A comparison of right posterior sectorectomy with formal right hepatectomy: a dual-institution study.
Right posterior sectorectomy (RPS) preserves liver volume but typically requires a longer parenchymal transection distance than does right hepatectomy (RH). This study was conducted to define the advantages of one approach over the other. Databases at two institutions were retrospectively reviewed for all patients submitted to RPS or RH between January 2000 and August 2012. Primary outcomes were perioperative complications and 90-day mortality. Patients undergoing RPS (n = 100) and RH (n = 480), respectively, were similar in demographics, comorbidities, operative indications and Model for End-stage Liver Disease (MELD) mean scores (7.8 in the RPS group and 7.7 in the RH group; P = 0.49). A comparison of the RPS group with the RH group showed no significant differences in mean estimated blood loss (697 ml versus 713 ml; P = 0.900), rate of transfusions (19.2% versus 17.1%; P = 0.720), margin-positive resection (9.2% versus 11.6%; P = 0.70), complications (41.8% versus 42.0%; P = 1.000), bile leak (3.0% versus 4.0%; P = 1.000), or length of stay (7.5 days versus 8.3 days; P = 0.360). Postoperative hepatic insufficiency (defined as a postoperative bilirubin level of >7 mg/dl or significant ascites), occurred less frequently after RPS (1.0% versus 8.5%; P = 0.005). Operation type remained an independent determinant of postoperative hepatic insufficiency after controlling for preoperative risk factors (RH: hazard ratio = 9.628, 95% confidence interval 1.295-71.573; P = 0.027). A total of 28 (4.8%) patients died within 90 days; these included 25 (5.2%) patients in the RH group and three (3.0%) in the RPS group (P = 0.449). Despite similar blood loss and overall morbidity, RPS is associated with less hepatic insufficiency than RH. Right posterior sectorectomy is parenchyma-sparing and should be strongly considered when it is technically feasible and oncologically sound.


Population genetic diversity and fitness in multiple environments.
When a large number of alleles are lost from a population, increases in individual homozygosity may reduce individual fitness through inbreeding depression. Modest losses of allelic diversity may also negatively impact long-term population viability by reducing the capacity of populations to adapt to altered environments. However, it is not clear how much genetic diversity within populations may be lost before populations are put at significant risk. Development of tools to evaluate this relationship would be a valuable contribution to conservation biology. To address these issues, we have created an experimental system that uses laboratory populations of an estuarine crustacean, Americamysis bahia with experimentally manipulated levels of genetic diversity. We created replicate cultures with five distinct levels of genetic diversity and monitored them for 16 weeks in both permissive (ambient seawater) and stressful conditions (diluted seawater). The relationship between molecular genetic diversity at presumptive neutral loci and population vulnerability was assessed by AFLP analysis. Populations with very low genetic diversity demonstrated reduced fitness relative to high diversity populations even under permissive conditions. Population performance decreased in the stressful environment for all levels of genetic diversity relative to performance in the permissive environment. Twenty percent of the lowest diversity populations went extinct before the end of the study in permissive conditions, whereas 73% of the low diversity lines went extinct in the stressful environment. All high genetic diversity populations persisted for the duration of the study, although population sizes and reproduction were reduced under stressful environmental conditions. Levels of fitness varied more among replicate low diversity populations than among replicate populations with high genetic diversity. There was a significant correlation between AFLP diversity and population fitness overall; however, AFLP markers performed poorly at detecting modest but consequential losses of genetic diversity. High diversity lines in the stressful environment showed some evidence of relative improvement as the experiment progressed while the low diversity lines did not. The combined effects of reduced average fitness and increased variability contributed to increased extinction rates for very low diversity populations. More modest losses of genetic diversity resulted in measurable decreases in population fitness; AFLP markers did not always detect these losses. However when AFLP markers indicated lost genetic diversity, these losses were associated with reduced population fitness.


Development of a mitochondria targetable ratiometric time-gated luminescence probe for biothiols based on lanthanide complexes.
A mitochondria targetable ratiometric luminescence probe based on a mixture of Eu3+ and Tb3+ complexes, Mito-NSTTA-Eu3+/Tb3+, has been developed for the specific recognition and time-gated luminescence detection of biothiols in aqueous and living samples. This probe was synthesized by conjugating a mitochondria-anchoring motif, triphenylphosphonium, with a biothiol-responsive terpyridine derivative, [4'-(2,4-dinitrobenzenesulfonyloxy)-2,2':6',2''-terpyridine-6,6''-diyl] bis(methylenenitrilo) tetrakis(acetic acid), for coordinating with Eu3+ and Tb3+ ions. When the probe interacts with biothiols, the cleavage of the 2,4-dinitrobenzenesulfonyl moiety leads to a remarkable enhancement of the Tb3+ emission at 540 nm, while the Eu3+ emission at 610 nm is unchanged, which allows Mito-NSTTA-Eu3+/Tb3+ to be used as a ratiometric probe for the time-gated luminescence detection of biothiols, with the luminescence intensity ratio of I540/I610 as a signal. The triphenylphosphonium group enables the probe molecules to be specifically driven into the mitochondria after cell loading for responding to biothiols therein. Mito-NSTTA-Eu3+/Tb3+ showed high selectivity and sensitivity for the detection of biothiols under physiological conditions, with detection limits of 0.098 μM for glutathione (GSH) and 0.14 μM for cysteine (Cys). In cell imaging experiments, Mito-NSTTA-Eu3+/Tb3+ displayed an excellent mitochondria-localization feature, which allowed biothiols in the mitochondria of live cells to be successfully imaged under ratiometric and time-gated luminescence modes. In addition, biothiols in living Daphnia magna were also imaged using Mito-NSTTA-Eu3+/Tb3+ as a probe. All of the results suggested that Mito-NSTTA-Eu3+/Tb3+ could serve as a useful tool for monitoring biothiols in vitro and in vivo with high specificity and sensitivity.


Antimicrobial susceptibility, risk factors and prevalence of bla cefotaximase, temoneira, and sulfhydryl variable genes among Escherichia coli in community-acquired pediatric urinary tract infection.
The emergence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has become an important challenge among pediatric patients with community-acquired urinary tract infection (UTI). The aim of this study was to assess the antimicrobial susceptibility patterns, associated risk factors and to survey the frequency of bla cefotaximase (CTX-M), bla temoneira (TEM), and bla sulfhydryl variable (SHV) genotypes in ESBL-producing E. coli isolated from children with community-acquired UTI. This was a prospective study conducted from November 2012 to March 2016 in a tertiary care center. E. coli isolated in urine cultures from children aged ≤18 years was identified and confirmed for ESBL production. ESBL-positive strains were screened for ESBL encoding genes. Chi-square test and Fisher's exact test were used to compare the difference in antibiotic susceptibility with respect to ESBL positive and negative, and binary logistic regression was used to identify the risk factors associated with ESBL production. Among 523 E. coli isolates, 196 (37.5%) were ESBL positive, >90% were resistant to cephalosporins, and 56% were resistant to fluoroquinolones. Least resistance was observed for imipenem, netilmicin, and nitrofurantoin (2%, 8.6%, 15.3%). Association between ESBL production and drug resistance was significant for ceftazidime (P < 0.001), cefixime (P < 0.001), cefotaxime (P = 0.010), ceftazidime-clavulanic acid (P < 0.001), levofloxacin (P = 0.037), and gentamicin (P = 0.047) compared to non-ESBL E. coli. CTX-M gene was the most prevalent (87.5%), followed by TEM (68.4%) and SHV (3.1%). Previous history of UTI and intake of antibiotics were the common risk factors. ESBL-producing E. coli from community-acquired pediatric UTI carries more than one type of beta-lactamase coding genes correlating their increased antibiotic resistance. Aggressive infection control policy, routine screening for detecting ESBL isolates in clinical samples, and antimicrobial stewardship are the keys to prevent their dissemination in community settings.


Aromatic Ring Currents at a Protein Surface: Use of (1)H-NMR Chemical Shifts to Refine the Structure of a Naked β Sheet.
Abstract The naked β sheet, a newly recognized motif of protein structure, exhibits ordered surfaces in the absence of a conventional hydrophobic core. A model is provided by an archaeal Zn ribbon homologous to eukaryotic RNA polymerase II subunit 9 (RPB9). This subunit, which regulates transcriptional start-site selection and downstream pausing, contains Zn(2+)-binding motifs similar to those of general transcription factors TFIIB and TFIIS. Interestingly, distance-geometry yields two models of the archaeal Zn ribbon differing in the orientation of a conserved tyrosine side chain on the well-ordered surface of the naked β-sheet. The models are equally consistent with conventional restraints and otherwise contain indistinguishable structural features, including a tetrahedral Cys(4) Zn(2+)-binding sites, four antiparallel β-strands, and disordered loop. Due to the change in tyrosine orientation and correlated changes in the configuration of neighboring side chains, the two models predict inequivalent patterns of aromatic ring-current shifts. The observed secondary shifts of adjoining resonances are shown to be consistent with one model but not the other. In the consistent model the surface of the β-sheet contains successive aromatic edge-to-face contacts in accord with semi-classical and ab initio potentials. We speculate that the aromatic-rich surface of the hyperthermophilic RPB9 domain contributes its thermodynamic stability and provides a nucleic-acid-binding site in the eukaryotic and archaeal transcriptional machinery. The present study demonstrates how the reduced dimensionality of a surface can lead to ambiguities in the interpretation of nuclear Overhauser enhancements. The results illustrate the utility of chemical shifts at such a surface in the cross-validation of a high-resolution solution structure.


A chicken achaete-scute homolog (CASH-1) is expressed in a temporally and spatially discrete manner in the developing nervous system.
We have identified a basic helix-loop-helix encoding cDNA from embryonic chicken retina which shares sequence similarity with the achaete-scute family of genes of Drosophila. The deduced amino acid sequence of this chicken achaete-scute homolog (CASH-1) is identical, over the region encoding the basic helix-loop-helix domain, to the recently identified mammalian achaete-scute homolog (MASH-1) and to the Xenopus homolog (XASH1), and 70% identical, over the same region, to Drosophila achaete-scute complex members. The expression of CASH-1 is restricted to subsets of neuronal progenitor cells in the developing chicken nervous system, similar in distribution to that reported for MASH-1 and XASH1. In addition, in situ localization in the retina reveals a dynamic character of expression of the gene in a particular region of the CNS, and suggests that the expression of CASH-1 may be important in defining a particular stage in the progenitor cell necessary for the differentiation of particular neuronal phenotypes.


Coordination, microprotonation equilibria and conformational changes of myo-inositol hexakisphosphate with pertinence to its biological function.
Within all the eukaryotic cells there is an important group of biomolecules that has been potentially related to signalling functions: the myo-inositol phosphates (InsPs). In nature, the most abundant member of this family is the so called InsP6 (phytate, L(12-)), for which our group has strived in the past to elucidate its intricate chemical behaviour. In this work we expand on our earlier findings, shedding light on the inframolecular details of its protonation and complexation processes. We evaluate systematically the chemical performance of InsP6 in the presence and absence of alkali and alkaline earth metal ions, through (31)P NMR measurements, in a non-interacting medium and over a wide pH range. The analysis of the titration curves by means of a model based on the cluster expansion method allows us to describe in detail the distribution of the different protonated microspecies of the ligand. With the aid of molecular modelling tools, we assess the energetic and geometrical characteristics of the protonation sequence and the conformational transition suffered by InsP6 as the pH changes. By completely characterizing the protonation pattern, conformation and geometry of the metal complexes, we unveil the chemical and structural basis behind the influence that the physiologically relevant cations, Na(+), K(+), Mg(2+) and Ca(2+) have over the phytate chemical reactivity. This information is essential in the process of gaining reliable structural knowledge about the most important InsP6 species in the in vitro and in vivo experiments, and how these features modulate their probable biological functions.


Three-dimensional speckle-noise reduction by using coherent integral imaging.
We present a 3D imaging method to reduce speckle noise that exists in coherent imaging systems. This approach is based on integral imaging (II). The elemental images set having speckle-noise patterns of a 3D object is obtained by II technique under coherent illumination. The computational geometrical ray-propagation algorithm is applied to the elemental images in order to reconstruct the original 3D object. A uniform probability-density function is assumed for modeling the phase distribution of the speckle patterns. The statistical point estimator is used for 3D speckle removal. Speckle index is calculated to compare the computational reconstruction using the proposed method with that of conventional coherent image degraded by speckle patterns for 3D object reconstruction and by object recognition. Experimental results are presented. The speckle index, mean square error, and signal-to-noise ratio are used as performance metrics and are shown to have been significantly improved by the proposed method to reduce speckle noise in the 3D object reconstruction. 3D reconstruction experiments of objects with reduced speckle noise are presented. To the best of our knowledge, this is the first report on 3D speckle removal using II and statistical estimation algorithms.


Seasonal variation of Batrachochytrium dendrobatidis in a threatened anuran species from Uruguay.
Chytridiomycosis, an emergent infectious disease caused by the fungus Batrachochytrium dendrobatidis (Bd), is considered one of the drivers of the current amphibian biodiversity loss. To inform endangered species conservation efforts, it is essential to improve our knowledge about the abiotic and biotic factors that influence Bd infection dynamics in the wild. Here, we analyzed variation of Bd infection in the redbelly toad Melanophryniscus montevidensis, a threatened bufonid from Uruguay. We tested the influence of temperature, precipitation, season, and host population size on Bd prevalence and intensity. Additionally, considering the sub-lethal effects of Bd, we tested if these variables, potentially through their effect on Bd, also explain the variation in host body condition. We determined a high Bd prevalence of 41% (100/241), and that population size influenced both Bd prevalence and infection intensity. We identified an effect of precipitation and season on Bd infection intensity and an effect of season on toad body condition. In addition, we found a negative effect of infection intensity on body condition; moreover, while some toads cleared the infection, their body condition did not improve, suggesting a long-term cost. This is the first report on host population size as an important factor in Bd infection dynamics in a threatened anuran species, and seasonal demographic changes appear to play an important role in the dynamics. Finally, we highlight the need for monitoring Bd in this and other endangered amphibian populations, especially those within the genus Melanophryniscus, which includes several Endangered and Data Deficient species in South America.


Risk of uterine rupture and placenta accreta with prior uterine surgery outside of the lower segment.
Women with a prior myomectomy or prior classical cesarean delivery often have early delivery by cesarean because of concern for uterine rupture. Although theoretically at increased risk for placenta accreta, this risk has not been well-quantified. Our objective was to estimate and compare the risks of uterine rupture and placenta accreta in women with prior uterine surgery. Women with prior myomectomy or prior classical cesarean delivery were compared with women with a prior low-segment transverse cesarean delivery to estimate rates of both uterine rupture and placenta accreta. One hundred seventy-six women with a prior myomectomy, 455 with a prior classical cesarean delivery, and 13,273 women with a prior low-segment transverse cesarean delivery were evaluated. Mean gestational age at delivery differed by group (P<.001), prior myomectomy (37.3 weeks), prior classical cesarean delivery (35.8 weeks), and low-segment transverse cesarean delivery (38.6 weeks). The frequency of uterine rupture in the prior myomectomy group (P-MMX group) was 0% (95% confidence interval [CI] 0-1.98%). The frequency of uterine rupture in the low-segment transverse cesarean delivery group (LTC group) (0.41%) was not statistically different from the risk in the P-MMX group (P>.99) or in the prior classical cesarean delivery group (PC group) (0.88%; P=.13). Placenta accreta occurred in 0% (95% CI 0-1.98%) of the P-MMX group compared with 0.19% in the LTC group (P>.99) and 0.88% in the PC group (P=.01 relative to the LTC group). The adjusted odds ratio for the PC group (relative to LTC group) was 3.23 (95% CI 1.11-9.39) for uterine rupture and 2.09 (95% CI 0.69-6.33) for accreta. The frequency of accreta for those with previa was 11.1% for the PC group and 13.6% for the LTC group (P>.99). A prior myomectomy is not associated with higher risks of either uterine rupture or placenta accreta. The absolute risks of uterine rupture and accreta after prior myomectomy are low.


Prevalence and significance of nonthromboembolic findings on chest computed tomography angiography performed to rule out pulmonary embolism: a multicenter study of 1,025 emergency department patients.
To evaluate the hypothesis that computed tomography (CT) angiography often yields a result interpreted as an alternative diagnosis to pulmonary embolism (PE) in emergency department (ED) patients. This was a multicenter, retrospective, and secondary analysis of consecutive patients in three academic emergency departments. ED patients with symptoms suspicious for PE were included. CT angiography was ordered at the discretion of the treating physician; patients were identified by query of the electronic medical record. Board-certified radiologists gave CT readings, which were reviewed by two independent emergency physicians who categorized the non-PE findings into one of four acuity categories: A = requiring specific and immediate intervention, B = requiring specific action on follow-up, C = requiring no action, and D = indeterminate findings. The prevalence of PE among the 1,025 patients studied was 10% (95% CI = 8% to 12%). In the 921 patients without PE, the mean prevalences (ranges between sites) of concordant categorized non-PE findings were: A = 7% (range 3%-11%), B = 10% (7%-13%), C = 17% (10%-20%), D = 4% (0%-8%), and no ancillary finding = 41% (29% to 45%). The most common category A findings included infiltrate or consolidation suggesting pneumonia (81%), aortic aneurysm or dissection (7%), and mass suggesting undiagnosed malignancy (7%). The overall unweighted agreement was 80% (kappa = 0.72) and weighted agreement was 93% (kappa(w) = 0.84). In ED patients with suspected PE, the CT angiogram frequently provides evidence suggesting an important alternative diagnosis to PE. Pulmonary infiltrate suggesting pneumonia was the most common non-PE finding.


Characterization of lymphocytic choriomeningitis virus-binding protein(s): a candidate cellular receptor for the virus.
The attachment of lymphocytic choriomeningitis virus (LCMV) to murine and primate cell lines was quantitated by a fluorescence-activated cell sorter assay in which binding of biotinylated virus was detected with streptavidin-fluorescein isothiocyanate. Cell lines that were readily infected by LCMV (e.g., MC57, Rin, BHK, Vero, and HeLa) bound virus in a dose-dependent manner, whereas no significant binding was observed to lymphocytic cell lines (e.g., RMA and WIL 2) that were not readily infected. Binding was specific and competitively blocked by nonbiotinylated LCMV. It was also blocked by LCMV-specific antiserum and a neutralizing monoclonal antibody to the virus glycoprotein GP-1 but not by antibodies specific for GP-2, indicating that attachment was likely mediated by GP-1. Treatment of cells with any of several proteases abolished LCMV binding, whereas phospholipases including phosphatidylinositol-specific phospholipase C had no effect, indicating that one or more membrane proteins were involved in virus attachment. These proteins were characterized with a virus overlay protein blot assay. Virus bound to protein(s) with a molecular mass of 120 to 140 kDa in membranes from cell lines permissive for LCMV but not from nonpermissive cell lines. Binding was specific, since unlabeled LCMV, but not the unrelated enveloped virus herpes simplex virus type 1, competed with 125I-labeled LCMV for binding to the 120- to 140-kDa band. The proteinaceous nature of the LCMV-binding substance was confirmed by the lack of virus binding to proteinase K-treated membrane components. By contrast, glycosidase treatment of membranes did not abolish virus binding. However, in membranes treated with endoglycosidase F/N-glycosidase F, and/or neuraminidase and in membranes from cells grown in tunicamycin, the molecular mass of the LCMV-binding entity was reduced. Hence, LCMV attachment to rodent fibroblastic cell lines is mediated by a glycoprotein(s) with a molecular mass of 120 to 140 kDa, with complex N-linked sugars that are not involved in virus binding.


Application of microbial risk assessment on a residentially-operated bio-toilet.
The Sustainable Sanitation System is a new wastewater treatment system that incorporates a non-flushing toilet (Bio-toilet) that converts excreta into a reusable resource (as fertilizer or humus for organic agriculture) and reduces the pollution load to environments of the rivers, the lakes, and the sea. However, the risk of exposure to pathogens should be considered, because excrement is stored in the Bio-toilet. The aim of the present work is to analyze the health risk of dealing with the matrix (excreta and urine mixed with sawdust) of the Bio-toilet. Therefore, the fate of pathogenic viruses was investigated using coliphages as a virus index, and the modeling of the die-off rate in matrix was introduced. Then the microbial risk assessment was applied to a Bio-toilet that was actually used in a residential house; the infection risks of rotavirus and enterovirus as reference pathogens were calculated. According to the lab-scale experiment using coliphages for investing the die-off rate of viruses in the Bio-toilet, Qbeta had a higher die-off, which was greatly influenced by the water content and temperature. On the other hand, T4 showed a lower rate and was independent of water content. Therefore, these two phages' data were used as critical examples, such as viruses having high or low possibilities of remaining in the Bio-toilet during the risk assessment analysis. As the result of the risk assessment, the storage time required for an acceptable infectious risk level has wide variations in both rotavirus and enterovirus cases depending on the phage that was used. These were 0-260 days' and 0-160 days' difference, respectively.


A Pilot Study Measuring Aluminum in Bone in Alzheimer's Disease and control Subjects Using in vivo Neutron Activation Analysis.
Aluminum, being the most abundant metal in the earth's crust, is widely distributed in the environment, and is routinely taken up by the human body through ingestion and inhalation. Aluminum is not considered an essential element and it can be toxic in high concentrations. Most of the body burden of aluminum is stored in the bones. Aluminum has been postulated to be involved in the causality of Alzheimer's disease. A system for non-invasive measurement of bone aluminum using the in vivo neutron activation analysis technique has been developed and previously reported in the literature by our group. The results are reported as ratio of Al to Ca in order to eliminate the variations in beam parameters and geometry as well as the physical variations among the subjects such as size of the hand and bone structure. This pilot study included 30 subjects, 15 diagnosed with Alzheimer's disease in mild and moderate stages and 15 control subjects, all of whom were 60 years of age or older. The mean value of aluminum for the control group was 2.7±8.2μg Al/g Ca (inverse-variance weighted mean 3.5±0.9μg Al/g Ca) and for the Alzheimer's disease subjects was 12.5±13.1μg Al/g Ca (inverse-variance weighted mean 7.6±0.6μg Al/g Ca). The difference between the mean of the Alzheimer's disease group and the mean of the control group was 9.8±15.9μg Al/g Ca, with a p-value of 0.02. An age-dependent linear increase in bone aluminum concentration was observed for all subjects. The difference in serum aluminum levels between the two groups did not reach significance.


A murine model of Lyme disease demonstrates that Borrelia burgdorferi colonizes the dura mater and induces inflammation in the central nervous system.
Lyme disease, which is caused by infection with Borrelia burgdorferi and related species, can lead to inflammatory pathologies affecting the joints, heart, and nervous systems including the central nervous system (CNS). Inbred laboratory mice have been used to define the kinetics of B. burgdorferi infection and host immune responses in joints and heart, however similar studies are lacking in the CNS of these animals. A tractable animal model for investigating host-Borrelia interactions in the CNS is key to understanding the mechanisms of CNS pathogenesis. Therefore, we characterized the kinetics of B. burgdorferi colonization and associated immune responses in the CNS of mice during early and subacute infection. Using fluorescence-immunohistochemistry, intravital microscopy, bacterial culture, and quantitative PCR, we found B. burgdorferi routinely colonized the dura mater of C3H mice, with peak spirochete burden at day 7 post-infection. Dura mater colonization was observed for several Lyme disease agents including B. burgdorferi, B. garinii, and B. mayonii. RNA-sequencing and quantitative RT-PCR showed that B. burgdorferi infection was associated with increased expression of inflammatory cytokines and a robust interferon (IFN) response in the dura mater. Histopathologic changes including leukocytic infiltrates and vascular changes were also observed in the meninges of infected animals. In contrast to the meninges, we did not detect B. burgdorferi, infiltrating leukocytes, or large-scale changes in cytokine profiles in the cerebral cortex or hippocampus during infection; however, both brain regions demonstrated similar changes in expression of IFN-stimulated genes as observed in peripheral tissues and meninges. Taken together, B. burgdorferi is capable of colonizing the meninges in laboratory mice, and induces localized inflammation similar to peripheral tissues. A sterile IFN response in the absence of B. burgdorferi or inflammatory cytokines is unique to the brain parenchyma, and provides insight into the potential mechanisms of CNS pathology associated with this important pathogen.


Opposing microRNA families regulate self-renewal in mouse embryonic stem cells.
When embryonic stem cells (ESCs) differentiate, they must both silence the ESC self-renewal program and activate new tissue-specific programs. In the absence of DGCR8 (Dgcr8(-/-)), a protein required for microRNA (miRNA) biogenesis, mouse ESCs are unable to silence self-renewal. Here we show that the introduction of let-7 miRNAs-a family of miRNAs highly expressed in somatic cells-can suppress self-renewal in Dgcr8(-/-) but not wild-type ESCs. Introduction of ESC cell cycle regulating (ESCC) miRNAs into the Dgcr8(-/-) ESCs blocks the capacity of let-7 to suppress self-renewal. Profiling and bioinformatic analyses show that let-7 inhibits whereas ESCC miRNAs indirectly activate numerous self-renewal genes. Furthermore, inhibition of the let-7 family promotes de-differentiation of somatic cells to induced pluripotent stem cells. Together, these findings show how the ESCC and let-7 miRNAs act through common pathways to alternatively stabilize the self-renewing versus differentiated cell fates.


Bioactive lipopeptides of ice-nucleating snow bacterium Pseudomonas syringae strain 31R1.
The production of secondary metabolite lipopeptides by ice-nucleating Pseudomonas syringae strain 31R1 was investigated. Pseudomonas syringae strain 31R1 is a rifampicin-resistant derivative of P. syringae no. 31 used for the commercial production of snow. It is shown that P. syringae strain 31R1 produces antifungal lipodepsipeptides, syringomycins E and G, and, in addition, a novel and unique lipopeptide, peptin31. Spectroscopic and spectrometric analyses revealed that peptin31 is a linear undecalipopeptide with sequence identities to N- and C-terminal portions but lacking 11 amino acids of known lipodepsipeptide syringopeptin SPPhv. Peptin31 displayed antifungal activities against Rhodotorula pilimanae, Rhizoctonia solani, and Trichoderma harzianum and also hemolytic and antibacterial activities. Extracts of P. syringae strain 31R1 grown in medium with chloride were fungicidal, but not when grown without chloride. The latter extracts lacked peptin 31 and contained des-chloro forms of syringomycins E and G with low antifungal activities. Thus, the three lipopeptides account for the fungicidal properties of P. syringae 31R1 extracts. The occurrence of these bioactive metabolites should be considered when P. syringae no. 31 and its derivatives are used in products for making artificial snow.


Reversing the Colavita visual dominance effect.
Many researchers have taken the Colavita effect to represent a paradigm case of visual dominance. Broadly defined, the effect occurs when people fail to respond to an auditory target if they also have to respond to a visual target presented at the same time. Previous studies have revealed the remarkable resilience of this effect to various manipulations. In fact, a reversal of the Colavita visual dominance effect (i.e., auditory dominance) has never been reported. Here, we present a series of experiments designed to investigate whether it is possible to reverse the Colavita effect when the target stimuli consist of repetitions embedded in simultaneously presented auditory and visual streams of stimuli. In line with previous findings, the Colavita effect was still observed for an immediate repetition task, but when an n-1 repetition detection task was used, a reversal of visual dominance was demonstrated. These results suggest that masking from intervening stimuli between n-1 repetition targets was responsible for the elimination and reversal of the Colavita visual dominance effect. They further suggest that varying the presence of a mask (pattern, conceptual, or absent) in the repetition detection task gives rise to different patterns of sensory dominance (i.e., visual dominance, an elimination of the Colavita effect, or even auditory dominance).


The prevalence of and survival in Mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK.
Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disease subdivided into three phenotypes of increasing severity: Scheie, Hurler-Scheie and Hurler. To gauge the effectiveness of treatments and to determine the load likely to fall on health-care systems, it is necessary to understand the prevalence and natural progression of the disease especially with regard to life-expectancy. In general such data on the natural history of lysosomal storage diseases is sparse. Analysis of prevalence and patient survival in MPS I disease using a unique longitudinal data set initiated and maintained over a period of more than 20 years by the Society for Mucopolysaccharide Diseases (UK). The birth prevalence of MPS I in England and Wales over the period 1981 to 2003 was 1.07/100,000 births and within +/- 5% of estimates reported in several studies that examined reasonably large populations. The median survival for MPS I patients (including all phenotypes irrespective of various treatments) was found by Kaplan-Meier analysis to be 11.6 years. This result was driven by the relatively poor survival of patients with the Hurler phenotype who, irrespective of any treatments received, had a median survival of 8.7 years; when censoring for receipt of bone marrow transplant (BMT) was implemented median survival of Hurler patients was diminished to 6.8 years. The difference between these survival curves was statistically significant by log rank test and can be attributed to beneficial effects of BMT and or selection of patients with superior prognosis for intervention with BMT. Survival curves for Hurler patients who received and did not receive BMT were very different. Probability of survival at 2 year after BMT was ~68% and was similar to this after 5 years (66%) and ten years (64%); the mean age of Hurler patients at receipt of BMT was 1.33 years (range 0.1 to 3 years). Follow up was insufficient to determine median survival of the milder phenotypes however, unsurprisingly, this was clearly superior to that for Hurler patients. The birth prevalence of MPS I in England and Wales is 1.07/100,000 and the median survival for MPS I patients is 11.6 years.


Msx1 and Msx2 promote meiosis initiation.
The mechanisms regulating germ line sex determination and meiosis initiation are poorly understood. Here, we provide evidence for the involvement of homeobox Msx transcription factors in foetal meiosis initiation in mammalian germ cells. Upon meiosis initiation, Msx1 and Msx2 genes are strongly expressed in the foetal ovary, possibly stimulated by soluble factors found there: bone morphogenetic proteins Bmp2 and Bmp4, and retinoic acid. Analysis of Msx1/Msx2 double mutant embryos revealed a majority of undifferentiated germ cells remaining in the ovary and, importantly, a decrease in the number of meiotic cells. In vivo, the Msx1/Msx2 double-null mutation prevented full activation of Stra8, a gene required for meiosis. In F9 cells, Msx1 can bind to Stra8 regulatory sequences and Msx1 overexpression stimulates Stra8 transcription. Collectively, our data demonstrate for the first time that some homeobox genes are required for meiosis initiation in the female germ line.


Editor's Choice - Abdominal Compartment Syndrome After Surgery for Abdominal Aortic Aneurysm: A Nationwide Population Based Study.
The understanding of abdominal compartment syndrome (ACS), and its importance for outcome, has increased over time. The aim was to investigate the incidence and clinical consequences of ACS after open (OR) and endovascular repair (EVAR) for ruptured and intact infrarenal abdominal aortic aneurysm (rAAA and iAAA, respectively). In 2008, ACS and decompression laparotomy (DL) were introduced as variables in the Swedish vascular registry (Swedvasc), offering an opportunity to study this complication in a prospective, population based design. Operations carried out in the period 2008-13 were analysed. Of 6,612 operations, 1,341 (20.3%) were for rAAA (72.0% OR) and 5,271 (79.7%) for iAAA (41.9% OR). In all, 3,171 (48.0%) were operated on by OR and 3,441 by EVAR. Prophylactic open abdomen (OA) treatment was validated through case records. Cross-matching with the national population registry secured valid mortality data. After rAAA repair, ACS developed in 6.8% after OR versus 6.9% after EVAR (p = 1.0). All major complications were more common after ACS (p < .001). Prophylactic OA was performed in 10.7% of patients after OR. For ACS, DL was performed in 77.3% after OR and 84.6% after EVAR (p = .433). The 30 day mortality rate was 42.4% with ACS and 23.5% without ACS (p < .001); at 1 year it was 50.7% versus 31.8% (p < .001). After iAAA repair, ACS developed in 1.6% of patients after OR versus 0.5% after EVAR (p < .001). Among those with ACS, DL was performed in 68.6% after OR and in 25.0% after EVAR (p = .006). Thirty day mortality was 11.5% with ACS versus 1.8% without it (p < .001); at 1 year it was 27.5% versus 6.3% (p < .001). When ACS developed, renal failure, multiple organ failure, intestinal ischaemia, and prolonged intensive care were much more frequent (p < .001). Morbidity and mortality were similar, regardless of primary surgical technique (OR/EVAR/iAAA/rAAA). ACS and OA were common after treatment for rAAA. ACS is a devastating complication after surgery for rAAA and iAAA, irrespective of operative technique, emphasizing the importance of prevention.


The electrophysiological effects of the serotonin 1A receptor agonist buspirone in emotional face processing.
Emotional face processing is critically modulated by the serotonergic system, and serotonin (5-HT) receptor agonists impair emotional face processing. However, the specific contribution of the 5-HT1A receptor remains poorly understood. Here we investigated the spatiotemporal brain mechanisms underpinning the modulation of emotional face processing induced by buspirone, a partial 5-HT1A receptor agonist. In a psychophysical discrimination of emotional faces task, we observed that the discrimination fearful versus neutral faces were reduced, but not happy versus neutral faces. Electrical neuroimaging analyses were applied to visual evoked potentials elicited by emotional face images, after placebo and buspirone administration. Buspirone modulated response strength (i.e., global field power) in the interval 230-248ms after stimulus onset. Distributed source estimation over this time interval revealed that buspirone decreased the neural activity in the right dorsolateral prefrontal cortex that was evoked by fearful faces. These results indicate temporal and valence-specific effects of buspirone on the neuronal correlates of emotional face processing. Furthermore, the reduced neural activity in the dorsolateral prefrontal cortex in response to fearful faces suggests a reduced attention to fearful faces. Collectively, these findings provide new insights into the role of 5-HT1A receptors in emotional face processing and have implications for affective disorders that are characterized by an increased attention to negative stimuli.


Postural balance during quiet standing in patients with total hip arthroplasty and surface replacement arthroplasty.
Primary total hip arthroplasty leads to better functional capacities but a general weakness of abductor muscles often persists. A larger head component may improve the postural balance in the medial-lateral direction. The aims of this study are (1) to compare postural stability in patients after total hip and surface replacement arthroplasties and (2) to evaluate the effect of the biomechanical reconstruction on postural stability. Six months post-surgery, three groups of ten subjects (total hip and surface replacement arthroplasties and control) performed quiet standing tasks in both dual and one leg stance and a hip abductor muscles strength test. The root-mean-square amplitude of centre of pressure and centre of mass displacement in the anterior-posterior and medial-lateral directions were calculated for dual stance task. Statistical analyses showed greater centre of pressure and centre of mass displacement amplitude in the medial-lateral direction during the dual stance for the total hip arthroplasty compared to the surface replacement and control subjects (P<0.05). All control subjects completed the one leg stance compared to nine in the surface replacement and five in the total hip arthroplasty group. No statistical difference was found between the groups in the hip abductor muscles strength. The better anatomical preservation, absence of femoral stem and the larger bearing component could account for the return to better postural stability in surface replacement patients in comparison to total hip patients. Further studies are needed to determine the impact of each of these factors on the postural balance.


Lack of human herpesvirus 8 and Epstein-Barr virus in Kikuchi's histiocytic necrotizing lymphadenitis.
Kikuchi's histiocytic necrotizing lymphadenitis is a self-limited disorder that typically involves the cervical lymph nodes of young women. Although a viral etiology has been postulated, a definitive viral agent has not been identified. Recent reports have suggested that human herpesvirus 8 (HHV 8) or Epstein-Barr virus (EBV) may play an etiologic role. We investigated the presence of HHV 8 and EBV in archival tissue from 34 cases of Kikuchi's histiocytic necrotizing lymphadenitis. We examined 29 cases for HHV 8 using a nested polymerase chain reaction (PCR) on paraffin-embedded or frozen tissue, and 24 cases for EBV RNA using in situ hybridization (ISH) for EBER1. Controls included reactive lymph nodes from 8 adult women presenting with cervical or axillary lymphadenopathy. The study patients included 7 men and 27 women with a mean age of 28 years. All patients were previously healthy without evidence of immunocompromise and presented with cervical, axillary, or inguinal lymphadenopathy. Two cases exhibited EBV RNA by ISH; this was confirmed by PCR for EBV DNA. HHV 8 DNA was not amplified by nested PCR in any of the cases of Kikuchi's histiocytic necrotizing lymphadenitis or reactive lymph nodes; control PCR demonstrated the presence of amplifiable DNA in all cases. These findings suggest that HHV 8 and EBV do not play causative roles in Kikuchi's histiocytic necrotizing lymphadenitis.


Decohering localized waves.
In the absence of confinement, localization of waves takes place due to randomness or nonlinearity and relies on their phase coherence. We quantitatively probe the sensitivity of localized wave packets to random phase fluctuations and confirm the necessity of phase coherence for localization. Decoherence resulting from a dynamical random environment leads to diffusive spreading and destroys linear and nonlinear localization. We find that maximal spreading is achieved for optimal phase fluctuation characteristics, which is a consequence of the competition between diffusion due to decoherence and ballistic transport within the mean free path distance.


Synthesis and Spectroscopic Properties of Fluorinated Coumarin Lysine Derivatives.
The site-selective incorporation of fluorescent amino acids into proteins has emerged as a valuable alternative to expressible protein reporters. For successful application, a robust and scalable, yet flexible, route to non-natural amino acids is required. This work describes an improved synthesis of coumarin-conjugated lysine derivatives where fluorinated variants are accessed. These analogues can be utilized at low pH and should find application probing biological processes that operate under acidic conditions.


A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development.
Although alterations in the p53 tumor suppressor gene are detected frequently in human breast cancers, mammary tumors are observed infrequently in p53(null) mice. This has led to the suggestion that absence of p53 alone is not sufficient for induction of mammary tumors. However, early death of p53(null) mice from thymic lymphomas may obscure tumor phenotypes that would develop later. Therefore, p53(null) mammary epithelium was transplanted into cleared mammary fat pads of wild type p53 BALB/c hosts to allow long-term analysis of mammary tumor phenotypes. Five treatments were compared for their effects on tumor incidence in hosts bearing transplants of p53(null) and p53wt mammary epithelium. The treatment groups were: (1) untreated; (2) continuous hormone stimulation with pituitary isografts; (3) multiple pregnancies; (4) DMBA alone; and (5) DMBA+pituitary isografts. The tumor incidences in p53(null) vs p53wt mammary transplants for each treatment group were 62% vs 0%, 100% vs 0%, 68% vs 0%, 60% vs 4% and 91% vs 14%, respectively. The mammary tumors that developed in the p53(null) mammary epithelium were all adenocarcinomas and were frequently aneuploid. These data demonstrate that the absence of p53 is sufficient to cause development of mammary tumors and that hormonal stimulation enhances the tumorigenicity of p53(null) mammary epithelium to a greater extent than DMBA exposure alone. This model provides an in situ approach to examine the molecular basis for the role of p53 in the regulation of mammary tumorigenesis.


Resilience and efficiency in transportation networks.
Urban transportation systems are vulnerable to congestion, accidents, weather, special events, and other costly delays. Whereas typical policy responses prioritize reduction of delays under normal conditions to improve the efficiency of urban road systems, analytic support for investments that improve resilience (defined as system recovery from additional disruptions) is still scarce. In this effort, we represent paved roads as a transportation network by mapping intersections to nodes and road segments between the intersections to links. We built road networks for 40 of the urban areas defined by the U.S. Census Bureau. We developed and calibrated a model to evaluate traffic delays using link loads. The loads may be regarded as traffic-based centrality measures, estimating the number of individuals using corresponding road segments. Efficiency was estimated as the average annual delay per peak-period auto commuter, and modeled results were found to be close to observed data, with the notable exception of New York City. Resilience was estimated as the change in efficiency resulting from roadway disruptions and was found to vary between cities, with increased delays due to a 5% random loss of road linkages ranging from 9.5% in Los Angeles to 56.0% in San Francisco. The results demonstrate that many urban road systems that operate inefficiently under normal conditions are nevertheless resilient to disruption, whereas some more efficient cities are more fragile. The implication is that resilience, not just efficiency, should be considered explicitly in roadway project selection and justify investment opportunities related to disaster and other disruptions.


Branching out in roots: uncovering form, function, and regulation.
Root branching is critical for plants to secure anchorage and ensure the supply of water, minerals, and nutrients. To date, research on root branching has focused on lateral root development in young seedlings. However, many other programs of postembryonic root organogenesis exist in angiosperms. In cereal crops, the majority of the mature root system is composed of several classes of adventitious roots that include crown roots and brace roots. In this Update, we initially describe the diversity of postembryonic root forms. Next, we review recent advances in our understanding of the genes, signals, and mechanisms regulating lateral root and adventitious root branching in the plant models Arabidopsis (Arabidopsis thaliana), maize (Zea mays), and rice (Oryza sativa). While many common signals, regulatory components, and mechanisms have been identified that control the initiation, morphogenesis, and emergence of new lateral and adventitious root organs, much more remains to be done. We conclude by discussing the challenges and opportunities facing root branching research.


High-resolution complementary spatial modulation of magnetization (CSPAMM) rat heart tagging on a 1.5 Tesla Clinical Magnetic Resonance System: a preliminary feasibility study.
The purpose of this study was to assess the feasibility of cardiac magnetic resonance (MR) tagging in rats on a standard clinical 1.5T MR system. Small animal models have been largely used as an experimental model in cardiovascular disease studies but mainly on high field systems (>4T) dedicated to research. Given the larger availability of routine clinical MR systems in centers with active cardiac research programs, it is of great interest to perform small animal imaging on whole-body MR systems of moderate field strength. The feasibility study was performed on 7 rats within 6 to 8 hours after myocardial infarction and 3 normal control rats. Myocardial strain was measured successfully in normal rats using the harmonic phase (ie, HARP) method, and a transmural gradient was demonstrated. In a rat model of acute occlusion/reperfusion, the myocardial circumferential strains were decreased, but the transmural strain gradient was preserved. This study demonstrated the feasibility of cardiac MR tagging in rats with a subendocardial resolution using a clinical 1.5T system.


A data-driven model of the COVID-19 spread among interconnected populations: epidemiological and mobility aspects following the lockdown in Italy.
An epidemic multi-group model formed by interconnected SEIR-like structures is formulated and used for data fitting to gain insight into the COVID-19 dynamics and into the role of non-pharmaceutical control actions implemented to limit the infection spread since its outbreak in Italy. The single submodels provide a rather accurate description of the COVID-19 evolution in each subpopulation by an extended SEIR model including the class of asymptomatic infectives, which is recognized as a determinant for disease diffusion. The multi-group structure is specifically designed to investigate the effects of the inter-regional mobility restored at the end of the first strong lockdown in Italy (June 3, 2020). In its time-invariant version, the model is shown to enjoy some analytical stability properties which provide significant insights on the efficacy of the implemented control measurements. In order to highlight the impact of human mobility on the disease evolution in Italy between the first and second wave onset, the model is applied to fit real epidemiological data of three geographical macro-areas in the period March-October 2020, including the mass departure for summer holidays. The simulation results are in good agreement with the data, so that the model can represent a useful tool for predicting the effects of the combination of containment measures in triggering future pandemic scenarios. Particularly, the simulation shows that, although the unrestricted mobility alone appears to be insufficient to trigger the second wave, the human transfers were crucial to make uniform the spatial distribution of the infection throughout the country and, combined with the restart of the production, trade, and education activities, determined a time advance of the contagion increase since September 2020.


The biological origin of linguistic diversity.
In contrast with animal communication systems, diversity is characteristic of almost every aspect of human language. Languages variously employ tones, clicks, or manual signs to signal differences in meaning; some languages lack the noun-verb distinction (e.g., Straits Salish), whereas others have a proliferation of fine-grained syntactic categories (e.g., Tzeltal); and some languages do without morphology (e.g., Mandarin), while others pack a whole sentence into a single word (e.g., Cayuga). A challenge for evolutionary biology is to reconcile the diversity of languages with the high degree of biological uniformity of their speakers. Here, we model processes of language change and geographical dispersion and find a consistent pressure for flexible learning, irrespective of the language being spoken. This pressure arises because flexible learners can best cope with the observed high rates of linguistic change associated with divergent cultural evolution following human migration. Thus, rather than genetic adaptations for specific aspects of language, such as recursion, the coevolution of genes and fast-changing linguistic structure provides the biological basis for linguistic diversity. Only biological adaptations for flexible learning combined with cultural evolution can explain how each child has the potential to learn any human language.


Marked lateral ST-segment elevation with inferior ST-segment depression in an asymptomatic 12 year-old girl: A normal variant?
Significant ST-segment changes raise concern for myocardial ischemia, cardiomyopathy or myocardial inflammation and therefore, warrant an extensive and often invasive cardiovascular evaluation. We report a 12 year-old asymptomatic African-American girl with marked ST-segment elevation in leads I and aVL and ST-segment depression in inferior leads II, III and aVF. Extensive cardiovascular evaluation did not reveal any abnormality suggesting that these findings, which have previously not been reported, are likely benign, at least in this young girl.


Immunization of mice with recombinant mosquito salivary protein D7 enhances mortality from subsequent West Nile virus infection via mosquito bite.
Mosquito salivary proteins (MSPs) modulate the host immune response, leading to enhancement of arboviral infections. Identification of proteins in saliva responsible for immunomodulation and counteracting their effects on host immune response is a potential strategy to protect against arboviral disease. We selected a member of the D7 protein family, which are among the most abundant and immunogenic in mosquito saliva, as a vaccine candidate with the aim of neutralizing effects on the mammalian immune response normally elicited by mosquito saliva components during arbovirus transmission. We identified D7 salivary proteins of Culex tarsalis, a West Nile virus (WNV) vector in North America, and expressed 36 kDa recombinant D7 (rD7) protein for use as a vaccine. Vaccinated mice exhibited enhanced interferon-γ and decreased interleukin-10 expression after uninfected mosquito bite; however, we found unexpectedly that rD7 vaccination resulted in enhanced pathogenesis from mosquito-transmitted WNV infection. Passive transfer of vaccinated mice sera to naïve mice also resulted in increased mortality rates from subsequent mosquito-transmitted WNV infection, implicating the humoral immune response to the vaccine in enhancement of viral pathogenesis. Vaccinated mice showed decreases in interferon-γ and increases in splenocytes producing the regulatory cytokine IL-10 after WNV infection by mosquito bite. Vector saliva vaccines have successfully protected against other blood-feeding arthropod-transmitted diseases. Nevertheless, the rD7 salivary protein vaccine was not a good candidate for protection against WNV disease since immunized mice infected via an infected mosquito bite exhibited enhanced mortality. Selection of salivary protein vaccines on the bases of abundance and immunogenicity does not predict efficacy.


Thyroid hormone levels in term and preterm neonates.
Screening for thyroid hormone levels in the first week of life is extremely important to identify infants with CH. Worldwide neonatal screening programs have been successful in decreasing childhood mental retardation related to CH by early detection and treatment. To successfully screen for CH, nurses must understand how to draw blood that will yield valid results on the metabolic screening filter paper. It is also important for the nurse to understand that thyroid levels are normally decreased in preterm infants and that regular follow-up of those low thyroid levels is crucial because levels may return to normal and eventual treatment is necessary. Early follow-up testing and treatment are essential. A thyroid scan or ultrasonography is optional and decided on by evaluating the risk-benefit ratio.


Behavioral and physiological responses to child-directed speech of children with autism spectrum disorders or typical development.
Young boys with autism were compared to typically developing boys on responses to nonsocial and child-directed speech (CDS) stimuli. Behavioral (looking) and physiological (heart rate and respiratory sinus arrhythmia) measures were collected. Boys with autism looked equally as much as chronological age-matched peers at nonsocial stimuli, but less at CDS stimuli. Boys with autism and language age-matched peers differed in patterns of looking at live versus videotaped CDS stimuli. Boys with autism demonstrated faster heart rates than chronological age-matched peers, but did not differ significantly on respiratory sinus arrhythmia. Reduced attention during CDS may restrict language-learning opportunities for children with autism. The heart rate findings suggest that young children with autism have a nonspecific elevated arousal level.


BCG vaccination status of children with tuberculous meningitis and the use of unsupervised isoniazid prophylaxis.
From 1985 to 1992, 193 children with tuberculous meningitis (TBM) with a median age of 26 months were admitted to the Department of Paediatrics and Child Health, Tygerberg Hospital. Of these children 143 (74%) were documented to have received BCG, either by reference to 'Road to Health' cards or by contact with local authority clinic staff. In a further 18 children a BCG scar was visible. Therefore at least 161 of the children (83%) had received BCG vaccination. As the Western Cape has also been shown to have the highest incidence of TBM in South Africa, there is concern that BCG as currently used does not have a significant protective effect against disseminated tuberculosis. Seventy-seven children (40%) were also reported to have a close household contact who had been treated for pulmonary tuberculosis within the previous 24 months. Only 17 of these children (22%), however, were prescribed prophylactic isoniazid and only 7 of these completed 3 months or more prophylaxis.


Developing an assessment of epistemic trust: a research protocol.
Epistemic trust (ET) describes the willingness to accept new information from another person as trustworthy, generalizable, and relevant. It has been recently proposed that a pervasive failure to establish epistemic trust may underpin personality disorders. Although the introduction of the concept of ET has been inspiring to clinicians and is already impacting the field, the idea that there may be individual differences in ET has yet to be operationalized and tested empirically. This report illustrates the development of an Epistemic trust assessment and describes the protocol for its validation. The sample will include 60 university students. The Trier Social Stress Test for Groups will be administered to induce a state of uncertainty and stress, thereby increasing the relevance of information for the participants. The experiment will entail asking information from the participants about their performance and internal states during a simulated employment interview, and then tracking how participants are able to revise their own judgments about themselves in light of the feedback coming from an expert committee. To control for social desirability and personality disorder traits, the short scale for social desirability (Kurzskala Soziale Erwunschtheit-Gamma) and the Inventory of Personality Organization are utilized. After the procedure, the participants will complete an app-based Epistemic trust questionnaire (ETQ) app. Confirmatory Factor Analysis will be utilized to investigate the structure and dimensionality of the ETQ, and ANOVAs will be used to investigate mean differences within and between persons for ET scores by item category. This study operationalizes a newly developed ET paradigm and provides a framework for the investigation of the theoretical assumptions about the connection of ET and personality functioning.


Sigma-1 receptor is a key genetic modulator in amyotrophic lateral sclerosis.
Sigma-1 receptor (S1R) is an endoplasmic reticulum (ER) chaperone that not only regulates mitochondrial respiration but also controls cellular defense against ER and oxidative stress. This makes S1R a potential therapeutic target in amyotrophic lateral sclerosis (ALS). Especially, as a missense mutation E102Q in S1R has been reported in few familial ALS cases. However, the pathogenicity of S1RE102Q and the beneficial impact of S1R in the ALS context remain to be demonstrated in vivo. To address this, we generated transgenic Drosophila that expresses human wild-type S1R or S1RE102Q. Expression of mutant S1R in fly neurons induces abnormal eye morphology and locomotor defects in a dose-dependent manner. This was accompanied by abnormal mitochondrial fragmentation, reduced adenosine triphosphate (ATP) levels and a higher fatigability at the neuromuscular junction during high energy demand. Overexpressing IP3 receptor or glucose transporter mitigates the S1RE102Q-induced eye phenotype, further highlighting the role of calcium and energy metabolism in its toxicity. More importantly, we showed that wild-type S1R rescues locomotor activity and ATP levels of flies expressing the key ALS protein, TDP43. Moreover, overexpressing wild-type S1R enhances resistance of flies to oxidative stress. Therefore, our data provide the first genetic evidence that mutant S1R recapitulates ALS pathology in vivo while increasing S1R confers neuroprotection against TDP43 toxicity.


Do biotic interactions shape both sides of the humped-back model of species richness in plant communities?
A humped-back relationship between species richness and community biomass has frequently been observed in plant communities, at both local and regional scales, although often improperly called a productivity-diversity relationship. Explanations for this relationship have emphasized the role of competitive exclusion, probably because at the time when the relationship was first examined, competition was considered to be the significant biotic filter structuring plant communities. However, over the last 15 years there has been a renewed interest in facilitation and this research has shown a clear link between the role of facilitation in structuring communities and both community biomass and the severity of the environment. Although facilitation may enlarge the realized niche of species and increase community richness in stressful environments, there has only been one previous attempt to revisit the humped-back model of species richness and to include facilitative processes. However, to date, no model has explored whether biotic interactions can potentially shape both sides of the humped-back model for species richness commonly detected in plant communities. Here, we propose a revision of Grime's original model that incorporates a new understanding of the role of facilitative interactions in plant communities. In this revised model, facilitation promotes diversity at medium to high environmental severity levels, by expanding the realized niche of stress-intolerant competitive species into harsh physical conditions. However, when environmental conditions become extremely severe the positive effects of the benefactors wane (as supported by recent research on facilitative interactions in extremely severe environments) and diversity is reduced. Conversely, with decreasing stress along the biomass gradient, facilitation decreases because stress-intolerant species become able to exist away from the canopy of the stress-tolerant species (as proposed by facilitation theory). At the same time competition increases for stress-tolerant species, reducing diversity in the most benign conditions (as proposed by models of competition theory). In this way our inclusion of facilitation into the classic model of plant species diversity and community biomass generates a more powerful and richer predictive framework for understanding the role of plant interactions in changing diversity. We then use our revised model to explain both the observed discrepancies between natural patterns of species richness and community biomass and the results of experimental studies of the impact of biodiversity on the productivity of herbaceous communities. It is clear that explicit consideration of concurrent changes in stress-tolerant and competitive species enhances our capacity to explain and interpret patterns in plant community diversity with respect to environmental severity.


First Report of Tomato yellow leaf curl virus in Acalypha australis in China.
Whitefly-transmitted geminiviruses (WTGs) can cause serious damage to many crops in China, so an investigation of weed hosts of WTGs was carried out in Jiangsu Province, China, in 2012. Fifty-seven symptomless samples of Acalypha australis L., a common weed known as Asian copperleaf, were randomly collected from seven tomato fields in Nanjing and Lianyungang, Jiangsu Province, from July to September. Total DNA of each sample was extracted and PCR was performed using degenerate primers PA and PB to amplify a specific region covering the AV2 gene of DNA-A and part of the adjacent intergenic region (1). DNA fragments were successfully amplified from 27 out of 57 samples and PCR amplicons of 16 samples were sequenced. Alignment results showed that the nucleotide sequence identities ranged from 98 to 100% with Tomato yellow leaf curl virus (TYLCV) accessions. The full-length viral circular DNA genome was amplified using primer pair 1AbF (ATGTGGGATCCACTTCTAAATGAATTTCC) and 1AsR (GCGTCGACAGTGCAAGACAAACTACTTGGGGACC) which were designed based on the known sequences amplified by PA and PB. The complete genome sequence (GenBank Accession No. JX910534) was 2,781 nucleotides in length and had 99 to 100% sequence identity with TYLCV accessions (GU434142, GU111505). The dot immunobinding assay using monoclonal antibody against TYLCV confirmed the 27 weed samples positive by PCR were infected by TYLCV. These results demonstrated that A. australis is a host of TYLCV that might play an important role in viral epidemics in tomato fields in China. TYLCV-infected A. australis did not show typical symptoms like leaf curl, chlorosis, and stunting and thus appears to be a symptomless host. In our investigation, the infection rate ranged from 14 to 79% depending on the field sampled, suggesting that the weed may be an important reservoir of TYLCV, especially during the non-tomato planting period. To our knowledge, this is the first report of A. australis as a host of TYLCV in China. Reference: (1) D. Deng et al. Ann. Appl. Biol. 125:327, 1994.


Condensed Monte Carlo simulations for the description of light transport.
A novel method, condensed Monte Carlo simulation, is presented that applies the results of a single Monte Carlo simulation for a given albedo micro(s)/(micro(alpha) & micro(s)) to obtaining results for other albedos; micro(s) and micro(alpha), are the scattering and absorption coefficients, respectively. The method requires only the storage of the number of interactions of each photon with the medium. The reflectance and transmittance of turbid slabs can thus be found from a limited number of condensed Monte Carlo simulations. We can use an inversion procedure to obtain the absorption and scattering coefficients from the total reflectance and total transmittance of slabs. Remitted photon densities from a semi-infinite medium as a function of the distance between the light source and the detector for all albedos can be found even from the results of a single condensed Monte Carlo simulation. The application of similarity rules may reduce further the number of Monte Carlo simulations that are needed to describe the influence of the distribution of scattering angles on the results.


[The first patient with the new variant of Creutzfeldt-Jakob's disease in The Netherlands].
A Dutch woman died at the age of 26 years, after a disease duration of 18 months, due to the new variant of Creutzfeldt-Jakob's disease (vCJD). She had never travelled to the United Kingdom and there was no history of potential iatrogenic exposure. However, she had worked in the catering and food production industry for the previous 6 years and had frequently consumed raw meat. The disease course showed the classical clinical picture of vCJD, which was confirmed by post-mortem examination of the brain. Contrary to classical sporadic CJD, patients with the variant disease are usually younger and present predominantly with psychiatric symptoms. Sensory complaints like pain and dysaesthesiae usually follow soon. Only later are these symptoms followed by rapidly progressive neurological symptoms and signs. All patients genotyped so far are homozygous for methionine on codon 129 of the prion protein gene. Recognition of the disease is of particular importance because of possible transmission via blood and tissues. In patients with rapidly progressive psychiatric symptoms and unexplained neurological signs, particularly sensory complaints, one must consider the possibility of vCJD.


Age and bone mass as predictors of fracture in a prospective study.
To study the effect of bone mass on the risk of fracture, we followed 521 Caucasian women over an average of 6.5 yr and took repeated bone mass measurements at the radius. We observed 138 nonspinal fractures in 3,388 person-yr. The person-years of follow-up and the incident fractures were cross-classified by age and bone mass. The incidence of fracture was then fitted to a log-linear model in age and bone mass. It was found that incidence of fracture increased with both increasing age and decreasing radius bone mass. When subsets of fractures were examined it was found that age was a stronger predictor of hip fractures, whereas midshaft radius bone mass was a stronger predictor of fractures at the distal forearm. We concluded that bone mass is a useful predictor of fractures but that other age-related factors associated with fractures need to be identified.


Factors affecting the association of single- and double-stranded RNAs with montmorillonite nanoclays.
Montmorillonite (MMT) nanoclays exist as single and stacked sheet-like structures with large surface areas that can form stable associations with many naturally occurring biomolecules, including nucleic acids. They have been utilized successfully as vehicles for delivery of both drugs and genes into cells. Most previous studies have focused on interactions of MMT with DNA. In the current study, we have investigated the binding of small RNAs similar to those used for RNA interference (RNAi) therapy to two major forms of the clay, Na-MMT and Ca-MMT. Association of both forms of MMT with several double-stranded RNAs (dsRNAs), including 25mers, 54mers and cloverleaf-shaped transfer RNAs, was weak and increased only slightly after addition of Mg2+ ions to the binding reactions. By contrast, ssRNA 25mers and 54mers bound poorly to Na-MMT but interacted strongly with Ca-MMT. The weak binding of ssRNAs to Na-MMT could be strongly enhanced by addition of Mg2+ ions. The strength of MMT-ssRNA interactions was also examined using inorganic anion competition and displacement assays, as well as electrophoretic mobility shift assays (EMSAs). The aggregate results point to a cation-bridging mechanism for binding of ssRNAs, but not dsRNAs, in the presence of divalent metal cations.


A novel phycobiliprotein alleviates allergic airway inflammation by modulating immune responses.
it has been claimed that phycocyanin exhibits pharmaceutical functions in inhibiting histamine release and leukotriene biosynthesis. In allergic asthma, these inflammatory mediators are crucial for disease progression. the aim of this study was to evaluate the therapeutic potential of R-phycocyanin (R-PC) against allergic airway inflammation. mouse bone marrow-derived dendritic cells (BMDCs) were used to evaluate the immunomodulatory functions of R-PC. In addition, an airway inflammatory model was used to evaluate the therapeutic potential of R-PC. R-PC treatment resulted in a decrease of endocytosis, increase of costimulatory molecule expression, and enhancement of interleukin-12 production in mouse BMDCs. Moreover, R-PC-treated cultured dendritic cells were able to promote CD4(+) T-cell stimulatory capacity and increase interferon-γ expression in CD4(+) T cells. Intraperitoneal administration of R-PC suppressed ovalbumin (OVA)-induced airway hyperresponsiveness, serum levels of OVA-specific IgE and IgG1, eosinophil infiltration, Th2 cytokine levels, and eotaxin in bronchoalveolar lavage fluid of mice. Antibody against Toll-like receptor-4 was able to inhibit R-PC-induced IL-12 p70 production. Moreover, inhibition of nuclear factor-κB (NF-κB) by helenalin and inhibition of the JNK pathway by JNK inhibitor II inhibited R-PC-induced IL-12 p70 production. Western blotting and electrophoretic mobility shift assays showed that R-PC augmented phosphorylation of the inhibitors of NF-κB and inhibitors of NF-κB kinase and facilitated NF-κB activity. our data demonstrated that R-PC promoted activation and maturation of cultured dendritic cells and skewed the immunological function toward Th1 activity. Therefore, R-PC may have potential in regulating immune responses and application in reducing allergic asthma.


Orientational order in gravity dispersed clay colloids: a synchrotron x-ray scattering study of Na fluorohectorite suspensions.
Colloidal suspensions of clay particles in aqueous salt solutions make ideal model systems for the study of interactions between plate-shaped particles, due to the ease in tuning their electrostatic repulsion with the concentration of the salt. Numerous gel and sol structures are possible, including nematic liquid crystalline order, although only qualitative identification of the latter in clay colloids has been available so far. We present synchrotron x-ray diffraction from gravity dispersed solutions of Na fluorohectorite, a synthetic swelling clay, over a large NaCl concentration range. Our use of liquid scattering techniques allows us to identify regions in which particles reorient from horizontal to vertical alignments in strata coexisting at different heights within the sample. We identify two distinct gel regions characterized by differences in orientational anisotropy and domain size. Our results provide direct evidence for nematic order, as well as unique structural information regarding particle morphology and alignment within each of the colloid phases.


IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1.
We report identification of interleukin (IL)-17E, a novel member of the IL-17 family of cytokines. IL-17E is a ligand for the recently identified protein termed EVI27/IL-17BR, which we term IL-17 receptor homolog 1 (IL-17Rh1) in light of the multiple reported ligand-receptor relationships. Murine EVI27 was identified through its location at a common site of retroviral integration in BXH2 murine myeloid leukemias. IL-17Rh1 shows highest level expression in kidney with moderate expression in multiple other organs, whereas IL-17E mRNA was detected at very low levels in several peripheral tissues. IL-17E induces activation of NF-kappaB and stimulates production of the proinflammatory chemokine IL-8.


Dysfunctional sleep-related cognition and anxiety mediate the relationship between multidimensional perfectionism and insomnia symptoms.
Perfectionism is one of several personality traits associated with insomnia. Whilst research has examined the relationships between perfectionism and insomnia, the mediating role of dysfunctional sleep-related cognition (i.e. sleep-related worry and dysfunctional beliefs about the biological attribution of and consequences of poor sleep) has yet to be examined. This study aimed to determine whether aspects of multidimensional perfectionism were related to increased reporting of insomnia symptoms. In addition, the potential mediating role of dysfunctional sleep-related cognition and anxiety symptoms was examined. Members of the general population (N = 624) completed the Dysfunctional Beliefs and Attitudes About Sleep Scale, the Insomnia Severity Index, the Hospital Anxiety and Depression Scale, and the Multidimensional Perfectionism Scale. The results showed that perfectionism dimensions, anxiety symptoms, and dysfunctional sleep-related cognition were significantly associated with insomnia symptoms. Regression-based mediation analyses further showed that both dysfunctional sleep-related cognition and anxiety significantly mediated the associations between insomnia symptoms and three perfectionism dimensions (i.e. doubts about action, parental expectations, and parental criticism). The experience of perfectionistic tendencies, anxiety, and dysfunctional sleep-related cognition may initiate behavioural strategies (e.g. daytime napping) when faced with an acute sleep problem. However, these strategies may serve to transition insomnia from an acute to a chronic condition.


Facial expressions of patients with dementia: a comparison of two methods of interpretation.
Two methods of interpreting the videotaped facial expressions of four patients with severe dementia of the Alzheimer type were compared. Interpretations of facial expressions performed by means of unstructured naturalistic judgments revealed episodes when the four patients exhibited anger, disgust, happiness, sadness, and surprise. When these episodes were assessed by use of a modified version of the Facial Action Coding System, there was, in total, 48% agreement between the two methods. The highest agreement, 98%, occurred for happiness shown by one patient. It was concluded that more emotions could be judged by means of the unstructured naturalistic method, which is based on an awareness of the total situation that facilitates imputing meaning into the patients' cues. It is a difficult task to find a balance between imputing too much meaning into the severely demented patients' sparse and unclear cues and ignoring the possibility that there is some meaning to be interpreted.


Effect of Procedural Volume on In-Hospital Outcomes After Percutaneous Coronary Intervention in Patients With Chronic Kidney Disease (from the Japanese National Clinical Data [J-PCI Registry]).
Chronic kidney disease (CKD) increases the risk of death and other poor outcomes in patients with cardiovascular diseases. This study investigated the relation between the institutional CKD percutaneous coronary intervention (PCI) volume and in-hospital clinical outcomes in patients with CKD. Among 1,199,901 patients who underwent PCI in 2014 to 2018 from the Japanese nationwide registry, we analyzed 220,509 patients with CKD. Patients were classified into quartiles (Q) according to the mean annual institutional CKD-PCI volume (Q1 <42 PCIs/year, Q2 <74 PCIs/year, Q3 <124 PCIs/year, Q4 ≥125 PCIs/year). The primary outcome was a composite of in-hospital death and periprocedural complications. The mean age of patients was 73 ± 10 years, and 36% (n = 78,332) were on dialysis. PCI was more likely to be performed with rotational atherectomy devices in high-volume institutions. Contrast volume was lower, the rate of radial access PCI was higher, and door-to-balloon time (for ST-elevation myocardial infarction) was shorter in the highest quartile institutions. Primary outcomes were observed in 6,539 patients (3.0%). The crude rate of the primary outcome was lowest in institutions with the highest PCI volume (Q1 3.4%, Q2 3.0%, Q3 3.0%, Q4 2.4%, p <0.001); higher PCI volume was associated with reduced frequency of the primary outcome (odds ratio [95% confidence interval] relative to Q1:Q2, 0.89 [0.83 to 0.96]; Q3 0.90 [0.84 to 0.97]; and Q4 0.76 [0.84 to 0.97]). In conclusion, the procedural characteristics and outcomes of PCI differed significantly by institutional volume in patients with CKD. When considering revascularization among these patients, institutional CKD-PCI volume needs to be incorporated in decision-making.


A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries.
The present study examined the hypothesis that potassium ions act as an endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in small mesenteric arteries displaying myogenic tone. Small mesenteric arteries isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg. After developing myogenic tone, responses to raising extracellular potassium were compared to those obtained with ACh (in the presence of nitric oxide synthase and cyclo-oxygenase inhibitors). The effects of barium and oubain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined. The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries. Rat small mesenteric arteries developed myogenic tone when pressurised. On the background of vascular tone set by a physiological stimulus (i.e pressure), ACh fully dilated the small arteries in a concentration-dependent manner. This response was relatively insensitive to the combination of barium and ouabain, and insensitive to capsaicin. Raising extracellular potassium produced a more inconsistent and modest vasodilator response in pressurised small mesenteric arteries. Responses to raising extracellular potassium were sensitive to capsaicin, and the combination of barium and ouabain. ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not. These data indicate that K+ is not the EDHF released in response to ACh in myogenically active rat mesenteric small arteries. Since the hyperpolarization produced by ACh was sensitive to carbenoxolone, gap junctions are the likely mediator of EDH responses under physiological conditions.


Single cells in nanoshells for the functionalization of living cells.
Inspired by the characteristics of cells in live organisms, new types of hybrids have been designed comprising live cells and abiotic materials having a variety of structures and functionalities. The major goal of these studies is to uncover hybridization approaches that promote cell stabilization and enable the introduction of new functions into living cells. Single-cells in nanoshells have great potential in a large number of applications including bioelectronics, cell protection, cell therapy, and biocatalysis. In this review, we discuss the results of investigations that have focused on the synthesis, structuration, functionalization, and applications of these single-cells in nanoshells. We describe synthesis methods to control the structural and functional features of single-cells in nanoshells, and further develop their applications in sustainable energy, environmental remediation, green biocatalysis, and smart cell therapy. Perceived limitations of single-cells in nanoshells have been also identified.


Calorimetric and x-ray diffraction studies of rye glucocerebroside mesomorphism.
Glucocerebrosides (GlcCer) isolated from the leaves of winter rye (Secale cereale L. cv Puma) differ from the more commonly investigated natural and synthetic cerebrosides, in that greater than 95% of the fatty acids are saturated and monounsaturated hydroxy fatty acids. Isomers of the trihydroxy long chain base hydroxysphingenine (t1(8:18 cis or trans)) and isomers of sphingadienine (d18:2(4trans, 8 cis or trans)) comprise 77% and 17%, respectively, of the total long chain bases. The phase behavior of fully hydrated and dry rye leaf GlcCer was investigated using differential scanning calorimetry (DSC) and x-ray diffraction. On initial heating, aqueous dispersions of GlcCer exhibit a single endothermic transition at 56 degrees C and have an enthalpy (delta H) of 46 J/g. Cooling to 0 degrees C is accompanied by a small exothermic transition (delta H = -8 J/g) at 8 degrees C. On immediate reheating, a broad exothermic transition (delta H = -39 J/g) is observed between 10 and 20 degrees C in addition to a transition at 56 degrees C. These transitions are not reversible, and the exothermic transition rapidly diminishes when the sample is held at low temperature. Using x-ray diffraction, it was determined that the endotherm at 56 degrees C represents a transition from a highly ordered lamellar crystalline phase (Lc) with a d-spacing of 57 A and a series of wide-angle reflections in the 3-10 A range, to a lamellar liquid crystalline (L alpha) phase having a d-spacing of 55 A and a diffuse wide-angle scattering peak centered at 4.7 A. Cooling leads to the formation of a metastable gel phase (L beta) with a d-spacing of 64.0 A and a single broad reflection at 4.28 A. Subsequent warming to above 15 degrees C restores the original Lc phase. Thus, rye GlcCer in excess water exhibit a series of irreversible transitions and gel phase metastability. Dry GlcCer undergo an initial heating endothermic transition at 130 degrees C, which is ascribed to a transformation into the HII phase from a two phase state characterized by the coexistence of phases with disordered (alpha) and helical (delta) type chain conformations but of unknown lattice identity: An exotherm at 67.5 degrees C observed upon subsequent cooling is of unknown origin. Since an undercooled HII phase persists down to 19 degrees C, the exotherm may derive in part from an alpha-to-delta type chain packing conformational change especially under slow cooling conditions. Upon reheating from low temperatures to 65 degrees C, a phase with a two-dimensional, primitive rectangular lattice and delta-like chain packing (R8 phase) in coexistence with the HI, phase emerges. With continued heating to 90 degrees C these coexisting phases give way to a phase with a two-dimensional, centered rectangular lattice and delta-like chain packing (P8phase) which again coexists with the HI, phase. Above 130 degrees C, the Pb phase disappears and the sample converts completely to the HI, phase as observed upon initial heating. These results indicate that the mesomorphic behavior of rye leaf GIcCer is distinct from that of other cerebrosides.


Risk reduction of non-vertebral fractures with intravenous ibandronate: post-hoc analysis from DIVA.
In the BONE study (3 years' duration), daily oral ibandronate 2.5 mg reduced vertebral fracture risk by 62% (vs. placebo; p = 0.0001). In the DIVA study (2 years' duration), i.v. ibandronate 2 mg every 2 months (q2mo) or 3 mg every 3 months (q3mo) was superior to daily oral ibandronate in terms of BMD gains (p < 0.001) and normalisation of bone turnover markers, suggesting potential antifracture efficacy with the licensed i.v. regimen (3 mg q3mo). To evaluate this, a post-hoc analysis of non-vertebral fracture incidence was performed using DIVA study individual patient data. Both i.v. doses had the same annual cumulative exposure (ACE) - 12 mg. Therefore, data for these two regimens were pooled. This higher dose was compared with 2.5 mg daily oral ibandronate (ACE 5.5 mg) to maintain trial randomisation. Osteoporotic non-vertebral fractures were captured as a secondary endpoint. Time-to-event analysis was conducted using Kaplan-Meier methodology; hazard ratios (HRs) were derived from a Cox model with adjustments for clinical fracture, age and BMD. The DIVA trial was not primarily designed to assess fracture efficacy. The rate of non-vertebral fractures was significantly reduced when ibandronate ACE 12 mg (3 mg q3mo and 2 mg q2mo i.v.) was compared with ACE 5.5 mg (2.5 mg daily oral). The non-vertebral fracture incidence was 3.1% versus 4.8%, respectively, representing a 43% relative risk reduction with i.v. ibandronate (p = 0.0489; adjusted HR 0.569 [95% confidence interval: 0.324, 0.997]). Time to non-vertebral fracture was also extended for high- versus low-dose ibandronate (p = 0.048). A significant effect on non-vertebral fracture risk reduction was seen when high i.v. ibandronate doses were compared with a lower oral dose. This post-hoc analysis indicates greater antifracture efficacy for the licensed quarterly i.v. regimen versus daily oral dosing.


Medial Longitudinal Arch Angle Presents Significant Differences Between Foot Types: A Biplane Fluoroscopy Study.
The structure of the medial longitudinal arch (MLA) affects the foot's overall function and its ability to dissipate plantar pressure forces. Previous research on the MLA includes measuring the calcaneal-first metatarsal angle using a static sagittal plane radiograph, a dynamic height-to-length ratio using marker clusters with a multisegment foot model, and a contained angle using single point markers with a multisegment foot model. The objective of this study was to use biplane fluoroscopy to measure a contained MLA angle between foot types: pes planus (low arch), pes cavus (high arch), and normal arch. Fifteen participants completed the study, five from each foot type. Markerless fluoroscopic radiostereometric analysis (fRSA) was used with a three-dimensional model of the foot bones and manually matching those bones to a pair of two-dimensional radiographic images during midstance of gait. Statistically significant differences were found between barefoot arch angles of the normal and pes cavus foot types (p = 0.036), as well as between the pes cavus and pes planus foot types (p = 0.004). Dynamic walking also resulted in a statistically significant finding compared to the static standing trials (p = 0.014). These results support the classification of individuals following a physical assessment by a foot specialist for those with pes cavus and planus foot types. The differences between static and dynamic kinematic measurements were also supported using this novel method.


Reproductive isolation in natural populations of Drosophila melanogaster from Brazzaville (Congo).
The aim of this work is to analyze the homogamy previously detected between two natural populations of Drosophila melanogaster from Brazzaville. It is shown that mating isolation was still maintained under laboratory conditions 10 years after the populations samples were trapped. Isolation seemed to be due mainly to premating isolation and we checked for any suggestion of post-mating mortality of hybrids. Pre-mating isolation was not symmetrical, and significant chi2 values were found in 3/4 possible 3-way mating choice experiments. The only exception involved a male from the countryside and two females (one from each population) for which no significant mating preference was detected. Mortality of hybrids was intermediate between those of the parental strains showing a clear maternal effect and the existence of partial dominance. Major differences in the cuticular hydrocarbons were also found and they could account for the isolation. These findings in populations from African breweries indicate that they are closely related to European ones, suggesting that this phenomenon is not a case of sympatric speciation, but probably attributable to the reintroduction of an allopatric population.


Pulmonary exacerbations in cystic fibrosis: young children with characteristic signs and symptoms.
A standard definition of pulmonary exacerbation based on signs and symptoms would be useful for categorizing cystic fibrosis (CF) patients and as an outcome measure of therapy. The frequently used definition of treatment with intravenous antibiotics varies with practice patterns. One approach to this problem is to use large data sets which include a patient's signs and symptoms along with their clinician's decision to treat with antibiotics for the diagnosis of pulmonary exacerbation. Previous analysis of such a data set, the Epidemiologic Study of Cystic Fibrosis (ESCF), found that new crackles, increased cough, increased sputum, and weight decline were the four clinical characteristics most strongly influencing providers to treat young CF patients for a pulmonary exacerbation. The objectives of this study were to confirm that these four characteristics influence the decision to treat with antibiotics for a pulmonary exacerbation in young CF patients; to evaluate their implications for future nutritional status and lung function; and to assess the effect of antibiotic treatment on these characteristic signs and symptoms. This was an observational, longitudinal cohort study of clinical care in children <6 years old cared for at sites participating in ESCF. Using data from children not included in the previous ESCF study, we confirmed that these four characteristics were significantly associated with the likelihood of physicians prescribing antibiotics to treat a pulmonary exacerbation. The number of these characteristics present at a single clinic visit before age 6 predicted hospitalization rate over the next year, the weight-for-age z-score, and the forced expiratory volume in 1 sec (FEV1) percent predicted at age 7. Treatment with antibiotics was associated with a greater decrease in the proportion of children with crackles, cough, and Pseudomonas aeruginosa at a follow-up visit within 6 months. New crackles, increased cough, increased sputum, and decline in weight percentile at a single clinic visit increase the risk of future malnutrition, hospitalization, and airflow obstruction in young children with CF. Treatment with antibiotics mitigates some of these signs and symptoms by the first follow-up visit. The presence of these four characteristic signs and symptoms is useful to define pulmonary exacerbations in young children with CF that respond to antibiotic treatment in the short-term and influence long-term prognosis.


Effects of foveal ablation on the pattern of peripheral refractive errors in normal and form-deprived infant rhesus monkeys (Macaca mulatta).
PURPOSE. The purpose of this study was to determine whether visual signals from the fovea contribute to the changes in the pattern of peripheral refractions associated with form deprivation myopia in monkeys. METHODS. Monocular form-deprivation was produced in 18 rhesus monkeys by securing diffusers in front of their treated eyes between 22 ± 2 and 155 ± 17 days of age. In eight of these form-deprived monkeys, the fovea and most of the perifovea of the treated eye were ablated by laser photocoagulation at the start of the diffuser-rearing period. Each eye's refractive status was measured by retinoscopy along the pupillary axis and at 15° intervals along the horizontal meridian to eccentricities of 45°. Control data were obtained from 12 normal monkeys and five monkeys that had monocular foveal ablations and were subsequently reared with unrestricted vision. RESULTS. Foveal ablation, by itself, did not produce systematic alterations in either the central or peripheral refractive errors of the treated eyes. In addition, foveal ablation did not alter the patterns of peripheral refractions in monkeys with form-deprivation myopia. The patterns of peripheral refractive errors in the two groups of form-deprived monkeys, either with or without foveal ablation, were qualitatively similar (treated eyes: F = 0.31, P = 0.74; anisometropia: F = 0.61, P = 0.59), but significantly different from those found in the normal monkeys (F = 8.46 and 9.38 respectively, P < 0.05). CONCLUSIONS. Central retinal signals do not contribute in an essential way to the alterations in eye shape that occur during the development of vision-induced axial myopia.


Attitudes to genetically modified food over time: How trust in organizations and the media cycle predict support.
This research examined public opinion toward genetically modified plants and animals for food, and how trust in organizations and media coverage explained attitudes toward these organisms. Nationally representative samples (N=8821) over 10 years showed Australians were less positive toward genetically modified animals compared to genetically modified plants for food, especially in years where media coverage was high. Structural equation modeling found that positive attitudes toward different genetically modified organisms for food were significantly associated with higher trust in scientists and regulators (e.g. governments), and with lower trust in watchdogs (e.g. environmental movement). Public trust in scientists and watchdogs was a stronger predictor of attitudes toward the use of genetically modified plants for food than animals, but only when media coverage was low. Results are discussed regarding the moral acceptability of genetically modified organisms for food, the media's role in shaping public opinion, and the role public trust in organizations has on attitudes toward genetically modified organisms.