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Imperfect (de)convolution may introduce spurious psychophysiological interactions and how to avoid it.
Psychophysiological interaction (PPI) is a widely used regression-based method to study connectivity changes in different experimental conditions. A PPI effect is generated by point-by-point multiplication of a psychological variable (experimental design) and a physiological variable (time series of a seed region). If the psychological variable is non-centered with a constant component, the constant component will add a physiological variable to the PPI term. The physiological component would in theory be accounted for by the physiological main effect in the model. But due to imperfect deconvolution and convolution with hemodynamic response function, the physiological component in PPI may no longer be exactly the same as the physiological main effect. This issue was illustrated by analyzing two block-designed fMRI datasets, one simple visual checkerboard task and a set of different tasks designed to activate different hemispheres. When PPI was calculated with deconvolution but without centering, significant results were usually observed between regions that are known to have baseline functional connectivity. These results could be suppressed by simply centering the psychological variable when calculating the PPI term or adding a deconvolve-reconvolved version of the physiological covariate. The PPI results with centering and with deconvolve-reconvolved physiological covariate are consistent with an explicit test for differences in coupling between conditions. It was, therefore, suggested that centering of the psychological variable or the addition of a deconvolve-reconvolved covariate is necessary for PPI analysis. Hum Brain Mapp 38:1723-1740, 2017. © 2017 Wiley Periodicals, Inc. | {
"pile_set_name": "PubMed Abstracts"
} |
Folding energetics of ligand binding proteins. I. Theoretical model.
Heat capacity curves as obtained from differential scanning calorimetry are an outstanding source for molecular information on protein folding and ligand-binding energetics. However, deconvolution of C(p) data of proteins in the presence of ligands can be compromised by indeterminacies concerning the correct choice of the statistical thermodynamic ensemble. By convent, the assumption of constant free ligand concentration has been used to derive formulae for the enthalpy. Unless the ligand occurs at large excess, this assumption is incorrect. Still the relevant ensemble is the grand canonical ensemble. We derive formulae for both constraints, constancy of total or free ligand concentration and illustrate the equations by application to the typical equilibrium Nx <=> N + x <=> D + x. It is demonstrated that as long as the thermodynamic properties of the ligand can be completely corrected for by performing a reference measurement, the grand canonical approach provides the proper and mathematically significantly simpler choice. We demonstrate on the two cases of sequential or independent ligand-binding the fact, that similar binding mechanisms result in different and distinguishable heat capacity equations. Finally, we propose adequate strategies for DSC experiments as well as for obtaining first estimates of the characteristic thermodynamic parameters, which can be used as starting values in a global fit of DSC data. | {
"pile_set_name": "PubMed Abstracts"
} |
Partial cloning, tissue distribution and effects of epigallocatechin gallate on hepatic 3-hydroxy-3-methylglutaryl-CoA reductase mRNA transcripts in goldfish (Carassius auratus).
Epigallocatechin gallate (EGCG), the major active component of the green tea, has recently been found to inhibit 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoAR) activity in vitro and to modulate lipogenesis in vivo. In this study we have evaluated the effects of short-term in vivo exposure to EGCG (6 μg g(-1) BW or 9 μg g(-1) BW) on hepatic HMGCoAR gene expression of goldfish (Carassius auratus). We initially characterized a partial sequence of goldfish HMGCoAR suggesting that the obtained fragment shares high similarity (>92%) with other fish HMGCoAR sequences. Further, the HMGCoAR transcript was detected in all goldfish tissues (except muscle) but primarily in liver, brain and gonads; on the contrary, low expression levels were found in intestine, heart, gill, and kidney. Both EGCG doses significantly decreased hepatic HMGCoAR mRNA levels 180 min post-injection. HMGCoAR was also significantly down-regulated at 90 min after injection in fish treated with the highest dose of EGCG. Our results demonstrate that hepatic HMGCoAR gene expression is acutely responsive to short-term EGCG exposure in goldfish. This finding suggests a potential role of EGCG in transcriptional regulation of the rate-limiting enzyme in cholesterol synthesis. | {
"pile_set_name": "PubMed Abstracts"
} |
The meaning of urgency in the allocation of scarce health care resources; a comparison between renal transplantation and psychogeriatric nursing home care.
In the juridical and ethical literature on patient selection criteria it is an unargued premise that those who are most urgently in need of treatment or care will be given priority. The aim of this study is to gain insight into the medical practice of waiting list problems and patient selection at the microlevel, especially with respect to urgency. Thus, the study intends to contribute to the medical ethical discussion on patient selection for scarce resources. The results of qualitative research into the meaning and occurrence of urgency in two health care services, renal transplantation and psychogeriatric nursing home care, are discussed. In the first sector, patients are seldom considered urgent. Criteria for urgency are technical dialysis problems or severe psychological burden due to protracted dialysis treatment. In contrast, psychogeriatric patients are often considered urgent, with the principal criterion being too heavy a care load for informal carers. Both health care services show variation in assigning urgency codes. It appears that the exact meaning of urgency is not self-evident and that admission of urgent patients to nursing homes can be negotiated by professionals or informal carers. This points to the necessity of a discussion within these services as to the actual content matter of urgency. Further, professionals involved in renal transplantation raise several moral and practical arguments against giving patients priority, even if they need treatment urgently. It shows that distributive justice cannot always be applied. Occasionally non-urgent patients are rated urgent as they have been waiting very long due to specific allocation procedures. In these cases urgency is granted in an unexpected way that is ultimately in accordance with the notion of procedural justice. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical evaluation of corneal diseases associated with floppy eyelid syndrome.
We examined 18 cases of floppy eyelid syndrome, first reported in the Orient, in patients ranging in age from 11 to 55 years (mean 24 years); 16 were men and two were women. In contrast to previous reports in which almost all patients were obese men, only three of our patients were mildly obese. The most common abnormal corneal finding was punctate epithelial keratopathy (five patients-28%). Keratoconus was detectable in three patients (17%) overall; it was bilateral in one case and unilateral in two. Other miscellaneous corneal findings were corneal astigmatism and corneal opacity. In two cases, we found a familial tendency to skin hyperextensibility and joint hypermobility, and in one case, floppy eyelid syndrome developed after pars plana vitrectomy. The pathogenesis of the syndrome is still unknown, but our findings suggest that the more important pathogenetic risk factors are not obesity and sleeping pattern, but genetic collagen and/or elastin abnormality. | {
"pile_set_name": "PubMed Abstracts"
} |
Recombinant retrovirus-like particle forming DNA vaccines in prime-boost immunization and their use for hepatitis C virus vaccine development.
The expression of Moloney murine leukemia virus (Mo-MLV) gag proteins is sufficient to generate retrovirus-like particles (retroVLPs) that can be used as antigen-display platforms by pseudotyping with heterologous envelope proteins or by insertion of epitopes in structural constituents. To circumvent the in vitro production of such retroVLPs, we used DNA plasmids generating recombinant retroVLPs (plasmo-retroVLPs) as immunogens. We previously demonstrated that plasmo-retroVLPs induce significantly better antigen-specific T cell responses and antiviral immune protection than plasmids bearing a single mutation preventing retroVLPs assembly. In the present study, we investigated the possibility of using such plasmo-retroVLPs in prime-boost immunization strategies for hepatitis C virus (HCV) vaccine development. To define the best immunization regimen with plasmo-retroVLPs and serotype 5 recombinant adenovirus vectors (rAd5), we used standardized methodologies measuring immune responses to the GP(33-41) 'gold standard' antigen. The protective efficacy of these immunization schedules was also evaluated in mice after tumor challenge. We then applied the optimal prime-boost immunization strategy using vectors expressing HCV-E1/E2 envelope glycoproteins. Using vectors expressing the model antigen, we demonstrated that rAd5(GP33-41)/plasmo-retroVLP(GP33-41) regimen induced significantly higher cellular immune responses than plasmo-retroVLP(GP33-41)/rAd5(GP33-41). Consequently, HCV-specific plasmo-retroVLPs (plasmo-retroVLP(E1E2)) were used as boost in mice primed with rAd5(E1E2) and we observed that plasmo-retroVLP(E1E2) significantly increased E1/E2-specific interferon-gamma cellular responses and E2-specific antibody generation. By contrast, plasmids unable to form E1/E2-pseudotyped retroVLPs had no boosting effect, revealing the importance of presenting E1/E2 in a particulate form. Altogether, combining plasmo-retroVLPs that represent a new class of genetic vaccines in a heterologous prime-boost vaccination strategy appears to be a promising strategy for HCV vaccine development. | {
"pile_set_name": "PubMed Abstracts"
} |
Older adults present better back endurance than young adults during a dynamic trunk extension exercise.
Poor back endurance is a predictor of low back pain. Few studies have investigated back muscle fatigue in older people. The purpose of this study was to compare the back muscle fatigue by endurance time and perceived effort between young and older adults during dynamic exercise. Sixteen older and 16 young adults, all healthy, participated in this study. The subjects performed a fatiguing trunk extension-flexion exercise on a Roman chair until exhaustion. Endurance time and perceived muscle fatigue (Borg CR-10 scale) were used as fatigue criteria. The older adults were significantly (T<formula>_{(30)}</formula> = -2,073; p = 0.039) more resistant to back muscle fatigue (time in mean 133 ± 52 s) than the young adults (mean 97 ± 27 s). In general, both groups had the same perception of high-level fatigue during the exercise bout (T<formula>_{(29)}</formula> = 1.73; p=0.092). The older adults presented better back endurance than young adults during a dynamic trunk extension exercise. These results have implications for back endurance in the primary prevention of low back pain in both young and older adults. | {
"pile_set_name": "PubMed Abstracts"
} |
In vitro release of endothelium-derived relaxing factor by acetylcholine is increased during the guinea pig pregnancy.
The relaxation of isolated blood vessels by acetylcholine is dependent on the presence of intact endothelium and its release of a smooth muscle relaxing nitroso-like compound. Pregnancy is associated with altered vascular responsiveness to a variety of agents. Because many of these agents stimulate the release of endothelium-derived relaxing factor, we investigated in vitro the effect of pregnancy on acetylcholine-mediated relaxation of guinea pig uterine and carotid artery rings. The presence of intact and functional endothelium was confirmed both by examination under the scanning electron microscope and by vessel relaxation after the addition of acetylcholine. The addition of acetylcholine to the vessel bath produced dose-dependent relaxation of both carotid and uterine artery segments obtained from pregnant and nonpregnant animals after they had been submaximally preconstricted with phenylephrine. There was a significant increase in both response and efficacy to acetylcholine during pregnancy for both uterine and carotid arteries (p less than 0.0001 for each). The concentrations of endothelial cells (cells per square micrometer) were similar in uterine arteries from pregnant and nonpregnant animals. We conclude that the most likely explanation for these findings is a pregnancy-mediated enhancement of endothelium-derived relaxing factor activity. | {
"pile_set_name": "PubMed Abstracts"
} |
Folding topology of the disulfide-bonded dimeric DNA-binding domain of the myogenic determination factor MyoD.
The myogenic determination factor MyoD is a member of the basic-helix-loop-helix (bHLH) protein family. A 68-residue fragment of MyoD encompassing the entire bHLH region (MyoD-bHLH) is sufficient for protein dimerization, sequence-specific DNA binding in vitro, and conversion of fibroblasts into muscle cells. The circular dichroism spectrum of MyoD-bHLH indicates the presence of significant alpha-helical secondary structure; however, the NMR spectrum lacks features of a well-defined tertiary structure. There is a naturally occurring cysteine at residue 135 in mouse MyoD that when oxidized to a disulfide induces MyoD-bHLH to form a symmetric homodimer with a defined tertiary structure as judged by sedimentation equilibrium ultracentrifugation and NMR spectroscopy. Oxidized MyoD-bHLH retains sequence-specific DNA-binding activity, albeit with an apparent 100-1000-fold decrease in affinity. Here, we report the structural characterization of the oxidized MyoD-bHLH homodimer by NMR spectroscopy. Our findings indicate that the basic region is unstructured and flexible, while the HLH region consists of two alpha-helices of unequal length connected by an as yet undetermined loop structure. Qualitative examination of interhelical NOEs suggests several potential arrangements for the two helix 1/helix 2 pairs in the symmetric oxidized dimer. These arrangements were evaluated for whether they could incorporate the disulfide bond, satisfy loop length constraints, and juxtapose the two basic regions. Only a model that aligns helix 1 parallel to helix 1' and antiparallel to helix 2 was consistent with all constraints. Thus, an antiparallel four-helix bundle topology is proposed for the symmetric dimer. This topology is hypothesized to serve as a general model for other bHLH protein domains. | {
"pile_set_name": "PubMed Abstracts"
} |
Complications of replantation surgery.
Potential complications after replantation surgery are numerous and varied in their nature. The average replantation patient can expect somewhere between two to three subsequent operations to maximize function. Many surgical complications and unsatisfactory functional outcomes can be avoided through careful assessment of patients and their injuries. | {
"pile_set_name": "PubMed Abstracts"
} |
Three-dimensional topographic survey of the human remains in Lamalunga cave (Altamura, Bari, southern Italy).
The aim of the Research Unit, in the framework of the "Programma Nazionale di Ricerca - MURST (Ministero dell'Universita e della Ricerca Scientifica e Tecnologica) 1998-2000", was to study human fossil remains and sites of paleoanthropological interest; the observations regard sites and remains found principally in Apulia, amongst which, the Lamalunga Cave - Altamura. The results of the survey phases of the cave and the three-dimensional topographic distribution of the human remains are reported. Three-dimensional spatial coordinates describing the collocation of the skeleton were sampled. These points were used as reference points for the spatial positioning of numerical models reproducing elements of an adult male skeleton. The survey allows the interactive observation of the remains and their relationship with the site, so that the remains can be observed from points of view actually impossible. On the basis of such views, it was possible to better deduce the relationship between the skeletal elements, confirming the hypothesis that the skeletonization phenomenon occurred in the actual site where the remains are now found. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of sleep deprivation on daytime sleepiness in primary insomnia.
This study investigated changes in MSLT scores and recovery sleep following total sleep deprivation in subjects with insomnia as compared to normal sleepers. Matched-groups design. A sleep disorders center in a large medical center. Ten individuals with psychophysiological insomnia and ten age- and sex-matched normal sleepers served as subjects. Subjects underwent total sleep deprivation after baseline polysomnography and MSLT. A post-deprivation MSLT was obtained, as well as polysomnography on the recovery night and an MSLT after the recovery night. Both groups showed significant decreases in MSLT scores following total sleep deprivation, as compared to baseline. Both groups had significantly shorter scores on a nighttime MSLT compared to a daytime MSLT. The insomnia group also showed a significant increase in total sleep time on the recovery night compared to baseline. The MSLT is sensitive to changes in sleepiness associated with total sleep deprivation in individuals with primary insomnia. | {
"pile_set_name": "PubMed Abstracts"
} |
Biologically active conformer of the effector region of human C5a and modulatory effects of N-terminal receptor binding determinants on activity.
A conformationally biased decapeptide agonist of human C5a (C5a55-74Y65,F67,P69,P71,D-Ala73 or YSFKPMPLaR) was used as a functional probe of the C5a receptor (C5aR) in order to understand the conformational features in the C-terminal effector region of C5a that are important for C5aR binding and signal transduction. YSFKPMPLaR was a potent, full agonist of C5a, but at higher concentrations had a superefficacious effect compared to the natural factor. The maximal efficacy of this analogue was 216 +/- 56% that of C5a in stimulating the release of beta-glucuronidase from human neutrophils. C5aR activation and binding curves both occurred in the same concentration range with YSFKPMPLaR, characteristics not observed with natural C5a or more conformationally flexible C-terminal agonists. YSFKPMPLaR was then used as a C-terminal effector template onto which was synthesized various C5aR binding determinants from the N-terminal core domain of the natural factor. In general, the presence of N-terminal binding determinants had little effect on either potency or binding affinity when the C-terminal effector region was presented to the C5aR in this biologically active conformation. However, one peptide, C5a12-20-Ahx-YSFKPMPLaR, expressed a 100-fold increase in affinity for the neutrophil C5aR and a 6-fold increase in potency relative to YSFKPMPLaR. These analyses showed that the peptides used in this study have up to 25% of the potency of C5a in human fetal artery and up to 5% of the activity of C5a in the PMN enzyme release assay. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis and structure-activity relationships of 8-(pyrid-3-yl)pyrazolo[1,5-a]-1,3,5-triazines: potent, orally bioavailable corticotropin releasing factor receptor-1 (CRF1) antagonists.
This report describes the syntheses and structure-activity relationships of 8-(substituted pyridyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF(1)) receptor antagonists. These CRF(1) receptor antagonists may be potential anxiolytic or antidepressant drugs. This research resulted in the discovery of compound 13-15, which is a potent, selective CRF(1) antagonist (hCRF(1) IC(50) = 6.1 +/- 0.6 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 13-15 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 13-15 has been advanced to clinical trials. | {
"pile_set_name": "PubMed Abstracts"
} |
Preoperative diagnosis of insulinoma: low body mass index, young age, and female gender are associated with negative imaging by endoscopic ultrasound.
Endoscopic ultrasound (EUS) is a highly reliable procedure to localize insulinomas preoperatively. It has been considered to be important in planning surgical strategy, especially considering a minimal invasive approach. However, even under ideal conditions experienced examiners miss about 10-20% of insulinomas by EUS imaging. This retrospective study aimed to identify factors associated with negative EUS imaging. Twenty-nine consecutive patients (24 benign and 5 malignant) with sporadic pancreatic insulinomas confirmed by successful surgery and positive histopathology were included. All EUS examinations were performed by one single experienced examiner over a period of one decade. Three of the tumors were not detected by preoperative EUS as they were isoechoic to the surrounding healthy pancreatic tissue; 25 could be detected as hypoechoic lesions, (including all malignant tumors), and one lesion was hyperechoic. Low body mass index (P=0.053) and young age (P=0.037) were associated with negative EUS imaging. All patients with negative imaging were females. The position on the examiner's learning curve, the diameter and location of insulinoma, and endocrine parameters (insulin concentrations and insulin-glucose ratios in the prolonged fasting test) had no influence on the success of EUS imaging. Some insulinomas are missed by preoperative EUS imaging as they are completely isoechoic. A low body mass index, female gender, and young age might be risk factors for negative imaging. | {
"pile_set_name": "PubMed Abstracts"
} |
The Combined Effects of ω -3 Fatty Acids and Nano-Curcumin Supplementation on Intercellular Adhesion Molecule-1 (ICAM-1) Gene Expression and Serum Levels in Migraine Patients.
Migraine is an episodic headache, which is an endothelial disorder with neurological inflammation. Intercellular Adhesion Molecule-1 (ICAM-1), as an endothelial factor, leads to the adhesion of leukocytes to the walls of the cerebral blood vessels, which is an important step in the inflammation process. Curcumin and omega-3 fatty acids, by affecting transcription factors, can regulate the gene expression and serum levels of ICAM-1. Thus, this study aimed to evaluate the synergistic effects of ω-3 fatty acids and nano-curcumin on ICAM-1 gene expression and serum levels in migraine patients. This clinical trial study was conducted on 72 episodic migraine patients in 4 groups for 2 months, with patients receiving ω-3 fatty acids, nano-curcumin, a combination of them, or a placebo during the study. At the beginning and end of the study, the gene expression and serum level of ICAM-1 were measured by real-time PCR and ELISA. The results showed no significant change in ICAM-1 gene expression in any of the 4 groups. The ICAM-1 serum concentration in the combination group, and omega-3 alone, showed a significant reduction at the end of the study compared to the beginning. In addition, a significant reduction in attack frequency was observed in the combination group. Considering the results of supplementation with omega-3 fatty acids plus curcumin led to reductions of both attack frequency and ICAM-1 serum level in patients, it seems that supplementation with these two nutrients not only can lead to improvements in the function of metabolic pathways, but can also be used effectively as a treatment or prevention of migraine complications. | {
"pile_set_name": "PubMed Abstracts"
} |
Liver Transplant and Improvements in Cholesterol Biosynthesis Defects: A Case Report of Smith-Lemli-Opitz Syndrome.
Smith-Lemli-Opitz syndrome is an autosomal recessive metabolic disease characterized by mental retardation and multiple congenital anomalies. The main pathology is the lack of the enzyme 3β-hydroxysterol Δ7-reductase, which is the last enzymatic step in cholesterol synthesis, ending with a low cholesterol level. Cholesterol is vitally important in cell membranes and myelination of the nervous system. The cholesterol level affects many systems of the body, especially the nervous system. The cause of liver involvement in Smith-Lemli-Opitz syndrome is unclear, and many hypotheses have been suggested. Here, we present the early results of a patient with Smith-Lemli-Opitz syndrome who underwent living-donor liver transplant due to cirrhosis. As a result of liver transplant, normal cholesterol levels were shown, as well as improvements in the patient's neurodevelopment and behavior. Early liver transplant may be considered for patients with a defect of cholesterol biosynthesis, even in the absence of cirrhosis, and may be a future treatment option to prevent risks of neurologic deterioration. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of alfapump™ system on kidney and circulatory function in patients with cirrhosis and refractory ascites.
The alfapump system has been proposed as a new treatment for the management of refractory ascites. The system removes ascites from the peritoneal cavity to urinary bladder, producing a continuous low-volume paracentesis. The aim of the study is to investigate the effects of treatment with the alfapump™ system on kidney and circulatory function in patients with cirrhosis and refractory ascites. This was a prospective study including 10 patients with cirrhosis and refractory ascites. Primary outcomes were changes in glomerular filtration rate (GFR), as assessed by isotopic techniques, and changes in circulatory function assessed by arterial pressure, cardiac output, and activity of vasoconstrictor systems. Secondary outcomes were the need for large-volume paracentesis and adverse events. Follow-up was 1 year. GFR decreased significantly from 67 mL/minute/1.73 m2 (41-90 mL/minute/1.73 m2 ) at baseline to 45 mL/minute/1.73 m2 (36-74 mL/minute/1.73 m2 ) at month 6 (P = 0.04). Mean arterial pressure and cardiac output did not change significantly; however, there was a marked increase in plasma renin activity and norepinephrine concentration (median percent increase with respect to baseline +191% and 59%, respectively). There were 68 episodes of complications of cirrhosis in 8 patients during follow-up, the most frequent being acute kidney injury. In conclusion, treatment with alfapump™ system was associated with marked activation of endogenous vasoconstrictor systems and impairment of kidney function. The chronological relationship observed between kidney impairment and vasoconstrictor systems activation after device insertion suggests a cause-effect relationship, raising the possibility that treatment with alfapump impairs effective arterial blood volume mimicking a postparacentesis circulatory dysfunction syndrome. In this context, the potential role of albumin in counteracting these effects should be investigated in future studies. Liver Transplantation 23 583-593 2017 AASLD. | {
"pile_set_name": "PubMed Abstracts"
} |
The deceleration [correction of declaration] time of pulmonary venous diastolic flow is more accurate than the pulmonary artery occlusion pressure in predicting left atrial pressure.
This study compared a prediction of mean left atrial pressure (P(LA)) ascertained by Doppler echocardiography of pulmonary venous flow (PVF), with predicted P(LA) using the pulmonary artery occlusion pressure (P(PAO)). In select patient groups, PVF variables correlate with P(PAO)) an indirect measure of P(LA). In 93 patients undergoing cardiac surgery, we recorded with transesophageal echocardiography mitral valve early (E) and late (A) wave velocities, deceleration time (DT) of E (DT(E)), and pulmonary vein systolic (S) and diastolic (D) wave velocities, DT of D (DT(D)) and systolic fraction. The P(PAO) was measured using a pulmonary artery catheter zeroed to midaxillary level. A further catheter was held at midatrial level to zero a transducer and was then inserted into the left atrium. A prediction rule for P(LA) from DT(D) was developed in 50 patients and applied prospectively to estimate P(LA) in 43 patients. A close correlation (r = -0.92) was found between P(LA) and DT(D). Systolic fraction (r = -0.63), DT(E) (r = -0.61), D wave (r = 0.57), E wave (r = 0.52), and E/A ratio (r = 0.13) correlated less closely with P(LA). The mean difference between predicted and measured P(LA) was 0.58 mm Hg for DT(D) method and 1.72 mm Hg for P(PAO), with limits of agreement (mean +/- 2 SE) of -2.94 to 4.10 mm Hg and -2.48 to 5.92 mm Hg, respectively. A DT(D)) of <175 ms had 100% sensitivity and 94% specificity for a P(LA) of >17 mm Hg. Deceleration time of pulmonary vein diastolic wave is more accurate than P(PAO) in estimating left atrial pressure in cardiac surgical patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Acculturation, diet, and psychological health among Asian students.
Objective: The study examined the association between acculturation level, dietary nutrient intake, and psychological health of Asian students at the University of Delaware. Participants: A total of 172 students completed the study. Methods: Data were collected, using questionnaires, through Qualtrics®. Linear regression models were used to examine the association between normally distributed diet and acculturation and demographic data. Results: As length of residence in the United States increased, acculturation level and maintenance of original culture both increased. There was no significant association between acculturation and nutrient intake. Chinese students were more likely than other Asian students to have nonspecific psychological distress. Conclusion: There was no significant association between diet and acculturation level. A larger sample population with longer US residence is needed to further investigate this association. In an effort to improve psychological health of Asian students, challenges specific to this population, such as the language barrier, should be addressed. | {
"pile_set_name": "PubMed Abstracts"
} |
Unusual femoral artery mycotic aneurysm complicated by infective spondylitis.
We present a patient who experienced an aortic aneurysm and a left femoral artery mycotic aneurysm, which resulted from L4-infective spondylitis via the iliopsoas compartment. This rare complication could be underdiagnosed in the absence of a more extended field of imaging view such as is provided by computed tomography. | {
"pile_set_name": "PubMed Abstracts"
} |
Splenic lymphoma: ferrite-enhanced MR imaging in rats.
Ferrite, a new magnetic resonance (MR) contrast agent, was evaluated in the detection and diagnosis of splenic lymphoma. Before administration of ferrite, normal rat spleens and spleens with diffuse lymphoma showed similar in vitro relaxation times and in vivo MR imaging signal-to-noise ratios (S/N). After the administration of ferrite (50 mumol Fe/kg), the T2 time of lymphomatous spleen was 27.0 msec +/- 2.9 (mean +/- standard deviation), which was significantly greater than that of normal spleen (10.7 msec +/- 1.5, P less than .005). The S/N of ferrite-enhanced in vivo MR images of lymphomatous spleen was 12.4 +/- 0.9, which was significantly greater than normal (5.7 +/- 0.2, P less than .005). Similar experiments with animal models of micronodular lymphoma also demonstrated that ferrite-enhanced MR imaging can distinguish micronodular lymphoma from normal spleen. Benign splenomegaly, studied with an animal model of erythroid hyperplasia, showed ferrite-enhanced MR tissue characteristics that were indistinguishable from those of normal spleen. | {
"pile_set_name": "PubMed Abstracts"
} |
The association of micronucleus frequency with obesity, diabetes and cardiovascular disease.
Obesity and metabolic syndrome (MetS) are serious and growing health care problems worldwide, leading an increased risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). Over the past decade, emerging evidence has shown that an increased chromosomal damage, as determined by the cytokinesis-block micronucleus (CBMN) assay, is correlated to the pathogenesis of metabolic and CVD. An increased micronuclei (MN) frequency has been demonstrated in peripheral blood lymphocytes of patients with polycystic ovary syndrome, a common condition in reproductive-aged women associated with impaired glucose tolerance, T2D mellitus and the MetS. High levels of MN have been detected to be significantly correlated with T2D as well as with the occurrence and the severity of coronary artery disease (CAD). Long-term follow-up studies have shown that an increased MN frequency is a predictive biomarker of cardiovascular mortality within a population of healthy subjects as well as of major adverse cardiovascular events in patients with known CAD. Overall, these findings support the hypothesis that CBMN assay may provide an useful tool for screening of the MetS and its progression to diabetes and CVD in adults as well in children. Large population-based cohorts are needed in order to compare the MN frequencies as well as to better define whether MN is a biomarker or a mediator of cardiometabolic diseases. | {
"pile_set_name": "PubMed Abstracts"
} |
New advances in antibiotic prophylaxis for colorectal surgery.
The major advances in antibiotic prophylaxis in colorectal surgery have come from an awareness of the need for appropriate agents against the known likely pathogens and from knowledge of the pharmacokinetics of these drugs. Intensive study has been undertaken to identify optimal regimens, but as there is great variability in the settings under which these operations take place, it is not always possible to compare the results of these various investigations. There is little doubt that in many cases there is gross contamination with faecal organisms and the term prophylaxis is inappropriate so that prolonged courses of antibiotics would appear to be safer. However, work towards identifying patients at increased susceptibility of developing septic complications may well further improve the outcome of colorectal surgery. | {
"pile_set_name": "PubMed Abstracts"
} |
Dietary restriction modifies certain aspects of the postoperative acute phase response.
Lifespan extension is achieved through long-term application of dietary restriction (DR), and benefits of short-term dietary restriction on acute stress and inflammation have been observed. So far, the effects of short-term DR in humans are relatively unknown. We hypothesized that short-term DR in humans reduces the acute phase response following a well defined surgical trauma. Thirty live kidney donors were randomized between 30% preoperative dietary restriction followed by 1 d of fasting (n=17) or a 4 d ad libitum regimen (n=13) prior to surgery. Leukocyte subsets and numbers and serum cytokine levels were determined. Whole blood was stimulated with lipopolysaccharide (LPS) and cytokine production was determined. A clear trend towards lower numbers of postoperative circulating leukocytes was observed in the DR group. IL-8 serum levels were significantly higher in the DR group over the first 6 postoperative d (P=0.018). After LPS stimulation, significantly less TNF-α (P=0.001) was produced by blood obtained postoperatively compared with preoperative blood from the DR group. This was not observed in the control group. A relatively short preoperative dietary restriction regimen was able to modify certain aspects of the postoperative acute phase response. These data warrant further studies into the dietary conditions that improve stress resistance in humans. (Dutch Trial Registry number: NTR1875). | {
"pile_set_name": "PubMed Abstracts"
} |
High prevalence and antimicrobial resistance of mecA Staphylococcus aureus in dairy cattle, sheep, and goat bulk tank milk in Jordan.
The aim of this study was to determine the prevalence and antimicrobial resistance of mecA and mecC methicillin-resistant Staphylococcus aureus (MRSA) in cattle, sheep, and goat dairy farms in Jordan. Milk samples were collected from bulk tanks at 117 dairy farms (44 cattle, 47 sheep, and 26 goat dairy farms) in each region of the country. MRSA were isolated on mecA and mecC chromogenic media and confirmed by PCR. The confirmed isolates were tested for resistance toward 15 antimicrobials by the disc diffusion method. None of the tested bulk milk samples were positive for mecC and 26% (95% CI 20-32%) were positive for mecA MRSA. Specifically, mecA MRSA was detected in 31.8% (95% CI 17.5-46.1) of cattle, 29.8% (95% CI 16.2-43.4) of sheep, and 11.5% (95% CI - 1.6-24.7%) of goat dairy farms. All isolates (n = 86) exhibited resistance to penicillin, oxacillin, cefoxitin; meanwhile, most isolates (70-85%) exhibited resistance toward gentamicin, clindamycin, rifampicin, neomycin, fusidic acid, erythromycin, tetracycline, and ciprofloxacin. All mecA MRSA isolates were resistant to at least one class of antimicrobials. Isolates from all goat milk, 88% of cattle milk, and 87% of sheep milk samples exhibited resistance to three classes of antimicrobials and were considered multidrug resistant (MDR). These data demonstrate widespread MDR MRSA in dairy ruminants in Jordan, and these rates are higher than those reported in other countries. Such high prevalence of MDR MRSA and mecA MRSA could lead to economic losses in the dairy industry in Jordan and poses a possible public health risk. | {
"pile_set_name": "PubMed Abstracts"
} |
Premature placental calcification in maternal cigarette smokers.
Ultrasonographic examinations, including placental grading, were done in 145 smoking and 100 nonsmoking low-risk obstetric patients at 37 weeks' gestation. Extensive calcification--grade III changes--occurred significantly more often in smokers than in nonsmokers (36 versus 14%; P less than .0001). Two groups of smokers, consuming five to 15 cigarettes per day or one or more packs per day, also had significant differences in grade III placenta when compared with nonsmokers. Smokers under age 20 years were more likely to have premature grade III changes; however, parity did not influence premature placental calcification in smokers and nonsmokers. The incidence of small for gestational age infants delivered was not significantly higher in smokers, and grade III placental changes appeared to occur no more often in SGA infants of smokers than of nonsmokers. Our findings suggest that the smoking gravida is at increased risk for premature placental calcification. | {
"pile_set_name": "PubMed Abstracts"
} |
[The knowledge and attitude of cancer prevention among junior high school teachers].
This study was to investigate the knowledge and attitude of cancer prevention among junior high school teachers. This study was based on the data collected through personal interviews by the Yang-Ming Crusade, organized by students of National Yang-Ming Medical College, during the summer vacation in 1986. Arranged by 21 city/country Education Bureaus, the crusaders gave lectures on cancer prevention for junior high school teachers in every city and town throughout Taiwan area. Totally 8,568 questionnaires (male 44.3%, female 55.7%) were filled out immediately before the lecture meetings. The results show that the cognizance rate of cervical cancer as the leading cancer (by that time) and the most curable one for women in Taiwan were 69.3% and 37.0% respectively. Pap smear test was known by 96.8% of the interviewees. As to the first source of information of the test, TV ranked highest 47.1%, followed by newspaper and hospital. The effect of "early diagnosis and early treatment" was accepted by 92.4% of the interviewees. A periodical check-up for cancer was thought essential by 93.0% of the interviewees. The concept that "herbs are effective to cure cancers" was agreed by 54.8% and disagreed by 45.2% of the interviewees. Psychological fear (43.0%), physiological suffering (30.9%), and worry of interfering family (14.6%) were considered the most dreadful situations by the interviewees in case of having cancer. Female interviewees were superior to male ones in the accuracy rate of answering the question of "what is the leading cancer and the most curable one for women in Taiwan?" (by that time). It was also found that the older the respondents were, the lower the percentage of the cognizance of knowledge about cancers. In comparison with the primary school teachers and the general population in Lu-Ku town, the results of the knowledge and attitude of cancer prevention for junior high school teachers found in this study were similar to those of the former and better than those of the latter. | {
"pile_set_name": "PubMed Abstracts"
} |
Course of intelligence deficits in early onset, first episode schizophrenia: a controlled, 5-year longitudinal study.
Only few prospective longitudinal studies have assessed the course of intelligence deficits in early onset schizophrenia (EOS), and these have used different age appropriate versions of Wechsler Intelligence Scales and age appropriate norms. The post-psychotic development of intelligence in EOS has predominantly been characterized as relatively stable in these studies. However, comparisons of IQs from different test versions based on the different norms may not permit unequivocal interpretations. The objective of the current study was to compare the development of intelligence in EOS patients (N = 10) from their first psychotic episode to 5 years of post onset with that of healthy controls (N = 35) and patients who at baseline had been diagnosed with other non-affective psychoses (N = 8). The same version of a Wechsler Intelligence Scale was administered at both baseline and follow-up assessments, and the same norms were used to derive IQs at baseline and follow-up. Significantly smaller change in mean full scale intelligence quotient (FSIQ) was found in diagnostically stable EOS patients compared with healthy controls during the follow-up period. However, no statistically significant difference in mean FSIQ change was observed between patients with EOS and patients with other non-affective psychoses, although this result must be interpreted with caution due to the small sample sizes. The results suggest abnormally slow acquisition of new intellectual information and skills in EOS patients during the first 5 years after full clinical presentation. | {
"pile_set_name": "PubMed Abstracts"
} |
Magnetic resonance imaging findings after laparoscopic renal cryoablation.
To assess the magnetic resonance imaging (MRI) appearance of renal masses after laparoscopic cryoablation. Between October 2000 and June 2004, 33 patients underwent laparoscopic cryoablation of 34 renal masses, 24 of whom (25 renal masses, size range 1.5 to 3.7 cm, mean 2.4) were followed up with MRI postoperatively. Postoperative MRI was done at 1, 3, and 6 months after ablation and every 6 months thereafter using a 1.5-T MRI scanner. T1-weighted dual-phase, coronal T1-weighted fat-saturated, and T2-weighted coronal and axial MRI was done before contrast administration. Postenhancement images were obtained in the coronal and axial planes during the arterial, venous, and delayed phases. Patient follow-up data were available for at least 6 months and up to 48 months for 18 patients. On the first follow-up MRI study, six lesions had increased in size, five had decreased in size, and seven showed no change. Of the 18 patients, 7 had peripheral rim enhancement within 3 months of follow-up. Four resolved. One patient developed rim enhancement at 7 months postoperatively. Subsequent images revealed lesion enlargement with heterogeneous enhancement. Biopsy was positive for renal cell carcinoma. One patient developed nodular enhancement at 10 months with a decrease in lesion size. Watchful waiting was chosen because the patient had significant medical comorbidities. Peripheral rim enhancement is a common finding on MRI immediately after laparoscopic renal cryoablation. Rim enhancement with an increase in lesion size or nodular enhancement is of more concern than rim enhancement alone. More data are necessary to understand the progression of renal lesions after cryoablation. | {
"pile_set_name": "PubMed Abstracts"
} |
Accelerative exchange diffusion kinetics of glucose between blood and brain and its relation to transport during anoxia.
An earlier study showed that unidirectional glucose transport from blood to brain decreases during perfusion with anoxic blood (Betz, A. L., Gilboe, D. D. and Drewes, L. R. (1974) Brain Res. 67, 307-316). Brain glucose levels also decrease during anoxia. Therefore, the present study was designed to investigate whether the decreased transport might be the result of decreased accelerative exchange diffusion when brain glucose levels are low. The rate of undirectional transport into brain (v) of D-[6-3H]glucose was studied in 22 isolated, perfused dog brains by means of an indicator dilution technique using 22Na as the intravascular reference. The kinetics of transport were determined over a range of blood glucose concentrations (S1) at each of five different brain glucose levels (S2). The existence of accelerative exchange diffusion for glucose was indicated by a decrease in the intercept (increase of apparent V) of a double reciprocal plot (1/v versus 1/S1) as S2 increased. This phenomenon is consistent with a model for facilitated diffusion in which the mobility of the loaded carrier is greater than that of the unloaded carrier. Although the data predict a decrease in glucose transport during anoxia, the predicted decrease (5%) is less than the observed decrease (35%). It is concluded that the simple mobile-carrier model for facilitated diffusion cannot, by itself, describe all properties of blood-brain glucose transport. | {
"pile_set_name": "PubMed Abstracts"
} |
Transepithelial ultrafiltration and fractal power diffusion of D-glucose in the perfused rat intestine.
Despite an enormous body of research investigating the mass transfer of D-glucose through biological membranes, carrier-mediated and first-order models have remained the prevalent models describing glucose's quantitative behavior even though they have proven to be inadequate over extended concentration ranges. Recent evidence from GLUT2 knockout studies further questions our understanding of molecular models, especially those employing Michaelis-Menten (MM)-type kinetic models. In this report, evidence is provided that D-glucose is absorbed by rat intestinal epithelium by a combination of convective ultrafiltration and nonlinear diffusion. The diffusive component of mass transfer is described by a concentration-dependent permeability coefficient, modeled as a fractal power function. Glucose and sodium chloride-dependent-induced aqueous convection currents are the result of prevailing oncotic and osmotic pressure effects, and a direct effect of glucose and sodium chloride on intestinal epithelium resulting in enhanced glucose, sodium ion, and water mobility. The fractal power model of glucose diffusion was superior to the conventional MM description. A convection-diffusion model of mass transfer adequately characterized glucose mass transfer over a 105-fold glucose concentration range in the presence and absence of sodium ion. | {
"pile_set_name": "PubMed Abstracts"
} |
Safety and efficacy of intra-articular sodium hyaluronate (Hyalgan) in a randomized, double-blind study for osteoarthritis of the ankle.
The potential benefit of hyaluronans in alleviating pain associated with osteoarthritis (OA) in joints other than the knee is of increasing interest. This double-blind, randomized, controlled study examined the safety and efficacy of intraarticular sodium hyaluronate (Hyalgan) in the treatment of pain associated with ankle OA. Thirty consecutive patients with ankle OA documented by X-ray were randomized to treatment with five weekly injections of either sodium hyaluronate 2 mL (HYL) or phosphate-buffered saline 2 mL (control) in the tibiotalar joint. The primary endpoint was pain on movement and weightbearing using the Ankle Osteoarthritis Scale (AOS) 3 months after injection (a 100-mm visual analog scale [VAS]). Additional measures included the Western Ontario and McMaster Universities (WOMAC) OA Index and patient global assessment through 6 months; the Short Form-12 (SF-12) Health Survey at 3 months and 6 months; and all reported adverse events (AEs). The study groups differed only in age, baseline WOMAC pain, and AOS total scores; 80% of the HYL and 73% of the control patients completed the study. At Month 3, the primary endpoint of the study, the HYL group demonstrated a significantly greater improvement from baseline in AOS total score than did the control group (HYL: -17.4 +/- 5.0 mm; -5.1 +/- 4.0 mm; p = 0.0407). The incidence of AEs was low, with no significant differences between the groups. There were no post-injection flares. Our study suggests that sodium hyaluronate may be a safe and effective option for pain associated with ankle OA, although larger studies are needed. | {
"pile_set_name": "PubMed Abstracts"
} |
Modifications in the metabolic pathways of benzene in streptozotocin-induced diabetic rat.
Benzene is a ubiquitous environmental pollutant primarily metabolized by a cytochrome P-450 (CYP-450) isoenzyme, CYP-450 IIE1. A consistent induction of CYP450 IIE1 has been observed in both rat and human affected by diabetes mellitus. The aim of this study was to evaluate whether streptozotocin (STZ)-induced diabetes determines modifications in the metabolic pathways of benzene in rat. Benzene (100 mg/kg per day, dissolved in corn oil) was administered i.p. once a day for 5 days. Urine samples were collected every day in STZ-treated and normoglycaemic animals, treated and untreated with benzene (n = 10). Urinary levels of trans,trans-muconic acid and of phenol, catechol and hydroquinone (free and conjugated with sulphuryl and glucuronic group) were measured by high-performance liquid chromatography (HPLC). In normoglycaemic rats during the 5 days of treatment with benzene we observed a progressive and significant decrement in the urinary excretion of phenol, phenyl sulphate and glucuronide, catechol, catechol glucuronide, hydroquinone, hydroquinone glucuronide and t,t-muconic acid (P < 0. 05). In the diabetic animals, conversely, the same metabolites showed progressively increasing urinary levels (P < 0.05). Catechol sulphate and hydroquinone sulphate levels were below the instrument's detection limit. In the comparison between diabetic and normoglycaemic benzene treated rats, the inter-group difference was significant (P < 0.05) from day 3 of treatment for t,t-muconic acid, and from day 1 for free and conjugated phenol, free and glucuronide catechol and free hydroquinone. In the normoglycaemic rat exposed to benzene the decreasing trend observed in urinary excretion of free and conjugated metabolites may be due to their capability to reduce cytochromial activity. Conversely, in the diabetic rat, urinary levels of benzene metabolites tended to increase progressively, probably due to the consistent induction of CYP-450 IIE1 observed in diabetes, which would overwhelm the inhibition of this isoenzyme caused by phenolic metabolites. Furthermore, the metabolic switch towards detoxification metabolites observed after administration of high doses of benzene is not allowed in the diabetic because of reduced glutathione-S-transferase activity. As a consequence, higher levels of hydroquinone, phenol and catechol, considered the actual metabolites responsible for benzene toxicity, will accumulate in the diabetic rat. Extrapolating these data to human, we may thus suggest that occupational exposure to benzene of a diabetic subject poses a higher risk level, as his metabolism tends to produce and accumulate higher levels of reactive benzene catabolites. | {
"pile_set_name": "PubMed Abstracts"
} |
Provision and use of personal protective equipment among home care and hospice nurses in North Carolina.
We investigated the frequency with which home care/hospice nurses are provided with and use personal protective equipment (PPE) and factors associated with use. We conducted a mail survey among home care/hospice nurses in North Carolina in 2006. The adjusted response rate was 69% (n = 833). Between 68% and 86% of nurses were always provided with the relevant types of PPE; these nurses were 2.5-3 times more likely to use the PPE in scenarios involving a potential for blood exposure compared with nurses who were not always provided with PPE. Nurses who always had sufficient time during home visits were 50% more likely to use PPE. Nurses who visited more homes with adverse working conditions were less likely to use PPE. The public health policy of providing PPE to health care workers and ensuring that they use that equipment to prevent occupational blood exposure is not being fully implemented for home care and hospice nurses. Greater provision of PPE could reduce blood exposure in this population. Conditions of the home care/hospice work environment may be impeding nurses' ability to use PPE. | {
"pile_set_name": "PubMed Abstracts"
} |
Telomerase activity and telomerase catalytic subunit in hepatocellular carcinoma.
Telomerase activation has been found in most malignant tumors. Human telomerase reverse transcriptase is a catalytic subunit of human telomerase and a rate-limiting factor of the enzymatic activity of telomerase. The present study was designed to examine the usefulness of detecting human telomerase catalytic subunit mRNA and telomerase activity as a molecular diagnostic marker for human liver cancers. Thirty-one specimens of hepatocellular carcinoma and corresponding adjacent tissues were analyzed for human telomerase reverse transcriptase expression by reverse transcription polymerase chain reaction and for telomerase activity by polymerase chain reaction-based telomeric repeat amplification protocol. Human telomerase reverse transcriptase mRNA expression was observed in 97% of hepatocellular carcinoma tissues, in contrast none of the non-tumorous liver tissues did. Telomerase activity was detected in 94% of hepatocellular carcinoma and in only 16% of adjacent liver tissues. Human telomerase reverse transcriptase mRNA expression and telomerase activity were observed in all 3 grade I (well-differentiated) hepatocellular carcinoma. Significant correlations between human telomerase reverse transcriptase mRNA expression and hepatocellular carcinoma and also between telomerase activity and HCC were found (both p<0.001). The results indicate that human telomerase catalytic subunit mRNA expression and telomerase activity might be associated with hepatocellular carcinogenesis and could be as markers for diagnosis of hepatocellular carcinoma. | {
"pile_set_name": "PubMed Abstracts"
} |
Changes of high density lipoprotein subfraction concentration and composition by intralipid in vivo and by lipolysis of intralipid in vitro.
Serum lipoproteins were measured during a single infusion of intralipid and during parenteral nutrition with intralipid and glucose. Postheparin plasma lipolytic enzymes and plasma LCAT activity were assayed before and after the parenteral nutrition. Both single and repeated infusions of intralipid were followed by a significant rise of HDL2 concentration (p less than 0.01), whereas the HDL3 decreased. The composition of HDL subclasses altered. The HDL2 triglyceride and phospholipids increased, while the HDL3 esterified cholesterol and protein decreased. In vitro incubation of serum with intralipid alone caused no changes in the zonal profile of HDL subclasses, but hydrolysis of intralipid by lipoprotein lipase was followed by conversion of HDL3 into lighter particles floating in the density range of HDL2. The present results provide additional evidence for a precursor-product relationship between the HDL2 and HDL3. During 4 days of parenteral nutrition with intralipid, the basal (morning) values of serum total and VLDL triglyceride did not change. The LDL phospholipids increased progressively (from 67 to 98 mg/dl, p less than 0.05). The total HDL cholesterol decreased and this change was due to the fall of HDL3 cholesterol esters (from 19 to 12 mg/dl, p less than 0.05). Also the basal values of apo A-I and A-II in HDL3 decreased. The basal level of the HDL2 remained constant. Postheparin plasma LPL activity increased by 52% (p less than 0.01) but hepatic lipase activity fell by 49% (p less than 0.05). These changes may account for the maintenance of plasma HDL2, whereas the progressive fall of the basal HDL3 is probably due to the lack of intestinal apoprotein synthesis during absent intestinal absorption. | {
"pile_set_name": "PubMed Abstracts"
} |
[Correlation of neuropsychological tests and density of brain white matter in schizophrenia].
In a group of 10 subjects, nine schizophrenic patients and one healthy twin (seven men and three women, i.e. two monozygotic twin pairs: two patients and a healthy man and his sick twin brother, one dizygotic pair of two female patients, three male patients and one female patient without their appropriate twin siblings) Halstead-Reitan Neuropsychological Battery (HRNB) was used and partial neuropsychological tests (Wechsler Memory Scale, the Stroop Color-Word Test, Tonal Memory). The parameters of white matter density were evaluated by computed tomography. The fundamental findings include: In our small group numerous statistically significant correlations were found between neuropsychological tests and white matter density. 2. Higher density is associated with poorer neuropsychological efficiency. There are very similar correlations between neuropsychological variables and density parameters in different areas of the brain. 4. The majority of correlations of neuropsychological parameters is from the area of tactile and motor functions. 5. It is striking that there are statistically significant correlations of density with the simultaneous performance of both hands and the performance of the non-dominant hand but not with the performance of the dominant hand alone. 6. Some correlations pertain in addition to density also to the very controversial problem of the brain size of schizophrenic patients. In the investigated group an association between better neuropsychological performance and larger size of the brain was found. All findings will have to be tested in larger groups of patients and healthy subjects. | {
"pile_set_name": "PubMed Abstracts"
} |
Validity of CT classification on management of occult pneumothorax: a prospective study.
In the setting of blunt trauma, abdominal CT, which routinely includes images of the lower thorax, frequently reveals pneumothoraces that have not been detected on routine supine chest radiographs. Proper management of these occult pneumothoraces remains controversial. The purpose of this study was to test the hypothesis that small (minuscule) to moderate (anterior) radiographically occult pneumothoraces can be safely managed without chest tube placement for patients in whom the need for positive pressure ventilation is not anticipated. We undertook a prospective study in which 44 occult pneumothoraces were classified into three groups, minuscule, anterior, or anterolateral, according to size and location on CT scans. Choice of initial management (tube thoracostomy versus close observation) was based in part on this classification system and in part on individual circumstances of a surgeon's decision. Of the 44 pneumothoraces found in 36 patients, 16 pneumothoraces were minuscule, 20 were anterior, and eight were anterolateral. Thirteen minuscule pneumothoraces and 11 anterior pneumothoraces initially managed with observation did not require subsequent tube thoracostomy. All eight patients with anterolateral pneumothoraces underwent tube thoracostomy. Most small (minuscule) occult pneumothoraces can successfully be managed with close observation. The risk that the pneumothorax will progress is slight. Moderate-sized (anterior) pneumothoraces may also be successfully managed without initial placement of a chest tube if the patient is not to undergo positive pressure ventilation. | {
"pile_set_name": "PubMed Abstracts"
} |
Modified rhyme test and synthetic sentence identification test scores of normal and hearing-impaired subjects listening in multitalker noise.
Articulation functions were established for 35 normal hearing, 6 flat sensorineural, and 6 high frequency sloping sensorineural hearing-impaired subjects using the modified rhyme test (MRT) and synthetic sentence identification test (SSIT) in three message competition ratios (MCRs) of multitalker noise. An analysis of variance revealed significant differences between tests, subject groups, presentation conditions, and interactions between variables. Post hoc analyses revealed that SSIT functions were not significantly different among groups, and that MRT functions were different for each group. The MRT and SSIT were found to be two significantly different tests, each taxing different areas of discrimination. Results suggest that both tests can be used clinically with various MCRs of multitalker noise, but that the poorest MCR for each test does not aid in defining discrimination abilities. | {
"pile_set_name": "PubMed Abstracts"
} |
Spectral signature of nonlinear effects in semiconductor optical amplifiers.
Optical spectra of signals at the output of semiconductor optical amplifiers (SOA) provide useful insight into amplifier nonlinearities. In this work, we determine the parameters of an analytical SOA model with a pump-probe experiment by evaluating the measured spectra of the pump and probe pulses at the SOA output. The analytical lumped SOA model considers carrier depletion, carrier recovery, spectral hole burning, two-photon absorption, and we include an additional effect termed 'two-photon induced free-carrier absorption', that is responsible for creating an identifiable blue-shifted component in the spectra. We are able to relate the underlying physical nonlinear effects to the spectral peculiarities of the output pump and probe spectra, and give guidelines for the exploitation of these nonlinear effects for optical signal processing. In addition, with a much-simplified SOA model and by replacing the pump pulse with modulated data we show that the output spectrum is altered in a manner consistent with phase patterning effects. | {
"pile_set_name": "PubMed Abstracts"
} |
Incorporation of β-amino acids into dihydrofolate reductase by ribosomes having modifications in the peptidyltransferase center.
Ribosomes containing modifications in three regions of 23S rRNA, all of which are in proximity to the ribosomal peptidyltransferase center (PTC), were utilized previously as a source of S-30 preparations for in vitro protein biosynthesis experiments. When utilized in the presence of mRNAs containing UAG codons at predetermined positions+β-alanyl-tRNA(CUA), the modified ribosomes produced enhanced levels of full length proteins via UAG codon suppression. In the present study, these earlier results have been extended by the use of substituted β-amino acids, and direct evidence for β-amino acid incorporation is provided. Presently, five of the clones having modified ribosomes are used in experiments employing four substituted β-amino acids, including α-methyl-β-alanine, β,β-dimethyl-β-alanine, β-phenylalanine, and β-(p-bromophenyl)alanine. The β-amino acids were incorporated into three different positions (10, 18 and 49) of Escherichia coli dihydrofolate reductase (DHFR) and their efficiencies of suppression of the UAG codons were compared with those of β-alanine and representative α-l-amino acids. The isolated proteins containing the modified β-amino acids were subjected to proteolytic digestion, and the derived fragments were characterized by mass spectrometry, establishing that the β-amino acids had been incorporated into DHFR, and that they were present exclusively in the anticipated peptide fragments. DHFR contains glutamic acid in position 17, and it has been shown previously that Glu-C endoproteinase can hydrolyze DHFR between amino acids residues 17 and 18. The incorporation of β,β-dimethyl-β-alanine into position 18 of DHFR prevented this cleavage, providing further evidence for the position of incorporation of the β-amino acid. | {
"pile_set_name": "PubMed Abstracts"
} |
Sustained release of niridazole from silicone rubber implants for the treatment of Schistosoma mansoni infections.
Niridazole was incorporated into silicone rubber implants to investigate the potential of a sustained release of the drug in the therapy of murine schistosomiasis mansoni. The infected animals (200 cercariae for 6 weeks) were randomly divided into three groups: one group received silicone rubber implants containing 50% by weight niridazole; a second group received blank silicone rubber implants with no drug; and the third group received no implants. Mortality 4 weeks later was in excess of 80% for animals with no implants or with the blank silicone rubber implants. In contrast, 10% mortality was observed in the mice receiving the niridazole-silicone rubber implants over a 10-week period. The worm burden in the niridazole-silicone rubber implant group was reduced at 10 weeks post implantation by 77%. | {
"pile_set_name": "PubMed Abstracts"
} |
The effect of hydroxyapatite nanoparticles on adipogenic differentiation of human mesenchymal stem cells.
Due to its excellent biocompatibility, nanosized hydroxyapatite (nHA) has drawn much attention for various applications in biomedical fields. There are growing concerns about its biosecurity; however, little is known about its effects on adipogenesis. In the present study, nHA with three different sizes were synthesized, and the in vitro effects of nHA on cell proliferation and adipogenic differentiation of human mesenchymal stem cells (hMSCs) were investigated. The results clearly show that nHA does not affect the cell viability, the lipids droplets formation, triglyceride (TG) synthesis, and the expression of adipogenic marker genes/proteins of hMSCs at concentrations lower than 50 μg/mL. It is concluded that the adipogenic differentiation potential of hMSCs is not affected by nHA at noncytotoxic concentrations. These will provide a reference for the applications of nHA in biomedical fields. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1822-1831, 2018. | {
"pile_set_name": "PubMed Abstracts"
} |
Amino acid sequence of a vitamin K-dependent Ca2+-binding peptide from bovine prothrombin.
The amino acid sequence of a 31-residue peptide from bovine prothrombin has been determined. This peptide has been shown to contain the vitamin K-dependent modification required for Ca2+ binding (Nelsestuen, G. L., and Suttie, J. W. (1973) Proc. Natl. Acad. Sci. U. S. A. 70, 3366-3370) and the modified amino acid, gamma-carboxyglutamic acid (Nelsestuen, G. L., Zytkovicz, T., and Howard, J. B. (1974) J. Biol. Chem. 249, 6347-6350). The peptide was shown to correspond to residues 12 to 42 of prothrombin. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of weed cover composition on insect pest and natural enemy abundance in a field of Dracaena marginata (Asparagales: Asparagaceae) in Costa Rica.
Weeds and their influence on pest and natural enemy populations were studied on a commercial ornamental farm during 2009 in the Atlantic Zone of Costa Rica. A baseline survey of the entire production plot was conducted in February, along a 5 by 5 m grid to characterize and map initial weed communities of plants, cicadellids, katydids, and armored scales. In total, 50 plant species from 21 families were found. Seven weed treatments were established to determine how weed manipulations would affect communities of our targeted pests and natural enemies. These treatments were selected based on reported effects of specific weed cover on herbivorous insects and natural enemies, or by their use by growers as a cover crop. Treatments ranged from weed-free to being completely covered with endemic species of weeds. Although some weed treatments changed pest abundances, responses differed among arthropod pests, with the strongest effects observed for Caldwelliola and Empoasca leafhoppers. Removal of all weeds increased the abundance of Empoasca, whereas leaving mostly cyperacaeous weeds increased the abundance of Caldwelliola. Weed manipulations had no effect on the abundance of katydid and scale populations. No weed treatment reduced the abundance of all three of the target pests. Differential responses of the two leafhopper species to the same weed treatments support hypotheses, suggesting that noncrop plants can alter the abundance of pests through their effects on arthropod host finding and acceptance, as well as their impacts on natural enemies. | {
"pile_set_name": "PubMed Abstracts"
} |
Isomeric trans fatty acids in the Spanish diet and their relationships with changes in fat intake patterns.
Eleven different groups of food products (total samples 378), representing about 90% of total fat intake in Spanish diet, were analysed by gas chromatography in order to determine their contents and variability of trans fatty acids. With official data of food consumption in Spain, trans fatty acid intake is calculated for recent decades and results are compared with data available from other countries. Mean intake in Spain obtained from this calculation is 2.4 g/person/day. This is lower than values for other food consumption models in which the major fats are of animal origin or industrially processed. | {
"pile_set_name": "PubMed Abstracts"
} |
Sealing ability of mineral trioxide aggregate, calcium phosphate cement, and glass ionomer cement in the repair of furcation perforations.
The purpose of this study was to evaluate the in vitro sealing ability of three repair materials. Mineral trioxide aggregate (MTA; Group A), calcium phosphate cement (CPC; Group B), and light cured glass ionomer cement (GIC; Group C) when used to repair the perforation created in the pulpal floor of fifty extracted human permanent molars. Preparation of access openings and furcation perforations were done, and the teeth divided into five experimental groups (A, B, C) including two controls (D, E) with ten samples in each group randomly. Following the repair procedure, the pulp chambers and access openings were filled with composite resin and immersed in 2% methylene blue solution for 48 hours. The teeth were sectioned longitudinally and the linear dye penetration measured under a stereomicroscope. The comparison of the linear length of micro-leakage (mm) among the experimental groups revealed no significant difference (p = 0.332). On calculating the percentage of depth of leakage to the total length of the perforation, it was observed that the mean leakage was 35.5% in Group A, 53.6% in Group B and the highest, 87.5% in Group C. The mean of leakage percentage was statistically significant by Kruskal-Wallis test (p = 0.003). The results indicated that the dye penetration used as furcation perforation repair material was least with mineral trioxide aggregate. Comparing the depth of penetration of dye, 50% of the Group A samples showed less than 25% of depth penetration. While 40% of Group B cases had more than 50% dye penetration. In our study, all Group C teeth had > or = 50% dye penetration. The present study indicated that GIC had the greatest dye penetration followed by CPC and MTA. Mineral trioxide aggregate and calcium phosphate cement had comparatively better sealing ability than glass ionomer cement. | {
"pile_set_name": "PubMed Abstracts"
} |
Reliability and Validity of a Maximal Treadmill Test for Predicting Aerobic Fitness in Norwegian Prospective Soldiers.
The Norwegian armed forces reintroduced physical fitness testing of prospective conscript soldiers in 2011. Since then, a customized maximal treadmill test (MILMAX) has been used to screen aerobic fitness in 15-20,000 young Norwegian men and women annually. The aim of the current study was to investigate reliability and validity of the MILMAX test. Sixty-seven young Army recruits (including 11 women) participated in this method comparison study. The subjects completed the MILMAX test twice (test-retest), consisting of walking and running at increasing speed and inclination until voluntarily exhaustion. Performance was registered as exercise tolerance time (ETT). Later, the subjects performed a treadmill test of direct maximal oxygen uptake (V̇O2max). All tests were conducted within 15 days. The study protocol was submitted to the Regional Committee for Medical and Health Research Ethics for review, prior to study initiation. The Committee considered the study to be exempted from notification. The study was carried out according to the guidelines in the Declaration of Helsinki. There was no significant mean difference in MILMAX ETT between test and retest. Test-retest intraclass correlation coefficient was 0.95 (0.91, 0.97), while 95% limits of agreement was ± 60 seconds. Regression analyses showed that MILMAX ETT and gender explained 78% of the variance in directly measured V̇O2max, and a prediction equation with these two independent variables was generated. The Pearson correlation coefficient between predicted and directly measured V̇O2max was 0.89 (0.83, 0.93), while limits of agreement was ± 5.6 mL·kg-1·min-1. The MILMAX is equally reliable and valid compared with well-known maximal indirect tests like the 2-mile run and the 20-m shuttle run test, and may serve as an alternative indoor test of aerobic fitness in the military, in other potentially physically strenuous occupations, or in healthy civilians. | {
"pile_set_name": "PubMed Abstracts"
} |
Efficacy of selamectin against experimentally induced and naturally acquired infections of Toxocara cati and Ancylostoma tubaeforme in cats.
The efficacy of selamectin against experimentally induced and naturally acquired infections of adult ascarids (Toxocara cati) and adult hookworms (Ancylostoma tubaeforme) was evaluated in five controlled studies in cats. Two studies evaluated the efficacy of selamectin against both ascarid (natural or induced) and hookworm (induced) infections; two studies evaluated the efficacy of selamectin against single natural infections of T. cati or A. tubaeforme; and the fifth study evaluated the efficacy of selamectin against induced infections of A. tubaeforme. Cats received selamectin topically in unit doses designed to deliver a minimum of 6mgkg(-1). Treatments were applied to the skin on each animal's back at the base of the neck in front of the scapulae. For experimentally induced infections, cats were inoculated orally with approximately 500 embryonated eggs of T. cati 56 days prior to treatment and/or approximately 150-250 larvae (L(3)) of A. tubaeforme 30 or 42 days prior to treatment. For both induced and naturally acquired infections, cats were allocated randomly to treatments (6-12 cats per treatment) on the basis of fecal egg counts to receive either selamectin or a vehicle containing the inert formulation ingredients. In all studies, adult worm counts were performed at necropsy 14 days after the last treatment administration. Against T. cati, a single application of selamectin provided a 100% reduction in the geometric mean number of adult worms for both experimentally induced and naturally acquired infections. Against A. tubaeforme, a single administration of selamectin provided a 99.4% reduction in the geometric mean number of adult worms in cats with natural infections, and an 84.7-99.7% reduction in adult worms in cats with induced infections. Two doses of selamectin administered at monthly intervals provided a 91.9% reduction in the geometric mean number of adult A. tubaeforme worms in cats with experimentally induced infections. The geometric mean numbers of adult worms (T. cati and A. tubaeforme) from selamectin-treated cats were significantly (P< or =0.0018) lower than for vehicle-treated cats in all studies. Thus, a single topical unit dosage providing a minimum dosage of 6mgkg(-1) selamectin was highly effective in the treatment of naturally acquired and experimentally induced infections of T. cati and A. tubaeforme in cats. | {
"pile_set_name": "PubMed Abstracts"
} |
SUBRETINAL DRUSENOID DEPOSIT IN AGE-RELATED MACULAR DEGENERATION: Histologic Insights Into Initiation, Progression to Atrophy, and Imaging.
To clarify the role of subretinal drusenoid deposits (SDD; pseudodrusen) in the progression of age-related macular degeneration through high-resolution histology. In 33 eyes of 32 donors (early age-related macular degeneration, n = 15; geographic atrophy, n = 9; neovascular age-related macular degeneration, n = 7; unremarkable, n = 2), and 2 eyes of 2 donors with in vivo multimodal imaging including optical coherence tomography, examples of SDD contacting photoreceptors were assessed. Subretinal drusenoid deposits were granular extracellular deposits at the apical retinal pigment epithelium (RPE); the smallest were 4-µm wide. Outer segment (OS) fragments and RPE organelles appeared in some larger deposits. A continuum of photoreceptor degeneration included OS disruption, intrusion into inner segments, and disturbance of neurosensory retina. In a transition to outer retinal atrophy, SDD appeared to shrink, OS disappeared, inner segment shortened, and the outer nuclear layer thinned and became gliotic. Stage 1 SDD on optical coherence tomography correlated with displaced OS. Confluent and disintegrating Stage 2 to 3 SDD on optical coherence tomography and dot pseudodrusen by color fundus photography correlated with confluent deposits and ectopic RPE. Subretinal drusenoid deposits may start at the RPE as granular, extracellular deposits. Photoreceptor OS, RPE organelles, and cell bodies may appear in some advanced deposits. A progression to atrophy associated with deposit diminution was confirmed. Findings support a biogenesis hypothesis of outer retinal lipid cycling. | {
"pile_set_name": "PubMed Abstracts"
} |
Histochemical studies of lectin binding patterns in keratinized lesions, including malignancy.
Histochemical detection of lectin binding was carried out using the HRP-conjugated lectin method in hyperkeratinized lesions including leukoplakia, carcinoma in situ, Paget's disease, keratoacanthoma, and condyloma acuminatum. The lectins used for demonstrating sugar residues were: Con A (hexose), PNA and RCA-1 (Gal), DBA and SBA (GalNAc), UEA -1 (Fuc), and WGA (GlcNAc). Lectin binding in normal squamous epithelium showed regional distribution patterns of keratinized, spinous and basal layer types. Histochemical localization of lectin binding was generally at the cellular surface and in the intercellular substance and sometimes in the cytoplasm of normal epithelial cells. Dysplastic cells or carcinoma cell, in contrast, displayed a loss of cellular surface and intercellular staining. Paget's cells were devoid of lectin staining. In keratoacanthoma and condyloma specimens, spinous cells, which were PAS-positive, showed an intense PA/Con A-HRP staining and moderate binding by other lectins, which was somewhat decreased when compared with that in the surrounding intact epithelium. The cytochemical distribution of epithelial lectin binding might be indicative of the expression of normal stratification and keratinocytic differentiation , and the disappearance of this typical epithelial pattern may suggest severe dysplasia and malignancy. | {
"pile_set_name": "PubMed Abstracts"
} |
Crimean-Congo hemorrhagic fever.
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV), which is a member of the Nairovirus genus (family Bunyaviridae). CCHF was first recognized during a large outbreak among agricultural workers in the mid-1940s in the Crimean peninsula. The disease now occurs sporadically throughout much of Africa, Asia, and Europe and results in an approximately 30% fatality rate. After a short incubation period, CCHF is characterized by a sudden onset of high fever, chills, severe headache, dizziness, back, and abdominal pains. Additional symptoms can include nausea, vomiting, diarrhea, neuropsychiatric, and cardiovascular changes. In severe cases, hemorrhagic manifestations, ranging from petechiae to large areas of ecchymosis, develop. Numerous genera of ixodid ticks serve both as vector and reservoir for CCHFV; however, ticks in the genus Hyalomma are particularly important to the ecology of this virus. In fact, occurrence of CCHF closely approximates the known world distribution of Hyalomma spp. ticks. Therefore, exposure to these ticks represents a major risk factor for contracting disease; however, other important risk factors are known and are discussed in this review. In recent years, major advances in the molecular detection of CCHFV, particularly the use of real-time reverse transcription-polymerase chain reaction (RT-PCR), in clinical and tick samples have allowed for both rapid diagnosis of disease and molecular epidemiology studies. Treatment options for CCHF are limited. Immunotherapy and ribavirin have been tried with varying degrees of success during sporadic outbreaks of disease, but no case-controlled trials have been conducted. Consequently, there is currently no antiviral treatment for CCHF approved by the U.S. Food and Drug Administration (FDA). However, renewed interested in CCHFV, as well as increased knowledge of its basic biology, may lead to improved therapies in the future. This article reviews the history, epidemiology, ecology, clinical features, pathogenesis, diagnosis, and treatment of CCHF. In addition, recent advances in the molecular biology of CCHFV are presented, and issues related to its possible use as a bioterrorism agent are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
[Molecular-targeted therapy for motor neuron disease].
The mechanisms underlying selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remain unknown. There have been several important clinical trials on the treatment of ALS and treatment efficacy studies using mouse (SOD1) models of ALS. The latter revealed that diminished mutant SOD1 expression in the astrocytes delayed microglial activation and slowed disease progression. Dyslipidemia has been reported to have a protective effect in ALS patients. Current evidence has implicated a 43-kDa TAR DNA-binding protein (TDP-43) in the pathologenesis of ALS. Several mutations in TDP-43 were discovered in families with inherited motor neuron disease. Although phase III trials revealed that creatine monohydrate and IGF-1 was not beneficial for patients with ALS, favorable outcomes in SOD1 mice were reported with lithium, NADPH oxidase inhibitor, free-radical scavenger, and ammonium tetrathiomolybdate. Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease affecting only males. Animal studies have revealed that the pathogenesis of SBMA depends on the serum testosterone level and that androgen deprivation mitigates neurodegeneration through inhibition of nuclear accumulation of the pathogenic androgen receptor (AR). Our studies have also identified several candidates for the treatment of SBMA. Selective inhibition of heat shock protein (HSP) facilitates the proteasomal degradation of pathogenic AR, leading to improvements in the signs and symptoms of SBMA mice. Oral administration of sodium butyrate--a histone deacetylase inhibitor--resulted in the improvement of neurological dysfunction in the SBMA mouse model, although its therapeutic dose range is narrow. | {
"pile_set_name": "PubMed Abstracts"
} |
Impairment of autologous mixed lymphocyte reaction in the spleen and peripheral blood lymphocytes of patients with idiopathic portal hypertension.
The etiology of idiopathic portal hypertension (IPH) is unknown, although many studies have suggested that it might be an autoimmune disease. The autologous mixed lymphocyte reaction (AMLR) involves the proliferation of T lymphocytes when co-cultured with autologous non-T cells and may reflect immune control mechanisms in vivo. The AMLRs in the spleen and peripheral blood of three patients with IPH were measured and it was shown that the AMLRs both in the spleen and peripheral blood were significantly suppressed compared to those of normal healthy subjects. By allogeneic MLR, there was a tendency that the disturbance of non-T cells was more intensive than that of T cells. The AMLR of peripheral blood did not improve by splenectomy. Thus, the depressed cause of AMLR in patients with IPH was suggested mainly to disturbance of the antigen-presenting ability of non-T cells, and it was suggested that not only the spleen cells, but systemic immune disturbance caused the impairment of AMLR in IPH. | {
"pile_set_name": "PubMed Abstracts"
} |
[Application of Transcutaneous Electrical Acupoint Stimulation Combined with Transversus Abdominis Plane Block to Enhanced Recovery After Surgery in Patients Undergoing Laparoscopic Colorectal Cancer Resection: A Randomized Controlled Clinical Trial].
To explore the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with transversus abdominis plane (TAP) block in the enhanced recovery after surgery (ERAS) in patients undergoing laparoscopic colorectal cancer resection (LCCR). A total of 101 patients undergoing LCCR were randomly divided into three groups: control (n＝34), TAP (n＝35) and TEAS＋TAP (n＝32). Conventional perioperative anesthesia management of the 3 groups was performed according to the ERAS guidelines. All the patients experienced patient controlled epidural analgesia (PCEA), and those of the TAP and TEAS＋TAP groups received TAP block by injection of 0.3% Roperca hydrochloride (15 mL) into the space between the internal oblique and the transverse abdominis after induction of anesthesia. For patients of the TEAS＋TAP group, TEAS (2 Hz/10 Hz, an endurable stimulation strength) was applied to bilateral Zusanli (ST 36) from 30 min before anesthesia to the end of the surgery. The blood glucose value and dosage of Remifentanil used were recorded. The pain severity was assessed at 4, 12, 24 and 48 h after surgery by using visual analogue scale (VAS). Moreover, postoperative anal exhaust time, postoperative oral feeding time, postoperative first ambulation time and postoperative hospital stay length were recorded. The total dosages of Remifentanil used during surgery, and the blood glucose levels were significantly lower in the TAP and TEAS＋TAP groups than in the control group (P<0.05), but had no significant differences between the TAP and TEAS＋TAP groups (P>0.05). The VAS scores of the TAP and TEAS＋TAP groups were considerably lower than those of the control group at 4, 12, 24 and 48 h after surgery (P<0.05, except 48 h of TAP group). Of the 34, 35 and 32 cases in the control, TAP and TEAS＋TAP groups, 5(14.7%), 3(8.6%) and 1(3.1%) on the 1st day post-surgery, and 2(5.9%), 0(0) and 0(0) on the 2nd day after surgery experienced nausea and vomiting. The postoperative anal exhaust time and postoperative oral feeding time were significantly earlier in both TAP and TEAS＋TAP groups than in the control group (P<0.05), and the exhaust time of the TEAS＋TAP group was even earlier than that of the TAP group (P<0.05). No significant differences were found among the 3 groups in the postoperative ambulation time and postoperative hospitalization time (P>0.05). TEAS combined with TAP block analgesia is superior to simple TAP block analgesia in relieving postoperative pain, shortening the recovery time of gastrointestinal function and promoting postoperative rehabilitation in patients undergoing LCCR. | {
"pile_set_name": "PubMed Abstracts"
} |
[Varix of intra-abdominal umbilical vein: report of two cases].
Varix of the intra-abdominal portion of the umbilical vein is an uncommon sonographic diagnosis, which may be increasing in the coming years for the improvement of ultrasound equipment and the advances in knowledge of fetal anatomy. It has been reported in the literature in many cases associated with chromosomal defects, additional sonographic abnormalities and poor fetal outcome, but, in contrary to earlier reports, especially in cases in which it appears isolated, a good fetal outcome is expected. We report two cases of umbilical vein varix diagnosed in our department at 20 and 33 weeks, both with good perinatal outcome. | {
"pile_set_name": "PubMed Abstracts"
} |
[Screening of subjects at high risk for diabetic microangiopathies].
Chronic hyperglycemia is the single most important pathogenic factor in the diabetic triad: retinopathy, glomerulopathy and neuropathy. But at equal serum glucose balance, diabetics are not equally at risk of microangiopathy. Hence the importance of timely screening of patients who should be convinced to accept the constraints and risk of perfect serum glucose balance or to whom specific therapy independent from serum glucose balance could be proposed. But at present, there is no genetic or immunologic marker allowing for the individual identification of at risk patients. Attention is thus directed towards factors which may be directly involved in the pathogenesis of diabetic microangiopathy: --Special sensitivity of vascular collagen to protein glycosylation which could be reflected in the involvement of tendon and aponeurotic collagen, --platelet abnormalities of which the exacerbating role appears to be confirmed by the significant efficacy of aspirin in the treatment of nonproliferative retinopathy in insulin-independent diabetics, --rheological abnormalities which might essentially be secondary to chronic hyperglycemia, --hormonal abnormalities, in particular hypersecretion of growth hormone and/or somatomedin C, whose role has long been suspected and could be established by therapeutic trials with new somatostatin analogues. But the most recent advances concern the study of hemodynamic factors. Irreversible organic diabetic microangiopathy is thought to be preceded by a phase of reversible functional microangiopathy, characterized by increased capillary blood flow, vascular dilatation, hyperpermeability and altered regulation of flow. Thus, diabetic glomerulopathy with decreased glomerular filtration is preceded by a phase of renal "hyperfunctioning" and irreversible proteinuria is the outcome of a progressive increase in microalbuminuria, reversible at least while the levels are not too high.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Cultivating Meaningful Work in Healthcare: A Paradigm and Practice.
The socioeconomic dynamics of the current healthcare system can challenge physicians to remain engaged with meaningful work, which is problematic given its role in mitigating burnout. In Man's Search For Meaning, Victor Frankl proposes that meaningful work is a prerequisite for a meaningful life. This article provides a road map for radiologists by applying key guiding principles outlined by Frankl as they intersect with current evidence in the field of physician burnout. | {
"pile_set_name": "PubMed Abstracts"
} |
[Clinical chemical and hematological blood values and adaptation reactions in suckling calves in the first weeks of life].
Suckler calves of the mother cow herd were used for this investigation. Body weight, growth rate and venous blood acid base status, gas content, creatinine, urea, lactate, total protein, albumin, Ca, Mg, Na, K and Cl were measured at 20, 60 and 90 days of postnatal life. Body weight and growth rate showed strong correlations with some blood values especially at 60 and 90 days of age meaning that adaptation is performed successful in some calves and incomplete in others. Disproportionate growth of body parts and the limited oxygen-carrying capacity below the oxygen needs of the tissues may cause the great lactate values in some calves of all age groups. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors associated with suicide attempts in patients with bipolar disorder type I.
The aim of this study is to identify the risk factors that are associated with suicide attempts in patients with bipolar disorder type I. This cross-sectional study was conducted with inpatients and outpatients with BD type I. Patients who met the study inclusion criteria (n=91) were evaluated in terms of sociodemographic variables, history of childhood trauma, comorbidity of adult attention deficit hyperactivity disorder and posttraumatic stress disorder, and the course of the disease. The patients were divided into two groups: those with a history of suicide attempts and those without a history of suicide attempts. The parameters of the study groups were compared with t and chi-square tests as appropriate. Logistic regression was used to identify the predictors of suicide attempt. Logistic regression analysis of the study parameters suggested that the number of major depressive episodes (odds ratio: 7.18; 95% confidence interval: 1.84-28) and history of emotional neglect (odds ratio: 1.83; 95% confidence interval: 1.15-2.90) were significant predictors of suicide attempt in patients with BD. In BD type I patients with a history of suicide attempts, the number of depressive episodes and emotional neglect, a subtype of childhood traumas, were the most remarkable risk factors. Considering the frequency of depressive episodes during the course of the disease and assessing traumas including those in childhood may help predict future suicide attempts in patients with BD. | {
"pile_set_name": "PubMed Abstracts"
} |
Tailoring of Pd-Pt bimetallic clusters with high stability for oxygen reduction reaction.
The composition-dependent equilibrium structure and thermal stability of Pd-Pt clusters with the size of 55 atoms, and CO, O, OH, and O(2) adsorption on these clusters have been studied using molecular simulation based on the Gupta empirical potential and density functional theory (DFT) calculations. It is found that Pd(43)Pt(12) with a three-shell onionlike structure (TS-cluster) exhibits the highest relative stability in both DFT and Gupta levels and also the highest melting point at the Gupta level among these Pd-Pt clusters. In addition, the Pd(43)Pt(12) TS-cluster possesses the weakest CO, O, OH, and O(2) adsorption strength, compared to the Pt(55), Pd(55), and Pd(13)Pt(42) clusters, indicating good catalytic activities toward the oxygen reduction reaction (ORR) among these Pd-Pt clusters considered. We expect that this kind of DFT-guided strategy by controlling the composition could provide a simple way for possibly searching new electrocatalysts. | {
"pile_set_name": "PubMed Abstracts"
} |
Phylogenetic relationships among Saccharum clones in Pakistan revealed by RAPD markers.
Forty sugarcane genotypes (clones), including elite lines, commercial cultivars of Saccharum officinarum and S. barberi clones, were fingerprinted with 30 RAPD markers, using a PCR-based marker assay. The genetic distance for RAPD data was determined according to Nei, and relationships between accessions were graphed in a dendrogram. Genetic distance values ranging from 16.2 to 86.3% were observed among the 40 sugarcane accessions. The lowest genetic distance was found between genotypes US-406 and US-186. These two genotypes differed from each other in only 25 bands with 15 different primers. Genotypes Col-54 and CP-72-2086 were the second most similar group, with a genetic distance of 19.46%. The most dissimilar of all the accessions were CP-77-400 and US-133, with a genetic distance of 86.3%. RAPD fingerprints help sugarcane breeders clarify the genetic pedigree of commercial sugarcane varieties and can be used to evaluate the efficiency of conventional breeding methods. | {
"pile_set_name": "PubMed Abstracts"
} |
A novel frequency distribution selection method for efficient plate layout of a diverse combinatorial library.
A deterministic method (frequency distribution method) for selecting compounds from a partitioned virtual combinatorial library for efficient synthesis is presented here. The method is based on reagent frequency analysis and can be applied to any library of molecules distributed in any given partitioned chemical space (cluster, cell-based, etc.). Compound selection by reagent frequency distribution can produce a unique, diverse set of molecules that adequately represents the library while requiring the least amount of compounds to be synthesized and minimizing the number of different reagents that must be used. This method also provides a practical solution to the configuration of plate layout. Because the method essentially identifies "expensive" regions in the chemical space to synthesize for a desired diversity or similarity coverage, decisions concerning the necessity to synthesize these compounds can be addressed. Minimum compound generation and efficient plate layout results in savings both in time of synthesis and cost of materials. This method always results in a discrete solution, which can be used for any given library size as well as any combination of reagents and is also readily adaptable to robotic automation. | {
"pile_set_name": "PubMed Abstracts"
} |
The feeding of copper sulphate to ducklings.
1. Aylesbury ducklings, from 8 to 63 d of age, were fed on diets with or without supplemental copper (100 mg/kg). 2. Copper resulted in significant increases in growth rate and significantly smaller caeca both as a proportion of body weight and as the weight of unit length. | {
"pile_set_name": "PubMed Abstracts"
} |
Fiber density index, fractional anisotropy, adc and clinical motor findings in the white matter of patients with glioblastoma.
Whether fractional anisotropy (FA), apparent diffusion coefficient (ADC), and fiber density index (FDi) values differ in the white matter close to glioblastomas of both symptomatic and asymptomatic patients was investigated. Twenty patients with glioblastomas underwent magnetic resonance imaging study. The FDi, FA and ADC values were calculated in areas of white matter in close proximity to the tumor (perWM) and encompassing fibers of cortico-spinal tract and in the contralateral normal-appearing white matter (nWM). The clinical compromise of the cortico-spinal tract was graded using Brunnstrom's criteria. FA and FDi were significantly decreased and ADC increased in perWM compared with the contralateral. Mean FDi, FA, and ADC values comparing perWM and nWM in symptomatic patients showed similar differences. Comparing the perWM of symptomatic and asymptomatic patients, mean FDi and ADC values were lower in symptomatic patients than in asymptomatic ones. A positive correlation was found between the clinical score (CS) and, separately, FDi, FA and ADC per WM values. In a multiple stepwise regression among the same factors, only the ADC of perWM values showed a positive correlation with the CS. An increased ADC plays a major role in reducing the number of fibers (reduced FDi) in symptomatic patients. | {
"pile_set_name": "PubMed Abstracts"
} |
A genetic algorithm for the optimization of prostate implants.
A genetic algorithm (GA) is presented for the optimization of template- and ultrasound-guided prostate implants. The end points for optimization are incorporated in an objective function of separable cardinal utility terms. As an application of the GA, the minimum 103Pd total source strength required to deliver a given dose was correlated with the average dimension for prostate implants carried out under the current template and seed spacing protocols. Significant improvements in quality were observed, in terms of both the minimum peripheral dose and tumor cell surviving fractions, when GA-optimized implants were compared to the corresponding unoptimized implants for given target volumes. In addition, numerical simulation of source displacements indicates that the dosimetric and radiobiologic advantages of GA optimization can tolerate a reasonable level of seed placement uncertainties observed clinically. In summary, the GA application provides an automated design strategy for prostate implant planning, and at the same time affords the potential for systematic optimization of a set of end points that can sustain practical variations. | {
"pile_set_name": "PubMed Abstracts"
} |
Cell signaling by protein tyrosine phosphorylation.
The above data, and others not described herein, indicate the following: First, that phosphatases are not scavenger enzymes, simply there to remove the phosphate groups introduced by the kinases. They cannot be viewed simply as providing an 'off' switch in an 'on/off' kinase/phosphatase system. Kinases and phosphatases do not carry out one-way and opposing reactions. The same enzyme, depending on where it localizes within the cell, or the molecule with which it might interact, can serve either as a positive or negative determinant in defining cell behavior. In many instances, it can act synergistically with the kinases to enhance the phosphorylation reaction. Second, the factors that determine whether a phosphatase would enhance or oppose a kinase reaction would seem to depend less on its state of activity than on its subcellular localization. This would suggest that if one wanted to call upon it to control transformation, one should try to tamper with its localization segments or whatever binding proteins it might be attached to--rather than with its catalytic domains. Displacement of these enzymes from where they are meant to bind would seem a more promising approach than trying to modulate their catalytic activity. Finally, their architectural features are so basically different from those of the kinases, with receptor tyrosine phosphatases displaying all the structural characteristics of cell adhesion molecules, that they must also have a mission of their own in cell development, survival and death, quite apart from that of the kinases. | {
"pile_set_name": "PubMed Abstracts"
} |
Determination of the maleic acid in rat urine and serum samples by isotope dilution-liquid chromatography-tandem mass spectrometry with on-line solid phase extraction.
A rapid and simple on-line solid-phase extraction coupled with isotope dilution-liquid chromatography-tandem mass spectrometry (SPE-ID-LC-MS/MS) method was developed to quantitate maleic acid in serum and urine of SpragueDawley (SD) rats. The aforementioned biological samples were spiked with (13)C2-maleic acid, vigorously vortexed, added with acetonitrile to precipitate proteins, and then injected into the on-line SPE-LC-MS/MS system for quantification. Upon validation, this method demonstrated excellent feasibility and sensitivity: calibration curves for maleic acid in serum and urine display excellent linearity with the coefficient of determination (R(2)) greater than 0.999; the limits of detection and quantitation (LOD and LOQ) for maleic acid were determined at 0.2 and 0.5μg L(-1), respectively. Additionally, intra-day accuracy for maleic acid in serum and urine samples ranged from 94.0% to 100.2% and 101.3% to 104.4%, respectively. Furthermore, inter-day accuracy ranged from 93.6% to 101.0% and from 102.3% to 111.4% in serum and urine samples, respectively. Intra-day precision %RSD of maleic acid in serum and urine samples was 13.8% or less, whereas the inter-day precision was 6.1% or less. The matrix effects were not found to be statistically significant (p=0.9145 and p=0.5378, correspondingly) based on the calculations of recovery functions. The collected serum and urine samples were analyzed using SPE-ID-LC-MS/MS. Our results reveal trace levels of maleic acid in the control rats, demonstrating that this method is capable of analyzing background levels of contaminants in biofluids with excellent sensitivity and specificity at part-per-billion levels concentrations in complex matrices. | {
"pile_set_name": "PubMed Abstracts"
} |
Recombinant-yeast-derived hepatitis B vaccine in healthy adults: safety and two-year immunogenicity of early investigative lots of vaccine.
We tested the safety and long-term immunogenicity of two of the early investigative lots of a recombinant-yeast-derived hepatitis B vaccine in immunocompetent adults. Three 10-micrograms doses of recombinant hepatitis B vaccine (Merck Sharp & Dohme Research Laboratories, West Point, PA) were administered by deltoid intramuscular injection at time 0, 1, and 6 months to 65 seronegative adult health workers. Following a complete three-injection course, 98% of vaccinees acquired anti-HBs, 97% at levels greater than 10 mlU/ml, and 95% maintained such "protective" antibody levels at 1 year. At 2 years, 93% retained antibody, but only 68% had levels greater than 10 mlU/ml. In those who responded to vaccination by achieving any detectable level of antibody, the peak geometric mean titer of anti-HBs, measured at 9 months, was 741 +/- 6 mlU/ml; the geometric mean titer fell to 348 +/- 6 at 1 year and to 66 +/- 7 at 2 years. Side effects were trivial, and levels of yeast antibody, as measured by radioimmunoassay, were not changed from prevaccine levels. No serious adverse effects were encountered, and neither type B nor non-B hepatitis occurred in any vaccine. These findings demonstrate that the recombinant yeast hepatitis B vaccine is safe and immunogenic but that 10 micrograms of the early investigative lots of the recombinant vaccine is less immunogenic than 20 micrograms of the plasma-derived vaccine. Recipients of early investigative vaccine lots should be considered for booster vaccination with currently available, more immunogenic vaccine lots. | {
"pile_set_name": "PubMed Abstracts"
} |
Elevated expression of matrix metalloproteinase-9 is associated with bladder cancer pathogenesis.
This study investigated the association between abnormal matrix metalloproteinase-9 (MMP-9) expression and bladder cancer (BC) development. In a retrospective analysis, this study used tissue samples derived from 92 patients pathologically diagnosed with BC (experimental group), who were hospitalized between September 2012 and June 2014 at the Urinary Surgery of Department of Urology, Lanzhou University Second Hospital. As controls (control group), 63 normal pericancerous bladder mucosal tissues (3 cm distant form edge of BC foci) with confirmed pathology were selected from the same time period. Immunohistochemistry was employed to detect MMP-9 protein expression in the tissues and enzyme-linked immunosorbent assay was performed to measure MMP-9 protein levels in tissue samples of patients and control subjects. Finally, a meta-analysis was conducted to understand the overall impact of MMP-9 on BC pathogenesis. STATA 12.0 software (Stata Corp, College Station, TX, USA) was used for all statistical analyses. The MMP-9 positive expression rate in tissue samples and MMP-9 levels were significantly greater in the experimental group compared to the control group (both P < 0.001). The frequency of MMP-9 positive status showed statistically significant differences between G1 (low-grade) and G3 (high-grade) (P < 0.001), between G2 and G3 (P < 0.05), and between G1/G2 and G3 (P = 0.001). Our meta-analysis findings provided further evidence that MMP-9 positive expression status and MMP-9 levels in the experimental group were significantly higher than the control group (positive expressions: Odds ratio [OR] = 18.59, 95% confidence interval [95% CI] = 11.63-29.71, P < 0.001; expression levels: Standard mean difference = 1.51, 95%CI = 0.63-2.39, P = 0.001). The positive expression status of MMP-9 was notably lower in G1/G2 compared to G3 (OR = 0.24, 95%CI = 0.15-0.36, P < 0.001). Our study demonstrated that both positive expression status in tumor tissue and expression levels of MMP-9 are significantly elevated in BC patients and correlate with disease progression. Thus, MMP-9 can serve as a biomarker to determine the degree of BC malignancy. | {
"pile_set_name": "PubMed Abstracts"
} |
Abnormal wall strain at distal end-to-side anastomoses.
Cyclic stretch has been demonstrated to induce proliferative and secretory activities by cultured arterial endothelial and smooth muscle cells, cellular processes that contribute to the development of intimal hyperplasia. A model of an end-to-side anastomosis was developed to examine the hypothesis that regions of the artery at such anastomoses are subjected to focally increased cyclic stretch, which may stimulate the development of intimal hyperplasia. Polytetrafluoroethylene grafts were anastomosed end to side to latex rubber tubes that have elastic properties similar to those of the human femoral artery. Pulse waves with physiologic pressure, rate, and contour were applied, and systolic and diastolic diameters were measured in two planes at longitudinal intervals. Circumferential strain imposed on the latex "artery" was calculated at each interval. Strain imposed perpendicular to the suture line was also measured. Circumferential strain was consistently maximal at a distinct region of the "artery" along the proximal third of the anastomosis (6.0 +/- 1.1% vs. 3.3 +/- 0.5% at other regions of the "artery"). The maximal strain across the suture line was found at precisely the same region (3.9 +/- 0.3% vs. 2.0 +/- 0.4%). The anastomotic region of the recipient artery in a distal end-to-side anastomosis is subjected to cyclic circumferential strains two times greater than those experienced by the remainder of the artery. This corresponds to a common location of intimal hyperplasia. Such strains may be a stimulus for intimal hyperplasia. | {
"pile_set_name": "PubMed Abstracts"
} |
Interplay between Substrate and Proton Donor Coordination in Reductions of Carbonyls by SmI2-Water Through Proton-Coupled Electron-Transfer.
The reduction of a carbonyl by SmI2-water is the first step in a range of reactions of synthetic importance. Although the reduction is often proposed to proceed through an initial stepwise electron-transfer-proton-transfer (ET-PT), recent work has shown that carbonyls and related functional groups are likely reduced though proton-coupled electron-transfer (PCET). In the present work, the reduction of an activated ester, aldehyde, a linear and cyclic ketone, and related sterically demanding carbonyls by SmI2-H2O was examined through a series of mechanistic experiments. Kinetic studies demonstrate that all substrates exhibit significant increases in the rate of reduction by SmI2 as [H2O] is increased. Under identical conditions, ketones and an aldehyde containing a methyl adjacent to the carbonyl are reduced slower than an unsubstituted variant by an order of magnitude, demonstrating the importance of substrate coordination. In the case of unactivated substrates, rates of reduction show excellent correlation with the calculated bond dissociation free energy of the O-H bond of the intermediate ketyl and the calculated free energy of intermediate ketyl radical anions derived from unhindered substrates: findings consistent with concerted PCET. Activated esters derived from methylbenzoate are likely reduced through stepwise or asynchronous PCET. Overall, this work demonstrates that the combination of the coordination of substrate and water to Sm(II) provides a configuration uniquely suited to a coupled electron- and proton-transfer process. | {
"pile_set_name": "PubMed Abstracts"
} |
Characterization of apoptosis signal transduction pathways in HL-5 cardiomyocytes exposed to ischemia/reperfusion oxidative stress model.
During ischemia/reperfusion (I/R), cardiomyocytes are exposed to sudden lack of nutrients and successively to radical oxygen species (ROS). In the present study, we used the HL-5 cardiac atrial myocyte cell line exposed to serum/glucose depletion added or not in H(2)O(2) to mimic ROS during ischemia, then replaced in their standard culture medium to simulate reperfusion. We investigated the effects of serum/glucose depletion combined or not to ROS exposure on AKT and MAP kinases activation to address the role of each event with respect to apoptosis. We demonstrate that serum/glucose depletion per se did not induce apoptosis when compared to ROS exposure. In particular, ROS recruited p38MAPK and JNK pathways. SB202190 preventing p38MAPK activity, partially protected HL-5 from apoptosis while blocking JNK, thanks to JNKI, further enhanced apoptosis. Blocking phosphatidylinositol (PI) 3-kinase with LY294002 or ERKs with U0126 was without consequence on apoptosis. Finally, BCL-2 and BCL-X(L/S) expression levels were analyzed in cells exposed to 1 h ischemia followed by 12-h reperfusion in the presence or not of SB202190; BCL-2, but not BCL-X(L/S), expression was decreased in ROS treated cells but SB202190 failed to restore BCL-2 level. Our data suggest that p38MAPK activation primarily mediates ROS-induced apoptosis while concomitant JNK activation would represent a scavenger pathway for cells trying to escape apoptosis. | {
"pile_set_name": "PubMed Abstracts"
} |
Spinning-disk confocal microscopy of yeast.
Spinning-disk confocal microscopy is an imaging technique that combines the out-of-focus light rejection of confocal microscopy with the high sensitivity of wide-field microscopy. Because of its unique features, it is well suited to high-resolution imaging of yeast and other small cells. Elimination of out-of-focus light significantly improves the image contrast and signal-to-noise ratio, making it easier to resolve and quantitate small, dim structures in the cell. These features make spinning-disk confocal microscopy an excellent technique for studying protein localization and dynamics in yeast. In this review, I describe the rationale behind using spinning-disk confocal imaging for yeast, hardware considerations when assembling a spinning-disk confocal scope, and methods for strain preparation and imaging. In particular, I discuss choices of objective lens and camera, choice of fluorescent proteins for tagging yeast genes, and methods for sample preparation. | {
"pile_set_name": "PubMed Abstracts"
} |
Immunoblotting with (sub)class-specific antibodies reveals a high frequency of monoclonal gammopathies in persons thought to be immunodeficient.
Immunoblotting, in combination with high-resolution electrophoresis and the use of mouse monoclonal antibodies to human (sub)class immunoglobulin (Ig) isotypes, substantially increased the sensitivity with which homogeneous Ig components (H-Ig) could be detected. Using this technique, we reinvestigated 40 selected sera, previously found to be negative for H-Ig by agar electrophoresis and immunofixation, from two groups of individuals thought to have an age-related immunodeficiency, i.e., persons older than 95 years and recipients of kidney grafts who were undergoing immunosuppressive treatment. In both groups, small single or multiple H-Ig components were found, in frequencies of 76% and 79%, respectively. For comparison, the Ig spectrum of 10 sera from patients on dialysis treatment and of 33 sera from young adult blood donors was ordinarily heterogeneous, except for one elderly patient and one blood donor with a previously unknown IgG2 deficiency. These results are complementary to the observations in some immunodeficiencies in children and indicate that the appearance of single or multiple H-Ig components in low concentration can be considered a very sensitive indicator of certain immune system disorders forming a separate category of monoclonal gammopathies. | {
"pile_set_name": "PubMed Abstracts"
} |
Not a usual suspect; rabeprazole therapy presenting as a severe neuropsychiatric illness: case report.
We report the case of a patient who, as a result of exposure to the proton pump inhibitor rabeprazole, developed a severe and disabling admixture of neuropsychiatric symptoms. Because of its widely appreciated placebo-like side effect profile, rabeprazole was never suspected as being the cause of his symptoms. Instead, a somatoform spectrum disorder was assigned based on the patient's atypical symptom presentation, progressive course, subjective psychological distress, intemperate consumption of healthcare resources over a relatively brief period of time and lack of any medical explanation for his symptoms at that time, despite exhaustive laboratory and radiologic work-ups. This case report reinforces the notion that even a medication such as rabeprazole, with an established safety and tolerability profile, may be associated with side effects severe enough to mimic disabling neuropsychiatric illness. | {
"pile_set_name": "PubMed Abstracts"
} |
Nose cone entrapment after transcatheter aortic valve implantation of a CoreValve self-expandable bioprosthesis.
: We describe the first reported case of a nose cone entrapment of the delivering catheter of a CoreValve self-expandable valve, during a transcatheter aortic valve implantation procedure. The complication was successfully treated after snaring the cone and retracting the system within the introducing sheath. | {
"pile_set_name": "PubMed Abstracts"
} |
Further evaluation of lectin affinity purified glycoprotein (GP90) in the enzyme linked immunosorbent assay (ELISA) for diagnosis of Trypanosoma cruzi infection.
Sera from 143 patients considered to be infected with Trypanosoma cruzi on the basis of epidemiological, clinical and standard serological evidence gave positive results in the enzyme-linked immunosorbent assay (ELISA) using a lectin affinity purified 90,000 molecular weight glycoprotein (GP90) antigen preparation. Levels of antibody did not discriminate between clinically classified groups of patients in the chronic phase of infection. The GP90 preparation was found to be heterogeneous. | {
"pile_set_name": "PubMed Abstracts"
} |
Serum immunoreactive beta-endorphin in the human ovulatory cycle.
Daily serum immunoreactive beta-endorphin (IR-beta-EP) levels, in conjunction with luteinizing hormone, follicle-stimulating hormone, 17 beta-oestradiol, progesterone, and prolactin, were measured during the ovulatory cycle in five healthy Chinese women. Standardization of raw data by conversion to the statistical "Z scores" and composite plot of the five cycles showed that serum IR-beta-EP levels fluctuated during the follicular, late luteal, and menstrual phases. A preovulatory rise occurred two to three days prior to the luteinizing hormone surge, followed by a postovulatory dip for two to three days. The concentrations of IR-beta-EP were (mean +/- S.E.M.): 85.5 +/- 10.5 pg/mL (n = 36) in the follicular phase; 92.4 +/- 36.5 pg/mL (n = 5) in the ovulatory phase; 72.3 +/- 16.6 pg/mL (n = 7) in the early luteal phase; 100.0 +/- 10.7 pg/mL (n = 38) in the late luteal phase. The values in the luteal phase were the highest of any in the ovulatory cycle. The findings suggest that the fluctuation of endogenous beta-EP is under the influence of, among other factors, ovarian sex steroids. The significance of beta-EP in the regulation of gonadotropin release during normal menstrual cycles is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Antibiotics in acrylic bone cement. In vivo studies.
In vivo experiments were performed to study elution rates of antibiotics combined with Surgical implex bone cement and efficacy in controlling bacterial infections. Cylinders of bone cement were implanted in animals and at the same time the surgical areas were infected with large numbers of bacteria. Gentamicin and Keflin were eluted from the cylinders in sufficient quantities to completely eliminate or markedly reduce the number of bacteria recovered from infected areas. Animals were also treated with an anti-inflammatory drug, hydrocortisone, prior to implantation of cylinders and infection. The antibiotics in the bone cement effectively destroyed the bacteria in these animals with impaired inflammatory responses as compared with control animals. | {
"pile_set_name": "PubMed Abstracts"
} |
DNA level and stereologic estimates of nuclear volume in squamous cell carcinomas of the uterine cervix. A comparative study with analysis of prognostic impact.
Grading of malignancy in squamous cell carcinomas of the uterine cervix is based on qualitative, morphologic examination and suffers from poor reproducibility. Using modern stereology, unbiased estimates of the three-dimensional, volume-weighted mean nuclear volume (nuclear vv), were obtained in pretreatment biopsies from 51 patients treated for cervical cancer in clinical Stages I through III (mean age of 56 years, follow-up period greater than 5 years). In addition, conventional, two-dimensional morphometric estimates of nuclear and mitotic features were obtained. DNA indices (DI) were estimated by flow cytometry. Finally, the semiquantitative malignancy grade score value (MGS) was determined according to previously published methods. Estimates of nuclear vv were on average increased in euploid lesions (2P = 0.01), but the overall relationship between nuclear vv and DI was poor. Different clinical stages of disease did not differ with regard to nuclear vv (2P = 0.99) and DI (2P = 0.56). No relationship was disclosed between MGS and nuclear vv (2P = 0.85). Single-factor analysis showed prognostic impact of clinical stage of disease (2P = 0.0001) and DI (2P = 0.04), whereas estimates of nuclear vv were only of marginal prognostic significance (2P = 0.07). However, Cox multivariate regression analysis showed independent prognostic value of patient age and nuclear vv along with clinical stage and DI. All other investigated variables were rejected from the model. A prognostic index with highly distinguishing capacity between prognostically poor and favorable cases was constructed (2P = 1.9 x 10(-7)). It is concluded that realistic estimates of nuclear volume are independent of nuclear DNA content and are of prognostic value for objective malignancy grading in patients with squamous cell carcinoma of the uterine cervix. | {
"pile_set_name": "PubMed Abstracts"
} |
Glutardialdehyde induced fluorescence technique (GIFT): a new method for the imaging of platelet adhesion on biomaterials.
One of the major limitations of biomaterials used in medicine is the adhesion and subsequent activation of platelets upon contact with blood. The development of new or modified materials necessitates adequate methods for the detection and quantification of platelet/material interactions. These interactions are commonly investigated by means of scanning electron microscopy (SEM), radioisotope and immunological techniques, or by quantification of released platelet contents. Given the lack of a simple, rapid, and inexpensive assay, we developed a novel method for the accurate assessment of platelet adhesion after contact with foreign surfaces, which enables quantitative measurements as well as imaging of the platelet shape change, and which omits conventional or immunological staining and time-consuming preparative steps. The glutardialdehyde induced fluorescence technique (GIFT) uses the epifluorescence of glutardialdehyde-fixed platelets detected by fluorescence microscopy and is suitable for opaque and transparent materials. Combined with computer-aided image analysis, numbers of adherent platelets, platelet-covered surface, and average platelet spread area can be determined as markers of surface thrombogenicity. To validate the technique, four materials of different thrombogenicity [polypropylene (PP), poly(D,L-lactide) (PDLLA), 2-hydroxyethyl-methacrylate-grafted PDLLA (PDLLA-HEMA), and heparin-coupled PDLLA-HEMA] were investigated by GIFT and SEM. We found concordant results with SEM and GIFT with the following ranking of thrombogenicity: PP > PDLLA > PDLLA-HEMA > or = PDLLA-HEMA-heparin. GIFT significantly discriminated between the investigated materials. The surface modifications led to improved thromboresistance with reduced platelet adhesion and shape change. The main advantages of GIFT as compared with SEM are: no vacuum-drying or dehydration, less time-consuming procedure, fixation and fluorescence "staining" in one step, and suitability for computer-aided image analysis allowing quantitative assessment of platelet adhesion as well as imaging of the platelet shape change with high-contrast images. In conclusion, GIFT is a valid, rapid, and simple method for the quantitative determination of platelet/material interactions intended for the evaluation of thrombogenicity of biomaterials surfaces. | {
"pile_set_name": "PubMed Abstracts"
} |
Memory aging and brain maintenance.
Episodic memory and working memory decline with advancing age. Nevertheless, large-scale population-based studies document well-preserved memory functioning in some older individuals. The influential ‘reserve’ notion holds that individual differences in brain characteristics or in the manner people process tasks allow some individuals to cope better than others with brain pathology and hence show preserved memory performance. Here, we discuss a complementary concept, that of brain maintenance (or relative lack of brain pathology), and argue that it constitutes the primary determinant of successful memory aging. We discuss evidence for brain maintenance at different levels: cellular, neurochemical, gray- and white-matter integrity, and systems-level activation patterns. Various genetic and lifestyle factors support brain maintenance in aging and interventions may be designed to promote maintenance of brain structure and function in late life. | {
"pile_set_name": "PubMed Abstracts"
} |
Anticancer therapy for breast cancer patients with skin metastases refractory to conventional treatments.
Skin metastases of breast cancer are usually late events in the course of tumor progression and signify a poor prognosis. They may remain as a therapeutic challenge especially after failure of standard treatments. Topical interventions, together with or without radiotherapy, may only palliate the symptoms temporarily. However, there may be alternative treatment modalities for unresectable breast cancer skin metastases resistant to chemotherapy and radiotherapy. There are various genetic alterations in tumors and therapeutic potential of expression patterns for factors like epidermal growth factor receptor may have important clinical implications in case of disease refractory to the conventional treatments. Here, we clarified the therapeutic options and genetic alterations in skin metastatic breast cancer patients refractory to standard chemotherapeutics. | {
"pile_set_name": "PubMed Abstracts"
} |
[Adjuvant drug therapies for breast cancer].
Most breast cancers are hormone receptor positive and exhibit a slow growth pattern. Based on biological properties, breast cancers are divided into four different biological subtypes. Furthermore, these subtypes are indicative of the risk of recurrence, which is also influenced by the size of the tumor and extension to lymph nodes. Postoperative adjuvant drug therapy is chosen on the basis of the biological type. Chemotherapy can be used in all subtypes. Hormonal therapies are used exclusively for the treatment of hormone receptor positive breast cancer. Trastuzumab antibody belongs to the treatment of the HER2 positive subtype. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of the effect of ruxolitinib on cardiac repolarization: A thorough QT study.
This was a randomized, four-way crossover study that evaluated the effects of placebo, single doses of ruxolitinib 25 and 200 mg, and a single dose of moxifloxacin 400 mg on heart rate-corrected QT interval in healthy subjects. Electrocardiograms (ECGs) and pharmacokinetic samples were obtained on each dosing day; baseline ECGs were taken pre-dose. The primary endpoint was placebo-subtracted change from baseline heart rate-corrected QT (Fridericia formula [ΔΔQTcF]). The ΔΔQTcF for either dose of ruxolitinib ranged from -3.09 to 3.28 milliseconds (1-sided 95% confidence interval of 0.06-6.62 milliseconds). The ΔΔQTcF for moxifloxacin (lower confidence interval) was significantly >5 milliseconds at 1, 2, and 3 hours post-dose. Individual QTcF >450 milliseconds and QTcF from baseline >30 milliseconds following ruxolitinib were similar to placebo. Based on the International Conference on Harmonization E14 guidance, the study results were considered negative for QTc prolongation. In conclusion, ruxolitinib did not have a clinically significant effect on QT interval. | {
"pile_set_name": "PubMed Abstracts"
} |
Relationship of human rhinovirus strain 2 and poliovirus as indicated by comparison of the polymerase gene regions.
cDNA clones representing the 3'-terminal region of the human rhinovirus strain 2 genome have been obtained. The sequence of 1425 nucleotides adjacent to the poly(A) tract is presented and contains an open reading frame of 1383 nucleotides. The derived amino acid sequence corresponding to the putative RNA polymerase-coding region is compared to those of poliovirus type 1 (Mahoney) and foot-and-mouth disease virus A12. A high degree of homology between human rhinovirus strain 2 and poliovirus type 1 (Mahoney) was found within the coding sequence but not within the 3'-untranslated region. | {
"pile_set_name": "PubMed Abstracts"
} |
[Diagnostic evaluation of the cervical nystagmus in cervical torsion test].
The aim of this work was comparative evaluation of the cervical nystagmus in cervical torsion test with the Nylen's positional nystagmus and their diagnostic value in correlation from anatomical state of cervical column. The authors examined 40 patients with degeneration of cervical spinal column and with normal radiograph of cervical spinal column. The obtained results showed that the cervical nystagmus in cervical torsion test was more frequent (47.5%) than the Nylen's positional nystagmus (37.5%). The cervical nystagmus in cervical torsion test was observed also in health subjects. The authors think that the above mentioned deviations can be caused by the discreet degeneration of cervical spinal column, unseizable in radiograph. The examinations showed that the cervical nystagmus in cervical torsion test could be used simultaneously with the Nylen's positional nystagmus in diagnostic of vertigo, first at all in patients with degeneration of cervical spinal column. | {
"pile_set_name": "PubMed Abstracts"
} |
Bacteriological, clinical and epidemiological characteristics of hospital-acquired Acinetobacter baumannii infection in a teaching hospital.
Over an 18 month period, the bacteriological, clinical and epidemiological characteristics of nosocomial Acinetobacter baumannii infections in a teaching hospital were studied. Typing studies were performed on 38 strains isolated from 36 patients. Twenty-two of the strains were isolated during the three outbreaks. Surgery, catheterization, mechanical ventilation, and antibiotic therapy for adult patients and respiratory distress syndrome, mechanical ventilation, and prematurity for paediatric patients were the main risk factors identified. All isolates were resistant to penicillins (except ampicillin-sulbactam), cephalosporins, gentamicin, and aztreonam but susceptible to carbapenems and colistin. Resistance to tobramycin, ciprofloxacin, ampicillin-sulbactam, trimethoprim-sulfamethoxazole, and amikacin was variable. Antibiotyping, arbitrarily-primed polymerase chain reaction (AP-PCR) and the pulse-field gel electrophoresis (PFGE) indicated the epidemiological relationship. The outbreak strains, demonstrated genetic distinction between our three outbreaks and isolates from specific areas in the hospital. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of the VA's Pilot Program in Institutional Reorganization toward Primary and Ambulatory Care: Part I, Changes in process and outcomes of care.
To evaluate the impact of the reorganization of an academic Veterans Affairs medical center toward primary and ambulatory care--including the implementation of a medical-center-wide interdisciplinary firm system and ambulatory care training program--on the quality of primary ambulatory care. Randomly selected male veterans visiting the Veterans Affairs Medical Center in Sepulveda, California, were surveyed in 1992, early in the implementation of the program, and in 1993, after the program had been fully implemented. Two surveys were used: one before the veterans saw their primary care providers (practice-based survey) and the other immediately after patient visits (visit-based survey). Survey-participant data were then linked to computerized utilization and mortality data. Survey topics were mapped to the medical center's strategic plan and goals for ambulatory care, and focused on patients' reports about the care they had received in terms of continuity, access, preventive care, and other aspects of the biopsychosocial model of care. Administrative computer data were then used to evaluate effects on medical center workload. Statistical analyses included analysis of variance, analysis of covariance, chi-square, and logistic regression. For practice-based comparisons, complete data were available for 1,262 veterans in 1992 and 1,373 in 1993. For visit-based comparisons, complete data were available for 1,407 veterans in 1992 and 643 in 1993. Results included statistically significant improvements in continuity of care and detection of depression as well as increased rates of preventive care counseling (smoking and exercise). The proportion of veterans reporting being seen by physicians increased, as did the proportion of patients seen for check-ups rather than for acute problems. Fewer patients were seen in subspecialty clinics than in general medicine clinics. Patient satisfaction increased, hospitalizations decreased, and death rates decreased. Alcohol counseling and access to care for acute symptoms declined. Workload shifted from subspecialists to generalists and from inpatient care to outpatient care. The institutional reorganization toward primary and ambulatory care succeeded in substantially improving the quality of ambulatory care, reflecting improvements in the system of care and of health care provider training in ambulatory care. | {
"pile_set_name": "PubMed Abstracts"
} |
Quantitative assessment of the BCR-ABL transcript using the Cepheid Xpert BCR-ABL Monitor assay.
Chronic myelogenous leukemia (CML) and the assessment of the BCR-ABL transcript has become a new paradigm. Novel tyrosine kinase inhibitors as mainstream therapeutic options for the CML patient warrant routine quantification of the BCR-ABL transcript. The Xpert BCR-ABL Monitor assay is a nested reverse transcriptase polymerase chain reaction that greatly reduces technical time by using a single cartridge to isolate RNA and run a quantitative reverse transcriptase polymerase chain reaction. To evaluate the Xpert BCR-ABL Monitor assay for quantitative assessment of the BCR-ABL transcript in CML patients. A standard curve of K-562 cells diluted in normal peripheral blood was used to test the sensitivity, linearity, and percent coefficient of variation of the assay. Specimen stability was tested by running standard curves immediately and after 24 hours or 96 hours of storage at 4 degrees C. Specimens from normal controls, patients known to have CML, or patients suspected of having CML were also tested. The sensitivity of the assay was sufficient to detect 1 K-562 cell in 10(5) normal cells. The R2 of the standard curve was 0.98 and the percent coefficient of variation for each data point was 15% to 24%. Eleven of 14 patients with known CML on imatinib treatment tested positive for the BCR-ABL transcript, whereas 10 normal controls tested negative. The Xpert BCR-ABL Monitor assay is a rapid, sensitive method for monitoring the presence of the BCR-ABL transcript in CML patients. The single-use cartridge minimizes hands-on technical time, minimizes the potential for contamination, and allows quantitative BCR-ABL testing to be performed in a random access fashion. | {
"pile_set_name": "PubMed Abstracts"
} |
Antibodies to adult T-cell leukemia virus (ATLV/HTLV-I) in AIDS patients and people at risk of AIDS in Germany.
A total of 2048 serum samples from Germany were examined for antibodies to adult T-cell leukemia virus (ATLV) structural polypeptides with an enzyme-linked immuno sorbent assay (ELISA) and confirmative immuno precipitation. The origin of the sera samples was: 850 samples taken for virological or protozoal diagnosis; 626 samples from male homosexuals, about 20% of whom had lymphadenopathy syndrome; 164 from hemophiliacs; 184 were from multiple transfused, mostly dialysis patients; 9 from intravenous drug abusers; 182 from suspected cases of acquired immuno deficiency syndrome (AIDS) and 33 from AIDS-patients. In none of these sera did we detect antibodies to ATLV, except in the serum of one patient who had been on hemodialysis for over 11 years. Obviously infection with ATLV or a serologically related agent is very rare in our country and an association with AIDS could not be observed. | {
"pile_set_name": "PubMed Abstracts"
} |
[Aminotransferase and lactate dehydrogenase activity in the blood of dogs exposed to the joint action of external gamma- and internal alpha-radiation].
After the effect of external gamma-radiation (6.5 to 51.6 mC/kg) and inhaled 239Pu submicron oxide, containing 25% of 241Am, (approximately 7 to 10 kBq/kg) delivered separately and in a combination, activities of alanine-aspartate aminotransferase and lactate dehydrogenase changed in an undulatory manner tending to increase at later times; the change rating was a function of type and level of radiation as well as the time lapsed from the onset of exposure. The combined effect of gamma- and alpha-radiation did not exceed the additive effect of the two factors delivered separately. | {
"pile_set_name": "PubMed Abstracts"
} |
[Hydrogen photoproduction from acetate by Rhodopseudomonas palustris].
Based on the characteristics of metabolism of photosynthetic bacteria and the major kinds of organic compounds produced in wastewater degradation, eleven kinds of organic compounds were chosen for hydrogen photoproduction using Rhodopseudomonas palustris Z strain. The maximal volumetric H2 productivity was obtained using acetate as the sole carbon source and electron donor. The kinetics of cell growth and H2 liberation, and the influences of several major limiting factors on photoevolution of H2 were examined using acetate as carbon source. It was shown that hydrogen production was partially correlated with cell growth. The medium composition of the preculture, the preculture time, and inoculation volume were confirmed to have big effects on hydrogen photoevolution. The time delay of H2 production was evidently shortened using the inoculum of late exponential growth phase or stationary phase using ammonium sulfate as nitrogen source or with the inoculum of middle exponential growth phase using glutamate as the nitrogen source. The identity of temperature and light intensity for H2 evolution and cell growth has significant potential application in the technology of splitting organic acid into H2 by photosynthetic bacteria. The concentrations of acetate and glutamate in the medium affected hydrogen photoevolution and cell growth significantly. The productivity of H2 increased with substrate concentrations when substrate concentrations of sodium acetate and sodium glutamate were lower than 70 mmol/L and 15 mmol/L, respectively. Hydrogen production was inhibited but the cell growth was faster when the concentration of sodium glutamate over 15 mmol/L due to forming free NH4+. The highest rate of hydrogen production was 19.4 mL.L-1.h-1 using 30 mmol/L of sodium acetate as hydrogen donor under the standard conditions, respectively. The optimal conditions for hydrogen production were 35-37 degrees C, 6000-8000 lx and pH 7.3-8.3. The effects of oxygen and inoculation volume on photoproduction of hydrogen were also discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Molecular characterization of LMW-GS genes from a somatic hybrid introgression line II-12 between Triticum aestivum and Agropyron elongatum in relation to quick evolution.
In order to exploit the evolution and find novel low-molecular-weight glutenin subunit (LMW-GS) for improvement of common wheat quality, thirteen variants from a somatic hybrid introgression line II-12 between Triticum aestivum cv. Jinan 177 (JN177) and Agropyron elongatum were characterized via genomic PCR. Four clones were pseudogenes because they contained an internal stop codon. The remaining nine variants contained intact open reading frames (ORFs). Sequence alignment indicates that the proteins deduced from the nine ORFs have similar primary structure with LMW-GS cloned from its parents previously. However, they have some unique modifications in the structures. For example, EU292737 contains not only an extra Cys residue in the C-terminal domain but also a long repetitive domain. Both EU159511 and EU292738 start their first Cys residue in the N-terminal repetitive domain, but not in the N-conserved domain traditionally. These structural alterations may have positive contributions to wheat flour quality. The results of phylogeny showed that most LMW-GS variances from II-12 were homologous to those from parent JN177 and other wheat lines. The reason for quick evolution of LMW-GS in II-12 was discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Lack of predictability of classical animal models for hypolipidemic activity: a good time for mice?
Hypolipidemic drugs that are efficacious in man are not always active in classical animal models of dyslipidemia. Inhibitors of HMG-CoA reductase (statins) do not lower plasma cholesterol in rats, but yet this species was alone in providing activity for fibrate-type drugs. Nicotinic acid possesses many desirable features with regard to clinical use, but most of these actions are lacking in rats and monkeys. The metabolism of low density lipoproteins in hamsters is widely thought to be similar to that in humans, yet neither statins or fibrates lower plasma lipids in these species. With the advent of mouse models expressing specific human genes (or disruption of genes) it is now possible to re-examine the effect of established drugs and to characterize new hypolipidemic compounds with respect to site and mechanism of action. Drug responses observed in humans are now being seen in such mouse models (e.g. HDL elevation with fenofibrate in mice with the human apo A-I gene). Moreover, mice are now being screened for compounds that lower plasma (human) Lp(a), or lower plasma cholesterol in the absence of LDL receptors. It is proposed that these new genetic mouse models may afford a more focused examination of drug action and provide, for new compounds, better prediction of the human response. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis of Pt-Ni/graphene via in situ reduction and its enhanced catalyst activity for methanol oxidation.
A simple in situ reduction approach was used to obtain Pt3Ni/reduced graphene oxide (rGO) with dominant {111} facets. The catalytic activity of Pt-Ni/rGO toward methanol electro-oxidation was studied by performing cyclic voltammetry. The Pt3Ni/rGO nanocatalysts exhibited improved catalytic activity and durability. | {
"pile_set_name": "PubMed Abstracts"
} |
Efficacy of inactivated whole HIV-2 vaccines with various adjuvants in cynomolgus monkeys.
Twenty-one cynomolgus monkeys were immunized with whole inactivated HIV-2 preparations administered with various adjuvants (incomplete Freund's adjuvant, Alum, Ribi, MDP, or Iscoms) and challenged with 10 or 100 MID50 of a homologous monkey-cell grown, cell-free HIV-2. Seven animals were completely protected against infection, three showed reduced virus replication. The vaccines elicited neutralizing and ADCC antibodies; the titers did not correlate with protection. Immunization with a whole inactivated vaccine can protect primates from intravenous challenge with a monkey-cell grown cell-free human immunodeficiency virus type 2. | {
"pile_set_name": "PubMed Abstracts"
} |
[Neural network modeling of multitarget RAGE inhibitory activity].
Based on the methodology of artificial neural networks, models describing the dependence of the level of RAGE inhibitory activity on the affinity of compounds for target proteins of the RAGE-NF-kB signal pathway have been costructed. A validated database of the structures and activity levels of 183 known compounds, which were tested for RAGE inhibitory activity was formed. The analysis of the AGE-RAGE signaling pathways was carried out, 14 key RAGE-NF-kB signal pathway nodes were found, for which 34 relevant target proteins were identified. A database of 66 valid 3D models of 22 target proteins of the RAGE-NF-kB signal chain was compiled. Ensemble molecular docking of 3D models of 183 known RAGE inhibitors into sites of 66 valid 3D models of 22 relevant RAGE target proteins was performed and minimum docking energies for each compound were determined for each target. According to the method of artificial multilayer perceptron neural networks, classification models were constructed to predict level of RAGE inhibitory activity based on the calculated affinity of compounds for significant target proteins of the RAGE-NF-kB signaling chain. The prognostic ability of these models of RAGE-inhibitory activity was evaluated, the maximum accuracy according to ROC-analysis was 90% for a high level of activity. The sensitivity analysis of the developed multitarget models were carried out, the most significant targets of the RAGE-NF-kB signal transmission chain were determined. It was found that for high level of RAGE inhibitory activity, the most significant biotargets are not AGE receptors, but eight signaling kinases of the RAGE-NF-kB pathway and transcription factor NF-kB1. Thus, it is suggested that known compounds with high RAGE-inhibitory activity are preferential inhibitors of signal kinases. | {
"pile_set_name": "PubMed Abstracts"
} |
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