Bacterial composition, function and the enrichment of plant growth promoting rhizobacteria (PGPR) in differential rhizosphere compartments of Al-tolerant soybean in acidic soil.
Low pH with aluminum (Al) toxicity are the main limiting factors affecting crop production in acidic soil. Selection of legume crops with acid tolerance and nitrogen-fixation ability should be one of the effective measures to improve soil quality and promote agricultural production. The role of the rhizosphere microorganisms in this process has raised concerns among the research community. In this study, BX10 (Al-tolerant soybean) and BD2 (Al-sensitive soybean) were selected as plant materials. Acidic soil was used as growth medium. The soil layers from the outside to the inside of the root are bulk soil (BS), rhizosphere soil at two sides (SRH), rhizosphere soil after brushing (BRH) and rhizosphere soil after washing (WRH), respectively. High-throughput sequencing of 16S rDNA amplicons of the V4 region using the Illumina MiSeq platform was performed to compare the differences of structure, function and molecular genetic diversity of rhizosphere bacterial community of different genotypes of soybean. The results showed that there was no significant difference in alpha diversity and beta diversity in rhizosphere bacterial community among the treatments. PCA and PCoA analysis showed that BRH and WRH had similar species composition, while BS and SRH also had similar species composition, which indicated that plant mainly affected the rhizosphere bacterial community on sampling compartments BRH and WRH. The composition and abundance of rhizosphere bacterial community among the treatments were then compared at different taxonomic levels. The ternary diagram of phylum level showed that Cyanobacteria were enriched in WRH. Statistical analysis showed that the roots of Al-tolerant soybean BX10 had an enrichment effect on plant growth promoting rhizobacteria (PGPR), which included Cyanobacteria, Bacteroides, Proteobacteria and some genera and species related to the function of nitrogen fixation and aluminum tolerance. The rhizosphere bacterial community from different sampling compartments of the same genotype soybean also were selectively enriched in different PGPR. In addition, the functional prediction analysis showed that there was no significant difference in the classification and abundance of COG (clusters of orthologous groups of proteins) function among different treatments. Several COGs might be directly related to nitrogen fixation, including COG0347, COG1348, COG1433, COG2710, COG3870, COG4656, COG5420, COG5456 and COG5554. Al-sensitive soybean BD2 was more likely to be enriched in these COGs than BX10 in BRH and WRH, and the possible reason remains to be further investigated in the future.


Experimental brain infarcts in cats. I. Pathophysiological observations.
In 48 cases the left middle cerebral artery was occluded under light barbiturate anaesthesia using a transorbital approach. The animals were kept alive for 1, 2, and 4 hours after vascular occlusion. Regional cerebral blood flow was measured by the intracardiac microsphere injection technique before ischemia, 15 min after the onset of ischemia, and at the end of experiments. The density of regional ischemia was correlated with EEG changes and with the electrolyte, water and metabolite content of the same tissue samples in which blood flow was assessed. In the territory of the occluded middle cerebral artery, cortical blood flow decreased from 41.4 +/- 3.8 to 21.3 +/- 4.0 ml/100 g/min (means +/- SE), the actual flow rate depending on the individual efficacy of collateral blood supply. At flow rates below 10--15 ml/100 g/min, ischemia involved more than 50% of the middle cerebral artery territory, water and electrolyte homeostasis was severely disturbed and ischemic brain edema developed. Adenosine triphosphate decreased to about 60% of the control value at flow rates below 40 ml/100 g/min, but it remained at this level down to flow rates as low as 5 ml/100 g/min. EEG intensity -- but not EEG frequency -- decreased in parallel with blood flow, indicating that with increasing density of ischemia an increasing portion of the excitable neuropil was inhibited. The development of ischemic brain edema determined the further progression of ischemia. When blood flow decreased below the threshold for water and ion disturbance, ischemia was progressive (critical ischemia), but an amelioration of flow occurred in animals in which flow remained above this level (non-critical ischemia). In the contralateral hemisphere the EEG, blood flow, water and electrolyte content did not change significantly during the initial few hours of ischemia. Diaschisis, in consequence, was not a prominent feature during the early phase of infarct development.


The effects of a transverse magnetic field on the dose enhancement of nanoparticles in a proton beam: a Monte Carlo simulation.
High-Z nanoparticles (NP) as radio-sensitization agents provide the feasibility of dose localization within the tumor in radiotherapy. Dose enhancement of NPs in the presence of a magnetic field (MF) could be challenged when magnetic resonance imaging (MRI) systems are used as an image-guided system. The MF can influence dose enhancement of NPs at their interfaces and surrounding medium and affect their dose deposition behavior. In the TOPAS Monte Carlo code, gold nanoparticle (GNP) and superparamagnetic iron oxide nanoparticle (SPION) were irradiated using 70 and 150 MeV proton beams, in presence of transverse MF strengths with 0, 1, 3, and 7 T. The changes in the liberated secondary electrons from NPs and their dose enhancement ratio (DER), magnetic dose enhancement ratio (MDER), and angular dose distribution in 10 nm shell thicknesses up to 500 nanometers from their centers were measured. The central plane of NPs was considered as a scorer. Its thickness was 2 nm and divided into 6-degree sectors with 10 nm radial length. The dose deposition in this voxelated scorer was calculated. The values of the deposited doses around NPs decrease rapidly while the DERs resulted from the secondary electrons are increased. MDERs are changed within [Formula: see text] and [Formula: see text] for 20 and 50 nm radius NPs, respectively. The variation in the angular dose distribution around a singular NP was not considerable when different MF strengths were applied. The dose values in the voxelated central plane show very similar results for the same NPs types in the different MF strengths. The typically used MF in the MRI systems would not considerably affect the energy deposition behavior of the secondary electrons produced in the interaction of proton beam with NPs, at least in the near vicinity of NPs. The DERs of NPs in a water medium resulted from emerged secondary electrons, experience a low degree of perturbation in the presence of an MF. The results of this study show that the NPs as dose enhancement agents can also be used in an MF without pronounced modification in their efficacy.


An electron microscopic study of endrin induced alterations in unmyelinated fibers of mouse sciatic nerve.
This study examined the ultrastructural alterations in peripheral nerve of adult mouse following repeated sublethal exposures to endrin, a toxic chlorinated hydrocarbon which produces symptoms indicative of neuromuscular dysfunction. Male mice were given 20 daily ip injections of endrin in sesame oil (0.2 ml) in doses that increased from 1.5 mg/kg on days 0-3, to 2.0 mg/kg on days 4-11, and to 4.0 mg/kg on days 12-19. Controls were given the same intraperitoneal volume of sesame oil without endrin. Animals were sacrificed by glutaraldehyde perfusion after 4, 7, 14, and 20 days of exposure and 14 and 92 days postinjection and sciatic nerve tissue was prepared for electron microscopy. Myelinated nerve fibers, myelin and associated Schwann cells from endrin exposed animals appeared similar to those of controls and normal animals. Various morphological alterations were observed in many unmyelinated axons from endrin exposed animals. Such alterations included swelling, dissolution of microtubules and neurofilaments, the presence of unusual numbers of axoplasmic vesicles, both scattered and in packets, and less often, extreme vacuolation. In those Schwann cells associated with damaged axons the cytoplasm and the adaxonal space frequently contained vesicles, often in packets invaginating the axolemma. The results of this study indicate that repeated subacute doses of endrin can produce morphological alterations in unmyelinated peripheral nerve fibers and their associated Schwann cells without apparent damage to myelinated nerve fibers. The results are discussed relative to other studies producing similar nerve damage and to the potential mechanisms responsible for such damage.


Polarization and density of Na-pumps in the inner ear of the chick embryo during early stages of development.
The otic vesicle consists of a pseudostratified epithelium with some features of transporting epithelia. The present work questions whether Na-pumps are polarized in this epithelium and what is the relation between the location or density of pumps and development. This was done by measuring the binding of [3H]ouabain to isolated otic vesicles in developmental stages 16 to 22. The results show the presence of specific ouabain-binding sites located in the inward-facing membrane of the otic vesicle epithelium. Binding was saturable at increasing concentrations of ouabain and was highly sensitive to the external K+ concentration with half-maximal inhibition below 0.5 mM, indicating that the binding sites and Na-pump sites are identical. A transient stage-dependent increase in the density of Na-pumps during the period that precedes growth was observed. Evidence is given against this being directly related to an increased net fluid transport rate despite the fact that pump sites were always polarized throughout these stages. The conclusions are that (1) the otic vesicle epithelium is a polarized structure with the possibility of vectorial transport of solutes and water and (2) the increased number of pumps may operate as a regulatory mechanism during normal proliferative growth.


High frequency of HIV precursor-target-specific B cells in sub-Saharan populations.
HIV gp120 engineered outer domain germline-targeting version 8 (eOD-GT8) was designed specifically to engage naive B cell precursors of VRC01-class antibodies. However, the frequency and affinity of naive B cell precursors able to recognize eOD-GT8 have been evaluated only in U.S. populations. HIV infection is disproportionally concentrated in sub-Saharan Africa, so we seek to characterize naive B cells able to recognize eOD-GT8 in sub-Saharan cohorts. We demonstrate that people from sub-Saharan Africa have a higher or equivalent frequency of naive B cells able to engage eOD-GT8 compared with people from the U.S. Genetically, the higher frequency of eOD-GT8-positive cells is accompanied by a higher level of naive B cells with gene signatures characteristic of the VRC01 class, as well as other CD4bs-directed antibodies. Our study demonstrates that vaccination with eOD-GT8 in sub-Saharan Africa could be successful at expanding and establishing a pool of CD4bs-directed memory B cells from naive precursors.


Vitamin A supplementation for postpartum women.
In areas where vitamin A deficiency (VAD) is a public health concern, the maternal dietary intake of vitamin A may be not sufficient to meet either the maternal nutritional requirements, or those of the breastfed infant, due the low retinol concentrations in breast milk. To evaluate the effects of vitamin A supplementation for postpartum women on maternal and infant health. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (8 February 2016), LILACS (1982 to December 2015), Web of Science (1945 to December 2015), and the reference lists of retrieved studies. Randomised controlled trials (RCTs) or cluster-randomised trials that assessed the effects of vitamin A supplementation for postpartum women on maternal and infant health (morbidity, mortality and vitamin A nutritional status). Two review authors independently assessed trials for inclusion, conducted data extraction, assessed risk of bias and checked for accuracy. We assessed the quality of the evidence using the GRADE approach. Fourteen trials of mainly low or unclear risk of bias, enrolling 25,758 women and infant pairs were included. The supplementation schemes included high, single or double doses of vitamin A (200,000 to 400,000 internation units (IU)), or 7.8 mg daily beta-carotene compared with placebo, no treatment, other (iron); or higher (400,000 IU) versus lower dose (200,000 IU). In all trials, a considerable proportion of infants were at least partially breastfed until six months. Supplement (vitamin A as retinyl, water-miscible or beta-carotene) 200,000 to 400,000 IU versus control (placebo or no treatment) Maternal: We did not find evidence that vitamin A supplementation reduced maternal mortality at 12 months (hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.44 to 2.21; 8577 participants; 1 RCT, moderate-quality evidence). Effects were less certain at six months (risk ratio (RR) 0.50, 95% CI 0.09 to 2.71; 564 participants; 1 RCT; low-quality evidence). The effect on maternal morbidity (diarrhoea, respiratory infections, fever) was uncertain because the quality of evidence was very low (50 participants, 1 RCT). We found insufficient evidence that vitamin A increases abdominal pain (RR 1.28, 95% CI 0.95 to 1.73; 786 participants; 1 RCT; low-quality evidence). We found low-quality evidence that vitamin A supplementation increased breast milk retinol concentrations by 0.20 µmol/L at three to three and a half months (mean difference (MD) 0.20 µmol/L, 95% CI 0.08 to 0.31; 837 participants; 6 RCTs). Infant: We did not find evidence that vitamin A supplementation reduced infant mortality at two to 12 months (RR 1.08, 95% CI 0.77 to 1.52; 6090 participants; 5 RCTs; low-quality evidence). Effects on morbidity (gastroenteritis at three months) was uncertain (RR 6.03, 95% CI 0.30 to 121.82; 84 participants; 1 RCT; very low-quality evidence). There was low-quality evidence for the effect on infant adverse outcomes (bulging fontanelle at 24 to 48 hours) (RR 2.00, 95% CI 0.61 to 6.55; 444 participants; 1 RCT). Supplement (vitamin A as retinyl) 400,000 IU versus 200,000 IUThree studies (1312 participants) were included in this comparison. None of the studies assessed maternal mortality, maternal morbidity or infant mortality. Findings from one study showed that there may be little or no difference in infant morbidity between the doses (diarrhoea, respiratory illnesses, and febrile illnesses) (312 participants, data not pooled). No firm conclusion could be drawn on the impact on maternal and infant adverse outcomes (limited data available).The effect on breast milk retinol was also uncertain due to the small amount of information available. There was no evidence of benefit from different doses of vitamin A supplementation for postpartum women on maternal and infant mortality and morbidity, compared with other doses or placebo. Although maternal breast milk retinol concentrations improved with supplementation, this did not translate to health benefits for either women or infants. Few studies reported on maternal and infant mortality and morbidity. Future studies should include these important outcomes.


Nonuniformity in ligaments is a structural strategy for optimizing functionality.
Ligaments serve as compliant connectors between hard tissues. In that role, they function under various load regimes and directions. The 3D structure of ligaments is considered to form as a uniform entity that changes due to function. The periodontal ligament (PDL) connects the tooth to the bone and sustains different types of loads in various directions. Using the PDL as a model, employing a fabricated motorized setup in a microCT, we demonstrate that the fibrous network structure within the PDL is not uniform, even before the tooth becomes functional. Utilizing morphological automated segmentation methods, directionality analysis, as well as second harmonic generation imaging, we find high correlation between blood vessel distribution and fiber density. We also show a structural feature in a form of a dense collar around the neck of the tooth as well as a preferred direction of the fibrous network. Finally, we show that the PDL develops as a nonuniform structure, with an architecture designed to sustain specific types of load in designated areas. Based on these findings, we propose that ligaments in general should be regarded as nonuniform entities, structured already at developmental stages for optimal functioning under variable load regimes.


Cutaneous heparin necrosis in a patient with heterozygous protein S deficiency.
A patient with heterozygous protein S deficiency experienced cutaneous necrosis following subcutaneous heparin administration. Deficiencies of both protein C and protein S, known risk factors for the more frequently encountered coumarin necrosis, may predispose patients to this complication of heparin therapy as well. The putative association of protein S deficiency with cutaneous heparin necrosis could not be proven, however, since attempts to reproduce the heparin necrosis were unsuccessful.


The snoring spectrum: acoustic assessment of snoring sound intensity in 1,139 individuals undergoing polysomnography.
To quantify the snoring sound intensity levels generated by individuals during polysomnographic testing and to examine the relationships between acoustic, polysomnographic, and clinical variables. The prospective acquisition of acoustic and polysomnographic data with a retrospective medical chart review. A sleep laboratory at a primary care hospital. All 1,139 of the patients referred to the sleep laboratory for polysomnographic testing from 1980 to 1994. The acoustic measurement of snoring sound intensity during sleep concurrent with polysomnographic testing. Four decibel levels were derived from snoring sound intensity recordings. L1, L5, and L10 are measures of the sound pressure measurement in decibels employing the A-weighting network that yields the response of the human ear exceeded, respectively, for 1, 5, and 10% of the test period. The Leq is a measure of the A-weighted average intensity of a fluctuating acoustic signal over the total test period. L10 levels above 55 dBA were exceeded by 12.3% of the patients. The average levels of snoring sound intensity were significantly higher for men than for women. The levels of snoring sound intensity were associated significantly with the following: polysomnographic testing results, including the respiratory disturbance index (RDI), sleep latency, and the percentage of slow-wave sleep; demographic factors, including gender and body mass; and clinical factors, including snoring history, hypersomnolence, and breathing stoppage. Men with a body mass index of > 30 and an average snoring sound intensity of > 38 dBA were 4.1 times more likely to have an RDI of > 10. Snoring sound intensity levels are related to a number of demographic, clinical, and polysomnographic test results. Snoring sound intensity is closely related to apnea/hypopnea during sleep. The noise generated by snoring can disturb or disrupt a snorer's sleep, as well as the sleep of a bed partner.


Isolated saccular aneurysm of the external jugular vein.
Venous aneurysm of the head and neck is a rare clinical entity due to its asymptomatic nature and tendency of clinicians to report only surgical results. Whereas the primary aneurysm of internal jugular vein (IJV) in children is being increasingly recognized, secondary aneurysms of veins of the head and neck in adults, notably the external jugular vein (EJV) aneurysm remains only in anecdotal case reports. We present the case of a 63-year-old previously healthy woman who presented with a gradually progressive right lateral neck swelling over the last 18 months. Following the evaluation, she was diagnosed as a case of isolated spontaneous right-sided EJV aneurysm and was managed by surgical excision of the aneurysm.


Energy needs versus environmental pollution: a reconciliation?
In this article I have presented, for discussion, a proposed system for energy generation by which the principal sources of environmental pollution by power plants could be eliminated. For stationary power plants the concept appears feasible technically and, according to my " horseback estimates," perhaps economically as well, depending upon the economic value of the by-products of sulfur, CO(2), water, and possibly nitrogen, and upon the price we are willing to pay for a clean environment .Thus, a more thorough engineering and economic analysis to explore these and other factors in greater depth seems warranted. In the case of turbine-driven vehicles, the technical and economic feasibility of widespread distribution and handling of the fuel constitutes a serious question, but one which deserves equally serious consideration before the possibility is discounted. The reports of the cited study panels notwithstanding, the technology required for the proposed system exists today, with one exception. This exception (which is not essential for trial of the system but will be required for its complete fruition) is the development of a nuclear reactor for the prime purpose of delivering process heat for the steam reforming of natural gas and, ultimately, for gas production from coal in a continuous process, such as those discussed by Pieroni et al. (16). Today's intermittent processes of coking and gas production are both archaic and themselves large sources of atmospheric pollution, and a development program aimed at advancing the technology of the coal industry in this regard would seem long overdue. The report of the PSAC Environmental Pollution Panel recommended "demonstration of the feasibility and economy of new developments for abating or controlling pollution through their use at Federal installations" and suggested the coalburning TVA power plants as a likely place for such demonstration. This suggestion is doubly appropriate since the TVA is in a region of subnormal " atmospheric ventilation" (8). By design these plants are adjacent to the AEC's Oak Ridge National Laboratory, and such a location would seem ideal for an experiment on the wedding of nuclear and fossil sources of energy. In comments on a preliminary draft of this article, proponents of "conventional " nuclear power pointed out that such power is hard to beat on the basis of cost, and that dissipation of heat to the air by way of cooling towers can also be accomplished in conventional plants (17). These observations are individually correct but not compatible: the low power costs cited are for very large plants [of the order of 1000 mega-watts lectrical) and larger], and the costs of cooling towers and associated equipment needed to dissipate such large amounts of heat [of the order of 2000 megawatts (thermal)] to air from a closed cycle would offset the power cost advantage of the large plant. In regard to the proposed use of nuclear process heat, Weinberg (20) has expressed doubt that much advantage can be derived from this approach because the temperatures involved are too high for low-cost reactors, and heat transfer from surfaces could involve materials problems. In the case of gas production, this is indeed an anticipated problem-not a technologically insuperable one, but a problem of reducing the cost of the materials required (16). Indeed, Weinberg himself has mentioned this possible use of nuclear heat in a recent publication discussing the steam reforming of coal to liquid fuel(21). Also, an improved process for synthesizing methane from lignitec has recently been reported (22). Since the earlier studies date back a decade, a new look at the problems and costs involved relative to the benefits to be derived (not the least of which could be new vigor for the coal industry) would seem to be in order. In the case of steam reforming of natural gas, the temperature level (about 1500 degrees F) is such that the technology is available today, and a process-heat-reactor design study could be initiated without awaiting further developments.


Inhibition of NF-kappaB by combination therapy with parthenolide and hyperthermia and kinetics of apoptosis induction and cell cycle arrest in human lung adenocarcinoma cells.
We investigated the mechanisms of thermosensitization related to combination therapy with sesquiterpene lactone parthenolide (PTL), a nuclear factor-kappaB (NF-kappaB) inhibitor, and hyperthermia using human lung adenocarcinoma cells A549. The kinetics of apoptosis induction and cell cycle of cells treated with PTL, heating, and combined treatment were examined by flow cytometric analysis. The flow cytometric distribution was calculated and expressed as a percentage. The ratios of the sub-G1 division, used to determine the induction of apoptosis, increased significantly with the combination therapy. Furthermore, the ratios of G2/M division increased and the ratios of G0/G1 division decreased, indicating cell cycle arrest in G2/M. The cell phase response to PTL by A549 cells synchronized in the G1/S border with hydroxyurea was also analyzed. PTL showed remarkable cytotoxicity at the S phase of the cell cycle in A549 cells at all concentrations as well as with hyperthermia, thus PTL reduced the number of cells in the proliferation phase. Inhibition of intracellular transcription factor NF-kappaB activation in A549 cells with various incubation periods after treatments with PTL, heating and combined treatment was examined by Western blot analysis. Unexpectedly, PTL alone did not inhibit NF-kappaB activation in cells stimulated with TNF-alpha, while heating alone inhibited NF-kappaB early after treatment and that effect faded over time. In contrast, PTL combined with heating completely inhibited NF-kappaB activation. Our results demonstrated that PTL and heating in combination cause significant thermosensitization of A549 cells via induction of apoptosis or cell cycle arrest in G2/M by inhibiting NF-kappaB activation in a synergistic manner.


Immunoregulatory lymphokines of T hybridomas from AIDS patients: constitutive and inducible suppressor factors.
Supernatants derived from peripheral blood mononuclear cell cultures of certain patients with the acquired immunodeficiency syndrome (AIDS) or its prodromes have the capacity to block T cell-dependent immune reactivity in vitro. T cells derived from a patient positive for antibody to the lymphadenopathy associated virus ( LAV ), and elaborating high titers of these soluble suppressor factors, were fused to a mutagenized clone of the human T lymphoblastoid cell line KE37 . Molecules capable of profoundly depressing T cell-dependent polyclonal antibody production and DNA synthetic responses, either directly or after incubation with normal adherent cells, were isolated from stable hybrid clones.


Role of monoamine oxidase, nitric oxide synthase and regional brain monoamines in the antidepressant-like effects of methylene blue and selected structural analogues.
Dual action antidepressants have important therapeutic implications. Methylene blue (MB), a charged compound structurally related to tricyclic antidepressants, acts on both monoamine oxidase (MAO) and the nitric oxide (NO)-cGMP pathway, and has demonstrated antidepressant activity in rodents. We investigated the antidepressant properties of MB and selected structural analogues and whether their actions involve MAO, NO synthase (NOS) and regional brain monoamines. Acute imipramine (IMI, 15 mg/kg), saline, MB, acriflavine (ACR), methylene green (MG), methylene violet (MV), thionine (THI) and tacrine (TAC) (1-60 mg/kg i.p.) were tested for antidepressant activity in the forced swim test (FST), as well as MAO-A/B inhibitory activity. Active antidepressant compounds were subsequently studied at their most effective dose during sub-chronic treatment, followed by behavioural sampling in the FST and assay of cortico-limbic monoamines and hippocampal nitrate (for NOS activity). Only IMI, MB (15, 30, 60 mg/kg) and MG (7.5, 25, 40 mg/kg) reduced immobility in the acute FST. MB, MG and ACR were potent inhibitors of especially MAO-A. Following sub-chronic treatment, IMI (15 mg/kg) increased noradrenergic behaviour in the FST, while MB (15 mg/kg) and MG (15 mg/kg) enhanced serotonergic behaviour. MB and MG bolstered cortico-limbic serotonin (5HT) levels and to a lesser extent l-norepinephrine (l-NE), but did not significantly alter regional dopamine (DA) levels. MB, and to lesser degree MG, reduced hippocampal nitrate levels. MB and MG present with structure-specific antidepressant-like effects following acute and sub-chronic treatment, possibly involving NOS and MAO-A inhibition and cortico-limbic 5HT and l-NE release. A role for MAO-B and DA appears minimal.


Altered functional connectivity of primary visual cortex in late blindness.
Previous studies demonstrated that early blindness is associated with abnormal intrinsic functional connectivity (FC) between the primary visual cortex (V1) and other sensory areas. However, the V1 pattern of spontaneous neural activity occurring in late blindness (LB) remains unknown. The purpose of this study was to investigate the intrinsic FC patterns of V1 in LB. Thirty LB individuals (18 males and 12 females; mean age: 38.76±14.43 years) and 30 sighted controls (SCs) individuals (18 males and 12 females; mean age: 38.67±13.85 years) closely matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. Region of interest analysis was performed to extract the correlation coefficient matrix among each pair of Brodmann area (BA) 17 and FC between V1 and vision-related subcortical nuclei. Compared with SCs, LB individuals showed a decreased FC between the left V1 and the bilateral cuneus (CUN)/lingual gyrus (LGG)/calcarine (CAL) (BA 18/19/30) and left precentral gyrus (PreCG) and the postcentral gyrus (PostCG) (BA 2/3/4). Also, LB individuals showed a decreased FC between the right V1 and the bilateral CUN/LGG/CAL (BA 18/19/30) and the left PreCG and PostCG (BA 2/3/4/6) (voxel-level: P<0.01, cluster-level: P<0.05). Meanwhile, LB individuals showed a decreased FC between the left V1 and the right V1 and increased FC between the left V1 and the right superior colliculus, the right V1, and the left hippocampus (P<0.05). Moreover, a positive correlation was observed between the onset age of blindness and FC values in V1 to CUN/LGG/CAL in LB. Our results highlighted that LB induces a decreased FC between V1 and higher visual areas, motor cortices, and somatosensory cortices at rest. This might indicate that LB humans could present with impaired top-down modulations, visual imagery, and vision-motor function.


CVD graphene as interfacial layer to engineer the organic donor-acceptor heterojunction interface properties.
We demonstrate the use of chemical-vapor-deposited (CVD) graphene as an effective indium-tin-oxide (ITO) electrode surface modifier to engineer the organic donor-acceptor heterojunction interface properties in an inverted organic solar cell device configuration. As revealed by in situ near-edge X-ray adsorption fine structure measurement, the organic donor-acceptor heterojunction, comprising copper-hexadecafluoro-phthalocyanine (F16CuPc) and copper phthalocyanine (CuPc), undergoes an obvious orientation transition from a standing configuration (molecular π-plane nearly perpendicular to the substrate surface) on the bare ITO electrode to a less standing configuration with the molecular π-plane stacking adopting a large projection along the direction perpendicular to the electrode surface on the CVD graphene-modified ITO electrode. Such templated less-standing configuration of the organic heterojunction could significantly enhance the efficiency of charge transport along the direction perpendicular to the electrode surface in the planar heterojunction-based devices. Compared with the typical standing organic-organic heterojunction on the bare ITO electrode, our in situ ultraviolet photoelectron spectroscopy experiments reveal that the heterojunction on the CVD graphene modified ITO electrode possesses better aligned energy levels with respective electrodes, hence facilitating effective charge collection.


An Optimization-Based Locomotion Controller for Quadruped Robots Leveraging Cartesian Impedance Control.
Quadruped robots require compliance to handle unexpected external forces, such as impulsive contact forces from rough terrain, or from physical human-robot interaction. This paper presents a locomotion controller using Cartesian impedance control to coordinate tracking performance and desired compliance, along with Quadratic Programming (QP) to satisfy friction cone constraints, unilateral constraints, and torque limits. First, we resort to projected inverse-dynamics to derive an analytical control law of Cartesian impedance control for constrained and underactuated systems (typically a quadruped robot). Second, we formulate a QP to compute the optimal torques that are as close as possible to the desired values resulting from Cartesian impedance control while satisfying all of the physical constraints. When the desired motion torques lead to violation of physical constraints, the QP will result in a trade-off solution that sacrifices motion performance to ensure physical constraints. The proposed algorithm gives us more insight into the system that benefits from an analytical derivation and more efficient computation compared to hierarchical QP (HQP) controllers that typically require a solution of three QPs or more. Experiments applied on the ANYmal robot with various challenging terrains show the efficiency and performance of our controller.


Sedimentation characteristics of newly synthesized Epstein-Barr viral DNA in superinfected cells.
Replicating Epstein-Barr virus (EBV) DNA molecules isolated from superinfected Raji cells were shown to consist of 80S to 65S and 58S (mature) molecules Pulse-chase experiments showed that radioactive label of DNAS molecules with the larger sedimentation coefficients was partially chased into 58S labeled forms. Formation of large concatemers of viral DNA could not be detected at any time after superinfection. The continuous presence of the 65S viral DNA intermediate throughout the replicative cycle combined with the observed inhibition of EBV DNA synthesis by addition of nontoxic levels of ethidium bromide to the superinfected cell culture led us to propose that EBV replication proceeds via a relaxed circular DNA intermediate.


The 18-kDa mitochondrial translocator protein in human gliomas: an 11C-(R)PK11195 PET imaging and neuropathology study.
The 18-kDa mitochondrial translocator protein (TSPO) is upregulated in high-grade astrocytomas and can be imaged by PET using the selective radiotracer (11)C-(R)PK11195. We investigated (11)C-(R)PK11195 binding in human gliomas and its relationship with TSPO expression in tumor tissue and glioma-associated microglia/macrophages (GAMs) within the tumors. Twenty-two glioma patients underwent dynamic (11)C-(R)PK11195 PET scans and perfusion MR imaging acquisition. Parametric maps of (11)C-(R)PK11195 binding potential (BPND) were generated. Coregistered MR/PET images were used to guide tumor biopsy. The tumor tissue was quantitatively assessed for TSPO expression and infiltration of GAMs using immunohistochemistry and double immunofluorescence. The imaging and histopathologic parameters were compared among different histotypes and grades and correlated with each other. BPND of (11)C-(R)PK11195 in high-grade gliomas was significantly higher than in low-grade astrocytomas and low-grade oligodendrogliomas. TSPO in gliomas was expressed predominantly by neoplastic cells, and its expression correlated positively with BPND in the tumors. GAMs only partially contributed to the overall TSPO expression within the tumors, and TSPO expression in GAMs did not correlate with tumor BPND. PET with (11)C-(R)PK11195 in human gliomas predominantly reflects TSPO expression in tumor cells. It therefore has the potential to effectively stratify patients who are suitable for TSPO-targeted treatment.


Open loop control theory algorithms for high-speed 3D MEMS optical switches.
There is a world-wide push to create the next-generation all-optical transmission and switching technologies for exascale data centers. In this paper we focus on the switching fabrics. Many different types of 2D architectures are being explored including MEMS/waveguides and semiconductor optical amplifiers. However, these tend to suffer from high, path-dependent losses and crosstalk issues. The technologies with the best optical properties demonstrated to date in large fabrics (>100 ports) are 3D MEMS beam steering approaches. These have low average insertion losses and, equally important, a narrow loss distribution. However, 3D MEMS fabrics are generally dismissed from serious consideration for this application because of their slow switching speeds (∼few milliseconds) and high costs ($100/port). In this paper we show how novel feedforward open loop controls can solve both problems by improving MEMS switching speeds by two orders of magnitude and costs by a factor of three. With these improvements in hand, we believe 3D MEMS fabrics can become the technology of choice for data centers.


Terpenoids biotransformation in mammals III: Biotransformation of alpha-pinene, beta-pinene, pinane, 3-carene, carane, myrcene, and p-cymene in rabbits.
The biotransformation of (+)-, (-)-, and (+-)-alpha-pinenes, (-)-beta-pinene (nopinene), (-)-cis-pinane, (+)-3-carene, (-)-cis-carane, myrcene, and p-cymene in rabbits was investigated. The major metabolites were as follows: (-)-trans-verbenol from (+)-, (-)-, and (+/-)-alpha-pinenes; (-)-10-pinanol and (-)-1-p-menthene-7,8-diol from (-)-beta-pinene; (-)-alpha-terpineol and (-)-trans-sobrerol from (-)-cis-pinane; (-)-m-mentha-4,6-dien-8-ol, 3-caren-9-ol, (-)-3-carene-9-carboxylic acid, and 3-carene-9,10-dicarboxylic acid from (+)-3-carene; carane-9,10-dicarboxylic acid from (-)-cis-carane; and myrcene-3(10)-glycol, myrcene-1,2-glycol, uroterpenol, and p-cymene-9-carboxylic acid from p-cymene. These metabolisms include allylic oxidation, epoxidation, stereoselective gem-dimethyl hydroxylation and its oxidation, cleavage of a conjugated double bond by epoxidation, and regioselective oxidation, some of which are not found usually in chemical reactions, and due to which various new compounds were determined. This biotransformation of the monoterpene hydrocarbons gave some insect pheromones in high yield.U


Differential regulation of renal glomerular and preglomerular vascular angiotensin II receptors.
The activity of the renin-angiotensin system (RAS) can be influenced by sodium intake and angiotensin II (ANG II) infusion. It has been shown that ANG II can regulate the density of its receptors. Therefore, we investigated the regulation of glomerular and preglomerular vascular ANG II receptors by changes in RAS activity. Sprague-Dawley rats were fed a low- or high-sodium diet or were infused with nonpressor or pressor doses of ANG II for 7 days. ANG II receptor characteristics were determined by radioligand binding assays with use of ANG II antagonists losartan and PD-123319. AT1 was the only receptor type found in membrane preparations from all groups. Glomerular ANG II receptor characteristics in all groups were unchanged compared with their controls, whereas vascular receptor density was significantly downregulated by sodium restriction. We conclude that glomerular and preglomerular vascular ANG II receptors are differentially regulated such that AT1 receptors in preglomerular vessels can be regulated by changes in endogenous RAS. ANG II infusion did not induce any modification of either glomerular or vascular AT1 receptors, suggesting a predominant role of the endogenous local renal RAS.


Sexual recombinants make a significant contribution to epidemics caused by the wheat pathogen Phaeosphaeria nodorum.
We conducted a 2-year mark-release-recapture field experiment to quantify the relative contributions of immigration and sexual and asexual reproduction to epidemics of Stagonospora nodorum blotch caused by Phaeosphaeria nodorum. The epidemic was initiated using nine genetically distinct P. nodorum isolates. Infected plants were sampled four times across two growing seasons. In total, 1,286 isolates were recovered and assayed with 10 microsatellite markers and 1 minisatellite marker. The proportion of isolates having multilocus haplotypes (MLHTs) identical to the inoculated isolates decreased steadily from 86% in the first collection to 25% in the fourth collection. The novel isolates that had different MLHTs compared with the marked inoculants originated through immigration and sexual recombination. By the end of the experiment, nearly three-quarters of the novel isolates originated from sexual recombination. Our results indicate that recombinant offspring and airborne immigrant ascospores can make significant contributions to epidemics of Stagonospora nodorum blotch during a growing season.


High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus.
Patients with type 2 diabetes mellitus have a higher susceptibility for colorectal cancer and poorer prognosis, but the mechanism is still unknown. Here, we investigated the effect of ADP-ribosyltransferase 1 (ART1) on the growth of colorectal cancer in an animal model of diabetes with high norepinephrine status, as well as the potential mechanism. We evaluated the size and weight of transplanted CT26 cell tumors with different ART1 expression levels in a mouse model of diabetes, as well as the survival time. CCK8 and flow cytometry were used to evaluate the growth of CT26 cells in vitro. Western blot was performed to analyze differentially expressed proteins in the ART1-modulated pathway. High levels of norepinephrine and ART1 favored the proliferation of CT26 cells in vitro and in vivo. Moreover, inhibition of norepinephrine-dependent proliferation was observed in ART1-silenced CT26 cells compared to those with normal ART1 expression. Following reduction of the serum norepinephrine level by surgery, the size and weight of transplanted CT26 cell tumors was significantly reduced compared to non-operated and sham-operated mice. Furthermore, the expression of ART1, mTOR, STAT3, and p-AKT protein in the tumor tissue of diabetic mice was higher than in non-diabetic mice. Following reduction of the norepinephrine level by renal denervation (RD), expression of the proliferation-related proteins mTOR, STAT3, p-AKT protein decreased, but no change was seen for ART1 expression. At the same concentration of norepinephrine, ART1 induced the expression of p-AKT, mTOR, STAT3, CyclinD1 and c-myc in CT26 cells in vitro. We conclude that faster growth of colorectal cancer in high norepinephrine conditions requires the expression of ART1, and that high ART1 expression may be a novel target for the treatment of diabetes-associated colorectal cancer.


Anterior-posterior patterning in early development: three strategies.
The anterior-posterior (AP) axis is the most ancient of the embryonic axes and exists in most metazoans. Different animals use a wide variety of mechanisms to create this axis in the early embryo. In this study, we focus on three animals, including two insects (Drosophila and Tribolium) and a vertebrate (zebrafish) to examine different strategies used to form the AP axis. While Drosophila forms the entire axis within a syncytial blastoderm using transcription factors as morphogens, zebrafish uses signaling factors in a cellularized embryo, progressively forming the AP axis over the course of a day. Tribolium uses an intermediate strategy that has commonalities with both Drosophila and zebrafish. We discuss the specific molecular mechanisms used to create the AP axis and identify conserved features.


Occurrence of renal tubular dysfunction in lupus nephritis.
We prospectively evaluated 30 patients who presented with active systemic lupus erythematosus (SLE) for the presence of tubular abnormalities. All patients fulfilled the American Rheumatology Association criteria for SLE. When appropriate, a renal biopsy was performed. Of the 30 patients studied, 12 had no abnormal tubular study results, whereas 18 patients had some form of defect in the handling of potassium, sodium, or hydrogen ions. Eight patients had distal renal tubular acidosis (dRTA) due to an isolated proton secretory defect. Five had dRTA of the gradient or acid back-leak type. Two had an unresponsive voltage-dependent form of dRTA; one had a responsive voltage-dependent form of dRTA. One individual had hyporeninemic hypoaldosteronism and one had dRTA plus hypoaldosteronism. Clinically, patients with the abnormal tubular study results more often presented with nephritis or nephrotic sediment, peripheral edema, or anemia. Renal biopsies failed to demonstrate any difference in glomerular histologic findings and calculated activity, chronicity, or interstitial indexes. We conclude that SLE may be associated with a variety of tubular defects.


Neural correlates of impaired emotion processing in manifest Huntington's disease.
The complex phenotype of Huntington's disease (HD) encompasses motor, psychiatric and cognitive dysfunctions, including early impairments in emotion recognition. In this first functional magnetic resonance imaging study, we investigated emotion-processing deficits in 14 manifest HD patients and matched controls. An emotion recognition task comprised short video clips displaying one of six basic facial expressions (sadness, happiness, disgust, fear, anger and neutral). Structural changes between patients and controls were assessed by means of voxel-based morphometry. Along with deficient recognition of negative emotions, patients exhibited predominantly lower neural response to stimuli of negative valences in the amygdala, hippocampus, striatum, insula, cingulate and prefrontal cortices, as well as in sensorimotor, temporal and visual areas. Most of the observed reduced activity patterns could not be explained merely by regional volume loss. Reduced activity in the thalamus during fear correlated with lower thalamic volumes. During the processing of sadness, patients exhibited enhanced amygdala and hippocampal activity along with reduced recruitment of the medial prefrontal cortex. Higher amygdala activity was related to more pronounced amygdala atrophy and disease burden. Overall, the observed emotion-related dysfunctions in the context of structural neurodegeneration suggest both disruptions of striatal-thalamo-cortical loops and potential compensation mechanism with greater disease severity in manifest HD.


Conatumumab, a fully human mAb against death receptor 5 for the treatment of cancer.
Conatumumab (AMG-655), under development by Amgen Inc and Japanese licensee Takeda Bio Development Center Ltd, is a fully human IgG1 mAb that binds to the extracellular domain of death receptor 5 (DR5) for the potential intravenous treatment of cancer. In vitro and in vivo studies have demonstrated that conatumumab induces apoptosis in cell lines derived from colon and pancreatic cancers, as well as in mice bearing xenograft tumors. Preclinical studies also indicated that conatumumab enhances the antitumor activity of agents, such as irinotecan and gemcitabine. The results of phase I clinical trials have demonstrated the safety of conatumumab as a monotherapy, as well as in combination with other antibody therapies or standard chemotherapeutic regimes. In addition, anti-conatumumab antibody responses have not been observed in the trials conducted to date. At the time of publication, initial results from phase I/II trials suggest a possible therapeutic role for conatumumab in patients with tumors expressing DR5.


The ClpP protease homologue is required for the transmission traits and cell division of the pathogen Legionella pneumophila.
Legionella pneumophila, the intracellular bacterial pathogen that causes Legionnaires' disease, exhibit characteristic transmission traits such as elevated stress tolerance, shortened length and virulence during the transition from the replication phase to the transmission phase. ClpP, the catalytic core of the Clp proteolytic complex, is widely involved in many cellular processes via the regulation of intracellular protein quality. In this study, we showed that ClpP was required for optimal growth of L. pneumophila at high temperatures and under several other stress conditions. We also observed that cells devoid of clpP exhibited cell elongation, incomplete cell division and compromised colony formation. Furthermore, we found that the clpP-deleted mutant was more resistant to sodium stress and failed to proliferate in the amoebae host Acanthamoeba castellanii. The data present in this study illustrate that the ClpP protease homologue plays an important role in the expression of transmission traits and cell division of L. pneumophila, and further suggest a putative role of ClpP in virulence regulation.


Improvement of the Vietnamese diet for women of reproductive age by micronutrient fortification of staples foods and condiments.
A micronutrient survey carried out in 2010 among randomly selected Vietnamese women in reproductive age indicated that anemia and micronutrient deficiencies are still prevalent. The objective of this study was thus to analyze the dietary micronutrient intakes of these women, to select the food vehicles to be fortified and to calculate their contributions to meet the recommended nutrient intake (RNI) for iron, zinc, vitamin A and folic acid. Consumption data showed that the median intake was 38.4% of the RNI for iron, 61.1% for vitamin A and 91.8% for zinc. However, more than 50% of the women had daily zinc consumption below the RNI. Rice and vegetable oil were consumed daily in significant amounts (median: 320.4 g/capita/day and 8.6 g/capita/day respectively) by over 90% of the women, making them suitable vehicles for fortification. Based on consumption data, fortified vegetable oil could contribute to an additional vitamin A intake of 27.1% of the RNI and fortified rice could increase the intake of iron by 41.4% of the RNI, zinc by 15.5% and folate by 34.1%. Other food vehicles, such as fish and soy sauces and flavoring powders, consumed respectively by 63% and 90% of the population could contribute to increase micronutrient intakes if they are properly fortified and promoted. Wheat flower was consumed by 39% of the women and by less than 20% women from the lowest socioeconomic strata. The fortification of edible vegetable oils with vitamin A and of rice with iron, zinc and folic acid are the most promising fortification strategies to increase micronutrient intakes of women in reproductive age in Vietnam. While rice fortification will be implemented, fortification of fish and soy sauces with iron, that has been proven to be effective, has to be supported and fortification of flavouring powders with micronutrients investigated.


Abnormal umbilical cord Doppler sonograms may predict impending demise in fetuses with sacrococcygeal teratoma. A report of two cases.
To identify factors predictive of fetal demise in fetuses with sacrococcygeal teratoma (SCT). The recent management of monochorionic twins discordant for a large SCT and a singleton with a large SCT was reviewed. Serial fetal echocardiography and ultrasonography with Doppler flow measurements documented rapid growth of the SCT in both cases with a relatively modest increase in combined cardiac output. No placentomegaly or hydrops was observed at any time. In both fetuses with SCT, evolution of abnormal umbilical artery waveforms was observed with the ultimate development of reversed end-diastolic umbilical arterial flow that was followed by sudden fetal demise. Death in these 2 fetuses with large SCTs in the absence of placentomegaly/hydrops or hemodynamic changes suggestive of evolving high-output failure suggests a previously unrecognized mechanism of death in fetuses with large rapidly growing SCTs. In these cases, fetal demise may only be heralded by abnormal umbilical artery waveforms that progress to the premorbid observation of reversed diastolic umbilical artery blood flow. Umbilical artery waveform analysis should be closely monitored with other hemodynamic parameters in fetuses with large SCTs. In such fetuses, depending on the gestational age, abnormalities in umbilical artery waveform should be considered indications for early delivery or in utero intervention to prevent fetal demise.


Integrating Chemical Biological, Radiologic, and Nuclear (CBRN) Protocols Into TCCC Introduction of a Conceptual Model - TCCC + CBRN = (MARCHE)2.
The authors would like to introduce TCCC [Tactical Combat Casualty Care] + CBRN [chemical, biological, radiological, and nuclear] = (MARCHE)2 as a conceptual model to frame the response to CBRN events. This model is not intended to replace existing and well-established literature on CBRNE events but rather to serve as a response tool that is an adjunct to agent specific resources.


Discernment between deliberate and natural infectious disease outbreaks.
Public health authorities should be vigilant to the potential for outbreaks deliberately caused by biological agents (bioterrorism). Such events require a rapid response and incorporation of non-traditional partners for disease investigation and outbreak control. The astute application of infectious disease epidemiological principles can promote an enhanced index of suspicion for such events. We discuss epidemiological indicators that should be considered during outbreak investigations, and also examine their application during bioterrorism incidents, an accidental release of an agent, outbreaks of infections that were alleged to have been deliberately initiated, and a model scenario. The Grunow & Finke epidemiological assessment tool is used to examine these historical events and the model scenario. The results received from this analysis, coupled with an understanding of epidemiological clues to unnatural events, and knowledge of how to manage such events, can aid in the improved response and resolution of epidemics.


Student evaluations of teaching tools: a qualitative examination of student perceptions.
Student evaluations of teaching (SET) are common and controversial, yet there is limited understanding of student perceptions of these evaluation tools. The authors examined an evidence-based SET tool for content validity using BSN, RN-to-BSN, and MSN student focus groups to explore individual question items and identify themes. Through communication and relationships with students, SET can influence teaching effectiveness and student learning, although student perceptions of individual items vary greatly.


Quality of clinical practice guidelines on interventional management of low back pain: A systematic review.
To appraise the quality of low back pain (LBP) clinical practice guidelines (CPG) that include interventional management recommendations and to associate their quality with characteristics including publication year and creating organization. TYPE: Systematic Review. LBP (subacute or chronic) CPGs in English (symptom based, governmental or professional society created, January 1990-May 2020) were found using MEDLINE, EMBASE, CINAHL, Ortho Guidelines, CPG Infobase, ECRI, Guidelines International Network, NICE, and SIGN. In this third order systematic review, search results were deduplicated, title and abstract screened by two independent reviewers, and full texts reviewed by four reviewers. Discrepancies were resolved by a third reviewer. Resulted CPGs were appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE II) Tool by four appraisers each. Association of their quality with creating organization, geographical region, and year of creation was calculated. Seven hundred fourteen screened documents resulted in 21 final CPGs. On appraisal, average overall CPG quality was 5.2 (range 2.5-6.75). Domain 5 (applicability) had the lowest average (44%) and domain 4 (clarity of presentation) had the highest average score (82%). For overall recommendation, 16 received "yes" or "yes with modifications," six received unanimous "yes" and two unanimous "no" votes. The interrater agreement of domain scoring was excellent (0.8-1.0; p < .001). There was no association found between quality of CPG and (1) year of publication (R2 = 0.0006), (2) whether the CPG was updated or new (p = .17), and (3) region of publication (p = .37). The majority of the 21 CPGs identified in this systematic review were of high quality, but overall quality and recommendation ratings were variable. The quality of appraised CPGs showed no association with their characteristics. Some domains such as "applicability" scored uniformly lower, revealing opportunity for improvement in future CPG development. LBP CPGs should be scrutinized before adopting their recommendations.


Innervation of interstitial cells of Cajal by vasoactive intestinal polypeptide containing nerves in canine colon.
The hypothesis was tested, through structural and functional studies, that interstitial cells of Cajal receive and can respond to direct innervation from nerves containing the vasoactive intestinal polypeptide neuromediator. The submucosal network of interstitial cells of Cajal has been postulated to provide pacemaking activity for the circular muscle and to be involved in neurotransmission from nonadrenergic, noncholinergic nerves for which vasoactive intestinal polypeptide is a putative mediator. The distribution of vasoactive intestinal polypeptide and substance P immunoreactive material in nerve profiles of the enteric nervous system of the canine colon was examined. In addition, electrophysiological studies were done on the interstitial cells bordering the submucosal side of the circular muscle layer after they were electrically isolated using heptanol. The vasoactive intestinal polypeptide immunoreactivity, located exclusively in nerve large granular vesicles, was found throughout the enteric nervous system (myenteric plexus, submucous plexus, and circular muscle--submucosa interface). The highest proportion (38% compared with 22-24%) of profiles of large granular vesicles with vasoactive intestinal polypeptide immunoreactivity was found in nerve profiles of the circular muscle--submucosa interface. In contrast, substance P immunoreactivity was found in nerve profiles of myenteric plexus (33% of large granular vesicles were positive) but not associated with submucosal interstitial cell nerve network. The vasoactive intestinal polypeptide hyperpolarized interstitial cells by 9 mV when electrically isolated by 1 mM heptanol and markedly reduced (about 50%) their input membrane resistance. We conclude that the distribution of vasoactive intestinal polypeptide immunoreactivity and its action are consistent with a postulated role of the interstitial cells as a major site of neurally mediated inhibition of colonic pacemaker activity.


Differential activation of Staphylococcus aureus heme detoxification machinery by heme analogues.
The reactive nature of heme enables its use as an enzymatic cofactor while rendering excess heme toxic. The importance of heme detoxification machinery is highlighted by the presence of various types of these homeostatic systems in Gram-positive and Gram-negative microorganisms. A number of pathogens possess orthologs of the HssRS/HrtAB heme detoxification system, underscoring a potential role this system plays in the survival of bacteria in heme-rich environments such as the vertebrate host. In this work, we sought to determine the role of this system in protection against metalloporphyrin heme analogues identified by previous studies as antimicrobial agents. Our findings demonstrate that only toxic metalloporphyrins maximally activate expression of the Staphylococcus aureus heme detoxification system, suggesting that the sensing mechanism of HssRS might require a component of the associated toxicity rather than or in addition to the metalloporphyrin itself. We further establish that only a subset of toxic metalloporphyrins elicit the oxidative damage previously shown to be a significant component of heme toxicity whereas all toxic noniron metalloporphyrins inhibit bacterial respiration. Finally, we demonstrate that, despite the fact that toxic metalloporphyrin treatment induces expression of S. aureus heme detoxification machinery, the HrtAB heme export pump is unable to detoxify most of these molecules. The ineffectiveness of HrtAB against toxic heme analogues provides an explanation for their increased antimicrobial activity relative to heme. Additionally, these studies define the specificity of HssRS/HrtAB, which may provide future insight into the biochemical mechanisms of these systems.


Psychometric Evaluation of the Polish Version of the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD).
The assessment of the quality of life is an important element of the clinical examination of the patient. The aim of this study was translation and cross-cultural adaptation of the "Caregiver Priorities and Child Health Index of Life with Disabilities" (CPCHILD) questionnaire into Polish language, and testing of reliability and validity of the CPCHILD-PL for children with cerebral palsy (CP). A Polish version of CPCHILD was created according to internationally accepted guidelines. Parents (n=77) of 51 boys/26 girls between 3 and 17 years with CP with Gross Motor Function Classification System I-V (GMFCS I-V) participated. To assess the reliability each domain and the total measure was tested for internal consistency and test-retest reliability. Convergent validity was evaluated by correlating the CPCHILD-PL with the CHAQ (Childhood Health Assessment Questionnaire) questionnaire. Test-retest reliability assessed by Spearman correlation coefficient for the final result of CPCHILD-PL and for most of domains were above 0.90. The values of Cronbach's-α coefficient (measuring internal consistency) were high for all domains (except for domain 5: Health) and the entire CPCHILD-PL, with the range 0.88-0.96. The comparison between CPCHILD-PL and the Disability Index (DI) of the CHAQ showed a negative correlation. The higher the DI, the lower the CPCHILD result. The Spearman's rank coefficient was -0.75. The Polish version for the CPCHILD for children with CP seems to be reliable and valid tool for assessing health-related quality of life from the caregiver perspective. It can be used in research and clinical practice for evaluation and comparison of health-related quality of life in children with CP in different countries.


Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation: A Pilot Randomized Trial.
To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. Randomized, controlled, unblinded study. Two ICUs of two university hospitals. Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601-16,031 U] vs 20,710 U [95% CI, 15,343-27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95% CI, 43.5-53.2 s] vs 55.5 s [95% CI, 50.4-61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95% CI, 0.07-0.18] vs 0.27 [95% CI, 0.17-0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes. Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation.


State Laws That Require Coprescribing Opioids and Naloxone and Codispensing Practices.
Coprescribing naloxone with opioids could reduce the risk of overdose. By the end of 2020, 8 U.S. states implemented coprescribing laws requiring the prescription of naloxone alongside certain opioid prescriptions. This study examined the impacts of state laws that require coprescribing opioids and naloxone on codispensing practices. Data included opioid prescriptions for commercially insured adults between 2014 and 2020. Augmented synthetic control analyses were used to examine the impacts of 8 coprescribing requirement laws implemented between 2017 and 2020 on the proportion of opioid prescription fills with a naloxone coprescription fill. Analyses were completed in spring 2023. Changes in the proportion of opioid prescription fills with a naloxone coprescription fill attributable to the laws varied across states. In 4 states (New Jersey, New Mexico, Rhodes Island, and Virginia), laws were associated with 0.8 (95% CI=0.3, 1.3) to 4.4 (95% CI=3.4, 5.4) percentage point increases in the proportion of opioid prescriptions with a naloxone coprescription fill (p<0.05). There were no statistically significant changes attributable to the other state laws (Arizona, Florida, Vermont, Washington). Laws requiring coprescribing naloxone with certain opioid prescriptions are associated with small-in-magnitude increases in codispensing in some states. Broadening the categories of opioid prescriptions covered in naloxone coprescribing requirement laws and implementing health system strategies to encourage providers to coprescribe naloxone could help to magnify the impacts of these laws.


Polysaccharide niche partitioning of distinct Polaribacter clades during North Sea spring algal blooms.
Massive releases of organic substrates during marine algal blooms trigger growth of many clades of heterotrophic bacteria. Algal polysaccharides represent the most diverse and structurally complex class of these substrates, yet their role in shaping the microbial community composition is poorly understood. We investigated, whether polysaccharide utilization capabilities contribute to niche differentiation of Polaribacter spp. (class Flavobacteriia; known to include relevant polysaccharide-degraders) that were abundant during 2009-2012 spring algal blooms in the southern North Sea. We identified six distinct Polaribacter clades using phylogenetic and phylogenomic analyses, quantified their abundances via fluorescence in situ hybridization, compared metagenome-assembled genomes, and assessed in situ gene expression using metaproteomics. Four clades with distinct polysaccharide niches were dominating. Polaribacter 2-a comprised typical first responders featuring small genomes with limited polysaccharide utilization capacities. Polaribacter 3-a were abundant only in 2010 and possessed a distinct sulfated α-glucoronomannan degradation potential. Polaribacter 3-b responded late in blooms and had the capacity to utilize sulfated xylan. Polaribacter 1-a featured high numbers of glycan degradation genes and were particularly abundant following Chattonella algae blooms. These results support the hypothesis that sympatric Polaribacter clades occupy distinct glycan niches during North Sea spring algal blooms.


Structural basis for recognition of phosphorylated high mannose oligosaccharides by the cation-dependent mannose 6-phosphate receptor.
Mannose 6-phosphate receptors (MPRs) play an important role in the targeting of newly synthesized soluble acid hydrolases to the lysosome in higher eukaryotic cells. These acid hydrolases carry mannose 6-phosphate recognition markers on their N-linked oligosaccharides that are recognized by two distinct MPRs: the cation-dependent mannose 6-phosphate receptor and the insulin-like growth factor II/cation-independent mannose 6-phosphate receptor. Although much has been learned about the MPRs, it is unclear how these receptors interact with the highly diverse population of lysosomal enzymes. It is known that the terminal mannose 6-phosphate is essential for receptor binding. However, the results from several studies using synthetic oligosaccharides indicate that the binding site encompasses at least two sugars of the oligosaccharide. We now report the structure of the soluble extracytoplasmic domain of a glycosylation-deficient form of the bovine cation-dependent mannose 6-phosphate receptor complexed to pentamannosyl phosphate. This construct consists of the amino-terminal 154 amino acids (excluding the signal sequence) with glutamine substituted for asparagine at positions 31, 57, 68, and 87. The binding site of the receptor encompasses the phosphate group plus three of the five mannose rings of pentamannosyl phosphate. Receptor specificity for mannose arises from protein contacts with the 2-hydroxyl on the terminal mannose ring adjacent to the phosphate group. Glycosidic linkage preference originates from the minimization of unfavorable interactions between the ligand and receptor.


Angiotensin I level and sporadic hypokalemic periodic paralysis.
A patient with secondary (sporadic type) hypokalemic periodic paralysis with relative hypertension had reninism with a high concentration of plasma angiotensin I (ANG-I) but no hyperaldosteronism or high angiotensin II value. Angiotensin-converting enzyme (ACE) activity was usually normal. Results of other hormonal analyses were also normal. However, the glomerular filtration rate and filtration fraction of the kidneys were greatly elevated. Despite severe hypokalemia, the patient's potassium clearance was high. No evidence of distinct hyperplasia of the juxtaglomerular cells was obtained. These results suggest that decreased affinity of ACE to the substrate ANG-I (so-called ACE dysfunction syndrome) produced the reninism and high concentration of plasma ANG-I, and that the latter induced an increase in the glomerular filtration rate of the kidneys with sequential occurrence of secondary hypokalemic periodic paralysis.


Cell cycle as a target of antineoplastic drugs.
The cell cycle consists of a number of complex biochemical pathways that ensure that the start of a particular event depends on the successful and right end of previous steps in the pathway. An important role is played by cyclin/cyclin-dependent kinase (cdk) complexes which are critical regulators of cell cycle progression and RNA transcription. To ensure proper progression through each phase, cells have developed a series of orchestrated checkpoints that govern the different cellular kinases required for distinct cell cycle events. In particular, several cell cycle protein kinases, including members of the Aurora family and the Polo-like kinases, play critical roles in mitotic entry and chromosome segregation that ensure the correct formation of daughter cells. Tumour cell proliferation is frequently associated to both genetic and epigenetic mechanisms commonly affecting the expression of cell cycle regulatory proteins or causing an incompetent checkpoint control, resulting in aberrant responses to cellular damage. These alterations result not only in proliferative advantages but also in an increased susceptibility to the accumulation of additional genetic alterations that contribute to tumour progression and acquisition of more aggressive phenotypes. In the last years, the identification of anticancer drugs directed against critical cell cycle regulators has received particular attention. Specifically, several preclinical and clinical trials are addressing cdks or cell cycle protein kinase inhibitors. Starting from a description of cell cycle, this review summarizes the most recent studies on drugs targeting cell cycle regulators that are being used in cancer therapy.


Early childhood depression, emotion regulation, episodic memory, and hippocampal development.
Depression in adults is associated with deficits in a number of cognitive domains, however it remains less clear how early in development theses deficits can be detected in early onset depression. There are several different hypotheses about the links between cognitive function and depression. For example, it has been argued that executive function deficits contribute to emotion regulation difficulties, which in turn increase risk for depression. Further, it has been suggested that some cognitive deficits, such as episodic memory, may reflect hippocampal abnormalities linked to both depression and episodic memory. We examined these questions in adolescents participating in a longitudinal study of preschool onset depression. We measured cognitive function at adolescence using the National Institutes of Health toolbox (vocabulary, processing speed, executive function, working memory and episodic memory), and examined relationships of cognitive deficits to depression, emotion regulation, life stress and adversity, as well as hippocampal volume trajectories over three imaging assessments starting at school age. Depression related deficits in episodic memory were found. Youths with either current and past depression showed episodic memory deficits even after controlling for other psychopathology and family income. Depression severity, emotion dysregulation, and life stress/adversity all predicted episodic memory impairment, as did smaller intercepts and slopes of hippocampal growth over time. Modest relationships of depression to hippocampal volume and strong relationships between emotion regulation and both episodic memory and hippocampal volume were found. These data are consistent with prior work in adults linking depression, episodic memory, emotion regulation, life stress/adversity, and hippocampal volume in adults and suggest similar relations are evident as early as adolescence when memory systems are under development. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Streptococcal infection in dogs: a retrospective study of 393 cases.
Streptococcus spp are opportunistic pathogens that normally reside in the upper respiratory, intestinal, lower urinary, and genital tracts but can cause localized infection or septicemia in dogs of all ages. A retrospective study of streptococcal infection in 393 dogs was conducted to identify the species of Streptococcus isolated, determine demographics of affected dogs, and characterize the disease processes associated with infection. The major streptococcal species isolated were S canis (88 cases, 22.4%), S dysgalactiae ssp equisimilis (13, 3.3%), and S equi ssp zooepidemicus (4, 1.0%). Sex was not a risk factor (P > .30). Fetuses and neonates were more likely to have streptococcal infection than were other age groups (P < .001). Streptococcal septicemia was considered an important cause of abortion and neonatal death and was isolated from all samples submitted for aerobic culture from dogs in that age group. There was a seasonal trend, with dogs more likely to have streptococcal infection in summer months. In dogs for which a disease process was identified, streptococcal infection was associated with dermatitis (29 dogs), pneumonia (24 dogs), adult septicemia (13 dogs), and fetal/neonatal septicemia leading to abortion or neonatal death (16 dogs). Identification of other clinically significant bacterial, viral, fungal, and parasitic organisms was common (267 of 393 dogs, 68%), especially in dogs with dermatitis or pneumonia. Infection with Streptococcus spp should be considered in the differential diagnosis in cases of abortion, septicemia, dermatitis, and pneumonia in dogs. Clinical significance of isolation of streptococcal organisms should be interpreted in context of clinical signs and pathologic findings.


A review of psychosocial outcomes for patients seeking cosmetic surgery.
The authors reviewed the literature on psychological and psychosocial outcomes for individuals undergoing cosmetic surgery, to address whether elective cosmetic procedures improve psychological well-being and psychosocial functioning and whether there are identifiable predictors of an unsatisfactory psychological outcome. They conducted a search of appropriate computerized databases for studies that evaluated psychological and psychosocial status both before and after elective cosmetic surgery. They identified 37 relevant studies of varying cosmetic procedures that utilized disparate methodologies. Overall, patients appeared generally satisfied with the outcome of their procedures, although some exhibited transient and some exhibited longer-lasting psychological disturbance. Factors associated with poor psychosocial outcome included being young, being male, having unrealistic expectations of the procedure, previous unsatisfactory cosmetic surgery, minimal deformity, motivation based on relationship issues, and a history of depression, anxiety, or personality disorder. Body dysmorphic disorder was also recognized by some studies as a predictor of poor outcome, a finding reinforced by reference to the psychiatric literature. The authors conclude that although most people appear satisfied with the outcome of cosmetic surgical procedures, some are not, and attempts should be made to screen for such individuals in cosmetic surgery settings.


Prevalence of zoonotic trematodes in fish from a Vietnamese fish-farming community.
The prevalence of fish-borne zoonotic trematode (FZT) metacercariae was investigated in fish farmed by rural households in Nghe An Province, located in northern Vietnam. In total, 716 fish, including tilapia (Oreochromis niloticus) and 6 carp species, i.e., grass carp (Ctenopharyngodon idellus), bighead carp (Aristichthys nobilis), mrigal (Cirrhinus mrigala), common carp (Cyprinus carpio), silver carp (Hypophthalmychthys molitrix), and roha (Labeo rohita), collected from 53 fish farms were examined. The overall prevalence of FZT metacercariae was 44.6%, ranging from 12.5% to 61.0% in fish species collected from grow-out ponds, which are the production system for growing fish from fingerling size to market size. The overall prevalence was 43.6% in fingerlings cultured in nurseries, ranging from 7.4% to 62.8% for different fish species. The FZT species recovered were heterophyids and echinostomatids and included Haplorchis pumilio, H. taichui, H. yokogawai, Centrocestus formosanus, Stellantchas musfalcatus, and Echinochasmus japonicus, all of which are intestinal flukes in humans, other mammals, and birds. This is the first report of H. yokogawai and E. japonicus in fish in Vietnam, and the first record for S. falcatus in northern Vietnam. Although a previous cross-sectional survey of the people living in these fish farm households revealed a very low prevalence of FZTs (< 1%), our results demonstrate that intestinal flukes are common in farmed fish in this area, suggesting that reservoir hosts such as dogs, cats, and pigs are more important in sustaining the life cycles of these flukes in fish farms than human hosts. This has implications for the effectiveness of control programs focused mainly on treatment of humans.


An evaluation of the effects of acute and chronic L-tyrosine administration on BDNF levels and BDNF mRNA expression in the rat brain.
Tyrosinemia type II, which is also known as Richner-Hanhart syndrome, is an inborn error of metabolism that is due to a block in the transamination reaction that converts tyrosine to p-hydroxyphenylpyruvate. Because the mechanisms of neurological dysfunction in hypertyrosinemic patients are poorly known and the symptoms of these patients are related to the central nervous system, the present study evaluated brain-derived neurotrophic factor (BDNF) levels and bdnf mRNA expression in young rats and during growth. In our acute protocol, Wistar rats (10 and 30 days old) were killed 1 h after a single intraperitoneal L-tyrosine injection (500 mg/kg) or saline. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old), and the rats were killed 12 h after the last injection. The brains were rapidly removed, and we evaluated the BDNF levels and bdnf mRNA expression. The present results showed that the acute administration of L-tyrosine decreased both BDNF and bdnf mRNA levels in the striatum of 10-day-old rats. In the 30-day-old rats, we observed decreased BDNF levels without modifications in bdnf transcript level in the hippocampus and striatum. Chronic administration of L-tyrosine increased the BDNF levels in the striatum of rats during their growth, whereas bdnf mRNA expression was not altered. We hypothesize that oxidative stress can interact with the BDNF system to modulate synaptic plasticity and cognitive function. The present results enhance our knowledge of the pathophysiology of hypertyrosinemia.


Parietal composition of Lichtheimia corymbifera: Differences between spore and germ tube stages and host-pathogen interactions.
The molecular composition and structural organization of the cell wall of filamentous fungi underlie the ability of the host to identify them as pathogens. Although the organization of the fungal cell wall, composed of 90% polysaccharides, is similar from one fungus to another, small variations condition their ability to trigger pattern recognition receptors. Because the incidence of mucormycosis, an emerging life-threatening infection caused by the species of the order Mucorales is increasing worldwide, the precise composition of the cell wall of two strains of Lichtheimia corymbifera was investigated in the early growth stages of germination (spores and germ-tubes) using trimethylsilylation and confocal microscopy. This study also characterizes the response of THP-1 cells to Mucorales. The study identified the presence of uncommon monosaccharides (fucose, galactose, and glucuronic acid) whose respective proportions vary according to the germination stage, revealing early parietal reorganization. Immunofluorescence studies confirmed the exposure of β-glucan on the surface of swollen spores and germ-tubes. Both spores and germ-tubes of L. corymbifera promoted an early and strong pro-inflammatory response, through TLR-2. Our results show the singularity of the cell wall of the order Mucorales, opening perspectives for the development of specific diagnostic biomarkers.


A randomized controlled trial of an online, modular, active learning training program for behavioral activation for depression.
This randomized-controlled trial assessed the efficacy of a trainer-led, active-learning, modular, online behavioral activation (BA) training program compared with a self-paced online BA training with the same modular content. Seventy-seven graduate students (M = 30.3 years, SD = 6.09; 76.6% female) in mental health training programs were randomly assigned to receive either the trainer-led or self-paced BA training. Both trainings consisted of 4 weekly sessions covering 4 core BA strategies. Primary outcomes were changes in BA skills as measured by an objective role-play assessment and self-reported use of BA strategies. Assessments were conducted at pre-, post-, and 6-weeks after training. A series of longitudinal mixed effect models assessed changes in BA skills and a longitudinal model implemented with generalized estimating equations assessed BA use over time. Significantly greater increases in total BA skills were found in the trainer-led training condition. The trainer-led training condition also showed greater increases in all core BA skills either at posttraining, follow-up, or both. Reported use of BA strategies with actual clients increased significantly from pre- to posttraining and maintained at follow-up in both training conditions. This trial adds to the literature on the efficacy of online training as a method to disseminate BA. Online training with an active learning, modular approach may be a promising and accessible implementation strategy. Additional strategies may need to be paired with the online BA training to assure the long-term implementation and sustainability of BA in clinical practice. (PsycINFO Database Record


Characterization of circulating and cutaneous IgA immune complexes in patients with dermatitis herpetiformis.
Dermatitis herpetiformis (DH) is a chronic, blistering skin disease characterized in part by deposits of IgA at the dermal-epidermal junction. Eighty-five percent of DH patients have granular IgA deposits and have an associated gluten-sensitive enteropathy (GSE). In contrast, 15% of DH patients have a linear pattern of IgA deposits and no associated intestinal abnormality. Although circulating IgA antibodies against skin are not present in these patients, 40% of DH patients do have IgA-containing circulating immune complexes (IgA-CIC). The role and origin of the cutaneous IgA and the IgA-CIC in patients with DH are unknown; however, the association of GSE with the granular IgA deposits suggests that a mucosal immune response may be important in the pathogenesis of DH. We have characterized the IgA subclass composition of the cutaneous IgA deposits in patients with DH, and have isolated and characterized the IgA-CIC from these patients. Twenty-nine of 29 patients with DH and granular IgA deposits were found to have only IgA1 deposits. Ten of 11 patients with linear IgA deposits also had only IgA1 deposits; one of 11 had IgA2 deposits. Isolated IgA-CIC from the sera of eight patients with DH and granular IgA deposits were found to contain both IgA1 (58% +/- 5, mean percent of total IgA +/- SEM) and IgA2 (42% +/- 5), as were IgA-CIC from two patients with ordinary GSE without cutaneous IgA deposits. The IgA subclass composition of the isolated immune complexes was significantly different from the serum IgA1 and IgA2 composition (serum IgA1 = 76% +/- 6; IgA2 = 24% +/- 5, p less than 0.025, Student's t-test), and suggests that the IgA-CIC may arise from gut-associated lymphoid tissue (GALT). Sequential anti-IgA1 absorption of serum which contained IgA-CIC did not remove all the IgA-CIC, suggesting that the complexes circulate as separate IgA1 and IgA2 complexes. The finding of IgA1 alone in the skin of patients with DH suggests that the cutaneous IgA may not arise from GALT, or that IgA1, possibly arising in GALT, is preferentially bound to DH skin. Because IgA-containing CIC which contain both IgA1 and IgA2 were found in the serum of patients with DH and with ordinary GSE, it seems unlikely that IgA-containing CIC are responsible for the cutaneous IgA deposits seen in DH.


Anticoagulation for prosthetic heart valves: unresolved questions requiring answers.
The efficacy of anticoagulation for valvular prostheses is the result of a delicate balance between the risk of thromboembolic (TE) events and bleeding. Here, we review data on anticoagulation for valve prostheses with a focus on clinical trials that address key unanswered questions. There are several unanswered questions in the field of prosthetic valve anticoagulation, including: optimal TE prophylaxis in the short term for bioprostheses, optimal TE prophylaxis following transcatheter aortic valve implantation, the safety and efficacy of lower levels of anticoagulation with the bileaflet mechanical prosthesis, the role of aspirin for patients with mechanical prostheses, and the management of anticoagulation for mechanical valves in pregnancy. Other areas of study include the role, if any, of nonwarfarin oral anticoagulants for prosthetic TE prophylaxis as well as self-INR monitoring. Finally, we briefly mention studies of newer anticoagulants, such as novel vitamin K antagonists and antisense oligonucleotides, that are on the horizon. Optimal antithrombotic management is a key issue for patients with valvular prostheses, and the publication of recent trials has provided much-needed guidance. We highlight areas of progress, in addition to the major unanswered questions for which well-designed, prospective clinical trials are forthcoming.


Resolution of the potassium ion pump in muscle fibers using barium ions.
When frog sartorius muscles recover from Na enrichment in the presence of external K, net K entry into the fibers occurs by both passive movement and active inward transport via a K pump. Under normal conditions, it has not been possible to experimentally distinguish these processes. Fractionation into the flux components must be accomplished from inferences concerning the K conductance or permeability during a period of rapid Na extrusion. The best estimates indicate that 60-80% of the K entry occurs via the K pump. In the presence of Ba ions, the membrane permeability to K is very much reduced. Under these conditions, Na-enriched muscles underwent a normal recovery in the presence of external K, and the amount of inward K movement due to the K pump rose to over 90% of the total K entry. The characteristics of the K pump studied by this means were: (a) essentially complete inhibition by 10(-4) M ouabain, (b) inhibition by [Na]omicron, (c) activation by [K]omicron according to a rectangular hyperbola in the absence of [Na]omicron, (d) linear activation by [Na]iota over a wide range in concentration, (e) zero or undetectably low pumping rate as [Na]iota leads to 0, (f) the number of Na ions actively transported per K ion actively transported is 1.4-1.7 normally and 1.1 in the presence of Ba.


Effects of diethylamine/nitric oxide on blood perfusion and oxygenation in the R3230Ac mammary carcinoma.
The effects of intravenous diethylamine/nitric oxide (DEA/NO), a short-acting nitric oxide (NO) donor, on systemic haemodynamics, muscle and tumour blood flow (MBF and TBF) and tumour oxygenation were examined in rats bearing subcutaneous R3230Ac carcinoma in the leg. The effects of DEA/NO on the diameters of tumour-feeding and normal arterioles were evaluated in window chambers with and without implanted tumours. DEA/NO reduced mean arterial pressure (MAP) when given at doses > or = 100 nmol kg(-1), with maximal suppression at 0.5-1 min followed by return to baseline within 20 min. DEA/NO did not affect MBF except at the highest doses (500 and 1000 nmol kg(-1)). In contrast, DEA/NO reduced TBF and constricted tumour arterioles at doses > or = 100 nmol kg(-1). Tumour arteriolar vasomotion occurred in more than half the animals during hypotension and with a significantly higher frequency than in normal granulating tissue at a dose of 500 nmol kg(-1). Normal arterioles rapidly and significantly vasodilated for about 3 min and then returned to baseline. The reductions in TBF and MAP were accompanied by synchronous reduction in tumour pO2. Our findings suggest that DEA/NO decreases TBF in two ways. In the window chamber model, vascular steal occurs as normal arterioles adjacent to tumour dilate more than tumour arterioles during the initial period of hypotension. In leg tumours, the predominant mechanism is attributable to reduced perfusion pressure induced by lowered MAP, which decreases flow to the tumour, probably because of relatively higher flow resistance. The vasoconstriction and vasomotion in tumour arterioles during DEA/NO-induced hypotension may reflect differences in regulatory metabolism of NO between neoplastic and normal arterioles. Thus, intravenous injection of a short-acting NO donor, DEA/NO, decreases MAP and heart rate, leading to subsequent decreases in tumour blood flow and oxygenation.


Social context and the real-world consequences of social anxiety.
Social anxiety lies on a continuum, and young adults with elevated symptoms are at risk for developing a range of psychiatric disorders. Yet relatively little is known about the factors that govern the hour-by-hour experience and expression of social anxiety in the real world. Here we used smartphone-based ecological momentary assessment (EMA) to intensively sample emotional experience across different social contexts in the daily lives of 228 young adults selectively recruited to represent a broad spectrum of social anxiety symptoms. Leveraging data from over 11 000 real-world assessments, our results highlight the central role of close friends, family members, and romantic partners. The presence of such close companions was associated with enhanced mood, yet socially anxious individuals had fewer confidants and spent less time with the close companions that they do have. Although higher levels of social anxiety were associated with a general worsening of mood, socially anxious individuals appear to derive larger benefits - lower levels of negative affect, anxiety, and depression - from their close companions. In contrast, variation in social anxiety was unrelated to the amount of time spent with strangers, co-workers, and acquaintances; and we uncovered no evidence of emotional hypersensitivity to these less-familiar individuals. These findings provide a framework for understanding the deleterious consequences of social anxiety in emerging adulthood and set the stage for developing improved intervention strategies.


A Randomized Clinical Trial of Caregiver-Delivered Reflexology for Symptom Management During Breast Cancer Treatment.
The objective of this study was to determine the effects of a home-based reflexology intervention delivered by a friend/family caregiver compared with attention control on health-related quality of life of women with advanced breast cancer undergoing chemotherapy, targeted and/or hormonal therapy. Patient-caregiver dyads (N = 256) were randomized to four weekly reflexology sessions or attention control. Caregivers in the intervention group were trained in a 30-minute protocol. During the four weeks, both groups had telephone symptom assessments, and intervention group had fidelity assessments. The intervention effects were assessed using linear mixed-effects models at weeks 5 and 11 for symptom severity and interference with daily activities, functioning, social support, quality of patient-caregiver relationship, and satisfaction with life. Significant reductions in average symptom severity (P = 0.02) and interference (P < 0.01) over 11 weeks were found in the reflexology group compared with control, with no group differences in functioning, social support, quality of relationship, or satisfaction with life at weeks 5 and 11. Stronger quality of relationship was associated with lower symptom interference in the entire sample (P = 0.02), but controlling for it did not diminish the effect of intervention on symptoms. Significant reductions in symptom severity in the reflexology group compared with attention control were seen during weeks 2-5 but were reduced at Week 11. Efficacy findings of caregiver-delivered reflexology with respect to symptom reduction open a new evidence-based avenue for home-based symptom management.


Mitigation of microbial contamination from waste water and aerosolization by sink design.
Healthcare-associated infections (HAIs) are a significant cause of increased medical costs, morbidity, mortality, and have been partly associated with sinks, their waste water outlets and associated pipework. To determine whether an engineered sink could limit microbial aerosol contaminants in the air and sink basin. Multiple comparisons were undertaken between an experimental sink, designed to limit aerosolization and p-trap contamination to a control hospital sink, both connected to a common drain system. The experimental sink was equipped with ultraviolet light (UV), an aerosol containment hood, ozonated water generator and a flush system to limit bacterial growth/aerosolization and limit microbial growth in the p-trap. Nutrient material was added daily to simulate typical material discarded into a hospital sink. Surface collection swabs, settle plates and p-trap contamination levels were assessed for bacteria and fungi. The experimental sink had significantly decreased levels of bacterial and fungal p-trap contamination (99.9% for Tryptic Soy (TSA) and Sabouraud agar (SAB) plates) relative to the initial levels. Aerosol-induced contaminant from the p-traps was significantly lower for the experimental vs the control sink for TSA (76%) and SAB (86%) agar settle plates. Limiting microbial contamination is critical for the control of nosocomial infections of in-room sinks, which provide a major source of contamination. Our experimental sink studies document that regular ozonated water rinsing of the sink surface, decontamination of p-trap water, and UV decontamination of surfaces limits microbial aerosolization and surface contamination, with potential to decrease patient exposure and reduce hospital acquired infections.


Commercial strain-derived clinical Saccharomyces cerevisiae can evolve new phenotypes without higher pathogenicity.
Saccharomyces cerevisiae is one of the most important microbes in food industry, but there is growing evidence on its potential pathogenicity as well. Its status as a member of human mycobiome is still not fully understood. In this study, we characterize clinical S. cerevisiae isolates from Hungarian hospitals along with commercial baking and probiotic strains, and determine their phenotypic parameters, virulence factors, interactions with human macrophages, and pathogenicity. Four of the clinical isolates could be traced back to commercial strains based on genetic fingerprinting. Our observations indicate that the commercial-derived clinical isolates have evolved new phenotypes and show similar, or in two cases, significantly decreased pathogenicity. Furthermore, immunological experiments revealed that the variability in human primary macrophage activation after coincubation with yeasts is largely donor and not isolate dependent. Isolates in this study offer an interesting insight into the potential microevolution of probiotic and food strains in human hosts. These commensal yeasts display various changes in their phenotypes, indicating that the colonization of the host does not necessarily impose a selective pressure toward higher virulence/pathogenicity.