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Lifetime and during pregnancy experience of violence and the risk of low birth weight and preterm birth.
In order to assess the relationship between lifetime and during pregnancy experience of violence and low birth weight (LBW) and preterm birth outcomes, we designed a prospective cohort study in which the birth outcomes of women who experienced violence before their pregnancy or who experienced violence during pregnancy were compared to women who reported no lifetime experience of violence. We found that the risk of having a low birth weight or preterm baby was higher for women who did not experience violence. The proportion of women who had LBW babies was 7.1% for women who experienced violence during pregnancy, 7.8% for women who experienced violence before the current pregnancy, and 9.1% for nonexposed women. The proportion of preterm births was 3.5% for women exposed to violence during pregnancy, 8.5% for women exposed before the current pregnancy, and 9.7% for nonexposed women. However, married women who experienced violence had a higher proportion of LBW and preterm infants compared to the reference group of nonvictims of violence. Overall, women who experienced violence during pregnancy and before their current pregnancy did not have a greater proportion of LBW babies or preterm births. The findings suggest that married women in certain populations may experience more frequent or more severe experience of violence than unmarried women.
18,984,508
Perceived changes in health and safety following participation in a health care-based domestic violence program.
This descriptive study explores perceived changes in health and safety and the potential process by which these changes occur. Forty-nine women experiencing intimate partner abuse participated in a health care-based domestic violence (DV) advocacy program for 6 months or more. An analysis of structured interviews in English and Spanish found that the majority of participants perceived positive changes in their personal safety and emotional health because of their involvement in the program. Some participants also perceived improvements in their physical health, unhealthy coping behaviors (e.g., overeating and smoking), and health care following program involvement. Participants' responses suggest a process of change whereby DV advocacy services first contribute to improved safety and emotional health, which then facilitates behavioral changes. Behavioral changes may subsequently contribute to improvements in physical health, which may also benefit emotional health. Longitudinal evaluations are needed to evaluate the impact of DV advocacy and other interventions for partner abuse on women's health and safety over time.
18,984,511
Rural mothers experiencing the stress of intimate partner violence or not: their newborn health concerns.
Pregnancy and the postpartum period is a time of great physical, psychological, and emotional upheaval. Women who experience intimate partner violence experience more depression and anxiety and a higher risk of adverse pregnancy outcomes (such as those related to the abuse). While the literature supports the presence of increased health care utilization for abused women, there is little information on the way that these mothers seek medical care for their infants. This secondary analysis is part of a larger study on smoking cessation in low-income, rural pregnant women called Baby Behavioral Education Enhancement of Pregnancy (Baby BEEP). Women (N = 616) were classified as abused or not abused based on their answers to the Abuse Assessment Screen. At 6 weeks postdelivery, each woman was asked, "Has your baby had any problems that you talked to the doctor or nurse about?" The abused women (n = 211) sought health care advice significantly more often than the nonabused women (n = 405; Pearson chi(2) = 4.89; P = .027). Stress scores were elevated for all women in the study, but women categorized as abused experienced significantly more stress (P < .001).
18,984,512
Who is willing to use complementary and alternative medicine?
The aim of this study was to identify individual differences associated with the willingness to use complementary and alternative medicine (CAM). A questionnaire was administered and the relationship between individual differences and the willingness to use CAM was examined using correlation and multiple regression analyses. The sample consisted of 276 undergraduate students (64% female) of diverse ethnicity (43% white, 33% Hispanic, 8% Native American, 16% other) and a wide range of incomes. The willingness to use 16 types of CAM was assessed for six categories: whole medical systems, mind-body medicine, biologically based practices, manipulative and body-based practices, energy medicine, and spiritually based practices. The individual differences assessed included age, gender, income, ethnicity, the Big Five personality characteristics, optimism, spirituality, religiosity, and three aspects of emotional intelligence: mood attention, mood clarity, and mood repair. The individual differences accounted for approximately one fifth of the variance in overall willingness to use CAM. Openness to experience, spirituality, and mood attention were the strongest predictors of overall willingness to use CAM and were related to the willingness to use most of the individual types of CAM. Older age or female gender was related to greater willingness to use most of the mind-body medicines. Hispanic ethnicity was related to greater willingness to use curanderismo, and Native American ethnicity was related to greater willingness to use Native American medicine and a spiritual/faith healer.
18,984,547
Exploring biological relationships between calving traits in primiparous cattle with a Bayesian recursive model.
Structural equation models (SEMs) of a recursive type with heterogeneous structural coefficients were used to explore biological relationships between gestation length (GL), calving difficulty (CD), and perinatal mortality, also known as stillbirth (SB), in cattle, with the last two traits having categorical expression. An acyclic model was assumed, where recursive effects existed from the GL phenotype to the liabilities (latent variables) to CD and SB and from the liability to CD to that of SB considering four periods regarding GL. The data contained GL, CD, and SB records from 90,393 primiparous cows, sired by 1122 bulls, distributed over 935 herd-calving year classes. Low genetic correlations between GL and the other calving traits were found, whereas the liabilities to CD and SB were high and positively correlated, genetically. The model indicated that gestations of approximately 274 days of length (3 days shorter than the average) would lead to the lowest CD and SB and confirmed the existence of an intermediate optimum of GL with respect to these traits.
18,984,571
Population genetic inference from resequencing data.
This article is concerned with statistical modeling of shotgun resequencing data and the use of such data for population genetic inference. We model data produced by sequencing-by-synthesis technologies such as the Solexa, 454, and polymerase colony (polony) systems, whose use is becoming increasingly widespread. We show how such data can be used to estimate evolutionary parameters (mutation and recombination rates), despite the fact that the data do not necessarily provide complete or aligned sequence information. We also present two refinements of our methods: one that is more robust to sequencing errors and another that can be used when no reference genome is available.
18,984,575
Molecular basis of the interaction of Saccharomyces cerevisiae Eaf3 chromo domain with methylated H3K36.
Eaf3 is a component of both NuA4 histone acetyltransferase and Rpd3S histone deacetylase complexes in Saccharomyces cerevisiae. It is involved in the regulation of the global pattern of histone acetylation that distinguishes promoters from coding regions. Eaf3 contains a chromo domain at the N terminus that can bind to methylated Lys-36 of histone H3 (H3K36). We report here the crystal structures of the Eaf3 chromo domain in two truncation forms. Unlike the typical HP1 and Polycomb chromo domains, which contain a large groove to bind the modified histone tail, the Eaf3 chromo domain assumes an autoinhibited chromo barrel domain similar to the human MRG15 chromo domain. Compared with other chromo domains, the Eaf3 chromo domain contains a unique 38-residue insertion that folds into two short beta-strands and a long flexible loop to flank the beta-barrel core. Both isothermal titration calorimetry and surface plasmon resonance studies indicate that the interaction between the Eaf3 chromo domain and the trimethylated H3K36 peptide is relatively weak, with a K(D) of approximately 10(-4) m. NMR titration studies demonstrate that the methylated H3K36 peptide is bound to the cleft formed by the C-terminal alpha-helix and the beta-barrel core. Site-directed mutagenesis study and in vitro binding assay results show that the conserved aromatic residues Tyr-23, Tyr-81, Trp-84, and Trp-88, which form a hydrophobic pocket at one end of the beta-barrel, are essential for the binding of the methylated H3K36. These results reveal the molecular mechanism of the recognition and binding of the methylated H3K36 by Eaf3 and provide new insights into the functional roles of the Eaf3 chromo domain.
18,984,594
G2Cdb: the Genes to Cognition database.
Neuroscience databases linking genes, proteins, (patho)physiology, anatomy and behaviour across species will be valuable in a broad range of studies of the nervous system. G2Cdb is such a neuroscience database aiming to present a global view of the role of synapse proteins in physiology and disease. G2Cdb warehouses sets of genes and proteins experimentally elucidated by proteomic mass spectroscopy of signalling complexes and proteins biochemically isolated from mammalian synapse preparations, giving an experimentally validated definition of the constituents of the mammalian synapse. Using automated text-mining and expert (human) curation we have systematically extracted information from published neurobiological studies in the fields of synaptic signalling electrophysiology and behaviour in knockout and other transgenic mice. We have also surveyed the human genetics literature for associations to disease caused by mutations in synaptic genes. The synapse proteome datasets that G2Cdb provides offer a basis for future work in synapse biology and provide useful information on brain diseases. They have been integrated in a such way that investigators can rapidly query whether a gene or protein is found in brain-signalling complex(es), has a phenotype in rodent models or whether mutations are associated with a human disease. G2Cdb can be freely accessed at http://www.genes2cognition.org.
18,984,621
Acute toxicity of organophosphorus compounds in guinea pigs is sex- and age-dependent and cannot be solely accounted for by acetylcholinesterase inhibition.
This study was designed to test the hypothesis that the acute toxicity of the nerve agents S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX), O-pinacolyl methylphosphonofluoridate (soman), and O-isopropyl methylphosphonofluoridate (sarin) in guinea pigs is age- and sex-dependent and cannot be fully accounted for by the irreversible inhibition of acetylcholinesterase (AChE). The subcutaneous doses of nerve agents needed to decrease 24-h survival of guinea pigs by 50% (LD(50) values) were estimated by probit analysis. In all animal groups, the rank order of LD(50) values was sarin > soman > VX. The LD(50) value of soman was not influenced by sex or age of the animals. In contrast, the LD(50) values of VX and sarin were lower in adult male than in age-matched female or younger guinea pigs. A colorimetric assay was used to determine the concentrations of nerve agents that inhibit in vitro 50% of AChE activity (IC(50) values) in guinea pig brain extracts, plasma, red blood cells, and whole blood. A positive correlation between LD(50) values and IC(50) values for AChE inhibition would support the hypothesis that AChE inhibition is a major determinant of the acute toxicity of the nerve agents. However, such a positive correlation was found only between LD(50) values and IC(50) values for AChE inhibition in brain extracts from neonatal and prepubertal guinea pigs. These results demonstrate for the first time that the lethal potencies of some nerve agents in guinea pigs are age- and sex-dependent. They also support the contention that mechanisms other than AChE inhibition contribute to the lethality of nerve agents.
18,984,651
Effect of novel negative allosteric modulators of neuronal nicotinic receptors on cells expressing native and recombinant nicotinic receptors: implications for drug discovery.
Allosteric modulation of nAChRs is considered to be one of the most promising approaches for drug design targeting nicotinic acetylcholine receptors (nAChRs). We have reported previously on the pharmacological activity of several compounds that seem to act noncompetitively to inhibit the activation of alpha3beta4(*) nAChRs. In this study, the effects of 51 structurally similar molecules on native and recombinant alpha3beta4 nAChRs are characterized. These 51 molecules inhibited adrenal neurosecretion activated via stimulation of native alpha3beta4(*) nAChR, with IC(50) values ranging from 0.4 to 13.0 microM. Using cells expressing recombinant alpha3beta4 nAChRs, these molecules inhibited calcium accumulation (a more direct assay to establish nAChR activity), with IC(50) values ranging from 0.7 to 38.2 microM. Radiolabeled nAChR binding studies to orthosteric sites showed no inhibitory activity on either native or recombinant nAChRs. Correlation analyses of the data from both functional assays suggested additional, non-nAChR activity of the molecules. To test this hypothesis, the effects of the drugs on neurosecretion stimulated through non-nAChR mechanisms were investigated; inhibitory effects ranged from no inhibition to 95% inhibition at concentrations of 10 microM. Correlation analyses of the functional data confirmed this hypothesis. Several of the molecules (24/51) increased agonist binding to native nAChRs, supporting allosteric interactions with nAChRs. Computational modeling and blind docking identified a binding site for our negative allosteric modulators near the orthosteric binding site of the receptor. In summary, this study identified several molecules for potential development as negative allosteric modulators and documented the importance of multiple screening assays for nAChR drug discovery.
18,984,653
Absence of somatic SQSTM1 mutations in Paget's disease of bone.
Paget's disease is a common focal bone disorder that appears to be caused by a combination of genetic and environmental factors. Mutations in the SQSTM1 gene are found in about one third of families with Paget's disease and 8% of sporadic cases. Other potential loci linked to the disease have also been identified, and a number of environmental factors have been suggested to be involved in the disease. However, the focal nature of Paget's is still unexplained. Therefore, we examined the possibility that somatic mutations in the SQSTM1 gene are present in the local lesions, using RNA collected from primary osteoblast and bone marrow cell cultures of patients with this condition. SQSTM1 was sequenced, and allelic discrimination for the common P392L mutation was performed in cDNA samples from 14 osteoblast cultures and from 14 cultures of bone marrow cells. In these 28 samples drawn from 23 patients, the wild-type sequence of SQSTM1 was found in all but one marrow sample, which was heterozygous for the P392L mutation. DNA from peripheral blood in this subject had an identical sequence of SQSTM1, indicating that this was a germline mutation. We conclude that somatic mutations for SQSTM1 are not commonly present in Paget's disease.
18,984,666
Hellea balneolensis gen. nov., sp. nov., a prosthecate alphaproteobacterium from the Mediterranean Sea.
A novel aerobic, heterotrophic, prosthecate bacterium, designated 26III/A02/215(T), was isolated from surface water of the north-western Mediterranean Sea. Cells stained Gram-negative and were straight to slightly curved rods, forming red colonies on agar plates. The strain grew at 15-37 degrees C inclusive (optimum 30 degrees C) and grew optimally at seawater salinity. Growth was observed on organic acids, amino acids and complex organic substrates. The fatty acids (>5 %) detected in strain 26III/A02/215(T) were C(17 : 1)omega6c, C(18 : 1)omega7c and C(17 : 0). The lipid pattern indicated the presence of phosphatidylglycerol, glucuronopyranosyldiglyceride, monoglycosyldiglyceride, an unidentified glycolipid and three unidentified phospholipids. Phosphatidylethanolamine and diphosphatidylglycerol were absent. Ubiquinone Q-10 was the only respiratory lipoquinone. The G+C content of the genomic DNA was 46.8 mol%. Comparative 16S rRNA gene sequence analysis indicated that strain 26III/A02/215(T) belonged to the Hyphomonas-Hirschia-Robiginitomaculum branch of the order Caulobacterales. This affiliation was consistent with the results of polar lipid analyses. Among this group, the novel isolate was most closely related to Robiginitomaculum antarcticum (93.9 % 16S rRNA gene sequence similarity to the type strain). On the basis of genotypic, chemotaxonomic and phenotypic distinctness, we propose a novel genus, Hellea gen. nov., with Hellea balneolensis sp. nov. as the type species. The type strain of Hellea balneolensis is 26III/A02/215(T) (=DSM 19091(T) =CIP 109500(T) =OOB 269(T)).
18,984,685
Thermoanaerobacter uzonensis sp. nov., an anaerobic thermophilic bacterium isolated from a hot spring within the Uzon Caldera, Kamchatka, Far East Russia.
Several strains of heterotrophic, anaerobic thermophilic bacteria were isolated from hot springs of the Uzon Caldera, Kamchatka, Far East Russia. Strain JW/IW010(T) was isolated from a hot spring within the West sector of the Eastern Thermal field, near Pulsating Spring in the Winding Creek area. Cells of strain JW/IW010(T) were straight to slightly curved rods, 0.5 mum in width and variable in length from 2 to 5 mum and occasionally up to 15 mum, and formed oval subterminal spores. Cells stained Gram-negative, but were Gram-type positive. Growth was observed between 32.5 and 69 degrees C with an optimum around 61 degrees C (no growth occurred at or below 30 degrees C, or at or above 72 degrees C). The pH(60 degrees C) range for growth was 4.2-8.9 with an optimum at 7.1 (no growth occurred at or below pH(60 degrees C) 3.9, or at 9.2 or above). The shortest observed doubling-time at pH(60 degrees C) 6.9 and 61 degrees C was 30 min. Strain JW/IW010(T) was chemo-organotrophic; yeast extract, peptone, Casamino acids and tryptone supported growth. Yeast extract was necessary for the utilization of non-proteinaceous substrates, and growth was observed with inulin, cellobiose, maltose, sucrose, glucose, fructose, galactose, mannose, xylose, trehalose, mannitol, pyruvate and crotonate. The G+C content of the genomic DNA of strain JW/IW010(T) was 33.6 mol% (HPLC method). The major phospholipid fatty acids were iso-15 : 0 (53.5 %), 15 : 0 (11.8 %), 16 : 0 (7.3 %), 10-methyl 16 : 0 (7.3 %) and anteiso-15 : 0 (5.3 %). 16S rRNA gene sequence analysis placed strain JW/IW010(T) in the genus Thermoanaerobacter of the family 'Thermoanaerobacteriaceae' (Firmicutes), with Thermoanaerobacter sulfurigignens JW/SL-NZ826(T) (97 % 16S rRNA gene sequence similarity) and Thermoanaerobacter kivui DSM 2030(T) (94.5 %) as the closest phylogenetic relatives with validly published names. The level of DNA-DNA relatedness between strain JW/IW010(T) and Thermoanaerobacter sulfurigignens JW/SL-NZ826(T) was 64 %. Based on the physiological, phylogenetic and genotypic data, strain JW/IW010(T) represents a novel taxon, for which the name Thermoanaerobacter uzonensis sp. nov. is proposed. The type strain is JW/IW010(T) (=ATCC BAA-1464(T)=DSM 18761(T)). The effectively published strain, 1501/60, of 'Clostridium uzonii' [Krivenko, V. V., Vadachloriya, R. M., Chermykh, N. A., Mityushina, L. L. & Krasilnikova, E. N. (1990). Microbiology (English translation of Mikrobiologiia) 59, 741-748] had approximately 88.0 % DNA-DNA relatedness with strain JW/IW010(T) and was included in the novel taxon.
18,984,694
Leucobacter tardus sp. nov., isolated from the phyllosphere of Solanum tuberosum L.
In the course of studying the composition of the microbial community in the phyllosphere of potato plants, a Gram-positive bacterium, strain K 70/01(T), was isolated. On the basis of 16S rRNA gene sequence analysis, it was shown that the investigated isolate represents a novel species in the genus Leucobacter; the closest phylogenetic neighbour was Leucobacter chromiireducens subsp. chromiireducens, with a sequence similarity of 96.8 % to the type strain. Chemotaxonomic characteristics supported affiliation to the genus Leucobacter. Strain K 70/01(T) displayed the diagnostic diamino acid 2,4-diaminobutyric acid in the cell-wall peptidoglycan. The major fatty acids were anteiso-C(15 : 0,) anteiso-C(17 : 0) and iso-C(16 : 0), which are typical of the genus. The quinone system consisted of the menaquinones MK-10, MK-11 and MK-9. Differences in several physiological features and the absence of the cell-wall amino acids gamma-aminobutyric acid and threonine enabled the isolate to be differentiated from all recognized Leucobacter species. Based on these phylogenetic and phenotypic results, it can be concluded that the isolate from the phyllosphere of potato plants represents a novel species, for which the name Leucobacter tardus sp. nov. is proposed. The type strain is K 70/01(T) (=DSM 19811(T) =LMG 24388(T)).
18,984,695
Photorhabdus temperata subsp. cinerea subsp. nov., isolated from Heterorhabditis nematodes.
During the characterization of symbiotic bacteria of Hungarian entomopathogenic nematode isolates, a number of bacteria (including strain 3107(T)) isolated from Heterorhabditis downesi and Heterorhabditis megidis showed only moderate 16S rRNA gene sequence similarity to the type strains of all described Photorhabdus species and subspecies. On the basis of the 16S rRNA gene sequence, the phylogenetic relationships of these isolates were uncertain, because of the low bootstrap values. Using gyrB sequences for phylogenetic analysis, these isolates were shown to be part of the species Photorhabdus temperata, with clear separation from both Palaearctic and American strains (phylogenetic distances are 6.9 and 7.9 %, respectively). Physiological properties and carbon-source utilization profiles supported the phylogenetic position of these strains; therefore, a novel subspecies, Photorhabdus temperata subsp. cinerea subsp. nov. is proposed, with the type strain 3107(T) (=DSM 19724(T) =NCAIM B 02271(T)).
18,984,696
Bacillus alkalitelluris sp. nov., an alkaliphilic bacterium isolated from sandy soil.
A Gram-positive, alkaliphilic bacterium, designated strain BA288(T), was isolated from sandy soil. Cells were facultatively anaerobic, endospore-forming rods that were motile by means of peritrichous flagella. The strain grew at 15-40 degrees C and pH 7.0-11.0 (optimally at 30 degrees C and pH 9.0-9.5) and at salinities of 0-4 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain BA288(T) belonged to the genus Bacillus and that Bacillus herbersteinensis D-1,5a(T), Bacillus humi LMG 22167(T), Bacillus cohnii DSM 6307(T) and Bacillus litoralis SW-211(T) were the closest neighbours (96.2, 96.0, 96.0 and 95.9 % sequence similarity, respectively). The genomic DNA G+C content was 37.9 mol% and the predominant menaquinone was MK-7. The major cellular fatty acids were anteiso-C(15 : 0), iso-C(15 : 0), C(16 : 0) and iso-C(14 : 0). The peptidoglycan type was A1gamma (meso-diaminopimelic acid). Therefore, on the basis of phylogenetic, phenotypic and chemotaxonomic properties, strain BA288(T) represents a novel species of the genus Bacillus, for which the name Bacillus alkalitelluris sp. nov. is proposed. The type strain is BA288(T) (=KCTC 3947(T) =DSM 16976(T)).
18,984,705
Taxonomic analysis of Sorangium strains based on HSP60 and 16S rRNA gene sequences and morphology.
The taxonomy of myxobacteria is based mainly on their morphological characteristics. The genus Sorangium belongs to the myxobacterial suborder Sorangiineae. Strains in the genus were classified either as one species, Sorangium cellulosum, by ignoring divergent morphological characteristics, or into several species; however, the latter classification is based on some dubious morphological characteristics and is inconsistent with the phylogeny constructed from 16S rRNA gene sequences. In this study, two HSP60 (groEL1 and groEL2) genes were amplified and sequenced from 22 Sorangium strains. The groEL1 and groEL2 gene sequences were highly conserved in Sorangium strains, suggesting that these two paralogous genes both play important roles in the life cycle. The phylogeny constructed by the groEL genes was rather consistent with the morphological characteristics of sporangioles. Including information from the phylogenetic analysis and morphological characteristics, it is suggested that the genus Sorangium includes two species.
18,984,709
All-trans retinoic acid inhibits type 1 diabetes by T regulatory (Treg)-dependent suppression of interferon-gamma-producing T-cells without affecting Th17 cells.
All-trans retinoic acid (ATRA), a potent derivative of vitamin A, can regulate immune responses. However, its role in inducing immune tolerance associated with the prevention of islet inflammation and inhibition of type 1 diabetes remains unclear. We investigated the mechanisms underlying the potential immunoregulatory effect of ATRA on type 1 diabetes using an adoptive transfer animal model of the disease. Our data demonstrated that ATRA treatment inhibited diabetes in NOD mice with established insulitis. In addition, it suppressed interferon (IFN)-gamma-producing CD4(+) and CD8(+) T effector (Teff) cells and expanded T regulatory (Treg) cells in recipient mice transferred with diabetic NOD splenocytes, without affecting either interleukin (IL)-17--or IL-4-producing cells. Consistent with these results, ATRA reduced T-bet and STAT4 expression in T-cells and decreased islet-infiltrating CD8(+) T-cells, suppressing their activation and IFN-gamma/granzyme B expression. Depletion of CD4(+)CD25(+) Treg cells impaired the inhibitory effect of ATRA on islet-infiltrating T-cells and blocked its protective effect on diabetes. Therefore, ATRA treatment induced Treg cell-dependent immune tolerance by suppressing both CD4(+) and CD8(+) Teff cells while promoting Treg cell expansion. These results demonstrate that ATRA treatment promoted in vivo expansion of Treg cells and induced Treg cell-dependent immune tolerance by suppressing IFN-gamma-producing T-cells, without affecting Th17 cells. Our study also provides novel insights into how ATRA induces immune tolerance in vivo via its effects on Teff and Treg cells.
18,984,738
Can 64-row computed tomography replace angiography after coronary bypass?
Multi-detector (64-row) computed tomography has become an alternative to coronary angiography to diagnose graft occlusion and stenosis after coronary artery bypass. We compared the power of evaluation of multi-detector computed tomography with that of conventional coronary angiography in 60 patients who underwent coronary artery bypass with 135 grafts and 210 graft anastomoses. The diagnostic power of multi-detector computed tomography for graft occlusion was: 100% (2/2) sensitivity, 98.5% (131/133) specificity, 50% (2/4) positive predictive value, and 100% (133/133) negative predictive value; there were no significant differences in rates of occlusion among the different types of graft. The diagnostic power of multi-detector computed tomography for stenosis of the graft anastomosis was: 100% (2/2) sensitivity, 95.1% (194/204) specificity, 16.6% (2/12) positive predictive value, and 100% (194/194) negative predictive value, with no significant differences among grafts. Multi-detector computed tomography permits evaluation of bypass grafts and is much less invasive for the patients.
18,984,751
Off-pump coronary revascularization for left main coronary artery stenosis.
Experience of on- and off-pump coronary artery bypass in 379 patients with significant left main coronary artery stenosis was retrospectively reviewed. Beating-heart operations were performed on 219 patients between January 2001 and October 2007. Their results were compared with 160 who underwent revascularization under cardiopulmonary bypass during the same period. All patients had multivessel grafting via a median sternotomy. Both groups were comparable demographically. Off-pump patients received significantly fewer grafts per patient (3.21 +/- 0.86 vs 3.74 +/- 0.82). The use of moderate or high doses of inotropics (> 5 microg kg(-1) min(-1)) was more frequent in the on-pump group (44% vs 26%). Postoperative blood transfusion requirement was lower in off-pump patients, and fewer of them experienced worsening of preexisting renal insufficiency. There were 2 operative deaths in the on-pump group and 1 in the off-pump group. The off-pump procedure is safe and effective in patients with left main coronary artery disease.
18,984,757
Smooth or attached solid indeterminate nodules detected at baseline CT screening in the NELSON study: cancer risk during 1 year of follow-up.
To retrospectively determine whether baseline nodule characteristics at 3-month and 1-year volume doubling time (VDT) are predictive for lung cancer in solid indeterminate noncalcified nodules (NCNs) detected at baseline computed tomographic (CT) screening. The study, conducted between April 2004 and May 2006, was institutional review board approved. Patient consent was waived for this retrospective evaluation. NCNs between 5 and 10 mm in diameter (n = 891) were evaluated at 3 months and 1 year to assess growth (VDT < 400 days). Baseline assessments were related to growth at 3 months and 1 year by using chi(2) and Mann-Whitney U tests. Baseline assessments and growth were related to the presence of malignancy by using univariate and multivariate logistic regression analyses. At 3 months and at 1 year, 8% and 1% of NCNs had grown, of which 15% and 50% were malignant, respectively. One-year growth was related to morphology (P < .01), margin (P < .0001), location (P < .001), and size (P < .01). All cancers were nonspherical and purely intraparenchymal, without attachment to vessels, the pleura, or fissures. In nonsmooth unattached nodules, a volume of 130 mm(3) or larger was the only predictor for malignancy (odds ratio, 6.3; 95% confidence interval [CI]: 1.7, 23.0). After the addition of information on the 3-month VDT, large volume (odds ratio, 4.9; 95% CI: 1.2, 20.1) and 3-month VDT (odds ratio, 15.6; 95% CI: 4.5, 53.5) helped predict malignancy. At 1 year, only the 1-year growth remained (odds ratio, 213.3; 95% CI: 18.7, 2430.9) as predictor for malignancy. In smooth or attached solid indeterminate NCNs, no malignancies were found at 1-year follow-up. In nonsmooth purely intraparenchymal NCNs, size is the main baseline predictor for malignancy. When follow-up data are available, growth is a strong predictor for malignancy, especially at 1-year follow-up.
18,984,780
Plasticity of cloned canine mammary spindle cell tumor, osteosarcoma and carcinoma cells.
Female dogs are frequently affected by mammary tumors, both carcinomas and sarcomas. The mechanisms behind mammary-tumor formation and the high degree of heterogeneity are not understood. To provide insight into this issue, it is important to determine the properties of the cells forming the different types of tumors. One question is if individual neoplastic cells can give rise to phenotypically distinct tumor types, i.e., show plasticity. We studied 3 different tumors (a spindle-cell tumor, an osteosarcoma, and a carcinoma) and followed the change of lineage marker expression between the primary canine mammary tumors, the clones derived from the corresponding tumors and in tumors generated after inoculation of tumor clones into nude mice (n = 75). Inoculation of clones derived from the spindle-cell tumor gave rise to spindle-cell tumors in nude mice. Several of these contained bone tissue, a sign of plasticity. Clones derived from the osteosarcoma were negative for a panel of lineage markers but, when inoculated into nude mice, they were able to form bone, again a sign of plasticity. In contrast to the primary carcinoma, most of the clones derived thereof lacked keratin expression, but keratin expression was recovered in most of the tumors formed after inoculation of clones into nude mice. Moreover, tumors generated from the carcinoma clones, in contrast to the primary tumor, were positive for smooth-muscle-cell markers. Our results point to plasticity in canine mammary tumors, as shown both by morphologic criteria and by expression patterns for lineage specific markers.
18,984,783
Review paper: modulation of mononuclear phagocyte function by Mycobacterium avium subsp. paratuberculosis.
Pathogenic mycobacteria are highly adapted for survival within host mononuclear phagocytes. This is largely due to the organism's capacity to prevent macrophage activation, block phagosome acidification and maturation, and attenuate presentation of antigens to the immune system. Mycobacterium avium subsp. paratuberculosis (MAP) is one such organism that modulates the ruminant innate immune response. It is the causative agent in paratuberculosis, a chronic progressive granulomatous enteritis in ruminants. MAP initially interacts with cell membrane receptors on bovine mononuclear phagocytes and initiates cell signaling responses and phagocytosis. Mannosylated liparabinomannan (Man-LAM) is a major component of the MAP cell wall that interacts with the cell membrane of mononuclear phagocytes and may be a major virulence factor. Toll-like receptor 2 (TLR2) has been incriminated as major signaling receptor that binds to MAP and initiates signaling though the mitogen-activated protein kinase (MAPK)-p38 pathway. This pathway induces transcription of interleukin (IL)-10. Early production of IL-10 suppresses proinflammatory cytokines, chemokines, IL-12, and major histocompatability factor class-II expression. Both IL-10 dependent and IL-10 independent mechanisms appear to be involved in attenuation of phagosome acidification and phagolysosome fusion. Many of the suppressive effects of MAP on bovine mononuclear phagocytes can be reproduced by exposure of bovine monocytes to Man-LAM. Therefore, MAP Man-LAM-induced TLR2-MAPK-p38 signaling with resultant excessive IL-10 expression has emerged as one of the mechanisms by which MAP organisms suppress inflammatory, immune, and antimicrobial responses and promote their survival within host mononuclear phagocytes.
18,984,786
Review paper: a review of the pathology of abnormal placentae of somatic cell nuclear transfer clone pregnancies in cattle, sheep, and mice.
Cloning of cattle, sheep, and mice by somatic cell nuclear transfer (SCNT) can result in apparently healthy offspring, but the probability of a successful and complete pregnancy is less than 5%. Failures of SCNT pregnancy are associated with placental abnormalities, such as placentomegaly, reduced vascularisation, hypoplasia of trophoblastic epithelium, and altered basement membrane. The pathogenesis of these changes is poorly understood, but current evidence implicates aberrant reprogramming of donor nuclei by the recipient oocyte cytoplast, resulting in epigenetic modifications of key regulatory genes essential for normal placental development. The purpose of this review is to provide an overview of the anatomic pathology of abnormal placentae of SCNT clones and to summarize current knowledge concerning underlying pathogenetic mechanisms.
18,984,789
Staphylococcus-associated abortions in ewes with long-term central venous catheterization.
Forty-two ewes had an intravenous catheter sewn in place in a prepared area over the jugular vein and beginning at 60 days of gestation received an infusion 3 times daily. The infusion consisted of sterile saline or sterile saline containing arginine. Twenty-six ewes in both control and treatment groups aborted between 81 days of gestation and term. Fetuses from 16 ewes that aborted were examined. Most were autolyzed or had early mummification. Macroscopic placentitis and noncollapsing lungs were noted. Large numbers of coagulase-positive Staphylococcus were isolated from fetal abomasal content, lungs, brains, or placentas. Histologically, suppurative placentitis with necrosis and pulmonary aspiration of meconium and amniotic debris often with suppurative bronchopneumonia were observed in abortuses. Four ewes euthanized and examined after abortion had suppurative endometritis. Three ewes had severe, chronic, jugular thrombophlebitis from which coagulase-positive Staphylococcus was isolated. The fourth ewe had mild phlebitis, and Staphylococcus aureus was isolated from both the catheter and the blood. Catheter-associated staphylococcal abortion was diagnosed.
18,984,790
Biphasic malignant testicular sex cord-stromal tumor in a cotton-top tamarin (Saguinus oedipus) with review of the literature.
A 20-year old male cotton-top tamarin (Saguinus oedipus) was presented with unilateral enlargement of an intrascrotal testicle. Fine-needle aspiration cytology demonstrated a neoplastic population with Call-Exner-like bodies and features of malignancy. The animal was castrated, and histologic examination revealed a biphasic sex cord-stromal tumor, with one region resembling Sertoli-cell tumor and one region resembling granulosa-cell tumor, with extensive microfollicular pattern and many Call-Exner bodies. Eight months after castration, the animal was euthanized on discovery of a caudal abdominal mass that displaced organs, was highly infiltrative, and extended into the paravertebral musculature with lysis of vertebral bone. Metastases to lymph node and lung were also present. Histologic examination of the abdominal tumor showed multifocal formation of Call-Exner bodies in an otherwise highly dedifferentiated population. Positive immunolabeling for alpha inhibin confirmed the sex cord-stromal origin of the abdominal and paravertebral tumor masses. This case has similarities to malignant testicular granulosa-cell tumor of humans.
18,984,797
Anaplastic astrocytoma in the spinal cord of an African pygmy hedgehog (Atelerix albiventris).
A 2-year-old, female hedgehog presented with an 8-month history of progressive, ascending paresis/paralysis and was tentatively diagnosed with wobbly hedgehog syndrome. She died awaiting further diagnostic tests, and the owners consented to postmortem examination. Grossly, the bladder was large and flaccid and the cervical and lumbar spinal cord were regionally enlarged, light grey, and friable with multifocal hemorrhages. The thoracic spinal cord was grossly normal. Microscopically all regions of the spinal cord had similar changes, although the cervical and lumbar sections were most severely affected. These regions were completely effaced by a moderately cellular infiltration of highly pleomorphic polygonal to spindle shaped cells, mineralization, and necrosis, which were most consistent with anaplastic astrocytoma. The thoracic spinal cord white matter was similarly infiltrated by the neoplastic cells, with perivascular extension into the otherwise normal grey matter. A diagnosis of anaplastic astrocytoma was confirmed using immunohistochemical stains that were positive for glial fibrillary acidic protein and S100.
18,984,799
Genetic structure of the asiatic black bear in Japan using mitochondrial DNA analysis.
The genetic structure of the Asiatic black bear (Ursus thibetanus) in Japan was studied to understand the events that occurred during its evolution. The left domain of the mitochondrial control region (about 240 bp) was sequenced, defining 27 haplotypes that consisted of 23 haplotypes from 333 bears in Japan and 22 bears in the Asian continent. The network tree of the control region indicated that the Japanese population formed a distinct clade from the continental population. The phylogeographic analysis of the haplotypes indicated that the Shikoku and Kii Hanto populations had diverged during the initial phase from the ancestral population. After the 3 dominant haplotypes were rapidly distributed throughout Japan in the early stage of the population dispersal, the Japanese population diverged into eastern and western populations. Using the entire mitochondrial cytochrome b sequence, divergence time between the Japanese and the Continental populations suggested that the Japanese population might have colonized into Japan through the land bridge from the Korean Peninsula around 500 ka, which is consistent with paleontological evidence. Our finding that bears in western Japan exhibit lower genetic diversity and higher levels of genetic differentiation than bears in eastern Japan provides a vital contribution to conservation policy for these isolated populations.
18,984,857
NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity.
Understanding the pathways that regulate the human T-cell acute lymphoblastic leukemia (T-ALL) initiating cells (T-LiC) activity has been hampered by the lack of biologic assays in which this human disease can be studied. Here we show that coculture of primary human T-ALL with a mouse stromal cell line expressing the NOTCH ligand delta-like-1 (DL1) reproducibly allowed maintenance of T-LiC and long-term growth of blast cells. Human T-ALL mutated or not on the NOTCH receptor required sustained activation of the NOTCH pathway via receptor/ligand interaction for growth and T-LiC activity. On the reverse, inhibition of the NOTCH pathway during primary cultures abolished in vitro cell growth and in vivo T-LiC activity. Altogether, these results demonstrate the major role of the NOTCH pathway activation in human T-ALL development and in the maintenance of leukemia-initiating cells.
18,984,862
Challenges in conducting a hospital-randomized trial of an educational quality improvement intervention in rural and small community hospitals.
The study design for this hospital-randomized controlled trial of an educational quality improvement intervention in rural and small community hospitals, following the implementation of a Web-based quality benchmarking and case review tool, specified a control group and a rapid-cycle quality improvement education group of >or= 30 hospitals each. Of the 64 hospitals initially interested in participating, 7 could not produce the required quality data and 10 refused consent to randomization. Of the 23 hospitals randomized to the educational intervention, 16 completed the educational program, 1 attended the didactic sessions but did not complete the required quality improvement project, 3 enrolled in "make-up" sessions, and 3 were unable to attend. Of the 42 individuals who attended educational sessions, 5 (12%) have left their positions. Quality improvement interventions require several different approaches to engage participating organizations and should include plans to train new staff given the high turnover of health care quality improvement personnel.
18,984,908
Study of Prevalence, Awareness,and control of Hypertension in a Suburban Area of Kathmandu, Nepal.
BACKGROUND, In the context of rapidly raising occurrence of cardiovascular diseases in the developing countries, it becomes imperative to study the scenario in its various aspects. The present study in Nepal deals with the hypertension as it is one of the major risk factors of cardiovascular diseases. METHODS AND RESULTS, A house-to-house survey was conducted in a suburban area of Kathmandu valley from February to June 2005 in adult population (age >/=18 years) to estimate the prevalence, awareness, treatment, and control rates of hypertension. Blood pressure was measured twice using standardized mercury sphygmomanometer, and an average of the two readings was taken. Total number of subjects were 1114 (men:541; women: 573; mean age: 37.8 -/+ 16.3 years). Overall prevalence of hypertension was 19.7% (22.2% in men and 17.3% in women, p < 0.05).Prevalence of hypertension in age group of >/=40 years was 36%.Awareness, treatment, and control rates were 41.1%, 26%, and 6%, respectively. CONCLUSION, Our study indicates that prevalence of hypertension is significant in Nepal and is comparable with other developing countries of this region. Awareness, treatment, and control rates are poor.
18,984,928
Alveolar macrophage from cigarette smoke-exposed mice inhibits B lymphocyte proliferation stimulated with LPS.
Smokers have higher incidences of pulmonary diseases. This increased susceptibility may result from cigarette smoke (CS)-induced impairment of the pulmonary immune system. However, the mechanism(s) is not fully understood. The aim of this study was to investigate the mechanism of the effect of alveolar macrophages (AM) from CS-exposed mice on B lymphocyte proliferation stimulated with bacterial lipopolysaccharide (LPS). Mice were exposed to CS using a Hamburg smoking machine, and AM were obtained by bronchoalveolar lavage. Lymphocytes were harvested from spleen in normal mice. AM-mediated B lymphocyte proliferation stimulated with LPS was assessed by the (3)H-thymidine method, using lymphocytes as responding cells and AM from CS-exposed or non-CS-exposed mice. Generations of superoxide and hydrogen peroxide were analyzed by flow cytometry, using hydroethidine and dichlorofluorescein diacetate. AM from CS-exposed mice significantly inhibited B lymphocyte proliferation stimulated with LPS compared with AM from non-CS-exposed mice. Generations of superoxide and hydrogen peroxide were significantly increased in CS-exposed AM compared with non-CS-exposed AM. Inhibition of B lymphocyte proliferation stimulated with LPS by AM from CS-exposed mice was clearly recovered by superoxide dismutase and catalase. These results suggest that the inhibition by CS-exposed AM of LPS-induced B lymphocyte proliferation may be caused by the increased superoxide and hydrogen peroxide generation of CS. Therefore, these immunological inhibitions by CS could be associated with increased risk of pulmonary diseases.
18,984,945
Noninvasive depiction of the lenticulostriate arteries with time-of-flight MR angiography at 7.0 T.
The lenticulostriate arteries (LSAs) are small penetrating branches which are feeding the basal ganglia. Thus far, no noninvasive imaging method has been capable of visualizing the LSAs. We explore the possibilities of three-dimensional time-of-flight (TOF) MR angiography (MRA) at 7 T to visualize the LSAs. We included 10 healthy volunteers (age range, 19-46 years; 4 men, 6 women). TOF MRA was performed on a 7.0-tesla ultra-high-field MR system equipped with a volume transmit and 16-channel receive head coil. Images were acquired with a 0.6-mm isotropic resolution with a scan time of 9 min and 33 s. The mean length and number of LSAs (with standard deviations) were evaluated on coronal and sagittal maximum intensity projections of the axial source data set. The mean total number of LSAs (+/- standard deviation) visualized on the left and right side combined was 7.0 +/- 1.8. Per side, the average number of visualized LSAs was 3.5 +/- 1.1, and the maximum number of visualized LSAs was 5. The mean length of the visualized LSAs was 23 +/- 6.6 mm. The most laterally visualized LSAs showed the longest length (29 +/- 5.0 mm), with a stepwise decrease in length for the more medially visualized LSAs. We show the ability of TOF MRA at 7.0 T to image the LSAs. Direct imaging of these LSAs in clinical studies may increase the understanding of the pathophysiology of brain tissue changes, such as lacunar infarcts, which are thought to be caused by small-vessel disease.
18,984,947
Heparin-induced thrombocytopenia: a serious complication of heparin therapy for acute stroke.
Despite the lack of supporting evidence, unfractionated heparin (UFH) is frequently given to acute ischemic stroke patients. This study was designed to determine the incidence of heparin-induced thrombocytopenia (HIT) during acute stroke and to elucidate the clinical features of stroke patients with HIT. Of 1,078 consecutive patients with acute ischemic stroke, 392 were given intravenous UFH. Ten of these developed prominent thrombocytopenia without any other underlying etiology; they were suspected of having HIT. These 10 patients were studied retrospectively. The clinical diagnosis of HIT was made according to two published scoring systems. Antiplatelet factor 4/heparin antibodies in the plasma were detected by the enzyme-linked immunosorbent assay (ELISA) and were confirmed by the 14C-serotonin release assay. Eight patients met the criteria for clinical HIT according to both scoring systems. Of these, serological tests were positive in 2 patients only on ELISA and in 2 patients on both assays. The amount of UFH given was greater in the 4 patients with positive serological findings than in the others (p = 0.043). Three patients developed further thromboembolic events, including 1 patient who developed possible cancer-associated thrombosis. Two patients were dead and the remaining 6 patients were dependent at the time of hospital discharge. The clinical severity and outcome of these patients were relatively unfavorable compared to other acute patients. The prevalence of HIT was 0.5% based on both the clinical scoring systems and serological assays. Monitoring for HIT should be included in the medical management of stroke to avoid further complications.
18,984,950
Presence and extent of cardiac magnetic resonance microvascular obstruction in reperfused non-ST-elevated myocardial infarction and correlation with infarct size and myocardial enzyme release.
Microvascular obstruction (MO) is a factor of adverse outcome in patients with ST-elevated myocardial infarction (STEMI). We assessed the presence and extent of MO and its relationship with infarct size and left ventricular (LV) functional parameters after acute non-ST-elevated myocardial infarction (NSTEMI). Twenty-five patients with first acute NSTEMI underwent a cine and first-pass perfusion cardiac magnetic resonance (CMR) study, with late gadolinium enhancement imaging 72 h after myocardial infarction. MO was detected in 32% of patients, and its extent comprised 0.5-3.1% of the total LV mass (mean 1.9 +/- 1.2%). Patients with MO had a significantly larger infarct size than patients without (14.1 +/- 5.9 vs. 5.3 +/- 4.1% LV mass; p < 0.001). There was no significant difference between both groups for the LV functional parameters and LV ejection fraction (58.5 +/- 6.8 vs. 62.6 +/- 9.6%; p = 0.29). Patients with MO showed a higher troponin I release (570 +/- 364 vs. 148 +/- 103 IU; p = 0.003) and a higher creatine kinase release (29,887 +/- 18,263 vs. 10,287 +/- 5,283 IU; p = 0.007). In patients with acute NSTEMI, MO has a frequency similar to that observed in patients with STEMI and also correlates with the infarct extent. The prognostic significance on clinical outcome remains to be shown in this specific population.
18,984,954
The effect of volume of chorionic villi on long-term cell culture.
It was the aim of our study to investigate the association between culture time and weight of villi obtained by transabdominal chorionic villus sampling (CVS). We analyzed 1,442 villus samples. The gestational age at sampling ranged from 10 to 14 weeks. The weight of villi in these samples ranged from 1 to 80 mg (median 10 mg, interquatile range 7-12 mg). The culture time ranged from 5 to 24 days. Culture time was significantly and inversely correlated with the weight of villi obtained (r = -0.258, p < 0.01). Time was significantly longer when 5 mg or less of villi was obtained but the difference was only up to 2 days. Because the difference in culture time for different groups of villus samples was within 1-2 days, this relationship is statistically significant but has no clinical significance.
18,984,962
[A case of Hennekam syndrome presenting with massive pericardial effusion].
Hennekam syndrome is an autosomal recessive disease characterized by intestinal lymphangiectasia accompanied by severe lymphedema of the limbs, genitalia, and face, and learning difficulties. A 38-month-old boy was admitted with breathing difficulty. He had facial abnormalities and preputial hyperplasia consistent with Hennekam syndrome. Lymphangiography showed lymphedema in the left eye and right foot. Teleradiography showed cardiomegaly and echocardiography showed massive pericardial effusion. He first underwent pericardiocentesis for the removal of pericardial effusion, but pericardial tube drainage was required upon recurrence of effusion. On the fifth day, the drain was removed because of significant decrease in the drainage.
18,984,984
A case of simultaneous anterior, inferior, and right ventricular ST-segment elevation myocardial infarction due to occlusion of the wrapped left anterior descending coronary artery.
Simultaneous anterior, inferior, and right ventricular ST-segment elevation myocardial infarction is an unusual condition. A 50-year-old male patient presented with severe, squeezing chest pain of an hour onset. ST-segment elevations were detected in all precordial derivations, DII, DIII, aVF and V3R, V4R. Coronary angiography showed a significant lesion in the left anterior descending (LAD) coronary artery, just below the second diagonal branch. Balloon predilatation was performed after 40 minutes of admission, followed by bare metal stent implantation, which resulted in ST-segment resolution in all leads and relief of chest pain. Echocardiography showed dyskinesia of the left ventricular apical wall, and hypokinesia of the interventricular septum and inferior wall. Left ventricular ejection fraction was 40%. Coronary angiography and cardiac CT angiography demonstrated a wrapped LAD. The patient was discharged five days after percutaneous coronary intervention (PCI) with stabilization of his clinical status. Ten days after PCI, he presented with chest pain associated with left ventricular anterior and inferior reinfarction. Successful balloon dilatation was performed for thrombotic in-stent restenosis. His clinical condition improved and he was asymptomatic for a month, during which no signs of deterioration were observed in electrocardiographic and echocardiographic findings.
18,984,987
Development of left ventricular apical akinesis and thrombus during pericardiocentesis for pericardial tamponade.
Although pericardiocentesis is a more practical and comfortable alternative to surgical drainage in patients with pericardial tamponade, it may sometimes be associated with transient ventricular dysfunction due to rapid drainage of the fluid. We presented a 42-year-old female patient who developed left ventricular systolic dysfunction and thrombus concomitant with segmental wall motion disorder in the left ventricle during pericardiocentesis for the treatment of massive pericardial effusion and cardiac tamponade. The patient developed acute dyspnea and tachycardia on the second day of pericardiocentesis with a drainage of 500 ml per day. Left ventricular ejection fraction decreased to 20%, and there was akinesis in the left ventricular apex, and severe hypokinesis in the septum. The amount of daily drainage was decreased to 250 ml. Echocardiography performed on the fifth day showed an image, 1 x 1 cm in size, compatible with an apically located thrombus and unfractionated heparin infusion was initiated. Coronary angiography showed normal coronary arteries. At the end of the first week, the drainage decreased below 50 ml/day. Ejection fraction returned to normal at the end of 10 days and the thrombus diminished and disappeared. Analysis of the pericardial fluid showed tuberculous pericarditis and antituberculous treatment was instituted.
18,984,988
[Audiological evaluation of a child with Klippel-Feil syndrome].
A 6-year-old boy with formerly diagnosed Klippel-Feil syndrome (KFS) presented with complaints of hearing loss, speech disorder, and problems related to his hearing aid. Clinical examination and computed tomography showed bilateral external and middle ear anomalies and audiological examination revealed bilateral severe conductive hearing impairment. The patient was prescribed a bone conduction hearing aid and, with necessary consultations, was examined for additional physical anomalies. All children with a diagnosis of KFS should be evaluated with audiologic and otologic examinations, consultations should be implemented with other disciplines concerning the presenting problems, a regular follow-up should be scheduled, and the parents should be informed on possible complications.
18,984,999
RNA aptamer blockade of osteopontin inhibits growth and metastasis of MDA-MB231 breast cancer cells.
Osteopontin (OPN) is a secreted phosphoprotein which mediates tumorigenesis, local growth, and metastasis in a variety of cancers. It is a potential therapeutic target for the regulation of cancer metastasis. RNA aptamer technology targeting OPN may represent a clinically viable therapy. In this study, we characterize the critical sequence of an RNA aptamer, termed OPN-R3, directed against human OPN. It has a K(d) of 18 nmol/l and binds specifically to human OPN as determined by RNA electrophoretic mobility assays. In MDA-MB231 human breast cancer cells examined under fluorescence microscopy, OPN-R3 ablates cell surface binding of OPN to its cell surface CD44 and alpha(v)beta(3) integrin receptors. Critical enzymatic components of the OPN signal transduction pathways, PI3K, JNK1/2, Src and Akt, and mediators of extracellular matrix degradation, matrix metalloproteinase 2 (MMP2) and uroplasminogen activator (uPA), are significantly decreased following exposure to OPN-R3. OPN-R3 inhibits MDA-MB231 in vitro adhesion, migration, and invasion characteristics by 60, 50, and 65%, respectively. In an in vivo xenograft model of breast cancer, OPN-R3 significantly decreases local progression and distant metastases. On the basis of this "proof-of-concept" study, we conclude that RNA aptamer targeting of OPN has biologically relevance for modifying tumor growth and metastasis.
18,985,031
Robust prognostic value of a knowledge-based proliferation signature across large patient microarray studies spanning different cancer types.
Tumour proliferation is one of the main biological phenotypes limiting cure in oncology. Extensive research is being performed to unravel the key players in this process. To exploit the potential of published gene expression data, creation of a signature for proliferation can provide valuable information on tumour status, prognosis and prediction. This will help individualizing treatment and should result in better tumour control, and more rapid and cost-effective research and development. From in vitro published microarray studies, two proliferation signatures were compiled. The prognostic value of these signatures was tested in five large clinical microarray data sets. More than 1000 patients with breast, renal or lung cancer were included. One of the signatures (110 genes) had significant prognostic value in all data sets. Stratifying patients in groups resulted in a clear difference in survival (P-values <0.05). Multivariate Cox-regression analyses showed that this signature added substantial value to the clinical factors used for prognosis. Further patient stratification was compared to patient stratification with several well-known published signatures. Contingency tables and Cramer's V statistics indicated that these primarily identify the same patients as the proliferation signature does. The proliferation signature is a strong prognostic factor, with the potential to be converted into a predictive test. Furthermore, evidence is provided that supports the idea that many published signatures track the same biological processes and that proliferation is one of them.
18,985,037
2-Methoxyoestradiol-3,17-O,O-bis-sulphamate and 2-deoxy-D-glucose in combination: a potential treatment for breast and prostate cancer.
Drug combination therapy is a key strategy to improve treatment efficacy and survival of cancer patients. In this study the effects of combining 2-methoxyoestradiol-3,17-O,O-bis-sulphamate (STX140), a microtubule disruptor, with 2-deoxy-D-glucose (2DG) were assessed in MCF-7 (breast) and LNCaP (prostate) xenograft models in vivo. In mice bearing MCF-7 xenografts, daily p.o. administration of STX140 (5 mg kg(-1)) resulted in a 46% (P<0.05) reduction of tumour volume. However, the combination of STX140 (5 mg kg(-1) p.o.) and 2DG (2 g kg(-1) i.p.) reduced tumour volume by 76% (P<0.001). 2-Methoxyoestradiol-3,17-O,O-bis-sulphamate also reduced tumour vessel density. 2-Deoxy-D-glucose alone had no significant effect on tumour volume or vessel density. A similar benefit of the combination treatment was observed in the LNCaP prostate xenograft model. In vitro the degree of inhibition of cell proliferation by STX140 was unaffected by oxygen concentrations. In contrast, the inhibition of proliferation by 2DG was enhanced under hypoxia by 20 and 25% in MCF-7 and LNCaP cells, respectively. The combination of STX140 and 2DG in LNCaP cells under normoxia or hypoxia inhibited proliferation to a greater extent than either compound alone. These results suggest that the antiangiogenic and microtubule disruption activities of STX140 may make tumours more susceptible to inhibition of glycolysis by 2DG. This is the first study to show the benefit of combining a microtubule disruptor with 2DG in the two most common solid tumours.
18,985,042
Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy.
Duplications in Xq28 involving MECP2 have been described in patients with severe mental retardation, infantile hypotonia, progressive spasticity, and recurrent infections. However, it is not yet clear to what extent these and accompanying symptoms may vary. In addition, the frequency of Xq28 duplications including MECP2 has yet to be determined in patients with unexplained X-linked mental retardation and (fe)males with severe encephalopathy. In this study, we used multiplex ligation-dependent probe amplification to screen Xq28 including MECP2 for deletions and duplications in these patient cohorts. In the group of 283 patients with X-linked mental retardation, we identified three Xq28 duplications including MECP2, which suggests that approximately 1% of unexplained X-linked mental retardation may be caused by MECP2 duplications. In addition, we found three additional MECP2 duplications in 134 male patients with mental retardation and severe, mostly progressive, neurological symptoms, indicating that the mutation frequency could be as high as 2% in this group of patients. In 329 female patients, no Xq28 duplications were detected. In total, we assessed 13 male patients with a MECP2 duplication from six unrelated families. Moderate to severe mental retardation and childhood hypotonia was noted in all patients. The majority of the patients also presented with absent speech, seizures, and progressive spasticity as well as ataxia or an ataxic gait and cerebral atrophy, two previously unreported symptoms. We propose to implement DNA copy number testing for MECP2 in the current diagnostic testing in all males with moderate to severe mental retardation accompanied by (progressive) neurological symptoms.
18,985,075
Alternative mechanisms for regulating racial responses according to internal vs external cues.
Personal (internal) and normative (external) impetuses for regulating racially biased behaviour are well-documented, yet the extent to which internally and externally driven regulatory processes arise from the same mechanism is unknown. Whereas the regulation of race bias according to internal cues has been associated with conflict-monitoring processes and activation of the dorsal anterior cingulate cortex (dACC), we proposed that responses regulated according to external cues to respond without prejudice involves mechanisms of error-perception, a process associated with rostral anterior cingulate cortex (rACC) activity. We recruited low-prejudice participants who reported high or low sensitivity to non-prejudiced norms, and participants completed a stereotype inhibition task in private or public while electroencephalography was recorded. Analysis of event-related potentials revealed that the error-related negativity component, linked to dACC activity, predicted behavioural control of bias across conditions, whereas the error-perception component, linked to rACC activity, predicted control only in public among participants sensitive to external pressures to respond without prejudice.
18,985,098
Increased feelings with increased body signals.
Since the beginning of psychology as a scientific endeavour, the question of whether the body plays a role in how a person experiences emotion has been the centre of emotion research. Patients with structural gastrointestinal disorders, such as Crohn's disease, provide an intriguing opportunity to study the influence of body signals on emotions and feelings. In the present study, emotionally salient films were presented to participants with Crohn's disease in either the active state (Crohn's-active, CA) or silent state (Crohn's-silent, CS), and to normal comparison (NC) participants. We hypothesized that CA participants would have increased feelings, compared with CS and NC participants, when viewing emotional films designed to elicit happiness, disgust, sadness and fear. Gastric myoelectrical activity (electrogastrogram, or EGG) was measured during the films, and after each film was presented, participants rated emotion intensity (arousal) and pleasantness (valence). All groups labelled the emotions similarly. In support of the hypothesis, CA participants showed an increase in subjective arousal for negative emotions compared with CS and NC participants. The CA participants also showed increased EGG during emotional film viewing, as well as a strong positive correlation of EGG with arousal ratings. Together, these findings can be taken as evidence that aberrant feedback from the gastrointestinal system up-regulates the intensity of feelings of negative emotions.
18,985,099
Model syndromes for investigating social cognitive and affective neuroscience: a comparison of Autism and Williams syndrome.
Autism and Williams syndrome are genetically based neurodevelopmental disorders that present strikingly different social phenotypes. Autism involves fundamental impairments in social reciprocity and communication, whereas people with Williams syndrome are highly sociable and engaging. This article reviews the behavioral and neuroimaging literature that has explored the neurocognitive mechanisms that underlie these contrasting social phenotypes, focusing on studies of face processing. The article concludes with a discussion of how the social phenotypes of both syndromes may be characterized by impaired connectivity between the amygdala and other critical regions in the 'social brain'.
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The liver and the moral organ.
Drawing on an analogy to language, I argue that a suite of novel questions emerge when we consider our moral faculty in a similar light. In particular, I suggest the possibility that our moral judgments are derived from unconscious, intuitive processes that operate over the causal-intentional structure of actions and their consequences. On this model, we are endowed with a moral faculty that generates judgments about permissible and forbidden actions prior to the involvement of our emotions and systems of conscious, rational deliberation. This framing of the problem sets up specific predictions about the role of particular neural structures and psychological processes in the generation of moral judgments as well as in the generation of moral behavior. I sketch the details of these predictions and point to relevant data that speak to the validity of thinking of our moral intuitions as grounded in a moral organ.
18,985,108
Music and mirror neurons: from motion to 'e'motion.
The ability to create and enjoy music is a universal human trait and plays an important role in the daily life of most cultures. Music has a unique ability to trigger memories, awaken emotions and to intensify our social experiences. We do not need to be trained in music performance or appreciation to be able to reap its benefits-already as infants, we relate to it spontaneously and effortlessly. There has been a recent surge in neuroimaging investigations of the neural basis of musical experience, but the way in which the abstract shapes and patterns of musical sound can have such profound meaning to us remains elusive. Here we review recent neuroimaging evidence and suggest that music, like language, involves an intimate coupling between the perception and production of hierarchically organized sequential information, the structure of which has the ability to communicate meaning and emotion. We propose that these aspects of musical experience may be mediated by the human mirror neuron system.
18,985,111
Mechanisms underlying sexual and affiliative behaviors of mice: relation to generalized CNS arousal.
The field of social neuroscience has grown dramatically in recent years and certain social responses have become amenable to mechanistic investigations. Toward that end, there has been remarkable progress in determining mechanisms for a simple sexual behavior, lordosis behavior. This work has proven that specific hormone-dependent biochemical reactions in specific parts of the mammalian brain regulate a biologically important behavior. On one hand, this sex behavior depends on underlying mechanisms of CNS arousal. On the other hand, it serves as a prototypical social behavior. The same sex hormones and the genes that encode their receptors as are involved in lordosis, also affect social recognition. Here we review evidence for a micronet of genes promoting social recognition in mice and discuss their biological roles.
18,985,112
Studying mind and brain with fMRI.
The explosion in publications using functional magnetic resonance imaging (fMRI) warrants an examination of how the technique is being used to study processes of mind and brain. Here, we propose a classification of fMRI studies that reveals how this technique is being used in the service of understanding psychological and neural processes and the relationship between the two.
18,985,126
No global processing deficit in the Navon task in 14 developmental prosopagnosics.
Faces are represented in a more configural or holistic manner than other objects. Substantial evidence indicates that this representation results from face-specific mechanisms, but some have argued that it is produced by configural mechanisms that can be applied to many objects including words. The face-specific hypothesis predicts that non-face configural processes will often be normal in prosopagnosic subjects, whereas the domain-general configural hypothesis predicts they will be deficient on all configural tasks. Although the weight of the evidence favors the face-specific hypothesis, a recent study reopened this issue when it was found that three out of five developmental prosopagnosics showed a larger local processing bias than controls in a global-local task (i.e. a Navon task). To examine this issue more thoroughly we tested a significantly larger sample of prosopagnosics (14 participants) who had severe face memory and face perception deficits. In contrast to the previous report, the developmental prosopagnosics performed normally in the global-local task. Like controls, they showed a typical global advantage and typical global-to-local consistency effects. The results demonstrate that the configural processing required by the Navon task is dissociable from face configural processing.
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Elevated stress-hemoconcentration in major depression is normalized by antidepressant treatment: secondary analysis from a randomized, double-blind clinical trial and relevance to cardiovascular disease risk.
Major depressive disorder (MDD) is an independent risk factor for cardiovascular disease (CVD); the presence of MDD symptoms in patients with CVD is associated with a higher incidence of cardiac complications following acute myocardial infarction (MI). Stress-hemoconcentration, a result of psychological stress that might be a risk factor for the pathogenesis of CVD, has been studied in stress-challenge paradigms but has not been systematically studied in MDD. Secondary analysis of stress hemoconcentration was performed on data from controls and subjects with mild to moderate MDD participating in an ongoing pharmacogenetic study of antidepressant treatment response to desipramine or fluoxetine. Hematologic and hemorheologic measures of stress-hemoconcentration included blood cell counts, hematocrit, hemoglobin, total serum protein, and albumin, and whole blood viscosity. Subjects with mild to moderate MDD had significantly increased hemorheologic measures of stress-hemoconcentration and blood viscosity when compared to controls; these measures were correlated with depression severity. Measures of stress-hemoconcentration improved significantly after 8 weeks of antidepressant treatment. Improvements in white blood cell count, red blood cell measures and plasma volume were correlated with decreased severity of depression. Our secondary data analyses support that stress-hemoconcentration, possibly caused by decrements in plasma volume during psychological stress, is present in Mexican-American subjects with mild to moderate MDD at non-challenged baseline conditions. We also found that after antidepressant treatment hemorheologic measures of stress-hemoconcentration are improved and are correlated with improvement of depressive symptoms. These findings suggest that antidepressant treatment may have a positive impact in CVD by ameliorating increased blood viscosity. Physicians should be aware of the potential impact of measures of hemoconcentration and consider the implications for cardiovascular risk in depressed patients.
18,985,146
Allene-alkyne cross-coupling for stereoselective synthesis of substituted 1,4-dienes and cross-conjugated trienes.
Titanium-mediated cross-coupling of allenic alcohols with alkynes has been investigated. Divergent reaction pathways were discovered that provide either stereodefined 1,4-dienes or substituted cross-conjugated trienes. In short, allene substitution plays a critical role in the determination of reaction pathway.
18,985,173
Evaluating the human likeness of an android by comparing gaze behaviors elicited by the android and a person.
Our research goal is to discover the principles underlying natural communication among individuals and to establish a methodology for the development of expressive humanoid robots. For this purpose we have developed androids that closely resemble human beings. The androids enable us to investigate a number of phenomena related to human interaction that could not otherwise be investigated with mechanical-looking robots. This is because more human-like devices are in a better position to elicit the kinds of responses that people direct toward each other. Moreover, we cannot ignore the role of appearance in giving us a subjective impression of human presence or intelligence. However, this impression is influenced by behavior and the complex relationship between appearance and behavior. This paper proposes a hypothesis about how appearance and behavior are related, and maps out a plan for android research to investigate this hypothesis. We then examine a study that evaluates the human likeness of androids according to the gaze behavior they elicit. Studies such as these, which integrate the development of androids with the investigation of human behavior, constitute a new research area that fuses engineering and science.
18,985,174
Pre-programmed bicomponent porous networks at the solid-liquid interface: the low concentration regime.
The control over the formation of a bicomponent porous network was attained by self-assembly at the solid-liquid interface, exploiting triple H-bonds between melamine and bis-uracyl modules.
18,985,186
An unexpected ruthenium complex and its unique behavior as catalyst in dynamic kinetic resolution of secondary alcohols.
A ruthenium complex was accidentally synthesized and its unique catalytic behavior in dynamic kinetic resolution of various types of secondary alcohols, particularly for those bearing additional functional groups, is described.
18,985,201
A metallopolymer case-history: polymer, ring or ligand reaction?
Multinuclear cobalt(II) complexes of ditopic ligands with alpha,omega-dioxy spacers linking two tpy metal-binding domains react with alcohols to generate mononuclear 4'-alkoxy-species.
18,985,210
Rhodium-catalysed cyclisation reaction of allenynes with arylboronic acids.
Allenynes having malonate-based tethers reacted with arylboronic acids in the presence of a rhodium(I) catalyst to sequentially form three carbon-carbon bonds, and arylated bicyclic skeletons were constructed in a stereoselective manner.
18,985,212
Deprotonative cadmation of functionalized aromatics.
This communication describes the deproto-metalation of a large range of aromatics including heterocycles using a newly developed lithium-cadmium base; the reaction proceeds at room temperature with an excellent chemoselectivity and efficiency, and proved to be regioselective in most cases.
18,985,215
Self-assembly of amphiphilic poly(phenylene ethynylene)s in water-potassium dodecanoate-decanol lyotropic liquid crystals.
Poly(phenylene ethynylene)s bearing a high density of branched amphiphilic side-chains self-assemble at the air-water interface and in water-potassium dodecanoate-decanol lyotropic liquid crystals.
18,985,219
Different effects of Fe2+ and Fe3+ on conjugated polymer PPESO3: a novel platform for sensitive assays of hydrogen peroxide and glucose.
Fe(2+) and Fe(3+) as a redox pair showing different effects on a water-soluble conjugated polymer PPESO(3) is definitely an interesting and useful phenomenon in view of signal transduction and has been utilized to develop sensitive assays of hydrogen peroxide and glucose.
18,985,228
A novel type of N-formylation and related reactions of amines via cyanides and esters as formylating agents.
A novel N-formylation and related reactions proceed from cyanides promoted by esters.
18,985,233
The role of "external" lone pairs in the chemical bonding of bare post-transition element clusters: the Wade-Mingos rules versus the jellium model.
The jellium sphere model of a volume of electrons, counterbalanced by a positive charge throughout the sphere, leads to an energy level sequence corresponding to special stabilities of bare post-transition element clusters with 20 valence electrons such as the known P4 and clusters with 40 valence electrons such as the known Ge9(4-), Ni@In10(10-), and In11(7-). In this model the otherwise "external" lone pairs on the vertex atoms participate at least indirectly in the skeletal bonding. Furthermore, this model predicts the most favorable polyhedra and electron counts in some cases to be quite different than those predicted by the Wade-Mingos rules of polyhedral borane chemistry.
18,985,236
Reactivity of UH3 with mild oxidants.
Addition of 2 equiv of I2 to a stirring suspension of UH3 in Et2O results in vigorous gas evolution and the formation of UI4(OEt2)2 (1), which can be isolated in good yields as an air- and moisture-sensitive brick-red powder. Addition of 3 equiv of AgBr to UH3 in DME produces UBr3(DME)2 (2), while addition of 4 equiv of AgX to UH3 in DME-CH2Cl2 provides UX4(DME)2 (X = Br, 3; Cl, 4). Similarly, the reaction of 4 equiv of AgOTf with UH3 in neat DME generates U(OTf)4(DME)2 (5). Each of these reactions proceeds with the evolution of hydrogen. Complex can also be generated by reaction of 4 equiv of Me3SiI with UCl4 in Et2O. All complexes were fully characterized, including analysis by X-ray crystallography.
18,985,243
Bisursodeoxycholate(ethylenediamine)platinum(II): a new autofluorescent compound. Cytotoxic activity and cell cycle analysis in ovarian and hematological cell lines.
The present paper describes for the first time an intrinsic fluorescent square-planar platinum(II) complex carrying two ursodeoxycholate ligands ([Pt(UDC)2(en)], where UDC(-) = ursodeoxycholate), that emits at room temperature once free in solution. Kinetic studies were carried out in aqueous solution and in the presence of different NaCl concentrations: 4 mM (similar to cytoplasmic concentration) and 150 mM (similar to plasmatic concentration). This novel compound was synthesized from a [PtCl2(en)] complex and shows increased cytotoxic activity against both resting and cycling HeLa cells, with no toxicity for cell lines derived from neoplastic haematopoietic cells.
18,985,248
Urinary symptoms and impact on quality of life in women after treatment for endometrial cancer.
The primary objective of our study is to describe urinary symptoms in women treated for endometrial cancer. We performed a cross-sectional survey of women who had undergone surgical treatment for endometrial cancer. Three validated questionnaires were utilized: the Sandvik Severity Index, the Urinary Distress Inventory-6 (UDI-6), and Incontinence Impact Questionaire-7 (IIQ-7). Our study included 70 women treated for endometrial cancer; 35.7% (25/70) of women reported adjuvant radiation therapy after surgical staging. Urinary incontinence was reported in over 80% of women. Mean UDI-6 and IIQ-7 scores for women treated with adjuvant radiation therapy were higher compared to women with no adjuvant radiation therapy [47(+/-26.8) vs. 35.6(+/-21.7; p = 0.05)] and [24.4(+/-28.5) vs. 8.1(+/-16.4; p = 0.004)], respectively. Treatment with adjuvant radiation therapy was associated with more severe incontinence symptoms and impact on quality of life.
18,985,266
Analysis of the extent of resection for adenocarcinoma of the gallbladder.
Gallbladder cancer has historically been considered an incurable malignancy; although, extended resection has been associated with cure in selected patients. However, the optimal extent of resection is unknown. The objective of this study was to analyze the impact of the extent of resection for gallbladder adenocarcinoma on disease-specific survival (DSS) and perioperative morbidity. Analysis of a prospective hepatobiliary surgery database identified patients undergoing surgical resection for gallbladder adenocarcinoma from 1990 to 2002. Clinicopathologic factors including extent of resection were analyzed for their association with DSS and perioperative morbidity. Long-term outcome was evaluable in 104 patients. With median follow-up of 58 months for survivors, the actuarial 5-year DSS was 42%. Thirty-six patients (35%) underwent major hepatectomy, but in 15 this was not mandatory to clear all disease. Sixty-eight patients (65%) underwent common bile duct (CBD) excision, but 32 were performed empirically. Twenty-one patients (20%) underwent en bloc resection of adjacent organs other than the liver. The performance of a major hepatectomy or a CBD excision was not associated with other clinicopathologic variables or long-term survival. Resection of adjacent organs were associated with advanced T stage but not with survival. T stage, N stage, histologic differentiation, and CBD involvement were independently associated with survival. Major hepatectomy and CBD excision were significantly associated with perioperative morbidity. We conclude that tumor biology and stage, rather than extent of resection, predict outcome after resection for gallbladder cancer. Major hepatic resections, including major hepatectomy and CBD excision, are appropriate when necessary to clear disease but are not mandatory in all cases.
18,985,272
Abortiporus biennis tolerance to insoluble metal oxides: oxalate secretion, oxalate oxidase activity, and mycelial morphology.
The ability of Abortiporus biennis to tolerate and solubilize toxic metal oxides (Cu(2)O, Al(2)O(3), ZnO, CuFe(2)O(4)Zn, CdO, and MnO(2)) incorporated into agar media was investigated and the growth rate, oxalic acid secretion, and mycelial morphology were monitored. Among the tested metal oxides, formation of clear zones underneath the mycelium growing on Cu(2)O- and ZnO-amended plates was observed. ZnO, CdO and Cu(2)O caused the highest rate of fungal growth inhibition. An increased level of oxalic acid concentration was detected as a response of A. biennis to the presence of Cu(2)O, MnO(2), ZnO and CuFe(2)O(4)Zn in growth medium. The oxalate oxidase (OXO) was found to be responsible for oxalic acid degradation in A. biennis cultivated in metal-amended media. An increased level of OXO was observed in media amended with Cu(2)O, ZnO and MnO(2). Confocal microscopy used in this study revealed changes in mycelial morphology which appeared as increased hyphal branching, increased septation and increased spore number.
18,985,279
The role of the "International Classification of Functioning, Disability and Health, ICF" in the description and classification of mental disorders.
Diagnoses according to ICD-10 or DSM are conclusions derived from diagnostic algorithms, based on symptoms, but also illness course, history and consequences of the illness state. But, there is only limited consensus about the definitions of the criteria which are the basis of diagnostic algorithms. In DSM there is only a small glossary of technical terms, while ICD does not provide any respective definitions at all. When the diagnostic criteria are unreliable or invalid, then also the diagnostic conclusions must be invalid, even when they are based on strict algorithms. Therefore, standardized definitions for diagnostic criteria are as important as standardized diagnostic algorithms. The ICF, published by WHO in 2001, defines in it's first chapter mental functions which are identical with descriptions of psychopathological terms, if there is a malfunctioning. As definitions of diagnostic criteria are missing in ICD or DSM, the ICF definitions for functions, and thus disorders of functions, are at present the only glossary of illness signs and symptoms. Therefore, the ICF can serve as the basis for diagnostic algorithms in ICD or DSM. Furthermore, illness definitions are, apart from symptoms, also based on illness consequences. These are also defined in ICF as capacities (or disorders of capacity) and participation. Disorders of functions, capacity and participation together can describe targets of treatment. In summary, ICD and ICF as members of the family of WHO classification systems can together provide a common language for the description of health, illness and treatment goals.
18,985,301
Interaction between noradrenaline and corticotrophin-releasing factor in the reinstatement of cocaine seeking in the rat.
Corticotropin-releasing factor (CRF) and noradrenaline (NA) have been shown in independent studies to mediate stress-induced reinstatement of drug seeking. To date, however, a functional interaction between the systems in reinstatement has not been demonstrated. The objectives of this study were to determine whether CRF and NA systems can interact to influence reinstatement responding and, if so, in what direction the interaction occurs. Rats were trained to self-administer cocaine (0.23 mg/kg per infusion) for 8-10 days. Subsequently, responding for drug was extinguished, and tests for reinstatement were conducted following: (1) pretreatment with the CRF receptor antagonist, D: -Phe CRF(12-41) [1 microg, intracerebroventricular (i.c.v.)], prior to i.c.v. injections of NA (10 microg; Experiment 1); (2) pretreatment with the alpha(2) adrenoceptor agonist, clonidine (40 microg/kg, i.p.), prior to i.c.v. injections of CRF (0.5 microg; Experiment 2); (3) pretreatment with D: -Phe (1, 5 microg, i.c.v.), prior to systemic injections of the alpha(2) adrenoceptor antagonist, yohimbine (1.25 mg/kg; Experiment 3A); or (4) pretreatment with clonidine (40 microg/kg, i.p.) prior to systemic injections of yohimbine (0.625 mg/kg, 1.25 mg/kg; Experiment 3B). NA reliably induced reinstatement, an effect that was blocked by pretreatment with D: -Phe. In contrast, CRF-induced reinstatement was not attenuated by pretreatment with clonidine. Pretreatment with neither D: -Phe nor clonidine was effective in blocking yohimbine-induced reinstatement. Together, the present findings suggest a functional interaction between NA and CRF systems in mediating stress-induced reinstatement of cocaine seeking, whereby activation of CRF receptors occurs subsequent to, and downstream of, the sites of action of NA.
18,985,323
Osteolysis with a cementless second generation metal-on-metal cup in total hip replacement.
This study examined the long-term results of a metal-on-metal total hip replacement with a Metasul-lined cup. Twenty-nine total hip arthroplasties were performed in 27 young patients (mean age 49 years). Twenty-two patients (23 hips) were available for clinical and radiographic analysis after a mean duration of 99 months. Mean preoperative Harris hip score of 60 improved to 93 at most recent follow-up. One patient required revision of his cup for periacetabular osteolysis. Radiographic analysis showed osteolysis in another four hips. The high rate of osteolysis found in this series has not previously been reported with this type of implant. The length of follow-up in this series is greater than other reports in the literature and may explain this difference.
18,985,349
Seasonal variations of pH, pCO2, pO2, HCO3- and Ca2+ in the haemolymph: implications on the calcification physiology in Anodonta cygnea.
A study about the relationship between the physical-chemical parameters and the calcium carbonate balance between the haemolymph fluid and mantle calcareous structures was carried out in Anodonta cygnea. An intense peak of HCO(3) (-) and a highest pH in December-January months may be understood as a preparation period for creating alkaline conditions. An intense pH decrease from January to February in parallel with the HCO(3) (-) reduction seems to indicate the beginning process of carbonate precipitation. On the other hand, the following calcium and HCO(3) (-) increases in February-May associated with a continuous and gradual pH fall profile may infer two combined aspects: calcium and HCO(3) (-) absorption from external environment and a simultaneous intense calcium carbonate deposition in the haemolymph. So, the pCO(2) peak in this period reflects a subsequent result on equilibrium balance between HCO(3) (-) absorption and deposition. The only significant pO(2) increase in the next period, from February to June, is related with an energetic increase to support the metabolic activity favouring the posterior intense pCO(2) peaks. The extended time of CO(2) production in the haemolymph from May to November should induce an increased metabolic acidosis with subsequent intense formation of both HCO(3) (-) and Ca(2+) ions in the same period. This seems to result from CaCO(3) deposits dissolution in the haemolymph, the most direct calcareous source. Additionally, the later increase of metabolic succinic acid during autumn may greatly potentiate this acidosis increasing the dissolution process. Consequently, the pH profile present two simultaneous alkaline peaks in July and October, probably due to a strong HCO(3) (-) release from the CaCO(3) dissolution. So, the present seasonal results indicate that in the freshwater bivalve A. cygnea, the low metabolism with higher pH from the early winter is the main cause which may favour a calcareous precipitation, while the high metabolism with lower pH from the early summer may function as an inductor of calcareous dissolution in the haemolymph.
18,985,356
Significance of pulmonary artery size and blood flow as a predictor of outcome in congenital diaphragmatic hernia.
To determine if pulmonary artery size and blood flow have prognostic value in congenital diaphragmatic hernia (CDH). Twenty-eight consecutive left-sided CDH patients treated according to a standard protocol with high frequency oscillatory ventilation (HFOV) + nitric oxide (NO) had right and left pulmonary artery (RPA, LPA) diameters, LPA/RPA diameter (L/R) ratios, and PA blood flows examined by echocardiography (EC) on days 0, 2, and 5 after birth and compared prospectively. Twenty-two patients (78.6%) survived. Of these, 15 required NO (NO-s), and seven did not (non-NO-s). All six patients that died required NO (NO-d). RPA in the NO-d group was significantly smaller than in the NO-s or non-NO-s groups on day 0 (2.90 +/- 0.41 vs. 3.40 +/- 0.49 or 4.01 +/- 0.43; P < 0.01, respectively). LPA in the NO-d group was significantly smaller than in the non-NO-s on day 0 (2.13 +/- 0.45 vs. 3.39 +/- 0.34; P < 0.01). L/R ratios in NO subjects were significantly smaller (NO-s 0.74 +/- 0.11; NO-d 0.73 +/- 0.11) than in non-NO-s subjects (0.84 +/- 0.03) on day 0 (P < 0.01). PA diameters and L/R ratios did not change significantly from day 0 to day 5 in all three groups. There was LPA flow on day 0 in all non-NO-s subjects, but none in all NO subjects. In the NO-s group, LPA flow was confirmed in 87% (13/15) on day 2 and in 100% on day 5, however, there was no LPA flow from day 0 to day 5 in any of the NO-d group. Our data indicate that PA diameters on day 0 and LPA flow are strongly prognostic in left-sided CDH and L/R ratio would appear to be a simple highly reliable indicator of the necessity for NO therapy.
18,985,361
Detailed analysis of retinal function and morphology in a patient with autosomal recessive bestrophinopathy (ARB).
The objective of the paper is to study the retinal microstructure and function in a patient with autosomal recessive bestrophinopathy (ARB). Retinal function and morphology assessment in a patient diagnosed with a biallelic mutation in the BEST1 gene (heterozygote mutations: Leu88del17 and A195V) included: full-field electroretinogram (ffERG) and multifocal electroretinogram (mfERG), electro-oculogram (EOG) testing, and imaging with a high-resolution Fourier-domain optical coherence tomography (Fd-OCT) system (UC Davis Medical Center; axial resolution: 4.5 microm, acquisition speed: 9 frames/s, 1,000 A-scans/frame) combined with a flexible scanning head (Bioptigen Inc.). The 11-year old asymptomatic boy showed a well-demarcated retinopathy with deposits. Functional assessment revealed normal visual acuity, reduced central mfERG responses, delayed rod and rod-cone b-wave ffERG responses, and reduced light rise in the EOG. Fd-OCT demonstrated RPE deposits, photoreceptor detachment, elongated and thickened photoreceptor outer segments, but preserved inner retinal layers. In conclusion, ARB associated retinal dystrophy shows functional and morphological changes that overlap with classic Best disease. For the first time, high-resolution imaging provided in vivo evidence of RPE and photoreceptor involvement in ARB.
18,985,398
[Validation of secondary data. Strengths and limitations].
Medical records databases (such as the General Practice Research Database-GPRD) and administrative databases (such as German Statutory Health Insurance (SHI) claims data) are useful sources for pharmacoepidemiology and health services research. However, these data are not primarily collected for research purposes. Validation studies are needed to examine their completeness and accuracy depending on the corresponding research question. This article reviews strategies for checks of internal consistency within the data from one SHI as well as between data from several SHIs and possibilities of internal data validation. Descriptive analyses of consistency can help to determine the integrity of data. The aim of internal validation is to separate uncertain from true cases based on information from secondary data alone or to reproduce known associations within the database. In addition external validation of secondary data is desirable using original prescriptions, medical records, hospital discharge letters and/or patient or physician interviews as a gold standard. A considerable number of external validation studies of diagnostic coding have been conducted within the GPRD. In contrast, such validation studies of German SHI claims data are mostly lacking and are urgently needed in the near future.
18,985,405
Cell volume as a factor limiting the replicative lifespan of the yeast Saccharomyces cerevisiae.
The number of cell divisions of the yeast Saccharomyces cerevisiae is limited, referred to as "replicative lifespan" of this organism and believed to be due to aging mechanisms similar to those of mammalian cells. We demonstrate, using three pairs of isogenic yeast strains (standard and a mutant deficient in an antioxidant defense protein) that although the lifespan differs significantly, the final volume attained after the last division is similar within each pair of strains. In a population, cells cease to bud after various number of cell cycles but attaining a similar final volume. These results indicate that the increase in the mother cell volume, intrinsic to the asymmetric cell division in S. cerevisiae, may be the main mechanism limiting the reproductive capacity of in this organism.
18,985,429
Octreotide uptake in intracranial metastasis of pancreatic ductal adenocarcinoma origin in a patient with a prolonged clinical course.
We describe a case with prolonged survival of 2 years in a female patient with pancreatic ductal adenocarcinoma who, at diagnosis, already had liver spread and eventually succumbed to brain metastases which scanned positive with [(111)In-DTPA] octreotide scintiscan (OctreoScan). Subsequently, the patient underwent a craniotomy for resection of the metastases, but her condition deteriorated. A chromogranin A stain was negative, showing that there was no neuroendocrinal component to the cerebral secondaries. In contrast, tumor labeling with a monoclonal antibody associated with a favorable prognosis in pancreatic neoplasms was positive. There is mounting evidence that somatostatin receptor status confers a relatively favorable prognosis in pancreatic adenocarcinoma, although OctreoScan-positive brain metastases have not been previously reported.
18,985,450
Risperidone safety in pregnancy. A case report.
The use of risperidone and other antipsychotic drugs during pregnancy is sometimes essential, although it is impossible to design clinical trials to demonstrate the safety of these kinds of drugs. The common method to communicate the absence of drug-related events is through case reports, even though they might be insufficient. This is a case report of a woman with a schizophreniform disorder who continued treatment with risperidone during all her pregnancy, and who gave birth to a healthy baby. The scientific evidence regarding risperidone safety during pregnancy is reviewed and the need to conduct followup studies evaluating the consequences of using antipsychotic drugs in pregnant women is stated.
18,985,459
Accurate ALSFRS-R scores can be generated from retrospective review of clinic notes.
Retrospective studies are important in ALS but require markers of disease severity to enable risk adjustment and to allow fair comparisons between patient groups. The ALSFRS-R could be used as such a measure. This study aimed to determine if accurate ALSFRS-R scores could be generated by reviewing clinic notes. Five investigators reviewed 100 de-identified clinic notes to generate estimated ALSFRS-R scores. These scores were compared to ALSFRS-R scores completed by patients within three months of the clinic note. The retrospective ALSFRS-R scores did not differ significantly from the actual scores (mean retrospective score 38.7+/-5 vs. actual score 38.4+/-6, p =0.5). The intra-class correlation coefficient between actual and retrospective scores confirmed reasonable agreement (rho = 0.53, p <0.001). Bland Altman analysis also confirmed good agreement between the actual and retrospective scores. This study indicates that ALSFRS-R scores can be accurately reproduced from information in clinic notes and should be considered as a marker of disease severity for use in retrospective studies.
18,985,465
Fetal liver-conditioned medium induces hepatic specification from mouse bone marrow mesenchymal stromal cells: a novel strategy for hepatic transdifferentiation.
Although different strategies have been established for hepatic differentiation of mesenchymal stromal cells (MSC), further studies are required to define an efficient strategy to produce hepatocytes from stem cells and uncover the mechanisms of hepatic differentiation. Bone marrow mesenchymal stromal cells (BMMSC), isolated from ICR mice, were induced by fetal liver-conditioned medium from different developmental stages, embryonic days (ED) 9.5, 11.5 and 13.5 and newborn (1 day). Differentiated cells were characterized by morphologic changes, liver-specific gene expression at mRNA and/or protein levels and in vitro functional features. BMMSC morphologically became epithelioid and binucleated after 7 days' exposure to fetal liver-conditioned medium from ED13.5, expressed liver-specific genes (AFP, HNF-3beta, TTR, CK18, ALB and CK19) at mRNA and/or protein levels and acquired in vitro functions characteristic of liver cells, including glycogen storage, urea production and albumin secretion. Conditioned medium derived from fetal liver at ED13.5 was most efficient on hepatic differentiation of BMMSC compared from the other three developmental stages. The present study not only provides a high-performance strategy for hepatic differentiation from BMMSC, but also implies liver at different developmental stages might secrete different types of cytokines that have diverse effects on hepatic differentiation, which could support further investigation to provide insight into fundamental processes that govern development and regeneration of the liver.
18,985,473
Pre-clinical safety testing supporting clinical use of allogeneic multipotent adult progenitor cells.
Successful clinical development of novel cellular therapeutics requires the evaluation of clinical acute toxicity endpoints in scoring patient adverse events (AE) contributing to dose-limiting toxicity (DLT) for establishment of the maximum-tolerated dose (MTD). However, many clinical pathology parameters are not routinely evaluated in pre-clinical safety testing. The objective of this pre-clinical study was to investigate thoroughly the acute toxicity of single- and multiple-dose administrations of allogeneic multipotent adult progenitor cells (MultiStem), which represent a class of stromal stem cells with therapeutic potential. MultiStem were tested as an adjunct treatment in a rat myeloablative hematopoietic stem cell transplantation (HSCT) model for impact on clinical parameters, clinical chemistry, hematology, immunology and histopathology parameters. Animals received MultiStem in a single dose of 12.5 million cells/kg on day 2 after HSCT or in five infusions at this dose on days 2, 9, 16, 23 and 30. Controls received phosphate-buffered saline injections and all animals were killed on day 37. There were no significant differences between tests and controls regarding evaluation of respiratory distress upon infusion, clinical assessment and hematology and clinical chemistry analysis. Gross necropsy and histopathology analysis showed no organ profile alterations. There was no significant evidence for allogeneic antibody production or T-cell sensitization upon MultiStem infusion. These studies demonstrate the safety of administration of allogeneic stromal stem cells in repeat dosing regimens in bone marrow transplant settings, and define pre-clinical safety testing standards relevant to the development of cellular therapeutics using allogeneic adherent adult stem cells.
18,985,479
A new C21 steroidal glycoside from Cynanchum inamoenum (Maxim.) Loes.
A new C21 steroidal glycoside, 5beta,6beta-epoxy-glaucogenin C-3-O-beta-D-glucopyranosyl-(1 --> 4)-beta-d-glucopyranosyl-(1 --> 4)-beta-D-cymaropyranosyl-(1 --> 4)-beta-D-oleandropyranosyl-(1 --> 4)-beta-D-oleandropyranoside, named inamoside D (1), was isolated from the MeOH extract of the roots of Cynanchum inamoenum (Maxim.) Loes (Asclepiadaceae). In addition, five known compounds, including 7-demethoxytylophorine (2), dehydrodiconiferyl alcohol gamma'-O-beta-D-glucopyranoside (3), beta-d-fructofuranosyl-(2 --> 1)-alpha-D-(6-O-sinapoyl)-glucopyranoside (4), neohancoside C (5), and cuchiloside (6), have also been isolated. The structure of 1 was determined by 1D- and 2D-NMR spectroscopies. All the compounds were isolated from this plant for the first time.
18,985,499
[Investigation of Demodex sp. using cellophane tape method among university students].
Demodex sp. is an obligatory ectoparasite of pilosebaceous units in humans. This study was carried out in order to investigate the frequency of Demodex sp. among high school students. For this purpose 75 women and 96 men, making a total of 171 students, were studied. Cellophane-tape preparations taken from their face, especially at the base of the nose, underside of the jaw and the side of the forehead, were examined microscopically. Demodex sp. was found to be positive in five (2.9%) cases.
18,985,578
Characterization of hepatocellular carcinoma developed after achieving sustained virological response to interferon therapy for hepatitis C.
Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC. Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver. The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients. Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients.
18,985,618
Solid-state natural abundance 25Mg NMR studies of Na2MgEDTA x 4 H2O--a possible new reference compound for 25Mg NMR spectroscopy.
Natural abundance solid-state (25)Mg NMR measurements were made of the disodium salt of magnesium ethylenediaminetetraacetate tetrahydrate (Na(2)MgEDTA x 4 H(2)O). Both magic angle spinning (MAS) and static experiments were employed to determine the quadrupole coupling constant (C(q)) and the asymmetry parameter (eta(q)) of the electric field gradient (EFG) tensor associated with (25)Mg in this compound, giving the values C(q) = 1.675(5) MHz and eta(q) = 0.15(1). The isotropic chemical shift was determined to be delta(iso) = 0.25(10) ppm (relative to 11 M MgCl(2) aqueous solution) and a small chemical shift anisotropy (CSA) contribution (approximately -13 ppm) was detected, one of the first CSA reports in (25)Mg NMR. This compound exhibited remarkably good (25)Mg NMR sensitivity, due to its fast spin-lattice relaxation and modest quadrupole coupling, which allowed its use as a secondary shift reference and as a test sample for the implementation and optimisation of signal-enhancement methods in (25)Mg NMR spectroscopy, such as double frequency sweeps (DFS) and the use of adiabatic hyperbolic secant (HS) and WURST pulses.
18,985,623
Tetramethyl-m-benziporphodimethene and isomeric alpha,beta-unsaturated gamma-lactam embedded N-confused tetramethyl-m-benziporphodimethenes.
The condensation reaction of alpha,alpha'-dihydroxy-1,3-diisopropylbenzene, pyrrole, and an aldehyde leads to the formation of tetramethyl-m-benziporphodimethene and outer alpha-pyrrolic carbon oxygenated N-confused tetramethyl-m-benziporphodimethenes containing a gamma-lactam ring in the macrocycle. Two isomers with the carbonyl group of the lactam ring either close to (O-Up) or away from (O-Down) the neighboring sp(3) meso carbon were synthesized and characterized. The single crystal X-ray diffraction analysis on the regular and gamma-lactam containing tetramethyl-m-benziporphodimethenes showed highly distorted macrocycles for all compounds. For O-Up and O-Down isomers, dimeric structures, assembling by intermolecular hydrogen-bonding interactions through lactam rings, were observed in the solid state. Fitting the concentration dependent chemical shifts of the outer NH proton using the non-linear regression method give a maximum association constant of 108.9 M(-1) for the meso 4-methylcarboxyphenyl substituted O-Down isomer. The DFT calculations concluded that the O-Up isomer is energetically more stable, and the keto form is more stable than the enol form.
18,985,649
Remodeling of fracture callus in mice is consistent with mechanical loading and bone remodeling theory.
During the remodeling phase of fracture healing in mice, the callus gradually transforms into a double cortex, which thereafter merges into one cortex. In large animals, a double cortex normally does not form. We investigated whether these patterns of remodeling of the fracture callus in mice can be explained by mechanical loading. Morphologies of fractures after 21, 28, and 42 days of healing were determined from an in vivo mid-diaphyseal femoral osteotomy healing experiment in mice. Bone density distributions from microCT at 21 days were converted into adaptive finite element models. To assess the effect of loading mode on bone remodeling, a well-established remodeling algorithm was used to examine the effect of axial force or bending moment on bone structure. All simulations predicted that under axial loading, the callus remodeled to form a single cortex. When a bending moment was applied, dual concentric cortices developed in all simulations, corresponding well to the progression of remodeling observed experimentally and resulting in quantitatively comparable callus areas of woven and lamellar bone. Effects of biological differences between species or other reasons cannot be excluded, but this study demonstrates how a difference in loading mode could explain the differences between the remodeling phase in small rodents and larger mammals.
18,985,689
Nodal signaling promotes the speed and directional movement of cardiomyocytes in zebrafish.
Members of the Nodal family regulate left-right asymmetry during vertebrate organogenesis, but it is unclear how Nodal signaling controls asymmetric morphogenesis at the cellular level. We used high-resolution time-lapse imaging in zebrafish to compare the movements of cardiomyocytes in the presence or absence of Nodal signaling. Loss of Nodal signaling in late-zygotic mutants for the Nodal co-receptor one-eyed pinhead (LZoep) abolished the leftward movement of cardiomyocytes. Global heart rotation was blocked but cardiomyocyte neighbor relationships were maintained as in wild type. Cardiomyocytes in LZoep mutants moved more slowly and less directionally than their wild-type counterparts. The phenotypes observed in the absence of Nodal signaling strongly resemble abnormalities found in BMP signaling mutants. These results indicate that a Nodal-BMP signaling cascade drives left-right heart morphogenesis by regulating the speed and direction of cardiomyocyte movement.
18,985,714
Phosphorylation of tropomyosin extends cooperative binding of myosin beyond a single regulatory unit.
Tropomyosin (Tm) is one of the major phosphoproteins comprising the thin filament of muscle. However, the specific role of Tm phosphorylation in modulating the mechanics of actomyosin interaction has not been determined. Here we show that Tm phosphorylation is necessary for long-range cooperative activation of myosin binding. We used a novel optical trapping assay to measure the isometric stall force of an ensemble of myosin molecules moving actin filaments reconstituted with either natively phosphorylated or dephosphorylated Tm. The data show that the thin filament is cooperatively activated by myosin across regulatory units when Tm is phosphorylated. When Tm is dephosphorylated, this "long-range" cooperative activation is lost and the filament behaves identically to bare actin filaments. However, these effects are not due to dissociation of dephosphorylated Tm from the reconstituted thin filament. The data suggest that end-to-end interactions of adjacent Tm molecules are strengthened when Tm is phosphorylated, and that phosphorylation is thus essential for long range cooperative activation along the thin filament.
18,985,725
Reversal of iron-induced dilated cardiomyopathy during therapy with deferasirox in beta-thalassemia.
A 15-year-old male with beta-thalassemia major developed dilated cardiomyopathy secondary to iron-overload (Z-scores of left ventricle (LV) dimensions >3, ejection fraction (EF) 33%). Treatment with deferoxamine was unsuccessful, presumably due to poor compliance. After 15 months of using deferasirox (DFX), LV end-diastolic dimension normalized (Z-scores <2), and EF improved to 58%. We conclude that treatment with DFX resulted in a reversal of iron-induced cardiomyopathy.
18,985,743
Aggressive and prosocial children's emotion attributions and moral reasoning.
Aggressive and prosocial children's emotion attributions and moral reasoning were investigated. Participants were 235 kindergarten children (M=6.2 years) and 136 elementary-school children (M=7.6 years) who were selected as aggressive or prosocial based on (kindergarten) teacher ratings. The children were asked to evaluate hypothetical rule violations, attribute emotions they would feel in the role of the victimizer, and justify their responses. Compared with younger prosocial children, younger aggressive children attributed fewer negative emotions and were more likely to provide sanction-oriented justifications when evaluating rule violations negatively. Furthermore, age-, gender- and context-effects in moral development occurred. The context-effects included both effects of transgression type (i.e., prosocial morality vs. fairness) on emotion attributions and moral reasoning and the effects of the context of moral evaluation and emotion attribution on moral reasoning. Findings are discussed in terms of the role of emotion attributions and moral reasoning as antecedents of children's aggressive and prosocial behavior.
18,985,747
Immobilization and controlled release of prostaglandin E2 from poly-L-lactide-co-glycolide microspheres.
Prostaglandin E(2) (PGE(2)) is an arachidonic acid metabolite involved in physiological homeostasis and numerous pathophysiological conditions. Furthermore, it has been demonstrated that prostaglandins have a stimulating effect not only on angiogenesis in situ and in vitro but also on chondrocyte proliferation in vitro. Thus, PGE(2) represents an interesting signaling molecule for various tissue engineering strategies. However, under physiological conditions, PGE(2) has a half-life time of only 10 min, which limits its use in biomedical applications. In the present study, we investigated if the incorporation of PGE(2) into biodegradable poly-L-lactide-co-glycolide microspheres results in a prolonged release of this molecule in its active form. PGE(2)-modified microspheres were produced by a cosolvent emulsification method using CHCl(3) and HFIP as organic solvents and PVA as emulsifier. Thirteen identical batches were produced; and to each batch 1.0 mL of serum-free medium was added. The medium was removed at defined time points and then analyzed by gas chromatography tandem mass spectrometry (GC/MS/MS) to measure the residual PGE(2) content. In this study we demonstrated the prolonged release of PGE(2), showing a linear increase over the first 12 h, followed by a plateau and a slow decrease. The microspheres were further characterized by scanning electron microscopy.
18,985,760
Nutritional management of newborn infants: practical guidelines.
The requirements of growth and organ development create a challenge in nutritional management of newborn infants, especially premature newborn and intestinal-failure infants. Since their feeding may increase the risk of necrotizing enterocolitis, some high-risk infants receive a small volume of feeding or parenteral nutrition (PN) without enteral feeding. This review summarizes the current research progress in the nutritional management of newborn infants. Searches of MEDLINE (1998-2007), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2007), abstracts and conference proceedings, references from relevant publications in the English language were performed, showing that breast milk is the preferred source of nutrients for enteral feeding of newborn infants. The number of nutrients found in human milk was recommended as a guideline in establishing the minimum and maximum levels in infant formulas. The fear of necrotizing enterocolitis and feeding intolerance are the major factors limiting the use of the enteral route as the primary means of nourishing premature infants. PN may help to meet many of the nutritional needs of these infants, but has significant detrimental side effects. Trophic feedings (small volume of feeding given at the same rate for at least 5 d) during PN are a strategy to enhance the feeding tolerance and decrease the side effects of PN and the time to achieve full feeding. Human milk is a key component of any strategy for enteral nutrition of all infants. However, the amounts of calcium, phosphorus, zinc and other nutrients are inadequate to meet the needs of the very low birth weight (VLBW) infants during growth. Therefore, safe and effective means to fortify human milk are essential to the care of VLBW infants.
18,985,802
Inhibition of pancreatic carcinoma cell growth in vitro by DPC4 gene transfection.
To detect the expression of DPC4 in malignant and non-malignant specimens of human pancreas, and observe the inhibition of retroviral pLXSN containing DPC4 on pancreatic carcinoma cells in vitro. The expression of DPC4 was determined in 40 pancreatic adenocarcinoma and 36 non-malignant pancreatic specimens by reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohisto-chemistry. Furthermore, we constructed retroviral vectors containing DPC4, which then infected the pancreatic carcinoma cell line BxPC-3. Cell growth in vitro after being infected was observed, and the vascular endothelial growth factor (VEGF) mRNA level in the daughter cells was determined by semi-quantitative PCR assay. The RT-PCR assay showed a positive rate of DPC4 mRNA in 100% (36/36) of normal specimens, compared to 40% (16/40) in adenocarcinoma specimens. The regional and intense positive cases of DPC4 expression in adenocarcinoma detected by immunohistochemistry were 10 and four, whereas it was all positive expression in normal tissues. There was a significant difference of DPC4 expression between them. The stable expression of DPC4 in the pancreatic carcinoma cells BxPC-3 could be resumed by retroviral vector pLXSN transfection, and could inhibit cell growth in vitro. Rather, DPC4 could decrease VEGF mRNA transcription levels. The deletion of DPC4 expression in pancreatic carcinoma suggests that loss of DPC4 may be involved in the development of pancreatic carcinoma. The retroviral vector pLXSN containing DPC4 can inhibit the proliferation of pancreatic carcinoma cells, and down-regulate the level of VEGF.
18,985,820
Recurrent Mycoplasma pneumoniae infection in a human immunodeficiency virus-positive child.
Mycoplasma pneumoniae is a frequent cause of community-acquired respiratory infections, especially in young children and adolescents. The significance of M. pneumoniae infection in HIV-positive patients, particularly children, is not well described. This report describes an HIV-positive female child with recurrent B-cell lymphoma and recurrent or relapsing pulmonary infections with M. Pneumoniae.
18,985,833
Republicans advocate change in the U.S. health care system including greater use of home and community-based care.
Senator John McCain is determined to implement changes to the U.S. health care system by making it more efficient and more responsive to consumers. Like the 50 state governors who on average see one fifth or more of their budgets taken up by Medicaid (their largest single expense), he has asserted that there is a crisis coming in the form of long-term care. Like the National Governors Association, he believes that moving from institutional care to home and community-based care is a large part of the answer. However, he favors bundling of health care services, and cash and counseling models which would give money to those in need, allowing them to hire their home care services directly. In respect to these ideas, he differs from his Democratic opponent. This is also true with respect to Senator McCain's belief that any changes in the health care system should be done through the private insurance market instead of expanding public insurance programs such as Medicare.
18,985,874
Rapid effect of dexamethasone on the permeability of visceral sheep peritoneum.
The peritoneal mesothelium is a biologic barrier to water and ion transport. Its functional and structural integrity is crucial for peritoneal dialysis treatment. In vivo studies have shown that corticosteroids increase transcellular water transport and ultrafiltration of the rat peritoneum. In the present study, we used Ussing chamber technique to investigate the effect of dexamethasone on the transmesothelial permeability of the visceral sheep peritoneum in vitro. Peritoneal samples from the omentum of adult sheep were collected in a cooled and oxygenated Krebs-Ringer bicarbonate (KRB) solution immediately after the death of the animals. Isolated intact sheets were mounted in an Ussing-type chamber. Dexamethasone (10(-6) mol/L) and its inhibitor mifepristone (10(-5) mol/L) were added apically and basolaterally, alone and in combination to the KRB solution. The transmesothelial resistance (R) was measured for 1 hour before and serially after the addition of the substances. Data are expressed as mean +/- standard error of 6 experiments in each case. The control R was 21.5 +/- 0.42 omega x cm2. Dexamethasone induced a significant reduction of R within 15 minutes, which continued for the entire experiment. The maximum effect (% deltaR) was observed at 30 - 60 minutes after the addition of dexamethasone apically 46.2% +/- 7.14% (p < 0.01) and basolaterally 35.3% +/- 7.76% (p < 0.01). Mifepristone acted as an agonist on both sides of the membrane and significantly inhibited the dexamethasone effect. Our findings clearly indicate that dexamethasone rapidly increases the transmesothelial permeability of visceral sheep peritoneum. The rapid effect implicates dexamethasone and probably mifepristone as being involved in a common nongenomic pathway. Further investigation is necessary to elucidate the underlying mechanisms and perspectives of these findings.
18,985,993
Surgical techniques for prevention of recurrence after total enterolysis in encapsulating peritoneal sclerosis.
We performed total enterolysis in 130 patients with encapsulating peritoneal sclerosis (EPS) between 1993 and 2007. The postoperative survival rate was 93.1%. However, 33 of the patients (25.4%) required additional surgery for recurrent bowel obstruction. To prevent recurrent bowel obstruction, we investigated various techniques following total enterolysis. In 7 patients, we employed the splinting method, in which the intestinal tract is fixed for 1 week after surgery by the insertion of a long intestinal tube. In 3 of the patients, recurrence was detected within 6 months after surgery. We therefore ceased using splinting. From April 2007, we performed the Noble plication procedure, in which intestine-to-intestine suturing is performed to prevent recurrent bowel obstruction, in 17 patients. None of those patients experienced a recurrence during 8 months of follow-up. In 7 patients showing marked calcification or repeated recurrence, we performed anastomosis of the superior jejunum and transverse colon after adhesiotomy. In 5 patients, excluding 2 with recurrence, improvement was achieved. Total enterolysis for EPS relieved bowel obstruction in most patients. However, after surgery, bowel obstruction recurred in some cases. Thus, strategies to reduce recurrence should be established. Currently, we use total enterolysis and Noble plication as our standard techniques. Further basic and clinical studies regarding EPS prevention and treatment should be conducted.
18,986,001
Enrollment fluid status is independently associated with long-term survival of peritoneal dialysis patients.
Fluid overload is a common complication in peritoneal dialysis (PD) patients. The prognostic importance of enrollment fluid status in long-term PD patients remains to be investigated. The objective of the present study was to investigate the prognostic importance of enrollment fluid status in the long-term survival of PD patients. We enrolled 53 PD patients (mean age: 53 years) from November 2000 to February 2006. On enrollment, demographic, clinical, and biochemical data were recorded. Bioelectrical impedance analysis (BIA) was used to determine the fluid status of PD patients, including extracellular water (ECW), intracellular water (ICW), and total body water (TBW). Fluid status was corrected for body surface area (BSA): ECW-BSA, ICW-BSA, and TBW-BSA respectively. Patients were followed to January 2008. The ECW-BSA correlated negatively with albumin, a marker of nutrition (r = -0.53, p < 0.0001). The ICW/ECW ratio (r = 0.36, p = 0.018) correlated directly and the ECW/ TBW ratio (r = -0.36, p = 0.019) correlated negatively with creatinine. Patients who survived during the study period had a significantly lower ECW-BSA (8.29 L/m2 vs. 9.91 L/m2, p = 0.001) than did those who did not survive. Patients with enrollment ECW-BSA below 9 L/m2 had a significantly better 7-year cumulative survival (Kaplan-Meier) than did patients with a ECW-BSA of 9 L/m2 or more (p = 0.019). Using multivariate Cox regression analysis, adjusting for age, race, diabetes, human immunodeficiency virus (HIV) status, and months on dialysis at enrollment, ECW-BSA was a significant independent predictor of mortality (relative risk: 1.50; p = 0.03). In conclusion, ECW-BSA was a significant independent predictor of long-term survival in PD patients.
18,986,007