast to the ground state, the calculation of the infrared (IR) spectroscopy of molecular singlet excited states represents a substantial challenge. Here, we use the structural IR fingerprint of the singlet excited states of a range of coumarin dyes to assess the accuracy of density functional theory based methods for the calculation of excited state IR spectroscopy. It is shown that excited state Kohn-Sham density functional theory provides a high level of accuracy and represents an alternative approach to time-dependent density functional theory for simulating the IR spectroscopy of singlet excited states.
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{
"pile_set_name": "PubMed Abstracts"
}
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Giant cell arteritis--a molecular approach to the multiple facets of the syndrome.
Molecular studies of giant cell arteritis indicate that T cells are recruited to the wall of medium-sized and large arteries, are activated locally, produce IL-2 and IFN-gamma, and regulate the activity of tissue-infiltrating macrophages. Downstream effects of T cell activation include the production of proinflammatory cytokines, metalloproteinases, and growth factors. Growth factors are instrumental in the process of intimal hyperplasia, leading to luminal occlusion and tissue ischemia. The amounts of IL-2, IFN-gamma, and the growth factor PDGF in the vascular lesions varies among patients and are correlated with differences in patterns of clinical manifestations. Giant cell arteritis complicated by cranial ischemia, such as anterior optic neuropathy or stroke, is characterized by high levels of IFN-gamma and PDGF. If the IFN-gamma-PDGF loop is less developed, fever and wasting can dominate the disease. Dominant production of IL-2 is associated with polymyalgia rheumatica. The finding of different inflammatory pathways translating into different clinical phenotypes may reflect differences in the contribution of the arterial wall. Alternative hypotheses include a role of multiple disease-inducing antigens with different tissue distributions or tropisms.
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{
"pile_set_name": "PubMed Abstracts"
}
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The clinical management of tumour lysis syndrome in haematological malignancies.
Tumour lysis syndrome (TLS) is caused by the disintegration of malignant cells, usually following the instigation of chemotherapy, although it may already be established at the time of initial presentation in a minority of cases. As a direct consequence of malignant cell breakdown, intracellular ions, proteins, nucleic acids and their metabolites are released into the plasma causing the characteristic metabolic abnormalities of TLS; hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia. In many cases the release of large amounts intracellular contents is so abrupt that the normal homeostatic mechanisms are rapidly overwhelmed and without prompt, effective management, the clinical effects of TLS soon become apparent.
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{
"pile_set_name": "PubMed Abstracts"
}
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No psychophysiological interactions between caffeine and stress?
In earlier studies, the predominantly beta-adrenergic effects of mental tasks and the alpha-adrenergic effects of caffeine on cardiovascular functions were observed to be simply additive without interaction. In the present study, annoying electrical shocks were superimposed on a mental task affording either active coping, which specifically raises beta-adrenergic activation, or passive coping, and the 40 female subjects were preselected so as to differ in subjective stress susceptibility. Caffeine as well as the type of coping and the considered personality dimension produced significant effects, but almost no interactions were obtained. The stress resistant subjects, who tended toward more extraversion, emotional stability and more masculinity, had lower anxiety scores, rated their performance higher and had a greater cardiac output than the stress non-resistant subjects, who represented a rather normal population according to the FPI personality dimensions. Caffeine increased EEG alpha and beta frequency and delta power and decreased beta power, raised blood pressure and enhanced stress reactions in respiration amplitude and pre-ejection period. Active stress coping induced greater stress reactions in heart rate (increase), left ventricular ejection time (decrease) and ear pulse arrival time (decrease) than passive coping.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Optimizing ADHD Treatment? Results of a Pilotstudy of the ADHD Selective Contract in Bremerhaven, Germany].
The attention deficit hyperactivity disorder (ADHD) is associated with substantial impairment and psychiatric comorbidities. Thus, an optimized treatment is essential. In 2011, a new multidisciplinary treatment strategy (so-called Versorgungsvertrag) was contracted for the model region of Bremerhaven, Germany. This manuscript describes the results of the feasibility testing, focusing on the effects of the Versorgungsvertrag on patients' ADHD symptoms and on the treatment satisfaction of patients' kins. Patients with ADHD (4-17 years) were assessed at baseline and at 9 months follow-up. Kins documented the current symptomatology using the FBB-ADHS questionnaire on both occasions, and rated their satisfaction with the Versorgungsvertrag at follow-up. The FBB-ADHS gives information on the severity of the ADHD core symptoms (0=normal, 3=very noticeable). 69 patients (77 kins) were included. At follow-up, data from 59 patients (67 kins) were available. FBB-ADHS data of both occasions was available for 44 patients. Improvements regarding the ADHD total score (1.27 at follow-up vs. 1.59 at baseline, p=0.003) and the subdomains inattention (1.42 vs. 1.81, p=0.001) and hyperactivity (0.96 vs. 1.22, p=0.032) were documented. In the subgroup of boys (n=34), inattention (p=0.001), impulsivity (p=0.019) and the ADHD total score (p=0.002) improved, while no changes were observed in the subgroup of girls (n=10). The majority of kins (52.4 to 68.4%) rated the treatment as helpful. Our study shows improvements for the ADHD core symptoms after 9 months and a high satisfaction of kins with the treatment strategy. Due to the lack of a control group from routine care, no certain statement about the additional benefit of the treatment strategy can be made. The null effect in the subgroup of girls might be explained by the underrepresentation of girls, but the gender distribution observed in our study is commonly observed in patients with ADHD. The positive effects during the observation period should be confirmed in further studies including a control group from routine care.
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{
"pile_set_name": "PubMed Abstracts"
}
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Dependency on serine concentration of the activity of tryptophan synthase. Cooperative properties.
The activity of the enzyme tryptophan synthase from Escherichia coli was tested as a function of the concentration of L-serine which serves as a substrate in the indole to tryptophan reaction as well as for the L-serine deaminase activity. L-Serine binding was found to follow the pattern of negative cooperativity both by kinetic and by equilibrium methods. The enzyme kinetic data support the view that a rapid equilibration model for the enzyme . substrates complex formation is not strictly obeyed.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Life as a way of the functioning of matter - Theory of organic being of Jędrzej Śniadecki].
In 2018 we celebrate the 250th anniversary of the Jędrzej Śniadecki's birth. This work aims to show the importance of his thoughts for the development of natural sciences. He studied at some of the largest universities in Europe, where he met great scientists of the enlightenment. The effects can be seen in his works. He was remembered as a founder of Polish biochemistry, anthropology and pathology, also as the author of chemical terminology and language. The essence of his thoughts is "Theory of Organic being", which is an attempt to answer the question: "what is life?". Jędrzej Śniadecki introduced a new definition of life based on the term "organic power". This work shows how import are the thoughts of Jędrzej Śniadecki in the context of the times in which he lived, as well as the following development of natural sciences, what makes him and his theories worth memory.
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{
"pile_set_name": "PubMed Abstracts"
}
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Modeling insulin resistance in rodents by alterations in diet: what have high-fat and high-calorie diets revealed?
For over half a century, researchers have been feeding different diets to rodents to examine the effects of macronutrients on whole body and tissue insulin action. During this period, the number of different diets and the source of macronutrients employed have grown dramatically. Because of the large heterogeneity in both the source and percentage of different macronutrients used for studies, it is not surprising that different high-calorie diets do not produce the same changes in insulin action. Despite this, diverse high-calorie diets continue to be employed in an attempt to generate a "generic" insulin resistance. The high-fat diet in particular varies greatly between studies with regard to the source, complexity, and ratio of dietary fat, carbohydrate, and protein. This review examines the range of rodent dietary models and methods for assessing insulin action. In almost all studies reviewed, rodents fed diets that had more than 45% of dietary energy as fat or simple carbohydrates had reduced whole body insulin action compared with chow. However, different high-calorie diets produced significantly different effects in liver, muscle, and whole body insulin action when insulin action was measured by the hyperinsulinemic-euglycemic clamp method. Rodent dietary models remain an important tool for exploring potential mechanisms of insulin resistance, but more attention needs to be given to the total macronutrient content and composition when interpreting dietary effects on insulin action.
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{
"pile_set_name": "PubMed Abstracts"
}
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Transient News Events Test: feasibility in assessment of post-temporal lobectomy remote memory deficits.
Although anterograde memory deficits are well documented in patients with epilepsy, the extent to which remote memory deficits occur is less clear. This is due in part to a lack of reliable methods for assessment. The present study examined the feasibility of using the Transient News Events Test (TNET) to assess remote memory in subjects status post anterior temporal lobectomy (ATL) for the treatment of refractory seizures. Results indicated significantly poorer performance of the patient group compared to healthy controls. The decrement in performance within the patient group was evident only for items from more recent time periods. Reasons for an apparent stability of the most remote memories with ATL and implications regarding hippocampal function are reviewed. In conclusion, the TNET provides a feasible method for assessment of remote memory function in patients with epilepsy, with decrements in performance noted in comparison to a healthy control group in this retrospective study.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Comparison on physicochemical properties and immun activities of polysaccharides from cultures at different development stages of Dendrobium huoshanense].
To compare the physicochemical properties and immun activities of polysaccharides extracted from cultures at different development stages of Dendrobium huoshanense. Polysaccharides were extracted by hot water and alcohol precipitation, and isolated by anion exchange chromatography. The physicochemical properties of polysaccharides were analyzed by spectrophotometry, GC-MS, IR and fluorophore-assisted carbohydrate electrophoresis (FACE). ELISA was used to determine the immun activities of polysaccharides. The polysaccharides from cultures at different development stages of D. huoshanense had no obvious discrepancy in contents. 5 polysaccharides were isolated by anion exchange chromatography with the same elution conditions. GC-MS analysis showed that the polysaccharides from cultures at different development stages of D. huoshanense consisted of glucose, mannose and galactose. IR and FACE displayed that different polysaccharides had no significant change in chemical properties. In vitro experiments with spleen cells proved that the polysaccharides from cultures at different development stages had similar effects on stimulating IFN-gamma and TNF-alpha releases. No significant differences are found in the physico-chemical properties and immun activities of polysaccharides extracted from cultures at different development stages of D. huoshanense, suggesting that the polysaccharides of D. huoshanense have stability in quality to some extent during tissue culture.
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{
"pile_set_name": "PubMed Abstracts"
}
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Nucleic acid approaches for detection and identification of biological warfare and infectious disease agents.
Biological warfare agents are the most problematic of the weapons of mass destruction and terror. Both civilian and military sources predict that over the next decade the threat from proliferation of these agents will increase significantly. In this review we summarize the state of the art in detection and identification of biological threat agents based on PCR technology with emphasis on the new technology of microarrays. The advantages and limitations of real-time PCR technology and a review of the literature as it applies to pathogen and virus detection are presented. The paper covers a number of issues related to the challenges facing biological threat agent detection technologies and identifies critical components that must be overcome for the emergence of reliable PCR-based DNA technologies as bioterrorism countermeasures and for environmental applications. The review evaluates various system components developed for an integrated DNA microchip and the potential applications of the next generation of fully automated DNA analyzers with integrated sample preparation and biosensing elements. The article also reviews promising devices and technologies that are near to being, or have been, commercialized.
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{
"pile_set_name": "PubMed Abstracts"
}
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Relationship of academic procrastination with perceived competence, coping, self-esteem and self-efficacy in nursing students.
The aim of this study was to study the role that perceived competence, resilient coping, self-esteem and self-efficacy can have as protective factors of the academic procrastination of nursing students. Participants were 237 nursing students, 202 women and 35 men. The participants answered a questionnaire that contained the Spanish forms of the following instruments: Tuckman Procrastination Scale (TPS), Perceived Personal Competence Scale (PPC), Brief Resilient Coping Scale (BRCS), Rosenberg Self-Esteem Scale (RSES) and General Self-Efficacy Scale (GSE). Significant and negative correlation coefficients (p<.01) were obtained between the procrastination scale and the rest of the measures used. The linear regression analysis identified Perceived Competence (PPC) as the only predictive variable of procrastinating behaviour, explaining 21.5% (R2aj) of the variance. The results of the study show the important protective role that the variables associated with 'positive' psychology have on procrastination. Of special relevance for the theory and practice of teaching is the result that indicates the predictive role of Perceived Competence on the academic procrastination of students.
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{
"pile_set_name": "PubMed Abstracts"
}
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Stochastic modeling of paper structure and Monte Carlo simulation of light scattering.
A simplified stochastic model for the fiber structure of paper is introduced. The packing density and optical thickness of the fiber network are derived analytically, and their dependence on fiber characteristics can be seen. We undertake a Monte Carlo simulation of light scattering that is based on geometrical optics, using a realization of the model, which gives packing densities and optical thicknesses well in accordance with those given by the stochastic model and the scattering quantities as functions of three angles.
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{
"pile_set_name": "PubMed Abstracts"
}
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Joint inference for nonlinear mixed-effects models and time to event at the presence of missing data.
In many longitudinal studies, the individual characteristics associated with the repeated measures may be possible covariates of the time to an event of interest, and thus, it is desirable to model the time-to-event process and the longitudinal process jointly. Statistical analyses may be further complicated in such studies with missing data such as informative dropouts. This article considers a nonlinear mixed-effects model for the longitudinal process and the Cox proportional hazards model for the time-to-event process. We provide a method for simultaneous likelihood inference on the 2 models and allow for nonignorable data missing. The approach is illustrated with a recent AIDS study by jointly modeling HIV viral dynamics and time to viral rebound.
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{
"pile_set_name": "PubMed Abstracts"
}
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Lipoprotein (a) and plasminogen are immunochemically related.
Earlier studies demonstrated that lipoprotein (a), a lipoprotein of high atherogenicity, possesses proteolytic activity. In this report, we provide evidence that the lipoprotein (a)-specific antigen, apoprotein (a) is immunochemically related to plasminogen. This was demonstrated by polyclonal antisera from rabbit, sheep and horse, and with three monoclonal antibodies from mouse. Using immunospecific adsorbers against lipoprotein (a), all plasminogen could be adsorbed from lipoprotein (a)-positive and apparently lipoprotein (a)-negative plasma. As an additional similarity to plasminogen, lipoprotein (a) binds selectively to lysine-Sepharose, but with a somewhat lower affinity. In an assay system for measuring the fibrinolytic activity challenged with streptokinase, lipoprotein (a) prolonged strikingly the fibrinolysis time under certain experimental conditions.
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{
"pile_set_name": "PubMed Abstracts"
}
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Hemarthrosis after femoral neck fracture fixation.
In 34 femoral neck fractures, CT was performed within 1-32 days after internal fixation. All the cases except one showed an increased distance between the femoral neck and the anterior aspect of the joint capsule as compared with the intact side, indicating varying degrees of hip joint effusion and/or synovitis. Hip joint aspiration in 11 patients revealed increased intracapsular pressure varying between 10 and 112 mmHg and volumes of aspirated joint effusion up to 23 ml. Pain relief and increased joint motion after drainage of the intracapsular effusion was observed in 3 patients whose postoperative mobilization was facilitated.
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{
"pile_set_name": "PubMed Abstracts"
}
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The clinical spectrum of chronic appendiceal abscess in cystic fibrosis.
To describe the varied characteristics seen in patients with cystic fibrosis who develop chronic abscess formation secondary to unrecognized appendicitis. Patient series. Cystic Fibrosis Care Centers in Columbus, Ohio, and Tucson, Ariz. Five patients with cystic fibrosis who developed chronic abdominal abscesses secondary to occult appendicitis are described. Two patients developed fistula formation with purulent fluid drainage before diagnosis. One patient developed an extensive psoas abscess. Another presented with prolonged fever of unknown origin. These patients were identified by retrospective review of the past 20-year experience at two Cystic Fibrosis Care Centers. Development of chronic abdominal abscess related to unrecognized appendicitis is a rare but important complication in patients with cystic fibrosis. Prompt diagnosis depends on physician familiarity with the varied presentations of this entity. Diagnostic abdominal computed tomography and/or ultrasonography should particularly be considered when patients with cystic fibrosis present with pain, mass, or drainage from the right flank; prolonged fever; a limp; or failure of suspected meconium ileus equivalent syndrome to respond promptly to cathartic measures.
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{
"pile_set_name": "PubMed Abstracts"
}
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Adult performance on three tests of equilibrium.
The purpose of this investigation was twofold: (a) to determine preliminary norms for young adult males and young adult females on three clinical tests of equilibrium, Tilt Board Tip (TBT), Tilt Board Reach (TBR), and Flat Board Reach (FBR), and (b) to determine sex differences in equilibrium performance. The three equilibrium tests were administered to a sample of 25 men and 29 women between the ages of 20 and 30 years. The results revealed a significant sex difference on TBT, with men obtaining significantly higher scores than women. FBR approached significance, and no significant difference was found on the TBR. These results support earlier findings of sex differences in performance on a variety of equilibrium measures and suggest that different normative criteria should be used to evaluate the performance of males and females on some tests of equilibrium. Possible reasons for males obtaining higher scores on TBT and for lack of differences between male and female performance on FBR and TBR are discussed.
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{
"pile_set_name": "PubMed Abstracts"
}
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Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration.
Thioredoxin 2 (TXN2; also known as Trx2) is a small mitochondrial redox protein essential for the control of mitochondrial reactive oxygen species homeostasis, apoptosis regulation and cell viability. Exome sequencing in a 16-year-old adolescent suffering from an infantile-onset neurodegenerative disorder with severe cerebellar atrophy, epilepsy, dystonia, optic atrophy, and peripheral neuropathy, uncovered a homozygous stop mutation in TXN2. Analysis of patient-derived fibroblasts demonstrated absence of TXN2 protein, increased reactive oxygen species levels, impaired oxidative stress defence and oxidative phosphorylation dysfunction. Reconstitution of TXN2 expression restored all these parameters, indicating the causal role of TXN2 mutation in disease development. Supplementation with antioxidants effectively suppressed cellular reactive oxygen species production, improved cell viability and mitigated clinical symptoms during short-term follow-up. In conclusion, our report on a patient with TXN2 deficiency suggests an important role of reactive oxygen species homeostasis for human neuronal maintenance and energy metabolism.
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{
"pile_set_name": "PubMed Abstracts"
}
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Pathogenesis of corneal damage from pseudomonas exotoxin A.
Pseudomonas aeruginosa exotoxin A was injected into rabbit corneas. Death of epithelial, endothelial, and stromal cells resulted, and necrosis of the cornea followed. Control eyes with exotoxin neutralized by specific antitoxin showed minimal damage. A dose-response pattern was evident. Antitoxin neutralization of pseudomonas exotoxin A in corneal ulcers may have possible therapeutic implications.
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{
"pile_set_name": "PubMed Abstracts"
}
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Simultaneous quantification of opiates, amphetamines, cocaine and metabolites and diazepam and metabolite in a single hair sample using GC-MS.
A method is described for the simultaneous identification and quantification of opiates, amphetamines, cocainics, diazepam and nordiazepam from one hair extract (typically 10-50mg hair). After decontamination by washing with shampoo, dichloromethane, isopropanol and acetone, drugs were extracted using 0.1M HCl followed by SPE clean-up using mixed-mode extraction cartridges. The SPE extracts were submitted to a two-step derivatisation using MBTFA and MSTFA+1% TCMS and analysis was performed by GC-MS using both SIM and scan modes. Four deuterated standards were used to monitor 14 compounds. The limit of quantification was the total drug detected from the sample. This was 5 ng for amphetamines and 10 ng for remaining drugs which is equivalent to 0.1 and 0.2 ng/mg from a 50mg sample. Standard curves for the range 5-400 ng total drug concentration for all drugs had regression coefficients greater than 0.98. An authentic hair sample was used to validate the method and gave R.S.D.s <25% for both inter and intra-day reproducibility. The results of the analysis of hair taken from four patients attending a drug treatment clinic and six hair samples including head hair, pubic hair, axial hair and beard taken at post-mortem are presented.
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{
"pile_set_name": "PubMed Abstracts"
}
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Normal growth and development with unrestricted protein intake after severe infantile propionic acidaemia.
A child with propionic acidaemia, after a stormy infantile course complicated by microcephaly, has shown normal subsequent growth and development without dietary protein restriction.
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{
"pile_set_name": "PubMed Abstracts"
}
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Prostatodynia and herpes simplex virus infection.
The etiology of chronic abacterial prostatitis remains obscure, although viral agents have been postulated. Herpes simplex virus was isolated from the prostatic fluid of a patient with symptoms of prostatitis and the implications are reviewed.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Registries for clinical trials -- a critical stock-taking].
A German working group had requested to introduce a national clinical trials registry. Keeping in mind the numerous existing German clinical trials registries requirements of such a registry, as well as the current international harmonization initiatives and the possibility of creating such a national registry were considered. To avoid multiple recording especially in regard to multicentric, international trials, it is recommended -- based on the spirit of the WHO recommendations -- to use the trial registry of the National Institutes of Health. For the time being, this trial registry represents the by far most frequently used database available for public use. It is equipped by internationally active pharmaceutical companies as well as universities and research facilities from all over the world and actually contains approximately 23,500 clinical studies. A national clinical trials registry could be installed at best only complementary and would have to get its data directly from the international registry without additional burden by research facilities.
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{
"pile_set_name": "PubMed Abstracts"
}
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Inactivation of Bacillus cereus spores in a tsuyu sauce using continuous ohmic heating with five sequential elbow-type electrodes.
The effect of ohmic heating (OH) in a pilot plant system which had a zig-zag shaped (elbow-type) ohmic heater with five sequential voltage electrodes was investigated on Bacillus cereus spores in a commercial tsuyu sauce. The electrical field was fixed at 26·7 V cm(-1) with an alternating current frequency of 25 kHz. Raw tsuyu sauce (50 l) inoculated with B. cereus spores was submitted in a 4 × 3 factorial design to the OH system and heated at 95, 105, 115, and 125°C each for 30, 60, and 90 s. Survival of B. cereus spores and colour change in the commercial tsuyu sauce were both measured before and after treatment. As the treatment temperature and time increased, the number of surviving B. cereus spores decreased. The OH treatment in a bath-type process at 105°C for more than 30 s resulted in the total inactivation of the inoculated B. cereus spores (average 5·4 log reductions to undetectable levels after treatment). The OH protocol of heating at 105°C for 60 s which ensure complete eradication of the inoculated spores without compromising product quality was chosen and investigated for its suitability for commercial application on bulk quantities of samples (500 l). Reliable and reproducible reductions in B. cereus spore counts of 4·7-5·5 log CFU ml(-1) (mean ± standard deviation = 5·1 ± 0·3 CFU ml(-1) ) were achieved by the selected protocol of the continuous OH treatment (105°C for 60 s). This study suggests that OH treatment with five sequential elbow-type electrodes has great potential as an industrial sterilizing method for liquid food contaminated with B. cereus spores. This procedure will enhance the microbiological quality of liquid foods while minimizing quality deterioration.
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{
"pile_set_name": "PubMed Abstracts"
}
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[In-vitro studies on the catabolism of acetyl urea in liver tissue].
In vitro-studies were carried out with hepatic tissue from freshley slaughtered cows using 14C acetyl urea (in which the urea-C-atom was labelled). Methods of thin-layer chromatography were used to investigate the process of acetyl urea degradation. The cows had not previouslybeen adapted to acetyl urea. The test mixtures used contained 3.3 mg or 20 mg acetyl urea per 100 ml of the homogenate. The pattern of acetyl urea degradation in these mixtures was investigated after 1 min, 3 mins, 10 mins and 30 mins. The degradation rates were found to be the same for both types of test mixtures. This indicated that a saturation of the substrate had not been accomplished, even when higher concentrations of acetyl urea were used. Supplementary addition of urease to the test mixture for decomposing the quantity of urea always produced did not alter the rates of acetyl urea degradation. From this it may be concluded that even under in vivo-conditions some urea will be liberated when acetyl urea passes through the liver.
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{
"pile_set_name": "PubMed Abstracts"
}
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Relationship between reproductive aging, body composition, hormonal status and metabolic syndrome in postmenopausal women.
To determine the relationship between different anthropometric indicators, reproductive aging and hormonal status in postmenopausal women with and without metabolic syndrome. One hundred and forty non-surgical, postmenopausal women were enrolled to this cross-sectional study. Each participant completed a questionnaire and underwent a medical examination, including measurements of body mass index, weight and body composition criteria. Body composition was evaluated with measurements of the waist-to-hip circumference ratio and skinfold thickness (triceps, suprailiac and front thigh). Levels were determined of serum lipids, including cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides, and also fasting blood sugar, sex hormone binding globulin (SHBG), estradiol and testosterone. The metabolic syndrome was defined according to the definition of the National Cholesterol Education Program Adult Treatment Panel III. Logistic regression analysis revealed a significant association between weight (p < 0.001), age (p < 0.01) and SHBG (p = 0.021) with risk for metabolic syndrome. Age, SHBG and weight are critical correlates of metabolic syndrome in postmenopausal women.
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{
"pile_set_name": "PubMed Abstracts"
}
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Healthcare resource utilization and costs in patients with HIV-1 who switched first-line antiretroviral therapy.
Objectives: This study compared healthcare utilization and costs associated with switching the first-line protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) based antiretroviral (ARV) regimen due to reasons other than virologic failure among patients with HIV-1. Methods: This was a retrospective analysis of commercial and Medicare Advantage with Part D enrollees in two US administrative claims databases. The study population comprised adults with HIV-1 infection initiating antiretroviral therapy (ART) on PI- or NNRTI-containing regimens from 1 January 2006 to 31 December 2015. Patients with a subsequent change in anchor agent were assigned to the switch cohort; the non-switch cohort was constructed using propensity score matching of three non-switching patients for each patient in the switch cohort. Patient characteristics and per patient per month healthcare resource utilization and costs were compared between the cohorts during the pre-switch, switch (15 days before and after switching) and post-switch periods. Costs during the switch period were also estimated with a multivariable-adjusted model. Results: The matched study population consisted of 1204 patients who switched their first-line PI- or NNRTI-based regimen and 3612 patients who did not. Compared with the non-switch cohort, patients who switched had higher healthcare resource utilization during the pre-switch, switch and post-switch periods. Mean unadjusted non-ART costs in the switch cohort were nearly double ($2944 versus $1530, p < .001), more than double ($2562 versus $1215, p < .001) and 1.5 times higher ($1473 versus $968, p < .001) than costs in the non-switch cohort in the pre-switch, switch and post-switch periods, respectively. Conclusions: Patients with HIV-1 who initiated PI- or NNRTI-based regimens and switched ARTs for reasons other than virologic failure used more healthcare resources and incurred greater costs relative to patients in the non-switch cohort. This study highlights the importance of initiating patients on appropriate first-line ART to avoid the need to switch due to reasons other than virologic failure.
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{
"pile_set_name": "PubMed Abstracts"
}
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Sodium-dependent uptake of [3H]scyllo-inositol by Tetrahymena: incorporation into phosphatidylinositol, phosphatidylinositol-linked glycans, and polyphosphoinositols.
[3H]Scyllo-inositol was taken up by Tetrahymena cells through a sodium-dependent pathway wherein unlabeled scyllo- and myo-inositol competed for uptake. d-Glucose was a competitor of [3H]myo-inositol uptake, but did not appear to compete for [3H]scyllo-inositol uptake. Transport of [3H]scyllo- and [3H]myo-inositol was inhibited when sodium was removed from the labeling buffer and by phlorizin, an inhibitor of sodium-dependent transporters. Cytochalasin B, an inhibitor of facilitated glucose transporters, had no significant effect on inositol transport. Internalized [3H]scyllo-inositol was readily incorporated intact into phosphatidylinositol, phosphatidylinositol-linked glycans, and polyphosphoinositols. Distribution of [3H]scyllo- and [3H]myo-inositol radioactivity into individual polyphosphoinositols was found to differ.
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{
"pile_set_name": "PubMed Abstracts"
}
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The effect of a nucleotide-nucleoside solution on hepatic regeneration in rats after partial hepatectomy and in primary monolayer culture of hepatocytes.
Purine and pyrimidine metabolism is a key process after hepatic surgery. To evaluate the effect of purine and pyrimidine supplementation on hepatic regeneration, the following clinical in vitro and in vivo experiments were performed. Changes in blood nucleotides, nucleosides and nucleobase were analyzed by high performance liquid chromatography in patients and rats after partial hepatectomy. The effect of supplementation of nucleotide-nucleoside solution (OG-VI) or their components on nucleic acids syntheses in primary monolayer cultured hepatocytes and preoperative intraperitoneal injection of OG-VI on hepatic regeneration in the partially hepatectomized rats were evaluated. Blood purine and pyrimidine levels in patients change after hepatectomy and their changes indicate increased salvage synthesis of purine and pyrimidine in the regenerating liver. Addition of appropriate amounts of inosine, GMP, uridine, or thymidine, the substrates for salvage purine and pyrimidine syntheses, to primary cultures of hepatocytes enhanced both DNA and RNA syntheses by the salvage and de novo pathways. The OG-VI mixture also enhanced the syntheses of DNA and RNA. Preoperative administration of OG-VI to partially-hepatectomized rats enhances hepatic DNA synthesis in a way similar to the in vitro study.
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{
"pile_set_name": "PubMed Abstracts"
}
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Prolonged duration local anesthesia with lipid-protein-sugar particles containing bupivacaine and dexamethasone.
Glucocorticoids prolong block duration from polymeric microspheres containing bupivacaine, but not from unencapsulated drug. Here we investigate this effect applies to particles with much more rapid drug release and improved long-term biocompatibility. Male Sprague-Dawley rats were given sciatic nerve blocks with 75 mg of 3% or 60% (w/w) dipalmitoylphosphatidylcholine (DPPC) spray-dried lipid-protein-sugar particles (LPSPs) containing 10% (w/w) bupivacaine and 0%, 0.05%, or 0.1% (w/w) dexamethasone. Sensory nerve block from bupivacaine-containing 3% and 60% (w/w) DPPC particles without dexamethasone yielded blocks lasting 301 +/- 56 and 321 +/- 127 min, respectively. Addition of 0.05% (w/w) dexamethasone increased block durations to 610 +/- 182 and 538 +/- 222 min, respectively; increasing dexamethasone loading to 0.1% did not further increase duration. One day after injection, dexamethasone-containing particles resulted in lower inflammation scores and capsule thickness than dexamethasone-free particles, but the difference was gone by day 4. Excipient composition had prominent effects at all time points. For all groups, inflammation was largely resolved by 2 weeks after injection. Dexamethasone approximately doubled the duration of nerve block from bupivacaine-loaded LPSPs, while maintaining excellent biocompatibility. Such formulations could be useful in clinical applications when nerve blockade is needed for 24 hours or less.
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{
"pile_set_name": "PubMed Abstracts"
}
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The Effect of Concomitant Rib Deformity in Congenital Scoliosis on Spinal Curve Correction After Segmental Pedicle Screw Instrumentation.
A single-center, prospective study. To investigate the effect of rib anomaly on surgical curve correction outcome in congenital scoliosis. The presence of rib anomalies may complicate surgical correction of congenital scoliosis. The outcome of surgical correction, however, has not been documented in scoliotic patients with and without rib deformity. Percent Cobb angle decrease (CAD) after operation was calculated in 94 patients with congenital scoliosis. Posterior segmental pedicle screw instrumentation (posterior approach) with or without previous anterior spinal release and fusion (anterior approach) was the method of correction. The impact of vertebral anomaly and rib deformity on CAD was examined. Although the type of vertebral anomaly had no significant effect on the mean CAD, it was significantly lower in 56 patients with rib deformity compared with that in the remaining patients without rib deformity (35.14%±15.83% vs. 51.54%±17.82%, P<0.001); particularly in those with complex, unilateral rib abnormalities, and in those with same-level vertebral and rib deformities. Patients' sex and age at the time of operation, rib number abnormality, and the type of operation (ie, posterior-only approach vs. anterior and posterior approach) did not contribute significantly to Cobb angle change after operation. Concomitant rib deformities, particularly of complex and unilateral types, significantly compromise operative curve correction outcome in congenital scoliosis.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Seizure-free paroxysms in epilepsy and migraine].
Fourty epileptic and 66 migraine patients were examined. The differences in clinical features of headache paroxysms, consciousness disorders, psycho-sensory++, viscero-autonomic++ and affective spells were determined. The elements of confused consciousness, short-lived and local autonomic responses were characteristic of seizure-free epileptic attacks. Migrainous paroxysms were multiform and pronounced in terms of autonomic disorders, had lesser depth and incidence of consciousness disorders with longer lasting vaso-autonomic++ crises.
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{
"pile_set_name": "PubMed Abstracts"
}
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Dexamethasone alone vs in combination with transcutaneous electrical acupoint stimulation or tropisetron for prevention of postoperative nausea and vomiting in gynaecological patients undergoing laparoscopic surgery.
Postoperative nausea and vomiting (PONV) is commonly reported after surgery and anaesthesia. We compared the effects of combinations of electrical acupoint stimulation or tropisetron with dexamethasone with the effects of dexamethasone alone, for inhibition of PONV in gynaecological patients undergoing laparoscopic surgery. We randomized 157 patients undergoing elective gynaecological laparoscopic surgery under general anaesthesia into the following three groups: acupoint stimulation+dexamethasone (Group Acu, n=53), tropisetron+dexamethasone (Group Trp, n=53), and dexamethasone alone (Group Dxm, n=51). The incidence of nausea, vomiting, and need for rescue antiemetics was recorded 2, 6, 24, and 48 h after surgery. We found significant differences in the incidence of PONV during 24 h after surgery between the combination therapy groups and the dexamethasone-alone group (P=0.021). In the first 24 h, 28% of patients in Group Acu, 26% of patients in Group Trp, and 50% of patients in Group Dxm experienced nausea, vomiting, or both. The incidence of 24 h PONV in Group Acu was significantly lower than that in Group Dxm (P=0.048; odds ratio 0.389; 95% CI 0.170-0.891). The incidence of 24 h PONV in Group Trp was also significantly lower than that in Group Dxm (P=0.042; odds ratio 0.359; 95% CI 0.157-0.819). There was no significant difference between Group Acu and Group Trp (P=0.857). The need for antiemetic rescue medication was similar in the three groups. All groups expressed similar patient satisfaction. Combined with dexamethasone, electrical acupoint stimulation or tropisetron is more effective in PONV prophylaxis than dexamethasone alone in gynaecological patients undergoing laparoscopic surgery. NCT 02096835.
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{
"pile_set_name": "PubMed Abstracts"
}
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Simulation of hydrogen sulphide absorption in alkaline solution using a packed column.
In this work, a simulation tool was developed for hydrogen sulphide (H₂S) removal in an alkaline solution in packed columns working at countercurrent. Modelling takes into account the mass-transfer enhancement due to the reversible reactions between H₂S and the alkaline species (CO(²⁻)(3), HCO⁻(3), and HO⁻) in the liquid film. Many parameters can be controlled by the user such as the gas and liquid inlet H₂S concentrations, the gas and liquid flow rates, the scrubbing liquid pH, the desired H₂S removal efficiency, the temperature, the alkalinity, etc. Since the influence of the hydrodynamic and mass-transfer performances in a packed column is well known, the numerical resolutions performed were dedicated to the study of the influence of the chemical conditions (through the pH and the alkalinity), the temperature and the liquid-to-gas mass flow rate ratio (L/G). A packed column of 3 m equipped with a given random packing material working at countercurrent and steady state has been modelled. The results show that the H₂S removal efficiency increases with the L/G, the pH, the alkalinity and more surprisingly with the temperature. Alkalinity has a very significant effect on the removal efficiency through the mass-transfer enhancement and buffering effect, which limits pH decreasing due to H₂S absorption. This numerical resolution provides a tool for designers and researchers involved in H₂S treatment to understand deeper the process and optimize their processes.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Role of endogenous intoxication in development of involutive and pathologic processes in patients of elderly and senile age with ischemic heart disease].
Blood toxicity and biochemical values were studied in 135 patients of different age with ischemic heart disease. Researches were carried out by means of bio-test method on "Cito-expert" apparatus. Blood toxicity was diagnosed in 85% patients of average age, in 87% patients of elderly age and in 95% patients of senile age with ischemic heart disease, which indicates endogenous intoxication. The study revealed correlation between age and blood toxicity (R=0,22; t=2,18; p<0,05). The increase of glucose, urea and lactate dehydrogenase content in blood was accompanied by growth of blood toxicity. Age-related raising of intoxication didn't have any relations with increasing of glucose, urea and lactate dehydrogenase content in blood, because there was no difference between concentration of these metabolites in patients of different age. The correlation between age and blood toxicity demonstrates pathogenetic role of endogenous intoxication in the development of involutive and pathologic process in elderly and senile patients with ischemic heart disease and confirms the necessity to stop it.
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{
"pile_set_name": "PubMed Abstracts"
}
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Design of a peptide inhibitor of tyrosine kinase 2.
Tyrosine kinase inhibitors show great promise as clinical therapies, but small molecule inhibitors that are available in the clinic and under development bind to the adenosine triphosphate binding domain of the kinase, potentially limiting efficacy and selectivity. The development of antisense peptide inhibitors is a relatively unexplored area of research, and here we investigate inhibitory peptides specific for the Janus-associated kinase (JAK) family member, tyrosine kinase 2 (TYK2). We have developed peptides that are 2-3 times more selective for TYK2 than other JAK family members, with a TYK2 IC50 of 1.2 μM. In addition, TYK2 inhibitory peptides show specificity for TYK2-mediated functions over JAK1 functions in cell-based assays. These peptides provide a new tool for the development of specific peptide inhibitors for closely related tyrosine kinases.
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{
"pile_set_name": "PubMed Abstracts"
}
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A case of Marchiafava-Bignami disease with complete recovery: sequential imaging documenting improvement of callosal lesions.
Serial CT and MR imaging findings in a 44-year-old woman with Marchiafava-Bignami disease (MBD) are reported. In the acute stage, CT studies disclosed subtle hypodensity in the splenium, and T2-weighted MR images revealed apparent high signal intensity of the splenium and the central portion of the corpus callosum. Treatment with vitamin B complex resulted in complete recovery. T2-weighted MR images obtained three weeks after admission revealed dramatic resolution of imaging abnormalities, with only faint high signal intensity remaining in the splenium. The sequential changes observed on CT and MR images provided early diagnosis of MBD and the resolution of the lesion considered as brain edema, which suggested that edema might, in addition to demyelination or necrosis, be involved in the acute progression of MBD.
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{
"pile_set_name": "PubMed Abstracts"
}
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Biosensing environmental pollution.
Whole-cell biosensors are finding increasing use for the detection of environmental pollution and toxicity. These biosensors are constructed through the fusion of promoters, responsive to the relevant environmental conditions, to easily monitored reporter genes. Depending on the choice of reporter gene, expression can be monitored by the production of colour, light, fluorescence or electrochemical reactions. Recent advances in this area have included the development of biosensors of compact size that enable the on-line and in situ monitoring of a large number of environmental parameters.
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{
"pile_set_name": "PubMed Abstracts"
}
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Platelet aggregation in whole blood, a new approach for understanding the antiplatelet effect of N-(3-hydroxy-1,3,5(10)-estratrien-17b-yl) butylamine (buame).
We have previously reported the effect of a compound derived from estradiol containing a radical amino butyl at the 17-beta position which has shown anticoagulant effects in whole blood and antiplatelet effects in light transmission aggregometry where platelets are isolated from other blood cells. In contrast, whole blood aggregometry includes the platelet interactions with blood elements such as erythrocytes and leukocytes. We examined the cooperative effect between leukocytes, erythrocytes and platelets and the antiplatelet effect of Buame in whole blood aggregometry, a tool to assess platelet function in its physiological environment. Buame (5-500 microM) dissolved in DMSO was tested in platelet aggregation induced by ADP (1.25 microM) or collagen (1 microg/mL) and the response recorded over 5 min. Controls were run with DMSO and the average control aggregation was taken as 100%. Results were obtained in both whole blood and platelet aggregometry. Buame was able to inhibit the secondary aggregation induced with ADP suggesting impairment in thromboxane A2 production. Also the first and second aggregation phases were inhibited when collagen-induced platelet activation was employed. This concentration-dependent pattern was shown in both whole blood and platelet aggregometry assays. When tested in light transmission aggregometry, a higher concentration of Buame was required in order to inhibit to the same degree ADP- or collagen-induced platelet aggregation (30 microM ,114 microM) than that required in the whole blood assay (IC50 84 microM, 191 microM). Interactions among different cell types in whole blood may modify the response of Buame-treated platelets to agonists suggesting a cooperative mechanism.
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{
"pile_set_name": "PubMed Abstracts"
}
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US and Scottish Health Professionals attitudes toward DNA biobanking.
The authors used a fifteen item survey to canvass 200 health care professionals in the United States and Scotland about their attitudes toward the potential utility of a DNA biobank. Results indicate a broadly favorable opinion in both locations. This finding seems to support further development of such a tool.
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{
"pile_set_name": "PubMed Abstracts"
}
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Post-operative management of primary glioblastoma multiforme in patients over 60 years of age.
Optimal treatment for elderly patients with glioblastoma multiforme is not well defined. We evaluated the efficacy of post-operative radiotherapy with or without concomitant and/or adjuvant temozolomide in patient, aged > or = 60 years to assess survival and identify prognostic factors of survival. A retrospective analysis of overall survival and progression-free survival in patients with newly diagnosed glioblastoma multiforme aged > or = 60 years treated with post-operative radiotherapy with or without temozolomide chemotherapy was conducted at our institutions. Prognostic factors were determined by univariate and multivariate analyses. Of 75 study participants (54.7% male; median age at first diagnosis, 65.1 years), 29 (38.7%) underwent gross total resection, whereas others underwent partial resection or biopsy only. All but 1 patient received radiotherapy. Twenty patients received concomitant temozolomic e only. Adjuvant temozolomide (1-50 cycles) was administered in 42 patients; 16 received > or = 6 cycles. Median overall survival was 10.3 months. One- and 2-year overall survival rates were 42.6% and 6.7%, respectively. Median progression-free survival was 4.1 months. Radiochemotherapy was generally well tolerated. Median overall survival was 15.3 and 29.6 months for patients who received 6-12 cycles and >12 cycles of adjuvant temozolomide, respectively. There were no significant differences in overall survival between age groups (60-64, 65-69, and > or = 70 years). Adjuvant temozolomide, Karnofsky performance status > or = 70, and additional surgery after progression were significant prognostic factors of longer overall survival (p<0.05). Radiochemotherapy, including > or = 6 cycles of adjuvant temozolomide, was safe and prolonged survival of glioblastoma patients aged > or = 60 years. Aggressive therapy should not be withheld from patients aged > or = 60 years with good performance status because of age.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effect of milrinone on small mesenteric artery vasoconstriction: role of K(+) channels.
We examined whether milrinone-mediated attenuation of small mesenteric artery vasoconstriction results predominantly from the activation of vascular smooth muscle K(+) channels. Resistance arteries (approximately 150 micrometers) were dissected from rat mesentery and were mounted on a wire myograph. Isometric force development in response to increasing concentrations of norepinephrine (NE) was monitored before and after treatment with the type 3 phosphodiesterase inhibitor milrinone. Milrinone significantly reduced NE-induced vasoconstriction, attenuating both NE sensitivity and maximal tension generation. Inhibition of ATP-sensitive K(+) channels or voltage-gated K(+) channels did not prevent the milrinone-induced attenuation of NE responses. Blockade of inwardly rectifying K(+) channels or Ca(2+)-sensitive K(+) channels prevented the milrinone-mediated reduction in NE sensitivity, but this effect was apparently due to direct enhancement of vasoconstrictor responsiveness rather than interference with the mechanism of milrinone action. In addition, milrinone elicited substantial relaxation in vessels preconstricted with 100 mM KCl. This effect was mimicked by the adenylyl cyclase activator forskolin and was reversed by the Rp diastereomer of cAMP, which is a cAMP-dependent protein kinase (PKA) inhibitor. Our results indicate that cAMP/PKA-mediated impairment of vasoconstriction may occur without the contribution of K(+) channel regulation.
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{
"pile_set_name": "PubMed Abstracts"
}
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Running symposium.
The running symposium has been designed to demonstrate to the reader the basic mechanics of the running gait, as compared to normal walking. It is imperative in order to understand the nature of the problems seen in runners to understand the forces and motions which are occurring in the various joints of the lower extremity, so that as much as possible, treatment can be based upon accurate anatomical diagnoses, rather than empiric treatment. The second part of this symposium discusses the nature of the injuries seen in the lower extremity in runners. Suggestions are made as to how to manage the problems as well as their prevention. Finally, a comment is included on the nature of the running shoe and on shoe selection.
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{
"pile_set_name": "PubMed Abstracts"
}
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Risk-benefit analysis of adalimumab versus traditional non-biologic therapies for patients with Crohn's disease.
Adalimumab is indicated for the treatment of moderately to severely active Crohn's disease (CD). A systematic analysis of risks and benefits of adalimumab versus traditional non-biologic therapies for patients refractory to non-biologic therapy is lacking. A base-case analysis compared expected benefits of adalimumab therapy with a 12-week stopping rule for non-responders versus non-biologic therapies using data from clinical trials (CHARM, CLASSIC I). Adverse events (AEs) recorded in clinical trials (CHARM, CLASSIC I, CLASSIC II, GAIN, open-label extensions) were compiled. Sensitivity analyses incorporated all observed benefits of adalimumab and placebo (CHARM, CLASSIC I, GAIN) and observed AEs from a systematic literature review of non-biologic therapies (MEDLINE search of randomized trials 1990-2007). Distributional information from maintenance clinical trial observations and benefit model predictions were used in a probabilistic simulation. Incremental net benefits were estimated based on utility estimates from the literature. Average time in remission (i.e., CDAI <150) over 1 year of therapy was 39.9% for adalimumab versus 6.6% for traditional non-biologic therapies. Adalimumab was associated with fewer expected hospitalizations, better fistula closure rates, and lower AE rates. These findings were robust in sensitivity analyses. In the probabilistic simulation, with serious AEs as a composite of risks, adalimumab provided greater benefits with fewer AEs versus non-biologic therapies (P < 0.01). Adalimumab demonstrated greater incremental net quality-adjusted life-years (0.12) versus non-biologic therapies. Adalimumab demonstrated greater benefits and lower rates of AEs versus traditional non-biologic therapies for patients with moderately to severely active CD who were refractory to non-biologic therapies.
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{
"pile_set_name": "PubMed Abstracts"
}
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A representational approach to patient education.
To describe the theoretical basis for a representational approach to patient education and the application of this approach to the development, implementation, and preliminary evaluation of a representational intervention for pain management. Leventhal's common sense model (CSM) was a guide for this approach to patient education. The CSM is based on the idea that people have common sense beliefs, or representations, that guide how they cope with health problems. Theoretically based interventions derived from the CSM have not been reported. Steps included: (a) designing a general approach to educational interventions, centered on illness representations; (b) specifying an intervention (RIDPAIN) to facilitate coping with cancer pain; (c) pilot-testing and revising the intervention; and (d) testing feasibility and acceptability of the intervention with 61 patients in a Midwestern American city. The RIDPAIN intervention was useful in eliciting misconceptions of pain and pain management from patients experiencing cancer pain. Many patients found RIDPAIN to be meaningful and useful, and they perceived it to have an effect on pain-related beliefs and behaviors. This theory-driven approach should be effective and widely applicable because it includes patients as active participants in all phases of the learning continuum, from information acquisition to behavior change.
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{
"pile_set_name": "PubMed Abstracts"
}
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Harvesting airway surface liquid: a comparison of two techniques.
The quantity and composition of airway surface liquid (ASL) are essential to host defense. To date, attempts to harvest ASL and measure its composition have yielded conflicting results. We investigated the physical principles underlying two techniques that were proposed for harvesting ASL: filter paper pledgets and polyethylene catheters. We compared the force and pressure generation and the kinematics of capillarity-induced fluid uptake with both techniques. Both have significant limitations for harvesting ASL, generating physiologically significant pressures (filter paper, 60.4 Pa; polyethylene, 14.3 Pa) that could potentially compromise epithelial integrity. Furthermore, filter paper generates a force 85-fold higher than the polyethylene catheter, which is associated with a very high rate of uptake of liquid and a large total amount of liquid relative to ASL thickness. While the PE catheter harvests liquid more gently, it is only effective when ASL surface tension is below 31 mN/m. These limitations likely account for some of the variability in reported ASL composition, and highlight the need for improved methods for harvesting ASL.
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{
"pile_set_name": "PubMed Abstracts"
}
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Global-local interference modulated by communication between the hemispheres.
Three experiments examined whether interhemispheric interaction modulates selective attention in a same-different version of D. Navon's (1977) global-local paradigm. In Experiments 1 and 2, interhemispheric interaction reduced interstimulus interference produced when two stimuli matched at a preassigned level (e.g., local) but differed at the irrelevant level (e.g., global). This effect was greater for stimuli made of a few large elements than for those made of many small elements. Experiment 3 demonstrated that (a) the ability of interhemispheric interaction to reduce interstimulus interference is not constrained by hemispheric differences for global and local processing and (b) interhemispheric interaction does not strongly modulate intrastimulus interference produced when the forms at the preassigned (e.g., local) and irrelevant (e.g., global) levels differ within an individual stimulus. These findings indicate that interaction between the hemispheres is a neural mechanism that may aid selective attention.
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{
"pile_set_name": "PubMed Abstracts"
}
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Use of subjective information in scientific psychology: VI. The inability to speak a foreign language experienced as a disability.
The author discusses his adaptation to language stress while living and working several months in a foreign country, specifically the ways in which the author coped with language stress; his thoughts and feelings about being unable to communicate verbally, and the insights he gained into the world of the disabled because he was unable to communicate.
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{
"pile_set_name": "PubMed Abstracts"
}
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Etoricoxib in the treatment of primary dysmenorrhea in Chinese patients: a randomized controlled trial.
Assess the efficacy and safety of etoricoxib 120 mg compared with ibuprofen 600 mg qid in the treatment of moderate to severe primary dysmenorrhea in Chinese women. This multicenter, double-blind, two-period, cross-over study randomized healthy, Chinese women ≥18 years of age to etoricoxib 120 mg qd or ibuprofen up to 2400 mg (600 mg qid) upon onset of moderate or severe primary dysmenorrhea symptoms during two menstrual cycles. The primary efficacy endpoint was Total Pain Relief score over the first 6 hours (TOPAR6). Secondary endpoints included Sum of Pain Intensity Difference scores over the first 6 hours (SPID6) and Patient's Global Evaluation (GLOBAL) of pain at 6 and 24 hours post initial dose. The primary hypothesis was that etoricoxib would be non-inferior to ibuprofen. Adverse experiences (AE) were monitored and evaluated. A total of 139 patients were included in this study. Difference in least squares (LS) mean (95% CI) TOPAR6 score for etoricoxib vs. ibuprofen was 0.89 (0.03, 1.76) (p = 0.043). LS mean (95% CI) difference for etoricoxib vs. ibuprofen SPID6, GLOBAL6, and GLOBAL24 were 0.20 (-1.16, 1.57) (p = 0.768), 0.26 (0.07, 0.45) (p = 0.007), and 0.36 (0.17, 0.54) (p < 0.001), respectively. AEs were rare, with the following AEs determined to be drug-related: hypomenorrhea (two patients on etoricoxib) and allergic dermatitis (one patient on ibuprofen). Limitations of the study design include a sample size that is not adequate for evaluation of rare adverse effects, an evaluation period that was limited to 24 hours, and inconsistent frequency of active treatment doses between etoricoxib (once daily) and ibuprofen (up to four times daily). The primary objective of the study was met, demonstrating that etoricoxib 120 mg qd was non-inferior to ibuprofen 600 mg qid; further, etoricoxib was statistically superior to ibuprofen 600 mg qid according to the primary endpoint (TOPAR6) and patient global assessments of study medication. Etoricoxib and ibuprofen were generally well tolerated.
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{
"pile_set_name": "PubMed Abstracts"
}
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Prediction of pathogenic mutations in mitochondrially encoded human tRNAs.
Some mutations in human mitochondrial tRNAs are severely pathogenic. The available computational methods have a poor record of predicting the impact of a tRNA mutation on the phenotype and fitness. Here patterns of evolution at tRNA sites that harbor pathogenic mutations and at sites that harbor phenotypically cryptic polymorphisms were compared. Mutations that are pathogenic to humans occupy more conservative sites, are only rarely fixed in closely related species, and, when located in stem structures, often disrupt Watson-Crick pairing and display signs of compensatory evolution. These observations make it possible to classify approximately 90% of all known pathogenic mutations as deleterious together with only approximately 30% of polymorphisms. These polymorphisms segregate at frequencies that are more than two times lower than frequencies of polymorphisms classified as benign, indicating that at least approximately 30% of known polymorphisms in mitochondrial tRNAs affect fitness negatively.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effect of antidepressants on brain-derived neurotrophic factor (BDNF) release from platelets in the rats.
Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family, and enhances the growth and maintenance of several neuronal systems. In addition, BDNF may promote neurogenesis and protect against hippocampal volume loss in depressive disorders. Although first detected in brain, BDNF also exists in peripheral tissues and is mainly stored in platelets and circulates in blood. Recent reports indicate that serum BDNF levels in depressive patients are lower than in control subjects, and antidepressant treatment increases serum BDNF levels in responders. A single report suggests that decreased serum BDNF in major depression is related to mechanisms of platelet BDNF release; however, the mechanisms of changes in BDNF blood levels are still poorly understood. In the present study, we investigated the direct influence of antidepressants on BDNF release from platelets and their effects on serum levels. We used samples of washed platelets prepared from rat blood, and investigated the platelet BDNF release and serum BDNF concentration changes in response to adding antidepressants. We found that BDNF was dose-dependently released from platelets by direct treatment with various kinds of antidepressants in vitro, and serum BDNF concentration was also increased by intravenous antidepressant treatment. These results confirm that BDNF release from platelets is affected by antidepressants, which may relate to the circulating BDNF level change in peripheral blood. The response of BDNF release differs depending on the type and amount of antidepressants, making BDNF a serious candidate as a predictor of antidepressant treatment response.
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{
"pile_set_name": "PubMed Abstracts"
}
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[The challenge of care teaching from the point of view of the professors of EEUFRGS].
The object of this study is teaching and practicing human care. It comprises the' third stage of the research on the theme: the challenge of teaching how to care from the point of view of the academic students, nurses and, in this one, the professors of EEUFRGS. It is a qualitative, phenomenological study with Martin Heidegger's theoretical and philosophical support. The purpose of this stage is knowing/understanding how the theoretical and practical teaching of human care occurs, considering that it is the curricular guidance of the graduation course. The phenomenological analysis evidences that the professors initiate the students'foundations regarding care from their daily experiences and from the scientific foundation; holistic care characterizes the human care.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Construction of the nucleic vaccine pVVP3L-18HN and its antitumor effect on human laryngeal carcinoma].
Nucleic vaccine of pVVP3IL-18HN expressing apoptin gene, Newcastle disease virus HN gene and IL-18 gene were constructed to observe the combinative antitumor effect of the above three genes. Eukaryotic expression plasmid pVVP3IL-18HN was constructed by inserting apoptin gene and fragment comprising fused IL-18HN gene and IRES promoter into the downstream of CMV promoter of vector pVAX1. The expression of inserted gene was identified by RT-PCR, indirect immunofluorescence and Western-blot. The recombinant plasmid was introduced into Hep-2 cells by liposome, then suppression rate of Hep-2 of different time and different quantity was calculated according to MTT results. The recombinant plasmid of pVVP3IL-18HN suppressed Hep-2 successfully and its suppression rate was up to 61.9% with 20 microg/ml, incubation of 72 hours. The nucleic vaccine constructed pVVP3IL-18HN had antitumor effect on Hep-2. It may can be used to the therapy and research of laryngeal carcinoma.
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{
"pile_set_name": "PubMed Abstracts"
}
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Histologic Appearance and Immunohistochemistry of DNA Mismatch Repair Protein and p53 in Endometrial Carcinosarcoma: Impact on Prognosis and Insights Into Tumorigenesis.
Endometrial carcinosarcoma (ECS) is a rare and aggressive mixed-type epithelial and mesenchymal tumor. This study focused on the histologic appearance, loss of DNA mismatch repair (MMR) protein expression, and aberrant p53 expression in the epithelial component, and overall prognosis of 57 cases with ECS. Histologically, 21 and 36 cases exhibited low-grade (endometrioid grade 1 and 2) and high-grade (others) epithelial components, respectively. In a Kaplan-Meier analysis, patients with a high-grade epithelial component exhibited worse progression-free survival (PFS), compared with those with a low-grade component. Although the former group also exhibited worse overall survival, the difference was not significant. Thirty-six cases exhibited aberrant p53 expression. Of these, 5 cases exhibited focally aberrant p53 expression in carcinomatous components with diffuse aberrant p53 expression in mesenchymal components. Aberrant expression of p53 did not show significant association with prognosis. Six patients with MMR deficiency exhibited relatively better PFS. In conclusion, a low-grade epithelial component is a superior predictor of the PFS of ECS, compared with MMR protein and p53 expression status. In some cases of ECS, TP53 mutation may be a late event associated with histogenesis of the sarcomatous component.
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{
"pile_set_name": "PubMed Abstracts"
}
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Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat Content but Is Dependent upon Capacity for β Cell Recovery.
The Diabetes Remission Clinical Trial reported return and persistence of non-diabetic blood glucose control in 46% of people with type 2 diabetes of up to 6 years duration. Detailed metabolic studies were performed on a subgroup (intervention, n = 64; control, n = 26). In the intervention group, liver fat content decreased (16.0% ± 1.3% to 3.1% ± 0.5%, p < 0.0001) immediately after weight loss. Similarly, plasma triglyceride and pancreas fat content decreased whether or not glucose control normalized. Recovery of first-phase insulin response (0.04[-0.05-0.32] to 0.11[0.0005-0.51] nmol/min/m2, p < 0.0001) defined those who returned to non-diabetic glucose control and this was durable at 12 months (0.11[0.005-0.81] nmol/min/m2, p = 0.0001). Responders were similar to non-responders at baseline but had shorter diabetes duration (2.7 ± 0.3 versus 3.8 ± 0.4 years; p = 0.02). This study demonstrates that β cell ability to recover long-term function persists after diagnosis, changing the previous paradigm of irreversible loss of β cell function in type 2 diabetes.
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{
"pile_set_name": "PubMed Abstracts"
}
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Deoxypodophyllotoxin triggers parthanatos in glioma cells via induction of excessive ROS.
Parthanatos is a new form of programmed cell death that is regulated by hyper-activated PARP-1, and is emerging as a new strategy to kill cancer cells. Deoxypodophyllotoxin (DPT) is a natural chemical that is found to induce cancer cell death, in which the role of parthanatos is unknown. Thus, we investigated this issue in this study by using glioma cell lines and mice model of xenograft glioma. We found that DPT induced glioma cell death in vitro and inhibited the growth of xenograft glioma in vivo, which was accompanied with parthanatos-related biochemical events including expressional upregulation of PARP-1, cytoplasmic accumulation of PAR polymer, and nuclear translocation of AIF. In vitro study revealed that genetic knockdown of PARP-1 with small interfering RNA attenuated DPT-induced elevation in the cytoplasmic PAR-polymer and the nuclear AIF, as well as protected glioma cells against the toxicity of DPT. Further, antioxidant NAC, as well as PARP-1 inhibitor 3AB, not only alleviated the overproduction of ROS caused by DPT, but also reversed the above-mentioned biochemical events, maintained mitochondrial membrane potential and rescued glioma cells death. Therefore, we demonstrated that deoxypodophyllotoxin triggered parthanatos in glioma cells via induction of excessive ROS.
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{
"pile_set_name": "PubMed Abstracts"
}
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Clinical outcomes of suspected ischemic myelopathy in cats.
Ischemic myelopathy is a disorder of acute onset that is characterized by nonprogressive paresis/plegia. Magnetic resonance imaging (MRI) is particularly helpful in supporting the antemortem diagnosis of ischemic myelopathy. Cats, which were suspected to have ischemic myelopathy between 2005 and 2008, were reviewed retrospectively. The acute onset of nonprogressive and nonpainful myelopathy, the conduct of spine MRI, and the availability of complete medical records were included in the inclusion criteria. The presumptive diagnosis was based on medical history as well as clinical, cerebrospinal fluid, and MRI findings. Six cats met the inclusion criteria based on medical records that had been made for about 3 years, and had relatively good prognoses. The less number of patients with ischemic myelopathy has been reported in cats than in dogs. However, the number of cats with ischemic myelopathy in clinical settings appears to be greater than previously considered.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Pharmacological treatment of aggressive impulsive behavior].
This article makes an initially tour of the definitions of violence, aggression and impulsiveness. Violence is a manifestation associated with various aspects of human behavior in different contexts of society and history. It can also be a clinical manifestation of a psychiatric disorder, the behavioral modality of some people with personality disorders, the expression of a somatic disorder, an action exercised by an individual under the influence of substances, as well as the expected reaction of an individual or a group to a specific trigger situation. Aggressiveness means "tendency to act or respond violently", using violent means to things or people and overcome their revulsion to do damage. After that, a brief overview of the different classifications of aggressive behaviour is made, to finish reviewing the bibliography published on the pharmacological treatment of emotional or impulsive aggression with the three main groups of drugs frequently used in clinical practice (antidepressants, mood stabilizers and antipsychotics), and a brief integration scheme is formulated.
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{
"pile_set_name": "PubMed Abstracts"
}
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Diurnal profiles of testosterone and pituitary hormones suggest different mechanisms for menstrual disturbances in endurance athletes.
The aim of this study was to evaluate the diurnal pattern of testosterone and pituitary hormones in endurance female athletes with different types of menstrual disorder. Age- and body mass index-matched groups of endurance athletes with amenorrhea (n = 10) and oligomenorrhea (n = 6), regularly cycling athletes (n = 8), and sedentary controls (n = 8) were compared with respect to 24-h hormonal profiles of testosterone, LH, prolactin (PRL), GH, insulin, IGF binding protein 1 (IGFBP-1), and cortisol. The 24-h hormone profiles in amenorrheic athletes were characterized by decreased LH pulsatility and peak amplitude of PRL and increased baseline levels of GH and cortisol. However, oligomenorrheic athletes displayed a significantly different pattern with higher diurnal testosterone secretion than all other groups. Furthermore, LH, PRL, GH, and cortisol secretions were comparable with regularly menstruating subjects. In the combined group of athletes with menstrual disturbances, diurnal secretions of testosterone, LH, and PRL were positively, whereas cortisol was negatively correlated with the number of menstruations the last year. Although this could be explained by a gradual inhibition of the hypothalamic-pituitary-gonadal axis, our results indicate that the symptoms of amenorrhea and oligomenorrhea may reflect two hormonally distinct conditions. Thus, amenorrheic athletes displayed a hormonal pattern in agreement with hypothalamic inhibition due to energy deficiency, whereas oligomenorrheic athletes demonstrated increased diurnal secretion of testosterone, suggesting a different mechanism, e.g. essential hyperandrogenism.
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{
"pile_set_name": "PubMed Abstracts"
}
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Fibronectin-adherent peripheral blood derived mononuclear cells as Paclitaxel carriers for glioblastoma treatment: An in vitro study.
Glioblastoma (GBM) represents the most aggressive malignant brain tumor in adults, with a risible median life expectancy despite gold standard treatment. Novel drug-delivery methods have been explored. Here we evaluated the possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic lineage as drug-carrier. MCs were obtained from 10 patients harboring a GBM, and from healthy volunteers, considered as controls. GBM tissue was also obtained from patients. MCs were cultured and the adherent population on fibronectin (FN-MCs), after immunocytochemistry and flow cytometry characterization, was loaded with Paclitaxel (FN-MCs-PTX). Antiproliferative and migration activity of FN-MCs-PTX was evaluated in two-dimensional (2D) and three-dimensional (3D) co-culture assays with red fluorescent U87 Malignant Glioma cells and primary GBM cells. Antiangiogenic properties of FN-MCs-PTX were tested on cultures with endothelial cells. Phenotypical characterization showed a high expression of monocytic-dendritic markers in GBM cells and FN-MCs. FN-MCs demonstrated to effectively uptake PTX and to strongly inhibit GBM growth in vitro (P <0.01). Moreover, tumor-induced migration of MCs, although partially affected by the PTX cargo, remained statistically significant when compared with unprimed cells and this was confirmed in a 3D Matrigel model (P <0.01) and in a Trans-well assay (P <0.01). FN-MCs-PTX also disclosed considerable antiangiogenic properties. Our results suggest that the fibronectin-adherent population of MCs isolated from peripheral blood can be an effective tool to inhibit GBM growth. Given the relative facility to obtain such cells and the short time needed for their culture and drug loading this approach may have potential as an adjuvant therapy for GBM.
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{
"pile_set_name": "PubMed Abstracts"
}
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Overexpression of short heterodimer partner recovers impaired glucose-stimulated insulin secretion of pancreatic beta-cells overexpressing UCP2.
The short heterodimer partner (SHP) (NR0B2) is an orphan nuclear receptor whose function in pancreatic beta-cells is unclear. Mitochondrial uncoupling protein (UCP2) in beta-cells is upregulated in obesity-related diabetes, causing impaired glucose-stimulated insulin secretion (GSIS). We investigated whether SHP plays a role in UCP2-induced GSIS impairment. We overexpressed SHP in normal islet cells and in islet cells overexpressing UCP2 by an adenovirus-mediated infection technique. We found that SHP overexpression enhanced GSIS in normal islets, and restored GSIS in UCP2-overexpressing islets. SHP overexpression increased the glucose sensitivity of ATP-sensitive K+ (KATP) channels and enhanced the ATP/ADP ratio. A peroxisome proliferator-activated receptor gamma (PPARgamma) antagonist, GW9662, did not block the SHP effect on GSIS. SHP overexpression also corrected the impaired sensitivity of UCP2-overexpressing beta-cells to methylpyruvate, another energy fuel that bypasses glycolysis and directly enters the Krebs cycle. KATP channel inhibition mediated by dihydroxyacetone, which gives reducing equivalents directly to complex II of the electron transport system, was similar in Ad-Null-, Ad-UCP2- and Ad-UCP2+Ad-SHP-infected cells. The mitochondrial metabolic inhibitor sodium azide totally blocked the effect of SHP overexpression on GSIS. These results suggest that SHP positively regulates GSIS in beta-cells and restores glucose sensitivity in UCP2-overexpressing beta-cells by enhancing mitochondrial glucose metabolism, independent of PPARgamma activation.
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{
"pile_set_name": "PubMed Abstracts"
}
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Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting.
Imprinted genes are epigenetically marked during gametogenesis so that they are exclusively expressed from either the paternal or the maternal allele in offspring. Imprinting prevents parthenogenesis in mammals and is often disrupted in congenital malformation syndromes, tumours and cloned animals. Although de novo DNA methyltransferases of the Dnmt3 family are implicated in maternal imprinting, the lethality of Dnmt3a and Dnmt3b knockout mice has precluded further studies. We here report the disruption of Dnmt3a and Dnmt3b in germ cells, with their preservation in somatic cells, by conditional knockout technology. Offspring from Dnmt3a conditional mutant females die in utero and lack methylation and allele-specific expression at all maternally imprinted loci examined. Dnmt3a conditional mutant males show impaired spermatogenesis and lack methylation at two of three paternally imprinted loci examined in spermatogonia. By contrast, Dnmt3b conditional mutants and their offspring show no apparent phenotype. The phenotype of Dnmt3a conditional mutants is indistinguishable from that of Dnmt3L knockout mice, except for the discrepancy in methylation at one locus. These results indicate that both Dnmt3a and Dnmt3L are required for methylation of most imprinted loci in germ cells, but also suggest the involvement of other factors.
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{
"pile_set_name": "PubMed Abstracts"
}
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Weight-of-evidence environmental risk assessment of dumped chemical weapons after WWII along the Nord-Stream gas pipeline in the Bornholm Deep.
In connection with installation of two natural gas pipelines through the Baltic Sea between Russia and Germany, there has been concern regarding potential re-suspension of historically dumped chemical warfare agents (CWA) in a nearby dump site and the potential environmental risks associated. 192 sediment and 11 porewater samples were analyzed for CWA residues, both parent and metabolites in 2008 and 2010 along the pipeline corridor next to the dump site. Macrozoobenthos and background variables were also collected and compared to the observed CWA levels and predicted potential risks. Detection frequencies and levels of intact CWA found were low, whereas CWA metabolites were more frequently found. Re-suspension of CWA residue-containing sediment from installation of the pipelines contributes marginally to the overall background CWA residue exposure and risk along the pipeline route. The multivariate weight-of-evidence analysis showed that physical and background parameters of the sediment were of higher importance for the biota than observed CWA levels.
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{
"pile_set_name": "PubMed Abstracts"
}
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Daily rhythm of serum lipase and alpha-amylase activity in fed and fasted dogs.
The aim of the current study was to investigate the influence of feeding and fasting on the daily rhythm of serum lipase and alpha-amylase activity in dogs. Fourteen purebred Beagle dogs were housed in individual pens lined with wood shavings under a 12:12 light:dark cycle. The dogs were divided into 2 groups. Group A received normal feeding once a day, and group B was fasted starting 12 hr prior to the first blood collection. Water was available ad libitum. Blood samples were collected every 4 hr for 48 hr. Serum lipase and alpha-amylase activity were analyzed with standard kits by means of an ultraviolet spectrophotometer. Statistical analysis of the data was performed by 2-way analysis of variance and by single cosinor method. Results showed no statistical influence of feeding schedule on lipase and alpha-amylase and a robust daily rhythmicity of lipase and alpha-amylase in fed and fasted dogs. The current study could provide additional documentation of the structure of the dog circadian timing system and increase the necessary information related to the clinical approach to pancreatic diseases and to the therapeutic efficacy of timed administration of drugs or rations.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators.
Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, longterm therapy with the angiotensin-converting--enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive doubleblind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group. The reduction in risk was 21 percent (95 percent confidence interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37 percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for the development of severe heart failure, 22 percent (95 percent confidence interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent; P = 0.015) for recurrent myocardial infarction. In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction.
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{
"pile_set_name": "PubMed Abstracts"
}
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Transsternal thymectomy for myasthenia gravis.
A consistent, planned approach to thymectomy for patients with myasthenia gravis has been used at the University of North Carolina since 1977. This involves a sternotomy, with excision of the entire thymus and adjacent fatty tissues from the thyroid to the diaphragm and laterally to 1 cm from each phrenic nerve. Between 1977 and 1993, 100 consecutive patients were treated in this manner with no mortality. Eight-four percent of patients were extubated in the operating room or within 1 hour of surgery, and no patients experienced postoperative respiratory difficulty. After a mean follow-up of 65 months, 78% of all patients improved by at least one modified Osserman classification, and 69% of patients with preoperative class I, II, or III disease (maximal preoperative severity) are in pharmacological remission. We conclude that transsternal thymectomy is associated with minimal morbidity and no mortality, and results in long-term improvement in symptoms for patients with myasthenia gravis.
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{
"pile_set_name": "PubMed Abstracts"
}
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Walking the Walk: Integrating Evidence Into Clinical Experiences.
Professional nurses are called to provide nursing care using an evidence-based approach. Health-care professionals are challenged to break away from old traditions and search for ways to improve health. Evidence-based practice (EBP) must be threaded throughout nursing curricula to produce critically-thinking professional nurses who will be meeting new and significant health-care challenges. Nursing education must be grounded in the translation of current evidence into practice. Nurse educators must acknowledge the obstacles faced when teaching concepts of research to students who have chosen a practice-focused career. The words evidence-based practice may be intimidating to nursing students. Nurse educators must shift this paradigm to invite students to realize that EBP is an integral component of modern health care that bridges the gap between health-care practices and improved patient outcomes. Faculty in a baccalaureate Adult Health course developed a unique approach inviting students to apply evidence to their student clinical experiences. Survey results showed that this innovative approach increased students' "excellent" or "good" understanding toward EBP concepts from pre-implementation scores of 46% to post-implementation scores of 94%. This active learning strategy allows students to "walk the walk" of EBP rather than simply listen to the "talk."
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{
"pile_set_name": "PubMed Abstracts"
}
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[Risk factors associated to vancomycin-resistant enterococccus colonization in the Army Hospital in Santiago].
Since the appearance of Vancomicin-resistant enterococci (VRE) in our country, the Chilean Ministry of Health recommended the surveillance of intestinal colonization in patients in critical wards. We report the results of surveillance in ICU and onco-hematological wards from 2002 to 2008, with analysis of possible risk factors: demographical data, use and type of antibiotic, days of hospitalization prior to sampling, and year of hospitalization. Colonization rate increased from 0.03 cases per 1000 bed-days in 2003 to 0.18 cases during 2008. Univariate analysis identified 7 risk factors associated with ERV colonization: hospitalization in ICU, use of antibiotics, use of 3 or more compounds, use of imipenem or colistin, >10 days of hospitalization prior to the study and year of hospitalization (before 2007 or after). Multivariate analysis by logistic binary regression showed that only the last two: >10 days of hospitalization prior to the study and year of hospitalization (before 2007 or after), were significantly associated to colonization by ERV.
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{
"pile_set_name": "PubMed Abstracts"
}
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Intramolecular interactions of the regulatory region with the catalytic core in the plasma membrane calcium pump.
The access of three proteases to their sites of cleavage was used as a measure of regulatory interactions in the plasma membrane Ca2+ pump isoform 4b (PMCA4b). When the proteases could not cut at their sites in the C-terminal regulatory region, the interaction was judged to be tight. This was the case in the absence of Ca2+, when chymotrypsin and caspase cut PMCA only very slowly. Ca2+ accelerated the fragmentation, but the digestion remained incomplete. In the presence of Ca2+ plus calmodulin, the digestion became nearly complete in all cases, indicating a more flexible conformation of the carboxyl terminus in the fully activated state. The acceleration of proteolysis by Ca2+ or Ca2+ plus calmodulin occurred equally at the caspase site upstream of the calmodulin-binding domain and the chymotrypsin and calpain sites downstream of that domain. Replacing Trp1093 (a key residue within the calmodulin-binding domain) with alanine had a much more specific effect, because it exposed only proteolytic sites within the calmodulin-binding domain that had previously been shielded in the native protein. At these sites, both calpain and chymotrypsin cut the Trp1093 --> Ala mutant in the absence of calmodulin. These data indicate that, in the auto-inhibited conformation, the calmodulin-binding/auto-inhibitory sequence and the regions both upstream and downstream are in close contact with the catalytic core. Trp1093 plays an essential role not only in stabilizing the Ca2+-calmodulin/calmodulin-binding domain complex but also in the formation or stability of the inhibitory conformation of that domain when it interacts with the catalytic core of PMCA4b.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Effect of Temperature on PAO Activity and Substrate Competition].
To investigate the effect of temperature on the activity of high-temperature phosphate accumulating organisms (PAOHT) and their competitive ability for the substrate, the sludge from an enhanced biological phosphorus removal (EBPR) reactor stably operated at the high temperature of 30℃ was used. The results showed that PAOHT activity and their competitive ability for the substrate increased with temperature increasing from 15℃ to 30℃. When the temperature was as higher as 30℃, the rates of anaerobic phosphorus release, aerobic phosphorus uptake and acetate uptake of PAOHT were 239.46 mg·(g·h)-1, 79.90 mg·(g·h)-1, 357.47 mg·(g·h)-1, respectively. The corresponding value of ΔP/ΔHAc was 0.628, which was considerably higher than that of PAO reported in literatures. A simplified Arrhenius equation was used to describe the effect of temperature on the rates of anaerobic phosphorus release, aerobic phosphorus uptake and acetate uptake, and the temperature coefficients were 1.08, 1.07 and 1.05, respectively.
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{
"pile_set_name": "PubMed Abstracts"
}
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Oxidative Stress-Induced Pentraxin 3 Expression Human Retinal Pigment Epithelial Cells is Involved in the Pathogenesis of Age-Related Macular Degeneration.
: (1) Background: Age-related macular degeneration (AMD) is closely related with retinal pigment epithelial (RPE) cell dysfunction. Although the exact pathogenesis of AMD remains largely unknown, oxidative stress-induced RPE damage is believed to be one of the primary causes. We investigated the molecular mechanisms of pentraxin 3 (PTX3) expression and its biological functions during oxidative injury. (2) Methods: Using enzyme-linked immunosorbent assays and real-time reverse transcription-polymerase chain reaction, we analyzed mRNA and protein levels of PTX3 in the presence or absence of oxidative stress inducer, sodium iodate (NaIO3), in primary human H-RPE and ARPE-19 cells. Furthermore, we assessed cell death, antioxidant enzyme expression, and AMD-associated gene expression to determine the biological functions of PTX3 under oxidative stress. (3) Results: NaIO3 increased PTX3 expression, in a dose- and time-dependent manner, in H-RPE and ARPE-19 cells. We found phosphorylated Akt, a downstream target of the PI3 kinase pathway, phosphor- mitogen-activated protein kinase kinase 1/2 (ERK), and intracellular reactive oxygen species (ROS) were predominantly induced by NaIO3. NaIO3-induced PTX3 expression was decreased in the presence of phosphoinositide 3 (PI3) kinase inhibitors, ERK inhibitors, and ROS scavengers. Furthermore, NaIO3 enhanced mRNA expression of antioxidant enzymes such as glucose-6-phosphate dehydrogenase (G6PDH), catalase (CAT), and glutathione S-reductase (GSR) in the control shRNA expressing RPE cells, but not in hPTX3 shRNA expressing RPE cells. Interestingly, NaIO3 did not induce mRNA expression of AMD marker genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), and toll-like receptor 4 (TLR4) in hPTX3 shRNA expressing RPE cells. 4) Conclusions: These results suggest that PTX3 accelerates RPE cell death and might be involved in AMD development in the presence of oxidative stress.
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{
"pile_set_name": "PubMed Abstracts"
}
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Detection of human papillomavirus genotypes associated with mucopurulent cervicitis and cervical cancer in Changchun, China.
To determine the prevalence and genotype distribution of human papillomavirus (HPV) infection among Chinese patients with mucopurulent cervicitis (MPC) or cervical cancer (CC). In total, 191 cases of CC (n=66), acute MPC (n=84), and healthy cervix controls (n=41) were initially included; samples were collected between May 21, 2008, and October 9, 2011. Cervical specimens were screened for HPV using a nested polymerase chain reaction assay and DNA sequencing. Overall prevalence of HPV infection was 20.0% in the control group, 53.3% in the MPC group, and 93.8% in the CC group. The predominant genotype detected in all 3 groups was the oncogenic variant HPV 16 (87.7%, 18.7%, and 10.0% in the CC, MPC and control specimens, respectively). The second most frequent genotype among patients with MPC was HPV 58. This variant is also oncogenic and was detected at a higher rate in the MPC group (9.3%) than in the control (2.5%) and CC (1.5%) groups. Infection with HPV was prevalent among Chinese women with MPC or CC. Furthermore, the high prevalence of oncogenic genotypes observed among HPV-positive patients with MPC suggests that this group is at increased risk of developing CC.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effect of sodium arachidonate on thrombin generation through platelet activation--inhibitory effect of aspirin.
Sodium arachidonate was used in this study to determine its capacity to generate thrombin through platelet activation. Whether aspirin prevent this effect was also investigated. Seventeen healthy volunteers without and after 160 mg/day aspirin intake for 3-5 days were studied. Lag-time and TG at basal condition and after platelet stimulation by sodium arachidonate (AA) were measured in normal non-aspirinated as well as "in vivo" aspirinated platelet rich plasma. (PRP). The lag-time was statistically significant shorter in non-aspirinated PRP activated with AA compared with non-activated PRP. This effect was inhibited by aspirin. In non-aspirinated PRP, there was an increase of TG at 4 and 6 min. incubation when platelets were activated with AA but the difference disappeared after 8 min. incubation, (84 +/- 71; 148 +/- 58 and 142 +/- 92 nmol/L respectively) compared with non-aspirinated. non-activated platelets (16 +/- 23; 55 +/- 56 and 111 +/- 76 nmol/L at 4,6 and 8 min, p < 0.0001, p < 0.0001 and p = 0.292, respectively). The AUCo-->22 min were 520.6 +/- 545.5 in non-aspirinated, non-stimulated PRP and 808.9 +/- 617, in non-aspirinated PRP activated with sodium arachidonate (p = 0.014). Aspirin administered in vivo produced a decrease of TG in PRP activated with AA. Platelet activated by AA trigged TG. This effect was inhibited by aspirin and could be an additional beneficial effect of aspirin in the prevention of thrombosis.
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{
"pile_set_name": "PubMed Abstracts"
}
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Surface CD14 positivity in B-cell chronic lymphocytic leukaemia is related to clinical outcome.
The aberrant expression of the myelomonocytic antigen CD14 was investigated in 128 untreated patients diagnosed with B-cell chronic lymphocytic leukaemia (B-CLL). A cut-off value of 5 x 10(9)/l CD14-positive cells was chosen for statistical analysis because it showed the best discriminating power among patients with different clinical features. 56 cases had a CD14+ cell count >5 x 10(9)/l. A significant correlation was found between Rai and Binet stages and total tumour mass (TTM) score on one hand, and the absolute CD14+ cell cut-off, on the other. This relationship was more evident in Rai 0-II and Binet A-B stages, where a CD14+ cell count >5 x 10(9)/l was preferentially distributed among patients with a higher tumoral mass. In univariate analysis the survival probability at 5 and 10 years showed a significant correlation with Rai and Binet stages, TTM score, CD14+ absolute cell count and median age. The median overall survival (OS) was 63 months for patients with a CD14+ cell count >5 x 10(9)/l and 136 months for those with a CD14+ cell count < 5 x 10(9)/l. In the multivariate Cox regression model, Rai stage, age and CD14+ cell count were independent significant factors for the prediction of OS. Finally, when the same analysis was restricted to Rai stages 0-II, CD14+ cell count was the only significant independent parameter influencing OS, with a relative death risk of 3.8. In conclusion, these data reveal that CD14+ represents an important marker for predicting OS in B-CLL patients and, therefore, we suggest that it should be included in the immunological characterization of B-CLL.
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{
"pile_set_name": "PubMed Abstracts"
}
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Preoptic and subthalamic connections with the caudal brainstem are important for copulation in the male rat.
Bilateral lesions of either the medial preoptic area/anterior hypothalamus (MPAH) or a subthalamic region that includes the caudal zona incerta eliminate copulation in male rats. Pathways connecting the MPAH and subthalamus with the caudal brainstem may help regulate sexual behavior. Experiment 1 showed that bilateral coronal transections of the pontine tegmentum reduce mating and that the combination of a unilateral tegmental cut with a contralateral excitotoxin lesion of either the MPAH (Experiment 2) or subthalamus (Experiment 3) virtually eliminates copulation. Asymmetric bilateral damage appears to eliminate mating through a bilateral effect common to the transection and the lesion--the destruction of connections linking the MPAH and subthalamus with the caudal brainstem. These results indicate that preoptic and subthalamic connections with the caudal brainstem are important for copulation in the male rat.
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{
"pile_set_name": "PubMed Abstracts"
}
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Membrane Interaction of botulinum neurotoxin A translocation (T) domain. The belt region is a regulatory loop for membrane interaction.
The translocation of the catalytic domain through the membrane of the endosome to the cell cytoplasm is a key step of intoxication by botulinum neurotoxin (BoNT). This step is mediated by the translocation (T) domain upon endosome acidification, although the mechanism of interaction of the T domain with the membrane is still poorly understood. Using physicochemical approaches and spectroscopic methods, we studied the interaction of the BoNT/A T domain with the membrane as a function of pH. We found that the interaction with membranes does not involve major secondary or tertiary structural changes, as reported for other toxins like diphtheria toxin. The T domain becomes insoluble around its pI value and then penetrates into the membrane. At that stage, the T domain becomes able to permeabilize lipid vesicles. This occurs for pH values lower than 5.5, in agreement with the pH encountered by the toxin within endosomes. Electrostatic interactions are also important for the process. The role of the so-called belt region was investigated with four variant proteins presenting different lengths of the N-extremity of the T domain. We observed that this part of the T domain, which contains numerous negatively charged residues, limits the protein-membrane interaction. Indeed, interaction with the membrane of the protein deleted of this extremity takes place for higher pH values than for the entire T domain. Overall, the data suggest that acidification eliminates repulsive electrostatic interactions between the T domain and the membrane, allowing its penetration into the membrane without triggering detectable structural changes.
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{
"pile_set_name": "PubMed Abstracts"
}
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Oral health is an important issue in end-of-life cancer care.
This study aims to assess the prevalence of oral morbidity in patients receiving palliative care for cancers outside the head and neck region and to investigate if information concerning oral problems was given. Patients were recruited from two Norwegian palliative care inpatient units. All patients went through a face-to-face interview, completed the Edmonton Symptom Assessment System (ESAS) covering 10 frequent cancer-related symptoms, and went through an oral examination including a mouth swab to test for Candida carriage. Ninety-nine of 126 patients (79 %) agreed to participate. The examined patients had a mean age of 64 years (range, 36-90 years) and 47 % were male. Median Karnofsky score was 40 (range, 20-80) and 87 % had metastatic disease. Estimated life expectancy was <3 months in 73 %. Dry mouth was reported by 78 %. The highest mean scores on the modified 0-10 ESAS scale were 4.9 (fatigue), 4.7 (dry mouth), and 4.4 (poor appetite). Clinical oral candidiasis was seen in 34 % (86 % positive cultures). Mouth pain was reported by 67 % and problems with food intake were reported by 56 %. Moderate or rich amounts of dental plaque were seen in 24 %, and mean number of teeth with visible carious lesions was 1.9. One patient was diagnosed with bisphosphonate-related osteonecrosis of the jaw. Overall, 78 % said they had received no information about oral adverse effects of cancer treatment. Patients in palliative care units need better mouth care. Increased awareness among staff about the presence and severity of oral problems is necessary. Systematic information about oral problems is important in all stages of cancer treatment.
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{
"pile_set_name": "PubMed Abstracts"
}
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The role of the human cerebellum in short- and long-term habituation of postural responses.
The aim of the present study was to investigate the role of the human cerebellum in short-term (STH) and long-term habituation (LTH) of postural responses to repeated platform perturbations. Ten cerebellar patients and ten age- and sex-matched healthy controls participated. Twenty backward platform translations were applied on each of 5 consecutive days. Changes of postural response size within each day were assessed to determine STH and changes across days to determine LTH. Both controls and cerebellar patients showed a significant reduction of postural response size within each day (i.e. STH). No significant reduction of postural response size was observed across days (i.e. no LTH). Both controls and cerebellar patients, however, showed a tendency of response size to increase across days suggesting long-term sensitization. The amount of changes within and across days did not significantly differ between groups. The present findings suggest that changes of postural response size to repeated perturbations do not depend upon the integrity of the cerebellum.
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{
"pile_set_name": "PubMed Abstracts"
}
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Evaluation of the chronic toxicity and oncogenicity of N,N-diethyl-m-toluamide (DEET).
Chronic toxicity and/or oncogenicity studies were conducted in rats, mice, and dogs with the insect repellent DEET. DEET was mixed in the diet and administered to CD rats for two years at concentrations that corresponded to dosage levels of 10, 30 or 100 mg/kg/day for males and 30, 100, or 400 mg/kg/day for females; to CD-1 mice for 18 months at dosage levels of 250, 500, or 1000 mg/kg/day; and to dogs for one year, via gelatin capsules, at dosage levels of 30, 100, or 400 mg/kg/day. In the rodent studies, each group consisted of 60 animals of each sex, and two concurrent independent control groups, each containing 60 animals/sex were included in each study. Each group in the dog study consisted of four male and four female dogs and one control group was included in the study. Treatment-related effects were observed at the highest dose level in all three studies. For rats, the effects included decreases in body weight and food consumption and an increase in serum cholesterol in females only. In mice, the effects observed were decreases in body weight and food consumption in both sexes. The effects observed in dogs included increased incidences of emesis and ptyalism, and levels of transient reduction in hemoglobin and hematocrit, increased alkaline phosphatase (males only), decreased cholesterol, and increased potassium. One male dog in the high-dose group also exhibited ataxia, tremors, abnormal head movements, and/or convulsions on several occasions during the study. The highest no-observed-effect levels (NO-ELs) for rats, mice and dogs were determined to be 100, 500, and 100 mg/kg/day, respectively. No specific target organ toxicity or oncogenicity was observed in any of the studies.
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{
"pile_set_name": "PubMed Abstracts"
}
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The treatment of factor VIII inhibitors--a general overview.
The management of patients with classic hemophilia who develop inhibitory antibodies against transfused factor VIII has been the frequent subject of international and national conferences. While treatment of such patients cannot be considered as standardized, several therapeutic approaches are currently available. These include the induction of immune tolerance, removal or eradication of inhibitory antibodies by immune adsorption and/or immune suppression, neutralization of the inhibitor by porcine factor VIII or high doses of human factor VIII, and bypassing of the inhibitor using recombinant factor VIIa or other bypassing agents. In addition to currently available therapeutic strategies, other approaches are under investigation, including the use of selected factor VIII peptides that block the inhibitor; the use of immunologically mute factor VIII products, for example a human-porcine factor VIII chimera not recognized by factor VIII inhibitors, and the use of anti-idiotypic antibodies. The ability to recognize those patients destined to develop inhibitors is also under active investigation.
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{
"pile_set_name": "PubMed Abstracts"
}
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Surgical treatment for chronic Charcot neuroarthropathy.
Charcot Neuro-arthropathy (CN) is a condition characterized by a progressive derangement of the joints, in individuals affected with sensitive and autonomic neuropathy. The pathogenesis of CN is multifactorial as neuropathy is a necessary, but insufficient condition for the onset of the disease. The most important indication for surgical treatment of Charcot foot is a severe deformity that compromises the functionality of the limb, causing a high risk for ulceration, infection and amputation. The goal in Charcot foot treatment is to obtain and maintain the correction of a severe deformity and/or prevent its development. There are many surgical approach to the CN, such as exostectomy, arthrodesis with internal or external fixation and amputation. Every method has a different indication and specific complication. The right surgical approach in the CN is a real challenge for orthopedic surgeon that need a complete knowing of technique, material and complication.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Alcoholism in the elderly (author's transl)].
Contrary to a widespread impression, dependence is not rare among the elderly. The numbers are clearly increasing. The results of therapy are more favorable than is usually assumed, especially when it is possible to form groups appropriate to the age which cope with the particular problems of this stage of life better than mixed age groups. Consideration must be given to the less verbalizing experience and lower physical fitness of older patients, they are then distinctly more cooperative and more easily adjusted to the therapeutic aim of future total abstinence than younger patients.
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{
"pile_set_name": "PubMed Abstracts"
}
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