title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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X-ray absorption measured in the resonant Auger scattering mode. | We report both experimental and theoretical studies on x-ray absorption measured in the resonant Auger scattering mode of gas phase carbon monoxide near the O1s-->2pi region. Both experiment and theory display a crucial difference between the x-ray absorption profiles obtained in the conventional and resonant scattering modes. Lifetime vibrational interference is the main source of the difference. It is demonstrated that such interference, which arises from a coherent excitation to overlapping intermediate levels, ruins the idea for obtaining x-ray absorption spectra in a lifetime broadening free regime. | 18,764,527 |
Monotonic convergent optimal control theory with strict limitations on the spectrum of optimized laser fields. | We present a modified optimal control scheme based on the Krotov method, which allows for strict limitations on the spectrum of the optimized laser fields. A frequency constraint is introduced and derived mathematically correct, without losing monotonic convergence of the algorithm. The method guarantees a close link to learning loop control experiments and is demonstrated for the challenging control of nonresonant Raman transitions, which are used to implement a set of global quantum gates for molecular vibrational qubits. | 18,764,528 |
Recoil-ion momentum distributions for two-photon double ionization of He and Ne by 44 eV free-electron laser radiation. | Recoil-ion momentum distributions for two-photon double ionization of He and Ne (variant Planck's over omega=44 eV) have been recorded with a reaction microscope at FLASH (the free-electron laser at Hamburg) at an intensity of approximately 1 x 10(14) W/cm2 exploring the dynamics of the two fundamental two-photon-two-electron reaction pathways, namely, sequential and direct (or nonsequential) absorption of the photons. We find strong differences in the recoil-ion momentum patterns for the two mechanisms pointing to the significantly different two-electron emission dynamics and thus provide serious constraints for theoretical models. | 18,764,529 |
Suppression of inelastic collisions between polar molecules with a repulsive shield. | We propose and analyze a technique that allows one to suppress inelastic collisions and simultaneously enhance elastic interactions between cold polar molecules. The main idea is to cancel the leading dipole-dipole interaction with a suitable combination of static electric and microwave fields in such a way that the remaining van der Waals-type potential forms a three-dimensional repulsive shield. We analyze the elastic and inelastic scattering cross sections relevant for evaporative cooling of polar molecules and discuss the prospect for the creation of stable crystalline structures. | 18,764,530 |
Optical near-field microscopy of light focusing through a photonic crystal flat lens. | We report here the direct observation by using a scanning near-field microscopy technique of the light focusing through a photonic crystal flat lens designed and fabricated to operate at optical frequencies. The lens is fabricated using a III-V semiconductor slab, and we directly visualize the propagation of the electromagnetic waves by using a scanning near-field optical microscope. We directly evidence spatially, as well as spectrally, the focusing operating regime of the lens. At last, in light of the experimental scanning near-field optical microscope pictures, we discuss the lens ability to focus light at a subwavelength scale. | 18,764,535 |
Short-scale turbulent fluctuations driven by the electron-temperature gradient in the national spherical torus experiment. | Measurements with coherent scattering of electromagnetic waves in plasmas of the National Spherical Torus Experiment indicate the existence of turbulent fluctuations in the range of wave numbers k perpendicular rho(e)=0.1-0.4, corresponding to a turbulence scale length nearly equal to the collisionless skin depth. Experimental observations and agreement with numerical results from a linear gyrokinetic stability code support the conjecture that the observed turbulence is driven by the electron-temperature gradient. | 18,764,544 |
Interaction of streamer discharges in air and other oxygen-nitrogen mixtures. | The interaction of streamers in nitrogen-oxygen mixtures such as air is studied. First, an efficient method for fully three-dimensional streamer simulations in multiprocessor machines is introduced. With its help, we find two competing mechanisms how two adjacent streamers can interact: through electrostatic repulsion and through attraction due to nonlocal photoionization. The nonintuitive effects of pressure and of the nitrogen-oxygen ratio are discussed. As photoionization is experimentally difficult to access, we finally suggest to measure it indirectly through streamer interactions. | 18,764,548 |
Breakdown of the two-step model in K-shell photoemission and subsequent decay probed by the molecular-frame photoelectron angular distributions of CO2. | We report results of measurements and of Hartree-Fock level calculations of molecular-frame photoelectron angular distributions (MFPADs) for C 1s photoemission from CO2. The agreement between the measured and calculated MFPADs is on average reasonable. The measured MFPADs display a weak but definite asymmetry with respect to the O+ and CO+ fragment ions at certain energies, providing evidence for an overlap of gerade and ungerade final ionic states giving rise to a partial breakdown of the two-step model of core-level photoionization and its subsequent Auger decay. | 18,764,609 |
Imaging intramolecular coulomb repulsions in multiply charged anions. | The properties of multiply charged anions are dominated by intramolecular Coulomb repulsion (ICR). Using photoelectron imaging, we show the effect of ICR on photoelectron angular distributions for a series of dianions, -O2C(CH2)_{n}CO_{2};{-} (D_{n};{2-}). The observed photoemission band of D_{n};{2-} was due to a perpendicular transition from the charged end group. However, photoemission intensities were observed to peak along the laser polarization for smaller n due to the strong ICR that forces electrons to be emitted along the molecular axis. This emission pattern weakens with increasing n and at D112- the angular distribution reverses back to peak at the perpendicular direction due to the reduced ICR. | 18,764,611 |
Microfluidic colloidal island formation and erasure induced by surface acoustic wave radiation. | Spatiotemporal patterns form in many nonlinear physicochemical or biological systems. Although unusual, microfluidic systems are no exception. We observe such patterns to form by colloids along the free surface of a drop beneath which surface acoustic waves propagate, and propose fundamental mechanisms to elucidate their formation. With increasing excitation amplitude, the colloids first assemble into concentric rings and then cluster into islands due to a combination of capillarity and surface acceleration. As the excitation is further increased, fluid streaming commences within the drop, inducing a transient metastable state in which the system alternates between colloidal island formation on the quiescent drop surface and subsequent erasure due to local vortex generation. | 18,764,621 |
Direct mapping of phonon dispersion relations in copper by momentum-resolved x-ray calorimetry. | We have developed a new method of mapping phonon dispersion relations based on momentum-resolved x-ray calorimetry. X-ray scattering intensities are measured at selected points in reciprocal space with suitably chosen polarization configurations; the thermal part of the scattering intensity is extracted by scanning the temperature of the sample. The intensity variations, governed by the phonon populations, are analyzed to yield the energies of the phonons. This method is applied to copper. With high-order effects under control, the results are in excellent agreement with the known phonon dispersion relations. | 18,764,635 |
Optimal capping layer thickness for stacked quantum dots. | We study the effect of strain on the vertical and lateral self-organization of nanoscale patterns and stacked quantum dots during epitaxial growth. The computational approach is based on the level set method in combination with an atomistic strain code. Strain changes the energetics of microscopic parameters during growth, and thus determines the nucleation sites and the growth of islands and dots. Our results show that strain can lead to vertical alignment as well as lateral organization. Moreover, our simulations suggest that there is an optimal thickness of the capping layer to get the best alignment and most uniform size distribution of stacked quantum dots, and that its variation can be used to control the formation of interesting structures. | 18,764,641 |
Spin-charge separation in the quantum spin Hall state. | The quantum spin Hall state is a topologically nontrivial insulator state protected by the time-reversal symmetry. We show that such a state always leads to spin-charge separation in the presence of a pi flux. Our result is generally valid for any interacting system. We present a proposal to experimentally observe the phenomenon of spin-charge separation in the recently discovered quantum spin Hall system. | 18,764,648 |
Strontium ranelate for the management of osteoporosis. | To evaluate the role of strontium ranelate in the management of osteoporosis. A MEDLINE (January 1966 to May 2007) search using the terms osteoporosis, strontium ranelate, bonemineral density, and fractures. All English-language articles identified from the data sources were evaluated. Strontium ranelate stimulates bone formation and inhibits bone resorption. Its safety and efficacy for osteoporosis were evaluated in four prospective, randomized, double-blind, placebo-controlled trials. The PREVOS (Prevention of Early Postmenopausal Bone Loss by Strontium Ranelate) trial suggested that 1 g daily is the optimal dose for preventing postmenopausal bone loss and was associated with a 1.41% increase in lumbar bone-mineral density (BMD). However, the STRATOS (Strontium Administration for Treatment of Osteoporosis) study found that a 1 g daily regimen was associated with a higher incidence of new vertebral deformities, and a 2 g daily regimen reduced lumbar BMD by 3% in postmenopausal, osteoporotic women. The SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) studies suggested that a 2 g daily regimen reduced vertebral fractures by 39% to 41%, nonvertebral fractures by 16%, in postmenopausal, osteoporotic women. Most common adverse events reported were nausea and diarrhea. Four clinical trials demonstrated the efficacy and safety of strontium ranelate for the management of postmenopausal osteoporosis; however, the Food and Drug Administration has not approved it for this indication. | 18,764,671 |
Evaluation of the effect of ranitidine on gastroduodenal contractile activity and gastric emptying in horses. | To determine the effect of ranitidine on gastric emptying in horses. 11 adult horses. In vitro, isolated muscle strips from the pyloric antrum and duodenum of 5 horses were suspended in baths and attached to isometric force transducers. Once stable spontaneous contractions were observed, ranitidine or diluent was added at cumulative increasing concentrations. Isometric stress responses were compared. In vivo, 6 horses were assigned to a group in a prospective randomized crossover study design with a wash-out period of 2 weeks between trials. Ranitidine (2.2 mg/kg) or saline (0.9% NaCl) solution was administered IV, and 15 minutes later, acetaminophen (20 mg/kg), diluted in 400 mL of water, was administered via nasogastric tube to evaluate the liquid phase of gastric emptying. Serum acetaminophen concentration was measured at several time points for 3 hours by use of liquid chromatography tandem mass spectrometry. Frequency of defecation was recorded during the 3 hours of the study. Ranitidine increased the contractile activity of the pyloric antrum smooth muscle at a concentration of 10(-4) M. No significant effect of ranitidine on plasma kinetics of acetaminophen was identified. Frequency of defecation did not differ between groups. Ranitidine did increase gastric motility in vitro, but no effect on liquid phase gastric emptying was identified in healthy horses by use of the acetaminophen absorption model. Results do not support the use of ranitidine to promote gastric emptying. | 18,764,686 |
Effect of colostrum administration by use of oroesophageal intubation on serum IgG concentrations in Holstein bull calves. | To determine the amount of colostral IgG required for adequate passive transfer in calves administered colostrum by use of oroesophageal intubation and evaluate the impact of other factors on passive transfer of colostral immunoglobulins in calves. 120 Holstein bull calves. Calves were randomly assigned to specific treatment groups on the basis of volume of colostrum administered and age of calf at administration of colostrum. Colostrum was administered once by oroesophageal intubation. Equal numbers of calves received 1, 2, 3, or 4 L of colostrum, and equal numbers of calves received colostrum at 2, 6, 10, 14, 18, or 22 hours after birth. Serum samples were obtained from calves 48 hours after birth for IgG determination by radial immunodiffusion assay. Effects of factors affecting transfer of colostral immunoglobulins were determined by use of a stepwise multiple regression model and logistic regression models. A minimum of 153 g of colostral IgG was required for optimum colostral transfer of immunoglobulins when calves were fed 3L of colostrum at 2 hours after birth. Substantially larger IgG intakes were required by calves fed colostrum > 2 hours after birth. Feeding 100 g of colostral IgG by oroesophageal intubation was insufficient for adequate passive transfer of colostral immunoglobulins. At least 150 to 200 g of colostral IgG was required for adequate passive transfer of colostral immunoglobulins. Use of an oroesophageal tube for administration of 3 L of colostrum to calves within 2 hours after birth is recommended. | 18,764,687 |
Comparison of four methods to assess colostral IgG concentration in dairy cows. | To determine sensitivity and specificity of 4 methods to assess colostral IgG concentration in dairy cows and determine the optimal cutpoint for each method. Cross-sectional study. 160 Holstein dairy cows. 171 composite colostrum samples collected within 2 hours after parturition were used in the study. Test methods used to estimate colostral IgG concentration consisted of weight of the first milking, 2 hydrometers, and an electronic refractometer. Results of the test methods were compared with colostral IgG concentration determined by means of radial immunodiffusion. For each method, sensitivity and specificity for detecting colostral IgG concentration < 50 g/L were calculated across a range of potential cutpoints, and the optimal cutpoint for each test was selected to maximize sensitivity and specificity. At the optimal cutpoint for each method, sensitivity for weight of the first milking (0.42) was significantly lower than sensitivity for each of the other 3 methods (hydrometer 1, 0.75; hydrometer 2, 0.76; refractometer, 0.75), but no significant differences were identified among the other 3 methods with regard to sensitivity. Specificities at the optimal cutpoint were similar for all 4 methods. Results suggested that use of either hydrometer or the electronic refractometer was an acceptable method of screening colostrum for low IgG concentration; however, the manufacturer-defined scale for both hydrometers overestimated colostral IgG concentration. Use of weight of the first milking as a screening test to identify bovine colostrum with inadequate IgG concentration could not be justified because of the low sensitivity. | 18,764,714 |
Emerging drugs for treatment of overactive bladder and detrusor overactivity. | Overactive bladder (OAB) signifies the presence of urinary urgency and can have major effects on quality of life and social functioning. Standard antimuscarinic drugs have good initial response rates but substantial adverse effects and long-term compliance problems. To review the complexities of the mechanisms underlying OAB and the current drugs available for treating its symptoms. The literature was reviewed to define current therapies and drugs in clinical trials. Articles were identified by means of a computerised PubMed and Cochrane Library search (using the following keywords: overactive bladder, detrusor overactivity, urgency and bladder), supported by a search of the PharmaProjects database. New drug classes, such as beta-3 adrenergic agonists, may work by reducing contractility or excitability of bladder muscle. Moderation of afferent activity may allow improved OAB symptoms, with lower risk of affecting voiding function. Agents acting on the CNS could influence OAB favourably, but target selection and adverse effects are an issue. The recognition of the functional contribution of the urothelium and the diversity of nerve transmitters has sparked interest in both peripheral and central modulation of OAB pathophysiology. | 18,764,721 |
Emerging drugs for ovarian cancer. | Long-term survival of patients with ovarian cancer remains poor and therapy disappointing despite decades of experience with various chemotherapies, including the current gold standard, carboplatin/paclitaxel (TC). To review current and emerging therapies for ovarian cancer in search of ways to improve outcome, reduce toxicity, and maintain quality of life. This is a review of the current status of chemotherapy for ovarian cancer, the ongoing clinical studies, emerging therapies, and proposals for future research. Novel chemotherapeutic agents are needed to reduce toxicity and improve efficacy. Effective biological agents must be found and tested, either in combination with TC or as maintenance therapy after TC. An appropriate regimen and number of repeat treatment cycles for intraperitoneal chemotherapy is urgently needed, and an effective regimen must be established for patients with clear cell/mucinous adenocarcinoma. The main strategy for recurrent ovarian cancer is to find the gene related to drug resistance, then treat the cancer based on its molecular biology. | 18,764,727 |
Locking solutions for hemodialysis catheters; heparin and citrate--a position paper by ASDIN. | There is wide variation in the use of solutions to "lock" or fill tunneled central venous catheters for dialysis. Some centers use undiluted heparin concentrations ranging from 1000 to 10,000 U/ml and other centers place from 1000 to 10,000 U per lumen. Based on available evidence, it appears that heparin 1000 U/ml, or 4% sodium citrate are suitable choices for lock solution to maintain patency of tunneled central venous catheters for dialysis. Risks from systemic anticoagulation are lower with heparin 1000 U/ml and 4% sodium citrate, compared with higher concentrations of heparin (5000 and 10,000 U/ml). The need for use of tissue plasminogen activator for maintaining catheter patency is increased by using heparin lock at 1000 U/ml, vs. higher concentrations. Higher concentrations of heparin lock should be reserved for patients who have evidence of catheter occlusion or thrombosis when heparin is used at 1000 U/ml. Similar choices for lock solution are sensible for acute hemodialysis catheters. When heparin is used for catheter lock, the injected volume should not exceed the internal volume of the catheter. | 18,764,795 |
Pain experience and the imagined researcher. | Little attention has been paid to what happens communicatively when members of the general population attempt to complete a postal survey. The questions - here, on the experience of pain - encapsulate health researchers' views of useful indicators of the scope of pain experience, hence displaying an 'official' representation of experienced pain, limitation, and disability. The respondent faces the double task of aligning their personal experience with this representation in a way that is meaningful and true both to their own experience and to the perceived demands of the questionnaire. For this to succeed, context is often crucial. The paper explores sources and indications of tension in this endeavour as part of a communicative process. Beginning from the observation that respondents frequently write unsolicited comments on their questionnaires, the paper proposes that the need for communication beyond the requested tick in the box treats the questionnaire as an attempt at dialogue with a figure I call 'the imagined researcher'. The paper discusses the communicative task that confronts respondents and the implications of 'the imagined researcher' for the research process. | 18,764,806 |
Is regression of left ventricular hypertrophy in maintenance hemodialysis patients possible? | Left ventricular hypertrophy (LVH), present in 70-80% of patients at the start of dialysis, results from chronic high blood pressure, volume overload, or both, in association with a number of metabolic and neurohumoral alterations. LVH is associated with poor outcome and was considered irreversible until the end of the 20th century. Conversely, in recent years, numerous studies have been published demonstrating that LVH may regress through various therapeutic strategies such as prevention and control of anemia, control of volume load, use of antihypertensive drugs, use of daily or nocturnal hemodialysis (HD), prevention and treatment of hyperphosphatemia, administration of vitamin D or with multifactorial interventional approaches. However, it must be emphasized that most of these studies have included a small number of patients, that many are single-arm and that few are randomized and controlled. In general, it seem that further, adequate, randomized, controlled studies are warranted to better define the optimal therapeutic approach to treat LVH in end-stage renal disease patients receiving chronic HD. | 18,764,802 |
Development of an ELA-DRA gene typing method based on pyrosequencing technology. | The polymorphism of equine lymphocyte antigen (ELA) class II DRA gene had been detected by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and reference strand-mediated conformation analysis. These methodologies allowed to identify 11 ELA-DRA exon 2 sequences, three of which are widely distributed among domestic horse breeds. Herein, we describe the development of a pyrosequencing-based method applicable to ELA-DRA typing, by screening samples from eight different horse breeds previously typed by PCR-SSCP. This sequence-based method would be useful in high-throughput genotyping of major histocompatibility complex genes in horses and other animal species, making this system interesting as a rapid screening method for animal genotyping of immune-related genes. | 18,764,814 |
The syntaxins SYP31 and SYP81 control ER-Golgi trafficking in the plant secretory pathway. | Overexpression of the Golgi and endoplasmic reticulum (ER) syntaxins SYP31 and SYP81 strongly inhibits constitutive secretion. By comparing the secreted reporter alpha-amylase with the ER-retained reporter alpha-amylase-HDEL, it was concluded that SYP81 overexpression inhibits both retrograde and anterograde transport, while SYP31 overexpression mainly affected anterograde transport. Of the other interacting SNAREs investigated, only the overexpression of MEMB11 led to an inhibition of protein secretion. Although the position of a fluorescent tag does not influence the correct localization of the fusion protein, only N-terminal-tagged SYP31 retained the ability of the untagged SNARE to inhibit transport. C-terminal-tagged SYP31 failed to exhibit this effect. Overexpression of both wild-type and N-terminal-tagged syntaxins caused standard Golgi marker proteins to redistribute into the ER. Nevertheless, green fluorescent protein (GFP)-SYP31 was still visible as fluorescent punctae, which, unlike SYP31-GFP, were resistant to brefeldin A treatment. Immunogold electron microscopy showed that endogenous SYP81 is not only present at the ER but also in the cis Golgi, indicating that this syntaxin cycles between these two organelles. However, when expressed at non-inhibitory levels, YFP-SYP81 was seen to locate principally to subdomains of the ER. These punctate structures were physically separated from the Golgi, suggesting that they might possibly reflect the position of ER import sites. | 18,764,818 |
A PDZ-binding motif controls basolateral targeting of syndecan-1 along the biosynthetic pathway in polarized epithelial cells. | The cell surface proteoglycan, syndecan-1, is essential for normal epithelial morphology and function. Syndecan-1 is selectively localized to the basolateral domain of polarized epithelial cells and interacts with cytosolic PDZ (PSD-95, discs large, ZO-1) domain-containing proteins. Here, we show that the polarity of syndecan-1 is determined by its type II PDZ-binding motif. Mutations within the PDZ-binding motif lead to the mislocalization of syndecan-1 to the apical surface. In contrast to previous examples, however, PDZ-binding motif-dependent polarity is not determined by retention at the basolateral surface but rather by polarized sorting prior to syndecan-1's arrival at the plasma membrane. Although none of the four known PDZ-binding partners of syndecan-1 appears to control basolateral localization, our results show that the PDZ-binding motif of syndecan-1 is decoded along the biosynthetic pathway establishing a potential role for PDZ-mediated interactions in polarized sorting. | 18,764,819 |
Comparison of the in vitro properties of apheresis platelets during 7-day storage after interrupting agitation for one or three periods. | Many platelet (PLT) components undergo multiple periods of shipment before transfusion. We have previously conducted studies investigating maintenance of apheresis PLT in vitro quality measures during a single 24- or 30-hour interruption of agitation, but data are not available for multiple periods without agitation. Apheresis PLTs were collected with both the Amicus (Fenwal, Inc.) and the Trima (Gambro BCT) cell separators to provide two identical PLT products, each with approximately 4 x 10(11) to 5 x 10(11) PLTs. One product was subjected to a single contiguous 24- or 30-hour period of interrupted agitation between Days 2 and 3 of storage by placement in a standard shipping box at room temperature. The matched product was not agitated on each of 3 days (Days 0, 1, and 3) for specified intervals totaling an identical period of time. Interrupting agitation for three periods resulted in greater maintenance of pH during storage than that observed using one contiguous period. These differences were significant for units held without agitation for 24 hours (Day 5, 0.08 pH units, p < 0.0001; Day 7, 0.10 pH units, p = 0.0059) and were also significant for units held without agitation for 30 hours (Day 5, 0.15, p < 0.0001; Day 7, 0.20, p < 0.0001). The two different interruption of agitation scenarios did not result in significant differences in the extent of shape change and hypotonic shock response variables after 5 or 7 days of storage. Apheresis PLTs subjected to three periods without agitation maintained overall pH levels slightly greater than those of matched units subjected to one contiguous period without agitation. Other measures showed comparability of PLT in vitro variables with the two scenarios for interruption of agitation. | 18,764,829 |
The orthotopic left lung transplantation in rats: a valuable experimental model without using cuff technique. | Advances in the field of clinical lung transplantation must rely on observations made in animal models. In this study, we introduced a new procedure in the rat, orthotopic left lung transplantation without using the cuff technique, in which the donor pulmonary artery, pulmonary vein, and membranous parts of the bronchus were anastomosed continuously in the lumen using a mattress suture under a surgical microscope; meanwhile, a second, low-pressure perfusion through the pulmonary artery and turnover of the vascular stump were made, which also made the vessel anastomosis easy. Transplantations were completed in 68 rats (89.5%), the mean time used for suturing the left lung hilar structure was 23.5 +/- 4.6 min. All lung grafts had good life-sustaining function because of there being no cuff-induced granulation tissue in bronchial anastomotic stoma, and three out of 12 allografts were observed with active bronchiolitis obliterans lesions at 8 weeks after transplantation. This model is a simple, valuable experimental model for studying lung transplantation and new therapies for preventing acute or chronic rejection. | 18,764,833 |
Maternal sensitivity: a concept analysis. | The aim of this paper is to report a concept analysis of maternal sensitivity. Maternal sensitivity is a broad concept encompassing a variety of interrelated affective and behavioural caregiving attributes. It is used interchangeably with the terms maternal responsiveness or maternal competency, with no consistency of use. There is a need to clarify the concept of maternal sensitivity for research and practice. A search was performed on the CINAHL and Ovid MEDLINE databases using 'maternal sensitivity', 'maternal responsiveness' and 'sensitive mothering' as key words. The searches yielded 54 records for the years 1981-2007. Rodgers' method of evolutionary concept analysis was used to analyse the material. Four critical attributes of maternal sensitivity were identified: (a) dynamic process involving maternal abilities; (b) reciprocal give-and-take with the infant; (c) contingency on the infant's behaviour and (d) quality of maternal behaviours. Maternal identity and infant's needs and cues are antecedents for these attributes. The consequences are infant's comfort, mother-infant attachment and infant development. In addition, three positive affecting factors (social support, maternal-foetal attachment and high self-esteem) and three negative affecting factors (maternal depression, maternal stress and maternal anxiety) were identified. A clear understanding of the concept of maternal sensitivity could be useful for developing ways to enhance maternal sensitivity and to maximize the developmental potential of infants. Knowledge of the attributes of maternal sensitivity identified in this concept analysis may be helpful for constructing measuring items or dimensions. | 18,764,848 |
Total serum bilirubin levels during cyclooxygenase inhibitor treatment for patent ductus arteriosus in preterm infants. | To determine whether ibuprofen use in VLBW infants is associated with increased serum bilirubin levels and impaired neurodevelopmental outcome at 2 years of age compared to indomethacin. We retrospectively evaluated bilirubin data and outcome parameters of 178 VLBW infants treated with COX inhibitors for a haemodynamically relevant patent ductus arteriosus (PDA) between 1998 and 2003 in a single institution. In our department ibuprofen replaced indomethacin for PDA treatment in 2001, while clinical and echocardiographic criteria for the indication of PDA invention have remained unchanged. Ibuprofen and indomethacin therapy groups did not differ in their baseline clinical profile. Peak serum bilirubin concentration was 10.2 mg/dL in the ibuprofen group and 8.6 mg/dL in the indomethacin group (p < 0.01), while phototherapy duration did not differ. At 2 years of age neurodevelopmental outcome was similar in both groups. In a single case analysis, four cases of adverse neurodevelopmental outcome despite inconspicuous clinical course were identified in the ibuprofen group. In VLBW infants with PDA, ibuprofen treatment was associated with higher bilirubin levels than indomethacin. | 18,764,861 |
Metagenomic and stable isotopic analyses of modern freshwater microbialites in Cuatro Ciénegas, Mexico. | Ancient biologically mediated sedimentary carbonate deposits, including stromatolites and other microbialites, provide insight into environmental conditions on early Earth. The primary limitation to interpreting these records is our lack of understanding regarding microbial processes and the preservation of geochemical signatures in contemporary microbialite systems. Using a combination of metagenomic sequencing and isotopic analyses, this study describes the identity, metabolic potential and chemical processes of microbial communities from living microbialites from Cuatro Ciénegas, Mexico. Metagenomic sequencing revealed a diverse, redox-dependent microbial community associated with the microbialites. The microbialite community is distinct from other marine and freshwater microbial communities, and demonstrates extensive environmental adaptation. The microbialite metagenomes contain a large number of genes involved in the production of exopolymeric substances and the formation of biofilms, creating a complex, spatially structured environment. In addition to the spatial complexity of the biofilm, microbial activity is tightly controlled by sensory and regulatory systems, which allow for coordination of autotrophic and heterotrophic processes. Isotopic measurements of the intracrystalline organic matter demonstrate the importance of heterotrophic respiration of photoautotrophic biomass in the precipitation of calcium carbonate. The genomic and stable isotopic data presented here significantly enhance our evolving knowledge of contemporary biomineralization processes, and are directly applicable to studies of ancient microbialites. | 18,764,874 |
A culture-independent study of free-living fungi in biological soil crusts of the Colorado Plateau: their diversity and relative contribution to microbial biomass. | Molecular methodologies were used to investigate free-living fungal communities associated with biological soil crusts (BSCs), along km-scale transects on the Colorado Plateau (USA). Two cyanobacteria-dominated crust types that did not contain significant lichen cover were examined. Fungal community diversity and composition were assessed with PCR-denaturing gradient gel electrophoresis (DGGE) fingerprinting and sequencing, and fungi-specific quantitative PCR was used to measure fungal population densities as compared with those of bacteria. Our results clearly indicate that free-living fungi, while ubiquitous in BSCs, are less diverse and contribute far less biomass than their bacterial counterparts. Biological soil crust fungal community structure differed from that of uncrusted soils in their surroundings. Phylogenetic analyses placed the majority of BSC fungi within the Ascomycota, confirmed the importance of dematiaceous fungi, and pointed to members of the genera Alternaria and Acremonium as the most common free-living fungi in these crusts. Phylotypes potentially representing novel taxa were recovered, as were several belonging to the Basidiomycota that would not have been readily recognized by culture-dependant means. | 18,764,875 |
Proteome analysis at the subcellular level of the cyanobacterium Spirulina platensis in response to low-temperature stress conditions. | The present study addresses the differential expression of Spirulina platensis proteins detected during cold-induced stress, analyzed at the subcellular level. In performing differential expression analysis, the results revealed upregulated proteins in every subcellular fraction, including two-component response systems, DNA repair, molecular chaperones, stress-induced proteins and proteins involved in other biological processes such as secretion systems and nitrogen assimilation. The chlorophyll biosynthetic proteins, protochlorophyllide oxidoreductase and ChlI, had unique expression patterns as detected in the thylakoid membrane; the levels of these proteins immediately decreased during the first 45 min of low-temperature exposure. In contrast, their expression levels significantly increased after low-temperature exposure, indicating the relevance of the chlorophyll biosynthesis in Spirulina in response to low-temperature stress in the light condition. In addition, this is the first report in which genome-based protein identification in S. platensis by peptide mass fingerprinting was performed using the database derived from the unpublished Spirulina genome sequence. | 18,764,876 |
Nitric oxide produces HLA-G nitration and induces metalloprotease-dependent shedding creating a tolerogenic milieu. | Human leucocyte antigen G (HLA-G) is a tolerogenic molecule that protects the fetus from maternal immune attack, may favour tumoral immunoescape and is up-regulated in viral and inflammatory diseases. The aim of this work was to discover if nitric oxide (NO) could affect HLA-G expression or function because NO is an important modulator of innate and adaptive immunity. For this purpose HLA-G expression and function were analysed following treatment with a NO donor or a peroxynitrite donor in various cell lines expressing HLA-G either spontaneously or upon transfection. Results showed NO-dependent nitration of both cellular and soluble HLA-G protein, but not all HLA-G moieties underwent nitration. Endogenous biosynthesis of NO by both U-937-HLA-G1 and M8-HLA-G5 stable transfectants also caused HLA-G nitration. The NO decreased total HLA-G cellular protein content and expression on the cell surface, while increasing HLA-G shedding into the culture medium. This effect was post-transcriptional and the result of metalloprotease activity. By contrast, NO pretreatment did not affect HLA-G capability to suppress NK cytotoxicity and lymphocyte proliferation. Our studies show that NO regulates the availability of HLA-G molecules without modifying their biological activities. | 18,764,882 |
Ultraviolet radiation as a limiting factor in leaf expansion and development. | Reductions in leaf growth are a commonly observed response to ultraviolet radiation, but the underlying mechanisms remain poorly defined. This study examined the response of leaves exposed to a UV environment across a range of organizational scales, including leaf expansion rate, epidermal cell size and number, biomechanical properties, leaf-water relations and activity of cell-wall peroxidases. Two experimental approaches were used; Lettuce (Lactuca sativa L.) plants were propagated under (a) supplementary UV-B (9 kJ m(-2) day(-1)) in controlled environment (CE) conditions, and (b) field conditions, where plants were placed under three horticultural films with differing UV transmissions. In both experiments, UV-B caused the greatest reductions in leaf expansion and final leaf size, with some reductions attributable to UV-A wavelengths. In supplementary UV-B conditions, adaxial cell size was reduced, while in field plants, both cell size and cell number were lower in an increased UV environment, as was the case with abaxial cells in CE plants. Although leaf turgor and leaf extensibility were not affected by UV wavelengths, breaking strain of leaf tissue was decreased under supplementary UV-B. Cell-wall peroxidase activity was increased in both supplementary UV conditions and in the field, where only a zero UV environment showed no upregulation of cell-wall peroxidase. | 18,764,892 |
Metabolic engineering towards the enhancement of photosynthesis. | Photosynthetic capacity is a promising target for metabolic engineering of crop plants towards higher productivity. Crop photosynthesis is limited by multiple factors dependent on the environmental conditions. This includes photosynthetic electron transport, regeneration of CO2 acceptor molecules in the reductive pentose phosphate cycle, the activity and substrate specificity of the CO2-fixing enzyme Ribulose-1,5-bisphosphate carboxylase/oxygenase, and the associated flow through the photorespiratory pathway. All these aspects of the photosynthetic network have been the subject of recently published metabolic engineering approaches in model species. Together, the novel results raise hopes that engineering of photosynthesis in crop species can significantly increase agricultural productivity. | 18,764,897 |
Expression of an Escherichia coli antigenic fusion protein comprising the heat labile toxin B subunit and the heat stable toxin, and its assembly as a functional oligomer in transplastomic tobacco plants. | Enterotoxigenic Escherichia coli (ETEC) strains are important pathogens in developing countries. Some vaccine formulations containing the heat labile toxin B subunit (LTB) have been used in clinical trials; however, the induction of neutralizing antibodies against the heat-stable toxin (ST), a poor immunogenic peptide, is necessary, as most ETEC strains can produce both toxins. In this study, a plant optimized synthetic gene encoding for the LTB-ST fusion protein has been introduced into plastids of tobacco leaf tissues, using biolistic microprojectile bombardment, in an effort to develop a single plant-based candidate vaccine against both toxins. Transplastomic tobacco plants carrying the LTB-ST transgene have been recovered. Transgene insertion into the plastid was confirmed by both PCR and Southern blot analysis. GM1-ELISA revealed that the LTB-ST fusion protein retained its oligomeric structure, and displayed antigenic determinants for both LTB and ST. Western blot analysis, using LTB antisera, confirmed the presence of a 17-KDa protein in transplastomic lines, with the correct antigenicity of the fusion protein. Expression levels of this fusion protein in different lines reached up to 2.3% total soluble protein. Oral immunization of mice with freeze-dried transplastomic tobacco leaves led to the induction of both serum and mucosal LTB-ST specific antibodies. Following cholera toxin challenge, a decrease of intestinal fluid accumulation was observed in mice immunized with LTB-ST-containing tobacco. These findings suggest that tobacco plants expressing LTB-ST could serve as a plant-based candidate vaccine model providing broad-spectrum protection against ETEC-induced diarrhoeal disease. | 18,764,920 |
CTD phosphatases in the attenuation of wound-induced transcription of jasmonic acid biosynthetic genes in Arabidopsis. | Trienoic fatty acids (TAs), the major constituents in plant membrane lipids, play essential roles in stress signalling as precursors of the phytohormone jasmonic acid (JA). Arabidopsis FAD7 encodes a plastidial omega-3 fatty acid desaturase, which catalyses the production of TAs. In coordination with other JA-biosynthetic genes, expression of FAD7 is induced locally by wounding. This provides a feedforward mechanism for the rapid and sustainable accumulation of JA. To identify molecular components involved in this mechanism, a transgenic Arabidopsis line carrying the FAD7 promoter (pFAD7) fused to the firefly luciferase gene (LUC) was constructed. Reciprocal crossing experiments revealed that the induction of FAD7 expression depends largely on JA biosynthesis and the SCF(COI1)-mediated signalling mechanism, whereas JA alone is insufficient for its maximal induction. Full induction required synergistic interactions between JA-dependent and -independent wound signalling mechanisms. A genetic screen for aberrant pFAD7::LUC expression yielded a recessive mutant showing enhanced wound-induced LUC bioluminescence. The mutation was associated with the cpl1 locus encoding an RNA polymerase II C-terminal domain (CTD) phosphatase, and conferred wound hyper-responsiveness on the promoters of several JA-biosynthetic genes. The picture of signalling mechanisms underlying the wound-regulated FAD7 expression, and potential roles of CPL proteins as attenuators of wound-induced JA biosynthesis, are discussed. | 18,764,923 |
Non-identical contributions of two membrane-bound cpSRP components, cpFtsY and Alb3, to thylakoid biogenesis. | The insertion of light-harvesting chlorophyll proteins (LHCPs) into the thylakoid membrane of the chloroplast is cpSRP-dependent, and requires the stromal components cpSRP54 and cpSRP43, the membrane-bound SRP receptor cpFtsY and the integral membrane protein Alb3. Previous studies demonstrated that the Arabidopsis mutant lacking both cpSRP54 and cpSRP43 had pale yellow leaves, but was viable, whereas the mutants lacking Alb3 exhibit an albino phenotype that is more severe and seedling lethality. We previously showed that a maize mutant lacking cpFtsY had a pale yellow-green phenotype and was seedling lethal. To compare the in vivo requirements of cpFtsY and Alb3 in thylakoid biogenesis in greater detail, we isolated Arabidopsis null mutants of cpftsY, and performed biochemical comparisons with the Arabidopsis alb3 mutant. Both cpftsY and alb3 null mutants were seedling lethal on a synthetic medium lacking sucrose, whereas on a medium supplemented with sucrose, they were able to grow to later developmental stages, but were mostly infertile. cpftsY mutant plants had yellow leaves in which the levels of LHCPs were reduced to 10-33% compared with wild type. In contrast, alb3 had yellowish white leaves, and the LHCP levels were less than or equal to 10% of those of wild type. Intriguingly, whereas accumulation of the Sec and Tat machineries were normal in both mutants, the Sec pathway substrate Cyt f was more severely decreased in the cpftsY mutant than in alb3, which may indicate a functional link between cpFtsY and Sec translocation machinery. These results suggest that cpFtsY and Alb3 have essentially similar, but slightly distinct, contributions to thylakoid biogenesis. | 18,764,927 |
Evidence that the Amyloid beta Precursor Protein-intracellular domain lowers the stress threshold of neurons and has a "regulated" transcriptional role. | Regulated intramembrane proteolysis of the beta-amyloid precursor protein by the gamma-secretase yields two peptides. One, amyloid-beta, is the major component of the amyloid plaques found in Alzheimer's disease patients. The other, APP IntraCellular Domain, has been involved in regulation of apoptosis, calcium flux and gene transcription. To date, a few potential target genes transcriptionally controlled by AID, alone or complexed with Fe65/Tip60, have been described. Although the reports are controversial: these include KAI1, Neprilysin, p53, EGFR, LRP and APP itself. Furthermore, p53 has been implicated in AID mediated susceptibility to apoptosis. To extend these findings, and assess their in vivo relevance, we have analyzed the expression of the putative target genes and of the total brain basal transriptoma in transgenic mice expressing AID in the forebrain. Also, we have studied the susceptibility of primary neurons from such mice to stress and pro-apoptotic agents. We found that AID-target genes and the mouse brain basal transcriptoma are not influenced by transgenic expression of AID alone, in the absence of Fe65 over-expression. Also, experiments conducted on primary neurons from AID transgenic mice, suggest a role for AID in sensitizing these cells to toxic stimuli. Overall, these findings hint that a role for AID, in regulating gene transcription, could be induced by yet undefined, and possibly stressful, stimuli in vivo. Overall, these data suggest that the release of the APP intracellular domain may modulate the sensitivity of neuronal cells to toxic stimuli, and that a transcriptional role of AID could be inscribed in signaling pathways thatare not activated in basal conditions. | 18,764,939 |
Male-killing endosymbionts: influence of environmental conditions on persistence of host metapopulation. | Male killing endosymbionts manipulate their arthropod host reproduction by only allowing female embryos to develop into infected females and killing all male offspring. Because of the reproductive manipulation, we expect them to have an effect on the evolution of host dispersal rates. In addition, male killing endosymbionts are expected to approach fixation when fitness of infected individuals is larger than that of uninfected ones and when transmission from mother to offspring is nearly perfect. They then vanish as the host population crashes. High observed infection rates and among-population variation in natural systems can consequently not be explained if defense mechanisms are absent and when transmission efficiency is perfect. By simulating the host-endosymbiont dynamics in an individual-based metapopulation model we show that male killing endosymbionts increase host dispersal rates. No fitness compensations were built into the model for male killing endosymbionts, but they spread as a group beneficial trait. Host and parasite populations face extinction under panmictic conditions, i.e. conditions that favor the evolution of high dispersal in hosts. On the other hand, deterministic 'curing' (only parasite goes extinct) can occur under conditions of low dispersal, e.g. under low environmental stochasticity and high dispersal mortality. However, high and stable infection rates can be maintained in metapopulations over a considerable spectrum of conditions favoring intermediate levels of dispersal in the host. Male killing endosymbionts without explicit fitness compensation spread as a group selected trait into a metapopulation. Emergent feedbacks through increased evolutionary stable dispersal rates provide an alternative explanation for both, the high male-killing endosymbiont infection rates and the high among-population variation in local infection rates reported for some natural systems. | 18,764,948 |
Simultaneous circulation of genotypes I and III of dengue virus 3 in Colombia. | Dengue is a major health problem in tropical and subtropical regions. In Colombia, dengue viruses (DENV) cause about 50,000 cases annually, 10% of which involve Dengue Haemorrhagic Fever/Dengue Shock Syndrome. The picture is similar in other surrounding countries in the Americas, with recent outbreaks of severe disease, mostly associated with DENV serotype 3, strains of the Indian genotype, introduced into the Americas in 1994. The analysis of the 3'end (224 bp) of the envelope gene from 32 DENV-3 strains recently recovered in Colombia confirms the circulation of the Indian genotype, and surprisingly the co-circulation of an Asian-Pacific genotype only recently described in the Americas. These results have important implications for epidemiology and surveillance of DENV infection in Central and South America. Molecular surveillance of the DENV genotypes infecting humans could be a very valuable tool for controlling/mitigating the impact of the DENV infection. | 18,764,951 |
Traumatic brain injury in young children: postacute effects on cognitive and school readiness skills. | Previous studies have documented weaknesses in cognitive ability and early academic readiness in young children with traumatic brain injury (TBI). However, few of these studies have rigorously controlled for demographic characteristics, examined the effects of TBI severity on a wide range of skills, or explored moderating influences of environmental factors on outcomes. To meet these objectives, each of three groups of children with TBI (20 with severe, 64 with moderate, and 15 with mild) were compared with a group of 117 children with orthopedic injuries (OI group). The children were hospitalized for their injuries between 3 and 6 years of age and were assessed an average of 1 1/2 months post injury. Analysis revealed generalized weaknesses in cognitive and school readiness skills in the severe TBI group and less pervasive effects of moderate TBI. Indices of TBI severity predicted outcomes within the TBI sample and environmental factors moderated the effects of TBI on some measures. The findings document adverse effects of TBI in early childhood on postacute cognitive and school readiness skills and indicate that these effects are related to both injury severity and the family environment. | 18,764,969 |
Cognitive and adaptive deficits in young children with Duchenne muscular dystrophy (DMD). | The goal of the current investigation was to examine adaptive behavior and cognitive skills in young children with Duchenne muscular dystrophy (DMD), a genetic disorder that causes progressive muscular weakness and concomitant cognitive deficits. Previous studies have documented specific language deficits in older children with DMD, but there are limited data on younger children. Twenty children with DMD who were between 3 and 6 years old and 20 unaffected family control children were recruited. Parents completed questionnaires relating to development and adaptive functioning, while children completed neuropsychological testing. Results of paired t tests indicate that children with DMD are rated as delayed relative to familial controls on measures of adaptive functioning, as assessed by the Vineland Adaptive Behavior Scales. Furthermore, children with DMD exhibit impairments on multiple measures of cognition, including measures of receptive language, expressive language, visuo-spatial skills, fine-motor skills, attention, and memory skills. Across all domains examined, the young children with DMD performed more poorly than their familial controls. These deficits appear to be more generalized than those reported in older children with this disorder. Dystrophin, a missing protein product, is hypothesized to be responsible for these cognitive and behavioral impairments. | 18,764,980 |
Directed forgetting in depression. | Subjects with depression exhibit deficits in prefrontal function. We posited that as a result, in a supraspan memory test, they would be impaired in their ability to inhibit recall of irrelevant words, and because of consequent overload of working and episodic memory capacity, would be impaired in their ability to recall relevant words. We tested this hypothesis in 30 inpatients and outpatients with a diagnosis of major depressive disorder and 30 controls subjects using a form of the Directed Forgetting Paradigm using exclusively neutral words. The depressed subjects did exhibit deficits in prefrontal function. All subjects were given four lists of 24 items each, in which half the words were followed by the instruction and half by the instruction Our hypothesis found support in a significant group by item type interaction effect exhibited when subjects were instructed to recall only those items followed by the instruction: depressed subjects recalled relatively more words to be forgotten and relatively fewer words to be remembered. A control experiment suggested that these results could not be accounted for by a differential effect of depression on memory encoding. | 18,764,986 |
[Risk behaviors for sexually transmitted diseases among truck drivers in Brazil]. | To evaluate the frequency of sexually transmitted diseases (STD) and associated risk factors based on self-reporting by long-haul truck drivers in Brazil. From October 2005-October 2006, 641 long-haul truck drivers that travel federal highway BR-153, traversing the country from south to north, were interviewed. A structured interview was used to collect sociodemographic data. The truck drivers also completed a self-administered questionnaire on risk behaviors and STD history. The data were adjusted and analyzed using logistic regression. Of 641 drivers interviewed, 620 (96.7%) provided answers on STD history. Of these, 35.6% (95% confidence interval (CI) = 31.9-39.6) reported past or current STD. Being 30 years of age or older was statistically associated with having a history of STD. In addition, truck drivers who reported using amphetamines (odds ratio (OR) = 1.7; 95%CI = 1.1-2.6), having been incarcerated (OR = 2.2; 95%CI = 1.2-4.2), and sexual relations with sex professionals (OR = 1.9; 95%CI = 1.3-2.8) had increased odds for having a history of STD. These results confirm that Brazilian truck drivers are highly vulnerable to STD and show the importance of prevention programs targeting this specific group, one that is constantly on the move and may efficiently disseminate STD. | 18,764,991 |
Expression analysis of TFIID in single human oocytes: new potential molecular markers of oocyte quality. | Molecular characterization of human female gametes should make it easier to understand the basis of certain infertility disorders. Biologically significant mRNAs have been analysed in single oocytes to search for molecular biomarkers of oocyte quality. Initial analysis was focused on mRNA for proteins involved in cell growth and cycle control, specifically those encoding members of the general transcription apparatus such as the subunits of the general transcription factor TFIID. This heteromultimeric protein, comprising about 15 subunits, is the most important general transcription factor of the second class. These proteins are essential for the initiation of transcription of protein-coding genes, so they must be present in mature oocytes for mRNA synthesis during the first phases of embryonic development. Semi-quantitative reverse transcriptionpolymerase chain reaction was used to identify different TFIID subunits in single oocytes and to search for differences in expression as compared with control tissues. The data show that the mRNAs for most TFIID subunits are indeed synthesized in oocytes, but their expression profiles differ markedly. TATAbox-binding protein associated factor 4B (TAF4B), TAF5 and TATAbox-binding protein-like 2 (TBPL2) are expressed at higher levels in oocytes than in control tissues. It is suggested that they could be used as biomarkers of oocyte quality. | 18,765,004 |
Workload and resource implications of upper gastrointestinal cancer surgical centralisation in South East Wales. | The aim of this study was to determine whether one specialist unit could manage all patients diagnosed with oesophagogastric cancer in Gwent and Cardiff and Vale NHS Trusts over a 6-month period with regard to workload, resource and training opportunities. All patients diagnosed with oesophagogastric (OG) cancer in Gwent and Cardiff and Vale NHS Trusts and referred to the regional South East Wales Upper GI multidisciplinary team over the 6-month period from 1 July to 31 December 2005 were studied prospectively and compared with the previous 6-month caseload at Cardiff and Vale. Out-patient workload increased from 160 new (33 OG cancers) and 533 follow-up patients (161 OG cancers) between 1 January and 30 June 2005, to 290 new (68 OG cancers, 106% increase) and 865 follow-up patients (230 OG cancers, 43% increase) between 1 July, and 31 December 2005. The number of patients undergoing radical surgery increased from 14 to 23 (D2 gastrectomy 8 versus 13; oesophagectomy 6 versus 10). Cancer-related workload in the latter period generated 118 intermediate equivalents (IEs) of operative work for two specialist surgeons and one SpR occupying 38% of the total time available on 104 scheduled operating lists, compared with 64 IEs in the previous 6 months, representing an 84% increase in cancer-related operative training opportunities. Centralisation of oesophagogastric cancer surgery is feasible and desirable if national guidelines are to be satisfied, and this strategy has significant positive implications for surgical training and audit. | 18,765,024 |
Laparoscopically assisted vaginal hysterectomy versus vaginal hysterectomy for enlarged uterus. | To compare the surgical and immediate postoperative outcomes for vaginal hysterectomy (VH) with those for laparoscopically assisted vaginal hysterectomy (LAVH) in patients with enlarged myomatous uterus. Eighty women requiring hysterectomy for an enlarged myomatous uterus were randomly allocated into 2 treatment arms: VH (n=40) and LAVH (n=40). The randomization procedure was based on a computer-generated list. The primary outcome was a comparison of the discharge times between the 2 procedures. Continuous outcome variables were analyzed using the Student t test. Discrete variables were analyzed with the chi-square test or Fisher's exact test. P<0.05 was considered statistically significant. The mean discharge time was longer for LAVH than for VH (72+/-4.2 vs 48+/-2.6 h; P=0.00). VH resulted in shorter times for paralytic ileus (19+/-3 vs 26+/-3 h; P=0.00) and surgery (71+/-3 vs 129+/-7 min; P=0.00). The intraoperative blood loss was less with VH (186.0+/-52 vs 362.7+/-65 mL; P=0.00). No intraoperative complications occurred, and no patient was returned to the operative theater in either group. Several surgical and immediate postoperative outcomes were significantly better in the VH group than in the LAVH group. However, further controlled prospective studies are required for identifying the best approach for hysterectomy in patients with enlarged uterus. | 18,765,046 |
Robot-assisted laparoscopic ileal ureter. | A patient with a solitary kidney, cysteine stones, and recurrent ureteral strictures underwent robot-assisted laparoscopic ureterectomy with ileal ureter formation. Using a transperitoneal, 4-port robotic approach, we removed the strictured ureter and created an ileal ureter. The ileal-pyelo and ileal-vesical anastomoses were performed using the robotic system. An extracorporeal bowel anastomosis was performed using stapling devices. Operative time was 9 hours with negligible blood loss, and the patient was discharged after 5 days. A cystogram at 10 days demonstrated patent anastomoses without extravasation. The patient continues to do well 48 months later. Robot-assisted laparoscopic ileal ureter replacement is feasible with excellent long-term outcome. | 18,765,059 |
Laparoscopic management of small bowel intussusception in a 16-year-old with Peutz-Jeghers syndrome. | Peutz-Jeghers is a rare autosomal dominant disorder characterized by hamartomatous polyps and discoloration of mucosal membranes. The polyps can occur anywhere in the gastrointestinal tract and can grow large enough to cause bowel obstructions. A 16-year-old male presented to the emergency department with signs and symptoms of an acute bowel obstruction. He had 2 days of abdominal pain, obstipation, and vomiting. He had a previous history of a colonoscopy with polypectomy at age 4, and hyperpigmentation of his mucous membranes. Computed tomographic (CT) scan revealed an intussusception of the small intestine. An exploratory laparoscopy found an intussusception of the mid jejunum. A laparoscopic-assisted small bowel resection was performed. Pathology showed a 5-cm polyp that acted as a lead point for the intussusception. Colonoscopy and upper endoscopy revealed 5 more polyps in the stomach and colon that were removed. Small bowel obstructions can be managed successfully with minimally invasive approaches. The treatment of obstruction in these patients is to remove the offending hamartomatous polyp(s). The rest of the intestine needs to be examined and those polyps found should be removed. This can be done intraoperatively with laparoscopic-assisted enteroscopy and colonoscopy. | 18,765,065 |
Laparoscopic resection of a virilizing adrenocortical tumor. | Virilizing adrenocortical tumors are rare. Laparoscopic unilateral adrenalectomy with serum androgen surveillance may provide curative treatment for benign, functional adenomas. Herein, we describe a case of laparoscopic resection of a testosterone-producing adrenal tumor in a sixteen-year-old female. | 18,765,068 |
Insights into natriuretic peptides in heart failure: an update. | Natriuretic peptides (NPs) secreted by the heart in response to volume overload are pleiotropic molecules with vasodilating, diuretic, natriuretic, antiproliferative, and antifibrotic actions. Functioning of the NP system is altered in congestive heart failure (CHF), suggesting that support of the NP system might be beneficial in treatment of acute and chronic CHF. Several approaches alone or in combination with other pharmacologic therapies have been shown to enhance function of the NP system: direct administration of native and designer NPs, inhibition of degradation of NPs and their second messenger (cyclic guanosine monophosphate ), and stimulation of cGMP generation. Despite increasing numbers of studies using NPs in therapy of acute and chronic CHF, several controversies regarding safety, efficacy, and dosing of NPs need to be addressed. Moreover, further research is warranted to identify the stages and etiologies of CHF that may profit from NP therapy. | 18,765,080 |
Prevention of atrial fibrillation in hypertension. | Hypertensive patients have an increased risk of developing atrial fibrillation (AF), which increases cardiovascular morbidity and mortality in this population. Primary prevention is a new strategy in treating AF; previously, it was more common to focus on preventing adverse outcomes and controlling the arrhythmia's rate and rhythm. In this review, we consider the possible preventive effects of antihypertensive treatment on new-onset AF seen in recent trials, especially with blockers of the renin-angiotensin system (RAS). Several secondary analyses of large, randomized trials regarding hypertension and heart failure have shown promising results with benefits beyond the expected blood pressure-lowering effect. A few prospective studies on prevention of AF recurrence with RAS blockade have been published, and more studies are expected to be published in the near future. | 18,765,086 |
Gram-negative endocarditis. | Aerobic gram-negative bacilli are rare causes of endocarditis. The epidemiology and risk factors for developing gram-negative endocarditis are evolving. New pathogens, some of which are multidrug resistant, are emerging. The role of nosocomial infections, particularly central venous catheter infections, is increasing. Medical and surgical outcomes appear to be improving with more effective antimicrobial therapy and aggressive surgical management. | 18,765,099 |
16S-Ribosomal DNA to diagnose culture-negative endocarditis. | Culture-negative endocarditis (CNE) accounts for 2.5% to 48% of all cases of infectious endocarditis (IE). Prior or concurrent antibiotic treatment at the time blood cultures are taken accounts for 45% to 60% cases of CNE; the remainder are caused by slow-growing and fastidious organisms. Although limited in sensitivity because of potential contaminating bacterial DNA, detection of bacterial 16S ribosomal (r) DNA (from the 16S rRNA gene) is nevertheless more sensitive than culture. It is accomplished by using polymerase chain reaction (PCR) that targets highly conserved regions of the 16S rRNA gene. The identity of noncultivated infecting agents can then be determined by sequencing PCR products and comparing them with known 16S rDNA sequences from a wide range of bacteria. This has served to broaden the etiologic diagnosis of CNE. We review the benefits and limitations of PCR to diagnose IE and we propose advances that will be necessary to secure a place for PCR in guiding therapy. | 18,765,101 |
Acute disseminated encephalomyelitis. | Acute disseminated encephalomyelitis (ADEM) is a demyelinating syndrome of the central nervous system. It is considered to be an autoimmune response to an antecedent antigenic stimulus, most frequently a prior infectious illness (postinfectious encephalitis) or immunization (postvaccination encephalitis) occurring in the days or weeks before neurologic illness. Clinically, ADEM is characterized by encephalopathy, or focal/multifocal neurologic signs; brain MRI is characterized by diffuse multifocal or patchy areas of demyelination. The differentiation between ADEM and a first episode of multiple sclerosis, a chronic central nervous system demyelinating disease, may be difficult but has important prognostic and treatment implications. Although no clinical trials have assessed the efficacy of treatment modalities in patients with ADEM, immunomodulators, including corticosteroids and intravenous immunoglobulin, are frequently used empirically. ADEM outcome is generally favorable, with resolution over weeks to months. | 18,765,104 |
Growth factors in benign prostatic hyperplasia: basic science implications. | Benign prostatic hyperplasia (BPH) is the most common proliferative disease of the prostate of men in the United States. The histopathology of BPH strongly implicates local paracrine and autocrine growth factors and inflammatory cytokines in its pathogenesis. A complex milieu of growth-regulatory proteins includes members of the fibroblast, insulin-like, and transforming growth factor families. It appears that these proteins and downstream effector molecules, in addition to a variety of interleukins, are overexpressed in BPH and, working together, create a landscape of increased stromal and epithelial growth and mesenchymal transdifferentiation that leads to disease progression. Inflammation, commonly present in BPH, may contribute to tissue injury, and cytokines produced by inflammatory cells may serve to drive local growth factor production and angiogenesis in the tissues as a "wound healing" response. As we begin to unravel the precise mechanisms involved, new treatments for BPH aimed at these interacting pathways may emerge. | 18,765,125 |
Combination 5-alpha-reductase inhibitors and alpha-blockers for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. | Open or transurethral resection of the prostate was once the only option for men afflicted with symptomatic benign prostatic hyperplasia (BPH). In the past 10 to 15 years, however, medical management has become a common step in the treatment of BPH, often postponing or eliminating the need for surgical intervention. The two drug classes used in the medical management of BPH are alpha-blockers and 5-alpha-reductase inhibitors. This paper reviews major studies related to the use of these medications in combination and discusses patient populations best served by combination therapy. | 18,765,128 |
Central mechanisms in the maintenance of chronic widespread noninflammatory muscle pain. | Chronic widespread pain (CWP) conditions such as fibromyalgia and myofascial syndromes are characterized by generalized pain, tenderness, morning stiffness, disturbed sleep, and pronounced fatigue. However, CWP pathophysiology is still unclear. A number of hypotheses have been proposed as the underlying pathophysiology of CWP: muscular dysfunction/ischemia, central sensitization, and a deficit in endogenous pain-modulating systems. This article reviews the current and emerging literature about the pathophysiology and neurobiology of chronic widespread -musculoskeletal pain. Widespread musculoskeletal pain results in changes in the central nervous system in human subjects and animal models. These changes likely reflect alterations in supraspinal modulation of nociception, and include increases in excitatory and decreases in inhibitory modulation pathways. These alterations in excitation and inhibition likely drive changes observed in the spinal cord to result in central sensitization, and the consequent pain and hyperalgesia. | 18,765,138 |
Prevalence and geographic distribution of childhood obesity in China in 2005. | China now joins the world epidemic of childhood obesity. Because of the large disparity of environmental conditions across various sub-populations, accurate prevalence of obesity/overweight cannot be estimated by population-based approaches. Using a resident-based targeted approach, we determined the geographical distribution of childhood obesity in China and analyzed the specific factors related to the increasing prevalence of obesity in each of its ten regions. An alarming increase in the prevalence of obesity has spread all over China, except for the poverty western rural areas. In 2005, the prevalence of combined childhood overweight and obesity in China reached 32.5% for males and 17.6% for females in the northern coastal big cities, suggesting that the obesity prevalence in some urban Chinese populations has approached that of the developed countries. The prevalence of obesity in the affluent rural sub-populations first exceeded that in some urban populations; then, as they learned their lessons and revised their lifestyles, the prevalence declined to a lower level approaching that of the transitional societies of other countries. The geographical distribution of obesity prevalence in China is mainly caused by the large disparity in the socioeconomic status related to dietary and lifestyle changes in modern China. Multiple and integrated interventions are urgently needed to halt the epidemic of childhood obesity by tackling its basic causes such as fast food, automobiles, television and lack of exercise. The differing prevalences in different regions of China offer an opportunity to reverse this alarming, growing epidemic of childhood obesity in the world's most populous country. | 18,765,165 |
Practical guide for three-dimensional transthoracic echocardiography using a fully sampled matrix array transducer. | Real-time three-dimensional (3D) echocardiography is a major innovation in the history of cardiovascular ultrasound. Advances in computer and transducer technologies, especially the fully-sampled matrix array transducer, have permitted real-time 3D image acquisition and display. Several vendors provide 3D imaging but use different terminology for similar functions, creating confusion for consumers. This article provides a practical guide on how to acquire and analyze 3D images on-cart using currently available ultrasound systems (iE33, Philips Medical System, Andover, MA; Vivid7, GE Healthcare, Wauwatosa, WI) in daily clinical practice. | 18,765,173 |
Low-flow perfusion of guinea pig isolated hearts with 26 degrees C air-saturated Lifor solution for 20 hours preserves function and metabolism. | Donor human hearts cannot be preserved for >5 hours between explantation and recipient implantation. A better approach is needed to preserve transplantable hearts for longer periods, ideally at ambient conditions for transport. We tested whether Lifor solution could satisfactorily preserve guinea pig isolated hearts perfused at low flow with no added oxygen at room temperature for 20 hours. Hearts were isolated from 18 guinea pigs and perfused initially with oxygenated Krebs-Ringer (KR) solution at 37 degrees C. Hearts were then perfused with recirculated Lifor or cardioplegia (CP) solution (K(+) 15 mmol/liter) equilibrated with room air at 20% of control flow at 26 degrees C for 20 hours. Hearts were then perfused at 100% flow with KR for 2 hours at 37 degrees C. Lifor and CP arrested all hearts. During the 20-hour low-flow perfusion with Lifor coronary pressure increased by 6 +/- 2 mm Hg and percent oxygen extraction by 29 +/- 2%, whereas oxygen consumption (MVo(2)) decreased by 74 +/- 4%. Similar changes were noted for CP, except that MVo(2) was decreased by 86 +/- 7%. After 20-hour low-flow perfusion with Lifor and 2 hours of warm reperfusion with KR solution, diastolic left ventricular pressure (LVP), maximal dLVP/dt and percent oxygen extraction returned completely to baseline values, whereas heart rate returned to 80 +/- 3%, developed LVP to 76 +/- 3%, minimal dLVP/dt (relaxation) to 65 +/- 4%, coronary flow to 80 +/- 4%, oxygen consumption to 82 +/- 4% and cardiac efficiency to 85 +/- 4% of baseline values. Flow responses to adenosine and nitroprusside after Lifor treatment were 65 +/- 3% and 64 +/- 3% of their baseline values. After cardioplegia, treatment there was no cardiac activity, with a diastolic pressure of 35 +/- 14 mm Hg and a return of coronary flow to only 45 +/- 3% of baseline value. Compared with a cardioplegia solution at ambient air and temperature conditions, Lifor solution is a much better medium for long-term cardiac preservation in this model. | 18,765,194 |
Non-heart-beating lung donation: how big is the pool? | Lungs from non-heart-beating (NHB) donors are seldom used in The Netherlands despite the good quality of these organs. Based on a retrospective analysis of 162 NHB donor procedures we found that only 5% of the lungs were actually utilized, but that 30% of the lungs were suitable for transplantation. Not recognizing the suitability of NHB lungs is likely the main reason for their non-availability. | 18,765,199 |
Genomics: risk and outcomes in cardiac surgery. | Coronary artery bypass graft surgery is associated with several frequent postoperative adverse events. Outcome prediction is valued by patients and practitioners, because it provides some measure of balancing risks and benefits and provides expensive or higher-risk therapies to individuals at highest risk. Surgeons and anesthesiologists traditionally have relied on demographic, preoperative, and intraoperative risk factors to predict outcomes after cardiac surgery. Yet, such predictions often have poor positive and negative predictive value for the individual patient. Perioperative genetics attempts to determine the impact of an individual's genetic variation on the risk of developing adverse postoperative outcomes. In this article, the authors discuss emerging evidence that a patient's genetic makeup predisposes him or her to adverse outcomes following cardiac surgery and provide examples from perioperative bleeding, myocardial injury/infarction, and atrial fibrillation. | 18,765,214 |
Hybrid coronary artery bypass grafting. | Owing to the high prevalence of atherosclerotic coronary artery disease, treatment has proceeded along three separate paths: medical, surgical, and percutaneous intervention. Medical treatment is now routinely combined with both surgical treatment and percutaneous methods; however, the surgical and percutaneous routes are often viewed as in competition. Hybrid coronary revascularization, also called robotic assisted integrated coronary revascularization (RAICER), is a way of combining these two approaches. Whether any hybrid procedure will prove beneficial to patients remains unproven; however, RAICER has promise for reducing short-term complications while providing excellent and enduring treatment for coronary artery disease. Much work remains to be done on the benefits of hybrid revascularization in comparison with conventional bypass surgery or percutaneous coronary procedures. | 18,765,217 |
A transient breach in the epithelial barrier leads to regulatory T-cell generation and resistance to experimental colitis. | Previous studies have indicated that a defective epithelial barrier leads to inflammation of the underlying lamina propria. Nevertheless, it is likely that physiologic breaks in the barrier must occur for homeostatic regulatory T cells to develop. We determined the effect of agents that disrupt epithelial tight junctions (ethanol and AT1002, a Vibrio cholerae zonula occludens toxin hexapeptide) on regulatory T-cell induction and resistance to induction of colitis by trinitrobenzene sulfonic acid (TNBS). The effects of ethanol and AT1002 on colon immune function were evaluated by their capacity to induce direct phenotypic or functional changes in effector and regulatory cell populations and their indirect effect on the development of TNBS-induced colitis. The basis of regulatory cell development was evaluated with in vitro studies of isolated dendritic cell populations. The role of innate immunity was evaluated by in vivo gene silencing studies utilizing Toll-like receptor (TLR)-2-specific small interfering RNA (siRNA). Both ethanol and AT1002 induced persistent latency-associated peptide-positive CD4(+) regulatory T cells that, as shown in adoptive transfer studies, render mice resistant to the induction of TNBS colitis. The development of these cells requires the presence of an intact microflora and the activity of CD11c(+) dendritic cells. Their induction is also influenced by innate immune factors operating through TLR-2, because attenuation of TLR-2 signaling by in vivo TLR-2 siRNA administration prevents their development. A mild and/or transient breach in epithelial barrier function leads to dominant regulatory T-cell responses that protect the mucosa from inflammation. | 18,765,239 |
Circulating prolactin, MPOA prolactin receptor expression and maternal aggression in lactating rats. | Maternal aggression is most intense in lactating rats from the 3rd to the 12th day postpartum. The purpose of this study was to determine if plasma prolactin (PRL) and prolactin receptor (PRL-R(L)) mRNA expression in the medial preoptic area (MPOA) of lactating rats are altered in association with maternal aggression. Lactating Sprague Dawley rats were divided into five groups and exposed for 10 min to an intruder male or to an object on postpartum day 8. Trunk blood and the brain of the dams were collected 30 or 240 min after exposure and from a non-exposed group. Lower levels of prolactin were found 30 min after the aggression test. No change was detected in the number of cells expressing PRL-R(L) mRNA by in situ hybridization histochemistry (ISHH) as a function of testing. However, the correlation between plasma PRL and PRL-R(L) mRNA expression in the mothers changed from positive in control females to negative in intruder exposed animals. These data support the concept that a maternal aggressive experience, while acutely altering PRL secretion, fails to affect PRL-R(L) mRNA expression. | 18,765,257 |
One-step isolation of plasma membrane proteins using magnetic beads with immobilized concanavalin A. | We have developed a simple method for isolating and purifying plasma membrane proteins from various cell types. This one-step affinity-chromatography method uses the property of the lectin concanavalin A (ConA) and the technique of magnetic bead separation to obtain highly purified plasma membrane proteins from crude membrane preparations or cell lines. ConA is immobilized onto magnetic beads by binding biotinylated ConA to streptavidin magnetic beads. When these ConA magnetic beads were used to enrich plasma membranes from a crude membrane preparation, this procedure resulted in 3.7-fold enrichment of plasma membrane marker 5'-nucleotidase activity with 70% recovery of the activity in the crude membrane fraction of rat liver. In agreement with the results of 5'-nucleotidase activity, immunoblotting with antibodies specific for a rat liver plasma membrane protein, CEACAM1, indicated that CEACAM1 was enriched about threefold relative to that of the original membranes. In similar experiments, this method produced 13-fold enrichment of 5'-nucleotidase activity with 45% recovery of the activity from a total cell lysate of PC-3 cells and 7.1-fold enrichment of 5'-nucleotidase activity with 33% recovery of the activity from a total cell lysate of HeLa cells. These results suggest that this one-step purification method can be used to isolate total plasma membrane proteins from tissue or cells for the identification of membrane biomarkers. | 18,765,283 |
Endoplasmic reticulum stress underlying the pro-apoptotic effect of epigallocatechin gallate in mouse hepatoma cells. | It has been recently reported that tea flavanols, including epigallocatechin gallate (EGCG), efficiently inhibit glucosidase II in liver microsomes. Since glucosidase II plays a central role in glycoprotein processing and quality control in the endoplasmic reticulum we investigated the possible contribution of endoplasmic reticulum stress and unfolded protein response (UPR) to the pro-apoptotic activity of EGCG in mouse hepatoma cells. The enzyme activity measurements using 4-methylumbelliferyl-alpha-d-glucopyranoside substrate confirmed the inhibition of glucosidase II in intact and alamethicin-permeabilized cells. EGCG treatment caused a progressive elevation of apoptotic activity as assessed by annexin staining. The induction of CHOP/GADD153, the cleavage of procaspase-12 and the increasing phosphorylation of eIF2alpha were revealed in these cells by Western blot analysis while the induction of endoplasmic reticulum chaperones and foldases was not observed. Time- and concentration-dependent depletion of the endoplasmic reticulum calcium stores was also demonstrated in the EGCG-treated cells by single-cell fluorescent detection. The massive alterations in the endoplasmic reticulum morphology revealed by fluorescent microscopy further supported the development of UPR. Collectively, our results indicate that EGCG interferes with protein processing in the endoplasmic reticulum presumably due to inhibition of glucosidase II and that the stress induces an incomplete unfolded protein response with dominantly pro-apoptotic components. | 18,765,294 |
Gimbals in the insect leg. | We studied the common kinematic features of the coxa and trochanter in cursorial and raptorial legs, which are the short size of the podomers, predominantly monoaxial joints, and the approximate orthogonality of adjacent joint axes. The chain coxa-trochanter with its short elements and serial orthogonality of joint axes resembles the gimbals which combine versatility and tolerance to external perturbations. The geometry of legs was studied in 23 insect species of 12 orders. Insects with monoaxial joints were selected. The joint between the trochanter and the femur (TFJ) is defined either by two vestigial condyles or by a straight anterior hinge. Direction of the joint axes in the two basal podomers was assessed by 3D measurements or by goniometry in two planes. Length of the coxa is <15% (mostly <8%) of the total length of the cursorial leg, that of the trochanter <10%. Angles between the proximal and distal joint axes in the middle coxa range from 124 to 84 degrees (mean 97+/-14 degrees ), in the trochanter (in all legs studied) from 125 to 72 degrees (mean 90+/-13 degrees ). Vectors of the distal axis in the coxa are concentrated about the normal to the plane defined by the proximal axis and the midpoint between the distal condyles. These vectors in the trochanter lie at various angles to the normal; angles are correlated with the direction of the TFJ relative to the femur. Range of reduction about the TFJ is over 60 degrees in the foreleg of Ranatra linearis, Mantispa lobata and the hind leg in Carabus coriaceus (confirming observations of previous authors), 40-60 degrees in the foreleg of Vespa crabro and in the middle one in Ammophila campestris, 10-30 degrees in other studied specimens. The special role of the trochanter in autotomy and in active propulsion in some insect groups is discussed. The majority of insects possess small trochanters and slightly movable TFJs with the joint axis laying in the femur-tibia plane. We pose the hypothesis that the TFJ damps external forces, the vectors of which lie off the femur-tibia plane, the reductor muscle acting as a spring. Thus the TFJ contributes to dynamic stability of legged locomotion. | 18,765,299 |
Bortezomib and the increased incidence of herpes zoster in patients with multiple myeloma. | Bortezomib has significantly advanced the treatment of patients with multiple myeloma (MM). However, considering that most patients with MM are elderly, bortezomib-related morbidity should be thoroughly studied to ensure the safe use of this drug. Herpes zoster has been reported as a possible adverse event associated with bortezomib because a major target of bortezomib, nuclear factor-kappaB, is known to be involved with T-cell immunity. We performed a retrospective analysis of the incidence of herpes zoster among 282 patients treated with a bortezomib-containing regimen. During the patients' pre-bortezomib treatment (median, 2.14 years), the incidence of herpes zoster was 11% (31 of 282 patients). However, after the patients were treated with bortezomib, the incidence increased to 22.3% (63 of 282 patients), of which almost all occurrences were within the first 3 cycles (median duration, 41 days). The time interval from diagnosis to bortezomib initiation date was shorter in herpes zoster-positive patients than in herpes zoster-negative patients (2.14 +/- 1.87 years vs. 3.38 +/- 2.95 years; P = .002). Disease duration, previous herpes zoster infection, disease stage and type of myeloma, and the type and intensity of previous treatments failed to show any relationship with herpes zoster. These findings suggest that longer history of disease and treatments did not affect the occurrence of herpes zoster, nor did the type of bortezomib regimens or their toxicities. Bortezomib can increase the incidence of herpes zoster regardless of disease duration, previous treatments, and concomitantly administered drugs. Thus, the occurrence of herpes zoster should be monitored during bortezomib treatment. | 18,765,311 |
Genome size and wing parameters in passerine birds. | Despite their status as the most speciose group of terrestrial vertebrates, birds exhibit the smallest and least variable genome sizes among tetrapods. It has been suggested that this is because powered flight imposes metabolic constraints on cell size, and thus on genome size. This notion has been supported by analyses of genome size and cell size versus resting metabolic rate and other parameters across birds, but most previous studies suffer from one or more limitations that have left the question open. The present study provides new insights into this issue through an examination of newly measured genome sizes, nucleus and cell sizes, body masses and wing parameters for 74 species of birds in the order Passeriformes. A positive relationship was found between genome size and nucleus/cell size, as well as between genome size and wing loading index, which is interpreted as an indicator of adaptations for efficient flight. This represents the single largest dataset presented for birds to date, and is the first to analyse a distinctly flight-related parameter along with genome size using phylogenetic comparative analyses. The results lend additional support to the hypothesis that the small genomes of birds are indeed related in some manner to flight, though the mechanistic and historical bases for this association remain an interesting area of investigation. | 18,765,340 |
New Caledonia: a very old Darwinian island? | New Caledonia has generally been considered a continental island, the biota of which largely dates back to Gondwanan times owing to its geological origin and the presence of phylogenetic relicts. This view is contradicted by geological evidence indicating long Palaeocene and Eocene submersions and by recent biogeographic and phylogenetic studies, with molecular or geophysical dating placing the biota no older than the Oligocene. Phylogenetic relicts do not provide conclusive information in this respect, as their presence cannot be explained by simple hypotheses but requires assumption of many ad hoc extinction events. The implication of this new scenario is that all the New Caledonian biota colonized the island since 37 Ma Local richness can be explained by local radiation and adaptation after colonization but also by many dispersal events, often repeated within the same groups of organisms. Local microendemism is another remarkable feature of the biota. It seems to be related to recent speciation mediated by climate, orography, soil type and perhaps unbalanced biotic interactions created by colonization disharmonies. New Caledonia must be considered as a very old Darwinian island, a concept that offers many more fascinating opportunities of study. | 18,765,357 |
Cryptic diversity, molecular phylogeny and biogeography of the rock- and leaf litter-dwelling land snails of Belau (Republic of Palau, Oceania). | The endemic diplommatinid land snails (Caenogastropoda: Mollusca) of Belau (Republic of Palau, Micronesia) are an exceptionally diverse group of largely undescribed species distributed among rock and leaf litter habitats on most of Belau's 586 islands. Diplommatinid shell morphology (e.g. shell sculpture) reflects habitat type. In this study, I analysed a subset of the 90 diplommatinid species representing a broad geographical spread of islands in order to reveal the species' phylogenetic relationships and biogeography within the Belau archipelago. Diplommatinid species from the islands of Yap, Pohnpei, Kosrae and Guam are also included in the analysis. One nuclear (28S rRNA) and two mitochondrial (16S rRNA, COI) gene regions comprising 1906bp were used for phylogenetic reconstruction. Results show that (i) the Belau Diplommatinidae are not monophyletic, as Guam and Yap species should be included as part of the radiation, (ii) Pohnpei and Kosrae species are highly divergent from Belau diplommatinids, (iii) there is little evidence for in situ radiation within individual Belau islands, (iv) spined and heavily calcified rock-dwelling species form a well-supported clade, and (v) Belau diplommatinid genera are in need of revision. | 18,765,361 |
Characterization and expression of a Pinus radiata putative ortholog to the Arabidopsis SHORT-ROOT gene. | We characterized a Pinus radiata D. Don putative ortholog to the Arabidopsis thaliana (L.) Heynh. SHORT--ROOT gene (AtSHR) and analyzed its expression in different organs during vegetative development and in response to exogenous auxin during adventitious rooting. The predicted protein sequence contained domains characteristic of the GRAS protein family and showed a strong similarity to the SHORT--ROOT (SHR) proteins. Quantitative reverse transcriptase--polymerase chain reaction (qRT-PCR) and in situ hybridization showed that the gene is predominantly expressed in roots, root primordia and in the cambial region of hypocotyl cuttings. Increased mRNA levels were observed, independently of the presence or absence of exogenous auxin, in the cambial region and rooting competent cells of hypocotyl cuttings within the first 24 h of adventitious rooting, before the activation of cell divisions and the organization of the adventitious root meristem. The expression pattern in organs and during adventitious rooting was similar to that of a Pinus radiata SCARECROW-LIKE (PrSCL1) gene, except that PrSCL1 is induced in response to exogenous auxin. Results suggest that the Pinus radiata SHORT-ROOT (PrSHR) gene has a role in root meristem formation and maintenance and in the cambial region of hypocotyl cuttings. | 18,765,368 |
Water stress responses of two Mediterranean tree species influenced by native soil microorganisms and inoculation with a plant growth promoting rhizobacterium. | Soil microorganisms, such as plant growth-promoting rhizobacteria (PGPR), play crucial roles in plant growth, but their influence on plant water relations remains poorly explored. We studied the effects of native soil microorganisms and inoculation with the PGPR strain Aur6 of Pseudomonas fluorescens on water stress responses of seedlings of the drought-avoiding Pinus halepensis Mill. and the drought-tolerant Quercus coccifera L. Plant growth, nutrient concentrations and physiology (maximum photochemical efficiency of photosystem II (PSII; F(v)/F(m)), electron transport rate (ETR), stomatal conductance (g(s)) and predawn shoot water potential (Psi(PD))) were measured in well-watered plants, and in plants under moderate or severe water stress. Inoculation with PGPR and native soil microorganisms improved tree growth, and their interactions had either additive or synergistic effects. Both F(v)/F(m) and ETR were significantly affected by PGPR and native soil microorganisms. Marked differences in g(s) and Psi(PD) were found between species, confirming that they differ in mechanisms of response to water stress. A complex tree species x treatment interactive response to drought was observed. In P. halepensis, F(v)/F(m) and ETR were enhanced by PGPR and native soil microorganisms under well-watered conditions, but the effects of PGPR on Psi(PD) and g(s) were negative during a period of water stress. In Q. coccifera, F(v)/F(m) and ETR were unaffected or even reduced by inoculation under well-watered conditions, whereas Psi(PD) and g(s) were increased by PGPR during a period of water stress. Our results indicate that microbial associates of roots can significantly influence the response of tree seedlings to drought, but the magnitude and sign of this effect seems to depend on the water-use strategy of the species. | 18,765,374 |
Hot flashes and subclinical cardiovascular disease: findings from the Study of Women's Health Across the Nation Heart Study. | Although evidence suggests adverse vascular changes among women with hot flashes, it is unknown whether hot flashes are associated with subclinical cardiovascular disease. The aim of this study was to examine relations between menopausal hot flashes and indices of subclinical cardiovascular disease. We hypothesized that women with hot flashes would show reduced flow-mediated dilation and greater coronary artery and aortic calcification compared with women without hot flashes. The Study of Women's Health Across the Nation Heart Study (2001 to 2003) is an ancillary study to the Study of Women's Health Across the Nation, a community-based cohort study. Participants were 492 women (35% black, 65% white) 45 to 58 years of age who were free of clinical cardiovascular disease and had a uterus and at least 1 ovary. Measures included a brachial artery ultrasound to assess flow-mediated dilation, electron beam tomography to assess coronary artery and aortic calcification, reported hot flashes (any/none, previous 2 weeks), and a blood sample for measurement of estradiol concentrations. Cross-sectional associations were evaluated with linear regression and partial proportional odds models. Hot flashes were associated with significantly lower flow-mediated dilation (beta=-1.01; SE, 0.41; P=0.01) and greater coronary artery (odds ratio, 1.48; 95% confidence interval, 1.04 to 2.12) and aortic (odds ratio, 1.55; 95% confidence interval, 1.10 to 2.19) calcification in age- and race-adjusted models. Significant associations between hot flashes and flow-mediated dilation (beta=-0.97; SE, 0.44; P=0.03) and aortic calcification (odds ratio, 1.63; 95% confidence interval, 1.07 to 2.49) remained in models adjusted for cardiovascular disease risk factors and estradiol. Women with hot flashes had reduced flow-mediated dilation and greater aortic calcification. Hot flashes may mark adverse underlying vascular changes among midlife women. | 18,765,392 |
Combined statin and niacin therapy remodels the high-density lipoprotein proteome. | Boosting low high-density lipoprotein (HDL) levels is a current strategy for preventing clinical events that result from cardiovascular disease. We previously showed that HDL(3) of subjects with coronary artery disease is enriched in apolipoprotein E and that the lipoprotein carries a distinct protein cargo. This observation suggests that altered protein composition might affect the antiatherogenic and antiinflammatory properties of HDL. We hypothesized that an intervention that increases HDL levels-combined statin and niacin therapy-might reverse these changes. HDL(3) isolated from 6 coronary artery disease subjects before and 1 year after combination therapy was analyzed by liquid chromatography-Fourier transform-mass spectrometry. Alterations in protein composition were detected by spectral counting and confirmed with extracted ion chromatograms. We found that combination therapy decreased the abundance of apolipoprotein E in HDL(3) while increasing the abundance of other macrophage proteins implicated in reverse cholesterol transport. Treatment-induced decreases in apolipoprotein E levels of HDL(3) were validated biochemically in a second group of 18 coronary artery disease subjects. Interestingly, the changes in HDL(3) proteome with niacin/statin treatment resulted in a protein composition that more closely resembled that of HDL(3) in healthy control subjects. Combined statin and niacin therapy partially reverses the changes in the protein composition seen in HDL(3) in coronary artery disease subjects. Our observations raise the possibility that quantifying the HDL proteome could provide insights into the therapeutic efficacy of antiatherosclerotic interventions. | 18,765,395 |
Perinatal outcome of fetal atrioventricular block: one-hundred-sixteen cases from a single institution. | Fetal atrioventricular (AV) block is an uncommon lesion with significant mortality. Because of the rarity of this disorder, the natural course, extensive evaluation of untreated fetuses, and late follow-up remain unclear. Of the 116 consecutive cases of fetal AV block studied from 1988 to 2006, only 1 was terminated, and 75% were live births. Fifty-nine cases of AV block were associated with major structural heart disease, mainly left atrial isomerism (n=40), with only 26% of neonatal survivors. Of the 57 fetuses with normal cardiac anatomy, 41 (72%) were positive for maternal antinuclear antibodies, and 32 of these seropositive mothers did not receive any treatment. This untreated group had live-birth and 1-year infant survival rates of 93% and 90% [corrected], respectively. Five fetuses from seronegative mothers showed regression to sinus rhythm during pregnancy. The presence of major structural heart disease, hydrops, an atrial rate <or=120 bpm, and a ventricular rate <or=55 bpm were identified as risk factors for mortality. Logistic regression analysis of the whole group showed that the presence of structural heart disease was the only independent predictor of death (P<0.001). This long-term study confirms that fetal AV block has a poor outcome when associated with structural heart disease and that spontaneous regression of AV block is possible in seronegative forms. The survival rate of >90% of our untreated patients with isolated forms of AV block raises concerns about any decision to intervene with immunosuppressive agents. | 18,765,396 |
Evaluating the impact of a national pilot screening programme for type 2 diabetes in deprived areas of England. | A pilot programme designed to systematically screen for type 2 diabetes was introduced in 24 general practices in England selected for their high levels of socio-economic deprivation and multi-ethnic populations. To evaluate the impact of screening on the prevalence of type 2 diabetes. A prospective audit of screening activity in pilot practices and comparison of the change in prevalence of diabetes in pilot and comparison practices were conducted. Of 41,400 individuals invited for screening from a population of 165,828 in pilot practices, 25,356 (61%) were screened. Three hundred and fifty-eight (0.22%) new cases of diabetes were detected among those screened. Only 69% of those with a positive screening test had diagnostic testing recorded and only 19% had a record of an oral glucose tolerance test. The absolute increase in the prevalence of diagnosed diabetes was 0.53% in pilot practices and 0.42% in comparison practices. The 'real world' nature of the programme and dependence on routine data collection systems makes results more difficult to interpret but also enabled problems with implementation, not evident from previous research, to be identified. It is likely that the low diagnostic yield was largely due to a high level of ad hoc screening activity outside the pilot protocol and inadequate access to diagnostic testing after a positive screening test. In particular, implementation of screening for diabetes in primary care should not be undertaken without robust assessment of the resources required for diagnostic testing and follow-up and adequate clinical audit. | 18,765,406 |
A meta-analysis on XRCC1 R399Q and R194W polymorphisms, smoking and bladder cancer risk. | To elucidate the role of X-ray repair cross-complementing group 1 (XRCC1) R399Q and R194W genotypes in bladder cancer risk, all available studies were considered in the present meta-analysis, with 4152 patients and 5372 controls for R399Q and 3215 patients and 4313 controls for R194W. Studies were identified in PubMed up to June 2008. Overall, the 399Q allele showed no significant effect on bladder cancer compared to 399R allele in all subjects. Insignificant association between R399Q and bladder cancer was observed under other genetic contrasts in worldwide population, Caucasians and never-smokers. Among ever-smokers, protective effects of 399QQ genotype were observed under recessive model [P = 0.004, fixed-effects (FEs) model odds ratio (OR) = 0.65; 95% confidence interval (CI) (0.49, 0.86), I(2) = 0% P(heterogeneity) = 0.57] and homozygote contrast (P = 0.01, FE OR = 0.66; 95% CI (0.49, 0.90), I(2) = 0%, P(heterogeneity) = 0.76). No apparent effect of 194W allele compared to 194R on bladder cancer risk was found in all subjects and Caucasians. It indicated that XRCC1 R399Q and R194W might not be risk factors to bladder cancer, but the 399QQ genotype decreased susceptibility of bladder cancer under recessive model and homozygote contrast among ever-smokers. Further studies based on larger, stratified population were required to explore the role of XRCC1 polymorphisms in bladder cancer risk. | 18,765,423 |
From the two-dimensional Th1 and Th2 phenotypes to high-dimensional models for gene regulation. | The T(h)1/T(h)2 paradigm has been used for decades to characterize phenotypically different immune responses. Recent discoveries, e.g. T(h)17 cells are adding more dimensions to the helper T cell framework, and the T(h)1/T(h)2 paradigm is currently being extended to include these new phenotypes. Previous mathematical models cannot easily be extended to accommodate these new phenotypes, and therefore these discoveries call for a new type of models. We devised a new model of helper T cell differentiation that describes expression of, and interactions between, the master regulators determining the phenotypic polarization of helper T cells. The model is able to describe any number of master regulators and is grounded on transcription factors binding promoter sites and binding each other. The model allows for stable switches between several different phenotypes. Furthermore, the model accounts for the kinetics of FoxP3 and GATA3 mRNA expression measured after stimulating naive helper (CD4+CD45RA+) T cells under various circumstances. Due to its n-dimensional character, this model may easily be applied to other developmental processes that involve master regulators. | 18,765,426 |
Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthritis; implications for pathogenesis of erosive disease. | Magnetic resonance imaging (MRI) bone oedema is an important predictor of bone erosion in rheumatoid arthritis (RA). This study aimed to determine the cellular components of MRI bone oedema, and clarify the relationship between bone erosion and MRI bone oedema. Twenty-eight bones from 11 patients with RA undergoing orthopaedic surgery were analysed by quantitative and semi-quantitative immunohistochemistry. Pre-operative contrast-enhanced MRI scans were analysed for bone oedema. The density of osteoclasts was higher in those samples with MRI bone oedema than those without MRI bone oedema (p = 0.01). Other cells identified within bone marrow included macrophages and plasma cells, and these were more numerous in samples with MRI bone oedema (p = 0.02 and 0.05 respectively). B cells were present in lower numbers, but B cell aggregates were identified in some samples with MRI bone oedema. There was a trend to increased RANKL expression in samples with MRI bone oedema (p = 0.09). Expression of RANKL correlated with the number of osteoclasts (r = 0.592, p = 0.004). The increased number of osteoclasts and RANKL expression in samples with MRI bone oedema supports the hypothesis that bone erosion in RA occurs through activation of local bone resorption mechanisms within subchondral bone as well as through synovial invasion into bone. | 18,765,428 |
Patient perspective of hand osteoarthritis in relation to concepts covered by instruments measuring functioning: a qualitative European multicentre study. | To explore whether the concepts important to patients with hand osteoarthritis (OA) are covered by the most commonly used instruments measuring functioning. A qualitative multicentre study using a focus group technique was performed in five European countries: Austria, The Netherlands, Norway, Sweden and the United Kingdom. The qualitative data analysis followed a modified form of "meaning condensation" and used the International Classification of Functioning, Disability and Health (ICF) as a theoretical framework. Finally, the concepts from the focus groups were compared with the content of the most commonly used instruments which had been identified in an earlier theoretical analysis. Fifty-six people (51 women, mean (SD) age 62.7 (7.9) years) with hand OA participated in this study in two focus groups per centre. 63 concepts were extracted from the focus groups. Twenty-one (33%) of the 63 concepts were covered by at least one instrument. Psychological consequences, different qualities of pain, aesthetic changes and leisure activities are important concepts from the focus groups which were not covered by the instruments. The qualitative analysis revealed detailed descriptions of pain-concerning sensations, levels and a certain relation to activity, none of which were fully represented in the instruments routinely used. It was possible to combine the concepts of the focus groups from each centre into a common qualitative analysis. The concepts important to people with hand OA are not fully represented in the most commonly used instruments. | 18,765,429 |
DNA replication timing is deterministic at the level of chromosomal domains but stochastic at the level of replicons in Xenopus egg extracts. | Replication origins in Xenopus egg extracts are located at apparently random sequences but are activated in clusters that fire at different times during S phase under the control of ATR/ATM kinases. We investigated whether chromosomal domains and single sequences replicate at distinct times during S phase in egg extracts. Replication foci were found to progressively appear during early S phase and foci labelled early in one S phase colocalized with those labelled early in the next S phase. However, the distribution of these two early labels did not coincide between single origins or origin clusters on single DNA fibres. The 4 Mb Xenopus rDNA repeat domain was found to replicate later than the rest of the genome and to have a more nuclease-resistant chromatin structure. Replication initiated more frequently in the transcription unit than in the intergenic spacer. These results suggest for the first time that in this embryonic system, where transcription does not occur, replication timing is deterministic at the scale of large chromatin domains (1-5 Mb) but stochastic at the scale of replicons (10 kb) and replicon clusters (50-100 kb). | 18,765,475 |
Non-parametric estimation of state occupation, entry and exit times with multistate current status data. | As a type of multivariate survival data, multistate models have a wide range of applications, notably in cancer and infectious disease progression studies. In this article, we revisit the problem of estimation of state occupation, entry and exit times in a multistate model where various estimators have been proposed in the past under a variety of parametric and non-parametric assumptions. We focus on two non-parametric approaches, one using a product limit formula as recently proposed in Datta and Sundaram(1) and a novel approach using a fractional risk set calculation followed by a subtraction formula to calculate the state occupation probability of a transient state. A numerical comparison between the two methods is presented using detailed simulation studies. We show that the new estimators have lower statistical errors of estimation of state occupation probabilities for the distant states. We illustrate the two methods using a pubertal development data set obtained from the NHANES III.(2). | 18,765,503 |
Overexpression of the zinc uptake transporter hZIP1 inhibits nuclear factor-kappaB and reduces the malignant potential of prostate cancer cells in vitro and in vivo. | Intracellular zinc levels and expression of the zinc uptake transporter, hZIP1, are markedly down-regulated in prostate adenocarcinomatous tissue compared with normal prostate tissue. Our previous studies have shown that zinc inhibits nuclear factor-kappaB (NF-kappaB) activity and reduces the malignant potential of prostate cancer cells in vitro. In this study, we investigate the functional effect of hZIP1 overexpression on NF-kappaB activity and tumorigenic potential in human prostate cancer cells in vitro and in vivo. NF-kappaB activity in PC-3 prostate cancer cells was examined by Western blotting and luciferase assay. ELISA was used to examine the expression of tumorigenic cytokines. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, adhesion, and invasiveness assays were used to assess the malignant potential of tumor cells. The effect of hZIP1 overexpression on prostate tumor progression in vivo was assessed using a xenograft model. Overexpression of the hZIP1 transporter in PC-3 cells results in significant inhibition of NF-kappaB activity in the presence of physiologic levels of zinc. NF-kappaB inhibition coincides with a reduction in expression of several NF-kappaB controlled prometastatic and antiapoptotic factors as well as sensitization of the cells to etoposide and tumor necrosis factor-mediated apoptosis-inducing ligand-mediated cell death. Moreover, overexpression of the hZIP1 transporter induces regression of prostate tumor growth in a xenograft model. Our results show that hZIP1 overexpression has a functional effect on the malignant potential of prostate cancer cells via inhibition of NF-kappaB-dependent pathways and support the concept that hZIP1 may function as a tumor suppressor gene in prostate cancer. | 18,765,529 |
Inhibition of the p53 E3 ligase HDM-2 induces apoptosis and DNA damage--independent p53 phosphorylation in mantle cell lymphoma. | The ubiquitin-proteasome pathway has been validated as a target in non-Hodgkin's lymphoma through demonstration of the activity of the proteasome inhibitor bortezomib. Another potentially attractive target is the human homologue of the murine double minute-2 protein, HDM-2, which serves as the major p53 E3 ubiquitin ligase; we therefore evaluated the activity of a novel agent, MI-63, which disrupts the HDM-2/p53 interaction. Treatment of wild-type p53 mantle cell lymphoma (MCL) cell lines with MI-63 resulted in a dose- and time-dependent inhibition of proliferation, with an IC(50) in the 0.5 to 5.0 micromol/L range. MI-63 induced p53 and HDM-2 accumulation, as well as other downstream p53 targets such as p53 up-regulated modulator of apoptosis and p21(Cip1). This was associated with cell cycle arrest at G(1)-S; activation of caspase-3, caspase-8, and caspase-9; cleavage of poly-(ADP-ribose) polymerase; and loss of E2F1. HDM-2 inhibition caused phosphorylation of p53 at multiple serine residues, including 15, 37, and 392, which coincided with low levels of DNA strand breaks. DNA damage occurred in a small percentage of cells and did not induce phosphorylation of the DNA damage marker H2A.X(Ser139). Combinations of MI-63 with the molecularly targeted agents bortezomib and rapamycin showed synergistic, sequence-dependent antiproliferative effects. Treatment of primary MCL patient samples resulted in apoptosis and induction of p53 and p21, which was not seen in normal controls. These findings support the hypothesis that inhibition of the HDM-2/p53 interaction may be a promising approach both by itself and in combination with currently used chemotherapeutics against lymphoid malignancies. | 18,765,533 |
Genetic clustering of clear cell renal cell carcinoma based on array-comparative genomic hybridization: its association with DNA methylation alteration and patient outcome. | The aim of this study was to clarify genetic and epigenetic alterations occurring during renal carcinogenesis. Copy number alterations were examined by array-based comparative genomic hybridization analysis using an array harboring 4,361 bacterial artificial chromosome clones, and DNA methylation alterations on CpG islands of the p16, human MutL homologue 1, von Hippel-Lindau, and thrombospondin 1 genes and the methylated in tumor (MINT-1, MINT-2, MINT-12, MINT-25, and MINT-31) clones were examined in 51 clear cell renal cell carcinomas (RCC). By unsupervised hierarchical clustering analysis based on copy number alterations, clear cell RCCs were clustered into the two subclasses, clusters A (n=34) and B (n=17). Copy number alterations were accumulated in cluster B. Loss of chromosome 3p and gain of 5q and 7 were frequent in both clusters A and B, whereas loss of 1p, 4, 9, 13q, and 14q was frequent only in cluster B. The average number of methylated CpG islands in cluster B was significantly higher than those in cluster A. Clear cell RCCs showing higher histologic grades, vascular involvement, renal vein tumor thrombi, and higher pathologic stages were accumulated in cluster B. The recurrence-free and overall survival rates of patients in cluster B were significantly lower than those of patients in cluster A. Multivariate analysis revealed that genetic clustering was a predictor of recurrence-free survival and was independent of histologic grade and pathologic stage. This genetic clustering of clear cell RCC is significantly associated with regional DNA hypermethylation and may become a prognostic indicator for patients with RCC. | 18,765,545 |
Magnetic resonance imaging-measured blood flow change after antiangiogenic therapy with PTK787/ZK 222584 correlates with clinical outcome in metastatic renal cell carcinoma. | To measure changes in tumor blood flow following treatment with PTK787/ZK 222584, a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, and their association with clinical response in patients with metastatic renal cell carcinoma. In 10 patients with metastatic renal cell carcinoma treated with PTK787/ZK 222584, tumor blood flow was evaluated by arterial spin labeling (ASL) magnetic resonance imaging before and 1 month on treatment. Changes in blood flow after 1 month of treatment were compared with bidimensional tumor response at 4 months of treatment using the Mann-Whitney test. Changes in blood flow at 1 month and changes in tumor size measured at 4 months or at time of disease progression were significantly correlated (P=0.01). Patients with progressive disease within 4 months on treatment (n=4) had a nonsignificant increase in tumor blood flow at 1 month (+25+/-33%; P=0.43), whereas patients with stable disease or partial response at 4 months (n=6) had a significant decrease in tumor blood flow at 1 month (-42+/-22%; P=0.02). These results suggest that decreasing tumor blood flow with PTK787/ZK 222584 therapy, as shown as soon as 1 month on therapy by ASL, may predict for a favorable clinical outcome. These data are consistent with a hypothetical functional role for tumor ischemia in the mechanism of response to anti-vascular endothelial growth factor therapy. ASL blood flow magnetic resonance imaging shows promise as an early predictor of clinical response to antiangiogenic therapies. | 18,765,547 |
A phase I study of bexarotene, a retinoic X receptor agonist, in non-M3 acute myeloid leukemia. | Bexarotene is a retinoic X receptor agonist that has been shown in vitro to inhibit growth and induce differentiation of myeloid leukemic cell lines. We therefore conducted a phase I dose escalation study to assess the maximum tolerated dose, toxicities, and activity of bexarotene in patients with non-M3 acute myeloid leukemia (AML). We enrolled patients with active non-M3 AML who had either relapsed or refractory disease or were not eligible for standard cytotoxic chemotherapy. Cohorts of three to six patients received escalating doses of daily oral bexarotene ranging from 100 to 400 mg/m(2) until evidence of disease progression or unacceptable adverse events occurred. Twenty-seven patients, with median age of 69 years (range, 51-82 years), were treated. Twenty-four (89%) patients had undergone prior chemotherapy. At the highest dose level tested (400 mg/m(2)), three of six patients had to reduce their dose of bexarotene due to grade 3 adverse events. The maximum tolerable dose of bexarotene was determined to be 300 mg/m(2). Clinical activity was manifested by 4 (15%) patients with reduction in bone marrow blasts to <or=5%, 11 (41%) patients with improved platelet counts, and 7 (26%) patients with improved neutrophil counts. Three patients with relapsed AML survived >1 year while taking bexarotene. Leukemic blast differentiation was suggested by the presence of the leukemic cytogenetic abnormality in mature circulating granulocytes and the occurrence of differentiation syndrome. The recommended dose of bexarotene for future studies is 300 mg/m(2)/d. Bexarotene is well tolerated in patients with non-M3 AML and has evidence of antileukemic activity. | 18,765,556 |
Recruitment of mismatch repair proteins to the site of DNA damage in human cells. | Mismatch repair (MMR) proteins contribute to genome stability by excising DNA mismatches introduced by DNA polymerase. Although MMR proteins are also known to influence cellular responses to DNA damage, how MMR proteins respond to DNA damage within the cell remains unknown. Here, we show that MMR proteins are recruited immediately to the sites of various types of DNA damage in human cells. MMR proteins are recruited to single-strand breaks in a poly(ADP-ribose)-dependent manner as well as to double-strand breaks. Using mutant cells, RNA interference and expression of fluorescence-tagged proteins, we show that accumulation of MutSbeta at the DNA damage site is solely dependent on the PCNA-binding domain of MSH3, and that of MutSalpha depends on a region near the PCNA-binding domain of MSH6. MSH2 is recruited to the DNA damage site through interactions with either MSH3 or MSH6, and is required for recruitment of MLH1 to the damage site. We found, furthermore, that MutSbeta is also recruited to UV-irradiated sites in nucleotide-excision-repair- and PCNA-dependent manners. Thus, MMR and its proteins function not only in replication but also in DNA repair. | 18,765,568 |
Effects of method of presynchronization and source of selenium on uterine health and reproduction in dairy cows. | The objectives of this study were to evaluate the effects of method of presynchronization and source of supplemental Se on uterine health and reproductive performance of lactating dairy cows. Holstein cows (n = 512) were assigned randomly to 2 methods of presynchronization, Presynch (2 PGF(2a) given 14 d apart) or CIDR-PS (controlled internal drug releasing inserted for 7 d with an injection of PGF(2a) at removal) and 2 sources of Se, sodium selenite (SS) or selenized yeast (SY) supplemented at 0.3 mg/kg from 25 d before calving to 80 d in milk (DIM) arranged in a 2 x 2 factorial. Cows were inseminated following the Ovsynch protocol (d 0 GnRH, d 7 PGF(2a), d 9 GnRH, timed artificial insemination (AI) 12 h after the final GnRH) starting at 12 and 3 d after Presynch and CIDR-PS, respectively. Cows were diagnosed for pregnancy at 28, 42, and 56 d after AI. Source of Se did not influence uterine health and resumption of cyclicity, but fewer CIDR-PS than Presynch cows were cyclic at the beginning of the Ovsynch, although differences in the proportion cyclic may have been caused by the timing when corpus luteum evaluations were performed in the different pre-synchronization treatments. Ovulatory responses were not influenced by source of Se. However, the CIDR-PS increased ovulation to the first GnRH, double ovulation to the final GnRH, and size of ovulatory follicle at PGF(2a) and final GnRH of the Ovsynch, but did not influence ovulation at the final GnRH of the Ovsynch. Concentrations of estradiol during the Ovsynch increased with follicle diameter and were greater for cows receiving CIDR-PS than Presynch, but they were not influenced by source of Se. Pregnancy per AI on d 28 (32.7%), 42 (28.5%), and 56 (25.9%) after AI, and pregnancy loss (20.5%) from 28 to 56 d were not influenced by source of Se or method of presynchronization. Although cows receiving CIDR-PS had an increased incidence of ovulation to the first GnRH (73.2 vs. 57.8%) and double ovulation to the final GnRH of the Ovsynch (18.7 vs. 9.0%), both of which enhanced pregnancy, the CIDR-PS protocol did not improve pregnancy per AI or reduce pregnancy loss compared with presynchronization with PGF(2a) alone. | 18,765,591 |
Developmental histology, segmental expression, and nutritional regulation of somatotropic axis genes in small intestine of preweaned dairy heifers. | Components of the somatotropic axis and nutrition regulate intestinal development and maturation of enterocytes. We measured gene expression in the mucosal layer of small intestine of preweaned dairy heifers to test the hypothesis that feeding increased amounts of protein and fat alters expression of somatotropic axis genes. Twenty-four newborn Holstein heifers were randomly assigned to 1 of 4 milk replacer (MR) diets: (1) 20% CP, 20% fat MR (DM basis) fed at 450 g/d (CON); (2) 28% CP, 20% fat MR fed at 970 g/d (HPLF); (3) 28% CP, 28% fat MR fed at 970 g/d (HPHF); and (4) 28% CP, 28% fat MR fed at 1,460 g/d (HPHF+). Dry calf starter (20% CP, 1.43% fat) was offered free choice. At 64 +/- 3 d of age heifers were killed and intestinal tissues were harvested for RNA isolation and histological examination. We measured the mRNA expression of growth hormone receptor (GHR), insulin-like growth factor-I (IGF-I), IGF-I receptor (IGF-IR), and IGF binding proteins (IGFBP)-1 to -6 in duodenum, jejunum, and ileum by quantitative real-time reverse transcription PCR. Expression of IGFBP-3 mRNA was lowest in the duodenum of HPHF+ and greatest in the ileum of the CON group, whereas expression of IGFBP-4 mRNA was greatest in the jejunum of the HPHF+ group. Expression of IGFBP-5 mRNA was greatest in the CON and lowest in the HPHF+. However, overall diet did not affect expression of GHR, IGF-I, IGF-IR, or IGFBP-1, -2, and -6. Expression of somatotropic axis genes differed among small intestinal locations. The GHR, IGF-IR, IGFBP-1, and IGFBP-5 mRNA were greatest in the ileum. Duodenum produced less IGF-IR, IGF-I, and IGFBP-5 mRNA. Villi were shortest in the ileum, but there was no difference in villus height between the duodenum and jejunum. There was no difference in crypt depth or villus circumference between locations. In conclusion, some components of the somatotropic axis in preweaned dairy heifers are differentially expressed in regions of the small intestine, and the gene expression tended to be affected by dietary protein and fat. | 18,765,593 |
How does live yeast differ from sodium bicarbonate to stabilize ruminal pH in high-yielding dairy cows? | The objectives of this study were to evaluate the capacity of 2 dietary feed additives, sodium bicarbonate and live yeast Saccharomyces cerevisiae (strain Sc 47), in optimizing ruminal pH in dairy cows and to determine their modes of action. Three early lactating Holstein cows, fitted with ruminal cannulas, were allocated in a 3 x 3 Latin square design. They were given a total mixed ration as control diet (CD) at a daily feeding rate of 28.0 kg of dry matter (DM)/cow supplemented with 150 g/d of sodium bicarbonate (SBD) or 5 g/d of live yeast (YD) during a 21-d experimental period (14 d of diet adaptation, 4 consecutive days of measurement and sampling and 3 d of transition). The pH and redox potential (E(h)) were measured from 1 h before feeding to 8 h after feeding at 1-h intervals, and samples of ruminal fluid were taken at 0, 2, 4, 6, and 8 h after feeding for the determination of volatile fatty acids and lactate concentrations. Total tract apparent digestibility of the diet was also determined. Ruminal pH fluctuated between 6.53 at feeding and 5.57 at 5 h postfeeding. Mean pH was greater with SBD (6.21) and YD (6.14) compared with CD (5.94), showing that both additives had a pH stabilization effect. The E(h) varied from -88 mV at 1 h before feeding to -165 mV at 1 h after feeding. Mean E(h) and Clark's Exponent (rH) were lower with YD (-149 mV and 7.31, respectively) than with SBD (-137 mV and 7.85, respectively) and CD (-115 mV and 8.05, respectively), indicating that the yeast strengthened the reducing power of the milieu. Total volatile fatty acids were greater in SBD (95.3 mM) and YD (99.4 mM) compared with CD (85.3 mM). Acetate concentration was greater in SBD (60.8 mM) and YD (59.1 mM) compared with CD (53.2 mM). Propionate concentration was greater in YD (25.8 mM) than in SBD (20.0 mM) and CD (18.0 mM). Butyrate remained constant between diets. Mean total lactate concentrations were 16.5, 12.2, and 5.4 mM for CD, SBD, and YD, respectively, with a 67% decrease with YD. Total tract organic matter digestibility was greater for YD (66.6%) compared with SBD (61.7%) and CD (62.2%). The neutral detergent fiber digestibility was greater with YD (41.6%) compared with SBD (34.3%) and CD (29.6%), whereas acid detergent fiber digestibility was greatest in YD (32.3%), intermediate in SBD (24.4%), and lowest in CD (18.1%). By inducing a lower ruminal E(h) and rH, live yeast prevented accumulation of lactate and allowed better fiber digestion, whereas sodium bicarbonate seemed to act only as an exogenous buffer. | 18,765,611 |
Quantitative trait loci underlying udder morphology traits in dairy sheep. | A genome scan was conducted on the basis of the daughter design to detect quantitative trait loci (QTL) influencing udder morphology traits in Spanish Churra dairy sheep. A total of 739 ewes belonging to 11 half-sib families were genotyped for 182 microsatellite markers covering 3,248.2 cM (Kosambi) of the ovine autosomal genome. Phenotypic traits included scores for 5 linear udder traits: udder depth, udder attachment, teat placement, teat size, and udder shape. Quantitative measurements for the QTL analysis were calculated for each trait from evaluation scores using within-family yield deviations corrected for fixed environmental effects. Joint analysis of all families using Haley-Knott regression identified 5 regions that exceeded the 5% chromosome-wise significance threshold on chromosomes 7, 14, 15, 20, and 26. Based on the across-family results, a within-family analysis was carried out to identify families segregated according to the QTL and to estimate the QTL effect. The allelic substitution effect for individual families ranged from 0.47 to 1.7 phenotypic standard deviation units for udder shape on chromosome 15 and udder depth on chromosome 14, respectively. These QTL regions provide a starting point for further research aimed at the characterization of genetic variability involved in udder traits in Churra sheep. This paper presents the first report of a sheep genome scan for udder-related traits in a dairy sheep outbred population. | 18,765,625 |
Short communication: new alleles of the bovine kappa-casein gene revealed by resequencing and haplotype inference analysis. | We tested the hypothesis that extensive undiscovered genetic diversity exists in important functional genes from domestic and wild cattle species (Bos spp.). We resequenced 483 bp of a key exon (exon IV) from the kappa (kappa)-casein gene (CSN3) for a panel of samples of domestic cattle from 8 countries and a close relative species, the gayal (Bos frontalis). Six single nucleotide polymorphisms were identified. Haplotype inference revealed 12 haplotypes, of which 8 were newly discovered. Among these 8 new haplotypes, 5 differed by one nonsynonymous mutation and 3 differed by one silent mutation from previously well-characterized CSN3 alleles. From those, one was shared by the gayal and Zebu, was different from CSN3*B at position Ile136Thr, and showed a close phylogenetic relationship with the banteng, gaur, and yak. The other 7 new haplotypes were detected in our panel of worldwide local cattle breeds but were absent from previously reported commercial breeds. These results support the hypothesis that genetic diversity at the coding region of CSN3 has been underestimated. This study also highlights how important it is to resequence functionally important genes in worldwide local cattle breeds, many of which are threatened by extinction or replacement by commercial breeds. | 18,765,626 |
Short communication: casein haplotype variability in sicilian dairy goat breeds. | In the Mediterranean region, goat milk production is an important economic activity. In the present study, 4 casein genes were genotyped in 5 Sicilian goat breeds to 1) identify casein haplotypes present in the Argentata dell'Etna, Girgentana, Messinese, Derivata di Siria, and Maltese goat breeds; and 2) describe the structure of the Sicilian goat breeds based on casein haplotypes and allele frequencies. In a sample of 540 dairy goats, 67 different haplotypes with frequency >or=0.01 and 27 with frequency >or=0.03 were observed. The most common CSN1S1-CSN2-CSN1S2-CSN3 haplotype for Derivata di Siria and Maltese was FCFB (0.17 and 0.22, respectively), whereas for Argentata dell'Etna, Girgentana and Messinese was ACAB (0.06, 0.23, and 0.10, respectively). According to the haplotype reconstruction, Argentata dell'Etna, Girgentana, and Messinese breeds presented the most favorable haplotype for cheese production, because the casein concentration in milk of these breeds might be greater than that in Derivata di Siria and Maltese breeds. Based on a cluster analysis, the breeds formed 2 main groups: Derivata di Siria, and Maltese in one group, and Argentata dell'Etna and Messinese in the other; the Girgentana breed was between these groups but closer to the latter. | 18,765,627 |
Heritability of the severity of diabetic retinopathy: the FIND-Eye study. | Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib-sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (chi(2) = 658.14, df = 20; P < 0.0001). The sib-sib correlation for DR severity was 0.1358 in the total sample and 0.1224 when limited to the Mexican-American sample. Broad sense heritabilities for DR were 27% overall and 24% in Mexican-American families. The polygenic heritability of liability for proliferative DR approximated 25% in this FIND-Eye sample. These data confirm that the severity of DR parallels the presence and severity of nephropathy in individuals with diabetes mellitus. The severity of DR in members of multiplex diabetic families appears to have a significant familial connection. | 18,765,632 |
Spinal anaesthesia for elective surgery: a comparison of hyperbaric solutions of racemic bupivacaine, levobupivacaine, and ropivacaine. | The aim of this study was to compare the clinical effects of 'hyperbaric' bupivacaine for spinal anaesthesia with those of similar preparations of levobupivacaine and ropivacaine. Sixty ASA grade I-II patients undergoing elective surgery under spinal anaesthesia were randomized to receive 3 ml of bupivacaine, levobupivacaine, or ropivacaine, each at 5 mg ml(-1) and made hyperbaric by the addition of glucose 30 mg ml(-1). A standard protocol was followed after which a blinded observer assessed the sensory and motor blocks. The level and duration of sensory (pinprick) block, intensity and duration of motor block, and time to mobilize and to micturate were also recorded. One patient (ropivacaine group) required general anaesthesia because of technical failure, but all the other blocks were adequate. There were no significant differences between the groups with regard to the mean time to onset of sensory block at T10, the extent of spread, or mean time to maximum spread. Regression of sensory block in the ropivacaine group was more rapid as demonstrated by duration at T10 (P<0.0167) and total duration of sensory block (P<0.0167). Patients in the ropivacaine group had more rapid recovery from motor block (P<0.0167) and shorter times to independent mobilization (P<0.0167). There were no significant differences between the bupivacaine and the levobupivacaine groups. 'Hyperbaric' ropivacaine provides reliable spinal anaesthesia of shorter duration than bupivacaine or levobupivacaine, both of which are clinically indistinguishable. The recovery profile of ropivacaine may be useful where prompt mobilization is required. | 18,765,643 |
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