Design and visualization of second-generation cyanoisoindole-based fluorescent strigolactone analogs.
Strigolactones (SLs) are a family of terpenoid allelochemicals that were recognized as plant hormones only a decade ago. They influence a myriad of both above- and below-ground developmental processes, and are an important survival strategy for plants in nutrient-deprived soils. A rapidly emerging approach to gain knowledge on hormone signaling is the use of traceable analogs. A unique class of labeled SL analogs was constructed, in which the original tricyclic lactone moiety of natural SLs is replaced by a fluorescent cyanoisoindole ring system. Biological evaluation as parasitic seed germination stimulant and hypocotyl elongation repressor proved the potency of the cyanoisoindole strigolactone analogs (CISAs) to be comparable to the commonly accepted standard GR24. Additionally, via a SMXL6 protein degradation assay, we provided molecular evidence that the compounds elicit SL-like responses through the natural signaling cascade. All CISAs were shown to exhibit fluorescent properties, and the high quantum yield and Stokes shift of the pyrroloindole derivative CISA-7 also enabled in vivo visualization in plants. In contrast to the previously reported fluorescent analogs, CISA-7 displays a large similarity in shape and structure with natural SLs, which renders the analog a promising tracer to investigate the spatiotemporal distribution of SLs in plants and fungi.


First Report of SARS-CoV-2 Detection in Cerebrospinal Fluid in a Child With Guillain-Barré Syndrome.
Underlying mechanisms on the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurologic complications are still poorly understood. Cases of Guillain-Barré Syndrome (GBS) have been linked to the SARS-CoV-2 infection as the result of dysregulated immune response with damage in neuronal tissues. In the current report, we present the first pediatric case of GBS with detection of SARS-CoV-2 in the cerebrospinal fluid (CFS). This unique case of COVID-19-associated GBS with detection of SARS-CoV-2 RNA in the CSF indicates direct viral involvement inducing peripheral nerve inflammation.


Stronger bilateral functional connectivity of the frontoparietal control network in near-centenarians and centenarians without dementia.
Centenarians without dementia can be considered as a model of successful ageing and resistance against age-related cognitive decline. Is there something special about their brain functional connectivity that helps them preserve cognitive function into the 11th decade of life? In a cohort of 57 dementia-free near-centenarians and centenarians (95-103 years old) and 66 cognitively unimpaired younger participants (76-79 years old), we aimed to investigate brain functional characteristics in the extreme age range using resting-state functional MRI. Using group-level independent component analysis and dual regression, results showed group differences in the functional connectivity of seven group-level independent component (IC) templates, after accounting for sex, education years, and grey matter volume, and correcting for multiple testing at family-wise error rate of 0.05. After Bonferroni correction for testing 30 IC templates, near-centenarians and centenarians showed stronger functional connectivity between right frontoparietal control network (FPCN) and left inferior frontal gyrus (Bonferroni-corrected p = 0.024), a core region of the left FPCN. The investigation of between-IC functional connectivity confirmed the voxel-wise result by showing stronger functional connectivity between bilateral FPCNs in near-centenarians and centenarians compared to young-old controls. In addition, near-centenarians and centenarians had weaker functional connectivity between default mode network and fronto-temporo-parietal network compared to young-old controls. In near-centenarians and centenarians, stronger functional connectivity between bilateral FPCNs was associated with better cognitive performance in the visuospatial domain. The current study highlights the key role of bilateral FPCN connectivity in the reserve capacity against age-related cognitive decline.


Flounder antifreeze protein synthesis under heat shock control in transgenic Drosophila melanogaster.
The gene coding for the most abundant antifreeze protein (AFP) in the winter flounder was placed downstream of the Drosophila melanogaster hsp70 promoter and introduced into the D. melanogaster germ line by P-element-mediated transformation. In each of six transgenic strains tested, heat shock treatment induced the expression of two major AFP gene transcripts and one minor one. All three transcripts were spliced despite the lack of an obvious D. melanogaster internal intron-splicing sequence. The variation in transcript length was caused by selection of different polyadenylation sites. Western blots showed the presence of immunoreactive AFP in hemolymph from heat-shocked transformants. The immunoreactive material had a molecular weight of 6,200, which is consistent with the loss of the signal sequence from the primary translation product and the retention of the pro sequence. Thus, all the signals for flounder pre-mRNA and preprotein processing were recognized in D. melanogaster.


Do cortical midline variability and low frequency fluctuations mediate William James' "Stream of Consciousness"? "Neurophenomenal Balance Hypothesis" of "Inner Time Consciousness".
William James famously characterized consciousness by 'stream of consciousness' which describes the temporal continuity and flow of the contents of consciousness in our 'inner time consciousness'. More specifically he distinguished between "substantive parts", the contents of consciousness, and "transitive parts", the linkages between different contents. While much research has recently focused on the substantive parts, the neural mechanisms underlying the transitive parts and their characterization by the balance between 'sensible continuity' and 'continuous change' remain unclear. The aim of this paper is to develop so-called neuro-phenomenal hypothesis about specifically the transitive parts and their two phenomenal hallmark features, sensible continuity and continuous change in 'inner time consciousness'. Based on recent findings, I hypothesize that the cortical midline structures and their high degree of variability and strong low frequency fluctuations play an essential role in mediating the phenomenal balance between sensible continuity and continuous change.


[Acute pneumonia in alcoholics: onset and course].
As indicated by the data on acute pneumonia (AP) analyzed from the case histories of chronic alcoholics who had died in the hospital for addicts, AP in alcoholics runs with scare symptoms in the absence of physical manifestations and takes a severe course. The authors provide recommendations on AP diagnosis and treatment in chronic alcoholics.


Incentives increase the rate of false but not true secondary confessions from informants with an allegiance to a suspect.
One hundred ninety-two students participated in an experimental simulation testing whether incentives would reduce the reluctance of informants to implicate a close other. Half of the students were made to feel interpersonally close to a confederate who either admitted to or denied a misdeed. All students were interrogated and encouraged to sign a secondary confession stating that the confederate had confessed to the misdeed; half were offered an incentive to do so. Contrary to expectations, closeness did not induce reluctance. Instead, the offer of incentive increased the number of participants willing to sign a secondary confession implicating a close other. Further analyses revealed that this increase occurred only for false secondary confessions. Implications for interrogation practices are discussed.


The EGFR demonstrates linear signal transmission.
Cells sense information encoded in extracellular ligand concentrations and process it using intracellular signalling cascades. Using mathematical modelling and high-throughput imaging of individual cells, we studied how a transient extracellular growth factor signal is sensed by the epidermal growth factor receptor system, processed by downstream signalling, and transmitted to the nucleus. We found that transient epidermal growth factor signals are linearly translated into an activated epidermal growth factor receptor integrated over time. This allows us to generate a simplified model of receptor signaling where the receptor acts as a perfect sensor of extracellular information, while the nonlinear input-output relationship of EGF-EGFR triggered signalling is a consequence of the downstream MAPK cascade alone.


Balance Training Versus Balance Training With STARS in Patients With Chronic Ankle Instability: A Randomized Controlled Trial.
Both balance training and selected interventions meant to target sensory structures (STARS) have been shown to be effective at restoring deficits associated with chronic ankle instability (CAI). Clinicians often use multiple treatment modalities in patients with CAI. However, evidence for combined intervention effectiveness in CAI patients remains limited. To determine if augmenting a balance-training protocol with STARS (BTS) results in greater improvements than balance training (BT) alone in those with CAI. Randomized-controlled trial. Research laboratory. 24 CAI participants (age 21.3 ± 2.0 y; height 169.8 ± 12.9 cm; mass 72.5 ± 22.2 kg) were randomized into 2 groups: BT and BTS. Participants completed a 4-week progression-based balance-training protocol consisting of 3 20-min sessions per week. The experimental group also received a 5-min set of STARS treatments consisting of calf stretching, plantar massage, ankle joint mobilizations, and ankle joint traction before each balance-training session. Outcomes included self-assessed disability, Star Excursion Balance Test reach distance, and time-to-boundary calculated from static balance trials. All outcomes were assessed before, and 24-hours and 1-week after protocol completion. Self-assessed disability was also captured 1-month after the intervention. No significant group differences were identified (P > .10). Both groups demonstrated improvements in all outcome categories after the interventions (P < .10), many of which were retained at 1-week posttest (P < .10). Although 90% CIs include zero, effect sizes favor BTS. Similarly, only the BTS group exceeded the minimal detectable change for time-to-boundary outcomes. While statistically no more effective, exceeding minimal detectable change scores and favorable effect sizes suggest that a 4-week progressive BTS program may be more effective at improving self-assessed disability and postural control in CAI patients than balance training in isolation.


Algibacter mikhailovii sp. nov., a novel marine bacterium of the family Flavobacteriaceae, and emended description of the genus Algibacter.
A novel marine bacterium, designated strain KMM 6171(T), was subjected to taxonomic analysis by using a polyphasic approach. Colonies were yellow-pigmented and cells were Gram-negative, heterotrophic rods displaying slow gliding motility. 16S rRNA gene sequence analysis indicated that strain KMM 6171(T) was closely related to the genus Algibacter, a member of the family Flavobacteriaceae, with sequence similarity of 96.7-96.8 %. The predominant cellular fatty acids were iso-C15 : 1, iso-C15 : 0, anteiso-C15 : 0, C15 : 0, iso-C15 : 0 3-OH, iso-C17 : 0 3-OH and summed feature 3, comprising C16 : 1omega7c and/or iso-C15 : 0 2-OH. The DNA G+C content was 35.1 mol%. On the basis of the phenotypic, genotypic, chemotaxonomic and phylogenetic data, strain KMM 6171(T) represents a novel species of the genus Algibacter, for which the name Algibacter mikhailovii sp. nov. is proposed. The type strain is KMM 6171(T) (=KCTC 12710(T)=LMG 23988(T)). An emended description of the genus Algibacter based on the new data is also given.


Comparative transcriptome analysis of zebrafish (Danio rerio) brain and spleen infected with spring viremia of carp virus (SVCV).
Spring viremia of carp virus (SVCV) is the pathogen of spring viremia of carp (SVC) and often causes acute hemorrhagic symptoms in various kinds of cyprinids and induces serious environmental and economic losses. However, the molecular mechanisms of infection remain poorly understood, especially at the individual level. In this study, zebrafish was employed as the infection model to explore the pathogenesis of SVCV. 4 groups of zebrafish tissues were set and RNA sequencing (RNA-Seq) technology was employed to analyze the differentially expressed genes (DEGs) after SVCV-infection. A total of 360,971,498 clean reads were obtained from 12 samples, 382 DEGs in the brain and 926 DEGs in the spleen were identified. These DEGs were annotated into three ontologies after gene ontology (GO) enrichment analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs were primarily related to Influenza A pathway and Herpes simplex infection pathway in brain and Tuberculosis and Toxoplasmosis pathways in spleen, and all of these pathways may be involved in response to pathogen invasion. At the same time, 3' and 5' alternative splicing (AS) events were significantly up-regulated in the spleen. The transcriptome analysis results demonstrated changes and tissue-specific influences caused by SVCV in vivo, which provided us with more information to understand the complex relationships between SVCV and its host.


Deoxyribonucleic acid of Cancer pagurus. II. Template activity for a DNA-dependent DNA polymerase of eukaryotic cells.
The template activity of Cancer pagurus DNA and its two components (poly d(A-T) and main component) in response to a DNA polymerase purified from regenerating rat liver has been studied and compared to the results previously obtained with synthetic templates. In the double-stranded native state, whole crab DNA and the main component were poor templates. Their replication was increased by thermal denaturation and inhibited by actinomycin. Like the synthetic copolymer poly[d(A-T).d(T-A)], native crab poly d(A-T) could be copied and its duplication was not inhibited by actinomycin. The structural difference between native poly d(A-T) Form I, isolated on a density gradient, and partially renatured poly d(A-T) Form II, isolated on hydroxylapatite, resulted in a modification of their template activity. The kinetic studies of [(3)H] dGMP and [(3)H] dAMP incorporation confirmed the importance of single-stranded regions (particulary dC regions) in the initiation of the in vitro duplication.


Dietary n-6 and n-3 PUFA alter the free oxylipin profile differently in male and female rat hearts.
Oxylipins are bioactive lipid mediators synthesised from PUFA. The most well-known oxylipins are the eicosanoids derived from arachidonic acid (ARA), and many of them influence cardiac physiology in health and disease. Oxylipins are also formed from other n-3 and n-6 PUFA such as α-linolenic acid (ALA), EPA, DHA and linoleic acid (LA), but fundamental data on the heart oxylipin profile, and the effect of diet and sex on this profile, are lacking. Therefore, weanling female and male Sprague-Dawley rats were given American Institute of Nutrition (AIN)-93G-based diets modified in oil composition to provide higher levels of ALA, EPA, DHA, LA and LA + ALA, compared with control diets. After 6 weeks, free oxylipins in rat hearts were increased primarily by their precursor PUFA, except for EPA oxylipins, which were increased not only by dietary EPA but also by dietary ALA or DHA. Dietary DHA had a greater effect than ALA or EPA on reducing ARA oxylipins. An exception to the dietary n-3 PUFA-lowering effects on ARA oxylipins was observed for several ARA-derived PG metabolites that were higher in rats given EPA diets. Higher dietary LA increased LA oxylipins, but it had no effect on ARA oxylipins. Overall, heart oxylipins were higher in female rats, but this depended on dietary treatment: the female oxylipin:male oxylipin ratio was higher in rats provided the ALA compared with the DHA diet, with other diet groups having ratios in between. In conclusion, individual PUFA and sex have unique and interactive effects on the rat heart free oxylipin profile.


The inhibition of β-catenin activity by luteolin isolated from Paulownia flowers leads to growth arrest and apoptosis in cholangiocarcinoma.
To develop an inhibitor targeting the Wnt/β-catenin signaling pathway, flavonoid monomer that can interact with β-catenin was isolated from Paulownia flowers. Luteolin may form stable hydrogen bonds with β-catenin by molecular docking. Fluorescence quenching analysis determined the physical interaction between luteolin and β-catenin. The binding of luteolin to β-catenin caused a loss of α-helical structure and induced a conformational change through circular dichroism spectroscopy. Luteolin inhibits the activity of the Wnt signaling, causing cholangiocarcinoma (CCA) cell cycle arrest in the G2/M phase, leading to cell apoptosis and inhibition of cell migration. In addition, transcriptome and proteomics analysis showed that the differentially expressed proteins were significantly enriched in the Wnt/β-catenin pathway. β-catenin protein in the nucleus was significantly decreased, while C-Myc and cyclin D1 in the CCA cells were significantly decreased after luteolin treatment. Additionally, activation of the Wnt/β-catenin signaling reversed the inhibitory effect of luteolin on the migration of CCA cells. Therefore, luteolin can directly interact with β-catenin and act as an inhibitor of β-catenin, inhibiting proliferation and reducing the migration ability of CCA cells by inhibiting the Wnt/β-catenin pathway. This study provides a scientific basis for the development of Wnt/β-catenin pathway inhibitors and the prevention and treatment of CCA.


Surgical implications of Behçet's disease.
Behcet's disease, though originally described as a triad of oral and genital aphthous ulcers and inflammatory ocular lesions, has had several new elements added to its description. The updated syndrome now includes gastrointestinal (GI) involvement as well as polyarthritis, neuritis, myocarditis, and glomerulonephritis. Of particular importance to the surgeon are the GI manifestations that include hemorrhage and perforation. A review of the literature indicates that the GI manifestations of Behcet's disease are not uncommon and, though usually mild, may necessitate surgical intervention. Our experience with a patient with GI hemorrhage and subsequent perforation underlines the occasional urgent complications of this disease.


Phenotypic and genotypic characterization of Streptococcus uberis isolated from bovine subclinical mastitis in Argentinean dairy farms.
The aim of this study was to investigate the phenotypic and genotypic characteristics of Streptococcus uberis isolated from subclinical mastitis (SCM) cases, and to examine the possible association between both characteristics. A total of 32 S. uberis were isolated from 772 quarter milk samples (SCM > 250,000 cells/ml) collected from 195 cows selected randomly from 18 dairy farms located in Argentina. The S. uberis strains were characterized phenotypically by the presence of virulence factors as plasminogen activator factor (PAF), hyaluronidase (HYA), capsule (CAP) and CAMP factor, and were further characterized genotypically by pulsed-field gel electrophoresis (PFGE). S. uberis strains expressed plasminogen activator factor, hyaluronidase or capsule (65.5 %, 56.3 %, 59.4 %, respectively), but only 25 % of isolates were CAMP factor positive. Thirteen different virulence profiles were identified on the basis of the combination of virulence factors. Eighteen PFGE patterns with 90% of similarity were identified among 32 S. uberis. A great diversity of virulence profiles and PFGE patterns were present among dairy farms. S. uberis strains with the same PFGE pattern showed different virulence profiles. Bovine S. uberis strains causing SCM included in the present study showed heterogeneity in regard to their phenotypic and genotypic characteristics, and the PFGE patterns are not associated with the virulence profiles.


System-on-chip design for ultrasonic target detection using split-spectrum processing and neural networks.
Ultrasonic detection and characterization of targets concealed by scattering noise is remarkably challenging. In this study, a neural network (NN) coupled to split-spectrum processing (SSP) is examined for target echo visibility enhancement using experimental measurements with input signal-to-noise ratio around 0 dB. The SSP-NN target detection system is trainable and consequently is capable of improving the target-to-clutter ratio by an average of 40 dB. The proposed system is exceptionally robust and outperforms the conventional techniques such as minimum, median, average, geometric mean, and polarity threshold detectors. For realtime imaging applications, a field-programmable gate array (FPGA)-based hardware platform is designed for system-onchip (SoC) realization of the SSP-NN target detection system. This platform is a hardware/software co-design system using parallel and pipelined multiplications and additions for highspeed operation and high computational throughput.


Isolation and preliminary characterization of that part of the plasma membrane which is apposed to the substratum.
We have developed a membrane isolation technique which allows us to isolate that part of the plasma membrane which is apposed to the solid substratum (LPM) to which cells in vitro attach free of the remainder of the plasma membrane (UPM). Our evidence suggests that the UPM is essentially free of contaminating cellular organelles while the LPM may be somewhat contaminated with endoplasmic reticulum fixed to it during the isolation procedure. Characterization of the peptides of the UPM and LPM suggests that some membrane components are nonrandomly distributed to one or the other membrane fraction while the bulk of the membrane peptides appear to be present in both membrane fractions; Membrane components labeled with 3H-fucose or 3H-glucosamine show a 3--5-fold higher specific activity in the LPM than in the UPM. A number of iodineateable surface components, in particular the LETS protein, show a preferential localization to the LPM. The development of this membrane isolation procedure should allow us to begin investigating the molecular basis of differences in cell-substratum adhesion and cell motility, two functions assigned operationally to the LPM.


Adoptive Immunotherapy and Interleukin-2 Following High-dose Therapy: A Potential Approach to Reduce Residual Tumor Cells.
Immune modulation and adoptive immunotherapy are being investigated as an additional cancer treatment modality. The influence of immunologic reactions, manifested as graft-vs-host disease (GVHD), has clearly been demonstrated in patients undergoing allogeneic bone marrow transplantation. More recently, adoptive immunotherapy by infusion of donor peripheral blood leukocyte products to recipients at relapse has shown benefit. As the immune system regenerates after high-dose therapy and stem cell transplantation, it is possible that we may be able to enhance an immune response against tumor cells. Trials are underway to evaluate the effect of interleukin-2 (IL-2) given early after transplantation to produce this effect.


L596-W733 bond between the start of the S4-S5 linker and the TRP box stabilizes the closed state of TRPV4 channel.
Unlike other cation channels, each subunit of most transient receptor potential (TRP) channels has an additional TRP-domain helix with an invariant tryptophan immediately trailing the gate-bearing S6. Recent cryo-electron microscopy of TRP vanilloid subfamily, member 1 structures revealed that this domain is a five-turn amphipathic helix, and the invariant tryptophan forms a bond with the beginning of the four-turn S4-S5 linker helix. By homology modeling, we identified the corresponding L596-W733 bond in TRP vanilloid subfamily, member 4 (TRPV4). The L596P mutation blocks bone development in Kozlowski-type spondylometaphyseal dysplasia in human. Our previous screen also isolated W733R as a strong gain-of-function (GOF) mutation that suppresses growth when the W733R channel is expressed in yeast. We show that, when expressed in Xenopus oocytes, TRPV4 with the L596P or W733R mutation displays normal depolarization-induced activation and outward rectification. However, these mutant channels have higher basal open probabilities and limited responses to the agonist GSK1016790A, explaining their biological GOF phenotypes. In addition, W733R current fails to inactivate during depolarization. Systematic replacement of W733 with amino acids of different properties produced similar electrophysiological and yeast phenotypes. The results can be interpreted consistently in the context of the homology model of TRPV4 molecule we have developed and refined using simulations in explicit medium. We propose that this bond maintains the orientation of the S4-S5 linker to keep the S6 gate closed. Further, the two partner helices, both amphipathic and located at the polar-nonpolar interface of the inner lipid monolayer, may receive and integrate various physiological stimuli.


Comparison between spatial interactions in perceived contrast and perceived brightness.
We examined the spatial integration of simultaneously induced achromatic contrast and compared it to the spatial integration of simultaneously induced brightness. This study extends the work of Zaidi et al. [(1992). Vision Research, 32, pp. 1695-1707], who showed that the total magnitude of induced brightness can be described as the weighted sum of the brightness induced by individual elements of the surround. The results show that contrast induction, though weaker than brightness induction, occurs over greater distances, and that a weighted spatial summation model for contrast induction requires an additional static non-linear compression, which is not required to model brightness induction. The analysis indicates that the contrast compression occurs prior to the lateral interactions that generate induced contrast.


Dynamics of relative chromosome position during the cell cycle.
The position of chromosomal neighborhoods in living cells was followed using three different methods for marking chromosomal domains occupying arbitrary locations in the nucleus; photobleaching of GFP-labeled histone H2B, local UV-marked DNA, and photobleaching of fluorescently labeled DNA. All methods revealed that global chromosomal organization can be reestablished through one cell division from mother to daughters. By simultaneously monitoring cell cycle stage in the cells in which relative chromosomal domain positions were tracked, we observed that chromosomal neighborhood organization is apparently lost in the early G1 phase of the cell cycle. However, the daughter cells eventually regain the general chromosomal organization pattern of their mothers, suggesting an active mechanism could be at play to reestablish chromosomal neighborhoods.


Broadcast of microbial aerosols by stacks of sewage treatment plants and effects of ozonation on bacteria in the gaseous effluent.
In the aeration basins of sewage treatment plants, compressed air is supplied to diffusers near the bottom of tanks to aid in the conversion by aerobic bacteria of dissolved and suspended solids of sewage into particles that will settle. Air bubbles breaking at the air-water interface will aerosolize bacteria that concentrate in the uppermost microlayer. The microbiological output of a plant in New York City with such a system was monitored. Samples of the gaseous effluent were collected inside the aeration building, inside the building's stack, 300 meters upwind (background sampler), and 300 meters downwind (test sampler), using Andersen samplers. Among the genera identified in the atmosphere in and around the plant were Mycobacterium, Klebsiella, and Streptococcus, all potentially pathogenic. The disinfection power of ozone, which is generally used for odor control, was also tested. Samples were taken from the ozone mixing chamber in the stack of the thickentng tank building. No significant difference in general bacterial counts could be detected at different levels of ozone production. It appears that in the air, ozone is an ineffective bactericidal agent. Results in this preliminary study demonstrate the need to evaluate the hazard of microbial aerosols generated by sewage treatment plants similar to the one studied. The possibility of such hazards is of special interest where facilities are located upwind of populations especially susceptible to infections, because of age of debility. Correlations with epidemiologic data are indicated.


Discovery of a seventh Rpp soybean rust resistance locus in soybean accession PI 605823.
A novel Rpp gene from PI 605823 for resistance to Phakopsora pachyrhizi was mapped on chromosome 19. Soybean rust, caused by the obligate biotrophic fungal pathogen Phakopsora pachyrhizi Syd. & P. Syd, is a disease threat to soybean production in regions of the world with mild winters. Host plant resistance conditioned by resistance to P. pachyrhizi (Rpp) genes has been found in numerous soybean accessions, and at least 10 Rpp genes or alleles have been mapped to six genetic loci. Identifying additional disease-resistance genes will facilitate development of soybean cultivars with durable resistance. PI 605823, a plant introduction from Vietnam, was previously identified as resistant to US populations of P. pachyrhizi in greenhouse and field trials. In this study, bulked segregant analysis using an F2 population derived from 'Williams 82' × PI 605823 identified a genomic region associated with resistance to P. pachyrhizi isolate GA12, which had been collected in the US State of Georgia in 2012. To further map the resistance locus, linkage mapping was carried out using single-nucleotide polymorphism markers and phenotypic data from greenhouse assays with an F2:3 population derived from Williams 82 × PI 605823 and an F4:5 population derived from '5601T' × PI 605823. A novel resistance gene, Rpp7, was mapped to a 154-kb interval (Gm19: 39,462,291-39,616,643 Glyma.Wm82.a2) on chromosome 19 that is different from the genomic locations of any previously reported Rpp genes. This new gene could be incorporated into elite breeding lines to help provide more durable resistance to soybean rust.


Ballistic Heat Transport in Nanocomposite: The Role of the Shape and Interconnection of Nanoinclusions.
In this article, the effect on the vibrational and thermal properties of gradually interconnected nanoinclusions embedded in an amorphous silicon matrix is studied using molecular dynamics simulations. The nanoinclusion arrangement ranges from an aligned sphere array to an interconnected mesh of nanowires. Wave-packet simulations scanning different polarizations and frequencies reveal that the interconnection of the nanoinclusions at constant volume fraction induces a strong increase of the mean free path of high frequency phonons, but does not affect the energy diffusivity. The mean free path and energy diffusivity are then used to estimate the thermal conductivity, showing an enhancement of the effective thermal conductivity due to the existence of crystalline structural interconnections. This enhancement is dominated by the ballistic transport of phonons. Equilibrium molecular dynamics simulations confirm the tendency, although less markedly. This leads to the observation that coherent energy propagation with a moderate increase of the thermal conductivity is possible. These findings could be useful for energy harvesting applications, thermal management or for mechanical information processing.


[Dilatation (congestive) cardiomyopathy: clinical aspects, diagnosis and treatment].
Clinical and electrocardiographic manifestations of congestive cardiomyopathy are considered on the basis of observations of 25 patients with this pathology of the myocardium. No clinico-electrocardiographic signs specific for this disease were found. Most characteristic were cardiomegaly, congestive cardiac failure and various disturbances of rhythm and conductivity. Thromboembolic complications in the lung and kidney vessels are frequently found. Cardiac glycosides, saluretics and vasodilators were employed in the treatment of patients with congestive cardiomyopathy but the prognosis was usually poor.


Urban net-zero water treatment and mineralization: experiments, modeling and design.
Water and wastewater treatment and conveyance account for approximately 4% of US electric consumption, with 80% used for conveyance. Net zero water (NZW) buildings would alleviate demands for a portion of this energy, for water, and for the treatment of drinking water for pesticides and toxic chemical releases in source water. However, domestic wastewater contains nitrogen loads much greater than urban/suburban ecosystems can typically absorb. The purpose of this work was to identify a first design of a denitrifying urban NZW treatment process, operating at ambient temperature and pressure and circum-neutral pH, and providing mineralization of pharmaceuticals (not easily regulated in terms of environmental half-life), based on laboratory tests and mass balance and kinetic modeling. The proposed treatment process is comprised of membrane bioreactor, iron-mediated aeration (IMA, reported previously), vacuum ultrafiltration, and peroxone advanced oxidation, with minor rainwater make-up and H2O2 disinfection residual. Similar to biological systems, minerals accumulate subject to precipitative removal by IMA, salt-free treatment, and minor dilution. Based on laboratory and modeling results, the system can produce potable water with moderate mineral content from commingled domestic wastewater and 10-20% rainwater make-up, under ambient conditions at individual buildings, while denitrifying and reducing chemical oxygen demand to below detection (<3 mg/L). While economics appear competitive, further development and study of steady-state concentrations and sludge management options are needed.


Cusp overlap method for self-expanding transcatheter aortic valve replacement.
Conduction disturbances and the need for permanent pacemaker (PPM) implantation remains a common complication for transcatheter aortic valve replacement (TAVR), particularly when self-expanding (SE) valves are used. We compared in-hospital and 30-day rates of new PPM implantation between patients undergoing TAVR with SE valves using the conventional three-cusp coplanar implantation technique and the cusp-overlap technique. We retrospectively compared patients without a pre-existing PPM who underwent a TAVR procedure with SE Evolut R or PRO valves using the cusp-overlap technique from July 2018 to September 2020 (n = 519) to patients who underwent TAVR using standard three-cusp technique from April 2016 to March 2017 (n = 128) in two high volume Canadian centers. There was no significant difference in baseline RBBB between the groups (10.4% vs. 13.2; p = 0.35). The rate of in-hospital new complete heart block (9.4% vs. 23.4%; p ≤ 0.001) and PPM implantation (8% vs. 21%; p ≤ 0.001) were significantly reduced when using the cusp-overlap technique. The incidence of new LBBB (30.4% vs. 29%; p = 0.73) was similar. At 30 days, the rates of new complete heart block (11% vs. 23%; p ≤ 0.001) and PPM implantation (10% vs. 21%, p ≤ 0.001) remained significantly lower in the cusp-overlap group, while the rate of new LBBB (35% vs. 30%; p = 0.73) was similar. Cusp-overlap approach offers several potential technical advantages compared to standard three-cusp view, and may result in lower PPM rates in TAVR with SE Evolut valve.


[Urological works and biography of Dr. Felipe Alcalá Santaella Nuñez (1927-1977). Historical documentary analysis].
In the middle of the 20th century, Urology in Valencia was fully consolidated as a surgical speciality since Prof. Molla started it about the end of the 19th century; Dr. Felipe Alcala Santaella Nuñez stands out as the chairman of the Department of Urology of the "Hospital Provincial de Valencia", after his father Dr. Rafael Alcalá Santaella. He achieved to form a group of renowned professionals, some of which still are in active practice. We reviewed all his scientific work and the journals it was published in, mainly Archivos Espaioles de Urologia, through the Department of Medical History of the University of Valencia. His biography was reconstructed using the "Biographic and Bibliographic History of Spanish Urology" by Drs. E. Maganto Pavón and M. Pérez Albacete, as well as direct interviews with family members. We emphasize the magnificent approach to the clinical presentations of tuberculosis he does in his doctoral thesis, analyzing its types by location, main features, and most adequate treatment. He also emphasized the importance of relapse in lithiasic patients and recommendations to be follow, as well as the condition of bladder neoplasias. We consider Dr. Felipe Alcalá Santaella Nuñez as a wide-experience-professional who mode solid contributions to the regional urology in his times, thanks to his excellent surgical abilities and dedication.


Electroweak Sudakov corrections to new physics searches at the LHC.
We compute the one-loop electroweak Sudakov corrections to the production process Z(νν)+n jets, with n=1, 2, 3, in pp collisions at the LHC. It represents the main irreducible background to new physics searches at the energy frontier. The results are obtained at the leading and next-to-leading logarithmic accuracy by implementing the general algorithm of Denner and Pozzorini in the event generator for multiparton processes alpgen. For the standard selection cuts used by the ATLAS and CMS Collaborations, we show that the Sudakov corrections to the relevant observables can grow up to -40% at sqrt[s ]= 14 TeV. We also include the contribution due to undetected real radiation of massive gauge bosons, to show to what extent the partial cancellation with the large negative virtual corrections takes place in realistic event selections.


The impact of immigration on the breastfeeding practices of Mainland Chinese immigrants in Hong Kong.
Researchers have found breastfeeding disparities between immigrant and native-born women in many countries. However, most studies on immigration and breastfeeding practices have been in Western countries. The aim of this study was to examine the effect of length of time since immigration on the breastfeeding practices of Mainland Chinese immigrants living in Hong Kong. We recruited 2704 mother-infant pairs from the postnatal wards of four public hospitals in Hong Kong. We examined the effect of migration status on the duration of any and exclusive breastfeeding. Breastfeeding duration was progressively shorter as the time since immigration increased. When compared with mothers who had lived in Hong Kong for <5 years, Hong Kong-born participants had a 30% higher risk of stopping any breastfeeding (hazard ratio [HR] 1.34 [95% confidence interval {CI} 1.10-1.63]) and exclusive breastfeeding (HR 1.33 [95% CI 1.11-1.58]). In both Hong Kong-born and immigrant participants, breastfeeding cessation was associated with return to work postpartum and the husband's preference for infant formula or mixed feeding. Intention to exclusively breastfeed and to breastfeed for >6 months, and previous breastfeeding experience substantially reduced the risk of breastfeeding cessation for both Hong Kong-born and immigrant participants. Health care professionals should consider immigration history in their assessment of pregnant women and provide culturally adapted breastfeeding support and encouragement to this population.


Surveillance of phlebotomine fauna and Didelphis marsupialis (Didelphimorphia: Didelphidae) infection in an area highly endemic for visceral leishmaniasis in Colombia.
The study of the interaction between the parasite, the vector and the mammalian hosts, including man, allows to understand the behavior of the leishmaniases. To determine the presence of Lutzomyia species and to detect the Leishmania infection in Didelphis marsupialis in an endemic area for visceral leishmaniasis. Phlebotomine fauna and individuals of D. marsupialis were collected with CDC and Tomahawk™ traps, respectively. The species of Lutzomyia were identified using the Young and Duncan key (1994). Ear and tail biopsies and blood samples from D. marsupialis were taken to identify the Leishmania species by amplifying a fragment of the gene associated with the 70 kD heat shock protein. Seven Lutzomyia species were identified: Lu. evansi, Lu. gomezi, Lu. panamensis, Lu. dubitans, Lu. cayennensis cayennensis, Lu. rangeliana and Lu. trinidadensis. The first three species have epidemiological importance in Colombia because of their implications in the transmission of the Leishmania parasite. Sixty-five tissue samples from 19 D. marsupialis individuals were negative for Leishmania spp. The presence of the Lutzomyia species that have been identified as vectors for Leishmania inside and around houses in the village of El Bledo, in El Carmen de Bolívar represents a risk of infection. Furthermore, the presence of Lu. panamensis is reported for first time in El Carmen de Bolívar in Colombia. Although the lack of detection of Leishmania spp. in D. marsupialis samples may suggest that D. marsupialis does not play an important role in the transmission cycle of Leishmania in this region, it is necessary to carry out further longitudinal studies to confirm this hypothesis.


Location of the Substrate Binding Site of the Cytochrome bo3 Ubiquinol Oxidase from Escherichia coli.
Cytochrome bo3 is a respiratory proton-pumping oxygen reductase that is a member of the heme-copper superfamily that utilizes ubiquinol-8 (Q8H2) as a substrate. The current consensus model has Q8H2 oxidized at a low affinity site (QL), passing electrons to a tightly bound quinone cofactor at a high affinity site (QH site) that stabilizes the one-electron reduced ubisemiquinone, facilitating the transfer of electrons to the redox active metal centers where O2 is reduced to water. The current work shows that the Q8 bound to the QH site is more dynamic than previously thought. In addition, mutations of residues at the QH site that do not abolish activity have been re-examined and shown to have properties expected of mutations at the substrate binding site (QL): an increase in the KM of the substrate ubiquinol-1 (up to 4-fold) and an increase in the apparent Ki of the inhibitor HQNO (up to 8-fold). The data suggest that there is only one binding site for ubiquinol in cyt bo3 and that site corresponds to the QH site.


Organization and distribution of the cellulosome in Clostridium thermocellum.
The properties of the cellulosome (the cellulose-binding, multicellulase-containing protein complex) in Clostridium thermocellum were examined by comparing the cellulase systems derived from the wild type and an adherence-defective mutant. The growth conditions--specifically, growth either on cellulose (Avicel) or on cellobiose as insoluble or soluble carbon sources, respectively--were found to be critical to the distribution of the cellulosome in the mutant system: the cellobiose-grown mutant (in contrast to the wild type) lacked the cellulosome on its surface and produced only minor quantities of the extracellular cellulosome accompanied by other relatively low-molecular-weight cellulases. The polypeptide composition of the respective purified cellulosome was dependent on the nature of the carbon source and was similar for both wild-type and mutant cells. Ultrastructural analysis revealed the presence of novel polycellulosomal protuberances on the cell surface of the cellobiose-grown wild type which were absent in the mutant.


Chlorophyll composition of photosystems II alpha, II beta and I in tobacco chloroplasts.
The antenna composition of the Photosystems II alpha, II beta and I was studied in tobacco chloroplasts. Absorbance spectra, recorded at 4 K, were analyzed for the wild type and the mutants Su/su and Su/su var. Aurea, containing higher concentrations of the photosystems. With chloroplasts of Su/su we measured the action spectra of the three photosystems from 625 to 690 nm. Above 675 nm absorption by Photosystem I dominated. This system had a maximum at 678 nm and a shoulder at 660 nm. Of the long-wavelength chlorophyll a forms, absorbing at 690, 697 and 705 nm at 4 K, which are generally assigned to Photosystem I, the 697 nm form occurred in an amount of four molecules per reaction center of Photosystem I in each type of chloroplast. The Photosystem II alpha spectrum was characterized by maxima at 650 and 672 nm, showing clearly the participation of the chlorophyll a and b containing light-harvesting complex. In the mutants the light-harvesting complex has a chlorophyll a to chlorophyll b ratio of more than 1; the amount of the 672 nm chlorophyll a was normal, whereas the amount of chlorophyll b was markedly decreased in the mutants relative to the wild type. The Photosystem II beta spectrum mainly consisted of a band at 683 nm.


In situ analysis of oxytetracycline tablets based on matrix-assisted laser desorption/ionization mass spectrometry imaging.
A thorough understanding of the content and distribution of active ingredients in pharmaceuticals is essential for drug efficacy and safety. Technological advancements in mass spectrometry imaging present an opportunity for methodological innovation by providing qualification and quantification analysis, as well as spatial information, in the same assay, which has great potential for applications in the rapid analysis and quality control of drugs. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was employed to directly analyze oxytetracycline tablets in order to map the distribution of the active constituent within the whole tablet. Quantitative analysis was capable of differentiating tablets containing various doses of the active pharmaceutical ingredient. To establish the methodology, detailed factors that influence matrix spraying and spatial resolution during sample preparation and the data acquisition process were optimized systematically. Quantitative analysis could differentiate the tablets containing various doses of the active compound. The proposed method was successfully applied to analyze real commercial tablets. The developed method could successfully achieve the spatial location of oxytetracycline in actual tablet samples. These results could contribute to pharmaceutical tracing technology, especially the formulation process of tablets, which is helpful for monitoring the quality of pharmaceutical products and guaranteeing drug security.


DNABarcodeCompatibility: an R-package for optimizing DNA-barcode combinations in multiplex sequencing experiments.
Using adequate DNA barcodes is essential to unambiguously identify each DNA library within a multiplexed set of libraries sequenced using next-generation sequencers. We introduce DNABarcodeCompatibility, an R-package that allows one to design single or dual-barcoding multiplex experiments by imposing desired constraints on the barcodes (including sequencer chemistry, barcode pairwise minimal distance and nucleotide content), while optimizing barcode frequency usage, thereby allowing one to both facilitate the demultiplexing step and spare expensive library-preparation kits. The package comes with a user-friendly interface and a web app developed in Java and Shiny (https://dnabarcodecompatibility.pasteur.fr), respectively, with the aim to help bridge the expertise of core facilities with the experimental needs of non-experienced users. DNABarcodeCompatibility can be easily extended to fulfil specific project needs. The source codes of the R-package and its user interfaces are publicly available along with documentation at [https://github.com/comoto-pasteur-fr] under the GPL-2 licence. Supplementary data are available at Bioinformatics online.


Pinning and depinning of the polarization of exciton-polariton condensates at room temperature.
A room temperature polariton condensate realized in a microcavity with embedded GaN quantum wells emits linearly polarized light at threshold with the plane of polarization pinned to one of the crystallographic axes. With increasing pumping power, a depinning of the polarization is observed resulting in a progressive decrease of the polarization degree of the emitted light. This depinning is understood in terms of polariton-polariton repulsion competing with the static disorder potential effect. The polarization behavior differs from that of conventional lasers where the polarization degree usually increases as a function of pumping power.


Rituximab for children with immune thrombocytopenia: a systematic review.
Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP). However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP. We searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients) were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count ≥ 100 × 10(9)/L) and response (platelet count ≥ 30 × 10(9)/L) rate after rituximab treatment were 39% (95% CI, 30% to 49%) and 68% (95%CI, 58% to 77%), respectively, with median response duration of 12.8 month. 4 studies (29 patients) were included for efficacy assessment in children with secondary ITP. 11 (64.7%) of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3%) were mild to moderate, and no death was reported. Randomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events associated with rituximab were mild to moderate, and no death was reported.


Comprehensive population-averaged arterial input function for dynamic contrast-enhanced vmagnetic resonance imaging of head and neck cancer.
To generate a population-averaged arterial input function (PA-AIF) for quantitative analysis of dynamic contrast-enhanced MRI data in head and neck cancer patients. Twenty patients underwent dynamic contrast-enhanced MRI during concurrent chemoradiation therapy. Imaging consisted of 2 baseline scans 1 week apart (B1/B2) and 1 scan after 1 week of chemoradiation therapy (Wk1). Regions of interest (ROIs) in the right and left carotid arteries were drawn on coronal images. Plasma concentration curves of all ROIs were averaged and fit to a biexponential decay function to obtain the final PA-AIF (AvgAll). Right-sided and left-sided ROI plasma concentration curves were averaged separately to obtain side-specific AIFs (AvgRight/AvgLeft). Regions of interest were divided by time point to obtain time-point-specific AIFs (AvgB1/AvgB2/AvgWk1). The vascular transfer constant (Ktrans) and the fractional extravascular, extracellular space volume (Ve) for primaries and nodes were calculated using the AvgAll AIF, the appropriate side-specific AIF, and the appropriate time-point-specific AIF. Median Ktrans and Ve values derived from AvgAll were compared with those obtained from the side-specific and time-point-specific AIFs. The effect of using individual AIFs was also investigated. The plasma parameters for AvgAll were a1,2 = 27.11/17.65 kg/L, m1,2 = 11.75/0.21 min(-1). The coefficients of repeatability (CRs) for AvgAll versus AvgLeft were 0.04 min(-1) for Ktrans and 0.02 for Ve. For AvgAll versus AvgRight, the CRs were 0.08 min(-1) for Ktrans and 0.02 for Ve. When AvgAll was compared with AvgB1/AvgB2/AvgWk1, the CRs were slightly higher: 0.32/0.19/0.78 min(-1), respectively, for Ktrans; and 0.07/0.08/0.09 for Ve. Use of a PA-AIF was not significantly different from use of individual AIFs. A PA-AIF for head and neck cancer was generated that accounts for differences in right carotid artery versus left carotid artery, day-to-day fluctuations, and early treatment-induced changes. The small CRs obtained for Ktrans and Ve indicate that side-specific AIFs are not necessary. However, a time-point-specific AIF may improve pharmacokinetic accuracy.


Intrachromosomal movement of genetically marked Saccharomyces cerevisiae transposons by gene conversion.
In this paper, we describe the movement of a genetically marked Saccharomyces cerevisiae transposon. Ty912(URA3), to new sites in the S. cerevisiae genome. Ty912 is an element present at the HIS4 locus in the his4-912 mutant. To detect movement of Ty912, this element has been genetically marked with the S. cerevisiae URA3 gene. Movement of Ty912(URA3) occurs by recombination between the marked element and homologous Ty elements elsewhere in the S. cerevisiae genome. Ty912(URA3) recombines most often with elements near the HIS4 locus on chromosome III, less often with Ty elements elsewhere on chromosome III, and least often with Ty elements on other chromosomes. These recombination events result in changes in the number of Ty elements present in the cell and in duplications and deletions of unique sequence DNA.


Adenovirally delivered IFN-β exerts antitumor effects through transient T-lymphocyte depletion and Ag-specific T-cell proliferation.
Type I interferons (IFNs), including IFN-β, are known to enhance antigen (Ag) presentation and to promote the expansion, survival and effector function of CD8+ cytotoxic lymphocytes (CTL) during viral infections. Furthermore, IFN-β is a potent candidate for antitumor drugs; however, recombinant IFN-β is too unstable for use in tumor therapy in vivo. In this study, we therefore examined the efficacy and mechanism of exogenous IFN-β as a biomolecule for tumor therapy, using adenovirus encoding IFN-β (Ad-IFNβ) as a therapeutic agent in a mouse model. Ag104Ld and 4T1 tumor cells exposed to Ad-IFNβ showed growth retardation and cell death in vitro, and tumor growth as well as tumor metastasis was inhibited in vivo. The Ad-IFNβ-mediated antitumor effect was dependent on CD8+ T cells in vivo, rather than on a direct cytotoxic effect of Ad-IFNβ. Transient T lymphocyte depletion was observed in tumor tissue after intratumoral injection with Ad-IFNβ. Despite the T lymphocyte depletion, the proliferation of Ag-specific CD8+ T cells was increased in Ad-IFNβ-treated mice compared to control virus-treated mice. These results suggest that IFN-β might contribute to the inhibition of tumor growth by depleting Ag-nonspecific T lymphocytes and enhancing proliferation of Ag-specific CD8+ T cells.


The Use of Rubrics in the Clinical Evaluation of Podiatric Medical Students: Objectification of the Subjective Experience.
We assessed the differences in podiatric medical students' clinical professionalism objective scores (CPOSs) by comparing a previous nonrubric evaluation tool with a more recently implemented objective-centered rubric evaluation tool. This type of study has never been performed or reported on in the podiatric medical education literature. We conducted a retrospective analysis of 89 third-year podiatric medical students between academic years 2010-2011 and 2011-2012. A Pearson correlation coefficient analysis was performed to compare CPOSs from the students' first (CPOS1) and second (CPOS2) rotations. A correlation analysis was performed comparing students' grade point averages (GPAs) with each of the individual CPOSs to verify the validity of the rubric evaluation tool. The Pearson correlation coefficients for the relationship between 2012 CPOS1 and CPOS2 and GPA were r = 0.233 (P ≤ .093) and r = 0.290 (P < .035) and for the relationship between 2013 CPOS1 and CPOS2 and GPA were r = 0.525 (P = .001) and r = 0.730 (P < .001). These findings suggest that the use of a rubric in the evaluation of podiatric medical students' CPOSs is correlated with their GPAs, and CPOS2 demonstrated a higher correlation than CPOS1. We believe that implementation of the rubric evaluation tool has increased the accuracy of the evaluation of podiatric medical students with respect to CPOSs.


Single and multi-frame auto-calibration for 3D endoscopy with differential rendering.
The use of 3D measurement in endoscopic images offers practicality in cancer diagnosis, computer-assisted interventions, and making annotations for machine learning training data. An effective approach is the implementation of an active stereo system, using a micro-sized pattern projector and an endoscope camera, which has been intensively developed. One open problem for such a system is the necessity of strict and complex calibration of the projector-camera system to precisely recover the shapes. Moreover, since the head of an endoscope should have enough elasticity to avoid harming target objects, the positions of the pattern projector cannot be tightly fixed to the head, resulting in limited accuracy. A straightforward approach to the problem is applying auto-calibration. However, it requires special markers in the pattern or a highly accurate initial position for stable calibration, which is impractical for real operation. In the paper, we propose a novel auto-calibration method based on differential rendering techniques, which are recently proposed and drawing wide attention. To apply the method to an endoscopic system, where a diffractive optical element (DOE) is used, we propose a technique to simultaneously estimate the focal length of the DOE as well as the extrinsic parameters between a projector and a camera. We also propose a multi-frame optimization algorithm to jointly optimize the intrinsic and extrinsic parameters, relative pose between frames, and the entire shape.Clinical relevance- One-shot endoscopic measurement of depth information is a practical solution for cancer diagnosis, computer-assisted interventions, and making annotations for machine learning training data.


The capacity of the TNF family members 4-1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells.
Activating signals generated by members of the tumour necrosis factor receptor superfamily upon interaction with their cognate ligands play important roles in T-cell responses. Members of the tumour necrosis factor family namely 4-1BBL, OX40L, CD70, GITRL, LIGHT and CD30L have been described to function as costimulatory molecules by binding such receptors on T cells. Using our recently described system of T-cell stimulator cells we have performed the first study where all these molecules have been assessed and compared regarding their capacity to costimulate proliferation and cytokine production of human T cells. 4-1BBL, which we found to be the most potent molecule in this group, was able to mediate sustained activation and proliferation of human T cells. OX40L and CD70 were also strong inducers of T-cell proliferation, whereas the costimulatory capacity of human GITRL was significantly lower. Importantly CD30L and LIGHT consistently failed to act costimulatory on human T cells, and we therefore suggest that these molecules might be functionally distinct from the costimulatory members of this family.


Molecular mechanism for prevention of N-acetyl-p-benzoquinoneimine cytotoxicity by the permeable thiol drugs diethyldithiocarbamate and dithiothreitol.
The present study was carried out to elucidate the mechanism by which the permeable thiol drug diethyldithiocarbamate (DEDC) exhibited an antidotal effect against acetaminophen-induced hepatotoxicity in vivo. DEDC was found to act as an antidote against acetaminophen-induced cytotoxicity in hepatocytes isolated from a pyrazole-pretreated rat without affecting cytochrome P-450 levels. The mechanism of protection exhibited against reactive intermediate N-acetyl-p-benzoquinoneimine (NAPQI)-induced cytotoxicity by DEDC was then investigated and compared with that exhibited by the permeable thiol-reductant dithiothreitol (DTT). Cytotoxicity induced by the dimethylated analogue 2,6-dimethyl-N-acetyl-p-benzoquinoneimine (2,6-diMeNAPQI) was prevented if the hepatocytes were preincubated with DEDC for 5 min and removed before addition of 2,6-diMeNAPQI. Both DEDC and DTT were also found to act as antidotes against NAPQI- and 2,6-diMeNAPQI-induced cytotoxicity in isolated rat hepatocytes if added within 2 min of the addition of the quinoneimines. However, the addition of DEDC or DTT 10 min after either quinoneimine did not prevent subsequent cytotoxicity or restore GSH levels, indicating that the alkylation of GSH and of protein thiols was irreversible at that time. Fast atom bombardment mass spectrometry was used to show that DEDC formed conjugates with both NAPQI and 2,6-diMeNAPQI. Furthermore, these conjugates were found to be nontoxic. This suggests that DEDC acts as a trap for the toxic quinoneimines, thus preventing alkylation of essential macromolecules. In contrast, DTT reduced the quinoneimines to their respective nontoxic parent compounds and presumably also reduced mixed-protein disulfides and GSSG, thereby regenerating protein thiols and GSH. Therefore, this study suggests that DEDC and DTT act as antidotes by two different mechanisms.


[Construction of the immunoenzyme test system "IFA-AtEBV-Strip" for detecting antibodies of the Epstein-Barr virus].
The first home immunoenzyme test-system for finding antibodies to the Epstein-Barr virus (EBV) has been created. The test-system laboratory prototype was called "IFA-AtEBV-strip". Production technology has been developed for specific components of immunoenzyme test system and all the analysis stage conditions have been optimized: the antigen sorption on plates, its interaction with the studied serum, finding out of the formed immune complex. The test system "IFA-AtEBV-strip" sensitivity made up 96%, specificity--100%.


Purification of phosphoglycerate kinase and glyceraldehyde phosphate dehydrogenase by DEAE-sepharose fast flow chromatography.
The purification of phosphoglycerate kinase (PGK) and glyceraldehyde phosphate dehydrogenase (GAPDH) from soy bean was studied by a DEAE-sepharose fast flow chromatography. When scaling up, the diameters of columns increase but the heights of columns were maintained in the range of 10 to 20 cm to avoid the problem of the high pressure drop. The recovery of GAPDH and PGK was 57% and 41%, respectively. The purification factor of GPADH and PGK was 144 and 44, respectively. The economical evaluation indicated that the cost of the process was 2.09$/ku GAPDH, which has some commercial values.


Antioxidant activity of Buglossoides purpureocaerulea (L.) I.M. Johnst. extracts.
Buglossoides purpureocaerulea is a little-known plant used in the folk tradition for the preparation of a decoction in Sud, Italy, where it is appreciated for its beneficial effects on liver diseases. These properties may be due to the presence of antioxidant compounds. This study presents the phenolic characterisation and the antioxidant activity (AA) of B. purpureocaerulea extracts obtained by decoction, ethanol infusion and ethanol and methanol macerations. Total phenols ranged between 69 and 100 mg g(-1 ) dry weight (DW). The main compounds were: rosmarinic acid, caffeic acid, lithospermic acid and salvianolic acid C. The extracts showed a good AA, particularly high for the decoction (142-283 µmol TE g(-1) DW; TE, Trolox equivalent) and ethanol maceration extract (214-364 µmol TE g(-1) DW) when determined by DPPH and ferric reducing antioxidant power test, respectively.


Exploring Nursing Students' Experiences of Learning Using Phenomenography: A Literature Review.
The purpose of this extensive international and national literature review was to explore how phenomenography identifies nursing students' experiences of learning within preregistration (or prelicensure) nursing education. Data were collected utilizing a comprehensive search of electronic databases. Full text, peer-reviewed, and scholarly articles published in English using the search terms phenomengraph*, nurs*, student, education, and learning were reviewed. Two discreet themes emerged exploring students' experiences of learning within preregistration nursing education: (a) Phenomenography was a beneficial method to expose variation in students' understandings of a challenging concept or topic and (b) phenomenography was beneficial to evaluate teaching methods in attempt to improve student learning of challenging and complex concepts. On the basis of these findings, future research utilizing phenomenography within nursing education has potential to uncover variation in students' understandings of mental health, with future consideration of implications to nursing curriculum design and development. [J Nurs Educ. 2017;56(10):591-598.].


The Cochlea in Branchio-Oto-Renal Syndrome: An Objective Method for the Diagnosis of Offset Cochlear Turns.
An "unwound" or "offset" cochlea has been described as a characteristic imaging feature in patients with branchio-oto-renal syndrome, and recently recognized to be associated in particular to those with EYA1 gene mutations. Determination of this feature has traditionally relied on subjective visual assessment. Our aim was to establish an objective assessment method for cochlear offset (the cochlear turn alignment ratio) and determine an optimal cutoff turn alignment ratio value that separates individuals with EYA1-branchio-oto-renal syndrome from those with SIX1-branchio-oto-renal syndrome and healthy controls. Temporal bone CT or MR imaging from 40 individuals with branchio-oto-renal syndrome and 40 controls was retrospectively reviewed. Cochlear offset was determined visually by 2 independent blinded readers and then quantitatively via a standardized technique yielding the cochlear turn alignment ratio. The turn alignment ratio values were compared between cochleae qualitatively assessed as "not offset" and "offset." Receiver operating characteristic analysis was used to determine the ability of the turn alignment ratio to differentiate between these populations and an optimal cutoff turn alignment ratio value. Cochlear offset and turn alignment ratio values were analyzed for each branchio-oto-renal syndrome genotype subpopulation and for controls. The turn alignment ratio can accurately differentiate between cochleae with and without an offset (P < .001). The optimal cutoff value separating these populations was 0.476 (sensitivity = 1, specificity = 0.986, J = 0.986). All except 1 cochlea among the EYA1-branchio-oto-renal syndrome subset and all with unknown genotype branchio-oto-renal syndrome had a cochlear offset and a turn alignment ratio of <0.476. All except 1 cochlea among the SIX1-branchio-oto-renal syndrome subset and all controls had no offset and a turn alignment ratio of >0.476. There is a statistically significant difference in turn alignment ratios between offset and nonoffset cochleae, with an optimal cutoff of 0.476. This cutoff value allows excellent separation of EYA1-branchio-oto-renal syndrome from SIX1-branchio-oto-renal syndrome and from individuals without branchio-oto-renal syndrome or sensorineural hearing loss. The turn alignment ratio is a reliable and objective metric that can aid in the imaging evaluation of branchio-oto-renal syndrome.


Recent advances in magnetic resonance neuroimaging of lumbar nerve to clinical applications: A review of clinical studies utilizing Diffusion Tensor Imaging and Diffusion-weighted magnetic resonance neurography.
Much progress has been made in neuroimaging with Magnetic Resonance neurography and Diffusion Tensor Imaging (DTI) owing to higher magnetic fields and improvements in pulse sequence technology. Reports on lumbar nerve DTI have also increased considerably. Many studies have shown that the use of DTI in lumbar nerve lesions, such as lumbar foraminal stenosis and lumbar disc herniation, makes it possible to capture images of interruptions of tractography at stenotic sties, enabling the diagnosis of stenosis. DTI can also reveal significant decreases in fractional anisotropy (FA) with significant increases in apparent diffusion coefficient (ADC) values in compression lesions. FA values have higher accuracy than ADC values. Furthermore, strong correlations exist between FA values and indications of neurological severity, including the Japanese Orthopedic Association (JOA) score, the Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RDQ) in patients with lumbar disc herniation-induced radiculopathy. Most lumbar DTI has become 3T; 3T MRI has made it possible to take high-resolution DTI measurements in a short period of time. However, increased motion artifacts in the magnetic susceptibility effect lead to signal irregularities and image distortion. In the future, high-resolution DTI with reduced field-of-view may become useful in clinical applications, since visualization of nerve lesions and quantification of DTI parameters could allow more accurate diagnoses of lumbar nerve dysfunctions. Future translational studies will be necessary to successfully bring MR neuroimaging of lumbar nerve into clinical use.


Classification of chronic orofacial pain using an intravenous diagnostic test.
The aim of this study was to evaluate the ability of a preliminary intravenous diagnostic test to classify chronic orofacial pain patients into different subgroups. Patients with chronic orofacial pain conditions that could not be unambiguously diagnosed. A retrospective evaluation of series of conducted pharmacodiagnostic tests, consisting of the consecutive intravenous administration of drugs. Visual analogue scale scores were retrieved from all patients, based on which they were classified into different responder groups. In total, 46 pain profiles were analysed. Of these, 16 patients (35%) could be classified into one or more pain categories, while 30 patients (65%) could not be classified into any pain category. The pain duration or medication use did not influence the classification. Based on the results of this retrospective study, it seems that classification into subgroups is possible after intravenous testing in a minority of clinically unclassifiable patients. In patients where there is a substantial need for additional diagnostic information, these results may be of value. Recommendations are made for further research, which should include validation in patients with known pain mechanisms.


Polo-like kinase interacts with proteasomes and regulates their activity.
The polo-like kinase (Plk) has been shown to be associated with the anaphase-promoting complex at the transition from metaphase to anaphase and to regulate ubiquitination, the process that targets proteins for degradation by proteasomes. In this study, we have identified proteasomal proteins interacting with Plk by mass spectrometry and found that Plk and 20S proteasome subunits could be reversibly immunoprecipitated from both human CA46 cells and HEK 293 cells transfected with HA-Plk. Furthermore, both coprecipitated Plk and baculovirus-expressed Plk were able to phosphorylate proteasome subunits, and metabolic labeling studies indicate that Plk is partially responsible for the phosphorylation of 20S proteasome subunits C9 and C8 in vivo. In addition, phosphorylation of proteasomes by Plk enhanced proteolytic activity toward an artificial substrate Suc-L-L-V-Y-AMC in vitro and in vivo. Finally, we were also able to detect Plk associated with 26S proteasomes under certain conditions. Together our results suggest that Plk is an important mitotic regulator of proteasome activity.


Upconversion System with Quantum Dots as Sensitizer: Improved Photoluminescence and PDT Efficiency.
Upconversion nanoparticles (UCNPs) are prospective platforms for bioimaging and phototherapy, but a critical bottleneck is the limited brightness due to the faint absorptivity of lanthanide ions and the low quantum yield. To circumvent this problem, we herein propose our strategy to reconstruct the energy cascade of UCNPs using semiconductor quantum dots (QDs) as light sensitizer of Nd3+/Yb3+ codoped UCNPs. Ag2Se QDs with strong absorption at 808 nm acted as efficient antenna and transferred their energy to Yb3+ via a resonance energy transfer process, significantly enhancing the luminescence of UCNPs. This nanocomposite was then combined with Rose Bengal and applied for photodynamic therapy. Both in vitro and in vivo studies revealed the introduction of QDs improved the therapeutic performance remarkably. Our study suggests Ag2Se QDs with excellent photophysical properties can be promising agents to overcome the shortcomings of UCNPs and further strengthen their applications.


The gull (Chroicocephalus brunnicephalus) as an environmental bioindicator and reservoir for antibiotic resistance on the coastlines of the Bay of Bengal.
The presence and frequency of multiresistant bacteria in wild birds act as indicators of the environmental contamination of antibiotic resistance. To explore the rate of contamination mediated by Escherichia coli, 150 fecal samples from the brown-headed gull (Chroicocephalus brunnicephalus) and 8 water samples from the Bay of Bengal area were collected, cultured, and tested for antibiotic susceptibility. Special attention was paid to extended-spectrum beta-lactamase (ESBL)-producing isolates, which were further characterized genetically. Antibiotic resistance was found in 42.3% (36/85) of the E. coli isolates and multidrug resistance in 11.8%. Isolates from the area with a higher human activity were more resistant than those from an area with a lower level of activity. Most frequent was resistance to ampicillin (29.4%), followed by trimethoprim-sulfamethoxazole (24.7%) and quinolones (22.4%). Carriage of ESBL-producing E. coli was relatively high (17.3%) in the gulls, whereas no ESBL producers were found in the water. All ESBL-producing E. coli isolates, but one, carried bla(CTX-M-15) or bla(CTX-M-15)-like genes. A bla(CTX-M-14)-like enzyme was found as an exception. Gulls from two different colonies shared E. coli clones and harbored the clinically relevant sequence types ST10, ST48, and ST131. The high frequency of antibiotic resistance and ESBL production among E. coli isolates from gulls indicates that the environmental contamination of antibiotic resistance has already gone far on the coastlines of the Bay of Bengal. Considering the limited control over the antibiotic consumption and waste from human activities in Bangladesh, there is no easy solution in sight.


Biofluid mechanics and the circulatory system.
A fluid is a medium which deforms, or undergoes motion, continuously under the action of a shearing stress and includes liquids and gases. Applying biofluid mechanics to the cardiovascular system requires knowledge of anatomy and geometry, pressure data and blood flow, volume and velocity measurements. A good example is the assessment of the haemodynamics of biological and mechanical heart valves.


Positional cloning in Arabidopsis. Why it feels good to have a genome initiative working for you.
Positional (or map-based) cloning techniques are widely used to identify the protein products of genes defined by mutation. In Arabidopsis the information generated by the Genome Initiative is giving this approach a decisive boost. A wealth of sequence polymorphisms and molecular markers is now available and can be exploited for fine mapping with technically simple and robust polymerase chain reaction-based methods. As a result it has become possible to complete positional cloning projects in a short time and with relatively little effort.


Cognitive, and behavioural and emotional functioning of young children awaiting elective cardiac surgery or catheter intervention.
To assess the cognitive, and behavioural and emotional functioning of children aged 3 months to 7 years shortly before elective cardiac surgery or elective interventional catheterisation. We used the Bayley Scales of Infant Development, and the McCarthy Scales of Children's Abilities, to measure cognitive functioning. The Child Behavior Checklist was used to assess behavioural and emotional problems. We found no significant differences in mean cognitive scores for children scheduled for cardiac surgery or interventional catheterisation when compared with reference groups. This was also the case for children awaiting cardiac surgery as opposed to those awaiting interventional catheterisation, and for those below as compared to those above the age of 2.5 years. Overall, our results regarding behavioural and emotional functioning were comparable to those of normative reference groups. The only difference found was that the children scheduled for cardiac surgery and aged from 2 to 3 years had significantly higher scores on the Child Behavior Checklist than did peers from normative groups. Cognitive, and behavioural and emotional functioning, both for young children awaiting elective cardiac surgery and interventional catheterisation, can be considered as quite favourable.


Mothering under political violence: Post-traumatic symptoms, observed maternal parenting practices and child externalising behaviour.
Using the family stress model as our conceptual framework, we explored whether observed maternal parenting practices (positive and coercive) account for the associations between mothers' post-traumatic stress symptoms and children's externalising behaviours. Mothers' self-reported post-traumatic stress symptoms, observed maternal practices, and reports of children's externalising behaviour were collected from 123 Israeli mothers and their children, who were exposed to ongoing rocket attacks in southern Israel. A structural equation model revealed that mothers' post-traumatic stress symptoms were linked with greater maternal coercive parenting practices, which in turn were associated with more externalising behaviours in children. The study highlights the crucial role of maternal distress and mothers' parenting skills in the development of externalising behaviours in children exposed to chronic political violence. These results suggest that prevention interventions designed to promote parenting skills for mothers exposed to political violence may be beneficial for children's healthy development.


Rectification of muscarinic K+ current by magnesium ion in guinea pig atrial cells.
Rectifying properties of the acetylcholine (ACh)-sensitive K+ channels were studied using a patch-clamp method in single atrial cells prepared enzymatically from adult guinea pig hearts. In the presence of micromolar concentration of nonhydrolyzable guanosine 5'-triphosphate (GTP) analogue 5'-guanylylimidodiphosphate (GppNHp) and the absence of Mg2+ at the inner surface of patch membrane [( Mg2+]i), the channel activity recovered in inside-out patch condition. The single channel conductance became ohmic between -80 and +80 mV (symmetrical 150 mM K+ solutions). The rapid relaxation of outward single channel currents was disclosed on a depolarization. [Mg2+]i blocked the outward current through the channel dose- and voltage-dependently and also induced a dose-dependent increase in the channel activation. The apparent paradoxical role of [Mg2+]i is important for the cholinergic control in the heart; voltage-dependent Mg block ensures a low K+ conductance of cell membrane at the plateau of action potentials during the exposure to ACh, thereby slowing the heart rate without unfavorable shortening of the action potentials.


Posttraumatic stress disorder, depression, and somatic symptoms in U.S. Mien patients.
This report describes treatment over a period of 6 years of Mien refugees from highland Laos in the Indochinese Psychiatric Program of the Oregon Health Sciences University (Portland, OR). The medical and psychiatric problems of 84 patients were presented through somatic symptoms such as headache, dizziness, or musculoskeletal pain. Primary care medical problems were identified and treated, with the major focus on the two most common psychiatric diagnoses: major depression and posttraumatic stress disorder. Cultural beliefs about illness and medication interfered with adherence to prescribed treatment. A marked sensitivity to side effects of certain antidepressants also resulted in subtherapeutic doses. Patients rarely volunteered their traumatic histories, psychiatric problems, or dissatisfaction with medications. However, the effective use of medication for somatic complaints, along with the continuing recognition of Mien health beliefs in psychosocial treatments, allowed for the development of a trusting doctor-patient relationship and continued psychiatric care.


Ca(V)3.1 is a tremor rhythm pacemaker in the inferior olive.
The rhythmic motor pathway activation by pacemaker neurons or circuits in the brain has been proposed as the mechanism for the timing of motor coordination, and the abnormal potentiation of this mechanism may lead to a pathological tremor. Here, we show that the potentiation of Ca(V)3.1 T-type Ca(2+) channels in the inferior olive contributes to the onset of the tremor in a pharmacological model of essential tremor. After administration of harmaline, 4- to 10-Hz synchronous neuronal activities arose from the IO and then propagated to cerebellar motor circuits in wild-type mice, but those rhythmic activities were absent in mice lacking Ca(V)3.1 gene. Intracellular recordings in brain-stem slices revealed that the Ca(V)3.1-deficient inferior olive neurons lacked the subthreshold oscillation of membrane potentials and failed to trigger 4- to 10-Hz rhythmic burst discharges in the presence of harmaline. In addition, the selective knockdown of Ca(V)3.1 gene in the inferior olive by shRNA efficiently suppressed the harmaline-induced tremor in wild-type mice. A mathematical model constructed based on data obtained from patch-clamping experiments indicated that harmaline could efficiently potentiate Ca(V)3.1 channels by changing voltage-dependent responsiveness in the hyperpolarizing direction. Thus, Ca(V)3.1 is a molecular pacemaker substrate for intrinsic neuronal oscillations of inferior olive neurons, and the potentiation of this mechanism can be considered as a pathological cause of essential tremor.


An extensive computational approach to analyze and characterize the functional mutations in the galactose-1-phosphate uridyl transferase (GALT) protein responsible for classical galactosemia.
Type I galactosemia is a very rare autosomal recessive genetic metabolic disorder that occurs because of the mutations present in the galactose-1-phosphate uridyl transferase (GALT) gene, resulting in a deficiency of the GALT enzyme. The action of the GALT enzyme is to convert galactose-1-phosphate and uridine diphosphate glucose into glucose-1-phosphate (G1P) and uridine diphosphate-galactose, a crucial second step of the Leloir pathway. A missense mutation in the GALT enzyme leads to variable galactosemia's clinical presentations, ranging from mild to severe. Our study aimed to employ a comprehensive computational pipeline to analyze the most prevalent missense mutations (p.S135L, p.K285 N, p.Q188R, and p.N314D) responsible for galactosemia; these genes could serve as potential targets for chaperone therapy. We analyzed the four mutations through different computational analyses, including amino acid conservation, in silico pathogenicity and stability predictions, and macromolecular simulations (MMS) at 50 ns The stability and pathogenicity predictors showed that the p.Q188R and p.S135L mutants are the most pathogenic and destabilizing. In agreement with these results, MMS analysis demonstrated that the p.Q188R and p.S135L mutants possess higher deviation patterns, reduced compactness, and intramolecular H-bonds of the protein. This could be due to the physicochemical modifications that occurred in the mutants p.S135L and p.Q188R compared to the native. Evolutionary conservation analysis revealed that the most prevalent mutations positions were conserved among different species except N314. The proposed research study is intended to provide a basis for the therapeutic development of drugs and future treatment of classical galactosemia and possibly other genetic diseases using chaperone therapy.


An introduction to the concept of "quality of life in Parkinson's disease".
The sense of well-being is central to the concept of quality of life (QoL), but there is not a universally accepted definition of health-related QoL. QoL refers to the patient's own evaluation of the impact of the disease. It includes physical, psychological and socioeconomic dimension, and its measurement is of paramount importance in evaluating research outcomes and in cost-benefit analyses. In addition, QoL assessment helps to identify problems and may be essential in chronic and disabling diseases such as in Parkinson's disease (PD). There are numerous reasons for the decrease in QoL suffered by PD patients: restrictions in mobility, falls, emotional disorders, social embarrassment, isolation, sleep disturbances, dyskinesias, and fluctuations. Many aspects of these disorders go unnoticed in clinical evaluation, and only QoL assessment allows them to be rated. Generic instruments have been used in a few studies measuring QoL in PD patients. Only recently have specific instruments as PDQ-39 and PDQL-37 been designed and validated. QoL assessment in PD is an important and expanding area, with a promising application in clinical trials and pharmacoeconomics.


Limitations of ultrasound evaluation in acute closed renal trauma.
Imaging of the kidneys following acute closed renal trauma may be undertaken using one of several available modalities. Ultrasound evaluation is often the first choice of imaging modality, as it is quick, non-invasive and often readily available for urgent assessment. We report three cases in which significant under-evaluation of major renal parenchymal injury occurred using B-mode ultrasound; the injury was detected only by subsequent computerized tomography (CT) imaging.


Actions of epoxygenase metabolites on the preglomerular vasculature.
Epoxygenase metabolites of arachidonic acid are produced by the kidney and have been implicated in the control of renal blood flow. This study examined the preglomerular actions of various epoxyeicosatrienoic acids (EET). By use of the in vitro blood-perfused juxtamedullary nephron preparation, interlobular and afferent arteriolar diameter responses to 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET were determined. Diameters of interlobular and afferent arterioles preconstricted with 0.5 microM norepinephrine averaged 24 +/- 1 microns (N = 27) and 17 +/- 1 microns (N = 32), respectively, at a renal perfusion pressure of 100 mm Hg. Superfusion with 0.01 to 100 nM 11,12-EET caused graded increases in diameters of the interlobular and afferent arterioles. At a dose of 100 nM, 11,12-EET increased the diameters of the interlobular and afferent arterioles by 18 +/- 2% (N = 10) and 20 +/- 3% (N = 9), respectively. The vasodilatory response to 11,12-EET was stereoselective because 11,12(R,S)-EET but not 11,12(S,R)-EET increased the diameters of the interlobular and afferent arterioles. 14,15-EET had a much smaller effect and increased the diameters of the these vessels by 10%; 8,9-EET did not significantly affect vascular diameters. In contrast, 5,6-EET constricted the interlobular and afferent arterioles by 16 +/- 3% (N = 6) and 21 +/- 3% (N = 7), respectively. The corresponding diols, 5,6-DIHETE and 11,12-DIHETE, had no effect on diameters of the interlobular and afferent arterioles at concentrations up to 1 microM. The vasodilatory response to 11,12-EET was not affected by removal of the endothelium or by inhibition of cyclooxygenase with indomethacin. In contrast, the vasoconstrictor response to 5,6-EET was abolished by both removal of the endothelium or cyclooxygenase inhibition. The thromboxane/ enderoperoxide receptor inhibitor, SQ 29,548, resulted in a 60% attenuation of the afferent arteriolar vasconstriction to 5,6-EET. These results indicate that the preglomerular vasoconstriction to 5,6-EET is cyclooxygenase dependent and requires an intact endothelium, whereas the vasodilation to 11,12-EET is stereoselective and is the result of direct action of the epoxide on the preglomerular vascular smooth muscle.


Effects of retinoids in mouse models of colitis: benefit or danger to the gastrointestinal tract?
In vitro and in vivo data have shown that retinoid treatment promotes an anti-inflammatory milieu with few adverse effects toward the gastrointestinal tract. The in vivo studies reported here further evaluate retinoid effects in 2 mouse models of inflammatory bowel disease. Chronic dextran sulfate sodium colitis was induced in age- and weight-matched C57Bl/6 mice by 4 cycles of dextran sulfate sodium administration (6-8 animals/group). At cycle 4, animals were administered 13-cis-retinoic acid (isotretinoin, 30 mg/kg) or vehicle (oral gavage) or 4-oxo-13-cis-retinoic acid (15 mg/kg, intraperitoneal) daily. T-cell transfer colitis was induced in CB17 SCID mice by transfer of naive CD4CD62L T cells and treated by transfer of regulatory CD4CD25 T cells (4-6 animals/group); isolated from BALB/c mice after treatment with isotretinoin or vehicle, as above, for 2 weeks. Assessments included endoscopic and histological scores, myeloperoxidase activity, serum cytokines, and plasma isotretinoin levels. Retinoid-treated animals with colitis showed comparable changes in myeloperoxidase activity, and endoscopic and histological scores, versus untreated animals with colitis. Modest and comparable changes were seen in body weight and colon length in animals injected with naive T cells from isotretinoin-treated donors versus those injected with T cells from vehicle-treated donors. Retinoid treatment was consistently associated with lower interleukin-12 levels, which, after the transfer of naive T cells from isotretinoin-treated donors, supported isotretinoin-mediated predisposition of naive T cells toward reduced proinflammatory cytokine expression. Colitis had no effect on isotretinoin exposure. Retinoids attenuate the proinflammatory cytokine response in vivo, with only modest effects on body weight and parameters of gastrointestinal morphology.


In vitro antiparasitic activity and chemical composition of the essential oil from Protium ovatum leaves (Burceraceae).
Leishmaniasis and trypanosomiasis are globally widespread parasitic diseases which have been responsible for high mortality rates. Since drugs available for their treatment are highly hepatotoxic, nephrotoxic and cardiotoxic, adherence to therapy has been affected. Thus, the search for new, more effective and safer drugs for the treatment of these diseases is necessary. Natural products have stood out as an alternative to searching for new bioactive molecules with therapeutic potential. In this study, the chemical composition and antiparasitic activity of the essential oil from Protium ovatum leaves against trypomastigote forms of Trypanosoma cruzi and the promastigote forms of Leishmania amazonensis were evaluated. The essential oil was promising against trypomastigote forms of T. cruzi (IC50= 28.55 μg.mL-1) and L. amazonensis promastigotes (IC50 = 2.28 μg.mL-1). Eighteen chemical constituents were identified by Gas Chromatography coupled to Mass Spectrometry (GC-MS) in the essential oil, whose major constituents were spathulenol (17.6 %), caryophyllene oxide (16.4 %), β-caryophyllene (14.0 %) and myrcene (8.4 %). In addition, the essential oil from P. ovatum leaves had moderate cytotoxicity against LLCMK2 adherent epithelial cell at the concentration range under analysis (CC50 = 150.9 μg.mL-1). It should be highlighted that this is the first report of the chemical composition and anti-Trypanosoma cruzi and anti-Leishmania amazonensis activities of the essential oil from Protium ovatum leaves.


Comparison of constitutive and thiabendazole-induced expression of five cytochrome P450 genes in fourth-stage larvae of Haemonchus contortus isolates with different drug susceptibility identifies one gene with high constitutive expression in a multi-resistant isolate.
Benzimidazoles (BZs) remain amongst the most widely used anthelmintic drug classes against gastro-intestinal nematode infections, although their efficacy is increasingly compromised by resistance. The primary underlying mechanisms for BZ resistance are single-nucleotide polymorphisms (SNPs) in the isotype 1 β-tubulin gene causing the substitutions F167Y, E198A or F200Y. However, resistance is believed to be multi-genic and previous studies have shown that isolates carrying 90-100% F200Y can vary considerably in their resistance level in the egg hatch assay (EHA). Cytochrome P450 monooxygenases (CYPs) are associated with drug resistance in mammals and arthropods and have been considered as mediators of anthelmintic resistance. In Caenorhabditis elegans, several members of the CYP34/35 and CYP31 families are BZ and/or xenobiotic inducible and thiabendazole (TBZ) is metabolised by CYP35D1. Here, expression of all 5 CYPs closely related to the C. elegans CYP34/35 and CYP31 families was investigated in fourth-stage larvae of two susceptible and three BZ-resistant Haemonchus contortus isolates following in vitro exposure to TBZ for 3 and 6 h using real-time RT-PCR. The resistance status of all isolates was determined using EHAs and quantification of resistance-associated β-tubulin SNPs using pyrosequencing. While none of the CYPs was TBZ inducible, constitutive expression of CYP34/35 family member HCOI100383400 was significantly 2.4-3.7-fold higher in the multi-drug resistant WR isolate with the strongest BZ resistance phenotype compared to susceptible and intermediate-level BZ-resistant isolates. Although this increase is only moderate, HCOI100383400 might still be involved in high-level BZ resistance by further decreasing susceptibility in isolates already carrying 100% of a β-tubulin SNP causing BZ resistance. Lower transcript levels were observed for all CYPs in the intermediately resistant IRE isolate in comparison to the susceptible HcH isolate, which, except for CYP HCOI01579500, were statistically non-significant. This suggests that none of the investigated CYPs may contribute to protection against TBZ in this particular isolate.


Understanding trends in concentrated poverty: 1980-2014.
Trends in concentrated neighborhood poverty in the United States have been volatile over the past several decades. Using data from the 1980 to 2000 decennial census and the 2010-2014 American Community Survey, we examine the association between concentrated poverty across metropolitan areas in the United States and key proximate factors, including overall changes in poverty, racial residential segregation, and income segregation. One of our unique contributions is assessing the relative contribution of each of these to long-term trends in such poverty using a decomposition analysis. We find that changes in the segregation of the poor explained the largest share of the change in concentrated poverty over most of the time period, with the exception of the 1990s, where the plunge in both black and white poverty rates had the largest role in explaining the considerable decline in concentrated poverty in that decade for both groups. The association between racial segregation and black concentrated poverty is positive but weaker, indicating that without declines in black segregation, concentrated poverty would have been higher. Overall, growing income segregation, along with weak economic performance in recent years, have put more poor people at risk for living in high-poverty communities.


Topical use of silver sulphadiazine and chlorhexidine in the prevention of infection in thermal injuries.
The control of sepsis in burn wounds has long been the unrealized ideal of surgeons. This has been most nearly achieved by topical applications of silver sulphadiazine and chlorhexidine cream. An account is given of its probable mode of action and the method of application, together with an anlysis of the bacteriological results in 809 patients from December, 1969, to March, 1974.


Resection of pancreas without production of fistula.
A method of management of the pancreatic stump after partial pancreatic resection is described which successfully prevented the development of postoperative pancreatic fistulas in 25 patients. After pancreaticoduodenectomy, performed upon ten of the patients, the pancreatic remnant was managed by ligation of the pancreatic duct, using an absorbable polyglycolic acid suture plus anastomotic invagination of the entire pancreatic stump into the jejunum. After distal subtotal pancreatectomy, performed upon 15 of the patients management of the pancreatic stump consisted of ductal ligation and provision of gentle occlusive coverage of the cut surface, using mattress sutures and an omental plug. Successful prevention of pancreatic fistulas in these patients probably depended upon ligation of the pancreatic ducts which precluded release of pancreatic enzymes into the jejunum and the juxtapancreatic region in the early postoperative period of healing.